article
dict | reports
listlengths 1
3.97k
|
|---|---|
{
"abstract": "To report a case of disseminated Nocardiosis with retinal and intracranial lesions.\nA 49-year-old woman immunosuppressed because of treatment given for bullous pemphigoid presented with altered mental status and multiple intracranial lesions on imaging. The patient was found to have multiple retinal lesions in both eyes, including a subretinal abscess in the right eye. The patient underwent brain biopsy, confirming Nocardia farcinica histopathologically and in culture.\nOcular Nocardiosis is a rare disease with varying prognosis that requires prompt diagnosis to ensure appropriate medical therapy.",
"affiliations": "Kentucky Lions Eye Center, University of Louisville, Louisville, KY, USA, 40202.;Kentucky Lions Eye Center, University of Louisville, Louisville, KY, USA, 40202.;Kentucky Lions Eye Center, University of Louisville, Louisville, KY, USA, 40202.;Kentucky Lions Eye Center, University of Louisville, Louisville, KY, USA, 40202.",
"authors": "Puri|Sidharth|S|;Hadayer|Amir|A|;Breaux|Andrea|A|;Barr|Charles C|CC|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1016/j.ajoc.2018.02.015",
"fulltext": "\n==== Front\nAm J Ophthalmol Case RepAm J Ophthalmol Case RepAmerican Journal of Ophthalmology Case Reports2451-9936Elsevier S2451-9936(17)30356-010.1016/j.ajoc.2018.02.015Brief reportDisseminated Nocardiosis with retinal abscess in a patient treated for bullous pemphigoid Puri Sidharth Hadayer Amir Breaux Andrea Barr Charles C. [email protected]∗Kentucky Lions Eye Center, University of Louisville, Louisville, KY, USA, 40202∗ Corresponding author. 301 E Muhammad Ali Blvd, Louisville, KY, USA, 40202. [email protected] 2 2018 6 2018 24 2 2018 10 145 147 3 12 2017 15 1 2018 21 2 2018 © 2018 The Authors. Published by Elsevier Inc.2018This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Purpose\nTo report a case of disseminated Nocardiosis with retinal and intracranial lesions.\n\nObservations\nA 49-year-old woman immunosuppressed because of treatment given for bullous pemphigoid presented with altered mental status and multiple intracranial lesions on imaging. The patient was found to have multiple retinal lesions in both eyes, including a subretinal abscess in the right eye. The patient underwent brain biopsy, confirming Nocardia farcinica histopathologically and in culture.\n\nConclusions and Importance\nOcular Nocardiosis is a rare disease with varying prognosis that requires prompt diagnosis to ensure appropriate medical therapy.\n\nKeywords\nAbscessNocardiaNocardiosisRetina\n==== Body\n1 Introduction\nNocardia are gram positive, aerobic, filamentous bacteria that can cause severe infection in immunocompromised individuals. Disseminated Nocardiosis can be a devastating multi-system disease, including ocular involvement. We wish to report a unique patient with retinal lesions secondary to disseminated Nocardiosis.\n\n2 Case report\nA 49-year-old Caucasian female had altered mental status and headache for 2 days. She had been treated with cyclosporine and prednisone for bullous pemphigoid for several months. The patient's mental status deteriorated and she was sedated and intubated because of a decline in respiratory status. She remained afebrile without leukocytosis. Computed Tomography (CT) of Chest and Abdomen revealed ground glass opacities suggestive of possible right lung pneumonia. Cerebrospinal fluid (CSF) and blood cultures for bacterial, viral, and fungal etiology were negative. The patient was given intravenous vancomycin, piperacillin-tazobactam, and micafungin.\n\nInitial ophthalmic examination of both eyes revealed a quiet anterior segment. Dilated ophthalmoscopic exam revealed a large (2 disc diameter size) elevated subretinal lesion with surrounding hemorrhage in the right eye and multiple small 1/2–1/4 disc diameter size, cream-colored lesions throughout the posterior pole and periphery in both eyes (Fig. 1A and B). There was no apparent vitritis or inflammation in either eye.Fig. 1 Dilated Fundus Photographs of Right and Left Eyes\n\n(A) Photograph of Right Eye revealing multiple cream colored subretinal lesions and large 2 disc diameter elevated subretinal lesion with surrounding hemorrhages\n\n(B) Photograph of Left Eye revealing cream colored retinal lesion similar to right eye.\n\nFig. 1\n\nMagnetic Resonance Imaging (MRI) scan revealed numerous small enhancing lesions throughout her brain (Fig. 2A and B). Brain biopsy and histopathology of one of the enhancing, superficial intracranial lesions revealed filamentous, gram-positive bacteria indicative of Nocardia (Fig. 3, Fig. 4). Fungal cultures yielded Nocardia farcinica. Intravenous imipenem, bactrim, and amikacin were started due to organism sensitivity. Given the possibility of an infectious choroiditis, the following day the patient underwent bilateral vitreous tap-and-inject with amikacin (0.4 mg/0.1 ml). Vitreous gram stain, cultures and polymerase chain reaction were negative. The patient's clinical status slowly improved and, in consultation with infectious disease, she was discharged on systemic bactrim and augmentin for a one year course.Fig. 2 Magnetic Resonance Imaging (MRI) Demonstrating Nocardial Central Nervous System (CNS) Infection\n\n(A) Axial T1 + Contrast, Weighted image showing numerous ring-enhancing lesions\n\n(B) Axial Diffusion Weighted Imaging (DWI) revealing numerous enhancing lesions.\n\nFig. 2Fig. 3 Histopathology of CNS Biopsy Demonstrating Nocardial Infection. Gomori methenamine silver (GMS) stain is positive for numerous branching filamentous organisms (red arrows) (40x). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)\n\nFig. 3Fig. 4 Acid Fast Bacilli (AFB) stain is weakly positive for thin, beaded, slightly branching rods (40x).\n\nFig. 4\n\nFour months after discharge, while continuing treatment, ophthalmic examination revealed visual acuity of 20/100 right eye (OD) and 20/25 left eye (OS). Anterior segment exam findings revealed mild nuclear sclerotic cataracts. Posterior segment exam revealed subretinal fibrosis in macula and superonasally OD and multiple chorioretinal scars in both eyes (OU) (Fig. 5).Fig. 5 Dilated Fundus Photographs of Right and Left Eyes\n\n(A) Photograph of Right Eye revealing large 2 disc diameter area of subretinal fibrosis superonasal to disc and focal area of subretinal fibrosis in temporal macula with traction\n\n(B) Photograph of Left Eye revealing multiple chorioretinal scars.\n\nFig. 5\n\n3 Discussion\nOcular infection due to Nocardia is exceedingly rare, with fewer than forty cases of Nocardia endogenous endophthalmitis reported since 1967.1 Systemically, Nocardia is associated most often with pulmonary infection.2 Most patients tend to be immunosuppressed, as was this patient.3,4 Moreover, this patient is the first to be described in the literature to have ocular Nocardiosis after the complications of immunosuppressive treatment with prednisone for bullous pemphigoid.1\n\nOcular manifestations of this filamentous, gram-positive bacteria range from keratitis to endophthalmitis.5,6 Severity of disease and symptoms can be highly variable, making diagnosis difficult. Presentation can range from minimal inflammation to significant vitritis and retinal detachment.2,5, 6, 7 Diagnosis may be established through tissue acquisition (e.g. enucleation, subretinal biopsy), or vitreous sampling.7,8 The diagnostic yield of vitreous sampling was low in this case as to the lack of apparent vitritis. MRI Brain can also demonstrate ring-enhancing lesions indicative of Nocardia, as in this patient.9 In this case, the typical MRI findings together with positive brain biopsy established the clinical diagnosis of Nocardia farcinica, allowing for more appropriate antibacterial management. Treatment initially involves systemic sulfonamide therapy, as was conducted for this patient.1,7,10 The prognosis in systemic Nocardiosis is guarded, in part, due to the difficulty in establishing the diagnosis and management of diffuse disease. In a review conducted in 2011 by Eschle-Meniconi et al., 10 (27%) of the reported 36 patients with ocular Nocardia from 1967 to 2007 died.1 This patient is one of the few to survive this high mortality disease, stressing the severity and importance of early diagnosis and treatment.\n\n4 Conclusion\nOcular Nocardiosis is a rare disease often in the setting of immunosuppression and may respond to approved medical therapy after prompt diagnosis.\n\nPatient consent\nThe patient consented to publication of the case in writing/orally.\n\nAcknowledgements and disclosures\nFunding\nSupported in part by an unrestricted grant from Research to Prevent Blindness, New York, NY\n\nConflicts of interest\nThe following authors have no financial disclosures: SP, AH, AB, CCB.\n\nAuthorship\nAll authors attest that they meet the current ICMJE criteria for Authorship.\n\nAcknowledgements\nNone.\n==== Refs\nReferences\n1 Eschle-Meniconi M.E. Guex-Crosier Y. Wolfensberger T.J. Endogenous ocular nocardiosis—an interventional case report with a review of the literature Surv Ophthalmol 56 5 2011 383 415 21813147 \n2 Yua E. Laughlin S. Kasell E.E. Nocardial endophthalmitis and subretinal abscess: CT and MR imaging features with pathologic correlation: a case report AJNR 26 2005 1220 1222 15891188 \n3 Rogers S.J. Johnson B.L. Endogenous nocardia endophthalmitis: report of a case in a patient treated for lymphocytic lymphoma Ann Ophthalmol 9 1977 1123 1131 332035 \n4 Suppiah R. Abraham G. Sekhar U. Nocardial endophthalmitis leading to blindness in a renal transplant recipient Nephrol Dial Transplant 14 1999 1576 1577 10383032 \n5 Scott M. Mehta S. Rahman H.T. Nocardia veterana endogenous endophthalmitis in a cardiac transplant patient J Ophthalmic Inflamm Infect 3 2013 44 23548110 \n6 Sridhar M.S. Gopinathan U. Garg P. Ocular nocardia infections with special emphasis on the cornea Surv Ophthalmol 45 2001 361 378 11274691 \n7 Ng E.W. Zimmer-gallerie Green W.R. Endogenous Nocardia asteroides endophthalmitis Arch Ophthalmol 120 2 2002 210 213 11831927 \n8 Phillips W.B. Shields C.L. Shields J.A. Nocardia choroidal abscess Br J Ophthalmol 76 1992 694 696 1477051 \n9 Trehan H. Kaushik J. Jain V.K. Parihar J.K.S. Avasthi A. Endogenous Nocardial endophthalmitis in an immunosuppressed patient: a serious warning of an underlying life threatening and blinding disorder J Ophthalmic Vis Res 12 1 2017 113 116 28299015 \n10 Ameen M. Arenas R. Vásquez del Mercado E. Efficacy of imipenem therapy for Nocardia actinomycetomas refractory to sulfonamides J Am Acad Dermatol 62 2 2010 239 246 20005007\n\n",
"fulltext_license": "CC BY-NC-ND",
"issn_linking": "2451-9936",
"issue": "10()",
"journal": "American journal of ophthalmology case reports",
"keywords": "Abscess; Nocardia; Nocardiosis; Retina",
"medline_ta": "Am J Ophthalmol Case Rep",
"mesh_terms": null,
"nlm_unique_id": "101679941",
"other_id": null,
"pages": "145-147",
"pmc": null,
"pmid": "29780924",
"pubdate": "2018-06",
"publication_types": "D016428:Journal Article",
"references": "21813147;11274691;23548110;20005007;1477051;10383032;15891188;332035;11831927;28299015",
"title": "Disseminated Nocardiosis with retinal abscess in a patient treated for bullous pemphigoid.",
"title_normalized": "disseminated nocardiosis with retinal abscess in a patient treated for bullous pemphigoid"
}
|
[
{
"companynumb": "US-MYLANLABS-2018M1098116",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "080292",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOSPORINE."
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Eye abscess",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Nocardiosis",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Respiratory depression",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PURI S, HADAYER A, BREAUX A, BARR CC. DISSEMINATED NOCARDIOSIS WITH RETINAL ABSCESS IN A PATIENT TREATED FOR BULLOUS PEMPHIGOID. AM-J-OPHTHALMOL-CASE-REP 2018?10:145-147.",
"literaturereference_normalized": "disseminated nocardiosis with retinal abscess in a patient treated for bullous pemphigoid",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190107",
"receivedate": "20190107",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15795706,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20190417"
},
{
"companynumb": "US-TEVA-2019-US-994630",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65078",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOSPORINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "080356",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Nocardiosis",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Respiratory depression",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Eye abscess",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PURI S, HADAYER A, BREAUX A, BARR CC. DISSEMINATED NOCARDIOSIS WITH RETINAL ABSCESS IN A PATIENT TREATED FOR BULLOUS PEMPHIGOID. AM-J-OPHTHALMOL-CASE-REP 2018?10:145-147.",
"literaturereference_normalized": "disseminated nocardiosis with retinal abscess in a patient treated for bullous pemphigoid",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190110",
"receivedate": "20190110",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15805199,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20190417"
},
{
"companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2018R1-195285",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "210913",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CICLOSPORIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Eye abscess",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Retinal injury",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Craniocerebral injury",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nocardiosis",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PURI S, HADAYER A, BREAUX A, BARR CC. DISSEMINATED NOCARDIOSIS WITH RETINAL ABSCESS IN A PATIENT TREATED FOR BULLOUS PEMPHIGOID. AM J OPHTHALMOL CASE REP. 2018?10145-147",
"literaturereference_normalized": "disseminated nocardiosis with retinal abscess in a patient treated for bullous pemphigoid",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190108",
"receivedate": "20190108",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15796719,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
}
] |
{
"abstract": "OBJECTIVE\nTo assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety.\n\n\nMETHODS\nFrom January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias.\n\n\nRESULTS\nAmong 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab.\n\n\nCONCLUSIONS\nIn some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia.",
"affiliations": "Cardivascular Division, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.",
"authors": "Wang|Yan|Y|;Patel|Dimpi|D|;Wang|Dao Wu|DW|;Yan|Jiang Tao|JT|;Hsia|Henry H|HH|;Liu|Hao|H|;Zhao|Chun Xia|CX|;Zuo|Hou Juan|HJ|;Wang|Dao Wen|DW|",
"chemical_list": "D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D058915:Purinergic P1 Receptor Antagonists; D000628:Aminophylline; D007545:Isoproterenol",
"country": "United States",
"delete": false,
"doi": "10.1111/pace.12196",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0147-8389",
"issue": "36(11)",
"journal": "Pacing and clinical electrophysiology : PACE",
"keywords": "isoprenaline; monomorphic ventricular tachycardia; ventricular premature beat; β1-adrenoceptor blocker",
"medline_ta": "Pacing Clin Electrophysiol",
"mesh_terms": "D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000328:Adult; D000628:Aminophylline; D005260:Female; D006801:Humans; D007545:Isoproterenol; D008297:Male; D008875:Middle Aged; D058915:Purinergic P1 Receptor Antagonists; D017180:Tachycardia, Ventricular; D016896:Treatment Outcome; D018879:Ventricular Premature Complexes",
"nlm_unique_id": "7803944",
"other_id": null,
"pages": "1348-56",
"pmc": null,
"pmid": "23750689",
"pubdate": "2013-11",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "β1-Adrenoceptor blocker aggravated ventricular arrhythmia.",
"title_normalized": "1 adrenoceptor blocker aggravated ventricular arrhythmia"
}
|
[
{
"companynumb": "CN-WATSON-2014-15345",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMINOPHYLLINE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNCONFIRMED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Unk",
"drugdosagetext": "1 MG/KG CONTINUOUSLY, WITH TWO OR THREE TIMES OF EXTRA INTERMITTENT BOLUS INJECTIONS (0.1 G EACH TIM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMINOPHYLLINE (UNKNOWN)"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METOPROLOL SUCCINATE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "076862",
"drugbatchnumb": "UNCONFIRMED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "47.5 - 95 MG ONCE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR TACHYCARDIA",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL SUCCINATE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ESMOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.15 MG/KG/MIN; REPEATED ADMINISTRATION",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESMOLOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMINOPHYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Unk",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OFF LABEL USE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMINOPHYLLINE (UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ISOPROTERENOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.2 ?G/KG, PER HOUR, GRADUALLY INCREASED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".2",
"drugstructuredosageunit": "008",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISOPRENALINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ESMOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.05 MG/KG/MIN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".05",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESMOLOL"
}
],
"patientagegroup": null,
"patientonsetage": "33",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "65",
"reaction": [
{
"reactionmeddrapt": "Ventricular arrhythmia",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WANG Y, PATEL D, WANG DW, YAN JT, HSIA HH, LIU H ET AL. ?1-ADRENOCEPTOR BLOCKER AGGRAVATED VENTRICULAR ARRHYTHMIA. PACING CLIN ELECTROPHYSIOL. 2013;36(11):1348-56.",
"literaturereference_normalized": "1 adrenoceptor blocker aggravated ventricular arrhythmia",
"qualification": "1",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20140711",
"receivedate": "20140711",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10298449,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150326"
},
{
"companynumb": "CN-WATSON-2014-15346",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ESMOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.05 MG/KG/MIN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".05",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESMOLOL"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METOPROLOL SUCCINATE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNCONFIRMED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "47.5 - 95 MG ONCE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR TACHYCARDIA",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL SUCCINATE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMINOPHYLLINE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": "87727",
"drugbatchnumb": "UNCONFIRMED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Unk",
"drugdosagetext": "1 MG/KG CONTINUOUSLY, WITH TWO OR THREE TIMES OF EXTRA INTERMITTENT BOLUS INJECTIONS (0.1 G EACH TIM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMINOPHYLLINE (UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ISOPROTERENOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.2 ?G/KG, PER HOUR, GRADUALLY INCREASED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".2",
"drugstructuredosageunit": "008",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISOPRENALINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMINOPHYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "87727",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Unk",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OFF LABEL USE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMINOPHYLLINE (UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ESMOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.15 MG/KG/MIN; REPEATED ADMINISTRATION",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESMOLOL"
}
],
"patientagegroup": null,
"patientonsetage": "40",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "54",
"reaction": [
{
"reactionmeddrapt": "Ventricular arrhythmia",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WANG Y, PATEL D, WANG DW, YAN JT, HSIA HH, LIU H ET AL. ?1-ADRENOCEPTOR BLOCKER AGGRAVATED VENTRICULAR ARRHYTHMIA. PACING CLIN ELECTROPHYSIOL. 2013;36(11):1348-56.",
"literaturereference_normalized": "1 adrenoceptor blocker aggravated ventricular arrhythmia",
"qualification": "1",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20140711",
"receivedate": "20140711",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10298980,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150326"
},
{
"companynumb": "CN-WATSON-2014-15333",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METOPROLOL SUCCINATE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNCONFIRMED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "47.5 - 95 MG ONCE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR TACHYCARDIA",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL SUCCINATE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ESMOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.15 MG/KG/MIN; REPEATED ADMINISTRATION",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESMOLOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMINOPHYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "87727",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Unk",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OFF LABEL USE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMINOPHYLLINE (UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ESMOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.05 MG/KG/MIN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".05",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESMOLOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMINOPHYLLINE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": "87727",
"drugbatchnumb": "UNCONFIRMED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Unk",
"drugdosagetext": "1 MG/KG CONTINUOUSLY, WITH TWO OR THREE TIMES OF EXTRA INTERMITTENT BOLUS INJECTIONS (0.1 G EACH TIM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMINOPHYLLINE (UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ISOPROTERENOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.2 ?G/KG, PER HOUR, GRADUALLY INCREASED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "VENTRICULAR ARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".2",
"drugstructuredosageunit": "008",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISOPRENALINE"
}
],
"patientagegroup": null,
"patientonsetage": "47",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "60",
"reaction": [
{
"reactionmeddrapt": "Ventricular arrhythmia",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WANG Y, PATEL D, WANG DW, YAN JT, HSIA HH, LIU H ET AL. ?1-ADRENOCEPTOR BLOCKER AGGRAVATED VENTRICULAR ARRHYTHMIA. PACING CLIN ELECTROPHYSIOL. 2013;36(11):1348-56.",
"literaturereference_normalized": "1 adrenoceptor blocker aggravated ventricular arrhythmia",
"qualification": "1",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20140711",
"receivedate": "20140711",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10298975,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150326"
}
] |
{
"abstract": "The identification of upper gastrointestinal (UGI) bleeding and perforated ulcers in claims data typically relies on inpatient diagnoses. The use of hemoglobin laboratory results might increase the detection of UGI events that do not lead to hospitalization.\n\n\n\nOur objective was to evaluate whether hemoglobin results increase UGI outcome identification in electronic databases, using non-steroidal anti-inflammatory drugs (NSAIDs) as a test case.\n\n\n\nFrom three data partner sites within the Mini-Sentinel Distributed Database, we identified NSAID initiators aged ≥18 years between 2008 and 2013. Numbers of events and risks within 30 days after NSAID initiation were calculated for four mutually exclusive outcomes: (1) inpatient UGI diagnosis of bleeding or gastric ulcer (standard claims-based definition without laboratory results); (2) non-inpatient UGI diagnosis AND ≥3 g/dl hemoglobin decrease; (3) ≥3 g/dl hemoglobin decrease without UGI diagnosis in any clinical setting; (4) non-inpatient UGI diagnosis, without ≥3 g/dl hemoglobin decrease.\n\n\n\nWe identified 2,289,772 NSAID initiators across three sites. Overall, 45.3% had one or more hemoglobin result available within 365 days before or 30 days after NSAID initiation; only 6.8% had results before and after. Of 7637 potential outcomes identified, outcome 1 accounted for 21.7%, outcome 2 for 0.8%, outcome 3 for 34.3%, and outcome 4 for 43.3%. Potential cases identified by outcome 3 were largely not suggestive of UGI events. Outcomes 1, 2, and 4 had similar distributions of specific UGI diagnoses.\n\n\n\nUsing available hemoglobin result values combined with non-inpatient UGI diagnoses identified few additional UGI cases. Non-inpatient UGI diagnostic codes may increase outcome detection but would require validation.",
"affiliations": "Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, 02120, USA. [email protected].;Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, 02120, USA.;Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.;HealthCore, Wilmington, DE, USA.;Kaiser Permanente Colorado Institute for Health Research, Denver, CO, USA.;University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.;University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.;Kaiser Permanente Colorado Institute for Health Research, Denver, CO, USA.",
"authors": "Patorno|Elisabetta|E|;Gagne|Joshua J|JJ|;Lu|Christine Y|CY|;Haynes|Kevin|K|;Sterrett|Andrew T|AT|;Roy|Jason|J|;Wang|Xingmei|X|;Raebel|Marsha A|MA|",
"chemical_list": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D006454:Hemoglobins",
"country": "New Zealand",
"delete": false,
"doi": "10.1007/s40264-016-0472-3",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0114-5916",
"issue": "40(1)",
"journal": "Drug safety",
"keywords": null,
"medline_ta": "Drug Saf",
"mesh_terms": "D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal; D059019:Clinical Coding; D015331:Cohort Studies; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006471:Gastrointestinal Hemorrhage; D006454:Hemoglobins; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D018571:Sentinel Surveillance; D013276:Stomach Ulcer; D013997:Time Factors",
"nlm_unique_id": "9002928",
"other_id": null,
"pages": "91-100",
"pmc": null,
"pmid": "27848201",
"pubdate": "2017-01",
"publication_types": "D016428:Journal Article; D013487:Research Support, U.S. Gov't, P.H.S.",
"references": "8664388;14585769;21670242;19623573;7722586;23137151;8113827;11864803;20140892;22262590;22262586;1906692;17285379;16253582;21387461;17982182;24677577;10408987",
"title": "The Role of Hemoglobin Laboratory Test Results for the Detection of Upper Gastrointestinal Bleeding Outcomes Resulting from the Use of Medications in Observational Studies.",
"title_normalized": "the role of hemoglobin laboratory test results for the detection of upper gastrointestinal bleeding outcomes resulting from the use of medications in observational studies"
}
|
[
{
"companynumb": "US-JNJFOC-20170116071",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IBUPROFEN"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "019012",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IBUPROFEN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IBUPROFEN"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "019012",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IBUPROFEN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Upper gastrointestinal haemorrhage",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Gastric ulcer",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PATORNO E, GAGNE JJ, LU CY, HAYNES K, STERRETT AT, ROY J, ET AL. THE ROLE OF HEMOGLOBIN LABORATORY TEST RESULTS FOR THE DETECTION OF UPPER GASTROINTESTINAL BLEEDING OUTCOMES RESULTING FROM THE USE OF MEDICATIONS IN OBSERVATIONAL STUDIES . DRUG SAFETY 01-JAN-2017;40 (1):91-100.",
"literaturereference_normalized": "the role of hemoglobin laboratory test results for the detection of upper gastrointestinal bleeding outcomes resulting from the use of medications in observational studies",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170130",
"receivedate": "20170130",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13162832,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
}
] |
{
"abstract": "Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.",
"affiliations": "*Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut; †Morgenstern Center for Orbital and Facial Plastic Surgery, Wayne, Pennsylvania; ‡Oculofacial Plastic Surgeons of Georgia, Atlanta, Georgia; and §Department of Ophthalmic Oncology, Smilow Cancer Hospital, Yale University School of Medicine, New Haven, Connecticut, U.S.A.",
"authors": "Rowlands|Megan A|MA|;Giacometti|Joseph N|JN|;Servat|Javier|J|;Materin|Miguel A|MA|;Levin|Flora|F|",
"chemical_list": "D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000077271:Imiquimod",
"country": "United States",
"delete": false,
"doi": "10.1097/IOP.0000000000000432",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0740-9303",
"issue": "33(1)",
"journal": "Ophthalmic plastic and reconstructive surgery",
"keywords": null,
"medline_ta": "Ophthalmic Plast Reconstr Surg",
"mesh_terms": "D000276:Adjuvants, Immunologic; D000287:Administration, Topical; D000368:Aged; D000634:Aminoquinolines; D003229:Conjunctival Diseases; D006801:Humans; D000077271:Imiquimod; D055623:Keratosis, Actinic; D008297:Male; D016896:Treatment Outcome",
"nlm_unique_id": "8508431",
"other_id": null,
"pages": "e21-e23",
"pmc": null,
"pmid": "25853505",
"pubdate": "2017",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.",
"title_normalized": "topical imiquimod in the treatment of conjunctival actinic keratosis"
}
|
[
{
"companynumb": "US-STRIDES ARCOLAB LIMITED-2017SP005653",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ERYTHROMYCIN"
},
"drugadditional": null,
"drugadministrationroute": "061",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "OINTMENT, CREAM",
"drugdosagetext": "UNK UNK, PRN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACTINIC KERATOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ERYTHROMYCIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "IMIQUIMOD"
},
"drugadditional": null,
"drugadministrationroute": "061",
"drugauthorizationnumb": "202002",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, AT BED TIME",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACTINIC KERATOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMIQUIMOD."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "IMIQUIMOD"
},
"drugadditional": null,
"drugadministrationroute": "061",
"drugauthorizationnumb": "202002",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMIQUIMOD."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Eye irritation",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ROWLANDS MA, GIACOMETTI JN, SERVAT J, MATERIN MA, LEVIN F. TOPICAL IMIQUIMOD IN THE TREATMENT OF CONJUNCTIVAL ACTINIC KERATOSIS. OPHTHAL-PLAST-RECONSTR-SURG. 2017;33(1):E21-E23",
"literaturereference_normalized": "topical imiquimod in the treatment of conjunctival actinic keratosis",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170711",
"receivedate": "20170711",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13740238,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20171127"
}
] |
{
"abstract": "BACKGROUND\nTNF alpha inhibitor (TNFAI) therapy has been associated with inflammatory neurological syndromes.\n\n\nOBJECTIVE\nTo present 10 new cases of TNFAI associated neurological disease and a review of the literature.\n\n\nMETHODS\nThe design and methods were based on case series collected from Oregon Health & Sciences University and the Department of Veterans Affairs Hospital in Portland, Oregon and PubMed review.\n\n\nRESULTS\nWe describe eight demyelinating central nervous system syndromes and two peripheral nervous system syndromes associated with TNFAI therapy. Characteristics from these cases are analyzed with data from 141 additional cases from the literature. Onset was between the ages of 36 and 65 years in 84% of CNS cases, distinguishing TNFAI-associated disease from sporadic multiple sclerosis. Symptoms occurred within one year of TNFAI therapy in 71%. Etanercept therapy was reported in the majority of cases of CNS syndromes and infliximab therapy in the majority of neuromuscular syndromes. Significant disability remained in 67% of cases although 82% had been followed for less than one year.\n\n\nCONCLUSIONS\nOur case series and literature review demonstrates an association between TNFAI therapy and inflammatory neurological disease. While a causal relationship is suggested, this remains uncertain. TNFAI-associated neurological syndromes are associated with significant disability and longer follow-up is needed to better determine natural history and evaluate appropriate treatment interventions.",
"affiliations": "Department of Neurology, University of Vermont College of Medicine, Fletcher Allen Health Care, University Health Center, Vermont 05401, USA. [email protected]",
"authors": "Solomon|Andrew J|AJ|;Spain|Rebecca I|RI|;Kruer|Michael C|MC|;Bourdette|Dennis|D|",
"chemical_list": "D014409:Tumor Necrosis Factor-alpha",
"country": "England",
"delete": false,
"doi": "10.1177/1352458511412996",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1352-4585",
"issue": "17(12)",
"journal": "Multiple sclerosis (Houndmills, Basingstoke, England)",
"keywords": null,
"medline_ta": "Mult Scler",
"mesh_terms": "D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid; D003711:Demyelinating Diseases; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis; D009422:Nervous System Diseases; D009902:Optic Neuritis; D014409:Tumor Necrosis Factor-alpha",
"nlm_unique_id": "9509185",
"other_id": null,
"pages": "1472-87",
"pmc": null,
"pmid": "21816758",
"pubdate": "2011-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't; D013486:Research Support, U.S. Gov't, Non-P.H.S.; D016454:Review",
"references": null,
"title": "Inflammatory neurological disease in patients treated with tumor necrosis factor alpha inhibitors.",
"title_normalized": "inflammatory neurological disease in patients treated with tumor necrosis factor alpha inhibitors"
}
|
[
{
"companynumb": "US-AMGEN-USASP2011066843",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ETANERCEPT"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "103795",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENBREL"
}
],
"patientagegroup": "5",
"patientonsetage": "61",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Optic neuritis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MICHAEL C KRUER. INFLAMMATORY NEUROLOGICAL DISEASE IN PATIENTS TREATED WITH TUMOR NECROSIS FACTOR ALPHA INHIBITORS. MULTIPLE SCLEROSIS JOURNAL. 2011;17(12):1472-1487",
"literaturereference_normalized": "inflammatory neurological disease in patients treated with tumor necrosis factor alpha inhibitors",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "GB",
"receiptdate": "20170421",
"receivedate": "20120111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 8332216,
"safetyreportversion": 4,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170830"
},
{
"companynumb": "US-AMGEN-USASP2011066849",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ETANERCEPT"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "103795",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNKNOWN DOSAGE FOR FOUR YEARS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PSORIATIC ARTHROPATHY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENBREL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ADALIMUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN DOSAGE FOR FOUR MONTHS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PSORIATIC ARTHROPATHY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ADALIMUMAB"
}
],
"patientagegroup": "5",
"patientonsetage": "42",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Optic neuritis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MICHAEL C KRUER. INFLAMMATORY NEUROLOGICAL DISEASE IN PATIENTS TREATED WITH TUMOR NECROSIS FACTOR ALPHA INHIBITORS. MULTIPLE SCLEROSIS. 2011;17(12):1472-1487",
"literaturereference_normalized": "inflammatory neurological disease in patients treated with tumor necrosis factor alpha inhibitors",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170425",
"receivedate": "20120111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 8332211,
"safetyreportversion": 4,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170830"
}
] |
{
"abstract": "BACKGROUND\nAntiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis.\n\n\nMETHODS\nThe LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety.\n\n\nRESULTS\nForty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation.\n\n\nCONCLUSIONS\nFor LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.",
"affiliations": "1 Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University, New York, NY. 2 Division of Gastroenterology and Hepatology, University of California, San Francisco, CA. 3 Division of Gastroenterology and Hepatology, University of Colorado, Denver, Aurora, CO. 4 Division of Hepatology and Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 5 Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA. 6 Department of Gastroenterology and Hepatology, Northwestern University, Chicago, IL.",
"authors": "Verna|Elizabeth C|EC|;Saxena|Varun|V|;Burton|James R|JR|;O'Leary|Jacqueline G|JG|;Dodge|Jennifer L|JL|;Stravitz|Richard T|RT|;Levitsky|Josh|J|;Trotter|James F|JF|;Everson|Gregory T|GT|;Brown|Robert S|RS|;Terrault|Norah A|NA|;|||",
"chemical_list": "D000998:Antiviral Agents; D015415:Biomarkers; D009842:Oligopeptides; D012367:RNA, Viral; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline",
"country": "United States",
"delete": false,
"doi": "10.1097/TP.0000000000000629",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0041-1337",
"issue": "99(8)",
"journal": "Transplantation",
"keywords": null,
"medline_ta": "Transplantation",
"mesh_terms": "D000998:Antiviral Agents; D015415:Biomarkers; D002779:Cholestasis; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus; D006526:Hepatitis C; D006801:Humans; D008103:Liver Cirrhosis; D016031:Liver Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D009842:Oligopeptides; D011392:Proline; D012367:RNA, Viral; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load",
"nlm_unique_id": "0132144",
"other_id": null,
"pages": "1644-51",
"pmc": null,
"pmid": "25715116",
"pubdate": "2015-08",
"publication_types": "D016428:Journal Article; D016448:Multicenter Study; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't",
"references": "19403902;17196700;19562707;11910340;21031537;22576324;18673428;23669289;23408534;15996238;23745027;20375406;20420649;19403903;24039107;17328985;23593993;20692693;24099469;17484872;18727694;24801415;21449784;18571272;16869810;22314429;24201995;16723165;12682884;23081888;21449783;21696308;21696307;11003634;23262248;18161839;22706796;11391241;17133585;19025933;21618566;18294165;14586888;23011083;21426450",
"title": "Telaprevir- and Boceprevir-based Triple Therapy for Hepatitis C in Liver Transplant Recipients With Advanced Recurrent Disease: A Multicenter Study.",
"title_normalized": "telaprevir and boceprevir based triple therapy for hepatitis c in liver transplant recipients with advanced recurrent disease a multicenter study"
}
|
[
{
"companynumb": "US-ROCHE-1459853",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "INTERFERON ALFACON-1"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEPATITIS C",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CONSENSUS INTERFERON"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PEGINTERFERON ALFA-2B"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEPATITIS C",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1.5",
"drugstructuredosageunit": "008",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PEGINTERFERON ALFA-2B"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TELAPREVIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEPATITIS C",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "750",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TELAPREVIR"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TELAPREVIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1125",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TELAPREVIR"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOSPORINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RIBAVIRIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021511",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEPATITIS C",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RIBAVIRIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOSPORINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050722",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "050722",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BOCEPREVIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEPATITIS C",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BOCEPREVIR"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PEGINTERFERON ALFA-2A"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "103964",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEPATITIS C",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "180",
"drugstructuredosageunit": "004",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PEG-INTERFERON ALFA 2A"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hepatic failure",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Rash",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Renal failure",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Bacteraemia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Transplant rejection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Leukopenia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatic cirrhosis",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Ascites",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Anaemia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "VERNA E, SAXENA V, BURTON J, OLEARY J, DODGE J, STRAVITZ R, LEVITSKY J, TROTTER J, EVERSON G, BROWN R AND TERRAULT N. TELAPREVIR- AND BOCEPREVIR-BASED TRIPLE THERAPY FOR HEPATITIS C IN LIVER TRANSPLANT RECIPIENTS WITH ADVANCED RECURRENT DISEASE: A MULTICENTER STUDY. TRANSPLANTATION 2015;99 (8):1644-1651.",
"literaturereference_normalized": "telaprevir and boceprevir based triple therapy for hepatitis c in liver transplant recipients with advanced recurrent disease a multicenter study",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20160929",
"receivedate": "20140919",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 10463048,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20161109"
}
] |
{
"abstract": "BACKGROUND\nNon-traumatic bowel perforation caused by cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections has become rare among patients with acquired immunodeficiency syndrome (AIDS) in the era of combination antiretroviral therapy (cART); however, CMV-associated and MAC-related immune reconstitution inflammatory syndrome (IRIS) has subsequently emerged owing to the wide use of integrase inhibitor-based regimens. Here we report a case of spontaneous perforation of the jejunum in a patient with human immunodeficiency virus (HIV) infection with good compliance to cART.\nA 32-year-old HIV-infected man developed CMV disease and DMAC infection, as unmasking IRIS, 3 days after the initiation of cART. After appropriate treatment for opportunistic infections, intermittent fever with enlarged lymph nodes in the abdomen occurred as paradoxical IRIS. The patient was administered prednisolone with subsequent tapering according to his clinical condition.\nUnexpected perforation of hollow organ during the titration of steroid dose with clinical presentations of severe abdominal pain was diagnosed by chest radiography.\n\n\nMETHODS\nHe underwent surgical repair with peritoneal toileting smoothly.\n\n\nRESULTS\nHe was discharged well with a clean surgical wound on post-operative day 10.\n\n\nCONCLUSIONS\nBowel perforation may be a life-threatening manifestation of IRIS in the era of cART. Steroids should be avoided, if possible, to decrease the risk of bowel perforation, especially in IRIS occurred after opportunistic diseases involving the gastrointestinal tract.",
"affiliations": "Department of Internal Medicine, Fu Jen Catholic University Hospital.;Department of Dermatology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi.;Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.;Department of Nursing, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.;Department of Internal Medicine, Fu Jen Catholic University Hospital.;Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.",
"authors": "Lee|Yi-Chien|YC|;Chiou|Chien-Chun|CC|;Wang|Jann-Tay|JT|;Yang|Yi-Chun|YC|;Tung|Shao-Hsien|SH|;Hsieh|Szu-Min|SM|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1097/MD.0000000000018163",
"fulltext": "\n==== Front\nMedicine (Baltimore)Medicine (Baltimore)MEDIMedicine0025-79741536-5964Wolters Kluwer Health 31804330MD-D-19-0246010.1097/MD.0000000000018163181636000Research ArticleClinical Case ReportNon-traumatic perforation of the jejunum in a human immunodeficiency virus-infected patient receiving combination antiretroviral therapy A case reportLee Yi-Chien MDabChiou Chien-Chun MDcWang Jann-Tay MD, PhDdeYang Yi-Chun MDfTung Shao-Hsien MDaHsieh Szu-Min MDd∗NA. a Department of Internal Medicine, Fu Jen Catholic University Hospitalb School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei Cityc Department of Dermatology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yid Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipeie Institute for Infectious Diseases and Vaccinology, National Health Research Institutesf Department of Nursing, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan.∗ Correspondence: Szu-Min Hsieh, Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Zhongshan South Road, Zhongzheng Dist., Taipei 10002, Taiwan (e-mail: [email protected]).12 2019 10 12 2019 98 49 e1816326 3 2019 18 10 2019 30 10 2019 Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.2019This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0Abstract\nRationale:\nNon-traumatic bowel perforation caused by cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections has become rare among patients with acquired immunodeficiency syndrome (AIDS) in the era of combination antiretroviral therapy (cART); however, CMV-associated and MAC-related immune reconstitution inflammatory syndrome (IRIS) has subsequently emerged owing to the wide use of integrase inhibitor-based regimens. Here we report a case of spontaneous perforation of the jejunum in a patient with human immunodeficiency virus (HIV) infection with good compliance to cART.\n\nPatient concerns:\nA 32-year-old HIV-infected man developed CMV disease and DMAC infection, as unmasking IRIS, 3 days after the initiation of cART. After appropriate treatment for opportunistic infections, intermittent fever with enlarged lymph nodes in the abdomen occurred as paradoxical IRIS. The patient was administered prednisolone with subsequent tapering according to his clinical condition.\n\nDiagnoses:\nUnexpected perforation of hollow organ during the titration of steroid dose with clinical presentations of severe abdominal pain was diagnosed by chest radiography.\n\nInterventions:\nHe underwent surgical repair with peritoneal toileting smoothly.\n\nOutcomes:\nHe was discharged well with a clean surgical wound on post-operative day 10.\n\nLessons:\nBowel perforation may be a life-threatening manifestation of IRIS in the era of cART. Steroids should be avoided, if possible, to decrease the risk of bowel perforation, especially in IRIS occurred after opportunistic diseases involving the gastrointestinal tract.\n\nKeywords\nbowel perforationcytomegalovirusimmune reconstitution inflammatory syndromeMycobacterium avium complexOPEN-ACCESSTRUE\n==== Body\n1 Introduction\nNon-traumatic perforation of the gastrointestinal tract is scarcely seen both in the general population and in patients with HIV infection.[1] The etiologies include immune-mediated diseases (e.g., Crohn disease), infections (e.g., CMV, Mycobacterium spp.), drugs (e.g., indomethacin, steroids), metabolic disorders, vascular insufficiencies and neoplasms.[2] CMV, a DNA virus belonging to the group of herpes viruses,[3] may lead to injuries in specific organs, including the retina, respiratory system, central nervous system, and gastrointestinal tract,[4] in patients with AIDS. The most frequently affected region of the gastrointestinal tract is the colon (47%), followed by the duodenum (21.7%), stomach (17.4%), esophagus (8.7%), and small intestine (4.3%).[5] Furthermore, the main location of bowel perforation in patients with AIDS is the colon (53%), followed by the distal ileum (40%) and the appendix (7%).[6]\n\nNontuberculous mycobacteria varying in pathogenicity are rather ubiquitous in the natural environment,[7] and MAC from water, soil, and food can cause infections in immunocompromised hosts through inhalation and ingestion.[8] This bacterium commonly causes disseminated MAC (DMAC) infection in HIV-positive patients with CD4 lymphocyte counts <50 cells/μL. Moreover, MAC infection can also involve the whole gastrointestinal tract with various appearances, including multiple raised nodules or normal-appearing mucosa in the stomach on endoscopy, thickened or edematous mucosal folds in the small bowel, and flattened mucosa in the colon on colonoscopic examination.[9]\n\nIRIS, also known as immune reconstitution disease, has been much more frequently encountered in clinical settings after the initiation of cART worldwide, and a wide range of pathologies have been disclosed.[10] Notwithstanding, all of the aforementioned HIV-associated gastrointestinal diseases rarely exhibit perforation of the involved hollow organs, implying the emergence of IRIS. Herein, we describe a HIV-positive patient with good adherence to cART who developed spontaneous perforation of the jejunum.\n\n2 Case report\nA 32-year-old man with HIV infection initially presented with oral candidiasis and latent syphilis. His baseline plasma HIV RNA load (PVL) was 1,110,000 copies/mL with a CD4 count of 25 cells/μL. Half a month after the HIV diagnosis, he started cART with dolutegravir/abacavir/lamivudine, and was admitted because of intermittent fever and diarrhea 3 days after the initiation of cART. Two-week intravenous ganciclovir was prescribed on the 4th hospital day with subsequent 10-day oral valganciclovir because CMV gastritis/duodenitis and colitis were diagnosed by biopsy via panendoscopy and colonoscopy after admission, respectively. Additionally, anti-MAC therapy with imipenem, amikacin, clarithromycin, and ethambutol was started on the 12th hospital day when MAC was isolated from cultures of the sputum, blood, and colon specimens. After 1 month of cART, his PVL decreased to 315 copies/mL and CD4 count increased to 33 cells/μL. However, intermittent fever persisted despite continuation of appropriate anti-MAC therapy for more than 2 weeks. Computed tomography of the abdomen on the 28th hospital day demonstrated splenomegaly with multiple enlarged mesenteric and para-aortic lymph nodes; however, no other significant pathogens were identified. Thus, the patient was started on twice-daily 15-mg prednisolone on the 31st hospital day under the tentative diagnosis of IRIS, and steroids were gradually tapered down. In the following days, his clinical condition became more stable and his fever subsided. He was discharged home on the 47th hospital day.\n\nNevertheless, 3 days after discharge, the patient was readmitted to the hospital for severe abdominal pain with nausea, poor appetite, and a spiking fever of 38.7°C. At presentation, his blood pressure was 121/78 mmHg and pulse rate was 138 beats/min. On physical examination, he showed an ill appearance with hypoactive bowel sound, rebound tenderness on the abdomen, and abdominal muscle guarding. Laboratory investigations showed a white blood cell count of 3000 cells/μL, hemoglobin level of 8.1 g/dL, platelet count of 194,000/μL, and elevated alanine amino transferase level of 102 U/L; other laboratory parameters were otherwise normal. Chest radiography revealed the presence of free air below the left-sided hemidiaphragm (Fig. 1), and perforation of the hollow organ was highly suspected. A surgeon was consulted immediately, and the patient was subsequently taken to the operating room. During the exploratory laparotomy, 1 small perforation was found 40 cm away from the ligament of Treitz in the jejunum, and surgical repair with peritoneal toileting was performed without problems. Enteral feeding was established on post-operative day 5, and cART with anti-MAC regimen was resumed later. He was discharged well with a clean surgical wound on post-operative day 10. After discharge, he received regular outpatient management for up to 30 months with a good adherence to cART, and undetected PVL with gradual recovery of CD4 count was observed.\n\nFigure 1 Chest radiography. Chest X-ray demonstrating the presence of free air below left side hemidiaphragm.\n\n3 Discussion\nWe presented here a complicated case. Our patient with AIDS initially presented with oral candidiasis. Intermittent fever developed 3 days after the initiation of cART. CMV disease and DMAC infection were diagnosed subsequently, which are compatible with unmasking IRIS.[10,11] However, after completion of at least 3-week of anti-CMV treatment with anti-MAC regimen for more than 5 weeks, intermittent fever with mesenteric and para-aortic lymphadenopathy supervened, suggesting the occurrence of paradoxical IRIS.[10,11] Furthermore, perforation of hollow organ unexpected occurred during steroid tapering. This is a rare case of spontaneous perforation of the jejunum in a patient with AIDS with CMV disease and DMAC infection who was compliant with cART. Unfortunately, no specimen was taken for pathological examination during the operation for bowel perforation; however, CMV- and MAC-associated IRIS and concurrent use of steroids might have contributed to the event.\n\nIn HIV-positive patients, most cases of intestinal perforation due to CMV infection occur in the advanced stage without a well-suppressed viral load;[4,6] however, a few case reports demonstrated presentations of bowel perforation secondary to CMV-associated IRIS with prescription of early cART.[12] Additionally, the involved organ in MAC-associated IRIS can be variable, but is most often the lymph nodes, liver, gastrointestinal tract, and even the lungs.[13] Different clinical phenomena of IRIS associated with MAC implicating intra-abdominal regions, including retroperitoneal abscess, colitis, mesenteric lymph node involvement, chylous ascites, and intestinal obstruction, have been previously reported.[14] There have been cases of intestinal perforation caused by Mycobacterium tuberculosis-related IRIS;[15] however, there is only 1 similar case report published in 2008.[16]\n\nWith the introduction of cART in 1996, the incidence rate of opportunistic infections, including CMV disease, DMAC infection, and AIDS-related death, dramatically declined in HIV-positive patients.[17] However, unexpected clinical events, known as IRIS, including paradoxical deterioration of treated opportunistic infections or unmasking of antecedently undetected untreated infections, might occur during the initial months, or even years, of cART.[18] Generally, making a diagnosis of CMV-related or MAC-associated IRIS is difficult because IRIS has remained a clinical syndrome caused by widely diverse pathogens and variable disease presentations. Our patient fulfilled those presumed criteria,[19] as mentioned above. Furthermore, several risk factors predisposed our patient to the development of IRIS, including rapid decrease in PVL due to the use of an integrase inhibitor-based regimen, lower baseline CD4 count before cART initiation, and an anti-retroviral naïve status. In contrast, cART, including integrase inhibitors, is currently recommended as a first-line therapy for HIV-infected patients, even in the advanced stage of AIDS,[20] because of its potent effect and good tolerability.[21] Yet, potential harmful results of IRIS may develop owing to fast decreasing in plasma HIV viral load[22]; thus, physicians should be aware of the emergence of IRIS during the treatment of HIV infection with integrase inhibitor-based regimens.\n\nMost cases of IRIS are benign and self-limited, although severe cases with eventual mortality have also been described.[14] As cART is crucial for improving immune function, the application of this treatment without interruption is recommended. Whether the adjunctive use of corticosteroid offers favorable prognosis among HIV-infected patients with IRIS remains controversial; however, its use for patients with life-threatening IRIS, for example, massive inflammation in the central nervous system, is indicated.[23] Notwithstanding, administration of systemic corticosteroid will lead to a variety of possible harmful outcomes, including infective complications,[24] glucose intolerance, increasing in blood pressure level, reduction in bone mineral density, and gastrointestinal ulceration.[11] Overall, the use of corticosteroids may increase the risk of gastrointestinal perforation by 40%.[25] In our patient, acute onset of abdominal pain with intestinal perforation occurred during the process of steroid tapering. Therefore, alertness to symptoms and signs of bowel perforation with judicious use of steroids will be helpful among HIV-infected patients with presumed IRIS following opportunistic diseases of the gastrointestinal tract.\n\n4 Conclusion\nThe incidence of CMV disease and DMAC infection will continuously decline with increased accessibility of cART; however, CMV- or MAC-associated IRIS will possibly be encountered much more commonly as integrase inhibitor-containing therapy becomes widely administered worldwide. Although no pathologic evidence could verify the etiology of bowel perforation in the presented case, CMV-related, MAC-associated IRIS and concurrent use of steroids might have contributed to the event. Hence, steroids should not be prescribed, if possible, to lower the risk of gut perforation, particularly in patients acquiring opportunistic infections involving the gastrointestinal tract with subsequent development of IRIS.\n\nAuthor contributions\nConceptualization: Yi-Chien Lee, Chien-Chun Chiou, Jann-Tay Wang.\n\nData curation: Yi-Chun Yang, Shao-Hsien Tung.\n\nInvestigation: Yi-Chun Yang, Shao-Hsien Tung.\n\nMethodology: Jann-Tay Wang, Szu-Min Hsieh.\n\nValidation: Jann-Tay Wang.\n\nWriting – original draft: Yi-Chien Lee, Chien-Chun Chiou.\n\nWriting – review & editing: Yi-Chien Lee, Chien-Chun Chiou, Szu-Min Hsieh.\n\nAbbreviations: AIDS = acquired immunodeficiency syndrome, cART = combination antiretroviral therapy, CMV = cytomegalovirus, DMAC = disseminated Mycobacterium avium complex, HIV = human immunodeficiency virus, IRIS = immune reconstitution inflammatory syndrome, MAC = Mycobacterium avium complex, PVL = plasma human immunodeficiency virus RNA load.\n\nHow to cite this article: Lee YC, Chiou CC, Wang JT, Yang YC, Tung SH, Hsieh SM. Non-traumatic perforation of the jejunum in a human immunodeficiency virus-infected patient receiving combination antiretroviral therapy: a case report. Medicine. 2019;98:49(e18163).\n\nYCL and CCC were first authors with contribution to this work equally.\n\nEthics approval and informed consent: In our institution, only an informed consent from the patient should be acquired while research of case report was conducted, so the need for ethical approval was waived. A written informed consent was obtained from the patient for publication of this report. The authors declare that they have no conflict of interests.\n==== Refs\nReferences\n[1] Eid HO Hefny AF Joshi S \nNon-traumatic perforation of the small bowel . Afr Health Sci \n2008 ;8 :36 –9 .19357730 \n[2] Freeman HJ \nSpontaneous free perforation of the small intestine in adults . World J Gastroenterol \n2014 ;20 :9990 –7 .25110427 \n[3] Galiatsatos P Shrier I Lamoureux E \nMeta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts . Dig Dis Sci \n2005 ;50 :609 –16 .15844689 \n[4] Michalopoulos N Triantafillopoulou K Beretouli E \nSmall bowel perforation due to CMV enteritis infection in an HIV-positive patient . BMC Res Notes \n2013 ;6 :45 .23379792 \n[5] Kawate S Ohwada S Sano T \nIleal perforation caused by cytomegalovirus infection in a patient with recurrent gastric cancer: report of a case . Surg Today \n2002 ;32 :1088 –90 .12541029 \n[6] Tsai HC Lee SS Wann SR \nColon perforation with peritonitis in an acquired immunodeficiency syndrome patient due to cytomegalovirus and amoebic colitis . J Formos Med Assoc \n2005 ;104 :839 –42 .16496064 \n[7] Kendall BA Winthrop KL \nUpdate on the epidemiology of pulmonary nontuberculous mycobacterial infections . Semin Respir Crit Care Med \n2013 ;34 :87 –94 .23460008 \n[8] Rotstein AH Stuckey SL \nMycobacterium avium complex spinal epidural abscess in an HIV patient . Australas Radiol \n1999 ;43 :554 –7 .10901982 \n[9] Bhaijee F Subramony C Tang SJ \nHuman immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses . Patholog Res Int \n2011 ;2011 :247923 .21559197 \n[10] Müller M Wandel S Colebunders R \nImmune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systemic review and meta-analysis . Lancet Infect Dis \n2010 ;10 :251 –61 .20334848 \n[11] Walker NF Scriven J Meintjes G \nImmune reconstitution inflammatory syndrome in HIV-infected patients . HIV AIDS (Auckl) \n2015 ;7 :49 –64 .25709503 \n[12] Gutiérrez-Delgado EM Villanueva-Lozano H García Rojas-Acosta MJ \nA case report of small bowel perforation secondary to cytomegalovirus related immune reconstitution inflammatory syndrome in an AIDS patient . Ann Med Surg (Lond) \n2016 ;13 :20 –3 .28018589 \n[13] Čurić K Poljak M Ihan A \nVery recent HIV infection accompanied by Pneumocystis jirovecii pneumonia and Mycobacterium avium complex immune reconstitution inflammatory syndrome: a case report . Acta Dermatovenerol Alp Pannonica Adriat \n2016 ;25 :57 –8 .27695869 \n[14] Lawn SD Bekker LG Miller RF \nImmune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals . Lancet Infect Dis \n2005 ;5 :361 –73 .15919622 \n[15] Guex AC Bucher HC Demartines N \nInflammatory bowel perforation during immune restoration after one year of antiretroviral and antituberculous therapy in an HIV-1-infected patient: report of a case . Dis Colon Rectum \n2002 ;45 :977 –8 .12130890 \n[16] Kawana M Starr RS Tashima KT \nSpontaneous perforation of the terminal ileum in an AIDS patient on highly active antiretroviral therapy with disseminated non-tuberculous mycobacterial infection . Int J Infect Dis \n2008 ;12 :603 –6 .18434225 \n[17] Palella FJ JrDelaney KM Moorman AC \nDeclining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators . N Engl J Med \n1998 ;338 :853 –60 .9516219 \n[18] Riddell J 4thKaul DR Karakousis PC \nMycobacterium avium complex immune reconstitution inflammatory syndrome: long term outcomes . J Transl Med \n2007 ;5 :50 .17937815 \n[19] Robertson J Meier M Wall J \nImmune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy . Clin Infect Dis \n2006 ;42 :1639 –46 .16652323 \n[20] Günthard HF Saag MS Benson CA \nAntiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel . JAMA \n2016 ;316 :191 –210 .27404187 \n[21] Clotet B Feinberg J van Lunzen J \nOnce-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naïve adults with HIV-1 infection (FLAMINGO): 48 weeks results from the randomised open-label phase 3b study . Lancet \n2014 ;383 :2222 –31 .24698485 \n[22] Dutertre M Cuzin L Demonchy E \nInitiation of antiretroviral therapy containing integrase inhibitors increases the risk of iris requiring hospitalization . J Acquir Immune Defic Syndr \n2017 ;76 :e23 –6 .28418992 \n[23] Johnson T Nath A \nNeurological complications of immune reconstitution in HIV-infected populations . Ann N Y Acad Sci \n2010 ;1184 :106 –20 .20146693 \n[24] Meintjes G Scriven J Marais S \nManagement of the immune reconstitution inflammatory syndrome . Curr HIV/AIDS Rep \n2012 ;9 :238 –50 .22752438 \n[25] Narum S Westergren T Klemp M \nCorticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis . BMJ Open \n2014 ;4 :e004587 .\n\n",
"fulltext_license": "CC BY",
"issn_linking": "0025-7974",
"issue": "98(49)",
"journal": "Medicine",
"keywords": null,
"medline_ta": "Medicine (Baltimore)",
"mesh_terms": "D017088:AIDS-Related Opportunistic Infections; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D003586:Cytomegalovirus Infections; D015658:HIV Infections; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D007416:Intestinal Perforation; D007579:Jejunal Diseases; D008297:Male; D015270:Mycobacterium avium-intracellulare Infection",
"nlm_unique_id": "2985248R",
"other_id": null,
"pages": "e18163",
"pmc": null,
"pmid": "31804330",
"pubdate": "2019-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "15844689;20334848;24833682;12130890;24698485;22752438;20146693;17937815;16496064;16652323;10901982;28418992;9516219;18434225;23379792;28018589;27404187;27695869;21559197;23460008;25110427;19357730;15919622;25709503;12541029",
"title": "Non-traumatic perforation of the jejunum in a human immunodeficiency virus-infected patient receiving combination antiretroviral therapy: A case report.",
"title_normalized": "non traumatic perforation of the jejunum in a human immunodeficiency virus infected patient receiving combination antiretroviral therapy a case report"
}
|
[
{
"companynumb": "TW-VISTAPHARM, INC.-VER202001-000226",
"fulfillexpeditecriteria": "1",
"occurcountry": "TW",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DOLUTEGRAVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOLUTEGRAVIR"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMIKACIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMIKACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS GASTROENTERITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VALGANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALGANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ABACAVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ABACAVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LAMIVUDINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMIVUDINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLARITHROMYCIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLARITHROMYCIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ETHAMBUTOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETHAMBUTOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VALGANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS GASTROENTERITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALGANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "IMIPENEM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMIPENEM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "040323",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MG TWICE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "32",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Jejunal perforation",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HSIEH S, LEE Y, CHIOU C, WANG J, YANG Y, TUNG S. NON-TRAUMATIC PERFORATION OF THE JEJUNUM IN A HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENT RECEIVING COMBINATION ANTIRETROVIRAL THERAPY A CASE REPORT. MED. 2019?98(49):.",
"literaturereference_normalized": "non traumatic perforation of the jejunum in a human immunodeficiency virus infected patient receiving combination antiretroviral therapy a case report",
"qualification": null,
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "TW",
"receiptdate": "20200207",
"receivedate": "20200207",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17392702,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200409"
},
{
"companynumb": "TW-BAUSCH-BL-2019-065819",
"fulfillexpeditecriteria": "1",
"occurcountry": "TW",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ABACAVIR SULFATE\\DOLUTEGRAVIR SODIUM\\LAMIVUDINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "RESUMED POST-OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ABACAVIR/DOLUTEGRAVIR/LAMIVUDINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "IMIPENEM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "STARTED ON 12TH HOSPITAL DAY WHEN MAC WAS ISOLATED FROM CULTURES OF SPUTUM, BLOOD, COLON SPECIMENS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMIPENEM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ETHAMBUTOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "STARTED ON 12TH HOSPITAL DAY WHEN MAC WAS ISOLATED FROM CULTURES OF SPUTUM, BLOOD, COLON SPECIMENS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETHAMBUTOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VALGANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS COLITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALGANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLARITHROMYCIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "STARTED ON 12TH HOSPITAL DAY WHEN MAC WAS ISOLATED FROM CULTURES OF SPUTUM, BLOOD, COLON SPECIMENS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLARITHROMYCIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ABACAVIR SULFATE\\DOLUTEGRAVIR SODIUM\\LAMIVUDINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": ".",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIRETROVIRAL THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ABACAVIR/DOLUTEGRAVIR/LAMIVUDINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS COLITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMIKACIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "RESUMED POST-OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMIKACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMIKACIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "STARTED ON 12TH HOSPITAL DAY WHEN MAC WAS ISOLATED FROM CULTURES OF SPUTUM, BLOOD, COLON SPECIMENS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MYCOBACTERIUM AVIUM COMPLEX INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMIKACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ETHAMBUTOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "RESUMED POST-OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETHAMBUTOL"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ON THE 31ST HOSPITAL DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4TH HOSPITAL DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS GASTROENTERITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VALGANCICLOVIR"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4TH HOSPITAL DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CYTOMEGALOVIRUS GASTROENTERITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALGANCICLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "IMIPENEM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "RESUMED POST-OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMIPENEM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLARITHROMYCIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "RESUMED POST-OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLARITHROMYCIN."
}
],
"patientagegroup": null,
"patientonsetage": "32",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Intestinal perforation",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LEE Y, CHIOU C, WANG J, YANG Y, TUNG S, HSIEH S. NON-TRAUMATIC PERFORATION OF THE JEJUNUM IN A HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENT RECEIVING COMBINATION ANTIRETROVIRAL THERAPY: A CASE REPORT. MEDICINE. 2019?98:49:1-4. DOI:HTTP://DX.DOI.ORG/10.1097/MD.0000000000018163",
"literaturereference_normalized": "non traumatic perforation of the jejunum in a human immunodeficiency virus infected patient receiving combination antiretroviral therapy a case report",
"qualification": "1",
"reportercountry": "TW"
},
"primarysourcecountry": "TW",
"receiptdate": "20191227",
"receivedate": "20191227",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17209945,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20200122"
}
] |
{
"abstract": "BACKGROUND\nEutectic mixtures of lidocaine and prilocaine are used during painful dermatological procedures. Poisoning is rarely reported in adults.\n\n\nMETHODS\nWe report three cases of women who experienced lidocaine and prilocaine poisoning after laser-assisted hair removal. Plasma levels of local anesthetics were assayed by a fully validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method.\n\n\nMETHODS\nThe rules of application of the anesthetic cream were observed apart from the maximum dose and/or maximum surface area. One patient applied a higher dose than the maximum recommended dose (140 instead of 60 g) and all patients failed to comply with the maximum recommended surface area (600 cm2). The patients presented an unusual clinical pattern as compared with other local anesthetics overdose: signs of cardiac toxicity with no ECG changes or arrhythmia, neurological toxicity without seizures or coma, and methemoglobinemia.\n\n\nCONCLUSIONS\nHealth authorities should publish explicit recommendations targeting users and prescribers with particular emphasis on the maximal surface area of application.",
"affiliations": "Centre antipoison et de toxicovigilance de Paris, hôpital Fernand-Widal, Paris, France. [email protected].;Laboratoire de toxicologie, hôpital Raymond Poincaré, hôpitaux universitaires Paris Ile-de- France Ouest, Garches, France.;Centre antipoison et de toxicovigilance de Paris, hôpital Fernand-Widal, Paris, France.;Centre antipoison et de toxicovigilance de Paris, hôpital Fernand-Widal, Paris, France.;Laboratoire de toxicologie, hôpital Raymond Poincaré, hôpitaux universitaires Paris Ile-de- France Ouest, Garches, France.;Centre antipoison et de toxicovigilance de Paris, hôpital Fernand-Widal, Paris, France.",
"authors": "Caré|Weniko|W|http://orcid.org/0000-0002-4559-8670;Larabi|Islam-Amine|IA|;Langrand|Jérôme|J|;Medernach|Chantal|C|;Alvarez|Jean-Claude|JC|;Villa|Antoine|A|",
"chemical_list": "D000779:Anesthetics, Local; D000077442:Lidocaine, Prilocaine Drug Combination",
"country": "Germany",
"delete": false,
"doi": "10.1007/s00414-018-1858-9",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0937-9827",
"issue": "133(3)",
"journal": "International journal of legal medicine",
"keywords": "Laser-assisted hair removal; Lidocaine; Mass spectrometry; Methemoglobinemia; Prilocaine",
"medline_ta": "Int J Legal Med",
"mesh_terms": "D000779:Anesthetics, Local; D002853:Chromatography, Liquid; D005260:Female; D006204:Hair Removal; D006801:Humans; D053685:Laser Therapy; D000077442:Lidocaine, Prilocaine Drug Combination; D008708:Methemoglobinemia; D012651:Self Medication; D053719:Tandem Mass Spectrometry",
"nlm_unique_id": "9101456",
"other_id": null,
"pages": "843-846",
"pmc": null,
"pmid": "29785585",
"pubdate": "2019-05",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "25226014",
"title": "Poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser-assisted hair removal: about 3 cases.",
"title_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases"
}
|
[
{
"companynumb": "FR-VITRUVIAS THERAPEUTICS-2071643",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "208822",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE\\PRILOCAINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE AND PRILOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "25",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Syncope",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, LARABI IA, LANGRAND J, MEDERNACH C, ALVAREZ JC, VILLA A. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER-ASSISTED HAIR REMOVAL: ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE. 2019? 133: 843-846.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": null,
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20190731",
"receivedate": "20190731",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 16653284,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20191004"
},
{
"companynumb": "FR-TOLMAR, INC.-TOLG20180295",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LIDOCAINE\\PRILOCAINE"
},
"drugadditional": "1",
"drugadministrationroute": "061",
"drugauthorizationnumb": "076320",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "CREAM",
"drugdosagetext": "2.5%/2.5%; APPLIED 55 GRAMS, APPLICATION AREA 2068 CM(2)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LOCAL ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE AND PRILOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cardiotoxicity",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Neurotoxicity",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Methaemoglobinaemia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, LARABI I, LANGRAND J, MEDERNACH C, ALVAREZ J, VILLA A. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER-ASSISTED HAIR REMOVAL: ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE. 2018?.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20180605",
"receivedate": "20180605",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14974397,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
},
{
"companynumb": "FR-TOLMAR, INC.-TOLG20180298",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LIDOCAINE\\PRILOCAINE"
},
"drugadditional": "1",
"drugadministrationroute": "061",
"drugauthorizationnumb": "076320",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "CREAM",
"drugdosagetext": "2.5%/2.5%; APPLIED 140 GRAMS, APPLICATION AREA 4510 CM(2)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LOCAL ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE AND PRILOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "42",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Cardiotoxicity",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Dizziness",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Incorrect dose administered",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Neurotoxicity",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Methaemoglobinaemia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, LARABI I, LANGRAND J, MEDERNACH C, ALVAREZ J, VILLA A. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER-ASSISTED HAIR REMOVAL: ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE. 2018?.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20180605",
"receivedate": "20180605",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14974396,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
},
{
"companynumb": "FR-VITRUVIAS THERAPEUTICS-2071642",
"fulfillexpeditecriteria": "2",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE\\PRILOCAINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE AND PRILOCAINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "208822",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE."
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Methaemoglobinaemia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, LARABI IA, LANGRAND J, MEDERNACH C, ALVAREZ JC, VILLA A. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER-ASSISTED HAIR REMOVAL: ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE. 2019? 133: 843-846.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": null,
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20190731",
"receivedate": "20190731",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 16653180,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20191004"
},
{
"companynumb": "FR-B. BRAUN MEDICAL INC.-2051654",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXTROSE\\LIDOCAINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "019830",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE HYDROCHLORIDE AND DEXTROSE"
}
],
"patientagegroup": null,
"patientonsetage": "42",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Methaemoglobinaemia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Dizziness",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Syncope",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, ET AL. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC?MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER?ASSISTED HAIR REMOVAL:?ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE 2018: MAY 2018.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20180710",
"receivedate": "20180710",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 15125880,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "FR-VITRUVIAS THERAPEUTICS-2071648",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "208822",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE\\PRILOCAINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE AND PRILOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "42",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Methaemoglobinaemia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Dizziness",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, LARABI IA, LANGRAND J, MEDERNACH C, ALVAREZ JC, VILLA A. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER-ASSISTED HAIR REMOVAL: ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE. 2019? 133: 843-846.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": null,
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20190731",
"receivedate": "20190731",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 16653395,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20191004"
},
{
"companynumb": "FR-TOLMAR, INC.-TOLG20180297",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LIDOCAINE\\PRILOCAINE"
},
"drugadditional": "1",
"drugadministrationroute": "061",
"drugauthorizationnumb": "076320",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "CREAM",
"drugdosagetext": "2.5%/2.5%; APPLIED 50 GRAMS, APPLICATION AREA 2068CM(2)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LOCAL ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE AND PRILOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "25",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Syncope",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Cardiotoxicity",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Neurotoxicity",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARE W, LARABI I, LANGRAND J, MEDERNACH C, ALVAREZ J, VILLA A. POISONING ASSOCIATED WITH INAPPROPRIATE USE OF A EUTECTIC MIXTURE OF LIDOCAINE AND PRILOCAINE BEFORE LASER-ASSISTED HAIR REMOVAL: ABOUT 3 CASES. INTERNATIONAL JOURNAL OF LEGAL MEDICINE. 2018?.",
"literaturereference_normalized": "poisoning associated with inappropriate use of a eutectic mixture of lidocaine and prilocaine before laser assisted hair removal about 3 cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20180605",
"receivedate": "20180605",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14974411,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
}
] |
{
"abstract": "OBJECTIVE\nFosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥ 6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration.\n\n\nMETHODS\nRetrospective analysis of individual patient data for all children aged 6-18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity.\n\n\nRESULTS\nNinety-two HIV-infected children aged 6-18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1-11 years), and median age at start of FPV/r was 15 years (12-17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported.\n\n\nCONCLUSIONS\nResults suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported",
"affiliations": null,
"authors": "Judd|Ali|A|;Duong|Trinh|T|;Galli|Luisa|L|;Goetghebuer|Tessa|T|;Ene|Luminita|L|;Noguera Julian|Antoni|A|;Ramos Amador|Jose Tomas|JT|;Pimenta|Jeanne Marie|JM|;Thorne|Claire|C|;Giaquinto|Carlo|C|;|||",
"chemical_list": "D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; C426859:fosamprenavir",
"country": "England",
"delete": false,
"doi": "10.1002/pds.3543",
"fulltext": "\n==== Front\nPharmacoepidemiol Drug SafPharmacoepidemiol Drug SafpdsPharmacoepidemiology and Drug Safety1053-85691099-1557BlackWell Publishing Ltd Oxford, UK 10.1002/pds.3543Brief ReportsPost-licensing safety of fosamprenavir in HIV-infected children in Europe† Judd Ali 1*Duong Trinh 1Galli Luisa 2Goetghebuer Tessa 3Ene Luminita 4Julian Antoni Noguera 5Amador Jose Tomas Ramos 6Pimenta Jeanne Marie 7Thorne Claire 8Giaquinto Carlo on behalf of the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord91 Medical Research Council Clinical Trials Unit at University College LondonLondon, UK2 Universita Degli Studi FirenzeFirenze, Italy3 Hopital St PierreBrussels, Belgium4 ‘Dr. Victor Babes’ Hospital for Infectious and Tropical DiseasesBucharest, Romania5 Unitat d'Infectologia, Servei de Pediatria, Hospital Sant Joan de Déu, Universitat de BarcelonaBarcelona, Spain6 Madrid Cohort of HIV-infected childrenMadrid, Spain7 Worldwide Epidemiology, GlaxoSmithKlineMiddlesex, UK8 University College London Institute of Child HealthLondon, UK9 Paediatric European Network for the Treatment of AIDSPadova, Italy\n*Correspondence to: Ali Judd, MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London WC2B 6NH, UK. E-mail: [email protected]† Previous presentation: This work is not being submitted elsewhere. Intermediate analyses were presented at IAS 2011 (Rome) and final analyses at ESPID 2012 (Thessaloniki).\n\n3 2014 25 11 2013 23 3 321 325 08 4 2013 28 8 2013 17 10 2013 © 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.2013This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Purpose\nFosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration.\n\nMethods\nRetrospective analysis of individual patient data for all children aged 6–18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity.\n\nResults\nNinety-two HIV-infected children aged 6–18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1–11 years), and median age at start of FPV/r was 15 years (12–17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported.\n\nConclusions\nResults suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported.\n\npharmacovigilanceepidemiologyfosamprenavirsafetyHIVchildrenpharmacoepidemiology\n==== Body\nINTRODUCTION\nFosamprenavir (FPV, Telzir™), combined with low-dose ritonavir (FPV/r), was approved in Europe for treatment of HIV-infected children aged ≥6 years in 2007. Dosing is by weight: 18/3 mg/kg twice daily (BID) up to a maximum of 700/100 mg for liquid formulations; for children ≥39 kg, 700/100 mg BID for tablets.\n\nSafety data from three FPV clinical trials in children (APV20003, APV29005, and APV20002) have been reported.1–3 Findings indicate that infections/infestation and gastrointestinal events were the most commonly reported adverse events (AEs). Treatment-emergent grade 3/4 neutropenia was reported in less than 20% of children across the studies but were considered unlikely to be related to FPV.4 However, only one study to date has assessed FPV/r in routine clinical practice. Palladino et al. studied 20 HIV-infected children over a median of 180 weeks and reported sustained antiviral response and immunological improvement.5\n\nWe conducted a pharmacoepidemiology study to assess the use and long-term safety of FPV in children in ‘real world’ clinical settings in Europe. Individual patient data originated from cohorts participating in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC), a network of European cohorts of prospectively observed mother–child pairs and children within EuroCoord (www.eurocoord.net).6\n\nMETHODS\nSix cohorts participated in this study and reported data for children aged 6–18 years who had ever taken FPV/r to the end of 2010. Ethical approval was granted for the study.\n\nChildren were considered to be on the licensed dose if aged 6–18 years when taking FPV within a window of +/−20% of the licensed dose of 18 mg/kg BID, or on the adult dose (700 mg BID, weight >39 kg), taken with ritonavir, and outside of pharmaceutical company trials.\n\nThe data specification followed the HIV Cohorts Data Exchange Protocol (HICDEP) (www.hicdep.org). Data collected included demographics, deaths, loss to follow-up, antiretroviral therapy (ART) treatment history, AIDS events, biochemistry and AEs, from the start of FPV/r use onwards. In addition, summary characteristics of all children (not just those on FPV/r) in follow-up in each cohort were provided, to estimate the extent of FPV/r use. Further, Intercontinental Medical Statistics (IMS) data on sales volumes of FPV oral suspension were used as a surrogate measure of paediatric exposure. We assumed that most children aged 6–12 years would take fosamprenavir oral suspension rather than tablets because of their body weight (tablets are not suitable for children <39 kg).\n\nDivision of AIDS (DAIDS) gradings for paediatric AEs were used to categorise severity of AEs,7 and rates of grade ≥3 events by time since FPV initiation (<12, 12–24, and >24 months) were estimated (per 100 person years). Analyses focussed on grade ≥3 AEs, and biochemical markers of interest were absolute neutrophil counts (ANC), total cholesterol (fasting) (TC) and triglycerides (fasting) (TG), and alanine transaminase (ALT). Clinical serious AEs were collected and coded using MedDRA. Other non-serious AEs (e.g., headache and gastrointestinal problems) were not included as they were not consistently collected by the participating cohorts. All analyses were undertaken using Stata version 12.0 (Stata Corp, College Station, TX, USA).\n\nRESULTS\nNinety-two children took the licensed dose of FPV. Additionally 20 children took FPV off label, of whom 15 were aged 6–18 years and took an unlicensed dose, and 5 were aged <6 years; these children are not described further in this report. Of the 92 on the licensed dose, 28 (30%) were from Belgium, 27 (29%) from Italy, 23 (25%) from Romania, 11 (12%) from Spain, and 3 (3%) from the UK/Ireland. The total number of children aged 6–18 years in follow-up in these cohorts during 2007 to 2010 was 2673, giving an overall prevalence of 3% taking the licensed FPV dose.\n\nForty-eight children (52%) were male, and of the 65 children with known ethnicity, 29 (45%) were white, and 24 (37%) black African. Among all children, most (71%) were infected with HIV through mother-to-child transmission; 25% infected parenterally were all from the Romanian cohort. A third (33%) of the total had an AIDS diagnosis during overall follow-up.\n\nMedian age at ART initiation was 6 years (interquartile range (IQR) 1–11 years), and median age at start of an FPV-containing regimen was 15 years (12–17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up.\n\nBiochemical toxicity data were available for 82 children. Rates of grade 3/4 events were generally low (Figure 1). For 82 children with ANC results, 57 (70%) had normal results, 11 (13%) grade 1 results, and 6 (7%) grade 2 results. Eight children had grade 3/4 neutropenia, with an overall rate of 5 per 100 person years (95% CI 2–9), and a higher rate in those taking FPV for <12 months (8/100 person years, 95% CI 3–17), although this was not statistically significant compared with those exposed for ≥12 months. Six of the eight children were also taking lamivudine, which is associated with neutropenia. Seven had a normal value following the last grade 3/4 result, and all continued FPV following the grade 3/4 event.\n\nFigure 1 Incidence of grade ≥3 adverse events for key laboratory markers by duration of time on FPV\n\nFor 78 children with TC results, 32 (41%) had normal results and 22 (28%) grade 1 results. Two children had grade 3 hypercholesterolemia, with an overall rate of events of 4 per 100 person years (95% CI 2–8), and similar rates by duration on FPV; one child subsequently stopped FPV because of non-compliance and dyslipidaemia. An addition of 22 children (28%) had a maximum of grade 2 events.\n\nFor 77 children with TG results, 72 (94%) had normal results and three (4%) grade 2 results. Two children had grade 4 hypertriglyceridemia, with an overall event rate of 3 per 100 person years (95% CI 1–6). Both continued to take FPV following the events.\n\nFinally, 51 children had ALT results, of whom 32 (63%) had normal results, 15 (29%) had grade 1 results, and three (6%) grade 2 results. One HBV-co-infected child (HBsAg positive with detectable HBV DNA and/or HBeAg positive) had one grade 3 and one grade 4 result, between 12–24 months after starting FPV (overall event rate for grade 3/4 of 2 per 100 person years (95% CI 0–6)). The child continued on FPV, stopping due to virological failure over a year later.\n\nNo serious AEs considered to be causally related to FPV/r were reported. Forty-two children stopped taking FPV during follow-up; reasons for stopping were non-compliance/carer's or child's decision (n = 12), immunological/virological failure (13), gastrointestinal tract toxicity (2), simplified treatment available (6), resistance (1), abnormal fat redistribution (1), structured treatment interruption (1), drug unavailability (1), ART change due to entering a trial (1), and unknown (4).\n\nWith the use of sales data from IMS for the study period, it is estimated that approximately 62 kg of the oral suspension was sold in countries in this study. The median weight of children aged 6–12 years (i.e. likely to take the oral suspension) in this study was 40.4 kg. On the basis of a 40-kg child receiving the recommended dose of fosamprenavir of 18 mg/kg twice daily, the estimated cumulative exposure to the oral suspension would be 118 person years.\n\nDISCUSSION\nThese findings suggest that FPV is infrequently prescribed to HIV-infected children in Europe. Contextual data from participating cohorts suggest that 3% of children in current follow-up had taken the FPV licensed dose, although this may be a slight underestimate of all FPV usage as it excludes those on unlicensed doses or children exposed during clinical trials. IMS data on oral suspension sales similarly suggest low exposure to FPV in children in Europe.\n\nThere are several potential reasons for the relatively low use of FPV in Europe. Firstly, other protease inhibitors (e.g., atazanavir) are now licensed for children for once-daily use, and atazanavir and darunavir are increasingly being used preferentially in older children. Secondly, treatment guidelines vary across Europe: recent Swedish guidelines recommend atazanavir and darunavir over lopinavir, FPV, and other protease inhibitors,8 whereas Italian and the Paediatric European Network for the Treatment of AIDS guidelines recommend FPV as a potential first-line PI treatment for patients aged >6 years.9,10\n\nThis study has some limitations. Firstly, AEs were only described for periods following FPV/r initiation, and children may have had pre-existing conditions (e.g., neutropenia). Secondly, we could not discern whether AEs were attributable to FPV, or to other drugs in the regimen. For example, the role of ritonavir in the development of dyslipidemia has been described, as has zidovudine and lamivudine with neutropenia.11 In addition, exposure as calculated by IMS data were only for oral suspension; the same size tablets are used for children as adults; thus, it was not possible to differentiate paediatric from adult sales volumes. Our estimates were based on the assumption that all paediatric use was in children weighing 40 kg.\n\nHowever, the number and rate of grade ≥3 events were low, with no discernible trend by duration of exposure. There were an elevated number of grade 2 hypercholesterolemia events, and increased serum cholesterol has previously been described in patients treated with protease inhibitors.12 No serious clinical AEs related to FPV/r were reported.\n\nIn summary, our results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. Any toxicities reported were consistent with the known safety profile of FPV. No serious events were reported.\n\nCONFLICT OF INTEREST\nViiV provided funding to support this post-marketing safety study and has also provided support for a similar study with a different drug. Jeanne Pimenta is a full time employee of GlaxoSmithKline. Carlo Giaquinto received consultancy fee from ViiV and GSK and has been reimbursed for international conference attendance. All other authors declare no conflicts of interest.\nKEY POINTS\nFosamprenavir, along with low-dose ritonavir, is infrequently prescribed to children with HIV in Europe.\n\nFindings suggest that the long-term licensed dose is well tolerated, and few toxicities were reported.\n\nNo serious events associated with fosamprenavir were reported.\n\nProspective cohort studies that routinely collect long-term safety data can provide a robust source of information for pharmacovigilance.\n\n\n\nWe thank all the cohort data managers for providing their data, and Charlotte Duff, the EPPICC data manager, for merging the data and running quality checks, and the fosamprenavir clinical/safety team at GSK for their input to study reports and review of the manuscript.\n\nFunding: ViiV Healthcare with additional funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement number 260694.\n\nETHICS STATEMENT\nEach participating study was responsible for ensuring that ethics approval for the analysis was in place and for compliance with local and national data protection requirements.\n\nAUTHOR CONTRIBUTIONS\nContributing cohorts (listed alphabetically by cohort name):\nCollaborative HIV Paediatric Study (CHIPS), UK & Ireland (Ali Judd)\n\nCoRISPE-cat, Spain (Antoni Noguera Julian)\n\nItalian Register (Luisa Galli)\n\nMadrid Cohort, Spain (Jose T. Ramos Amador)\n\nNational Study of HIV in Pregnancy and Childhood (NSHPC), UK & Ireland (Pat Tookey)\n\nSt Pierre Paediatric Cohort, Belgium (Tessa Goetghebuer)\n\n‘Victor Babes’ cohort, Bucharest, Romania (Luminita Ene)\n\n\n\nAuthor roles:\n\nAli Judd, Trinh Duong, Jeanne Pimenta, Claire Thorne and Carlo Giaquinto were responsible for the study concept and design. Trinh Duong undertook statistical analyses. Ali Judd wrote the first draft of the manuscript. Ali Judd, Luisa Galli, Tessa Goetghebuer, Luminita Ene, Antoni Noguera Julian, and Jose Tomas Ramos Amador provided data for the study. All authors participated in discussions about the design of the study. They also critically reviewed the article and approved its final version to be submitted.\n==== Refs\nREFERENCES\n1 Chadwick E Safety and antiviral activity of fosamprenavir/ritonavir once daily regimens in HIV-infected paediatric subjects ages 2 to 18 years (48-week interim data, study APV20003) 14th Conference on Retroviruses and Opportunistic Infections 2007 Los Angeles \n2 Cotton M Pharmacokinetics, safety and antiviral activity of fosamprenavir/ritonavir-containing regimens in HIV-positive four weeks to <two year-old children (48-week data study APV20002, a prospective open-label, multi-centre, 48-week cohort study) 2012 Washington, DC 19th International AIDS Conference (IAC) Abstract TUAB0202 \n3 Voronin E Pharmacokinetics, safety and antiviral activity of fosamprenavir-containing regimens in HIV-positive 2 to 18 year-old children (48-week data, Study APV29005, a prospective, open-label, multi-centre, 48-week cohort study) 2012 Washington, DC 19th International AIDS Conference (IAC) Abstract no. MOPE049 \n4 GSK Clinical Study Register Available at http://www.gsk-clinicalstudyregister.com/index.jsp \n5 Palladino C Long-term efficacy and safety of fosamprenavir in human immunodeficiency virus-infected pediatric patients Pediatr Infect Dis J 2010 29 6 563 566 20160659 \n6 de Wolf F Developing a multidisciplinary network for clinical research on HIV infection: the EuroCoord experience Clinical Investigation 2012 2 255 264 \n7 Division of AIDS Division of AIDS table for grading the severity of adult and pediatric adverse events. Version 1.0, December clarification August 2009 2004 Bethesda, MD National Institutes of Health \n8 Anon Antiretroviral treatment of HIV infection—updated Swedish recommendations 2009 2011 3 Information from the Swedish Medical Product Agency 8 35 (Article in Swedish) \n9 Giaquinto C Italian consensus statement on paediatric HIV infection Infection 2010 38 4 301 319 20514509 \n10 Welch S PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection HIV Med 2009 10 10 591 613 19878352 \n11 Calmy A Clinical update: adverse effects of antiretroviral therapy Lancet 2007 370 9581 12 14 17617255 \n12 Torres HA Arduino RC Fosamprenavir calcium plus ritonavir for HIV infection Expert Rev Anti Infect Ther 2007 5 3 349 363 17547501\n\n",
"fulltext_license": "CC BY-NC-ND",
"issn_linking": "1053-8569",
"issue": "23(3)",
"journal": "Pharmacoepidemiology and drug safety",
"keywords": null,
"medline_ta": "Pharmacoepidemiol Drug Saf",
"mesh_terms": "D000293:Adolescent; D019380:Anti-HIV Agents; D002219:Carbamates; D002648:Child; D015331:Cohort Studies; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005663:Furans; D015658:HIV Infections; D006801:Humans; D006937:Hypercholesterolemia; D008297:Male; D010755:Organophosphates; D011247:Pregnancy; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D013449:Sulfonamides",
"nlm_unique_id": "9208369",
"other_id": null,
"pages": "321-5",
"pmc": null,
"pmid": "24741696",
"pubdate": "2014-03",
"publication_types": "D016428:Journal Article",
"references": "19878352;17547501;20514509;20160659;17617255",
"title": "Post-licensing safety of fosamprenavir in HIV-infected children in Europe.",
"title_normalized": "post licensing safety of fosamprenavir in hiv infected children in europe"
}
|
[
{
"companynumb": "GB-MYLANLABS-2017M1000391",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITONAVIR"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITONAVIR."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "FOSAMPRENAVIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "204060",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FOSAMPRENAVIR"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Alanine aminotransferase increased",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Treatment failure",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "JUDD A, DUONG T, GALLI L, GOETGHEBUER T, ENE L, JULIAN AN, ET AL. POST-LICENSING SAFETY OF FOSAMPRENAVIR IN HIV-INFECTED CHILDREN IN EUROPE. PHARMACOEPIDEMIOL-DRUG-SAF 2014;23(3):321-325.",
"literaturereference_normalized": "post licensing safety of fosamprenavir in hiv infected children in europe",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20170111",
"receivedate": "20170111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13105658,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
}
] |
{
"abstract": "Mycophenolate mofetil (MMF) is increasingly used to prevent acute and chronic rejection following kidney transplantation and in autoimmune diseases. Here, we report on a patient after kidney transplantation, who developed an acute inflammatory syndrome characterized by fever and oligoarthritis within 1 week after increasing the MMF dosage. MMF was discontinued resulting in a complete resolution of the syndrome within 48 h. We demonstrated in vitro that the patient's phorbol myristate acetate (PMA-) and formyl Met-Leu-Phe (fMLP-) stimulated polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MMF. This report demonstrates that MMF can also induce acute inflammatory syndrome in patients following kidney transplantation and that this syndrome might be due to a paradox, pro-inflammatory reaction of PMNs.",
"affiliations": "Clinical Division of Nephrology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. [email protected]",
"authors": "Hochegger|K|K|;Gruber|J|J|;Lhotta|K|K|",
"chemical_list": "D007166:Immunosuppressive Agents; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009173:Mycophenolic Acid; D013755:Tetradecanoylphorbol Acetate",
"country": "United States",
"delete": false,
"doi": "10.1111/j.1600-6143.2006.01251.x",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1600-6135",
"issue": "6(4)",
"journal": "American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons",
"keywords": null,
"medline_ta": "Am J Transplant",
"mesh_terms": "D000368:Aged; D000843:Ankle Joint; D001168:Arthritis; D005334:Fever; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils; D016897:Respiratory Burst; D013577:Syndrome; D013755:Tetradecanoylphorbol Acetate",
"nlm_unique_id": "100968638",
"other_id": null,
"pages": "852-4",
"pmc": null,
"pmid": "16539644",
"pubdate": "2006-04",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Acute inflammatory syndrome induced by mycophenolate mofetil in a patient following kidney transplantation.",
"title_normalized": "acute inflammatory syndrome induced by mycophenolate mofetil in a patient following kidney transplantation"
}
|
[
{
"companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2018-01847",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "091249",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Systemic inflammatory response syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HOCHEGGER K, GRUBER J AND LHOTTA K.. ACUTE INFLAMMATORY SYNDROME INDUCED BY MYCOPHENOLATE MOFETIL IN A PATIENT FOLLOWING KIDNEY TRANSPLANTATION. AM J TRANSPLANT.. 2006?6:852?4",
"literaturereference_normalized": "acute inflammatory syndrome induced by mycophenolate mofetil in a patient following kidney transplantation",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180413",
"receivedate": "20180413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14754769,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
}
] |
{
"abstract": "Hair analysis is very useful for toxicological investigations since, by providing a wider detection window, it gives the possibility to perform a retrospective study on the historical consumption of a substance. Unfortunately, there are no data available for hair concentrations in metformin-related deaths. In this study, the authors present 2 cases of fatal metformin intoxication in which, for the first time, hair analysis was performed using a specific GC-MS/MS method. Metformin was tested positive in femoral blood (112.3 mg/L and 64.7 mg/L respectively) and cardiac blood (226.9 and 203.2 mg/L) of the two subjects. For case 1, other samples were also tested positive, including vitreous humor (31.1 mg/L) and gastric contents (773.5 mg/L). In case 2, metformin was measured at 844.9 mg/L in urine. Metformin hair concentrations were 28.3-44.8 and 22.5 ng/mg for both cases, respectively. The concentrations found in the 2 fatal cases are clearly higher than those obtained in a previous study with subjects under treatment (0.3-3.8 ng/mg) or those found in 3 post-mortem cases where metformin death was excluded (0.6-1.4 ng/mg). Excessive sweating during the agonal phase due to fatal hypoglycemia could explain these elevated concentrations as sweat can have contaminated the hair.",
"affiliations": "Institut de médecine légale, 11 rue Humann, 67000 Strasbourg, France. Electronic address: [email protected].;Institut de médecine légale, 11 rue Humann, 67000 Strasbourg, France.;Institut de médecine légale, 11 rue Humann, 67000 Strasbourg, France.;Institut de médecine légale, 11 rue Humann, 67000 Strasbourg, France.;Institut de médecine légale, 11 rue Humann, 67000 Strasbourg, France; X-Pertise Consulting, 42 rue principale, 67206 Mittelhausbergen, France.",
"authors": "Arbouche|Nadia|N|;Farrugia|Audrey|A|;Walch|Alexis|A|;Raul|Jean-Sébastien|JS|;Kintz|Pascal|P|",
"chemical_list": "D008687:Metformin",
"country": "Ireland",
"delete": false,
"doi": "10.1016/j.legalmed.2020.101803",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1344-6223",
"issue": "48()",
"journal": "Legal medicine (Tokyo, Japan)",
"keywords": "GC–MS/MS; Hair; Hypoglycemic drug; Metformin",
"medline_ta": "Leg Med (Tokyo)",
"mesh_terms": "D000328:Adult; D001344:Autopsy; D017809:Fatal Outcome; D005260:Female; D005554:Forensic Medicine; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair; D006801:Humans; D008297:Male; D008687:Metformin; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution",
"nlm_unique_id": "100889186",
"other_id": null,
"pages": "101803",
"pmc": null,
"pmid": "33109450",
"pubdate": "2021-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Specific interpretation of hair concentrations in 2 fatal metformin intoxication cases.",
"title_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases"
}
|
[
{
"companynumb": "FR-CADILA HEALTHCARE LIMITED-FR-ZYDUS-058611",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSED MOOD",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "077060",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LANTUS"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSED MOOD",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL J-S, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG-MED-TOKYO. 2020",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201130",
"receivedate": "20201130",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18559114,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-TEVA-2020-FR-1853832",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075979",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "AMOUNT ADMINISTERED IN OVERDOSE NOT STATED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "GLICLAZIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLICLAZIDE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075979",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMITRIPTYLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMITRIPTYLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOBAZAM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOBAZAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LANTUS"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
}
],
"patientagegroup": "5",
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL J?S, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG?MED?TOKYO 2020?:.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20210121",
"receivedate": "20201201",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18566184,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210419"
},
{
"companynumb": "FR-MYLANLABS-2020M1097188",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMITRIPTYLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMITRIPTYLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LANTUS"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075973",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "AMOUNT ADMINISTERED IN OVERDOSE NOT STATED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "GLICLAZIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLICLAZIDE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOBAZAM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOBAZAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075973",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL J-S, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG-MED-TOKYO 2020?NULL:NULL.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201130",
"receivedate": "20201130",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18559267,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-INDICUS PHARMA-000728",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL/ATENOLOL HYDROCHLORIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "079148",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "(100 UNITS/ML), EXTENDED-RELEASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Visceral congestion",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hepatic steatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG MED (TOKYO). 2020 OCT 22:101803.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201110",
"receivedate": "20201110",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18488437,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-INVENTIA-000437",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "201991",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN GLARGINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG MED (TOKYO). 2020 OCT 22:101803.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201113",
"receivedate": "20201113",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18500567,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-BEXIMCO-2020BEX00166",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207427",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 U/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, ET EL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES.. LEGAL MED.. 2020",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201119",
"receivedate": "20201119",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18524238,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-INVENTIA-000436",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "201991",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "(100 UNITS/ML), EXTENDED-RELEASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL/ATENOLOL HYDROCHLORIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Visceral congestion",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hepatic steatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG MED (TOKYO). 2020 OCT 22:101803.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201110",
"receivedate": "20201110",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18488436,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-IPCA LABORATORIES LIMITED-IPC-2020-FR-003505",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "78422",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 UNIT",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hepatic steatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADIA ARBOUCHE, AUDREY FARRUGIA, ALEXIS WALCH, ET AL. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEGAL MEDICINE. 2020?XXX(XXX):1-5",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201124",
"receivedate": "20201124",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18541446,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "NVSC2020FR307611",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "75985",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LANTUS"
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEGAL MEDICINE. 2020?1-5",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201120",
"receivedate": "20201118",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18518406,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-IPCA LABORATORIES LIMITED-IPC-2020-FR-003506",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "78422",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADIA ARBOUCHE, AUDREY FARRUGIA, ALEXIS WALCH, ET AL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEGAL MEDICINE. 2020?XXX(XXX):1-5",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201125",
"receivedate": "20201125",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18546896,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-MYLANLABS-2020M1097189",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075973",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075973",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "AMOUNT ADMINISTERED IN OVERDOSE NOT STATED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 UNITS/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hepatic steatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Visceral congestion",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL J-S, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG-MED-TOKYO 2020?NULL:NULL.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201125",
"receivedate": "20201125",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18545069,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "NVSC2020FR307607",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "75985",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEGAL MEDICINE. 2020?1-5",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201120",
"receivedate": "20201118",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18518409,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-INDICUS PHARMA-000729",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "079148",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN GLARGINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG MED (TOKYO). 2020 OCT 22:101803.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201113",
"receivedate": "20201113",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18500522,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-BEXIMCO-2020BEX00167",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LANTUS"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207427",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, ET EL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES.. LEGAL MED.. 2020",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201119",
"receivedate": "20201119",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18524232,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-PRINSTON PHARMACEUTICAL INC.-2020PRN00389",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN GLARGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LANTUS"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "208880",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, ET EL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES.. LEGAL MED.. 2020",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201117",
"receivedate": "20201117",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18513540,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-CADILA HEALTHCARE LIMITED-FR-ZYDUS-058594",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "077060",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (100 UNITS/ML)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hepatic steatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Visceral congestion",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL J-S, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG-MED-TOKYO. 2020",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201130",
"receivedate": "20201130",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18559115,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-TEVA-2020-FR-1853833",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075979",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "AMOUNT ADMINISTERED IN OVERDOSE NOT STATED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 UNITS/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075979",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
}
],
"patientagegroup": "5",
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Visceral congestion",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hepatic steatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL J?S, KINTZ P. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEG?MED?TOKYO 2020?:.",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20210204",
"receivedate": "20201204",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18581765,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210419"
},
{
"companynumb": "FR-ALKEM LABORATORIES LIMITED-FR-ALKEM-2021-00823",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GLICLAZIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLICLAZIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREGABALIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREGABALIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "091184",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOXETINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROZAC"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMITRIPTYLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMITRIPTYLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ZOPICLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "7.5 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "7.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZOPICLONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLOBAZAM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOBAZAM."
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, ET AL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEGAL MEDICINE. 2021?48:101803",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20210223",
"receivedate": "20210223",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18925371,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210420"
},
{
"companynumb": "FR-PRINSTON PHARMACEUTICAL INC.-2020PRN00388",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "208880",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN DETEMIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 U/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN DETEMIR"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, ET EL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES.. LEGAL MED.. 2020",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201117",
"receivedate": "20201117",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18513543,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "FR-ALKEM LABORATORIES LIMITED-FR-ALKEM-2021-00822",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "091184",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1000 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1000",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ALCOHOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALCOHOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RAMIPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RAMIPRIL."
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 UNITS/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EXTENDED?RELEASE INSULIN DETEMIR"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MIRTAZAPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRTAZAPINE."
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Visceral congestion",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cyanosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARBOUCHE N, FARRUGIA A, WALCH A, RAUL JS, ET AL.. SPECIFIC INTERPRETATION OF HAIR CONCENTRATIONS IN 2 FATAL METFORMIN INTOXICATION CASES. LEGAL MEDICINE. 2021?48:101803",
"literaturereference_normalized": "specific interpretation of hair concentrations in 2 fatal metformin intoxication cases",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20210223",
"receivedate": "20210223",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18925373,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210420"
}
] |
{
"abstract": "Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.",
"affiliations": "Department of Internal Medicine, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA.;Department of Internal Medicine, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA.;Department of Internal Medicine, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA.;Department of Internal Medicine, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA.;Department of Pathology, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA.;Division of Hematology and Oncology, Department of Internal Medicine, Stratton Veterans Affairs Medical Center, 113 Holland Ave., Albany, NY 12208, USA.",
"authors": "Azar|Ibrahim|I|0000-0002-1008-1807;Esfandiarifard|Saghi|S|;Sinai|Pedram|P|;Wazir|Ali|A|;Foulke|Llewellyn|L|;Mehdi|Syed|S|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1155/2017/6328204",
"fulltext": "\n==== Front\nCase Rep Oncol MedCase Rep Oncol MedCRIONMCase Reports in Oncological Medicine2090-67062090-6714Hindawi 10.1155/2017/6328204Case ReportSunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient http://orcid.org/0000-0002-1008-1807Azar Ibrahim [email protected]\n1\nEsfandiarifard Saghi \n1\nSinai Pedram \n1\nWazir Ali \n1\nFoulke Llewellyn \n2\nMehdi Syed \n3\n\n1Department of Internal Medicine, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA\n2Department of Pathology, Albany Medical Center, 47 New Scotland Ave., Albany, NY 12208, USA\n3Division of Hematology and Oncology, Department of Internal Medicine, Stratton Veterans Affairs Medical Center, 113 Holland Ave., Albany, NY 12208, USAAcademic Editor: Peter F. Lenehan\n\n2017 22 11 2017 2017 63282049 7 2017 14 9 2017 11 10 2017 Copyright © 2017 Ibrahim Azar et al.2017This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.\n==== Body\n1. Introduction\nRecently, the use of tyrosine kinase inhibitors (TKIs) as antineoplastic agents has increased exponentially. The current National Comprehensive Cancer Network (NCCN) [1] and the European Association of Urology (EAU) [2] guidelines recommend the use of the vascular endothelial growth factor (VEGF) TKI sunitinib [2], among other options (pazopanib, interferon, and bevacizumab), as first-line treatment for metastatic renal cell carcinoma (mRCC). Given their oral availability and their generally well-tolerated side-effects profile, these antiangiogenesis agents have become the standard of care. Despite their widespread use, our understanding of this relatively new class of drugs and their side-effect profile is rudimentary.\n\nAcute interstitial nephritis (AIN) is a characteristic inflammatory infiltrate in the renal tubule-interstitium that is a leading cause of acute renal failure. Drug-induced injuries are thought to be responsible for 60–70% of cases [3], with systemic, autoimmune, and infectious diseases accounting for the rest. In this report, we describe a case of biopsy-proven AIN in an mRCC patient receiving sunitinib.\n\n2. Case Report\nA 69-year-old male with a history of stage IV left kidney clear cell carcinoma with metastases to spine and brain presented with a four-day history of gross hematuria, oliguria, fever of 38.5°C, fatigue, and a decreased appetite. He had been started on sunitinib (50 mg daily at bedtime) two weeks ago. Hematuria persisted despite stopping acetylsalicylic acid/dipyridamole prescribed for a previous stroke (for over 5 years), discontinuing sunitinib and a course of amoxicillin for presumed UTI. Upon presentation to ED, vitals were significant for a blood pressure of 160/72 mmHg. A digital rectal exam was negative for occult blood. Laboratory investigations revealed mild anemia (hemoglobin of 11.9 g/dl), thrombocytopenia (platelets of 68,000/mm3), hyponatremia (sodium of 120 mEq/L), and acute renal failure (BUN of 41 and creatinine of 2.7 mg/dL with a baseline creatinine of 1.0). Coagulation labs were within normal limits (activated partial thromboplastin time (aPTT) 29, prothrombin (PT) 12.1, and international normalized ratio (INR) 1.1). A urine dipstick was positive for blood and protein. Urine sodium was less than 10 mEq/L, indicating dehydration. Total urine protein collected in 24 hours was 484 mg. Haptoglobin was not decreased, and a peripheral smear examination was negative for schistocytes, ruling out hemolytic uremic syndrome. While nonspecific inflammatory markers (C-reactive protein (CRP) of 55 mg/L and erythrocyte sedimentation rate (ESR) of 80 mm/hr) were elevated, multiple serologies associated with nephritic syndromes (peripheral and cytoplasmic antineutrophilic cytoplasmic antibodies (p- and c-ANCA): antimyeloperoxidase (MPO), antiproteinase 3 (PR3), complement levels, antinuclear antibody (ANA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), hepatitis B and C panels, and cryoglobulins) were all negative.\n\nDespite a significant risk of bleeding, a renal biopsy after platelet transfusion was performed to aid in diagnosis. The renal biopsy (Figure 1) showed extensive interstitial inflammation with frequent eosinophils and interstitial edema, consistent with drug-induced acute interstitial nephritis (AIN). The inflammation was more marked in the cortex than in the medulla. There was associated acute tubular injury in regions of inflammation. There were occasional foci of lymphocytic and eosinophilic tubulitis. There was minimal chronicity evident. No evidence of glomerulitis or vasculitis was present. No evidence of immune complex deposits was identified on direct immunofluorescence studies or on ultrastructural analysis. No evidence of thrombotic microangiopathy was present. He was started on oral course of steroids and required intermittent hemodialysis. Throughout his hospital stay, he continued to experience gross hematuria requiring multiple pRBC transfusions. Unfortunately, while the patient's renal function somewhat recovered (Figure 2), he succumbed to hospital-acquired pneumonia 2 months after his diagnosis of AIN.\n\n3. Discussion\nThis report describes an exceptional diagnostic challenge. The initial presentation of hematuria, thrombocytopenia, and renal failure raised the flag for a thrombotic microangiopathy (TMA), namely, hemolytic-uremic syndrome (HUS), a well-described side effect [4] of VEGF inhibition. However, the absence of schistocytes on the peripheral smear along with the normal haptoglobin pointed away from this diagnosis. Similarly, the constellation of hematuria and mild proteinuria pointed to a possible nephritic disease presentation. However, multiple serologies of systemic diseases associated with nephritic pattern pathology were negative. In the setting of a worsening renal failure requiring dialysis and an uncertain diagnosis, the decision to obtain a kidney biopsy was contemplated. However, the unabating thrombocytopenia exacerbated the risk of retroperitoneal hematoma, the most common side effect of kidney biopsy, to 40% according to one study [5]. After extended discussions between oncology, nephrology, and interventional radiology, the kidney biopsy was performed and revealed the diagnosis of AIN.\n\nInterestingly, when faced with a patient with thrombocytopenia and renal failure following the administration of sunitinib, Khurana [6] decided against performing a biopsy. A notable diagnostic difference between the two cases is that of the classically described AIN triad (rash, fever, and eosinophilia); our case presented with the very nonspecific fever, while the patient seen by Khurana had a peripheral eosinophilia of 40%. The presumed diagnosis of AIN in the Khurana case was further strengthened when renal failure eosinophilia recurred when the patient was rechallenged with sorafenib, another VEGF inhibitor. Unfortunately, despite recovering some kidney function with the course of corticosteroids, our patient succumbed to pneumonia briefly afterwards. Given our experience, we recommend monitoring renal function with VEGF inhibition and advocating a prompter biopsy and treatment in cases of renal failure.\n\nGiven the patient use of acetylsalicylic acid/dipyridamole for over five years, interstitial nephritis secondary to acetylsalicylic acid and dipyridamole was on the differential. However, the corresponding biopsy would show evidence of chronic interstitial nephritis, that is, increased interstitial fibrosis and tubular atrophy that is more than what is expected for the patient's age. However, the biopsy demonstrated minimal interstitial fibrosis and tubular atrophy (estimated to be 5–10%) less than the 25–35% expected with a 69-year-old gentleman. As such, acetylsalicylic acid/dipyridamole as the offending drug was ruled out.\n\nThis report describes the second known case of biopsy-proven sunitinib-induced acute interstitial nephritis [7]. Current techniques in rational drug design do not allow for the extreme specificity in the era of personalized medicine promised. While sunitinib was ostensibly designed as a VEGF inhibitor, it is in fact a multikinase inhibitor that includes the following receptor tyrosine kinases (RTKs) [8, 9] among its targets: platelet-derived growth factor receptor (PDGFR), stem cell factor receptor c-kit, FMS-like tyrosine kinase 3 (FLT3), and colony-stimulating factor 1 (CSF-1). Similar case reports involving the VEGF-targeting drugs sorafenib (TKI) [6, 10] and bevacizumab (monoclonal antibody) [11, 12] imply a class effect specific to VEGF. No similar case reports were found with other targets. The incidence of AIN with nonrenal cancer [11, 12] indicates that the presence of underlying renal oncogenesis is not associated with AIN.\n\nPreviously reported renal adverse events of sunitinib include hypertension, proteinuria, renal insufficiency, and thrombotic microangiopathy; all are present in this case except thrombotic microangiopathy. Thus, thrombocytopenia in this case may be secondary to bone marrow suppression or immunologic in nature [13].\n\nWhile sunitinib-induced AIN is exceedingly rare, it should be considered in patients with acute renal failure. Given the multiple case reports implicating VEGF-targeting drugs in cases of AIN, further study is required to elicit the link between the VEGF pathway and AIN.\n\nConflicts of Interest\nThe authors declare that there are no conflicts of interest regarding the publication of this paper.\n\nFigure 1 Renal biopsy demonstrating acute interstitial nephritis (H&E staining): there is edema and an extensive dense interstitial chronic inflammatory infiltrate in the cortex and medulla. (a) In the lower power photomicrograph (left, 100x), the renal cortex shows extensive interstitial chronic inflammation with occasional lymphocytic tubulitis (arrow). In areas of inflammation, there is evidence of acute tubular injury with proximal tubules demonstrating lumenal distension with epithelial flattening. There was no evidence of glomerulitis, vasculitis, or thrombotic microangiopathy. (b) The higher magnification photomicrograph (right, 600x) shows that the interstitial inflammatory cells comprised frequent eosinophils (arrows) as well as lymphocytes and fewer plasma cells.\n\nFigure 2 Timeline showing the temporal relationship between the start of sunitinib and the rise of creatinine. Note the normal creatinine at baseline and the decrease of creatinine with steroids and hemodialysis.\n==== Refs\n1 National Comprehensive Cancer Network Kidney cancer (version 2) 2017, https://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf \n2 Ljungberg B. Bensalah K. Canfield S. EAU guidelines on renal cell carcinoma: 2014 update European Urology 2015 67 5 913 924 10.1016/j.eururo.2015.01.005 2-s2.0-84926219735 25616710 \n3 Perazella M. A. Markowitz G. S. Drug-induced acute interstitial nephritis Nature Reviews Nephrology 2010 6 8 461 470 10.1038/nrneph.2010.71 2-s2.0-77955086666 20517290 \n4 Bollée G. Patey N. Cazajous G. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib Nephrology Dialysis Transplantation 2009 24 2 682 685 10.1093/ndt/gfn657 2-s2.0-58449096748 \n5 Simard-Meilleur M. C. Troyanov S. Roy L. Dalaire E. Brachemi S. Risk factors and timing of native kidney biopsy complications Nephron Extra 2014 4 1 42 49 10.1159/000360087 24803920 \n6 Khurana A. Allergic interstitial nephritis possibly related to sunitinib use American Journal of Geriatric Pharmacotherapy 2007 5 4 341 344 10.1016/j.amjopharm.2007.12.011 2-s2.0-37549036619 18179992 \n7 Winn S. K. Ellis S. Savage P. Sampson S. Marsh J. E. Biopsy-proven acute interstitial nephritis associated with the tyrosine kinase inhibitor sunitinib: a class effect? Nephrology Dialysis Transplantation 2009 24 2 673 675 10.1093/ndt/gfn625 2-s2.0-58449116080 \n8 Chow L. Q. M. Eckhardt S. G. Sunitinib: from rational design to clinical efficacy Journal of Clinical Oncology 2007 25 7 884 896 10.1200/JCO.2006.06.3602 2-s2.0-33947504730 17327610 \n9 Papaetis G. S. Syrigos K. N. Sunitinib: a multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies BioDrugs 2009 23 6 377 389 10.2165/11318860-000000000-00000 2-s2.0-70450197345 19894779 \n10 Izzedine H. Brocheriou I. Rixe O. Deray G. Interstitial nephritis in a patient taking sorafenib Nephrology Dialysis Transplantation 2007 22 8 p. 2411 10.1093/ndt/gfm199 2-s2.0-34547830298 \n11 Barakat R. K. Singh N. Lal R. Verani R. R. Finkel K. W. Foringer J. R. Interstitial nephritis secondary to bevacizumab treatment in metastatic leiomyosarcoma Annals of Pharmacotherapy 2007 41 4 707 710 10.1345/aph.1H635 2-s2.0-34247257779 17374619 \n12 Lomax A. J. Hill P. A. Ashley D. M. Case report of interstitial nephritis induced by bevacizumab therapy for glioblastoma multiforme Journal of Oncology Pharmacy Practice 2013 19 4 365 368 10.1177/1078155212466421 2-s2.0-84888118275 23235917 \n13 Shekarriz R. Koulaeinejad N. Nosrati A. Salehifa E. Sunitinib induced immune thrombocytopenia Iranian Journal of Pharmaceutical Research 2015 14 4 1295 1297 26664400\n\n",
"fulltext_license": "CC BY",
"issn_linking": null,
"issue": "2017()",
"journal": "Case reports in oncological medicine",
"keywords": null,
"medline_ta": "Case Rep Oncol Med",
"mesh_terms": null,
"nlm_unique_id": "101581035",
"other_id": null,
"pages": "6328204",
"pmc": null,
"pmid": "29359059",
"pubdate": "2017",
"publication_types": "D002363:Case Reports",
"references": "18179992;25616710;19894779;20517290;24803920;17327610;17374619;26664400;17470456;19054798;23235917;19039026",
"title": "Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.",
"title_normalized": "sunitinib induced acute interstitial nephritis in a thrombocytopenic renal cell cancer patient"
}
|
[
{
"companynumb": "US-BAYER-2018-200855",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIPYRIDAMOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIPYRIDAMOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "SUNITINIB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SUNITINIB"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYLSALICYLIC ACID({=100 MG)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMOXICILLIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "URINARY TRACT INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMOXICILLIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CORTICOSTEROID NOS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TUBULOINTERSTITIAL NEPHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CORTICOSTEROID NOS"
}
],
"patientagegroup": "6",
"patientonsetage": "69",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Haematuria",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Anaemia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "AZAR I, ESFANDIARIFARD S, SINAI P, WAZIR A, FOULKE L, MEHDI S. SUNITINIB-INDUCED ACUTE INTERSTITIAL NEPHRITIS IN A THROMBOCYTOPENIC RENAL CELL CANCER PATIENT. CASE REPORTS IN ONCOLOGICAL MEDICINE. 2017?6328204:XX",
"literaturereference_normalized": "sunitinib induced acute interstitial nephritis in a thrombocytopenic renal cell cancer patient",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181031",
"receivedate": "20181031",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15570937,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190205"
},
{
"companynumb": "US-PFIZER INC-2018041508",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMOXICILLIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "URINARY TRACT INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMOXICILLIN."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "SUNITINIB MALATE"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "021938",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG, DAILY AT BED TIME",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CLEAR CELL RENAL CELL CARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201611",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SUNITINIB MALATE."
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (FOR OVER 5 YEARS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CEREBROVASCULAR ACCIDENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYLSALICYLIC ACID W/DIPYRIDAMOLE"
}
],
"patientagegroup": null,
"patientonsetage": "69",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Renal failure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Hypertension",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Proteinuria",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Tubulointerstitial nephritis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "AZAR, I.. SUNITINIB-INDUCED ACUTE INTERSTITIAL NEPHRITIS IN A THROMBOCYTOPENIC RENAL CELL CANCER PATIENT. CASE REPORTS IN ONCOLOGICAL MEDICINE. 2017?2017:PAGES 1-4",
"literaturereference_normalized": "sunitinib induced acute interstitial nephritis in a thrombocytopenic renal cell cancer patient",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180131",
"receivedate": "20180131",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14471630,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180509"
}
] |
{
"abstract": "Fanconi anemia is the most common inherited bone marrow failure syndrome, and hematopoietic stem cell transplantation (HSCT) is the only curative option. Post-transplant cyclophosphamide (PTCy) is challenging in this group of children, given their increased sensitivity to chemotherapy. We performed a retrospective analysis of the data on children diagnosed with Fanconi anemia who underwent a haploidentical HSCT with PTCy from January 2014 to December 2019. Nineteen children (male/female, 0.75:1) underwent 21 haplo-HSCTs with PTCy. Fludarabine, low-dose cyclophosphamide, and 200 centi-gray total body irradiation were included in the conditioning regimen with 25 mg/kg PTCy on days +3 and +4. Haplo-graft was from a sibling in 38% and father in 57% of transplants. The source of stem cells was peripheral blood stem cells in 81% and bone marrow in 19% of transplants, with a median CD34 dose of 5.0 × 106/kg. We documented engraftment in 84% and primary graft failure in 10% of transplants. N-acetylcysteine (NAC) was infused concomitantly during cyclophosphamide in 13 children. Grade 2 and 3 mucositis was lower among those who received NAC as compared to those who did not (30% and 15% versus 33% and 50%), while transaminitis was higher among those who did not receive the infusion. The incidence of acute graft-versus-host disease (GVHD) was 68%, and 81% of these were steroid responsive (grade I/II). We documented chronic GVHD in 25% children, predominantly involving the skin and mouth, which responded to low-dose steroids and ruxolitinib. Serum ferritin was monitored twice weekly as a surrogate marker for cytokine release syndrome due to nonavailability of IL-6 levels. A 1- or 2-log increase in the titers of ferritin associated with clinical features guided the early addition of steroids in the periengraftment period. The mean survival was found to be less among those with high serum ferritin (>10,000 ng/dL) in the periengraftment period as compared to those with ferritin <10,000 ng/dL (mean survival of 25 ± 10 months versus 50 ± 6 months, respectively). The overall survival in our cohort was 68.4%, with a mean survival time of 41.5 months (95% confidence interval, 29.3 to 53.8 months), with a statistically significant correlation between inferior outcome and having received over 15 transfusions before HSCT (P = .01). PTCy can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of HSCTs. Focused interventions in this subset of children help improve survival outcomes. Early identification of cytokine release syndrome and risk-adapted steroid therapy during engraftment helps prevent mortality. The concomitant use of NAC during cyclophosphamide infusion helps reduce oxygen free radical related tissue damage and regimen-related toxicity.",
"affiliations": "Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India. Electronic address: [email protected].;Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.;Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.;Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.;Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.;Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.;Department of Pediatric Critical Care, Apollo Hospitals, Chennai, India.;Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India.",
"authors": "Uppuluri|Ramya|R|;Swaminathan|Venkateswaran Vellaichamy|VV|;Ramanan|Kesavan Melarcode|KM|;Meena|Satishkumar|S|;Varla|Harika|H|;Ramakrishnan|Balasubramaniam|B|;Jayakumar|Indira|I|;Raj|Revathi|R|",
"chemical_list": "D003520:Cyclophosphamide",
"country": "United States",
"delete": false,
"doi": "10.1016/j.bbmt.2020.08.019",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1083-8791",
"issue": "26(12)",
"journal": "Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation",
"keywords": "Fanconi anemia; Ferritin; Haploidentical stem cell transplantation; N-acetyl cysteine; Post-transplant cyclophosphamide; Ruxolitinib",
"medline_ta": "Biol Blood Marrow Transplant",
"mesh_terms": "D002648:Child; D003520:Cyclophosphamide; D005199:Fanconi Anemia; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007194:India; D008297:Male; D012189:Retrospective Studies; D019172:Transplantation Conditioning",
"nlm_unique_id": "9600628",
"other_id": null,
"pages": "2292-2298",
"pmc": null,
"pmid": "32835780",
"pubdate": "2020-12",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Fanconi Anemia: Improving Outcomes with Improved Supportive Care in India.",
"title_normalized": "haploidentical stem cell transplantation with post transplant cyclophosphamide in fanconi anemia improving outcomes with improved supportive care in india"
}
|
[
{
"companynumb": "IN-MYLANLABS-2021M1028707",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FLUDARABINE PHOSPHATE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "200647",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUDARABINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BONE MARROW CONDITIONING REGIMEN",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FLUDARABINE PHOSPHATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "200647",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "30 MILLIGRAM/SQ. METER, QD RECEIVED FROM DAY ?7 TO DAY ?2",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BONE MARROW CONDITIONING REGIMEN",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "30",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUDARABINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOPHOSPHAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INFUSION",
"drugdosagetext": "5 MILLIGRAM/SQ. METER, QD RECEIVED ON DAY ?3 AND DAY ?2",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BONE MARROW CONDITIONING REGIMEN",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOPHOSPHAMIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "060",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOPHOSPHAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INFUSION",
"drugdosagetext": "25 MILLIGRAM/KILOGRAM RECEIVED ON DAY 3 AND DAY 4 POST TRANSPLANT",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "25",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOPHOSPHAMIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MESNA"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "DOSE: 1.4 TIMES THE DOSE OF CYCLOPHOSPHAMIDE, AS A ?..",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLACTIC CHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MESNA."
}
],
"patientagegroup": "3",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Alanine aminotransferase increased",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "UPPULURI R, SWAMINATHAN VV, RAMANAN KM, MEENA S, VARLA H, RAMAKRISHNAN B, ET AL. HAPLOIDENTICAL STEM CELL TRANSPLANTATION WITH POST?TRANSPLANT CYCLOPHOSPHAMIDE IN FANCONI ANEMIA: IMPROVING OUTCOMES WITH IMPROVED SUPPORTIVE CARE IN INDIA. BIOL?BLOOD?MARROW?TRANSPLANT 2020?26(12):2292?2298.",
"literaturereference_normalized": "haploidentical stem cell transplantation with post transplant cyclophosphamide in fanconi anemia improving outcomes with improved supportive care in india",
"qualification": "1",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20210519",
"receivedate": "20210519",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 19275227,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
}
] |
{
"abstract": "BACKGROUND\nTacrolimus has been associated with several ocular adverse effects, such as optic neuropathy.\n\n\nRESULTS\nA 56-year-old woman noted sudden, severe, painless visual loss in her left eye. She had undergone liver transplantation for alcoholic related cirrhosis 6 months before. Her chronic immunosuppressive regimen consisted of prednisone and tacrolimus at dosage of 1.5 mg orally once daily. Consequently, the patient developed a left optic neuropathy.\n\n\nCONCLUSIONS\nWe report the first case of unilateral optic neuropathy associated with oral tacrolimus medication. Surgeons and ophthalmologists must evaluate ocular symptoms in the post-transplantation period, and suspicion should be maintained even if unilaterality or asymmetry of symptoms against a toxic etiology.",
"affiliations": "Department of Ophthalmology, Lozano Blesa University Clinic Hospital, Zaragoza, Spain. [email protected]",
"authors": "Ascaso|Francisco J|FJ|;Mateo|Javier|J|;Huerva|Valentin|V|;Cristóbal|José A|JA|",
"chemical_list": "D007166:Immunosuppressive Agents; D016559:Tacrolimus",
"country": "England",
"delete": false,
"doi": "10.3109/15569527.2011.629325",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1556-9527",
"issue": "31(2)",
"journal": "Cutaneous and ocular toxicology",
"keywords": null,
"medline_ta": "Cutan Ocul Toxicol",
"mesh_terms": "D001766:Blindness; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D016031:Liver Transplantation; D008875:Middle Aged; D009901:Optic Nerve Diseases; D016559:Tacrolimus; D041623:Tomography, Optical Coherence",
"nlm_unique_id": "101266892",
"other_id": null,
"pages": "167-70",
"pmc": null,
"pmid": "22035458",
"pubdate": "2012-06",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Unilateral tacrolimus-associated optic neuropathy after liver transplantation.",
"title_normalized": "unilateral tacrolimus associated optic neuropathy after liver transplantation"
}
|
[
{
"companynumb": "ES-ASTELLAS-2012EU003861",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "204096",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "MODIFIED-RELEASE CAPSULE, HARD",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ADVAGRAF"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CALCIUM\\VITAMIN D"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUPPLEMENTATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CALCIUM W/VITAMIN D NOS"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PANTOPRAZOLE SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PANTOPRAZOLE SODIUM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DACORTIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ALENDRONIC ACID"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OSTEOPENIA",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALENDRONIC ACID"
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Optic neuropathy",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Optic atrophy",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "3"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ASCASO FJ, MATEO J, HUERVA V, CRISTOBAL JA.. UNILATERAL TACROLIMUS-ASSOCIATED OPTIC NEUROPATHY AFTER LIVER TRANSPLANTATION. CUTANEOUS AND OCULAR TOXICOLOGY. 2012;31(2):167-70",
"literaturereference_normalized": "unilateral tacrolimus associated optic neuropathy after liver transplantation",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20150827",
"receivedate": "20150827",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11422632,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20151125"
}
] |
{
"abstract": "Rheumatoid arthritis (RA) is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV) is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patient's colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reaction-positive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patient's complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis.",
"affiliations": "Department of Internal Medicine, School of Medicine, Gaziantep University. [email protected].",
"authors": "Dag|M S|MS|;Turkbeyler|I H|IH|;Ozturk|Z A|ZA|;Kısacık|B|B|;Tutar|E|E|;Kadayıfçı|A|A|",
"chemical_list": "D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077562:Valganciclovir; D015774:Ganciclovir",
"country": "Italy",
"delete": false,
"doi": "10.4081/reumatismo.2015.793",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0048-7449",
"issue": "67(1)",
"journal": "Reumatismo",
"keywords": null,
"medline_ta": "Reumatismo",
"mesh_terms": "D000998:Antiviral Agents; D001172:Arthritis, Rheumatoid; D003424:Crohn Disease; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir; D006801:Humans; D007166:Immunosuppressive Agents; D008875:Middle Aged; D016896:Treatment Outcome; D000077562:Valganciclovir",
"nlm_unique_id": "0401302",
"other_id": null,
"pages": "13-6",
"pmc": null,
"pmid": "26150269",
"pubdate": "2015-06-30",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review.",
"title_normalized": "cytomegalovirus ileocolitis in a rheumatoid arthritis patient case report and literature review"
}
|
[
{
"companynumb": "TR-ORION CORPORATION ORION PHARMA-TREX2017-1406",
"fulfillexpeditecriteria": "1",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHOTREXATE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "2",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHOTREXATE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEFLUNOMIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "2",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEFLUNOMIDE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "2",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cytomegalovirus infection",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Enterocolitis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DAG M,TURKBEYLER I. CYTOMEGALOVIRUS ILEOCOLITIS IN A RHEUMATOID ARTHRITIS PATIENT: CASE REPORT AND LITERATURE REVIEW. REUMATISMO. 2015 JUN 30;67(1):13-6.",
"literaturereference_normalized": "cytomegalovirus ileocolitis in a rheumatoid arthritis patient case report and literature review",
"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20170517",
"receivedate": "20170517",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13552496,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170830"
},
{
"companynumb": "TR-SA-2016SA090902",
"fulfillexpeditecriteria": "1",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "LEFLUNOMIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020905",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEFLUNOMIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METRONIDAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIARRHOEA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METRONIDAZOLE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "METHOTREXATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHOTREXATE"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
}
],
"patientagegroup": "5",
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Red blood cell sedimentation rate increased",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Abdominal discomfort",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "C-reactive protein increased",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Gastrointestinal oedema",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Gastrointestinal mucosa hyperaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Biopsy intestine abnormal",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Cytomegalovirus infection",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Diarrhoea",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Abdominal pain",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Mucosal inflammation",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Intestinal ulcer",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Enterocolitis",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Gastrointestinal erosion",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DAG MS, TURKBEYLER IH, OZTURK ZA, KISACIK B, TUTAR E, KADAYIFCI A. CYTOMEGALOVIRUS ILEOCOLITIS IN A RHEUMATOID ARTHRITIS PATIENT: CASE REPORT AND LITERATURE REVIEW. REUMATISMO 2015;67(1):13-6.",
"literaturereference_normalized": "cytomegalovirus ileocolitis in a rheumatoid arthritis patient case report and literature review",
"qualification": "3",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20160513",
"receivedate": "20160513",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12368089,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160815"
},
{
"companynumb": "TR-MYLANLABS-2017M1028737",
"fulfillexpeditecriteria": "1",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEFLUNOMIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEFLUNOMIDE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHOTREXATE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MG/WEEK FOR 2 YEARS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHOTREXATE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "202179",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cytomegalovirus infection",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Enterocolitis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DAG MS, TURKBEYLER IH, OZTURK ZA, KISACIK B, TUTAR E, KADAYIFCI A. CYTOMEGALOVIRUS ILEOCOLITIS IN A RHEUMATOID ARTHRITIS PATIENT: CASE REPORT AND LITERATURE REVIEW. REUMATISMO 2015;67(1):13-6.",
"literaturereference_normalized": "cytomegalovirus ileocolitis in a rheumatoid arthritis patient case report and literature review",
"qualification": "3",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20170517",
"receivedate": "20170517",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13554032,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170830"
},
{
"companynumb": "TR-FRESENIUS KABI-FK201704470",
"fulfillexpeditecriteria": "1",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METRONIDAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIARRHOEA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METRONIDAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHOTREXATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "040263",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHOTREXATE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LEFLUNOMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RHEUMATOID ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEFLUNOMIDE."
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Enterocolitis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DAG M,TURKBEYLER I,OZTURK Z,KISACIK B,TUTAR E,KADAYIFCI A. CYTOMEGALOVIRUS ILEOCOLITIS IN A RHEUMATOID ARTHRITIS PATIENT: CASE REPORT AND LITERATURE REVIEW.. REUMATISMO 2015;67(1):13-16.",
"literaturereference_normalized": "cytomegalovirus ileocolitis in a rheumatoid arthritis patient case report and literature review",
"qualification": "3",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20170524",
"receivedate": "20170524",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13578011,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170830"
}
] |
{
"abstract": "Introduction. Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like Aspergillus galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the Aspergillus galactomannan assay is not frequent. Case presentation. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution. Conclusion. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.",
"affiliations": "Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium.;Department of Microbiology, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.;Department of Pulmonary Medicine, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.;Department of Cardiac Surgery, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.;Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium.;Department of Nephrology, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.;Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium.;Department of Infectious Diseases, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.;Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium.",
"authors": "Lheureux|Olivier|O|;Montesinos|Isabel|I|;Taton|Olivier|O|;Antoine|Martine|M|;Preiser|Jean-Charles|JC|;Nortier|Joelle|J|;Creteur|Jacques|J|;Jacobs|Frederique|F|;Grimaldi|David|D|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1099/jmmcr.0.005116",
"fulltext": "\n==== Front\nJMM Case RepJMM Case RepJMMCRJMM Case Reports2053-3721Microbiology Society jmmcr00511610.1099/jmmcr.0.005116Case ReportRespiratoryFalse-positive galactomannan assay in broncho-alveolar lavage after enteral nutrition solution inhalation: a case report http://jmmcr.microbiologyresearch.orgLheureux Olivier 1Montesinos Isabel 2Taton Olivier 3Antoine Martine 4Preiser Jean-Charles 1Nortier Joelle 5Creteur Jacques 1Jacobs Frederique 6Grimaldi David 11 Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium2 Department of Microbiology, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium3 Department of Pulmonary Medicine, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium4 Department of Cardiac Surgery, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium5 Department of Nephrology, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium6 Department of Infectious Diseases, CUB - Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium*Correspondence: Olivier Lheureux, [email protected] Grimaldi, [email protected] material is available with the online version of this paper.\n\n9 2017 18 9 2017 4 9 e00511621 6 2017 05 9 2017 © 2017 The Authors2017This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.Introduction. Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like Aspergillus galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the Aspergillus galactomannan assay is not frequent.\n\nCase presentation. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution.\n\nConclusion. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.\n\nAspergillosisPneumoniafeeding solutionnutritional supportimmunosuppressionrespiratory failurefungal infectionvoriconazoleOpenAccessEmbargo0\n==== Body\nAbbreviations\nBAL, broncho-alveolar lavage; GM, galactomannan; IA, invasive aspergillosis; ICU, intensive care unit; VAP, ventilator-associated pneumonia.\n\nIntroduction\nWe describe the first report of a false-positive broncho-alveolar galactomannan due to aspiration of enteral nutrition. As enteral nutrition solutions are prescribed daily in critically ill patients and aspiration pneumonia is a common complication in intensive care, physicians should consider this possibility in case of broncho-alveolar lavage positive galactomannan assay under artificial enteral feeding.\n\nWe believe this finding will be of great interest to microbiologists and physicians, especially to those in contact with patients in intensive care.\n\nCase report\nA 65-year-old man was admitted in our intensive care unit (ICU) for pneumonia with septic shock. He was a heart transplant recipient since 1998 and had a renal graft in 2015 because of immunosuppressive treatment toxicity. Current immunosuppressive therapy consisted of methylprednisolone, mycophenolate mofetil and cyclosporine. Septic shock was associated with acute renal failure and severe acute respiratory distress syndrome requiring mechanical ventilation. No infectious pathogen was identified. The shock resolved in 4 days but respiratory conditions, only slowly improved, and the presence of a severe ICU-acquired weakness required a tracheotomy after 10 days of mechanical ventilation. The ICU stay was further complicated by a ventilator-associated pneumonia (VAP) due to Pseudomonas aeruginosa, a primary Enterococcus faecalis bacteremia and a severe herpetic stomatitis. A new respiratory deterioration at day 23 led to suspicion of a new episode of VAP treated by meropenem. Bronchoscopy revealed an important aspiration of enteral nutrition solution (Nutrison Protein Plus multifibre; Nutricia) due to incorrect position of the nasogastric tube. The procedure was followed by a pneumothorax, with pleural effusion, which required chest tube drainage. The pleural liquid had the same macroscopic aspect as the enteral nutrition solution. Aspergillus galactomannan (GM) assays performed in broncho-alveolar lavage (BAL) and pleural fluid, using the one-stage commercialized immunoenzymatic sandwich microplate assay (Platelia Aspergillus Ag; Bio-Rad), were highly positive in both fluids [optical density (OD) index 4.6 and >6, respectively; cut-off value >1]. Serum GM OD index was 0.08 (cut-off value >0.50) and fungal cultures of both BAL and pleural fluid remained sterile. We initiated voriconazole treatment and completed the work up with chest and sinus CT scans; both showed no signs suggestive of invasive fungal infection (see supplementary material). Considering these inconsistent findings for an invasive aspergillosis (IA), we performed Aspergillus GM detection in the enteral nutrition solution, which proved highly positive (index >6) whereas fungal culture remained negative. We therefore tested two other commercialized enteral nutrition solutions [Isosource standard fibre(Nestlé) and Fresubin original fibre (Fresenius Kabi)] also used in our institution and confirmed that all were also higher than the upper detection threshold (index >6). We therefore stopped voriconazole after 8 days of treatment. Evolution was favourable without any further fungal infection.\n\nDiscussion\nSpecies of the genus Aspergillus are ubiquitous in nature, and inhalation of infectious conidia is a common event that can give rise to various clinical conditions depending essentially on the host’s immunological status. IA occurs most frequently in the setting of severe immunosuppression (prolonged neutropenia, haematopoietic stem-cell transplantation, solid organ transplantation or acquired immune deficiency syndrome) [1].\n\nDiagnosis of IA is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in patients with severe respiratory insufficiency and critical illness [2]. Despite the lack of sufficiently sensitive or specific non-invasive test to establish definite diagnosis, the detection of a fungal cell wall component like Aspergillus GM remains a key component of the diagnostic procedure. Aspergillus GM are polysaccharides released during growth of the fungus and are detected by ELISA in biological fluid. In the serum, a positive GM is a strong argument in favour of invasive aspergillosis but the test lacks sensitivity [3]. Therefore, detection of Aspergillus GM has been proposed in the BAL and seems to have a greater sensitivity. According to a meta-analysis, BAL GM sensitivity and specificity reach 92 and 96 %, respectively with a threshold of 1.5 µg l−1 in adult haematology patients [4]. Results are however lower in other immunosuppressed patient populations such as solid organ transplant recipients.\n\nA false-positive result of the Aspergillus GM assay is not frequent. In BAL, false-positive GM assays have been observed in case of histoplasmosis [5] and in other mycoses [6, 7]. Indeed, some fungal species such as Penicillium and Paecilomyces have shown cross-reactivity with the rat EBA-2 monoclonal antibody used in our report, which has been characterized in previous studies [8]. False-positive BAL GM have been demonstrated after lavage with Plasmalyte (Baxter, Lessines, Belgium) and under treatment with piperacillin-tazobactam [9, 10]. Several reports incriminate GM-containing foods (pasta, rice, energy drinks, etc) as the source of positive serum GM through a chemotherapy-induced permeability of the intestinal mucosal barrier [11–13] but this was not reported in BAL fluids. A positive serum GM test linked to enteral feeding products has been mentioned exceptionally [14]. To the best of our knowledge, this is the first report of positive BAL GM assay induced by aspiration of enteral nutrition solution. Whether subclinical micro-aspiration of enteral nutrition solutions could also induce false-positive BAL GM should be further studied.\n\nConclusion\nThis is the first report of a false-positive BAL GM due to aspiration of enteral nutrition. Physicians should consider this possibility in case of BAL positive GM assay under artificial enteral feeding.\n\nFunding information\nThe authors received no specific grant from any funding agency.\n\nConflicts of interest\nThe authors declare that there are no conflicts of interest.\n\nSupplementary Data\n446Supplementary File 1\nClick here for additional data file.\n==== Refs\nReferences\n1 Meersseman W Van Wijngaerden E Invasive aspergillosis in the ICU: an emerging disease Intensive Care Med 2007 33 1679 1681 10.1007/s00134-007-0792-y 17646965 \n2 Koulenti D Garnacho-Montero J Blot S Approach to invasive pulmonary aspergillosis in critically ill patients Curr Opin Infect Dis 2014 27 174 183 10.1097/QCO.0000000000000043 24514164 \n3 Leeflang MM Debets-Ossenkopp YJ Wang j Visser CE Scholten RJ Galactomannan detection for invasive aspergillosis in immunocompromised patients Cochrane Database Syst Rev 2015 12 CD007394 \n4 Heng SC Morrissey O Chen SC Thursky K Manser RL Utility of bronchoalveolar lavage fluid galactomannan alone or in combination with PCR for the diagnosis of invasive aspergillosis in adult hematology patients: a systematic review and meta-analysis Crit Rev Microbiol 2015 41 124 134 10.3109/1040841X.2013.804033 23799871 \n5 Vergidis P Walker RC Kaul DR Kauffman CA Freifeld AG False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis Transpl Infect Dis 2012 14 213 217 10.1111/j.1399-3062.2011.00675.x 22093368 \n6 Borrás R Roselló P Chilet M Bravo D de Lomas JG Positive result of the Aspergillus galactomannan antigen assay using bronchoalveolar lavage fluid from a patient with an invasive infection due to Lichtheimia ramosa J Clin Microbiol 2010 48 3035 3036 10.1128/JCM.00902-10 20554823 \n7 Capoor MR Agarwal P Goel M Jain S Shivaprakash MR Invasive pulmonary mycosis due to Chaetomium globosum with false-positive galactomannan test: a case report and literature review Mycoses 2016 59 186 193 10.1111/myc.12446 26691935 \n8 Latgé JP Kobayashi H Debeaupuis JP Diaquin M Sarfati J Chemical and immunological characterization of the extracellular galactomannan of Aspergillus fumigatus Infect Immun 1994 62 5424 5433 7960122 \n9 Hage CA Reynolds JM Durkin M Wheat LJ Knox KS Plasmalyte as a cause of false-positive results for Aspergillus galactomannan in bronchoalveolar lavage fluid J Clin Microbiol 2007 45 676 677 10.1128/JCM.01940-06 17166959 \n10 Park SY Lee SO Choi SH Sung H Kim MN Aspergillus galactomannan antigen assay in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis J Infect 2010 61 492 498 10.1016/j.jinf.2010.08.014 20833201 \n11 Rachow T Dornaus S Sayer HG Hermann B Hochhaus A Case report: false positive elevated serum-galactomannan levels after autologous hematopoietic stem cell transplantation caused by oral nutritional supplements Clin Case Rep 2016 4 505 508 10.1002/ccr3.516 27188260 \n12 Gangneux JP Lavarde D Bretagne S Guiguen C Gandemer V Transient aspergillus antigenaemia: think of milk Lancet 2002 359 1251 10.1016/S0140-6736(02)08238-7 11955571 \n13 Guigue N Menotti J Ribaud P False positive galactomannan test after ice-pop ingestion N Engl J Med 2013 369 97 98 10.1056/NEJMc1210430 23822795 \n14 Girmenia C Santilli S Ballarò D Del Giudice I Armiento D Enteral nutrition may cause false-positive results of Aspergillus galactomannan assay in absence of gastrointestinal diseases Mycoses 2011 54 e883–e884 10.1111/j.1439-0507.2011.02022.x 21623937\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2053-3721",
"issue": "4(9)",
"journal": "JMM case reports",
"keywords": "Aspergillosis; Pneumonia; feeding solution; fungal infection; immunosuppression; nutritional support; respiratory failure; voriconazole",
"medline_ta": "JMM Case Rep",
"mesh_terms": null,
"nlm_unique_id": "101639133",
"other_id": null,
"pages": "e005116",
"pmc": null,
"pmid": "29114397",
"pubdate": "2017-09",
"publication_types": "D002363:Case Reports",
"references": "11955571;27188260;26691935;26716951;17166959;7960122;20554823;24514164;22093368;20833201;21623937;17646965;23822795;23799871",
"title": "False-positive galactomannan assay in broncho-alveolar lavage after enteral nutrition solution inhalation: a case report.",
"title_normalized": "false positive galactomannan assay in broncho alveolar lavage after enteral nutrition solution inhalation a case report"
}
|
[
{
"companynumb": "BE-ACCORD-061226",
"fulfillexpeditecriteria": "1",
"occurcountry": "BE",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CICLOSPORIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLIC ACID"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "065416",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLIC ACID."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "65",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Septic shock",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Oral herpes",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pneumonia",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pleural effusion",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute respiratory distress syndrome",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LHEUREUX O, MONTESINOS I, TATON O, ANTOINE M, PREISER JC, NORTIER J, ET AL. FALSE-POSITIVE GALACTOMANNAN ASSAY IN BRONCHO-ALVEOLAR LAVAGE AFTER ENTERAL NUTRITION SOLUTION INHALATION: A CASE REPORT. JMM CASE REP. 2017 SEP 18;4(9):E005116",
"literaturereference_normalized": "false positive galactomannan assay in broncho alveolar lavage after enteral nutrition solution inhalation a case report",
"qualification": "3",
"reportercountry": "BE"
},
"primarysourcecountry": "BE",
"receiptdate": "20171121",
"receivedate": "20171121",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14206902,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180321"
}
] |
{
"abstract": "This case represents the development of dizziness, palpitation, tightness in chest, flushing, and tremor on consumption of a single dose of tapentadol (100 mg) for acute lower back pain. The patient was admitted in the intensive cardiac care unit for continuous monitoring. At admission, electrocardiogram showed tachycardia (140/min) along with ST segment elevation in second chest lead (V2). The patient was monitored and advised not to take further doses of tapentadol. He was discharged after 36 hours of admission. Tapentadol should be used cautiously in patients with cardiovascular diseases and receiving sympathomimetic drugs.",
"affiliations": "Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, India.",
"authors": "Vachhani|A|A|;Barvaliya|M|M|;Naik|V|V|;Tripathi|C B|CB|",
"chemical_list": "D000701:Analgesics, Opioid; D010636:Phenols; D000077432:Tapentadol",
"country": "India",
"delete": false,
"doi": "10.4103/0022-3859.132341",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0022-3859",
"issue": "60(2)",
"journal": "Journal of postgraduate medicine",
"keywords": null,
"medline_ta": "J Postgrad Med",
"mesh_terms": "D000701:Analgesics, Opioid; D001145:Arrhythmias, Cardiac; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D018376:Cardiovascular Abnormalities; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography; D006329:Heart Conduction System; D006801:Humans; D017116:Low Back Pain; D008297:Male; D010636:Phenols; D000077432:Tapentadol; D016896:Treatment Outcome; D055815:Young Adult",
"nlm_unique_id": "2985196R",
"other_id": null,
"pages": "189-91",
"pmc": null,
"pmid": "24823521",
"pubdate": "2014",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Cardiovascular abnormalities with single dose of tapentadol.",
"title_normalized": "cardiovascular abnormalities with single dose of tapentadol"
}
|
[
{
"companynumb": "IN-COLLEGIUM PHARMACEUTICAL, INC.-IN-2019COL000385",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TAPENTADOL"
},
"drugadditional": "1",
"drugadministrationroute": "048",
"drugauthorizationnumb": "022304",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "100 MG, SINGLE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BACK PAIN",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TAPENTADOL"
}
],
"patientagegroup": null,
"patientonsetage": "24",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": "62",
"reaction": [
{
"reactionmeddrapt": "Chest discomfort",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Palpitations",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Flushing",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Tremor",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "VACHHANI A, BARVALIYA M1, NAIK V, TRIPATHI CB. CARDIOVASCULAR ABNORMALITIES WITH SINGLE DOSE OF TAPENTADOL. JOURNAL OF POSTGRADUATE MEDICINE. 2014?60(2):189-191",
"literaturereference_normalized": "cardiovascular abnormalities with single dose of tapentadol",
"qualification": "1",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20190401",
"receivedate": "20190401",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16142501,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190711"
}
] |
{
"abstract": "BACKGROUND\nAspirin (ASA) is the drug of choice in patients with coronary artery disease for primary and secondary prevention. This poses a problem for those patients reporting hypersensitivity to this drug or class of drugs.\n\n\nOBJECTIVE\nDesensitization to ASA may be carried out safely and effectively in patients with reported ASA or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity needing ASA for cardiac indications. Our 7-step protocol is one choice for a rapid desensitization protocol.\n\n\nMETHODS\nA retrospective chart review was conducted evaluating ASA desensitization in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA.\n\n\nRESULTS\nIn 160 evaluations over 15 years, 89 desensitizations were performed in both the inpatient and outpatient setting with only 16 reactions (18%). Eleven of these 16 patients (68.7%) were able to take daily ASA. Twenty-six desensitization procedures were performed with our 7-step rapid desensitization protocol in 10 inpatients and 16 outpatients with 3 reactions (18.75% of reactions). Initial reaction to ASA involving angioedema and reacting to ASA within the past year increased the risk of having a reaction to desensitization.\n\n\nCONCLUSIONS\nDesensitization may be safely performed in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. Our 7-step rapid protocol may be used in both the inpatient and outpatient setting to desensitize these patients. Patients who had angioedema with ASA ingestion or a reaction to ASA within the past year are at higher risk for reaction during the desensitization protocol. The authors have no funding, financial relationships, or conflicts of interest to disclose.",
"affiliations": "Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. [email protected]",
"authors": "McMullan|Kathryn L|KL|;Wedner|H James|HJ|",
"chemical_list": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin",
"country": "United States",
"delete": false,
"doi": "10.1002/clc.22054",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0160-9289",
"issue": "36(1)",
"journal": "Clinical cardiology",
"keywords": null,
"medline_ta": "Clin Cardiol",
"mesh_terms": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D002318:Cardiovascular Diseases; D003888:Desensitization, Immunologic; D004342:Drug Hypersensitivity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012189:Retrospective Studies",
"nlm_unique_id": "7903272",
"other_id": null,
"pages": "25-30",
"pmc": null,
"pmid": "22990948",
"pubdate": "2013-01",
"publication_types": "D003160:Comparative Study; D016428:Journal Article",
"references": "21933761;15695141;22365313;15613671;18306836;21562370;18328841;21631520;15242723;20934625;17521312;21217919;17200429;19232198;19293072;10808182;20739873",
"title": "Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease.",
"title_normalized": "safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease"
}
|
[
{
"companynumb": "US-INGENUS PHARMACEUTICALS NJ, LLC-ING201702-000066",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ASPIRIN\\CARISOPRODOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040832",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE TOLERANCE INDUCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARISOPRODOL AND ASPIRIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Wheezing",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MCMULLAN K,WEDNER H. SAFETY OF ASPIRIN DESENSITIZATION IN PATIENTS WITH REPORTED ASPIRIN ALLERGY AND CARDIOVASCULAR DISEASE. CLIN CARDIOL 2013;36(1):25-30.",
"literaturereference_normalized": "safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170214",
"receivedate": "20170214",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13231986,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "US-INGENUS PHARMACEUTICALS NJ, LLC-ING201702-000051",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ASPIRIN\\CARISOPRODOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040832",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE TOLERANCE INDUCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARISOPRODOL AND ASPIRIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Angioedema",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MCMULLAN K,WEDNER H. SAFETY OF ASPIRIN DESENSITIZATION IN PATIENTS WITH REPORTED ASPIRIN ALLERGY AND CARDIOVASCULAR DISEASE. CLIN CARDIOL 2013;36(1):25-30.",
"literaturereference_normalized": "safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170214",
"receivedate": "20170214",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13232225,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "US-INGENUS PHARMACEUTICALS NJ, LLC-ING201702-000053",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ASPIRIN\\CARISOPRODOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040832",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE TOLERANCE INDUCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "27",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARISOPRODOL AND ASPIRIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Angioedema",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MCMULLAN K,WEDNER H. SAFETY OF ASPIRIN DESENSITIZATION IN PATIENTS WITH REPORTED ASPIRIN ALLERGY AND CARDIOVASCULAR DISEASE. CLIN CARDIOL 2013;36(1):25-30.",
"literaturereference_normalized": "safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170214",
"receivedate": "20170214",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13232235,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "US-INGENUS PHARMACEUTICALS NJ, LLC-ING201702-000067",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ASPIRIN\\CARISOPRODOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040832",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE TOLERANCE INDUCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARISOPRODOL AND ASPIRIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Chest pain",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hyperhidrosis",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Bradycardia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MCMULLAN K,WEDNER H. SAFETY OF ASPIRIN DESENSITIZATION IN PATIENTS WITH REPORTED ASPIRIN ALLERGY AND CARDIOVASCULAR DISEASE. CLIN CARDIOL 2013;36(1):25-30.",
"literaturereference_normalized": "safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170214",
"receivedate": "20170214",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13231995,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "US-INGENUS PHARMACEUTICALS NJ, LLC-ING201702-000052",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ASPIRIN\\CARISOPRODOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040832",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNE TOLERANCE INDUCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARISOPRODOL AND ASPIRIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pruritus",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Angioedema",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MCMULLAN K,WEDNER H. SAFETY OF ASPIRIN DESENSITIZATION IN PATIENTS WITH REPORTED ASPIRIN ALLERGY AND CARDIOVASCULAR DISEASE. CLIN CARDIOL 2013;36(1):25-30.",
"literaturereference_normalized": "safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170214",
"receivedate": "20170214",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13232233,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
}
] |
{
"abstract": "Minocycline is widely used as a first-line agent for papulopustular acne, and has previously been reported as causing stains on teeth that are still forming. This article reports a case of staining to only the crowns of unerupted third molars in a girl prescribed minocycline at age 16 for papulopustular acne. We review the literature in the area of minocycline teeth staining, consider the role of minocycline as a first-line agent for papulopustular acne, and outline strategies on the prevention of minocycline teeth staining. The case highlights current deficiencies in the disclosure information for minocycline, and provides information that is relevant to practitioners who may prescribe this drug.",
"affiliations": "Concord General Repatriation Hospital, Sydney, NSW, Australia.;Concord General Repatriation Hospital & The University of Sydney, Sydney, NSW, Australia.",
"authors": "Raymond|James|J|;Cook|David|D|",
"chemical_list": null,
"country": "Canada",
"delete": false,
"doi": "10.4066/AMJ.2015.2335",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1836-1935",
"issue": "8(4)",
"journal": "The Australasian medical journal",
"keywords": "crowns; minocycline; staining; third molars; unerupted",
"medline_ta": "Australas Med J",
"mesh_terms": null,
"nlm_unique_id": "101558564",
"other_id": null,
"pages": "139-42",
"pmc": null,
"pmid": "26045724",
"pubdate": "2015",
"publication_types": "D002363:Case Reports",
"references": "11427798;17016895;17986300;21656385;14004715;3861819;6592526;12566804;16262034;18358884;3867718;2674217;9468876;15972585;11325156;12932226;2584464;9893512;15485524;9762375",
"title": "Still leaving stains on teeth-the legacy of minocycline?",
"title_normalized": "still leaving stains on teeth the legacy of minocycline"
}
|
[
{
"companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2015-01778",
"fulfillexpeditecriteria": "2",
"occurcountry": "AU",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "091424",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACNE PUSTULAR",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Tooth discolouration",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "RAYMOND J, COOK D. STILL LEAVING STAINS ON TEETH-THE LEGACY OF MINOCYCLINE?. AUSTRALIAN MEDICAL JOURNAL. 2015?8 (4):139-142.",
"literaturereference_normalized": "still leaving stains on teeth the legacy of minocycline",
"qualification": "3",
"reportercountry": "AU"
},
"primarysourcecountry": "AU",
"receiptdate": "20160307",
"receivedate": "20160307",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 12153600,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160526"
}
] |
{
"abstract": "We report the case of a catheter-related bloodstream infection caused by Chryseobacterium indologenes, an uncommon and multi-resistant pathogen, in a pediatric patient with a long-term vascular access device placed for chemotherapy treatment. The infection was successfully treated with ciprofloxacin antibiotic-lock therapy. This is the first report on successful salvage of a long-term device colonized by multi-resistant Chryseobacterium indologenes.",
"affiliations": "Servizio di Biometria ed Epidemiologia Clinica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Microbiologia e Virologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Microbiologia e Virologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Anestesia e Rianimazione 2, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Anestesia e Rianimazione 2, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;Direzione Medica di Presidio, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.;S.C. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.",
"authors": "Corbella|Marta|M|;Brandolini|Micaela|M|;Cambieri|Patrizia|P|;Decembrino|Nunzia|N|;Pagani|Michele|M|;Bottazzi|Andrea|A|;Muzzi|Alba|A|;Zecca|Marco|M|;Mariani|Bianca|B|;Marone|Piero|P|",
"chemical_list": "D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin",
"country": "Italy",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1121-7138",
"issue": "40(3)",
"journal": "The new microbiologica",
"keywords": "CRBSI; CVC; Chryseobacterium indologenes; Lock-therapy",
"medline_ta": "New Microbiol",
"mesh_terms": "D000900:Anti-Bacterial Agents; D016470:Bacteremia; D055499:Catheter-Related Infections; D062905:Central Venous Catheters; D002648:Child; D045247:Chryseobacterium; D002939:Ciprofloxacin; D045826:Flavobacteriaceae Infections; D006801:Humans; D008297:Male; D012512:Sarcoma, Ewing; D016896:Treatment Outcome",
"nlm_unique_id": "9516291",
"other_id": null,
"pages": "223-225",
"pmc": null,
"pmid": "28675244",
"pubdate": "2017-07",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "A catheter-related bloodstream infection caused by Chryseobacterium indologenes successfully treated with antibiotic-lock rescue therapy.",
"title_normalized": "a catheter related bloodstream infection caused by chryseobacterium indologenes successfully treated with antibiotic lock rescue therapy"
}
|
[
{
"companynumb": "IT-PFIZER INC-2018064652",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "DOXORUBICIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050467",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ADRIAMYCIN"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "DACTINOMYCIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACTINOMYCIN D"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE, TRIMETHOPRIM, BROMHEXINE HY"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "VINCRISTINE SULFATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "071484",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VINCRISTINE SULFATE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "DOXORUBICIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "050467",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXORUBICIN HCL"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "CYCLOPHOSPHAMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOPHOSPHAMIDE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IFOSFAMIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACYCLOVIR"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIVIRAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACYCLOVIR."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
}
],
"patientagegroup": null,
"patientonsetage": "11",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pyrexia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Chills",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Flavobacterium infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "C-reactive protein increased",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Neutropenia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORBELLA, MARTA. A CATHETER-RELATED BLOODSTREAM INFECTION CAUSED BY CHRYSEOBACTERIUM INDOLOGENES SUCCESSFULLY TREATED WITH ANTIBIOTIC-LOCK RESCUE THERAPY. NEW MICROBIOLOGICA. 2017?40(3):223-225",
"literaturereference_normalized": "a catheter related bloodstream infection caused by chryseobacterium indologenes successfully treated with antibiotic lock rescue therapy",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180221",
"receivedate": "20180216",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14543067,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180509"
},
{
"companynumb": "IT-MYLANLABS-2019M1001430",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IFOSFAMIDE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "CYCLOPHOSPHAMIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOPHOSPHAMIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE AND TRIMETHOPRIM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "DACTINOMYCIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "203385",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DACTINOMYCIN"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "DOXORUBICIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ADRIAMYCIN"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "VINCRISTINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EWING^S SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VINCRISTINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACYCLOVIR"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIVIRAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACYCLOVIR /00587301/"
}
],
"patientagegroup": null,
"patientonsetage": "11",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Chills",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pyrexia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Disease recurrence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "C-reactive protein increased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Neutropenia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Bacterial infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORBELLA M, BRANDOLINI M, CAMBIERI P, DECEMBRINO N, PAGANI M, BOTTAZZI A, ET AL.. A CATHETER-RELATED BLOODSTREAM INFECTION CAUSED BY CHRYSEOBACTERIUM INDOLOGENES SUCCESSFULLY TREATED WITH ANTIBIOTIC-LOCK RESCUE THERAPY.. NEW MICROBIOLOGICA. 2017?40(3):223-5",
"literaturereference_normalized": "a catheter related bloodstream infection caused by chryseobacterium indologenes successfully treated with antibiotic lock rescue therapy",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20190110",
"receivedate": "20190110",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15807256,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190417"
}
] |
{
"abstract": "Kratom (Mitragyna speciosa) is a plant extract that exhibits opioid agonistic activity at the µ-opioid receptor. The use of this substance has increased recently due to widespread local availability across the United States, primarily at gas stations. Repeated kratom use has been shown to have major adverse effects leading to physiological dependence and addiction similar to other opioids. We used a novel contingency management (CM) program utilizing nonmonetary reinforcers along with medication-assisted treatment (MAT) using buprenorphine in an office-based setting to treat kratom use disorder in two cases. MAT with buprenorphine in a CM-based setting was found to be an effective strategy for treating kratom use disorder.",
"affiliations": "House Officer, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi.;House Officer, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi.;Medical Director, Addiction Program, Assistant Professor of Psychiatry, Department of Psychiatry and Hu-man Behavior, University of Mississippi Medical Center, Jackson, Mississippi.",
"authors": "Kalin|Seth|S|;Dakhlalla|Salaahuddin|S|;Bhardwaj|Saurabh|S|",
"chemical_list": "D000701:Analgesics, Opioid; D002047:Buprenorphine",
"country": "United States",
"delete": false,
"doi": "10.5055/jom.2020.0594",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1551-7489",
"issue": "16(5)",
"journal": "Journal of opioid management",
"keywords": null,
"medline_ta": "J Opioid Manag",
"mesh_terms": "D000701:Analgesics, Opioid; D002047:Buprenorphine; D006801:Humans; D032065:Mitragyna; D058850:Opiate Substitution Treatment; D019966:Substance-Related Disorders; D014481:United States",
"nlm_unique_id": "101234523",
"other_id": null,
"pages": "391-394",
"pmc": null,
"pmid": "33226096",
"pubdate": "2020",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Treatment for kratom abuse in a contingency-management-based MAT setting: A case series.",
"title_normalized": "treatment for kratom abuse in a contingency management based mat setting a case series"
}
|
[
{
"companynumb": "US-MYLANLABS-2021M1006239",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HERBALS\\MITRAGYNINE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER",
"drugdosagetext": "HE USED THE SUBSTANCE BY STUFFING THE POWDER IN TOILET PAPER BALLS AND SWALLOWING IT",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DETOXIFICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "KRATOM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HERBALS\\MITRAGYNINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG DEPENDENCE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "KRATOM"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "BUPRENORPHINE HYDROCHLORIDE\\NALOXONE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "060",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1 DOSAGE FORM, QD FILMS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG USE DISORDER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "032",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPRENORPHINE HYDROCHLORIDE/NALOXONE HYDROCHLORIDE"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "BUPRENORPHINE HYDROCHLORIDE\\NALOXONE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "060",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TOOK MORE THAN 1 FILM PER DAY AND EXHAUSTED HIS SUPPLY PREMATURELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPRENORPHINE HYDROCHLORIDE/NALOXONE HYDROCHLORIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANXIETY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMADOL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "075986",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ARTHRALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2013",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMADOL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "CROSS TAPERED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANXIETY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE"
}
],
"patientagegroup": null,
"patientonsetage": "31",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Constipation",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug abuse",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Headache",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug use disorder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Intentional product misuse",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2013"
}
},
"primarysource": {
"literaturereference": "KALIN S, DAKHLALLA S, BHARDWAJ S. TREATMENT FOR KRATOM ABUSE IN A CONTINGENCY?MANAGEMENT?BASED MAT SETTING: A CASE SERIES. J?OPIOID?MANAG 2020?16(5):391?394.",
"literaturereference_normalized": "treatment for kratom abuse in a contingency management based mat setting a case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210202",
"receivedate": "20210202",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18821696,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210419"
},
{
"companynumb": "US-TEVA-2021-US-1877575",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BUPRENORPHINE\\NALOXONE"
},
"drugadditional": null,
"drugadministrationroute": "060",
"drugauthorizationnumb": "091422",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TOOK MORE THAN 1 FILM PER DAY AND EXHAUSTED HIS SUPPLY PREMATURELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPRENORPHINE?NALOXONE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMADOL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75977",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ARTHRALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2013",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMADOL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "CROSS TAPERED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANXIETY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BUPRENORPHINE\\NALOXONE"
},
"drugadditional": null,
"drugadministrationroute": "060",
"drugauthorizationnumb": "091422",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1 DOSAGE FORMS DAILY; FILMS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG USE DISORDER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "032",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPRENORPHINE?NALOXONE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "20 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANXIETY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE"
}
],
"patientagegroup": "5",
"patientonsetage": "31",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug use disorder",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Loss of personal independence in daily activities",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Impaired quality of life",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Headache",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Intentional product misuse",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Impaired work ability",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug withdrawal syndrome",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Constipation",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug abuse",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2013"
}
},
"primarysource": {
"literaturereference": "KALIN S, DAKHLALLA S, BHARDWAJ S. TREATMENT FOR KRATOM ABUSE IN A CONTINGENCY?MANAGEMENT?BASED MAT SETTING: A CASE SERIES. J?OPIOID?MANAG 2020?16(5):391?394.",
"literaturereference_normalized": "treatment for kratom abuse in a contingency management based mat setting a case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210715",
"receivedate": "20210211",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18883649,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
},
{
"companynumb": "US-JNJFOC-20201250537",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMADOL HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "020281",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PAIN",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2013",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ULTRAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMADOL HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "020281",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG WITHDRAWAL MAINTENANCE THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ULTRAM"
}
],
"patientagegroup": "5",
"patientonsetage": "36",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug use disorder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2013"
}
},
"primarysource": {
"literaturereference": "KALIN S, DAKHLALLA S, BHARDWAJ S. TREATMENT FOR KRATOM ABUSE IN A CONTINGENCY?MANAGEMENT?BASED MAT SETTING: A CASE SERIES. JOURNAL OF OPIOID MANAGEMENT. 2020?16(5):391?94. DOI: 10.5055/JOM.2020.0594.",
"literaturereference_normalized": "treatment for kratom abuse in a contingency management based mat setting a case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210104",
"receivedate": "20210104",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18696190,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210419"
},
{
"companynumb": "US-DRREDDYS-USA/USA/20/0130648",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "BUPRENORPHINE\\NALOXONE"
},
"drugadditional": null,
"drugadministrationroute": "060",
"drugauthorizationnumb": "205299",
"drugbatchnumb": "UNKNOWN,UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TOTAL DOSE OF 24 MG OF BUPRENORPHINE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG USE DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2018",
"drugstartdateformat": "602",
"drugstructuredosagenumb": "24",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPRENORPHINE AND NALOXONE SUBLINGUAL FILM 2 MG/0.5 MG AND 8MG/2MG"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ALBUTEROL"
},
"drugadditional": "3",
"drugadministrationroute": "055",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INHALATION GAS",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ASTHMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SALBUTAMOL"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN,UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "CROSS TAPERED WITH VENLAFAXINE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2018",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "078301",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2018",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE HYDROCHLORIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN,UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANXIETY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "GABAPENTIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BACK PAIN",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "032",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GABAPENTIN 300 MG"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "BUPRENORPHINE\\NALOXONE"
},
"drugadditional": null,
"drugadministrationroute": "060",
"drugauthorizationnumb": "205299",
"drugbatchnumb": "UNKNOWN,UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MORE THAN 1 FILM PER DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201811",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPRENORPHINE AND NALOXONE SUBLINGUAL FILM 2 MG/0.5 MG AND 8MG/2MG"
}
],
"patientagegroup": "5",
"patientonsetage": "36",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Constipation",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Headache",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2019"
}
},
"primarysource": {
"literaturereference": "KALIN S, DAKHLALLA S, BHARDWAJ S. TREATMENT FOR KRATOM ABUSE IN A CONTINGENCY?MANAGEMENT?BASED MAT SETTING: A CASE SERIES. JOURNAL OF OPIOID MANAGEMENT. 2020?16(5):391?94. DOI: 10.5055/JOM.2020.0594.",
"literaturereference_normalized": "treatment for kratom abuse in a contingency management based mat setting a case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210504",
"receivedate": "20210107",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18714960,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210717"
}
] |
{
"abstract": "Acute myocardial infarction (AMI) diagnosis in patients with pre-existing left bundle branch block (LBBB) can be difficult. Undiagnosed or delayed diagnosis of AMI in these patients can put them at risk of having shock, mechanical complications, and death. We present a case of 77-year-old Caucasian male with a known LBBB and coronary artery bypass surgery for coronary artery disease who presented to the emergency department with a chief complaint of chest pain and shortness of breath. The patient had recurrent chest pain despite using aspirin, nitroglycerine, and morphine. An electrocardiogram (ECG) showed a new notch in the upslope of the R wave in leads I, AVL that indicated a positive Chapman's sign. Troponin levels were initially normal, but serial troponin showed elevated enzyme giving evidence of acute coronary syndrome (ACS). The patient was started on heparin drip and underwent subsequent coronary catheterization. Physicians should be aware of Chapman's sign on ECG in patients presenting with chest pain who have baseline LBBB as it might represent myocardial ischemia and warrant emergent treatment for ACS.",
"affiliations": "University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; North Florida Regional Medical Center, Internal Medicine, Gainesville, FL, USA. Electronic address: [email protected].;University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; North Florida Regional Medical Center, Internal Medicine, Gainesville, FL, USA.;Marshall University Joan C. Edwards School of Medicine, Cardiovascular Medicine, Huntington, WV, USA.",
"authors": "Idris|Amr|A|;Hatahet|Mohamad|M|;Edris|Basel|B|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1016/j.ajem.2019.158378",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0735-6757",
"issue": "37(10)",
"journal": "The American journal of emergency medicine",
"keywords": "Acute myocardial infarction; Chapman's sign; Left bundle branch block",
"medline_ta": "Am J Emerg Med",
"mesh_terms": "D000368:Aged; D002037:Bundle-Branch Block; D006328:Cardiac Catheterization; D002637:Chest Pain; D004417:Dyspnea; D004562:Electrocardiography; D006801:Humans; D008297:Male; D009203:Myocardial Infarction; D016896:Treatment Outcome",
"nlm_unique_id": "8309942",
"other_id": null,
"pages": "1991.e5-1991.e7",
"pmc": null,
"pmid": "31395406",
"pubdate": "2019-10",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Acute myocardial infarction in the setting of left bundle branch block: Chapman's sign.",
"title_normalized": "acute myocardial infarction in the setting of left bundle branch block chapman s sign"
}
|
[
{
"companynumb": "US-USP-000009",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "NITROGLYCERIN"
},
"drugadditional": "3",
"drugadministrationroute": "060",
"drugauthorizationnumb": "020145",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANGINA PECTORIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NITROGLYCERIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANGINA PECTORIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "324",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYLSALICYLIC ACID"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ONE DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANGINA PECTORIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "NITROGLYCERIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "020145",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANGINA PECTORIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NITROGLYCERIN."
}
],
"patientagegroup": "6",
"patientonsetage": "77",
"patientonsetageunit": "801",
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Disease recurrence",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug effective for unapproved indication",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Angina pectoris",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "IDRIS A, HATAHET M, EDRIS B. ACUTE MYOCARDIAL INFARCTION IN THE SETTING OF LEFT BUNDLE BRANCH BLOCK: CHAPMAN^S SIGN. AM J EMERG MED. 2019 JUL 29:158378. DOI: 10.1016/J.AJEM.2019.158378.",
"literaturereference_normalized": "acute myocardial infarction in the setting of left bundle branch block chapman s sign",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190820",
"receivedate": "20190820",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16719515,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20191005"
}
] |
{
"abstract": "OBJECTIVE\nTo investigate whether the incidence of thromboembolic events (venous and arterial) increases when bevacizumab-based chemotherapy and erythropoietin stimulating agents (ESAs) are used in combination versus alone.\n\n\nMETHODS\nA retrospective, pilot study of 79 colorectal cancer patients treated with chemotherapy were divided into 3 groups: bevacizumab (n = 28), ESA (n = 21), and bevacizumab plus ESA (n = 28). The primary end point was the incidence of thromboembolic events. Secondary endpoints included median time-to-event; effect of anticoagulation; and association with concurrent chemotherapy, baseline risk factors, hemoglobin, and performance status.\n\n\nRESULTS\nThe incidence of thromboembolic events was 11% in the bevacizumab group, 23.8% in the ESA group, and 30% in the combination group (P = 0.194). The median time-to-event was 7.5, 3.5, and 2.5 months, respectively (P = 0.060). The 5 month difference in time-to-event between the bevacizumab group and combination group was significant (P = 0.045). When combining all patients, ESA treatment, prior venous thromboembolic event (VTE), obesity, cardiac disease, and use of exogenous hormones were strong predictors for thromboembolic events. Prior VTE was a strong predictor in those patients in the combination group.\n\n\nCONCLUSIONS\nThe incidence of thromboembolic events was increased with the combination of bevacizumab plus ESA compared with either agent alone with chemotherapy. Median time-to-event in the combination group was significantly shorter compared with the bevacizumab group. Prior VTE, cardiac disease, obesity, and exogenous hormone use should be taken in consideration when using the combination of bevacizumab and ESAs.",
"affiliations": "Department of Pharmacy Services, The University Hospital, University of Cincinnati, Cincinnati, Ohio, USA. [email protected]",
"authors": "Roddy|Julianna V F|JV|;Partridge|Suzanne M|SM|;Rockey|Michelle L|ML|;Pruemer|Jane M|JM|;Guo|Jeff J|JJ|;Desai|Shaili J|SJ|;Safa|Malek M|MM|",
"chemical_list": "D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D000068258:Bevacizumab",
"country": "United States",
"delete": false,
"doi": "10.1097/COC.0b013e31819cccaf",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0277-3732",
"issue": "33(1)",
"journal": "American journal of clinical oncology",
"keywords": null,
"medline_ta": "Am J Clin Oncol",
"mesh_terms": "D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015179:Colorectal Neoplasms; D004359:Drug Therapy, Combination; D004921:Erythropoietin; D005260:Female; D006454:Hemoglobins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D011994:Recombinant Proteins; D012189:Retrospective Studies; D015996:Survival Rate; D013923:Thromboembolism; D042461:Vascular Endothelial Growth Factor A",
"nlm_unique_id": "8207754",
"other_id": null,
"pages": "36-42",
"pmc": null,
"pmid": "19652579",
"pubdate": "2010-02",
"publication_types": "D016428:Journal Article; D016448:Multicenter Study",
"references": null,
"title": "Thromboembolic events in patients with colorectal cancer receiving the combination of bevacizumab-based chemotherapy and erythropoietin stimulating agents.",
"title_normalized": "thromboembolic events in patients with colorectal cancer receiving the combination of bevacizumab based chemotherapy and erythropoietin stimulating agents"
}
|
[
{
"companynumb": "US-AMGEN-USASP2019202278",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "BEVACIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, Q2WK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLORECTAL CANCER",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BEVACIZUMAB."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "WARFARIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "WARFARIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ERYTHROPOIETIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "103234",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNK UNK, Q2WK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EPOETIN ALFA"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pulmonary embolism",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Aortic thrombosis",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Deep vein thrombosis",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Myocardial infarction",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ROCKEY, ML. THROMBOEMBOLIC EVENTS IN PATIENTS WITH COLORECTAL CANCER RECEIVING THE COMBINATION OF BEVACIZUMAB-BASED CHEMOTHERAPY AND ERYTHROPOIETIN STIMULATING AGENTS. AMERICAN JOURNAL OF CLINICAL ONCOLOGY PUBLICATION. 2010?33 (1):36-42",
"literaturereference_normalized": "thromboembolic events in patients with colorectal cancer receiving the combination of bevacizumab based chemotherapy and erythropoietin stimulating agents",
"qualification": "2",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20191211",
"receivedate": "20191211",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17138609,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200122"
}
] |
{
"abstract": "\"Black bone disease\" is a term commonly used to describe a condition characterized by a blue/green/brown discoloration to the bone that often resembles infracted or necrotic bone. The chronic use of minocycline or tetracycline has been reported in previous data as a cause of this discoloration to the skin, bone, and teeth. However, the occurrence in bone is rare, with few studies reported regarding the discoloration. We previously presented a case of this condition encountered during cheilectomy of the first metatarsophalangeal joint in a patient who had had long-term usage of minocycline for adult acne. Two years after the initial case, the patient returned for correction of a hammertoe deformity on the second left proximal phalanx of the same foot. We present the findings and photographs from the second surgery. In addition, we have provided the relevant case data and figures from the first case for ease of comparison.",
"affiliations": "PGY1 DVA NM, Western University of Health Sciences, Pomona, CA. Electronic address: [email protected].;Surgeon, Western University of Health Sciences, Pomona, CA.",
"authors": "Cornejo|Adam|A|;Kerbleski|Gerard J|GJ|",
"chemical_list": "D000900:Anti-Bacterial Agents; D008911:Minocycline",
"country": "United States",
"delete": false,
"doi": "10.1053/j.jfas.2018.03.032",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1067-2516",
"issue": "57(6)",
"journal": "The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons",
"keywords": "black metatarsal; blue bone; hyperpigmentation; minocycline; tetracycline",
"medline_ta": "J Foot Ankle Surg",
"mesh_terms": "D000152:Acne Vulgaris; D000900:Anti-Bacterial Agents; D001847:Bone Diseases; D005528:Foot; D037801:Hammer Toe Syndrome; D006801:Humans; D008297:Male; D008683:Metatarsophalangeal Joint; D008875:Middle Aged; D008911:Minocycline; D010859:Pigmentation Disorders",
"nlm_unique_id": "9308427",
"other_id": null,
"pages": "1259-1262",
"pmc": null,
"pmid": "30001940",
"pubdate": "2018",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Black Bone Disease of the Foot: A Two-Year Follow-Up Case Study.",
"title_normalized": "black bone disease of the foot a two year follow up case study"
}
|
[
{
"companynumb": "US-MYLANLABS-2013S1005281",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "090911",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 MG,BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACNE",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Chondropathy",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Bone hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORNEJO A, KERBLESKI GJ. BLACK BONE DISEASE OF THE FOOT: A TWO-YEAR FOLLOW-UP CASE STUDY. JOURNAL OF FOOT AND ANKLE SURGERY: OFFICIAL PUBLICATION OF THE AMERICAN COLLEGE OF FOOT AND ANKLE SURGEONS 57: 1259-1262, NO. 6, DEC 2018",
"literaturereference_normalized": "black bone disease of the foot a two year follow up case study",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181128",
"receivedate": "20181128",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15665967,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190205"
},
{
"companynumb": "US-ALVOGEN-2018-ALVOGEN-096891",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "63067",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACNE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": [
{
"drugrecuraction": "Bone disorder"
}
],
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Bone disorder",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORNEJO A, KERBLESKI GJ. BLACK BONE DISEASE OF THE FOOT: A TWO?YEAR FOLLOW?UP CASE STUDY. J FOOT ANKLE SURG. 2018 JUL 9. PII: S1067?2516(18)30104?2.",
"literaturereference_normalized": "black bone disease of the foot a two year follow up case study",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180801",
"receivedate": "20180801",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15225636,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "US-TEVA-391680USA",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "063065",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACNE",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Chondropathy",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Bone hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Arthralgia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORNEJO A. BLACK BONE DISEASE OF THE FOOT: A TWO-YEAR FOLLOW-UP CASE STUDY.",
"literaturereference_normalized": "black bone disease of the foot a two year follow up case study",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181128",
"receivedate": "20180123",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14425346,
"safetyreportversion": 4,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190204"
},
{
"companynumb": "US-DRREDDYS-USA/USA/18/0105748",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": "2",
"drugadministrationroute": "048",
"drugauthorizationnumb": "065436",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACNE",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE HYDROCHLORIDE 100 MG"
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Bone hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "3"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORNEJO A, KERBLESKI G. BLACK BONE DISEASE OF THE FOOT: A TWO-YEAR FOLLOW-UP CASE STUDY. THE JOURNAL OF FOOT + ANKLE SURGERY. 2018?57:1259-1262.",
"literaturereference_normalized": "black bone disease of the foot a two year follow up case study",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181211",
"receivedate": "20181211",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15708412,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190205"
},
{
"companynumb": "US-BAUSCH-BL-2015-019354",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACNE",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Bone hyperpigmentation",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CORNEJO A, KERBLESKI G. BLACK BONE DISEASE OF THE FOOT: A TWO?YEAR FOLLOW?UP CASE STUDY. THE JOURNAL OF FOOT AND ANKLE SURGERY. 2018?1?4.",
"literaturereference_normalized": "black bone disease of the foot a two year follow up case study",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180807",
"receivedate": "20180807",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15249741,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
}
] |
{
"abstract": "Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DKA in a patient on an SGLT2 inhibitor and ketogenic diet (KD). A 47-year-old male with a history of poorly controlled T2DM on metformin and empagliflozin presented to the emergency department (ED) with several days of pharyngitis, dyspnea, emesis, abdominal pain, and anorexia. Of note, one month prior to this event, he presented to the ED with malaise and was found to have an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, 3+ ketonuria, and a glucose level of 7 mmol/L (127 mg/dl). Additional workup was negative, and findings were attributed to his KD. His use of empagliflozin was not identified on his medication list. At second presentation, the patient was tachypneic and tachycardic and had mild abdominal tenderness. Labs revealed anion gap 28, bicarbonate 5 mmol/l, pH 6.94, 3+ ketonuria, glucose 14.9 mmol/L (269 mg/dl), and beta-hydroxybutyrate 8.9 mmol/L. The patient was diagnosed with DKA and was treated accordingly. With closure of anion gap, the patient was transitioned to insulin and metformin, and his empagliflozin was discontinued indefinitely. Before prescribing this medication class, physicians should inquire about low-carbohydrate diets given the higher risk for DKA, though knowledge of this risk is still not widespread.",
"affiliations": "Department of Medicine, Larner College of Medicine at the University of Vermont, 111 Colchester Ave, Burlington, VT, USA.;Department of Medicine, Larner College of Medicine at the University of Vermont, 111 Colchester Ave, Burlington, VT, USA.;Department of Medicine, Larner College of Medicine at the University of Vermont, 111 Colchester Ave, Burlington, VT, USA.",
"authors": "Steinmetz-Wood|Samantha|S|https://orcid.org/0000-0002-5718-1397;Gilbert|Matthew|M|https://orcid.org/0000-0003-0267-4327;Menson|Katherine|K|https://orcid.org/0000-0002-3673-7210",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1155/2020/8832833",
"fulltext": "\n==== Front\nCase Rep Endocrinol\nCase Rep Endocrinol\nCRIE\nCase Reports in Endocrinology\n2090-6501 2090-651X Hindawi \n\n10.1155/2020/8832833\nCase Report\nA Case of Diabetic Ketoacidosis in a Patient on an SGLT2 Inhibitor and a Ketogenic Diet: A Critical Trio Not to Be Missed\nhttps://orcid.org/0000-0002-5718-1397Steinmetz-Wood Samantha [email protected] https://orcid.org/0000-0003-0267-4327Gilbert Matthew [email protected] https://orcid.org/0000-0002-3673-7210Menson Katherine [email protected] Department of Medicine, Larner College of Medicine at the University of Vermont, 111 Colchester Ave, Burlington, VT, USA\nAcademic Editor: Lucy Mastrandrea\n\n\n2020 \n13 8 2020 \n2020 883283316 4 2020 24 7 2020 Copyright © 2020 Samantha Steinmetz-Wood et al.2020This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DKA in a patient on an SGLT2 inhibitor and ketogenic diet (KD). A 47-year-old male with a history of poorly controlled T2DM on metformin and empagliflozin presented to the emergency department (ED) with several days of pharyngitis, dyspnea, emesis, abdominal pain, and anorexia. Of note, one month prior to this event, he presented to the ED with malaise and was found to have an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, 3+ ketonuria, and a glucose level of 7 mmol/L (127 mg/dl). Additional workup was negative, and findings were attributed to his KD. His use of empagliflozin was not identified on his medication list. At second presentation, the patient was tachypneic and tachycardic and had mild abdominal tenderness. Labs revealed anion gap 28, bicarbonate 5 mmol/l, pH 6.94, 3+ ketonuria, glucose 14.9 mmol/L (269 mg/dl), and beta-hydroxybutyrate 8.9 mmol/L. The patient was diagnosed with DKA and was treated accordingly. With closure of anion gap, the patient was transitioned to insulin and metformin, and his empagliflozin was discontinued indefinitely. Before prescribing this medication class, physicians should inquire about low-carbohydrate diets given the higher risk for DKA, though knowledge of this risk is still not widespread.\n==== Body\n1. Introduction\nRecent results from major clinical trials such as CANVAS, CREDENCE, EMPA-REG OUTCOME, and DAPA-HF have shown significant cardiovascular and renal protective benefits of SGLT2 inhibitors [1–4]. These findings have led to increased use of this class of medication in patients with type 2 diabetes (T2DM). Although reported as rare, a serious side effect of SGLT2 inhibitors is diabetic ketoacidosis (DKA), which can present more covertly with euglycemic DKA and has been described numerous times. There are some thoughts about patients that might be at greater risk for developing this condition such as longer duration of diabetes, insulin deficiency, or even possible variants of the SGLT molecule [5, 6]. Identification of additional modifiable risk factors such as special diets would be an important step in helping clinicians choose which patients should avoid using this medication. In this case report, we present a case of profound DKA in a patient on an SGLT2 inhibitor on a ketogenic diet.\n\n2. Case Presentation\nA 47-year-old male, with a 10-year history of T2DM, presented to the emergency department (ED) with several days of sore throat, dyspnea, nonbloody emesis, abdominal pain, and poor oral intake. He denied any fever, chills, cough, chest pain, or diarrhea. He had a urinary tract infection (UTI) 2 weeks prior, which had resolved with a course of antibiotics. Over several months, he had made significant changes in his diet which resulted in a 60 lb weight loss. The patient reported that he was following an Atkins or ketogenic diet. In addition to diet control, he had been on metformin and empagliflozin started approximately 5 months ago. His last hemoglobin A1c was 76 mmol/dl (9.1%). Of note, one month prior to this presentation, he presented to the emergency department with weakness, intermittent chest discomfort, and shortness of breath with an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, and 3+ urinary ketones with a glucose level of 7 mmol/L (127 mg/dl). Cardiac workup was negative, lactate was normal, and liver enzymes and D-dimer were within normal limits. The patient was given 1 L fluid bolus with some improvement. Findings were attributed to a keto diet. The patient was discharged with recommendations to increase carbohydrate intake for 2 weeks and repeat electrolytes. His use of empagliflozin was not identified on his medication list in the emergency department nor was it mentioned in the ED notes. His repeat labs one week later did result in closure of his anion gap to 10. When this second presentation to the emergency department 24 days later, he was afebrile, tachypneic with a respiratory rate of 30, and tachycardic with a heart rate of 130 beats per minute, blood pressure was 160/89 mmHg, and SpO2 was 100% on room air. Other than respiratory discomfort, the exam only showed mild abdominal discomfort to palpation. Labs were significant for an anion gap of 28, a pH level of 6.94, with a bicarbonate level of 5 mmol/L, 3+ urinary ketones, a beta-hydroxybutyrate level of 8.9 mmol/L, and a glucose level of 14.9 mmol/L (269 mg/dl), as well as acute kidney injury with a creatinine level of 107 umol/L (1.21 mg/dl). His glutamic acid decarboxylase antibody assay ordered during this admission eventually returned negative. His C-peptide was 0.77 nmol/L (2.3 ng/ml). Cardiac workup was negative. CT scan did reveal possible aspiration pneumonitis. The patient was diagnosed with diabetic ketoacidosis, received several litres of fluid, started on insulin drip, and admitted to the medical ICU. With closure of anion gap, on the following day, the patient was transitioned to insulin basal bolus regimen, and metformin was eventually restarted. His empagliflozin was stopped indefinitely. Hospital course was also complicated by development of a new UTI, and the patient was treated with ceftriaxone/cephalexin. Finally, he was deemed medically stable for discharge with plans to follow up with endocrinology and his primary care provider.\n\n3. Discussion\nOur case illustrates a case of profound DKA of a patient on an SGLT2 inhibitor and following a ketogenic diet. Interestingly, our patient also developed a UTI twice in the same month, which is another reported side effect of this medication. Randomized control trials studying SGLT2 inhibitors have indicated DKA to be a rare side effect, with an estimated incidence rate of DKA varying from 0.13 to 0.76 events per 1000 patient years [6].\n\nOn review of the literature, this is not the first case of DKA in a patient on an SGLT2 inhibitor following a ketogenic or low-carbohydrate diet [7–10]. Another case reports a similar story of a 44-year-old man who had been on sitagliptin, metformin, and an Atkins diet, and 3-4 days after starting canagliflozin, he developed euglycemic DKA which was first missed by the ED and later recognized by his primary internist [10]. As in our case, our patient had already presented with euglycemic DKA to the ED, which was diagnosed as dehydration and starvation ketosis. Luckily, at that time, he recovered by one week with change in diet. Later, he presented with profound dehydration and severe anion gap metabolic acidosis with a bicarbonate level of <5 mEq/L, requiring inpatient critical care. Recognition of the association of this medication with euglycemic DKA and asking about medications is most important.\n\nStudies have measured patients on SGLT2 inhibitors to have low-grade asymptomatic ketonemia [11, 12], and in a Japanese multicenter, randomized, 3-arm parallel comparative study, patients with T2DM assigned to low-carbohydrate diet on luseogliflozin had significantly higher serum ketone bodies than their study counterparts on higher carbohydrate diets [12]. Although ketonemia may be perceived as a negative effect of SGLT2 inhibitors, this seems to be their main mechanism of benefit. SGLT2 inhibitors are thought to act through calorie-restriction mimicry and by a proketogenic effect [13]. This also decreases the insulin to glucagon ratio, thereby improving insulin sensitivity. Ketone bodies are additionally a more efficient source of fuel for cardiac muscle [13].\n\nA Canadian clinical literature review reviewed 46 cases of SGLT2-associated DKA and found that the most common precipitants of DKA were inappropriate insulin reduction or cessation, surgery, excessive alcohol intake, excessive physical exercise, and dietary restriction such as low-carbohydrate or reduced intake [14]. As SGLT2 inhibitors themselves mimic a low-carbohydrate diet and promote ketosis, it follows that the pairing of SGLT2 inhibitors and a ketogenic diet, in addition to stressors, may more easily precipitate a ketoacidotic state.\n\n4. Conclusion\nBefore prescribing this medication class which is now starting to be more widely prescribed, physicians should ask whether patients are following low-carbohydrate diets as this likely puts them at higher risk for DKA. Knowledge of this risk is still not widespread.\n\nConflicts of Interest\nThe authors declare that they have no conflicts of interest.\n==== Refs\n1 Neal B. Perkovic V. Matthews D. R. Canagliflozin and cardiovascular and renal events in type 2 diabetes New England Journal of Medicine 2017 377 21 p. 2099 10.1056/nejmoa1611925 2-s2.0-85023777061 \n2 Perkovic V. Jardine M. J. Neal B. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy New England Journal of Medicine 2019 380 24 2295 2306 10.1056/nejmoa1811744 2-s2.0-85066483412 30990260 \n3 Zinman B. Wanner C. Lachin J. M. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes New England Journal of Medicine 2015 373 22 2117 2128 10.1056/nejmoa1504720 2-s2.0-84944800184 26378978 \n4 McMurray J. J. V. Solomon S. D. Inzucchi S. E. Dapagliflozin in patients with heart failure and reduced ejection fraction New England Journal of Medicine 2019 381 \n5 Finucane F. M. SGLT2 inhibitor-induced euglycaemic diabetic ketoacidosis may be due to abrupt, severe and transient impaired glucose sensing in susceptible individuals with a hitherto unrecognised beta cell SGLT variant Medical Hypotheses 2018 114 11 12 10.1016/j.mehy.2018.02.025 2-s2.0-85042694517 29602453 \n6 Erondu N. Desai M. Ways K. Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program Diabetes Care 2015 38 9 1680 1686 10.2337/dc15-1251 2-s2.0-84962381148 26203064 \n7 Smyth T. Acute illness while on a SGLT2 inhibitor and keto diet Medicine Matters 2018 \n8 Tougaard N. H. Very low carbohydrate diet and SGLT-2-inhibitor: double jeopardy in relation to ketoacidosis BMJ Case Report 2019 12 4 \n9 Hayami T. Kato Y. Kamiya H. Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet Journal of Diabetes Investigation 2015 6 5 587 590 10.1111/jdi.12330 2-s2.0-84940594950 26417418 \n10 Sood M. Euglycemic diabetic ketoacidosis with SGLT2 inhibitor use in a patient on the Atkins diet: a unique presentation of a known side effect American Association of Clinical Endocrinologists Journals 2018 4 2 10.4158/ep171860.cr \n11 Min S. H. Oh T. J. Baek S.-I. Degree of ketonaemia and its association with insulin resistance after dapagliflozin treatment in type 2 diabetes Diabetes & Metabolism 2018 44 1 73 76 10.1016/j.diabet.2017.09.006 2-s2.0-85031894849 29074329 \n12 Yabe D. Iwasaki M. Kuwata H. Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: a randomized, open-label, 3-arm parallel comparative, exploratory study Diabetes, Obesity and Metabolism 2017 19 5 739 743 10.1111/dom.12848 2-s2.0-85013497959 \n13 Kalra S. Jain A. Ved J. Unnikrishnan A. Sodium-glucose cotransporter 2 inhibition and health benefits: the Robin Hood effect Indian Journal of Endocrinology and Metabolism 2016 20 5 725 729 10.4103/2230-8210.183826 2-s2.0-84988566256 27730088 \n14 Goldenberg R. M. Berard L. D. Cheng A. Y. Y. SGLT2 inhibitor-associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis Clinical Therapeutics 2016 38 12 2654 2664 10.1016/j.clinthera.2016.11.002 2-s2.0-85006820094 28003053\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2090-651X",
"issue": "2020()",
"journal": "Case reports in endocrinology",
"keywords": null,
"medline_ta": "Case Rep Endocrinol",
"mesh_terms": null,
"nlm_unique_id": "101576457",
"other_id": null,
"pages": "8832833",
"pmc": null,
"pmid": "32855828",
"pubdate": "2020",
"publication_types": "D002363:Case Reports",
"references": "30895697;27730088;29166232;30954957;26417418;29602453;28003053;29074329;27990776;30990260;26203064;26378978",
"title": "A Case of Diabetic Ketoacidosis in a Patient on an SGLT2 Inhibitor and a Ketogenic Diet: A Critical Trio Not to Be Missed.",
"title_normalized": "a case of diabetic ketoacidosis in a patient on an sglt2 inhibitor and a ketogenic diet a critical trio not to be missed"
}
|
[
{
"companynumb": "US-GLENMARK PHARMACEUTICALS-2020GMK049534",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "EMPAGLIFLOZIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EMPAGLIFLOZIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "078170",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN HYDROCHLORIDE."
}
],
"patientagegroup": null,
"patientonsetage": "47",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Diabetes mellitus inadequate control",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "STEINMETZ?WOOD S, GILBERT M, MENSON K.. A CASE OF DIABETIC KETOACIDOSIS IN A PATIENT ON AN SGLT2 INHIBITOR AND A KETOGENIC DIET: A CRITICAL TRIO NOT TO BE MISSED.. CASE REPORTS IN ENDOCRINOLOGY.. 2020?2",
"literaturereference_normalized": "a case of diabetic ketoacidosis in a patient on an sglt2 inhibitor and a ketogenic diet a critical trio not to be missed",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200916",
"receivedate": "20200916",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18273918,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
}
] |
{
"abstract": "A new class of chemotherapeutic agents, MEK inhibitors, has recently been developed and is proving to be an effective treatment for a number of cancers. A pattern of ocular adverse events has followed these drugs through clinical trials and their association with retinopathy is only just beginning to be recognized. We present two cases of MEK inhibitor-associated retinopathy followed by a review of the current literature on ocular toxicity associated with MEK inhibitors. Patients undergoing treatment with MEK inhibitors appear to have high rates of multifocal serous retinal detachments as well as retinal vein occlusions. We present the first report of cystoid macular edema associated with MEK inhibitor use. The mechanism of these adverse events is still unclear though they seem to be related to oxidative stress and blood retinal barrier breakdown. Management of the ocular toxicity can range from observation to topical treatments or intravitreal injections. Fortunately most ocular adverse events appear to be self-limited and do not require discontinuing the MEK inhibitor. Discontinuation or decreased dosing of MEK inhibitors may be reserved for cases of severe sight-threatening ocular toxicity.",
"affiliations": "Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.;University of Maryland School of Medicine, Baltimore, MD, USA.;Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.",
"authors": "Duncan|K E|KE|;Chang|L Y|LY|;Patronas|M|M|",
"chemical_list": "D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases",
"country": "England",
"delete": false,
"doi": "10.1038/eye.2015.82",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0950-222X",
"issue": "29(8)",
"journal": "Eye (London, England)",
"keywords": null,
"medline_ta": "Eye (Lond)",
"mesh_terms": "D000970:Antineoplastic Agents; D005260:Female; D006801:Humans; D008269:Macular Edema; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases; D047428:Protein Kinase Inhibitors; D012164:Retinal Diseases",
"nlm_unique_id": "8703986",
"other_id": null,
"pages": "1003-12",
"pmc": null,
"pmid": "26043707",
"pubdate": "2015-08",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": "22761467;18390968;15483017;23555064;16009947;12068308;20215549;22663011;17194493;24864047;23248257;20179232;19929595;23584575;24852144;12697856;19424603;22805292;24840079;23587417;22805291;22649132",
"title": "MEK inhibitors: a new class of chemotherapeutic agents with ocular toxicity.",
"title_normalized": "mek inhibitors a new class of chemotherapeutic agents with ocular toxicity"
}
|
[
{
"companynumb": "US-GLAXOSMITHKLINE INC.-US2015GSK131278",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMETINIB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "204114",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMETINIB"
}
],
"patientagegroup": null,
"patientonsetage": "58",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cystoid macular oedema",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Vision blurred",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DUNCAN KE, CHANG LY, PATRONAS M. MEK INHIBITORS: A NEW CLASS OF CHEMOTHERAPEUTIC AGENTS WITH OCULAR TOXICITY. EYE. 2015;29:1003-1012",
"literaturereference_normalized": "mek inhibitors a new class of chemotherapeutic agents with ocular toxicity",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20150917",
"receivedate": "20150917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11518656,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20151125"
},
{
"companynumb": "US-GLAXOSMITHKLINE-US2015GSK140989",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMETINIB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "204114",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "METASTATIC MALIGNANT MELANOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAMETINIB"
}
],
"patientagegroup": null,
"patientonsetage": "58",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cystoid macular oedema",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Vision blurred",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DUNCAN KE, CHANG LY, PATRONAS M.. MEK INHIBITORS: A NEW CLASS OF CHEMOTHERAPEUTIC AGENTS WITH OCULAR TOXICITY. EYE. 2015?29:1003-1012",
"literaturereference_normalized": "mek inhibitors a new class of chemotherapeutic agents with ocular toxicity",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20151005",
"receivedate": "20151005",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11593691,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160304"
},
{
"companynumb": "PHHY2015US130641",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRAMETINIB DIMETHYL SULFOXIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "204114",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "METASTATIC MALIGNANT MELANOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MEKINIST"
}
],
"patientagegroup": null,
"patientonsetage": "58",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Vision blurred",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Cystoid macular oedema",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DUNCAN KE, CHANG LY, PATRONAS M. MEK INHIBITORS: A NEW CLASS OF CHEMOTHERAPEUTIC AGENTS WITH OCULAR TOXICITY. EYE. 2015?29:1003-12",
"literaturereference_normalized": "mek inhibitors a new class of chemotherapeutic agents with ocular toxicity",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180423",
"receivedate": "20180423",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14794233,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
}
] |
{
"abstract": "Purpura fulminans (PF) is a rare, life-threatening disorder characterized by disseminated intravascular coagulation (DIC), circulatory collapse, and hemorrhagic cutaneous purpura. It typically occurs secondary to acute infections, usually meningococcal septicemia, although there are also congenital and acquired causes. We report a case of a 56-year old female who presented to our institution with clinical signs of PF in the setting of acetaminophen overdose and Klebsiella pneumoniae sepsis. Given the rarity of the disease, we also review cases of PF in similar clinical scenarios that have been described in the literature.",
"affiliations": "Department of Medicine, Division of Nephrology, Saint Louis University School of Medicine, Saint Louis, USA.;Department of Medicine, Division of Nephrology, Saint Louis University School of Medicine, Saint Louis, USA.;Department of Medicine, Division of Nephrology, Saint Louis University School of Medicine, Saint Louis, USA.",
"authors": "Nguyen|Vincent|V|;Myint|Janine A|JA|;Philipneri|Marie|M|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.7759/cureus.11633",
"fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184 Cureus Palo Alto (CA) \n\n10.7759/cureus.11633\nDermatology\nInternal Medicine\nHematology\nPurpura Fulminans in the Setting of Klebsiella Pneumoniae Bacteremia and Acetaminophen Overdose\nMuacevic Alexander Adler John R Nguyen Vincent 1 Myint Janine A 1 Philipneri Marie 1 \n1 \nDepartment of Medicine, Division of Nephrology, Saint Louis University School of Medicine, Saint Louis, USA \n\nMarie Philipneri [email protected]\n22 11 2020 \n11 2020 \n12 11 e1163322 11 2020 Copyright © 2020, Nguyen et al.2020Nguyen et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/44316-purpura-fulminans-in-the-setting-of-klebsiella-pneumoniae-bacteremia-and-acetaminophen-overdosePurpura fulminans (PF) is a rare, life-threatening disorder characterized by disseminated intravascular coagulation (DIC), circulatory collapse, and hemorrhagic cutaneous purpura. It typically occurs secondary to acute infections, usually meningococcal septicemia, although there are also congenital and acquired causes. We report a case of a 56-year old female who presented to our institution with clinical signs of PF in the setting of acetaminophen overdose and Klebsiella pneumoniae sepsis. Given the rarity of the disease, we also review cases of PF in similar clinical scenarios that have been described in the literature.\n\npurpura fulminansacute infectious purpura fulminansdisseminated intravascular coagulationklebsiella pneumoniaeacetaminophen toxicityThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\nPurpura fulminans (PF) is a rare, life-threatening disorder with a mortality rate of up to 60% [1, 2]. It is characterized by disseminated intravascular coagulation (DIC), circulatory collapse, and dermal vascular thrombosis that results in hemorrhagic cutaneous purpura in the trunk and limbs [1, 3-6]. PF is typically seen in three clinical settings; inherited or acquired coagulation disorder, acute infection, or idiopathic [3, 7]. Most commonly, it is seen in children and is due to endotoxin-production from meningococcal disease [1, 3].\n\nCutaneous manifestations of PF include widespread ecchymoses, hemorrhagic bullae, and epidermal necrosis [6]. Patients initially present with erythema and petechiae that evolve into ecchymoses and purpuric plaques. With time, there is symmetric gangrene of distal extremities that extend proximally [4, 8]. Histopathology reveals dermal vascular thrombosis with the presence of microthrombi in the dermal blood vessels [1, 4, 8].\n\nBecause of the high mortality rate, it is imperative that timely diagnosis and treatment of PF are undertaken. It is also important to point out atypical presentations, such as PF in adults, and potential causes other than meningococcal disease or coagulation disorder. \n\nIn our case report, we present a case of PF in the setting of Klebsiella pneumoniae and acetaminophen toxicity. \n\nCase presentation\nA 56-year-old female with a past medical history significant for depression, gastric cancer status post partial gastrectomy, and nonalcoholic steatohepatitis (NASH) presented as a transfer from an outside hospital for acute liver failure, concerning for acetaminophen overdose. She was noted to have altered mental status with laboratory studies revealing transaminitis and elevated acetaminophen level indicating “possible hepatic toxicity” per the Rumack-Matthew nomogram. She was admitted to the intensive care unit (ICU) with shock and multi-organ failure requiring vasopressors and mechanical ventilation. N-acetylcysteine (NAC) was administered for possible acetaminophen overdose, followed by Continuous Renal Replacement Therapy (CRRT) for worsening metabolic panel due to acute kidney injury. Physical examination was significant for cold bilateral distal extremities and skin mottling in the upper and lower extremities which progressed to involve the majority of the body over the course of several hours. Computerized tomography (CT) scans of chest, abdomen, and pelvis were notable for bilateral lower lobe lung consolidations with scattered ground-glass opacities, hepatomegaly, bowel wall thickening, and cortical necrosis in both kidneys. Blood cultures were positive for Klebsiella pneumoniae and she was started on meropenem and vancomycin. Laboratory tests revealed anemia, thrombocytopenia, elevated PT/PTT, elevated d-dimer, and low fibrinogen concerning for DIC. Skin mottling continued to worsen, later developing bullae over the bilateral anterior thighs. Dermatology was consulted and noted retiform purpura involving bilateral thighs, legs, feet, arms, hands, the tip of the nose, upper ear, and lower abdomen (Figure 1). Gangrenous changes were observed over the fingers and nails on both hands. Left upper arm biopsy demonstrated epidermal necrosis with extravasated red blood cells and scattered microthrombi in the papillary dermis. She was started on therapeutic heparin at this time although this was later discontinued. Plastic Surgery and Interventional Radiology were later consulted for management of gangrenous hands, but the decision was made to allow the necrotic areas to declare with no acute intervention (Figure 2). Thrombophilia and autoimmune evaluation were remarkable for positive lupus anticoagulant and decreased protein C and S activity, albeit she was receiving therapeutic heparin at this time. After initiation of antibiotics, she continued to improve and was stepped down from ICU to floor with wound care. Some return of blood flow to the proximal part of her hands was noted and she was discharged to a Long-term Acute Care (LTAC) facility. She was readmitted to the hospital less than a month later for right elbow disarticulation and left-hand amputation for progression of dry gangrene to wet gangrene. \n\nFigure 1 Early presentation of cutaneous findings. a,b. Retiform purpura on right arm with gangrenous changes in nails. c,d,e. Bullae on bilateral thighs and purpura extending down to toes. f. Purpura on the tip of the nose.\nFigure 2 Late presentation of cutaneous findings. a. Dry gangrene of the right forearm/hand. b. Dry gangrene of the left hand. c. Gangrenous changes to the legs and distal toes bilaterally.\nDiscussion\nWe describe a case of rapidly progressive retiform purpura in a patient who was found to have Klebsiella pneumoniae bacteremia. Two additional differential diagnoses were considered at the time of presentation; vasopressor-induced necrosis and vasculitis. Vasopressor-induced necrosis was a consideration given her gangrenous hands, although unlikely because of the hemorrhagic bullae formation in early presentation, rapid spread to her proximal extremities, and laboratory findings suggestive of DIC. Vasculitis was also considered but less likely given the unremarkable autoimmune workup. She did have a positive lupus anticoagulant, but according to Colling and Bendapudi, lupus anticoagulant can be positive at the time of presentation in patients with PF [1].\n\nSeveral studies have noted that laboratory findings associated with PF include prolonged coagulation times, decreased fibrinogen, elevated d-dimer, abnormalities in protein C function, and thrombocytopenia [1, 5]. As for skin biopsy, the presence of microthrombi in dermal blood vessels is typical [1, 4, 5]. In our patient, DIC, decreased protein C and S activity, skin biopsy findings, and clinical improvement after antibiotic initiation made PF secondary to Klebsiella pneumoniae sepsis the most likely diagnosis. There have been a few case reports of PF in the setting of Klebsiella species infection (Table 1). In one case report of PF caused by Klebsiella pneumoniae, there was also involvement of the nose as seen in our patient, which was deemed an unusual location of PF manifestation. \n\nTable 1 Literature review of cases of PF from Klebsiella or Acetaminophen\nPF: Purpura fulminans\n\nAuthor\tAge at diagnosis\tLikely Cause(s)\tManagement\tOutcomes (including complications)\t\nTsubouchi et al. (2019) [9]\t75-year old woman\tKlebsiella Oxytoca\tIntensive care\tDeath\t\nDisse et al. (2018) [2]\t17-day old neonate\tKlebsiella Oxytoca sepsis from central venous catheter\tBroad-spectrum antibiotics, ventilation, diuretics, protein C substitution, burn protocol \tLimbs successfully preserved with scarring\t\nSingh and Kampani (2018) [7]\t19-year old female\tKlebsiella Pneumoniae\tIV fluids, broad-spectrum antibiotics, platelets\tUnknown\t\nUmar (2018) [10]\t2-month old boy\tKlebsiella Pneumoniae\tCeftriaxone, blood transfusions, FFP considered\tParents left against medical advice (AMA)\t\nGuccione et al. (1993) [8]\t32-year old woman\tAcetaminophen and Alcohol toxicity\tHeparin, Vitamin K, Cefuroxime\tResolution of Purpuric Lesions\t\nThis presentation is most consistent with acute infectious PF. Several researchers have noted that during infection, bacterial endotoxins induce coagulation secondary to consumption of protein C and S [5]. This results in an acquired hypercoagulable state that leads to thromboses in dermal vessels, DIC, and hemorrhagic skin necrosis. \n\nOur patient also had signs of concomitant acetaminophen toxicity that may have contributed to the development of PF. Although her transaminitis was not very high to suggest acute liver failure, the acetaminophen-induced liver injury may have led to further decline in protein C and S function. Guccione et al. published a report of PF with acquired protein C and S deficiency induced by alcohol and acetaminophen [8]. They speculated that the reduction in hepatic glutathione caused by acetaminophen toxicity led to the impairment of anticoagulation proteins synthesis, resulting in the activation of the DIC cascade and Purpura Fulminans [8].\n\nIn acute infectious PF, the treatment is to address the underlying cause with antibiotic therapy in addition to supportive care. Currently, there is no consensus on the treatment of PF. A few treatments that have been utilized include broad-spectrum antibiotics, anticoagulation, protein C, platelets, and FFP [1, 2, 5-8]. There may be a role for protein C replacement as seen in a small study where all patients survived despite high predicted mortality [11]. The RESOLVE study found that the use of protein C in the treatment of severe sepsis in children resulted in no significant improvement in organ failure or 28-day mortality but increased intracranial hemorrhage. Although this study did not analyze the use of protein C in PF specifically, there is enough overlap to suggest that protein C should be used with caution [5]. \n\nConclusions\nPurpura fulminans is a rare, yet life-threatening condition that can result in DIC, hemodynamic collapse, and hemorrhagic cutaneous necrosis. PF is mostly seen in children in the setting of meningococcus bacteremia. Diagnostic delay can lead to major adverse clinical consequences to the patient, such as amputation of limbs and death. Our case presents a unique example of an adult with signs and symptoms of Purpura Fulminans in the setting of Klebsiella pneumoniae bacteremia and Acetaminophen toxicity. This case emphasizes the importance of considering Purpura fulminans in adults with acquired protein C and S deficiency states, including certain bacterial infections and compromised liver function.\n\nThe authors have declared that no competing interests exist.\n\nHuman Ethics\nConsent was obtained by all participants in this study\n==== Refs\nReferences\n1 Purpura fulminans: mechanism and management of dysregulated hemostasis Transfus Med Rev Colling ME Bendapudi PK 69 76 32 2018 29157918 \n2 Sepsis-associated purpura fulminans due to klebsiella oxytoca Dtsch Arztebl Int Disse SC Meyer S Baghai-Arassi A 784 115 2018 \n3 Uncommon location of purpura fulminans: case report and literature review Case Rep Dermatol Alsharif SH Al-Omair A Andijani F 5 11 12 2020 32095125 \n4 Acute purpura fulminans - a rare cause of skin necrosis: a single institution clinicopathological experience J Cutan Pathol Brozyna JR Sardiña LA Sharma A Theil K Bergfeld W 2020 \n5 Purpura fulminans: recognition, diagnosis and management Arch Dis Child Chalmers E Cooper P Forman K 1066 1071 96 2011 21233082 \n6 Adult purpura fulminans associated with non-steroidal anti-inflammatory drug use J Postgrad Med Kosaraju N Korrapati V Thomas A 145 146 57 2011 21654144 \n7 Acute infectious purpura fulminans due to klebsiella pneumoniae Journal of Medical Science And Clinical Research Singh P Kampani G 6 2018 \n8 Acquired purpura fulminans induced by alcohol and acetaminophen. Successful treatment with heparin and vitamin K Arch Dermatol Guccione JL Zemtsov A Cobos E 1267 1269 129 1993 8215490 \n9 Acute infectious purpura fulminans caused by klebsiella oxytoca Intern Med Tsubouchi N Tsurukiri J Numata J Sano H 1801 1802 58 2019 30713331 \n10 Purpura fulminans with disseminated intravascular coagulopathy and symmetric peripheral gangrene complicating sepsis in an infant: a case report Ann Med Health Sci Res Umar LW Ya’uba MS Olorukooba AA Abubakar Y Mohammed AJ Chom ND 69 72 7 2017 https://www.ajol.info/index.php/amhsr/article/view/158633 \n11 Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans Lancet Smith OP White B Vaughan D Rafferty M Claffey L Lyons B Casey W 1590 1593 350 1997 9393338\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2168-8184",
"issue": "12(11)",
"journal": "Cureus",
"keywords": "acetaminophen toxicity; acute infectious purpura fulminans; disseminated intravascular coagulation; klebsiella pneumoniae; purpura fulminans",
"medline_ta": "Cureus",
"mesh_terms": null,
"nlm_unique_id": "101596737",
"other_id": null,
"pages": "e11633",
"pmc": null,
"pmid": "33376646",
"pubdate": "2020-11-22",
"publication_types": "D002363:Case Reports",
"references": "21233082;9393338;30713331;32356378;32095125;8215490;29157918;21654144;30602411",
"title": "Purpura Fulminans in the Setting of Klebsiella Pneumoniae Bacteremia and Acetaminophen Overdose.",
"title_normalized": "purpura fulminans in the setting of klebsiella pneumoniae bacteremia and acetaminophen overdose"
}
|
[
{
"companynumb": "US-LEUCADIA PHARMACEUTICALS-2021LEU000001",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "202605",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETAMINOPHEN."
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Purpura fulminans",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug-induced liver injury",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NGUYEN V, MYINT JA, PHILLIPNERI M. PURPURA FULMINANS IN THE SETTING OF KLEBSIELLA PNEUMONIAE BACTEREMIA AND ACETAMINOPHEN OVERDOSE. CUREUS. 2020?12(11):E11633",
"literaturereference_normalized": "purpura fulminans in the setting of klebsiella pneumoniae bacteremia and acetaminophen overdose",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210114",
"receivedate": "20210114",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18743569,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20210419"
},
{
"companynumb": "US-GLAXOSMITHKLINE-US2021GSK001708",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETAMINOPHEN."
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatotoxicity",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Livedo reticularis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Gastrointestinal wall thickening",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Bullous haemorrhagic dermatosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Hypercoagulation",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Acute hepatic failure",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Mental status changes",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Transaminases increased",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Shock",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Disseminated intravascular coagulation",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Epidermal necrosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Purpura fulminans",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Dry gangrene",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Purpura",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Lung consolidation",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Lung opacity",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Renal cortical necrosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Drug level increased",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Klebsiella bacteraemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Anaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Peripheral coldness",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Hepatomegaly",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Extravasation blood",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Gangrene",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NGUYEN V, MYINT JA, PHILIPNERI M. PURPURA FULMINANS IN THE SETTING OF KLEBSIELLA PNEUMONIAE BACTEREMIA AND ACETAMINOPHEN OVERDOSE. CUREUS. 2020?12 (11):E11633",
"literaturereference_normalized": "purpura fulminans in the setting of klebsiella pneumoniae bacteremia and acetaminophen overdose",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210115",
"receivedate": "20210115",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18745053,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20210419"
}
] |
{
"abstract": "Hairy cell leukaemia (HCL) is an uncommon, low-grade B-cell lymphoproliferative disorder. HCL-variant describes an entity of HCL that is important from the point of view of requiring differential diagnosis from HCL, and for requiring careful consideration of the treatment approach. HCL-variant differs from the classic form with respect to the lack of monocytopaenia, its elevated WBC and unique morphology and immunophenotype. Indeed, there is currently no adequate standard treatment for this condition - HCL-variant is generally resistant to interferon-alpha, and complete remission is rarely achieved with either pentostatin or cladribine. We report a 57-year-old female patient who presented at our institution in November 2004 with high white blood counts and splenomegaly. Based on her blood morphology, bone marrow and spleen histology, immunophenotype and clinical characteristics, the patient was diagnosed as having HCL-variant, with blastoid variant transformation. The patient had advanced-stage disease. She was initially treated with spleenctomy, which resulted in short-term normalization of blood counts. One month later the blood counts deteriorated, she developed peripheral and abdominal lymphadenopathy and had poor performance status. One cycle of cladribine combined with rituximab was immediately administered. We started with rituximab 375 mg/m(2), which resulted in a remarkable recovery of blood counts, followed by cladribine 0.1 mg/kg for 7 days. However, the patient's general condition worsened, and she subsequently died from heart failure. Our experience from this case suggests that rituximab is a promising therapy for patients with HCL-variant, particularly when combined with cladribine. However, further clinical study is required before rituximab can be considered as a front-line therapy for this form of malignancy.",
"affiliations": "Haematology Department, Clinical Centre, Skopje, Republic of Macedonia. [email protected]",
"authors": "Hadzi-Pecova|Liljana|L|;Stojanovik|A|A|;Petrusevska|G|G|;Panovska|I|I|",
"chemical_list": "D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D017338:Cladribine; D000069283:Rituximab",
"country": "Germany",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0351-3254",
"issue": "29(2)",
"journal": "Prilozi",
"keywords": null,
"medline_ta": "Prilozi",
"mesh_terms": "D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D017338:Cladribine; D005260:Female; D006801:Humans; D007943:Leukemia, Hairy Cell; D008875:Middle Aged; D000069283:Rituximab",
"nlm_unique_id": "101189513",
"other_id": null,
"pages": "355-60",
"pmc": null,
"pmid": "19259059",
"pubdate": "2008-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Rituximab in the treatment of the variant of hairy cell leukaemia: a case report.",
"title_normalized": "rituximab in the treatment of the variant of hairy cell leukaemia a case report"
}
|
[
{
"companynumb": "US-ROCHE-1274661",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "103705",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INFUSION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HAIRY CELL LEUKAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "375",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLADRIBINE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INFUSION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".1",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLADRIBINE."
}
],
"patientagegroup": null,
"patientonsetage": "57",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cardiac failure",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": ", STOJANOVIK A, PETRUSEVSKA G AND PANOVSKA I. RITUXIMAB IN THE TREATMENT OF THE VARIANT OF HAIRY CELL LEUKAEMIA: A CASE REPORT.. PRILOZI 2008 JAN 01;29:355-360.",
"literaturereference_normalized": "rituximab in the treatment of the variant of hairy cell leukaemia a case report",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170907",
"receivedate": "20170907",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13944456,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20171128"
}
] |
{
"abstract": "Dofetilide is a class III antiarrhythmic used for treating atrial dysrhythmias. Though its adverse effects are well described in routine use, very little is known about dofetilide toxicity in overdose. This is a retrospective case series of consecutive patients reported to our poison center after dofetilide overdose. Twenty-seven cases were included. Seventeen patients were treated at a healthcare facility, and of these, eight were admitted. Twenty-one patients took one extra capsule, four took someone else's medication, one took three extra capsules, and one had a large intentional overdose. Ten patients had co-ingestants reported, including three QT-prolonging agents. No one required cardioversion, defibrillation, CPR, or overdrive pacing. The patient who reported taking 90 times his usual dose in suicide attempt was the only patient to have significant clinical effects. He experienced an 8-beat run of non-sustained ventricular tachycardia, frequent multifocal PVCs, and ventricular bigeminy. He received magnesium sulfate and potassium chloride supplementation. In this series, unintentional small overdoses did not result in significant clinical effects and were often managed successfully at home, despite the fact that information showing a single capsule can cause torsades. This study is limited by its small sample size, retrospective design, and reliance on incomplete information.",
"affiliations": "Division of Clinical Toxicology, Department of Emergency Medicine, VCU Medical Center, 1250 E. Marshall Street, 2nd Floor, Richmond, VA, 23298, USA. [email protected].;Division of Clinical Toxicology, Department of Emergency Medicine, VCU Medical Center, 1250 E. Marshall Street, 2nd Floor, Richmond, VA, 23298, USA.;Department of Emergency Medicine, VCU Medical Center, Richmond, VA, 23298, USA.;Department of Emergency Medicine, VCU Medical Center, Richmond, VA, 23298, USA.;Division of Clinical Toxicology, Department of Emergency Medicine, VCU Medical Center, 1250 E. Marshall Street, 2nd Floor, Richmond, VA, 23298, USA.",
"authors": "Hieger|M A|MA|;Maskell|K F|KF|;Moss|M J|MJ|;Powell|S W|SW|;Cumpston|K L|KL|",
"chemical_list": "D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide",
"country": "United States",
"delete": false,
"doi": "10.1007/s12012-016-9384-9",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1530-7905",
"issue": "17(3)",
"journal": "Cardiovascular toxicology",
"keywords": "Antiarrhythmic; Dofetilide; Dysrhythmia; Overdose; Poison center; QTc prolongation; Tikosyn; Torsades; Ventricular tachycardia",
"medline_ta": "Cardiovasc Toxicol",
"mesh_terms": "D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents; D015331:Cohort Studies; D062787:Drug Overdose; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines; D011039:Poison Control Centers; D012189:Retrospective Studies; D013223:Statistics as Topic; D013406:Suicide, Attempted; D013449:Sulfonamides",
"nlm_unique_id": "101135818",
"other_id": null,
"pages": "368-371",
"pmc": null,
"pmid": "27565970",
"pubdate": "2017-07",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Dofetilide in Overdose: A Case Series from Poison Center Data.",
"title_normalized": "dofetilide in overdose a case series from poison center data"
}
|
[
{
"companynumb": "US-PFIZER INC-2017289443",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOFETILIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "020931",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "22500 UG, UNK (AT ONE TIME)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "22500",
"drugstructuredosageunit": "004",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOFETILIDE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Suicide attempt",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Intentional overdose",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Arrhythmia",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HIEGER, M.. DOFETILIDE IN OVERDOSE: A CASE SERIES FROM POISON CENTER DATA. CARDIOVASCULAR TOXICOLOGY. 2017;17(3):368-371",
"literaturereference_normalized": "dofetilide in overdose a case series from poison center data",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170707",
"receivedate": "20170707",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13729308,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "US-SIGMAPHARM LABORATORIES, LLC-2018SIG00014",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOFETILIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207746",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "250 ?G, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "004",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOFETILIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOFETILIDE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "207746",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "22500 ?G, ONCE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "22500",
"drugstructuredosageunit": "004",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOFETILIDE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Intentional overdose",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Ventricular extrasystoles",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Ventricular tachycardia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Suicide attempt",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HIEGER MA, MASKELL KF, MOSS MJ, POWELL SW, CUMPSTON KL. DOFETILIDE IN OVERDOSE: A CASE SERIES FROM POISON CENTER DATA. CARDIOVASC TOXICOL (DOI: 10.1007/S12012-016-9384-9). 2017?17:368-371",
"literaturereference_normalized": "dofetilide in overdose a case series from poison center data",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180501",
"receivedate": "20180501",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14832889,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20180711"
},
{
"companynumb": "US-MAYNE PHARMA INC.-2016MYN000665",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOFETILIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "207058",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "22500 MCG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUICIDE ATTEMPT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOFETILIDE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Intentional overdose",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Ventricular extrasystoles",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Ventricular tachycardia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Suicide attempt",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HIEGER MA, ET AL.. DOFETILIDE IN OVERDOSE: A CASE SERIES FROM POISON CENTER DATA. REACTIONS WEEKLY. 2016;1618:76",
"literaturereference_normalized": "dofetilide in overdose a case series from poison center data",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20161014",
"receivedate": "20161014",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12850930,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170207"
}
] |
{
"abstract": "Femoral fractures in pregnancy are a rare complication, with an incidence of approximately 1%. Case reports and small trials leave perioperative obstetric management and route of delivery largely unclear. Three cases of femoral fracture are presented that occurred at 24, 30, and 31 weeks of gestation. The causes of femoral fracture were gunshot, motor vehicle collision, and fragility fracture. All fractures were surgically repaired, 1 utilizing neuraxial anesthesia and the others with general anesthesia. A 30-day postoperative course of low-molecular-weight heparin was prescribed, and all patients subsequently had vaginal deliveries. Femoral fractures in the viable pregnancy confer high maternal and fetal morbidity and mortality. Intraoperative fetal monitoring and postoperative anticoagulation should be considered, and vaginal delivery should not be contraindicated.",
"affiliations": "Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.;Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.;Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA.",
"authors": "Harold|Justin A|JA|;Isaacson|Erin|E|;Palatnik|Anna|A|",
"chemical_list": null,
"country": "New Zealand",
"delete": false,
"doi": "10.2147/IJWH.S198345",
"fulltext": "\n==== Front\nInt J Womens HealthInt J Womens HealthIJWHintjwhInternational Journal of Women's Health1179-1411Dove 19834510.2147/IJWH.S198345Case SeriesFemoral fracture in pregnancy: a case series and review of clinical management Harold et alHarold et alHarold Justin A 1Isaacson Erin 1Palatnik Anna 11 Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USACorrespondence: Anna PalatnikDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI53226, USATel +1 414 805 6600Fax +1 414 805 6622Email [email protected] 4 2019 2019 11 267 271 30 12 2018 16 3 2019 © 2019 Harold et al.2019Harold et al.This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).Abstract\nFemoral fractures in pregnancy are a rare complication, with an incidence of approximately 1%. Case reports and small trials leave perioperative obstetric management and route of delivery largely unclear. Three cases of femoral fracture are presented that occurred at 24, 30, and 31 weeks of gestation. The causes of femoral fracture were gunshot, motor vehicle collision, and fragility fracture. All fractures were surgically repaired, 1 utilizing neuraxial anesthesia and the others with general anesthesia. A 30-day postoperative course of low-molecular-weight heparin was prescribed, and all patients subsequently had vaginal deliveries. Femoral fractures in the viable pregnancy confer high maternal and fetal morbidity and mortality. Intraoperative fetal monitoring and postoperative anticoagulation should be considered, and vaginal delivery should not be contraindicated.\n\nKeywords\nfemoral fractureantepartum testingtrauma in pregnancyvenous thromboembolism preventionosteoporosis in pregnancy\n==== Body\nIntroduction\nOrthopedic injury in pregnancy, though rare, is associated with significant morbidity and mortality to the mother and fetus.1 Some reports estimate that the risk of intrauterine fetal demise (IUFD) is as high as 40.1%, depending on the location of the fracture. Pelvic and acetabular fractures convey the highest morbidity and mortality.2–4 We present three cases of femoral fracture that occurred at our institution over a period of 2 years and discuss teaching points of perioperative obstetric management, postoperative venous thromboembolism (VTE) prophylaxis, and route of delivery. Local institutional review board approval was not required for this case series. Written consent was obtained from each patient to publish the case details.\n\nCases\nPatient 1: A 31-year-old gravida 5 para 4 woman at 24 weeks and 4 days of gestation presented to the emergency department after having suffered 5 gunshot wounds to her bilateral lower extremities. On admission, her Glasgow Coma Scale Score was 15 and she was hemodynamically stable. Plain film radiography of the pelvis and left femur was performed. There was a comminuted, segmented, displaced fracture of the left mid-femoral diaphysis with multiple osseous and metallic fragments as well as a nearby dominant bullet fragment (Figure 1A). There were no additional injuries. Her obstetric history consisted of four previous pregnancies with uncomplicated term spontaneous vaginal deliveries. The patient reported no additional medical problems or prior surgical history. Laboratory evaluation was significant for a low serum calcium level of 8.2 mg/dL.Figure 1 (A) Comminuted, segmented, displaced fracture with nearby dominant bullet fragment. (B) Basicervical femoral neck fracture. (C) Mildly comminuted and displaced femoral shaft fracture with foreshortening.\n\n\n\nThe patient underwent retrograde intramedullary nailing under general endotracheal anesthesia. Intraoperative fetal monitoring demonstrated moderate variability with occasional shallow variable decelerations. The total radiation dosage both preoperatively and intraoperatively was 20.1 milligray (mGy). A lead apron was used to shield the maternal abdomen during all images required pre- and- intraoperatively. In the postoperative care unit, uterine tocometry showed contractions every 3–5 mins that the patient stated were non-painful. Cervical examination was performed due to continued non-painful contractions, and her cervix was closed. She was transferred to labor and delivery for the remainder of her postoperative care.\n\nThe patient received betamethasone and magnesium postoperatively due to concern for possible preterm delivery due to initially non-reassuring fetal heart tones. With intrauterine resuscitation, delivery was not required and contractions spaced out. The patient was started on 5,000 units of heparin three times daily for VTE prophylaxis. Physical therapy was initiated while inpatient. She was discharged on postoperative day five with a 30-day supply of 30 mg twice daily low-molecular-weight heparin (LMWH) after ambulating with a walker and had a spontaneous vaginal delivery at term.\n\nPatient 2: A 34-year-old gravida 8 para 6 woman at 30 weeks of gestation presented to the emergency department with 3 weeks of severe hip pain after stepping off a curb. Plain film radiography demonstrated a minimally displaced right basicervical femoral neck fracture (Figure 1B). Her obstetric history included six preterm deliveries and an ectopic pregnancy treated surgically with a laparoscopic salpingectomy. She had inconsistently received intramuscular 17-hydroxyprogesterone injections during her pregnancy for prevention of preterm delivery. She had a past medical history of hypothyroidism, methadone dependence (185 mg daily since 21 weeks of gestation), and a 20-pack-year smoking history. She was smoking ½ pack of cigarettes per day throughout her pregnancy. Laboratory evaluation was remarkable for a low serum calcium (8.1 mg/dL) with a low serum albumin of 2.7 g/dL and a low serum 25-hydroxy vitamin (7.1 ng/mL).\n\nThe patient underwent an uncomplicated femoral neck pinning on the day of admission utilizing a 0.5% bupivacaine spinal anesthetic. Total preoperative and intraoperative radiation exposure was 9.6 mGy. Similar to the first case, a lead apron was used to shield the maternal abdomen during all images required pre-and- intraoperatively. Subcutaneous LMWH 30 mg twice daily was started postoperatively for VTE prophylaxis. She was transferred to labor and delivery for recovery and there were no postoperative complications. Both vitamin D and calcium were orally supplemented, physical therapy was initiated while inpatient, and antenatal fetal monitoring was conducted and was reassuring. The patient was ambulatory with the assistance of a walker and discharged to home on postoperative day 2. She subsequently presented to labor and delivery at 35 weeks and 5 days of gestation in preterm labor and had a vaginal delivery of a viable female fetus followed by an uneventful postpartum course.\n\nPatient 3: A 24-year-old gravida 6 para 4 female at 31 weeks of gestation presented to the emergency department as a belted passenger in a 45-mph motor vehicle collision. Her pregnancy had been complicated by anemia and obesity. Plain film radiography demonstrated a mildly comminuted and displaced right femoral shaft fracture with foreshortening (Figure 1C). Her obstetric history included four previous full-term spontaneous vaginal deliveries and one elective abortion. She had no other significant past medical history. Laboratory evaluation was remarkable for a white blood cell count of 20.7×103/μL and hemoglobin of 9.1 g/dL, with a normal calcium level of 8.6 mg/dL. She was transferred to labor and delivery where fetal monitoring was reassuring. Uterine tocometry showed contractions every 2–10 mins and the decision was made to give a 12 mg dose of intramuscular betamethasone for fetal lung maturity prior to surgical intervention.\n\nOn hospital day 1, the patient underwent an uncomplicated anterograde rod insertion of her right femur under general endotracheal anesthesia. Fetal monitoring before and during surgery was reassuring. Total preoperative and intraoperative radiation dosage was 135.2 mGy and a lead apron was used to shield the maternal abdomen during all images. The patient was started on 30 mg twice daily enoxaparin sodium for VTE prophylaxis, physical therapy as well as oral cholecalciferol and calcium acetate for daily supplementation. Throughout her postoperative course, the patient was not meeting ambulation goals necessary for discharge and on postoperative day 5, she was diagnosed with preterm premature rupture of membranes. Azithromycin and amoxicillin were started as latency antibiotics. On postoperative day 7, the patient complained of increasing pain and pressure, the cervix was found to be fully dilated, and she vaginally delivered a live born male fetus at 32 weeks and 1-day gestation from the breech presentation. The patient had an unremarkable postpartum course and after ambulating with a walker was discharged home on postpartum day 2.\n\nDiscussion\nOrthopedic injury in pregnancy is an uncommon event, with most sources citing an incidence of 1–6%.3,4 Though rare, it is established that both the maternal and fetal morbidity and mortality are high, with some estimates of IUFD as high as 40.1% in patients with pelvic ring fractures.5 There have been case reports detailing the orthopedic operative management of acetabular and femoral fractures in pregnancy, but obstetric management before, during, and after these procedures is unclear. Literature on this topic is limited to one report of an acetabular fracture repaired in a viable pregnancy and a retrospective case series of 8 patients with gestational ages ranging from 5–26 weeks gestation at the time of surgery.6,7 Here we review obstetric peri-operative management of three cases of femoral fracture complicating second and third trimester pregnancies in a single university hospital, where a multi-disciplinary approach was implemented to mitigate the high morbidity associated with maternal femoral fractures in pregnancy.\n\nThe multidisciplinary approach in all three cases included the following teams: maternal-fetal medicine, orthopedics, anesthesiology, and neonatology After diagnosis of a long-bone fracture, maternal stabilization, and the need for operative intervention is decided, the appropriate anesthetic was determined. The patients we described were managed with different anesthetic techniques, two with a general anesthetic and one with neuraxial anesthesia. Review of literature revealed no robust data regarding which anesthetic route should be undertaken for non-obstetric surgery in a pregnant patient. Inhaled general anesthetic agents have not been found to be teratogenic at the levels given for surgery but have been associated with increased risk of preterm labor in the second trimester.8 In our case series, although all three surgeries were conducted at the same tertiary care center, the choice of anesthetic agent and route was individualized for each patient and planned surgical repair. The patient in case one had several injuries to the lower extremities, and the care of the patient in case three was complicated by maternal obesity, both of which may have made the conversion from neuraxial anesthesia to general during surgery challenging. Finally, the patient in case two was a good candidate for neuraxial anesthesia based on her body mass index and less complex fracture.\n\nIntraoperative management is of critical importance in the management of the viable pregnancy with maternal femoral fracture. The obstetric team worked closely with the operating room personnel for proper positioning of the patients with left lateral tilt (approximately 15 degrees) to avoid compression of the inferior vena cava by the gravid uterus. The patients were offered continuous intraoperative fetal monitoring based on their desire for surgical intervention on fetal behalf after neonatology and maternal-fetal-medicine preoperative consulation.8,9 Preoperative and intraoperative fetal protection with a lead apron placed over maternal abdomen was used to minimize fetal exposure to radiation. There is evidence that plates compared to intramedullary nailing confer decreased radiation doses.10 Intramedullary nailing was only used for femoral fracture repair in one of the included patients. Even though the radiation dose used in all three cases was minimal, this demonstrates the importance of multi-disciplinary preoperative planning to reduce the pre-and- intraoperative radiation exposure to the fetus.\n\nPostoperatively, the patients received VTE prophylaxis with subcutaneous heparin or LMWH.11 The dosage recommended by the American College of Chest Physicians11 is 30 mg enoxaparin sodium subcutaneous daily for 28–35 days. Modifications to this dosage and the length of therapy in the pregnant population with femur fracture is not known. Our patients had a planned 30-day regimen for their anticoagulation with 30 mg BID of LMWH. In addition, intensive physical therapy was initiated on postoperative day 1 and was continued in the outpatient setting.\n\nData regarding the route of delivery in patients that have suffered a lower extremity fracture is lacking. One retrospective series reviewed pelvic fractures in women of childbearing age and found a cesarean section rate of 62% at a single institution. One case report of an acetabular femoral fracture that underwent fixation resulted in a vaginal delivery at term.6 In a retrospective case series with 8 patients that underwent late-preterm or term delivery, 50% had cesarean sections but their obstetric history was not reported.7 In our case series, all patients had spontaneous vaginal deliveries. The hypothesis for higher rates of cesarean deliveries in previous reports was suspected impaired ability of affected women to perform hip abduction. In our three cases, physical therapy was initiated in the immediate post-operative period with emphasis to continue working on hip abduction. All three patients were able to abduct their hips and place their legs in stirrups; therefore, cesarean section was reserved solely for obstetric indications.\n\nThe second case report we described is unique as the fracture occurred in a young woman in the absence of trauma. The etiology of that femur fracture was presumed to be osteoporotic in origin, secondary to smoking12 and methadone13 with low levels of calcium and vitamin D. Although the patient did not undergo bone mineral density testing, clinical diagnosis of osteoporosis was made in the presence of fragility fracture14 and she was started on vitamin D and calcium supplementation. Although some studies suggest that pregnancy itself is a risk factor for temporary osteoporosis, the data is overall inconclusive and rarely leads to clinical manifestations during pregnancy and postpartum.15–18 However, in the presence of additional risk factors, osteoporosis can complicate pregnancy, as occurred in our second case; this enhanced our awareness of the possibility of this diagnosis in a younger population.\n\nIn conclusion, a comprehensive multidisciplinary approach to successful management of femoral fracture in pregnancy was reviewed in this case report series. Despite different etiologies of femoral fracture, all women benefited from VTE prophylaxis with LMWH, early initiation of physical therapy with emphasis on hip abduction, supplementation with vitamin D and calcium, and all were able to safely achieve vaginal delivery.\n\nDisclosure\nThe authors report no conflicts of interest in this work. \n==== Refs\nReferences\n1. Almog \nG , Liebergall \nM , Tsafrir \nA , Barzilay \nY , Mosheiff \nR . Management of pelvic fractures during pregnancy . Am J Orthop (Belle Mead NJ). 2007;36(11):E153-9. \n2. Cannada \nLK , Barr \nJ . Pelvic fractures in women of childbearing age . Clin Orthop Relat Res . 2010 ;468 (7 ):1781 –1789 . doi:10.1007/s11999-010-1333-5 20333494 \n3. Cannada \nLK , Pan \nP , Casey \nBM , McIntire \nDD , Shafi \nS , Leveno \nKJ . Pregnancy outcomes after orthopedic trauma . J Trauma . 2010 ;69 (3 ):694–8; discussion 698. doi:10.1097/TA.0b013e3181ec2b11 \n4. El Kady \nD , Gilbert \nWM , Xing \nG , Smith \nLH . Association of maternal fractures with adverse perinatal outcomes . Am J Obstet Gynecol . 2006 ;195 (3 ):711 –716 . doi:10.1016/j.ajog.2006.06.067 16949401 \n5. Weinlein \nJC , Mashru \nRP , Perez \nEA , Johnson \nSE . Lateral compression-I pelvic ring injury: not benign to the developing fetus . J Orthop Trauma . 2018 ;32 (2 ):100 –103 . doi:10.1097/BOT.0000000000001030 28906307 \n6. Kloen \nP , Flik \nK , Helfet \nDL . Operative treatment of acetabular fracture during pregnancy: a case report . Arch Orthop Trauma Surg . 2005 ;125 (3 ):209 –212 . doi:10.1007/s00402-005-0798-2 15742191 \n7. Porter \nSE , Russell \nGV , Qin \nZ , Graves \nML . Operative fixation of acetabular fractures in the pregnant patient . J Orthop Trauma . 2008 ;22 (8 ):508 –516 . doi:10.1097/BOT.0b013e31816080d6 18758280 \n8. Ogle \nJA . Improving web site performance using commercially available analytical tools . Indian J Anaesth . 2010 ;468 (10 ):2604 –2611 . doi:10.4103/0019-5049.179445 \n9. Nonobstetric surgery during pregnancy. Committee Opinion No. 696. American College of Obstetricians and Gynecologists . Obstet Gynecol . 2017 ;129 :777 –778 . doi:10.1097/AOG.0000000000002014 28333816 \n10. Labronici \nPJ , Lyra \nFS , Moreira \nIL , et al. Fractures of the distal extremity of the tibia treated with intramedullary nail or bridge plate: comparison of radiation exposure between the two methods . Rev Bras Ortop . 2010 ;45 (2 ):132 –135 . doi:10.1016/S2255-4971(15)30281-0 27022530 \n11. Falck-Ytter \nY , Francis \nCW , Johanson \nNA , et al. Prevention of VTE in orthopedic surgery patients: antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines . Chest . 2012 ;141 (2Suppl ):e278S –e325S . doi:10.1378/chest.11-2404 22315265 \n12. Siris \nES , Chen \nY-T , Abbott \nTA , et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures . Arch Intern Med . 2004 ;164 (10 ):1108 –1112 . doi:10.1001/archinte.164.10.1108 15159268 \n13. Teng \nZ , Zhu \nY , Wu \nF , et al. Opioids contribute to fracture risk: a meta-analysis of 8 cohort studies . PLoS One . 2015 ;10 (6 ):e0128232 . doi:10.1371/journal.pone.0128232 26030421 \n14. Siris \nES , Adler \nR , Bilezikian \nJ , et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group . Osteoporos Int . 2014 ;25 (5 ):1439 –1443 . doi:10.1007/s00198-014-2655-z 24577348 \n15. Karlsson \nMK , Ahlborg \nHG , Karlsson \nC . Maternity and bone mineral density . Acta Orthop . 2005 ;76 (1 ):2 –13 . doi:10.1080/00016470510030274 15788303 \n16. Naylor \nKE , Iqbal \nP , Fledelius \nC , Fraser \nRB , Eastell \nR . The effect of pregnancy on bone density and bone turnover . J Bone Miner Res . 2000 ;15 (1 ):129 –137 . doi:10.1359/jbmr.2000.15.9.1798 10646122 \n17. Aj \nB , Topping \nJ , Durham \nB , Rg \nF , Wd \nF . A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy . J Bone Miner Res . 2000 ;15 (3 ):557 –563 . doi:10.1359/jbmr.2000.15.9.1798 10750571 \n18. Sowers \nM , Crutchfield \nM , Jannausch \nM , Updike \nS , Corton \nG . A prospective evaluation of bone mineral change in pregnancy . Obstet Gynecol . 1991 ;77 (6 ):841 –845 .2030854\n\n",
"fulltext_license": "CC BY-NC",
"issn_linking": "1179-1411",
"issue": "11()",
"journal": "International journal of women's health",
"keywords": "antepartum testing; femoral fracture; osteoporosis in pregnancy; trauma in pregnancy; venous thromboembolism prevention",
"medline_ta": "Int J Womens Health",
"mesh_terms": null,
"nlm_unique_id": "101531698",
"other_id": null,
"pages": "267-271",
"pmc": null,
"pmid": "31114393",
"pubdate": "2019",
"publication_types": "D002363:Case Reports",
"references": "10646122;10750571;15159268;15742191;15788303;16949401;18075613;18758280;2030854;20333494;20361280;20838141;22315265;24577348;26030421;27022530;28333816;28906307",
"title": "Femoral fracture in pregnancy: a case series and review of clinical management.",
"title_normalized": "femoral fracture in pregnancy a case series and review of clinical management"
}
|
[
{
"companynumb": "US-PFIZER INC-2019233216",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CHOLECALCIFEROL"
},
"drugadditional": "3",
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUPPLEMENTATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CHOLECALCIFEROL"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ENOXAPARIN SODIUM"
},
"drugadditional": "3",
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "30 MG, 2X/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "30",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENOXAPARIN SODIUM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "AMOXICILLIN"
},
"drugadditional": "3",
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMOXICILLIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "AZITHROMYCIN ANHYDROUS"
},
"drugadditional": "3",
"drugadministrationroute": "064",
"drugauthorizationnumb": "050670",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZITHROMYCIN ANHYDROUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CALCIUM ACETATE"
},
"drugadditional": "3",
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUPPLEMENTATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CALCIUM ACETATE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "BETAMETHASONE"
},
"drugadditional": "3",
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "12 MG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MATERNAL THERAPY TO ENHANCE FOETAL LUNG MATURITY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "12",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BETAMETHASONE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Premature baby",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Maternal exposure during pregnancy",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HAROLD, J.. FEMORAL FRACTURE IN PREGNANCY A CASE SERIES AND REVIEW OF CLINICAL MANAGEMENT. INTERNATIONAL JOURNAL OF WOMEN^S HEALTH. 2019?11:267-271",
"literaturereference_normalized": "femoral fracture in pregnancy a case series and review of clinical management",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190604",
"receivedate": "20190604",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16390697,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190711"
},
{
"companynumb": "HIKMA PHARMACEUTICALS USA INC.-US-H14001-19-04283",
"fulfillexpeditecriteria": "1",
"occurcountry": null,
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHADONE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "006134",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHADONE"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "17-HYDROXYPROGESTERONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHADONE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "006134",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHADONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VITAMIN D NOS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUPPLEMENTATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VITAMIN D"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "BUPIVACAINE"
},
"drugadditional": null,
"drugadministrationroute": "051",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPIVACAINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CALCIUM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUPPLEMENTATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CALCIUM"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PREMATURE LABOUR",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "17-HYDROXYPROGESTERONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "UNSPECIFIED INGREDIENT"
},
"drugadditional": null,
"drugadministrationroute": "058",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THROMBOSIS PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LMWH"
}
],
"patientagegroup": null,
"patientonsetage": "34",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Maternal exposure during pregnancy",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Femoral neck fracture",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HAROLD J, ISAACSON E, PALATNIK A. FEMORAL FRACTURE IN PREGNANCY: A CASE SERIES AND REVIEW OF CLINICAL MANAGEMENT. INTERNATIONAL JOURNAL OF WOMEN^S HEALTH. 2019?11:267-271.",
"literaturereference_normalized": "femoral fracture in pregnancy a case series and review of clinical management",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190719",
"receivedate": "20190719",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16598138,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20191004"
}
] |
{
"abstract": "Since the effects of prostaglandin synthetase inhibitors on the developing human fetal pulmonary vasculature are unknown, we studied the lungs of two infants, one whose mother took salicylates and the other whose mother took indomethacin during pregnancy. Lungs were fixed by perfusion and fifth generation (resistance) vessels identified. The infant with chronic exposure to aspirin had premature constriction of the ductus arteriosus, tricuspid insufficiency, increased pulmonary arterial medial width/external diameter ratio due to increased smooth muscle, and a decreased number of pulmonary vessels/cm2 lung tissue. The infant with short-term exposure to indomethacin had hypoxemia, increased pulmonary arterial m/d ratio due to increased smooth muscle, and a normal number of pulmonary vessels/cm2 lung tissue. These abnormalities may be due to the effects of prostaglandin synthetase inhibitor drugs on the ductus arteriosus and/or the pulmonary vessels of the human fetus.",
"affiliations": null,
"authors": "Levin|D L|DL|;Fixler|D E|DE|;Morriss|F C|FC|;Tyson|J|J|",
"chemical_list": "D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D012459:Salicylates; D007213:Indomethacin",
"country": "United States",
"delete": false,
"doi": "10.1016/s0022-3476(78)80453-3",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0022-3476",
"issue": "92(3)",
"journal": "The Journal of pediatrics",
"keywords": null,
"medline_ta": "J Pediatr",
"mesh_terms": "D000328:Adult; D001808:Blood Vessels; D016861:Cyclooxygenase Inhibitors; D004373:Ductus Arteriosus; D005260:Female; D005333:Fetus; D006801:Humans; D007213:Indomethacin; D007231:Infant, Newborn; D008168:Lung; D008297:Male; D011247:Pregnancy; D011448:Prostaglandin Antagonists; D012459:Salicylates; D014261:Tricuspid Valve",
"nlm_unique_id": "0375410",
"other_id": null,
"pages": "478-83",
"pmc": null,
"pmid": "416191",
"pubdate": "1978-03",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013487:Research Support, U.S. Gov't, P.H.S.",
"references": null,
"title": "Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors.",
"title_normalized": "morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors"
}
|
[
{
"companynumb": "US-PFIZER INC-2016398402",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INDOMETHACIN"
},
"drugadditional": null,
"drugadministrationroute": "064",
"drugauthorizationnumb": "204118",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "25 MG, 1X/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "25",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INDOMETHACIN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": "3.04",
"reaction": [
{
"reactionmeddrapt": "Pulmonary vascular disorder",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Maternal exposure during pregnancy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LEVIN, D.. MORPHOLOGIC ANALYSIS OF THE PULMONARY VASCULAR BED IN INFANTS EXPOSED IN UTERO TO PROSTAGLANDIN SYNTHETASE INHIBITORS. JOURNAL OF PEDIATRICS. 1978;92 (3):478-483",
"literaturereference_normalized": "morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20160829",
"receivedate": "20160829",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12694271,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20161109"
}
] |
{
"abstract": "Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is increasing in incidence and is associated with increased mortality in liver transplantation (LT) recipients. We performed a retrospective cohort study of all patients transplanted between January 2010 and January 2013 to identify the incidence and risk factors for post-LT CRKP infection and evaluate the impact of this infection on outcomes in a CRKP-endemic area. We studied 304 recipients, of whom 20 (6.6%) developed CRKP and 36 (11.8%) carbapenem-susceptible Klebsiella pneumoniae (CSKP) infections in the year following LT. Among the 20 recipients with post-LT CRKP infection, 8 (40%) were infected in ≥ 2 sites; 13 (65%) had surgical site-intra-abdominal infections; 12 (60%) had pneumonia; and 3 (15%) had a urinary tract infection. There were 6 patients with a CRKP infection before LT, 5 of whom developed a CRKP infection after LT. Significant risk factors for post-LT CRKP infection in multivariate analysis included laboratory Model for End-Stage Liver Disease at LT (odds ratio [OR], 1.07; P = 0.001), hepatocellular carcinoma (OR, 3.19; P = 0.02), Roux-en-Y biliary choledochojejunostomy (OR, 3.15; P = 0.04), and bile leak (OR, 5.89; P = 0.001). One-year estimated patient survival was 55% (95% confidence interval, 31%-73%), 72% (55%-84%), and 93% (89%-96%), for patients with CRKP, CSKP, and no Klebsiella pneumoniae infection, respectively. In multivariate analysis, CRKP (hazard ratio [HR], 6.92; P < 0.001) and CSKP infections (CSKP, HR, 3.84; P < 0.001), as well as bile leak (HR, 2.10; P = 0.03) were the strongest predictors of post-LT mortality. In an endemic area, post-LT CRKP infection is common, occurring in 6.6% of recipients, and is strongly associated with post-LT mortality. Improved strategies for screening and prevention of CRKP infection are urgently needed.",
"affiliations": "Division of Infectious Diseases.;Department of Medicine.;Department of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH.;Division of Infectious Diseases.;Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY.;Department of Surgery.;Department of Medicine.",
"authors": "Pereira|Marcus R|MR|;Scully|Brendan F|BF|;Pouch|Stephanie M|SM|;Uhlemann|Anne-Catrin|AC|;Goudie|Stella|S|;Emond|Jean E|JE|;Verna|Elizabeth C|EC|",
"chemical_list": "D015780:Carbapenems",
"country": "United States",
"delete": false,
"doi": "10.1002/lt.24207",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1527-6465",
"issue": "21(12)",
"journal": "Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society",
"keywords": null,
"medline_ta": "Liver Transpl",
"mesh_terms": "D015780:Carbapenems; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007710:Klebsiella Infections; D007711:Klebsiella pneumoniae; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009519:New York City; D011183:Postoperative Complications; D012189:Retrospective Studies; D012307:Risk Factors",
"nlm_unique_id": "100909185",
"other_id": null,
"pages": "1511-9",
"pmc": null,
"pmid": "26136397",
"pubdate": "2015-12",
"publication_types": "D016428:Journal Article",
"references": "20970577;17606211;15980389;23883973;22173517;22093103;19638006;24463280;16315310;22447265;19459805;25420864;18538699;1443756;15023150;25557556;16741932;22467548;24217959;20209598;23453411;23331505;22563180;15206053;19715892;15237367;21786404;24100228;7524204",
"title": "Risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients.",
"title_normalized": "risk factors and outcomes of carbapenem resistant klebsiella pneumoniae infections in liver transplant recipients"
}
|
[
{
"companynumb": "US-SA-2016SA132694",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEFEPIME HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEFEPIME HYDROCHLORIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "POLYMYXIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "POLYMYXIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMETHOPRIM/SULFAMETHOXAZOLE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RIFAMPIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050420",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RIFAMPICIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TIGECYCLINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TIGECYCLINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": "5",
"patientonsetage": "52",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Bacteraemia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Abdominal infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Klebsiella infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Postoperative wound infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PEREIRA MR, SCULLY BF, POUCH SM, UHLEMANN A-C, GOUDIE S, EMOND JE, ET AL. RISK FACTORS AND OUTCOMES OF CARBAPENEM-RESISTANT KLEBSIELLA PNEUMONIAE INFECTIONS IN LIVER TRANSPLANT RECIPIENTS. LIVER TRANSPL. 2015 DEC;21(12):1511-9. DOI:10.1002/LT.24207.",
"literaturereference_normalized": "risk factors and outcomes of carbapenem resistant klebsiella pneumoniae infections in liver transplant recipients",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20160721",
"receivedate": "20160721",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12580226,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20161109"
},
{
"companynumb": "US-SA-2016SA132700",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MEROPENEM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MEROPENEM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RIFAMPIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050420",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RIFAMPICIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMETHOPRIM/SULFAMETHOXAZOLE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TIGECYCLINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TIGECYCLINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "POLYMYXIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "POLYMYXIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "NYSTATIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "SWISH AND SWALLOW",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NYSTATIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": "6",
"patientonsetage": "69",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Klebsiella infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Postoperative wound infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Abdominal infection",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Bacteraemia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pneumonia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PEREIRA MR, SCULLY BF, POUCH SM, UHLEMANN A-C, GOUDIE S, EMOND JE ET AL. RISK FACTORS AND OUTCOMES OF CARBAPENEM-RESISTANT KLEBSIELLA PNEUMONIAE INFECTIONS IN LIVER TRANSPLANT RECIPIENTS. LIVER TRANSPL. 2015 DEC;21(12):1511-9. DOI:10.1002/LT.24207.",
"literaturereference_normalized": "risk factors and outcomes of carbapenem resistant klebsiella pneumoniae infections in liver transplant recipients",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20160725",
"receivedate": "20160725",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12589731,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20161109"
}
] |
{
"abstract": "The purpose of the present study is to determine the role of lidocaine, caffeine and dextromethorphan, used as adulterant substances, in five cases of drug overdose which have come to our attention. Taking into account the pharmacological mechanism, blood concentration and route of administration (intravenous) we evaluated the hypothesis that these substances could act with a synergistic effect - or at least additive - with the illicit drugs on the central nervous system and cardiovascular system.",
"affiliations": "Department G.F. Ingrassia, Laboratory of Forensic Toxicology, University of Catania, Italy.",
"authors": "Barbera|Nunziata|N|;Busardò|Francesco Paolo|FP|;Indorato|Francesca|F|;Romano|Guido|G|",
"chemical_list": "D000779:Anesthetics, Local; D000996:Antitussive Agents; D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D009022:Morphine Derivatives; D009294:Narcotics; D011759:Pyrrolidines; D017367:Serotonin Uptake Inhibitors; D015283:Citalopram; D002110:Caffeine; D003915:Dextromethorphan; D009020:Morphine; D008012:Lidocaine; C026979:6-O-monoacetylmorphine; D008691:Methadone; D003061:Codeine; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine",
"country": "Ireland",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0379-0738",
"issue": "227(1-3)",
"journal": "Forensic science international",
"keywords": null,
"medline_ta": "Forensic Sci Int",
"mesh_terms": "D000328:Adult; D000779:Anesthetics, Local; D000996:Antitussive Agents; D001646:Bile; D001923:Brain Chemistry; D002110:Caffeine; D000697:Central Nervous System Stimulants; D015283:Citalopram; D003061:Codeine; D003915:Dextromethorphan; D004340:Drug Contamination; D062787:Drug Overdose; D055030:Drug Users; D005260:Female; D049429:Forensic Pathology; D053593:Forensic Toxicology; D005766:Gastrointestinal Contents; D006801:Humans; D013287:Illicit Drugs; D007668:Kidney; D008012:Lidocaine; D008099:Liver; D008168:Lung; D008297:Male; D008691:Methadone; D009020:Morphine; D009022:Morphine Derivatives; D009294:Narcotics; D011759:Pyrrolidines; D017367:Serotonin Uptake Inhibitors; D019966:Substance-Related Disorders; D014822:Vitreous Body",
"nlm_unique_id": "7902034",
"other_id": null,
"pages": "74-6",
"pmc": null,
"pmid": "23000137",
"pubdate": "2013-04-10",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "The pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome.",
"title_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome"
}
|
[
{
"companynumb": "PHHY2013IT148764",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CODEINE PHOSPHATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CODEINE PHOSPHATE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXTROMETHORPHAN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXTROMETHORPHAN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CAFFEINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CAFFEINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIACETYLMORPHINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAMORPHINE HYDROCHLORIDE"
}
],
"patientagegroup": null,
"patientonsetage": "37",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BARBERA N, BUSARDO FP, INDORATO F, ROMANO G. THE PATHOGENETIC ROLE OF ADULTERANTS IN 5 CASES OF DRUG ADDICTS WITH A FATAL OUTCOME. FORENSIC SCIENCE INTERNATIONAL. 2013;227(13):74-76",
"literaturereference_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20150521",
"receivedate": "20131223",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9779024,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20150821"
},
{
"companynumb": "IT-MYLANLABS-2017M1079961",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DIAMORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": "201103",
"drugenddateformat": "610",
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201103",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEROIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHADONE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "021624",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": "201103",
"drugenddateformat": "610",
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201103",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHADONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DEXTROMETHORPHAN HYDROBROMIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": "201103",
"drugenddateformat": "610",
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201103",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXTROMETHORPHAN HYDROBROMIDE."
}
],
"patientagegroup": null,
"patientonsetage": "37",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BARBERA N, BUSARDO FP, INDORATO F, ROMANO G.. THE PATHOGENETIC ROLE OF ADULTERANTS IN 5 CASES OF DRUG ADDICTS WITH A FATAL OUTCOME. THE 50TH ANNUAL MEETING OF THE INTERNATIONAL ASSOCIATION OF FORENSIC TOXICOLOGISTS. FORENSIC SCI INT. 2013. 2012;227 (1-3):74-76",
"literaturereference_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20171221",
"receivedate": "20171221",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14315464,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180321"
},
{
"companynumb": "PHHY2013IT148763",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIACETYLMORPHINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAMORPHINE HYDROCHLORIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CAFFEINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CAFFEINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXTROMETHORPHAN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXTROMETHORPHAN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CODEINE PHOSPHATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CODEINE PHOSPHATE"
}
],
"patientagegroup": null,
"patientonsetage": "33",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 201012"
}
},
"primarysource": {
"literaturereference": "BARBERA N, BUSARDO FP, INDORATO F, ROMANO G. THE PATHOGENETIC ROLE OF ADULTERANTS IN 5 CASES OF DRUG ADDICTS WITH A FATAL OUTCOME. FORENSIC SCIENCE INTERNATIONAL. 2013;227(13):74-76",
"literaturereference_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20150521",
"receivedate": "20131220",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9776062,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20150821"
},
{
"companynumb": "PHHY2013IT148762",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIACETYLMORPHINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAMORPHINE HYDROCHLORIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CODEINE PHOSPHATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CODEINE PHOSPHATE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CITALOPRAM HYDROBROMIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "077040",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CITALOPRAM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CAFFEINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CAFFEINE."
}
],
"patientagegroup": null,
"patientonsetage": "26",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Myocardial necrosis",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug abuse",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2010"
}
},
"primarysource": {
"literaturereference": "BARBERA N, BUSARDO FP, INDORATO F, ROMANO G. THE PATHOGENETIC ROLE OF ADULTERANTS IN 5 CASES OF DRUG ADDICTS WITH A FATAL OUTCOME. FORENSIC SCIENCE INTERNATIONAL. 2013;227(13):74-76",
"literaturereference_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20150521",
"receivedate": "20131223",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9779020,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150821"
},
{
"companynumb": "PHHY2013IT148765",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CODEINE PHOSPHATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CODEINE PHOSPHATE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIACETYLMORPHINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAMORPHINE HYDROCHLORIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXTROMETHORPHAN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXTROMETHORPHAN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CAFFEINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CAFFEINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
}
],
"patientagegroup": null,
"patientonsetage": "23",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BARBERA N, BUSARDO FP, INDORATO F, ROMANO G. THE PATHOGENETIC ROLE OF ADULTERANTS IN 5 CASES OF DRUG ADDICTS WITH A FATAL OUTCOME. FORENSIC SCIENCE INTERNATIONAL. 2013;227(13):74-76",
"literaturereference_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20150522",
"receivedate": "20131223",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9779025,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20150821"
},
{
"companynumb": "PHHY2013IT148743",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COCAINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COCAINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LIDOCAINE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "080198",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE."
}
],
"patientagegroup": null,
"patientonsetage": "26",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pulmonary congestion",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug administration error",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pulmonary oedema",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BARBERA N, BUSARDO FP, INDORATO F, ROMANO G. THE PATHOGENETIC ROLE OF ADULTERANTS IN 5 CASES OF DRUG ADDICTS WITH A FATAL OUTCOME. FORENSIC SCIENCE INTERNATIONAL. 2013;227(13):74-76",
"literaturereference_normalized": "the pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20150521",
"receivedate": "20131226",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9783793,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150821"
}
] |
{
"abstract": "The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1-, 3-, and 5-year recurrence-free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1-, 3-, and 5-year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha-fetoprotein × protein induced by vitamin K absence/antagonist-II (AP) score (≥20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (≥2.1; P < 0.01), and a large original tumor (≥7 cm; P = 0.03) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23:19-27 2017 AASLD.",
"affiliations": "Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.;Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.;Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.",
"authors": "Lee|Kwang-Woong|KW|;Suh|Suk-Won|SW|;Choi|YoungRok|Y|;Jeong|Jaehong|J|;Yi|Nam-Joon|NJ|;Kim|Hyeyoung|H|;Yoon|Kyung Chul|KC|;Hong|Suk Kyun|SK|;Kim|Hyo-Sin|HS|;Lee|Kyung-Bun|KB|;Suh|Kyung-Suk|KS|",
"chemical_list": "D015415:Biomarkers; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin",
"country": "United States",
"delete": false,
"doi": "10.1002/lt.24610",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1527-6465",
"issue": "23(1)",
"journal": "Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society",
"keywords": null,
"medline_ta": "Liver Transpl",
"mesh_terms": "D000328:Adult; D000368:Aged; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular; D000075202:Contraindications; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D011169:Portal Vein; D011379:Prognosis; D011498:Protein Precursors; D011516:Prothrombin; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D020858:Tissue and Organ Harvesting; D016896:Treatment Outcome; D019043:Vascular Neoplasms; D020246:Venous Thrombosis; D000509:alpha-Fetoproteins",
"nlm_unique_id": "100909185",
"other_id": null,
"pages": "19-27",
"pmc": null,
"pmid": "27540701",
"pubdate": "2017-01",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Macrovascular invasion is not an absolute contraindication for living donor liver transplantation.",
"title_normalized": "macrovascular invasion is not an absolute contraindication for living donor liver transplantation"
}
|
[
{
"companynumb": "PHHY2019KR182204",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SORAFENIB"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SORAFENIB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SORAFENIB"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SORAFENIB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "39",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Malignant neoplasm progression",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LEE KW, SUH SW, CHOI Y, JEONG J, YI NAM-JOON, KIM H ET AL.. MACROVASCULAR INVASION IS NOT AN ABSOLUTE CONTRAINDICATION FOR LIVING DONOR LIVER TRANSPLANTATION. LIVER TRANSPLANTATION. 2017?23:19-7",
"literaturereference_normalized": "macrovascular invasion is not an absolute contraindication for living donor liver transplantation",
"qualification": "3",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20190808",
"receivedate": "20190808",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16684396,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20191004"
},
{
"companynumb": "PHHY2019KR182199",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": null,
"patientonsetage": "72",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hepatocellular carcinoma",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Malignant neoplasm progression",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LEE K, SUH S, CHOI Y, JEONG J, YI N, KIM H ET AL.. MACROVASCULAR INVASION IS NOT AN ABSOLUTE CONTRAINDICATION FOR LIVING DONOR LIVER TRANSPLANTATION. LIVER TRANSPLANTATION. 2017?23:19-27",
"literaturereference_normalized": "macrovascular invasion is not an absolute contraindication for living donor liver transplantation",
"qualification": "3",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20190811",
"receivedate": "20190811",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16690679,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20191004"
},
{
"companynumb": "PHHY2019KR182192",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "44",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Malignant neoplasm progression",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LEE K, SUH S, CHOI Y, JEONG J, YI N, KIM H ET AL.. MACROVASCULAR INVASION IS NOT AN ABSOLUTE CONTRAINDICATION FOR LIVING DONOR LIVER TRANSPLANTATION. LIVER TRANSPLANTATION. 2017?23:19-27",
"literaturereference_normalized": "macrovascular invasion is not an absolute contraindication for living donor liver transplantation",
"qualification": "3",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20190811",
"receivedate": "20190811",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16690672,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20191004"
}
] |
{
"abstract": "To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD).\n\n\n\nWe retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR).\n\n\n\nA total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF (p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA.\n\n\n\nThe use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status.\n\n\n\nThat study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse.",
"affiliations": "From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France.;From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France. [email protected].",
"authors": "Poupart|Julien|J|;Giovannelli|Jonathan|J|0000-0002-7516-4670;Deschamps|Romain|R|;Audoin|Bertrand|B|0000-0002-9860-7657;Ciron|Jonathan|J|;Maillart|Elisabeth|E|0000-0001-7699-0328;Papeix|Caroline|C|;Collongues|Nicolas|N|0000-0002-3683-5582;Bourre|Bertrand|B|;Cohen|Mickael|M|;Wiertlewski|Sandrine|S|;Outteryck|Olivier|O|;Laplaud|David|D|;Vukusic|Sandra|S|;Marignier|Romain|R|;Zephir|Hélène|H|0000-0003-4029-2012;|||",
"chemical_list": "D000906:Antibodies; D051401:Aquaporin 4; D007166:Immunosuppressive Agents; D000069283:Rituximab; D009173:Mycophenolic Acid; D001379:Azathioprine",
"country": "United States",
"delete": false,
"doi": "10.1212/WNL.0000000000009245",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0028-3878",
"issue": "94(15)",
"journal": "Neurology",
"keywords": null,
"medline_ta": "Neurology",
"mesh_terms": "D000328:Adult; D000906:Antibodies; D051401:Aquaporin 4; D001379:Azathioprine; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid; D009471:Neuromyelitis Optica; D012008:Recurrence; D000069283:Rituximab",
"nlm_unique_id": "0401060",
"other_id": null,
"pages": "e1645-e1656",
"pmc": null,
"pmid": "32170036",
"pubdate": "2020-04-14",
"publication_types": "D023362:Evaluation Study; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Evaluation of efficacy and tolerability of first-line therapies in NMOSD.",
"title_normalized": "evaluation of efficacy and tolerability of first line therapies in nmosd"
}
|
[
{
"companynumb": "FR-TEVA-2020-FR-1793325",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65457",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NEUROMYELITIS OPTICA SPECTRUM DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "65457",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": "6",
"patientonsetage": "7",
"patientonsetageunit": "800",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pneumonia",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Escherichia urinary tract infection",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "POUPART J, GIOVANNELLI J, DESCHAMPS R, AUDOIN B, CIRON J, MAILLART E, ET AL. EVALUATION OF EFFICACY AND TOLERABILITY OF FIRST?LINE THERAPIES IN NMOSD. NEUROLOGY 2020?94(15):E1645?E1656.",
"literaturereference_normalized": "evaluation of efficacy and tolerability of first line therapies in nmosd",
"qualification": "1",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20210628",
"receivedate": "20200629",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 17954308,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "FR-MYLANLABS-2020M1060673",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "065520",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NEUROMYELITIS OPTICA SPECTRUM DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "065520",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": null,
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Urinary tract infection",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Intentional product use issue",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "POUPART J, GIOVANNELLI J, DESCHAMPS R, AUDOIN B, CIRON J, MAILLART E. ET.AL.. EVALUATION OF EFFICACY AND TOLERABILITY OF FIRST?LINE THERAPIES IN NMOSD.. AMERICAN ACADEMY OF NEUROLOGY.. 2020?94:E1645?1656",
"literaturereference_normalized": "evaluation of efficacy and tolerability of first line therapies in nmosd",
"qualification": "1",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20200709",
"receivedate": "20200709",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18000600,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
},
{
"companynumb": "FR-TEVA-2020-FR-1793326",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65457",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NEUROMYELITIS OPTICA SPECTRUM DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "65457",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
"patientagegroup": "6",
"patientonsetage": "7",
"patientonsetageunit": "800",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Urinary tract infection",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Citrobacter infection",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "POUPART J, GIOVANNELLI J, DESCHAMPS R, AUDOIN B, CIRON J, MAILLART E, ET AL. EVALUATION OF EFFICACY AND TOLERABILITY OF FIRST?LINE THERAPIES IN NMOSD. NEUROLOGY 2020?94(15):E1645?E1656.",
"literaturereference_normalized": "evaluation of efficacy and tolerability of first line therapies in nmosd",
"qualification": "1",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20210628",
"receivedate": "20200629",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 17954413,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
}
] |
{
"abstract": "BACKGROUND\nRecurrent respiratory papillomatosis (RRP) is a known but rare disease, caused by human papilloma virus and characterised by multiple exophytic lesions and uncontrolled growth of papilloma in the respiratory tract. The most common complication of RRP is stenosis of the trachea. Medical therapeutic options have so far been less effective. However, inhibition of vascular endothelial growth factor (VEGF) by bevacizumab does appear to be an effective treatment option for RRP.\n\n\nMETHODS\nThe case of a 32-year-old male patient with RRP who has been treated for his symptomatic tracheal stenosis four times a year since 1996 is described. Only treatment by laser ablation showed any efficacy. Alternative treatment options did not show any effect. In May 2006 intrapulmonary lesions of RRP were also diagnosed but without any malignancy. From December 2007 to June 2008 the patient has been treated with bevacizumab. A visible regression of RRP and markedly less symptoms were observed. During this treatment no further laser ablation was necessary.\n\n\nCONCLUSIONS\nInhibition of VEGF by bevacizumab seems to offer a new and effective option in the medical management of RRP.",
"affiliations": "Krankenhaus Martha-Maria, Halle-Dölau gGmbH, Klinik für Innere Medizin II, Halle. [email protected]",
"authors": "Nagel|S|S|;Busch|C|C|;Blankenburg|T|T|;Schütte|W|W|",
"chemical_list": "D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab",
"country": "Germany",
"delete": false,
"doi": "10.1055/s-0029-1214714",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0934-8387",
"issue": "63(7)",
"journal": "Pneumologie (Stuttgart, Germany)",
"keywords": null,
"medline_ta": "Pneumologie",
"mesh_terms": "D000328:Adult; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D006801:Humans; D008297:Male; D010212:Papilloma; D014134:Tracheal Neoplasms; D016896:Treatment Outcome",
"nlm_unique_id": "8906641",
"other_id": null,
"pages": "387-9",
"pmc": null,
"pmid": "19591084",
"pubdate": "2009-07",
"publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article",
"references": null,
"title": "Treatment of respiratory papillomatosis--a case report on systemic treatment with bevacizumab.",
"title_normalized": "treatment of respiratory papillomatosis a case report on systemic treatment with bevacizumab"
}
|
[
{
"companynumb": "US-ROCHE-1985274",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BEVACIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125085",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BEVACIZUMAB."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BEVACIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125085",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RESPIRATORY PAPILLOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BEVACIZUMAB."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "No adverse event",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Intentional product use issue",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NAGEL S, BUSCH C, BLANKENBURG T ET AL. TREATMENT OF RESPIRATORY PAPILLOMATOSIS-A CASE REPORT ON SYSTEMIC TREATMENT WITH BEVACIZUMAB. PNEUMOLOGIE 2009?63:387-389.",
"literaturereference_normalized": "treatment of respiratory papillomatosis a case report on systemic treatment with bevacizumab",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180501",
"receivedate": "20180501",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14833976,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180711"
}
] |
{
"abstract": "BACKGROUND\nPrimary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. There are no cases of esophageal metastases from lung cancer which refer to its particular treatment.\n\n\nMETHODS\nWe report a case of esophageal metastases from lung cancer. The patient was a 55-year-old Han Chinese man who first attended our hospital due to dry cough and was diagnosed with late-stage lung cancer. Three months later, the patient complained of dysphagia. Endoscopic ultrasonography (EUS) and pathological examination of the biopsy specimen was performed to confirm the lesion was metastases from lung cancer. Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A were positive by immunohistochemistry examination. These results reconfirmed the diagnosis of esophageal metastases from lung cancer.\n\n\nCONCLUSIONS\nEsophageal metastasis from lung cancer is very rare. It may be alleviated with personalized chemotherapy. In addition, molecular targeted therapy for patients with epidermal growth factor receptor (EGFR) mutations may be reasonable.",
"affiliations": "Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing, 210000, Jiangsu, China.;Department of Cardiothoracic Surgery, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210000, Jiangsu, China.;Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing, 210000, Jiangsu, China.;Department of Cardiothoracic Surgery, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210000, Jiangsu, China. [email protected].",
"authors": "Wang|Chang-Yong|CY|http://orcid.org/0000-0002-5348-5406;Xu|Gang|G|http://orcid.org/0000-0003-2487-7002;Gao|Chuan|C|http://orcid.org/0000-0003-0248-1269;Wang|Dong|D|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1186/s13256-021-02765-x",
"fulltext": "\n==== Front\nJ Med Case Rep\nJ Med Case Rep\nJournal of Medical Case Reports\n1752-1947\nBioMed Central London\n\n2765\n10.1186/s13256-021-02765-x\nCase Report\nEsophageal metastases from primary lung cancer: a case report\nhttp://orcid.org/0000-0002-5348-5406\nWang Chang-Yong [email protected]\n\n1\nhttp://orcid.org/0000-0003-2487-7002\nXu Gang [email protected]\n\n2\nhttp://orcid.org/0000-0003-0248-1269\nGao Chuan [email protected]\n\n1\nWang Dong [email protected]\n\n2\n1 grid.440259.e 0000 0001 0115 7868 Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing, 210000 Jiangsu China\n2 grid.41156.37 0000 0001 2314 964X Department of Cardiothoracic Surgery, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210000 Jiangsu China\n12 5 2021\n12 5 2021\n2021\n15 26524 1 2020\n1 3 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBackground\n\nPrimary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. There are no cases of esophageal metastases from lung cancer which refer to its particular treatment.\n\nCase presentation\n\nWe report a case of esophageal metastases from lung cancer. The patient was a 55-year-old Han Chinese man who first attended our hospital due to dry cough and was diagnosed with late-stage lung cancer. Three months later, the patient complained of dysphagia. Endoscopic ultrasonography (EUS) and pathological examination of the biopsy specimen was performed to confirm the lesion was metastases from lung cancer. Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A were positive by immunohistochemistry examination. These results reconfirmed the diagnosis of esophageal metastases from lung cancer.\n\nConclusions\n\nEsophageal metastasis from lung cancer is very rare. It may be alleviated with personalized chemotherapy. In addition, molecular targeted therapy for patients with epidermal growth factor receptor (EGFR) mutations may be reasonable.\n\nKeywords\n\nLung cancer\nEsophageal metastases\nCase report\nissue-copyright-statement© The Author(s) 2021\n==== Body\nBackground\n\nLung cancer is a major cause of cancer-related death worldwide [1]. When diagnosed, approximately 50% of patients present with metastases. The most common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system [2]. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare [3]. Furthermore, most cases of esophageal metastases are asymptomatic, and are finally discovered at autopsy [4] rather than in clinics.\n\nHere we report a case of primary lung cancer metastasized to the esophagus and discuss diagnostic and treatment strategies, in order to give other doctors some supplemental information and references when treating such uncommon patients.\n\nCase presentation\n\nA 55-year-old Han Chinese man with a long-term history (30 years) of heavy smoking was referred to our hospital in March 2015 due to dry cough. His past medical history and family history were unremarkable. On a routine health checkup, an elevated carcinoembryonic antigen (CEA) value of 182.6 g/L (normal value, 0–9.8 g/L; Fig. 1) was found. A computed tomography (CT) scan of the chest showed a 48 × 42 mm tumor in the left lower lobe (Fig. 2a). A positron emission tomography (PET)-CT scan revealed multiple metastases in the left lower lung, bilateral supraclavicular fossa, hilus pulmonis, mediastinal lymph nodes and bone (Fig. 2d). The patient underwent CT-guided biopsy of the lung lesion. The biopsy tissue was identified as adenocarcinoma by pathological examination (Fig. 3a). Immunohistochemistry (IHC) examination showed that the tumor cells were positive for thyroid transcription factor 1 (TTF-1) and cytokeratin 7 (CK-7) (Fig. 3b, c). The epidermal growth factor receptor (EGFR) gene of the primary lung cancer harbored a mutation of the 19th exon. Clinically, the patient was diagnosed with stage IV lung adenocarcinoma, with the primary lesion in the left lower lobe. After communicating with the patient and his family, gefitinib (250 mg once a day) was initially commenced in April 2015. The primary tumor shrank about one-fifth after 2 months of treatment, and the patient did not experience obvious adverse effects.Fig. 1 Alteration of carcinoembryonic antigen (CEA) level and treatment at different time points. The patient first presented with an increased CEA level. The carcinoembryonic antigen level gradually decreased to 6.7g/L (normal value, 0–9.8 g/L) following 5 months of gefitinib and chemotherapy treatment\n\nFig. 2 Imaging study of a patient with esophageal metastases from lung cancer. a Computed tomography (CT) scan of the chest showed a 48 × 42 mm defined tumor at the ascending left lung (arrow), with a scallop-shaped contour and focal enhancement. b Gastroscopy images showed a 17.7 mm wall thickening at the distal esophagus 38 cm from the upper incisors (arrow), with the mucous epithelium being mildly hemorrhagic but without a distinct break. c Barium esophagography. Esophagography showed irregular thickening of the wall and narrowing of the lumen of the lower thoracic esophagus (arrow). d Positron emission tomography (PET)-CT. PET-CT showed multiple metastases (lower left lung, bilateral supraclavicular fossa, hilus pulmonis, mediastinum lymph node, bone).\n\nFig. 3 Histological and immunohistochemical staining results. a Cancer tissue revealing the atypical nest shape of the cell arrangement (stain, hematoxylin and eosin [HE]; magnification, ×100). The positive immunohistochemical staining (magnification, ×200) for b TTF-1 and c CK-7 indicates that the cancer originated in the lung. TTF-1 is specific for tumors of lung origin. TTF-1 (thyroid transcription factor 1); CK (cytokeratin)\n\nThree months later, during follow-up, the patient complained of dysphagia without melena. The patient could only eat fluids. Laboratory examinations indicated a an elevated CEA level of 112.3 g/L. Barium esophagography showed irregular thickening of the wall and narrowing of the lumen of the lower thoracic esophagus (Fig. 2c). Endoscopic ultrasonography (EUS) showed a 17.7 mm wall thickening at the distal esophagus 38 cm from the upper incisors, with mucous epithelium being mildly hemorrhagic but without a distinct break (Fig. 2b). There was also no evidence of active bleeding. The patient underwent biopsy of the esophageal lesion tissue under endoscopic ultrasonography (EUS). Pathological examination of the esophageal lesion tissue showed similar results as those of the primary lung adenocarcinoma (Fig. 4a). TTF-1 and CK-7 were positive by IHC (Fig. 4a, b). Napsin A staining was positive (Fig. 4d). Brain magnetic resonance imaging (MRI) revealed multiple metastases. The patient then received additional chemotherapy with docetaxel (60 mg day 1, day 8) and cisplatin (20 mg days 1–5), with gefitinib terminated. After one cycle of chemotherapy, the patient complained of chest tightness after activity. A CT scan showed pleural effusion and progression of the primary tumor. Closed thoracic drainage and injections of lentinan and cisplatin (two cycles) into the chest were conducted to alleviate the patient’s symptoms. The chemotherapy was then adjusted to pemetrexed (0.8 g day 1) and cisplatin (20 mg days 1–5). After six cycles of chemotherapy, the patient gradually returned to a normal diet. Follow-up CT scans showed complete response in the esophageal lesion, and the CEA level decreased to 6.7 g/L in September 2015. The primary lung tumor had partially shrunk. The patient then continued to take gefitinib (250 mg once daily), and the primary tumor was stable. In June, 2016, the patient began having headaches. Brain MRI revealed that the metastases had progressed. The CEA level rebounded to 21.3 g/L. The patient then received AZD9291 orally (80 mg once daily) without T790m mutation testing. His headache symptoms were alleviated, and there was no further follow-up of the patient. We learned by telephone follow-up that the patient died in January 2017.Fig. 4 Histological and immunohistochemical staining results. a Hematoxylin and eosin (HE) staining of the esophageal lesions (magnification, ×100). The cancer tissue exhibits similar HE morphology as lung adenocarcinoma. Positive immunohistochemical staining (magnification, ×100) for b thyroid transcription factor 1 and c cytokeratin 7, which is the same result as found in the lung adenocarcinoma. d Napsin A of the core biopsy of the esophageal mass shows stippled cytoplasmic positive staining. Napsin A is specific for tumors of lung origin\n\nDiscussion\n\nThis case reported a patient who was diagnosed with primary lung cancer with multiple metastases at the first visit, and the tumor metastasized to the esophagus during treatment. We recorded this case not only because it is a rare case in clinics, but also because of the many clinical characteristics during the whole course of treatment.\n\nLung cancer typically spreads to the liver, bones, brain, adrenal glands and central nervous system [4]. However, according to autopsy studies, the overall incidence of esophageal metastasis in patients dying of any type of cancer is approximately 3–6%, among which breast and lung represent the most common sites of the primary tumor [3].\n\nThere are several possible routes by which lung cancer can metastasize to the esophagus: bloodstream and lymphatic metastases, implantation metastases and direct invasion from nearby organs, namely the larynx, hypopharynx, trachea, bronchus, stomach and mediastinal lymph nodes [5]. According to the almost normal overlying mucosa observed by endoscopy in our patient’s esophagus, we consider that the metastases came from the bloodstream or lymphatic route, as this mechanism leads mainly to submucosal lesions.\n\nMost patients with metastases to the esophagus have no specific symptoms. Even when symptoms are present, they are usually nonspecific. Only a small number of patients complain of dysphagia, hoarseness and weight loss [6]. Our patient showed dysphagia due to stricture as a result of lymphatic or bloodstream metastases. Esophagography and endoscopy are useful diagnostic tools. Esophagram demonstration is characterized by regular stenosis of the esophagus. However, endoscopy often shows a normal mucosal surface when there is no serious growth of the esophageal metastasis. With the help of endoscopic ultrasound (EUS), more accurate information will be provided about the submucosal lesion [7]. Biopsies guided by EUS will reveal pathological findings. Histological and immunohistochemical staining can provide crucial information to distinguish whether the esophageal lesion comes from the lung adenocarcinoma. TTF-1 is specific for tumors of lung origin. TTF-1 is expressed in the epithelial cells of the thyroid gland and lung, while adenocarcinomas are malignant transformations evolved from these cells [8]. TTF-1 has been shown to be a sensitive and highly specific marker of adenocarcinomas of pulmonary origin, in tissue biopsies and cytological preparations. TTF-1 is expressed mainly in 68–80% of primary lung adenocarcinomas, but expressed in less than 1% of adenocarcinomas of non-pulmonary origin [9, 10]. Napsin A is also specific for tumors originating from the lung. Napsin A is expressed in 84.5% of primary lung adenocarcinomas, but not expressed in adenocarcinomas of other sites. Double staining of TTF-1 and napsin A has been proposed to increase the sensitivity and specificity of pulmonary-originated adenocarcinomas. [11]. Moreover, CK-7 can identify primary lung cancer. However, some studies found that primary adenocarcinomas of the rectum and small intestine may also express CK-7 in a small number of cases [12]. In our case, due to the marker’s high specificity, positive results for TTF-1 and napsin A provided strong evidence of the pulmonary origin of the esophageal lesions, with addition of the clinical and morphological findings.\n\nAccurate distinction between esophageal metastasis and the primary cancer is of key importance, as it determines the treatment and prognosis of patients [4]. Once the patient was diagnosed with esophageal metastasis originating from the pulmonary tumor, we administered chemotherapy, which achieved good results in the esophageal metastasis. However, the primary lung adenocarcinoma did not response sensitively. This phenomenon may be explained by the molecular diversity of tumors in different locations [13].\n\nThe prognosis for lung cancer with metastasis to the esophagus is poor [14]. Therefore, the therapeutic strategy should be comprehensive and personalized. Our patient had an EGFR gene mutation in exon 19 and was treated with gefitinib. In June 2016, the patient’s brain metastases progressed. He took the original drug AZD9291 (osimertinib) on his own. It may be effective, as his headache symptoms subsided, although with a lack of clinical imaging evidence. Mounting evidence has now demonstrated that AZD9291 treatment is independently associated with longer overall survival in patients with a T790M mutation [15, 16]. In general, surgery is contraindicated in patients with organ metastases originating from lung cancer. However, some authors have reported prolonged survival in cases following management of oligometastasis of the bone, brain and small bowel [17] from lung cancer. There are no cases to date of patients who received local treatment for esophageal metastases from lung cancer. However, surgical intervention is often adopted when gastrointestinal metastases lead to continuous bleeding, obstruction or perforation [4].\n\nConclusion\n\nEsophageal metastases from lung cancer are extremely rare. However, clinicians should be aware of their occurrence. The diagnosis of esophageal metastasis is specific and is important to guide follow-up therapy. Comprehensive and personalized treatment may be beneficial in these patients. Molecular targeted therapy may be a reasonable choice in patients with EGFR mutations.\n\nArticle highlights\n\nCase characteristics\n\nThe patient was a 55-year-old man who presented to our hospital due to stimulated cough.\n\nClinical diagnosis\n\nThe patient was diagnosed with lung cancer.\n\nDifferential diagnosis\n\nMucosal biopsy from endoscopy was useful for differential diagnosis, and histological analysis revealed lung cancer.\n\nLaboratory diagnosis\n\nLaboratory findings revealed elevated tumor markers (CEA).\n\nImaging diagnosis\n\nA computed tomography (CT) scan of the chest revealed a 48×42 mm defined tumor at the ascending left lung.\n\nPathological diagnosis\n\nPathological report of the tissue biopsy. Immunohistochemistry was positive for thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A. These results confirmed the diagnosis of esophageal metastasis from the lung.\n\nTreatment\n\nThe patient underwent an EGFR gene testing of the primary lung cancer which harbored a 19th exon mutation. Gefitinib treatment and first-line chemotherapy based on docetaxel and cisplatin. After the chemotherapy, the patient then received the closed thoracic drainage and injected the lentinan and cisplatin (two cycles). Then the patient received six cycles of second-line chemotherapy with pemetrexed and cisplatin.\n\nAbbreviations\n\nEUS Endoscopic ultrasonography\n\nTTF-1 Thyroid transcription factor 1\n\nCK Cytokeratin\n\nCEA Carcinoembryonic antigen\n\nCT Computed tomography\n\nAcknowledgements\n\nWe would like to acknowledge the patient and his family for allowing us to use his medical records in our case report and allowing this case to be published.\n\nAuthors' contributions\n\nGX designed the case report and reviewed the manuscript. CYW and CG wrote the manuscript. All authors discussed the case and commented on the manuscript. All authors read and approved the final manuscript.\n\nFunding\n\nSpecific funding was not used to perform this study.\n\nAvailability of data and materials\n\nWe respect the patient’s rights to privacy, and to protect his identity, we do not wish to share our patient data. We presented in the manuscript all the necessary information about the case report. Raw data regarding our patient is in his admission file, a file that is strictly confidential, without the possibility of publishing raw data from it.\n\nDeclarations\n\nEthics approval and consent to participate\n\nThis clinical study of the above mentioned case report was waived by the institutional review board at our center.\n\nPatient consent for publication\n\nWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\n\nCompeting interests\n\nThe authors declare that they have no competing interests.\n\nPublisher's Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Jemal A Bray F Center MM Ferlay J Ward E Forman D Global cancer statistics CA Cancer J Clin 2011 61 2 69 90 10.3322/caac.20107 21296855\n2. van Meerbeeck JP Fennell DA De Ruysscher DKM Small-cell lung cancer Lancet 2011 378 9804 1741 1755 10.1016/S0140-6736(11)60165-7 21565397\n3. Abrams HL Spiro R Goldstein N Metastases in carcinoma; analysis of 1000 autopsied cases Cancer 1950 3 1 74 85 10.1002/1097-0142(1950)3:1<74::AID-CNCR2820030111>3.0.CO;2-7 15405683\n4. Antler AS Ough Y Pitchumoni CS Davidian M Thelmo W Gastrointestinal metastases from malignant tumors of the lung Cancer 1982 49 1 170 172 10.1002/1097-0142(19820101)49:1<170::AID-CNCR2820490134>3.0.CO;2-A 6274500\n5. Simchuk EJ Low DE Direct esophageal metastasis from a distant primary tumor is a submucosal process: a review of six cases Dis Esoph 2001 14 3–4 247 250 10.1046/j.1442-2050.2001.00195.x\n6. Goldberg RI Rams H Stone B Barkin JS Dysphagia as the presenting symptom of recurrent breast carcinoma Cancer 1987 60 5 1085 1088 10.1002/1097-0142(19870901)60:5<1085::AID-CNCR2820600527>3.0.CO;2-8 3300948\n7. Teh GXJ Tan D Khor JL Wan WK Wang YT Esophageal metastatic adenocarcinoma diagnosed with endoscopic ultrasound Case Reports Gastroenterol 2017 11 3 694 700 10.1159/000484133\n8. Pelosi G Fraggetta F Pasini F Maisonneuve P Sonzogni A Iannucci A Terzi A Bresaola E Valduga F Lupo C Immunoreactivity for thyroid transcription factor-1 in stage I non–small cell carcinomas of the lung Am J Surg Pathol 2001 25 3 363 372 10.1097/00000478-200103000-00011 11224607\n9. Zamecnik J Kodet R Value of thyroid transcription factor-1 and surfactant apoprotein A in the differential diagnosis of pulmonary carcinomas: a study of 109 cases Virchows Arch 2002 440 4 353 361 10.1007/s00428-001-0552-2 11956814\n10. Ordóñez NG Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas Adv Anat Pathol 2000 7 2 123 127 10.1097/00125480-200007020-00007 10721419\n11. Han H-S Eom D-W Kim JH Kim K-H Shin H-M An JY Lee KM Choe KH Lee KH Kim ST EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases Clin Lung Cancer 2011 12 6 380 386 10.1016/j.cllc.2011.02.006 21729655\n12. Chen Z Wang HL Alteration of cytokeratin 7 and cytokeratin 20 expression profile is uniquely associated with tumorigenesis of primary adenocarcinoma of the small intestine Am J Surg Pathol 2004 28 10 1352 1359 10.1097/01.pas.0000135520.72965.50 15371952\n13. Italiano A Vandenbos FB Otto J Mouroux J Fontaine D Marcy PY Cardot N Thyss A Pedeutour F Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors Ann Oncol 2006 17 6 981 985 10.1093/annonc/mdl038 16524970\n14. Kobayashi O Murakami H Yoshida T Cho H Yoshikawa T Tsuburaya A Sairenji M Motohashi H Sugiyama Y Kameda Y Clinical diagnosis of metastatic gastric tumors: clinicopathologic findings and prognosis of nine patients in a single cancer center World J Surg 2004 28 6 548 551 10.1007/s00268-004-7216-8 15366743\n15. Joo JW Hong MH Shim HS Clinical characteristics of T790M-positive lung adenocarcinoma after resistance to epidermal growth factor receptor-tyrosine kinase inhibitors with an emphasis on brain metastasis and survival Lung Cancer 2018 121 12 17 10.1016/j.lungcan.2018.04.013 29858020\n16. Auliac JB Pérol M Planchard D Monnet I Wislez M Doubre H Guisier F Pichon E Greillier L Mastroianni B Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation Lung Cancer 2019 127 56 10.1016/j.lungcan.2018.11.037\n17. Kim MS Kook EH Ahn SH Jeon SY Yoon JH Han MS Kim CH Lee JC Gastrointestinal metastasis of lung cancer with special emphasis on a long-term survivor after operation J Cancer Res Clin Oncol 2009 135 2 297 301 10.1007/s00432-008-0424-0 18512073\n\n",
"fulltext_license": "CC BY",
"issn_linking": "1752-1947",
"issue": "15(1)",
"journal": "Journal of medical case reports",
"keywords": "Case report; Esophageal metastases; Lung cancer",
"medline_ta": "J Med Case Rep",
"mesh_terms": "D019160:Endosonography; D004938:Esophageal Neoplasms; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary",
"nlm_unique_id": "101293382",
"other_id": null,
"pages": "265",
"pmc": null,
"pmid": "33975638",
"pubdate": "2021-05-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "11869331;21565397;11956814;3300948;16524970;30642559;6274500;18512073;11224607;15405683;21296855;29858020;10721419;15366743;21729655;15371952;29430220",
"title": "Esophageal metastases from primary lung cancer: a case report.",
"title_normalized": "esophageal metastases from primary lung cancer a case report"
}
|
[
{
"companynumb": "2021A800106",
"fulfillexpeditecriteria": "1",
"occurcountry": null,
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "GEFITINIB"
},
"drugadditional": "1",
"drugadministrationroute": "048",
"drugauthorizationnumb": "206995",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Tablet",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Lung adenocarcinoma stage IV",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201504",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GEFITINIB"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "GEFITINIB"
},
"drugadditional": "1",
"drugadministrationroute": "048",
"drugauthorizationnumb": "206995",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Tablet",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Lung adenocarcinoma stage IV",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201504",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GEFITINIB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "OSIMERTINIB"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Tablet",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Lung adenocarcinoma stage IV",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "201606",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "80",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TAGRISSO"
}
],
"patientagegroup": null,
"patientonsetage": "55",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Malignant neoplasm progression",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Metastases to oesophagus",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Metastases to central nervous system",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Wang D, Wang C-Y, Xu G, Gao C. Esophageal metastases from primary lung cancer: a case report. Journal of Medical Case Reports 2021;15(1):265.",
"literaturereference_normalized": "esophageal metastases from primary lung cancer a case report",
"qualification": "3",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20211118",
"receivedate": "20211118",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20087666,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
}
] |
{
"abstract": "Heat stroke is a medical emergency which may lead to mortality unless diagnosed early and treated effectively. Heat stroke may manifest rapidly, hence making it difficult to differentiate it from other clinical causes in a collapsed victim.1 We are presenting a case report of twelve patients who were admitted to our emergency department from a music festival held on 13-15th of March 2014. They developed complications arising from a combination of severe adverse weather condition, prolonged outdoor physical exertion due to long hours of dancing and drug-use, resulting in heat stroke. Three of them died while the remaining patients survived. Their condition was initially misdiagnosed as a classical illicit drug overdose. This was based on the history of drug ingestion by some of the patients who attended the music festival on that day. The information in this case report aims, to create awareness amongst members of the medical team on duty in outdoor events, pre hospital responders and ED physicians when treating and managing similar cases in the future. In addition it is intended to warn the organizers of such events to take adequate precautions to avoid such tragedies in the future.",
"affiliations": "Department of Forensic Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: [email protected].;Department of Emergency Medicine, University of Malaya, Kuala Lumpur, Malaysia.;Department of Emergency Medicine, University of Malaya, Kuala Lumpur, Malaysia.",
"authors": "Nadesan|K|K|;Kumari|Chandra|C|;Afiq|Mohd|M|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1016/j.jflm.2017.05.008",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1752-928X",
"issue": "50()",
"journal": "Journal of forensic and legal medicine",
"keywords": "Disseminated intravascular coagulation; Drug abuse; Heat stroke; MDMA",
"medline_ta": "J Forensic Leg Med",
"mesh_terms": "D000328:Adult; D003615:Dancing; D004636:Emergency Service, Hospital; D005260:Female; D018883:Heat Stroke; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D008297:Male; D009206:Myocardium; D005082:Physical Exertion; D019966:Substance-Related Disorders; D055815:Young Adult",
"nlm_unique_id": "101300022",
"other_id": null,
"pages": "1-5",
"pmc": null,
"pmid": "28651196",
"pubdate": "2017-08",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Dancing to death: A case of heat stroke.",
"title_normalized": "dancing to death a case of heat stroke"
}
|
[
{
"companynumb": "MY-MYLANLABS-2017M1053783",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MIDOMAFETAMINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ECSTASY"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "KETAMINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "076092",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "KETAMINE"
}
],
"patientagegroup": null,
"patientonsetage": "22",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170831",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13925177,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-MYLANLABS-2017M1053792",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "200824",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
}
],
"patientagegroup": null,
"patientonsetage": "24",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Substance use",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Coma",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170831",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13925168,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-MYLANLABS-2017M1053793",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "KETAMINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "076092",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "KETAMINE"
}
],
"patientagegroup": null,
"patientonsetage": "24",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170831",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13925166,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-MYLANLABS-2017M1053791",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "200824",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
}
],
"patientagegroup": null,
"patientonsetage": "26",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Substance use",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Coma",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170831",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13925169,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-MYLANLABS-2017M1053788",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "200824",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
}
],
"patientagegroup": null,
"patientonsetage": "26",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coma",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Substance use",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170830",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13922959,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-MYLANLABS-2017M1053794",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "KETAMINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "076092",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "KETAMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
}
],
"patientagegroup": null,
"patientonsetage": "25",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170831",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13925170,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-MYLANLABS-2017M1053787",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MORPHINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "200824",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DIAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAZEPAM."
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coma",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Substance use",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED 2017;50:1-5.",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170918",
"receivedate": "20170830",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13922951,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
},
{
"companynumb": "MY-LANNETT COMPANY, INC.-MY-2017LAN001036",
"fulfillexpeditecriteria": "1",
"occurcountry": "MY",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DIAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "204433",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAZEPAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MORPHINE SULFATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MORPHINE SULFATE."
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coma",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Heat stroke",
"reactionmeddraversionpt": "20.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NADESAN K, KUMARI C, AFIQ M. DANCING TO DEATH: A CASE OF HEAT STROKE. J-FORENS-LEGAL-MED. 2017;501-505",
"literaturereference_normalized": "dancing to death a case of heat stroke",
"qualification": "1",
"reportercountry": "MY"
},
"primarysourcecountry": "MY",
"receiptdate": "20170912",
"receivedate": "20170912",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13961653,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20171128"
}
] |
{
"abstract": "We describe the case of a 68-year-old woman with an acute episode of severe low back pain (LBP) resistant to opioids, who had experienced a sacral insufficiency fracture (SIF) two years earlier. At clinical examination, patient reported constant, dull, non-localizable pain at lumbar and sacral level, exacerbated by paravertebral palpation, particularly at L4-L5 and the sacroiliac joint, with a concomitant and remittent neuropathic component, difficult to localize at lumbar and sacral level. The latest magnetic resonance imaging study revealed disc herniations at L3-L4, L4-L5, and L5-S1 levels. The patient was treated with intramuscularparavertebral injections of oxygen-ozone (O2O3) mixture for 4 weeks (once a week), using a O3 concentration of 20 mcg/mL (5 mL in L4-L5 zone and 5 mL in L5-S1 zone, bilaterally). At 1 week after the first injection, the pain (assessed by Numerical Pain Rating Scale and Brief Pain Inventory) was considerably reduced and the patient's health-related quality of life (assessed by Short Form 12-Item Health Survey and European Quality of Life Index) had improved; these findings were confirmed at follow-up 1 month after the last injection. This paradigmatic case of nociplastic pain successfully treated by paravertebral O2O3 therapy might be a starting point for further studies on the effects of this treatment in terms of decreasing pain and improving HRQoL in patients affected by opioid-resistant LBP.",
"affiliations": null,
"authors": "de Sire|A|A|;Baricich|Alessio|A|;Minetto|Marco Alessandro|MA|;Cisari|C|C|;Invernizzi|M|M|",
"chemical_list": "D010126:Ozone; D010100:Oxygen",
"country": "Italy",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0393-5264",
"issue": "34(2)",
"journal": "Functional neurology",
"keywords": null,
"medline_ta": "Funct Neurol",
"mesh_terms": "D000368:Aged; D005260:Female; D015775:Fractures, Stress; D006801:Humans; D007405:Intervertebral Disc Displacement; D017116:Low Back Pain; D059225:Nociception; D010100:Oxygen; D010126:Ozone; D010147:Pain Measurement; D012447:Sacrum; D016896:Treatment Outcome",
"nlm_unique_id": "8707746",
"other_id": null,
"pages": "119-122",
"pmc": null,
"pmid": "31556392",
"pubdate": "2019",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Low back pain related to a sacral insufficiency fracture: role of paravertebral oxygen-ozone therapy in a paradigmatic case of nociplastic pain.",
"title_normalized": "low back pain related to a sacral insufficiency fracture role of paravertebral oxygen ozone therapy in a paradigmatic case of nociplastic pain"
}
|
[
{
"companynumb": "IT-SUN PHARMACEUTICAL INDUSTRIES LTD-2019R1-229963",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN\\OXYCODONE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "090535",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Tablet",
"drugdosagetext": "10 MG/325 MG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Back pain",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "12",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETAMINOPHEN\\OXYCODONE HYDROCHLORIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN\\OXYCODONE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "090535",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Tablet",
"drugdosagetext": "20 MG/650, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "12",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETAMINOPHEN\\OXYCODONE HYDROCHLORIDE"
}
],
"patientagegroup": null,
"patientonsetage": "68",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug resistance",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "De Sire A, Baricich A, Minetto MA, Cisari C, Invernizzi M. Low back pain related to a sacral insufficiency fracture: Role of paravertebral oxygen-ozone therapy in a paradigmatic case of nociplastic pain. Funct Neurol. 2019;34(2):119-122",
"literaturereference_normalized": "low back pain related to a sacral insufficiency fracture role of paravertebral oxygen ozone therapy in a paradigmatic case of nociplastic pain",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20220202",
"receivedate": "20191213",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17149519,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220423"
}
] |
{
"abstract": "Standard methods for enumerating Mycobacterium tuberculosis in patient sputum can miss large populations of viable M. tuberculosis cells that are unable to grow either on solid medium or in liquid medium unless the medium has been extensively diluted. Because these bacteria can be detected in liquid medium after limiting dilution, they have been termed differentially culturable or differentially detectable M. tuberculosis (DD-Mtb). Treatment with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) for 1 to 2 weeks has been shown to increase the representation of DD-Mtb in the sputum of drug-sensitive (DS) tuberculosis (TB) patients. However, little is known about DD-Mtb after longer periods of treatment with HRZE or in patients with drug-resistant (DR) TB who receive second-line therapies. Here, we measured the proportion of DD-Mtb cells in the sputum of 47 subjects, 29 with DS TB and 18 with DR TB, before initiation of treatment and at 2 weeks and 2 months thereafter. Prior to treatment, DD-Mtb cells represented the majority of M. tuberculosis cells in the sputum of 21% of subjects with DS TB, and this proportion rose to 65% after 2 weeks of treatment with first-line drugs. In subjects with DR TB, DD-Mtb cells were found in the sputum of 29% of subjects prior to treatment initiation, and this proportion remained steady at 31% after 2 weeks of treatment with second-line drugs. By 2 months, DD-Mtb cells were detected in the sputum of only 2/15 (13.3%) subjects with DS TB and in 0/15 of subjects with DR TB. One of the DS subjects whose sputum was positive for DD-Mtb at month 2 later experienced treatment failure.",
"affiliations": "Center for Global Health, Weill Cornell Medicine, New York, New York, USA.;Center for Global Health, Weill Cornell Medicine, New York, New York, USA.;Les Centres GHESKIO, Port-au-Prince, Haiti.;Les Centres GHESKIO, Port-au-Prince, Haiti.;Center for Global Health, Weill Cornell Medicine, New York, New York, USA.;Department of Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA.;Department of Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA.;Center for Global Health, Weill Cornell Medicine, New York, New York, USA.;Center for Global Health, Weill Cornell Medicine, New York, New York, USA.;Department of Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA.;Center for Global Health, Weill Cornell Medicine, New York, New York, USA.",
"authors": "Zainabadi|Kayvan|K|;Walsh|Kathleen Frances|KF|;Vilbrun|Stalz Charles|SC|;Mathurin|Laurent Daniel|LD|;Lee|Myung Hee|MH|;Saito|Kohta|K|;Mishra|Saurabh|S|;Ocheretina|Oksana|O|;Pape|Jean William|JW|;Nathan|Carl|C|;Fitzgerald|Daniel W|DW|",
"chemical_list": "D000995:Antitubercular Agents; D004364:Pharmaceutical Preparations",
"country": "United States",
"delete": false,
"doi": "10.1128/AAC.00608-21",
"fulltext": "\n==== Front\nAntimicrob Agents Chemother\nAntimicrob Agents Chemother\naac\nAntimicrobial Agents and Chemotherapy\n0066-4804\n1098-6596\nAmerican Society for Microbiology 1752 N St., N.W., Washington, DC\n\n34060896\n00608-21\n10.1128/AAC.00608-21\nClinical Therapeutics\nCharacterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy\nhttps://orcid.org/0000-0003-3134-1783\nZainabadi Kayvan ab\nhttps://orcid.org/0000-0002-9001-3918\nWalsh Kathleen Frances ac\nVilbrun Stalz Charles d\nMathurin Laurent Daniel d\nLee Myung Hee a\nSaito Kohta b\nMishra Saurabh b\nOcheretina Oksana a\nPape Jean William ad\nhttps://orcid.org/0000-0002-7744-8896\nNathan Carl [email protected]\n\nFitzgerald Daniel W. [email protected]\n\na Center for Global Health, Weill Cornell Medicine, New York, New York, USA\nb Department of Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA\nc Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York, USA\nd Les Centres GHESKIO, Port-au-Prince, Haiti\nCarl Nathan and Daniel W. Fitzgerald are co-senior authors of this study.\n\nCitation Zainabadi K, Walsh KF, Vilbrun SC, Mathurin LD, Lee MH, Saito K, Mishra S, Ocheretina O, Pape JW, Nathan C, Fitzgerald DW. 2021. Characterization of differentially detectable Mycobacterium tuberculosis in the sputum of subjects with drug-sensitive or drug-resistant tuberculosis before and after two months of therapy. Antimicrob Agents Chemother 65:e00608-21. https://doi.org/10.1128/AAC.00608-21.\n\n1 6 2021\n16 7 2021\n8 2021\n65 8 e00608-2124 3 2021\n9 5 2021\n19 5 2021\nCopyright © 2021 Zainabadi et al.\n2021\nZainabadi et al.\nhttps://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.\n\nABSTRACT\n\nStandard methods for enumerating Mycobacterium tuberculosis in patient sputum can miss large populations of viable M. tuberculosis cells that are unable to grow either on solid medium or in liquid medium unless the medium has been extensively diluted. Because these bacteria can be detected in liquid medium after limiting dilution, they have been termed differentially culturable or differentially detectable M. tuberculosis (DD-Mtb). Treatment with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) for 1 to 2 weeks has been shown to increase the representation of DD-Mtb in the sputum of drug-sensitive (DS) tuberculosis (TB) patients. However, little is known about DD-Mtb after longer periods of treatment with HRZE or in patients with drug-resistant (DR) TB who receive second-line therapies. Here, we measured the proportion of DD-Mtb cells in the sputum of 47 subjects, 29 with DS TB and 18 with DR TB, before initiation of treatment and at 2 weeks and 2 months thereafter. Prior to treatment, DD-Mtb cells represented the majority of M. tuberculosis cells in the sputum of 21% of subjects with DS TB, and this proportion rose to 65% after 2 weeks of treatment with first-line drugs. In subjects with DR TB, DD-Mtb cells were found in the sputum of 29% of subjects prior to treatment initiation, and this proportion remained steady at 31% after 2 weeks of treatment with second-line drugs. By 2 months, DD-Mtb cells were detected in the sputum of only 2/15 (13.3%) subjects with DS TB and in 0/15 of subjects with DR TB. One of the DS subjects whose sputum was positive for DD-Mtb at month 2 later experienced treatment failure.\n\nKEYWORDS\n\nMycobacterium tuberculosis\ndiagnostics\nmultidrug resistance\npulmonary infection\nviable but nonculturable\nHHS | NIH | Fogarty International Center (FIC) https://doi.org/10.13039/100000061 D43 TW009337 Zainabadi Kayvan HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) https://doi.org/10.13039/100000060 K08 AI139360 Saito Kohta HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) https://doi.org/10.13039/100000060 U19AI111143 Nathan Carl Fitzgerald Daniel W. HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) https://doi.org/10.13039/100000060 K24AI098627 Fitzgerald Daniel W. cover-dateAugust 2021\n==== Body\nINTRODUCTION\n\nIn 2019, 10 million cases of tuberculosis (TB) led to approximately 1.4 million deaths, making TB the leading cause of death from a single infectious agent prior to COVID-19 (1). TB exerts a devastating toll in the developing world, where more than 95% of deaths occur, and is projected to lead to an economic loss of U.S. $1 trillion from 2015 to 2030 (2). New drug regimens are needed to shorten the currently required 6-month treatment protocol for drug-sensitive (DS) TB and to combat drug-resistant (DR) TB.\n\nTo evaluate the efficacy of new drug regimens in phase I/II early bactericidal activity (EBA) trials, viable Mycobacterium tuberculosis cells are quantified from the sputum of pulmonary TB patients during the first 2 to 8 weeks of therapy. The gold-standard method for enumerating M. tuberculosis is culturing sputum on solid agar and counting the number of CFU. This approach is often supplemented or replaced by assessing time to positivity (TTP) of sputum samples in an automated liquid culture system that measures the rate of depletion of oxygen from culture medium as a proxy for M. tuberculosis growth and quantity. These techniques may miss subpopulations of M. tuberculosis that are incapable of growing on solid medium or in liquid medium if the suspension has not been extensively diluted (3–12). These bacteria have been called by the interchangeable terms “viable but nonculturable” (VBNC-Mtb) (13), “differentially culturable” (DCTB) (10), and “differentially detectable” M. tuberculosis (DD-Mtb) (8). Here, we refer to these bacteria as “DD-Mtb” because they are often culturable and because they can sometimes be identified by methods other than culture, such as by inoculation into an experimental host. The role of limiting dilution in detection of DD-Mtb has been linked to imposition of a delay in onset of replication, which allows for repair of oxidative injury (K. Saito, S. Mishra, T. Warrier, N. Cicchetti, J. Mi, E. Weber, J. Roberts, A. Gouzy, E. Kaplan, C. D. Brown, B. Gold, and C. Nathan, unpublished data). Notably, DD-Mtb cells show profound phenotypic tolerance to anti-TB chemotherapy (8, 14, 15).\n\nDD-Mtb bacteria were suspected to exist in humans when lung homogenates prepared at autopsy detected no M. tuberculosis based on CFU, but aliquots of the same homogenates caused TB in guinea pigs (16). These suspicions were validated in 2010 when Mukamolova et al. (9) reported that DD-Mtb constituted 80 to 99.9% of the viable M. tuberculosis bacteria in sputa from 20 of 25 (80%) treatment-naive TB patients, as revealed by comparing CFU counts to the most probable number (MPN) estimation from liquid medium using a limiting dilution (LD) assay. Treatment with rifampin for 7 to 11 days reduced the number of M. tuberculosis bacteria detected by CFU in the sputa to a much greater extent than it reduced M. tuberculosis bacteria detected by the MPN-LD method, indicating proportionate enrichment of DD-Mtb populations during therapy (9). Similarly, Chengalroyen et al. (10) reported that DD-Mtb represented the majority of viable M. tuberculosis cells in the sputa of >70% of 110 treatment-naive TB patients in South Africa. In both studies, DD-Mtb populations were detectable in some specimens only when the LD assay was performed in medium supplemented with culture filtrate (CF), that is, cell-free medium from a growing culture of a laboratory strain of M. tuberculosis. However, in the studies of Chengalroyen et al. (10) and McAulay et al. (11), MPN-LD assays performed with CF impaired the detection of DD-Mtb from some sputum samples (17).\n\nWith methodological and statistical methods designed to increase stringency (8), sputum samples from 21% of treatment-naive Haitian subjects with TB were found to be dominated by DD-Mtb, and this proportion increased to 69% after 2 weeks of isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) treatment (11). That study left unanswered the questions of how long DD-Mtb populations persist during treatment and how treatments other than HRZE may affect their persistence and/or generation.\n\nCollectively, these findings suggest that not taking DD-Mtb into account could complicate interpretation of EBA trials of investigational TB drugs and contribute to the ambiguous clinical significance of sputum conversion—the apparent elimination of viable M. tuberculosis bacteria— after 2 months of treatment (5, 8, 9, 11, 14, 15). The present study is meant to help lay the groundwork for filling the following knowledge gaps about DD-Mtb. Does their prevalence differ between specimens from subjects with DS or DR TB? Is the impact of HRZE on their prevalence different from the impact of other treatment regimens? What happens to DD-Mtb bacteria in sputum when measured at 2 weeks and at 2 months of treatment, at a later time point than those in earlier studies? To address these questions, we used the methods of Saito et al. (8) and McAulay et al. (11) to study additional subjects with DS TB and those with DR TB, to perform DD-Mtb tests before treatment and at 2 weeks and 2 months after the onset of treatment, and to monitor the clinical outcome at 6 months.\n\nRESULTS\n\nPatient characteristics.\n\nBetween May 2018 and September 2020, we enrolled 29 participants with DS TB and 18 participants with DR TB. Their characteristics are described in Table 1. The prevalences of bilateral disease, dyspnea (grade 2+), and prior treatment with first-line drugs were significantly higher at time of enrollment for participants with DR versus those with DS TB (Table 1).\n\nTABLE 1 Characteristics of the drug-sensitive and drug-resistant TB cohorts at time of enrollment\n\nCharacteristicb\tCohortc\tP\t\nDS (n = 29)\tDR (n = 18)\t\nMale (% [n])\t62.1 (18)\t50 (9)\t0.546\t\nHIV+ (% [n])a\t3.4 (1)\t22.2 (4)\t0.063\t\nPresence of cavities (% [n])\t48.3 (14)\t44.4 (8)\t1.0\t\nBilateral disease (% [n])\t31.0 (9)\t72.2 (13)\t0.008\t\nPrior first-line TB treatment (% [n])\t0 (0)\t83.3 (15)\t<0.001\t\nBlood-tinged sputum (% [n])\t0 (0)\t11.1 (2)\t0.142\t\nPleuritic chest pain (% [n])\t34.5 (10)\t55.6 (10)\t0.226\t\nFever (% [n])\t34.5 (10)\t11.1 (2)\t0.095\t\nAge in yrs (median [IQR])\t33 (28–37)\t32 (28–41)\t0.793\t\nHemoglobin, g/dl (median [IQR])\t10.7 (9.8–11.3)\t11.0 (10.3–11.5)\t0.456\t\nCreatinine, mg/dl (median [IQR])\t0.7 (0.6–0.8)\t0.6 (0.5–0.7)\t0.159\t\nPulse oximetry, % (median [IQR])\t97 (95–98)\t98 (97–99)\t0.113\t\nBMI (median [IQR])\t19.0 (17.1–21.0)\t17.7 (16.8–19.6)\t0.381\t\nDyspnea (% [n])\t\t\t<0.001\t\n Not present\t44.8 (13)\t16.7 (3)\t\t\n Grade 1\t55.2 (16)\t22.2 (4)\t\t\n Grade 2\t0 (0)\t55.6 (10)\t\t\n Grade 3\t0 (0)\t5.6 (1)\t\t\nCough (% [n])\t\t\t0.074\t\n Not present\t0 (0)\t5.6 (1)\t\t\n Grade 1\t89.7 (26)\t66.7 (12)\t\t\n Grade 2\t10.3 (3)\t22.2 (4)\t\t\n Grade 3\t0 (0)\t5.6 (1)\t\t\nXpert positivity (% [n])\t\t\t0.948\t\n Very low\t3.4 (1)\t0 (0)\t\t\n Low\t13.8 (4)\t11.1 (2)\t\t\n Medium\t37.9 (11)\t50 (9)\t\t\n High\t44.8 (13)\t38.9 (7)\t\t\na All HIV+ participants were on antiretroviral therapy at time of enrollment and during the duration of this study.\n\nb IQR, interquartile range; BMI, body mass index.\n\nc DS, drug susceptible; DR, drug resistant.\n\nOf the 18 DR participants, 15 had prior treatment with first-line anti-TB drugs. All isolates were resistant to rifampin (with isolates from 14 subjects showing resistance to rifabutin as well); 17 also showed resistance to isoniazid, and 15 were resistant to additional drugs besides rifamycins and isoniazid (see Table S1 in the supplemental material).\n\nProportion of TB subjects with DD-Mtb before and after initiation of therapy.\n\nM. tuberculosis numbers were quantified from the sputa of DS and DR TB subjects in three different ways, as follows: (i) CFU counting using solid agar plates, (ii) MPN using a limiting dilution (MPN-LD) assay without culture filtrate (MPN−CF), and (iii) MPN-LD assay with 50% sterile culture filtrate (MPN+CF). DD-Mtb was said to be present when the CFU value was less than the lower bound of the 95% confidence interval of the MPN−CF or MPN+CF value. Some sample collections were missed because of civic unrest and the COVID-19 pandemic, and some samples were lost to contamination, so that day 0 and week 2 data were both available for 23/29 and 17/18 subjects with DS and DR TB, respectively; and month 2 data were available for 15/29 and 15/18 subjects with DS and DR TB, respectively.\n\nThe proportion of participants whose sputa were DD-Mtb positive was comparable before onset of therapy in treatment-naive subjects with DS TB (20.7%) and in those with DR TB before administration of second-line therapy (29.4%) (Fig. 1 and Table 2). This was apparent when performing the MPN-LD assay without CF (17.2% versus 22.2% positivity for DD-Mtb in the sputa of subjects with DS and DR TB, respectively), although when the MPN-LD assay was performed with CF, a 2.3-fold higher proportion of subjects with DR TB showed presence of DD-Mtb in their sputa in comparison to subjects with DS TB (10.3% versus 23.5% for sputa from DS and DR TB subjects, respectively) (Table 2). In comparison, only 1/29 (3.4%) subjects with DS TB and 1/18 (5.6%) of those with DR TB provided sputum with a CFU value higher than the upper bound of the 95% confidence interval of the MPN−CF or MPN+CF value.\n\nFIG 1 Ratio of most probable number (MPN) to CFU (MPN/CFU), with and without culture filtrate (CF), for sputum from subjects with drug-sensitive (DS) and drug-resistant (DR) TB at day 0 and week 2 post initiation of therapy. The dashed line represents an MPN/CFU ratio of 1. Raw numbers can be found in Table S4 in the supplemental material. An asterisk (*) indicates data not available due to contamination.\n\nTABLE 2 Proportion of subjects with drug-sensitive or drug-resistant TB whose sputum was positive for DD-Mtb before and after initiation of therapy\n\nCulture filtrate status\tTime pointb\t% (n) of subjects positive for DD-Mtb in cohortc:\tPa\t\nDS\tDR\t\nAll\tDay 0\t20.7 (6/29)\t29.4 (5/17)\t0.726\t\nWk 2\t65.2 (15/23)\t31.3 (5/16)\t0.054\t\nMo 2\t13.3 (2/15)\t0 (0/15)\tNA\t\n−CF\tDay 0\t17.2 (5/29)\t22.2 (4/18)\t0.716\t\nWk 2\t65.2 (15/23)\t17.6 (3/17)\t0.004\t\nMo 2\t0 (0/15)\t0 (0/15)\tNA\t\n+CF\tDay 0\t10.3 (3/29)\t23.5 (4/17)\t0.397\t\nWk 2\t60.9 (14/23)\t25.0 (4/16)\t0.049\t\nMo 2\t13.3 (2/15)\t0 (0/15)\tNA\t\na Comparing DS to DR. NA, not applicable.\n\nb Day 0 was prior to initiation of therapy.\n\nc Positivity was defined as when the CFU value was less than the lower bound of the 95% confidence interval of the MPN value (with or without culture filtrate [CF]). DD, differentially detectable.\n\nAt 2 weeks post initiation of therapy, the proportion of subjects with DS TB whose sputa were DD-Mtb positive increased by about 3-fold, to 65.2% (15/23) and 60.9% (14/23) when the MPN-LD assay was performed without or with CF, respectively (Fig. 1 and Table 2). This, too, is similar to what was observed in an earlier study (69%) that examined a similar cohort of subjects with DS TB at the same study site after 2 weeks of treatment with HRZE (11). Of 5 subjects with DS TB whose sputa were positive for DD-Mtb at day 0, 4 (80%) had sputa that remained positive for DD-Mtb at week 2 (Fig. 2). Of the subjects with DS TB whose sputa lacked DD-Mtb at day 0, approximately 61% showed DD-Mtb positivity after 2 weeks of therapy with first-line drugs (Fig. 3 and Table 3).\n\nFIG 2 The MPN to CFU ratio (MPN/CFU), with and without culture filtrate (CF), for sputum from subjects with drug-sensitive (DS) and drug-resistant (DR) TB where data for both day 0 (DO) and week 2 (W2) samples were available. The dashed line represents an MPN/CFU ratio of 1. Raw numbers can be found in Table S4. An asterisk (*) indicates data not available due to contamination.\n\nFIG 3 The MPN to CFU ratio (MPN/CFU), with and without culture filtrate (CF), at day 0 (D0) and week 2 (W2) for sputum from subjects with drug-sensitive (DS) and drug-resistant (DR) TB whose sputa showed no DD-Mtb at day 0 (D0). The dashed line represents an MPN/CFU ratio of 1. Raw numbers can be found in Table S4.\n\nTABLE 3 Proportion of subjects with drug-sensitive or drug-resistant TB whose sputum showed apparent selection or induction of DD-Mtb after initiation of treatmenta\n\nCulture filtrate status\t% (n) of subjects showing selection/induction in cohort:\tPb\t\nDS\tDR\t\nAll\t61.1 (11/18)\t25.0 (3/12)\t0.072\t\n−CF\t63.2 (12/19)\t21.4 (3/14)\t0.033\t\n+CF\t57.1 (12/21)\t16.7 (2/12)\t0.033\t\na Defined as their sputum having no DD-Mtb cells at day 0 but showing DD-Mtb at week 2 post initiation of therapy, as determined by comparing MPN with or without culture filtrate (CF) to CFU.\n\nb Comparing DS to DR cohorts.\n\nIn contrast, the sputa of subjects with DR TB showed comparable levels of DD-Mtb both before (29.4%) and after 2 weeks of therapy with second-line drugs (31.3%) (Fig. 1 and Table 2). This was apparent when the MPN-LD assays were performed both with or without CF (Table 2). Of the four participants in this cohort who had DD-Mtb-positive sputa at day 0 and from whom a week 2 sample was also available, only 2 remained positive for DD-Mtb at week 2 (Fig. 2). Of the DR TB subjects whose sputa lacked DD-Mtb at day 0, only 25% showed DD-Mtb positivity after 2 weeks of therapy (Fig. 3 and Table 3).\n\nBy month 2, the sputa of 84% (26/31) of all subjects showed no detectable M. tuberculosis growth, and the median count of viable M. tuberculosis in the remaining samples was very low (<20 M. tuberculosis/ml) (see Tables S2 and S3 in the supplemental material). None of the 9 subjects with DS TB whose sputa were positive for DD-Mtb at week 2 (including 4 whose sputa were positive for DD-Mtb at both day 0 and week 2) showed any M. tuberculosis growth at month 2 (Table S2). In contrast, of the 4 subjects with DR TB whose sputa were DD-Mtb positive at week 2, two showed M. tuberculosis growth at month 2 (although neither was positive for DD-Mtb) (Table S3). In neither cohort was DD-Mtb positivity at day 0 associated with sputum positivity for M. tuberculosis at month 2 (see Table S4 in the supplemental material).\n\nOf the 5 sputa that showed detectable M. tuberculosis growth at 2 months, two were positive for DD-Mtb, but only when comparing MPN+CF to CFU, and both belonged to the DS TB cohort. Neither subject’s sputum was positive for DD-Mtb at day 0 (week 2 samples were lacking for both). Therefore, the proportion of subjects with DS TB who had DD-Mtb-positive sputum fell from 65.2% at week 2 to 13.3% at month 2, and in subjects with DR TB it fell from 31.3% at week 2 to 0% at month 2 (Table 2).\n\nRelationship of DD-Mtb to clinical characteristics and outcomes.\n\nWe assessed whether baseline characteristics at enrollment were associated with the occurrence of DD-Mtb at either week 0 or week 2 (see Table S5 in the supplemental material). No patient characteristics were associated with the presence of DD-Mtb in the sputa of DS TB subjects. HIV positivity (P = 0.015), lower hemoglobin (P = 0.014), and lower body mass index (BMI; P = 0.040) were positively associated with DD-Mtb for the cohort with DR TB.\n\nWhen limiting analyses to presence of DD-Mtb only at day 0 (prior to initiation of treatment), no association with patient characteristics was found in the DS cohort. In the DR cohort, HIV positivity (P = 0.044) and lack of bilateral disease (P = 0.008) were positively associated with DD-Mtb. No patient characteristics were associated with the presence of DD-Mtb in the sputa of either cohort at week 2 (Table S5).\n\nAll 29 DS participants completed 6 months of therapy; 28 achieved either treatment completion or cure, while 1 participant had treatment failure (positive acid-fast bacillus [AFB] smear at month 5) as defined by WHO guidelines. Presence of DD-Mtb at month 2 was associated with the only treatment failure of this study (DS no. 12).\n\nOf the 18 participants with DR TB, the median time to culture conversion to negative was 2 months, and mean weight gain at 2 months was 2 kg. The mean time to discharge from the inpatient service was 4 months, and 2 of 18 patients required rehospitalization after initial discharge. There was no significant difference in these parameters between subjects whose sputa were DD-Mtb positive versus those who were negative. It is of note that the DR patient with the longest hospitalization (6 months) and persistent symptoms after discharge, which resulted in a rehospitalization, was one of the 5 DR patients with DD-Mtb at week 2 (DR no. 21).\n\nRelative proportions of DD-Mtb bacteria in sputum from subjects with DS and DR TB.\n\nFor all DD-Mtb-positive samples in this study, DD-Mtb constituted the majority (>50%) of the total M. tuberculosis bacteria present in the sputum (as defined by an MPN/CFU ratio of >2-fold) (Fig. 1; see also Table S6 in the supplemental material). The median MPN/CFU ratio for DD-Mtb-positive samples was 4.4 (interquartile range [IQR], 2.7 to 7.0), meaning that DD-Mtb cells comprised a median of nearly 80% of the viable M. tuberculosis cells in the sputa of these participants. When samples from subjects with DS and DR TB were compared, the median MPN/CFU ratios at day 0 were 2.6 and 4.2, respectively; whereas at week 2, the median MPN/CFU ratio increased to 5.0 in sputa from subjects with DS TB but held nearly steady at 3.3 for those with DR TB (Table S6).\n\nSubjects with DS and DR TB showed comparable levels of M. tuberculosis in their sputum prior to initiation of therapy and at 2 weeks post initiation (see Table S7 in the supplemental material). Consistent with this, the rate of decline of M. tuberculosis from day 0 to week 2 was also similar for both cohorts (see Table S8 in the supplemental material). However, as seen in Table S7, at day 0, DD-Mtb-positive sputa from the cohort with DR TB showed a 389-fold lower median CFU (P = 0.018), a 550-fold lower median MPN−CF (P = 0.011), and a 10-fold lower median MPN+CF value (P = 0.067) in comparison to those of DD-Mtb-positive sputa from the DS cohort. By week 2, these differences were absent. At day 0, DD-Mtb-positive sputa from the cohort with DR TB also showed a 1,259-fold lower median CFU (P = 0.004), a 550-fold lower median MPN−CF (P = 0.007), and a 27-fold lower median MPN+CF value (P = 0.011) in comparison to those of DD-Mtb-negative sputa from the same cohort. This distinction in levels of viable M. tuberculosis bacteria according to presence or absence of DD-Mtb was not seen in sputa from the cohort with DS TB.\n\nDS- and DR-Mtb samples show differing responses to CF.\n\nThe median MPN+CF/MPN−CF ratio was 1.6-fold higher for sputa from subjects with DR TB than for those with DS TB at day 0 (P = 0.032). This ratio was 3.2-fold when the comparison was limited to DD-Mtb-positive samples (Table S7). When the comparison was made between MPN+CF and MPN−CF values for individual sputa that contained DD-Mtb, the MPN+CF assay detected a 2.3-fold higher median DD-Mtb number for samples from subjects with DR TB but a 1.5-fold lower median DD-Mtb number for samples from subjects with DS TB. In other words, on average, CF appeared to promote the growth of DD-Mtb bacteria from the DR cohort while inhibiting the growth of DD-Mtb bacteria in sputa from the DS cohort at day 0.\n\nDISCUSSION\n\nHere, we report that subjects with DS and DR TB show differing incidence of DD-Mtb in their sputa after initiation of therapy. We found that similar proportions of subjects with DS and DR TB—20.7% and 29.4%, respectively—presented with sputum positive for DD-Mtb prior to therapy. These proportions resemble what was reported earlier (21%) for subjects with DS TB by a different experimental investigator applying the same methods at the same study site (11). After 2 weeks of HRZE, the proportion of subjects whose sputa were DD-Mtb-positive more than tripled, again mirroring earlier observations (11). In contrast, the proportion of subjects with DR TB whose sputa were DD-Mtb positive changed little after 2 weeks on a multidrug regimen that included pyrazinamide but lacked rifampin, isoniazid, and ethambutol. These observations are consistent with the hypotheses that HRZE or one of its components, perhaps rifampin (8), promotes an increased proportion of DD-Mtb bacteria in the sputum by selective elimination of M. tuberculosis bacteria that are not DD-Mtb or by induction of DD-Mtb (and second-line therapy does not do so), or that the more extensive disease or prior treatment in most subjects receiving second-line therapy (along with any potential accompanying resistance-associated mutations) limits selection or induction of DD-Mtb.\n\nStudies of DD-Mtb cells generated in vitro reveal that they are bacteria that have sustained oxidative damage at a sublethal level and can regain the capacity to form colonies on agar if their replication is delayed until they undergo repair (Saito et al., unpublished). While disengaged from replication, DD-Mtb are profoundly antibiotic resistant (8, 14, 15). While intermediate levels of oxidative damage give rise to DD-Mtb, more extensive oxidative damage kills them (Saito et al., unpublished). Perhaps the exposure of subjects with DR TB to oxidant-generating drugs like clofazimine (18) damages a higher proportion of their M. tuberculosis bacteria beyond the point of repair.\n\nThe notion that sublethal damage can promote formation of DD-Mtb cells is consistent with the finding that HIV-positive (HIV+) subjects with TB who had peripheral blood CD4 counts of >200 cells/ml were more likely to have DD-Mtb in their sputum than those with CD4 counts of <200 cells/ml (10). In the present study, subjects with DS TB who had DD-Mtb-positive sputum at day 0 had a 3.5-fold lower median CFU count in their sputum than those whose sputum lacked DD-Mtb (see Table S7 in the supplemental material). Perhaps there is a level of host immunity that suffices to reduce but not eliminate M. tuberculosis and inflicts the intermediate level of damage that favors formation of DD-Mtb. Similarly, subjects with DR TB who had DD-Mtb-positive sputum at day 0 had a >1,000-fold lower median CFU count in their sputum than that of their DD-Mtb-negative counterparts, perhaps highlighting the additive effects of host immunity and previous exposure to first-line therapies. Consistent with this, Xpert positivity indicative of very low or low M. tuberculosis counts in sputum was positively associated with the presence of DD-Mtb (P = 0.014) (see Table S5 in the supplemental material).\n\nDD-Mtb populations in the sputum did not persist beyond the first 2 months of therapy for most subjects. Specifically, 9/9 subjects with DS TB and 7/7 with DR TB whose sputum previously contained DD-Mtb bacteria lacked evidence of DD-Mtb at 2 months. Nonetheless, DD-Mtb was detected at month 2 in the sputa of 2 subjects with DS TB whose sputa did not show DD-Mtb at day 0 (week 2 samples were missing for both). More generally, sputa from most subjects showed no evidence of viable M. tuberculosis cells at 2 months by any of the assays used, and when M. tuberculosis was detected at 2 months, the levels were very low. These findings are consistent with a report that found no M. tuberculosis growth after 3 months of treatment in the sputum of 17 subjects with DS TB using assays similar to those employed here (5). Therefore, detection of DD-Mtb at an earlier time point did not foretell sputum positivity by any assay used at 2 months of treatment.\n\nNonetheless, those subjects whose sputum contains detectable DD-Mtb at some point before or during their treatment may face a more challenging clinical course than those whose sputum does not. The two subjects who responded most poorly to treatment in each cohort, namely, the subject with DS TB whose treatment failed and the subject with DR TB who required rehospitalization, both had DD-Mtb detected during treatment. However, the number of subjects who did poorly was too small for statistical assessment, highlighting a limitation of the current study. Larger studies with longer follow-up times will be needed to draw firm conclusions about the role of DD-Mtb in treatment outcome. Beltran et al. (6) identified DD-Mtb in the sputum of two subjects with DS TB who subsequently relapsed, while Almeida Júnior et al. (5) found no association between DD-Mtb and treatment failure or relapse during the first 6 months of treatment for DS TB. While CF had a variable effect on M. tuberculosis growth in this and previous studies (10–12, 17), for both subjects for whom DD-Mtb was associated with poorer clinical outcome, CF markedly improved M. tuberculosis recovery in the MPN-LD assay, similarly to what Beltran et al. (6) observed in their subjects who went on to relapse.\n\nAdditionally, CF tended to promote recovery of DD-Mtb in sputum from subjects with DR TB but tended to suppress recovery of DD-Mtb in sputum from subjects with DS TB. The latter effect was alleviated in sputa from the cohort with DS TB after initiation of drug treatment, suggesting that the prior drug exposure experienced by subjects with DR TB may have contributed to this difference. What components of CF exert these effects and by what mechanisms remain unknown (12), making it difficult to draw biologic inferences. As a practical matter, it is advisable to perform MPN-LD assays both with and without CF to maximize detection of DD-Mtb.\n\nIn the future, a rapid, quantitative, and culture-independent means of estimating the number of DD-Mtb cells in clinical specimens could help address the many open questions that remain regarding DD-Mtb. Given that culture conversion is already known to be a poor predictor of TB cure, there is a need for the development of diagnostics that more accurately reflect total viable M. tuberculosis populations in sputa, which can be used to screen investigational anti-TB drugs and identify individuals who qualify for shorter treatments, with the aim of ultimately improving TB outcomes.\n\nMATERIALS AND METHODS\n\nStudy design and patient populations.\n\nThis prospective observational study was performed at the Groupe Haïtien d’Étude du Sarcome de Kaposi et des Infectieuses Opportuniste (GHESKIO) centers in Port au Prince, Haiti, and approved by the institutional review boards of both GHESKIO and Weill Cornell Medicine. All participants provided written informed consent and scored at least 90% on an assessment of understanding quiz before enrollment. HIV+ subjects from both cohorts were on antiretroviral therapy at the time of enrollment and remained on treatment during the period of the study.\n\nThe DS cohort met the following criteria: the participants were ≥ 18 years of age; had been diagnosed as having active pulmonary TB based on clinical symptoms and signs, chest radiography, and Xpert Mtb/RIF assay (Cepheid, Sunnyvale, CA) positivity, without indication of rifampin resistance; were free of extrapulmonary manifestations of TB or concomitant illnesses that might interfere with treatment in the opinion of the participant’s care provider; had no history of TB or its treatment; and were planning to initiate treatment at the GHESKIO clinic. The DR cohort met the same criteria, except that the Xpert test indicated rifampin resistance and participants were not excluded if they had previously been treated for drug-sensitive TB. Sputum was collected from both cohorts prior to initiation of therapy, and at 2 weeks and 2 months after initiation of therapy. TB symptoms (cough, dyspnea, hemoptysis, fever, and pleuritic chest pain) were graded according to the Division of AIDS (DAIDS) grading system (19).\n\nParticipants with DS TB were followed in the GHESKIO outpatient clinic for the duration of their directly observed therapy (DOT). Participants received isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z) for 2 months, then HR for 4 months. During the first 2 months, participants had clinical visits every 2 weeks at which time signs and symptoms were recorded, and then every month for the remainder of their treatment regimen. Treatment outcome was determined based on Haitian and WHO guidelines—spot sputum samples were collected during clinical visits for AFB smear at months 2, 5, and 6 and underwent culture only if AFB positive. Subjects also provided overnight sputum samples on day 0 and at week 2 and month 2 for the laboratory analyses performed in this study. One month after completion of therapy, participants had a final clinical visit and were counseled to return if their condition worsened. Participants were not actively followed after completion of treatment, and so the relationship with posttreatment recurrence could not be assessed.\n\nParticipants with DR TB were hospitalized in GHESKIO’s inpatient multidrug-resistant (MDR)-TB hospital for approximately the first 4 months of treatment. They were discharged once they demonstrated clinical improvement and negative M. tuberculosis cultures and had designated family support to ensure treatment adherence upon discharge. Treatment was in accordance with Haitian and WHO guidelines, with DOT regimens comprised of bedaquiline, levofloxacin, linezolid, clofazimine, and pyrazinamide. Bedaquiline was discontinued after 6 months and linezolid after 12 months, with the remaining drugs continued to complete 20 months of therapy. Once discharged, participants were followed in GHESKIO’s outpatient MDR-TB clinics with monthly outpatient follow-up. Spot sputum samples were provided monthly for AFB smear and monthly for culture during months 1 to 8, every other month during months 9 to 18, and then monthly for the final 3 months of treatment. For the current study, we documented the following outcomes: length of hospitalization and any readmission, change in weight by month 2, persistent TB symptoms, and time to culture conversion.\n\nSputum processing and microbiological assays.\n\nSubjects collected overnight sputum into a cool box with ice packs (4°C) from 5 p.m. to 9 a.m. Samples reached the GHESKIO laboratory the same morning, with >79% of samples being processed the same day, >92% being processed within 2 days, and all being processed within 5 days. Experimental work took place in a biosafety level 3 laboratory with appropriate safety guidelines and personal protective equipment.\n\nDecontamination of sputum, preparation of culture filtrate (CF), and CFU and MPN-LD assays were conducted as reported previously (11). Decontamination was monitored by plating aliquots on blood agar. Results of LD assays performed without CF are referred to as MPN−CF and those with CF as MPN+CF. CFU and MPN plates were placed inside partially sealed Ziploc bags and placed inside a 37°C incubator (unhumidified and without CO2) for up to 9 weeks, with reads performed after 3 weeks and then every 2 weeks thereafter until no additional growth was observed between two consecutive reads. Positive colonies were identified visually, and any suspect positive wells were confirmed for presence of M. tuberculosis by using an SD Bioline TB AG MPT64 rapid antigen test (only for MPN−CF plates). Contamination was ruled out by plating on blood agar.\n\nData analysis.\n\nData were uploaded to REDCap (20, 21), a secure web-based software platform designed to support data capture for research studies. A second investigator used the raw data files to repeat and verify the calculations. Confidence intervals (95%) were calculated separately for assays with and without CF from the results of 10 independent dilution series per sample (22). These were compared to the average CFU values on two agar plates for a sample taken from each dilution of each LD series. DD-Mtb was recorded as present when the number of CFU calculated for the original sample was less than the lower 95% confidence interval of the number of viable M. tuberculosis bacteria in the original sample calculated by the MPN method based on growth of M. tuberculosis in the LD series. CFU and MPN-LD assays had a lower limit of detection (LLD) of 3 M. tuberculosis CFU/ml. In instances of contamination of CFU and/or MPN-LD plates, the LLD increased proportionately. If a sample showed no M. tuberculosis growth, the next whole number below the LLD was used for the purposes of MPN/CFU ratios. Samples were assigned an MPN/CFU ratio of 1 if <10 M. tuberculosis/ml were detected in all three assay formats (CFU, MPN−CF, and MPN+CF).\n\nNumbers of viable M. tuberculosis are presented as log10 values per ml of sputum. The ratio of DD-Mtb to CFU in a sample is calculated by subtracting the log10 values for CFU assays from the log10 value for MPN-LD assays and determining the antilog of the difference, which is presented as a whole number. Results at day 0 and week 2 were compared only for subjects whose data were available at both time points. The Wilcoxon signed rank test (a nonparametric version of the paired t test) was used to compare two quantitative results at one time point and the change in one quantitative result with time. The Wilcoxon rank sum test (a nonparametric version of a two-sample t test) was used to compare distribution of continuous features between samples from subjects with DS versus DR TB. Fisher’s exact test was used to assess the association between two categorical features (presence of DD-Mtb and DS/DR status of the M. tuberculosis at the outset). All tests were performed for two-tailed hypotheses, and P values of <0.05 were considered statistically significant. Statistical analyses were performed using R v4.0.2.\n\nACKNOWLEDGMENTS\n\nWe thank the subjects who volunteered for this study, as well as the clinical, research, and administrative staff of GHESKIO who made this study possible, including Circee Phara Jean, Rose Laure Heriveaux, Daphie Jean-François, Marie-Marcelle Mabou, Alexandra Apollon, and Kathrine McAulay. We are grateful to the Foundation Mérieux for helping to build and maintain the biosafety level 3 facility at GHESKIO.\n\nThis work was supported by NIH grants U19AI111143 and K24AI098627 and the Milstein Program in Chemical Biology and Translational Medicine. The Department of Microbiology and Immunology is supported by the William Randolph Hearst Trust. K.S. is supported by NIH grant K08 AI139360, and K.Z. is supported by a VECD Global Health Fellowship funded by the Fogarty International Center (FIC) of the NIH (D43 TW009337).\n\nThe views expressed are solely those of the authors and do not necessary represent the views of the NIH.\n\nSupplemental material is available online only.\n\n10.1128/AAC.00608-21.1 Supplemental file 1 Supplemental Tables S1 to S3 and S5 to S8. Download AAC00608-21_Supp_1_seq9.pdf, PDF file, 0.8 MB\n\n10.1128/AAC.00608-21.2 Supplemental file 2 Supplemental Table S4. Download AAC00608-21_Supp_2_seq3.xlsx, XLSX file, 0.02 MB\n==== Refs\nREFERENCES\n\n1 World Health Organization. 2019. World tuberculosis report 2019. World Health Organization, Geneva, Switzerland.\n2 Burki TK. 2018. The global cost of tuberculosis. Lancet Respir Med 6 :13. doi:10.1016/S2213-2600(17)30468-X.\n3 Dhillon J, Fourie PB, Mitchison DA. 2014. Persister populations of Mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture media. J Antimicrob Chemother 69 :437–440. doi:10.1093/jac/dkt357.24072170\n4 Huang W, Qi Y, Diao Y, Yang F, Zha X, Ren C, Huang D, Franken KLMC, Ottenhoff THM, Wu Q, Shen J. 2014. Use of resuscitation-promoting factor proteins improves the sensitivity of culture-based tuberculosis testing in special samples. Am J Respir Crit Care Med 189 :612–614. doi:10.1164/rccm.201310-1899LE.24579840\n5 Almeida Júnior PS, Schmidt Castellani LG, Peres RL, Combadao J, Tristão TC, Dietze R, Hadad DJ, Palaci M. 2020. Differentially culturable tubercle bacteria dynamics during standard anti-tuberculosis treatment: a prospective cohort study. Tuberculosis (Edinb) 124 :101945. doi:10.1016/j.tube.2020.101945.32692652\n6 Beltran CGG, Heunis T, Gallant J, Venter R, Du Plessis N, Loxton AG, Trost M, Winter J, Malherbe ST, Kana BD, Walzl G. 2020. Investigating non-sterilizing cure in TB patients at the end of successful anti-TB therapy. Front Cell Infect Microbiol 10 :443. doi:10.3389/fcimb.2020.00443.32984071\n7 Dusthackeer A, Balasubramanian M, Shanmugam G, Priya S, Nirmal CR, Sam Ebenezer R, Balasubramanian A, Mondal RK, Thiruvenkadam K, Hemanth Kumar AK, Ramachandran G, Subbian S. 2019. Differential culturability of Mycobacterium tuberculosis in culture-negative sputum of patients with pulmonary tuberculosis and in a simulated model of dormancy. Front Microbiol 10 :2381. doi:10.3389/fmicb.2019.02381.31749768\n8 Saito K, Warrier T, Somersan-Karakaya S, Kaminski L, Mi J, Jiang X, Park S, Shigyo K, Gold B, Roberts J, Weber E, Jacobs WR, Nathan CF. 2017. Rifamycin action on RNA polymerase in antibiotic tolerant Mycobacterium tuberculosis results in differentially detectable populations. Proc Natl Acad Sci U S A 114 :E4832–E4840. doi:10.1073/pnas.1705385114.28559332\n9 Mukamolova GV, Turapov O, Malkin J, Woltmann G, Barer MR. 2010. Resuscitation-promoting factors reveal an occult population of tubercle bacilli in sputum. Am J Respir Crit Care Med 181 :174–180. doi:10.1164/rccm.200905-0661OC.19875686\n10 Chengalroyen MD, Beukes GM, Gordhan BG, Streicher EM, Churchyard G, Hafner R, Warren R, Otwombe K, Martinson N, Kana BD. 2016. Detection and quantification of differentially culturable tubercle bacteria in sputum from patients with tuberculosis. Am J Respir Crit Care Med 194 :1532–1540. doi:10.1164/rccm.201604-0769OC.27387272\n11 McAulay K, Saito K, Warrier T, Walsh KF, Mathurin LD, Royal-Mardi G, Lee MH, Ocheretina O, Pape JW, Fitzgerald DW, Nathan CF. 2018. Differentially detectable Mycobacterium tuberculosis cells in sputum from treatment-naive subjects in Haiti and their proportionate increase after initiation of treatment. mBio 9 :e02192-18. doi:10.1128/mBio.02192-18.30459198\n12 Gordhan BG, Peters JS, McIvor A, Machowski EE, Ealand C, Waja Z, Martinson N, Kana BD. 2021. Detection of differentially culturable tubercle bacteria in sputum using mycobacterial culture filtrates. Sci Rep 11 :6493. doi:10.1038/s41598-021-86054-z.33753820\n13 Colwell RR, Brayton PR, Grimes DJ, Roszak DB, Huq SA, Palmer LM. 1985. Viable but non-culturable Vibrio cholerae and related pathogens in the environment: implications for release of genetically engineered microorganisms. Nat Biotechnol 3 :817–820. doi:10.1038/nbt0985-817.\n14 Turapov O, O’Connor BD, Sarybaeva AA, Williams C, Patel H, Kadyrov AS, Sarybaev AS, Woltmann G, Barer MR, Mukamolova GV. 2016. Phenotypically adapted Mycobacterium tuberculosis populations from sputum are tolerant to first-line drugs. Antimicrob Agents Chemother 60 :2476–2483. doi:10.1128/AAC.01380-15.26883695\n15 Nathan C. 2012. Fresh approaches to anti-infective therapies. Sci Transl Med 4 :140sr2. doi:10.1126/scitranslmed.3003081.22745440\n16 Opie E, Aronson J. 1927. Tubercle bacilli in latent tuberculous lesions and in lung tissue without tuberculous lesion. Arch Pathol Lab Med 4 :1–21.\n17 Dartois V, Saito K, Warrier T, Nathan C. 2016. New evidence for the complexity of the population structure of Mycobacterium tuberculosis increases the diagnostic and biologic challenges. Am J Respir Crit Care Med 194 :1448–1451. doi:10.1164/rccm.201607-1431ED.27976945\n18 Grant SS, Kaufmann BB, Chand NS, Haseley N, Hung DT. 2012. Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. Proc Natl Acad Sci U S A 109 :12147–12152. doi:10.1073/pnas.1203735109.22778419\n19 NIAID. 2014. Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events. National Institutes of Health. Bethesda, MD.\n20 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. 2009. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42 :377–381. doi:10.1016/j.jbi.2008.08.010.18929686\n21 Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN, REDCap Consortium. 2019. The REDCap consortium: building an international community of software partners. J Biomed Inform 95 :103208. doi:10.1016/j.jbi.2019.103208.31078660\n22 Jarvis B, Wilrich C, Wilrich PT. 2010. Reconsideration of the derivation of most probable numbers, their standard deviations, confidence bounds and rarity values. J Appl Microbiol 109 :1660–1667. doi:10.1111/j.1365-2672.2010.04792.x.20602657\n\n",
"fulltext_license": "CC BY",
"issn_linking": "0066-4804",
"issue": "65(8)",
"journal": "Antimicrobial agents and chemotherapy",
"keywords": "Mycobacterium tuberculosis; diagnostics; multidrug resistance; pulmonary infection; viable but nonculturable",
"medline_ta": "Antimicrob Agents Chemother",
"mesh_terms": "D000995:Antitubercular Agents; D006801:Humans; D009169:Mycobacterium tuberculosis; D004364:Pharmaceutical Preparations; D013183:Sputum; D018088:Tuberculosis, Multidrug-Resistant; D014397:Tuberculosis, Pulmonary",
"nlm_unique_id": "0315061",
"other_id": null,
"pages": "e0060821",
"pmc": null,
"pmid": "34060896",
"pubdate": "2021-07-16",
"publication_types": "D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't",
"references": "18929686;29239796;24072170;24579840;22778419;27976945;32692652;27387272;19875686;31078660;26883695;33753820;28559332;22745440;20602657;30459198;32984071;31749768",
"title": "Characterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy.",
"title_normalized": "characterization of differentially detectable mycobacterium tuberculosis in the sputum of subjects with drug sensitive or drug resistant tuberculosis before and after two months of therapy"
}
|
[
{
"companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2021-03714",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ISONIAZID"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": "202610",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Tuberculosis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISONIAZID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RIFAMPIN"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Tuberculosis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RIFAMPIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PYRAZINAMIDE"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Tuberculosis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PYRAZINAMIDE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ETHAMBUTOL HYDROCHLORIDE"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Tuberculosis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETHAMBUTOL"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Treatment failure",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Zainabadi K, Walsh KF, Vilbrun SC, Mathurin LD, et al. Characterization of differentially detectable Mycobacterium tuberculosis in the sputum of subjects with drug sensitive or drug resistant tuberculosis before and after two months of therapy. Unk. 2021;Unk:Unk",
"literaturereference_normalized": "characterization of differentially detectable mycobacterium tuberculosis in the sputum of subjects with drug sensitive or drug resistant tuberculosis before and after two months of therapy",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20211214",
"receivedate": "20211214",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20179856,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 2,
"transmissiondate": "20220303"
}
] |
{
"abstract": "The HeartWare HVAD has been used as a bridge to cardiac transplantation in the pediatric population. We describe outcomes following HeartWare HVAD implantation at a single center. A retrospective chart review was performed of all HeartWare HVAD implants performed at our institution between May 2013 and March 2015. Eight children between the ages of 9 and 17 years underwent HVAD implantation as a bridge to transplant (N = 7 cardiomyopathy, N = 1 complex single ventricle). There was one operative death in the complex single ventricle patient. Seven patients (87%) were successfully bridged to transplant. Median time of support was 24.5 days (range, 6-91 days). All transplanted patients are alive and well at a median follow-up of 448 days. Our results demonstrated that mechanical support with HeartWare HVAD is feasible in patients of varying sizes (from older children to adolescents).",
"affiliations": "Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX, USA.;Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX, USA.;Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX, USA.;Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX, USA.;Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX, USA.;Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX, USA.",
"authors": "Ferro|Giuseppe|G|;Murthy|Raghav|R|;Williams|Derek|D|;Sebastian|Vinod A|VA|;Forbess|Joseph M|JM|;Guleserian|Kristine J|KJ|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1111/aor.12637",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0160-564X",
"issue": "40(1)",
"journal": "Artificial organs",
"keywords": "Cardiac transplantation; Heart failure; Pediatric; Ventricular assist device",
"medline_ta": "Artif Organs",
"mesh_terms": "D000293:Adolescent; D000367:Age Factors; D002648:Child; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D011474:Prosthesis Design; D020127:Recovery of Function; D012189:Retrospective Studies; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left",
"nlm_unique_id": "7802778",
"other_id": null,
"pages": "85-9",
"pmc": null,
"pmid": "26581159",
"pubdate": "2016-01",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Early Outcomes With HeartWare HVAD as Bridge to Transplant in Children: A Single Institution Experience.",
"title_normalized": "early outcomes with heartware hvad as bridge to transplant in children a single institution experience"
}
|
[
{
"companynumb": "US-BAYER-2021A276620",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1 DF, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Anticoagulant therapy",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "032",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN"
}
],
"patientagegroup": "3",
"patientonsetage": "9",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "26.939",
"reaction": [
{
"reactionmeddrapt": "Right ventricular failure",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Renal impairment",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Ferro G; Murthy R; Williams D; Sebastian VA; Forbess JM; Guleserian KJ. Early Outcomes With HeartWare HVAD as Bridge to Transplant in Children: A Single Institution Experience. Artificial Organs. 2016;40(1):85-89",
"literaturereference_normalized": "early outcomes with heartware hvad as bridge to transplant in children a single institution experience",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20220106",
"receivedate": "20220106",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 20304554,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220423"
},
{
"companynumb": "US-BAYER-2021A276624",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN"
}
],
"patientagegroup": "4",
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": "64",
"reaction": [
{
"reactionmeddrapt": "Renal impairment",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Ferro G; Murthy R; Williams D; Sebastian VA; Forbess JM; Guleserian KJ. Early Outcomes With HeartWare HVAD as Bridge to Transplant in Children: A Single Institution Experience. Artificial Organs. 2016;40(1):85-89",
"literaturereference_normalized": "early outcomes with heartware hvad as bridge to transplant in children a single institution experience",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20220103",
"receivedate": "20220103",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 20280229,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220423"
}
] |
{
"abstract": "In many stem cell transplant centres, BCNU, etoposide, cytarabine and melphalan (BEAM) high-dose chemotherapy (HDCT) has been replaced by the more economic and available bendamustine, etoposide, cytarabine, melphalan (BeEAM) regimen. However, there is a paucity of information on the efficacy and safety of BeEAM HDCT. We describe our experience with BeEAM HDCT in terms of safety, efficacy and cost-savings. We compare overall and progression-free survival to a cohort of patients previously transplanted at our institution with the older BEAM regimen. We performed a retrospective chart review of 41 lymphoma patients undergoing BeEAM HDCT at the Royal University Hospital in Saskatoon, Saskatchewan between 2015 and 2019 to elicit regimen safety in the first 100 days post-transplant. Furthermore, we calculated overall and progression-free survival and constructed corresponding Kaplan-Meier curves, comparing the results to a historical cohort of BEAM patients (n = 86). Finally, we conducted an economic analysis using the financials available at our centre's pharmacy. With regards to BeEAM HDCT, we report a 100-day transplant-related mortality of 2.4%. Additionally, we report acceptable rates of typhlitis (27%), grade III-IV mucositis (4.9%) and grade III-IV nephrotoxicity (2.4%). In terms of overall and progression-free survival, we found no statistical difference between BeEAM and BEAM (p = 0.296; 0.762, respectively). Finally, our economic analysis revealed a net savings of $21,200 CAD per transplant when BeEAM is used in replacement of BEAM. The acceptable safety profile of BeEAM and its comparable efficacy to BEAM are encouraging for the perseverance of this cost-effective HDCT regimen.",
"affiliations": "Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.;Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, SK, Canada.;Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.;Provincial Hematology and Blood and Marrow Transplant Program, Saskatchewan Cancer Agency, Saskatoon, SK, Canada.;Provincial Hematology and Blood and Marrow Transplant Program, Saskatchewan Cancer Agency, Saskatoon, SK, Canada.;Provincial Hematology and Blood and Marrow Transplant Program, Saskatchewan Cancer Agency, Saskatoon, SK, Canada.;Provincial Hematology and Blood and Marrow Transplant Program, Saskatchewan Cancer Agency, Saskatoon, SK, Canada.;Provincial Hematology and Blood and Marrow Transplant Program, Saskatchewan Cancer Agency, Saskatoon, SK, Canada. [email protected].",
"authors": "Hahn|Logan|L|;Lim|Hyun|H|;Dusyk|Tanner|T|;Sabry|Waleed|W|;Elemary|Mohamed|M|;Stakiw|Julie|J|;Danyluk|Pat|P|;Bosch|Mark|M|",
"chemical_list": "D003561:Cytarabine; D005047:Etoposide; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine",
"country": "England",
"delete": false,
"doi": "10.1038/s41598-021-93516-x",
"fulltext": "\n==== Front\nSci Rep\nSci Rep\nScientific Reports\n2045-2322\nNature Publishing Group UK London\n\n93516\n10.1038/s41598-021-93516-x\nArticle\nBeEAM conditioning regimen is a safe, efficacious and economical alternative to BEAM chemotherapy\nHahn Logan 1\nLim Hyun 2\nDusyk Tanner 1\nSabry Waleed 3\nElemary Mohamed 3\nStakiw Julie 3\nDanyluk Pat 3\nBosch Mark [email protected]\n\n3\n1 grid.25152.31 0000 0001 2154 235X Department of Medicine, University of Saskatchewan, Saskatoon, SK Canada\n2 grid.25152.31 0000 0001 2154 235X Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, SK Canada\n3 grid.419525.e 0000 0001 0690 1414 Provincial Hematology and Blood and Marrow Transplant Program, Saskatchewan Cancer Agency, Saskatoon, SK Canada\n7 7 2021\n7 7 2021\n2021\n11 1407112 2 2021\n25 6 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.\nIn many stem cell transplant centres, BCNU, etoposide, cytarabine and melphalan (BEAM) high-dose chemotherapy (HDCT) has been replaced by the more economic and available bendamustine, etoposide, cytarabine, melphalan (BeEAM) regimen. However, there is a paucity of information on the efficacy and safety of BeEAM HDCT. We describe our experience with BeEAM HDCT in terms of safety, efficacy and cost-savings. We compare overall and progression-free survival to a cohort of patients previously transplanted at our institution with the older BEAM regimen. We performed a retrospective chart review of 41 lymphoma patients undergoing BeEAM HDCT at the Royal University Hospital in Saskatoon, Saskatchewan between 2015 and 2019 to elicit regimen safety in the first 100 days post-transplant. Furthermore, we calculated overall and progression-free survival and constructed corresponding Kaplan–Meier curves, comparing the results to a historical cohort of BEAM patients (n = 86). Finally, we conducted an economic analysis using the financials available at our centre’s pharmacy. With regards to BeEAM HDCT, we report a 100-day transplant-related mortality of 2.4%. Additionally, we report acceptable rates of typhlitis (27%), grade III–IV mucositis (4.9%) and grade III–IV nephrotoxicity (2.4%). In terms of overall and progression-free survival, we found no statistical difference between BeEAM and BEAM (p = 0.296; 0.762, respectively). Finally, our economic analysis revealed a net savings of $21,200 CAD per transplant when BeEAM is used in replacement of BEAM. The acceptable safety profile of BeEAM and its comparable efficacy to BEAM are encouraging for the perseverance of this cost-effective HDCT regimen.\n\nSubject terms\n\nDiseases\nMedical research\nSigns and symptoms\nOncology\nCancer\nStem cells\nAdult stem cells\nHaematopoietic stem cells\nHealth care\nHealth care economics\nissue-copyright-statement© The Author(s) 2021\n==== Body\nIntroduction\n\nAs a result of the ground-breaking PARMA and CORAL trials, high dose chemotherapy (HDCT) and subsequent autologous stem cell transplantation (ASCT) has become standard of care in the treatment of relapsed and chemotherapy-sensitive Non-Hodgkin’s lymphoma (NHL)1,2. Similarly, HDCT and ASCT has proven effective in the treatment of relapsed and resistant Hodgkin’s Lymphoma (HL)3,4. Despite the widespread use of HDCT in stem cell transplantation, the various conditioning protocols have seldomly been compared. Notably, there are limited studies comparing HDCT regimens5. BEAM (BCNU, etoposide, cytarabine and melphalan) conditioning has been the most widely-used conditioning regimen for the past 30 years1. Recently, some centers have discontinued the use of BEAM chemotherapy in favor of BeEAM (bendamustine, etoposide, cytarabine, melphalan) chemotherapy. Additionally, the unavailability of BCNU has prompted a shift to Bendamusine-based regimens6. Additionally, there are concerns over BCNU-related pulmonary toxicity7–11. Unfortunately, there is a paucity of research comparing BEAM and BeEAM conditioning regimens in terms of safety, efficacy and cost-effectiveness.\n\nBendamustine was first synthesized in the early 1960s in the former German Democratic Republic12. In vitro studies have shown bendamustine to be highly effective in cell lines with dysfunctional apoptotic pathways causing mitotic failure13. A phase I–II trial including 77 patients showed bendamustine-containing chemotherapy to be safe and efficacious in the ASCT setting. Importantly, the authors reported a 100-day transplant-related mortality (TRM) of 0%, and 81% of the trial patients achieved complete remission after a median observation of 18 months12.\n\nCreatinine elevations after bendamusine-containing HDCT administration has led to concerns over renal toxicity. Several studies have documented nephrotoxicity related to BeEAM chemotherapy, ranging from clinically-insignificant creatinine rises to dialysis necessitation6,8,14–17. Interestingly, a study conducted by Noesslinger et al. found that the majority of patients (33/41) experienced a rise in creatinine within a few days of bendamustine administration. Unlike other studies, no therapeutic intervention was required for any of the patients14. However, BeEAM-related nephrotoxicity has been demonstrated to have more severe consequences. For instance, a recent study reported that 10% of patients who were administered BeEAM conditioning developed grade III/IV renal toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) v4.0 guidelines, with one of these patients even requiring dialysis8.\n\nCohort studies comparing nephrotoxicity in the conditioning regimens has been similarly inconclusive. A cohort study comparing BEAM and BeEAM safety profiles found a significant difference in nephrotoxicity with 48% of the BeEAM cohort experiencing renal impairment, while this toxicity was only noted in 7% of the BEAM cohort (p < 0.001)17. A cohort study published in 2018 found the incidence of nephrotoxicity with BeEAM and BEAM to be 12% and 6%, respectively16. However, all reported cases of renal impairment constituted grade 1 toxicities. A large cohort study conducted by Frankiewicz et al. found no difference in grade 2–4 nephrotoxicity incidence between BeEAM and BEAM with each group demonstrating only a small risk of renal impairment (1.6% and 0.6%, respectively)18.\n\nWhile there has been concerns over BeEAM-related nephrotoxicity, there is optimism that the regimen has reduced the risk of IPS8,12. This represents a significant advantage of the conditioning regimen, as IPS is associated with a higher rate of TRM and shorter progression-free survival (PFS) and overall survival (OS)9. HDCT regimens containing BCNU have been shown to cause IPS at incidences of 1–64%, thus presenting a significant drawback of BEAM therapy19–21. A hypothesized advantage of BeEAM chemotherapy is a lower risk of IPS. For instance, a recent study conducted by Gilli et al. demonstrated that IPS is a possible, albeit rare, consequence in BeEAM conditioning8.\n\nCurrent studies have produced widely varying results with regards to the safety and toxicological profile of BeEAM HDCT. Clearly, there is a need to evaluate the safety of BeEAM conditioning, with particular attention to nephrotoxicity and IPS. In this retrospective, single-center study we document our experience with BeEAM conditioning in terms of safety, efficacy and economics.\n\nMaterials and methods\n\nPatients\n\nIn this single-center, retrospective chart review, we analyzed consecutive patients with Hodgkin’s lymphoma (n = 7) or Non-Hodgkin’s lymphoma (n = 34) who have been treated with BeEAM HDCT followed by ASCT between 2015 and 2019 at the Royal University Hospital in Saskatoon, Canada. These patients were followed and charts were reviewed through the Provincial Hematology and Blood and Bone Marrow Transplant Program at the SCA. All patients signed consent prior to proceeding with ASCT. Furthermore, the BeEAM cohort was compared to a previously studied cohort of patients undergoing BEAM ASCT (n = 86) at the aforementioned institution for the purpose of survival analysis. BEAM transplants occurred between 2009 and 2016, as the BeEAM protocol became standard of care at our institution in 2015. This study was approved by the local ethics committee and the Saskatchewan Cancer Agency in accordance with the relevant guidelines and regulations. Detailed patient characteristics can be found in Table 1.Table 1 Patient characteristics.\n\nPatients\tBeEAM\tBEAM\tp valuea\t\nn = 41\tn = 86\t\nAge, mean, SD\t55 (12)\t51 (13)\t0.123\t\nAge groups (n, %)\t\n≤ 60\t24 (58.5)\t61 (70.9)\t0.165\t\n> 60\t17 (41.5)\t25 (29.1)\t\t\nSex (n, %)\t\nFemale\t10 (24.4)\t36 (41.9)\t0.055\t\nMale\t31 (75.6)\t50 (58.1)\t\t\nDiagnosis (n, %)\t\nHodgkin lymphoma/nodular sclerosis\t7 (17.1)\t28 (32.6)\t0.068\t\nAll others\t34 (82.9)\t58 (67.4)\t\t\nTotal deaths (n, %)\t\nYes\t8 (19.5)\t27 (31.4)\t0.161\t\nNo\t33 (80.5)\t59 (68.6)\t\t\nDeaths 3 years after ASCT (n, %)\t\nYes\t8 (19.5)\t18 (20.9)\t0.853\t\nNo\t33 (80.5)\t68 (79.1)\t\t\nTotal relapsed patients (n, %)\t\nYes\t8 (19.5)\t28 (32.6)\t0.127\t\nNo\t33 (80.5)\t58 (67.4)\t\t\nRelapsed patients after ASCT (n, %)\t\nYes\t8 (19.5)\t23 (26.7)\t0.375\t\nNo\t33 (80.5)\t63 (73.3)\t\t\naChi-square test: ASCT autologous stem cell transplantation.\n\nTreatment\n\nBEAM: 300 mg/m2 BCNU was given on day − 6. On days − 5 to − 2, 400 mg/m2 cytarabine was administered every 12 h as a 30-min infusion in 100 mL 0.9% NaCl. On days − 5 to − 2, 200 mg/m2 etoposide was administered once daily as a 120 min infusion in 1000 mL 0.9% NaCl. Melphalan at 140 mg/m2 was administered as a single 60 min infusion in 1000-mL 0.9% NaCl. A minimum of 2.0 × 106 CD34 + cells/kg body weight were reinfused on day 0.\n\nBeEAM: Bendamustine at 200 mg/m2 was given as a single 1-h infusion in 1000 mL in 0.9% NaCl on days − 7 and − 6. On days − 5 to − 2, 200 mg/m2 cytarabine was administered every 12 h as a 30-min infusion in 100 mL 0.9% NaCl. On days − 5 to − 2, 200 mg/m2 etoposide was administered once daily as a 120 min infusion in 1000 mL 0.9% NaCl. Melphalan at 140 mg/m2 was administered as a single 60 min infusion in 1000-mL 0.9% NaCl. A minimum of 2.0 × 106 CD34 + cells/kg body weight were reinfused on day 0.\n\nAll patients on BEAM and BeEAM received weight-adapted G-CSF (filgrastim 300mcg if ≤ 70 kg or 480mch if ≥ 70 kg) starting at day + 7 until neutrophils exceeded 1.0 g/L. As per institutional protocol, patients received antiviral (oral valacyclovir 500 mg twice daily) and antifungal prophylaxis (oral fluconazole 200 mg once weekly and oral sulfamethoxazole/ trimethoprim 800/160 mg three times per week). Antibiotic prophylaxis was not used. Patients were transfused with platelets when platelet counts dropped below 10 × 109/L. Patients received red cell transfusions at a hemoglobin threshold of 70 g/L. Patients were hospitalized at the initiation of HDCT and remained in-hospital until hematologic and adequate performance status was achieved.\n\nMeasurements and definitions\n\nNephrotoxicity was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 guidelines. The institutional upper limit of normal for creatinine (104 µmol/L) was used to define recovery at discharge. Typhlitis was only reported if it was confirmed via CT assessment. OS was defined as the time from ASCT to death. PFS was defined as time from ASCT to first relapse/progression, death, or last follow-up, whichever occurred first. Neutrophil engraftment was defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) was 500 cells/mm3 (0.5 × 109/L) or greater. Platelet engraftment was defined as a platelet count of 20,000/mm3 (20 × 109/L) unsupported by a platelet transfusion (> 3 days post-transfusion).\n\nStatistical analysis\n\nDescriptive analysis was performed to summarize the data. Mean and standard deviation estimates of each continuous variable were calculated separately and compared between HDCT regimens using Student’s t tests. For categorical variables, proportion estimates were calculated separately and compared between BEAM and BeEAM using a χ2 or Fischer’s exact test when appropriate. The primary endpoints analyzed were progression free survival (PFS) and overall survival (OS). We used the Kaplan–Meier method to understand the survival distribution and to produce survival curves for PFS and OS for both HDCT regimens. Then, we compared the survival distributions between the two groups to determine equivalency using log-rank test. Univariable and multivariate Cox regression models were used to analyze each HDCT and multiple risk factors for OS and PFS separately. The results are given with a hazard rate (HR), confidence interval (CI) of 95% and p value. Statistical analyses and associated figures were generated with the Statistical Package for the Social Sciences (SPSS) Version 26 (SPSS Inc. Armonk, NY: IBM Corp.). Statistical significance was defined by an alpha level of p ≤ 0.05.\n\nEconomical analysis\n\nOur economic analysis was based on comparison of the list pharmaceutical costs. Only the direct cost of chemotherapy agents was analyzed, and ancillary costs were not factored in the analysis.\n\nEthics approval\n\nThe following study was approved by the local ethics committee at the Saskatchewan Cancer Agency.\n\nConsent to participate\n\nData transfer agreements were signed with the Saskatchewan Cancer Agency.\n\nConsent for publication\n\nApproval for publication was granted by the Saskatchewan Cancer Agency. The results and conclusions presented here represent the work of the authors and no endorsement by the SCA or by any third party is to be inferred.\n\nResults\n\nEngraftment, transfusions and hospitalization (BeEAM patients)\n\nThe median time to platelet engraftment was 12.6 days (range: 7–19 days), whereas median time for neutrophil engraftment was 11.7 days (9–15 days) for BeEAM HDCT patients. The median number of platelet transfusions was 4.3 units (range: 2–9 units) per admission for BeEAM ASCT. The median number of packed red blood cell (pRBC) transfusion units was 2.3 units (range: 0–5 units). Interestingly, 53.7% of BeEAM patients required less than two pRBC transfusions. The median number of days of admission to hospital for BeEAM transplantation was 24.2 days (range: 18–33 days) (Table 2).Table 2 BeEAM toxicities.\n\nPatients\tBeEAM\t\nn = 41\t\nDeath prior to Day 100\t2.4% (n = 1)\t\nGastrointestinal toxicity\t\nMucositis\t88% (n = 36)\t\n Grade I–II\tn = 34\t\n Grade III–IV\tn = 2\t\nTyphlitis\t27% (n = 11)\t\nRenal toxicity\t\nAll grades\t32% (n = 13)\t\nGrade I–II\tn = 12\t\nGrade III–IV\tn = 1\t\nCardiac toxicity\t\nNew onset atrial fibrillation\t15% (n = 6)\t\nMyocardial infarction\t2.4% (n = 1)\t\nInfectious complications\t\nFebrile neutropenia\t100% (n = 41)\t\nSeptic shock\t12.2% (n = 5)\t\nICU admissions\t2.4% (n = 1)\t\nBacterial infections\t56% (n = 23)\t\nBacteria gram + ve (%)\t66.7%\t\nBacteria gram − ve (%)\t33.3%\t\nViral infections\t14.6 (n = 6)\t\nFungal infections\t2.4% (n = 1)\t\nNo organism identified\t29.3% (n = 12)\t\nTransfusion and engraftment\t\nMedian days to platelet engraftment\t12.6 (7–19)\t\nMedian days to neutrophil engraftment\t11.7 (9–15)\t\nMedian platelet transfusions\t4.3 (2–9)\t\nMedian red blood cell transfusions\t2.3 (0–5)\t\nHospitalization\t\nMedian days in hospital\t24.2 (18–33)\t\n\nToxicities (BeEAM patients only)\n\nThirteen BeEAM patients (32%) experienced nephrotoxicity according to CTCAE v5.0 guidelines. Twelve of these patients experienced grade I–II toxicity, while one patient suffered grade III renal toxicity. Mean baseline creatinine for patients experiencing nephrotoxicity was 87.6 µmol/L (range: 51–128 µmol/L), compared to 76.5 µmol/L (range: 38–157 µmol/L) in patients who did not experience nephrotoxicity. All patients were treated expectantly with no patient requiring dialysis. Interestingly, nine of these thirteen patients had elevated creatinine levels at discharge, indicating some persistence of renal impairment. Thirty-six patients (88%) experienced documented mucositis. Thirty-four of these patients suffered grade I-II mucositis, whereas two patients experienced grade III mucositis. Eleven patients (27%) experienced CT-confirmed typhlitis, and all patients were treated with IV antibiotics and bowel rest. Six patients (15%) experienced new-onset atrial fibrillation during the course of their admission for ASCT (Table 2).\n\nInfections (BeEAM patients)\n\nAll patients undergoing BeEAM ASCT experienced at least one episode of febrile neutropenia. No organism was identified in twelve (29.3%) of these aforementioned patients. 23 patients had a documented bacterial infection. Among documented bacterial infections, 66.7% of isolated species were gram positive and 33.3% were gram negative species. Six patients (14.6%) had documented viral infections. Five of these viral infections were with common respiratory viruses (rhinovirus, coronavirus, parainfluenza) and one patient experienced cystitis related to BK virus reactivation. One patient (2.4%) experienced a fungal infection in the form of aspergillus. Five patients (12.2%) experienced septic shock, with one of these patients being admitted to the ICU and another requiring consultation from ICU. No patients died from infectious complications during ASCT (Table 2).\n\nSurvival\n\nOne sudden death occurred in the BeEAM cohort. This death occurred on day + 14 from stem cell infusion and was felt to be due to a cardiac arrest in a patient with known cardiac disease, yielding a TRM of 2.4%. The 3-year OS was 78.1% for BEAM, and 71.0% for BeEAM. The 3-year PFS was 71.3% for BEAM, and 74.1% for BeEAM. Our 3-year calculation of OS and PFS showed no significant differences between the two HDCT regimens (Table 3). Interestingly, multivariate analysis of covariates such as age, sex and diagnosis yielded no significant effect on OS or PS at 3-year follow-up. Multivariate analysis revealed no significant difference in OS or PFS between the two conditioning regimens (p = 0.372, 0.801; respectively) (Tables 4, 5).Table 3 Probability of 3-year survival.\n\n\tNumber of patients\tOverall survival (OS)\tProgression free survival (PFS)\t\n3-Year probability (%)\t95% CI\tp value\t3-Year probability (%)\t95% CI\tp value\t\nLower\tUpper\tLower\tUpper\t\nWhole cohort\t127\t76\t67.8\t84.2\t–\t71\t62.2\t79.8\t–\t\nBEAM\t86\t78.1\t69.08\t87.12\t0.296\t71.3\t61.3\t81.3\t0.762\t\nBeEAM\t41\t71\t52.4\t89.6\t\t74.1\t58.2\t90.0\t\t\nAge\t\n≤ 60\t85\t75.3\t65.5\t85.1\t0.718\t68.1\t57.1\t79.1\t0.433\t\n> 60\t42\t76.6\t61.1\t92.1\t\t77.3\t63.2\t91.4\t\t\nSex\t\nFemale\t46\t76.3\t63.4\t89.2\t0.815\t68.5\t54.2\t82.8\t0.953\t\nMale\t81\t75.6\t65.0\t86.2\t\t72.6\t61.6\t83.6\t\t\nDx\t\nHodgkin lymphoma/nodular sclerosis\t92\t71.9\t61.5\t82.3\t0.267\t70.5\t59.9\t81.1\t0.671\t\nAll others\t35\t84.7\t72.4\t97.0\t\t71.4\t55.5\t87.3\t\t\n\nTable 4 Overall survival: multivariate Cox regression model.\n\nTime to death\tHR\t95% CI\tp value\t\nLower\tUpper\t\nRegimen\t\nBEAM\t\t\t\t\t\nBeEAM\t1.483\t0.625\t3.518\t0.372\t\nAge\t\n≤ 60\t\t\t\t\t\n> 60\t0.733\t0.33\t1.63\t0.446\t\nSex\t\nFemale\t\t\t\t\t\nMale\t0.995\t0.494\t2.001\t0.988\t\nDx\t\nAll others\t\t\t\t\t\nHodgkin lymphoma/nodular sclerosis\t0.603\t0.262\t1.391\t0.236\t\n\nTable 5 Progression-free survival: multivariate Cox regression model.\n\nTime to Relapse\tHR\t95% CI\tp value\t\nLower\tUpper\t\nRegimen\t\nBEAM\t\t\t\t\t\nBeEAM\t1.114\t0.482\t2.574\t0.801\t\nAge\t\n≤ 60\t\t\t\t\t\n> 60\t0.677\t0.306\t1.494\t0.334\t\nSex\t\nFemale\t\t\t\t\t\nMale\t0.942\t0.472\t1.877\t0.864\t\nDx\t\nAll others\t\t\t\t\t\nHodgkin lymphoma/nodular sclerosis\t0.756\t0.34\t1.684\t0.494\t\n\nEconomic analysis\n\nOur economic analysis, which used local pharmacy data, revealed tremendous cost benefits of BeEAM HDCT in comparison to BEAM HDCT. At our center in Saskatchewan, Canada, the cost of a BeEAM ASCT is $12,181 CAD, whereas the cost of a BEAM ASCT is $33,381 CAD. This equates to a net savings of $21,200 CAD per transplant. The introduction of BeEAM at our centre in 2015 has resulted in a total savings of approximately $890,000 CAD from 2015 to 2019.\n\nDiscussion\n\nThere is a paucity of research comparing HDCT regimens in the context of stem cell transplantation. The present study depicts our institution’s experience with BeEAM chemotherapy in terms of toxicity, efficacy and cost in reference to the previous BEAM regimen. To our knowledge, it is the first study to explore both the clinical and financial considerations associated with this widespread HDCT transition. This single-centre study suggests several reasons for the perseverance of BeEAM as the conditioning regimen of choice at our institution.\n\nOur study found an incidence of grade I–IV renal toxicity of 32% in the BeEAM HDCT cohort. This is consistent with previous retrospective studies, however the incidence of nephrotoxicity varies widely in the literature from 1.6 to 48%6,15–18. The incidence of BeEAM nephrotoxicity reported here is higher than that reported for BEAM in previous cohort studies16–18. However, the significance of our findings should be interpreted cautiously as all patients with renal impairment were treated expectantly and renal function did not delay the HDCT/ASCT regimen for any patient followed. Additionally, it has been reported in the literature that renal insufficiency during ASCT does not impact hematopoietic stem cell collection, affect mucositis incidence, delay engraftment or increase transfusion requirements22,23. Also, the renal toxicity experienced by ASCT patients may not be fully imputable to bendamustine, as patients undergoing ASCT are frequently exposed to other nephrotoxic agents such as vancomycin. Despite this, precautions such as the provision of adequate hydration and the avoidance of bendamustine dose escalations beyond 200 mg/m2/day are generally recommended14,16.\n\nThe prevalence of oral mucositis amongst BeEAM patients was 88%, which is concordant with other studies6,8,10. Interestingly, we report relatively low rates of grade III–IV oral mucositis, with only 2 patients experiencing grade III toxicity, whereas a recent study conducted by Visani et al. reported that approximately 25% of patients receiving BeEAM HDCT experienced grade III–IV mucositis12. Another study reported the incidence of grade III–IV oral mucositis to be 42.9% in NHL patients receiving the older BEAM chemotherapy24. Thus, these results are suggestive of a favourable toxicological profile with regards to oral mucositis. Interestingly, our institutional mucositis protocol only involves club soda mouthwashes four times a day.\n\nTyphlitis is an important toxicological consideration with associated mortality rates as high as 50% reported in the literature25. Eleven patients (27%) developed CT-confirmed typhlitis in the present study. Diagnostic criteria and incidences of typhlitis vary amongst comparable studies with incidences of 17–35% reported in the literature6,12,17. Cohort studies comparing the digestive toxicity of BeEAM and BEAM have also garnered mixed results16–18. None of the patients who developed typhlitis required surgery. We suspect typhlitis rates are high at our centre as we do not employ prophylactic antibiotics, due to hospital antibiotic stewardship measures.\n\nAdditionally, we report 6 cases of new-onset atrial fibrillation within our BeEAM cohort. This finding is congruous with previous studies which report a small to moderate risk of BeEAM-associated cardiotoxicity6,8,14. Additionally, one cardiac-related death was reported in the present study. All cases of new-onset atrial fibrillation were managed conventionally with beta-blockers. It is important to note that cardiotoxicity is not exclusive to the BeEAM conditioning regimen. For instance, a large cohort study conducted by Robinson et al. reported 3 cases of fatal cardiac toxicity associated with BEAM chemotherapy26.\n\nWithin our small BeEAM cohort, 56% of patients experienced a culture-positive bacterial infection. However, this is consistent with previous studies which report BeEAM-associated bacteremia rates ranging from 24 to 64%8,16,17. While no patient in our BeEAM cohort died of infectious complications, one patient did require treatment in the ICU. It is important to note that cohort studies comparing the toxicity of BeEAM and BEAM have not yielded significant differences between the conditioning regimens in terms of bacteremia rates16,17.\n\nNo patients in our BeEAM cohort developed IPS, which is a dreaded transplant complication. This may reflect a potential advantage over BCNU chemotherapies which carry a known risk of IPS19–21. However, the research remains uncertain as to the true risk of BCNU with regards to IPS. A recent study, for instance, found that BCNU doses of 300 mg/m2 were only associated with a 0.7% incidence of pulmonary toxicity27. Thus, the cost utility of mitigating IPS is unknown at this time.\n\nWe constructed Kaplan–Meier curves comparing OS and PFS in our BeEAM cohort and a historical BEAM cohort from our centre (Figs. 1, 2). We found no difference in OS and PFS between the conditioning regimens in multivariate analysis (p = 0.372, 0.801; respectively). This is consistent with other cohort studies16–18. We report a 100-day TRM of 2.4% in our BeEAM cohort, indicating acceptable safety and efficacy of the conditioning regimen. Interestingly, our multivariate analysis did not yield any significant differences with respect to age, sex or diagnosis of the patient undergoing transplantation. Perhaps this is indicative of widespread acceptability of the HDCT.Figure 1 Kaplan–Meier analysis of overall survival. Overall survival (OS) in patients who underwent an ASCT with BEAM or BeEAM. ASCT autologous stem cell transplantation, BEAM BCNU, etoposide, cytarabine, melphalan, BeEAM bendamustine, etoposide, cytarabine, melphalan. p values were determined using the log-rank test.\n\nFigure 2 Kaplan–Meier analysis of progression-free survival. Progression-free survival in patients who underwent an ASCT with BEAM or BeEAM. ASCT autologous stem cell transplantation, BEAM BCNU, etoposide, cytarabine, melphalan, BeEAM bendamustine, etoposide, cytarabine, melphalan. p values were determined using the log-rank test.\n\nUnfortunately, the present study is unable to directly compare the toxicological profiles of each HDCT regimen, as we do not presently have access to acute transplant toxicity data for the BEAM cohort. Another disadvantage of the present study is a relatively short duration of follow-up associated with BeEAM HDCT due to its recent enrolment at our centre. Furthermore, our cost analysis was limited to the raw cost of the chemotherapies at our institution. Therefore, ancillary costs related to administration of the HDCTs were not included but not expected to be significantly different between cohorts.\n\nOur data confirms that BeEAM chemotherapy has adequate PFS and OS, an acceptable safety profile and marked cost-savings in comparison to BEAM chemotherapy. Based on this study, BeEAM chemotherapy will remain standard of care at our institution. Our centre’s experience with the BeEAM regimen suggests that the small risk of often clinically-insignificant nephrotoxicity is offset by tremendous cost-effectiveness. However, larger, prospective trials are necessary to fully elucidate the benefits and risks of BeEAM chemotherapy.\n\nAcknowledgements\n\nWe would like to thank our patients and the Saskatchewan Cancer Agency for their assistance. Also, we wish to thank the University of Saskatchewan College of Medicine’s Dean’s project program for fostering collaboration between the authors. Additionally, we would like to thank Ambika Chandrasekhar for her assistance in editing the paper.\n\nAuthor contributions\n\nL.H. and M.B. designed and wrote the paper. H.L. performed all statistical analyses. T.D. and P.D. assisted with data collection. All authors reviewed and approved the paper.\n\nFunding\n\nNo funding sources to disclose.\n\nData availability\n\nNot applicable.\n\nCode availability\n\nNot applicable.\n\nCompeting interests\n\nThe authors declare no competing interests.\n\nPublisher's note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Philip T Guglielmi C Hagenbeek A Somers R Van Der Lelie H Bron D Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma N. Engl. J. Med. 1995 333 23 1540 1545 10.1056/NEJM199512073332305 7477169\n2. Gisselbrecht C Glass B Mounier N Gill DS Linch DC Trneny M Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era J. Clin. Oncol. 2010 28 27 4184 10.1200/JCO.2010.28.1618 20660832\n3. Linch D Goldstone AH McMillan A Chopra R Hudson GV Winfield D Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: Results of a BNLI randomised trial Lancet 1993 341 8852 1051 1054 10.1016/0140-6736(93)92411-l 8096958\n4. Schmitz N Pfistner B Sextro M Sieber M Carella AM Haenel M Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: A randomised trial Lancet 2002 359 9323 2065 2071 10.1016/S0140-6736(02)08938-9 12086759\n5. Colita A Colita A Bumbea H Croitoru A Orban C Lipan LE LEAM vs. BEAM vs. CLV conditioning regimen for autologous stem cell transplantation in malignant lymphomas. Retrospective comparison of toxicity and efficacy on 222 patients in the first 100 days after transplant, on behalf of the Romanian society for bone marrow transplantation Front. Oncol. 2019 9 892 10.3389/fonc.2019.00892 31552193\n6. Chantepie S Tchernonog E Peyrade F Larcher MV Diouf M Fornecker LM Bendamustine-based (BeEAM) conditioning before autologous stem cell transplantation: Result of a French multicenter study of 386 patients from Lysa Centers Blood 2016 128 22 3450 10.1182/blood.V128.22.3450.3450\n7. Durant JR Norgard MJ Murad TM Bartolucci AA Langford KH Pulmonary toxicity associated with bischloroethylnitrosourea (BCNU) Ann. Intern. Med. 1979 90 191 194 10.7326/0003-4819-90-2-191 443651\n8. Gilli S Novak U Taleghani BM Baerlocher GM Leibundgut K Banz Y BeEAM conditioning with bendamustine-replacing BCNU before autologous transplantation is safe and effective in lymphoma patients Ann. Hematol. 2017 96 421 429 10.1007/s00277-016-2900-y 28011985\n9. Chen YB Lane AA Logan BR Zhu X Akpek G Aljurf MD Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation Biol. Blood Marrow Transplant. 2015 21 6 1046 1053 10.1016/j.bbmt.2015.02.005 25687795\n10. Caballero MD Rubio V Rifon J Heras I Garcia-Sanz R Vazquez L BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: Analysis of efficacy, toxicity and prognostic factors Bone Marrow Transplant. 1997 20 6 451 458 10.1038/sj.bmt.1700913 9313877\n11. Bhatia S Robison LL Francisco L Carter A Liu Y Grant M Late mortality in survivors of autologous hematopoietic-cell transplantation: Report from the bone marrow transplant survivor study Blood 2005 105 11 4215 4222 10.1182/blood-2005-01-0035 15701723\n12. Visani G Malerba L Stefani PM Capria S Galieni P Gaudio F BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients Blood 2011 118 12 3419 3425 10.1182/blood-2011-04-351924 21816830\n13. Leoni LM Bailey B Reifert J Bendall HH Zeller RW Corbeil J Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents Clin. Cancer Res. 2008 14 1 309 317 10.1158/1078-0432.CCR-07-1061 18172283\n14. Noesslinger T Panny M Simanek R Moestl M Boehm A Menschel E High-dose Bendamustine-EAM followed by autologous stem cell rescue results in long-term remission rates in lymphoma patients, without renal toxicity Eur. J. Haematol. 2018 101 3 326 331 10.1111/ejh.13102 29799642\n15. Ribrag V Saleh K Danu A Koscielny S Pilorge S Castilla-Lorente C BEAM or BeEAM high-dose chemotherapy followed by ASCT: A single center comparative analysis of toxicity Blood 2016 128 22 4648 10.1182/blood.V128.22.4648.4648\n16. Saleh K Danu A Koscielny S Legoupil C Pilorge S Castilla-Llorente C A retrospective, matched paired analysis comparing bendamustine containing BeEAM versus BEAM conditioning regimen: Results from a single center experience Leuk. Lymphoma 2018 59 11 2580 2587 10.1080/10428194.2017.1403019 29164977\n17. Garciaz S Coso D De Collela JS Broussais F Stoppa AM Aurran T Bendamustine-based conditioning for non-Hodgkin lymphoma autologous transplantation: An increasing risk of renal toxicity Bone Marrow Transplant. 2016 51 2 319 321 10.1038/bmt.2015.257 26524266\n18. Frankiewicz A Saduś-Wojciechowska M Najda J Czerw T Mendrek W Sobczyk-Kruszelnicka M Comparable safety profile of BeEAM (bendamustine, etoposide, cytarabine, melphalan) and BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning before autologous haematopoietic cell transplantation Contemp. Oncol. 2018 22 2 113 117 10.5114/wo.2018.77046\n19. Lane AA Armand P Feng Y Neuberg DS Abramson JS Brown JR Risk factors for development of pneumonitis after high-dose chemotherapy with cyclophosphamide, BCNU and etoposide followed by autologous stem cell transplant Leuk. Lymphoma 2012 53 6 1130 1136 10.3109/10428194.2011.645208 22132836\n20. Afessa B Abdulai RM Kremers WK Hogan WJ Litzow MR Peters SG Risk factors and outcome of pulmonary complications after autologous hematopoietic stem cell transplant Chest 2012 141 2 442 450 10.1378/chest.10-2889 21778261\n21. Till BG Madtes DK BCNU-associated pneumonitis: portrait of a toxicity Leuk. lymphoma 2012 53 6 1019 1020 10.3109/10428194.2011.654341 22220936\n22. Farnault L Venton G Pourroy B Jourde-Chiche N Ivanov V Arcani R Severe renal insufficiency is not an absolute pitfall to autologous stem cell transplantation with BeEAM (bendamustine, etoposide, cytarabine, melphalan) conditioning regimen Bone Marrow Transplant. 2019 54 7 1173 1175 10.1038/s41409-019-0467-7 30718799\n23. Tricot G Alberts DS Johnson C Roe DJ Dorr RT Bracy D Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study Clin. Cancer Res. 1996 2 947 952 9816255\n24. Jo JC Kang BW Jang G Sym SJ Lee SS Koo JE BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma patients: Comparative analysis of efficacy and toxicity Ann. Hematol. 2008 87 1 43 48 10.1007/s00277-007-0360-0 17710401\n25. Ullery BW Pieracci FM Rodney JR Barie PS Neutropenic enterocolitis Surg. Infect. 2009 10 3 307 314 10.1089/sur.2008.061\n26. Robinson SP Boumendil A Finel H Dreger P Sureda A Hermine O High-dose therapy with BEAC conditioning compared to BEAM conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: no differences in toxicity or outcome. A matched-control study of the EBMT-Lymphoma Working Party Bone Marrow Transplant. 2018 53 12 1553 1559 10.1038/s41409-018-0196-3 29884850\n27. Olivieri J Mosna F Pelosini M Fama A Rattotti S Giannoccaro M A comparison of the conditioning regimens BEAM and FEAM for autologous hematopoietic stem cell transplantation in lymphoma: An observational study on 1038 patients from Fondazione Italiana Linfomi Biol. Blood Marrow Transplant. 2018 24 9 1814 1822 10.1016/j.bbmt.2018.05.018 29857196\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2045-2322",
"issue": "11(1)",
"journal": "Scientific reports",
"keywords": null,
"medline_ta": "Sci Rep",
"mesh_terms": "D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D002330:Carmustine; D003561:Cytarabine; D005047:Etoposide; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan; D008875:Middle Aged; D009369:Neoplasms; D017063:Outcome Assessment, Health Care; D011034:Podophyllotoxin; D019172:Transplantation Conditioning",
"nlm_unique_id": "101563288",
"other_id": null,
"pages": "14071",
"pmc": null,
"pmid": "34234243",
"pubdate": "2021-07-07",
"publication_types": "D016428:Journal Article",
"references": "8096958;17710401;21778261;443651;28011985;29799642;31552193;20660832;7477169;22220936;9313877;21816830;30150889;30718799;9816255;19566419;26524266;25687795;29857196;18172283;29884850;12086759;15701723;29164977;22132836",
"title": "BeEAM conditioning regimen is a safe, efficacious and economical alternative to BEAM chemotherapy.",
"title_normalized": "beeam conditioning regimen is a safe efficacious and economical alternative to beam chemotherapy"
}
|
[
{
"companynumb": "CA-ACCORD-232793",
"fulfillexpeditecriteria": "1",
"occurcountry": "CA",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MELPHALAN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "SINGLE 60 MIN INFUSION IN 1000?ML 0.9% NACL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "140",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MELPHALAN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "BENDAMUSTINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "A SINGLE 1?H INFUSION IN 1000 ML IN 0.9% NACL ON DAYS ? 7 AND ? 6",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENDAMUSTINE HYDROCHLORIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYTARABINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ON DAYS ? 5 TO ? 2, 30?MIN INFUSION IN 100 ML 0.9% NACL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYTARABINE/CYTARABINE HYDROCHLORIDE/CYTARABINE OCFOSFATE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VALACYCLOVIR HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALACICLOVIR"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "800/160 MG THREE TIMES PER WEEK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE/TRIMETHOPRIM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "074513",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ON DAYS ?5 TO ?2, AS A 120 MIN INFUSION IN 1000 ML 0.9% NACL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FILGRASTIM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FILGRASTIM"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Febrile neutropenia",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nephropathy toxic",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HAHN L, LIM H, DUSYK T, SABRY W, ELEMARY M, STAKIW J ET AL. BEEAM CONDITIONING REGIMEN IS A SAFE, EFFICACIOUS AND ECONOMICAL ALTERNATIVE TO BEAM CHEMOTHERAPY. SCI REP. 2021 JUL 7?11(1):14071.",
"literaturereference_normalized": "beeam conditioning regimen is a safe efficacious and economical alternative to beam chemotherapy",
"qualification": "3",
"reportercountry": "CA"
},
"primarysourcecountry": "CA",
"receiptdate": "20210722",
"receivedate": "20210722",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 19595674,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
}
] |
{
"abstract": "A 40-year-old woman was admitted due to an urticarial rash that was attributed to recent onset of methimazole treatment for a diagnosis of Grave's disease. The patient had no prior significant medical history and used no medications, including over-the-counter or herbal medications. Her sister had Grave's disease. On admission, the patient received corticosteroids with improvement in her rash. On the second day of the hospitalization, the patient complained of abdominal discomfort. Abdominal ultrasound revealed a large amount of new onset ascites. Peritoneal tap yielded a milky fluid with high triglyceride level (12.2 mmol/L or 1080 mg/dL), consistent with chylous ascites. After discontinuation of the methimazole, the ascites disappeared. The patient later underwent therapeutic thyroidectomy, after which all features of thyrotoxicosis had improved.",
"affiliations": "Department of Medicine, Hadassah-Hebrew University Medical Center, P.O. Box 12000, IL-91120 Jerusalem, Israel.;Department of Nephrology, Hadassah-Hebrew University Medical Center, P.O. Box 12000, IL-91120 Jerusalem, Israel.",
"authors": "Khoury|Tawfik|T|;Schneider|Ronen|R|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1155/2015/649303",
"fulltext": "\n==== Front\nCase Rep EndocrinolCase Rep EndocrinolCRIECase Reports in Endocrinology2090-65012090-651XHindawi Publishing Corporation 10.1155/2015/649303Case ReportChylous Ascites: A Rare Adverse Effect of Methimazole Treatment for Grave's Disease—A Case Report and Review of the Literature Khoury Tawfik \n1\n\n*\nSchneider Ronen \n2\n1Department of Medicine, Hadassah-Hebrew University Medical Center, P.O. Box 12000, IL-91120 Jerusalem, Israel2Department of Nephrology, Hadassah-Hebrew University Medical Center, P.O. Box 12000, IL-91120 Jerusalem, Israel*Tawfik Khoury: [email protected] Editor: Michael P. Kane\n\n2015 23 8 2015 2015 64930319 6 2015 12 8 2015 Copyright © 2015 T. Khoury and R. Schneider.2015This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A 40-year-old woman was admitted due to an urticarial rash that was attributed to recent onset of methimazole treatment for a diagnosis of Grave's disease. The patient had no prior significant medical history and used no medications, including over-the-counter or herbal medications. Her sister had Grave's disease. On admission, the patient received corticosteroids with improvement in her rash. On the second day of the hospitalization, the patient complained of abdominal discomfort. Abdominal ultrasound revealed a large amount of new onset ascites. Peritoneal tap yielded a milky fluid with high triglyceride level (12.2 mmol/L or 1080 mg/dL), consistent with chylous ascites. After discontinuation of the methimazole, the ascites disappeared. The patient later underwent therapeutic thyroidectomy, after which all features of thyrotoxicosis had improved.\n==== Body\n1. Introduction\nHyperthyroidism can be a result of several disease states including Grave's disease, toxic adenoma, toxic multinodular goiter, Hashimoto's thyroiditis, and more. Graves' disease is the most common cause (95%) of hyperthyroidism, an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies [1]. Some of the manifestations of Grave's disease, like warm skin and sweating, stare and lid lag, increased cardiac output, tachycardia, and congestive heart failure are common to the other etiologies, but some are unique. Among the unique features are ophthalmopathy and infiltrative dermopathy [2]. In addition, rare manifestations of Grave's disease have been described, including pulmonary hypertension and chylous ascites, for which we found only one case reported in the literature [3].\n\nTreatment of Grave's disease may consist of antithyroid drugs such as methimazole and propylthiouracil (PTU) which are thionamide drugs. Among the adverse events of antithyroid treatment are fever, rash, agranulocytosis, and hepatitis. These reactions usually occur within the first few months on initiating treatment [4]. We could not find literature relating chylous ascites to methimazole or PTU treatment.\n\nIn this report we describe the first case of chylous ascites secondary to antithyroid treatment with methimazole for hyperthyroidism with atrial fibrillation and pulmonary hypertension.\n\n2. Case Presentation\nA previously healthy 40-year-old woman presented with one-week history of diffuse urticarial rash to the dermatology ward which was successfully treated with systemic steroids and antihistamine medications. Three weeks prior to admission, treatment with methimazole 10 mg twice daily had been initiated due to a presumptive diagnosis of Grave's thyroiditis. The diagnosis was made in an outpatient clinic according to typical clinical picture, with low TSH level 0.01 MU/L (normal range 0.35–5.5 MU/L) and high T4 level of 59.1 Pmol/L (normal range 10–20 Pmol/L).\n\nOn admission the patient had no symptoms suggestive of hyperthyroidism; on physical examination, an extensive urticarial rash was observed on the limbs and trunk. The patient had a blood pressure of 131/60 mm/Hg, temperature of 36.°C, respiration rate of 16 breaths/min, and a pulse rate of 83 beats/min. Her hands were warm and displayed resting tremor. Cardiac examination was normal, but jugular venous distention was noted. Lungs were clear to auscultation. There was no peripheral edema. Extra ocular movements were normal. There was no proptosis or periorbital edema. Thyroid gland was not tender, was slightly enlarged, and had a rubbery consistency on palpation.\n\nLaboratory examinations revealed a white blood cell count: 15.5 × 109 cells/millilitre (normal range: 4–10 × 109 cells/millilitre) with 90% neutrophils and hemoglobin was 12.7 g/dL. On the second day of her hospitalization the patient began to complain of worsening abdominal pain. Liver function tests were taken initially on day two and showed mild abnormality in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gama-glutamil transferase (GGT) levels (86, 72, and 88 U/L, resp.). At this time point, methimazole treatment was discontinued. On the third day of the hospitalization enzyme levels were as follows: ALT 270 U/L, AST 430 U/L, and GGT 210 U/L (normal ranges 0–40 U/L for ALT, 0–35 U/L for AST, and 5–36 U/L for GGT). T4 level was 47 Pmol/L (normal range 10–20 Pmol/L) and T3 level was 5.5 Nmol/L (normal range 1.2–3 Nmol/L).\n\nAn abdominal ultrasound showed a large amount of ascites. A diagnostic tap showed fluid with a milky white appearance. Triglyceride level was 12.2 mmol/L (1080 mg/dL), and total protein and lactate dehydrogenase (LDH) levels in ascites were 3.3 g/dL and 326 U/L, respectively. Gram stain was negative for bacteria and fluid cultures were negative. Purified protein derivative (PPD) skin test, acid fast stains of peritoneal fluid, and fluid cultures for tuberculosis were all negative. Serologies for hepatitis A virus, hepatitis B virus, and hepatitis C virus were all negative. Serologies for Epstein-Barr virus and Cytomegalovirus were consistent with prior exposure. Abdominal computed tomography (CT) showed peritoneal fluid, an undefined ovarian mass on the right, and no other abnormalities. Liver size and consistency were normal. Vaginal US did not define the mass better. A lymphangiogram showed no anatomical abnormalities of abdominal lymph vessels or nodes. A gynecological exam was normal, including vaginal ultrasound (US) to define the ovarian mass found on CT scan. The ovarian mass represented a corpus luteum most probably. A follow-up abdominal US after four days showed that the peritoneal fluid had disappeared.\n\nIn parallel to this workup the patient started developing signs and symptoms of thyrotoxicosis such as rapid atrial fibrillation which was not present before the discontinuation of methimazole, worsening tremor, and moderate pulmonary hypertension diagnosed with echocardiography. Since treatment with other antithyroid drugs was considered dangerous and since treatment with iodine was expected to have influence only after 4–8 weeks, and the patient had severe symptoms, a therapeutic thyroidectomy was performed two months after admission.\n\nAfter the procedure the patient was free of symptoms and a follow-up echocardiography showed marked improvement in her pulmonary hypertension. After 1 year of follow-up the patient was asymptomatic, without pulmonary hypertension and with no peritoneal fluid.\n\n3. Discussion\nWe report a case of Grave's disease treated with methimazole with two rare and interesting features. The first is chylous ascites which is an uncommon finding.\n\nIt is usually caused by a chronic disruption of the lymphatic system. Several mechanisms had been proposed for the pathophysiology of chylous ascites, including exudation of lymph material through the walls of acquired or congenital dilated retroperitoneal vessels into the abdominal cavity, direct trauma of the thoracic duct, and obstruction of the lymph flow through the dilated subserosal lymphatics into the peritoneal cavity which produces collagen deposition, fibrosis, and protein-losing enteropathy [5]. The diagnosis is based on the biochemical study of the ascetic fluid. The most important diagnostic criterion is the presence of >2.3 mmol (>200 mg/dL) of triglycerides in ascites fluid [6–9].\n\nThere are several causes of chylous ascites; among them are many pathological processes such as infections, cirrhosis, malignancy, congenital defects, inflammatory process, trauma, and cardiac and renal diseases. Almost two-thirds of all chylous ascites present in developed countries as a consequence of abdominal malignancy [6, 10] and cirrhosis [11–14]. On the other hand, infectious etiologies, such as tuberculosis or filariasis, are responsible for the majority of the cases in developing countries [15, 16].\n\nThe cornerstone management in chylous ascites is treating the underlying cause whenever possible [17–19]. The resolution of chylous ascites usually takes several weeks [20, 21]. But in our case, it resolved few days after the discontinuation of methimazole. Furthermore, when ascites persists after the resolution of the underlying cause, it is recommended to provide a low lipid diet and high protein diet: the former should be supplied in the form of medium chain triglyceride (MCT) which is directly absorbed to the portal circulation from the intestine bypassing the lymph nodes and it reduces the production and flow of lymph. On the other hand, long chain triglycerides in diet must be avoided, as these are converted into free fatty acids and monoglycerides which are transported through the lymphatic system [17, 18, 20]. Moreover, somatostatin analogs which have an inhibitory effect on gastrointestinal hormones and processes have been successfully used in the treatment of chylous ascites, although the mechanism of action in these disorders remains unclear and needs further clarification [22–25]. And lastly, patients who do not improve with enteral nutrition and somatostatin analogs can be managed with total parenteral nutrition with variable results [26–28].\n\nThe etiologic list guided our workup as described above. Although the patient was an Israeli resident, she had emigrated from the Philippines two years prior to admission, and hence an infectious workup was carried out. As mentioned, no evidence of malignancy or intra-abdominal infection was found, and no evidence of anatomical aberrations in lymph structures, including lymphangioleiomyomatosis, was found, using imaging modalities such as abdominal ultrasound, CT scan, and lymphangiogram. The negative workup, and the disappearance of ascites in parallel to improvement in LFTs after discontinuation of methimazole, led us to the conclusion that hepatitis and chylous ascites in our patient were secondary to methimazole treatment.\n\nAfter extensive medical database search on Medline and Embase we could not find such a relation with chylous ascites described in the literature. Thus, our case is the first case describing the causative association between methimazole and chylous ascites.\n\nThe second interesting phenomenon presented by our patient was pulmonary hypertension secondary to thyrotoxicosis. This is much better described in the literature but still represents an uncommon finding [29]. Pulmonary hypertension in our patient resolved completely after thyroidectomy, emphasizing the relation of these findings.\n\nIn conclusion, this case emphasizes the diversity of possible adverse events of antithyroid drugs and the diverse presentation of Grave's disease.\n\nConflict of Interests\nThe authors declare that there is no conflict of interests regarding the publication of this paper.\n==== Refs\n1 Jaruratanasirikul S. Leethanaporn K. Sriplung H. Thyrotoxicosis in children: treatment and outcome Journal of the Medical Association of Thailand 2006 89 7 967 973 2-s2.0-33746255321 16881428 \n2 Bartley G. B. Fatourechi V. Kadrmas E. F. Clinical features of Graves' ophthalmopathy in an incidence cohort The American Journal of Ophthalmology 1996 121 3 284 290 10.1016/s0002-9394(14)70276-4 2-s2.0-0029868358 8597271 \n3 Hiroi N. Sakamoto Y. Urita Y. Higa M. Kuboki K. Yoshino G. Graves' disease with intractable diarrhea, chylous ascites, and chylothorax: a case report Thyroid 2007 17 12 1299 1303 10.1089/thy.2007.0006 2-s2.0-37849032741 18047423 \n4 Cooper D. S. Antithyroid drugs The New England Journal of Medicine 1984 311 21 1353 1362 10.1056/nejm198411223112106 2-s2.0-0021671462 6387489 \n5 Browse N. L. Wilson N. M. Russo F. Al-Hassan H. Allen D. R. Aetiology and treatment of chylous ascites British Journal of Surgery 1992 79 11 1145 1150 10.1002/bjs.1800791110 2-s2.0-0026458653 1467885 \n6 Press O. W. Press N. O. Kaufman S. D. Evaluation and management of chylous ascites Annals of Internal Medicine 1982 96 3 358 364 10.7326/0003-4819-96-3-358 2-s2.0-0020063341 7059101 \n7 Cárdenas A. Chopra S. Chylous ascites American Journal of Gastroenterology 2002 97 8 1896 1900 10.1016/s0002-9270(02)04268-5 2-s2.0-0036678343 12190151 \n8 Moss R. Hinds S. Fedullo A. J. Chylothorax: a complication of the nephrotic syndrome The American Review of Respiratory Disease 1989 140 5 1436 1437 10.1164/ajrccm/140.5.1436 2-s2.0-0024414532 2817608 \n9 Kato A. Kohno S. Ohtake T. Takita T. Hirshida A. Chylous ascites in an adult patient with nephrotic syndrome due to membranous nephropathy Nephron 2001 89 3 361 362 10.1159/000046103 2-s2.0-0035742577 11598407 \n10 Kinney T. B. Ferrara S. L. Miller F. J. Roberts A. C. Hassanein T. Transjugular intrahepatic portosystemic shunt creation as treatment for refractory chylous ascites and chylothorax in a patient with cirrhosis Journal of Vascular and Interventional Radiology 2004 15 1 I 85 89 10.1097/01.rvi.0000106391.63463.4c 2-s2.0-1642576998 14709693 \n11 Cheng W. S. C. Gough I. R. Ward M. Croese J. Powell L. W. Chylous ascites in cirrhosis: a case report and review of the literature Journal of Gastroenterology and Hepatology 1989 4 1 95 99 10.1111/j.1440-1746.1989.tb00811.x 2-s2.0-0024513228 2490947 \n12 Rector W. G. Jr. Spontaneous chylous ascites of cirrhosis Journal of Clinical Gastroenterology 1984 6 4 369 372 2-s2.0-0021178798 6481122 \n13 Runyon B. A. Montano A. A. Akriviadis E. A. Antillon M. R. Irving M. A. McHutchison J. G. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites Annals of Internal Medicine 1992 117 3 215 220 10.7326/0003-4819-117-3-215 2-s2.0-0026645393 1616215 \n14 Sultan S. Pauwels A. Poupon R. Lévy V. G. Chylous ascites in cirrhosis. Retrospective study of 20 cases Gastroentérologie Clinique et Biologique 1990 14 11 842 847 2177427 \n15 Jhittay P. S. Wolverson R. L. Wilson A. O. Acute chylous peritonitis with associated intestinal tuberculosis Journal of Pediatric Surgery 1986 21 1 75 76 10.1016/S0022-3468(86)80662-5 2-s2.0-0022640144 3944763 \n16 Patel K. C. Filariasis, chyluria and chylous effusion Journal of the Association of Physicians of India 1983 31 12 801 803 2-s2.0-0021009048 6674307 \n17 Runyon B. A. Akriviadis E. A. Keyser A. J. The opacity of portal hypertension-related ascites correlates with the fluid's triglyceride concentration American Journal of Clinical Pathology 1991 96 1 142 143 2-s2.0-0025721994 2069132 \n18 Runyon B. A. Hoefs J. C. Morgan T. R. Ascitic fluid analysis in malignancy-related ascites Hepatology 1988 8 5 1104 1109 10.1002/hep.1840080521 2-s2.0-0023766008 3417231 \n19 Isenberg J. I. Gilbert S. B. Pitcher J. L. Ascites with peritoneal involvement in Whipple's disease. Report of a case Gastroenterology 1971 60 2 305 310 2-s2.0-0015012199 4101101 \n20 Leibovitch I. Mor Y. Golomb J. Ramon J. The diagnosis and management of postoperative chylous ascites Journal of Urology 2002 167 2 I 449 457 10.1016/s0022-5347(01)69064-5 2-s2.0-0036144610 11792897 \n21 Lee Y.-Y. Soong W.-J. Lee Y.-S. Hwang B. Total parenteral nutrition as a primary therapeutic modality for congenital chylous ascites: report of one case Acta Paediatrica Taiwanica 2002 43 4 214 216 2-s2.0-0036630538 12238910 \n22 Leong R. W. L. House A. K. Jeffrey G. P. Chylous ascites caused by portal vein thrombosis treated with octreotide Journal of Gastroenterology and Hepatology 2003 18 10 1211 1213 10.1046/j.1440-1746.2003.02850.x 2-s2.0-0242571758 12974913 \n23 Runyon B. A. Care of patients with ascites The New England Journal of Medicine 1994 330 5 337 342 10.1056/nejm199402033300508 2-s2.0-0028762425 8277955 \n24 Weinstein L. D. Scanlon G. T. Hersh T. Chylous ascites—management with medium-chain triglycerides and exacerbation by lymphangiography The American Journal of Digestive Diseases 1969 14 7 500 509 10.1007/bf02283890 2-s2.0-0014541768 4306924 \n25 Reubi J. C. Horisberger U. Waser B. Gebbers J. O. Laissue J. Preferential location of somatostatin receptors in germinal centers of human gut lymphoid tissue Gastroenterology 1992 103 4 1207 1214 2-s2.0-0026781086 1356871 \n26 Kroczek R. A. Congenital chyloperitoneum: direct comparison of medium-chain triglyceride treatment with total parenteral nutrition European Journal of Pediatrics 1985 144 1 77 79 10.1007/bf00491932 2-s2.0-0021892843 3926502 \n27 Alliët P. Young C. Lebenthal E. Chylous ascites: total parenteral nutrition as primary therapeutic modality European Journal of Pediatrics 1992 151 3 213 214 10.1007/BF01954387 2-s2.0-0026517026 1534755 \n28 Huang Q. Jiang Z.-W. Jiang J. Li N. Li J.-S. Chylous ascites: treated with total parenteral nutrition and somatostatin World Journal of Gastroenterology 2004 10 17 2588 2591 2-s2.0-4444383939 15300913 \n29 Mathot V. Oosterwerff E. Van Pampus M. G. Riezebos R. Pulmonary hypertension in a pregnant patient with thyrotoxicosis due to Graves' disease: considerations with respect to treatment BMJ Case Reports 2014 10.1136/bcr-2013-201916 2-s2.0-84896903661\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2090-651X",
"issue": "2015()",
"journal": "Case reports in endocrinology",
"keywords": null,
"medline_ta": "Case Rep Endocrinol",
"mesh_terms": null,
"nlm_unique_id": "101576457",
"other_id": null,
"pages": "649303",
"pmc": null,
"pmid": "26366308",
"pubdate": "2015",
"publication_types": "D016428:Journal Article",
"references": "2177427;1467885;1534755;11598407;7059101;6387489;1356871;18047423;4101101;24526195;2490947;6481122;2817608;3417231;2069132;1616215;3944763;4306924;12190151;3926502;14709693;8277955;6674307;12974913;12238910;16881428;11792897;15300913;8597271",
"title": "Chylous Ascites: A Rare Adverse Effect of Methimazole Treatment for Grave's Disease-A Case Report and Review of the Literature.",
"title_normalized": "chylous ascites a rare adverse effect of methimazole treatment for grave s disease a case report and review of the literature"
}
|
[
{
"companynumb": "IL-SUN PHARMACEUTICAL INDUSTRIES LTD-2015R1-103753",
"fulfillexpeditecriteria": "1",
"occurcountry": "IL",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHIMAZOLE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "40870",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BASEDOW^S DISEASE",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "12",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHIMAZOLE."
}
],
"patientagegroup": null,
"patientonsetage": "40",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Ascites",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Urticaria",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Drug-induced liver injury",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KHOURY T, SCHNEIDER R. CHYLOUS ASCITES: A RARE ADVERSE EFFECT OF METHIMAZOLE TREATMENT FOR GRAVE^S DISEASE-A CASE REPORT AND REVIEW OF THE LITERATURE. CASE REP ENDOCRINOL. 2015;1-4",
"literaturereference_normalized": "chylous ascites a rare adverse effect of methimazole treatment for grave s disease a case report and review of the literature",
"qualification": "3",
"reportercountry": "IL"
},
"primarysourcecountry": "IL",
"receiptdate": "20170125",
"receivedate": "20151006",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11595754,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170428"
},
{
"companynumb": "IL-MYLANLABS-2015M1033450",
"fulfillexpeditecriteria": "1",
"occurcountry": "IL",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHIMAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "040350",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BASEDOW^S DISEASE",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THIAMAZOLE"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Ascites",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatitis",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KHOURY T, SCHNEIDER R. CHYLOUS ASCITES: A RARE ADVERSE EFFECT OF METHIMAZOLE TREATMENT FOR GRAVE^S DISEASE - A CASE REPORT AND REVIEW OF THE LITERATURE. CASE-REP-ENDOCRINOL 2015? :.",
"literaturereference_normalized": "chylous ascites a rare adverse effect of methimazole treatment for grave s disease a case report and review of the literature",
"qualification": "3",
"reportercountry": "IL"
},
"primarysourcecountry": "IL",
"receiptdate": "20151005",
"receivedate": "20151005",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11594192,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160304"
}
] |
{
"abstract": "Scleroderma (SSc) is a disease caused by collagen deposition resulting in fibrosis within multiple organs, including the gastrointestinal tract, skin, joints, kidneys, lungs, and heart. We report a rare case of a patient with diffuse SSc who presented with a large bowel obstruction from a fecal bezoar impaction. The bezoar was successfully removed using colonoscopy after lavage, cold forceps, balloon dilator, and cap-assisted disimpaction. We demonstrate that patients with SSc are at risk for bezoar formation and true mechanical obstruction in the lower gastrointestinal tract, which may require more aggressive endoscopic treatment if conservative measures fail.",
"affiliations": "Department of Medicine, NYU School of Medicine, New York, NY.;Department of Medicine, NYU School of Medicine, New York, NY.;Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, New York, NY.;Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, New York, NY.;Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, New York, NY.",
"authors": "Sarnoff|Rachel|R|;Girmay|Blen|B|;Bhakta|Dimpal|D|;Mocharla|Robert|R|;Williams|Renee|R|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.14309/crj.0000000000000059",
"fulltext": "\n==== Front\nACG Case Rep JACG Case Rep JACGCRJACGCRJAC9ACG Case Reports Journal2326-3253Wolters Kluwer Maryland, MD ACGCR-18-047810.14309/crj.000000000000005900012Case ReportColonAn Obstructing Fecal Bezoar in a Patient with Scleroderma with Successful Colonoscopic Disimpaction Sarnoff Rachel MS41Girmay Blen MS41Bhakta Dimpal MD2Mocharla Robert MD23Williams Renee MD21 Department of Medicine, NYU School of Medicine, New York, NY2 Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, New York, NY3 Division of Digestive Diseases, Department of Medicine, UCLA Health, Beverly Hills, CACorrespondence: Rachel Sarnoff, Department of Medicine, New York University School of Medicine, 550 1st Avenue, New York, NY 10016 ([email protected]).11 4 2019 4 2019 6 4 e0005904 7 2018 31 1 2019 © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.2019This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.ABSTRACT\nScleroderma (SSc) is a disease caused by collagen deposition resulting in fibrosis within multiple organs, including the gastrointestinal tract, skin, joints, kidneys, lungs, and heart. We report a rare case of a patient with diffuse SSc who presented with a large bowel obstruction from a fecal bezoar impaction. The bezoar was successfully removed using colonoscopy after lavage, cold forceps, balloon dilator, and cap-assisted disimpaction. We demonstrate that patients with SSc are at risk for bezoar formation and true mechanical obstruction in the lower gastrointestinal tract, which may require more aggressive endoscopic treatment if conservative measures fail.\n\nOPEN-ACCESSTRUE\n==== Body\nINTRODUCTION\nScleroderma (SSc) is a systemic disease characterized by collagen deposition that frequently involves the gastrointestinal (GI) tract. GI involvement of SSc manifests in various ways including gastroesophageal reflux (GERD), dysphagia, small intestinal bacterial overgrowth (SIBO), constipation, diarrhea, and intestinal pseudo-obstruction. Rarely, dysmotility from colonic involvement of SSc can lead to fecal bezoar formation, which can lead to intestinal obstructions.1 We report a case of a patient with SSc who suffered a true mechanical bowel obstruction secondary to fecal impaction in the transverse colon. Her obstruction was successfully disimpacted using colonoscopy.\n\nCASE REPORT\nA 44-year-old woman with diffuse SSc presented with abdominal pain, nausea, and vomiting for 2 days. Her pain was crampy, diffuse, intermittent, and progressive. It was accompanied by diminished appetite, several episodes of vomiting, and small-volume diarrhea. She tried taking loperamide for the diarrhea with no relief. She denied any fevers, chills, hematemesis, melena, hematochezia, or constipation. Her medical history was also positive for hypertension and GERD, but otherwise, she reported no personal or family history of any GI conditions. Medications included oral prednisone 7 mg daily and a proton-pump inhibitor.\n\nOn physical examination, she was cachectic with SSc-related skin changes. Her abdomen was soft but distended and tender in all 4 quadrants. A firm mass was palpated in the right upper quadrant. Abdominal computed tomography with contrast revealed a 6-cm fecal bezoar in the transverse colon with proximal large and small bowel dilatation (Figure 1). Her serum potassium was 3 mEq/L and magnesium was 0.67 mmol/L; otherwise, her laboratory values were within normal limits.\n\nFigure 1. Contrast-enhanced abdominal computed tomography. (A) Axial view showing 4.6 × 5.7 cm mass with mottled appearance consistent with fecal bezoar in transverse colon along with inflammatory bowel wall thickening. (B) Coronal view showing moderate diffuse fluid-filled distention of loops of small and large bowel proximal to fecal bezoar in the proximal transverse colon, consistent with a developing upstream large and small bowel obstruction.\n\nThe patient was diagnosed with a large bowel obstruction secondary to a fecal bezoar. She was given 4 liters of polyethylene glycol (PEG) by mouth, but she was unable to tolerate the full dose. Her symptoms persisted despite passing flatus and watery stool. Repeat abdominal imaging by x-ray showed minimal movement of the stool ball, therefore colonoscopy was recommended for disimpaction (Figure 2). During colonoscopy, the fecal bezoar was found at the hepatic flexure (Figure 3). Mechanical disimpaction was attempted with a rat tooth, cold snare, and aggressive water irrigation with partial success. The patient then continued oral PEG treatment to further disrupt and pass the bezoar after the colonoscopy; however, abdominal x-ray the following morning revealed no significant improvement of her obstruction. Colonoscopy was repeated and revealed the fecal bezoar to be in the same location at the hepatic flexure. Several balloon dilation sweeps with a controlled radial expansion wire-guided balloon (Boston Scientific, Marlborough, MA) were used to advance the bezoar out of the hepatic flexure, further distal in the transverse colon for better access. There was poor visualization proximal to the bezoar, and the distal tip of the balloon was guided blindly. Repeated washings were used to soften the bezoar so that tools such as cold biopsy forceps, rat tooth forceps, and a snare and lasso technique could more effectively break the bezoar into smaller pieces that were easier to pass spontaneously. Cap-assisted colonoscopy was helpful in protecting the camera from debris obstructing the view. After 3 hours of irrigation and mechanical disimpaction, the obstruction was relieved.\n\nFigure 2. Plain abdominal radiograph showing the 6-cm fecal bezoar, unchanged in location in the transverse colon.\n\nFigure 3. Colonoscopy showing (A) the full view of fecal bezoar in transverse colon prior to disimpaction, and (B) the fecal bezoar lodged in the hepatic flexure of the transverse colon prior to disimpaction.\n\nThe patient's GI symptoms resolved postprocedure. After she could tolerate a normal diet, she was discharged with an aggressive oral bowel regimen and motility specialist follow-up.\n\nDISCUSSION\nSSc can affect any part of the GI tract, resulting in fibrosis and dysmotility of the gut wall. SSc's GI manifestations account for 6%–12% of the mortality rate of these patients.2 The GI pathophysiology of SSc is explained by Sjogren's theory.3 In response to an unknown initial injury, collagen deposits in blood vessels within the gut wall.4 This causes recurrent vascular derangement, compression of nerves, and autoimmune-mediated injury.3 Immune cells infiltrate the smooth muscle, causing dysfunction, atrophy, and fibrosis.\n\nThe most common GI manifestation of SSc is esophageal dysfunction due to fibrosis of the lower two-thirds of the esophagus. It can lead to an incompetent lower esophageal sphincter, inadequate peristalsis, GERD, and/or stricture formation.5 Another common site of SSc involvement is the small intestine, resulting in hypomotility and stasis. Consequently, 10%–30% of these patients have SIBO, leading to malabsorption and diarrhea.6\n\nLess commonly, SSc results in colonic hypomotility. Symptoms most often include bloating, abdominal pain, and constipation, which can ultimately result in overflow diarrhea that passes around the hardened stool. The progressive hypomotility of the colon can result in pseudo-obstruction, which refers to obstruction without a mechanical cause. However, in rare instances, a true mechanical obstruction can occur because of stool completely blocking the large intestine, but few case reports exist in the literature.1 This rarity may be because SIBO and malabsorption lead to small intestinal diarrhea, which often mitigates stool impaction.2 Nonetheless, for patients with severe colonic SSc, stool transit can be significantly impaired, allowing a fecal bezoar to accumulate over time despite overflow diarrhea.\n\nRegarding management of bezoar-induced obstruction in patients with SSc, physicians should consider oral osmotic laxatives such as PEG, prokinetic agents, and, if the obstruction is distal to the transverse colon, mineral oil enemas.7 If conservative measures fail, colonoscopic intervention may be successful.8 In cases of mechanical obstruction, in all patients, surgical management is reserved for patients who do not respond to endoscopic treatment or who have bowel perforation. Limited resection of the colon outside of these circumstances is unlikely to be helpful, especially in patients with SSc due to the pan-colonic fibrosis inherent to the disease.9 Surgery is therefore almost never performed on these patients. For prevention of bowel obstruction, the same conservative measures (PEG, prokinetic agents and mineral oil enemas) can be used in lower doses and frequencies, both in patients with SSc and other at-risk patients.10\n\nBecause of its rarity, recurrence rates—and epidemiologic data in general—for true bowel obstruction in patients with SSc are not known, although some data exist pertaining to pseudo-obstruction. One study showed that the mortality rate from acute intestinal pseudo-obstruction in patients with SSc was 16%.11 Female patients who presented with pseudo-obstruction were more likely to have recurrence than male patients, although male patients had a higher mortality rate after pseudo-obstruction [ibid].\n\nWe present a rare case of a true mechanical bowel obstruction secondary to fecal bezoar formation in a patient with systemic SSc. The patient's obstruction was successfully relieved with medical and endoscopic therapy. Although most data on SSc-related bowel obstructions focus on pseudo-obstructions, our report highlights the potential for true mechanical obstruction in the GI tract. We demonstrate that endoscopic intervention can successfully disimpact obstructing fecal bezoars in patients with SSc.\n\nDISCLOSURES\nAuthor contributions: R. Sarnoff and B. Girmay wrote the manuscript. R. Mocharla edited the manuscript. All other authors contributed equally to the manuscript. R. Sarnoff is the article guarantor.\n\nFinancial disclosure: None to report.\n\nInformed patient consent was obtained for this case report.\n==== Refs\nREFERENCES\n1. Matsuo Y Yasuda H Nakano H \nSuccessful endoscopic fragmentation of large hardened fecaloma using jumbo forceps . World J Gastrointest Endosc . 2017 ;9 (2 ):91 –4 .28250902 \n2. Forbes A Marie I \nGastrointestinal complications: The most frequent internal complications of systemic sclerosis . Rheumatology (Oxford) . 2009 ;48 (Suppl 3 ):iii36 –9 .19487222 \n3. Sjogren RW \nGastrointestinal motility disorders in scleroderma . Arthritis Rheum . 1994 ;37 (9 ):1265 –82 .7945489 \n4. Denton CP Black CM Korn JH de Crombrugghe B \nSystemic sclerosis: Current pathogenetic concepts and future prospects for targeted therapy . Lancet . 1996 ;347 (9013 ):1453 –8 .8676631 \n5. Pasha SF Pasha SF Acosta RD \nThe role of endoscopy in the evaluation and management of dysphagia . Gastrointest Endosc . 2014 ;79 (2 ):191 –201 .24332405 \n6. Kadam PD Chuan HH \nErratum to: Rectocutaneous fistula with transmigration of the suture: A rare delayed complication of vault fixation with the sacrospinous ligament . Int Urogynecol J . 2016 ;27 (3 ):505 .26811110 \n7. Nagaraja V McMahan ZH Getzug T Khanna D \nManagement of gastrointestinal involvement in scleroderma . Curr Treatm Opt Rheumatol . 2015 ;1 (1 ):82 –105 .26005632 \n8. Yoon SS Kim MS Kang DY \nA case of successful colonoscopic treatment of colonic obstruction caused by phytobezoar . J Korean Soc Coloproctol . 2011 ;27 (4 ):211 –4 .21980592 \n9. Hansi N Thoua N Carulli M \nConsensus best practice pathway of the UK scleroderma study group: Gastrointestinal manifestations of systemic sclerosis . Clin Exp Rheumatol . 2014 ;32 (6 Suppl 86 ):S-214 –21 .\n10. Bharucha AE Pemberton JH Locke GR \nAmerican Gastroenterological Association technical review on constipation . Gastroenterology. \n2013 ;144 (1 ):218 –38 .23261065 \n11. Mecoli C Purohit S Sandorfi N Derk CT \nMortality, recurrence, and hospital course of patients with systemic sclerosis-related acute intestinal pseudo-obstruction . J Rheumatol . 2014 ;41 (10 ):2049 –54 .25128517\n\n",
"fulltext_license": "CC BY-NC-ND",
"issn_linking": "2326-3253",
"issue": "6(4)",
"journal": "ACG case reports journal",
"keywords": null,
"medline_ta": "ACG Case Rep J",
"mesh_terms": null,
"nlm_unique_id": "101638398",
"other_id": null,
"pages": "e00059",
"pmc": null,
"pmid": "31616740",
"pubdate": "2019-04",
"publication_types": "D002363:Case Reports",
"references": "25128517;26005632;26811110;25372804;21980592;19487222;7945489;28250902;23261065;8676631;24332405",
"title": "An Obstructing Fecal Bezoar in a Patient with Scleroderma with Successful Colonoscopic Disimpaction.",
"title_normalized": "an obstructing fecal bezoar in a patient with scleroderma with successful colonoscopic disimpaction"
}
|
[
{
"companynumb": "US-BAYER-2019-126359",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "POLYETHYLENE GLYCOL 3350"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "022015",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER FOR ORAL SOLUTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BEZOAR",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRALAX"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "POLYETHYLENE GLYCOL 3350"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "022015",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER FOR ORAL SOLUTION",
"drugdosagetext": "4 L",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LARGE INTESTINAL OBSTRUCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "011",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MIRALAX"
}
],
"patientagegroup": "5",
"patientonsetage": "44",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug intolerance",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Contraindicated product administered",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "SARNOFF R, GIRMAY B, BHAKTA D, MOCHARLA R, WILLIAMS R. AN OBSTRUCTING FECAL BEZOAR IN A PATIENT WITH SCLERODERMA WITH SUCCESSFUL COLONOSCOPIC DISIMPACTION. ACG CASE REPORTS JOURNAL. 2019?6:1-4:XX-XX",
"literaturereference_normalized": "an obstructing fecal bezoar in a patient with scleroderma with successful colonoscopic disimpaction",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190705",
"receivedate": "20190705",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16531427,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20191004"
}
] |
{
"abstract": "Intravascular large B-cell lymphoma (IVLBCL) is an aggressive and rare type of diffuse extranodal B-cell lymphoma. Diagnosis and treatment are challenging and clinical presentation is variable. Physicians should be aware of this rare but life-threatening lymphoma without adenopathy and treatment should be promptly started. We describe the case of a 70-year-old woman who presented with general malaise, acute dyspnoea, platypnoea and lactic acidosis. Echocardiography revealed an extracardiac shunt, the cause of her orthodeoxia. The patient developed rapid liver failure and underwent liver biopsy. Anatomopathological findings suggested IVLBCL, non-germinal center type. She achieved complete remission after rituximab, cyclophosphamide, doxorubicin, vincristine, methylprednisolone chemotherapy but relapsed 1 year after initial presentation with multiple organ involvement. The patient's relapsed disease was treated with rituximab, iphosphamide, carboplatin, etoposide and she is still in complete remission 2 years later.",
"affiliations": "Internal Medicine, Erasmus Hospital, Brussels, Belgium [email protected].;Geriatrics, Brugmann University Hospital, Brussels, Belgium.;Internal Medicine, Iris Ziekenhuizen Zuid, Brussels, Belgium.;Haematology, Erasmus Hospital, Brussels, Belgium.",
"authors": "Englert|Pierre|P|;Levy|Sophie|S|;Vekemans|Marc|M|;De Wilde|Virginie|V|",
"chemical_list": "D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone",
"country": "England",
"delete": false,
"doi": "10.1136/bcr-2020-241067",
"fulltext": "\n==== Front\nBMJ Case Rep\nBMJ Case Rep\nbmjcr\nbmjcasereports\nBMJ Case Reports\n1757-790X\nBMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR\n\n34162604\nbcr-2020-241067\n10.1136/bcr-2020-241067\nCase Report\n1506\n175\n508\n1327\n122\nIntravascular lymphoma presenting with hypoxaemia, platypnoea and lactic acidosis\nEnglert Pierre 1\nLevy Sophie 2\nVekemans Marc 3\nDe Wilde Virginie 4\n1 Internal Medicine, Erasmus Hospital, Brussels, Belgium\n2 Geriatrics, Brugmann University Hospital, Brussels, Belgium\n3 Internal Medicine, Iris Ziekenhuizen Zuid, Brussels, Belgium\n4 Haematology, Erasmus Hospital, Brussels, Belgium\nCorrespondence to Dr Pierre Englert; [email protected]\n2021\n23 6 2021\n23 6 2021\n14 6 e24106701 6 2021\n© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n2021\nhttps://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.\n\nIntravascular large B-cell lymphoma (IVLBCL) is an aggressive and rare type of diffuse extranodal B-cell lymphoma. Diagnosis and treatment are challenging and clinical presentation is variable. Physicians should be aware of this rare but life-threatening lymphoma without adenopathy and treatment should be promptly started. We describe the case of a 70-year-old woman who presented with general malaise, acute dyspnoea, platypnoea and lactic acidosis. Echocardiography revealed an extracardiac shunt, the cause of her orthodeoxia. The patient developed rapid liver failure and underwent liver biopsy. Anatomopathological findings suggested IVLBCL, non-germinal center type. She achieved complete remission after rituximab, cyclophosphamide, doxorubicin, vincristine, methylprednisolone chemotherapy but relapsed 1 year after initial presentation with multiple organ involvement. The patient’s relapsed disease was treated with rituximab, iphosphamide, carboplatin, etoposide and she is still in complete remission 2 years later.\n\nhaematology (incl blood transfusion)\nrespiratory medicine\nmalignant and benign haematology\nliver disease\nspecial-featureunlocked\n==== Body\nBackground\n\nIntravascular large B-cell lymphoma (IVLBCL) is a rare but aggressive non-Hodgkin’s lymphoma characterised by the presence of neoplastic cells in the lumen of small and intermediate blood vessels.1 2 As IVLBCL is a rare entity, few large series are available. The main series in the literature describe a wide variety of clinical presentations that have been historically grouped into a ‘Western’ variant, characterised mainly by cutaneous and neurological involvement, and an ‘Asian’ variant in which more organs are affected.3 Recently, a new classification of three clinical types with different prognoses has been proposed: a cutaneous form with better prognosis, a form that is associated with haemophagocytic syndrome (HS) and carries the worst prognosis, and a ‘classical’ form that involves multiple organ involvement without HS, and has variable severity.4 Although some series have suggested that, in the rituximab era, the overall prognosis for IVLBCL may approach that of other diffuse large B-cell lymphomas, the disease is commonly diagnosed at stage IV and has a high International Prognosis Index, reflecting poor prognosis.5 6 Moreover, the extranodal and variable clinical presentation of IVLBCL makes diagnosis harder. Therefore, awareness of the disease and knowledge of clinical or biological signs that might bring the diagnosis to mind are essential to starting treatment in time. This patient case illustrates presentation of an acute course of IVLBCL with multiple organ involvement and some specific features that are worth remembering.\n\nCase presentation\n\nThis patient was a 70-year-old Caucasian woman without any relevant past medical history. She was on vacation abroad in Europe and had been travelling in Africa 2 months before admission. She presented herself at the emergency department with general malaise, epigastric and upper right abdominal pain, palpitations, dyspnoea, and a slight fever for the past few days. She had been prescribed levofloxacin for suspected pneumonia without any improvement. She had experienced a self-resolved episode of diarrhoea a few weeks before. Vital signs at admission were as follows: blood pressure 115/80 mm Hg, pulse oximetry 95%, cardiac pulse 95 per minute, temperature 36.3°C. Physical examination revealed slight dehydration, tachypnoea without respiratory distress, platypnoea and a painful abdomen with normal sounds, mostly epigastric and right hypochondrium without any tenderness. Cardiac and pulmonary auscultation were normal. No neurological abnormalities, adenopathy or rash were detected. Initial blood analysis showed slight inflammation, elevated lactate dehydrogenase level and altered hepatic function (details in the ‘Investigations’ section). Blood gases indicated lactic acidosis and hypoxaemia: pH 7.42, PaCO2 28 mm Hg, PaO2 68 mm Hg, lactate 4.5 mmol/L. Computed tomography (CT) of pulmonary arteries was negative for pulmonary embolism and the pulmonary parenchyma was normal. Research to identify potential infectious causes was conducted. After initial investigations, the patient was admitted to the department of internal medicine without any diagnosis.\n\nAbdominal ultrasound and CT suggested low blood flow in dilated portal and sushepatic veins though they were both permeable. In addition, the walls of the duodenum and gall bladder appeared thickened. Cardiac ultrasound, otherwise normal, showed a delayed contrast passage between the right and left cavities, suggesting an extracardiac shunt, explaining the patient’s platypnoea. With no evidence of infection and no clear diagnosis, examination of bone marrow was carried out and revealed that 25% of the cells were abnormal, large-sized with elevated nucleus/cytoplasm ratios. Unfortunately, no immunohistochemistry could be performed due to technical issues. Peripheral lymphocyte smear did not show any monoclonality.\n\nAfter 72 hours, though clinically and haemodynamically stable, lactate dehydrogenase levels, lactic acidosis and liver function test results got worse, reaching worrisome values: platelets 42x109/L, albumin 24 g/L, aspartate transaminase 800 IU/L, alkaline phosphatase and γ-glutamyl-transferase of 696 IU/L and 804 IU/L, respectively, lactate dehydrogenase 2008 IU/L, and lactate up to 8 mmol/L. The patient was admitted to the intensive care unit. A transjugular liver biopsy was undertaken to search for a diagnosis. The patient’s hepatic venous pressure gradient (HVPG) was 5 mm Hg. Anatomopathological examination revealed a parenchymal invasion by large CD20+ lymphomatous cells (figure 1). The immunohistological profile was compatible with an IVLBCL, non-germinal center type (ABC-type B-cells by the Hans algorithm): AE1/AE3 (−), CD3 (−), CD20 (+), CD10 (−), BCL6 (+/−), BCL2 (+), MUM1 (+>40%), anti-Ki67 (100%).7 Detection of c-MYC rearrangement by fluorescence in situ hybridisation (FISH using LSI C-MYC Break Apart probes) was negative. Unfortunately, testing for BCL-2 rearrangement could not be performed due to technical reasons. An initial ¹⁸F-fluorodeoxyglucose positron emission tomography – CT (¹⁸F-FDG PET/CT) was performed after the first round of chemotherapy and the only metabolically active signal was a pulmonary-pleural focal point in the right upper lobe (figure 2). Investigations for possible central nervous system infection by brain MR and lumbar puncture were negative.\n\nFigure 1 Transjugular liver biopsy. Immunohistochemistry: CD20 positivity and Hematoxylin and Eosin staining. Nodular and sinusoidal parenchymatous invasion by large lymphomatous cells.\n\nFigure 2 The first fluorodeoxyglucose positron emission tomography—CT was performed after the first round of chemotherapy with the only metabolically active signal a pulmonary-pleural focal point in the right upper lobe.\n\nInvestigations\n\nBlood tests at admission: haemoglobin 155 g/L, platelets 168 x109/L, haematocrit 46.2%, WCC 6.3x109/L, neutrophils 4.7x109/L, eosinophils 0x109/L, D-dimers 802 ng/mL, prothrombin time 67%, C reactive protein 88 mg/mL, urea 34 mg/dL, creatinine 0.8 mg/dL, sodium 136 mmol/L, potassium 4.2 mmol/L, chlorine 94 mmol/L, albumin 35 g/L, total bilirubin 0.87 mg/dL, haptoglobin 138 mg/dL, total CO2 19 mmol/L, uric acid 5.2 mg/dL, lipase 31 IU/L, γ-glutamyl-transferase 356 U/L, alkaline phosphatase 289 U/L, aspartate transaminase 112 U/L, alanine transaminase 88 U/L, lactate dehydrogenase 798 U/L.\n\nDifferential diagnosis\n\nThe patient’s travel history, fever and elevation of serum lactate levels led us to search for sepsis and infectious causes with liver involvement. Urinary, blood cultures and a broad spectrum of analyses were carried out including: Plasmodium spp, hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus(HCV), hepatitis E virus (HEV), cytomegalovirus (CMV), Epstein-Barr (EBV), human immunodeficiency virus (HIV), typhoid fever, Chikungunya, West Nile virus, Brucellosis, Q-fever, Bartonellosis, dengue fever, Entamoeba histolytica, Leptospira biflexa, Leishmania donovani, Ascaris lumbricoides, Fasciola hepatica, Schistosoma mansoni, Strongyloides stercoralis, Toxocara canis, Chlamydia pneumoniae, Mycoplasma pneumoniae. All of these investigations came back negative. The absence of eosinophilia and no focal lesions in the liver made parasitic aetiologies improbable. The absence of rash, arthralgia, high levels of inflammation, and high-grade fever was not in favour of malaria, viral fever or bacterial causes. Deep infectious foci and endocarditis were excluded by chest and abdominal CT and echocardiography. Sepsis was considered, but with a relatively good general condition, without any clear source of infection and no haemodynamic instability, it was thought improbable.\n\nThe second set of diagnoses that were initially considered included pulmonary embolism and/or cardiac involvement with liver impact. These were excluded by chest CT and echocardiography.\n\nToxic hepatitis and autoimmune disorders were also considered but anamnesis for exposure and blood screening for autoimmune conditions were negative.\n\nNeoplastic aetiologies, though foreseen since admission, became seriously suspected after the different above-mentioned diagnoses were excluded and given the high levels of lactate dehydrogenase. The results of the medullar puncture confirmed malignancy despite the fact that no clear identification of the neoplastic cells could by performed because of technical issues. The worsening of liver function test results motivated us to perform a liver biopsy and enabled us to arrive at the final diagnosis.\n\nTreatment\n\nThe patient was treated for an intravascular diffuse large B-cell lymphoma with liver, bone marrow and possibly small bowel and lung involvement, with possible ‘hepatopulmonary-like’ syndrome. She received an urgent course of cyclophosphamide 750 mg/m2, etoposide 100 mg/m2 and methylprednisolone in the intensive care unit, followed by rituximab 375 mg/m2 and doxorubicin 50 mg/m2 in the haematology department.\n\nThe patient received eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, methylprednisolone (R-CHOP) (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristin 1–1.4 mg/m2, methylprednisolone 80 mg every day for 5 days) and standard supportive care. Given the high International Prognostic Index, two cycles of high-dose methotrexate were administered for meningeal prophylaxis, with a 2-week interval, 1500 mg/m2.\n\nOutcome and follow-up\n\nClinical and biological responses were rapidly achieved after the first course of chemotherapy. All biological abnormalities resolved and the patient felt well enough to be discharged 11 days after admission. Clinical and biological follow-up was performed at least once a month and ¹⁸F-FDG PET/CT was carried out twice during the 6 months of therapy. Complete remission was confirmed by ¹⁸F-FDG PET/CT 7 months after initial presentation and after the last of the eight cycles of R-CHOP.\n\nNine months after treatment and complete remission, the patient presented with general malaise, abdominal discomfort, diarrhoea and dyspnoea with severe hypoxaemia with the following blood gas values: pH 7.45, PaCO2 36 mm Hg, PaO2 43 mmHg, lactate 3.5 mmol/L. ECG showed an atrial flutter, chest CT showed bilateral ground glass opacities (figure 3), ¹⁸F-FDG PET/CT suggested massive lymphomatous relapse: new cervical, mediastinal, abdominal bilateral lymphadenopathies and hypermetabolic spans in the pericardium, lungs, liver, bones, peritoneum and retroperitoneal area (figure 4). Since the images of the chest CT were suspicious, bronchoalveolar lavage was carried out to rule out opportunistic infections. Bone marrow examination was negative but trans-bronchial biopsies confirmed the same neoplastic cells as in the initial liver biopsy. The patient received two rounds of rituximab, revlimid, iphosphamide, carboplatin, etoposide (ICE) chemotherapy and two rounds of rituximab-ICE) for relapse of IVLBCL. Tolerance to treatment was acceptable except for the presence of peripheral sensory polyneuropathy. The patient responded well to therapy and went home a few weeks after admission. After 4 months, complete clinical, biological, and radiological remission was achieved once again. Patient is still in complete remission 2 years after last chemotherapy.\n\nFigure 3 Chest CT at relapse showed pericardial effusion and ground glass bilateral opacities.\n\nFigure 4 ¹⁸F-fluorodeoxyglucose positron emission tomography—CT at relapse: new cervical, mediastinal, abdominal bilateral lymphadenopathies and hypermetabolic spans in pericardium, lungs, liver, bones, peritoneum and retroperitoneal area.\n\nDiscussion\n\nThis case of IVLBCL that we have described is categorised as ‘classical’ type in the recently proposed classification of three clinical types of IVLBCL: multiple organ involvement without HS.4 In a recent review of 10 cases of ‘non-mainly cutaneous’ IVLBCL the main biological and clinical features were fever, weight loss, night sweats, cytopenia, skin and neurological signs in patients of a median age of 67 years old without significant sex prevalence and a high International Prognosis Index.6 These findings are consistent with most of the other case series, where elevated LDH levels and splenomegaly are common features.5 8 9 Our case presents some interesting features.\n\nFirst, to our knowledge, only one other case of orthodeoxia associated with IVLBCL has been well-described in the literature.10 In our case, this sign might be associated with an ‘hepatopulmonary-like syndrome’ usually described in advanced liver disease, even if the HVPG of 5 mm Hg observed in our patient is usually considered to be the upper limit of normal.11 12 The low blood flow in a globally dilated venous portal and sushepatic network in the abdominal imaging by ultrasound and CT, without any description of pulmonary hypertension, might also be a clue in favour of such a hypothesis. However, even though this is interesting from a physiological perspective, understanding the details of this theory probably has no clinical implications and these radiological signs were not included in the follow-up.\n\nSecond, the patient had biopsy-proven bone marrow, liver, and lung involvement, despite no radiological signs in these organs at initial presentation. As cytopenia of one or more cell lines is a common feature of classical IVLBCL, bone marrow is a frequent site of biopsy and is reported as an affected organ.6 ¹⁸F-FDG-PET seems to be critical, but not perfect, for evaluation of the extent of IVLBCL.13 However, standard radiological findings that enable targeted biopsy of liver and lung do not always provide good correlations with involvement of these organs; random biopsies (or autopsies) can sometimes be positive.14–16 Moreover, our patient did not present any abnormalities in the different cell lines and thrombocytopenia was related to hepatic dysfunction. This is also consistent with the positivity of random skin biopsies in some case series.17 This might reflect a wider extent of the disease than that suggested by radiological findings, perhaps related to the physiopathology of IVLBCL which involves cells located in small and intermediate blood vessels.2 Any unexplained sign, whether radiological, biological or clinical, might motivate clinicians to perform a biopsy that could be positive. This discussion is complicated in our case by the timing of the first ¹⁸F-FDG PET/CT, which might have been positive if performed before the first course of chemotherapy. Finally, pericardial involvement, at the forefront during the relapse of the disease in this case, seems to be uncommon, or underreported in published series.5 9 17\n\nAnother unique feature of this presentation was lactic acidosis. While usually due to tissue hypoxia or sepsis and referred as ‘type A’ lactic acidosis, ‘type B’ lactic acidosis can be infrequently related to malignancy, as in our case.18 The majority of lactic acidosis related to haematological neoplasms is usually associated with poor prognosis.19 Obviously, it can be difficult to differentiate the cause of elevated blood lactate in critically ill patients suffering from cancer, since they might concomitantly be affected by malignancy and sepsis. Our patient showed no sign of infection whatsoever and few clear descriptions of similar reports are available in literature.19 20 However, altered hepatic lactate clearance related to liver dysfunction might have played an important role in this case.\n\nIn conclusion, this case of IVLBCL highlights important features that should raise suspicion of this malignancy during the differential diagnosis. In particular, the presence of platypnoea, the presence of lactic acidosis in the absence of infection, and the presence of clinical or biological signs that are not explained by radiological findings should lead to additional follow-up. IVLBCL may respond well to treatment, if detected in a timely manner.\n\nPatient’s perspective\n\n‘I had this impression that I had never been really sick. I have always thought that I was in excellent health and could get through anything…\n\nAt first, as I was taking a walk, I felt that I was short of breath at the slightest little hill. Two days later, we went abroad. On our arrival, our family welcomes us with a delicious meal but in the evening already, when I was about to go to bed, I felt heavy. The following day, I was feeling a little nauseous, I took a nap, which I rarely do, and I threw up for the first time. Then, little by little, I had difficulty going up the stairs, I had to sit down after a few steps, I was out of breath. Finally, the day after, we went to the emergency of a local hospital. They took me in charge right away and after some exams, they told me that either they were keeping me there and had me transferred to a bigger city, or I needed to return immediately and go to a hospital back home. This is what we did. My husband and a friend were driving alternately for the trip (during which I was throwing up at each stop …) and dropped me off at a university hospital at 4:00 in the morning. I had trouble breathing and also felt pain under my ribs. But there, at the hospital, I felt reassured. For a few days, my condition was getting really worse, I felt I was slowly leaving, but I had total trust. The doctors could not understand what I was suffering of, they were still searching. Easter weekend was coming closer and people were leaving for holidays. They asked a specialist to come back in order to perform to me a liver puncture. Same thing for the analysis, it could not wait until the end of the weekend. Finally, on Sunday evening the chemotherapy started, just in time and there I felt that everything was going up again. And I was coping well with them. I stayed in the hospital for another fortnight. As I was very weak and had not eaten for 10 days, it took me some time to recover, when I got home, but everything ended well, 7 months later.\n\nThe following summer, I started having new disturbance, tiredness, shortness of breath; I was getting weaker, but less quickly than the first time. We were once again on holidays and we definitely did not expect that the lymphoma was going to attack me again.\n\nAfter a telephone consultation with my oncologist, we returned home and went once again to the hospital. There, I had a lot of exams, some of them quite hurtful, in order to eliminate different scenarios but in the end, we realised that the lymphoma was there again and the treatment started again. I think that I have being taken in charge in a marvellous way, both by my oncologist and by the various doctors and the team of nurses.\n\nBut I still do not understand why these lymphomas attacked me, since I have always eaten in a balanced way without too much fat, without too much meat, with a lot of vegetables, I am active, I am not overweight, … well, everything that is recommended.’\n\nLearning points\n\nIntravascular large B-cell lymphoma (IVLBCL) is a rare but life-threatening condition and prompt diagnosis is necessary for rapid treatment.\n\nClinical presentation is extranodal and variable in space and time. Diagnosis is challenging, IVLBCL should be kept in mind early in differential diagnosis of syndromes with unclear aetiologies.\n\nImaging, though necessary to progress towards definite diagnosis, is not perfectly sensitive and investigations should be made according to clinical and/or biological signs.\n\nThe extent of the disease is possibly wider than expected based on radiology. Random biopsies, in particular of the lungs and skin, should be performed according to unexplained biological or clinical features.\n\nDespite a quick response, close follow-up should be set up as good responses to treatment do not guarantee absence of early relapse.\n\nEthics statements\n\nPatient consent for publication\n\nObtained.\n\nContributors: The first author was involved in the initial clinical management and responsible for the drafting process and literature review. The third author was responsible of reviewing the last version of the article. Both other authors were in charge of the diagnosis, clinical management and treatment of the patient.\n\nFunding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.\n\nCompeting interests: None declared.\n\nProvenance and peer review: Not commissioned; externally peer reviewed.\n==== Refs\nReferences\n\n1 Rajyaguru DJ, Bhaskar C, Borgert AJ, et al . Intravascular large B-cell lymphoma in the United States (US): a population-based study using surveillance, epidemiology, and end results program and National cancer database. Leuk Lymphoma 2017;58 :2080–8. 10.1080/10428194.2017.1287363\n2 Bhawan J, Wolff SM, Ucci AA, et al . Malignant lymphoma and malignant angioendotheliomatosis: one disease. Cancer 1985;55 :570–6. 10.1002/1097-0142(19850201)55:3<570::AID-CNCR2820550316>3.0.CO;2-0 3880661\n3 Shimada K, Kinoshita T, Naoe T, et al . Presentation and management of intravascular large B-cell lymphoma. Lancet Oncol 2009;10 :895–902. 10.1016/S1470-2045(09)70140-8 19717091\n4 Ponzoni M, Campo E, Nakamura S. Intravascular large B-cell lymphoma: a chameleon with multiple faces and many masks. Blood 2018;132 :1561–7. 10.1182/blood-2017-04-737445 30111607\n5 Shimada K, Matsue K, Yamamoto K, et al . Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL Study group in Japan. Journal of Clinical Oncology 2008;26 :3189–95. 10.1200/JCO.2007.15.4278 18506023\n6 Ong Y-C, Kao H-W, Chuang W-Y, et al . Intravascular large B-cell lymphoma: a case series and review of literatures. Biomed J 2020. 10.1016/j.bj.2020.04.005. [Epub ahead of print: 25 Apr 2020].\n7 Hans CP, Weisenburger DD, Greiner TC, et al . Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103 :275–82. 10.1182/blood-2003-05-1545 14504078\n8 Brunet V, Marouan S, Routy J-P, et al . Retrospective study of intravascular large B-cell lymphoma cases diagnosed in Quebec. Medicine 2017;96 :e5985. 10.1097/MD.0000000000005985 28151891\n9 Ferreri AJM, Campo E, Seymour JF, et al . Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'. Br J Haematol 2004;127 :173–83. 10.1111/j.1365-2141.2004.05177.x 15461623\n10 Leelayuwatanakul N, Kongpolprom N. Orthodeoxia as a presentation of intravascular large B cell lymphoma. Respirol Case Rep 2018;6 :e00299. 10.1002/rcr2.299 29796279\n11 Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome--a liver-induced lung vascular disorder. N Engl J Med 2008;358 :2378–87. 10.1056/NEJMra0707185 18509123\n12 Berzigotti A, Seijo S, Reverter E, et al . Assessing portal hypertension in liver diseases. Expert Rev Gastroenterol Hepatol 2013;7 :141–55. 10.1586/egh.12.83 23363263\n13 Colavolpe C, Ebbo M, Trousse D, et al . Fdg-Pet/Ct is a pivotal imaging modality to diagnose rare intravascular large B-cell lymphoma: case report and review of literature. Hematol Oncol 2015;33 :99–109. 10.1002/hon.2140 24850057\n14 Kaku N, Seki M, Doi S, et al . A case of intravascular large B-cell lymphoma (IVLBCL) with no abnormal findings on chest computed tomography diagnosed by random transbronchial lung biopsy. Intern Med 2010;49 :2697–701. 10.2169/internalmedicine.49.3986 21173545\n15 Kim M-J, Park H-S, Yhim H-Y. Intravascular large B-cell lymphoma diagnosed via transjugular liver biopsy in a patient with liver dysfunction and thrombocytopenia. Medicine 2017;96 :e6925. 10.1097/MD.0000000000006925 28489811\n16 Nakazato T, Sanada Y, Mihara A, et al . PET-negative pulmonary intravascular large B cell lymphoma diagnosed by a random transbronchial lung biopsy. Ann Hematol 2012;91 :811–2. 10.1007/s00277-011-1333-x 21909695\n17 di Fonzo H, Contardo D, Carrozza D, et al . Intravascular large B cell lymphoma presenting as fever of unknown origin and diagnosed by random skin biopsies: a case report and literature review. Am J Case Rep 2017;18 :482–6. 10.12659/AJCR.903816 28461685\n18 Kraut JA, Madias NE. Lactic acidosis. N Engl J Med 2014;371 :2309–19. 10.1056/NEJMra1309483 25494270\n19 Ruiz JP, Singh AK, Hart P. Type B lactic acidosis secondary to malignancy: case report, review of published cases, insights into pathogenesis, and prospects for therapy. ScientificWorldJournal 2011;11 :1316–24. 10.1100/tsw.2011.125 21789467\n20 Mase H, Ogawa Y, Takeuchi J, et al . Successful intensive care treatment of severe lactic acidosis and tumor lysis syndrome related to intravascular lymphoma. J Nippon Med Sch 2020;87 :32–6. 10.1272/jnms.JNMS.2019_86-606 31308316\n\n",
"fulltext_license": "CC BY-NC",
"issn_linking": "1757-790X",
"issue": "14(6)",
"journal": "BMJ case reports",
"keywords": "haematology (incl blood transfusion); liver disease; malignant and benign haematology; respiratory medicine",
"medline_ta": "BMJ Case Rep",
"mesh_terms": "D000140:Acidosis, Lactic; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide; D004317:Doxorubicin; D004417:Dyspnea; D005260:Female; D006801:Humans; D000860:Hypoxia; D016403:Lymphoma, Large B-Cell, Diffuse; D011241:Prednisone; D000069283:Rituximab; D014750:Vincristine",
"nlm_unique_id": "101526291",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "34162604",
"pubdate": "2021-06-23",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "31308316;28489811;32344119;29796279;21173545;23363263;28461685;21909695;3880661;25494270;24850057;19717091;30111607;28151891;18509123;21789467;15461623;28278725;18506023;14504078",
"title": "Intravascular lymphoma presenting with hypoxaemia, platypnoea and lactic acidosis.",
"title_normalized": "intravascular lymphoma presenting with hypoxaemia platypnoea and lactic acidosis"
}
|
[
{
"companynumb": "BE-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-305277",
"fulfillexpeditecriteria": "1",
"occurcountry": "BE",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIFFUSE LARGE B-CELL LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "77926",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IPHOSPHAMIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REVLIMID"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE."
}
],
"patientagegroup": null,
"patientonsetage": "70",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peripheral sensory neuropathy",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ENGLERT P, LEVY S, VEKEMANS M, DE WILDE V. INTRAVASCULAR LYMPHOMA PRESENTING WITH HYPOXAEMIA, PLATYPNOEA AND LACTIC ACIDOSIS. BMJ CASE REP. 2021?14(6):E241067",
"literaturereference_normalized": "intravascular lymphoma presenting with hypoxaemia platypnoea and lactic acidosis",
"qualification": "3",
"reportercountry": "BE"
},
"primarysourcecountry": "BE",
"receiptdate": "20210726",
"receivedate": "20210726",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19612479,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
},
{
"companynumb": "BE-CELLTRION INC.-2022BE000563",
"fulfillexpeditecriteria": "1",
"occurcountry": "BE",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "761088",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Concentrate for solution for infusion",
"drugdosagetext": "375 MICROGRAM/SQ. METER",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "375",
"drugstructuredosageunit": "010",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "761088",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Concentrate for solution for infusion",
"drugdosagetext": "EVERY 4 CYCLES",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "EVERY 4 CYCLES",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LENALIDOMIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 MILLIGRAM/SQ. METER",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "EVERY 4 CYCLES",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IFEX"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "(DOSE FORM: 5)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REVLIMID"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "(PER TWO CYCLES) TWO ROUNDS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REVLIMID"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "EVERY 4 CYCLES",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IFOSFAMIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CYCLOPHOSPHAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "750 MILLIGRAM/SQ. METER",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "750",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOPHOSPHAMIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "VINCRISTINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VINCRISTINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOXORUBICIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM/SQ. METER",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXORUBICIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peripheral sensory neuropathy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Pierre E, Marc V.. Intravascular lymphoma presenting with hypoxaemia, platypnoea and lactic acidosis.. BMJ Case Reports",
"literaturereference_normalized": "intravascular lymphoma presenting with hypoxaemia platypnoea and lactic acidosis",
"qualification": "1",
"reportercountry": "BE"
},
"primarysourcecountry": "BE",
"receiptdate": "20220310",
"receivedate": "20220128",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20389351,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220423"
},
{
"companynumb": "BE-ACCORD-231297",
"fulfillexpeditecriteria": "1",
"occurcountry": "BE",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIFFUSE LARGE B-CELL LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIFFUSE LARGE B-CELL LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IFOSFAMIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIFFUSE LARGE B-CELL LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REVLIMID"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "074513",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIFFUSE LARGE B-CELL LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIFFUSE LARGE B-CELL LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
}
],
"patientagegroup": null,
"patientonsetage": "70",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peripheral sensory neuropathy",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ENGLERT P, LEVY S, VEKEMANS M, DE WILDE V. INTRAVASCULAR LYMPHOMA PRESENTING WITH HYPOXAEMIA, PLATYPNOEA AND LACTIC ACIDOSIS. BMJ CASE REP. 2021 JUN 23?14(6):E241067",
"literaturereference_normalized": "intravascular lymphoma presenting with hypoxaemia platypnoea and lactic acidosis",
"qualification": "1",
"reportercountry": "BE"
},
"primarysourcecountry": "BE",
"receiptdate": "20210722",
"receivedate": "20210722",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19593621,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
},
{
"companynumb": "BE-MLMSERVICE-20210705-2983055-1",
"fulfillexpeditecriteria": "1",
"occurcountry": "BE",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBOPLATIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "076517",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (TWO ROUNDS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBOPLATIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (TWO ROUNDS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ETOPOSIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (TWO ROUNDS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (TWO ROUNDS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REVLIMID"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IFOSFAMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK (TWO ROUNDS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Diffuse large B-cell lymphoma recurrent",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IFOSFAMIDE"
}
],
"patientagegroup": null,
"patientonsetage": "70",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peripheral sensory neuropathy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Englert, P.. Intravascular lymphoma presenting with hypoxaemia, platypnoea and lactic acidosis. BMJ Case Reports. 2021;14(6):10.1136/bcr-2020-241067.",
"literaturereference_normalized": "intravascular lymphoma presenting with hypoxaemia platypnoea and lactic acidosis",
"qualification": "1",
"reportercountry": "BE"
},
"primarysourcecountry": "BE",
"receiptdate": "20211005",
"receivedate": "20210722",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19594533,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
}
] |
{
"abstract": "Kounis syndrome is the concurrence of an acute coronary syndrome (ACS) caused by coronary vasospasms, acute myocardial infarctions, or stent thromboses in case of allergic or hypersensitivity reactions. Kounis syndrome is mediated by mast cells that interact with macrophages and T-lymphocytes, causing degranulation and inflammation with cytokine release. It is a life-threatening condition that has many trigger factors and is most commonly caused by medicines. Case Presentation. A 71-year-old male was admitted with a fever of five days' duration associated with cellulitis, for which he had been treated with clindamycin and flucloxacillin before admission. He was a diagnosed patient with hypertension and dyslipidemia five years ago. After taking the antibiotics, he had developed generalized itching followed by urticaria suggesting an allergic reaction. Therefore, he was admitted to the hospital. After admission, he developed an ischaemic-type chest pain associated with autonomic symptoms and shortness of breath. An immediate ECG was taken that showed ST-segment depressions in the chest leads V4-V6, confirmed by a repeat ECG. Troponin I was 8 ng/mL. Acute management of ACS was started, and prednisolone 10 mg daily dose was given. After complete recovery, the patient was discharged with aspirin, clopidogrel, atorvastatin, metoprolol, losartan, isosorbide mononitrate, and nicorandil. Prednisolone 10 mg daily dose was given for five days after discharge.\nIn immediate hypersensitivity, with persistent cardiovascular instability, Kounis syndrome should be considered, and an electrocardiogram and other appropriate assessments and treatments should be initiated. Prompt management of the allergic reaction and the ACS is vital for a better outcome of Kounis syndrome.",
"affiliations": "Department of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.;Department of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.;Department of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.;Department of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.",
"authors": "Karunathilake|Parackrama|P|https://orcid.org/0000-0002-7029-7781;Ralapanawa|Udaya|U|https://orcid.org/0000-0002-7416-7984;Jayalath|Thilak|T|;Abeyagunawardena|Shamali|S|https://orcid.org/0000-0002-8458-8168",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1155/2021/4485754",
"fulltext": "\n==== Front\nCase Rep Med\nCase Rep Med\nCRIM\nCase Reports in Medicine\n1687-9627\n1687-9635\nHindawi\n\n10.1155/2021/4485754\nCase Report\nKounis Syndrome Secondary to Medicine-Induced Hypersensitivity\nhttps://orcid.org/0000-0002-7029-7781\nKarunathilake Parackrama [email protected]\n\nhttps://orcid.org/0000-0002-7416-7984\nRalapanawa Udaya\nJayalath Thilak\nhttps://orcid.org/0000-0002-8458-8168\nAbeyagunawardena Shamali\nDepartment of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka\nAcademic Editor: Timothy J. Craig\n\n2021\n1 10 2021\n2021 448575419 8 2021\n18 9 2021\n24 9 2021\nCopyright © 2021 Parackrama Karunathilake et al.\n2021\nhttps://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\nIntroduction\n\nKounis syndrome is the concurrence of an acute coronary syndrome (ACS) caused by coronary vasospasms, acute myocardial infarctions, or stent thromboses in case of allergic or hypersensitivity reactions. Kounis syndrome is mediated by mast cells that interact with macrophages and T-lymphocytes, causing degranulation and inflammation with cytokine release. It is a life-threatening condition that has many trigger factors and is most commonly caused by medicines. Case Presentation. A 71-year-old male was admitted with a fever of five days' duration associated with cellulitis, for which he had been treated with clindamycin and flucloxacillin before admission. He was a diagnosed patient with hypertension and dyslipidemia five years ago. After taking the antibiotics, he had developed generalized itching followed by urticaria suggesting an allergic reaction. Therefore, he was admitted to the hospital. After admission, he developed an ischaemic-type chest pain associated with autonomic symptoms and shortness of breath. An immediate ECG was taken that showed ST-segment depressions in the chest leads V4–V6, confirmed by a repeat ECG. Troponin I was 8 ng/mL. Acute management of ACS was started, and prednisolone 10 mg daily dose was given. After complete recovery, the patient was discharged with aspirin, clopidogrel, atorvastatin, metoprolol, losartan, isosorbide mononitrate, and nicorandil. Prednisolone 10 mg daily dose was given for five days after discharge.\n\nConclusion\n\nIn immediate hypersensitivity, with persistent cardiovascular instability, Kounis syndrome should be considered, and an electrocardiogram and other appropriate assessments and treatments should be initiated. Prompt management of the allergic reaction and the ACS is vital for a better outcome of Kounis syndrome.\n==== Body\npmc1. Introduction\n\nCardiovascular manifestations associated with allergy, hypersensitivity, and anaphylactic or anaphylactoid reactions began to emerge seven decades ago in the medical literature. However, the clinical condition of allergic angina syndrome, which progresses to allergic acute myocardial infarction, was not described until 1991 [1]. Allergic angina syndrome and allergic myocardial infarction are ubiquitous diseases that affect patients of any age. They cover a broad spectrum of mast cell-activation disorders that are referred to as Kounis syndrome. The definition of this syndrome is the concurrence of an acute coronary syndrome (ACS) in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults. These cases of ACS may occur due to coronary spasms, acute myocardial infarctions, or stent thromboses [2]. The primary inflammatory cells involved in the development of Kounis syndrome are mast cells that interact with macrophages and T-lymphocytes. It causes mast cell degranulation and release of inflammatory mediators such as histamine, neutral proteases chymase, tryptase, heparin, and cathepsin-D, with increased production of leukotrienes [3].\n\nMedicines represent the most common trigger for Kounis syndrome in clinical practice. The most commonly reported medicines include nonsteroidal anti-inflammatory drugs (e.g., ibuprofen), antibiotics such as amoxicillin/clavulanate, and anticancer drugs (e.g., fluorouracil) [4]. Kounis syndrome is a complex situation involving two severe circumstances, an acute allergic reaction and an acute coronary event. Thus, the prognosis of Kounis syndrome is relatively poor [5]. Therefore, the management should address both prior given concerns that envisage the complexity of the management. Herein, we report a case of Kounis syndrome possibly triggered by antibiotics administered due to cellulitis of the right lower limb.\n\n2. Case Presentation\n\nA 71-year-old male was admitted with a fever of five days' duration and a reddish swollen right lower limb that had occurred following a wound caused by a leech bite. He had initially consulted a general practitioner before admission who had diagnosed cellulitis, and the patient had been prescribed clindamycin and flucloxacillin on day 2 of the fever. After taking the antibiotics, he had developed generalized itching followed by urticaria. However, there had not been any shortness of breath. Then, antibiotics had been changed on day 4 of fever by the general practitioner due to the possibility of an allergic reaction. Then, he was given cephalexin. However, the allergic symptoms were persisting, and the wound condition had not been improved. Therefore, he was admitted to the local hospital on day 5 of fever. After being admitted to the hospital, he developed ischaemic-type chest pain associated with autonomic symptoms and shortness of breath. The pain was slightly reduced by a glyceryl trinitrate sublingual tablet given. An electrocardiogram (ECG) was taken immediately, showing ST-segment depressions in the chest leads, V4–V6 (Figure 1). A repeat ECG confirmed similar findings (Figure 2).\n\nThe acute management of ACS was carried out at the local hospital, and the patient was transferred to a tertiary-care center for further management. At the tertiary-care center, the antiplatelets and statins were continued. Enoxaparin 60 mg, six doses, and prednisolone 10 mg daily dose were given. ECGs (Figure 3) taken at the tertiary-care center showed normal findings. Troponin I level was initially 8 ng/mL and then reduced to 0.28 ng/mL four days after the onset of chest pain.\n\nHe was a patient diagnosed with hypertension and dyslipidemia for five years without any hypertensive complications. He had also taken treatment for gastro-oesophageal reflux disease for seven years. Nevertheless, he did not have any previous history of diabetes mellitus, transient ischaemic attacks, or cerebrovascular accidents. He had a significant history of allergies to tetracycline, amoxicillin, flucloxacillin, clindamycin, and mushrooms. He did not have any family history of ischaemic heart disease. He was a heavy smoker who had consumed 40 pack-years of cigarettes and was an alcoholic who had taken four to five bottles of toddy per day for thirty years which amounted to 15 units per day; however, he claimed abstinence for five years.\n\nAfter full recovery, he was discharged with aspirin, clopidogrel, atorvastatin, metoprolol, losartan, isosorbide mononitrate, and nicorandil. Prednisolone 10 mg daily dose was prescribed for five days.\n\nHe was next followed up at the cardiac rehabilitation clinic. Six months after the initial presentation, he presented again with stable angina, and the exercise ECG showed stage II inferolateral ischemia. A 2D echocardiogram revealed an ejection fraction of 59% with normal left ventricular systolic dysfunction. We calculated his TIMI score, which was 6 out of 7. Although a coronary angiogram was planned, the patient defaulted follow-up.\n\n3. Discussion\n\nKounis syndrome was defined in 1991 as “the coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of classic angina pectoris caused by inflammatory mediators released during the allergic insult” [6]. It comprises the whole clinical spectrum of acute myocardial ischemia, from stable angina to acute myocardial infarction, which coincides with “allergic” (hypersensitivity, anaphylactic, or anaphylactoid) reaction [6].\n\nThree variants of Kounis syndrome have been described. The type I variant includes normal or nearly normal coronary arteries without risk factors for coronary artery disease. The type II variant includes the culprit but quiescent preexisting atheromatous disease. The type III variant includes coronary artery stent thrombosis in which aspirated thrombus specimens are stained with hematoxylin-eosin and Giemsa that demonstrate the presence of eosinophils and mast cells [2]. Type III variant has two subtypes; subtype a includes patients with coronary stent thrombosis, and subtype b includes patients with stent restenosis due to allergic inflammation [7]. Recently, a new variant IV of Kounis syndrome has been proposed, not scientifically established yet [8].\n\nInvolvement of the cardiovascular system in anaphylaxis occurs in two-thirds of cases [9]. Nevertheless, the incidence of Kounis syndrome during acute allergic reactions has not been precisely established [5]. In a prospective study performed at an emergency department, 27 out of 793 patients consulting for allergic reactions were diagnosed with Kounis syndrome, rendering an incidence of 3.4% [10]. Myocardial injury detected by elevation of troponin I was diagnosed in 22 cases (7.3%) in another retrospective study reviewing 300 cases of anaphylaxis [11].\n\nAlthough anaphylactic reactions associated with cardiovascular alterations are frequent and transient, in some cases, they may result in extensive and life-threatening myocardial damage. In such incidence, many mast cells have been found in the tunica media and the adventitia of large coronary vessels and small intramural coronary arteries. During anaphylaxis, coronary hypoperfusion caused by systemic vasodilation, plasma leakage, volume loss due to increased vascular permeability, and reduced venous return can contribute to cardiac output suppression, leading to further myocardial damage and ventricular dysfunction [12].\n\nThe primary inflammatory cells involved in the development of Kounis syndrome are mast cells that interact with macrophages and T-lymphocytes via multidirectional stimuli. During allergy, hypersensitivity, and anaphylaxis, mast cell degranulation occurs, and various stored and newly formed inflammatory mediators are released locally and to the systemic circulation. These inflammatory mediators include biogenic amines such as histamine, chemokines, enzymes such as the neutral proteases chymase and tryptase, cathepsin-D, peptides, proteoglycans, cytokines, growth factors, and arachidonic acid products such as leukotrienes, thromboxane, prostacyclin, PAF, and tumor necrosis factor-α (TNF-α) [1]. It is shown that mast cells in human coronary atheromas contain TNF-α [13]. Mast cells can be typically activated via several pathways, which may contribute to Kounis syndrome. One is through allergen cross linking with allergen-specific IgE bound to high-affinity Fc epsilon receptor. Non-IgE-mediated mast cell degranulation can also occur via the anaphylatoxins, including complement C1q, C3a C4, C5a, and Factor B. This complement pathway activation involves IL-5 and tryptase, more commonly recognized in patients who develop renal failure or fatal cerebral events. Mast cells can also be activated via low-affinity Mas-related G protein-coupled receptor X2 (MRGPRX2), which activates mast cells via non-Fcε receptors. Another possible pathway is through neuropeptides, including corticotropin-releasing hormone, neurotensin (NT), and substance P (SP) via high-affinity receptors [14].\n\nRisk factors of Kounis syndrome include a history of previous allergy, hypertension, smoking, diabetes, and hyperlipidemia. Various causes have been found to trigger Kounis syndrome, and more triggers are being identified. The most common trigger of Kounis syndrome is antibiotics (27.4%), followed by insect bites. Other causes include foods, latex, and dialysate [3]. Medicines that may trigger Kounis syndrome include analgesics, antibiotics, glucocorticoids, nonsteroidal anti-inflammatory drugs, and anticancer drugs.\n\nRegarding Kounis syndrome triggered by antibiotics, cases have been reported on amoxicillin, amikacin, cefuroxime, penicillin, sulbactam/cefoperazone, piperacillin/tazobactam, trimethoprim-sulfamethoxazole, and vancomycin [1]. Clinical studies indicate that allergic patients who are simultaneously exposed to several allergens have more symptoms than monosensitized individuals. The more medicines an atopic patient is exposed to, the easier and quicker anaphylaxis and Kounis syndrome can occur [15]. Our patient was previously allergic to amoxicillin, flucloxacillin, clindamycin, and tetracycline. Nevertheless, the general practitioner had put on flucloxacillin and clindamycin without taking a proper allergic history. After identifying the allergic reaction, the antibiotics were changed to cephalexin, and the patient developed Kounis syndrome. Thus, there is a possibility that this patient was exposed to three possible allergens, which would have easily triggered Kounis syndrome [15].\n\nA case of clindamycin-triggered Kounis syndrome has been reported in a 17-year-old boy who has taken treatment for acute tonsillitis and subsequently developing acute anterolateral myocardial infarction with ST-segment elevation [12]. Our patient was treated with clindamycin and flucloxacillin, which might be the possible triggers of Kounis syndrome, manifested as acute anterolateral myocardial infarction with ST-segment depression in V4–V6 leads. However, it is difficult to determine which caused the symptoms since the patient claimed to be allergic to both antibiotics. There are no reported cases of Kounis syndrome secondary to flucloxacillin.\n\nThe diagnosis of Kounis syndrome is based on clinical symptoms and signs and laboratory, electrocardiographic, echocardiographic, and angiographic evidence. A variety of these findings might accompany allergic symptomatology that helps to establish the correct diagnosis. The symptoms include acute chest pain, chest discomfort, dyspnea, faintness, headache, nausea, pruritus, and skin itching. Therefore, entertaining a high index of paramount suspicion is important. Patients with systemic allergic reactions associated with clinical, electrocardiographic, and laboratory findings of acute myocardial ischemia should be suspected of having Kounis syndrome [1]. Newer diagnostic techniques such as cardiac magnetic resonance imaging (MRI) and myocardial scintigraphy can help to confirm the diagnosis. Increased serum tryptase, histamine, cardiac biomarkers, and cardiac troponins are beneficial findings [12]. In this case, the patient developed an ischaemic-type chest pain, and the immediately taken electrocardiogram showed ischaemic changes. He had an elevated troponin I level with symptoms of hypersensitivity, and the diagnosis of Kounis syndrome was made.\n\nManagement of Kounis syndrome is a complex task that requires rapid treatment decisions aimed at myocardium revascularisation and treating the concomitant allergic reaction. Currently, guidelines for the treatment of Kounis syndrome are lacking. Most of the evidence on the efficacy of the treatment is based on individual case reports or case series [16]. A recent review conducted by Kounis himself recommends different management approaches for the multiple kinds of variants [2].\n\nThe two main aspects of management include cardiological evaluation and treatment of ACS and emergency treatment of acute allergic reactions. As initial steps for managing ACS, nitroglycerine infusion or tablets can be given, and calcium channel blockers such as verapamil or diltiazem can be considered. Intramuscular epinephrine, oxygen therapy, intravenous fluids, glucocorticoid, and H1-blockers can be given to manage the allergic reaction after removing the tentative allergen. Next, continuous monitoring is indicated for the type I variant, and dual antiplatelet therapy and percutaneous coronary intervention can be performed for type II and type III variants. It is also essential to evaluate the ejection fraction and hemodynamic instability. Timely referrals for the CCU or ICU should be done [16]. This patient was managed initially with nitroglycerin sublingual tablet and next with dual antiplatelet therapy. Six doses of subcutaneous enoxaparin and prednisolone to control the allergic reaction were also given. He was discharged with nitrates, dual antiplatelets, and antihypertensives, considering his chronic medical conditions. According to the literature, although metoprolol was given to this patient, it is contraindicated in Kounis syndrome. Beta-blockers can aggravate coronary vasospasms in patients with type II Kounis syndrome [17].\n\nSo far, there are only seven cases of Kounis syndrome reported in Sri Lanka. Among them, five cases have depicted ST-elevation myocardial infarctions. One case has reported amoxicillin/clavulanic acid-induced Kounis syndrome with widespread ST elevations [18]. In another case, the patient has presented with acute ST-elevation myocardial infarction associated with peripheral blood eosinophilia without any obvious trigger of hypersensitivity [19]. Two other cases of Kounis syndrome have been reported following snake bites, one following a hump-nosed pit viper bite [17] and another a cobra bite [20]. Another case has been reported following a hornet sting causing widespread T inversions in the electrocardiogram [21]. In two cases, the patients have succumbed following Kounis syndrome, one following ceftazidime injection where postmortem found myocardial necrosis with elevated tryptase level suspecting the diagnosis of Kounis syndrome [22]. The other fatal case of Kounis syndrome was an anterior ST-elevation myocardial infarction following anaphylaxis after ingestion of prawns [23]. Therefore, we report the second case of Kounis syndrome with non-ST-elevation of myocardial infarction and the first one with ST-segment depression in Sri Lanka.\n\n4. Conclusions\n\nThis case emphasizes that physicians should be aware of allergic angina syndrome, also known as Kounis syndrome, when a patient simultaneously develops symptoms of ACS and hypersensitivity features. In such cases, other supportive investigations such as electrocardiograms and cardiac biomarkers should be conducted to support the diagnosis, and the management should be initiated promptly. Peripheral blood eosinophilia also supports the diagnosis of Kounis syndrome even in the absence of other features of hypersensitivity. Kounis syndrome is a life-threatening clinical entity regardless of the triggering allergen. Since the management of Kounis syndrome is more complex than solitary ACS, the recognized bodies need to make an evidence-based clinical guideline to manage the condition effectively. At the same time, pharmacovigilance is essential when prescribing medicines, especially when a patient has a significant allergic history.\n\nAcknowledgments\n\nThe authors express their gratitude to the patient who kindly gave consent for this case to be presented in this paper. They appreciate the editorial assistance extended by Mahesh Salgado, the former Head of the English Language Teaching Unit, University of Peradeniya, and current Coordinator of the ELTU Medical Faculty, Peradeniya.\n\nConflicts of Interest\n\nThe authors declare no conflicts of interest regarding the publication of this article.\n\nFigure 1 Electrocardiogram taken immediately after admission, showing ST-segment depression in the chest leads, V4–V6.\n\nFigure 2 Repeat electrocardiogram taken after admission, showing ST-segment depression in the chest leads, V4–V6.\n\nFigure 3 Electrocardiogram taken at the tertiary-care center after treatment showing normal findings.\n==== Refs\n1 Kounis N. G. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management Clinical Chemistry and Laboratory Medicine (CCLM) 2016 54 10 1545 1559 10.1515/cclm-2016-0010 2-s2.0-84987703564 26966931\n2 Kounis N. G. Coronary hypersensitivity disorder: the kounis syndrome Clinical Therapeutics 2013 35 5 563 571 10.1016/j.clinthera.2013.02.022 2-s2.0-84877923688 23490289\n3 Abdelghany M. Subedi R. Shah S. Kozman H. Kounis syndrome: a review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome International Journal of Cardiology 2017 232 1 4 10.1016/j.ijcard.2017.01.124 2-s2.0-85010934605 28153536\n4 Raschi E. Fertonani Affini L. Antonazzo I. C. Diemberger I. Poluzzi E. De Ponti F. Drug-induced kounis syndrome: a matter of pharmacovigilance International Journal of Cardiology 2019 274 p. 381 10.1016/j.ijcard.2018.07.119 2-s2.0-85056568951\n5 Guilarte M. Cardona V. Labrador-Horrillo M. Kounis syndrome Current Treatment Options in Allergy 2019 6 3 289 296 10.1007/s40521-019-00210-5\n6 Fassio F. Almerigogna F. Kounis syndrome (allergic acute coronary syndrome): different views in allergologic and cardiologic literature Internal and Emergency Medicine 2012 7 6 489 495 10.1007/s11739-012-0754-4 2-s2.0-84861366364 22271392\n7 Kounis N. G. Koniari I. Velissaris D. Tzanis G. Hahalis G. Kounis syndrome-not a single-organ arterial disorder but a multisystem and multidisciplinary disease Balkan Medical Journal 2019 36 4 212 221 10.4274/balkanmedj.galenos.2019.2019.5.62 2-s2.0-85069626257 31198019\n8 Giovannini M. Koniari I. Mori F. Barni S. Novembre E. Kounis N. G. Reply to the letter: “kounis syndrome: towards a new classification” International Journal of Cardiology 2021 339 19 20 10.1016/j.ijcard.2021.05.038 34048857\n9 Worm M. Moneret-Vautrin A. Scherer K. First European data from the network of severe allergic reactions (NORA) Allergy 2014 69 10 1397 1404 10.1111/all.12475 2-s2.0-84907960536 24989080\n10 Akoz A. Tanboga H. I. Emet M. Bayramoglu A. A prospective study of kounis syndrome: clinical experience and cardiac magnetic resonance imaging findings for 21 patients Acta Medica Mediterranea 2013 29 4 811 816\n11 Cha Y. S. Kim H. Bang M. H. Evaluation of myocardial injury through serum troponin i and echocardiography in anaphylaxis The American Journal of Emergency Medicine 2016 34 2 140 144 10.1016/j.ajem.2015.09.038 2-s2.0-84957962677 26597331\n12 Kounis N. G. Cervellin G. Koniari I. Anaphylactic cardiovascular collapse and kounis syndrome: systemic vasodilation or coronary vasoconstriction? Annals of Translational Medicine 2018 6 17 p. 332 10.21037/atm.2018.09.05\n13 Marone G. Genovese A. Varricchi G. Granata F. Human heart as a shock organ in anaphylaxis Allergo Journal International 2014 23 2 60 66 10.1007/s40629-014-0007-3 26120516\n14 Kounis N. G. Koniari I. Koniari I. Gregorio C. D. Covid-19 and kounis syndrome: deciphering their relationship Balkan Medical Journal 2021 38 3 145 149 10.5152/balkanmedj.2021.21097 34142957\n15 Kounis N. Mazarakis A. Kounis G. Tsigkas G. Almpanis G. Gkouias K. The more allergens an atopic patient is exposed to, the easier and quicker anaphylactic shock and kounis syndrome appear: clinical and therapeutic paradoxes Journal of Natural Science, Biology and Medicine 2014 5 2 240 244 10.4103/0976-9668.136145 2-s2.0-84904186638\n16 Fassio F. Losappio L. Antolin-Amerigo D. Kounis syndrome: a concise review with focus on management European Journal of Internal Medicine 2016 30 7 10 10.1016/j.ejim.2015.12.004 2-s2.0-84954287768 26795552\n17 Limpo B. Martínez de Tejada Á. M. Kounis syndrome: is it rare or is it underdiagnosed? Kardiologia Polska 2017 75 5 p. 505 10.5603/KP.2017.0083 2-s2.0-85019593097\n18 Ralapanawa D. M. P. Kularatne S. A. M. Kounis syndrome secondary to amoxicillin/clavulanic acid administration: a case report and review of literature case reports BMC Research Notes 2015 8 1 4 9 10.1186/s13104-015-1072-5 2-s2.0-84927946115 25592837\n19 Gunawardena M. D. V. M. Weerasinghe A. Herath J. Amarasena N. Myocardial infarction associated with eosinophilia and plasma extravasation at multiple sites. a variant of kounis syndrome multiple sites. A variant of Kounis syndrome BMJ Case Reports 2015 2015 10.1136/bcr-2014-207987 2-s2.0-84921651567\n20 Priyankara W. D. D. Manoj E. M. Gunapala A. Cardiogenic shock due to kounis syndrome following cobra bite Case Reports in Critical Care 2019 2019 3 5185716 10.1155/2019/5185716\n21 Ralapanawa D. M. Kularatne S. A. A case of kounis syndrome after a hornet sting and literature review BMC Research Notes 2014 7 1 1 5 10.1186/1756-0500-7-867 2-s2.0-84964312426 24382056\n22 Kitulwatte I. Gangahawatte S. Perera U. Edirisinghe P. Death following ceftazidime-induced kounis syndrome Medico-Legal Journal 2017 85 4 215 218 10.1177/0025817217695904 2-s2.0-85053053257\n23 Jayamali W. D. Herath H. M. M. T. B. Kulathunga A. Myocardial infarction during anaphylaxis in a young healthy male with normal coronary arteries- is epinephrine the culprit? BMC Cardiovascular Disorders 2017 17 1 1 5 10.1186/s12872-017-0670-7 2-s2.0-85028696358 28052754\n\n",
"fulltext_license": "CC BY",
"issn_linking": null,
"issue": "2021()",
"journal": "Case reports in medicine",
"keywords": null,
"medline_ta": "Case Rep Med",
"mesh_terms": null,
"nlm_unique_id": "101512910",
"other_id": null,
"pages": "4485754",
"pmc": null,
"pmid": "34630571",
"pubdate": "2021",
"publication_types": "D002363:Case Reports",
"references": "28153536;25608982;25097390;28530026;26120516;29210337;26795552;34142957;24989080;26597331;30306071;28870153;26966931;31198019;25889048;22271392;23490289;34048857;31467731;25465208;30057169",
"title": "Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity.",
"title_normalized": "kounis syndrome secondary to medicine induced hypersensitivity"
}
|
[
{
"companynumb": "LK-MLMSERVICE-20211027-3186918-1",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "FLUCLOXACILLIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Product prescribing error",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis syndrome secondary to medicine-induced hypersensitivity. Case reports in medicine. 2021 OCT 01;1-6. doi:10.1155/2021/4485754",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211122",
"receivedate": "20211111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20056394,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 2,
"transmissiondate": "20220304"
},
{
"companynumb": "LK-Appco Pharma LLC-2121732",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN PALMITATE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207047",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN PALMITATE HYDROCHLORIDE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypersensitivity",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeya Gunawardena S. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Reports in Medicine. 2021 Oct 1;2021. Doi: 10.1155/2021/4485754.",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": null,
"receiptdate": "20211111",
"receivedate": "20211111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 20056117,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-AMNEAL PHARMACEUTICALS-2021-AMRX-04492",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN PALMITATE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "203513",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN PALMITATE HYDROCHLORIDE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hypersensitivity",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Contraindicated product prescribed",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Contraindicated product administered",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P., Ralapanawa U., Jayalath T., Abeyagunawardena S.. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Rep Med. 2021;4485754",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211103",
"receivedate": "20211103",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20031307,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-LUPIN PHARMACEUTICALS INC.-2021-22476",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": "065234",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "4",
"drugadministrationroute": null,
"drugauthorizationnumb": "065234",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Limb injury",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Limb injury",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Limb injury",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METOPROLOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Hypertension",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "NITROGLYCERIN"
},
"drugadditional": null,
"drugadministrationroute": "060",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Tablet",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Angina pectoris",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NITROGLYCERIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ENOXAPARIN"
},
"drugadditional": null,
"drugadministrationroute": "058",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "SIX DOSES",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Angina pectoris",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "60",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENOXAPARIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Drug hypersensitivity",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Antiplatelet therapy",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLOPIDOGREL BISULFATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Antiplatelet therapy",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOPIDOGREL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATORVASTATIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Dyslipidaemia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATORVASTATIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LOSARTAN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Hypertension",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LOSARTAN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis Syndrome Secondary to medicine-induced hypersensitivity. Case Reports in Medicine. 2021;2021:1-6",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211117",
"receivedate": "20211117",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20082398,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-MLMSERVICE-20211027-3186918-1",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Acute coronary syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Left ventricular dysfunction",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug hypersensitivity",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Acute myocardial infarction",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Reports in Medicine. 2021;Article Number 4485754:2021. DOI:10.1155/2021/4485754",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "1",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211122",
"receivedate": "20211111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20057978,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-317809",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "62791006",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Rep Med. 2021;1 Oct;2021:4485754(1-6)",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211118",
"receivedate": "20211118",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20088469,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-ALVOGEN-2021-ALVOGEN-117697",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "62800",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "1",
"drugrecurrence": [
{
"drugrecuraction": "10069167"
},
{
"drugrecuraction": "10069167"
},
{
"drugrecuraction": "10046735"
},
{
"drugrecuraction": "10046735"
},
{
"drugrecuraction": "10037087"
},
{
"drugrecuraction": "10037087"
}
],
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "1",
"drugrecurrence": [
{
"drugrecuraction": "10069167"
},
{
"drugrecuraction": "10046735"
},
{
"drugrecuraction": "10037087"
}
],
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Urticaria",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pruritus",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Rep Med. 2021 Oct 1;2021:4485754.",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211029",
"receivedate": "20211029",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20013359,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-OrBion Pharmaceuticals Private Limited-2122170",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "065248",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "1",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "CEPHALEXIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hypersensitivity",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Medication error",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Rep Med. 2021 Oct 1; 2021:4485754.",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "1",
"reportercountry": "LK"
},
"primarysourcecountry": null,
"receiptdate": "20211123",
"receivedate": "20211123",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 20099920,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-MLMSERVICE-20211027-3186918-2",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": "50162",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Capsule, hard",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCLOXACILLIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Contraindicated product administered",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake, P.. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity. Case Reports in Medicine. 2021;10.1155/2021/4485754",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211122",
"receivedate": "20211105",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20038845,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "LK-GLASSHOUSE PHARMACEUTICALS LIMITED CA-2021GLH00005",
"fulfillexpeditecriteria": "1",
"occurcountry": "LK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "209846",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUCLOXACILLIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "2",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "FLUCLOXACILLIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Cellulitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALEXIN"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Kounis syndrome",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug hypersensitivity",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Karunathilake P, Ralapanawa U, Jayalath T, Abeyagunawardena S. Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity.. Case Rep Med. 2021",
"literaturereference_normalized": "kounis syndrome secondary to medicine induced hypersensitivity",
"qualification": "3",
"reportercountry": "LK"
},
"primarysourcecountry": "LK",
"receiptdate": "20211122",
"receivedate": "20211122",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20097865,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 2,
"transmissiondate": "20220304"
}
] |
{
"abstract": "Mycotic aneurysm of the hepatic artery (HA) is a rare, unpredictable, and potentially lethal complication of liver transplantation (LT). Pediatric LT is not exempt from it but the related literature is rather scanty. We present our experience with post-LT mycotic aneurysm of the HA in pediatric age, describing four cases occurred with a special focus on the possible risk factors for its development and a proposal for the management of high-risk recipients.",
"affiliations": "Department of Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy.;Paediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.;Infectious Diseases Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.;Department of Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy.;Department of Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy.;Paediatric Intensive Care Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.;Paediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.;Department of Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy.",
"authors": "Camagni|S|S|http://orcid.org/0000-0002-3037-7904;Stroppa|P|P|;Tebaldi|A|A|;Lucianetti|A|A|;Pinelli|D|D|;Pellicioli|I|I|;D'Antiga|L|L|;Colledan|M|M|",
"chemical_list": "D000935:Antifungal Agents",
"country": "Denmark",
"delete": false,
"doi": "10.1111/tid.12861",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1398-2273",
"issue": "20(3)",
"journal": "Transplant infectious disease : an official journal of the Transplantation Society",
"keywords": "hepatic artery; invasive fungal infection; mycotic aneurysm; pediatric liver transplantation",
"medline_ta": "Transpl Infect Dis",
"mesh_terms": "D000293:Adolescent; D000785:Aneurysm, Infected; D000935:Antifungal Agents; D002648:Child; D002675:Child, Preschool; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D000072742:Invasive Fungal Infections; D016031:Liver Transplantation",
"nlm_unique_id": "100883688",
"other_id": null,
"pages": "e12861",
"pmc": null,
"pmid": "29481733",
"pubdate": "2018-06",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Mycotic aneurysm of the hepatic artery in pediatric liver transplantation: A case series and literature review.",
"title_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review"
}
|
[
{
"companynumb": "IT-MYLANLABS-2018M1051199",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "POST?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTRA?OPERATIVE BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090596",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN /00002701/"
}
],
"patientagegroup": null,
"patientonsetage": "2",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Fungal sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15150504,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-ASTELLAS-2018US029369",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CASPOFUNGIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CASPOFUNGIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "050708",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "0.04 MG/KG, TWICE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "6",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMMUNOGLOBULIN /00025201/"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THYMOGLOBULIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
}
],
"patientagegroup": null,
"patientonsetage": "9",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Fungal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterobacter infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Aeromonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET. AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW.. TRANSPL INFECT DIS. 2018?20 (3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180629",
"receivedate": "20180629",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15090744,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180711"
},
{
"companynumb": "IT-ASTELLAS-2018US029367",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050708",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "0.04 MG/KG, TWICE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METILPREDNISOLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B, LIPOSOME"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METILPREDNISOLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "6",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
}
],
"patientagegroup": null,
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Proteus infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Staphylococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Arterial rupture",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET. AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW.. TRANSPL INFECT DIS. 2018?20 (3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180702",
"receivedate": "20180702",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15095907,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-STRIDES ARCOLAB LIMITED-2018SP005794",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "90687",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.04 MG/KG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MG/KG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "6 MG/KG ONCE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INFUSION",
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, DOSE WAS TAPPERED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50MG/KG EVERY 6 HOURS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG/KG, BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pyrexia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Bacterial sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fungal sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS. 2018?20(3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180726",
"receivedate": "20180713",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15138407,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-ASTELLAS-2018US029262",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "050708",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "0.04 MG/KG, TWICE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METILPREDNISOLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "6",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METILPREDNISOLONE"
}
],
"patientagegroup": null,
"patientonsetage": "2",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Peritoneal haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Arterial rupture",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fungal sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET. AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW.. TRANSPL INFECT DIS. 2018?20 (3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180702",
"receivedate": "20180702",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15095937,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-MYLANLABS-2018M1051200",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTRA?OPERATIVE BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090596",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "POST?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN /00002701/"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
}
],
"patientagegroup": null,
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Proteus infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Staphylococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15150497,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-TEVA-2018-IT-926312",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090402",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYL SALICYLIC ACID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THYMOGLOBULIN"
}
],
"patientagegroup": null,
"patientonsetage": "9",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Enterobacter infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180717",
"receivedate": "20180717",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15152176,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-BIOTEST PHARMACEUTICALS CORPORATION-IT-2018ADM000026",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THYMOGLOBULIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "1253890",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HUMAN IMMUNOGLOBULIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG/KG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": ".04 MG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT REJECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "9",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW.. TRANSPL?INFECT?DIS. 2018?20(3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "1",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180905",
"receivedate": "20180905",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15353546,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-FRESENIUS KABI-FK201807886",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "BOLUS DOSE GIVEN INTRA?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "2 MG/KG (MAXIMUM 20 MG) ONCE DAILY WITH PROGRESSIVE TAPERING",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
}
],
"patientagegroup": null,
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Staphylococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Proteus infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatic artery aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL INFECT DIS. 2018?20:1?7.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15150129,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-FRESENIUS KABI-FK201807887",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "BOLUS DOSE GIVEN INTRA?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "2 MG/KG (MAXIMUM 20 MG) ONCE DAILY WITH PROGRESSIVE TAPERING",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Septic shock",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatic artery aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Acute hepatic failure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL INFECT DIS. 2018?20:1?7.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180717",
"receivedate": "20180717",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15155119,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-STRIDES ARCOLAB LIMITED-2018SP005795",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MG/KG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "90687",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.04 MG/KG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, DOSE WAS TAPPERED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG/KG, UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50MG/KG EVERY SIX HOURS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS. 2018?20(3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180726",
"receivedate": "20180713",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15138399,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-TEVA-2018-IT-926315",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "POST?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090402",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYL SALICYLIC ACID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTRA?OPERATIVE BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
}
],
"patientagegroup": null,
"patientonsetage": "2",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Fungal sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180717",
"receivedate": "20180717",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15152132,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-FRESENIUS KABI-FK201807888",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "2 MG/KG (MAXIMUM 20 MG) ONCE DAILY WITH PROGRESSIVE TAPERING",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "BOLUS DOSE GIVEN INTRA?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOCHEMOTHERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMMUNOGLOBULIN HUMAN NORMAL"
}
],
"patientagegroup": null,
"patientonsetage": "9",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Enterobacter infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Aeromonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hepatic artery aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL INFECT DIS. 2018?20:1?7.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15150162,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "PHHY2018IT041255",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "65461",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65461",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Septic shock",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute hepatic failure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Arterial injury",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPLANT INFECTIOUS DISEASE. 2018?20:1?7",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15150610,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-MYLANLABS-2018M1051201",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090596",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.04 MG/KG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTRA?OPERATIVE BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "POST?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN /00002701/"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15150505,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-MYLANLABS-2018M1051204",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THYMOGLOBULIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090596",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN /00002701/"
}
],
"patientagegroup": null,
"patientonsetage": "9",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Enterobacter infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15150541,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-VELOXIS PHARMACEUTICALS, INC.-2018VELIT1035",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "206406",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "PROLONGED-RELEASE TABLET",
"drugdosagetext": "0.04 MG/KG (10?15 NG/ML), TWICE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".08",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENVARSUS XR"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MG/KG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MG/KG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMMUNOGLOBULIN /00025201/"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THYMOGLOBULIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterobacter infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Intentional product use issue",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Graft ischaemia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Aeromonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW.. TRANSPL INFECT DIS. 2018?20 (3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180712",
"receivedate": "20180712",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15133911,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-TEVA-2018-IT-926314",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090402",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTRA?OPERATIVE BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYL SALICYLIC ACID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "POST?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Staphylococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Proteus infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180717",
"receivedate": "20180717",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15152151,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-ACCORD-108886",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYLSALICYLIC ACID"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN SODIUM/SULBACTAM SODIUM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CASPOFUNGIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CASPOFUNGIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "INTRA-OPERATIVE BOLUS, ALSO RECEIVED INTRAVENOUS (NOT OTHERWISE SPECIFIED) 2 MG/KG INTERVAL (1 DAY)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "091195",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "0.04 MG/KG, TWICE DAILY, ALSO RECEIVED FOR IMMUNOSUPPRESSANT DRUG THERAPY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Haemorrhage",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Septic shock",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute hepatic failure",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Post procedural bile leak",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPLANT INFECTIOUS DISEASE. 2018?20:1-7",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20190227",
"receivedate": "20190227",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16011041,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190418"
},
{
"companynumb": "IT-STRIDES ARCOLAB LIMITED-2018SP005796",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, DOSE WAS TAPPERED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMMUNE GLOBULIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CASPOFUNGIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CASPOFUNGIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50MG/KG EVERY SIX HOURS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "90687",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.04 MG/KG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MG/KG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "6 MG/KG ONCE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "BASILIXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BASILIXIMAB"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG/KG, BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterobacter infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pyrexia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS. 2018?20(3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180726",
"receivedate": "20180713",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15138921,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-STRIDES ARCOLAB LIMITED-2018SP005793",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MG/KG, ONCE A DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, DOSE WAS TAPPERED",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "6 MG/KG ONCE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "040",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG/KG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INFUSION",
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "90687",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.04 MG/KG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG/KG, EVERY 6 HRS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peritoneal haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatic artery aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pyrexia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fungal sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS. 2018?20(3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180726",
"receivedate": "20180713",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15138403,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-TEVA-2018-IT-926313",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "POST?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "1",
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTRA?OPERATIVE BOLUS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "090402",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": "3",
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 U/KG/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTICOAGULANT THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN SODIUM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYL SALICYLIC ACID"
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2018?20(3):E12861.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180717",
"receivedate": "20180717",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15152153,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-FRESENIUS KABI-FK201807855",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "2 MG/KG (MAXIMUM 20 MG) ONCE DAILY WITH PROGRESSIVE TAPERING",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "040583",
"drugbatchnumb": "UNK,UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": "BOLUS DOSE GIVEN INTRA?OPERATIVELY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "2",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatic artery aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fungal sepsis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET AL.. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW. TRANSPL INFECT DIS. 2018?20:1?7.",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180716",
"receivedate": "20180716",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15150143,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20181010"
},
{
"companynumb": "IT-ASTELLAS-2018US029368",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METILPREDNISOLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPICILLIN SODIUM\\SULBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "6",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPICILLIN AND SULBACTAM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CASPOFUNGIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CASPOFUNGIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METILPREDNISOLONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FLUCONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL TREATMENT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUCONAZOLE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "050708",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FORMULATION UNKNOWN",
"drugdosagetext": "0.04 MG/KG, TWICE DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LIVER TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".04",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "16",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Shock haemorrhagic",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Septic shock",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Post procedural bile leak",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute hepatic failure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infective aneurysm",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pseudomonas infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Enterococcal infection",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMAGNI S, STROPPA P, TEBALDI A, LUCIANETTI A, PINELLI D, PELLICIOLI I, ET. AL. MYCOTIC ANEURYSM OF THE HEPATIC ARTERY IN PEDIATRIC LIVER TRANSPLANTATION: A CASE SERIES AND LITERATURE REVIEW.. TRANSPL INFECT DIS. 2018?20 (3):E12861",
"literaturereference_normalized": "mycotic aneurysm of the hepatic artery in pediatric liver transplantation a case series and literature review",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20180629",
"receivedate": "20180629",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15090683,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
}
] |
{
"abstract": "Statins as lipid lowering drugs, are safe and effective in reducing cardiovascular disease risk, but rarely produce myopathy like myalgia, myositis or rhabdomyolysis. We report the case of Rosuvastatin induced rhabdomyolytic acute renal failure and quadriparesis in a 67-year old male, a known case of type-2 diabetes mellitus and with a history of coronary angioplasty four months back. He was on antihypertensive, oral hypoglycemic and antiplatelet medications with Rosuvastatin 40mg/day. He was admitted with altered sensorium, breathlessness, vomiting, muscle weakness and decreased urine output and had raised serum creatinine, creatinine phosphokinase and myoglobin. After ruling out all other causation for rhabdomyolysis, we stopped Rosuvastatin and started supportive management and hemodialysis. Patient showed gradual recovery in renal function and quadriparesis. Patient was discharged with good urine output and on antihypertensive, hypoglycemic drug and diet restrictions for lipid control. He recovered completely and had normal renal function with well controlled lipid level on follow up of 6 months after discharge. Thus, prompt diagnosis of Rhabdomyolysis due to Rosuvastatin in absence of other aetiology and the multidisciplinary management can prevent further complication with favorable outcome.",
"affiliations": "Assistant Professor, Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS) , Ahmedabad, India .;Professor, Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS) , Ahmedabad, India .;Professor, Department of Nephrology and Transplantation Medicine, (IKDRC-ITS) , Ahmedabad, India .",
"authors": "Suthar|Kamlesh S|KS|;Vanikar|Aruna V|AV|;Trivedi|Hargovind L|HL|",
"chemical_list": null,
"country": "India",
"delete": false,
"doi": "10.7860/JCDR/2015/12117.5909",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0973-709X",
"issue": "9(5)",
"journal": "Journal of clinical and diagnostic research : JCDR",
"keywords": "Acute renal failure; Muscular diseases; Statin",
"medline_ta": "J Clin Diagn Res",
"mesh_terms": null,
"nlm_unique_id": "101488993",
"other_id": null,
"pages": "OD08-9",
"pmc": null,
"pmid": "26155510",
"pubdate": "2015-05",
"publication_types": "D002363:Case Reports",
"references": "8935674;12142128;19354002;11430535;21384516;23511950;10906171;12740143",
"title": "Acute Kidney Injury and Quadriparesis Due to Rosuvastatin Induced Rhabdomyolysis- A Case Report.",
"title_normalized": "acute kidney injury and quadriparesis due to rosuvastatin induced rhabdomyolysis a case report"
}
|
[
{
"companynumb": "IN-SUN PHARMACEUTICAL INDUSTRIES LTD-2015R1-98682",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ROSUVASTATIN"
},
"drugadditional": "1",
"drugadministrationroute": "048",
"drugauthorizationnumb": "79169",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "40 MG, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROSUVASTATIN."
}
],
"patientagegroup": null,
"patientonsetage": "67",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Quadriparesis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Rhabdomyolysis",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "SUTHAR KS, VANIKAR AV, TRIVEDI HL. ACUTE KIDNEY INJURY AND QUADRIPARESIS DUE TO ROSUVASTATIN INDUCED RHABDOMYOLYSIS- A CASE REPORT. J CLIN DIAGNOSTIC RES. 2015;MAY; 9(5):OD08-OD09",
"literaturereference_normalized": "acute kidney injury and quadriparesis due to rosuvastatin induced rhabdomyolysis a case report",
"qualification": "1",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20170415",
"receivedate": "20170415",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13445412,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170830"
}
] |
{
"abstract": "OBJECTIVE\nThis study sought to evaluate the outcome of maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis following intravenous gamma globulin (IVIG) and corticosteroid therapy.\n\n\nBACKGROUND\nWe have previously shown that 85% of fetuses and infants with maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis suffer demise or need for transplant. In an attempt to improve this outcome, in 1998, we began to empirically treat affected patients with IVIG and corticosteroids.\n\n\nMETHODS\nWe reviewed the clinical records and echocardiograms of 20 affected patients encountered in our institutions and treated with IVIG and corticosteroids from 1998 to 2009.\n\n\nRESULTS\nAll 20 were initially referred at a median gestational age of 23 weeks (range 18 to 38 weeks). Nineteen mothers were anti-Ro antibody positive, 8 anti-La antibody positive, and 7 had clinical autoimmune disease. Endocardial fibroelastosis was seen in 16 and was not obvious in 4 others with reduced ventricular function, and 16 (80%) had reduced or borderline ventricular shortening fraction (≤30%) before or after birth. Eighteen had atrioventricular block at referral (16 in 3°). During pregnancy, maternal IVIG was given in 9 and dexamethasone in 17. After birth, 17 infants received IVIG (n = 14) and/or corticosteroids (n = 15). Twelve underwent pacemaker implantation. Four with hydrops at presentation died perinatally, despite initial improvement in function in 3. At a median follow-up of 2.9 years (1.1 to 9.8 years), 16 (80%) patients are currently alive with normal systolic ventricular function and 6 are not paced.\n\n\nCONCLUSIONS\nTreatment of maternal autoantibody-mediated fetal cardiomyopathy/endocardial fibroelastosis with IVIG and corticosteroids potentially improves the outcome of affected fetuses. Further studies are needed to determine the optimal dose and timing of IVIG administration.",
"affiliations": "Pediatric Cardiology, University of California, San Francisco, USA.",
"authors": "Trucco|Sara M|SM|;Jaeggi|Edgar|E|;Cuneo|Bettina|B|;Moon-Grady|Anita J|AJ|;Silverman|Earl|E|;Silverman|Norman|N|;Hornberger|Lisa K|LK|",
"chemical_list": "D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous",
"country": "United States",
"delete": false,
"doi": "10.1016/j.jacc.2010.09.044",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0735-1097",
"issue": "57(6)",
"journal": "Journal of the American College of Cardiology",
"keywords": null,
"medline_ta": "J Am Coll Cardiol",
"mesh_terms": "D000305:Adrenal Cortex Hormones; D000328:Adult; D001323:Autoantibodies; D004695:Endocardial Fibroelastosis; D005260:Female; D005315:Fetal Diseases; D054502:Histocompatibility, Maternal-Fetal; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases; D011247:Pregnancy; D012189:Retrospective Studies; D055815:Young Adult",
"nlm_unique_id": "8301365",
"other_id": null,
"pages": "715-23",
"pmc": null,
"pmid": "21292131",
"pubdate": "2011-02-08",
"publication_types": "D016428:Journal Article; D016448:Multicenter Study",
"references": null,
"title": "Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy.",
"title_normalized": "use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody mediated cardiomyopathy"
}
|
[
{
"companynumb": "PHHY2016CA102585",
"fulfillexpeditecriteria": "1",
"occurcountry": "CA",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIGOXIN"
},
"drugadditional": null,
"drugadministrationroute": "064",
"drugauthorizationnumb": "40481",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "FOETAL EXPOSURE DURING PREGNANCY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIGOXIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXAMETHASONE"
},
"drugadditional": null,
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MATERNAL DOSE: 3 MG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "FOETAL EXPOSURE DURING PREGNANCY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TERBUTALINE"
},
"drugadditional": null,
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "FOETAL EXPOSURE DURING PREGNANCY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TERBUTALINE"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Foetal exposure during pregnancy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Premature baby",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HORNBERGER LK, TRUCCO SM, JAEGGI E, CUNEO B, MOON-GRADY AJ, SILVERMAN E ET.AL. USE OF INTRAVENOUS GAMMA GLOBULIN AND CORTICOSTEROIDS IN THE TREATMENT OF MATERNAL AUTOANTIBODY-MEDIATED CARDIOMYOPATHY. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. 2011;57(6):715-23",
"literaturereference_normalized": "use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody mediated cardiomyopathy",
"qualification": "3",
"reportercountry": "CA"
},
"primarysourcecountry": "CA",
"receiptdate": "20160728",
"receivedate": "20160728",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12602847,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20161109"
},
{
"companynumb": "PHHY2016CA102597",
"fulfillexpeditecriteria": "1",
"occurcountry": "CA",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIGOXIN"
},
"drugadditional": null,
"drugadministrationroute": "064",
"drugauthorizationnumb": "40481",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "FOETAL EXPOSURE DURING PREGNANCY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIGOXIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXAMETHASONE"
},
"drugadditional": null,
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "FOETAL EXPOSURE DURING PREGNANCY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
}
],
"patientagegroup": "1",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Foetal exposure during pregnancy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Premature baby",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HORNBERGER LK, TRUCCO SM, JAEGGI E, CUNEO B, MOON-GRADY AJ, SILVERMAN E ET.AL. USE OF INTRAVENOUS GAMMA GLOBULIN AND CORTICOSTEROIDS IN THE TREATMENT OF MATERNAL AUTOANTIBODY-MEDIATED CARDIOMYOPATHY. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. 2011;57(6):715-23",
"literaturereference_normalized": "use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody mediated cardiomyopathy",
"qualification": "3",
"reportercountry": "CA"
},
"primarysourcecountry": "CA",
"receiptdate": "20160728",
"receivedate": "20160728",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12602838,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20161109"
}
] |
{
"abstract": "The authors present a case of a 81-year-old non-smoker woman who was diagnosed with extended, bilateral bronchial adenocarcinoma in 2008. Two years later the tumor showed marked progression. EGFR sensitizing mutation (exon 19 deletion) was detected and gefitinib treatment was started in March 2010. After 12 months of spectacular and complete remission and 8 months of slow progression docetaxel therapy was applied and yielded partial remission. When progression redeveloped rebiopsy was performed and revealed EGFR exon 19 deletion again. Gefitinib retreatment was introduced in February 2013 and resulted in partial remission with excellent clinical status. In March, 2014 the patient is still on gefitinib treatment without any signs or symptoms of lung cancer but with very slow radiological progression. The authors overview the most important theoretical and practical questions regarding rebiopsy and retreatment in lung cancer with EGFR-TKI therapy.",
"affiliations": "Pulmonológiai Klinika, Semmelweis Egyetem, Budapest, Hungary. [email protected].;I. Sz. Patológiai és Kísérleti Rákkutató Intézet, Semmelweis Egyetem, Budapest, Hungary.;I. Sz. Patológiai és Kísérleti Rákkutató Intézet, Semmelweis Egyetem, Budapest, Hungary.;Radiológiai Diagnosztikai Központ, Semmelweis Egyetem, Budapest, Hungary.;Pulmonológiai Klinika, Semmelweis Egyetem, Budapest, Hungary. [email protected].;Pulmonológiai Klinika, Semmelweis Egyetem, Budapest, Hungary. [email protected].",
"authors": "Moldvay|Judit|J|;Pápay|Judit|J|;Kovalszky|Ilona|I|;Balázs|György|G|;Puskás|Rita|R|;Losonczy|György|G|",
"chemical_list": "D000970:Antineoplastic Agents; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib",
"country": "Hungary",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0025-0244",
"issue": "58(2)",
"journal": "Magyar onkologia",
"keywords": null,
"medline_ta": "Magy Onkol",
"mesh_terms": "D000230:Adenocarcinoma; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents; D001706:Biopsy; D001984:Bronchial Neoplasms; D018450:Disease Progression; D000077143:Docetaxel; D066246:ErbB Receptors; D005091:Exons; D005260:Female; D000077156:Gefitinib; D017353:Gene Deletion; D018773:Genes, erbB-1; D006801:Humans; D058990:Molecular Targeted Therapy; D011799:Quinazolines; D012074:Remission Induction; D019233:Retreatment; D043823:Taxoids; D016896:Treatment Outcome",
"nlm_unique_id": "9313833",
"other_id": null,
"pages": "133-7",
"pmc": null,
"pmid": "25010762",
"pubdate": "2014-06",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Gefitinib treatment in lung cancer -- rebiopsy, retreatment, remission.",
"title_normalized": "gefitinib treatment in lung cancer rebiopsy retreatment remission"
}
|
[
{
"companynumb": "HU-SA-2014SA100905",
"fulfillexpeditecriteria": "1",
"occurcountry": "HU",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOCETAXEL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020449",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LUNG NEOPLASM MALIGNANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOCETAXEL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GEFITINIB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LUNG NEOPLASM MALIGNANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201302",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GEFITINIB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOCETAXEL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020449",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "CYCLE:1-3",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LUNG NEOPLASM MALIGNANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201111",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOCETAXEL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GEFITINIB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LUNG NEOPLASM MALIGNANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201003",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GEFITINIB"
}
],
"patientagegroup": "6",
"patientonsetage": "81",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Neuropathy peripheral",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Peroneal nerve palsy",
"reactionmeddraversionpt": "17.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MOLDVAY J, PAPAY J, KOVALSZKY I, BALAZS G, PUSKAS R, LOSONCZY G. GEFITINIB TREATMENT IN LUNG CANCER - REBIOPSY, RETREATMENT, REMISSION. HUNGARIAN ONCOLOGY 2014 FEB;58:133-7.",
"literaturereference_normalized": "gefitinib treatment in lung cancer rebiopsy retreatment remission",
"qualification": "1",
"reportercountry": "HU"
},
"primarysourcecountry": "HU",
"receiptdate": "20140808",
"receivedate": "20140808",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10371134,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150326"
},
{
"companynumb": "HU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017R1-153679",
"fulfillexpeditecriteria": "1",
"occurcountry": "HU",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOCETAXEL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "022534",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 CYCLES",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ADENOCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201111",
"drugstartdateformat": "610",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOCETAXEL."
}
],
"patientagegroup": null,
"patientonsetage": "81",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peroneal nerve palsy",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Quality of life decreased",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Neuropathy peripheral",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "JUDIT M, JUDIT P, ILONA K, GYORGY B, RITA P, GYORGY L. GEFITINIB TREATMENT IN LUNG CANCER -- REBIOPSY, RETREATMENT, REMISSION. MAGY ONKOL. 2014?58(2):133-7",
"literaturereference_normalized": "gefitinib treatment in lung cancer rebiopsy retreatment remission",
"qualification": "1",
"reportercountry": "HU"
},
"primarysourcecountry": "HU",
"receiptdate": "20180123",
"receivedate": "20171101",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14149182,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180508"
}
] |
{
"abstract": "Eccrine porocarcinoma is a rare and aggressive skin neoplasm; only two cases of sarcomatoid differentiation have been reported. Whereas surgery is effective as first line treatment, optimal management of recurrent or metastatic porocarcinoma is not defined and needs multidisciplinary approach. Here we described the first reported case of metastatic sarcomatoid porocarcinoma. Our patient experienced multiple recurrences, mainly loco-regional, and was treated with a multidisciplinary treatment, involving surgery, radiotherapy, chemotherapy and target therapy, leading to a more than 4 years survival, from the first recurrence. We conclude that multidisciplinary approach in metastatic porocarcinoma must involve surgeon, radiotherapist and medical oncologist. The combination of local and systemic treatments can delay recurrence and prolong survival also in very aggressive cases.",
"affiliations": "Medical Oncology Division, Department of Hematology and Oncology, \"Città della Scienza e della Salute\", San Giovanni Battista Hospital, Turin, Italy.;Dermatologic Surgery Unit, Department of Hematology and Oncology, \"Città della Scienza e della Salute\", San Giovanni Battista Hospital, Turin, Italy - [email protected].;Dermatologic Surgery Unit, Department of Hematology and Oncology, \"Città della Scienza e della Salute\", San Giovanni Battista Hospital, Turin, Italy.;Medical Oncology Division, Department of Hematology and Oncology, \"Città della Scienza e della Salute\", San Giovanni Battista Hospital, Turin, Italy.;Dermatologic Surgery Unit, Department of Hematology and Oncology, \"Città della Scienza e della Salute\", San Giovanni Battista Hospital, Turin, Italy.;Medical Oncology Division, Department of Hematology and Oncology, \"Città della Scienza e della Salute\", San Giovanni Battista Hospital, Turin, Italy.",
"authors": "Ponzetti|Agostino|A|;Ribero|Simone|S|;Caliendo|Virginia|V|;Spadi|Rosella|R|;Macripò|Giuseppe|G|;Lista|Patrizia|P|",
"chemical_list": "D000970:Antineoplastic Agents; D000068818:Cetuximab",
"country": "Italy",
"delete": false,
"doi": "10.23736/S0392-0488.16.04778-7",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0392-0488",
"issue": "152(1)",
"journal": "Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia",
"keywords": null,
"medline_ta": "G Ital Dermatol Venereol",
"mesh_terms": "D000970:Antineoplastic Agents; D000068818:Cetuximab; D003131:Combined Modality Therapy; D057090:Eccrine Porocarcinoma; D006801:Humans; D033183:Interdisciplinary Communication; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012509:Sarcoma; D015996:Survival Rate; D013544:Sweat Gland Neoplasms",
"nlm_unique_id": "8102852",
"other_id": null,
"pages": "66-70",
"pmc": null,
"pmid": "25236317",
"pubdate": "2017-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Long-term survival after multidisciplinary management of a metastatic sarcomatoid porocarcinoma with repeated exeresis, radiotherapy, chemotherapy and cetuximab: case report and review of literature.",
"title_normalized": "long term survival after multidisciplinary management of a metastatic sarcomatoid porocarcinoma with repeated exeresis radiotherapy chemotherapy and cetuximab case report and review of literature"
}
|
[
{
"companynumb": "IT-ACCORD-050739",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CISPLATIN"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "206774",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": "2008",
"drugenddateformat": "602",
"drugindication": "POROCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "200804",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CISPLATIN."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CISPLATIN"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "206774",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "WEEKLY",
"drugenddate": "2008",
"drugenddateformat": "602",
"drugindication": "POROCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "200804",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CISPLATIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOCETAXEL"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "WEEKLY",
"drugenddate": "2008",
"drugenddateformat": "602",
"drugindication": "POROCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2008",
"drugstartdateformat": "602",
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOCETAXEL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CETUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FIRST WEEK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "POROCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "201109",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "400",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CETUXIMAB."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUOROURACIL"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "040743",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "PER DAY",
"drugenddate": "2008",
"drugenddateformat": "602",
"drugindication": "POROCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "200804",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUOROURACIL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "FLUOROURACIL"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "040743",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "PER DAY",
"drugenddate": "2008",
"drugenddateformat": "602",
"drugindication": "POROCARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "200804",
"drugstartdateformat": "610",
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUOROURACIL."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Thrombocytopenia",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypersensitivity",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2008"
}
},
"primarysource": {
"literaturereference": "PONZETTI A, RIBERO S, CALIENDO V, SPADI R, MACRIPO G, LISTA P. LONG-TERM SURVIVAL AFTER MULTIDISCIPLINARY MANAGEMENT OF A METASTATIC SARCOMATOID POROCARCINOMA WITH REPEATED EXERESIS, RADIOTHERAPY, CHEMOTHERAPY AND CETUXIMAB: CASE REPORT AND REVIEW OF LITERATURE. GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA. 2017;152(1):66-70.",
"literaturereference_normalized": "long term survival after multidisciplinary management of a metastatic sarcomatoid porocarcinoma with repeated exeresis radiotherapy chemotherapy and cetuximab case report and review of literature",
"qualification": "1",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20170425",
"receivedate": "20170425",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13485128,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170830"
}
] |
{
"abstract": "A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.",
"affiliations": "Department of Critical Care Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India.;Department of Critical Care Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India.;Department of Critical Care Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India.;Department of Critical Care Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India.",
"authors": "Hisham|Mohamed|M|;Sivakumar|Mundalipalayam N|MN|;Nandakumar|V|V|;Lakshmikanthcharan|S|S|",
"chemical_list": "D000900:Anti-Bacterial Agents; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D000069349:Linezolid",
"country": "India",
"delete": false,
"doi": "10.4103/0253-7613.174573",
"fulltext": "\n==== Front\nIndian J PharmacolIndian J PharmacolIJPharmIndian Journal of Pharmacology0253-76131998-3751Medknow Publications & Media Pvt Ltd India IJPharm-48-9110.4103/0253-7613.174573Drug WatchLinezolid and Rasagiline – A culprit for serotonin syndrome Hisham Mohamed Sivakumar Mundalipalayam N. Nandakumar V. Lakshmikanthcharan S. Department of Critical Care Medicine, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, IndiaCorrespondence to: Dr. Mohamed Hisham, E-mail: [email protected] 2016 48 1 91 92 11 5 2015 18 7 2015 30 11 2015 Copyright: © Indian Journal of Pharmacology2016This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.\n\nKEY WORDS\nLinezolidmonoamine oxidase inhibitorserotonin syndrome\n==== Body\nIntroduction\nSerotonin syndrome refers to a disorder which results from excess serotonergic stimulation at central and peripheral serotonin receptors, usually caused by drugs or drug interactions. It was first defined in 1955, but the precipitating drugs, signs, and symptoms became more common only after 1990s.[1] Despite its high prevalence; serotonin syndrome is often under-diagnosed. This case report highlights a rare incidence of serotonin syndrome due to drug interactions of linezolid with rasagiline; monoamine oxidase (MAO) inhibitor.\n\nCase Report\nA 65-year-old female patient was admitted to the hospital with fever, chills and pain in left leg. She was a known case of parkinsonism and diabetes mellitus. She was prescribed levodopa / carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide since 2 years. She also had multiple hospital and Intensive Care Unit (ICU) admissions for worsening parkinsonism. She was admitted to the ward for cellulitis and treated with intravenous clindamycin 600 mg thrice daily and intravenous benzylpenicillin 2 million units 4 times daily. Her anti-parkinsonism and diabetic medications were continued.\n\nOn the 3rd day of hospital admission, she had persistently high-temperature spikes (above 102°F), tachycardia and tachypnea. She became hypotensive and encephalopathic in the ward hence; she was shifted to ICU. Considering sepsis with multi-organ dysfunction syndrome antibiotics was escalated to intravenous linezolid 600 mg twice daily and intravenous piperacillin with tazobactam 4.5 gm thrice daily. Vancomycin was not considered taking into account her borderline renal parameters. On admission to the ICU, her hemodynamics improved with minimal inotropic supports. Her anti-parkinsonism drugs were continued; oral hypoglycemic agents were stopped and switched to insulin on ICU admission. Later, in the ICU she was confused, drowsy, disoriented and had altered sensorium. The patient also had myoclonus, tremors, jerky movements, and there was no neck stiffness. Computed tomography of the brain and cerebrospinal fluid analysis were not significant. Her laboratory investigation revealed improving white blood cell counts from 14,200 cells/mm3 to 11,000 cells/mm3 (normal range - 4500–12,500 cells/mm3), better glycemic control and no other abnormalities. Her blood and pus cultures were sterile.\n\nThe second day of ICU admission, her status remained the same with a high temperature of 103°F, altered mental status, myoclonus, jerky movements and tremors. No other drugs were added, the same treatment was continued, and the medications she received were scrutinized. She was on rasagiline and started on linezolid 2 days since ICU admission. Serotonin syndrome was suspected after ruling out other possibilities such as infection, drug abuse, cerebrovascular, and metabolic etiologies. The suspected causal drug linezolid had a probable adverse drug reaction. Causal association of serotonin syndrome as assessed by Naranjo causality scale and World Health Organisation-Uppsala\n\nMonitoring Centre causality assessment system with a Naranjo score of six. The drug interaction probability scale assessment also revealed probable causality of serotonin syndrome due to rasagiline and linezolid. Hence, both the drugs were stopped on the 2nd day. After 8 hours temperature settled, next day the patient's heart rate was normal, her sensorium improved and tremors completely subsided. Day 4, she was shifted out of the ICU. After 10 days, she started walking with support and was discharged from the hospital. The patient was discharged with anti-parkinsonism drugs and later added rasagiline. She has a regular follow-up with the neurologist. She was stable and remained asymptomatic for serotonin syndrome.\n\nDiscussion\nLinezolid is an oxazolidinone class of antibiotic and a weak, reversible MAO inhibitor. In 2003, records from postmarketing voluntary adverse event reporting system database identified 29 cases of serotonin syndrome associated with linezolid.[2]\n\nIn this case, a combination of serotonergic drugs; linezolid and rasagiline were most likely to be responsible for serotonin syndrome. Diagnosis of serotonin syndrome is purely on the basis of patient presentation as there are no laboratory investigations or blood serotonin levels for confirmation. It requires a strong clinical suspicion, proper medication history of serotonergic drugs and identification of specific signs and symptoms. Clinical examination, laboratory investigations, imaging, and cultures ruled out the other possibilities that favour towards an infectious focus of fever in our case. We excluded substance abuse or withdrawal, metabolic, and psychiatric etiologies. Hence, non-infectious etiology for fever was suspected. The offending drugs in our case, linezolid and rasagiline were the only temporal cause for fever associated with serotonin syndrome.\n\nThe distinction between neuroleptic malignant syndrome and malignant hyperthermia is also important. The serotonergic toxidrome is identified using Hunter Serotonin Toxicity Criteria, Boyer's and Sternbach's criteria.[3] The clinical presentation is marked by a triad of cognitive changes (confusion, visual hallucinations, elevated mood, agitation, insomnia, nervousness, delirium or coma), autonomic instability (fever, hyperhidrosis, hypertension, palpitations, or tachycardia), and neuromuscular excitability (myoclonus, tremors, chills, rigidity, hyperreflexia or akathisia).[45] Our case presented with fever, confusion, drowsiness, tremors, myoclonus, and jerky movements which were typical features to fulfill the diagnosis of serotonin syndrome.\n\nThe onset of serotonin syndrome ranges from few hours to 3 weeks of increase in dose or initiation of drugs that may increase serotonin levels. In our case report, the patient was on rasagiline and presented with serotonin syndrome within 36 hours of initiation of linezolid. Time to resolution of serotonin syndrome after discontinuation of the culprit drugs ranges from <6 hours to 5 days. In our case, signs and symptoms resolved 8 hours after stopping both serotonergic drugs without any other treatment.[6] Cyproheptadine, a serotonin antagonist, can be given in severe serotonin syndrome. An initial dose of 4–8 mg given orally, and maximum dose is 32 mg/day.[1]\n\nMicromedex suggests concomitant use of linezolid and serotonergic agents are contraindicated. If linezolid is to be administered, it is recommended that the serotonergic drug must be discontinued, or there must be a washout period of at least 2 weeks and observe the patient for serotonin syndrome.[3] Patients with unresolving fever, prescribers should think of the drugs and drug interactions causing the serotonergic syndrome. Prescribers should know the medication history of the patient and washout period of serotonergic drugs. Serotonin syndrome is self-limiting if identified early, culprit drugs are discontinued, and supportive care is initiated.\n\n\nFinancial Support and Sponsorship\nNil.\n\nConflicts of Interest\nThere are no conflicts of interest.\n==== Refs\n1 Hall M Serotonin syndrome Aust Prescr 2003 26 62 3 \n2 Lawrence KR Adra M Gillman PK Serotonin toxicity associated with the use of linezolid: A review of postmarketing data Clin Infect Dis 2006 42 1578 83 16652315 \n3 Quinn DK Stern TA Linezolid and serotonin syndrome Prim Care Companion J Clin Psychiatry 2009 11 353 6 20098528 \n4 Kamath A Revisiting serotonin syndrome J Clin Biomed Sci 2015 1 5 8 \n5 Malik A Junglee N A case of the serotonin syndrome secondary to phenelzine monotherapy at therapeutic dosing Case Rep Med 2015 2015 931963 \n6 Taylor JJ Wilson JW Estes LL Linezolid and serotonergic drug interactions: A retrospective survey Clin Infect Dis 2006 43 180 7 16779744\n\n",
"fulltext_license": "CC BY-NC-SA",
"issn_linking": "0253-7613",
"issue": "48(1)",
"journal": "Indian journal of pharmacology",
"keywords": "Linezolid; monoamine oxidase inhibitor; serotonin syndrome",
"medline_ta": "Indian J Pharmacol",
"mesh_terms": "D000368:Aged; D000900:Anti-Bacterial Agents; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007189:Indans; D000069349:Linezolid; D008996:Monoamine Oxidase Inhibitors; D020230:Serotonin Syndrome",
"nlm_unique_id": "7902477",
"other_id": null,
"pages": "91-2",
"pmc": null,
"pmid": "26997732",
"pubdate": "2016",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "16779744;16652315;20098528;25861278",
"title": "Linezolid and Rasagiline - A culprit for serotonin syndrome.",
"title_normalized": "linezolid and rasagiline a culprit for serotonin syndrome"
}
|
[
{
"companynumb": "IN-IMPAX LABORATORIES, INC-2016-IPXL-00200",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMANTADINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMANTADINE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MULTIPLE ORGAN DYSFUNCTION SYNDROME",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ROPINIROLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROPINIROLE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RASAGILINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RASAGILINE"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "CARBIDOPA\\LEVODOPA"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "076521",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "PROLONGED-RELEASE TABLET",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBIDOPA-LEVODOPA ER"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GLIPIZIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLIPIZIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TRIHEXYPHENIDYL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIHEXYPHENIDYL"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "600 MG, 2 /DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SEPSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
}
],
"patientagegroup": null,
"patientonsetage": "65",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Serotonin syndrome",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HISHAM M, SIVAKUMAR MN, NANDAKUMAR V, LAKSHMIKANTHCHARAN S.. LINEZOLID AND RASAGILINE - A CULPRIT FOR SEROTONIN SYNDROME. INDIAN JOURNAL OF PHARMACOLOGY. 2016?48:91-2",
"literaturereference_normalized": "linezolid and rasagiline a culprit for serotonin syndrome",
"qualification": "1",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20160304",
"receivedate": "20160304",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12147279,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160526"
},
{
"companynumb": "IN-MYLANLABS-2016M1008665",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "RASAGILINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RASAGILINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SEPSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4.5",
"drugstructuredosageunit": "002",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PIPERACILLIN AND TAZOBACTAM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMANTADINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMANTADINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLINDAMYCIN\\CLINDAMYCIN PHOSPHATE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CELLULITIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "UNSPECIFIED INGREDIENT"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTI-PARKINSON"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GLIPIZIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLIPIZIDE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "078845",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SEPSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ROPINIROLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROPINIROLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TRIHEXYPHENIDYL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIHEXYPHENIDYL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENICILLIN G"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "2 MILLION UNITS 4 TIMES DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CELLULITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENZYLPENICILLIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Serotonin syndrome",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HISHAM M, SIVAKUMAR M, NANDAKUMAR V, LAKSHMIKANTHCHARAN S. LINEZOLID AND RASAGILINE - A CULPRIT FOR SEROTONIN SYNDROME. INDIAN-J-PHARMACOL 2016?48(1):91-92.",
"literaturereference_normalized": "linezolid and rasagiline a culprit for serotonin syndrome",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20160301",
"receivedate": "20160301",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12134849,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160526"
},
{
"companynumb": "IN-TEVA-736458ISR",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GLIPIZIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLIPIZIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PIPERACILLIN AND TAZOBACTAM"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "RASAGILINE MESYLATE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "021641",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PARKINSONISM",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RASAGILINE MESILATE TABLET"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMANTADINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMANTADINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1200 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SEPSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TRIHEXYPHENIDYL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIHEXYPHENIDYL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CARBIDOPA\\LEVODOPA"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVODOPA/CARBIDOPA"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ROPINIROLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROPINIROLE."
}
],
"patientagegroup": null,
"patientonsetage": "65",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Serotonin syndrome",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HISHAM M,SIVAKUMAR M,NANDAKUMAR V,LAKSHMIKANTHCHARAN S. LINEZOLID AND RASAGILINE - A CULPRIT FOR SEROTONIN SYNDROME. INDIAN JOURNAL OF PHARMACOLOGY. 2016 JAN 01;48 (1):91-92.",
"literaturereference_normalized": "linezolid and rasagiline a culprit for serotonin syndrome",
"qualification": "1",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20170210",
"receivedate": "20170210",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13213075,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "IN-ALKEM LABORATORIES LIMITED-IN-ALKEM-2019-04308",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "RASAGILINE MESYLATE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "201889",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RASAGILINE MESYLATE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TRIHEXYPHENIDYL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIHEXYPHENIDYL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMANTADINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMANTADINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ROPINIROLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROPINIROLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "600 MILLIGRAM, TID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CELLULITIS",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "8",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN NOS"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENICILLIN G"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2 MILLION UNITS, QID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CELLULITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENZYLPENICILLIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "GLIPIZIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GLIPIZIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4.5 MILLIGRAM, TID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "8",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PIPERACILLIN/TAZOBACTAM"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "600 MILLIGRAM, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SEPSIS",
"drugintervaldosagedefinition": "805",
"drugintervaldosageunitnumb": "12",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CARBIDOPA\\LEVODOPA"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVODOPA/CARBIDOPA"
}
],
"patientagegroup": null,
"patientonsetage": "65",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Serotonin syndrome",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HISHAM M, SIVAKUMAR MN, NANDAKUMAR V AND LAKSHMIKANTHCHARAN S.. LINEZOLID AND RASAGILINE - A CULPRIT FOR SEROTONIN SYNDROME. INDIAN JOURNAL OF PHARMACOLOGY. 2016?48(1):91-92",
"literaturereference_normalized": "linezolid and rasagiline a culprit for serotonin syndrome",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20190823",
"receivedate": "20190823",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16732791,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20191005"
}
] |
{
"abstract": "The risk of severe precipitated opioid withdrawal (POW) is amplified when precipitated by a long-acting opioid antagonist. IM extended release naltrexone (XRNTX;Vivitrol®) is an FDA approved therapy to prevent relapse of opioid and alcohol abuse. Two cases of precipitated opioid withdrawal from XRNTX are presented that illustrate different patient reactions to POW. A 56-year-old woman developed a hypertensive emergency and required continuous intravenous vasodilator, clonidine, and intensive care monitoring after re-initiation of XRNTX following opioid relapse. A 25-year-old man developed agitation and altered mental status after receipt of XRNTX at the conclusion of a twelve-day detoxification program during which he continued surreptitious use of heroin. The patient received benzodiazepines and haloperidol without adequate affect, and required intubation with propofol, lorazepam, and dexmedetomidine infusions. Management of POW from XRNTX is a challenge to emergency providers and protocols to guide management do not exist. Recommended therapies include intravenous fluids, anti-emetics, clonidine, or benzodiazepines as well as therapy tailored to the organ system affected. To minimize risk of POW it is important for providers instituting XRNTX to adhere to the manufacturers warnings and clinic protocols including a naloxone challenge and ensure an adequate opioid free period prior to administration of XRNTX.",
"affiliations": "Warren Alpert Medical School of Brown University, Department of Emergency Medicine, Brown Emergency Medicine, Providence, RI, 02903, USA. Electronic address: [email protected].;Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.;NYU School of Medicine, Department of Population Health, New York, NY, 10016, USA.;Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.;Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, 10016, USA; Institute for Innovations in Medical Education, NYU Langone Health, New York, NY, 10016, USA.",
"authors": "Wightman|R S|RS|;Nelson|L S|LS|;Lee|J D|JD|;Fox|L M|LM|;Smith|S W|SW|",
"chemical_list": "D009292:Narcotic Antagonists; C000624616:vivitrol; D009271:Naltrexone",
"country": "United States",
"delete": false,
"doi": "10.1016/j.ajem.2018.03.052",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0735-6757",
"issue": "36(6)",
"journal": "The American journal of emergency medicine",
"keywords": "Addiction medicine; Medication safety; Naltrexone; Opioid withdrawal; Toxicology",
"medline_ta": "Am J Emerg Med",
"mesh_terms": "D000328:Adult; D004632:Emergency Medical Services; D005260:Female; D006556:Heroin Dependence; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone; D009292:Narcotic Antagonists; D009293:Opioid-Related Disorders; D013375:Substance Withdrawal Syndrome; D016896:Treatment Outcome",
"nlm_unique_id": "8309942",
"other_id": null,
"pages": "1128.e1-1128.e2",
"pmc": null,
"pmid": "29605483",
"pubdate": "2018-06",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Severe opioid withdrawal precipitated by Vivitrol®.",
"title_normalized": "severe opioid withdrawal precipitated by vivitrol"
}
|
[
{
"companynumb": "US-B.I. PHARMACEUTICALS,INC./RIDGEFIELD-2018-BI-019307",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NICARDIPINE INFUSION"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INCREASED TO 12 MG/ HR OVERNIGHT",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "12",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NICARDIPINE INFUSION"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG WITHDRAWAL SYNDROME",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "XRNTX"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ONDANSETRON"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ONDANSETRON"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAZEPAM."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LOPERAMIDE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LOPERAMIDE"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "1 L OF 0.9%",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "0.9% NS IV"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLONIDINE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".1",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLONIDINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DIAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAZEPAM."
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Treatment failure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WIGHTMAN R, NELSON L, LEE J, FOX L, SMITH S. SEVERE OPIOID WITHDRAWAL PRECIPITATED BY VIVITROL. AMERICAN JOURNAL OF EMERGENCY MEDICINE. 2018?.",
"literaturereference_normalized": "severe opioid withdrawal precipitated by vivitrol",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180413",
"receivedate": "20180413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14759119,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180711"
},
{
"companynumb": "US-ALKERMES INC.-ALK-2018-002044",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "NALTREXONE"
},
"drugadditional": "3",
"drugadministrationroute": "030",
"drugauthorizationnumb": "021897",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "380 MG, QMO",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG DEPENDENCE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "380",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VIVITROL"
}
],
"patientagegroup": "5",
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug withdrawal syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Diarrhoea",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Mydriasis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Restlessness",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Dizziness",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypertensive emergency",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Tachycardia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Gastrointestinal sounds abnormal",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Vomiting",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nausea",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Abdominal pain",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Headache",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Anxiety",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Syncope",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug screen positive",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WIGHTMAN, RACHEL S ET AL. SEVERE OPIOID WITHDRAWAL PRECIPITATED BY VIVITROL. AMERICAN JOURNAL OF EMERGENCY MEDICINE. 2018",
"literaturereference_normalized": "severe opioid withdrawal precipitated by vivitrol",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180409",
"receivedate": "20180409",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14735329,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20180711"
},
{
"companynumb": "US-ALKERMES INC.-ALK-2018-002045",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "NALTREXONE"
},
"drugadditional": "3",
"drugadministrationroute": "030",
"drugauthorizationnumb": "021897",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "380 MG, QMO",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DRUG DEPENDENCE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "380",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VIVITROL"
}
],
"patientagegroup": "5",
"patientonsetage": "25",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Confusional state",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Mydriasis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Delirium",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Sinus tachycardia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Anxiety",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Agitation",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Withdrawal syndrome",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Mental disorder",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hyperhidrosis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WIGHTMAN, RACHEL S. ET AL. SEVERE OPIOID WITHDRAWAL PRECIPITATED BY VIVITROL. AMERICAN JOURNAL OF EMERGENCY MEDICINE. 2018",
"literaturereference_normalized": "severe opioid withdrawal precipitated by vivitrol",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180409",
"receivedate": "20180409",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14734260,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20180711"
}
] |
{
"abstract": "Despite substantial improvements following the introduction of novel agents and antibodies, amyloid light-chain (AL)-amyloidosis still carries a grim prognosis. Here, we report on the case of a severely frail 86-year-old patient suffering from monoclonal gammopathy of renal significance (MGRS)-associated AL-amyloidosis with a diuretic-refractory nephrotic syndrome. In this patient, treatment with bortezomib-dexamethasone effectively induced a serological response, but was unfortunately poorly tolerated and failed to promote renal recovery fast enough to prevent secondary complications. Facing ongoing nephrotic syndrome, we performed unilateral kidney embolization and observed a substantial improvement of hypoalbuminemia accompanied by a significant gain in overall quality of life despite the necessity for thrice weekly dialysis. It can be concluded that systemic drugs in MGRS typically do not lead to instantaneous organ recovery but may initially rather be associated with substantial treatment-related morbidity. In this setting, unilateral renal artery embolization is effective to treat nephrotic syndrome and its secondary complications. The risk of potentially adverse effects, including post-embolization syndrome, can be minimized by unilateral embolization, still noting that also one-sided renal ablation has to be balanced against the requirement for life-long renal replacement therapy. Prospective controlled trials in a more comprehensive cohort will be needed to estimate the overall benefit of kidney embolization relative to novel agent therapies in frail patients with MGRS-related AL-amyloidosis.",
"affiliations": "Department of Medicine IV, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Medicine IV, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Radiology, University Medical Center Freiburg, Freiburg, Germany.;Institute for Surgical Pathology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Medicine IV, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Medicine IV, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.;Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
"authors": "Küchlin|Sebastian|S|;Duffner|Johannes|J|;Scheubeck|Sophia|S|;Schoeller|Katja|K|;Maruschke|Lars|L|;Seidl|Maximilian|M|;Engelhardt|Monika|M|;Walz|Gerd|G|;Prager|Eric Peter|EP|;Waldschmidt|Johannes Moritz|JM|0000-0001-5340-1818",
"chemical_list": null,
"country": "Canada",
"delete": false,
"doi": "10.1111/hdi.12707",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1492-7535",
"issue": "23(2)",
"journal": "Hemodialysis international. International Symposium on Home Hemodialysis",
"keywords": "AL-amyloidosis; MGRS; R-MCI; medical nephrectomy; nephrotic syndrome; treatment-related morbidity",
"medline_ta": "Hemodial Int",
"mesh_terms": "D000369:Aged, 80 and over; D000686:Amyloidosis; D004621:Embolization, Therapeutic; D005260:Female; D006801:Humans; D007668:Kidney; D011446:Prospective Studies",
"nlm_unique_id": "101093910",
"other_id": null,
"pages": "E59-E64",
"pmc": null,
"pmid": "30548910",
"pubdate": "2019-04",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Kidney embolization induces prompt organ response in a 86-year-old patient with MGRS-related AL-amyloidosis.",
"title_normalized": "kidney embolization induces prompt organ response in a 86 year old patient with mgrs related al amyloidosis"
}
|
[
{
"companynumb": "DE-BAUSCH-BL-2019-000719",
"fulfillexpeditecriteria": "1",
"occurcountry": "DE",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DEXAMETHASONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "40700",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NEPHROTIC SYNDROME",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BORTEZOMIB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL AMYLOIDOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BORTEZOMIB."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DEXAMETHASONE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "40700",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL AMYLOIDOSIS",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BORTEZOMIB"
},
"drugadditional": null,
"drugadministrationroute": "058",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NEPHROTIC SYNDROME",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1.3",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BORTEZOMIB."
}
],
"patientagegroup": null,
"patientonsetage": "86",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug intolerance",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WALDSCHMIDT J, DUFFNER J, SCHOELLER K, MARUSCHKE L, SEIDL M, SCHEUBECK S, KUCHLIN S, ENGELHARDT M, WALZ G, PRAGER E. KIDNEY EMBOLIZATION INDUCES PROMPT ORGAN RESPONSE IN A 86-YEAR-OLD PATIENT WITH MGRS-RELATED AL-AMYLOIDOSIS. HEMODIALYSIS INTERNATIONAL. 2018?1-6.",
"literaturereference_normalized": "kidney embolization induces prompt organ response in a 86 year old patient with mgrs related al amyloidosis",
"qualification": "1",
"reportercountry": "DE"
},
"primarysourcecountry": "DE",
"receiptdate": "20190125",
"receivedate": "20190125",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15866093,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
}
] |
{
"abstract": "Transcatheter edge-to-edge mitral valve repair with MitraClip System (Abbott Vascular, Menlo Park, CA) needs a trans-septal access for positioning the 22-Fr guiding catheter in the left atrium. To the best of our knowledge no data are currently available about the hemodynamic consequences of a congenital atrial septal defect (ASD) after MitraClip repair. We report a case of MitraClip repair in a patient with ostium secundum ASD and ischemic cardiomyopathy, who needed intraprocedural closure of the defect for serious hemodynamic complications, secondary to worsening of the right ventricular function, increased pulmonary pressure and inversion of the interatrial shunt in right-to-left direction. These events, which were exacerbated by high blood levels of PaCO2 for the anesthesiological protocol used, led to left-side low-output syndrome and cardiorespiratory arrest. © 2015 Wiley Periodicals, Inc.",
"affiliations": "Department of Cardiovascular Disease, Tor Vergata University of Rome, Rome, Italy.;Department of Cardiovascular Disease, Tor Vergata University of Rome, Rome, Italy.;Department of Cardiovascular Disease, Tor Vergata University of Rome, Rome, Italy.",
"authors": "Cammalleri|Valeria|V|;Romeo|Francesco|F|;Ussia|Gian Paolo|GP|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1002/ccd.26223",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1522-1946",
"issue": "88(2)",
"journal": "Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions",
"keywords": "ASD/PDA/PFO; Mitral valve disease; catheterization; closure; percutaneous intervention; percutaneous valve therapy; transseptal",
"medline_ta": "Catheter Cardiovasc Interv",
"mesh_terms": "D000368:Aged; D006328:Cardiac Catheterization; D006348:Cardiac Surgical Procedures; D018618:Echocardiography, Doppler, Color; D017548:Echocardiography, Transesophageal; D006344:Heart Septal Defects, Atrial; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008943:Mitral Valve; D008944:Mitral Valve Insufficiency; D016896:Treatment Outcome",
"nlm_unique_id": "100884139",
"other_id": null,
"pages": "307-11",
"pmc": null,
"pmid": "26354685",
"pubdate": "2016-08",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Hemodynamic complications during transcatheter MitraClip repair in presence of congenital atrial septal defect.",
"title_normalized": "hemodynamic complications during transcatheter mitraclip repair in presence of congenital atrial septal defect"
}
|
[
{
"companynumb": "IT-MYLANLABS-2017M1031960",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LEVOSIMENDAN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVOSIMENDAN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "REMIFENTANIL"
},
"drugadditional": null,
"drugadministrationroute": "050",
"drugauthorizationnumb": "020630",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "CONTINUOUS INFUSION",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REMIFENTANIL"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Cardio-respiratory arrest",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CAMMALLERI V, ROMEO F, USSIA GP. HEMODYNAMIC COMPLICATIONS DURING TRANSCATHETER MITRACLIP REPAIR IN PRESENCE OF CONGENITAL ATRIAL SEPTAL DEFECT. CATHETER-CARDIOVASC-INTERV 2016;88(2):307-11.",
"literaturereference_normalized": "hemodynamic complications during transcatheter mitraclip repair in presence of congenital atrial septal defect",
"qualification": "1",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20170526",
"receivedate": "20170526",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13587345,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20170830"
}
] |
{
"abstract": "Histiocytic sarcoma (HS) is a rare aggressive malignancy with a dismal prognosis and no agreed-upon standard treatment. Classically, the diagnosis of HS has been difficult to confirm and has relied on inaccurate, crude techniques. Therapy often involves intensive chemotherapeutic regimens, surgery, and/or radiotherapy, which are poorly tolerated with variable response rates. Patients often die of diffusely metastatic disease. Modern diagnostic techniques are helping to slowly uncover more uniquely customized therapeutic approaches in this enigmatic disease. We present a review of the current literature regarding HS diagnosis, treatment, and outcomes. Additionally, we describe the first reported case of HS transdifferentiated from follicular lymphoma that had a dramatic and durable response to rituximab/bendamustine alone as initial treatment. Unlike traditional chemotherapy regimens, this treatment was well tolerated and had a good toxicity profile. The combination of rituximab and bendamustine warrants further investigation in the treatment of HS, especially those originating from prior follicular lymphoma. Modern immunohistochemical and molecular profiling techniques are beginning to reveal heterogeneity among HS tumors and potentially therapeutic targets.",
"affiliations": "Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC. Electronic address: [email protected].;Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC.;Department of Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC.;Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC.;Department of Pathology, Stanford University, Stanford, CA.;Department of Pathology, Stanford University, Stanford, CA.;Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC.",
"authors": "Farris|Michael|M|;Hughes|Ryan T|RT|;Lamar|Zanetta|Z|;Soike|Michael H|MH|;Menke|Joshua R|JR|;Ohgami|Robert S|RS|;Winkfield|Karen|K|",
"chemical_list": "D000069283:Rituximab; D000069461:Bendamustine Hydrochloride",
"country": "United States",
"delete": false,
"doi": "10.1016/j.clml.2018.10.004",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2152-2669",
"issue": "19(1)",
"journal": "Clinical lymphoma, myeloma & leukemia",
"keywords": "Dendritic cell; Mediastinal; Non-langerhans; Transdifferentiation; Translocation",
"medline_ta": "Clin Lymphoma Myeloma Leuk",
"mesh_terms": "D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D000069461:Bendamustine Hydrochloride; D054747:Histiocytic Sarcoma; D006801:Humans; D008224:Lymphoma, Follicular; D008297:Male; D011379:Prognosis; D000069283:Rituximab",
"nlm_unique_id": "101525386",
"other_id": null,
"pages": "e1-e8",
"pmc": null,
"pmid": "30396823",
"pubdate": "2019-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Histiocytic Sarcoma Associated With Follicular Lymphoma: Evidence for Dramatic Response With Rituximab and Bendamustine Alone and a Review of the Literature.",
"title_normalized": "histiocytic sarcoma associated with follicular lymphoma evidence for dramatic response with rituximab and bendamustine alone and a review of the literature"
}
|
[
{
"companynumb": "US-TEVA-2018-US-976981",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "BENDAMUSTINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "022249",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NON-HODGKIN^S LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TREANDA"
},
{
"actiondrug": "6",
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NON-HODGKIN^S LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENDECA"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "BENDAMUSTINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "022249",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER FOR INJECTION",
"drugdosagetext": "96 MG/M2, CYCLIC (6 CYCLES)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HISTIOCYTIC SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "20170710",
"drugstartdateformat": "102",
"drugstructuredosagenumb": "96",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TREANDA"
},
{
"actiondrug": "6",
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER FOR INJECTION",
"drugdosagetext": "96 MG/M2, CYCLIC (6 CYCLES)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HISTIOCYTIC SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "96",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENDECA"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "700 MG, OTHER (Q 8 WEEKS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HISTIOCYTIC SARCOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "20170710",
"drugstartdateformat": "102",
"drugstructuredosagenumb": "700",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXAN"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NON-HODGKIN^S LYMPHOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXAN"
}
],
"patientagegroup": null,
"patientonsetage": "75",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Abdominal discomfort",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "FARRIS M. HISTIOCYTIC SARCOMA ASSOCIATED WITH FOLLICULAR LYMPHOMA: EVIDENCE FOR DRAMATIC RESPONSE WITH RITUXIMAB AND BENDAMUSTINE ALONE AND A REVIEW OF THE LITERATURE. CLINICAL LYMPHOMA, MYELOMA AND LEUKEMIA. 2019?19(1):.",
"literaturereference_normalized": "histiocytic sarcoma associated with follicular lymphoma evidence for dramatic response with rituximab and bendamustine alone and a review of the literature",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190326",
"receivedate": "20181122",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15647957,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190417"
}
] |
{
"abstract": "There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART).\nWe studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART.\nDuring the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V.\nDespite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.",
"affiliations": "Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA.;Department of Infectious Diseases, Kaiser Permanente Northern California, South San Francisco, California, USA.;Department of Infectious Diseases, Kaiser Permanente Northern California, San Francisco, California, USA.;Division of Epidemiology and Population Health, Department of Medicine, Stanford University, Stanford, California, USA.;Division of Epidemiology and Population Health, Department of Medicine, Stanford University, Stanford, California, USA.;Department of Infectious Diseases, Kaiser Permanente Northern California, San Francisco, California, USA.;Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.;Department of Infectious Diseases, Kaiser Permanente Northern California, Oakland, California, USA.;Department of Pathology, Stanford University, Stanford, California, USA.;Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.;Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA.",
"authors": "Rhee|Soo-Yon|SY|;Clutter|Dana|D|;Hare|C Bradley|CB|;Tchakoute|Christophe T|CT|;Sainani|Kristin|K|;Fessel|W Jeffrey|WJ|;Hurley|Leo|L|;Slome|Sally|S|;Pinsky|Benjamin A|BA|;Silverberg|Michael J|MJ|;Shafer|Robert W|RW|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1093/ofid/ofaa316",
"fulltext": "\n==== Front\nOpen Forum Infect Dis\nOpen Forum Infect Dis\nofid\nOpen Forum Infectious Diseases\n2328-8957\nOxford University Press US\n\n10.1093/ofid/ofaa316\nofaa316\nMajor Articles\nAcademicSubjects/MED00290\nVirological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens\nRhee Soo-Yon 1\nClutter Dana 2\nHare C Bradley 3\nTchakoute Christophe T 4\nSainani Kristin 4\nFessel W Jeffrey 3\nHurley Leo 5\nSlome Sally 6\nPinsky Benjamin A 7\nSilverberg Michael J 5\nShafer Robert W 1\n1 Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA\n2 Department of Infectious Diseases, Kaiser Permanente Northern California, South San Francisco, California, USA\n3 Department of Infectious Diseases, Kaiser Permanente Northern California, San Francisco, California, USA\n4 Division of Epidemiology and Population Health, Department of Medicine, Stanford University, Stanford, California, USA\n5 Division of Research, Kaiser Permanente Northern California, Oakland, California, USA\n6 Department of Infectious Diseases, Kaiser Permanente Northern California, Oakland, California, USA\n7 Department of Pathology, Stanford University, Stanford, California, USA\nCorrespondence: S.-Y. Rhee, PhD, Division of Infectious Diseases, Stanford University Medical Center, 1000 Welch Rd, Suite 202, Stanford, CA 94304 ([email protected]).\n9 2020\n06 8 2020\n06 8 2020\n7 9 ofaa31602 3 2020\n15 7 2020\n27 7 2020\n01 9 2020\n© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.\n2020\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact [email protected]\n\nAbstract\n\nBackground\n\nThere are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART).\n\nMethods\n\nWe studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART.\n\nResults\n\nDuring the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V.\n\nConclusions\n\nDespite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.\n\nIn a U.S. clinic population, the proportion of persons with HIV who experience virological failure or drug resistance on initial ART is low but may no longer be decreasing. Further efforts are required to improve long-term ART virological responses.\n\nantiretroviral therapy\ndrug resistance\nHIV-1\nvirological outcome\nJanssen Scientific Affairs National Institute of Allergy and Infectious Diseases 10.13039/100000060 National Institutes of Health 10.13039/100000002 AI136618\n==== Body\nMany clinical trials and several longitudinal cohort studies in Europe and North America have reported that since 2000 antiretroviral therapy (ART) has become progressively more effective, with fewer persons with HIV-1 (PWH) developing virologic failure (VF) or acquiring drug resistance [1–11]. However, large numbers of PWH in these studies received ART regimens no longer recommended by current expert guidelines [12]. To evaluate the risk of VF and acquired HIV-1 drug resistance (HIVDR) in PWH receiving contemporary ART regimens, we examined the incidence of these end points in a large US clinic population initiating therapy during an 8-year period between 2010 and 2017.\n\nWe recently published a study of nucleoside RT inhibitor (NRTI)–, non-nucleoside RT inhibitor (NNRTI)–, and protease inhibitor (PI)–associated transmitted drug resistance (TDR) between 2003 and 2016 in the same clinic population described here [13]. The overall prevalence of TDR in that study was 13.9%, with a prevalence of 16% to 19% between 2012 and 2016. Many of the transmitted mutations were associated with drugs that had not been used since the early 2000s (eg, thymidine analogs) and likely resulted from ongoing transmission of drug-resistant strains that emerged years earlier. Therefore, in the current study, we sought to identify drug resistance mutations associated with contemporary ART regimens.\n\nMETHODS\n\nStudy Population\n\nWe identified all ART-naïve adult PWH in the Kaiser Permanente Northern California (KPNC) medical care program who had a baseline genotypic resistance test and initiated ART between January 1, 2010, and December 31, 2017. According to KPNC ART guidelines, genotypic resistance testing was recommended for all PWH initiating ART during this time period, and to our knowledge, adherence to this policy was close to 100%. PWH were followed on first-line ART until December 31, 2018, unless they experienced VF or were censored as defined below.\n\nDemographic data, HIV-1 acquisition risk factors, virus load (VL), CD4 counts, and ART history data were obtained from an electronic KPNC research database. Genotypic resistance testing was performed at the Stanford University Healthcare Clinical Virology Laboratory. During the study, tenofovir alafenamide was substituted for tenofovir disoproxil fumarate after its approval in 2016. Here, we use tenofovir to refer to tenofovir disoproxil fumarate and tenofovir alafenamide. The Stanford University and KPNC institutional review boards approved this study.\n\nVF and Censoring\n\nVirologic suppression was defined as attaining a VL <200 copies/mL [14]. Between 2010 and 2014, plasma HIV-1 RNA levels (virus load [VL]) were monitored using the VERSANT assay (Siemans Molecular Diagnostics), which quantifies VL between 75 and 500 000 copies/mL. Between 2014 and 2018, VL was monitored using the Ampliprep/Cobas Taqman assay (Roche Laboratories), which quantifies VL between 48 and 10 million copies/mL. To adjust for this change, we used 500 000 copies/mL as the VL upper limit.\n\nVF was defined as not attaining virological suppression or as experiencing virological rebound. The former was defined as displaying no evidence of virologic response, prompting a change in therapy within the first 6 months of starting ART, or not attaining virologic suppression after 6 months of starting ART. PWH who did not attain virologic suppression and died before completing 6 months of therapy were considered to have had VF. However, PWH who did not attain virologic suppression and discontinued KPNC care before completing 6 months of therapy were censored. Among PWH attaining initial virologic suppression, VF was defined as loss of virologic suppression prompting a change in therapy, as well as ART discontinuation for any reason. PWH were censored at the time of death, discontinuing KPNC medical care, switching to another regimen while virologically suppressed, or reaching December 31, 2018, without experiencing VF.\n\nHIV Drug Resistance\n\nTDR was defined as drug resistance before the start of ART. HIVDR was defined as acquiring 1 or more nonpolymorphic mutations associated with reduced susceptibility to NRTIs, PIs, or integrase-strand transfer inhibitors (INSTIs) that were not present before ART [15–17].\n\nStatistical Methods\n\nVF and HIVDR end points were reported as the proportion of PWH developing the end point, the incidence per 100 person-years, and the cumulative incidence for the population at risk following the start of therapy. Fisher exact tests were used for comparing proportions of categorical variables, and Wilcoxon rank sum tests were used for comparing continuous variables between PWH without VF and with VF, and between PWH without VF and with HIVDR.\n\nUnivariable and multivariable Cox regressions were used to estimate VF and HIVDR hazard ratio for age, gender, ethnicity (Caucasian, non-Caucasian), baseline CD4 cell count, baseline VL, companion ARVs, and presence of TDR. The effect of baseline CD4 cell count was estimated as a continuous variable and a categorical variable (<300, 300–500, ≥500 cells/μL). The effect of baseline VL was estimated as a continuous variable and a categorical variable (<4.0, 4.0–5.0, ≥5.0 copies/mL). Because of the strong association of abacavir/lamivudine with dolutegravir, we did not include the NRTI backbone in any of the regression models. Examining the Schoenfeld residuals of the model showed that the Cox regression proportional hazards assumption was not violated for any of the variables included in the final model [18]. Statistical significance was defined as P < .05.\n\nRESULTS\n\nStudy Cohort\n\nBetween January 2010 and December 2017, 2315 PWH began ART following a baseline genotypic resistance test. The median age (interquartile range [IQR]) was 39 (29–49) years; 90.8% were male. Race/ethnicity was identified as Caucasian in 41.4%, Hispanic in 22.9%, black/African American in 21.5%, Asian in 10.1%, and unrecorded in 4.1%. HIV-1 acquisition risk factors included men who have sex with men (MSM) in 60.4%, heterosexual contact in 18.0%, bisexual contact in 11.9%, injection drug use in 5.5%, transfusion recipient in 0.4%, and unrecorded in 3.8%.\n\nThe median baseline CD4 count (IQR) was 373 (201–537) cells/μL, and the median baseline VL (IQR) was 4.5 (4.0–5.1) log copies/mL. TDR was present in 13.8% of PWH. The overall proportions with NNRTI, NRTI, PI, and multiclass TDR were 9.5%, 3.5%, 3.0%, and 2.0%, respectively. Of 140 PWH who underwent a baseline integrase genotypic resistance test, 4 (2.9%) had a nonpolymorphic INSTI-associated mutation. Three of these PWH also had NRTI- or NNRTI-associated TDR.\n\nThe median year of ART initiation (IQR) was 2014 (2011–2015). The median number of months of follow-up by year was 65 for the 302 starting ART in 2010, 56 for the 313 starting ART in 2011, 49 for the 307 starting ART in 2012, 55 for the 233 starting ART in 2013, 49 for the 329 starting ART in 2014, 39 for the 310 starting ART in 2015, 28 for the 300 starting ART in 2016, and 16 for the 221 starting ART in 2017. VL testing was performed a median (IQR) of every 4.6 (3.4–6.2) months. During the study period, there was a significant yearly decrease in the age of PWH starting ART (coefficient, –0.5 per year; P < .001), and there was a significant yearly increase in the proportions of non-MSM (OR, 1.08; P < .001) and non-Caucasians (OR, 1.06; P = .002). Baseline CD4 cell counts (coefficient, 20.3; P < .001) and baseline VL (coefficient, 0.03; P < .001) also significantly increased over the study period.\n\nFirst-line ART Regimens\n\nFigure 1 shows the proportion of the most common companion ARVs received as part of an ART regimen. Six ARVs—efavirenz, elvitegravir/cobicistat (elvitegravir/c), dolutegravir, rilpivirine, darunavir/ritonavir or darunavir/cobicistat (b-darunavir), and raltegravir—accounted for 93.3% of the 2315 ART regimens. The remaining companion ARVs included atazanavir/ritonavir or atazanavir/cobicistat (b-atazanavir; 2.9%), lopinavir/ritonavir (lopinavir/r; 0.6%), nevirapine (0.6%), and etravirine (0.3%). A regimen containing more than 1 companion ARV was received by 2.3% of the cohort—two-thirds of whom had baseline TDR.\n\nFigure 1. Yearly distribution of the 6 most common ART companion drugs used as part of the initial ART (n = 2315). Abbreviations: ART, antiretroviral therapy; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; IQR, interquartile range; PWH, people with HIV; RAL, raltegravir; RPV, rilpivirine.\n\nSingle-tablet regimens accounted for 69.8% of the 2315 ART regimens. The most common NRTI backbones, tenofovir/emtricitabine and abacavir/lamivudine, were used in 82.3% and 12.2% of ART regimens, respectively. Among those receiving abacavir/lamivudine, 80.1% received it as part of a fixed-dose combination with dolutegravir.\n\nVirological Failure and Acquired Drug Resistance\n\nOf the 2315 PWH receiving ART, 214 (9.2%) experienced VF, including 55 (2.4%) who never attained virologic suppression and 159 (6.9%) who developed VF after attaining initial virologic suppression. Forty PWH (1.7%) left KPNC within 6 months of starting ART without attaining virologic suppression, and 2061 (89.0%) PWH never experienced VF (Figure 2).\n\nFigure 2. Disposition of virological outcomes, genotypic resistance testing, and acquired drug resistance in the overall cohort of PWH starting ART between January 2010 and December 2017. Forty PWH who left KPNC within 6 months of starting therapy without having attained virologic suppression were censored in the primary analysis. Abbreviations: ART, antiretroviral therapy; GART, genotypic antiretroviral resistance test; KPNC, Kaiser Permanente Northern California; New DRMs, drug-resistance mutations that emerged on therapy; PWH, people with HIV; VF, virological failure; VS, virologic suppression.\n\nOf the 55 PWH not attaining virologic suppression, 7 died within 6 months of starting ART. Of the remaining 48 PWH, 26 underwent genotypic resistance testing, and 16 of these were found to have HIVDR. Five of the 10 PWH who underwent resistance testing but did not have HIVDR had discontinued therapy at least 3 months before testing. The 22 PWH with VF who did not undergo resistance testing included 11 who had discontinued ART before developing VF.\n\nOf the 2220 PWH attaining virologic suppression, 159 (6.9% of the cohort) experienced VF after a median follow-up (IQR) of 21.4 (12.1–41.0) months, including 76 who underwent resistance testing, of whom 46 were found to have HIVDR. Fifteen of the 30 PWH who underwent resistance testing but did not have drug resistance had discontinued therapy at least 3 months before resistance testing. Of the 83 PWH with VF who did not undergo resistance testing, 59 discontinued therapy before developing VF and 9 discontinued KPNC care shortly after developing VF.\n\nThe rates of VF and HIVDR in the entire population were 2.8 and 0.8 cases per 100 person-years of follow-up, respectively. The rates of VF and of HIVDR in the subset of 2220 PWH attaining initial virologic suppression were 2.1 and 0.6 cases per 100 person-years of follow-up, respectively. Figure 3 shows that the yearly incidence of VF was highest in the first year of therapy, with 3.5 events per 100 person-years; it then decreased to 2.7 events per 100 person-years in the second year and 2.0 events per 100 person-years in the third year.\n\nFigure 3. Cumulative incidence of VF and VF plus acquired HIVDR for the 2315 PWH over a period of 60 months. PWH were censored if they died, discontinued KPNC care, switched to a third ART regimen, or reached December 31, 2018 without experiencing VF. Abbreviations: ART, antiretroviral therapy; HIVDR, HIV drug resistance; KPNC, Kaiser Permanente Northern California; HIVDR, drug-resistance mutations that emerged on therapy; PWH, people with HIV; VF, virological failure.\n\nAmong the 2061 PWH without VF (89.0% of the cohort), the median follow-up (IQR) was 38.1 (19.8–61.6) months. Of these PWH, 1035 (44.7% of the cohort) were followed until December 31, 2018; 331 (14.3% of the cohort) discontinued KPNC care; 575 (24.8% of the cohort) switched to a second regimen without experiencing VF; and 41 (1.8% of the cohort) died.\n\nFactors Associated With VF and HIVDR\n\nTable 1 shows the demographics, HIV acquisition risk factors, and baseline laboratory tests in the 2061 PWH without VF, the 214 with VF, and the 62 with VF and HIVDR. Compared with PWH without VF, those with VF were more likely to have lower baseline CD4 counts, higher baseline VLs, and to be non-Caucasian. Compared with PWH without VF, those with HIVDR were more likely to have lower baseline CD4 counts and higher baseline VL.\n\nTable 1. Demographics, HIV Risk Factors, and Baseline Laboratory Tests in People With HIV With Sustained Virologic Suppression, Virologic Failure, and Virologic Failure Plus Acquired HIVDR\n\n\tVS\tAny VF\tVF+HIVDR\t\n\t(n = 2061)\t(n = 214)\t(n = 62)\t\nAge, median (IQR), y\t39 (29–50)\t38 (29–49)\t43 (33–49)\t\nGender (male), %\t91.0\t87.9\t90.3\t\nEthnicity, %\t\t\t\t\n Caucasian\t42.6\t33.2 a\t30.6\t\n Hispanic\t22.6\t22.9\t32.3\t\n Black/African American\t20.6\t30.8\t25.8\t\n Asian\t10.8\t9.8\t8.1\t\n Not recorded\t3.4\t3.3\t3.2\t\nHIV acquisition risk, %\t\t\t\t\n MSM\t60.7\t55.1\t58.1\t\n Heterosexual contact\t18.0\t20.6\t21.0\t\n Bisexual\t12.2\t9.8\t8.1\t\n Intravenous drug use\t5.3\t7.0\t4.8\t\n Transfusion\t0.4\t0.9\t1.6\t\n Not recorded\t3.4\t6.5\t6.4\t\nSubtype B, %\t94.8\t93.9\t98.4\t\nCD4 count, median (IQR), cells/μL\t384 (217–551)\t275 (55–401) a\t109 (38–281)b\t\nVL, median (IQR), log copies/mL\t4.5 (4–5)\t4.7 (4.3–5.2)a\t5.0 (4.6–5.5)b\t\nTDR, %\t13.7\t13.1\t9.7\t\n NNRTI\t9.0\t11.2\t9.7\t\n NRTI\t3.8\t1.9\t1.6\t\n PI\t3.2\t1.9\t1.6\t\n Multiclass TDR\t2.0\t1.9\t3.2\t\nSignificant difference in people with HIV with virological failure and in people with HIV with virological failure plus acquired HIVDR compared with people with HIV with sustained virological suppression is indicated in boldface type.\n\nAbbreviations: HIVDR, HIV-1 drug resistance; IQR, interquartile range; MSM, men who have sex with men; PWH, people with HIV; TDR, transmitted drug resistance; VF, virological failure; VL, virus load (plasma HIV-1 RNA log copies/mL); VS, virological suppression.\n\naCompared with PWH without VF, those with VF had lower baseline CD4 counts (P < .001), higher baseline VLs (P < .001), and were more likely to be non-Caucasian (P = .008).\n\nbCompared with PWH without VF, those with VF plus HIVDR had lower baseline CD4 counts (P < .001) and higher baseline VLs (P < .001).\n\nTable 2 shows the results of univariable and multivariable regression analyses of factors potentially associated with the incidence of VF. In multivariable regression analysis, there was a significantly increased incidence of VF per 100 person-years, with lower baseline CD4 counts, higher baseline VLs, and younger age but not non-Caucasian race/ethnicity. Compared with efavirenz, b-atazanavir was associated with an increased VF incidence. For each 100-cell CD4 count decrease, there was a 17.9% increased VF incidence. For each 1.0 log VL increase, there was a 47.0% increased VF incidence. For each 10-year decrease in age, there was a 26.1% increased VF incidence.\n\nTable 2. Association of Demographics, HIV Risk Factors, Baseline Laboratory Results, and Companion ARV With Virological Failure Incidence per 100 Person-Years\n\nVariable\tNo. of PWH\tPerson-Years\tNo. of VF\tNo. of VF/100 Person-Years\tUnadjusted HRa (95% CI)\tAdjusted HRb,c (95% CI)\t\nAge\t\t\t\t\t\t\t\n 10-y decrement\t\t\t\t\t1.13 (1.12–1.15)\t1.26 (1.24–1.28)\t\nGender\t\t\t\t\t\t\t\n M\t2103\t7030\t188\t2.67\tRef\t\t\n F\t212\t691\t26\t3.76\t1.40 (0.93–2.11)\t1.18 (0.697–2.01)\t\nRace/ethnicity\t\t\t\t\t\t\t\n Caucasian\t960\t3358\t71\t2.11\tRef\t\t\n Non-Caucasian\t1274\t4150\t136\t3.28\t1.53 (1.15–2.03)\t1.33 (0.97–1.84)\t\nHIV acquisition risk\t\t\t\t\t\t\t\n MSM\t1398\t4774\t118\t2.47\tRef\t\t\n Non-MSM\t830\t2664\t82\t3.08\t1.23 (0.93–1.63)\t1.12 (0.79–1.57)\t\nCD4 count, cells/μL\t\t\t\t\t\t\t\n ≥500\t668\t2095\t31\t1.48\tRef\t\t\n 300–500\t755\t2686\t63\t2.35\t1.64 (1.06–2.52)\t1.35 (0.85–2.14)\t\n <300\t838\t2789\t114\t4.09\t2.81 (1.89–4.19)\t2.08 (1.32–3.27)\t\nVL, log copies/mL\t\t\t\t\t\t\t\n <4.0\t501\t1834\t24\t1.31\tRef\t\t\n 4.0–5.0\t1086\t3725\t101\t2.71\t2.05 (1.31–3.20)\t2.10 (1.28–3.44)\t\n ≥5.0\t682\t2041\t83\t4.07\t2.98 (1.89–4.70)\t2.95 (1.74–5.0)\t\nTDR\t\t\t\t\t\t\t\n No\t1995\t6734\t186\t2.76\tRef\t\t\n Yes\t320\t987\t28\t2.84\t0.99 (0.67–1.49)\t0.97 (0.60–1.55)\t\nCompanion drug\t\t\t\t\t\t\t\n Efavirenz\t588\t2570\t69\t2.68\tRef\t\t\n Elvitegravir/c\t580\t1603\t35\t2.18\t0.72 (0.47–1.07)\t0.65 (0.41–1.03)\t\n Dolutegravir\t355\t756\t22\t2.91\t0.87 (0.53–1.41)\t0.90 (0.54–1.52)\t\n b-darunavir\t213\t739\t28\t3.79\t1.33 (0.85–2.06)\t1.06 (0.65–1.71)\t\n Rilpivirine\t222\t836\t17\t2.03\t0.72 (0.43–1.23)\t0.95 (0.53–1.69)\t\n Raltegravir\t202\t774\t16\t2.07\t0.75 (0.44–1.29)\t0.87 (0.49–1.54)\t\n b-atazanavir\t66\t176\t15\t8.52\t2.83 (1.61–4.96)\t2.37 (1.26–4.47)\t\n Lopinavir/r\t15\t31\t3\t9.68\t3.23 (1.01–10.3)\t3.08 (0.72–13.3)\t\n Nevirapine\t13\t34\t2\t5.88\t2.02 (0.50–8.26)\t3.02 (0.73–12.5)\t\n Etravirine\t6\t28\t2\t7.14\t2.68 (0.66–10.9)\t1.43 (0.20–10.4)\t\nVariables associated with a significantly increased or decreased risk of virological failure per 100 person-years are indicated in boldface type.\n\nAbbreviations: HR, hazard ratio; MSM, men who have sex with men; PWH, people with HIV; TDR, transmitted drug resistance; VL, virus load (plasma HIV-1 RNA log copies/mL).\n\naUnadjusted HRs derived from univariate Cox regression analysis.\n\nbAdjusted HRs derived from multivariable Cox regression.\n\ncFor the variables age, gender, TDR, and companion drug, there were no missing values. For the remaining 4 variables, baseline CD4 cell counts, baseline virus load, race/ethnicity, and HIV acquisition risk factor, the missing values varied between 1.5% and 4.1%. Thus, the multivariable Cox regression model was based on 89.5% (n = 2072) of the cohort.\n\nTable 3 shows the results of univariable and multivariable regression analyses of potential factors associated with the incidence of HIVDR. In multivariable analysis, lower baseline CD4 counts and higher baseline VLs were associated with an increased risk of HIVDR. Compared with efavirenz, b-darunavir, dolutegravir, and raltegravir were associated with a decreased risk of HIVDR, while nevirapine was associated with an increased risk of HIVDR.\n\nTable 3. Association of Demographics, HIV Risk Factors, Baseline Laboratory Results, and Companion ARV With the Incidence of Virologic Failure Plus HIVDR Over 100 Person-Years\n\nVariable\tNo. of PWH\tPerson-Years\tNo. of VF\tNo. of VF/100 Person-Years\tUnadjusted HRa (95% CI)\tAdjusted HRb,c (95% CI)\t\nAge\t\t\t\t\t\t\t\n 10-y decrement\t\t\t\t\t1.03 (1–1.05)\t1.1 (1.08–1.13)\t\nGender\t\t\t\t\t\t\t\n M\t1931\t6793\t56\t0.82\tRef\t\t\n F\t192\t648\t6\t0.93\t1.12 (0.48–2.59)\t1.19 (0.39–3.6)\t\nRace/ethnicity\t\t\t\t\t\t\t\n Caucasian\t896\t3258\t19\t0.58\tRef\t\t\n Non-Caucasian\t1154\t3981\t41\t1.03\t1.77 (1.03–3.05)\t1.73 (0.94–3.16)\t\nHIV acquisition risk\t\t\t\t\t\t\t\n MSM\t1287\t4609\t36\t0.78\tRef\t\t\n Non-MSM\t761\t2565\t22\t0.86\t1.09 (0.64–1.86)\t0.87 (0.45–1.65)\t\nCD4 count, cells/μL\t\t\t\t\t\t\t\n ≥500\t632\t2048\t4\t0.20\tRef\t\t\n 300–500\t686\t2572\t10\t0.39\t2.00 (0.63–6.38)\t1.33 (0.407–4.37)\t\n <300\t757\t2673\t48\t1.80\t9.18 (3.31–25.5)\t5.4 (1.85–15.8)\t\nVL, log copies/mL\t\t\t\t\t\t\t\n <4.0\t475\t1793\t3\t0.17\tRef\t\t\n 4.0–5.0\t993\t3569\t25\t0.70\t4.24 (1.28–14.0)\t5.24 (1.22–22.5)\t\n ≥5.0\t612\t1961\t31\t1.58\t9.51 (2.90–31.1)\t8.68 (1.98–38)\t\nTDR\t\t\t\t\t\t\t\n No\t1834\t6494\t56\t0.86\tRef\t\t\n Yes\t289\t948\t6\t0.63\t0.73 (0.31–1.69)\t1.63 (0.616–4.29)\t\nCompanion drug\t\t\t\t\t\t\t\n Efavirenz\t541\t2480\t32\t1.29\tRef\t\t\n Elvitegravir/c\t539\t1565\t12\t0.77\t0.56 (0.28–1.10)\t0.65 (0.31–1.37)\t\n Dolutegravir\t328\t728\t1\t0.14\t0.09 (0.01–0.70)\t0.10 (0.01–0.79)\t\n b-darunavir\t186\t691\t3\t0.43\t0.33 (0.09–1.06)\t0.08 (0.01–0.59)\t\n Rilpivirine\t210\t818\t6\t0.73\t0.57 (0.24–1.38)\t0.96 (0.36–2.56)\t\n Raltegravir\t185\t754\t2\t0.27\t0.20 (0.05–0.84)\t0.11 (0.01–0.80)\t\n b-atazanavir\t53\t155\t2\t1.29\t0.96 (0.23–4.02)\t0.79 (0.18–3.41)\t\n Lopinavir/r\t12\t25\t0\t0.00\t7.61e-08 (0–inf)\t1e-07 (0–inf)\t\n Nevirapine\t13\t34\t2\t5.88\t4.40 (1.05–18.5)\t6.98 (1.58–30.9)\t\n Etravirine\t6\t28\t2\t7.14\t5.64 (1.35–23.7)\t3.83 (0.49–30.1)\t\nVariables associated with a significantly increased or decreased risk of virological failure plus HIVDR per 100 person-years are indicated in boldface type.\n\nAbbreviations: HR, hazard ratio; MSM, men who have sex with men; PWH, people with HIV; TDR, transmitted drug resistance; VL, virus load (plasma HIV-1 RNA log copies/mL).\n\naUnadjusted HRs derived from univariate Cox regression analysis.\n\nbAdjusted HRs derived from multivariable Cox regression analysis.\n\ncFor the variables age, gender, TDR, and companion drug, there were no missing values. For the remaining 4 variables, baseline CD4 cell counts, baseline virus load, race/ethnicity, and HIV acquisition risk factor, the missing values varied between 1.5% and 4.1%. Thus, the multivariable Cox regression model was based on 89.5% (n = 2072) of the cohort.\n\nIn a multivariable regression analysis including the year of ART initiation and all other covariates except for ART companion drug, the incidence of VF was not associated with calendar year (adjusted HR, 1.03; 95% CI, 0.95–1.12; P = .46). In this analysis, lower baseline CD4 cell counts, higher VL, and younger age remained associated with an increased incidence of VF. The ART companion drug variable was excluded from this analysis because it displayed high levels of collinearity with the year of ART initiation.\n\nAcquired Drug Resistance Mutations\n\nTable 4 summarizes the drug resistance mutations associated with the companion ARV received at the time of acquired HIVDR. Of the 62 PWH with HIVDR, 42 received an NNRTI-containing regimen, 15 an INSTI-containing regimen, and 5 a PI-containing regimen.\n\nTable 4. Drug Resistance Mutations in 62 People With HIV With Drug Resistance During First-line ART According to the Companion ARV at the Time of VF\n\n\tNo. PWH (All)\tPretherapy CD4, Mediana\tPretherapy VL, Mediana\tNRTI\t\t\t\tNNRTI\tINSTI\tPI\t\n\t\t\t\tAny\tM184I/V\tK65R\tK70E/Q\tAny\tAny\tAny\t\nNNRTI\t\t\t\t\t\t\t\t\t\t\t\n Efavirenz\t32\t93\t4.9\t18\t16\t3\t4\t31\t-\t-\t\n Rilpivirine\t6\t155\t5.0\t6\t5\t1\t2\t5\t-\t-\t\n Nevirapine\t2\t126\t5.2\t1\t1\t1\t-\t2\t-\t-\t\n Etravirine\t2\t238\t4.9\t2\t2\t-\t1\t1\t-\t-\t\nINSTI\t\t\t\t\t\t\t\t\t\t\t\n Elvitegravir/c\t12\t114\t5.0\t11\t11\t4\t0\t-\t10\t-\t\n Raltegravir\t2\t360\t4.5\t1\t1\t-\t-\t-\t1\t-\t\n Dolutegravir\t1\t25\t4.7\t1\t1\t-\t-\t-\t-\t-\t\nPI\t\t\t\t\t\t\t\t\t\t\t\n b-darunavir\t3\t214\t5.3\t3\t3\t-\t-\t-\t-\t0\t\n b-atazanavir\t2\t58\t4.9\t2\t2\t-\t-\t-\t-\t0\t\nAbbreviations: ART, antiretroviral therapy; ARV, antiretroviral; INSTI, integrase-strand transfer inhibitor; NNRTI, non-nucleoside RT inhibitor; NRTI, nucleoside RT inhibitor; PI, protease inhibitor; PWH, people with HIV; VL, virus load.\n\naThe median pretherapy CD4 and VL in those with VF and drug resistance.\n\nAmong the 42 PWH with HIVDR while receiving an NNRTI-containing regimen, NNRTI resistance mutations emerged in 39 (93%), including 31 receiving efavirenz, 5 receiving rilpivirine, 2 receiving nevirapine, and 1 receiving etravirine. Acquired NNRTI resistance mutations included K103N (n = 24), L100I (n = 5), G190A/S (n = 5), K101E (n = 5), Y181C (n = 4), and Y188L/H (n = 3) for those receiving efavirenz or nevirapine; E138K (n = 3), L100I (n = 2), and Y181C (n = 1) for those receiving rilpivirine; and K101E+Y181C for the 1 PWH receiving etravirine. Acquired NRTI resistance mutations included M184V/I in 24 (57%) and K65R or K70E in 10 (24%) PWH.\n\nAmong the 15 PWH with HIVDR while receiving an INSTI-containing regimen, INSTI resistance mutations emerged in 10 receiving elvitegravir/c and 1 receiving raltegravir. Acquired INSTI resistance mutations included E92Q (n = 6), T66I (n = 4), N155H (n = 2), E92G (n = 1), S147G (n = 1), Q148R (n = 1), F121Y (n = 1), and N155T (n = 1). M184V/I developed in 13 of 15 PWH, including 1 PWH receiving dolutegravir. K65R developed in 4 PWH receiving elvitegravir/c.\n\nAmong the 5 PWH with HIVDR while receiving a boosted PI-containing regimen, the NRTI resistance mutation M184V was the only acquired drug resistance mutation.\n\nSupplementary Table 1 lists the drug resistance mutations emerging in the 62 PWH with HIVDR. It also shows that 6 of these PWH had TDR (ie, pretherapy drug resistance mutations) and that each of the pretherapy mutations was also present at VF.\n\nMortality\n\nOverall, 48 PWH (2.1% of the cohort) died, including 7 not attaining virologic suppression and 41 not experiencing VF. The 7 PWH not experiencing virologic suppression died a median of 2 months following ART initiation. They were characterized by low CD4 counts (median [IQR], 36 [26–338]) and older age (median [IQR], 52 [44–62] years).\n\nThe 41 PWH without VF who died had lower CD4 counts (median [IQR], 273 [158–426]) and were older (median [IQR], 51 [41–58] years) than the remainder of the cohort. Although their causes of death were not known, only 7 had a CD4 count <200 at their last measurement. There were no apparent differences in the ART regimens of those who died compared with the complete cohort.\n\nDiscussion\n\nThis is one of the largest studies reporting the incidence of VF and HIVDR during first-line ART in a cohort of PWH receiving a contemporary regimen, defined as the regimen that was recommended or considered acceptable for first-line treatment by the US Public Health Service [12]. The study also describes factors associated with VF and HIVDR and the drug resistance mutations developing in PWH with HIVDR.\n\nDuring a median follow-up of 36 months, the incidences of VF and HIVDR were 2.8 and 0.8 per 100 person-years, respectively. In multivariable analyses, younger age, lower baseline CD4 count, and higher baseline VL were associated with an increased risk of VF, while the same variables except for younger age were associated with an increased risk of HIVDR. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with a reduced risk of HIVDR. Of those developing HIVDR while receiving an NNRTI-containing or first-generation INSTI-containing regimen, 62% developed dual class resistance and 33% developed tenofovir resistance. Those developing resistance while receiving dolutegravir or a boosted PI developed just the cytidine analog resistance mutation M184V.\n\nThe finding that VF incidence was ~3.5 higher than that of HIVDR suggests that VF does not necessarily result in HIVDR and that HIVDR may not be the main cause of VF. Indeed, the relatively small proportion of PWH with VF who had HIVDR may reflect the increased use of single-tablet regimens, which are associated with a reduced risk of HIVDR in nonadherent PWH, as missed doses will be less likely to result in a partially suppressive regimen [19]. Additionally, a significant proportion of VF episodes resulted from treatment discontinuation, which is also less likely to result in HIVDR.\n\nThe low incidence of resistance should be qualified by the fact that just 102 (47.7%) of the 214 PWH with VF underwent resistance testing; thus, some proportion of cases of HIVDR may not have been detected. However, of the PWH with VF not undergoing resistance testing, most had discontinued ART or were unavailable for testing because they had low-level viremia or discontinued KPNC shortly after developing VF. Indeed, the absence of resistance testing appeared unexplained for just a small proportion of untested PWH with VF.\n\nSeveral recently published cohort studies described reduced rates of VF and/or HIVDR over time between 1996–2000 and 2011–2015 [3–5, 9]. Our study, which began in 2010, did not demonstrate this trend. This suggests that despite the many improvements in ART efficacy and safety, treatment nonadherence and discontinuation remain a concern. The stable rate of VF and HIVDR throughout the study may reflect the fact that although treatments improved, PWH in the later years were more likely to be younger and non-Caucasian, demographic factors associated with an increased risk of nonadherence [4, 5, 20].\n\nIn the United States, between 2012 and 2016, newly diagnosed HIV among young adults age <30 increased by 6%, whereas newly diagnosed HIV among older adults declined or stabilized [21, 22]. In 2017, PWH under 30 accounted for 41% of new HIV-1 infections. We observed a similar trend, with 40% of those starting ART in 2017 being younger than 30. In 2017, 74% of newly diagnosed PWH in the United States were non-Caucasian. Although the overall proportion of non-Caucasian PWH in our cohort was 59%, it had increased to 70% by the final study year.\n\nOne important aspect of this study is that the population comprised PWHs receiving ART in an integrated health care system, defined as a network of hospitals, physicians, and other providers that coordinate care in return for fees covered by self- or employer-funded insurance. The population in our cohort is therefore more socioeconomically similar to the 34% of the US PWH population that has private insurance [23].\n\nOur study has several limitations. First, because it was based solely on an electronic medical research database and not a chart review, we do not know the basis for VF or the decision of whether to do genotypic resistance testing in persons with VF. The PWH who discontinued therapy may have had intolerance, side effects, or been nonadherent for other reasons. Second, because it was based on clinical practice and not a prospectively followed cohort, the frequency of clinic visits and laboratory monitoring varied within the cohort. As in any multivariate analysis, residual confounding cannot be excluded, particularly with respect to ART, as PWH baseline characteristics often influence therapy and the perceived risk of VF [24]. Finally, 21% of the population was censored as a result of loss to follow-up; however, this occurs commonly in the United States as persons often leave a health care system as a result of moving, changing employment, or no longer being able to afford private insurance.\n\nIn conclusion, despite the frequent use of modern regimens, including an increasing number of single-tablet regimens, the proportion of PWH starting ART who experience VF or HIVDR is low but perhaps not decreasing. Public health efforts should focus on PWH of younger age, non-Caucasian race, or those who present to care late, as evidenced by lower CD4 counts and higher VLs. Further efforts to facilitate long-term treatment virological response rates will prevent the consequences of ongoing virus replication, including those associated with chronic inflammation, virus transmission, and the development of drug resistance.\n\nSupplementary Data\n\nSupplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.\n\nofaa316_suppl_Supplementary_Table_1 Click here for additional data file.\n\nAcknowledgments\n\nFinancial support. This study was supported by a research grant from Janssen Scientific Affairs. S.Y.R. and R.W.S. were also supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH; award number AI136618). Janssen Scientific Affairs participated in the study design and reviewed drafts of the manuscript.\n\nPotential conflicts of interest. This study was supported by a research grant from Janssen Scientific Affairs, which also participated in the study design and reviewed drafts of the manuscript. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.\n==== Refs\nReferences\n\n1. Carr A , Richardson R , Liu Z Success and failure of initial antiretroviral therapy in adults: an updated systematic review. AIDS 2019; 33 :443–53.30475265\n2. Weijsenfeld AM , Blokhuis C , Stuiver MM , et al Longitudinal virological outcomes and factors associated with virological failure in behaviorally HIV-infected young adults on combination antiretroviral treatment in the Netherlands, 2000 to 2015. Medicine 2019; 98 :e16357.31393344\n3. Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV 2017; 4 :e349–56.28501495\n4. Tanner Z , Lachowsky N , Ding E , et al ; Canadian Observation Cohort (CANOC) Collaboration Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort. BMC Infect Dis 2016; 16 :590.27769246\n5. Nance RM , Delaney JAC , Simoni JM , et al HIV viral suppression trends over time among HIV-infected patients receiving care in the United States, 1997 to 2015: a cohort study. Ann Intern Med 2018; 169 :376–84.30140916\n6. Bontell I , Häggblom A , Bratt G , et al Trends in antiretroviral therapy and prevalence of HIV drug resistance mutations in Sweden 1997–2011. PLoS One 2013; 8 :e59337.23533618\n7. De Luca A , Dunn D , Zazzi M , et al ; SEHERE collaboration in Chain Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe. J Infect Dis 2013; 207 :1216–20.23315324\n8. Davy-Mendez T , Eron JJ , Brunet L , et al. New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations. AIDS 2018; 32 :2593–603.30134298\n9. Scherrer AU , von Wyl V , Yang WL , et al ; Swiss HIV Cohort Study Emergence of acquired HIV-1 drug resistance almost stopped in Switzerland: a 15-year prospective cohort analysis. Clin Infect Dis 2016; 62 :1310–7.26962075\n10. Lodi S , Günthard HF , Dunn D , et al ; HIV-CAUSAL Collaboration Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance. AIDS 2018; 32 :327–35.29135583\n11. Li X , Brown TT , Ho KS , et al Recent trends and effectiveness of antiretroviral regimens among men who have sex with men living with HIV in the United States: the Multicenter AIDS Cohort Study (MACS) 2008–2017. Open Forum Infect Dis 2019; 6 :XXX–XX.\n12. US Public Health Service. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV 2019 Available at: https://aidsinfo.nih.gov/guidelines. Accessed 6 December 2019.\n13. Rhee SY , Clutter D , Fessel WJ , et al. Trends in the molecular epidemiology and genetic mechanisms of transmitted human immunodeficiency virus type 1 drug resistance in a large US clinic population. Clin Infect Dis 2019; 68 :213–21.29846534\n14. Saag MS , Benson CA , Gandhi RT , et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society-USA Panel. JAMA 2018; 320 :379–96.30043070\n15. Bennett DE , Camacho RJ , Otelea D , et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 2009; 4 :e4724.19266092\n16. Paredes R , Tzou PL , van Zyl G , et al. Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation. PLoS One 2017; 12 :e0181357.28753637\n17. Tzou PL , Rhee SY , Descamps D , et al ; WHO HIVResNet Working Groups Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance. J Antimicrob Chemother 2020; 75 :170–82.31617907\n18. Schoenfeld D Partial residuals for the proportional hazards regression model. Biometrika 1982; 69 :239–41.\n19. Gordon LL , Gharibian D , Chong K , Chun H Comparison of HIV virologic failure rates between patients with variable adherence to three antiretroviral regimen types. AIDS Patient Care STDS 2015; 29 :384–8.26114665\n20. Youn B , Shireman TI , Lee Y , et al Trends in medication adherence in HIV patients in the US, 2001 to 2012: an observational cohort study. J Int AIDS Soc 2019; 22 :e25382.31441221\n21. Centers for Disease Control and Prevention. Diagnoses of HIV infection in the United States and dependent areas 2017 Available at: https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2017-vol-29.pdf. Accessed 1 May 2020.\n22. Guilamo-Ramos V , Thimm-Kaiser M , Benzekri A , Futterman D Youth at risk of HIV: the overlooked US HIV prevention crisis. Lancet HIV 2019; 6 :e275–8.30826281\n23. Dawson L , Kates J An update on insurance coverage among people with HIV in the United States 2019 Available at: https://www.kff.org/report-section/an-update-on-insurance-coverage-among-people-with-hiv-in-the-united-states-findings/. Accessed 1 May 2020.\n24. Alejos B , Suárez-García I , Bisbal O , et al ; CoRIS cohort Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors. PLoS One 2019; 14 :e0221598.31449566\n\n",
"fulltext_license": "CC BY-NC-ND",
"issn_linking": "2328-8957",
"issue": "7(9)",
"journal": "Open forum infectious diseases",
"keywords": "HIV-1; antiretroviral therapy; drug resistance; virological outcome",
"medline_ta": "Open Forum Infect Dis",
"mesh_terms": null,
"nlm_unique_id": "101637045",
"other_id": null,
"pages": "ofaa316",
"pmc": null,
"pmid": "32904894",
"pubdate": "2020-09",
"publication_types": "D016428:Journal Article",
"references": "30475265;31393344;29846534;19266092;30140916;31617907;23315324;26962075;31449566;31660409;30826281;30043070;28501495;31441221;30134298;27769246;29135583;23533618;26114665;28753637",
"title": "Virological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens.",
"title_normalized": "virological failure and acquired genotypic resistance associated with contemporary antiretroviral treatment regimens"
}
|
[
{
"companynumb": "US-GLAXOSMITHKLINE-US2020GSK185346",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOLUTEGRAVIR"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOLUTEGRAVIR"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LAMIVUDINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "020564",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMIVUDINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ABACAVIR"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ABACAVIR."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Virologic failure",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Viral mutation identified",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pathogen resistance",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "RHEE S?Y, CLUTTER D, HARE CB, TCHAKOUTE CT, SAINANI K, FESSEL WJ ET AL.. VIROLOGICAL FAILURE AND ACQUIRED GENOTYPIC RESISTANCE ASSOCIATED WITH CONTEMPORARY ANTIRETROVIRAL TREATMENT REGIMENS. OPEN FORUM INFECTIOUS DISEASES. 2020?7(9)",
"literaturereference_normalized": "virological failure and acquired genotypic resistance associated with contemporary antiretroviral treatment regimens",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200923",
"receivedate": "20200923",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 18302074,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
},
{
"companynumb": "US-VIIV HEALTHCARE LIMITED-US2020GSK185346",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOLUTEGRAVIR"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "204790",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOLUTEGRAVIR"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LAMIVUDINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMIVUDINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ABACAVIR"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ABACAVIR."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Virologic failure",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Viral mutation identified",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pathogen resistance",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "RHEE S?Y, CLUTTER D, HARE CB, TCHAKOUTE CT, SAINANI K, FESSEL WJ ET AL.. VIROLOGICAL FAILURE AND ACQUIRED GENOTYPIC RESISTANCE ASSOCIATED WITH CONTEMPORARY ANTIRETROVIRAL TREATMENT REGIMENS. OPEN FORUM INFECTIOUS DISEASES. 2020?7(9)",
"literaturereference_normalized": "virological failure and acquired genotypic resistance associated with contemporary antiretroviral treatment regimens",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200923",
"receivedate": "20200923",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 18302076,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
},
{
"companynumb": "US-009507513-2012USA009449",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RALTEGRAVIR POTASSIUM"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "022145",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISENTRESS"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Virologic failure",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pathogen resistance",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "RHEE SY, CLUTTER D, HARE CB, TCHAKOUTE CT, SAINANI K, FESSEL WJ, ET AL.. VIROLOGICAL FAILURE AND ACQUIRED GENOTYPIC RESISTANCE ASSOCIATED WITH CONTEMPORARY ANTIRETROVIRAL TREATMENT REGIMENS. OPEN FORUM INFECTIOUS DISEASES. 2020?7 (9)",
"literaturereference_normalized": "virological failure and acquired genotypic resistance associated with contemporary antiretroviral treatment regimens",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20201221",
"receivedate": "20201221",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18647066,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "US-009507513-2012USA005785",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RALTEGRAVIR POTASSIUM"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "022145",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISENTRESS"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Virologic failure",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pathogen resistance",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "RHEE SY, CLUTTER D, HARE CB, TCHAKOUTE CT, SAINANI K, FESSEL WJ, ET AL.. VIROLOGICAL FAILURE AND ACQUIRED GENOTYPIC RESISTANCE ASSOCIATED WITH CONTEMPORARY ANTIRETROVIRAL TREATMENT REGIMENS. OPEN FORUM INFECTIOUS DISEASES. 2020?7 (9)",
"literaturereference_normalized": "virological failure and acquired genotypic resistance associated with contemporary antiretroviral treatment regimens",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210201",
"receivedate": "20201221",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18641631,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210419"
}
] |
{
"abstract": "BACKGROUND\nTreatment-resistant bipolar disorder (TRBD) is an increasingly prevalent, debilitating condition with substandard treatment outcomes. Polypharmacy has become the mainstay among practitioners though long-term efficacy of this method has not been adequately tested.\n\n\nOBJECTIVE\nDetermine retrospectively if individualized, integrative treatment strategies applied while withdrawing pharmaceuticals were beneficial and safe among a TRBD clinic population.\n\n\nMETHODS\nA chart review was performed for six adult patients, treated in a private psychiatric practice. Data were collected regarding psychiatric diagnosis, hospitalizations, medications, side effects, substance abuse, and applied treatments.\n\n\nRESULTS\nUsing individualized, integrative psychiatric treatment methods, the majority of medications were eliminated. Long-term remission was attained in all cases, defined as clinical stability with no discernable symptoms of bipolar disorder for at least one year.\n\n\nCONCLUSIONS\nApplying an integrative treatment approach, and eliminating most medications, provided lasting resolution of symptoms and side effects in a selected sample of TRBD outpatients. These data may provide the basis for future randomized, controlled trials.",
"affiliations": "997 Glen Cove Avenue, Glen Head, NY 11545. Electronic address: [email protected].;Helfgott Research Institute, National College of Natural Medicine, 2220 SW 1st Avenue, Portland, OR 97201.",
"authors": "Gurevich|Michael I|MI|;Robinson|Cassandra L|CL|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1550-8307",
"issue": "12(4)",
"journal": "Explore (New York, N.Y.)",
"keywords": "bipolar disorder; holistic medicine; integrative medicine",
"medline_ta": "Explore (NY)",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder; D000529:Complementary Therapies; D005260:Female; D006694:Holistic Health; D006801:Humans; D055048:Integrative Medicine; D008297:Male; D055815:Young Adult",
"nlm_unique_id": "101233160",
"other_id": null,
"pages": "237-45",
"pmc": null,
"pmid": "27179557",
"pubdate": "2016",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "An Individualized Approach to Treatment-Resistant Bipolar Disorder: A Case Series.",
"title_normalized": "an individualized approach to treatment resistant bipolar disorder a case series"
}
|
[
{
"companynumb": "US-MYLANLABS-2017M1011719",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LAMOTRIGINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMOTRIGINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LOXAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LOXAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OXCARBAZEPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OXCARBAZEPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TOPIRAMATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TOPIRAMATE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LORAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LORAZEPAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HALOPERIDOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HALOPERIDOL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CITALOPRAM HYDROBROMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CITALOPRAM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DOXEPIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXEPINE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLOZAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "075417",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOZAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OLANZAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OLANZAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "NEFAZODONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NEFAZODONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DIAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAZEPAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TRIAZOLAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIAZOLAM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ALPRAZOLAM"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALPRAZOLAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "RISPERIDONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RISPERIDONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PAROXETINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PAROXETINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CARBAMAZEPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBAMAZEPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLONAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLONAZEPAM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PHENOBARBITAL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PHENOBARBITAL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "QUETIAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "QUETIAPINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BUPROPION"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPROPION."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DULOXETINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DULOXETINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BENZTROPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENZTROPINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DIVALPROEX SODIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIVALPROEX"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CHLORAL HYDRATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CHLORAL HYDRATE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ARIPIPRAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ARIPIPRAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ZIPRASIDONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZIPRASIDONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TRIHEXYPHENIDYL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIHEXYPHENIDYL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LITHIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LITHIUM."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TRAZODONE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAZODONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TEMAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TEMAZEPAM."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Treatment noncompliance",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Suicide attempt",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Depression",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Bipolar disorder",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "GUREVICH MI, ROBINSON CL.. AN INDIVIDUALIZED APPROACH TO TREATMENT-RESISTANT BIPOLAR DISORDER: A CASE SERIES.. EXPLORE: THE JOURNAL OF SCIENCE AND HEALING.. 2016;12(4):237-45",
"literaturereference_normalized": "an individualized approach to treatment resistant bipolar disorder a case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170223",
"receivedate": "20170223",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13265694,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "US-GLAXOSMITHKLINE-US2017GSK014787",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLOZAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOZAPINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LORAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LORAZEPAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ESCITALOPRAM OXALATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ESCITALOPRAM"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXEPIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXEPINE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "QUETIAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "QUETIAPINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ARIPIPRAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ARIPIPRAZOLE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DIAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIAZEPAM."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ALPRAZOLAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALPRAZOLAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "HALOPERIDOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HALOPERIDOL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DULOXETINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DULOXETINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CARBAMAZEPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBAMAZEPINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LOXAPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LOXAPINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CITALOPRAM HYDROBROMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CITALOPRAM"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PAROXETINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PAROXETINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TEMAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TEMAZEPAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TRIAZOLAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIAZOLAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TOPIRAMATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TOPIRAMATE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLONAZEPAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLONAZEPAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "BUPROPION"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BUPROPION."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ZIPRASIDONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ZIPRASIDONE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CHLORPROMAZINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CHLORPROMAZINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "NEFAZODONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NEFAZODONE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "VENLAFAXINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VENLAFAXINE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TRAZODONE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRAZODONE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TRIHEXYPHENIDYL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIHEXYPHENIDYL"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CHLORAL HYDRATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CHLORAL HYDRATE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LITHIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LITHIUM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "BENZTROPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BENZTROPINE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DIVALPROEX SODIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIVALPROEX"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "RISPERIDONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RISPERIDONE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LAMOTRIGINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "020241",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMOTRIGINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "OXCARBAZEPINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OXCARBAZEPINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PHENOBARBITAL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PHENOBARBITAL."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug resistance",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypomania",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Suicide attempt",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapy cessation",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Depression",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "GUREVICH MI, ROBINSON CL. AN INDIVIDUALIZED APPROACH TO TREATMENT-RESISTANT BIPOLAR DISORDER: A CASE SERIES. EXPLORE. 2016;12(4):237-245",
"literaturereference_normalized": "an individualized approach to treatment resistant bipolar disorder a case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170206",
"receivedate": "20170206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13190574,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "PHHY2017US023723",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ASCORBIC ACID"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHELATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VITAMIIN C"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBAMAZEPINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBAMAZEPINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HALOPERIDOL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HALOPERIDOL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": ".ALPHA.-LIPOIC ACID"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHELATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALPHA LIPOIC ACID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OXCARBAZEPINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021014",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OXCARBAZEPINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "GARLIC"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHELATION THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GARLIC."
}
],
"patientagegroup": null,
"patientonsetage": "42",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Withdrawal syndrome",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "GUREVICH MI, ROBINSON CL. AN INDIVIDUALIZED APPROACH TO TREATMENT-RESISTANT BIPOLAR DISORDER: A CASE SERIES.. EXPLORE: THE JOURNAL OF SCIENCE AND HEALING. 2016;12(4):237-45",
"literaturereference_normalized": "an individualized approach to treatment resistant bipolar disorder a case series",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170221",
"receivedate": "20170221",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13255536,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
}
] |
{
"abstract": "OBJECTIVE\nPreclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC).\n\n\nMETHODS\nPatients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease.\n\n\nRESULTS\nForty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months.\n\n\nCONCLUSIONS\nCombination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).",
"affiliations": "Breast Cancer Medicine Service, Departments of Radiology, Biostatistics, and Renal Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.",
"authors": "Traina|Tiffany A|TA|;Rugo|Hope S|HS|;Caravelli|James F|JF|;Patil|Sujata|S|;Yeh|Benjamin|B|;Melisko|Michele E|ME|;Park|John W|JW|;Geneus|Stephanie|S|;Paulson|Matthew|M|;Grothusen|Jill|J|;Seidman|Andrew D|AD|;Fornier|Monica|M|;Lake|Diana|D|;Dang|Chau|C|;Robson|Mark|M|;Theodoulou|Maria|M|;Flombaum|Carlos D|CD|;Norton|Larry|L|;Hudis|Clifford A|CA|;Dickler|Maura N|MN|",
"chemical_list": "D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009570:Nitriles; D014230:Triazoles; D000068258:Bevacizumab; D000077289:Letrozole",
"country": "United States",
"delete": false,
"doi": "10.1200/JCO.2009.21.8784",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0732-183X",
"issue": "28(4)",
"journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
"keywords": null,
"medline_ta": "J Clin Oncol",
"mesh_terms": "D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D001943:Breast Neoplasms; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008175:Lung Neoplasms; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles; D011379:Prognosis; D012983:Soft Tissue Neoplasms; D015996:Survival Rate; D016896:Treatment Outcome; D014230:Triazoles",
"nlm_unique_id": "8309333",
"other_id": null,
"pages": "628-33",
"pmc": null,
"pmid": "19841327",
"pubdate": "2010-02-01",
"publication_types": "D016428:Journal Article; D016448:Multicenter Study; D013485:Research Support, Non-U.S. Gov't",
"references": "18711196;18695137;11454883;2702835;17261421;10735889;11145928;9724788;14613032;12778165;14602804;17998546;17404074;14601081;15681523;12196720;10376603;18690886;8702220;15894097;12090977;18695259;15774498;18337603;14551341;15014181;18160686;15701879;12775735;18824714;10655437;11078488;8940388;17200148;7530174",
"title": "Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.",
"title_normalized": "feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer"
}
|
[
{
"companynumb": "US-MYLANLABS-2017M1011492",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "BEVACIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MG/KG EVERY 3 WEEKS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BREAST CANCER METASTATIC",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BEVACIZUMAB"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LETROZOLE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "078190",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "2.5MG DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BREAST CANCER METASTATIC",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LETROZOLE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Inappropriate antidiuretic hormone secretion",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hyponatraemia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypertension",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TRAINA TA, RUGO HS, CARAVELLI JF, PATIL S, YEH B, MELISKO ME, ET AL. FEASIBILITY TRIAL OF LETROZOLE IN COMBINATION WITH BEVACIZUMAB IN PATIENTS WITH METASTATIC BREAST CANCER. J-CLIN-ONCOL 2010;28(4):628-33.",
"literaturereference_normalized": "feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170227",
"receivedate": "20170227",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 13274426,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
}
] |
{
"abstract": "Auditory neuropathy spectrum disorder (ANSD) can cause significant hearing impairment; it occurs when there is intact outer hair cell function in the inner ear, with a dyssynchronous neural response, thought to be due to dysfunction of the inner hair cells (IHCs), the synapse of the IHCs and the auditory nerve, or of the auditory nerve itself. This case report describes the onset of ANSD in a Malawian child after severe malaria treated with quinine. Diagnosis of ANSD was made by confirming the presence of otoacoustic emissions, together with the absence of auditory brainstem response and absent acoustic reflexes.",
"affiliations": "Clinical Scientist (Audiology), African Bible College Hearing Clinic and Training Centre, Lilongwe, Malawi.",
"authors": "Brough|Helen|H|https://orcid.org/0000-0002-4432-1207",
"chemical_list": "D011803:Quinine",
"country": "England",
"delete": false,
"doi": "10.1177/0049475520917236",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0049-4755",
"issue": "50(3)",
"journal": "Tropical doctor",
"keywords": "Auditory neuropathy spectrum disorder; hearing loss; malaria",
"medline_ta": "Trop Doct",
"mesh_terms": "D000293:Adolescent; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006313:Hearing Loss, Central; D006801:Humans; D008288:Malaria; D017084:Otoacoustic Emissions, Spontaneous; D000081015:Ototoxicity; D011803:Quinine",
"nlm_unique_id": "1301706",
"other_id": null,
"pages": "246-248",
"pmc": null,
"pmid": "32290759",
"pubdate": "2020-07",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Acquired auditory neuropathy spectrum disorder after malaria treated with quinine.",
"title_normalized": "acquired auditory neuropathy spectrum disorder after malaria treated with quinine"
}
|
[
{
"companynumb": "MW-SUN PHARMACEUTICAL INDUSTRIES LTD-2020R1-245593",
"fulfillexpeditecriteria": "1",
"occurcountry": "MW",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "QUININE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "021799",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MALARIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "QUININE"
}
],
"patientagegroup": "3",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Auditory neuropathy spectrum disorder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BROUGH H. ACQUIRED AUDITORY NEUROPATHY SPECTRUM DISORDER AFTER MALARIA TREATED WITH QUININE. TROP DOCT. 2020?50(3):246?248",
"literaturereference_normalized": "acquired auditory neuropathy spectrum disorder after malaria treated with quinine",
"qualification": "3",
"reportercountry": "MW"
},
"primarysourcecountry": "MW",
"receiptdate": "20200908",
"receivedate": "20200501",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17731652,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201102"
}
] |
{
"abstract": "Central nervous system (CNS) involvement of scrub typhus infection is well known. Most CNS involvement of scrub typhus infection present as meningitis or encephalitis. We report on a patient suffering from hemorrhagic transformation of intracranial lesions caused by Orientia tsutsugamushi. A 53-year-old female farmer who was infected by scrub typhus was treated with doxycycline and recovered from the systemic illness. However, headache persisted. Brain radiologic studies revealed acute intracranial hemorrhage and enhancing lesion, which implied a CNS involvement. Hemorrhagic transformation of encephalitis by scrub typhus is very rare complication and to our best knowledge, this is the first report of hemorrhagic transformation of scrub typhus encephalitis. Clinician should consider the possibility of hemorrhagic transformation of encephalitis in cases of scrub typhus infection.",
"affiliations": "Department of Neurosurgery, Dankook University College of Medicine, 201 Manghyang-ro Dongnam-gu, 330-715, Cheonan, Chungnam, Republic of Korea.;Department of Neurosurgery, Dankook University College of Medicine, 201 Manghyang-ro Dongnam-gu, 330-715, Cheonan, Chungnam, Republic of Korea.;Department of Neurosurgery, Dankook University College of Medicine, 201 Manghyang-ro Dongnam-gu, 330-715, Cheonan, Chungnam, Republic of Korea.;Department of Neurosurgery, Dankook University College of Medicine, 201 Manghyang-ro Dongnam-gu, 330-715, Cheonan, Chungnam, Republic of Korea. [email protected].",
"authors": "Kim|H-C|HC|;Yoon|K-W|KW|;Yoo|D-S|DS|;Cho|C-S|CS|",
"chemical_list": null,
"country": "Germany",
"delete": false,
"doi": "10.1007/s00062-014-0348-9",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1869-1439",
"issue": "25(4)",
"journal": "Clinical neuroradiology",
"keywords": null,
"medline_ta": "Clin Neuroradiol",
"mesh_terms": "D002543:Cerebral Hemorrhage; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D000069544:Infectious Encephalitis; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D035583:Rare Diseases; D012612:Scrub Typhus; D014057:Tomography, X-Ray Computed",
"nlm_unique_id": "101526693",
"other_id": null,
"pages": "415-8",
"pmc": null,
"pmid": "25373351",
"pubdate": "2015-12",
"publication_types": "D002363:Case Reports; D016422:Letter; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Hemorrhagic Transformation of Scrub Typhus Encephalitis: A Rare Entity.",
"title_normalized": "hemorrhagic transformation of scrub typhus encephalitis a rare entity"
}
|
[
{
"companynumb": "KR-PFIZER INC-2016456451",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "050533",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "FILM-COATED TABLET",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPHUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "53",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Treatment failure",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KIM, H.. HEMORRHAGIC TRANSFORMATION OF SCRUB TYPHUS ENCEPHALITIS: A RARE ENTITY.. CLINICAL NEURORADIOLOGY. 2015;25 (4):415-418",
"literaturereference_normalized": "hemorrhagic transformation of scrub typhus encephalitis a rare entity",
"qualification": "1",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20160930",
"receivedate": "20160930",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12799353,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20161109"
}
] |
{
"abstract": "In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery.",
"affiliations": null,
"authors": "Laiton-Donato|Katherine|K|;Ávila-Robayo|Paola|P|;Páez-Martinez|Andrés|A|;Benjumea-Nieto|Paula|P|;Usme-Ciro|José A|JA|;Pinzón-Nariño|Nicole|N|;Giraldo|Ivan|I|;Torres-Castellanos|Diego|D|;Nakazawa|Yoshinori|Y|;Patel|Nishi|N|;Wilkins|Kimberly|K|;Li|Yu|Y|;Davidson|Whitni|W|;Burgado|Jillybeth|J|;Satheshkumar|Panayampalli Subbian|PS|;Styczynski|Ashley|A|;Mauldin|Matthew R|MR|;Gracia-Romero|Martha|M|;Petersen|Brett W|BW|",
"chemical_list": "D000998:Antiviral Agents",
"country": "United States",
"delete": false,
"doi": "10.3201/eid2603.191365",
"fulltext": "\n==== Front\nEmerg Infect Dis\nEmerging Infect. Dis\nEID\nEmerging Infectious Diseases\n1080-6040\n1080-6059\nCenters for Disease Control and Prevention\n\n32091366\n19-1365\n10.3201/eid2603.191365\nDispatch\nDispatch\nProgressive Vaccinia Acquired through Zoonotic Transmission in a Patient with HIV/AIDS, Colombia\nProgressive Vaccinia Acquired through Zoonotic Transmission in a Patient with HIV/AIDS, Colombia\nProgressive Vaccinia in a Patient with HIV/AIDS\nLaiton-Donato Katherine 1\nÁvila-Robayo Paola 1\nPáez-Martinez Andrés\nBenjumea-Nieto Paula\nUsme-Ciro José A.\nPinzón-Nariño Nicole\nGiraldo Ivan\nTorres-Castellanos Diego\nNakazawa Yoshinori\nPatel Nishi\nWilkins Kimberly\nLi Yu\nDavidson Whitni\nBurgado Jillybeth\nSatheshkumar Panayampalli Subbian\nStyczynski Ashley\nMauldin Matthew R.\nGracia-Romero Martha\nPetersen Brett W.\nInstituto Nacional de Salud, Bogotá, Colombia (K. Laiton-Donato, J.A. Usme-Ciro, M. Gracia-Romero);\nHospital Universitario Mayor Méderi-Universidad del Rosario, Bogotá (P. Ávila-Robayo, P. Benjumea-Nieto, N. Pinzón-Nariño, I. Giraldo, D. Torres-Castellanos);\nUniversidad de La Salle, Bogotá (A. Páez-Martínez);\nUniversidad Cooperativa de Colombia, Santa Marta, Colombia (J.A. Usme-Ciro);\nCenters for Disease Control and Prevention, Atlanta, Georgia, USA (Y. Nakazawa, N. Patel, K. Wilkins, Y. Li, W. Davidson, J. Burgado, P.S. Satheshkumar, A. Styczynski, M.R. Mauldin, B.W. Petersen)\nAddress for correspondence: Katherine Laiton-Donato, Virology Group, Department of Public Health Network, Instituto Nacional de Salud, Av Calle 26 No 51-20, Bogotá, Colombia; email: [email protected]\n3 2020\n26 3 601605\nIn March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery.\n\nKeywords:\n\nprogressive vaccinia\nHIV/AIDS\nzoonotic vaccinia\nvaccine-preventable diseases\nsmallpox\nOrthopoxvirus\nviruses\nzoonoses\nColombia\nVACV\nvaccinia virus\n==== Body\nVaccinia virus (VACV) belongs to the genus Orthopoxvirus (OPXV) and was the main component of vaccines used during the 1960s and 1970s against smallpox (1). More recently, VACV has caused several zoonotic outbreaks in South America (2,3), where human cases are mainly associated with occupational exposure of farmworkers to infected cows. Progressive vaccinia is a severe and often lethal condition caused by infection and uncontrolled replication of VACV in immunocompromised patients (4,5).\n\nThe Study\n\nIn November 2014, a 30-year-old man with HIV/AIDS living and working at a rural dairy cattle farm in the department of Cundinamarca, Colombia, with no prior hospitalizations for opportunistic infections sought treatment for a suppurative ulcer with initial sharply raised defined edges on his right hand (Figure 1, panel A), right ear, and distal left leg that appeared 1 week after he had milked cows with similar lesions on their udders. He had recently interrupted antiretroviral therapy after onset of depression because of his father’s death 4 months before. Despite treatment with self-formulated antimicrobial drugs and home therapies (application of alcohol, methylene blue, and herbs), the lesions continued and spread within 1 month to his nostrils, glans penis, right leg, right knee, and ankles. On November 14, 2014, the patient was treated with antimicrobial drugs at a local hospital and instructed to comply with his antiretroviral therapy. On December 9, 2014, after failing to respond to treatment, the patient was referred to the Hospital Universitario Mayor Méderi in Bogotá, Colombia. Laboratory tests showed a CD4 cell count of 11 cells/mL and HIV viral load of 44,201 copies/mL. The patient was treated with acyclovir after suspected initial diagnosis of alphaherpesvirus infection and was discharged on December 23, 2014, with antimicrobial therapy prophylaxis for opportunistic infections (trimethoprim/sulfamethoxazole) and persuaded to continue his previous antiretroviral therapy (lamivudine/zidovudine and efavirenz).\n\nFigure 1 Clinical progression of vaccinia virus infection in a patient with HIV/AIDS, Colombia. A) On December 9, 2014, the patient was referred to the Hospital Universitario Mayor Méderi because of a suppurative ulcer with sharply raised, defined edges on his right hand. B, C) In March 2015, lesions increased in size and disseminated over his face and extremities. D) In July 2015, most lesions completely healed, with mild scarring and depigmentation.\n\nThe patient was readmitted to the hospital on March 24, 2015, because of a deteriorating clinical condition that included deep, severe, and extended foul-smelling ulcers with raised and undefined edges throughout his face and extremities (Figure 1, panels B and C), as well as fever, tachycardia, hearing and vision impairment, anemia, and leukopenia. He received a blood transfusion, prophylactic antimicrobial drugs against opportunistic infections, analgesics, and supportive care. The case was suggestive of poxvirus infection because the patient had not received smallpox vaccination, the pathologic study showed the presence of cytoplasmic B-type inclusion bodies, and the patient reported previous contact with cattle with vesicular lesions in their udders. Therefore, biological samples were remitted to the Instituto Nacional de Salud for viral diagnostics, and, subsequently, to the US Centers for Disease Control and Prevention for confirmation of VACV diagnosis and further characterization.\n\nOn March 30, 2015, HIV resistance to antiretroviral drugs was confirmed, and the pharmacologic therapy was changed to raltegravir and darunavir/ritonavir. Within 2 weeks, the lesions had healed considerably, and the patient was discharged from the hospital on April 20. Follow-up visits revealed complete healing of the lesions, mild scarring, and depigmentation (Figure 1, panel D), with the exception of a persistent ulcer on the patient’s left leg. This lesion did not respond to initial antimicrobial treatment or a 2-week course of topical imiquimod.\n\nExperimental assays included ELISA and neutralization tests for OPXV IgM and IgG detection, virus isolation in BSC-40 cells, and molecular detection through OPXV-generic and VACV-specific real-time PCR (Appendix). OPXV IgM and IgG antibodies were detected in serum in March 2015 (5 months after illness onset). IgG but not IgM was in serum in July 2015 (9 months after illness onset). Viral neutralization assays had 50% effective concentration values of 1:517 for the March sample and 1:223 for the July sample (Table). VACV persisted in lesions despite the presence of OPXV IgM and IgG, suggesting that humoral immunity alone might be insufficient to clear infection, as demonstrated previously (6). Recovery occurred only after improving adherence and optimizing antiretroviral therapy on the basis of antiretroviral-resistance testing. This finding suggests that cell-mediated immunity is required for complete VACV clearance and that reversing any underlying immunosuppressive condition should be pursued whenever possible for recovery from progressive vaccinia (7) (Appendix Figure).\n\nTable Laboratory testing for orthopoxvirus diagnosis in an HIV/AIDS patient who acquired progressive vaccinia through zoonotic transmission, Colombia*\n\nSample date and type\tSerology\t\tPCR\tViral culture\t\nIgM ELISA\tIgG ELISA\tNeutralization\ntiter\tOPXV-specific (Ct)\tVaccinia-specific\t\n2015 Mar\t\t\nSerum\tPos\tPos\t1:517\t\t\t\t\t\nScab\t\t\t\t\tPos (31.9)\tPos\tPos\t\nScab\t\t\t\t\tPos (28.6)\tPos\tPos\t\n2015 Jul\t\t\nSerum\tNeg\tPos\t1:223\t\t\t\t\t\nScab, left leg\t\t\t\t\tPos (36.2)\tPos\tPos†\t\nSwab, left leg\t\t\t\t\tPos (29.2)\tPos\tPos†\t\n2016 Apr\t\t\nParaffin block, left leg\t\t\t\t\tNeg\t\t\t\nParaffin block, left leg\t\t\t\t\tNeg\t\t\t\nParaffin block, left leg\t\t\t\t\tNeg\t\t\t\n*Ct, cycle threshold; Neg, negative; Pos, positive.\n†Slow-growing.\n\nMolecular tests performed on serum and scab samples were positive for OPXV and VACV in March 2015 and remained positive in July 2015 (Table). To better characterize the VACV strain, we used specific primers targeting the A56R hemagglutinin gene (1,134 bp) for amplification and sequencing (3). Phylogenetic analysis (Appendix) confirmed infection with a VACV strain whose A56R gene sequence was closely related to those recently reported in Colombia and grouped as a sister lineage of the VACV group 1 in Brazil (Figure 2).\n\nFigure 2 Phylogenetic inference of Orthopoxvirus genus based on the A56R hemagglutinin gene. Nucleotide sequences of 829 bp representing the different species were aligned and used for Bayesian inference (Appendix). Black diamonds indicate previously reported sequences of VACV in Colombia; red diamond indicates sequence from the strain from the patient in this study (POX0009). GenBank accession numbers are provided for reference sequences. CPXV, cowpox virus; MPXV, monkeypox virus; VACV, vaccinia virus; VARV, variola virus.\n\nA biopsy of the persistent leg lesion collected in April 2016 tested negative for OPXV DNA by real-time PCR (Table) and positive for Pseudomonas aeruginosa and Escherichia coli by classic microbiological assays. The lesion healed after focused antimicrobial treatment.\n\nConclusions\n\nThe clinical case we describe meets all criteria for progressive vaccinia (4): immunodeficiency from HIV infection was documented with a CD4 cell count of <50 cells/mL; multiple lesions developed and failed to heal despite antimicrobial therapy; and VACV infection was confirmed by several laboratory methods. Our results document progressive vaccinia acquired through zoonotic transmission.\n\nBecause smallpox eradication led to the discontinuation of routine smallpox vaccination before the global spread of HIV, little is known about VACV infections in persons with HIV (8,9). Progressive vaccinia is thought to occur only in patients with substantial cell-mediated immunodeficiency (4). This hypothesis is further supported by the observation that VACV infection (through smallpox vaccination) in 10 HIV-infected persons with CD4 cell counts >200 cells/mL did not lead to progressive vaccinia (10). In the case we describe, VACV lesions persisted despite the documentation of VACV neutralizing antibodies. The lesions resolved only after immune reconstitution, indicating that cell-mediated immunity is required for complete viral clearance.\n\nThe persistent leg lesion was unexpected given the resolution of the patient’s other lesions and because latent VACV infection has not been described previously. Although testing of this lesion in July 2015 detected VACV, previous studies have demonstrated that VACV can be isolated from smallpox vaccination site lesions even after the separation of scab when the viral infection is presumably recovered (11). The positive bacterial cultures and absence of evidence of VACV in the lesion biopsy in April 2016 suggest that this lesion was most likely attributable to secondary bacterial infection resulting from the compromised dermal barrier rather than persistence or reactivation of latent VACV infection.\n\nOur findings suggest that, in VACV infection cases, reversing any underlying immunosuppressive condition should be pursued whenever possible because of the potential role of the cellular immune response in clearing the infection. Because of waning global immunity against OPXVs (12), increasing immunosuppressed populations (13), and the potential nosocomial (14) and demonstrated zoonotic transmission of VACV (3), additional infection prevention, treatment, and control strategies are needed.\n\nAppendix\n\nAdditional information about progressive vaccinia acquired through zoonotic transmission in a patient with HIV/AIDS, Colombia.\n\nAcknowledgments\n\nWe thank the following persons who provided essential assistance during the case investigation and subsequent laboratory testing of samples: Luis Ernesto Ayala, Faiber Antonio Gutierrez Lozada, Alberto de la Ossa, Rodrigo Posada and Juan Manuel Peláez Serna.\n\nThis work was supported by the Public Health Network at the Instituto Nacional de Salud, Colombia, and the US Centers for Disease Control and Prevention.\n\nThis study was performed in accordance with the ethical standards noted in the 1964 Declaration of Helsinki and its later amendments, and followed the national regulation contained in the 1993 resolution no. 008430 related to the ethical aspects of scientific research involving human beings where it is categorized as a minimal risk research. Samples were remitted to the Colombian National Institute of Health as part of the active virologic surveillance of potentially emerging threats.\n\nMs. Laiton-Donato is a researcher in the Sequencing and Genomic Unit, Virology Group, at the Instituto Nacional de Salud, Colombia. Her research is focused on molecular virology of emerging viruses. Dr. Ávila-Robayo is a medical doctor at Hospital Universitario Mayor Méderi, Colombia. Her work focuses on the care of patients with infectious diseases.\n\nSuggested citation for this article: Laiton-Donato K, Ávila-Robayo P, Páez-Martinez A, Benjumea-Nieto P, Usme-Ciro JA, Pinzón-Nariño N, et al. Progressive vaccinia acquired through zoonotic transmission in a patient with HIV/AIDS, Colombia. Emerg Infect Dis. 2020 Mar [date cited]. https://doi.org/10.3201/eid2603.191365\n\n1 These authors contributed equally to this article.\n==== Refs\nReferences\n\n1. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. Smallpox and its eradication. 1988 [cited 2019 Sep 19]. https://apps.who.int/iris/handle/10665/39485\n2. Trindade GS, Emerson GL, Carroll DS, Kroon EG, Damon IK. Brazilian vaccinia viruses and their origins. Emerg Infect Dis. 2007;13 :965–72. 10.3201/eid1307.061404 18214166\n3. Usme-Ciro JA, Paredes A, Walteros DM, Tolosa-Pérez EN, Laiton-Donato K, Pinzón MD, et al. Detection and molecular characterization of zoonotic poxviruses circulating in the Amazon region of Colombia, 2014. Emerg Infect Dis. 2017;23 :649–53. 10.3201/eid2304.161041 28322708\n4. Bray M, Wright ME. Progressive vaccinia. Clin Infect Dis. 2003;36 :766–74. 10.1086/374244 12627361\n5. Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med. 1987;316 :673–6. 10.1056/NEJM198703123161106 3821799\n6. Bray M. Henry Kempe and the birth of vaccinia immune globulin. Clin Infect Dis. 2004;39 :767–9. 10.1086/423005 15472805\n7. Letz AG, McFarland RW, Dice JP. Delay of chemotherapy to prevent progressive vaccinia. Mil Med. 2006;171 :788–9. 10.7205/MILMED.171.8.788 16933825\n8. Amorosa VK, Isaacs SN. Separate worlds set to collide: smallpox, vaccinia virus vaccination, and human immunodeficiency virus and acquired immunodeficiency syndrome. Clin Infect Dis. 2003;37 :426–32. 10.1086/375823 12884168\n9. Bartlett JG. Smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome. Clin Infect Dis. 2003;36 :468–71. 10.1086/368093 12567305\n10. Tasker SA, Schnepf GA, Lim M, Caraviello HE, Armstrong A, Bavaro M, et al. ; US Department of Defense Tri-Service AIDS Clinical Consortium. Unintended smallpox vaccination of HIV-1-infected individuals in the United States military. Clin Infect Dis. 2004;38 :1320–2. 10.1086/420938 15127348\n11. Pittman PR, Garman PM, Kim SH, Schmader TJ, Nieding WJ, Pike JG, et al. Smallpox vaccine, ACAM2000: Sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response. Vaccine. 2015;33 :2990–6. 10.1016/j.vaccine.2015.04.062 25930115\n12. Reynolds MG, Carroll DS, Karem KL. Factors affecting the likelihood of monkeypox’s emergence and spread in the post-smallpox era. Curr Opin Virol. 2012;2 :335–43. 10.1016/j.coviro.2012.02.004 22709519\n13. Parrino J, Graham BS. Smallpox vaccines: Past, present, and future. J Allergy Clin Immunol. 2006;118 :1320–6. 10.1016/j.jaci.2006.09.037 17157663\n14. Zafar A, Swanepoel R, Hewson R, Nizam M, Ahmed A, Husain A, et al. Nosocomial buffalopoxvirus infection, Karachi, Pakistan. Emerg Infect Dis. 2007;13 :902–4. 10.3201/eid1306.061068 17553232\n\n",
"fulltext_license": "CC BY",
"issn_linking": "1080-6040",
"issue": "26(3)",
"journal": "Emerging infectious diseases",
"keywords": "Colombia; HIV/AIDS; Orthopoxvirus; VACV; progressive vaccinia; smallpox; vaccine-preventable diseases; vaccinia virus; viruses; zoonoses; zoonotic vaccinia",
"medline_ta": "Emerg Infect Dis",
"mesh_terms": "D000163:Acquired Immunodeficiency Syndrome; D000328:Adult; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents; D003105:Colombia; D015658:HIV Infections; D006801:Humans; D008297:Male; D014615:Vaccinia; D014616:Vaccinia virus; D015047:Zoonoses",
"nlm_unique_id": "9508155",
"other_id": null,
"pages": "601-605",
"pmc": null,
"pmid": "32091366",
"pubdate": "2020-03",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't; D013487:Research Support, U.S. Gov't, P.H.S.",
"references": "12627361;28322708;17157663;15127348;12567305;18214166;12884168;17553232;16933825;22709519;25930115;3821799;15472805",
"title": "Progressive Vaccinia Acquired through Zoonotic Transmission in a Patient with HIV/AIDS, Colombia.",
"title_normalized": "progressive vaccinia acquired through zoonotic transmission in a patient with hiv aids colombia"
}
|
[
{
"companynumb": "CO-VIIV HEALTHCARE LIMITED-CO2020GSK060636",
"fulfillexpeditecriteria": "1",
"occurcountry": "CO",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "EFAVIRENZ"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": "20150330",
"drugenddateformat": "102",
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EFAVIRENZ."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLENE BLUE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ULCER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLENE BLUE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LAMIVUDINE\\ZIDOVUDINE"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "020857",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": "20150330",
"drugenddateformat": "102",
"drugindication": "HIV INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMIVUDINE AND ZIDOVUDINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ALCOHOL"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ULCER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALCOHOL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ACYCLOVIR"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HERPES VIRUS INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACYCLOVIR."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMERAZINE SODIUM\\TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OPPORTUNISTIC INFECTION PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMETHOPRIM + SULFAMETHOXAZOL"
}
],
"patientagegroup": null,
"patientonsetage": "30",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "General physical health deterioration",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "4"
},
{
"reactionmeddrapt": "Treatment noncompliance",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Tachycardia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Pathogen resistance",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Skin lesion",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "4"
},
{
"reactionmeddrapt": "Progressive vaccinia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "4"
},
{
"reactionmeddrapt": "Pyrexia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin ulcer",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "4"
},
{
"reactionmeddrapt": "Hypoacusis",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Visual impairment",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Leukopenia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Virologic failure",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Anaemia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2014"
}
},
"primarysource": {
"literaturereference": "LAITON-DONATO K, AVILA-ROBAYO P, PAEZ-MARTINEZ A, BENJUMEA-NIETO P, USME-CIRO JA, PINZON-NARINO N ET AL.. PROGRESSIVE VACCINIA ACQUIRED THROUGH ZOONOTIC TRANSMISSION IN A PATIENT WITH HIV/AIDS, COLOMBIA. EMERGING INFECTIOUS DISEASES. 2020?26 (3):601-605 DOI.ORG/10.3201/EID260",
"literaturereference_normalized": "progressive vaccinia acquired through zoonotic transmission in a patient with hiv aids colombia",
"qualification": "1",
"reportercountry": "CO"
},
"primarysourcecountry": "CO",
"receiptdate": "20200415",
"receivedate": "20200415",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17672027,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200713"
}
] |
{
"abstract": "Cutaneous side effects related to vancomycin therapy have been reported including histamine-related reactions, linear IgA bullous dermatosis, Stevens-Johnson syndrome, maculopapular rash and drug rash with eosinophilia and systemic symptoms. In all instances, these reports were due to the systemic administration of vancomycin and subsequent immunological reactions to the medication. Drug extravasation into soft tissues can result in a variety of clinical outcomes usually related to physiochemical properties of the drug extravasated and its diluents or pharmacologic effects on the vasculature and tissue. The authors report a patient who experienced vancomycin extravasation that resulted in a localized bullous eruption resembling linear IgA bullous dermatosis, a phenomenon not previously described in the literature.",
"affiliations": "Department of Pharmacy Services and Division of General Internal Medicine and Geriatrics, Medical University of South Carolina, Charleston, South Carolina.;Department of Medicine, Medical University of South Carolina, Charleston, South Carolina. Electronic address: [email protected].",
"authors": "Bohm|Nicole M|NM|;Wong|Jeffrey G|JG|",
"chemical_list": "D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D014640:Vancomycin; D008775:Methylprednisolone",
"country": "United States",
"delete": false,
"doi": "10.1097/MAJ.0b013e318237bb47",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0002-9629",
"issue": "343(2)",
"journal": "The American journal of the medical sciences",
"keywords": null,
"medline_ta": "Am J Med Sci",
"mesh_terms": "D000368:Aged; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D001327:Autoimmune Diseases; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006801:Humans; D008775:Methylprednisolone; D012872:Skin Diseases, Vesiculobullous; D013022:South Carolina; D016896:Treatment Outcome; D014640:Vancomycin; D014930:Women",
"nlm_unique_id": "0370506",
"other_id": null,
"pages": "177-179",
"pmc": null,
"pmid": "22104428",
"pubdate": "2012-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Bullous dermatosis associated with vancomycin extravasation.",
"title_normalized": "bullous dermatosis associated with vancomycin extravasation"
}
|
[
{
"companynumb": "US-BAXTER-2018BAX021366",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "VANCOMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "050671",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EVIDENCE BASED TREATMENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VANCOMYCIN INJECTION, USP"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "040",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "GOUTY ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "62.5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "VANCOMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050671",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INFUSION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CELLULITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "002",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VANCOMYCIN INJECTION, USP"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "VANCOMYCIN"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "050671",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ARTHRITIS INFECTIVE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VANCOMYCIN INJECTION, USP"
}
],
"patientagegroup": null,
"patientonsetage": "72",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Linear IgA disease",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Administration site extravasation",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BOHM N, WONG J. BULLOUS DERMATOSIS ASSOCIATED WITH VANCOMYCIN EXTRAVASATION. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES. 2012 FEB?343(2):177?179.",
"literaturereference_normalized": "bullous dermatosis associated with vancomycin extravasation",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180815",
"receivedate": "20180815",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15282179,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
}
] |
{
"abstract": "OBJECTIVE\nCetuximab, a chimeric monoclonal antibody, is the only targeted therapy approved for squamous cell carcinoma of the head and neck (SCCHN). Infusion reactions (IRs) occur in 6-18% of patients pre-medicated with diphenhydramine. Evidence for clinical risk factors for IRs is limited and the benefit of additional pre-medication to prevent IRs is unclear.\n\n\nMETHODS\nA retrospective, single institution study of 243 SCCHN patients treated with cetuximab to evaluate potential risk factors for IRs and to assess the efficacy of additional pre-medications (nebulized albuterol and intravenous (IV) corticosteroids and/or H2-blockers) to decrease the risk of IR.\n\n\nRESULTS\nIR (grades 1-4) and high grade (grades 3-4 only) IR occurred in 47 (19.3%) and 16 (6.6%) patients, respectively. Multivariate analysis identified Caucasian race (OR7.11, p=0.003), medication allergy (OR3.74, p=0.002), and blood eosinophils >3% (OR2.75, p=0.01) independently increased the risk of IR; Caucasian race (OR5.57, p=0.007) and medication allergy (OR4.10, p=0.0007) increased the risk of high grade IR. IR (grades 1-4) and high grade IR occurred in 31.8% and 22.7% pre-medicated with diphenhydramine alone. Univariate analysis identified albuterol, famotidine, and corticosteroids decreased the risk of high grade IR. Furthermore, there was a significant difference between the possible combinations of the pre-medications and the risk of high grade IR by Fisher Exact test (p=0.003) whereby the combination of albuterol, famotidine and corticosteroids was effective in preventing high grade IR. Thirty (64%) of the 47 patients who developed an IR were re-challenged and did not experience a recurrence of an IR.\n\n\nCONCLUSIONS\nThese data may be used to identify patients at higher risk for cetuximab-induced IR who may be advised to not receive cetuximab or who may benefit from additional pre-medications to decrease the risk of a high grade IR.",
"affiliations": "Division of Hospital Medicine, Department of Internal Medicine, St. Louis, MO, United States.;Division of Medical Oncology, Department of Internal Medicine, St. Louis, MO, United States.;Division of Medical Oncology, Department of Internal Medicine, St. Louis, MO, United States.;Division of Medical Oncology, Department of Internal Medicine, St. Louis, MO, United States; Alvin J. Siteman Cancer Center, St. Louis, MO, United States.;Division of Medical Oncology, Department of Internal Medicine, St. Louis, MO, United States; Alvin J. Siteman Cancer Center, St. Louis, MO, United States.;Division of Biostatistics, St. Louis, MO, United States.;Division of Medical Oncology, Department of Internal Medicine, St. Louis, MO, United States; Alvin J. Siteman Cancer Center, St. Louis, MO, United States. Electronic address: [email protected].",
"authors": "Touma|Waseem|W|;Koro|Sami S|SS|;Ley|Jessica|J|;Wildes|Tanya M|TM|;Michel|Loren|L|;Tao|Yu|Y|;Adkins|Douglas|D|",
"chemical_list": "D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab",
"country": "England",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1368-8375",
"issue": "50(9)",
"journal": "Oral oncology",
"keywords": "Cetuximab; Infusion reaction; Pre-medication; Risk factors",
"medline_ta": "Oral Oncol",
"mesh_terms": "D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002294:Carcinoma, Squamous Cell; D000068818:Cetuximab; D005260:Female; D006258:Head and Neck Neoplasms; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult",
"nlm_unique_id": "9709118",
"other_id": null,
"pages": "895-900",
"pmc": null,
"pmid": "25037161",
"pubdate": "2014-09",
"publication_types": "D016428:Journal Article; D052061:Research Support, N.I.H., Extramural",
"references": "20100773;14993230;17538161;2911321;20143444;23135806;18337601;17909865;16461139;16467544;20464886;24243920;18784101;20147576;18854570;18019853;15269313;19114683;17704414",
"title": "Risk factors for and pre-medications to prevent cetuximab-induced infusion reactions in patients with squamous cell carcinoma of the head and neck.",
"title_normalized": "risk factors for and pre medications to prevent cetuximab induced infusion reactions in patients with squamous cell carcinoma of the head and neck"
}
|
[
{
"companynumb": "US-JNJFOC-20140819134",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DIPHENHYDRAMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "005845",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PREMEDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIPHENHYDRAMINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FAMOTIDINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020325",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PREMEDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FAMOTIDINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ALBUTEROL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PREMEDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALBUTEROL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FAMOTIDINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020325",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FAMOTIDINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CETUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SQUAMOUS CELL CARCINOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CETUXIMAB"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CORTICOSTEROID NOS"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PREMEDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CORTICOSTEROIDS"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DIPHENHYDRAMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNSPECIFIED",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DIPHENHYDRAMINE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug ineffective for unapproved indication",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TOUMA W, KORO SS, LEY J, WILDES TM, MICHEL L, TAO Y, ET AL. RISK FACTORS FOR AND PRE-MEDICATIONS TO PREVENT CETUXIMAB-INDUCED INFUSION REACTIONS IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK. ORAL ONCOLOGY 2014;50 (9):895-900.",
"literaturereference_normalized": "risk factors for and pre medications to prevent cetuximab induced infusion reactions in patients with squamous cell carcinoma of the head and neck",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20150723",
"receivedate": "20150723",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11304194,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20151125"
}
] |
{
"abstract": "We conducted a multicenter, open-label Phase I study of single-agent carfilzomib in Japanese patients with relapsed or refractory multiple myeloma. The primary endpoints were tolerability and safety. Carfilzomib was administrated for 30 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, doses for days 1 and 2 were 20 mg/m2, followed by 45 or 56 mg/m2. Three and four subjects were enrolled in the 20/45 mg/m2 cohort and 20/56 mg/m2 cohort. No dose-limiting toxicity was observed, and the tolerability of carfilzomib was confirmed. Pyrexia, hypertension, nausea and vomiting were considered as noteworthy adverse events (AE) when carfilzomib was administered at high doses. Moreover, pyrexia, blood creatinine increased, and body weight gain were observed as acute dose effects. These findings suggest that addition of dexamethasone is important to alleviate acute dose effect. The overall response rates of the 20/45 mg/m2 and 20/56 mg/m2 cohort were 66.7 % (two out of three) and 50 % (two out of four), respectively. Carfilzomib administrated at up to 20/56 mg/m2 was well tolerated and seemed active in Japanese patients with relapsed or refractory multiple myeloma.\n\n\nBACKGROUND\nJapicCTI-122020.",
"affiliations": "Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. [email protected].;Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.;Division of Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.;Department of Oncology Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan.;Department of Oncology Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan.;Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.",
"authors": "Iida|Shinsuke|S|;Tobinai|Kensei|K|;Taniwaki|Masafumi|M|;Shumiya|Yoshihisa|Y|;Nakamura|Toru|T|;Chou|Takaaki|T|",
"chemical_list": "D009842:Oligopeptides; C524865:carfilzomib; D003907:Dexamethasone",
"country": "Japan",
"delete": false,
"doi": "10.1007/s12185-016-2070-7",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0925-5710",
"issue": "104(5)",
"journal": "International journal of hematology",
"keywords": "Carfilzomib; Dose escalation; Japanese patients; Phase I study; Relapsed or refractory multiple myeloma",
"medline_ta": "Int J Hematol",
"mesh_terms": "D044466:Asians; D003907:Dexamethasone; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005334:Fever; D006801:Humans; D006973:Hypertension; D020714:Maximum Tolerated Dose; D009101:Multiple Myeloma; D009325:Nausea; D009842:Oligopeptides; D012008:Recurrence; D014839:Vomiting",
"nlm_unique_id": "9111627",
"other_id": null,
"pages": "596-604",
"pmc": null,
"pmid": "27460677",
"pubdate": "2016-11",
"publication_types": "D017426:Clinical Trial, Phase I; D016428:Journal Article; D016448:Multicenter Study",
"references": "26671818;22833546;26732066;15244382;25482145;25225420;17970782;21881879;21752943;17616698;16855634;9753033;17975015",
"title": "Phase I dose escalation study of high dose carfilzomib monotherapy for Japanese patients with relapsed or refractory multiple myeloma.",
"title_normalized": "phase i dose escalation study of high dose carfilzomib monotherapy for japanese patients with relapsed or refractory multiple myeloma"
}
|
[
{
"companynumb": "JP-CELGENEUS-JPN-2016126545",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARFILZOMIB"
},
"drugadditional": "3",
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PLASMA CELL MYELOMA",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARFILZOMIB"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LENALIDOMIDE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "021880",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "CAPSULES",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PLASMA CELL MYELOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REVLIMID"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARFILZOMIB"
},
"drugadditional": "3",
"drugadministrationroute": "041",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "56",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARFILZOMIB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DEXAMETHASONE ACETATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PLASMA CELL MYELOMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LENADEX"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Colon cancer",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "IIDA S, IIDA S. PHASE I DOSE ESCALATION STUDY OF HIGH DOSE CARFILZOMIB MONOTHERAPY FOR JAPANESE PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA.. INTERNATIONAL JOURNAL OF HEMATOLOGY. 2016;.",
"literaturereference_normalized": "phase i dose escalation study of high dose carfilzomib monotherapy for japanese patients with relapsed or refractory multiple myeloma",
"qualification": "3",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20170104",
"receivedate": "20170104",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13084634,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
}
] |
{
"abstract": "Mepolizumab (MEP) is the first anti Interleukin (IL)-5 add-on therapy approved for the treatment of severe refractory eosinophilic asthma.\nWe describe here the case of a 49 years-old woman with Aspirin-exacerbated respiratory disease (AERD), chronic rhinosinusitis, nasal polyposis and eosinophilic gastroenteritis successfully treated with MEP. Several laboratory and clinical items improved during therapy; moreover MEP showed to be useful as steroid sparing agent.\nThis case supports that the use of mepolizumab can be effective also in other eosinophilic conditions different from asthma and this opens to new therapeutic perspectives.",
"affiliations": "1Allergy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.;1Allergy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.;3IBD UNIT Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.;4Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.;5Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.;4Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.;6Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.;7Polo Scienze della Salute della Donna e del Bambino-Area Anatomia Patologica-Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.;8Department of Internal Medicine and Gastroenterology, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy.;Casa di Cura Quisisana, Rome & Fondazione Mediterranea G.B. Morgagni, Catania, Italy.;3IBD UNIT Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.",
"authors": "Caruso|C|C|;Colantuono|S|S|;Pugliese|D|D|;Di Mario|C|C|;Tolusso|B|B|;Gremese|E|E|;Papparella|G|G|;Castrì|F|F|;Gasbarrini|A|A|;Romano|A|A|;Armuzzi|A|A|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1186/s13223-020-00423-3",
"fulltext": "\n==== Front\nAllergy Asthma Clin Immunol\nAllergy Asthma Clin Immunol\nAllergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology\n1710-1484 1710-1492 BioMed Central London \n\n423\n10.1186/s13223-020-00423-3\nCase Report\nSevere eosinophilic asthma and aspirin-exacerbated respiratory disease associated to eosinophilic gastroenteritis treated with mepolizumab: a case report\nCaruso C. [email protected] 1 Colantuono S. [email protected] 12 Pugliese D. [email protected] 3 Di Mario C. [email protected] 4 Tolusso B. [email protected] 5 Gremese E. [email protected] 45 Papparella G. [email protected] 6 Castrì F. [email protected] 7 Gasbarrini A. [email protected] 8 Romano A. [email protected] 9 Armuzzi A. [email protected] 3 1 grid.414603.4Allergy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy \n2 grid.7841.aDepartment of Translational and Precision Medicine, Sapienza University, Rome, Italy \n3 grid.414603.4IBD UNIT Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy \n4 grid.8142.f0000 0001 0941 3192Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy \n5 grid.414603.4Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy \n6 grid.414603.4Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy \n7 grid.8142.f0000 0001 0941 3192Polo Scienze della Salute della Donna e del Bambino-Area Anatomia Patologica-Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy \n8 grid.8142.f0000 0001 0941 3192Department of Internal Medicine and Gastroenterology, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy \n9 Casa di Cura Quisisana, Rome & Fondazione Mediterranea G.B. Morgagni, Catania, Italy \n22 4 2020 \n22 4 2020 \n2020 \n16 273 2 2020 3 4 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background\nMepolizumab (MEP) is the first anti Interleukin (IL)-5 add-on therapy approved for the treatment of severe refractory eosinophilic asthma.\n\nCase presentation\nWe describe here the case of a 49 years-old woman with Aspirin-exacerbated respiratory disease (AERD), chronic rhinosinusitis, nasal polyposis and eosinophilic gastroenteritis successfully treated with MEP. Several laboratory and clinical items improved during therapy; moreover MEP showed to be useful as steroid sparing agent.\n\nConclusions\nThis case supports that the use of mepolizumab can be effective also in other eosinophilic conditions different from asthma and this opens to new therapeutic perspectives.\n\nKeywords\nAERDEosinophilicAsthmaGastroenteritisissue-copyright-statement© The Author(s) 2020\n==== Body\nBackground\nAspirin-exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic nasal polyps, asthma, and airway reactions upon cyclooxygenase (COX) 1 inhibition and affects 1.9% of the European population [1]. Eosinophilic gastroenteritis (EGE) is a rare primary eosinophilic gastrointestinal disorder (EGID), of unknown etiology, characterized by the presence of an intense eosinophilic infiltrate on histopathological examination of the gastric and intestinal mucosa.\n\nThe overall prevalence of eosinophilic enteritis is estimated at 5.1/100,000 persons, with peaks of incidence between the third and fifth decade of life [2]. Hypersensitivity response seems to play a key role in pathogenesis of EGE and several patients show association with other conditions such as seasonal allergies, food allergy, asthma, and eczema.\n\nMepolizumab (MEP) is the first anti Interleukin (IL)-5 add-on therapy approved for the treatment of severe refractory eosinophilic asthma [3]. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma [4]. Recently, one case report of a successfully treatment of both severe asthma and EGE with mepolizumab plus omalizumab (anti-immunoglobulin E monoclonal antibody) has been reported [5].\n\nWe describe here the case of a woman suffering from severe eosinophilic asthma and AERD associated to EGE successfully treated with MEP.\n\nCase presentation\nA 49 years-old woman with ten-year recurrent non-bloody watery diarrhea and abdominal pain came to our observation in 2015. No family history of gastrointestinal disorders was detected. A full ileocolonscopy performed 5 years before (no biopsies collected) was normal, leading to a diagnosis of an irritable bowel syndrome, so managed with symptomatic drugs without significant clinical benefit. She had also an history of repeated endoscopic sinus surgery (ESS) because of polyps’ recurrence, aspirin-exacerbated respiratory disease and severe eosinophilic asthma with frequent exacerbations, requiring short courses of oral corticosteroids. Over the years, it appeared that oral steroids induced also a complete relief of gastrointestinal symptoms, with a relapse at withdrawal. Therefore, the patient had repeated steroids exposure, developing dependence and several side-effects.\n\nAt admission to our department, she complained watery diarrhea (5–6 bowel movements/day) preceded by abdominal pain. Her vital signs were: SpO2 95% (room air), Temperature 35.8 °C, Heart Rate 100 bpm, Respiratory Rate 18/m, Blood Pressure 108/60 mmHg.\n\nPhysical examination was significant only for mild tenderness in the mesogastric area with intact bowel sounds. No organomegaly was found. Visual analog scale (VAS) score for abdominal pain was moderate/severe (60). Besides elevated peripheral blood eosinophil (0.38 × 109/L) laboratory tests were unremarkable. Stool examinations were negative for parasitic, bacteria and clostridium difficile infections. Pulmonary functional tests revealed a Forced Expiratory Volume in the first second (FEV1) of 63% (of predicted value), Asthma Control Test (ACT) score was 13, Sino-Nasal Outcome Test (SNOT-22) was 93, Lund–Mackay (LM) score was 20. Baseline mean OCS dose was 15 mg of prednisone per day. Four OCS requiring asthmatic exacerbations occurred during the previous year.\n\nAn ileocolonscopy revealed a normal aspect of the mucosa of each explored segment, except for a small polyp (2 mm) in the rectum, that was removed. Biopsies collected from apparently normal mucosa showed instead an important linfoplasmacellular and granulocytic infiltrate in the lamina propria with a predominance of eosinophils (Fig. 1a, b).Fig. 1 a (Hematoxylin and Eosin, ×10): in this picture an important linfoplasmacellular ad granulocytic infiltrate is appreciable in the lamina propria with a predominance of eosinophilis, with an infiltrating pattern sometimes disrupting glandular integrity. b (Hematoxylin and Eosin, ×20): a particular of the previous where eosinophils granulocytes surround and infiltrate the glands. As a consequence, glandular structures are depleted of their goblet cells and show reactive hyperchromatic nuclei. c (Hematoxylin and Eosin, ×40): this is an atrophic field where the linfomonocytic and eosinophil granulocitic infiltrate disrupt the glandular structures evocating atrophy and reactive changes. d (Hematoxylin and Eosin, ×10): this is a picture of the same patient after therapy. You can appreciate the lamina propria devoid of inflammatory infiltrate. The glands are well separated, normoconformed and with a goblet component normorapresented. Just in a focal small field there’s a linfomonocytic infiltrate, where no one can appreciate eosinophilic component. e (Hematoxylin and Eosin, ×20): a particular of the previous, where glands are normal and neither a significant eosinophilic infiltrate, nor reactive hyperchromatic changes, nor mucin depletion can be appreciated. f (Hematoxylin and Eosin, ×20): as the previous one, glandular mucosal component is conserved and just a focal eosinophilic infiltrate in three different glands is present, but without any specific feature\n\n\n\nMoreover, no significant findings emerged from gastroscopy, but biopsy specimens, collected in antrum, showed as well as the linfomonocytic and eosinophil granulocytic infiltrate disrupting the glandular structures (Fig. 1c).\n\nAccording to the immunopathogenetic mechanisms of the diseases and in order to spare oral steroids, in 2017, we started treatment with subcutaneous MEP at the standard dose of 100 mg every 4 weeks, using the severe eosinophilic asthma schedule.\n\nAs expected, blood eosinophil count was reduced after the first administration, and became lower and lower during the next 48 weeks (30 cells/mm3). After 3 months, patient experienced a significant improvement of sinusitic, respiratory as well as gastrointestinal symptoms. FEV1 and SNOT-22 were evaluated at 6 and 12 month, showing a global improvement (75% and 95%; 51 and 21 respectively). ACT raised to 23. LM score reduced to 8 at month 12. VAS score for abdominal pain reduced to 20 after 3 months so gradually all oral corticosteroids were successfully reduced by patient. After 6 months, patient was in steroid-free clinical remission with a stool frequency of 1–2 movements/day of normal feces (type 3 according to the Bristol stool chart) and a complete resolution of abdominal pain. BMI (Body Mass Index) reduced from 28 to 23 and none asthma exacerbation occurred during the first year of treatment and until the last follow-up evaluation (24 months) [6].\n\nEndoscopies were repeated in order to obtain new biopsy specimens, showing a remission of the disease in term of eosinophilic inflammation, glands where normal and neither reactive hyperchromatic changes, nor mucin depletion can be appreciated (Fig. 1d–f).\n\nBasophils activation was evaluated after 12 months of MEP, using the surface molecules CD203c, CD63 and CD125, showing a reduction of activation percentages. Results are shown in Fig. 2a, b [7]. Serum IL-5 levels (R&D Systems; sensitivity: 0.29 pg/ml) were measured at baseline and after 3, 6 and 12 months of treatment and are shown in Fig. 2. Serum IL-5 was non-quantifiable at baseline and showed an increase with peak on 6 months as expected and previously demonstrated by Pouliquen et al. in 2015 (Fig. 2c) [8].Fig. 2 a, b Flow cytometric analysis of basophils activation. Whole blood was used immediately after collection from the patients. Stimulation of basophils was performed on whole blood according to the instructions of the supplier (Beckman Coulter, France), using the following monoclonal antibodies: CD3-PC7 (clone UCHT1, Beckman Coulter), CRTH2-FITC (clone BM16, Beckman Coulter), CD203c-PE (clone 97A6, Beckman Coulter), CD63-PC5 (clone H5C6, Beckton Dickinson) and CD125-APC (clone 26815, R&D Systems) and the Navios Flow Cytometer (Beckman Coulter). All data generated were analyzed using Kaluza software (Beckman Coulter). c Serum levels of IL5 (ELISA; R&D Systems; sensitivity: 0.29 pg/ml) at baseline and after 3, 6 and 12 months of treatment were tested\n\n\n\nDiscussion\nThe case of this woman affected by AERD, chronic rhinosinusitis, nasal polyposis and EGE successfully treated with MEP supports recent literature data that show how new biological agents may be useful in eosinophilic conditions other than asthma. Several laboratory and clinical items improved during therapy; moreover MEP showed to be useful as steroid sparing agent. As for AERD, interestingly, at the moment, after 2 years treatment, symptom scores for anosmia (Question 21 from the SNOT-22) and nasal congestion (Question 22 from the SNOT-22) are significantly decreased. Also the response of nasal symptoms and the CT findings obtained with MEP in this patient are remarkable and confirm more recent literature data [9].\n\nConclusion\nThis case suggests that MEP could be effective in the treatment of eosinophilic disorders other than asthma, i.e. EGE and AERD. Obviously long term observations and further investigations are needed to define better the therapeutic management of these diseases, however the description of different cases with different comorbidities could help to define different aspects of therapy in terms of schedule, drug dosage, duration and so on.\n\n\nAbbreviations\nMEPMepolizumab\n\nAERDAspirin-exacerbated respiratory disease\n\nCOXCyclooxygenase\n\nEGEEosinophilic gastroenteritis\n\nEGIDEosinophilic gastrointestinal disorder\n\nPublisher's Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nC. Caruso and S. Colantuono equally contributed to paper\n\nAcknowledgements\nNot applicable.\n\nAuthors’ contributions\nCC and SC equally contributed in writing the paper. CDM, BT and EG contributed to laboratory assay, GP performed endoscopic procedures, FC performed and described the histological findings, AG, AR and AA coordinated multidisciplinary work. All authors read and approved the final manuscript.\n\nFunding\nI declare that I didn’t received any form of funding for the writing of this clinical case.\n\nAvailability of data and materials\nThe data used during the current report are available from the corresponding author on reasonable request.\n\nEthics approval and consent to participate\nNot applicable.\n\nConsent for publication\nI obtained the patient’s informed consent for the publication of the images and biopsy data on tissue.\n\nCompeting interests\nI declare that I haven’t competing interests.\n==== Refs\nReferences\n1. Cortellini G Caruso C Romano A Aspirin challenge and desensitization: how, when and why Curr Opin Allergy Clin Immunol 2017 17 4 247 254 10.1097/ACI.0000000000000374 28590311 \n2. Pineton de Chambrun G Diagnosis, natural history and treatment of eosinophilic enteritis: a review Curr Gastroenterol Rep 2018 20 8 37 10.1007/s11894-018-0645-6 29968127 \n3. Lombardi C Analysis of the drop-out rate in patients receiving mepolizumab for severe asthma in real life Pulm Pharmacol Ther 2019 54 87 89 10.1016/j.pupt.2018.12.003 30597278 \n4. Potaczek DP Epigenetics and allergy: from basic mechanisms to clinical applications Epigenomics. 2017 9 4 539 571 10.2217/epi-2016-0162 28322581 \n5. Han D Lee JK Severe asthma with eosinophilic gastroenteritis effectively managed by mepolizumab and omalizumab Ann Allergy Asthma Immunol 2018 121 6 742 743 10.1016/j.anai.2018.07.030 30056148 \n6. Kurosawa M Favorable clinical efficacy of mepolizumab on the upper and lower airways in severe eosinophilic asthma: a 48-week pilot study Eur Ann Allergy Clin Immunol. 2019 51 5 213 221 10.23822/EurAnnACI.1764-1489.94 30983308 \n7. Suzuki Y Airway basophils are increased and activated in eosinophilic asthma Allergy 2017 72 10 1532 1539 10.1111/all.13197 28474352 \n8. Pouliquen IJ Characterization of the relationship between dose and blood eosinophil response following subcutaneous administration of mepolizumab Int J Clin Pharmacol Ther 2015 53 12 1015 1027 10.5414/CP202446 26445140 \n9. Hagin D Mepolizumab for the treatment of aspirin-exacerbated respiratory disease associated with coronary spasm J Allergy Clin Immunol Pract. 2019 7 3 1076 1077 10.1016/j.jaip.2018.07.045 30172017\n\n",
"fulltext_license": "CC BY",
"issn_linking": "1710-1484",
"issue": "16()",
"journal": "Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology",
"keywords": "AERD; Asthma; Eosinophilic; Gastroenteritis",
"medline_ta": "Allergy Asthma Clin Immunol",
"mesh_terms": null,
"nlm_unique_id": "101244313",
"other_id": null,
"pages": "27",
"pmc": null,
"pmid": "32336975",
"pubdate": "2020",
"publication_types": "D002363:Case Reports",
"references": "26445140;30056148;28322581;30597278;30983308;30172017;28474352;29968127;28590311",
"title": "Severe eosinophilic asthma and aspirin-exacerbated respiratory disease associated to eosinophilic gastroenteritis treated with mepolizumab: a case report.",
"title_normalized": "severe eosinophilic asthma and aspirin exacerbated respiratory disease associated to eosinophilic gastroenteritis treated with mepolizumab a case report"
}
|
[
{
"companynumb": "IT-PFIZER INC-2020215940",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "011153",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "UNK (PROLONGED USE)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ASTHMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "49",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Blood pressure abnormal",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Insomnia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Weight increased",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Irritability",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "CARUSO, C.. SEVERE EOSINOPHILIC ASTHMA AND ASPIRIN-EXACERBATED RESPIRATORY DISEASE ASSOCIATED TO EOSINOPHILIC GASTROENTERITIS TREATED WITH MEPOLIZUMAB: A CASE REPORT. ALLERGY, ASTHMA AND CLINICAL IMMUNOLOGY. 2020?16(1):27",
"literaturereference_normalized": "severe eosinophilic asthma and aspirin exacerbated respiratory disease associated to eosinophilic gastroenteritis treated with mepolizumab a case report",
"qualification": "1",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20200610",
"receivedate": "20200603",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17857109,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200714"
}
] |
{
"abstract": "BACKGROUND\nCardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Description of arrhythmias in myopathies and muscular dystrophies is very important, because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable.\n\n\nMETHODS\nA girl with severe congenital RYR1-related myopathy exhibited atrial tachycardia and sinus node dysfunction during infancy. She was born after uncomplicated caesarian delivery. She showed no breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness. At 5 months old, she developed persistent tachycardia around 200-210 beats per minutes. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia and occasional sinus pauses with junctional escape beats. Propranolol effectively alleviated tachyarrhythmia but was discontinued due to increased frequency and duration of the sinus pauses that led to bradyarrhythmia. There was no evidence of structural heart diseases or heart failure. The arrhythmia gradually resolved spontaneously and at 11 months old, she showed complete sinus rhythm.\n\n\nCONCLUSIONS\nAlthough supraventricular arrhythmia is sometimes encountered in congenital myopathies, this is the first report of cardiac arrhythmia requiring drug intervention in RYR1-associated myopathy.",
"affiliations": "Division of Neurology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. [email protected].;Division of Neurology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.;Division of Cardiology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.;Division of Neurology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.",
"authors": "Hayakawa|Itaru|I|http://orcid.org/0000-0002-6384-0205;Abe|Yuichi|Y|;Ono|Hiroshi|H|;Kubota|Masaya|M|",
"chemical_list": "D019837:Ryanodine Receptor Calcium Release Channel; D011433:Propranolol",
"country": "England",
"delete": false,
"doi": "10.1186/s13052-019-0756-1",
"fulltext": "\n==== Front\nItal J PediatrItal J PediatrItalian Journal of Pediatrics1824-7288BioMed Central London 75610.1186/s13052-019-0756-1Case ReportSevere congenital RYR1-associated myopathy complicated with atrial tachycardia and sinus node dysfunction: a case report http://orcid.org/0000-0002-6384-0205Hayakawa Itaru [email protected] 1Abe Yuichi [email protected] 1Ono Hiroshi [email protected] 2Kubota Masaya [email protected] 11 0000 0004 0377 2305grid.63906.3aDivision of Neurology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535 Japan 2 0000 0004 0377 2305grid.63906.3aDivision of Cardiology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535 Japan 19 12 2019 19 12 2019 2019 45 16513 5 2019 3 12 2019 © The Author(s). 2019Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nCardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Description of arrhythmias in myopathies and muscular dystrophies is very important, because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable.\n\nCase presentation\nA girl with severe congenital RYR1-related myopathy exhibited atrial tachycardia and sinus node dysfunction during infancy. She was born after uncomplicated caesarian delivery. She showed no breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness. At 5 months old, she developed persistent tachycardia around 200–210 beats per minutes. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia and occasional sinus pauses with junctional escape beats. Propranolol effectively alleviated tachyarrhythmia but was discontinued due to increased frequency and duration of the sinus pauses that led to bradyarrhythmia. There was no evidence of structural heart diseases or heart failure. The arrhythmia gradually resolved spontaneously and at 11 months old, she showed complete sinus rhythm.\n\nConclusions\nAlthough supraventricular arrhythmia is sometimes encountered in congenital myopathies, this is the first report of cardiac arrhythmia requiring drug intervention in RYR1-associated myopathy.\n\nKeywords\nRYR1Sinus node dysfunctionAtrial tachycardiaCongenital myopathyissue-copyright-statement© The Author(s) 2019\n==== Body\nIntroduction\nCardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Because of the increasing lifespan of these patients, prevalence of cardiac involvement is also increasing. Because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable, description of arrhythmias in myopathies and muscular dystrophies is very important [1, 2]. To date, arrhythmia has never been reported in cases of congenital RYR1-related myopathy.\n\nHere we report a girl with severe congenital RYR1-related myopathy [2–4] who exhibited atrial tachycardia and sinus node dysfunction without cardiomyopathy during infancy.\n\nCase presentation\nThe female patient was born to non-consanguineous healthy parents by caesarian delivery due to breech presentation at 36 weeks 3 days of gestational age. Polyhydramnios and decreased fetal movements were pointed out during pregnancy. After delivery, she showed neither spontaneous breathing nor spontaneous limb movements. She received standard resuscitative measures. On examination, no spontaneous breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness with diminished tendon reflexes were noted. Height, weight, and head circumference were within normal limits. No dysmorphic features were present. Severe congenital myopathy was suspected. She underwent muscle biopsy and genetic analysis that resulted in a diagnosis of severe congenital RYR1-associated centronuclear myopathy (Fig. 1a–c). She inherited compound heterozygous pathogenic or likely-pathogenic rare variants in the RYR1 gene (RYR1 NM_000540, p.D2529N from her father, p.L2155P and p.R682P in cis from her mother). The other genes in the congenital myopathy and myasthenia panel were negative.\nFig. 1 a–c Skeletal muscle (thyrohyoid muscle) histopathology was consistent with centronuclear myopathy. d and e Holter monitoring demonstrates sinus pause and junctional rhythms, confirming the diagnosis of sinus node dysfunction. a, hematoxylin & eosin; b, NADH-TR; c, modified Gomori-trichrome; calibration bar 20 μm; NADH-TR, nicotinamide adenine dinucleotide dehydrogenase - tetrazolium reductase.\n\n\n\nAt the age of 5 months old, she developed persistent tachycardia around 200–210 beats per minutes (bpm). She did not show fever, hypotension, abnormal urination, stool abnormality, diaphoresis, or mydriasis during the tachycardia. Routine laboratory investigation failed to show any extra-cardiac cause of tachycardia including infection, hyperthyroid status, or anemia. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia up to 200–210 bpm, junctional escape beats with sinus pauses after cessation of atrial tachycardia, and occasional sinus bradycardia around 50 bpm. Cardiac ultrasonography showed no evidence of structural heart disease or cardiomyopathy. The tachycardia was refractory to intravenous adenosine triphosphate trial and to intravenous procainamide. Atrial tachycardia and sinus node dysfunction, due presumably to her underlying severe congenital RYR1-associated centronuclear myopathy, were diagnosed.\n\nAdministration of propranolol (0.5–1.0 mg/kg/day) was initiated and was effective. Her heart rate lowered from 200-210 bpm to 130–150 bpm. Unfortunately, paroxysmal bradycardia around 30 bpm for several seconds began to occur almost daily after propranolol treatment. Repeated Holter monitoring revealed alleviation of atrial tachycardia, but increased frequency and duration of the sinus pauses with junctional rhythms that led to bradyarrhythmia (maximum R-R interval of 2.44 s) (Fig. 1d, e). As the patient had complete ophthalmoplegia and limb weakness, we could not determine whether the bradycardia was associated with any other signs or symptoms. Propranolol was discontinued at the age of 6 months. Fortunately, severe tachyarrhythmia did not recur after propranolol discontinuation. Her heart rates were mostly around 170–180 bpm, with occasional episodic drops down to 50–60 bpm. She was discharged home when she was 10 months old, with a tracheostomy, home respirator support, and a gastric tube. At planned follow-up (11 months old), Holter monitoring revealed complete sinus rhythm with occasional sinus bradycardia down to 50 bpm. She was still completely ophthalmoplegic, but her weakness improved slightly, and she and her family could communicate with each other by her subtle hand gestures and very slight facial muscle movements.\n\nDiscussion and conclusions\nThis is to our knowledge the first report of arrhythmia requiring drug intervention in RYR1-associated myopathy [3, 4]. Although supraventricular arrhythmia is sometimes encountered in congenital myopathies [5], the reason why RYR1 mutation led to atrial tachycardia and sinus node dysfunction in our patient remains unclear. RYR1 is expressed predominantly in skeletal muscles and to a lesser extent in vascular smooth muscles, but does not exert any effects on cardiac muscles [6, 7].\n\nBecause arrhythmias have a strong impact on the outcomes for myopathy patients and are potentially treatable, early recognition and treatment of primary cardiac arrhythmia in myopathy patients is vitally important. We identified our patient’s atrial tachycardia with sinus node dysfunction through bedside observation and Holter monitoring. Prompt treatment with low-dose propranolol effectively alleviated the atrial tachycardia. The heart rate abnormality in congenital myopathy patients is usually a result of some respiratory or gastrointestinal infection. The otherwise unexplained tachycardia in severely affected myopathy patients may easily be overlooked to the point where tachycardia-induced heart failure becomes evident. We suggest that neurologists should be aware of the possibility of primary cardiac arrhythmias and perform Holter monitoring in severely affected congenital myopathy patients with an otherwise unexplained heart rate abnormality.\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nAcknowledgements\nWe thank Drs. Masashi Ogasawara and Ichizo Nishino at the National Center for Neurology and Psychiatry for histopathology and genetic analysis; Drs. Mei Ikenori, Hiro Nakao, Yosuke Ogawa, and Noriko Morimoto at the National Center for Child Health and Development for patient care; and the medical editors from the Division of Education for Clinical Research at the National Center for Child Health and Development for editing this manuscript.\n\nAuthors’ contributions\nIH took care of the patient, designed the study, and drafted the initial manuscript. YA, HO, and MK supervised the care and extensively revised the manuscript.\n\nFunding\nThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\n\nAvailability of data and materials\nAll the data presented in this article is stored in our Unit.\n\nEthics approval and consent to participate\nThis study has been approved by the institutional review board at the National Center for Child Health and Development [trial number 2018–2011].\n\nConsent for publication\nThe guardians consented for publication.\n\nCompeting interests\nThe authors declare that they do not have any potential conflicts of interest to disclose.\n==== Refs\nReferences\n1. Finsterer J Stöllberger C Keller H Arrhythmia-related workup in hereditary myopathies J Electrocardiol 2012 45 376 384 10.1016/j.jelectrocard.2012.02.003 22424849 \n2. Arbustini E Toro A Giuliani L Favalli V Narula N Grasso M Cardiac phenotypes in hereditary muscle disorders J Am Coll Cardiol 2018 72 2485 2506 10.1016/j.jacc.2018.08.2182 30442292 \n3. Bharucha-Goebel D Santi M Medne L Zukosky K Zukosky K Dastgir J Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum Neurology 2013 80 1584 1589 10.1212/wnl.0b013e3182900380 23553484 \n4. Neto O de Moreno C Malfatti E Donkervoort S Böhm J Guimarães J Common and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients Neuromuscul Disord 2017 27 975 985 10.1016/j.nmd.2017.05.016 28818389 \n5. Steele HE Harris E Barresi R Marsh J Beattie A Bourke JP Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study Neurology 2016 87 1031 1035 10.1212/wnl.0000000000003064 27511179 \n6. Greiser M Kerfant B-G Williams GS Voigt N Harks E Dibb KM Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes J Clin Investigation 2014 124 4759 4772 10.1172/jci70102 \n7. Petegem F Ryanodine receptors: structure and function J Biol Chem 2012 287 31624 31632 10.1074/jbc.r112.349068 22822064\n\n",
"fulltext_license": "CC BY",
"issn_linking": "1720-8424",
"issue": "45(1)",
"journal": "Italian journal of pediatrics",
"keywords": "Atrial tachycardia; Congenital myopathy; RYR1; Sinus node dysfunction",
"medline_ta": "Ital J Pediatr",
"mesh_terms": "D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D020914:Myopathies, Structural, Congenital; D011433:Propranolol; D018570:Risk Assessment; D019837:Ryanodine Receptor Calcium Release Channel; D012720:Severity of Illness Index; D012804:Sick Sinus Syndrome; D013612:Tachycardia, Ectopic Atrial; D013617:Tachycardia, Supraventricular; D016896:Treatment Outcome",
"nlm_unique_id": "101510759",
"other_id": null,
"pages": "165",
"pmc": null,
"pmid": "31856875",
"pubdate": "2019-12-19",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": "22822064;25329692;27511179;30442292;28818389;22424849;23553484",
"title": "Severe congenital RYR1-associated myopathy complicated with atrial tachycardia and sinus node dysfunction: a case report.",
"title_normalized": "severe congenital ryr1 associated myopathy complicated with atrial tachycardia and sinus node dysfunction a case report"
}
|
[
{
"companynumb": "US-NORTHSTAR HEALTHCARE HOLDINGS-JP-2020NSR000009",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PROPRANOLOL HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "078213",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.5?1.0 MG/KG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ATRIAL TACHYCARDIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPRANOLOL HYDROCHLORIDE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PROPRANOLOL HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "078213",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SINUS NODE DYSFUNCTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPRANOLOL HYDROCHLORIDE."
}
],
"patientagegroup": null,
"patientonsetage": "5",
"patientonsetageunit": "802",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Bradyarrhythmia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HAYAKAWA I, ABE Y, ONO H, KUBOTA M. SEVERE CONGENITAL RYR1?ASSOCIATED MYOPATHY COMPLICATED WITH ATRIAL TACHYCARDIA AND SINUS NODE DYSFUNCTION: A CASE REPORT. ITAL. J. PEDIATR. 2019?45",
"literaturereference_normalized": "severe congenital ryr1 associated myopathy complicated with atrial tachycardia and sinus node dysfunction a case report",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210208",
"receivedate": "20200304",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17495128,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210419"
},
{
"companynumb": "JP-IPCA LABORATORIES LIMITED-IPC-2020-JP-000254",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPRANOLOL HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "78955",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TACHYARRHYTHMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPRANOLOL"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Bradyarrhythmia",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ITARU HAYAKAWA,YUICHI ABE, HIROSHI ONO, ET AL. SEVERE CONGENITAL RYR1-ASSOCIATED MYOPATHY COMPLICATED WITH ATRIAL TACHYCARDIA AND SINUS NODE DYSFUNCTION: A CASE REPORT. ITALIAN JOURNAL OF PEDIATRICS. 2019?45:1-3",
"literaturereference_normalized": "severe congenital ryr1 associated myopathy complicated with atrial tachycardia and sinus node dysfunction a case report",
"qualification": "3",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20200127",
"receivedate": "20200127",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17324135,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200409"
}
] |
{
"abstract": "BACKGROUND\nLittle is known about the development of drug allergy during pregnancy or in patients with altered immune status.\n\n\nOBJECTIVE\nTo report a case of new-onset penicillin allergy during pregnancy in a woman with rheumatoid arthritis.\n\n\nMETHODS\nA 39-year-old woman with rheumatoid arthritis developed intrapartum anaphylaxis that led to fetal demise. She had previously received penicillin-based antibiotics without any allergic reactions. Because of group B streptococcus colonization, an intravenous infusion of penicillin G was started during labor. Within minutes, she developed severe anaphylaxis.\n\n\nRESULTS\nA fluorescent enzyme immunoassay revealed a moderate level of specific IgE to penicilloyl G and penicilloyl V (3.15 kU/L and 2.77 kU/L, respectively). Given the patient's history, these positive results were considered confirmatory of penicillin allergy. This case raises a number of salient points. First, patients can develop severe allergy to penicillin despite having safely received penicillins in the past. Possible factors that influenced the development of severe penicillin sensitivity in this patient are discussed. Second, unexpected intrapartum anaphylaxis can occur, which can be life threatening to the mother or fetus. Third, safe and reliable methods for diagnosis of drug allergy must be available.\n\n\nCONCLUSIONS\nThis case illustrates that during the current unavailability of skin testing reagents in the United States, a positive result on in vitro testing can be helpful in confirming penicillin allergy in cases in which drug challenge is deemed unsafe.",
"affiliations": "Department of Medicine, Division of Allergy & Inflammation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. [email protected]",
"authors": "Sheikh|Javed|J|",
"chemical_list": "D007073:Immunoglobulin E; D010400:Penicillin G; D010404:Penicillin V",
"country": "United States",
"delete": false,
"doi": "10.1016/S1081-1206(10)60667-9",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1081-1206",
"issue": "99(3)",
"journal": "Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology",
"keywords": null,
"medline_ta": "Ann Allergy Asthma Immunol",
"mesh_terms": "D000328:Adult; D000707:Anaphylaxis; D001172:Arthritis, Rheumatoid; D004342:Drug Hypersensitivity; D005260:Female; D005313:Fetal Death; D006801:Humans; D007073:Immunoglobulin E; D007262:Infusions, Intravenous; D036801:Parturition; D010400:Penicillin G; D010404:Penicillin V; D011247:Pregnancy",
"nlm_unique_id": "9503580",
"other_id": null,
"pages": "287-9",
"pmc": null,
"pmid": "17910335",
"pubdate": "2007-09",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Intrapartum anaphylaxis to penicillin in a woman with rheumatoid arthritis who had no prior penicillin allergy.",
"title_normalized": "intrapartum anaphylaxis to penicillin in a woman with rheumatoid arthritis who had no prior penicillin allergy"
}
|
[
{
"companynumb": "US-CASPER PHARMA LLC-2021CAS000693",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PENICILLIN G BENZATHINE"
},
"drugadditional": "3",
"drugadministrationroute": "015",
"drugauthorizationnumb": "060014",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENICILLIN G BENZATHINE"
}
],
"patientagegroup": "1",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Asphyxia",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Foetal exposure during pregnancy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Sheikh J. Intrapartum anaphylaxis to penicillin in a woman with rheumatoid arthritis who had no prior penicillin allergy.. Ann Allergy Asthma Immunol. 2007;99(3):287-9",
"literaturereference_normalized": "intrapartum anaphylaxis to penicillin in a woman with rheumatoid arthritis who had no prior penicillin allergy",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20220105",
"receivedate": "20220105",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20301008,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 1,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220423"
}
] |
{
"abstract": "OBJECTIVE\nMicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients.\n\n\nMETHODS\nThis retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR.\n\n\nRESULTS\nDown-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression-free and overall survival (p=0.055 and p=0.006).\n\n\nCONCLUSIONS\nThe results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 down-regulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.",
"affiliations": "Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic [email protected].;Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.;Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.;Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.;Department of Surgery, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.;Department of Surgery, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.;Department of Immunochemistry Diagnostics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.;Department of Immunochemistry Diagnostics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.;Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.;Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.;Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.",
"authors": "Fiala|Ondrej|O|;Sorejs|Ondrej|O|;Hosek|Petr|P|;Liska|Vaclav|V|;Vycital|Ondrej|O|;Bruha|Jan|J|;Kucera|Radek|R|;Topolcan|Ondrej|O|;Finek|Jindrich|J|;Maceckova|Diana|D|;Pitule|Pavel|P|",
"chemical_list": "D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; C487931:mirnlet7 microRNA, human; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab",
"country": "Greece",
"delete": false,
"doi": "10.21873/cgp.20217",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1109-6535",
"issue": "17(5)",
"journal": "Cancer genomics & proteomics",
"keywords": "Colorectal cancer; cetuximab; chemotherapy; let-7c; miR-125b; miR-17; microRNA; panitumumab",
"medline_ta": "Cancer Genomics Proteomics",
"mesh_terms": "D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor; D000068818:Cetuximab; D015179:Colorectal Neoplasms; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D000077544:Panitumumab; D000077982:Progression-Free Survival; D047428:Protein Kinase Inhibitors; D012189:Retrospective Studies; D015854:Up-Regulation",
"nlm_unique_id": "101188791",
"other_id": null,
"pages": "605-613",
"pmc": null,
"pmid": "32859639",
"pubdate": "2020",
"publication_types": "D016428:Journal Article",
"references": "20736745;25124875;25628647;24304648;20533884;29858404;28714375;10655437;18202412;19779035;14744438;31819515;17110380;18946061;28800315;30018946;31659100;26693202;25115304;24503111;18316791;25197016;17174894;14573789;32118734;16854228;15766527;16618717;29039606;16557279;21296855;19843336;21935352;23121918;27278684;21567082;24423609;30850362;21305640;21984339;16505370;18230780;31882547;32104088;31118777;24024839;24774301",
"title": "Association of miR-125b, miR-17 and let-7c Dysregulations With Response to Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With Metastatic Colorectal Cancer.",
"title_normalized": "association of mir 125b mir 17 and let 7c dysregulations with response to anti epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer"
}
|
[
{
"companynumb": "CZ-AMGEN-CZESP2020143254",
"fulfillexpeditecriteria": "2",
"occurcountry": "CZ",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PANITUMUMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125147",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "6 MILLIGRAM, Q2WK (EVERY 14 DAYS)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLORECTAL CANCER METASTATIC",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "6",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VECTIBIX"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "IRINOTECAN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, Q2WK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLORECTAL CANCER METASTATIC",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IRINOTECAN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUOROURACIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, Q2WK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLORECTAL CANCER METASTATIC",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "5?FU [FLUOROURACIL]"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "OXALIPLATIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, Q2WK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLORECTAL CANCER METASTATIC",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OXALIPLATIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LEUCOVORIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK UNK, Q2WK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLORECTAL CANCER METASTATIC",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "2",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEUCOVORIN [FOLINIC ACID]"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Therapy partial responder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Death",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Disease progression",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HOSEK P. ASSOCIATION OF MIR?125B, MIR?17 AND LET?7C DYSREGULATIONS WITH RESPONSE TO ANTI?EPIDERMAL GROWTH FACTOR RECEPTOR MONOCLONAL ANTIBODIES IN PATIENTS WITH METASTATIC COLORECTAL CANCER. CANCER GENOMICS + PROTEOMICS. 2020?17 (5):605?613",
"literaturereference_normalized": "association of mir 125b mir 17 and let 7c dysregulations with response to anti epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer",
"qualification": "3",
"reportercountry": "CZ"
},
"primarysourcecountry": "CZ",
"receiptdate": "20200907",
"receivedate": "20200907",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18237790,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
}
] |
{
"abstract": "Tetracyclines, including doxycycline, are widely used drugs that form an integral part of daily prescribing, and serious adverse reactions (SARs) are rarely reported. The frequency of hypoglycaemia complicating tetracycline treatment remains unknown, and is not a recognized complication. We describe an 80-year-old man with a history of insulin-dependent diabetes who was recruited into a large research study, and subsequently experienced the unexpected SAR of hypoglycaemia following treatment with doxycycline.",
"affiliations": "Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester, UK.;Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester, UK.;Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester, UK.",
"authors": "Tan|C H|CH|;Shelley|C|C|;Harman|K E|KE|",
"chemical_list": "D000900:Anti-Bacterial Agents; D004318:Doxycycline",
"country": "England",
"delete": false,
"doi": "10.1111/ced.12692",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0307-6938",
"issue": "41(1)",
"journal": "Clinical and experimental dermatology",
"keywords": null,
"medline_ta": "Clin Exp Dermatol",
"mesh_terms": "D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents; D004318:Doxycycline; D006801:Humans; D007003:Hypoglycemia; D008297:Male; D010391:Pemphigoid, Bullous",
"nlm_unique_id": "7606847",
"other_id": null,
"pages": "43-4",
"pmc": null,
"pmid": "26053970",
"pubdate": "2016-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Doxycycline-induced hypoglycaemia.",
"title_normalized": "doxycycline induced hypoglycaemia"
}
|
[
{
"companynumb": "GB-MYLANLABS-2016M1009909",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "062337",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN CH, SHELLEY C, HARMAN KE. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLIN-EXP-DERMATOL 2016?41(1):43-44.",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20160307",
"receivedate": "20160307",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12157047,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "GB-SUN PHARMACEUTICAL INDUSTRIES LTD-2016R1-112751",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "65053",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN CH, SHELLEY C, HARMAN KE. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLIN-EXP-DERMATOL. 2016?41(1):43-44",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20160316",
"receivedate": "20160316",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 12183778,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "GB-LUPIN PHARMACEUTICALS INC.-2015-02078",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "201678",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN C, SHELLEY C, HARMAN K. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLINICAL AND EXPERIMENTAL DERMATOLOGY. 2015;1-2.",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "1",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20150713",
"receivedate": "20150713",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 11263668,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20151125"
},
{
"companynumb": "GB-HERITAGE PHARMACEUTICALS-2016HTG00090",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "091605",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG, 1X/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Depressed level of consciousness",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN CH, SHELLEY C, HARMAN KE. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLINICAL AND EXPERIMENTAL DERMATOLOGY (DOI:10.1111/CED.12692). 2016?41(1):43-44",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20160329",
"receivedate": "20160329",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12217818,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "GB-MAYNE PHARMA-2016MYN000121",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INSULIN NOS"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INSULIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE HYCLATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "050795",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE HYCLATE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN, C.H ? SHELLY,C ? HARMAN, K.E. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CED: CLINICAL AND EXPERIMENTAL DERMATOLOGY. 2016?41:43-44",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20160317",
"receivedate": "20160317",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12189176,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "GB-COREPHARMA LLC-2015COR00140",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "065182",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG, 1X/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Depressed level of consciousness",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN CH, SHELLEY C, HARMAN KE. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLIN EXP DERMATOL [DOI:10.1111/CED.12692]. 2015;1-2",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20150709",
"receivedate": "20150709",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11256109,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20151125"
},
{
"companynumb": "GB-PFIZER INC-2015207650",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "050006",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "200 MG, 1X/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE MONOHYDRATE"
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN, C.. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLINICAL AND EXPERIMENTAL DERMATOLOGY. 2016;41(1):43-44",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20170505",
"receivedate": "20150629",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 11225219,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170829"
},
{
"companynumb": "GB-G+W LABS-GW2017GB000010",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "204446",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "CAPSULE",
"drugdosagetext": "200 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemic unconsciousness",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN CH, SHELLEY C, HARMAN KE. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLINICAL AND EXPERIMENTAL DERMATOLOGY. 2016;41(1):43-4",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "1",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20170113",
"receivedate": "20170113",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13114739,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "GB-TEVA-643322ISR",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "62497",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN CH, SHELLEY C, HARMAN KE. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLIN-EXP-DERMATOL 2016?41(1):43-44.",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "1",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20160317",
"receivedate": "20160317",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 12189169,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "GB-BAUSCH-BL-2016-006707",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "65281",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "200",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE."
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Lethargy",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Dizziness",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "TAN C, SHELLEY C, HARMAN K. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLINICAL AND EXPERIMENTAL DERMATOLOGY. 2016?41:43-44.",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20160329",
"receivedate": "20160329",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 12216735,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "GB-ENDO PHARMACEUTICALS INC-2016-001752",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "DOXYCYCLINE HYCLATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "62538",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": "2012",
"drugenddateformat": "602",
"drugindication": "PEMPHIGOID",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": "2012",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOXYCYCLINE HYCLATE 100MG"
}
],
"patientagegroup": null,
"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hypoglycaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2012"
}
},
"primarysource": {
"literaturereference": "TAN C, SHELLEY C, HARMAN K. DOXYCYCLINE-INDUCED HYPOGLYCAEMIA. CLINICAL AND EXPERIMENTAL DERMATOLOGY. 2016 JAN?41(1):43-44.",
"literaturereference_normalized": "doxycycline induced hypoglycaemia",
"qualification": null,
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "GB",
"receiptdate": "20160317",
"receivedate": "20160317",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 12186601,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
}
] |
{
"abstract": "Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction.",
"affiliations": "Department of Psychiatry, Central Institute of Psychiatry, Ranchi, Jharkhand, India.;Department of Psychiatry, Central Institute of Psychiatry, Ranchi, Jharkhand, India.",
"authors": "Umesh|Shreekantiah|S|;Sinha|Vinod Kumar|VK|",
"chemical_list": null,
"country": "India",
"delete": false,
"doi": "10.4103/0971-6580.139816",
"fulltext": "\n==== Front\nToxicol IntToxicol IntTIToxicology International0971-65800976-5131Medknow Publications & Media Pvt Ltd India TI-21-22210.4103/0971-6580.139816Case ReportAcute High Dose Lithium-Induced Exacerbation of Obsessive Compulsive Symptoms Umesh Shreekantiah Sinha Vinod Kumar Department of Psychiatry, Central Institute of Psychiatry, Ranchi, Jharkhand, IndiaAddress for correspondence: Dr. S Umesh, Senior Resident, Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi - 834 006, Jharkhand, India. E-mail: [email protected] 2014 21 2 222 223 Copyright: © Toxicology International2014This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction.\n\nGlutamatelithiumobsessive compulsive disorder\n==== Body\nINTRODUCTION\nObsessive compulsive disorder (OCD) is thought to be one of the most intractable and disabling mental disorders in the community.[1] It is well known that OCD responds to drugs which increase the serotonergic (5-HT) transmission at the synapse. Other neurotransmitters such as dopamine, noradrenaline and glutamate also have role in the causation. Recent literatures have shown that glutamatergic hyperactivity at N-methyl-D-aspartate (NMDA) receptor level is involved in the patho-physiology of OCD.[2] Lithium, as an adjunctive for management of OCD, is based on its putative effect on enhancing 5-HT transmission. But acute high dose lithium administration also increases glutamate transmission[3] which may be hypothesized to exacerbate obsessive compulsive (OC) symptoms. Here, we are reporting a case of OCD on stable dose of sertraline for 3 weeks, who developed exacerbation of OC symptoms with acute high dose of lithium but improved after dose reduction.\n\nCASE REPORT\nAn 18-years-old Indian male with no past psychiatric or medical history presented with a history of repetitive distressing thoughts of dirt and contamination with repetitive washing behavior for one and half years. He was diagnosed as OCD, mixed obsessional thoughts, and acts as per International Classification of Diseases (ICD-10).[4] Yale-Brown Obsessive Compulsive scale (Y-BOCS) was administered at the time of admission which indicated severe (obsessions = 13; compulsions = 15; total = 28) and started on sertraline 25 mg/day and hiked to 150 mg/day over 4 weeks. Patient showed minimal improvement after 4 weeks (obsessions = 12; compulsions = 15; total = 27). He started developing side-effects like headache, thus sertraline was not hiked further and lithium 900 mg was added as augmenting agent. Patient started reporting exacerbation of repetitive thoughts (obsessions = 15; compulsions = 18; total = 33 indicating extreme) and fine tremors on fourth day after starting lithium. Serum lithium level was done at 900 mg/day (Serum lithium-1.2 mmol/L) and hence lithium was tapered to 600 mg/day and serum lithium level decreased to 0.65 mmol/L. There was improvement in Y-BOCS score within a week after reducing the dose of lithium (obsessions = 11; compulsion = 14; total = 25 indicating severe) and the dose was maintained on the same dose. Four weeks later, there was further improvement on Y-BOCS (obsessions = 9; compulsions = 12; total = 21 indicating moderate) score. Patient was discharged on sertraline (150 mg/day) and lithium (600 mg/day).\n\nDISCUSSION\nTill date, numerous hypotheses have contributed to the pathophysiology of OCD, including abnormalities in glutamate neurotransmission. Neuro-imaging studies have demonstrated increased cerebral blood flow, metabolism and activation in the cortico-striato-thalamo-cortical (CSTC) circuitry of individuals with OCD. The excitatory glutamatergic projections from the cerebral cortex, thalamus, and hippocampus target the striatum but the striatal neurons are GABAergic and projects to globus pallidus and substantia nigra that ultimately inhibits glutamatergic neurons of anterior thalamus. These thalamic neurons project back to cingulate and orbitofrontal cortex which forms a negative feedback loop to balance glutamate in these cortical regions.[2] Thus, an increased glutamatergic activity in the cortico-striatal projections may result in a disinhibited thalamus and thereby creating a self-perpetuating circuit between the thalamus and orbito-frontal cortex that may drive OC symptoms.[5]\n\nDixon et al.[3] have shown that acute lithium administration at therapeutic concentration may release glutamate in rhesus monkey and mouse cerebral cortex slices. Lithium at supratherapeutic concentrations may exert its excitotoxicity by elevating synaptic glutamate.[6] We hypothesize that there was increase in glutamatergic neuro-transmission within the CSTC circuitry due to acute high dose lithium administration that might have caused exacerbation of OC symptoms which reduced after decreasing the dose. To our knowledge, there are no reports of lithium-induced OCD exacerbation.\n\nCONCLUSION\nLithium, despite being used as an adjunctive in the treatment of OCD may exacerbate symptoms of OCD which may be due to enhanced glutamatergic neurotransmission at the CSTC circuitry on acute high dose administration.\n\nSource of Support: Nil.\n\nConflict of Interest: None declared.\n==== Refs\nREFERENCES\n1 Robins LN Helzer JE Weissman MM Orvaschel H Gruenberg E Burke JD Jr Lifetime prevalence of specific psychiatric disorders in three sites Arch Gen Psychiatry 1984 41 949 58 6332590 \n2 Pittenger C Bloch MH Williams K Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment Pharmacol Ther 2011 132 314 32 21963369 \n3 Dixon JF Los GV Hokin LE Lithium stimulates glutamate “release” and inositol 1,4,5-trisphosphate accumulation via activation of the N-methyl-D-aspartate receptor in monkey and mouse cerebral cortex slices Proc Natl Acad Sci U S A 1994 91 8358 62 8078888 \n4 World Health Organization The ICD-10 classification of Mental and Behavioural Diosrders: Diagnsotic Criteria for Research 1993 Geneva WHO \n5 Menzies L Chamberlain SR Laird AR Thelen SM Sahakian BJ Bullmore ET Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited Neurosci Biobehav Rev 2008 32 525 49 18061263 \n6 Dixon JF Hokin LE Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex Proc Natl Acad Sci U S A 1998 95 8363 8 9653192\n\n",
"fulltext_license": "CC BY-NC-SA",
"issn_linking": "0971-6580",
"issue": "21(2)",
"journal": "Toxicology international",
"keywords": "Glutamate; lithium; obsessive compulsive disorder",
"medline_ta": "Toxicol Int",
"mesh_terms": null,
"nlm_unique_id": "101191279",
"other_id": null,
"pages": "222-3",
"pmc": null,
"pmid": "25253935",
"pubdate": "2014-05",
"publication_types": "D002363:Case Reports",
"references": "9653192;21963369;18061263;8078888;6332590",
"title": "Acute high dose lithium-induced exacerbation of obsessive compulsive symptoms.",
"title_normalized": "acute high dose lithium induced exacerbation of obsessive compulsive symptoms"
}
|
[
{
"companynumb": "IN-MYLANLABS-2014M1006593",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "076671",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "25 MG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OBSESSIVE-COMPULSIVE DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "076671",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "HIKED TO 150 MG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "LITHIUM CARBONATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OFF LABEL USE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LITHIUM"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "LITHIUM CARBONATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "900 MG/DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OBSESSIVE-COMPULSIVE DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LITHIUM"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Headache",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Obsessive-compulsive disorder",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "UMESH S, SINHA V. ACUTE HIGH DOSE LITHIUM-INDUCED EXACERBATION OF OBSESSIVE COMPULSIVE SYMPTOMS. TOXICOL-INT 2014; 21(2) 222-223",
"literaturereference_normalized": "acute high dose lithium induced exacerbation of obsessive compulsive symptoms",
"qualification": "1",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20141010",
"receivedate": "20141010",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10511152,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20150528"
},
{
"companynumb": "IN-ROXANE LABORATORIES, INC.-2014-BI-48414GD",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "LITHIUM CARBONATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "017812",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "900 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OBSESSIVE-COMPULSIVE DISORDER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "900",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LITHIUM"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "076934",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "STARTED ON 25 MG AND HIKED TO 150 MG OVER 4 WEEKS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "076934",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "150 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "OBSESSIVE-COMPULSIVE DISORDER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "150",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE"
}
],
"patientagegroup": null,
"patientonsetage": "18",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Tremor",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Headache",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Obsessive-compulsive disorder",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "UMESH S,SINHA V. ACUTE HIGH DOSE LITHIUM-INDUCED EXACERBATION OF OBSESSIVE COMPULSIVE SYMPTOMS. TOXICOL INT 2014 MAY;21:2:222-223.",
"literaturereference_normalized": "acute high dose lithium induced exacerbation of obsessive compulsive symptoms",
"qualification": "3",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "IN",
"receiptdate": "20141015",
"receivedate": "20141015",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10519770,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150528"
}
] |
{
"abstract": "To determine what issues are experienced during the first few weeks of therapy by patients, and their parents/carers, when a child/young person has been prescribed a new medicine.\nOne hundred patients aged ≤18 years of age prescribed a new medicine for ≥6 weeks were recruited from a single UK National Health Service specialist paediatric hospital outpatient pharmacy. Six weeks after the first dispensing of their new medicine the patient or their parent/carer received telephone follow-up by a researcher and verbally completed a questionnaire containing both open and closed questions. Patient or parent/carer experiences were identified and analysed using thematic analysis and descriptive statistics.\nEighty-six participants were available for telephone follow-up. Six (7%) had not started their medicine. Paediatric patients and their parents/carers experienced a range of issues during the first few weeks after starting a new medicine. These included additional concerns/questions (24/80, 30%), administration issues (21/80, 26.3%), adverse effects (29/80, 36.3%) and obtaining repeat supplies (12/80, 15%). The Morisky Medication Adherence Scale indicated that 34/78 (43.6%) participants had a high adherence rating, 35/78 (44.9%) medium and 9/78 (11.5%) a low rating.\nPaediatric patients and their parents/carers experience a range of issues during the first few weeks after starting a new medicine. Further research is required to determine the type of interventions that may further support medicines use in this group of patients.",
"affiliations": "Pharmacy Department, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.;School of Life and Health Sciences, Aston University, Birmingham, UK.;Pharmacy Department, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.;School of Life and Health Sciences, Aston University, Birmingham, UK.",
"authors": "Aston|Jeff|J|;Wilson|Keith A|KA|;Sinclair|Anthony|A|;Terry|David|D|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1136/ejhpharm-2016-000925",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2047-9956",
"issue": "24(5)",
"journal": "European journal of hospital pharmacy : science and practice",
"keywords": "CLINICAL PHARMACY; PAEDIATRICS; medication adherence; medication therapy management; united kingdom",
"medline_ta": "Eur J Hosp Pharm",
"mesh_terms": null,
"nlm_unique_id": "101578294",
"other_id": null,
"pages": "266-271",
"pmc": null,
"pmid": "31156956",
"pubdate": "2017-09",
"publication_types": "D016428:Journal Article",
"references": "15175485;15327462;15527475;15948931;18453793;19119348;20706818;21219201;21458391;21953846;24289059;24593304;24777444;25412402",
"title": "A telephone survey to determine the experiences of children and their parents/carers, following the initiation of a new medicine.",
"title_normalized": "a telephone survey to determine the experiences of children and their parents carers following the initiation of a new medicine"
}
|
[
{
"companynumb": "GB-CIPLA LTD.-2017GB21035",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ATORVASTATIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "204846",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATORVASTATIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Jaundice",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ASTON J, WILSON KA, SINCLAIR A, TERRY D.. A TELEPHONE SURVEY TO DETERMINE THE EXPERIENCES OF CHILDREN AND THEIR PARENTS/CARERS, FOLLOWING THE INITIATION OF A NEW MEDICINE. EUR J HOSP PHARM. 2017?24:266 TO 271",
"literaturereference_normalized": "a telephone survey to determine the experiences of children and their parents carers following the initiation of a new medicine",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20180206",
"receivedate": "20171127",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14228345,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180508"
}
] |
{
"abstract": "BACKGROUND\nPythiosis is a serious life- and limb-threatening infection endemic to Thailand, but rarely seen in the Western hemisphere. Here, we present a unique case of vascular pythiosis initially managed with limb-sparing vascular bypass grafts complicated by a pseudoaneurysm in our repair.\n\n\nMETHODS\nThe patient is a 17 year-old Jamaican male with severe aplastic anemia. He sustained a minor injury to his left leg while fishing in Jamaica, which evolved to become an exquisitely tender inguinal swelling. His physical exam and imaging were significant for arteriovenous fistula with limb ischemia. Pathology obtained during surgery for an extra-anatomic vascular bypass showed extensive invasion by Pythium insidiosum. He later developed a pseudoaneurysm at the site of proximal anastomosis and required urgent intervention.\n\n\nCONCLUSIONS\nThis patient presented with a rare, but classic case of vascular pythiosis, which was unrecognized at the time of presentation. A variety of therapeutic modalities have been used to treat this disease, including antibiotics, antifungals, and immunotherapy, but the ultimate management of vascular pythiosis is surgical source control.\n\n\nCONCLUSIONS\nA high index of suspicion in susceptible patients is needed for timely diagnosis of vascular pythiosis to achieve optimal source control.",
"affiliations": "Surgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.;Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.;National Institute of Health (NIH), Heart Center at Suburban Hospital, Bethesda, MD 20814, USA.;Surgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.;Surgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: [email protected].",
"authors": "Pan|Jenny H|JH|;Kerkar|Sid P|SP|;Siegenthaler|Michael P|MP|;Hughes|Marybeth|M|;Pandalai|Prakash K|PK|",
"chemical_list": null,
"country": "Netherlands",
"delete": false,
"doi": null,
"fulltext": "\n==== Front\nInt J Surg Case RepInt J Surg Case RepInternational Journal of Surgery Case Reports2210-2612Elsevier S2210-2612(14)00132-110.1016/j.ijscr.2014.05.018ArticleA complicated case of vascular Pythium insidiosum infection treated with limb-sparing surgery Pan Jenny H. aKerkar Sid P. bSiegenthaler Michael P. cHughes Marybeth aPandalai Prakash K. [email protected]@gmail.coma⁎a Surgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USAb Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USAc National Institute of Health (NIH), Heart Center at Suburban Hospital, Bethesda, MD 20814, USA⁎ Correspondence to: Center for Cancer Research, NCI, NIH, 10 Center Drive, Rm 3-3940, Bethesda, MD 20892, USA. Tel.: +1 301 496 4164. [email protected]@gmail.com01 8 2014 01 8 2014 2014 5 10 677 680 26 1 2014 2 5 2014 29 5 2014 This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).INTRODUCTION\nPythiosis is a serious life- and limb-threatening infection endemic to Thailand, but rarely seen in the Western hemisphere. Here, we present a unique case of vascular pythiosis initially managed with limb-sparing vascular bypass grafts complicated by a pseudoaneurysm in our repair.\n\nPRESENTATION OF CASE\nThe patient is a 17 year-old Jamaican male with severe aplastic anemia. He sustained a minor injury to his left leg while fishing in Jamaica, which evolved to become an exquisitely tender inguinal swelling. His physical exam and imaging were significant for arteriovenous fistula with limb ischemia. Pathology obtained during surgery for an extra-anatomic vascular bypass showed extensive invasion by Pythium insidiosum. He later developed a pseudoaneurysm at the site of proximal anastomosis and required urgent intervention.\n\nDISCUSSION\nThis patient presented with a rare, but classic case of vascular pythiosis, which was unrecognized at the time of presentation. A variety of therapeutic modalities have been used to treat this disease, including antibiotics, antifungals, and immunotherapy, but the ultimate management of vascular pythiosis is surgical source control.\n\nCONCLUSION\nA high index of suspicion in susceptible patients is needed for timely diagnosis of vascular pythiosis to achieve optimal source control.\n\nKeywords\nPythium insidiosumPythiosisVascular bypassPseudoaneurysm\n==== Body\n1 Introduction\nFirst described by veterinarians,1 pythiosis is a serious life- and limb-threatening infection endemic to Thailand, but rarely seen in the Western hemisphere.2 Known to infect immunocompetent horses, dogs, and other large animals,2, 3\nPythium infection was first reported in humans in 1989 in association with thalassemic hemoglobinopathy.4, 5 Human pythiosis is known to present in one of four clinical entities: subcutaneous, ocular, vascular, and disseminated.6 Here, we present a unique case of vascular pythiosis managed with limb-sparing vascular bypass grafts complicated by pseudoaneurysm formation.\n\n2 Presentation of case\nThe patient is a 17 year-old Jamaican male with a history of paroxysmal nocturnal hemoglobinuria and severe aplastic anemia refractory to horse anti-thymoglobulin treatment, which was transfusion-dependent. One month prior to admission at our institution, he went fishing in a fresh water pond in Jamaica and his left lower leg was caught in a bush. On the following day, he noticed a small bullae with a black center and later developed severely painful left inguinal swelling. He was admitted to a local hospital for the next several weeks, where all diagnostic testing performed was unremarkable. His pain persisted despite antibiotic and antifungal therapy, and he was later transferred to our institution for consideration of bone marrow transplant.\n\nOn admission, he was a febrile with a white blood cell count of 6.2 (K/μL) and platelet count of 18 (K/μL) and was complaining of severe left leg pain. He had a 9 × 8 cm2 soft tissue defect with overlying escar on the posterior aspect of his left leg (Fig. 1A), and his exam was also notable for an exquisitely tender and erythematous left inguinal mass. Motor and sensory exam were intact in both lower extremities without pain upon passive hip flexion. Several small, dark macules were noted along the lateral aspect of his left foot (Fig. 1B) and his left dorsalis pedis pulse was weaker than the right. Most significantly, he exhibited pain out of proportion to exam findings.\n\nMRI showed a T2 bright left groin mass with edema along the fascial planes, and lower extremity angiogram demonstrated occlusion of the left common femoral artery with distal profunda femoris and mid-superficial femoral artery reconstitution (Fig. 2). Due to the length of the diseased vessel, the patient was not a candidate for percutaneous intervention, and was taken to the operating room for exploration. Visual inspection of the common femoral artery after exposure was significant for several patches of necrotic vessel wall. Initial attempt with thrombectomy was unsuccessful, as the Fogarty catheter actually perforated the anterior wall at the areas of necrosis. The patient ultimately received an extra-anatomic left external iliac to superficial femoral artery bypass using a nonreversed greater saphenous vein graft, as the external iliac was the closest available inflow that did not visually appear to be involved with the infection.\n\nIntraoperative wound cultures were positive for Pythium insidiosum and the patient was started on a combination of voriconazole, terbinafine, and amphotericin B. Given his critical condition, an emergency Investigational New Drug request was drafted for permission to administer a P. insidiosum antigen vaccine available for compassionate use from the Pan American Veterinary Laboratories. The vaccine was given once daily in one-week intervals in conjunction with subcutaneously injected interferon gamma (IFN-γ), for a total of four weeks. Iron chelation therapy was also started as adjunctive treatment.\n\nThree weeks after his initial surgery, the patient developed new sites of pain along the graft site and repeat imaging showed a 2.5 cm pseudoaneurysm at the proximal anastomosis to the external iliac artery with contrast extravasation (Fig. 3). He was taken to the operating room for an extra-anatomic left common iliac artery to the previous femoral popliteal bypass graft using a reverse saphenous vein graft. Staining of intraoperative tissue demonstrated an extremely high burden of fungal elements (Fig. 4), indicating that the pythium infection remained uncontrolled. The patient later developed a polymicrobial superinfection of his wounds, and his vascular repair continued to break down leading to increased ischemic pain. After several multidisciplinary discussions with the family that all medical interventions were exhausted, and that even highly aggressive surgical measures including hip disarticulation or hemipelvectomy could not guarantee source control, conservative measures were initiated and ultimately, the patient expired.\n\n3 Discussion\nThis patient presented a major diagnostic challenge, and his disease process and subsequent management were previously unknown to our hospital. In retrospect, he presented with a classic case of vascular pythiosis, with an antecedent history of exposure to surface water and exam findings of vascular insufficiency, including pain out of proportion to exam, distal emboli, and an ischemic ulcer. The correct infectious diagnosis was not made until 1 month after exposure, after a vascular bypass was already performed. Indeed, in a large multi-institutional study from Thailand with a total of 102 cases of pythiosis,7 60 patients received a diagnosis of vascular pythiosis, and only the patients who had undergone amputation survived. Further review of the literature for reports of vascular pythiosis demonstrated that the majority of patients were treated with amputation without any signs of recurrence, and were followed for 5 to 35 months post-operatively.4, 6, 8, 9 In our case, complete source control was not achieved during the first operation since the common femoral artery and the proximal portion of the superficial femoral artery were oversewn and left in place, standard practice for the treatment of peripheral arterial disease. Incomplete source control eventually led to development of a pseudoaneurysm at the proximal anastomosis and additional surgery. While the second repair was cited in previously uninvolved tissue planes, it did not protect against further infection, likely because P. insidiosum is known to invade through proteinase secretion.10 The authors could find no reported cases of confirmed vascular pythiosis treated with limb-sparing procedures.2, 7, 11, 12\n\nMedical therapy in the treatment of vascular pythiosis involves antifungal agents, immunotherapy, and iron chelation therapy.13 Much of the difficulty in eradicating this organism stems from its complicated phylogenesis;2, 6, 14 it shares features with true fungi at the same time it is phylogenetically more closely related to algae and diatomeae.14\nP. insidiosum develops mycelium like fungi, but its cell walls do not contain chitin and its cytoplasmic membrane lacks ergosterol,2 both of which are important targets of traditional antifungal drugs. Despite this, drugs that affect cellular permeability, including amphotericin B, terbinafine, and the azoles, have been used with some clinical success.2, 15\n\nMore recently, immunotherapy has been used as an adjunct to surgery and antimycotics. Immunotherapy was first successfully used in humans in 1998 in a patient with a vascular P. insidiosum infection refractory to surgery and antifungals.2, 16 A P. insidiosum vaccine delivered twice with a two-week interval resulted in a cure 1 year later. Data collected from clinical trials and other reports estimate vaccine efficacy to be 55–60%.2, 17 The proposed mechanism of action of the P. insidiosum vaccine is to shift host adaptive immune response from a predominantly T helper 2 (Th2) response to a T helper 1 (Th1) response.2, 17\nPythium exoantigens are typically processed by antigen presenting cells (APCs) and presented to naïve CD4+ helper T cells (Th0). This induces Th0 cells to adopt a Th2 phenotype secreting IL-4 and IL-5, which trigger many downstream effects, including mast cell and eosinophil migration to the site of infection with subsequent degranulation, releasing inflammatory mediators and causing tissue damage. Loss of tissue architecture then creates a more favorable environment for these pathogenic hyphae to take hold. Conversion of a Th2 to Th1 response would favor secretion of IFN-γ and IL-2, leading to increased cytotoxic T lymphocyte recruitment and therefore, direct killing of P. insidiosum. In this case, the purpose of injecting IFN-γ subcutaneously was to augment a Th1 response, and co-administration of GM-CSF was to increase the efficiency of exoantigen presentation to APCs.\n\nAnother treatment modality used to control this infection is iron chelation therapy. Given the association between pythium infection in patients with hemoglobinopathies with a long-standing history of blood transfusions4, 7 and the discovery of a ferrochelatase gene in P. insidiosum,18 other research efforts have focused on elucidating the role of iron overload in P. insidiosum pathogenesis.13 There is evidence that iron overload from transfusions contributes to derangements in host immunity by impairing lymphocyte function and altering phagocytosis, leading to a more susceptible state for infection6, 19 and is in fact, a key virulence factor for the survival of P. insidiosum in the host.13 Correcting iron overload has been cited as a treatment in infections common in thalassemia,20 and has also been used in pythiosis. In our patient, iron chelation with deferasirox seemed to achieve some symptom relief.\n\n4 Conclusion\nIn conclusion, this patient's vascular P. insidiosum infection was refractory to optimized medical treatment, immunotherapy with cytokine injections, and surgery. Attempted source control with limb salvage necessitating vascular bypass was unsuccessful in treating this case of vascular pythiosis.\n\nConflict of interest\nThe authors have no conflicts of interest.\n\nEthical approval\nWritten informed consent was obtained from the patient's guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.Key learning points\n• Clinicians should maintain a high level of suspicion for vascular pythiosis when presented with a patient with an underlying hemoglobinopathy, exposure to flat water, and exam findings of vascular insufficiency.\n\n• The most important part in managing vascular pythiosis limb infection is adequate source control with amputation.\n\n\n\n\n\nAcknowledgments\nThis research was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute.\n\nFig. 1 (A) Ischemic ulcer with overlying escar and (B) distal emboli.\n\nFig. 2 (A) Left common femoral artery occlusion with distal profunda femoris reconstitution with (B) small and underperfused superficial femoral artery with mid-vessel reconstitution.\n\nFig. 3 Left external iliac artery pseudoaneurysm (A) axial and (B) coronal section.\n\nFig. 4 (A) Hematoxylin and eosin staining of pseudoaneurysm wall shown at 10× demonstrating extensive vessel wall necrosis and (B) Grocott's methenamine silver stain of pseudoaneurysm showing clusters of Pythium.\n==== Refs\nReferences\n1 Smith F. The pathology of bursattee Vet J 19 1884 16 17 \n2 Gaastra W. Lipman L.J. De Cock A.W. Exel T.K. Pegge R.B. Scheurwater J. Pythium insidiosum: an overview Vet Microbiol 146 1–2 2010 1 16 20800978 \n3 De Cock A.W. Mendoza L. Padhye A.A. Ajello L. Kaufman L. Pythium insidiosum sp. nov., the etiologic agent of pythiosis J Clin Microbiol 25 2 1987 344 349 3818928 \n4 Sathapatayavongs B. Leelachaikul P. Prachaktam R. Atichartakarn V. Sriphojanart S. Trairatvorakul P. Human pythiosis associated with thalassemia hemoglobinopathy syndrome J Infect Dis 159 2 1989 274 280 2644370 \n5 Thianprasit M. Fungal infection in Thailand Jpn J Dermatol 96 1986 1343 1345 \n6 Laohapensang K. Rutherford R.B. Supabandhu J. Vanittanakom N. Vascular pythiosis in a thalassemic patient Vascular 17 4 2009 234 238 19698307 \n7 Krajaejun T. Sathapatayavongs B. Pracharktam R. Nitiyanant P. Leelachaikul P. Wanachiwanawin W. Clinical and epidemiological analyses of human pythiosis in Thailand Clin Infect Dis 43 5 2006 569 576 16886148 \n8 Sudjaritruk T. Sirisanthana V. Successful treatment of a child with vascular pythiosis BMC Infect Dis 11 2011 33 21276255 \n9 Keoprasom N. Chularojanamontri L. Chayakulkeeree M. Chaiprasert A. Wanachiwanawin W. Ruangsetakit C. Vascular pythiosis in a thalassemic patient presenting as bilateral leg ulcers Med Mycol Case Rep 2 2012 25 28 24432209 \n10 Ravishankar J.P. Davis C.M. Davis D.J. MacDonald E. Makselan S.D. Millward L. Mechanics of solid tissue invasion by the mammalian pathogen Pythium insidiosum Fungal Genet Biol 34 3 2001 167 175 11728155 \n11 McMullan W.C. Joyce J.R. Hanselka D.V. Heitmann J.M. Amphotericin B. for the treatment of localized subcutaneous phycomycosis in the horse J Am Vet Med Assoc 170 11 1977 1293 1298 863774 \n12 Mendoza L. Alfaro A.A. Equine pythiosis in Costa Rica: report of 39 cases Mycopathologia 94 2 1986 123 129 3088454 \n13 Zanette R.A. Alves S.H. Pilotto M.B. Weiblen C. Fighera R.A. Wolkmer P. Iron chelation therapy as a treatment for Pythium insidiosum in an animal model J Antimicrob Chemother 68 5 2013 1144 1147 23329785 \n14 Martin F.N. Tooley P.W. Phylogenetic relationships among Phytophthora species inferred from sequence analysis of mitochondrially encoded cytochrome oxidase I and II genes Mycologia 95 2 2003 269 284 21156613 \n15 Shenep J.L. English B.K. Kaufman L. Pearson T.A. Thompson J.W. Kaufman R.A. Successful medical therapy for deeply invasive facial infection due to Pythium insidiosum in a child Clin Infect Dis 27 6 1998 1388 1393 9868648 \n16 Thitithanyanont A. Mendoza L. Chuansumrit A. Pracharktam R. Laothamatas J. Sathapatayavongs B. Use of an immunotherapeutic vaccine to treat a life-threatening human arteritic infection caused by Pythium insidiosum Clin Infect Dis 27 6 1998 1394 1400 9868649 \n17 Mendoza L. Newton J.C. Immunology and immunotherapy of the infections caused by Pythium insidiosum Med Mycol 43 6 2005 477 486 16320491 \n18 Krajaejun T. Khositnithikul R. Lerksuthirat T. Lowhnoo T. Rujirawat T. Petchthong T. Expressed sequence tags reveal genetic diversity and putative virulence factors of the pathogenic oomycete Pythium insidiosum Fungal Biol 115 7 2011 683 696 21724174 \n19 Walker E.M. Jr. Walker S.M. Effects of iron overload on the immune system Ann Clin Lab Sci 30 4 2000 354 365 11045759 \n20 Wanachiwanawin W. Infections in E-beta thalassemia J Pediatr Hematol Oncol 22 6 2000 581 587 11132234\n\n",
"fulltext_license": "CC BY-NC-SA",
"issn_linking": "2210-2612",
"issue": "5(10)",
"journal": "International journal of surgery case reports",
"keywords": "Pseudoaneurysm; Pythiosis; Pythium insidiosum; Vascular bypass",
"medline_ta": "Int J Surg Case Rep",
"mesh_terms": null,
"nlm_unique_id": "101529872",
"other_id": null,
"pages": "677-80",
"pmc": null,
"pmid": "25194603",
"pubdate": "2014",
"publication_types": "D016428:Journal Article",
"references": "3818928;9868648;11728155;2644370;3088454;21156613;21724174;24432209;9868649;21276255;23329785;16320491;11132234;19698307;20800978;11045759;863774;16886148",
"title": "A complicated case of vascular Pythium insidiosum infection treated with limb-sparing surgery.",
"title_normalized": "a complicated case of vascular pythium insidiosum infection treated with limb sparing surgery"
}
|
[
{
"companynumb": "PHHY2014US151633",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PYTHIUM INSIDIOSUM INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INTERFERON GAMMA"
},
"drugadditional": null,
"drugadministrationroute": "058",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PYTHIUM INSIDIOSUM INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INTERFERON GAMMA NOS"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VORICONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "200265",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PYTHIUM INSIDIOSUM INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VORICONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TERBINAFINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PYTHIUM INSIDIOSUM INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TERBINAFINE"
}
],
"patientagegroup": null,
"patientonsetage": "17",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Death",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PANDALAI PK, PAN JH, KERKAR SP, SIEGENTHALER MP, HUGHES M. A COMPLICATED CASE OF VASCULAR PYTHIUM INSIDIOSUM INFECTION TREATED WITH LIMB-SPARING SURGERY.. INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS",
"literaturereference_normalized": "a complicated case of vascular pythium insidiosum infection treated with limb sparing surgery",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20141201",
"receivedate": "20141201",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 10617460,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20150529"
}
] |
{
"abstract": "We report a case of a 29-year-old man with schizoaffective disorder in which diabetes mellitus and hypertriglyceridemia developed with quetiapine (Seroquels). We reviewed the literature on the relationship between antipsychotic therapy and development of metabolic disorders and found serious concerns. This case demonstrates the importance of a careful monitoring of glucose and other metabolic parameters in patients receiving atypical antipsychotics.",
"affiliations": "Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA.",
"authors": "Yamauchi|Teruo|T|;Tice|Alan|A|",
"chemical_list": "D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate",
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0017-8594",
"issue": "66(1)",
"journal": "Hawaii medical journal",
"keywords": null,
"medline_ta": "Hawaii Med J",
"mesh_terms": "D000328:Adult; D014150:Antipsychotic Agents; D003920:Diabetes Mellitus; D003987:Dibenzothiazepines; D006801:Humans; D015228:Hypertriglyceridemia; D008297:Male; D011618:Psychotic Disorders; D000069348:Quetiapine Fumarate; D012307:Risk Factors",
"nlm_unique_id": "2984209R",
"other_id": null,
"pages": "12-3",
"pmc": null,
"pmid": "17381036",
"pubdate": "2007-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Metabolic abnormalities associated with atypical antipsychotics: a case report and alert.",
"title_normalized": "metabolic abnormalities associated with atypical antipsychotics a case report and alert"
}
|
[
{
"companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2018-03001",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "QUETIAPINE FUMARATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "201504",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "QUETIAPINE FUMARATE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Diabetes mellitus",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypertriglyceridaemia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "YAMAUCHI T AND TICE A. METABOLIC ABNORMALITIES ASSOCIATED WITH ATYPICAL ANTIPSYCHOTICS: A CASE REPORT AND ALERT. HAWAII MED J.. 2007?1:12-13",
"literaturereference_normalized": "metabolic abnormalities associated with atypical antipsychotics a case report and alert",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190412",
"receivedate": "20190412",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16189915,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190711"
}
] |
{
"abstract": "A 71-year-old man is admitted for nose bleeds recurring for several days. His medical background shows in particular major depression for which he has been receiving sertraline for several years. The workup shows anemia, and no anomalies on head and neck CT angiography. However, further explorations suggest an acquired thrombopathy that could have contributed to the bleeding. During sertraline exposure, platelet functional exploration and platelet secretion were abnormal. Sertraline is often used as first-line treatment of depression. Pharmacological data and spontaneous notifications suggest increased potential risk with sertraline. It appears necessary to pay attention to bleeding with sertraline use.",
"affiliations": "Centre Régional de Pharmacovigilance et d'information sur les médicaments Toulouse, 37 allées Jules Guesdes, Toulouse, 31000, France.;Hôpital de Rangueil - Laboratoire d'hématologie, Toulouse, Midi-Pyrénées, France.;Hôpital de Rangueil - Laboratoire d'hématologie, Toulouse, Midi-Pyrénées, France.;Hôpital de Rangueil - Laboratoire d'hématologie, Toulouse, Midi-Pyrénées, France.;Inserm - Inserm U563, CHU-Purpan, Toulouse, 31024, France.;Universite Toulouse III Paul Sabatier Faculte de Medecine Purpan - Epidémiologie et Analyses en Santé Publique, Toulouse, 31000, France.",
"authors": "Strumia|Mathilde|M|;Guerrero|Felipe|F|;Maurel-Ribes|Agnès|A|;Garcia|Cédric|C|;Payrastre|Bernard|B|;Bagheri|Haleh|H|",
"chemical_list": "D017367:Serotonin Uptake Inhibitors; D020280:Sertraline",
"country": "England",
"delete": false,
"doi": "10.1111/fcp.12552",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0767-3981",
"issue": "34(5)",
"journal": "Fundamental & clinical pharmacology",
"keywords": "hemorrhage; long-term adverse effects; platelet aggregation; sertraline",
"medline_ta": "Fundam Clin Pharmacol",
"mesh_terms": "D000368:Aged; D001792:Blood Platelets; D003866:Depressive Disorder; D003937:Diagnosis, Differential; D004844:Epistaxis; D006801:Humans; D008297:Male; D017367:Serotonin Uptake Inhibitors; D020280:Sertraline",
"nlm_unique_id": "8710411",
"other_id": null,
"pages": "632-636",
"pmc": null,
"pmid": "32125025",
"pubdate": "2020-10",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Platelet function defects and sertraline-induced bleeding: a case report.",
"title_normalized": "platelet function defects and sertraline induced bleeding a case report"
}
|
[
{
"companynumb": "FR-TEVA-2020-FR-1835323",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PAROXETINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "76618",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MAJOR DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2017",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PAROXETINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR SEVERAL YEARS",
"drugenddate": "20171109",
"drugenddateformat": "102",
"drugindication": "MAJOR DEPRESSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE"
}
],
"patientagegroup": "6",
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Platelet dysfunction",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Epistaxis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "STRUMIA M, GUERRERO F, MAUREL-RIBES A, GARCIA C, PAYRASTRE B, BAGHERI H. PLATELET FUNCTION DEFECTS AND SERTRALINE-INDUCED BLEEDING: A CASE REPORT. FUNDAM-CLIN-PHARMACOL 2020?34(5):632-636.",
"literaturereference_normalized": "platelet function defects and sertraline induced bleeding a case report",
"qualification": "3",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20201005",
"receivedate": "20201005",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18343224,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210113"
},
{
"companynumb": "FR-PFIZER INC-2019502458",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": "1",
"drugadministrationroute": "048",
"drugauthorizationnumb": "019839",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG, 1X/DAY",
"drugenddate": "20171109",
"drugenddateformat": "102",
"drugindication": "MAJOR DEPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE HCL"
}
],
"patientagegroup": null,
"patientonsetage": "71",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": "82",
"reaction": [
{
"reactionmeddrapt": "Anaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Epistaxis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Platelet aggregation abnormal",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Platelet function test abnormal",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 20151201"
}
},
"primarysource": {
"literaturereference": "STRUMIA, M.. PLATELET FUNCTION DEFECTS AND SERTRALINE?INDUCED BLEEDING: A CASE REPORT. FUNDAMENTAL + CLINICAL PHARMACOLOGY. 2020?34 (5):632?636",
"literaturereference_normalized": "platelet function defects and sertraline induced bleeding a case report",
"qualification": "1",
"reportercountry": "FR"
},
"primarysourcecountry": "FR",
"receiptdate": "20200925",
"receivedate": "20191122",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17064394,
"safetyreportversion": 5,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20201102"
}
] |
{
"abstract": "BACKGROUND\nPrimary closure of the dura in posterior fossa (p-fossa) surgeries is technically difficult and usually requires the use of a dural substitute. A variety of substitutes are currently available and data suggest that autologous materials are preferred in comparison with nonautologous substitutes.\n\n\nOBJECTIVE\nTo report our experience using locally harvested autologous pericranium as a dural substitute in patients who underwent p-fossa surgeries.\n\n\nMETHODS\nRetrospective analysis of patients who had undergone p-fossa craniotomies between 2005 and 2011. All patients received locally harvested autologous pericranium for duraplasty augmented with a dural sealant. Data were reviewed for complications including: surgical site infection, meningitis, cerebrospinal fluid leak, the radiographic formation of a pseudomeningocele, and any new neurological symptoms related to the incision or repair.\n\n\nRESULTS\nOne hundred patients were identified. Indications for surgery included tumor, vascular lesions, or hemorrhage requiring surgical intervention, symptomatic Chiari I malformation, microvascular decompression for trigeminal neuralgia, and trauma requiring surgical decompression. The complication rate was 1% with 1 patient developing an nonsteroidal anti-inflammatory drug-induced aseptic meningitis and graft dehiscence requiring surgical revision.\n\n\nCONCLUSIONS\nAutologous pericranium with dural sealant augmentation is an effective way to repair the durotomy in p-fossa surgeries. To the best of our knowledge, this is currently the largest study using this technique in the adult neurosurgical literature. Our results report a much lower rate of complications in comparison with other duraplasty studies.",
"affiliations": "Division of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard University, 110 Francis St, Boston, MA 01125, USA.",
"authors": "Lam|Fred C|FC|;Kasper|Ekkehard|E|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1227/NEU.0b013e31826a8ab0",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0148-396X",
"issue": "71(2 Suppl Operative)",
"journal": "Neurosurgery",
"keywords": null,
"medline_ta": "Neurosurgery",
"mesh_terms": "D016025:Bone Transplantation; D003388:Cranial Fossa, Posterior; D003399:Craniotomy; D004388:Dura Mater; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019651:Reconstructive Surgical Procedures; D012189:Retrospective Studies; D014182:Transplantation, Autologous",
"nlm_unique_id": "7802914",
"other_id": null,
"pages": "ons302-7",
"pmc": null,
"pmid": "22843136",
"pubdate": "2012-12",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Augmented autologous pericranium duraplasty in 100 posterior fossa surgeries--a retrospective case series.",
"title_normalized": "augmented autologous pericranium duraplasty in 100 posterior fossa surgeries a retrospective case series"
}
|
[
{
"companynumb": "US-JNJFOC-20181025361",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FIBRINOGEN HUMAN\\THROMBIN HUMAN"
},
"drugadditional": null,
"drugadministrationroute": "061",
"drugauthorizationnumb": "125010",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HAEMOSTASIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "2",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EVICEL"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Dehiscence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cerebrospinal fluid leakage",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LAM FC, KASPER E. AUGMENTED AUTOLOGOUS PERICRANIUM DURAPLASTY IN 100 POSTERIOR FOSSA SURGERIES?A RETROSPECTIVE CASE SERIES. NEUROSURGERY 2012?71(2):302-307.",
"literaturereference_normalized": "augmented autologous pericranium duraplasty in 100 posterior fossa surgeries a retrospective case series",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181026",
"receivedate": "20181026",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15556769,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190205"
}
] |
{
"abstract": "Histoplasmosis is an endemic mycosis in some areas of North and South America. This disease is usually asymptomatic, but it can result in severe and disseminated infection involving gastrointestinal tract, especially in immunocompromised individuals. We report a case of a 33-years-old Ecuadorian male treated with infliximab who developed disseminated histoplasmosis with gastrointestinal affection. Due to the non-specific presentation of gastrointestinal histoplasmosis, the diagnosis is often delayed and it causes poor outcomes. It is important to consider this diagnosis in immunocompromised patients with compatible symptoms, like patients on TNF inhibitors.",
"affiliations": "Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain. [email protected].;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.;Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, C/França SN, 17007, Girona, Spain.",
"authors": "Oliveras|Berta|B|http://orcid.org/0000-0002-7529-2998;Albert|Marc|M|;López|Carme|C|;Fort|Esther|E|;Peries|Laia|L|;Gutiérrez|Laia|L|;Busquets|David|D|;Uchima|Hugo|H|;Aldeguer|Xavier|X|;Piñol|Virginia|V|",
"chemical_list": "D000069285:Infliximab",
"country": "Japan",
"delete": false,
"doi": "10.1007/s12328-020-01298-y",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1865-7265",
"issue": "14(2)",
"journal": "Clinical journal of gastroenterology",
"keywords": "Case report; Gastrointestinal histoplasmosis; Infliximab",
"medline_ta": "Clin J Gastroenterol",
"mesh_terms": "D000328:Adult; D041981:Gastrointestinal Tract; D006660:Histoplasmosis; D006801:Humans; D016867:Immunocompromised Host; D000069285:Infliximab; D008297:Male",
"nlm_unique_id": "101477246",
"other_id": null,
"pages": "690-692",
"pmc": null,
"pmid": "33231849",
"pubdate": "2021-04",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "30210949",
"title": "A case report of gastrointestinal histoplasmosis in a patient treated with infliximab.",
"title_normalized": "a case report of gastrointestinal histoplasmosis in a patient treated with infliximab"
}
|
[
{
"companynumb": "ES-SAMSUNG BIOEPIS-SB-2020-36383",
"fulfillexpeditecriteria": "1",
"occurcountry": "EC",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "INFLIXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNKNOWN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "JUVENILE IDIOPATHIC ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2016",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INFLIXIMAB"
}
],
"patientagegroup": "5",
"patientonsetage": "33",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Histoplasmosis disseminated",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 201712"
}
},
"primarysource": {
"literaturereference": "OLIVERAS B, ALBERT M, LOPEZ C, FORT E, PERIES L, GUTIERREZ L, BUSQUETS D, UCHIMA H, ALDEGUER X, PINOL V. A CASE REPORT OF GASTROINTESTINAL HISTOPLASMOSIS IN A PATIENT TREATED WITH INFLIXIMAB. CLINICAL JOURNAL OF GASTROENTEROLOGY. 2020 NOV 24?. DOI:10.1007/S12328-020-01298-Y",
"literaturereference_normalized": "a case report of gastrointestinal histoplasmosis in a patient treated with infliximab",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20201208",
"receivedate": "20201208",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18591242,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210114"
},
{
"companynumb": "ES-JNJFOC-20201149148",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "INFLIXIMAB"
},
"drugadditional": "1",
"drugadministrationroute": "042",
"drugauthorizationnumb": "103772",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INFUSION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "JUVENILE IDIOPATHIC ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2016",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REMICADE"
}
],
"patientagegroup": "5",
"patientonsetage": "33",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Histoplasmosis disseminated",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "OLIVERAS B, LOPEZ C, FORT E, PERIES L, GUTIERREZ L, BUSQUETS D, UCHIMA H, ALDEGUER X, PINOL V, ALBERT M. A CASE REPORT OF GASTROINTESTINAL HISTOPLASMOSIS IN A PATIENT TREATED WITH INFLIXIMAB. CLIN J GASTROENTEROL. 2020?1-3.",
"literaturereference_normalized": "a case report of gastrointestinal histoplasmosis in a patient treated with infliximab",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20201201",
"receivedate": "20201201",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18567460,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
},
{
"companynumb": "ES-CELLTRION INC.-2021ES004204",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "INFLIXIMAB"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "POWDER FOR SOLUTION FOR INFUSION",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "JUVENILE IDIOPATHIC ARTHRITIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": "2016",
"drugstartdateformat": "602",
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INFLIXIMAB (UNKNOWN)"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Histoplasmosis disseminated",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Large intestine perforation",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Colectomy",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Ileostomy",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2016"
}
},
"primarysource": {
"literaturereference": "OLIVERAS, B.. A CASE REPORT OF GASTROINTESTINAL HISTOPLASMOSIS IN A PATIENT TREATED WITH INFLIXIMAB.. CLINICAL JOURNAL OF GASTROENTEROLOGY. 2020",
"literaturereference_normalized": "a case report of gastrointestinal histoplasmosis in a patient treated with infliximab",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20210726",
"receivedate": "20210331",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19075613,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
}
] |
{
"abstract": "Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100 × 109/l) in the absence of other causes or disorders associated. The incidence of ITP in pregnancy is one to two cases per 1000 gestations. ITP could be diagnosed before or during pregnancy; sometimes a relapse of a previously diagnosed ITP can occur. Intravenous immune globulins (IVIg) and corticosteroids are the standard frontline therapy because of their well known safety profile either for the mother or for the neonate. Treatments for refractory patients are limited by potential fetal risk. We report the case of a patient with ITP along pregnancy, refractory to corticosteroids and IVIg, successfully treated with, the thrombopoietin receptor agonist (TPO-RA) eltrombopag. Patient received this compound for almost the whole pregnancy and in particular for the whole first trimester, without any complication for the mother and the neonate. Although transient administration of TPO-RAs in pregnancy seems to be well tolerated, their use during the whole gestation is still controversial; this is the reason of the description of this case, which did not show any complications, and thus it could add useful information on this field.",
"affiliations": "Hematology Unit AO of Cosenza, Cosenza.;Hematology, University Hospital Policlinico Umberto I.;Hematology Unit AO of Cosenza, Cosenza.;Hematology Unit AO of Cosenza, Cosenza.;Hematology, University Hospital Policlinico Umberto I.;Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome.;Obstetrics and Ginecology Unit AUSL of Parma, Parma.;Hematology Unit AO of Cosenza, Cosenza.;Hematology Unit AO of Cosenza, Cosenza.;Hematology Unit AO of Cosenza, Cosenza.;Obstetrics and Gynecology Unit AO of Cosenza, Cosenza, Italy.;Hematology Unit AO of Cosenza, Cosenza.",
"authors": "Mendicino|Francesco|F|;Santoro|Cristina|C|;Martino|Enrica|E|;Botta|Cirino|C|;Baldacci|Erminia|E|;Ferretti|Antonietta|A|;Muto|Brunella|B|;Lucia|Eugenio|E|;Caracciolo|Daniele|D|;Vigna|Ernesto|E|;Morelli|Michele|M|;Gentile|Massimo|M|",
"chemical_list": "D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C520809:eltrombopag",
"country": "England",
"delete": false,
"doi": "10.1097/MBC.0000000000001085",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0957-5235",
"issue": "32(7)",
"journal": "Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis",
"keywords": null,
"medline_ta": "Blood Coagul Fibrinolysis",
"mesh_terms": "D000293:Adolescent; D001565:Benzoates; D005260:Female; D006801:Humans; D006834:Hydrazines; D007231:Infant, Newborn; D010976:Platelet Count; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D016553:Purpura, Thrombocytopenic, Idiopathic; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin",
"nlm_unique_id": "9102551",
"other_id": null,
"pages": "519-521",
"pmc": null,
"pmid": "34520405",
"pubdate": "2021-10-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report.",
"title_normalized": "eltrombopag treatment for severe immune thrombocytopenia during pregnancy a case report"
}
|
[
{
"companynumb": "IT-NOVARTISPH-NVSC2021IT232795",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ELTROMBOPAG"
},
"drugadditional": "4",
"drugadministrationroute": "064",
"drugauthorizationnumb": "22291",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MATERNAL DOSE: 50 MG, QD (RANGING FROM 25-50)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Foetal exposure during pregnancy",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ELTROMBOPAG"
}
],
"patientagegroup": "1",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "2",
"patientweight": "2.28",
"reaction": [
{
"reactionmeddrapt": "Premature baby",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Low birth weight baby",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Foetal exposure during pregnancy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Mendicino F, Santoro C, Martino E, Botta C, Baldacci E, Ferretti A et al.. Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report. BLOOD COAGULATION AND FIBRINOLYSIS. 2021;30:1-3",
"literaturereference_normalized": "eltrombopag treatment for severe immune thrombocytopenia during pregnancy a case report",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20211219",
"receivedate": "20211015",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19958054,
"safetyreportversion": 3,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "IT-BEH-2021137075",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "080292",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM, QD 1 MG/KG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Immune thrombocytopenia",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ERYTHROMYCIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Streptococcal abscess",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ERYTHROMYCIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ERYTHROMYCIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Breast abscess",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ERYTHROMYCIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": "4",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Injection",
"drugdosagetext": "1 GRAM PER KILOGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Immune thrombocytopenia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HUMAN IMMUNOGLOBULIN G"
}
],
"patientagegroup": null,
"patientonsetage": "21",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Abortion spontaneous",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Breast abscess",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Streptococcal abscess",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Therapeutic product effect incomplete",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Maternal exposure during pregnancy",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Mendicino F., Santoro C., Martino E., Botta C., Baldacci E., Ferretti A et al.. Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report.. Blood coagulation + fibrinolysis : an international journal in haemostasis and t. 2021",
"literaturereference_normalized": "eltrombopag treatment for severe immune thrombocytopenia during pregnancy a case report",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20220608",
"receivedate": "20211208",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20162297,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220721"
},
{
"companynumb": "IT-SUN PHARMACEUTICAL INDUSTRIES LTD-2022R1-339856",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "089247",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Immune thrombocytopenia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ELTROMBOPAG"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Immune thrombocytopenia",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ELTROMBOPAG"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ELTROMBOPAG"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "25-50 MILLIGRAM, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ELTROMBOPAG"
}
],
"patientagegroup": null,
"patientonsetage": "23",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Exposure during pregnancy",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Premature delivery",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Mendicino F, Santoro C, Martino E, Botta C, Baldacci E, Ferretti A, et al. Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report. Blood Coagul Fibrinolysis. 2021;Oct;32(7):519-521",
"literaturereference_normalized": "eltrombopag treatment for severe immune thrombocytopenia during pregnancy a case report",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20220620",
"receivedate": "20220620",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20980410,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220720"
},
{
"companynumb": "IT-SUN PHARMACEUTICAL INDUSTRIES LTD-2022R1-341345",
"fulfillexpeditecriteria": "1",
"occurcountry": "IT",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "4",
"drugadministrationroute": "064",
"drugauthorizationnumb": "089247",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK MILLIGRAM, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Immune thrombocytopenia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ELTROMBOPAG"
},
"drugadditional": "4",
"drugadministrationroute": "064",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "25-50 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Immune thrombocytopenia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ELTROMBOPAG"
}
],
"patientagegroup": "1",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": "2.28",
"reaction": [
{
"reactionmeddrapt": "Foetal exposure during pregnancy",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Low birth weight baby",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Premature baby",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Mendicino F, Santoro C, Martino E, Botta C, Baldacci E, Ferretti A et al. Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report. Blood Coagul Fibrinolysis. 2021;32:519-21",
"literaturereference_normalized": "eltrombopag treatment for severe immune thrombocytopenia during pregnancy a case report",
"qualification": "3",
"reportercountry": "IT"
},
"primarysourcecountry": "IT",
"receiptdate": "20220621",
"receivedate": "20220621",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20983995,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220720"
}
] |
{
"abstract": "Temozolomide is an alkylating agent used in the treatment for glioblastoma multiforme (GBM), the most frequent primary malignant brain tumor in adults. Temozolomide was approved in March 2005 for treatment of GBM, with the Stupp protocol (radiotherapy and concomitant use of temozolomide). Despite initial studies demonstrating mild and well-tolerated side effects, several recent reports describe severe hematologic adverse effects associated with temozolomide use. We report the case of a 51-year-old female diagnosed with GBM who received the standard treatment protocol of radiotherapy and concomitant temozolomide. The patient developed prolonged pancytopenia. Bone marrow biopsy demonstrated hypocellular bone marrow with diminished trilineage hematopoiesis, suggestive of drug-induced aplastic anemia. Although temozolomide is regarded as a safe drug with few side effects, severe hematologic toxicities have been reported.",
"affiliations": "Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Bismarck, USA.;Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Bismarck, USA.;Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Bismarck, USA.",
"authors": "Newton|Shauna L|SL|;Kalamaha|Kadra|K|;Fernandes|Hermina D|HD|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.7759/cureus.3329",
"fulltext": "\n==== Front\nCureusCureus2168-8184Cureus2168-8184Cureus Palo Alto (CA) 10.7759/cureus.3329Internal MedicineOncologyOtherTemozolomide-induced Aplastic Anemia Treated with Eltrombopag and Granulocyte Colony Stimulating Factor: A Report of a Rare Complication Muacevic Alexander Adler John R Newton Shauna L 1Kalamaha Kadra 1Fernandes Hermina D 1\n1 \nInternal Medicine, University of North Dakota School of Medicine and Health Sciences, Bismarck, USA \nHermina D. Fernandes [email protected] 9 2018 9 2018 10 9 e332913 9 2018 18 9 2018 Copyright © 2018, Newton et al.2018Newton et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/15003-temozolomide-induced-aplastic-anemia-treated-with-eltrombopag-and-granulocyte-colony-stimulating-factor-a-report-of-a-rare-complicationTemozolomide is an alkylating agent used in the treatment for glioblastoma multiforme (GBM), the most frequent primary malignant brain tumor in adults. Temozolomide was approved in March 2005 for treatment of GBM, with the Stupp protocol (radiotherapy and concomitant use of temozolomide). Despite initial studies demonstrating mild and well-tolerated side effects, several recent reports describe severe hematologic adverse effects associated with temozolomide use. We report the case of a 51-year-old female diagnosed with GBM who received the standard treatment protocol of radiotherapy and concomitant temozolomide. The patient developed prolonged pancytopenia. Bone marrow biopsy demonstrated hypocellular bone marrow with diminished trilineage hematopoiesis, suggestive of drug-induced aplastic anemia. Although temozolomide is regarded as a safe drug with few side effects, severe hematologic toxicities have been reported.\n\ntemozolomideaplastic anaemiaglioblastoma multiforme (gbm)eltrombopagstupp protocolThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\nTemozolomide is an oral alkylating agent used as the first-line treatment for glioblastoma multiforme (GBM) [1]. Before its approval, standard therapy consisted of surgical resection, radiotherapy, and adjuvant carmustine [2]. The United States Food and Drug Administration (FDA) initially approved temozolomide in March 2005 [1]. The common side effects are well tolerated and include nausea, vomiting, constipation, fatigue, headache, with some of the more serious complications including myelosuppression and seizures [3]. Myelosuppression is the most severe side effect but considered dose limiting and reversible [1]. The Stupp protocol, which consists of radiotherapy with concomitant use of temozolomide followed by adjuvant temozolomide, is currently the standard of care [2]. Grade 3 and 4 hematologic toxic effects were observed in 14% of patients receiving adjuvant temozolomide therapy and in 7% of patients receiving concomitant radiotherapy with temozolomide during the clinical trial. No grade 3 or 4 hematologic toxic effects were observed with radiotherapy alone. Since its approval, several case studies have reported severe hematologic adverse events associated with temozolomide use. We describe the occurrence of aplastic anemia in a patient with GBM treated with surgical resection followed by concomitant temozolomide and radiation therapy.\n\nCase presentation\nA 51-year-old female with a history of asthma, hypertension, dyslipidemia, and atherosclerotic heart disease presented to the emergency department with seizures. Through magnetic resonance imaging (MRI) of the brain, three left-sided intracranial lesions associated with mild vasogenic edema were discovered. Because of the metastatic appearance of lesions and her history of smoking, computed tomography (CT) imaging of the chest, abdomen, and pelvis was performed to evaluate for other sites of primary malignancy. However, CT imaging showed no other sites of a primary malignancy. The patient was placed on levetiracetam for seizure prophylaxis and dexamethasone for treatment of vasogenic edema. After an evaluation by neurology and neurosurgery, she underwent a left-sided craniotomy for removal of a left frontal brain lesion. Initial frozen sections were suspicious for primary brain malignant neoplasm, and final pathology confirmed the diagnosis of GBM (WHO grade IV).\n\nHer initial treatment plan was temozolomide 75 mg/m2 once per day with concurrent radiation therapy, given in 30 fractions of 2 gray (Gy) five days per week for a total dose of 60 Gy, to be followed four weeks later by adjuvant temozolomide monotherapy at 150 mg/m2 a day for five days of a 28-day cycle [1,2]. Due to complications with insurance authorization, the temozolomide was started a week after her radiation therapy start date. Therefore, the patient received six weeks of radiation therapy and five weeks of temozolomide. No cytopenias were noted during her treatment course. She was prescribed trimethoprim-sulfamethoxazole (TMP-SMX) 800-160 mg once a day on Monday, Wednesday, and Friday for prophylaxis of Pneumocystis jiroveci infections. Home medications during concurrent temozolomide and radiation therapy included nebivolol, hydrocodone-acetaminophen, pantoprazole, triamterene-hydrochlorothiazide, lisinopril, albuterol, simvastatin, levetiracetam, dexamethasone, ondansetron, and TMP-SMX.\n\nOn day 54 following initial dose of temozolomide, she presented to the emergency department with epistaxis. Her complete blood cell count showed pancytopenia with a white blood cell count (WBC) of 0.4 K/µL (normal range: 4.0–11.0 K/µL), hemoglobin of 8.5 g/dL (normal range: 11.5–15.8 g/dL), and platelet count of 6 K/µL (normal range: 140–400 K/µL). The epistaxis was controlled with pressure and wound seal powder. The patient was also given two units of platelets for treatment of thrombocytopenia, which brought her platelet count to 78 K/µL (normal range: 140–400 K/µL). She was subsequently discharged home and instructed to follow up with oncology. During the follow-up appointment, her medication list was reviewed. The patient reported non-compliance with her oral TMP-SMX pill as prescribed. She was instructed to discontinue oral TMP-SMX and triamterene-hydrochlorothiazide to reduce the possibility of other drug-induced cytopenias.\n\nOn day 65 following initial dose of temozolomide, she continued to remain pancytopenic. She presented with confusion and altered mental status consistent with a postictal state and was hospitalized for concomitant hematemesis. She was febrile with a temperature of 101.7°F, pulse rate of 104 beats per minute, blood pressure of 93/73 mmHg, and respirations of 20 per minute. Abnormal lab values included a total WBC count of 0.7 K/µL (normal range: 4.0–11.0 K/µL), percentage of neutrophils at 1.5% with absolute neutrophil count (ANC) of 10.5 cells/µL, red blood cell count of 2.22 million/µL (normal range: 3.80–5.30 million/µL), hemoglobin of 7.1 g/dL (normal range: 11.5–15.8 g/dL), and platelet count of 11 K/µL (normal range: 140–400 K/µL) consistent with pancytopenia due to severe bone marrow suppression. The etiology of the pancytopenia was thought to be secondary to drug side effects and therefore, levetiracetam was discontinued and seizure prophylaxis was switched to lacosamide. Similar to aplastic anemia, the degree of bone marrow suppression was classified as “very severe” with depression of at least two of three cell lines, and ANC less than 200 cells/µL [4]. Since the pancytopenia persisted beyond 28 days after the last temozolomide dose (despite discontinuation of TMP-SMX, triamterene-hydrochlorothiazide and levetiracetam), it was attributed to temozolomide-induced bone marrow suppression [4]. Additional abnormalities include a chloride of 95 mEq/L (98–110 mEq/L), blood urea nitrogen of 28 mg/dL (normal range: 7–22 mg/dL), alanine amino transferase of 54 U/L (normal range: <40 U/L), albumin of 2.8 g/dL (normal range: 3.5–5.0 g/dL), C-reactive protein of 498 mg/L (normal range: <5.0 mg/L), glomerular filtration rate of 51 mL/min/1.73 m2 (normal range: >=60 mL/min/1.73 m2) and a prolactin 37.1 ng/mL (normal range: <23.0 ng/mL). Prothrombin time/International normalized ratio, troponin, ammonia, thyroid stimulating hormone, free T4, and partial thromboplastin time were within normal limits. Imaging studies with a CT brain to evaluate altered mentation in the setting of thrombocytopenia, showed no acute intracranial hemorrhage.\n\nThe patient was given supportive platelet transfusions to keep platelet counts greater than 50 K/µL, due to active clinical bleeding with hematemesis. She was given supportive erythropoietic transfusions with packed red blood cells (PRBCs). She was started on Granulocyte-Colony Stimulating Factor (G-CSF) to stimulate granulocytopoiesis and improve WBC counts. No further adjuvant temozolomide was administered. An esophagogastroduodenoscopy (EGD) was performed to evaluate etiology of hematemesis. This revealed esophageal ulcers with pathologic findings consistent with herpes simplex virus (HSV) esophagitis. Given her febrile neutropenia, she was started on empiric treatment with intravenous cefepime. She was also started on antifungal prophylaxis with fluconazole due to ongoing immunosuppression. The HSV esophagitis was treated with oral acyclovir. Her HSV esophagitis and fevers resolved with this treatment.\n\nThe patient continued to receive supportive treatment with G-CSF injections, PRBC, and platelet transfusions. A bone marrow biopsy was performed due to persisting pancytopenia on day 71 following initial dose of temozolomide. However, this was non-diagnostic due to dilute specimen. A repeat bone marrow biopsy was subsequently performed on day 77. The bone marrow biopsy and aspirate revealed predominantly trabecular bone with very little intact bone marrow. Myeloid maturation was markedly diminished and demonstrated a left shift. There were no increased blasts. Erythropoiesis was markedly diminished but without evidence of dyserythropoiesis. Rare nuclear irregularity was noted. Megakaryocytes were scarce to essentially absent. There were occasional lymphocytes and monocytes present. No significantly increased pathologic ringed sideroblasts were identified. Cellularity was estimated to be at less than 15%. Trilineage maturation was decreased overall. Normal female cytogenetics were noted. Flow cytometry revealed left shifted, immature granulocytes with CD56 expression on granulocytes and monocytes. These findings on her bone marrow biopsy revealed an aplastic or hypoplastic cause of pancytopenia, and were supportive of an acquired aplastic anemia.\n\nAfter confirming the etiology of pancytopenia by bone marrow biopsy, the oral thrombopoietin agonist eltrombopag was started to aid in count recovery while formulating a treatment plan for consideration of immunosuppression with cyclosporine and anti-thymocyte globulin (ATG) [4,5]. In addition to the eltrombopag, G-CSF injections, PRBC, and platelet transfusions were continued. Her ANC started to improve three days following initiation of eltrombopag with resolution of neutropenia nine days following initiation. She continued to exhibit an improvement of anemia requiring infrequent PRBC transfusions, and protracted but improving thrombocytopenia. G-CSF support was continued daily until her ANC improved to greater than 1500 cells/µL and then discontinued. The eltrombopag was discontinued after four weeks of use due to transaminitis. She was discharged from hospital due to a reasonable degree of hematopoietic recovery at day 131 following first dose of temozolomide. At the time of discharge, she had a stable and moderate anemia without transfusion support, had recovered her neutrophil counts, and platelet counts had recovered to 30 K/µL requiring infrequent (one to two times per month) platelet transfusions for goal platelets greater than 20 K/µL. Therefore, consideration of allogeneic hematopoietic stem cell transplantation (alloHSCT) was deferred. On day 314 following first dose of temozolomide, her platelet counts continued to improve, and were in the range of 80–90 K/µL unsupported by platelet transfusions.\n\nBevacizumab was considered as second-line treatment for her GBM but was not started when platelet counts were under 50 K/µL because of the risk of fatal hemorrhage in the setting of thrombocytopenia. Bevacizumab is known to inhibit vascular endothelial growth factor (VEGF) resulting in decreased matrix deposition in blood vessels, making them susceptible to bleeding [6]. Maintenance therapy with tumor-treating fields (TTF) with temozolomide had now been approved for newly diagnosed glioblastomas after surgery [7]. Our patient was then started on antineoplastic therapy with TTF without temozolomide to treat her GBM to which she exhibited good disease control over a three-month time interval. She continued to exhibit hematopoietic recovery over this time interval with intermittent and infrequent platelet transfusions. At three months following TTF use, she exhibited disease progression of her GBM. Radiation or surgery was not option for treatment at the time, in the opinion of the treating surgical and radiation oncology teams, necessitating use of bevacizumab. At the time, her platelet counts were in the range of 80–90 K/µL unsupported by transfusions. One month following the start of bevacizumab, she developed infected wound flap at site of prior cranial surgery. She required a craniotomy for evacuation of subdural infection with drains. She was also placed on intravenous ceftriaxone and metronidazole for six weeks. Bevacizumab was deferred to allow for wound healing. Unfortunately, during this time interval she experienced acute respiratory failure needing hospitalization due to respiratory syncytial virus pneumonia. Due to declining quality of life from multiple medical issues, the patient and family elected to pursue hospice. She passed away 16 months from initial diagnosis of GBM due to disease progression from malignancy.\n\nA complete summarization of the timeline of events has been presented in Table 1.\n\nTable 1 Timeline of events.\nWBC: White blood cell; ANC: Absolute neutrophil count; RT: Radiation therapy; G-CSF: Granulocyte-colony stimulating factor; TTF: Tumor-treating fields; GBM: Glioblastoma multiforme.\n\n\nTimeline\n\t\nDay of treatment\n\t\nWBC count (K/µL)\n\t\nHemoglobin (g/dL)\n\t\nPlatelet (K/µL)\n\t\nANC (cells/µL)\n\t\n\nRT start\n\t\n-7\n\t\n-\n\t\n-\n\t\n-\n\t\n-\n\t\n\nTemozolomide start\n\t\n1\n\t\n12.6\n\t\n14.2\n\t\n300\n\t\n9500\n\t\n\nDuring concurrent temozolomide/RT\n\t\n27\n\t\n8.4\n\t\n14.3\n\t\n302\n\t\n6400\n\t\n\nFinal week of temozolomide/RT\n\t\n35\n\t\n6.7\n\t\n13.3\n\t\n107\n\t\n5300\n\t\n\nEmergency room with epistaxis, nadir\n \n\t\n54\n\t\n0.4\n\t\n8.5\n\t\n6\n\t\n0\n\t\n\nHospitalized, G-CSF injection\n\t\n65\n\t\n0.2\n\t\n7.0\n\t\n29\n\t\n0\n\t\n\nBone marrow biopsy, non-diagnostic\n\t\n71\n\t\n0.2\n\t\n8.6\n\t\n6\n\t\n0\n\t\n\nBone marrow biopsy, repeat\n\t\n77\n\t\n0.7\n\t\n8.2\n\t\n5\n\t\n0\n\t\n\nEltrombopag\n\t\n86\n\t\n0.5\n\t\n8.1\n\t\n5\n\t\n0\n\t\n\nNeutrophil recovery\n\t\n89\n\t\n0.4\n\t\n8.2\n\t\n17\n\t\n100\n\t\n\nResolution of neutropenia\n\t\n95\n\t\n2.0\n\t\n7.6\n\t\n16\n\t\n1500\n\t\n\nHospital discharge\n\t\n131\n\t\n5.1\n\t\n8.1\n\t\n29\n\t\n3300\n\t\n\nTTF therapy\n\t\n194\n\t\n3.2\n\t\n9.1\n\t\n23\n\t\n2500\n\t\n\nGBM progression, bevacizumab\n\t\n314\n\t\n4.3\n\t\n12.6\n\t\n81\n\t\n3100\n\t\n\nHospice\n\t\n378\n\t\n3.4\n\t\n10.6\n\t\n57\n\t\n2600\n\t\nDiscussion\nGBM is the most frequent primary malignant brain tumor in adults [2]. The median survival of patients with GBM is generally one year from the time of diagnosis, with most patients succumbing to the illness within two years [2]. The clinical trial of the Stupp protocol showed a 37% relative reduction in the risk of death and a clinically meaningful median overall survival of 14.6 months for patients treated with radiotherapy plus temozolomide as compared with those who received radiotherapy alone [2]. The statistically significant increase in survival resulted in temozolomide approval for first-line treatment of GBM.\n\nTemozolomide is an oral alkylating agent, which shares a cytotoxic mechanism with dacarbazine and other methylating compounds [8]. Its active metabolite, 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC), methylates the N7 and O6 position of guanine and the O3 position of adenine [9]. Methylation of the O6 position of guanine stimulates the activity of the base excision repair protein, methylguanine-DNA methyltransferase (MGMT). MGMT subsequently demethylates this position on guanine, resulting in inactivation of the enzyme [9]. Daily temozolomide therapy at a dose of 75 mg/m2 depletes MGMT levels, resulting in the activation of alternative repair pathways [2]. Mismatch repair enzymes attempt to repair the methylated DNA molecule, but failed attempts result in fragmentation of DNA and apoptosis of the cell [9]. Studies have demonstrated that lower levels of MGMT are associated with prolonged survival in patients with GBM [2]. One report observed that methylation of the MGMT promoter is associated with a substantial survival benefit in patients treated with concomitant temozolomide and radiotherapy [2]. Radiotherapy is known to induce MGMT [2]. Therefore, the addition of temozolomide allows the treatment modalities to work synergistically.\n\nA similar mechanism is proposed to explain temozolomide-related bone marrow suppression [8]. Higher levels of MGMT are thought to protect cells from temozolomide cytotoxicity [8]. As stated above, when MGMT is present, it removes the methyl group from the O6 guanine position of DNA to repair the molecule. Bone marrow precursors have low levels of MGMT, which increases the susceptibility of these cells to temozolomide [8]. A study published by Sabharwal et al. noted that low levels of pretreatment MGMT in peripheral blood cells were associated with an increased risk of thrombocytopenia and neutropenia with temozolomide use [8]. Hematologic toxicity is a well-reported side effect of temozolomide, with thrombocytopenia, leukopenia, and neutropenia being most common [2,10]. Aplastic anemia has also been described [10]. However, the myelosuppression induced by temozolomide is thought to be dose limiting and reversible after two weeks of discontinuing the drug [11]. Overall, temozolomide is regarded as a safe and well-tolerated drug with the most serious side effects occurring in less than 5% of patients [1,3,10,12].\n\nAplastic anemia is a rare disease in which the hematopoietic stem cells of bone marrow are damaged. It results in pancytopenia (deficiency of erythrocytes, leukocytes, and platelets) [3]. Causes of aplastic anemia can be inherited or acquired. Common causes of acquired aplastic anemia include infection, exposure to chemicals, and medications [3]. Some medications that are known to induce cytopenias include nonsteroidal anti-inflammatory drugs, sulfonamides, chloramphenicol, anti-thyroid drugs, furosemide, anti-convulsant drugs, corticosteroids, and allopurinol [3,13]. Destruction of hematopoietic precursors is thought to be immune-mediated, with drugs and other chemicals triggering an aberrant T-cell response targeting hematopoietic stem cells [11,14]. It is unclear whether this is driven by antigens or immunological disarray [14]. Additionally, predispositions to this immune response have been difficult to identify due to the rare nature of idiosyncratic drug reactions [14].\n\nTo diagnose aplastic anemia, both peripheral blood cytopenias and a bone marrow biopsy demonstrating hypocellular marrow must be present. The remaining bone marrow should be free of malignant infiltrates or evidence of megaloblastic hematopoiesis [15].\n\nVillano et al. reported one of the first cases of temozolomide-induced aplastic anemia in 2006 [1]. The paper describes a 45-year-old male who underwent standard fractionated radiotherapy with concomitant temozolomide. After initiating temozolomide monotherapy, the patient developed profound pancytopenia [1]. A bone marrow biopsy revealed aplastic anemia. Causality of the aplastic anemia could not be definitively determined because the patient was also prescribed phenytoin and carbamazepine while undergoing treatment with temozolomide [1]. However, discontinuation of the drugs did not lead to a recovery of bone marrow suppression, which is uncommon with anticonvulsants. Prior to this case, one phase II trial documented a case of aplastic anemia with temozolomide treatment. The patient in this trial was concomitantly taking TMP-SMX with temozolomide, and therefore causality could not be determined with this case as well [1].\n\nSince 2006, several additional case reports of temozolomide-induced aplastic anemia have been reported. In 2007, a drug safety letter was released by the FDA that reported 18 cases from 1999 to 2006 [3]. No patients in this newsletter had prior pancytopenia or aplastic anemia. One-third (six of eighteen) of these patients had been exposed to other drugs during treatment with temozolomide that may have contributed to the development of aplastic anemia. Only five patients experienced marrow recovery within one to four months of discontinuing temozolomide, and five other patients ultimately died from complications of aplastic anemia or complications related to allogeneic transplant [3]. A systematic review of temozolomide-related idiosyncratic and other uncommon toxicities was performed in 2012 [9]. This report analyzed 73 cases of temozolomide-induced toxicity. Of the 73 cases, 21 cases of hematologic idiosyncratic drug reactions were identified. Risk factors identified from this report include female gender and patients receiving temozolomide concomitantly with radiotherapy. Only three out of the 21 reported cases were not taking any medication known to have hematologic side effects [9]. In 2015, Mayo Clinic performed a cohort study with patients treated with temozolomide by Mayo Clinic Rochester from 2003 to 2014 plus 15 additional reported cases identified from the literature [4]. Of 2,356 patients treated at Mayo Clinic with temozolomide, only 15 patients (0.6%) developed bone marrow suppression. Therefore, 30 total patients were included in this study. The average age when bone marrow suppression was diagnosed was 55. Twenty-seven out of 30 patients (90%) received temozolomide with concomitant radiation, while only three single agent cases were found (10%). Consistent with the report from Dixit et al., the study also reported a female predominance (80%) [9]. Lastly, the study indicated that the majority of cases demonstrated temozolomide-induced bone marrow suppression after the first cycle of therapy (63%) [4].\n\nEarly diagnosis of temozolomide-induced aplastic anemia is imperative since it is associated with high morbidity and mortality [4]. Management begins with immediate discontinuation of causative agents [13]. Empiric broad-spectrum antibiotic therapy should be initiated to prevent sepsis or secondary infection [13]. Current treatment options include supportive therapy with transfusions and growth factors, eltrombopag, immunosuppressive therapy (IST) and alloHSCT [3-5,9,12]. Hematopoietic growth factors have been shown to shorten the duration of antibiotic therapy and drug count recovery. Frequently, IST with horse ATG and cyclosporine has been used to treat aplastic anemia, especially in those who are not eligible for alloHSCT [14]. Our patient described in the case report above recovered her neutrophil and erythrocyte counts with supportive transfusions, G-CSF injections and eltrombopag. Also, discontinuation of offending drugs has been known to play a role in the spontaneous recovery of drug-induced aplastic anemia, usually noted one to two months following discontinuation of drug [16]. Following the use of eltrombopag, her transfusion requirements were minimal with no infectious complications due to a normal neutrophil count, and therefore IST was deferred. The oral thrombopoietin agonist eltrombopag was initially developed to stimulate thrombopoiesis in patients with thrombocytopenia [4,5]. Through mouse models, the essential role of thrombopoietin in hematopoietic stem cell (HSC) hemostasis has been demonstrated [5]. It is theorized that eltrombopag acts not only to stimulate thrombopoiesis, but also to directly stimulate residual HSCs in patients with aplastic anemia [5]. In the cohort study by Kourelis et al., immunosuppressive treatment was attempted (two out of 30) without benefit, and patients on eltrombopag (one out of 30) demonstrated prolonged improvements in blood counts [4]. While alloHSCT may be curative, lethal complications related to transplant are not uncommon [1,4]. In younger patients who are refractory to treatment, alloHSCT is a potentially curative therapy [14].\n\nConclusions\nTemozolomide is an alkylating agent that is first-line therapy for the treatment of GBM. Although regarded as a relatively safe drug with a favorable side-effect profile, many cases of bone marrow suppression and aplastic anemia have been reported while using temozolomide. It is difficult to determine definitive causality in most of these cases because of the concomitant use of other medications known to induce aplastic anemia. However, some cases of aplastic anemia induced by temozolomide monotherapy have been described. The optimal treatment for temozolomide-induced aplastic anemia is not well defined due to its rare presentation. Physicians should be aware of this potentially fatal complication related to temozolomide and due consideration should be given when prescribing treatment for GBM. Patients should be monitored frequently with complete blood indices for early detection and treatment of this complication.\n\nThe authors have declared that no competing interests exist.\n\nHuman Ethics\nConsent was obtained by all participants in this study\n==== Refs\nReferences\n1 Aplastic anemia in patient with glioblastoma multiforme treated with temozolomide Lancet Oncol Villano JL Collins CA Manasanch EE Ramaprasad C van Besien K 436 438 7 2006 16648049 \n2 Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N Engl J Med Stupp R Mason WP van den Bent MJ 987 996 352 2005 15758009 \n3 A rare case of aplastic anemia caused by temozolomide South Med J George BJ Eichinger JB Richard TJ 974 976 102 2009 19668033 \n4 Temozolomide induced bone marrow suppression-A single institution outcome analysis and review of the literature Am J Hematol Kourelis TV Buckner JC Gangat N Patnaik MM 0 90 2015 \n5 Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of the drug Blood Desmond R Townsley DM Dumitriu B 1818 1825 123 2014 24345753 \n6 Practical management of bevacizumab-related toxicities in glioblastoma Oncologist Brandes AA Bartolotti M Tosoni A Poggi R Franceschi E 166 175 20 2015 25568148 \n7 Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial JAMA Stupp R Taillibert S Kanner AA 2535 2543 314 2015 26670971 \n8 Hematologic adverse events associated with temozolomide Cancer Chemother Pharmacol Villano JL Letarte N Yu JM Abdur S Bressler LR 107 113 69 2012 21614470 \n9 Temozolomide-related idiosyncratic and other uncommon toxicities: a systematic review Anticancer Drugs Dixit S Baker L Walmsley V Hingorani M 1099 1106 23 2012 22850321 \n10 Aplastic anemia as a cause of death in a patient with glioblastoma multiforme treated with temozolomide Strahlenther Onkol Kopecký J Priester P Slovácek L Petera J Kopecký O Macingova Z 452 457 186 2010 20803286 \n11 An unusual case of aplastic anemia caused by temozolomide Case Rep Med Comez G Sevinc A Sever ON Babacan T Sarı I Camci C 2 2010 2010 \n12 Unexpected case of aplastic anemia in a patient with glioblastoma multiforme treated with temozolomide J Neurooncol Jalali R Singh P Menon H Gujral S 105 107 85 2007 17505778 \n13 Idiosyncratic drug-induced agranulocytosis or acute neutropenia Curr Opin Hematol Andrès E Maloisel F 15 21 15 2008 18043241 \n14 Aplastic anemia Curr Opin Hematol Young NS Scheinberg P Calado RT 162 168 15 2008 18391779 \n15 Aplastic anemia with concurrent temozolomide treatment in a patient with glioblastoma multiforme Curr Oncol Oh J Kutas GJ Davey P Morrison M Perry JR 124 126 17 2010 20697524 \n16 Acquired marrow failure syndromes: aplastic anemia, paroxysmal nocturnal hemoglobinuria, and myelodysplastic syndromes The American Society of Hematology Self-Assessment Program (ASH-SAP) Scheinberg P DeZern AE Steensma DP 489 520 Washington, DC American Society of Hematology 6 2016 http://www.ash-sap.org/content/2016/489.extract\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2168-8184",
"issue": "10(9)",
"journal": "Cureus",
"keywords": "aplastic anaemia; eltrombopag; glioblastoma multiforme (gbm); stupp protocol; temozolomide",
"medline_ta": "Cureus",
"mesh_terms": null,
"nlm_unique_id": "101596737",
"other_id": null,
"pages": "e3329",
"pmc": null,
"pmid": "30473962",
"pubdate": "2018-09-18",
"publication_types": "D002363:Case Reports",
"references": "21209809;25568148;20697524;16648049;20803286;19668033;26010271;18043241;26670971;17505778;15758009;18391779;22850321;24345753;21614470",
"title": "Temozolomide-induced Aplastic Anemia Treated with Eltrombopag and Granulocyte Colony Stimulating Factor: A Report of a Rare Complication.",
"title_normalized": "temozolomide induced aplastic anemia treated with eltrombopag and granulocyte colony stimulating factor a report of a rare complication"
}
|
[
{
"companynumb": "US-ACCORD-095879",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TEMOZOLOMIDE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "201528",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ADJUVANT TEMOZOLOMIDE MONOTHERAPY 150 MG/M2 A DAY FOR FIVE?DAYS OF A 28-DAY CYCLE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "GLIOBLASTOMA MULTIFORME",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "75",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TEMOZOLOMIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "SIMVASTATIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SIMVASTATIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "DEXAMETHASONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ONDANSETRON"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ONDANSETRON"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PANTOPRAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PANTOPRAZOLE"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROCHLOROTHIAZIDE/TRIAMTERENE"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROCODONE BITARTRATE/PARACETAMOL"
},
{
"actiondrug": null,
"activesubstance": null,
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "(TMPSMX) 800-160",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIBIOTIC PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE/TRIMETHOPRIM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "NEBIVOLOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NEBIVOLOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LISINOPRIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LISINOPRIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ALBUTEROL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ALBUTEROL."
}
],
"patientagegroup": null,
"patientonsetage": "51",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Herpes oesophagitis",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Bone marrow failure",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Aplastic anaemia",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NEWTON SL, KALAMAHA K, FERNANDES HD. TEMOZOLOMIDE-INDUCED APLASTIC ANEMIA TREATED WITH ELTROMBOPAG AND GRANULOCYTE COLONY STIMULATING FACTOR: A REPORT OF A RARE COMPLICATION. CUREUS. 2018 SEP 18?10(9):E3329.",
"literaturereference_normalized": "temozolomide induced aplastic anemia treated with eltrombopag and granulocyte colony stimulating factor a report of a rare complication",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181217",
"receivedate": "20181217",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15726850,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190205"
}
] |
{
"abstract": "OBJECTIVE\nMetoclopramide is a commonly used medication in pediatric practice, and dystonia is a common adverse effect of it. The present study aims to evaluate the clinical characteristics of metoclopramide-induced acute dystonic reactions (MIADRs) in pediatric patients admitted to the pediatric emergency unit.\n\n\nMETHODS\nTwenty-eight patients were admitted with MIADRs between June 2004 and April 2016; they were enrolled into the study retrospectively.\n\n\nRESULTS\nThe study group was composed of 13 females and 15 males with the mean ± SD age of the females higher than that of the males, 12.3 ± 4.5 and 7.8 ± 4.3 years, respectively. Only 9 (32.1%) of the patients were diagnosed as MIADRs at the time of admission. Seventeen patients (60.7%) received over the recommended daily dose of metoclopramide. Dystonia was focal in most of the patients, with the most affected parts consisting of the neck, eyes, and orolingual regions. In 9 of the patients, the dystonia was episodic in nature. Pharmacological treatment was used for 18 patients. No patients died, and none suffered long-term injury related to MIADRs.\n\n\nCONCLUSIONS\nMetoclopramide administration may be associated with the occurrence of acute dystonic reaction. Metoclopramide-induced acute dystonic reactions may be misdiagnosed, so detailed medical history gathering and a high index of suspicion are warranted. Our data suggest that MIADRs may be dose related and that there may be age- and sex-related differences in the epidemiology of MIADRs.",
"affiliations": "From the Departments of Pediatric Neurology.;From the Departments of Pediatric Neurology.;From the Departments of Pediatric Neurology.;Pediatric Emergency, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir.;Department of Pediatric Neurology, Samsun Education and Research Hospital, Samsun.;Departments of Neurology.;Biostatistics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.",
"authors": "Yarar|Coskun|C|;Yakut|Ayten|A|;Carman|Kursat Bora|KB|;Sahin|Sabiha|S|;Kocak|Ozan|O|;Ozkan|Serhat|S|;Bal|Cengiz|C|",
"chemical_list": "D008787:Metoclopramide",
"country": "United States",
"delete": false,
"doi": "10.1097/PEC.0000000000001960",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0749-5161",
"issue": "37(9)",
"journal": "Pediatric emergency care",
"keywords": null,
"medline_ta": "Pediatr Emerg Care",
"mesh_terms": "D000293:Adolescent; D002648:Child; D004421:Dystonia; D020821:Dystonic Disorders; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D008297:Male; D008787:Metoclopramide; D012189:Retrospective Studies",
"nlm_unique_id": "8507560",
"other_id": null,
"pages": "e528-e533",
"pmc": null,
"pmid": "32118836",
"pubdate": "2021-09-01",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Metoclopramide-Induced Acute Dystonia: Data From a Pediatric Emergency Unit.",
"title_normalized": "metoclopramide induced acute dystonia data from a pediatric emergency unit"
}
|
[
{
"companynumb": "TR-LUPIN PHARMACEUTICALS INC.-2021-18888",
"fulfillexpeditecriteria": "2",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METOCLOPRAMIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "202191",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Vomiting",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOCLOPRAMIDE"
}
],
"patientagegroup": null,
"patientonsetage": "11",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Dystonia",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Yarar C, Yakut A, Carman KB, Sahin S, Kocak O, Ozkan S, et al. Metoclopramide-induced acute dystonia: Data from a pediatric emergency unit. Pediatric emergency care. 2021;37(9):e528-e533",
"literaturereference_normalized": "metoclopramide induced acute dystonia data from a pediatric emergency unit",
"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20211007",
"receivedate": "20211007",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19930198,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "TR-LUPIN PHARMACEUTICALS INC.-2021-18889",
"fulfillexpeditecriteria": "2",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METOCLOPRAMIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "202191",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Vomiting",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOCLOPRAMIDE"
}
],
"patientagegroup": null,
"patientonsetage": "15",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Dystonia",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Yarar C, Yakut A, Carman KB, Sahin S, Kocak O, Ozkan S, et al. Metoclopramide-induced acute dystonia: Data from a pediatric emergency unit. Pediatric emergency care. 2021;37(9):e528-e533",
"literaturereference_normalized": "metoclopramide induced acute dystonia data from a pediatric emergency unit",
"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20211007",
"receivedate": "20211007",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19929891,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "TR-LUPIN PHARMACEUTICALS INC.-2021-18890",
"fulfillexpeditecriteria": "2",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "METOCLOPRAMIDE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "202191",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Vomiting",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOCLOPRAMIDE"
}
],
"patientagegroup": null,
"patientonsetage": "15",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Dystonia",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Yarar C, Yakut A, Carman KB, Sahin S, Kocak O, Ozkan S, et al. Metoclopramide-induced acute dystonia: Data from a pediatric emergency unit. Pediatric emergency care. 2021;37(9):e528-e533",
"literaturereference_normalized": "metoclopramide induced acute dystonia data from a pediatric emergency unit",
"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20211007",
"receivedate": "20211007",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19929091,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
}
] |
{
"abstract": "OBJECTIVE\nThe purpose of this review is to provide an update on the clinical features, diagnosis, pathogenesis, epidemiology, and treatment of the rare primary headache disorders short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA). Together these entities are known as short-lasting unilateral neuralgiform headache attacks (SUNHA).\n\n\nRESULTS\nRecent case reports of secondary SUNCT and SUNA due to medullary infarcts support the theory that the trigeminohypothalamic pathway is involved in the pathophysiology of SUNHA. While medical therapy for SUNHA has not significantly changed, surgical therapy for refractory SUNCT and SUNA has made advancements with a recent case series demonstrating the efficacy of deep brain stimulation. We will discuss the pathophysiology of both the pain and the autonomic symptoms experienced in SUNCT and SUNA attacks as well the medical, procedural, and surgical options for treatment with emphasis on recent advances. Specific secondary causes reported in the recent literature will be discussed in brief.",
"affiliations": "Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA. [email protected].;Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA.",
"authors": "Arca|Karissa N|KN|;Halker Singh|Rashmi B|RB|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1007/s11916-018-0707-3",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1534-3081",
"issue": "22(8)",
"journal": "Current pain and headache reports",
"keywords": "SUNA; SUNCT; SUNHA; TAC; Trigeminal autonomic cephalalgia",
"medline_ta": "Curr Pain Headache Rep",
"mesh_terms": "D006801:Humans; D050798:SUNCT Syndrome; D051303:Trigeminal Autonomic Cephalalgias",
"nlm_unique_id": "100970666",
"other_id": null,
"pages": "56",
"pmc": null,
"pmid": "29931416",
"pubdate": "2018-06-21",
"publication_types": "D016428:Journal Article; D016454:Review",
"references": "16905753;25841267;28188632;28730562;24349865;24792341;24662321;10554000;26008143;18821829;8933996;23800827;20425205;28708008;15910571;15910575;21628443;27393015;16556252;27226002;28542727;27671025;23771276;26885826;22734103;17115989;15929061;27445629;27524793;24045569;26553730;12849458;24888770",
"title": "SUNCT and SUNA: an Update and Review.",
"title_normalized": "sunct and suna an update and review"
}
|
[
{
"companynumb": "US-CIPLA LTD.-2018US20010",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DIHYDROERGOTAMINE MESYLATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TRIGEMINAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DHE /00017802/"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "GABAPENTIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "090705",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TRIGEMINAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GABAPENTIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MELATONIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TRIGEMINAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MELATONIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "INDOMETHACIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TRIGEMINAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INDOMETHACIN /00003801/"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "GABAPENTIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "090705",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GABAPENTIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CARBAMAZEPINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TRIGEMINAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CARBAMAZEPINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "BACLOFEN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TRIGEMINAL NEURALGIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BACLOFEN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Lacrimation increased",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Therapeutic response shortened",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Drug effect decreased",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Vascular compression",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Eyelid ptosis",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Conjunctival hyperaemia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Treatment failure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nerve compression",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARCA KN, HALKER SINGH RB. SUNCT AND SUNA: AN UPDATE AND REVIEW. CURRENT PAIN AND HEADACHE REPORTS. 2018?22:56 (1 TO 6)",
"literaturereference_normalized": "sunct and suna an update and review",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180723",
"receivedate": "20180723",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15179147,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
}
] |
{
"abstract": "We report 2 cases of serotonin syndrome and myelosuppression in bone marrow transplant recipients who received linezolid in combination with a selective serotonin reuptake inhibitor (SSRI). Given the risks to patients in this high-risk group, we recommend that this combination of medications be avoided if alternative antibiotic therapy is possible. If no alternative therapy is possible, prescribers should discontinue SSRI therapy and monitor these patients closely for evidence of serotonin syndrome or the development of hematological toxicity.",
"affiliations": "Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. [email protected]",
"authors": "Hachem|Ray Y|RY|;Hicks|Krystal|K|;Huen|Auris|A|;Raad|Issam|I|",
"chemical_list": "D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D017367:Serotonin Uptake Inhibitors; D000069349:Linezolid",
"country": "United States",
"delete": false,
"doi": "10.1086/375689",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1058-4838",
"issue": "37(1)",
"journal": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",
"keywords": null,
"medline_ta": "Clin Infect Dis",
"mesh_terms": "D000081:Acetamides; D000328:Adult; D000890:Anti-Infective Agents; D016026:Bone Marrow Transplantation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones; D020230:Serotonin Syndrome; D017367:Serotonin Uptake Inhibitors",
"nlm_unique_id": "9203213",
"other_id": null,
"pages": "e8-11",
"pmc": null,
"pmid": "12830431",
"pubdate": "2003-07-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients.",
"title_normalized": "myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients"
}
|
[
{
"companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2018-05988",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "205517",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CITALOPRAM HYDROBROMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CITALOPRAM"
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Serotonin syndrome",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HACHEM RY, HICKS K, HUEN A, ET AL.. MYELOSUPPRESSION AND SEROTONIN SYNDROME ASSOCIATED WITH CONCURRENT USE OF LINEZOLID AND SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN BONE MARROW TRANSPLANT RECIPIENTS. CLIN INFECT DIS.. 2003?37(1):E8-E11",
"literaturereference_normalized": "myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181017",
"receivedate": "20181017",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15516599,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190205"
},
{
"companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2018-05989",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SERTRALINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "205517",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID."
}
],
"patientagegroup": null,
"patientonsetage": "36",
"patientonsetageunit": "801",
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Serotonin syndrome",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HACHEM RY, HICKS K, HUEN A, ET AL.. MYELOSUPPRESSION AND SEROTONIN SYNDROME ASSOCIATED WITH CONCURRENT USE OF LINEZOLID AND SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN BONE MARROW TRANSPLANT RECIPIENTS. CLIN INFECT DIS.. 2003?37(1):E8-E11",
"literaturereference_normalized": "myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20181017",
"receivedate": "20181017",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15516563,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190205"
}
] |
{
"abstract": "OBJECTIVE\nThe differential diagnosis of psychotic symptoms is broad and extends beyond primary psychotic and affective disorders. We aim to illustrate that the chronology and phenomenological nature of hallucinatory symptoms may provide clues towards alternative diagnoses, such as hallucinogen persisting perceptual disorder (HPPD). We describe the resurgence of visual pseudo-hallucinations in a young woman in the context of previous substance-induced hallucinatory symptoms and a prior diagnosis of occipital lobe epilepsy. She presented a diagnostic challenge, saw several emergency and specialist doctors and attracted stigmatising diagnoses leading to anxiety and depressive symptoms. Her symptoms were finally recognised as HPPD, and she was treated appropriately with lamotrigine.\n\n\nCONCLUSIONS\nPatients with perceptual disturbance can present in various clinical settings, and HPPD is an under-recognised diagnostic possibility. Delayed or misdiagnosis prolongs profound functional impairment and social decline, and predisposes the patient to the development of anxiety and depression and related increased risk of suicide.",
"affiliations": "Medical Officer, Royal Melbourne Hospital, Department of Psychiatry, Parkville, VIC, Australia.;Psychiatrist Royal Melbourne Hospital, Department of Psychiatry, Parkville, VIC, Australia.;Neuropsychiatrist Royal Melbourne Hospital, Department of Neuropsychiatry, Parkville, VIC, Australia.",
"authors": "Anderson|Lauren|L|;Lake|Hannah|H|;Walterfang|Mark|M|",
"chemical_list": "D006213:Hallucinogens",
"country": "England",
"delete": false,
"doi": "10.1177/1039856217726694",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1039-8562",
"issue": "26(1)",
"journal": "Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists",
"keywords": "HPPD; hallucinogen; hallucinogen persisting perceptual disorder; visual hallucination",
"medline_ta": "Australas Psychiatry",
"mesh_terms": "D000328:Adult; D005260:Female; D006212:Hallucinations; D006213:Hallucinogens; D006801:Humans; D010468:Perceptual Disorders",
"nlm_unique_id": "9613603",
"other_id": null,
"pages": "11-12",
"pmc": null,
"pmid": "28836813",
"pubdate": "2018-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "The trip of a lifetime: hallucinogen persisting perceptual disorder.",
"title_normalized": "the trip of a lifetime hallucinogen persisting perceptual disorder"
}
|
[
{
"companynumb": "AU-CIPLA LTD.-2018AU08363",
"fulfillexpeditecriteria": "1",
"occurcountry": "AU",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RISPERIDONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SCHIZOPHRENIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RISPERIDONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RISPERIDONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SUBSTANCE-INDUCED PSYCHOTIC DISORDER",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RISPERIDONE."
},
{
"actiondrug": "3",
"activesubstance": {
"activesubstancename": "LAMOTRIGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "077783",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MG, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EPILEPSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMOTRIGINE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EPILEPSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": "3",
"activesubstance": {
"activesubstancename": "LAMOTRIGINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "077783",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 MG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMOTRIGINE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Disease recurrence",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Anxiety",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Depressed mood",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hallucination",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Epilepsy",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Illusion",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ANDERSON L, LAKE H, WALTERFANG M. THE TRIP OF A LIFETIME: HALLUCINOGEN PERSISTING PERCEPTUAL DISORDER. AUSTRALASIAN PSYCHIATRY. 2018?26 (1):11 TO 12",
"literaturereference_normalized": "the trip of a lifetime hallucinogen persisting perceptual disorder",
"qualification": "3",
"reportercountry": "AU"
},
"primarysourcecountry": "AU",
"receiptdate": "20180301",
"receivedate": "20180301",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14585869,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180509"
}
] |
{
"abstract": "OBJECTIVE\nTo evaluate the efficacy and safety of superselective trans-catheter arterial embolization (TAE) with N-butyl-2-cyanoacrylate (NBCA) for patients with acute non-variceal upper and lower gastrointestinal (GI) bleeding.\n\n\nMETHODS\nTAE using NBCA was performed in 21 patients (13 males, 8 females, mean age 60.9 years) with acute non-variceal upper (n = 15) and lower (n = 6) GI bleeding. TAE using other embolic agents was performed in 25 patients (13 males, 12 females, mean age 69.1 years) with acute non-variceal upper (n = 16) and lower (n = 9) GI bleeding. Technical success, clinical success, clinical failure, major and minor complications, bleeding-related 30-day mortality, and overall in-hospital mortality were analyzed.\n\n\nRESULTS\nIn 21 patients who underwent TAE with NBCA, the overall technical success was 100% (21/21) and overall clinical success was 72.2% (13/18). Uncontrolled bleeding, recurrent bleeding, and clinical failure were seen in 11.1% (2/18), 16.7% (3/18), and 27.8% (5/18) of cases, respectively. The minor complication rate was 16.7% (4/21) and no major complications occurred. Three patients showed ischemic damage in the treated lesion and one patient showed epigastric pain. The bleeding-related 30-day mortality and overall in-hospital mortality rates were 16.7% (3/18) and 28.6% (6/21), respectively. Two patients died of septic shock and one died of myocardial infarction within 30 days after TAE. In 25 patients who underwent TAE with other agents, the overall technical success was 100% (25/25), and the overall clinical success was 68.2% (15/22). The rates of uncontrolled bleeding, recurrent bleeding, clinical failure, bleeding-related 30-day mortality, and overall in-hospital mortality were 0.5% (1/22), 22.7% (5/22), 31.8% (7/22), 22.7% (5/22), and 32.0% (8/25), respectively.\n\n\nCONCLUSIONS\nTAE with NBCA for acute non-variceal upper and lower GI bleeding proved to be a technically feasible, safe, and effective treatment modality. Thus, NBCA could be used as a primary embolic agent for controlling GI bleeding.",
"affiliations": "Department of Radiology, Dongguk University Ilsan Hospital, Dongguk University Graduate School of Medicine, 27 Dongguk-ro, Siksa-dong, Ilsandong-gu, Gyeonggi-do, Goyang, 10326, South Korea. [email protected].;Department of Radiology, Dongguk University Ilsan Hospital, Dongguk University Graduate School of Medicine, 27 Dongguk-ro, Siksa-dong, Ilsandong-gu, Gyeonggi-do, Goyang, 10326, South Korea.",
"authors": "Kwon|Jae Hyun|JH|http://orcid.org/0000-0001-7303-770X;Han|Yoon Hee|YH|",
"chemical_list": "D004659:Enbucrilate",
"country": "United States",
"delete": false,
"doi": "10.1007/s10140-017-1552-0",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1070-3004",
"issue": "25(2)",
"journal": "Emergency radiology",
"keywords": "Embolization; Endoscopy; Gastrointestinal bleeding; N-butyl-2-cyanoacrylate",
"medline_ta": "Emerg Radiol",
"mesh_terms": "D000208:Acute Disease; D000368:Aged; D002404:Catheterization; D004621:Embolization, Therapeutic; D004659:Enbucrilate; D005260:Female; D006471:Gastrointestinal Hemorrhage; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome",
"nlm_unique_id": "9431227",
"other_id": null,
"pages": "111-120",
"pmc": null,
"pmid": "28971259",
"pubdate": "2018-04",
"publication_types": "D016428:Journal Article",
"references": "10823636;19800541;12855879;16015559;18987861;14709694;11230648;17327553;23380738;25714300;22563285;18725091;24365503;17277563;20870162;24286939;11698624;19455109;28256302;21875815;24143308;19643634;26054245;15231881;11265883",
"title": "Efficacy and safety of superselective trans-catheter arterial embolization of upper and lower gastrointestinal bleeding using N-butyl-2-cyanoacrylate.",
"title_normalized": "efficacy and safety of superselective trans catheter arterial embolization of upper and lower gastrointestinal bleeding using n butyl 2 cyanoacrylate"
}
|
[
{
"companynumb": "KR-GUERBET-KR-20180007",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ETHIODIZED OIL"
},
"drugadditional": null,
"drugadministrationroute": "013",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THERAPEUTIC EMBOLISATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIPIODOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "UNSPECIFIED INGREDIENT"
},
"drugadditional": null,
"drugadministrationroute": "013",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THERAPEUTIC EMBOLISATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "N-BUTYL-2-CYANOACRYLATE"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug ineffective for unapproved indication",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KWON J. EFFICACY AND SAFETY OF SUPERSELECTIVE TRANS-CATHETER ARTERIAL EMBOLIZATION OF UPPER AND LOWER GASTROINTESTINAL BLEEDING USING N-BUTYL-2-CYANOACRYLATE. EMERG RADIOL. 2018?25:111-120.",
"literaturereference_normalized": "efficacy and safety of superselective trans catheter arterial embolization of upper and lower gastrointestinal bleeding using n butyl 2 cyanoacrylate",
"qualification": "1",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20180412",
"receivedate": "20180412",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 14752347,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180711"
},
{
"companynumb": "KR-GUERBET-KR-20180012",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "UNSPECIFIED INGREDIENT"
},
"drugadditional": null,
"drugadministrationroute": "013",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THERAPEUTIC EMBOLISATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "N-BUTYL-2-CYANOACRYLATE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ETHIODIZED OIL"
},
"drugadditional": null,
"drugadministrationroute": "013",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THERAPEUTIC EMBOLISATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIPIODOL"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Drug ineffective for unapproved indication",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KWON J. EFFICACY AND SAFETY OF SUPERSELECTIVE TRANS-CATHETER ARTERIAL EMBOLIZATION OF UPPER AND LOWER GASTROINTESTINAL BLEEDING USING N-BUTYL-2-CYANOACRYLATE. EMERG RADIOL. 2018?25:111-120.",
"literaturereference_normalized": "efficacy and safety of superselective trans catheter arterial embolization of upper and lower gastrointestinal bleeding using n butyl 2 cyanoacrylate",
"qualification": "1",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20180412",
"receivedate": "20180412",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 14752357,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180711"
},
{
"companynumb": "KR-GUERBET-KR-20180006",
"fulfillexpeditecriteria": "1",
"occurcountry": "KR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ETHIODIZED OIL"
},
"drugadditional": null,
"drugadministrationroute": "013",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THERAPEUTIC EMBOLISATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIPIODOL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "UNSPECIFIED INGREDIENT"
},
"drugadditional": null,
"drugadministrationroute": "013",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "THERAPEUTIC EMBOLISATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "N-BUTYL-2-CYANOACRYLATE"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug ineffective for unapproved indication",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KWON J. EFFICACY AND SAFETY OF SUPERSELECTIVE TRANS-CATHETER ARTERIAL EMBOLIZATION OF UPPER AND LOWER GASTROINTESTINAL BLEEDING USING N-BUTYL-2-CYANOACRYLATE. EMERG RADIOL. 2018?25:111-120.",
"literaturereference_normalized": "efficacy and safety of superselective trans catheter arterial embolization of upper and lower gastrointestinal bleeding using n butyl 2 cyanoacrylate",
"qualification": "1",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20180412",
"receivedate": "20180412",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 14752346,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20180711"
}
] |
{
"abstract": "BACKGROUND\nWe report a case of a morbidly obese patient who developed life-threatening airway obstruction due to angioedema.\n\n\nMETHODS\nA 50-year-old Japanese morbidly obese female was treated with enalapril for 10 years, with no history of angioedema. After 3 h of completion of breast cancer resection under general anesthesia with tracheal intubation, she developed airway obstruction and respiratory arrest. Her oral cavity was occupied with a swollen tongue. It was extremely difficult to determine the airway anatomical orientation although tracheal intubation was attempted using a videolaryngoscope. At this time, she probably started gasping respiration, which generated a faint bubble and revealed a possible airway. Her airway was established using a tracheal tube without confirming the glottis or the vocal cord.\n\n\nCONCLUSIONS\nAngioedema induced by angiotensin-converting enzyme (ACE) inhibitors is rare; however, once it occurs, it can be potentially life threatening, especially for patients with possible difficult airway. Considering the risk-benefit ratio, we must be careful in administering ACE inhibitor therapy in morbidly obese patients.",
"affiliations": "Division of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.;Division of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. [email protected].;Division of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.;Division of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.;Division of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.",
"authors": "Konda|Makiko|M|;Inoue|Satoki|S|;Naito|Yusuke|Y|;Egawa|Junji|J|;Kawaguchi|Masahiko|M|",
"chemical_list": null,
"country": "Germany",
"delete": false,
"doi": "10.1186/s40981-020-00408-6",
"fulltext": "\n==== Front\nJA Clin Rep\nJA Clin Rep\nJA Clinical Reports\n2363-9024 Springer Berlin Heidelberg Berlin/Heidelberg \n\n408\n10.1186/s40981-020-00408-6\nCase Report\nLife-threatening airway obstruction caused by angioedema in a morbidly obese postoperative patient: a case report\nKonda Makiko Inoue Satoki [email protected] Naito Yusuke Egawa Junji Kawaguchi Masahiko grid.410814.80000 0004 0372 782XDivision of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522 Japan \n4 1 2021 \n4 1 2021 \n12 2021 \n7 111 12 2020 22 12 2020 26 12 2020 © The Author(s) 2021Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background\nWe report a case of a morbidly obese patient who developed life-threatening airway obstruction due to angioedema.\n\nCase presentation\nA 50-year-old Japanese morbidly obese female was treated with enalapril for 10 years, with no history of angioedema. After 3 h of completion of breast cancer resection under general anesthesia with tracheal intubation, she developed airway obstruction and respiratory arrest. Her oral cavity was occupied with a swollen tongue. It was extremely difficult to determine the airway anatomical orientation although tracheal intubation was attempted using a videolaryngoscope. At this time, she probably started gasping respiration, which generated a faint bubble and revealed a possible airway. Her airway was established using a tracheal tube without confirming the glottis or the vocal cord.\n\nConclusions\nAngioedema induced by angiotensin-converting enzyme (ACE) inhibitors is rare; however, once it occurs, it can be potentially life threatening, especially for patients with possible difficult airway. Considering the risk–benefit ratio, we must be careful in administering ACE inhibitor therapy in morbidly obese patients.\n\nKeywords\nAngioedemaAngiotensin-converting enzyme inhibitorEnalaprilDifficult airwayissue-copyright-statement© The Author(s) 2021\n==== Body\nBackground\nObesity tends to impair airway patency [1]. Therefore, it is obvious that airway edema can have a severer effect on airway patency in morbidly obese individuals than in lean individuals. Although angiotensin-converting enzyme (ACE) inhibitors have been extensively used for controlling hypertension, angioedema is one of the critical side effects. Herein, we report a case of a morbidly obese patient who developed life-threatening airway obstruction due to angioedema in the postoperative period, which was probably mediated by an ACE inhibitor.\n\nCase presentation\nWritten informed consent was obtained from the patient for publication of this case report and accompanying images. A 50-year-old Japanese female with a medical history of diabetes mellitus, chronic kidney disease (stage 4), and hypertension was admitted to our hospital for surgical removal of cancer in her left breast. She was morbidly obese (height = 160 cm, weight = 144 kg), had no history of asthma and allergy to any drugs or food, and had no memory of suffering from urticarial rashes. She had been taking daily doses of enalapril 10 mg, olmesartan 20 mg, amlodipine 5 mg, metoprolol 60 mg, trichlormethiazide 2 mg, and furosemide 20 mg for the management of her hypertension for approximately 10 years. On the day of surgery, she was treated only with amlodipine. The last dose of enalapril was administered in the evening of the day before surgery. General anesthesia was induced with propofol 120 mg, fentanyl 0.15 mg, and rocuronium 80 mg, followed by successful orotracheal intubation using a videolaryngoscope (McGrath® MAC video laryngoscope, Aircraft Medical, UK). Anesthesia was maintained with desflurane 5%, remifentanil 0.1 μg/kg/min, and an additional dose of fentanyl 0.05 mg and rocuronium 20 mg. After tracheal intubation, cefazolin 1 g was administered intravenously. Resection of her breast cancer was completed uneventfully in 111 min. Muscular relaxation was reversed by administering sugammadex 600 mg. The tracheal tube was removed after confirming her response, eye opening, and sufficient spontaneous breathing. Immediately after emergence from anesthesia, she was transferred to the intensive care unit (ICU). During anesthesia, the estimated blood loss was 40 mL, urine output was 230 mL, and 560 mL of crystalloids were infused. Around the completion of anesthesia, acetaminophen 1 g was administered for 15 min. Soon after admission to the ICU, famotidine 20 mg was administered.\n\nApproximately 3 h after admission to the ICU, the patient complained of dyspnea and was rapidly desaturated over the next 15 min. She lost her consciousness and experienced airway obstruction and respiratory arrest. Immediately, manual mask ventilation was initiated; however, it was extremely difficult. Her tongue swelled heavily and protruded from the mouth. Tracheal intubation was attempted using a videolaryngoscope; however, the oral cavity was occupied with the swollen tongue. It was extremely difficult to determine the airway anatomical orientation. Her oxygen saturation decreased to 9%, and her heart rate dropped to 30 bpm. At this time, she regained her breath or started gasping respiration, which generated a faint bubble and revealed a possible airway. Fortunately, her airway was established using an ID 7.0-mm cuffed endotracheal tube without confirming the glottis or the vocal cord (Fig. 1a). At this juncture, we just considered ourselves to be extremely fortunate because emergent surgical airway establishment would have been frightfully difficult or impossible because of the patient’s physical appearance. Her oxygenation was improved up to 99–100%; no other allergic reactions such as urticaria, bronchospasm, and hemodynamic suppression were observed.\nFig. 1 a The swollen tongue was protruding from the oral cavity after reintubation in the intensive care unit after surgery. b The massive tongue swelling was improved gradually on the next day.\n\n\n\nBecause of localized edema, she was treated for angioedema. Dexamethasone 6.6 mg/day was tentatively administered for 3 days. During the next 2 days, her massive tongue swelling was improved gradually (Fig. 1b) and the tracheal tube was removed on the second postoperative day. The later course was uneventful. Laboratory blood test approximately 1 h after reintubation demonstrated normal levels of complement component 4, complement 1 inhibitor function, and complement 1q, suggesting that it was unlikely bradykinin-induced or hereditary angioedema [2, 3]. On the basis of these laboratory results, and because of the lack of family and past history, hereditary angioedema appeared to be negative. Topical infection was also negative in the view of clinical course. Therefore, we strongly suspected that it was due to drug-induced angioedema although other causes such as gene mutations, such as the FXII gene, should be excluded in advance [2, 3]. Incidentally, the total tryptase level in the same blood sample was also within the normal limit. Although the negative predictive value (NPV) for the clinical diagnosis of anaphylaxis was not so high (NPV = 0.4) [4], it was reasonable to assume that this event was not due to anaphylaxis considering the lack of other anaphylactic reactions. Lastly, her general practitioner was notified, and the adverse effect of the ACE inhibitor was documented in her medical record.\n\nDiscussion\nAngioedema is commonly mediated by histamine as a type I immunoglobulin E-mediated hypersensitivity to a variety of allergens (allergic angioedema) [2]. We initially ascribed angioedema in this case to famotidine or acetaminophen used in the ICU, because it occurred 3–4 h after surgery and for the first time in this patient. However, allergic angioedema is generally accompanied by other systemic allergic reactions such as urticaria [2], which was not observed in this patient, suggesting that it was unlikely an allergic reaction to agents used in the IUC or for anesthesia. Alternatively, we supposed bradykinin as a mediator of angioedema, based on previous reports showing that bradykinin-induced angioedema generally lacks urticaria and its onset is slower than allergic angioedema [2, 3].\n\nACE inhibitors are closely associated with bradykinin-related angioedema [2, 3]. It occurs from several hours to years after starting the use of ACE inhibitors. Of importance, ACE inhibitor-related angioedema occurs several months after its last dose. Our case had a long history of taking enalapril, an ACE inhibitor. Although it is difficult to determine the first episode of angioedema after starting the use of enalapril and the direct cause of it, previous reports also showed angioedema developed 15 min after extubation in a patient who started taking enalapril 10 days before surgery [4].\n\nAlthough ACE inhibitors and angiotensin II receptor blockers (ARBs) contribute to improved renal outcomes [5], the blockade of the renin–angiotensin system does not have superiority over other antihypertensive medications to reduce cardiovascular and renal outcomes [6]. The possibility of inducing angioedema should always be considered particularly in the perioperative period and in morbidly obese patients. In this connection, we would like to discuss our difficult airway management in this case. We tried tracheal intubation using a videolaryngoscope under the situation that manual mask ventilation was extremely difficult. This “one best intubation” is advocated by the JSA difficult airway management guideline [7]. However, as this guideline recommends, the supraglottic airway devices might have allowed us to choose safer strategies [7]. To do so, it is very important that supraglottic airway devices are always ready to use even in the ICU.\n\nWe used only dexamethasone for treatment of angioedema. However, previous studies have shown that histamine H1 and H2 antagonists, corticosteroids, and adrenaline are unlikely effective for improving bradykinin-mediated angioedema [2, 3]. Dexamethasone might have also been ineffective in the present case, as shown by the prolonged time for extubation. Other treatments like fresh-frozen plasma, component 1 inhibitors, or icatibant, a bradykinin-2 receptor antagonist, might have facilitated the relief of symptoms [2, 3].\n\nIn conclusion, although ACE inhibitor-induced angioedema is rare, it is difficult to determine when and in whom it will occur. In addition, once it occurs, it can be potentially life threatening, especially for patients with possible difficult airway although there is still no evidence to support our message. In such patients, it has been suggested that marked obesity, resulting in airway narrowing, is a risk factor for upper airway obstruction secondary to ACE inhibitor-induced angioedema [8]. Considering the risk–benefit ratio, we must be more careful in administering ACE inhibitor therapy in morbidly obese patients.\n\nAbbreviations\nACEAngiotensin-converting enzyme\n\nICUIntensive care unit\n\nNPVNegative predictive value\n\nARBAngiotensin II receptor blocker\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nAcknowledgements\nThe authors would like to thank ENAGO for the English editing of the manuscript.\n\nAuthors’ contributions\nAll authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Makiko Konda, Yusuke Naito, and Satoki Inoue. The first draft of the manuscript was written by Satoki Inoue and all authors, especially Junji Egawa and Masahiko Kawaguchi who commented on previous versions of the manuscript. All authors read and approved the final manuscript.\n\nFunding\nThis study was supported only by departmental funding from our institution.\n\nAvailability of data and materials\nNot applicable\n\nEthics approval and consent to participate\nNot applicable\n\nConsent for publication\nConsent to publish was obtained from the patient.\n\nCompeting interests\nThe authors declare having no competing interests.\n==== Refs\nReferences\n1. Langeron O Birenbaum A Le Saché F Raux M Airway management in obese patient Minerva Anestesiol. 2014 80 382 392 24122033 \n2. Bernstein JA Cremonesi P Hoffmann TK Hollingsworth J Angioedema in the emergency department: a practical guide to differential diagnosis and management Int J Emerg Med Int J Emerg Med. 2017 10 15 10.1186/s12245-017-0141-z 28405953 \n3. LoVerde D Files DC Krishnaswamy G Angioedema Crit Care Med. 2017 45 725 735 10.1097/CCM.0000000000002281 28291095 \n4. Kharasch ED Angiotensin-converting enzyme inhibitor-induced angioedema associated with endotracheal intubation Anesth Analg. 1992 74 602 604 10.1213/00000539-199204000-00023 1554129 \n5. Strippoli GF, Bonifati C, Craig M, Navaneethan SD, Craig JC. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2006;2006:CD006257.\n6. Bangalore S Fakheri R Toklu B Messerli FH Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials BMJ. 2016 352 i438 10.1136/bmj.i438 26868137 \n7. Japanese Society of Anesthesiologists JSA airway management guideline 2014: to improve the safety of induction of anesthesia J Anesth. 2014 28 482 493 10.1007/s00540-014-1844-4 24989448 \n8. Jain M Armstrong L Hall J Predisposition to and late onset of upper airway obstruction following angiotensin-converting enzyme inhibitor therapy Chest. 1992 102 871 874 10.1378/chest.102.3.871 1325341\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2363-9024",
"issue": "7(1)",
"journal": "JA clinical reports",
"keywords": "Angioedema; Angiotensin-converting enzyme inhibitor; Difficult airway; Enalapril",
"medline_ta": "JA Clin Rep",
"mesh_terms": null,
"nlm_unique_id": "101682121",
"other_id": null,
"pages": "1",
"pmc": null,
"pmid": "33398469",
"pubdate": "2021-01-04",
"publication_types": "D016428:Journal Article",
"references": "28291095;17054288;26868137;24122033;28405953;1554129;24989448;1325341",
"title": "Life-threatening airway obstruction caused by angioedema in a morbidly obese postoperative patient: a case report.",
"title_normalized": "life threatening airway obstruction caused by angioedema in a morbidly obese postoperative patient a case report"
}
|
[
{
"companynumb": "JP-BAUSCH-BL-2021-001172",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ENALAPRIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "018998",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENALAPRIL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DEXAMETHASONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "40069",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANGIOEDEMA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METOPROLOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "60",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TRICHLORMETHIAZIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRICHLORMETHIAZIDE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FUROSEMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FUROSEMIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "OLMESARTAN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OLMESARTAN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMLODIPINE BESYLATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMLODIPINE"
}
],
"patientagegroup": null,
"patientonsetage": "50",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "144",
"reaction": [
{
"reactionmeddrapt": "Obstructive airways disorder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Angioedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Therapy non-responder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KONDA M, INOUE S, NAITO Y, EGAWA J, KAWAGUCHI M. LIFE?THREATENING AIRWAY OBSTRUCTION CAUSED BY ANGIOEDEMA IN A MORBIDLY OBESE POSTOPERATIVE PATIENT: A CASE REPORT. JA CLINICAL REPORTS. 2021 JAN 04?7:1:1?4. DOI:10.1186/S40981?020?00408?6",
"literaturereference_normalized": "life threatening airway obstruction caused by angioedema in a morbidly obese postoperative patient a case report",
"qualification": "1",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20210126",
"receivedate": "20210126",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18791027,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20210419"
},
{
"companynumb": "JP-TEVA-2021-JP-1874553",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FENTANYL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INDUCTION DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "INDUCTION AND MAINTENANCE OF ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FENTANYL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "REMIFENTANIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MAINTENANCE OF ANAESTHESIA",
"drugintervaldosagedefinition": "806",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".1",
"drugstructuredosageunit": "008",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "REMIFENTANIL"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRICHLORMETHIAZIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "2",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRICHLORMETHIAZIDE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "FENTANYL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".05",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FENTANYL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CEFAZOLIN"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "002",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEFAZOLIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FAMOTIDINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FAMOTIDINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ROCURONIUM BROMIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INDUCTION DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "INDUCTION AND MAINTENANCE OF ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "80",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROCURONIUM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "AMLODIPINE BESYLATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMLODIPINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "DESFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MAINTENANCE OF ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DESFLURANE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FUROSEMIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FUROSEMIDE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ENALAPRIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "075501",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ENALAPRIL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "INDUCTION OF ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "120",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SUGAMMADEX"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NEUROMUSCULAR BLOCKADE REVERSAL",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SUGAMMADEX"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ACETAMINOPHEN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "1",
"drugstructuredosageunit": "002",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETAMINOPHEN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "OLMESARTAN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OLMESARTAN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METOPROLOL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "60",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "ROCURONIUM BROMIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "20",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ROCURONIUM"
}
],
"patientagegroup": "5",
"patientonsetage": "50",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "144",
"reaction": [
{
"reactionmeddrapt": "Respiratory arrest",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Angioedema",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Obstructive airways disorder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Loss of consciousness",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Swollen tongue",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KONDA M, INOUE S, NAITO Y, EGAWA J, KAWAGUCHI M. LIFE?THREATENING AIRWAY OBSTRUCTION CAUSED BY ANGIOEDEMA IN A MORBIDLY OBESE POSTOPERATIVE PATIENT: A CASE REPORT. JA?CLIN?REP 2021?7(1):NO PAGINATION.",
"literaturereference_normalized": "life threatening airway obstruction caused by angioedema in a morbidly obese postoperative patient a case report",
"qualification": "3",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20210130",
"receivedate": "20210130",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18811826,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20210419"
}
] |
{
"abstract": "Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition.",
"affiliations": "Department of Family Medicine, Aga Khan University Hospital, Karachi.;Department of Family Medicine, Aga Khan University Hospital, Karachi.",
"authors": "Arsalan|Rabeeya|R|;Sabzwari|Saniya|S|",
"chemical_list": "D000995:Antitubercular Agents; D014803:Vitamin B Complex; D025101:Vitamin B 6; D007538:Isoniazid",
"country": "Pakistan",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0030-9982",
"issue": "65(10)",
"journal": "JPMA. The Journal of the Pakistan Medical Association",
"keywords": "Isoniazid, Neuropathy, Pyridoxine, Anti tuberculous therapy.",
"medline_ta": "J Pak Med Assoc",
"mesh_terms": "D000995:Antitubercular Agents; D005260:Female; D006801:Humans; D007538:Isoniazid; D008875:Middle Aged; D018908:Muscle Weakness; D010523:Peripheral Nervous System Diseases; D012021:Reflex, Abnormal; D025101:Vitamin B 6; D014803:Vitamin B Complex",
"nlm_unique_id": "7501162",
"other_id": null,
"pages": "1131-3",
"pmc": null,
"pmid": "26440850",
"pubdate": "2015-10",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Isoniazid induced motor-dominant neuropathy.",
"title_normalized": "isoniazid induced motor dominant neuropathy"
}
|
[
{
"companynumb": "PK-SUN PHARMACEUTICAL INDUSTRIES LTD-2015R1-105018",
"fulfillexpeditecriteria": "1",
"occurcountry": "PK",
"patient": {
"drug": [
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "ISONIAZID"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "080136",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MG/KG, DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TUBERCULOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ISONIAZID."
}
],
"patientagegroup": null,
"patientonsetage": "45",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Peripheral motor neuropathy",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Peripheral sensory neuropathy",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "3"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ARSALAN R, SABZWARI S. ISONIAZID INDUCED MOTOR-DOMINANT NEUROPATHY. J-PAK-MED-ASSOC. 2015?65(10):1131-1133",
"literaturereference_normalized": "isoniazid induced motor dominant neuropathy",
"qualification": "3",
"reportercountry": "PK"
},
"primarysourcecountry": "PK",
"receiptdate": "20151027",
"receivedate": "20151027",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11663827,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160304"
}
] |
{
"abstract": "A man in his 60s presents with chronic dyspnoea and cough for 3 years. EKG and nuclear stress test were not diagnostic. An echocardiogram revealed moderate pericardial effusion. His symptoms improved with ibuprofen temporarily and a repeat echocardiogram showed resolution of the effusion. However, when his symptoms recurred, re-imaging showed a large intracardiac tumour causing right ventricular outflow obstruction. Subsequent histological examination revealed metastatic paraganglioma. He was found to carry a germline mutation in the SDHB gene which is associated with higher malignant risk. Knowledge of his underlying mutation allowed the patient and his family to receive appropriate gene-specific counselling and surveillance.",
"affiliations": "Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.",
"authors": "Moline|Jessica|J|;Ngeow|Joanne|J|;Rajiah|Prabhakar|P|;Eng|Charis|C|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1757-790X",
"issue": "2011()",
"journal": "BMJ case reports",
"keywords": null,
"medline_ta": "BMJ Case Rep",
"mesh_terms": "D002908:Chronic Disease; D003371:Cough; D004417:Dyspnea; D006338:Heart Neoplasms; D006801:Humans; D008297:Male; D008875:Middle Aged; D010236:Paraganglioma, Extra-Adrenal; D012008:Recurrence",
"nlm_unique_id": "101526291",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "22670000",
"pubdate": "2011-12-20",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "17200167;19825962;17102103;19497985;210330;15369446;8296267;19190077;15328326;4824541;19454582;11198571;17237836;12000816;19864450",
"title": "Evil lurks in the heart of man: cardiac paraganglioma presenting as recurrent dyspnoea and chronic cough.",
"title_normalized": "evil lurks in the heart of man cardiac paraganglioma presenting as recurrent dyspnoea and chronic cough"
}
|
[
{
"companynumb": "US-STRIDES ARCOLAB LIMITED-2016SP016584",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "IBUPROFEN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PERICARDIAL EFFUSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IBUPROFEN."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MOLINE J, NGEOW J, RAJIAH P, ENG C. EVIL LURKS IN THE HEART OF MAN: CARDIAC PARAGANGLIOMA PRESENTING AS RECURRENT DYSPNOEA AND CHRONIC COUGH. BMJ CASE REP.. 2011;1-4",
"literaturereference_normalized": "evil lurks in the heart of man cardiac paraganglioma presenting as recurrent dyspnoea and chronic cough",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20170331",
"receivedate": "20170331",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13389505,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170429"
}
] |
{
"abstract": "Primary hyperparathyroidism (PHPT) predominantly affects older adults, and parathyroidectomy can achieve definitive cure in symptomatic PHPT and asymptomatic meeting surgical criteria. As the population continues to age, the treatment of PHPT in octogenarians and nonagenarians presents a clinical conundrum. This case series presents the management of eight patients 85 years of age and older diagnosed with PHPT. A retrospective chart review of patients diagnosed with primary hyperparathyroidism were identified in a single institution. Those patients 85 years of age and older who were followed up for over one year were included in this case series. The literature on treatment options for this age group was also reviewed. Eight cases of PHPT patients aged 88 ± 2.5 years old with a follow-up average of 5.6 ± 4.4 years were reported in our case series. Six PHPT patients were medically managed and two PHPT patients underwent parathyroid resection. Most of the medically managed PHPT patients except for one had long-term stability of disease for over five years. The treatment of PHPT diagnosed in patients over 85 years of age presents a clinical challenge for which there is no clear consensus guideline. Our case series supports that medical therapy is a feasible option for PHPT patients over 85 years old.",
"affiliations": "Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Jersey, NJ 08903, USA.;Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Jersey, NJ 08903, USA.;Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Jersey, NJ 08903, USA.;Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Jersey, NJ 08903, USA.;Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Jersey, NJ 08903, USA.",
"authors": "Sluis|Kenneth|K|;Kim|Hyon|H|;He|Yuling|Y|;Wong|Beatrice|B|;Wang|Xiangbing|X|https://orcid.org/0000-0002-8242-7475",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1155/2019/4807081",
"fulltext": "\n==== Front\nCase Rep EndocrinolCase Rep EndocrinolCRIECase Reports in Endocrinology2090-65012090-651XHindawi 10.1155/2019/4807081Case SeriesTherapeutic Challenges for Elderly Patients with Primary Hyperparathyroidism Sluis Kenneth Kim Hyon He Yuling Wong Beatrice https://orcid.org/0000-0002-8242-7475Wang Xiangbing [email protected] of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Jersey, NJ 08903, USAAcademic Editor: Mihail A. Boyanov\n\n2019 23 10 2019 2019 480708126 7 2019 16 9 2019 25 9 2019 Copyright © 2019 Kenneth Sluis et al.2019This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Primary hyperparathyroidism (PHPT) predominantly affects older adults, and parathyroidectomy can achieve definitive cure in symptomatic PHPT and asymptomatic meeting surgical criteria. As the population continues to age, the treatment of PHPT in octogenarians and nonagenarians presents a clinical conundrum. This case series presents the management of eight patients 85 years of age and older diagnosed with PHPT. A retrospective chart review of patients diagnosed with primary hyperparathyroidism were identified in a single institution. Those patients 85 years of age and older who were followed up for over one year were included in this case series. The literature on treatment options for this age group was also reviewed. Eight cases of PHPT patients aged 88 ± 2.5 years old with a follow-up average of 5.6 ± 4.4 years were reported in our case series. Six PHPT patients were medically managed and two PHPT patients underwent parathyroid resection. Most of the medically managed PHPT patients except for one had long-term stability of disease for over five years. The treatment of PHPT diagnosed in patients over 85 years of age presents a clinical challenge for which there is no clear consensus guideline. Our case series supports that medical therapy is a feasible option for PHPT patients over 85 years old.\n==== Body\n1. Introduction\nPrimary Hyperparathyroidism (PHPT) is a common disease that increases in prevalence with advancing age. Prevalence peaks in women around 70–79 years of age (492 per 100,000) and in men over 80 years old (264 per 100,000) [1]. Most patients with PHPT initially present with asymptomatic hypercalcemia. Those that are symptomatic present with axial and extremity fractures, nephrolithiasis, and psychiatric disturbance [2]. Surgical resection of the involved glands is the standard of care for young or symptomatic patients with PHPT. Medical management is used as a bridge to surgery or in patients who refuse or cannot safely undergo surgery. Strategies include hydration with expectant management, stopping offending agents such as calcium supplementation and medications (thiazides, lithium) and using diuretics, bisphosphonates, selective estrogen receptor modulators, and cinacalcet [2]. Expectant management involves serial monitoring for worsening of symptoms without specific therapeutic intervention [3, 4].\n\nMost of the literature on the treatment of PHPT is not age-specific. About 1.5% of patients over the age of 70 have PHPT [5]. As our population continues to age and as average life expectancy increases, the proportion of elderly patients with PHPT will also grow. Though the standard of care to manage PHPT is surgery to achieve cure, the role of surgery is less clear in the very elderly. The objective of our study is to report eight cases of PHPT patients over 85 years of age who were managed using medical or surgical treatment to elucidate differences in prognosis and outcomes.\n\n2. Cases Presentation\nWe conducted a retrospective chart review of PHPT patients evaluated at Robert Wood Johnson University Hospital from January 2000 to September 2016. Our institution's IRB provided approval for our investigations. There were 556 patients diagnosed with PHPT during this time. The diagnostic criteria of PHPT included: (1) intact PTH > 65 pg/mL (normal range: 10–65 pg/mL) or inappropriately normal levels in the presence of elevated serum calcium, (2) serum calcium > 10.6 mg/dL (normal range: 8.5–10.4 mg/dL), and (3) 24-hour urinary calcium > 100 mg/day (normal range: 100–250 mg/day). Eight PHPT patients aged 85 years and older with follow-up duration longer than one year were included for this study. Patient demographics, baseline characteristics, clinical presentation and overall clinical follow-up were examined.\n\nEight patients diagnosed with PHPT at the age of 85 years or older were included. The average age at diagnosis was 88 ± 2.5 years old. The average follow-up duration was 5.6 ± 4.4 years. The average calcium was 11.3 ± 0.78 mg/dL, iPTH was 166 ± 154 pg/mL and 24-hour urine calcium was 183 ± 35.5 mg at the time of diagnosis. All eight patients met guidelines [2, 5] for surgery by the serum calcium levels >1 mg/dl upper limit of normal, creatinine clearance <60 cc/min or T-score <2.5 (Table 1). Six PHPT patients were medically managed for one to eight years and two PHPT patients underwent parathyroid resection. The surgical group had a pre-operative serum calcium of 12.3 mg/dL while the medically managed group had an average of 10.9 mg/dL. For two patients treated surgically, one patient was cured with normal calcium and PTH levels but was only followed up for two years. One patient had recurrence of PHPT five years after surgery and required medical management with cinacalcet, loop diuretic, and bisphosphonate for ten years. Six patients were managed medically for an average of 5.2 years with minimal complications. Only one of the six patients experienced PHPT-related mortality. This patient had severe dementia, was on medical treatment for eight years, and passed away on hospice after a hip fracture. Of the other medically managed patients, three patients were managed with pharmaceutical therapy, one with bisphosphonate and two with cinacalcet. Two other patients were treated with nonpharmaceutical expectant management, which included oral hydration, discontinuation of HCTZ and maintaining physical activity. They had favorable outcomes after three to six years.\n\nPatient vignettes are demonstrated in Table 1.\n\n3. Discussion\nThe Endocrine Society consensus guidelines recommend parathyroidectomy for both symptomatic and asymptomatic PHPT. Surgery is readily offered for biochemical cure in younger, symptomatic or asymptomatic patients with PHPT meeting surgical criteria [2]. The benefits of parathyroidectomy include advantages in survival, increased bone density, reduced fatigue, and other subjective measures [6, 7].\n\nMuch of the current literature advocates for more aggressive surgical therapy for the elderly. However, the benefit of surgery at achieving cure for octogenarians and nonagenarians is less straightforward than for the young. There is increased risk for complications, prolonged operation time and increased length of stay in hospitals for patients over the age of 80 years [7, 8]. As our understanding of PHPT has evolved, different phenotypes of the disease have been recognized, the symptoms of which can be confounded by the aging process in this population [9]. Studies have shown that medically managed patients with PHPT could have stable disease for over ten years [9, 10]. Our expanded case series supports medical management as a reasonable option in the very elderly, especially those with comorbidities.\n\nLiterature in favor of medical management of the very old shows promise despite its smaller scope. Khan et al. [4] and Marcocci et al. [11] reviewed the rationale and evidence behind medical management and expectant monitoring. They found that medical management can be effective, and that patients' quality of life can be similar to those treated surgically. Jacobs et al. [3] described four patients with PHPT aged 79 to 87 years treated with medical management as a bridge to surgery or as sole therapy in poor surgical candidates or those refusing surgery. They employed saline hydration, pamidronate and cinacalcet. Medical therapy was a successful bridge to surgical cure with parathyroidectomy for two patients after two weeks to two months of treatment. Medical therapy was not tolerated for another and pursued indefinitely for the final patient. Wong reported two PHPT patients over the age of 90 treated with oral rehydration, bisphosphonate or cinacalcet. They experienced no PHPT related complications or fractures in a follow-up duration of seven months to four years [12].\n\nThe limitations of our study include small sample size and short duration of follow-up. One patient had baseline dementia, and 3 nonagenarian patients passed away after 6–10 years follow up, we did not have the data and therefore cannot compare quality of life, cognitive and muscle function before and after intervention.\n\nIn summary, our data suggest that medical therapy is a reasonable option for PHPT patients over 85 years old. As life expectancy increases and more patients are diagnosed with PHPT later in life, further consensus guidelines may need to specifically address treatment recommendations for patients over the age of 85 years. Studies with larger patient populations and randomized controlled trials are needed to support our findings.\n\nConflicts of Interest\nThe authors declare that they have no conflicts of interest.\n\nTable 1 Eight cases of PHPT in patients over age 85.\n\nCase #\tClinical description\t\nCase 1\tAn 86-year-old woman with a history of osteopenia, hyperlipidemia, and GERD was diagnosed with PHPT with a calcium level of 13 mg/dl, iPTH level of 66 pg/ml, 25OHD 34 ng/ml and creatinine 1.07 mg/dl. She underwent surgery and had successful removal of a right upper parathyroid gland. She achieved surgical cure with normalized calcium and iPTH levels. Her last calcium was 9.7 mg/dl, iPTH 12.4 pg/ml and 25OHD 54 ng/ml at her 2 year follow up visit.\t\nCase 2\tA 91-year-old woman with a history of hyperparathyroidism with parathyroidectomy of 3.5 glands 5 years ago, hypothyroidism, osteoporosis, and goiter presented with a calcium level of 11.6 and iPTH level of 500. She was diagnosed with relapse of PHPT, and was managed with cinacalcet, furosemide, and risendronate. Serum calcium was controlled for about 8 years, but creatinine started to rise. Ten years after the recurrence of PHPT, cinacalcet had to be lowered and her bisphosphonate had to be discontinued after a further increase in creatinine. She suffered a left hip fracture and a possible aspiration event during the subsequent hospitalization. She passed away from sepsis after 10 years' medical treatment of recurrence of PHPT.\t\nCase 3\tAn 85-year-old woman with a history of a resected follicular Hurthle cell neoplasm presented with a calcium level of 11.5 mg/dl and iPTH of 279 pg/ml. She was diagnosed with PHPT and treated with cessation of hydrochlorothiazide, initiation of furosemide, and cinacalcet for 5 years. Cinacalcet dosage had to be increased after a year, but then subsequently discontinued due to worsening renal function (Cr 2.98–3.3 mg/dl). Five years after diagnosis her PTH level increased (483–511 pg/ml) but calcium was 10–11 mg/dL. She was hospitalized for cellulitis 6 years later and was discharged to hospice care for end-stage renal disease. She passed away at the age of 91.\t\nCase 4\tA 91-year-old man with a history of type 2 diabetes, hyperlipidemia, dementia, atrial fibrillation, and congestive heart failure was hospitalized for sepsis. He was found to have a calcium level of 11.1 mg/dl, iPTH 59 pg/ml, 24-hour calcium 203 mg, and 25OHD 26 ng/ml. He was diagnosed with PHPT. He was treated with calcitonin, oral hydration and furosemide. He was discharged to his long-term care facility. His calcium level remained normal up to 10.9 mg/dL with Cr 1.8 mg/dl at 1-year follow up.\t\nCase 5\tA 96-year-old woman with a history vitamin D deficiency, osteoporosis, and hypothyroidism was found to have a calcium level of 11.2 mg/dl, iPTH 165 pg/ml, and 24-hour urine calcium of 204 mg. A parathyroid scan showed a possible left lower pole adenoma. She refused surgery and was treated with zoledronic acid infusion for her osteoporosis. Calcium decreased to 10.2 mg/dL three years after diagnosis she was given a second zoledronic acid infusion. She was followed for 4 years and did well with serum calcium maintained from 10.2 to 10.7 md/dL and iPTH 147 pg/ml.\t\nCase 6\tAn 86-year-old woman with a history of osteoporosis, hypertension and dementia was found to have a calcium level of 11.1 mg/dl, iPTH 100 pg/ml, and 25OHD 32 ng/mL. She did not tolerate bisphosphonate therapy and was treated with oral hydration, cessation of thiazide diuretic, and encouragement of physically activity. Two years after diagnosis, calcium levels were maintained in the high-normal range (10.2–10.5 mg/dl). Her dementia worsened and she suffered a left hip fracture 8 years after diagnosis. She passed away on hospice from a gangrenous wound after 8 years of expectant medical management of PHPT at age of 96.\t\nCase 7\tAn 86-year-old woman with osteopenia treated with bisphosphonates and a selective estrogen receptor modulator, hypothyroidism, vitamin D deficiency and DVT was found to have a calcium level of 11.8 mg/dl, iPTH 128 pg/ml, 24-hour urine 142 mg, and 25OHD 31 ng/mL Sestamibi scan did not locate an adenoma. Expectant management with increased oral hydration, decreased milk intake, cessation of thiazides, and encouragement to increase activity was begun. Her calcium rose as high as 12.9 mg/dL but then settled to 11.2 mg/dL on subsequent measurement. She was followed without incident for 3 years.\t\nCase 8\tAn 89-year-old woman with a history of hypothyroidism was found with a calcium level of 11.5 mg/dl, iPTH 95 pg/ml and 25OHD 24.6 ng/mL. She was asymptomatic and was managed expectantly with oral hydration and increased physical activity. Calcium was maintained from 10.2to 10.9 mg/dL and PTH 77–107 pg/ml. She was hospitalized for hypertensive urgency but otherwise had no sequelae for 6 years.\t\nNote: PHPT = Primary hyperparathyroidism, iPTH = Intact parathyroid hormone, 25OHD = 25 hydroxyvitamin D.\n==== Refs\n1 Yeh M. W. Ituarte P. H. Zhou H. C. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population The Journal of Clinical Endocrinology & Metabolism 2013 98 3 1122 1129 10.1210/jc.2012-4022 2-s2.0-84874883807 23418315 \n2 Bilezikian J. P. Brandi M. L. Eastell R. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the fourth international workshop The Journal of Clinical Endocrinology & Metabolism 2014 99 10 3561 3569 10.1210/jc.2014-1413 2-s2.0-84906689673 25162665 \n3 Jacobs L. Samson M. M. Verhaar H. J. Koek H. L. Therapeutic challenges in elderly patients with symptomatic hypercalcemia caused by primary hyperparathyroidism The Netherlands Journal of Medicine 2012 70 1 35 38 22271812 \n4 Khan A. Grey A. Shoback D. Medical management of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop Journal of Clinical Endocrinology & Metabolism 2009 94 2 373 381 19193912 \n5 Chen H. Parkerson S. Udelsman R. Parathyroidectomy in the elderly: do the benefits outweigh the risks? World Journal of Surgery 1998 22 6 531 536 10.1007/s002689900431 2-s2.0-0031954447 9597924 \n6 Bollerslev J. Jansson S. Mollerup C. L. Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial The Journal of Clinical Endocrinology & Metabolism 2007 92 5 1687 1692 10.1210/jc.2006-1836 2-s2.0-34249856689 17284629 \n7 Talpos G. B. Bone H. G. 3rd Kleerekoper M. Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey Surgery 2000 128 6 1013 1021 10.1067/msy.2000.110844 2-s2.0-0033666126 11114637 \n8 Thomas D. C. Roman S. A. Sosa J. A. Parathyroidectomy in the elderly: analysis of 7313 patients Journal of Surgical Research 2011 170 2 240 246 10.1016/j.jss.2011.03.014 2-s2.0-80052668178 21571309 \n9 Bilezikian J. P. Primary hyperparathyroidism The Journal of Clinical Endocrinology & Metabolism 2018 103 11 3993 4004 10.1210/jc.2018-01225 2-s2.0-85054896489 30060226 \n10 Rubin M. R. Bilezikian J. P. McMahon D. J. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years The Journal of Clinical Endocrinology & Metabolism 2008 93 9 3462 3470 10.1210/jc.2007-1215 2-s2.0-51649095701 18544625 \n11 Marcocci C. Bollerslev J. Khan A. A. Shoback D. M. Medical management of primary hyperparathyroidism: proceedings of the fourth international workshop on the management of asymptomatic primary hyperparathyroidism The Journal of Clinical Endocrinology & Metabolism 2014 99 10 3607 3618 10.1210/jc.2014-1417 2-s2.0-84907637552 25162668 \n12 Wong B. Wang X. Treatment of nonagenarians with primary hyperparathyroidism Journal of the American Geriatrics Society 2016 64 10 e112 e113 10.1111/jgs.14412 2-s2.0-84983666664 27564595\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2090-651X",
"issue": "2019()",
"journal": "Case reports in endocrinology",
"keywords": null,
"medline_ta": "Case Rep Endocrinol",
"mesh_terms": null,
"nlm_unique_id": "101576457",
"other_id": null,
"pages": "4807081",
"pmc": null,
"pmid": "31885946",
"pubdate": "2019",
"publication_types": "D002363:Case Reports",
"references": "9597924;27564595;11114637;30060226;17284629;18544625;21571309;19193912;25162665;23418315;22271812;25162668",
"title": "Therapeutic Challenges for Elderly Patients with Primary Hyperparathyroidism.",
"title_normalized": "therapeutic challenges for elderly patients with primary hyperparathyroidism"
}
|
[
{
"companynumb": "US-AMGEN-USASP2019199147",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FUROSEMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERPARATHYROIDISM PRIMARY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FUROSEMIDE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CINACALCET HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021688",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERPARATHYROIDISM PRIMARY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CINACALCET HCL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CINACALCET HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021688",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "INCREASED DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CINACALCET HCL"
}
],
"patientagegroup": "6",
"patientonsetage": "85",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "End stage renal disease",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Renal impairment",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Death",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Cellulitis",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WANG X.? SLUIS K.? KIM H. ET AL.. THERAPEUTIC CHALLENGES FOR ELDERLY PATIENTS WITH PRIMARY HYPERPARATHYROIDISM. CASE REPORTS IN ENDOCRINOLOGY. 2019?1-3",
"literaturereference_normalized": "therapeutic challenges for elderly patients with primary hyperparathyroidism",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20191204",
"receivedate": "20191204",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17110394,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200122"
},
{
"companynumb": "US-AMGEN-USASP2019199088",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CINACALCET HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021688",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERPARATHYROIDISM PRIMARY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CINACALCET HCL"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CINACALCET HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "021688",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "LOWERED DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CINACALCET HCL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RISEDRONATE SODIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERPARATHYROIDISM PRIMARY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RISEDRONATE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FUROSEMIDE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERPARATHYROIDISM PRIMARY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FUROSEMIDE."
}
],
"patientagegroup": "6",
"patientonsetage": "91",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Aspiration",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Hip fracture",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Blood creatinine increased",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "WANG X.? SLUIS K.? KIM H. ET AL.. THERAPEUTIC CHALLENGES FOR ELDERLY PATIENTS WITH PRIMARY HYPERPARATHYROIDISM. CASE REPORTS IN ENDOCRINOLOGY. 2019?1-3",
"literaturereference_normalized": "therapeutic challenges for elderly patients with primary hyperparathyroidism",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20191202",
"receivedate": "20191202",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17098903,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200122"
}
] |
{
"abstract": "Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here, we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.",
"affiliations": "Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.;Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.;Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.;Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.;Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.",
"authors": "Puing|Alfredo G|AG|https://orcid.org/0000-0002-9836-4835;Couture-Cossette|Antoine|A|;Wang|Aileen X|AX|https://orcid.org/0000-0002-1097-9270;Zygourakis|Corinna C|CC|;Cheng|Xingxing|X|https://orcid.org/0000-0002-0542-8749;Stevens|Bryan A|BA|;Banaei|Niaz|N|;Novoa|Roberto A|RA|;Ho|Dora Y|DY|;Subramanian|Aruna K|AK|",
"chemical_list": "D000935:Antifungal Agents",
"country": "Denmark",
"delete": false,
"doi": "10.1111/tid.13365",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1398-2273",
"issue": "22(6)",
"journal": "Transplant infectious disease : an official journal of the Transplantation Society",
"keywords": "coccidioidomycosis; kidney transplant; phaeohyphomycosis",
"medline_ta": "Transpl Infect Dis",
"mesh_terms": "D000935:Antifungal Agents; D001203:Ascomycota; D001706:Biopsy; D003045:Coccidioides; D003047:Coccidioidomycosis; D060085:Coinfection; D006801:Humans; D016867:Immunocompromised Host; D016030:Kidney Transplantation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections; D060446:Phaeohyphomycosis; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome",
"nlm_unique_id": "100883688",
"other_id": null,
"pages": "e13365",
"pmc": null,
"pmid": "32533741",
"pubdate": "2020-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient: A case report and literature review.",
"title_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review"
}
|
[
{
"companynumb": "US-DRREDDYS-USA/USA/21/0131796",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "090509",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "EXTENDED RELEASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN,UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "REDUCED TO HALF",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN,UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTI?THYMOGLOBULIN"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": null,
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TRICE WEEKLY, 400 MG, 80 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE 400 MG, TRIMETHOPRIM 80 MG"
}
],
"patientagegroup": "5",
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coccidioidomycosis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Fungal infection",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Phaeohyphomycosis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PUING A, COUTURE?COSSETTE A, WANG A, ZYGOURAKIS C, CHENG X, STEVENS B, ET AL. SIMULTANEOUS COCCIDIOIDOMYCOSIS AND PHAEOHYPHOMYCOSIS IN A KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT AND LITERATURE REVIEW. TRANSPL INFECT DIS. 2020?22(6):UNKNOWN?UNKNOWN. DOI:10.1111/TID.13365",
"literaturereference_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210720",
"receivedate": "20210215",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18891574,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
},
{
"companynumb": "US-MYLANLABS-2021M1013449",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "LOWER DOSE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MILLIGRAM/KILOGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "T-CELL DEPLETION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "065520",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "250 MILLIGRAM, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "VORICONAZOLE"
},
"drugadditional": "1",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MILLIGRAM/KILOGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COCCIDIOIDOMYCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VORICONAZOLE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "80?400 MG TRICE WEEKLY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMETHOPRIM SULFAMETHOXAZOLE"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.15 MILLIGRAM/KILOGRAM, QD.....",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Phaeohyphomycosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hallucination, visual",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Coccidioidomycosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PUING AG, COUTURE?COSSETTE A, WANG AX, ZYGOURAKIS CC, CHENG X, STEVENS BA, ET AL. SIMULTANEOUS COCCIDIOIDOMYCOSIS AND PHAEOHYPHOMYCOSIS IN A KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2020?22(6):E13365.",
"literaturereference_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210305",
"receivedate": "20210305",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18973167,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210420"
},
{
"companynumb": "US-TEVA-2021-US-1890756",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ANTI?THYMOGLOBULIN",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LYMPHODEPLETION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTI?THYMOGLOBULIN"
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "080356",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": ".15 MG/KG DAILY; EXTENDED RELEASE WITH A 24?HOUR TROUGH OF 6?7 NG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "VORICONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MG/KG DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COCCIDIOIDOMYCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VORICONAZOLE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65457",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "080356",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "80?400 MG TRICE WEEKLY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMETHOPRIM?SULFAMETHOXAZOLE"
}
],
"patientagegroup": "5",
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Phaeohyphomycosis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hallucination, visual",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Coccidioidomycosis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PUING AG, COUTURE?COSSETTE A, WANG AX, ZYGOURAKIS CC, CHENG X, STEVENS BA, ET AL. SIMULTANEOUS COCCIDIOIDOMYCOSIS AND PHAEOHYPHOMYCOSIS IN A KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT AND LITERATURE REVIEW. TRANSPL?INFECT?DIS 2020?22(6):E13365.",
"literaturereference_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210831",
"receivedate": "20210321",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19036029,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20211014"
},
{
"companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP002776",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "210785",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "LOWER DOSE OF PREDNISONE AT 4 MG DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INITIALLY REDUCED TO HALF, AND THEN STOPPED AFTER THE CONFIRMATION OF COCCIDIOIDES INFECTION",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "210785",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MILLIGRAM DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, WAS SWITCHED TO INTERMEDIATE RELEASE AT A LOWER DOSE WITH GOAL TROUGH LEVEL OF 6 NG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "T-CELL DEPLETION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN"
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "EXTENDED RELEASE 0.15 MILLIGRAM/KILOGRAM WITH A 24 HOUR",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MILLIGRAM/KILOGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "250 MILLIGRAM, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COTRIMOXAZOLE"
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coccidioidomycosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Phaeohyphomycosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PUING AG, COUTURE?COSSETTE A, WANG AX, ZYGOURAKIS CC, CHENG X, STEVENS BA, ET AL.. SIMULTANEOUS COCCIDIOIDOMYCOSIS AND PHAEOHYPHOMYCOSIS IN A KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT AND LITERATURE REVIEW. TRANSPL?INFECT?DIS. 2020?22(6)",
"literaturereference_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210326",
"receivedate": "20210326",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19059280,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210420"
},
{
"companynumb": "NVSC2020US183509",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "80336",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MG/KG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "T-CELL DEPLETION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, DOSE REDUCED TO HALF",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65461",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.15 MG/KG, QD (WITH A 24-HOUR)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": "1",
"drugadministrationroute": null,
"drugauthorizationnumb": "65461",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "65379",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "250 MG, BID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TRIMETHOPRIM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "80 MG, TID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "80",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TRIMETHOPRIM."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "400 MG, TID",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PNEUMOCYSTIS JIROVECII INFECTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "400",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "80336",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "RENAL TRANSPLANT",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coccidioidomycosis",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Phaeohyphomycosis",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PUING AG, COUTURE?COSSETTE A, WANG AX, ZYGOURAKIS CC, CHENG X, STEVENS BA ET AL.. SIMULTANEOUS COCCIDIOIDOMYCOSIS AND PHAEOHYPHOMYCOSIS IN A KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT AND LITERATURE REVIEW. TRANSPLANT INFECTIOUS DISEASE. 2020?EL3365",
"literaturereference_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200630",
"receivedate": "20200630",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 17965030,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20200714"
},
{
"companynumb": "US-009507513-2102USA002855",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK, REDUCED TO HALF",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "80?400 MG TRICE WEEKLY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIFUNGAL PROPHYLAXIS",
"drugintervaldosagedefinition": "803",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SULFAMETHOXAZOLE (+) TRIMETHOPRIM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VORICONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COCCIDIOIDOMYCOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VORICONAZOLE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "POSACONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "205053",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "300 MG DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COCCIDIOIDOMYCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "300",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NOXAFIL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VORICONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MILLIGRAM/KILOGRAM DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PHAEOHYPHOMYCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VORICONAZOLE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MILLIGRAM/KILOGRAM DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PHAEOHYPHOMYCOSIS",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "4 MG DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "4",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "POSACONAZOLE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "205053",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PHAEOHYPHOMYCOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "NOXAFIL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TACROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "0.15 MG/KG DAILY; 24?HOUR TROUGH OF 6?7 NG/ML; EXTENDED RELEASE (UNSPECIFIED)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".15",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TACROLIMUS."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COCCIDIOIDOMYCOSIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "250 MG TWICE A DAY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "250",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "5 MG DAILY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "IMMUNOSUPPRESSION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "64",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PUING AG, COUTURE?COSSETTE A, WANG AX, ZYGOURAKIS CC, CHENG X, STEVENS BA, ET AL.. SIMULTANEOUS COCCIDIOIDOMYCOSIS AND PHAEOHYPHOMYCOSIS IN A KIDNEY TRANSPLANT RECIPIENT: A CASE REPORT AND LITERATURE REVIEW. TRANSPLANT INFECTIOUS DISEASE. 2020?22 (6)",
"literaturereference_normalized": "simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient a case report and literature review",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210305",
"receivedate": "20210305",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18973635,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210420"
}
] |
{
"abstract": "BACKGROUND\nDuring times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation.\n\n\nMETHODS\nCadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay.\n\n\nRESULTS\nNinety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance.\n\n\nCONCLUSIONS\nThis first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.",
"affiliations": "1 Institute of Anaesthesiology, University Hospital Zurich, Zurich, Switzerland. 2 Swiss HPB and Transplant Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland. 3 Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, Hospital das Clinicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil. 4 Discipline of Anesthesiology, Hospital das Clinicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil. 5 Department of Anaesthesiology, Ghent University Hospital, Ghent, Belgium. 6 Transplantation Center and Department of General and Hepatobiliary Surgery, Ghent University Hospital, Ghent, Belgium. 7 Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. 8 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 9 Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.",
"authors": "Beck-Schimmer|Beatrice|B|;Bonvini|John M|JM|;Schadde|Erik|E|;Dutkowski|Philipp|P|;Oberkofler|Christian E|CE|;Lesurtel|Mickael|M|;DeOliveira|Michelle L|ML|;Figueira|Estela R R|ER|;Rocha Filho|Joel A|JA|;Auler|Jose Otavio Costa|JO|;D'Albuquerque|Luiz A C|LA|;Reyntjens|Koen|K|;Wouters|Patrick|P|;Rogiers|Xavier|X|;Debaerdemaeker|Luc|L|;Ganter|Michael T|MT|;Weber|Achim|A|;Puhan|Milo A|MA|;Clavien|Pierre-Alain|PA|;Breitenstein|Stefan|S|",
"chemical_list": "D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D015415:Biomarkers; D008738:Methyl Ethers; D000077149:Sevoflurane; D001219:Aspartate Aminotransferases; D015742:Propofol",
"country": "United States",
"delete": false,
"doi": "10.1097/TP.0000000000000644",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0041-1337",
"issue": "99(8)",
"journal": "Transplantation",
"keywords": null,
"medline_ta": "Transplantation",
"mesh_terms": "D000328:Adult; D000368:Aged; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001219:Aspartate Aminotransferases; D001530:Belgium; D015415:Biomarkers; D001938:Brazil; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008738:Methyl Ethers; D008875:Middle Aged; D016017:Odds Ratio; D055031:Primary Graft Dysfunction; D015742:Propofol; D012307:Risk Factors; D000077149:Sevoflurane; D013557:Switzerland; D013997:Time Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome",
"nlm_unique_id": "0132144",
"other_id": null,
"pages": "1606-12",
"pmc": null,
"pmid": "25769076",
"pubdate": "2015-08",
"publication_types": "D003160:Comparative Study; D016428:Journal Article; D016448:Multicenter Study; D016449:Randomized Controlled Trial; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial.",
"title_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial"
}
|
[
{
"companynumb": "CH-ABBVIE-13P-151-1148180-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BREITENSTEIN S, BONVINI J, SCHADDE E, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530094,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
},
{
"companynumb": "CH-ABBVIE-13P-151-1148178-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BECK-SCHIMMER B, BREITENSTEIN S, BONVINI J, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530097,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
},
{
"companynumb": "CH-ABBVIE-13P-151-1146956-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BECK-SCHIMMER B, BONVINI J, SCHADDE E, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530088,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
},
{
"companynumb": "CH-ABBVIE-13P-151-1148182-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BREITENSTEIN S, BONVINI J, SCHADDE E, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530098,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
},
{
"companynumb": "CH-ABBVIE-13P-151-1148179-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BREITENSTEIN S, BONVINI J, SCHADDE E, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530099,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
},
{
"companynumb": "CH-ABBVIE-13P-151-1148181-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BREITENSTEIN S, BONVINI J, SCHADDE E, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530100,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
},
{
"companynumb": "CH-ABBVIE-13P-151-1148183-00",
"fulfillexpeditecriteria": "1",
"occurcountry": "CH",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "020478",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "BETWEEN 3 AND 6 MCG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATRACURIUM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANAESTHESIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": ".5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATRACURIUM"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Complications of transplanted liver",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Transplant dysfunction",
"reactionmeddraversionpt": "18.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BREITENSTEIN S, BONVINI J, SCHADDE E, ET AL. CONDITIONING WITH SEVOFLURANE IN LIVER TRANSPLANTATION: RESULTS OF A MULTICENTER RANDOMIZED CONTROLLED TRIAL. TRANSPLANTATION. 2015;.",
"literaturereference_normalized": "conditioning with sevoflurane in liver transplantation results of a multicenter randomized controlled trial",
"qualification": "1",
"reportercountry": "COUNTRY NOT SPECIFIED"
},
"primarysourcecountry": "CH",
"receiptdate": "20150324",
"receivedate": "20130917",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 9530095,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20150721"
}
] |
{
"abstract": "Relapsed/refractory B-precursor acute lymphoblastic leukemia (BCP-ALL) remains a major therapeutic challenge in pediatric hematology. Chimeric antigen receptor (CAR) T cells targeting CD19 have shown remarkable initial response rates in BCP-ALL patients, while long-term leukemia control rate is only about 50%. So far, main mechanisms of BCP-ALL relapse after CD19-CAR T-cell therapy have been either insufficient CAR T-cell persistence in vivo or loss of surface CD19.\n\n\n\nHere, we report an exceptional presentation of BCP-ALL relapse in the eye during the systemic control through CAR T-cell therapy. We report a case of fatal intraocular relapse in a pediatric patient with pro-B-ALL after initial response to CD19-CAR T-cell therapy. One month after CD19-CAR T-cell therapy, remission was documented by bone marrow aspirate analysis with absence of CD19+ cells and CD19-CAR T cells could be detected in both peripheral blood and bone marrow. At the same time, however, the patient presented with progressive visual disturbance and CD19+ cells were found within the anterior chamber of the eye. Despite local and systemic therapy, ocular relapse led to BCP-ALL dissemination and systemic relapse within weeks. The eye represents a rare site for local manifestation of BCP-ALL, but isolated intraocular relapse is a clinically unreckoned presentation of BCP-ALL in the era of CD19-CAR T cells.\n\n\n\nDuring systemic control of BCP-ALL through CD19-CAR T cells, relapse can emerge in the eye as an immune-privileged organ. Ocular symptoms after CD19-CAR T-cell therapy should guide the clinician to elucidate the etiology in a timely fashion in order to adjust leukemia treatment strategy. Both, local immune escape as well as insufficient CAR T-cell persistence may have contributed to relapse in the reported patient. Mechanisms of relapse in an immune desert under CAR T-cell therapy require future clinical and experimental attention. In particular, ocular symptoms after CAR T-cell therapy should be considered a potentially early sign of leukemia relapse.",
"affiliations": "Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Department of Radiotherapy, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;German Cancer Research Center (DKFZ), Heidelberg, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany.;Department of Ophthalmology, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.;Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany [email protected].",
"authors": "Willier|Semjon|S|0000-0001-9472-2191;Raedler|Johannes|J|;Blaeschke|Franziska|F|;Stenger|Dana|D|;Pazos Escudero|Montserrat|M|;Jurgeleit|Florian|F|;Grünewald|Thomas G P|TGP|;Binder|Vera|V|;Schmid|Irene|I|;Albert|Michael H|MH|;Wolf|Armin|A|;Feuchtinger|Tobias|T|0000-0002-8517-9681",
"chemical_list": "D018941:Antigens, CD19; D000076962:Receptors, Chimeric Antigen",
"country": "England",
"delete": false,
"doi": "10.1136/jitc-2020-001052",
"fulltext": "\n==== Front\nJ Immunother Cancer\nJ Immunother Cancer\njitc\njitc\nJournal for Immunotherapy of Cancer\n2051-1426 BMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR \n\njitc-2020-001052\n10.1136/jitc-2020-001052\nCase Report\n1506\n2518 1619\nLeukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells\nhttp://orcid.org/0000-0001-9472-2191Willier Semjon 1 Raedler Johannes 1 Blaeschke Franziska 1 Stenger Dana 12 Pazos Escudero Montserrat 3 Jurgeleit Florian 1 Grünewald Thomas G P 2456 Binder Vera 1 Schmid Irene 1 Albert Michael H 1 Wolf Armin 78 http://orcid.org/0000-0002-8517-9681Feuchtinger Tobias 1 1 Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Bavaria, Germany\n2 German Cancer Research Center (DKFZ), Heidelberg, Germany\n3 Department of Radiotherapy, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany\n4 Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany\n5 Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany\n6 Partner site Munich, German Cancer Consortium (DKTK), Munich, Germany\n7 Department of Ophthalmology, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany\n8 Department of Ophthalmology, University of Ulm, Ulm, Germany\nCorrespondence to Dr Tobias Feuchtinger; [email protected]\n2020 \n16 9 2020 \n8 2 e00105206 8 2020 © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.2020http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.Background\nRelapsed/refractory B-precursor acute lymphoblastic leukemia (BCP-ALL) remains a major therapeutic challenge in pediatric hematology. Chimeric antigen receptor (CAR) T cells targeting CD19 have shown remarkable initial response rates in BCP-ALL patients, while long-term leukemia control rate is only about 50%. So far, main mechanisms of BCP-ALL relapse after CD19-CAR T-cell therapy have been either insufficient CAR T-cell persistence in vivo or loss of surface CD19.\n\nCase Report\nHere, we report an exceptional presentation of BCP-ALL relapse in the eye during the systemic control through CAR T-cell therapy. We report a case of fatal intraocular relapse in a pediatric patient with pro-B-ALL after initial response to CD19-CAR T-cell therapy. One month after CD19-CAR T-cell therapy, remission was documented by bone marrow aspirate analysis with absence of CD19+ cells and CD19-CAR T cells could be detected in both peripheral blood and bone marrow. At the same time, however, the patient presented with progressive visual disturbance and CD19+ cells were found within the anterior chamber of the eye. Despite local and systemic therapy, ocular relapse led to BCP-ALL dissemination and systemic relapse within weeks. The eye represents a rare site for local manifestation of BCP-ALL, but isolated intraocular relapse is a clinically unreckoned presentation of BCP-ALL in the era of CD19-CAR T cells.\n\nConclusion\nDuring systemic control of BCP-ALL through CD19-CAR T cells, relapse can emerge in the eye as an immune-privileged organ. Ocular symptoms after CD19-CAR T-cell therapy should guide the clinician to elucidate the etiology in a timely fashion in order to adjust leukemia treatment strategy. Both, local immune escape as well as insufficient CAR T-cell persistence may have contributed to relapse in the reported patient. Mechanisms of relapse in an immune desert under CAR T-cell therapy require future clinical and experimental attention. In particular, ocular symptoms after CAR T-cell therapy should be considered a potentially early sign of leukemia relapse.\n\nreceptorschimeric antigenimmunotherapyadoptivepediatricstumor escapeT-Lymphocytesspecial-featureunlocked\n==== Body\nBackground\nRelapsed/refractory B-precursor acute lymphoblastic leukemia (BCP-ALL) remains a major therapeutic challenge. Chimeric antigen receptor (CAR) T cells targeting CD19 have shown remarkable initial response rates but relevant relapse rates later on.1 2 Mechanisms of immune escape have been either loss of target structure or insufficient CAR T-cell persistence in vivo.3 4 Here, we report a novel clinical presentation of BCP-ALL relapse under CAR T-cell therapy, relapse within the eye as an immunologically privileged organ. CD19-CAR T cells are currently evaluated in numerous clinical trials5 and especially pediatric BCP-ALL shows initial response rates to CD19-CAR T cells of more than 80% in refractory or relapsed, heavily pretreated patients.1 Despite these promising response rates, about half of pediatric patients and the vast majority of adult patients experience relapse within 2 years after CD19-CAR T-cell therapy. CD19 antigen loss under selective pressure is mediated through downregulation of CD19, splice variants/mutations of CD19 or myeloid differentiation of leukemic blasts. To our knowledge, an intraocular relapse has not been reported. The eye represents a sequestered compartment within the body that enjoys immune privilege through various immunomodulatory mechanisms such as immunosuppressant chemokine and ocular FasL expression.6 Extramedullary manifestations of pediatric ALL have been described in cerebrospinal fluid, testis and the eye and those manifestations are characterized as immune privileged sites.7 Here, we report the case of a 3-year-old boy with relapsed pro-B ALL and previous extensive extramedullary disease after two allogeneic hematopoietic stem cell transplantations (HSCT) and previous CD19-CAR T-cell therapy, who presented with an intraocular relapse after second CD19-CAR T-cell therapy, progressing to fatal systemic relapse.\n\nCase presentation\nThe boy was diagnosed with pro-B ALL, t(9;11) MLL-rearrangement, central nervous system (CNS) involvement and initial white cell count of 30x10ˆ9/L at 5 months of age. Minimal residual disease (MRD) markers persisted after initial treatment according to the Interfant-06 protocol8 and a first HSCT from a HLA-compatible (10/10) matched unrelated donor (conditioning with fludarabine, treosulfan, ATG-Grafalon) was performed at 12 months of age (figure 1A). Despite complete donor chimerism on day +55, combined bone marrow (BM) and CNS relapse occurred at week 12. Remission was achieved with blinatumomab in combination with pembrolizumab and the patient subsequently received a second HSCT with peripheral blood stem cells from his HLA-haploidentical mother at 16 months of age (conditioning with clofarabine, thiotepa, melphalan, ATG-Grafalon). A second combined relapse in BM and CNS 5 months after second HSCT proved refractory to blinatumomab and inotuzumab ozogamicin. At 27 months of age the patient received a first CD19-CAR T-cell therapy (4-1BB second generation CD19-CAR). BM analysis showed complete remission after 1 month. A CD34+ stem cell boost was performed for prolonged BM insufficiency.\n\nFigure 1 Clinical course. (A) LDH (lactate dehydrogenase) and MRD (genetic minimal residual disease) are displayed as leukemic markers. Red boxes indicate major events in the patient’s history. (B) CD19 expression as measured by flow cytometry (clone SJ25C1, BD) was seen on bone marrow aspirates at initial diagnosis, third relapse and peripheral blood on day +65 after second CD19-CAR T-cell therapy. At the time of invasive ocular diagnostics, 12 days after ocular symptom onset on day +28 after second CD19-CAR T-cell therapy, no CD19 expression was detected within the bone marrow. (C) Flow cytometry analysis of second CD19-CAR product demonstrating a CD4:CD8 ratio of 7.6:1. (D) flow cytometry analysis of CD19-CAR transduction of second CD19-CAR product. FITC-labeled recombinant CD19 protein was used to detect CD19-CAR transduced CD3+ cells within the CAR product. A negative control using non-transduced T-cells is displayed as reference. (E) CD95 expression on CD3+ T cells in the second CD19-CAR product was measured by flow cytometry (red histogram, “second CAR T-cell product”). as reference, non-transduced T-cells were included in the histogram (orange histogram ‘control T cells’). B, blinatumomab cycle; BM, bone marrow; CAR, chimeric antigen receptor; CNS, central nervous system; CTx, chemotherapy; HSCT, hematopoietic stem cell transplantation; I, inotuzumab ozogamicin cycle; P, pembrolizumab cycle; RT, radiotherapy; SSC-A: side scatter area; FITC: Fluorescein isothiocyanate.\n\nFour months after CD19-CAR T-cell therapy, the patient suffered from a third combined BM and extramedullary relapse with a solitary skin lesion (immunohistochemistry CD19+). A local irradiation with 3D-plan, 6MeV photons, to a total dose of 18 Gy (4×4.5 Gy) was carried out with good clinical response. Despite blinatumomab therapy, extramedullary leukemic progression occurred in testes and multiple subcutaneous chloromas. With CD19 still being expressed on leukemic cells of the patient after two lines of anti-CD19 therapy (blinatumomab and first CD19-CAR T-cell therapy), we expected the patient to benefit from a second CD19-CAR T-cell therapy. Consequently, treatment with tisagenlecleucel (Kymriah) was initiated at our institution with confirmed persistent CD19+ disease in the BM (figure 1B). After confirmation of complete donor chimerism in peripheral blood, lymphocyte apheresis of the patient was performed. No clinical symptoms of ocular pathology were present at that time point and cranial MRI with contrast medium did not show any ocular pathology, either. Second CD19-CAR T-cell treatment was performed after lymphocyte depletion with fludarabine and cyclophosphamide at 39 months of age. The patient received 8.7×106 cells per kg body weight, the CD4:CD8 ratio was 7.6:1 and the CD19-CAR transduction rate was 21% (figure 1C, D). The patient experienced cytokine release syndrome grade 1 on day +11 which was treated with nonsteroidal anti-inflammatory drugs. CD34+ stem cell boost from the second HSCT donor was given for prolonged cellular aplasia complicated by bacterial sepsis. BM and CNS analysis on day +28 documented remission by microscopy, flow cytometry and genetic MRD testing (figure 1A, B). Moreover, CD19-CAR T cells could be detected in both peripheral blood and bone marrow by flow cytometry using FITC-labeled recombinant CD19 protein and by real-time PCR, although in low frequency (∼1% of viable T cells).\n\nOn day +16 the patient displayed erythema of the left eye and was initially diagnosed with conjunctivitis. However, symptoms progressed with pain, hyposphagma, vision impairment, mild proptosis and ptosis within 1 week. Swab testing was negative for viral infection (adenovirus, cytomegalovirus (CMV) and Epstein-Barr virus) and local antibiotic therapy did not improve symptoms. On ophthalmological assessment on day +28, the eye showed progressive conjunctival chemosis and anterior chamber cellular infiltration along with increased intraocular pressure (IOP). Intraocular bleeding was suspected due to thrombocytopenia. The patient was treated with platelet transfusion, systemic acetazolamide to reduce the IOP and local immunosuppressant dexamethasone. After progressive findings with hypopyon and worsening of the fundus reflex (figure 2A, B), biopsy of episclera and conjunctiva and an anterior chamber fluid tap with a single port vitrectomy for vitreous tap were performed.\n\nFigure 2 Clinical manifestation of binocular relapse of pro-B ALL after second CD19-CAR T-cell therapy. (A) Left eye before surgery. No intraocular structures are identifiable, the cornea appears clear but the anterior chamber is filled with a pus-like yellowish fluid, which resembles hypopyon in endophthalmitis. Note the hemorrhagic (reddish) appearance of the fluid which is not typically seen in infectious hypopyon. Additionally, the conjunctiva/sclera show a salmon-pink, ‘fleshy’ appearance, typically seen in conjunctival lymphoma. (B) Left eye after rinsing of the anterior chamber with extraction of the anterior chamber material. Now large dilated vessels on the surface of the iris can be identified at the periphery of the iris. The lens demonstrated a clear appearance. (C) CD3 and CD19 immunohistochemistry (IHC) of conjunctiva biopsy of the left eye. CD3+ T cells are concentrated at the surface of the conjunctiva. CD19+ cells show subepithelial localization and are widely observed within the connective tissue with additional perivascular accumulation. (D) CD3 and CD19 IHC from anterior ocular chamber lavage of the left eye. Most importantly, within anterior chamber lavage only CD19+ cells are present while in the CD3 IHC nucleated cells are CD3 negative. Black rectangles in left panel graphs illustrate the regions which are displayed in right panel graphs. for IHC, 4 µm sections of formalin-fixed paraffin-embedded tissue blocks were cut and antigen retrieval was carried out with microwave treatment and antigen target retrieval solution (Agilent technologies) for 64 min (pH 8.4). incubation for 28 min with either monoclonal rabbit anti-CD3 (1:150 dilution, clone Sp7, Zytomed) or monoclonal mouse anti-CD19 (1:20 dilution, clone EP169, Cellmarque) followed. Then, slides were incubated with a secondary anti-rabbit IgG antibody (MP-7401, ImmPress reagent kit, peroxidase-conjugated) followed by target detection using ultraView universal DAB detection kit (Ventana). BM, bone marrow; CAR, chimeric antigen receptor.\n\nUnfortunately, intraoperative findings and histology demonstrated episcleral and intraocular infiltration by atypical CD19+ lymphoid cells, confirming intraocular ALL relapse after second CD19-CAR T-cell therapy (figure 3). CD19+ cells were found inside the lamina propria of the conjunctiva with a perivascular accumulation, whereas CD3+ cells were found preferentially within the epithelium of the conjunctiva (figure 2C). Immunohistochemistry of nucleated cells in the lavage material of the anterior chamber confirmed presence of CD19+ cells and complete absence of CD3+ cells inside the eye (figure 2D). The patient showed no signs of systemic or CNS relapse with absence of CD19+ cells in BM (figure 1B), peripheral blood or cerebral spinal fluid. Prophylactic intrathecal chemotherapy was administered on day +37 (methotrexate, cytarabine, prednisolone) to prevent per continuitatem invasion of the CNS. Despite missing histological material from the right eye, clinical involvement with hyperemia led to the conclusion of a binocular disease. Subsequently, a bilateral orbital radiotherapy to a total dose of 20 Gy in ten fractions with 6 MeV photon beam was initiated on day +40 as a palliative measure. Intraocular administration of chemotherapy was not performed. Radiotherapy was well tolerated with only minor local erythema and the patient showed temporary symptom relief. Unfortunately, the patient’s condition deteriorated rapidly and peripheral blood testing confirmed systemic progression with leukocytosis (34.5x10ˆ9/L) and 51% CD19+ peripheral blasts. Palliative chemotherapy with cytarabine was performed but the patient deceased 6 weeks after intraocular relapse on day +75 after second CD19-CAR T-cell therapy.\n\nFigure 3 Donor chimerism at time of lymphocyte apheresis and detection of CD19 targeted CAR T cells at time of ocular relapse. (A) Donor chimerism in peripheral blood as determined by Fluorescence in situ analysis analysis based on X/Y chromosome analysis with a female donor for a male patient. Shortly before lymphocyte apheresis from the patient (blue dotted line), 100% donor chimerism was documented. (B) Real-time PCR (RT-PCR) analysis of peripheral blood prior to second CAR T-cell therapy (PB d-29), peripheral blood (PB d+28) and bone marrow (BM d+28) 1 month after second CAR T-cell therapy and a positive control (in vitro generated CD19 CAR T-cells from our lab) using primers specific for the CAR molecule. A weak signal can be seen in both samples after second CAR T-cell therapy both in peripheral blood (4.6x negative control) and BM (21.5x negative control). (C) Flow cytometry analysis of the same two biosamples used for RT-PCR, taken at d +28 after second CAR T-cell therapy. after gating on lymphocytes (SSC-A vs FSC-A), single cells (FSC-H vs FSC-A), CD45hi, CD3+ and TCRalpha/beta+ we measured expression of CD19 CAR with recombinant, FITC-labeled CD19 molecule (Stained) and used recombinant, FITC-labeled CD22 molecule as negative control (Control). within BM, 1.4% of CAR T cells can be detected and 0.7% CAR T cells are detected within peripheral blood. CAR, chimeric antigen receptor, FSC-A, forward scatter area, FSC, forward scatter height.\n\nDiscussion and conclusions\nIn recent literature, CD19-CAR T cells have been shown to clear CNS disease after intravenous administration9 and a trial with 86 patients documented no effect of extramedullary disease prior to CD19-CAR T-cell therapy on prognosis.10 Ocular involvement of BCP-ALL at time of diagnosis is associated with CNS or BM relapse and a decrease in overall survival greater than 50%.11 Glaucoma has been mentioned as possible symptom of ocular involvement.12 However, to our knowledge, there are no available data on frequency of extramedullary disease or ocular relapse after CD19-CAR T-cell therapy.\n\nThe concept of immune privilege is an evolutionary adaptation to protect indispensable tissues and was first described in testes and eyes13–15 and more recently in other organs such as the CNS16 and is mediated by expression of immunosuppressant chemokines, FasL expression and absence of MHC-1 on ocular tissues.17 Moreover, it has been shown that CAR T cells are susceptible to FasL-induced cell death due to Fas (CD95) expression on CAR T cells.18 Indeed, CAR T cells administered prior to intraocular relapse showed high CD95 expression by flow cytometry (figure 1E). We hypothesize that extramedullary-prone blasts and the immune privileged milieu within the eye may have led to immune evasion from CD19-CAR T-cell attack. This concept is supported by the simultaneous presence of CD19+ blasts within the anterior chamber of the left eye in complete absence of T cells while no CD19+ events could be detected within the BM or peripheral blood (figure 1, figure 2C, D). CD19-CAR T cells have been previously described to infiltrate immune privileged sites beyond the CNS, documented by, for example, a recent case report on bilateral retinal detachment after CD19-CAR T-cell therapy in a patient with retinal infiltration19 and by the efficacy of CD19-CAR T cells in testicular CD19+ leukemia.20–22 In addition to local immune escape, mechanisms of insufficient CAR T-cell persistence may have led to relapse in our patient. The possible overlap and rapid evolvement of systemic leukemia after local relapse limit definitive mechanistic conclusions in our case. Future clinical and experimental studies will be required to clarify the mechanistic role of immune desert for relapse under selective pressure of CD19-CAR T cells.\n\nFinally, we want to raise awareness for leukemia relapse after CD19-CAR T-cell therapy presenting with ocular symptoms resembling intraocular infection or thrombocytopenic hemorrhage. As most relevant differential diagnosis, intraocular infection may occur in immune-compromised patients, typically as CMV retinitis, or as bacterial or fungal infection. Intraocular relapse must be considered in patients presenting with ocular symptoms after CD19-CAR T-cell therapy, especially in patients with rapid symptom progression and elevated IOP. Accordingly, we suggest to initiate appropriate invasive diagnostic procedures in those patients, to clearly differentiate between leukemia-related and non-leukemia-related etiology of ocular symptoms. Early detection and local treatment intervention might prevent fatal relapse progression.\n\nThe authors wish to thank the team at the von Hauner University Children’s Hospital for the care of the patient, Gertrud und Hugo Adler Stiftung for support and Alexandra Skorupa (Novartis) for advice. SW was supported by the Else-Kröner-Fresenius Stiftung and DS by the German Cancer Consortium (DKTK).\n\nSW and JR contributed equally.\n\nContributors: The concept was set up by TF. The patient was treated by VB, MHA, IS, JR, SW, FB, AW, MPE and TF. TGPG performed immunohistochemistry and DS, FJ and SW performed flow cytometry. SW, JR and TF wrote the manuscript. All authors read and approved the final manuscript.\n\nFunding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.\n\nCompeting interests: None declared.\n\nPatient consent for publication: Not required.\n\nEthics approval: This study was performed in accordance with the Declaration of Helsinki and authorized by the local ethics committee (Ethikkommission der LMU München, project 17-163).\n\nProvenance and peer review: Not commissioned; externally peer reviewed.\n==== Refs\nReferences\n1 Maude SL , Laetsch TW , Buechner J , et al \nTisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia\n. N Engl J Med \n2018 ;378 :439 –48\n. 10.1056/NEJMoa1709866 29385370 \n2 Chen L , Xu B , Long X , et al \nCar T-cell therapy for a relapsed/refractory acute B-cell lymphoblastic lymphoma patient in the context of Li-Fraumeni syndrome\n. J Immunother Cancer \n2020 ;8 :e000364 . 10.1136/jitc-2019-000364 32345625 \n3 Blaeschke F , Willier S , Stenger D , et al \nLeukemia-induced dysfunctional TIM-3+CD4+ bone marrow T cells increase risk of relapse in pediatric B-precursor ALL patients\n. Leukemia \n2020 . 10.1038/s41375-020-0793-1 . [Epub ahead of print: 13 Mar 2020].\n4 Xu X , Sun Q , Liang X , et al \nMechanisms of relapse after CD19 CAR T-cell therapy for acute lymphoblastic leukemia and its prevention and treatment strategies\n. Front Immunol \n2019 ;10 :2664. 10.3389/fimmu.2019.02664 31798590 \n5 CLL - List Results \nSearch of: CD19 CAR T cells\n. Available: https://clinicaltrials.gov/ct2/results?cond=CLL&term=CD19+CAR+T+Cells&cntry=&state=&city=&dist=&Search=Search [Accessed 7 May 2019 ].\n6 Griffith TS , Brunner T , Fletcher SM , et al \nFas ligand-induced apoptosis as a mechanism of immune privilege\n. Science \n1995 ;270 :1189 –92\n. 10.1126/science.270.5239.1189 7502042 \n7 Russo V , Scott IU , Querques G , et al \nOrbital and ocular manifestations of acute childhood leukemia: clinical and statistical analysis of 180 patients\n. Eur J Ophthalmol \n2008 ;18 :619 –23\n. 10.1177/112067210801800420 18609485 \n8 Pieters R , Schrappe M , De Lorenzo P , et al \nA treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial\n. The Lancet \n2007 ;370 :240 –50\n. 10.1016/S0140-6736(07)61126-X \n9 Rheingold SR , Chen LN , Maude SL , et al \nEfficient Trafficking of Chimeric Antigen Receptor (CAR)-Modified T Cells to CSF and Induction of Durable CNS Remissions in Children with CNS/Combined Relapsed/Refractory ALL\n. Blood \n2015 ;126 :3769\n10.1182/blood.V126.23.3769.3769 \n10 Zhang X , Lu X-an , Yang J , et al \nEfficacy and Safety of CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for B-Cell Acute Lymphocytic Leukemia (B-cell ALL) in a Large Cohort Including Patients with Extramedullary Disease(EMD), High Leukemia Burden, BCR-ABL (+) Mutation, TP53 Mutation, and Post-Transplant Relapse\n. Blood \n2018 ;132 :280\n10.1182/blood-2018-99-115642 \n11 Ohkoshi K , Tsiaras WG \nPrognostic importance of ophthalmic manifestations in childhood leukaemia\n. Br J Ophthalmol \n1992 ;76 :651 –5\n. 10.1136/bjo.76.11.651 1477038 \n12 Sharma T , Grewal J , Gupta S , et al \nOphthalmic manifestations of acute leukaemias: the ophthalmologist's role\n. Eye \n2004 ;18 :663 –72\n. 10.1038/sj.eye.6701308 15002029 \n13 Niederkorn JY , Streilein JW \nLymphoma allografts abrogate immune privilege within the anterior chamber of the eye\n. Invest Ophthalmol Vis Sci \n1986 ;27 :1235 –43\n.3089965 \n14 Head JR , Neaves WB , Billingham RE \nImmune privilege in the testis\n. Transplantation \n1983 ;36 :423 –30\n. 10.1097/00007890-198310000-00014 6353710 \n15 Benhar I , London A , Schwartz M \nThe privileged immunity of immune privileged organs: the case of the eye\n. Front Immunol \n2012 ;3 :296. 10.3389/fimmu.2012.00296 23049533 \n16 Niederkorn JY \nSee no evil, hear no evil, do no evil: the lessons of immune privilege\n. Nat Immunol \n2006 ;7 :354 –9\n. 10.1038/ni1328 16550198 \n17 Abi-Hanna D , Wakefield D , Watkins S \nHla antigens in ocular tissues. I. in vivo expression in human eyes\n. Transplantation \n1988 ;45 :610 –3\n. 10.1097/00007890-198803000-00021 3347938 \n18 Tschumi BO , Dumauthioz N , Marti B , et al \nCart cells are prone to Fas- and DR5-mediated cell death\n. J Immunother Cancer \n2018 ;6 :71 . 10.1186/s40425-018-0385-z 30005714 \n19 Denton CC , Gange WS , Abdel-Azim H , et al \nBilateral retinal detachment after chimeric antigen receptor T-cell therapy\n. Blood Adv \n2020 ;4 :2158 –62\n. 10.1182/bloodadvances.2020001450 32428218 \n20 Chen X , Wang Y , Ruan M , et al \nTreatment of testicular relapse of B-cell acute lymphoblastic leukemia with CD19-specific chimeric antigen receptor T cells\n. Clin Lymphoma Myeloma Leuk \n2020 ;20 :366 –70\n. 10.1016/j.clml.2019.10.016 32205078 \n21 Yu J , Hu Y , Pu C , et al \nSuccessful chimeric Ag receptor modified T cell therapy for isolated testicular relapse after hematopoietic cell transplantation in an acute lymphoblastic leukemia patient\n. Bone Marrow Transplant \n2017 ;52 :1065 –7\n. 10.1038/bmt.2017.64 28436979 \n22 Ping N , Qu C , Bai L , et al \nSuccessful chimeric antigen receptor T cell therapy in a case of primary testicular diffuse large-B-cell lymphoma with central nervous system progression\n. Leuk Lymphoma \n2019 ;60 :2814 –6\n. 10.1080/10428194.2019.1605507 31088197\n\n",
"fulltext_license": "CC BY-NC",
"issn_linking": "2051-1426",
"issue": "8(2)",
"journal": "Journal for immunotherapy of cancer",
"keywords": "T-Lymphocytes; adoptive; chimeric antigen; immunotherapy; pediatrics; receptors; tumor escape",
"medline_ta": "J Immunother Cancer",
"mesh_terms": "D018941:Antigens, CD19; D002675:Child, Preschool; D005128:Eye Diseases; D006801:Humans; D007938:Leukemia; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D000076962:Receptors, Chimeric Antigen",
"nlm_unique_id": "101620585",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "32938628",
"pubdate": "2020-09",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": "7502042;16550198;23049533;32205078;18609485;17658395;28436979;31088197;30005714;29385370;3347938;32345625;6353710;31798590;32428218;3089965;32203137;1477038;15002029",
"title": "Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells.",
"title_normalized": "leukemia escape in immune desert intraocular relapse of pediatric pro b all during systemic control by cd19 car t cells"
}
|
[
{
"companynumb": "DE-AMGEN-DEUSP2020154476",
"fulfillexpeditecriteria": "2",
"occurcountry": "DE",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "THIOTEPA"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "THIOTEPA."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MELPHALAN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MELPHALAN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GRAFALON"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PEMBROLIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PEMBROLIZUMAB."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLOFARABINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFARABINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BLINATUMOMAB"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "125557",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "B PRECURSOR TYPE ACUTE LEUKAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "BLINATUMOMAB"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "INOTUZUMAB OZOGAMICIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INOTUZUMAB OZOGAMICIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "FLUDARABINE PHOSPHATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA RECURRENT",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUDARABINE"
}
],
"patientagegroup": "2",
"patientonsetage": "1",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Leukaemic infiltration extramedullary",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Leukocytosis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cytokine release syndrome",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "B-cell aplasia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Bacterial sepsis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute lymphocytic leukaemia recurrent",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "FEUCHTINGER T.? WILLIER S.? RAEDLER J. ET AL.. LEUKEMIA ESCAPE IN IMMUNE DESERT: INTRAOCULAR RELAPSE OF PEDIATRIC PRO?B?ALL DURING SYSTEMIC CONTROL BY CD19?CAR T CELLS. JOURNAL FOR IMMUNOTHERAPY OF CANCER. 2020?8 (2):1?6",
"literaturereference_normalized": "leukemia escape in immune desert intraocular relapse of pediatric pro b all during systemic control by cd19 car t cells",
"qualification": "3",
"reportercountry": "DE"
},
"primarysourcecountry": "DE",
"receiptdate": "20200929",
"receivedate": "20200929",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18324634,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
}
] |
{
"abstract": "Limited population-based data on penicillin-, carbapenem-, monobactam-, and clindamycin-associated reported adverse reactions exist.\n\n\n\nTo collect data on penicillin, carbapenem, monobactam, and clindamycin usage and associated adverse reactions.\n\n\n\nData from January 1, 2009, to December 31, 2017, in Kaiser Permanente Southern California were collected.\n\n\n\nThere were 6,144,422 unique individuals, mean age 33.6 ± 21.1 years, 52.2% females, with at least 1 health care visit during the 9-year study interval, for a total of 37,387,313 patient-years of follow-up. This population was exposed to 5,617,402 courses of oral penicillins, 370,478 courses of parenteral penicillins, 59,645 courses of parenteral carbapenems or monobactams, 817,232 courses of oral clindamycin, and 215,880 courses of parenteral clindamycin. New penicillin allergies were reported more commonly after parenteral (0.85%) compared with oral (0.74%) exposures (P < .0001). There were 22 cases (1 in 255,320) of oral penicillin-associated anaphylaxis and 3 cases (1 in 123,792) of parenteral penicillin-associated anaphylaxis (P < .001). There were 2 clindamycin-associated anaphylaxis cases, 1 (1 in 817,232) oral and 1 (1 in 215,880) parenteral. There were 2 (1 in 2,993,940) penicillin-associated serious cutaneous adverse reaction (SCAR) cases, but both also had co-trimoxazole coexposure within 45 days. There was 1 (1 in 1,033,112) clindamycin-associated SCAR. Clostridioides difficile infection was more common after parenteral exposures, and with extended-spectrum penicillins, beta-lactamase combinations, carbapenems, monobactam, and clindamycin exposures compared with oral penicillins or clindamycin.\n\n\n\nOnly 1 of 1543 (0.065%) oral and 1 of 1030 (0.097%) parenteral penicillin-associated allergy reports were confirmed to be anaphylaxis. C. difficile was more common after parenteral versus oral penicillin, carbapenem, monobactam, and clindamycin exposures, and with broader spectrum antibiotic exposures.",
"affiliations": "Southern California Permanente Medical Group, Department of Allergy, Los Angeles Medical Center, Los Angeles, Calif.;Department of Research and Evaluation, Kaiser Permanente Health Care Program, Pasadena, Calif.;Southern California Permanente Medical Group, Department of Allergy, San Diego Medical Center, San Diego, Calif. Electronic address: [email protected].",
"authors": "Liang|Emily H|EH|;Chen|Lie H|LH|;Macy|Eric|E|",
"chemical_list": "D000900:Anti-Bacterial Agents; D015780:Carbapenems; D008997:Monobactams; D010406:Penicillins; D002981:Clindamycin",
"country": "United States",
"delete": false,
"doi": "10.1016/j.jaip.2019.11.035",
"fulltext": null,
"fulltext_license": null,
"issn_linking": null,
"issue": "8(4)",
"journal": "The journal of allergy and clinical immunology. In practice",
"keywords": "Adverse drug reaction; Allergy; Anaphylaxis; Beta-lactam; Carbapenem; Clindamycin; Epidemiology; Hypersensitivity; Infection; Monobactam; Oral; Parenteral; Penicillin; Serious cutaneous adverse reaction",
"medline_ta": "J Allergy Clin Immunol Pract",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002648:Child; D002981:Clindamycin; D016360:Clostridioides difficile; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008997:Monobactams; D010406:Penicillins; D012189:Retrospective Studies; D055815:Young Adult",
"nlm_unique_id": "101597220",
"other_id": null,
"pages": "1302-1313.e2",
"pmc": null,
"pmid": "31821919",
"pubdate": "2020-04",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study.",
"title_normalized": "adverse reactions associated with penicillins carbapenems monobactams and clindamycin a retrospective population based study"
}
|
[
{
"companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-287768",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "3",
"drugadministrationroute": "051",
"drugauthorizationnumb": "65061",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Liang EH, Chen LH, Macy E. Adverse Reactions Associated with Penicillins,Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study. J Allergy Clin Immunol Pract. 2020;Apr 8(4):1302-1313",
"literaturereference_normalized": "adverse reactions associated with penicillins carbapenems monobactams and clindamycin a retrospective population based study",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20220404",
"receivedate": "20210325",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 19056037,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220721"
},
{
"companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-287767",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLINDAMYCIN"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "65061",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLINDAMYCIN"
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Liang EH, Chen LH, Macy E. Adverse Reactions Associated with Penicillins,Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study. J Allergy Clin Immunol Pract. 2020;Apr 8(4):1302-1313",
"literaturereference_normalized": "adverse reactions associated with penicillins carbapenems monobactams and clindamycin a retrospective population based study",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20220404",
"receivedate": "20210325",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 19056033,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220720"
}
] |
{
"abstract": "Background Subarachnoid hemorrhage (SAH) secondary to rupture of a blister aneurysm (BA) results in high morbidity and mortality. Endovascular treatment with the pipeline embolization device (PED) has been described as a new treatment strategy for these lesions. We present the first reported case of PED retraction and foreshortening after treatment of a ruptured internal carotid artery (ICA) BA. Case description A middle-aged patient presented with SAH secondary to ICA BA rupture. The patient was treated with telescoping PED placement across the BA. After 5 days from treatment, the patient developed a new SAH due to re-rupture of the BA. Digital subtraction angiography revealed an increase in caliber of the supraclinoid ICA with associated retraction and foreshortening of the PED that resulted in aneurysm uncovering and growth. Conclusions PED should be oversized during ruptured BA treatment to prevent device retraction and aneurysm regrowth. Frequent imaging follow up after BA treatment with PED is warranted to ensure aneurysm occlusion.",
"affiliations": "1 Department of Radiology, Neuroimaging and Neurointervention Division, Stanford University Medical Center, Stanford, CA, USA.;1 Department of Radiology, Neuroimaging and Neurointervention Division, Stanford University Medical Center, Stanford, CA, USA.;1 Department of Radiology, Neuroimaging and Neurointervention Division, Stanford University Medical Center, Stanford, CA, USA.;2 Department of Neurosurgery, Stanford University Medical Center, Stanford, CA, USA.;2 Department of Neurosurgery, Stanford University Medical Center, Stanford, CA, USA.;1 Department of Radiology, Neuroimaging and Neurointervention Division, Stanford University Medical Center, Stanford, CA, USA.",
"authors": "Heit|Jeremy J|JJ|;Telischak|Nicholas A|NA|;Do|Huy M|HM|;Dodd|Robert L|RL|;Steinberg|Gary K|GK|;Marks|Michael P|MP|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1177/1591019917722514",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1591-0199",
"issue": "23(6)",
"journal": "Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences",
"keywords": "Blister aneurysm; embolization; foreshortening; pipeline; subarachnoid hemorrhage",
"medline_ta": "Interv Neuroradiol",
"mesh_terms": "D017542:Aneurysm, Ruptured; D015901:Angiography, Digital Subtraction; D002343:Carotid Artery, Internal; D000072226:Computed Tomography Angiography; D004621:Embolization, Therapeutic; D006801:Humans; D002532:Intracranial Aneurysm; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage",
"nlm_unique_id": "9602695",
"other_id": null,
"pages": "614-619",
"pmc": null,
"pmid": "28758549",
"pubdate": "2017-12",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "25792038;25763295;24389375;24297367;27075485;27471186;21990462;23190640;24578484;26381557",
"title": "Pipeline embolization device retraction and foreshortening after internal carotid artery blister aneurysm treatment.",
"title_normalized": "pipeline embolization device retraction and foreshortening after internal carotid artery blister aneurysm treatment"
}
|
[
{
"companynumb": "US-009507513-1802USA011140",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CLOPIDOGREL BISULFATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "75 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "75",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOPIDOGREL"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "81 MG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "81",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "EPTIFIBATIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "020718",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "INTEGRILIN"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Subarachnoid haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HEIT JJ, TELISCHAK NA, DO HM, DODD RL, STEINBERG GK, MARKS MP. PIPELINE EMBOLIZATION DEVICE RETRACTION AND FORESHORTENING AFTER INTERNAL CAROTID ARTERY BLISTER ANEURYSM TREATMENT. INTERVENTIONAL NEURORADIOLOGY. 2017?23(6):614?9",
"literaturereference_normalized": "pipeline embolization device retraction and foreshortening after internal carotid artery blister aneurysm treatment",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180806",
"receivedate": "20180227",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14577335,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
"companynumb": "US-BAYER-2018-038519",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "EPTIFIBATIDE"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EPTIFIBATIDE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "999999",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "81 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "81",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ACETYLSALICYLIC ACID({=100 MG)"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CLOPIDOGREL BISULFATE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "3",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "75 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ANTIPLATELET THERAPY",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "75",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOPIDOGREL"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Labelled drug-drug interaction medication error",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Subarachnoid haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
},
{
"reactionmeddrapt": "Drug administration error",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": null
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HEIT JJ, TELISCHAK NA, DO HM, DODD RL, STEINBERG GK, MARKS MP. PIPELINE EMBOLIZATION DEVICE RETRACTION AND FORESHORTENING AFTER INTERNAL CAROTID ARTERY BLISTER ANEURYSM TREATMENT. INTERVENTIONAL NEURORADIOLOGY. 2017?23:6:614-619",
"literaturereference_normalized": "pipeline embolization device retraction and foreshortening after internal carotid artery blister aneurysm treatment",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180228",
"receivedate": "20180228",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 14583021,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180509"
}
] |
{
"abstract": "A subset of multibacillary (MB) leprosy patients manifest with clinical \"nonresponsiveness\" to the fixed-duration, World Health Organization multidrug therapy MB regimen (WHO-MDT-MBR). The aim of this retrospective study was to assess the effectiveness and safety of alternate anti-leprosy therapy (ALT) in such patients. This is an analysis of patients' records, registered in the leprosy clinic of our institute over a period of 6 years (2010-2015). The criteria for inadequate response/nonresponsiveness to treatment were as follows: 1) persistent/new lesions after completing ≥ 12 months of WHO-MDT-MBR (isolated reactions were ruled out histopathologically) and 2) persistent positive/increasing value of the morphological index (MI) and a 2 log increase in the bacteriological index (BI) after ≥ 12 months of WHO-MDT-MBR. Such cases were treated with ALT consisting of minocycline, clofazimine, and ofloxacin (24 months). Of 556 patients registered during the study period, 40.3% (224) were slit-skin smear (SSS) positive and 59.7% (332) were SSS negative. Of all, 35 patients (6.3%) satisfied the criteria for clinical nonresponsiveness. Of 224 SSS-positive patients, these 35 patients amounted to 15.6%. The mean BI and MI of these patients after completion of ≥ 12 months of WHO-MDT-MBR were 5.3 ± 0.6 and 14 ± 6.8%, respectively. After 6 months of treatment with ALT, MI became negative (0) in all these patients. After completion of ALT, the mean BI and MI became 1.7 ± 0.7 and 0%, respectively (P < 0.0001). There were 16 patients with corticosteroid-dependent recurrent/chronic erythema nodosum leprosum, who had excellent response with significant reduction in the number of reactional episodes and mean dose of prednisolone required (P < 0.0001). No serious adverse effects were noted. We conclude that ALT is safe and effective in the management of MB leprosy patients who are nonresponsive to 12 months of WHO-MDT-MBR.",
"affiliations": "Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.;Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.;Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.;Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.;National Institute of Nursing Education, Postgraduate Institute of Medical Education and Research, Chandigarh, India.",
"authors": "Narang|Tarun|T|;Bishnoi|Anuradha|A|;Dogra|Sunil|S|;Saikia|Uma Nahar|UN|;Kavita|||",
"chemical_list": "D007917:Leprostatic Agents; D002991:Clofazimine; D008911:Minocycline",
"country": "United States",
"delete": false,
"doi": "10.4269/ajtmh.18-0256",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0002-9637",
"issue": "100(1)",
"journal": "The American journal of tropical medicine and hygiene",
"keywords": null,
"medline_ta": "Am J Trop Med Hyg",
"mesh_terms": "D000328:Adult; D002991:Clofazimine; D019468:Disease Management; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007194:India; D007917:Leprostatic Agents; D056006:Leprosy, Multibacillary; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D008911:Minocycline; D009166:Mycobacterium leprae; D012189:Retrospective Studies; D062606:Tertiary Care Centers; D014944:World Health Organization; D055815:Young Adult",
"nlm_unique_id": "0370507",
"other_id": null,
"pages": "24-30",
"pmc": null,
"pmid": "30298809",
"pubdate": "2019-01",
"publication_types": "D016428:Journal Article",
"references": "7602214;10920610;24834639;25274993;26314915;22020137;29723371;20496569;23739719;2427626;23741883;28693853;27550711;16830652;11355514;28861986;12781508;23441623;25991507;25509718;25874961;10603717",
"title": "Alternate Anti-Leprosy Regimen for Multidrug Therapy Refractory Leprosy: A Retrospective Study from a Tertiary Care Center in North India.",
"title_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india"
}
|
[
{
"companynumb": "IN-BAUSCH-BL-2019-003187",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
}
],
"patientagegroup": null,
"patientonsetage": "28",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929224,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003192",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
}
],
"patientagegroup": null,
"patientonsetage": "25",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929227,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003193",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
}
],
"patientagegroup": null,
"patientonsetage": "42",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929228,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003197",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190205",
"receivedate": "20190205",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15920378,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003190",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
}
],
"patientagegroup": null,
"patientonsetage": "28",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929226,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003191",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
}
],
"patientagegroup": null,
"patientonsetage": "26",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929229,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003198",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
}
],
"patientagegroup": null,
"patientonsetage": "43",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15926179,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003186",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
}
],
"patientagegroup": null,
"patientonsetage": "25",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929222,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003196",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
}
],
"patientagegroup": null,
"patientonsetage": "21",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929230,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003185",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
}
],
"patientagegroup": null,
"patientonsetage": "34",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190205",
"receivedate": "20190205",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15920335,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003189",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
}
],
"patientagegroup": null,
"patientonsetage": "28",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929225,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003184",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
}
],
"patientagegroup": null,
"patientonsetage": "35",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190205",
"receivedate": "20190205",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15920315,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003195",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
}
],
"patientagegroup": null,
"patientonsetage": "22",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929231,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003019",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
}
],
"patientagegroup": null,
"patientonsetage": "32",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929221,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003194",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12,882.5 PLUS OR MINUS 5,130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "LEPROMATOUS LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2,505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190205",
"receivedate": "20190205",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15920353,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
},
{
"companynumb": "IN-BAUSCH-BL-2019-003188",
"fulfillexpeditecriteria": "1",
"occurcountry": "IN",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MAINTENANCE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "HYDROXYCHLOROQUINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HYDROXYCHLOROQUINE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MULTIPLE COURSES (MEAN DOSE OF 12.882.5 PLUS OR MINUS 5.130.3 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "OFLOXACIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OFLOXACIN."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PENTOXIFYLLINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PENTOXIFYLLINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MINOCYCLINE\\MINOCYCLINE HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "050781",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MINOCYCLINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "INTENSIVE PHASE",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BORDERLINE LEPROSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "CLOFAZIMINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "3",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CLOFAZIMINE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100-150 MG/DAY FOR VARIABLE DURATIONS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "TYPE 2 LEPRA REACTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "75250",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TAPERED OFF WITHIN 6-12 MONTHS (2.505 PLUS OR MINUS 614 MG)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
}
],
"patientagegroup": null,
"patientonsetage": "20",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Type 2 lepra reaction",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Infection",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug dependence",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Skin hyperpigmentation",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Therapeutic response decreased",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "DOGRA S, BISHNOI A, NARANG T, SAIKIA U, KAVITA. ALTERNATE ANTI-LEPROSY REGIMEN FOR MULTIDRUG THERAPY REFRACTORY LEPROSY: A RETROSPECTIVE STUDY FROM A TERTIARY CARE CENTER IN NORTH INDIA. THE AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 2019?100(1):24-30.",
"literaturereference_normalized": "alternate anti leprosy regimen for multidrug therapy refractory leprosy a retrospective study from a tertiary care center in north india",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": null,
"receiptdate": "20190206",
"receivedate": "20190206",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15929223,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
}
] |
{
"abstract": "Pemphigus is a rare family of autoimmune disorders characterized by epithelial and mucosal blisters. Pemphigus foliaceus (PF) commonly affects the scalp, face, and trunk. Lesions often arise as superficial blisters and develop into scaly, crusted erosions. Management includes corticosteroids with immunosuppressants. Novel therapies include immunoadsorption and active clinical trials. We present the only reported case of metoprolol-induced PF in the United States (US), with an extremely complicated hospital course. A 66-year-old male patient with a history of hypertension, diabetes, and hyperlipidemia presented to his doctor with a blistering, pruritic rash that started after switching to metoprolol for hypertension treatment. PF is very rare in North America. Given its solely superficial penetration, it creates no direct fatal complication. However, the developing blisters and subsequent wounds are susceptible to a wide array of secondary infections, which can be life-threatening.",
"affiliations": "Plastic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.;Plastic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.;Plastic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.;Plastic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.;Plastic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.",
"authors": "Lagziel|Tomer|T|;Ramos|Margarita|M|;Rozycki|Grace F|GF|;Hultman|Charles S|CS|;Asif|Mohammed|M|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.7759/cureus.9203",
"fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184 Cureus Palo Alto (CA) \n\n10.7759/cureus.9203\nDermatology\nPlastic Surgery\nAllergy/Immunology\nThe First Reported Case of Metoprolol-Induced Pemphigus Foliaceus in the United States: A Critical Report and Review of Literature\nMuacevic Alexander Adler John R Lagziel Tomer 12 Ramos Margarita 1 Rozycki Grace F 1 Hultman Charles S 1 Asif Mohammed 1 \n1 \nPlastic Surgery, Johns Hopkins University School of Medicine, Baltimore, USA \n\n2 \nMedicine, Tel-Aviv University, Sackler School of Medicine, Tel-Aviv, ISR \n\nTomer Lagziel [email protected]\n15 7 2020 \n7 2020 \n12 7 e92036 7 2020 15 7 2020 Copyright © 2020, Lagziel et al.2020Lagziel et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/36851-the-first-reported-case-of-metoprolol-induced-pemphigus-foliaceus-in-the-united-states-a-critical-report-and-review-of-literaturePemphigus is a rare family of autoimmune disorders characterized by epithelial and mucosal blisters. Pemphigus foliaceus (PF) commonly affects the scalp, face, and trunk. Lesions often arise as superficial blisters and develop into scaly, crusted erosions. Management includes corticosteroids with immunosuppressants. Novel therapies include immunoadsorption and active clinical trials. We present the only reported case of metoprolol-induced PF in the United States (US), with an extremely complicated hospital course. \n\nA 66-year-old male patient with a history of hypertension, diabetes, and hyperlipidemia presented to his doctor with a blistering, pruritic rash that started after switching to metoprolol for hypertension treatment. \n\nPF is very rare in North America. Given its solely superficial penetration, it creates no direct fatal complication. However, the developing blisters and subsequent wounds are susceptible to a wide array of secondary infections, which can be life-threatening.\n\npemphigusautoimmunedermatologyinfectionmetoprololThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\nPemphigus is a family of devastating blistering conditions that are characterized by disrupted keratinocyte to keratinocyte adhesion which forms blisters in the epithelium of the skin and mucous membranes [1]. The prevalence of pemphigus in the United States (US) is 0.005% of overall adults [2]. One subtype is pemphigus foliaceus (PF) that only affects the cutaneous layer (sparing mucosal membrane) and includes subcorneal acantholytic blisters [3]. PF most commonly affects the scalp, face, and trunk. The lesions contributing to this condition usually begin presenting as superficial blisters but eventually develop into scaly and crusted erosions. During the course of development of the condition, the skin lesions can either remain local or spread to cover larger areas of the body [4].\n\nAs it is an autoimmune condition, the factors that lead to or cause PF are not well understood. It is generally accepted that both genetic and environmental factors contribute to the development of pemphigoid diseases. It has also been recorded that certain drugs, thiols in particular, can induce PF [2,5]\n\nHowever, PF due to treatment with metoprolol has never been reported in the US, as is seen with our case report.\n\nIn cases where PF is environmentally triggered or drug induced, the trigger should be determined and removed from contact with the patient. Medical intervention for pemphigus includes corticosteroids in combination with steroid-sparing immunosuppressant drugs, such as azathropine, mycophenolate, and cyclosprin [3,4,6]. \n\nSurgical intervention is usually not necessary for isolated-cutaneous lesions and usually only implemented in severe mucosal invasion [7].\n\nCase presentation\nA 66-year-old male patient with a medical history of hypertension, diabetes, and hyperlipidemia presented to his primary care physician with a blistering, pruritic rash that started after switching to metoprolol from atenolol for treatment of uncontrolled hypertension. The rash became infected with superimposed Staphylococcus aureus and when symptoms worsened he was sent to the emergency department (ED) for evaluation (Figure 1). \n\nFigure 1 Initial Presentation with Pemphigus Foliaceus. (A – Anterior Torso, B – Posterior Torso)\nThe on-call dermatologist was consulted, and perilesional punch biopsy from the left lateral trunk was collected for wound culture and expert dermatopathologist histopathological examination. The culture confirmed Staphylococcus aureus which suggested possible staphylococcal-scalded-skin-syndrome. However, the dermatopathologist assessed the sample via direct immunofluorescence (IF) and reported heavy linear deposition of IgG and C3 on the cell surface of keratinocytes with subcorneal acantholysis in the epidermis. The patient's blood was also sent for indirect IF and enzyme-linked immunosorbent assay (ELISA) for desmoglein (DSG) 1 and 3 (DSG1 > 100, reference < 18). These findings along with the clinical picture are diagnostic for PF. The patient was discharged with instructions for antibiotic control of the infection. Two weeks later, he re-presented to the ED with a diffuse body rash, swelling, and uncontrollable pain. Workup suggested acute kidney injury (AKI) and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. He was admitted for inpatient management of his bacteremia and PF where he was treated with long-term steroids, a five-day course of intravenous Immunoglobulin (IVIG), and one dose of rituximab, stabilizing his PF. He was discharged with planned treatment of weaning off steroids, monthly IVIG, and a single dose of rituximab every three months. Upon discharge, the patient was also advised to seek continuing follow-up consultations to monitor his pemphigus. After six weeks, he was readmitted to our ED with a worsening weeping, blistering rash, declining mental status, and dyspnea (Figure 2). \n\nFigure 2 Presentation Upon Admittance to Burn Center. (A – Anterior Head, B – Anterior Torso, C – Posterior Torso)\nPemphigus wounds are not usually surgically managed, but due to persistent systemic infections the patient required excision, restructuring, and resurfacing for which he was transferred to our burn unit. He developed bacteremia from his wounds and was treated with a fifth-generation cephalosporin which cleared it. However, on rounds he was noticed to have abdominal distention and an X-ray suggested ileus. Given the severe clinical deterioration a CT scan was obtained and it confirmed pneumatosicoli and pneumoperitoneum. He was immediately taken to the operating room where the acute surgical care team performed an emergent exploratory laparotomy demonstrating viable bowel and no intraabdominal pathology as the cause of his decline. His pneumonia was treated with 10 days of ceftolozane/tazobactam. He improved hemodynamically and his PF is under better control with tapered steroids and local wound care. He is scheduled for outpatient IVIG and rituximab treatment. A brief illustrated timeline of the events is shown in Figure 3.\n\nFigure 3 Timeline of events in the burn unit\nMRSA, methicillin-resistant Staphylococcus aureus\n\nDiscussion\nPF is an autoimmune disorder with no cure [8]. While it is not fatal and its symptoms are less life-threatening than other pemphigus subtypes, quality of life is severely reduced, limiting the patient’s ability to carry out daily tasks as well as negatively affecting their psychological state [9-11]. The current gold standard for chronic management of PF is systemic corticosteroids with steroid-sparing immunosuppressants [12].\n\nTreatment of our patient was complicated due to multiple systemic inflammatory insults. However, we adhered to expert dermatologic guidelines with an immunosuppressant regimen which included four courses of IVIG (five days per month), two courses of rituximab (every three months), and high-dose prednisone (60 mg/day) throughout the patient’s hospitalization. Although the patient’s overall skin disease burden improved over time, the complications of AKI and multidrug-resistant bacteremia, including fungemia (Candida albicans) and sepsis, frequently happened following administration of IVIG therapy. The patient did not suffer any significant adverse effects from the rituximab treatment and prednisone therapy, which was weaned down to 10 mg/day from 60 mg/day at onset. In light of these observations, it is prudent to maintain adequate hydration, aggressive wound care, and caution for systemic infections because they can be fatal. Surgical wound debridement is non-standard treatment but in order to control fatal infectious complications, we suggest surgical excision is often needed. Fortunately, our patient’s condition improved significantly and his wounds were manageable allowing for discharge to a skilled nursing facility. \n\nPF is very rare in North America and more prevalent in South America and North Africa with an annual sporadic incidence of less than one per million individuals per year [3,13,14]. The combination of low mortality and low prevalence in the Western world leads to lack of innovation in the development of curative therapy. There are only four ongoing clinical trials testing new drug therapies, one of which is outside of the US. These new targeted therapies include the use of naturally occurring regulatory T cells to potentially replace chronic immunosuppressive therapies, disruption of B-cell receptor signaling, and neonatal Fc receptor inhibition [15]. In addition to new drug therapies being developed, other treatment methods are being utilized outside of the US. For example, particularly in Europe, extracorporeal immunoadsorption is performed to remove the autoantibodies from the blood [16-18]. PF patients are suffering and they need more effective treatment methods that do not carry an increased risk of harm.\n\nConclusions\nGiven its purely superficial penetration, PF has no direct fatal complication and has even been shown to have historically positive outcomes. However, blisters and subsequent wounds are susceptible to dangerous secondary infections. Since there is no acute life threat from PF, few treatments are available for the condition itself. Instead, therapy relies on managing PF and treating subsequent infections. Because PF is an autoimmune disorder it is managed using immunosuppressants. However, these drugs can make the patient susceptible to multiple systemic infections, which can be life-threatening. The development of new treatment methods is crucial for more efficient management of the condition as well as to improve the patients' quality of life.\n\nThe authors have declared that no competing interests exist.\n\nHuman Ethics\nConsent was obtained by all participants in this study. Johns Hopkins IRB issued approval Not Applicable. No IRB approval was required for this research.\n==== Refs\nReferences\n1 Mechanisms of disease: pemphigus and bullous pemphigoid Annu Rev Pathol Hammers CM Stanley JR 175 197 11 2016 26907530 \n2 Prevalence estimates for pemphigus in the United States: a sex-adjusted and age-adjusted population analysis JAMA Dermatol Wertenteil S Garg A Strunk A Alloo A 627 629 155 2019 30892569 \n3 Pemphigus Nat Rev Dis Primers Kasperkiewicz M Ellebrecht CT Takahashi H Yamagami J Zillikens D Payne AS Amagai M 17026 3 2017 28492232 \n4 Diagnosis and clinical features of pemphigus foliaceus Dermatol Clin James KA Culton DA Diaz LA 405 412 29 2011 21605805 \n5 Diagnosis and classification of pemphigus and bullous pemphigoid Autoimmun Rev Kershenovich R Hodak E Mimouni D 477 481 13 2014 24424192 \n6 Pemphigus trigger factors: special focus on pemphigus vulgaris and pemphigus foliaceus Arch Dermatol Res Tavakolpour S 95 106 310 2018 29110080 \n7 Pemphigus vulgaris and pemphigus foliaceus: an overview of the clinical presentation, investigations and management Clin Exp Dermatol Melchionda V Harman KE 740 746 44 2019 31378971 \n8 Autoantibodies in the autoimmune disease pemphigus foliaceus induce blistering via p38 mitogen-activated protein kinase-dependent signaling in the skin Am J Pathol Berkowitz P Chua M Liu Z Diaz LA Rubenstein DS 1628 1636 173 2008 18988808 \n9 Quality of life in patients with bullous dermatoses Clin Dermatol Sebaratnam DF McMillan JR Werth VP Murrell DF 103 107 30 2012 22137233 \n10 Quality of life index in autoimmune bullous dermatosis patients An Bras Dermatol Penha MA Farat JG Miot HA Barraviera SR 190 194 90 2015 25830988 \n11 Mental health in patients with pemphigus: an issue to worth consideration Indian J Dermatol Arbabi M Ghodsi Z Mahdanian A 541 545 56 2011 22121274 \n12 Management of pemphigus F1000Prime Rep Daniel BS Murrell DF 32 6 2014 24860654 \n13 Pemphigus: a brief review Clin Med Groves RW 371 375 9 2009 \n14 Pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis) Clin Dermatol Joly P Litrowski N 432 436 29 2011 21679871 \n15 Current clinical trials in pemphigus and pemphigoid Front Immunol Izumi K Bieber K Ludwig RJ 978 10 2019 31130959 \n16 Immunoadsorption in the treatment of pemphigus Atheroscler Suppl Mlynek A Meurer M 107 109 10 2009 20129386 \n17 Immunoadsorption in pemphigus Autoimmunity Eming R Hertl M 609 616 39 2006 17101505 \n18 Treatment of pemphigus vulgaris: part 1 - current therapies Expert Rev Clin Immunol Yanovsky RL McLeod M Ahmed AR 1047 1060 15 2019 31566020\n\n",
"fulltext_license": "CC BY",
"issn_linking": "2168-8184",
"issue": "12(7)",
"journal": "Cureus",
"keywords": "autoimmune; dermatology; infection; metoprolol; pemphigus",
"medline_ta": "Cureus",
"mesh_terms": null,
"nlm_unique_id": "101596737",
"other_id": null,
"pages": "e9203",
"pmc": null,
"pmid": "32821557",
"pubdate": "2020-07-15",
"publication_types": "D002363:Case Reports",
"references": "21679871;31378971;17101505;24860654;25830988;29110080;31566020;18988808;19728517;22137233;30892569;24424192;26907530;21605805;31130959;22121274;20129386;28492232",
"title": "The First Reported Case of Metoprolol-Induced Pemphigus Foliaceus in the United States: A Critical Report and Review of Literature.",
"title_normalized": "the first reported case of metoprolol induced pemphigus foliaceus in the united states a critical report and review of literature"
}
|
[
{
"companynumb": "US-SHIRE-US202028221",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "1255960",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HUMAN NORMAL IMMUNOGLOBULIN"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": "1255960",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FIVE DAYS PER MONTH",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "STAPHYLOCOCCAL BACTERAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HUMAN NORMAL IMMUNOGLOBULIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "UNSPECIFIED INGREDIENT"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BACTERAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEPHALOSPORIN NOS"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "METOPROLOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "ATENOLOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATENOLOL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "STAPHYLOCOCCAL BACTERAEMIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CEFTOLOZANE SULFATE\\TAZOBACTAM SODIUM"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PNEUMONIA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEFTOLOZANE;TAZOBACTAM"
}
],
"patientagegroup": null,
"patientonsetage": "66",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Candida infection",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Drug effective for unapproved indication",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Fungaemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Bacteraemia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LAGZIEL, T.? RAMOS, M.? ROZYCKI, G.F.? HULTMAN, C.S.? ASIF, M.. THE FIRST REPORTED CASE OF METOPROLOL?INDUCED PEMPHIGUS FOLIACEUS IN THE UNITED STATES: A CRITICAL REPORT AND REVIEW OF LITERATURE. CUREUS. 2020?12 (7):1?6",
"literaturereference_normalized": "the first reported case of metoprolol induced pemphigus foliaceus in the united states a critical report and review of literature",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200909",
"receivedate": "20200909",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18249942,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
},
{
"companynumb": "US-VALIDUS PHARMACEUTICALS LLC-US-2020VAL000745",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METOPROLOL TARTRATE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "017963",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERTENSION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METOPROLOL TARTRATE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FOUR COURSES,FIVE DAYS PER MONTH",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMMUNOGLOBULIN /00025201/"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "SINGLE DOSE EVERY THREE MONTHS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "RITUXIMAB"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "ONE DOSE OF RITUXIMAB (STABILIZING HIS PF)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "RITUXIMAB."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "60 MG, QD (HIGH?DOSE)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "60",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "10 MG, QD (WEANED DOWN)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HUMAN IMMUNOGLOBULIN G"
},
"drugadditional": "3",
"drugadministrationroute": "042",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "FIVE DAY COURSE (STABILIZING HIS PF)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "IMMUNOGLOBULIN /00025201/"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pneumonia",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Staphylococcal infection",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Gastric ulcer haemorrhage",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pemphigus",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Pneumatosis intestinalis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "LAGZIEL T, RAMOS M, ROZYCKI GF, HULTMAN CS, ASIF M.. THE FIRST REPORTED CASE OF METOPROLOL?INDUCED PEMPHIGUS FOLIACEUS IN THE UNITED STATES: A CRITICAL REPORT AND REVIEW OF LITERATURE. CUREUS. 2020?12(7):E9203",
"literaturereference_normalized": "the first reported case of metoprolol induced pemphigus foliaceus in the united states a critical report and review of literature",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200913",
"receivedate": "20200913",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18260221,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20201103"
}
] |
{
"abstract": "We report a case of a 46-year-old man with ulcerative colitis being treated with oral prednisolone and azathioprine. Two weeks after the initiation of azathioprine he presented with fever, fatigue, myalgias and arthralgias and a painful cutaneous eruption that was most marked in a sun-exposed distribution. This was accompanied by loose, non-bloody diarrhoea. Histopathological assessment of a skin biopsy supported a diagnosis of a neutrophilic dermatosis. The azathioprine was temporarily withheld and oral prednisolone was increased as it was thought that the neutrophilic dermatosis was associated with the underlying ulcerative colitis. The patient's symptoms and cutaneous eruption resolved quickly and azathioprine was re-introduced. Within 24 h, systemic symptoms returned along with a florid recrudescence of his cutaneous eruption. This rapidly improved upon withdrawal of azathioprine.",
"affiliations": "Department of Dermatology, Royal Perth Hospital, Western Australia, Australia. [email protected]",
"authors": "Yiasemides|Eleni|E|;Thom|Graham|G|",
"chemical_list": "D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D001379:Azathioprine",
"country": "Australia",
"delete": false,
"doi": "10.1111/j.1440-0960.2008.00503.x",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0004-8380",
"issue": "50(1)",
"journal": "The Australasian journal of dermatology",
"keywords": null,
"medline_ta": "Australas J Dermatol",
"mesh_terms": "D001379:Azathioprine; D003093:Colitis, Ulcerative; D004359:Drug Therapy, Combination; D005938:Glucocorticoids; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D016463:Sweet Syndrome",
"nlm_unique_id": "0135232",
"other_id": null,
"pages": "48-51",
"pmc": null,
"pmid": "19178493",
"pubdate": "2009-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man with ulcerative colitis.",
"title_normalized": "azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man with ulcerative colitis"
}
|
[
{
"companynumb": "GB-RISING PHARMA HOLDINGS, INC.-2021RIS000030",
"fulfillexpeditecriteria": "1",
"occurcountry": "GB",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "30 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "30",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISOLONE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075568",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PEMPHIGUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "4",
"activesubstance": {
"activesubstancename": "METFORMIN HYDROCHLORIDE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "DIABETES MELLITUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METFORMIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CEPHALEXIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "500 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "URINARY TRACT INFECTION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "500",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CEFALEXIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROCHLORPERAZINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "NAUSEA",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PROCHLORPERAZINE."
}
],
"patientagegroup": null,
"patientonsetage": "54",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug hypersensitivity",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Acute generalised exanthematous pustulosis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "YIASEMIDES E, THOM G. AZATHIOPRINE HYPERSENSITIVITY PRESENTING AS A NEUTROPHILIC DERMATOSIS IN A MAN WITH ULCERATIVE COLITIS.. AUSTRALAS J DERMATOL.. 2009?50(1):48?51",
"literaturereference_normalized": "azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man with ulcerative colitis",
"qualification": "3",
"reportercountry": "GB"
},
"primarysourcecountry": "GB",
"receiptdate": "20210413",
"receivedate": "20210413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19132367,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "NZ-RISING PHARMA HOLDINGS, INC.-2021RIS000027",
"fulfillexpeditecriteria": "1",
"occurcountry": "NZ",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075568",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CROHN^S DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "40 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CROHN^S DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "45",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug hypersensitivity",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "YIASEMIDES E, THOM G. AZATHIOPRINE HYPERSENSITIVITY PRESENTING AS A NEUTROPHILIC DERMATOSIS IN A MAN WITH ULCERATIVE COLITIS. AUSTRALAS J DERMATOL. 2009?50(1):48?51",
"literaturereference_normalized": "azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man with ulcerative colitis",
"qualification": "3",
"reportercountry": "NZ"
},
"primarysourcecountry": "NZ",
"receiptdate": "20210413",
"receivedate": "20210413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19130397,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "NZ-RISING PHARMA HOLDINGS, INC.-2021RIS000028",
"fulfillexpeditecriteria": "1",
"occurcountry": "NZ",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075568",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "50 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLITIS ULCERATIVE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "50",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "15 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLITIS ULCERATIVE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "15",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MESALAMINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "3 GRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "COLITIS ULCERATIVE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "3",
"drugstructuredosageunit": "002",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MESALAZINE"
}
],
"patientagegroup": null,
"patientonsetage": "41",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug hypersensitivity",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "YIASEMIDES E, THOM G.. AZATHIOPRINE HYPERSENSITIVITY PRESENTING AS A NEUTROPHILIC DERMATOSIS IN A MAN WITH ULCERATIVE COLITIS.. AUSTRALAS J DERMATOL. 2009?50(1):48?51",
"literaturereference_normalized": "azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man with ulcerative colitis",
"qualification": "3",
"reportercountry": "NZ"
},
"primarysourcecountry": "NZ",
"receiptdate": "20210413",
"receivedate": "20210413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19130970,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
},
{
"companynumb": "NZ-RISING PHARMA HOLDINGS, INC.-2021RIS000026",
"fulfillexpeditecriteria": "1",
"occurcountry": "NZ",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "AZATHIOPRINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "075568",
"drugbatchnumb": "UNK",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "100 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CROHN^S DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "1",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AZATHIOPRINE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNK",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "9 MILLIGRAM",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CROHN^S DISEASE",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "9",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
}
],
"patientagegroup": null,
"patientonsetage": "39",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Drug hypersensitivity",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "YIASEMIDES E, THOM G. AZATHIOPRINE HYPERSENSITIVITY PRESENTING AS A NEUTROPHILIC DERMATOSIS IN A MAN WITH ULCERATIVE COLITIS. AUSTRALAS J DERMATOL. 2009?50(1):48?51",
"literaturereference_normalized": "azathioprine hypersensitivity presenting as a neutrophilic dermatosis in a man with ulcerative colitis",
"qualification": "3",
"reportercountry": "NZ"
},
"primarysourcecountry": "NZ",
"receiptdate": "20210413",
"receivedate": "20210413",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19129991,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210717"
}
] |
{
"abstract": "BACKGROUND\nVitamin K antagonist (VKA) reversal in patients with acute major bleeding and coagulopathy is an example of an urgent intervention in the emergency department. Intravenous (IV) prothrombin complex concentrate (PCC) may reverse VKA-induced coagulopathy in <30 min. In patients lacking IV access, effective PCC administration becomes problematic. No previous case reports have documented PCC infusion via intraosseous (IO) or alternative routes in this setting.\n\n\nMETHODS\nA 74-year-old man presented to the emergency department (ED) after a head injury, with sudden onset of left-sided facial droop, weakness, hypertension, and dizziness. Initial vital signs include blood pressure of 221/102 mm Hg, a heart rate of 75 beats/min, and oxygen saturation of 96% on room air. Warfarin 3 mg once daily was among his medications. His international normalized ratio (INR) was 3.9 with a computed tomography scan showing intraparenchymal hemorrhage in the right temporal lobe. Multiple attempts for IV access at various sites were unsuccessful. Therefore, IO access was established. Because of his prolonged prothrombin time, elevated INR, and intraparenchymal hemorrhage, the decision was made to use 4-factor PCC to reverse the supratherapeutic INR. The INR normalized as an emergent right parietal hematoma evacuation was performed. After an inpatient course, the patient was eventually discharged. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: VKAs, like warfarin, are commonly prescribed medications. When life-threatening hemorrhage is present, rapid reversal of a VKA-induced coagulopathy may be a life-saving therapy. In the event that IV access has not been established, we have demonstrated that IO access is a viable alternative route for PCC administration.",
"affiliations": "Department of Pharmacy, St. Elizabeth Hospital - Boardman, Boardman, Ohio.;Department of Emergency Medicine, St. Elizabeth Hospital - Boardman, Boardman, Ohio.;Department of Emergency Medicine, St. Elizabeth Hospital - Boardman, Boardman, Ohio.;Department of Emergency Medicine, St. Elizabeth Hospital - Boardman, Boardman, Ohio.",
"authors": "Peyko|Vincent|V|;Shams|Darius|D|;Urbanski|Richard|R|;Noga|Joseph|J|",
"chemical_list": "D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D014859:Warfarin",
"country": "United States",
"delete": false,
"doi": "10.1016/j.jemermed.2019.03.005",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0736-4679",
"issue": "57(1)",
"journal": "The Journal of emergency medicine",
"keywords": "bleeding; prothrombin complex concentrate; reversal; vitamin K antagonist",
"medline_ta": "J Emerg Med",
"mesh_terms": "D000368:Aged; D000925:Anticoagulants; D001779:Blood Coagulation Factors; D004244:Dizziness; D006470:Hemorrhage; D006801:Humans; D006973:Hypertension; D017148:Infusions, Intraosseous; D008297:Male; D018908:Muscle Weakness; D013997:Time Factors; D014859:Warfarin",
"nlm_unique_id": "8412174",
"other_id": null,
"pages": "82-84",
"pmc": null,
"pmid": "31060844",
"pubdate": "2019-07",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "4-Factor Prothrombin Complex Concentrate Administration via Intraosseous Access for Urgent Reversal of Warfarin.",
"title_normalized": "4 factor prothrombin complex concentrate administration via intraosseous access for urgent reversal of warfarin"
}
|
[
{
"companynumb": "US-TEVA-2019-US-1102361",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "WARFARIN"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "40145",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "3 MILLIGRAM DAILY;",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ATRIAL FIBRILLATION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "3",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "WARFARIN"
}
],
"patientagegroup": null,
"patientonsetage": "74",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": "72.7",
"reaction": [
{
"reactionmeddrapt": "Cerebral haematoma",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Facial paralysis",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Haemorrhagic stroke",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Cerebral haemorrhage",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Loss of personal independence in daily activities",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "3"
},
{
"reactionmeddrapt": "Coagulation factor deficiency",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Paralysis",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Brain herniation",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PEYKO V, SHAMS D, URBANSKI R, NOGA J. 4-FACTOR PROTHROMBIN COMPLEX CONCENTRATE ADMINISTRATION VIA INTRAOSSEOUS ACCESS FOR URGENT REVERSAL OF WARFARIN. J-EMERG-MED 2019?57(1):82-84.",
"literaturereference_normalized": "4 factor prothrombin complex concentrate administration via intraosseous access for urgent reversal of warfarin",
"qualification": "2",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190914",
"receivedate": "20190903",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16769316,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": null,
"transmissiondate": "20191005"
},
{
"companynumb": "US-MYLANLABS-2019M1079470",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "WARFARIN"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "040415",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "3 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ATRIAL FIBRILLATION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "3",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "WARFARIN"
}
],
"patientagegroup": null,
"patientonsetage": "74",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": "72.7",
"reaction": [
{
"reactionmeddrapt": "Cerebral haematoma",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Cerebral haemorrhage",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Paralysis",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Facial paralysis",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Coagulation factor deficiency",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Haemorrhagic stroke",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PEYKO V, SHAMS D, URBANSKI R, NOGA J. 4-FACTOR PROTHROMBIN COMPLEX CONCENTRATE ADMINISTRATION VIA INTRAOSSEOUS ACCESS FOR URGENT REVERSAL OF WARFARIN. J-EMERG-MED 2019?57(1):82-84.",
"literaturereference_normalized": "4 factor prothrombin complex concentrate administration via intraosseous access for urgent reversal of warfarin",
"qualification": "2",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190827",
"receivedate": "20190827",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16744633,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20191005"
}
] |
{
"abstract": "BACKGROUND\nKeloid scarring is a pathologic proliferation of scar tissue that often causes pruritus, pain, and disfigurement. Keloids can be difficult to treat and have a high risk of recurrence. Recent studies have shown promising results in the treatment of cutaneous metastases with intralesional calcium combined with electroporation (calcium electroporation). As calcium electroporation has shown limited side effects it has advantages when treating benign keloid lesions, and on this indication we performed a phase I study.\n\n\nMETHODS\nPatients with keloids were treated with at least 1 session of calcium electroporation and followed up for 2 years. Calcium was administered intralesionally (220 mM) followed by the application of eight 100-µs pulses (400 V) using linear-array electrodes and Cliniporator (IGEA, Italy). Treatment efficacy was evaluated clinically (size, shape, erythema), by patient self-assessment (pruritus, pain, other) and assessed histologically.\n\n\nRESULTS\nSix patients were included in this small proof of concept study. Treatment was well tolerated, with all patients requesting further treatment. Two out of 6 patients experienced a decrease in keloid thickness over 30%. A mean reduction of 11% was observed in volume size, and a mean flattening of 22% was observed (not statistically significant). Five out of 6 patients reported decreased pain and pruritus. No serious adverse effects or recurrences were observed over a mean follow-up period of 338 days.\n\n\nCONCLUSIONS\nIn this first phase I clinical study on calcium electroporation for keloids, treatment was found to be safe with minor side effects. Overall, patients experienced symptom relief, and in some patients keloid thickness was reduced.",
"affiliations": "Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.;Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark.;Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.;Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark.",
"authors": "Falk|Hanne|H|;Vissing|Mille|M|;Wooler|Gitte|G|;Gehl|Julie|J|",
"chemical_list": null,
"country": "Switzerland",
"delete": false,
"doi": "10.1159/000514307",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1018-8665",
"issue": "237(6)",
"journal": "Dermatology (Basel, Switzerland)",
"keywords": "Calcium; Electroporation; Keloid; Scar management",
"medline_ta": "Dermatology",
"mesh_terms": null,
"nlm_unique_id": "9203244",
"other_id": null,
"pages": "961-969",
"pmc": null,
"pmid": "33789301",
"pubdate": "2021",
"publication_types": "D016428:Journal Article",
"references": "28760856;26633834;29577784;29842892;24342489;22282658;28812409;24782355;27553611;19097774;12521975;15253184;22731832;25853661;23027217;29868638;22549747;28816072;20927486;29673795;16918564;24888226;20627836;28118487;24076710;11231236;17576505;30828619;16135153;9635922;16865862;28562201",
"title": "Calcium Electroporation for Keloids: A First-in-Man Phase I Study.",
"title_normalized": "calcium electroporation for keloids a first in man phase i study"
}
|
[
{
"companynumb": "DK-ALKEM LABORATORIES LIMITED-DK-ALKEM-2021-01968",
"fulfillexpeditecriteria": "1",
"occurcountry": "DK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CALCIUM CARBONATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "9 MG/ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Keloid scar",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CALCIUM CARBONATE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LIDOCAINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207810",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Local anaesthesia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "40",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pain",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Falk H, Vissing M, Wooler G, Gehl J.. Calcium Electroporation for Keloids: A First-in-Man Phase I Study. Dermatology. 2021;UNK:UNK",
"literaturereference_normalized": "calcium electroporation for keloids a first in man phase i study",
"qualification": "3",
"reportercountry": "DK"
},
"primarysourcecountry": "DK",
"receiptdate": "20220429",
"receivedate": "20220429",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20768335,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 2,
"transmissiondate": "20220720"
},
{
"companynumb": "DK-ALKEM LABORATORIES LIMITED-DK-ALKEM-2021-02032",
"fulfillexpeditecriteria": "1",
"occurcountry": "DK",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CALCIUM CARBONATE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "9 MG/1ML",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Keloid scar",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CALCIUM CARBONATE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LIDOCAINE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207810",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Local anaesthesia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LIDOCAINE"
}
],
"patientagegroup": null,
"patientonsetage": "20",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Oedema",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Ulcer",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Falk H, Vissing M, Wooler G, Gehl J.. Calcium Electroporation for Keloids: A First-in-Man Phase I Study. Dermatology. 2021;unk:unk",
"literaturereference_normalized": "calcium electroporation for keloids a first in man phase i study",
"qualification": "3",
"reportercountry": "DK"
},
"primarysourcecountry": "DK",
"receiptdate": "20220429",
"receivedate": "20220429",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20768333,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 2,
"transmissiondate": "20220720"
}
] |
{
"abstract": "We present a patient who underwent cryoballoon ablation for symptomatic atrial fibrillation, with gastroparesis five days later. The case was resolved with conservative measures such as prokinetics. The case was a 72-year-old female with a history of symptomatic paroxysmal atrial fibrillation treated with edoxaban. Pulmonary vein isolation using a cryoballoon catheter was performed. Five days later, she presented with upper abdominal pain, bloating and vomiting.",
"affiliations": "UGC Aparato Digestivo, Hospital Universitario Clínico San Cecilio, España.;UGC Aparato Digestivo, Hospital Universitario Clínico San Cecilio.;UGC Aparato Digestivo, Hospital Universitario Clínico San Cecilio.",
"authors": "Vidal Vílchez|Begoña|B|;Roa Colomo|Amparo|A|;Martín-Lagos Maldonado|Alicia|A|",
"chemical_list": null,
"country": "Spain",
"delete": false,
"doi": "10.17235/reed.2020.7275/2020",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1130-0108",
"issue": "113(3)",
"journal": "Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva",
"keywords": null,
"medline_ta": "Rev Esp Enferm Dig",
"mesh_terms": "D000368:Aged; D001281:Atrial Fibrillation; D017115:Catheter Ablation; D003452:Cryosurgery; D005260:Female; D018589:Gastroparesis; D006801:Humans; D011667:Pulmonary Veins; D012008:Recurrence; D016896:Treatment Outcome; D014839:Vomiting",
"nlm_unique_id": "9007566",
"other_id": null,
"pages": "229-230",
"pmc": null,
"pmid": "33222475",
"pubdate": "2021-03",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Gastroparesis secondary to pulmonary vein cryoablation: a factor to consider.",
"title_normalized": "gastroparesis secondary to pulmonary vein cryoablation a factor to consider"
}
|
[
{
"companynumb": "ES-DSJP-DSE-2020-137000",
"fulfillexpeditecriteria": "1",
"occurcountry": "ES",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "EDOXABAN TOSYLATE"
},
"drugadditional": "3",
"drugadministrationroute": null,
"drugauthorizationnumb": "206316",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ATRIAL FIBRILLATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "EDOXABAN"
}
],
"patientagegroup": null,
"patientonsetage": "72",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Impaired gastric emptying",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Cardiac ablation",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "VIDAL VB, ROA CA, MARTIN-LAGOS MA. GASTROPARESIS SECONDARY TO PULMONARY VEIN CRYOABLATION: A FACTOR TO CONSIDER. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS. 2020",
"literaturereference_normalized": "gastroparesis secondary to pulmonary vein cryoablation a factor to consider",
"qualification": "3",
"reportercountry": "ES"
},
"primarysourcecountry": "ES",
"receiptdate": "20201207",
"receivedate": "20201207",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18587294,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20210114"
}
] |
{
"abstract": "BACKGROUND\nInvasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential.\n\n\nOBJECTIVE\nThe aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses.\n\n\nMETHODS\nThis was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality.\n\n\nRESULTS\nA total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10cells/μL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia.\n\n\nCONCLUSIONS\nBoth confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.",
"affiliations": "Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil.;Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil.;Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil.;Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil.;Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil.;Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil.;Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil. Electronic address: [email protected].",
"authors": "Rodrigues|Lorrane Caroline Braga|LCB|;Guimaraes|Alessandro Fernandes|AF|;de Oliveira|Isamara Simas|IS|;de Sousa|Pedro Henrique Medici|PHM|;de Castro Romanelli|Roberta Maia|RM|;Kakehasi|Fabiana Maria|FM|;de Sá Rodrigues|Karla Emília|KE|",
"chemical_list": null,
"country": "Brazil",
"delete": false,
"doi": "10.1016/j.htct.2020.08.016",
"fulltext": "\n==== Front\nHematol Transfus Cell Ther\nHematol Transfus Cell Ther\nHematology, Transfusion and Cell Therapy\n2531-1379\n2531-1387\nSociedade Brasileira de Hematologia e Hemoterapia\n\nS2531-1379(20)31283-9\n10.1016/j.htct.2020.08.016\nOriginal Article\nAcute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases\nRodrigues Lorrane Caroline Braga\nGuimaraes Alessandro Fernandes\nde Oliveira Isamara Simas\nde Sousa Pedro Henrique Medici\nde Castro Romanelli Roberta Maia\nKakehasi Fabiana Maria\nde Sá Rodrigues Karla Emília [email protected]\n*\nHospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil\n⁎ Corresponding author at: Hospital das Clínicas da Universidade Federal Minas Gerais (HC UFMG), Belo Horizonte, MG, Brazil. [email protected]\n09 11 2020\nJan-Mar 2022\n09 11 2020\n44 1 3239\n3 7 2020\n21 8 2020\n© 2020 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda.\n2020\nAssociação Brasileira de Hematologia, Hemoterapia e Terapia Celular\nhttps://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).\nIntroduction\n\nInvasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential.\n\nObjectives\n\nThe aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses.\n\nMethods\n\nThis was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality.\n\nResults\n\nA total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10 cells/μL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia.\n\nConclusion\n\nBoth confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.\n\nKeywords\n\nPediatrics\nHematologic diseases\nFebrile neutropenia\nInvasive fungal infection\nFusarium\n==== Body\npmcIntroduction\n\nInvasive fungal diseases (IFDs) represent important causes of morbidity and mortality among pediatric oncohematological patients. Early diagnosis and treatment of an IFD is associated with a better outcome and this requires the use of fast and precise methods that can support clinicians in its management.1\n\nFungal rhinosinusitis (FRS) can be classified as invasive or noninvasive, based on the histopathological evidence of tissue invasion by the fungus, which results in necrosis and local tissue destruction. This invasive disease is subdivided into acute invasive FRS (AIFRS), granulomatous invasive FRS and chronic invasive FRS.2, 3, 4\n\nAIFRS is a rare and aggressive disease that occurs mainly in immunocompromised patients, particularly in those with neutropenia, with oncohematological diseases representing a major predisposing factor.4, 5 Infection is characterized by fungal invasion of the nasal or paranasal cavity, which may affect adjacent organs, such as the orbits and intracranial structures.6 Numerous fungi can cause invasive infection, however, the most commonly identified fungi in AIFRS are Aspergillus and Zygomycetes (Rhizopus, Mucor, Rhizomucor).2, 7, 8, 9, 10\n\nThe diagnosis is challenging and fever is often the only presenting symptom. Other signs and symptoms may be very slight due to the reduced local inflammatory response capacity, which is a consequence of neutropenia. The complications include delayed chemotherapy treatment that may result in cancer recurrence, bone erosion, orbital invasion, brain abscess, meningitis, hematogenous spread and death. The mortality rate is high, ranging from 20 to 80% and therefore, accurate and early diagnosis is essential.5, 7, 11, 12, 13\n\nThe aim of this study was to assess the frequency of AIFRS among pediatric oncohematological patients evaluated by the otorhinolaryngology service and determine the characteristics of patients with confirmed diagnoses.\n\nMethods\n\nThe study was approved by the Institutional Research Ethics Committee (number 1.425.036) and participants were included after proxy informed consent was obtained from the children’s guardians.\n\nPatients diagnosed with malignant neoplasia or aplastic anemia from January to December 2017 were included.\n\nInclusion criteria were patients aged less than 18 years, hospitalized for the treatment of oncohematological diseases and who exhibited indications for otorhinolaryngological evaluation and possible infection, as well as neutropenia (a neutrophil count of <500/μL or <1,000/μL, with a tendency to undergo further decrease), fever (axillary temperature ≥37,8 °C) and/or nasosinusal symptoms.\n\nMedical record analysis collected the following data: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedure performed and clinical outcome.\n\nThe medical records were reviewed and the data were collected by a multidisciplinary team responsible for the routine care of oncohematological patients. In this period, the team met regularly to discuss and standardize data registration in a previously prepared form. All study members were trained in data collection and regular meetings were held to discuss methodology and findings.\n\nResults\n\nIn total, 27 patients were evaluated and among three suspected cases of AIFRS, two cases (7.41% 95% CI: 0.9–24.3) were confirmed with histopathological and microbiological evidence of fungal infection (Table 1). The unconfirmed patient died before undergoing the surgical approach.Table 1 Clinical/laboratory data of patients in a retrospective cohort of immunocompromised patients at a cancer reference center.\n\nTable 1Patient\tAge\tSex\tDiagnosis\tNumber of ORL evaluations\tMain reason for the evaluation\tORL symptoms\tORL evaluation findings\tCRP mg/L\tAbsolute neutrophil count (cells × 103/μL)\tPlatelet count (×10³/μL)\tGMNa at the ORL evaluation\tOutcome\t\n1\t12\tFemale\tAML; AIFRS\t11\tFever persistence or recurrence and ORL symptoms\tRhinorrhea\tPaleness and crusting of septum and middle turbinate\t135\t0,01\t63\tNP\tInfection resolved\t\n2\t14\tFemale\tBMA; AIFRS\t3\tFever persistence or recurrence and ORL symptoms\tCrusting\tPaleness, Crusting, and Necrosis of\nSeptum and Inferior turbinate\t414\t0,01\t29\t4.12\tDeath\t\n3\t1\tMale\tAML\t1\tFever persistence or recurrence\tNo\tNormal\t170.72\t0,03\t15\t0,13\tDischarged by the ORL clinic\t\n4\t16\tMale\tNHL\t2\tORL symptoms\tRhinorrhea, posterior nasal discharge and cough\tNormal\tNP\t6,170\t177\tNP\tDischarged by the ORL clinic\t\n5\t8\tMale\tNHL\t4\tFever persistence or recurrence\tNo\tPaleness of the middle turbinate\t89.36\t0\t36\t0.39\tDischarged by the ORL clinic\t\n6\t5\tMale\tRMS\t2\tFever persistence or recurrence\tNo\tNP\t34.97\t0,06\t355\tNP\tDischarged by the ORL clinic\t\n7\t10\tFemale\tRMS\t2\tFever persistence or recurrence\tNo\tNormal\tNP\t0,13\t416\t0.5\tDischarged by the ORL clinic\t\n8\t14\tMale\tALL\t2\tFever persistence or recurrence and ORL symptoms\tCough\tPaleness of the middle turbinate and nasal septum\t383.41\t0,01\t8\tNP\tDeath\t\n9\t12\tMale\tFanconi’s anemia\t1\tFever persistence or recurrence and ORL symptoms\tRhinorrhea, nasal congestion and nasal sinus pain\tNP\tNP\t8,33\t16\tNP\tDischarged by the ORL clinic\t\n10\t15\tMale\tALL\t1\tFever persistence or recurrence\tNo\tNP\t168.19\t0\t37\tNP\tInfection resolved\t\n11\t13\tMale\tAML\t1\tORL symptoms\tCough\tNormal\tNP\t0,98\t324\tNP\tDischarged by the ORL clinic\t\n12\t7\tFemale\tMDS\t1\tORL symptoms\tRhinorrhea, nasal congestion, cough and nasal sinus pain\tNormal\tNP\t0,280\t27\tNP\tDischarged by the ORL clinic\t\n13\t7\tMale\tALL\t3\tFever persistence or recurrence and ORL symptoms\tRhinorrhea, cough and headache\tHyalin secretion on nasal floor\t321.51\t0,050\t31\t0.09\tDischarged by the ORL clinic\t\n14\t8\tMale\tALL\t5\tFever persistence or recurrence4and ORL symptoms\tRhinorrhea, nasal congestion and cough\tBilateral mucoid secretion and crusts On the left nasal septum\t226.15\t0,020\t29\t3.2\tDeath\t\n15\t15\tFemale\tMDS\t1\tFever persistence or recurrence and ORL symptoms\tRhinorrhea, nasal congestion and nasal sinus pain\tMucosal edema and hyalin secretion on nasal floor\t87.03\t1,740\t97\tNP\tDischarged by the ORL clinic\t\n16\t5\tMale\tALL\t1\tFever persistence or recurrence and ORL symptoms\tRhinorrhea and cough\tHyalin secretion on nasal floor and congestion of the inferior turbinate\t187.19\t0,550\t240\t0.33\tDischarged by the ORL clinic\t\n17\t5\tFemale\tMDS\t1\tFever persistence or recurrence and ORL symptoms\tRhinorrhea, cough and headache\tHyalin secretion on the middle turbinate\t46.68\t0,038\t429\tNP\tDischarged by the ORL clinic\t\n18\t10\tFemale\tNBL\t1\tFever persistence or recurrence and ORL symptoms\tRhinorrhea and cough\tNP\t43.45\t0,01\t22\tNP\tDischarged by the ORL clinic\t\n19\t14\tFemale\tALL\t1\tFever persistence or recurrence and ORL symptoms\tNo\tNormal\tNP\t0,19\t34\tNP\tDischarged by the ORL clinic\t\n20\t14\tMale\tNHL\t1\tORL symptoms\tRhinorrhea, nasal congestion, cough, nasal sinus pain and sneezing\tHyalin secretion on nasal floor and congestion of the Inferior turbinate\t78.07\t4,7\t371\tNP\tDischarged by the ORL clinic\t\n21\t12\tMale\tAML\t1\tORL symptoms\tRhinorrhea and cough\tHyalin secretion on the middle meatus and congestion of the inferior turbinate\tNP\t0,470\t20\tNR\tDischarged by the ORL clinic\t\n22\t13\tFemale\tFanconi’s anemia\t2\tFever persistence or recurrence and ORL symptoms\tCough\tNP\t168.67\t0,06\t1\tNP\tDeath\t\n23\t7\tFemale\tAML\t2\tFever persistence or recurrence and ORL symptoms\tNasal congestion, cough, nasal sinus pain\tNormal\t248.7\t0,05\t13\t0,13\tDischarged by the ORL clinic\t\n24\t10\tFemale\tBMA\t7\tFever persistence or recurrence and ORL symptoms\tCough\tNormal\t147.42\t0\t7\t0.11\tDischarged by the ORL clinic\t\n25\t14\tFemale\tAML\t12\tFever persistence or recurrence and ORL symptoms; previous RSFIA\tNasal bleeding\tDiffuse pallor, hematic crust on nasal floor\tNP\t0,02\t36\tNP\tDischarged by the ORL clinic\t\n26\t16\tFemale\tLNH\t2\tORL symptoms\tRhinorrhea, posterior nasal Discharge and sneezing\tPurulent secretion in right middle meatus\t20.83\t2,470\t248\tNP\tDischarged by the ORL clinic\t\n27\t3\tMale\tBMA\t1\tFever persistence or recurrence\tNo\tNormal\t155.67\t0,07\t16\tNP\tDischarged by the ORL clinic\t\nAML: acute myeloid leukemia; AIFRS: acute invasive fungal rhinosinusitis; ORL: otorhinolaryngology; BMA: bone marrow aplasia; NHL: non-Hodgkin’ lymphoma; RMS: rhabdomyosarcoma; ALL: acute lymphoblastic leukemia; MDS: myelodysplastic syndrome; NBL: neuroblastoma; CRP: C-reactive protein, PLAT: platelets, NP: not performed.\n\na GALACTOMANNAN, ANTIGENO ASPERGILLUS, Method: Enzyme Immunoassay (ELISA), REFERENCE VALUES: NEGATIVE SERUM: less than 0.5.\n\nThe two confirmed cases of AIFRS were female, aged 12 and 14 years, and both had an absolute neutrophil count of 10 cells/μL. The first patient (P1) had acute myeloid leukemia (subtype M5) as an underlying disease and was in the induction phase of the treatment, with an interval of 15 days between the beginning of chemotherapy and the first otorhinolaryngological evaluation. The second patient (P2) was diagnosed with severe aplastic anemia.\n\nFever, hyaline rhinorrhea and nasal crusting were the symptoms observed in the two patients with confirmed diagnoses. Patient P1 presented with fever recurrence after 12 days of being afebrile under meropenem treatment for 14 days. Patient P2 presented with persistent fever for 23 days, despite the use of meropenem, polymyxin, liposomal amphotericin, linezolid and micafungin (Table 1).\n\nIn both cases, the sites of nasal involvement were the anterior septum, associated with a lesion in the left inferior turbinate or right middle turbinate, with direct examination revealing adhered crusts and pale mucosa. However, patient P2 had evolved to necrosis at the time of surgery. Only patient P1 underwent sinus computed tomography, which revealed nonspecific findings of mucosal thickening of the maxillary, frontal and sphenoid sinuses.\n\nBoth patients received treatment with a systemic antifungal (liposomal amphotericin and liposomal amphotericin associated with micafungin) and surgical debridement. No granulocyte colony-stimulating factor was used. The surgical samples removed were sent for histopathological examination and culture. In both cases, the pathogen isolated in the cultures was Fusarium sp. Histopathological evaluation revealed respiratory mucosa with areas of necrosis and the presence of numerous filamentous fungi with hyaline, acute-branching septate hyphae.\n\nWeekly postoperative follow-up was performed, with nasosinusal endoscopy in P1, until neutrophil recovery. Recurrent infection or post-operative complications, such as pain, vomiting, bleeding, infection, abscess, or synechiae were not observed. Patient P2 died 6 days after surgery with septic shock and multiple-organ failure.\n\nDiscussion\n\nAIFRS is a severe opportunistic infection with high morbidity and mortality that usually occurs in immunosuppressed patients. Risk factors include hematologic malignancies and aplastic anemia, which lead to the reduction in, and dysfunction of, neutrophils.2, 3, 4, 5 As in adults, the most important risk factor in pediatric patients is hematologic neoplasia, probably due to the long periods of intense neutropenia that these patients often experience during their treatment.6, 7\n\nUpper airway fungal infection should be investigated whenever a neutropenic patient continues to exhibit persistent or recurrent fever after 4–7 days of broad-spectrum antibiotic therapy or exhibits signs and symptoms suggestive of airway infection, such as persistent cough, rhinorrhea and nasal obstruction.14\n\nThe most common initial symptoms of AIFRS are fever, nasal discharge, facial pain, rhinorrhea and nasal congestion.11, 15, 16 Similarly, we observed nonspecific early symptoms including fever, hyaline rhinorrhea and nasal crust formation. Visual and neurological symptoms, such as ophthalmoplegia, proptosis, orbital cellulitis, visual loss, changes in mental status and palate erosion, are signs of an extensive disease and indicate orbital or intracranial invasion.17, 18, 19\n\nThe presence of such symptoms in immunocompromised patients is the condition requiring mandatory nasal endoscopy, which can be performed with a flexible nasofibroscope or a rigid endoscope. Suggestive findings include discoloration or blackening (a sign of ischemia), edema, ulcerations, granulation and crusting of the mucosa, vestibule or columella. In cases of suspected extra-sinusal extension of the disease, paranasal sinus computed tomography is the appropriate tool for proper surgical planning. However, it reveals nonspecific changes in the early phase of the disease, such as unilateral thickening of the nasal cavity or paranasal sinuses. If orbital or cranial invasion is suspected, nuclear magnetic resonance becomes essential.3, 11\n\nThe definitive diagnosis of AIFRS is established by culture and histopathological evaluation, which can reveal tissue invasion by hyphae.2 Whenever possible, treatment consists of reversing immunosuppression, discontinuing chemotherapy and using granulocyte colony-stimulating factor, combined with antifungal therapy and urgent surgical intervention, which involves aggressive debridement and resection of the entire affected area.3, 7\n\nFirst symptoms of AIFRS are often nonspecific, which contributes to the difficulty in making an early diagnosis, especially among children who are not able to describe their symptoms in detail.2, 8 In this study, the two cases occurred in adolescents, both showing increased inflammatory marker C-reactive protein (444 and 135 mg/dL) and thrombocytopenia (29,000 and 63,000 platelets/μL). The galactomannan test was only performed on patient P2 (4,12) and, despite decreasing, it remained altered and positive until death.\n\nThe main etiological agent described for AIFRS in oncologic and hematological patients is Aspergillus. These microorganisms are saprophytes that are found in decomposed substances, soil and fruits, as well as in the throat, nasal cavities and feces of healthy individuals, but can become pathogenic in immunocompromised patients.2, 9 In this report, samples from both cases were sent for culture and the infectious agent Fusarium sp. was identified in both cases. This was also the most commonly isolated fungus in a pediatric series of AIFRS reported by Park et al. and Vinh et al.15, 20 However, Ardeshirpour et al. identified Alternaria as the causative agent, whereas Tarkan et al. identified Mucor as the causative agent in eight out of 13 pediatric oncohematological patients.21, 22 A similar report by Yakirevitch et al. examined 13 children and identified Mucor (in five patients), Aspergillus (in five patients), Mucor and Aspergillus (in one patient), Exserohilum rostratum (in one patient) and Fusarium (in one patient).23\n\nFusarium species have emerged as responsible for a broad spectrum of infections, including superficial, locally invasive and disseminated ones, especially in the hospital environment, where reservoirs of infectious species have been reported, especially in the plumbing and water systems.24, 25, 26, 27\n\nFusariosis in immunocompromised patients, mainly children, is usually an invasive and frequently serious disseminated disease, which is the most frequent and challenging clinical form of this infection, accounting for approximately 70% all cases.24 The upper respiratory tract is the main entrance for Fusarium spp., followed by the skin mucosal membranes. Various organs can be affected, including nasal cavities, sinuses, lungs, joints, retina, liver, spleen and kidneys.28, 29\n\nThe incidence of invasive fusariosis in immunosuppressed patients is variable. An epidemiologic study conducted at eight Brazilian centers between 2007 and 2009 reported a 1-year cumulative incidence of 5.2% among allogeneic hematopoietic cell transplant recipients and of 3.8% in patients with acute myeloid leukemia.30 Incidence of invasive fusariosis here seems higher than that reported in other regions of the world and it is not clear why.\n\nAcute leukemia and T-cell immunodeficiency, in addition to prolonged and deep neutropenia, is one of the main risk factors for invasive fusariosis.31 In our study, the underlying disease was acute myeloid leukemia and severe aplastic anemia and all of the patients presented febrile neutropenia.\n\nGillespie et al. described the most frequently affected locations as follows (in order of frequency): the middle concha, septum, hard palate, and inferior turbinate.11 Here, discoloration, crusting or granulation were more common findings than ulcerations. Similarly, the most commonly affected locations found by Tarkan et al. were the middle concha and the septum.22 In the present study, the most affected locations were the nasal septum, middle turbinate and inferior turbinate.\n\nA study by Vinh et al. examined all causes of mortality and demonstrated a survival rate of 59% at 30 days and 41% at 6 months.20 Gillespie et al. observed 25 patients, of whom 10 recovered, 9 died due to the disease and 6 died due to other causes.11 On the contrary, Ardeshirpour et al. reported a cure of all 11 patients (100%) without relapse, but three patients eventually died from unrelated causes.21 In our case series, one patient with acute myeloid leukemia was considered cured, with no evidence of recurrent fungal infection after one year of follow-up. The clinical outcome of the patient diagnosed with aplastic anemia was death due to other causes besides RSFIA.\n\nIt is recommended that after surgery and while neutropenia is still present, a nasosinusal endoscopic follow-up of AIFRS patients be performed weekly. After neutrophil count recovery, such a follow-up should be performed monthly for an additional six months.31 At our service, this follow-up protocol is performed by the pediatrician and the oncologist who administers the associated systemic antifungal therapy. This study helped define the management protocol that will be followed at this service (Figure 1).Figure 1 Flowchart for management of neutropenic patients suspected of invasive fungal infection.\n\nFigure 1\n\nConclusion\n\nIn this chart review, AIFRS was observed in 7.4% of oncohematological pediatric patients assessed with suspected fungal infection at our hospital. They presented with minor local signs of nasal and sinusital inflammation, as well as constitutional signs and symptoms. This demonstrates the importance of fever as a symptom and that it should prompt otorhinolaryngological investigation in immunocompromised patients, especially considering they have a higher potential of fungal infection. Prompt assessment and management are crucial to decrease morbidity and mortality. AIFRS should be considered in all patients with an immunosuppressive disease with fever or nasosinusal symptoms, especially in the presence of septal mucosa and turbinate changes, such as discoloration or blackening, edema, ulcerations, granulation and crusting. We are currently expanding the study population for future studies.\n\nConflicts of interest\n\nThe authors declare no conflicts of interest.\n\nAcknowledgments\n\nWe would like to thank Editage (www.editage.com) for English language editing.\n==== Refs\nReferences\n\n1 Saffioti C. Mesini A. Bandettini R. Castagnola E. Diagnosis of invasive fungal disease in children: a narrative review Expert Rev Anti Infect Ther 13 2019 1 15\n2 deShazo R.D. O’Brien M. Chapin K. Soto-Aguilar M. Gardner L. Swain R. A new classification and diagnostic criteria for invasive fungal sinusitis Arch Otolaryngol Head Neck Surg 123 1997 1181 1188 9366697\n3 Pignatari S.S.N. Anselmo-Lima W.T. Otorhinolaryngology treaty 2018 Elsevier Rio de Janeiro\n4 Wiley A. Schell M.S. Histopathology of fungal rhinosinusitis Otolaryngol Clin North Am 33 2000 251–27\n5 Chen C.Y. Sheng W.H. Cheng A. Chen C.Y. Tsay W. Tang J.L. Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan BMC Infect Dis 11 2011 250 259 21939544\n6 Drakos P.E. Nagler A. Or R. Naparstek E. Kapelushnik J. Engelhard D. Invasive fungal sinusitis in patients undergoing bone marrow transplantation Bone Marrow Transplant 12 1993 203 208 8241977\n7 Turner J.H. Soudry E. Nayak J.V. Hwang P.H. Survival outcomes in acute invasive fungal sinusitis: a systematic review and quantitative synthesis of published evidence Laryngoscope 123 2013 1112 1118 23300010\n8 Rhizopus, Rhizomucor, Absidia, and other agents of systemic and subcutaneous zygomycosis Richardson M.D. Koukila-Kähkölä P. Murray P.R. Baron E.J. Jorgensen J.H. Landry M.L. Manual of clinical microbiology 9th ed. 2007 ASM Press Washington\n9 Brandwein M. Histopathology of sinonasal fungal disease Otolaryngol Clin North Am 26 1993 949 981 8290288\n10 Monroe M.M. McLean M. Sautter N. Wax M.K. Andersen P.E. Smith T.L. Invasive fungal rhinosinusitis: a 15-year experience with 29 patients Laryngoscope 123 2013 1583 1587 23417294\n11 Gillespie M.B. O’Malley B.W. Francis H.W. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host Arch Otolaryngol Head Neck Surg 124 1998 520 526 9604977\n12 Kennedy C.A. Adams G.L. Neglia J.P. Giebink G.S. Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients Otolaryngol Head Neck Surg 116 1997 610 616\n13 Del Gaudio J.M. Clemson L.A. An early detection protocol for invasive fungal sinusitis in neutropenic patients successfully reduces extent of disease at presentation and long-term morbidity Laryngoscope 119 2009 180 183 19117301\n14 Rejin K. Hande K. Febrile neutropenia in children with cancer: approach to diagnosis and treatment Curr Pediatr Rev 14 2018 204 209 29737253\n15 Park A.H. Muntz H.R. Smith M.E. Afify Z. Pysher T. Pavia A. Pediatric invasive fungal rhinosinusitis in immunocompromised children with cancer Otolaryngol Head Neck Surg 133 2005 411 416 16143192\n16 Kasapoglu F. Coskun H. Ozmen O.A. Akalin H. Ener B. Acute invasive fungal rhinosinusitis: evaluation of 26 patients treated with endonasal or open surgical procedures Otolaryngol Head Neck Surg 143 2010 614 620 20974328\n17 Gillespie M.B. O’Malley B.W. An algorithmic approach to the diagnosis and management of invasive fungal rhinosinusitis in the immunocompromised patient Otolaryngol Clin North Am 33 2000 323 334 10736407\n18 Ketenci I. Unlü Y. Kaya H. Somdaş M.A. Kontaş O. Oztürk M. Rhinocerebral mucormycosis: experience in 14 patients J Laryngol Otol 125 2011 e3 21729455\n19 Anselmo-Lima W.T. Lopes R.P. Valera F.C. Demarco R.C. Invasive fungal rhinosinusitis in immunocompromised patients Rhinology 42 2004 141 144 15521667\n20 Vinh D. Yim M. Dutta A. Jones J.K. Zhang W. Sitton M. Pediatric invasive fungal rhinosinusitis: an investigation of 17 patients Int J Pediatr Otorhinolaryngol 99 2017 111 116 28688551\n21 Ardeshirpour F. Bohm L.A. Belani K.K. Sencer S.F. Lander T.A. Sidman J.D. Surgery for pediatric invasive fungal sinonasal disease Laryngoscope 124 2014 1008 1012 24105873\n22 Tarkan O. Karagün B. Ozdemir S. Tuncer U. Sürmelioğlu O. Cekiç E. Endonasal treatment of acute invasive fungal rhinosinusitis in immunocompromised pediatric hematology–oncology patients Int J Pediatr Otorhinolaryngol 76 2012 1458 1464 22795740\n23 Yakirevitch A. Barg A.A. Bedrin L. Primov-Fever A. Wolf M. Migirov L. Acute invasive fungal rhinosinusitis in children with hematologic malignancies: outcome of surgical treatment Pediatr Hematol Oncol 32 2015 568 575 26558653\n24 Nucci M. Anaissie E. Fusarium infections in immunocompromised patients Clin Microbiol Rev 20 2007 695 704 17934079\n25 Litvinov N. da Silva M.T. van der Heijden I.M. Grac¸a M.G. Marques de Oliveira L. Fu L. An outbreak of invasive fusarium in a children’s cancer hospital Clin Microbiol Infect 21 2015 1 7 25636919\n26 Short D.P.G. O’Donnell K. Zhang N. Juba J.H. Geiser D.M. Widespread occurrence of diverse pathogenic types of the fungus Fusarium in bathroom plumbing drains J Clin Microbiol 49 2011 4264 4272 21976755\n27 Sautour M. Edel-Hermann V. Steinberg C. Sixt N. Laurent J. Dalle F. Fusarium species recovered from the water distribution system of a French university hospital Int J Hyg Environ Health 215 2012 286 292 22177529\n28 Arnoni M.V. Paula C.R. Auler M.E. Simões C.C.N. Nakano S. Szeszs M.W. Infections caused by Fusarium species in pediatric cancer patients and review of published literature Mycopathologia 183 2018 941 949 29564632\n29 Nucci M. Anaissie E.J. Queiroz-Telles F. Martins C.A. Trabasso P. Solza C. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection Cancer 98 2003 315 319 12872351\n30 Nucci M. Garnica M. Gloria A.B. Lehugeur D.S. Dias V.C.H. Palma L.C. Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acutemyeloid leukemia or myelodysplasia in Brazil Clin Microbiol Infect 19 2013 745 751 23009319\n31 Nucci M. Anaissie J. Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management Clin Infect Dis J 35 2002 909 920\n\n",
"fulltext_license": "CC BY-NC-ND",
"issn_linking": "2531-1379",
"issue": null,
"journal": "Hematology, transfusion and cell therapy",
"keywords": "Febrile neutropenia; Fusarium; Hematologic diseases; Invasive fungal infection; Pediatrics",
"medline_ta": "Hematol Transfus Cell Ther",
"mesh_terms": null,
"nlm_unique_id": "101725732",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "33288493",
"pubdate": "2020-11-09",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases.",
"title_normalized": "acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases"
}
|
[
{
"companynumb": "BR-GILEAD-2022-0574277",
"fulfillexpeditecriteria": "1",
"occurcountry": "BR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "50740",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Injection",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Fungal infection",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MICAFUNGIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Injection",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MICAFUNGIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MEROPENEM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Formulation unknown",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MEROPENEM"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "POLYMYXIN"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Formulation unknown",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "POLYMYXIN"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "Formulation unknown",
"drugdosagetext": "UNK UNK, UNKNOWN FREQ.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Product used for unknown indication",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID"
}
],
"patientagegroup": null,
"patientonsetage": "14",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Rodrigues L, Guimaraes A, de OI, de SP, de CR, Kakehasi F, de SR. Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases. Hematology, Transfusion and Cell Therapy. 2022;44:32-39",
"literaturereference_normalized": "acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases",
"qualification": "3",
"reportercountry": "BR"
},
"primarysourcecountry": "BR",
"receiptdate": "20220324",
"receivedate": "20220324",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 20632342,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220423"
},
{
"companynumb": "BR-LUPIN PHARMACEUTICALS INC.-2022-04395",
"fulfillexpeditecriteria": "2",
"occurcountry": "BR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": "207526",
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Acute sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "4",
"drugadministrationroute": null,
"drugauthorizationnumb": "207526",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Fusarium infection",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MEROPENEM"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Acute sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MEROPENEM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MEROPENEM"
},
"drugadditional": "4",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Fusarium infection",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MEROPENEM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Acute sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": "4",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Fusarium infection",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MICAFUNGIN"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "Unknown",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Acute sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MICAFUNGIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MICAFUNGIN"
},
"drugadditional": "4",
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Fusarium infection",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MICAFUNGIN"
}
],
"patientagegroup": null,
"patientonsetage": "14",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug ineffective for unapproved indication",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Rodrigues LCB, Guimaraes AF, De Oliveira IS, De Sousa PHM, De Castro Romanelli RM, Kakehasi FM, et al. Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases. Hematology, Transfusion and Cell Therapy. 2022;44(1):32-39",
"literaturereference_normalized": "acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases",
"qualification": "3",
"reportercountry": "BR"
},
"primarysourcecountry": "BR",
"receiptdate": "20220331",
"receivedate": "20220331",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20656732,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": 2,
"seriousnessother": 2,
"transmissiondate": "20220424"
},
{
"companynumb": "BR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022R1-331343",
"fulfillexpeditecriteria": "1",
"occurcountry": "BR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": "212514",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MEROPENEM"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MEROPENEM"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "LINEZOLID"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LINEZOLID"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "MICAFUNGIN"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MICAFUNGIN"
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "POLYMYXIN"
},
"drugadditional": "4",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "POLYMYXIN"
}
],
"patientagegroup": null,
"patientonsetage": "14",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug ineffective",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Organ failure",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Septic shock",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Rodrigues LCB, Guimaraes AF, de Oliveira IS, de Sousa PHM, de Castro Romanelli RM, Kakehasi FM, et al. Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases. Hematol Transfus Cell Ther. 2022;44(1):32-39",
"literaturereference_normalized": "acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases",
"qualification": "3",
"reportercountry": "BR"
},
"primarysourcecountry": "BR",
"receiptdate": "20220405",
"receivedate": "20220405",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20673075,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 1,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220721"
},
{
"companynumb": "BR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022R1-331342",
"fulfillexpeditecriteria": "1",
"occurcountry": "BR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "AMPHOTERICIN B"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "212514",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Acute sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "AMPHOTERICIN B"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "MEROPENEM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Acute sinusitis",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": "14",
"drugtreatmentdurationunit": "804",
"medicinalproduct": "MEROPENEM"
}
],
"patientagegroup": null,
"patientonsetage": "12",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Disease recurrence",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Rodrigues LCB, Guimaraes AF, de Oliveira IS, de Sousa PHM, de Castro Romanelli RM, Kakehasi FM, et al. Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases. Hematol Transfus Cell Ther. 2022;44(1):32-39",
"literaturereference_normalized": "acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases",
"qualification": "3",
"reportercountry": "BR"
},
"primarysourcecountry": "BR",
"receiptdate": "20220405",
"receivedate": "20220405",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 20673073,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": 2,
"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220721"
}
] |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.