CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-17012572 I. REACTION INFORMATION 1. PATIENT INITIALS 1a. COUNTRY 2. DATE OF BIRTH 2a. AGE 3. SEX 4-6 REACTION ONSET privacy DE DA MO YR 85 DA MO YR (Year) Female 27 11 2016 Exitus letalis bei Leberversagen unklarer Genese, a.e. medikamentös-toxisch [ MedDRA 20.0 LLT (10019663): Hepatic failure ] [ MedDRA 20.0 LLT (10014481): Elevated liver enzymes ] 8-1 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) (cont.) PATIENT DIED þ INVOLVED OR PROLONGED INPATIENT HOSPITALISATION Results of tests and procedures relevant to the investigation of the patient: Hepatitisserologie vom 05.12.2016: Anti-HAV IgM negativ, Anti-HBc negativ, HBs-Antigen negativ, Anti-HCV(EIA) negativ, Anti-HDV negativ, Hepatitis E Blot IgG positiv, Hepatitis E Blot IgM negativ. Vorwerte aus 2014/2015 zeigten normale Leber- und Nierenwerte, was sie These einer toxischen Genese zusätzlich stützt. Reporter's comments: Maßnahme: Ausschluss Cholestase, protektive Drainageeinlage in den DHC aufgrund massiver II. SUSPECT DRUG(S) INFORMATION 14. SUSPECT DRUG(S) (include generic name) cefuroxim 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION "daily dose: 1000 Mg millgram(s) every Days" [ 3000 Mg Oral milligram(s) { 500 Mg milligram(s), 2 in 1 Day } ] 17. INDICATION(S) FOR USE Infection respiratory 18. THERAPY DATES (from/to) 19. THERAPY DURATION from 25-NOV-2016 to 27-NOV-2016 3 Day III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) ceftriaxon from 01-DEC-2016 to 05-DEC-2016 ceftriaxon from 01-DEC-2016 to 05-DEC-2016 (cont.) 20. 21. INVOLVED PERSISTENCE OR SIGNIFICANT DISABILITY OR INCAPACITY LIFE THREATENING CONGENITAL ANOMALY / BIRTH DEFECT OTHER MEDICALLY IMPORTANT CONDITION DID REACTION ABATE AFTER STOPPING DRUG? YES NO NA DID REACTION REAPPEAR AFTER REINTRODUCTION? YES NO NA (cont.) 23. OTHER RELEVANT HISTORY (e.g. diagnostics, allergics, pregnancy with last month of period, etc.) [ MedDRA 20.0 (10007661): Cardioversion ] Continuing: No [ MedDRA 20.0 (10003658): Atrial fibrillation ] Continuing: Unknown [ MedDRA 20.0 (10008611): Cholecystectomy ] Continuing: No (cont.) IV. SENDER INFORMATION 24a. NAME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 30-MAR-2017 DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-17012572 24d. REPORT SOURCE þ STUDY 25a. REPORT TYPE LITERATURE HEALTH PROFESSIONAL þ INITIAL FOLLOW UP FINAL (Cont.) = Continuation on attached sheet(s)
Report Page: 2 of 12 7. + 13. Describe Reaction(s) (including relevant tests/lab data) (... continuation...) Hyperbilirubinämie, Ausschluss Autoimmunhepatopathie und sonstiger hepatischer Störungen. Reaction text as reported MedDRA coding Duration Outcome* Term highlighted Exitus letalis bei Leberversagen unklarer Genese, a.e. medikamentös-toxisch [MedDRA 20.0 PT (10019663): Hepatic failure ] [ MedDRA 20.0 LLT (10019663): Hepatic failure ] fatal Time interval 1** Time interval 2*** 3 Day 1 Day 27-NOV-2016 [MedDRA 20.0 PT (10060795): Hepatic enzyme increased ] [ MedDRA 20.0 LLT (10014481): Elevated liver enzymes ] fatal 3 Day 1 Day 27-NOV-2016 * Outcome of reaction/event at the time of last observation ** Time interval between beginning of suspect drug *** and start of reaction/event Results of tests Date Test Result Unit Normal low range Normal high range More inform. available 05-DEC-2016 Hepatitis viral test vorhanden/present NA 05-DEC-2016 SGOT 84 U/l 0 35 05-DEC-2016 SGPT 73 U/l 0 45 05-DEC-2016 Urea 117 mg/dl 10 22 05-DEC-2016 LDH 492 U/l 120 240 05-DEC-2016 Alkaline phosphatase 460 U/l 0 165 05-DEC-2016 GGT 291 U/l 0 55 05-DEC-2016 Bilirubin total 25.8 mg/dl 0.2 1.0 05-DEC-2016 C-reactive protein 1.9 mg/dl 0.0 0.8 05-DEC-2016 Ammonia 33.0 µmol/l 11.0 32.0 05-DEC-2016 INR 1.8 NA <1.3 06-DEC-2016 INR 3.8 NA <1.3 12-DEC-2016 Cystatin C 6.29 mg/l 0.57 0.96 12-DEC-2016 Urea 202 mg/dl 10 22 12-DEC-2016 Creatinine 3.4 mg/dl 0.6 1.3 09-DEC-2016 SGOT 61 U/l 0 35 09-DEC-2016 SGPT 92 U/l 0 45 09-DEC-2016 Cholinesterase 4393 U/l 5400 13200 12-DEC-2016 Alkaline phosphatase 482 U/l 0 165 12-DEC-2016 GGT 305 U/l 0 55
Report Page: 3 of 12 12-DEC-2016 Bilirubin total 17.4 mg/dl 0.2 1.0 08-DEC-2016 INR 1.2 NA <1.3 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of cefuroxim 25-NOV- 27-NOV- 3 Day A: daily dose: 1000 2016 2016 Mg millgram(s) every Days 3000Mg milligram(s) C: 500Mg milligram(s) 2 1Day Oral Infection respiratory 3 Day Cumulative dose number (to first reaction) C: Structure dosages number cefuroxime sodium Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10019663): Hepatic failure ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10014481): Elevated liver enzymes ] AkdÄ Global Introspection (WHO GI) possible 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) ceftriaxon 01-DEC- 2016 05-DEC- 2016 5 Day A: C: Cholangitis
Report Page: 4 of 12 Cululative dose number (to first reaction) ceftriaxone 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) metronidazol 01-DEC- 2016 05-DEC- 2016 5 Day A: C: Cholangitis
Report Page: 5 of 12 Cululative dose number (to first reaction) metronidazole 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) marcumar A: C: Cululative dose number (to first reaction) phenprocoumon 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) torem A: C: 20Mg milligram(s)
Report Page: 6 of 12 Cululative dose number (to first reaction) torasemide 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) ramipril A: C: 5Mg milligram(s) Cululative dose number (to first reaction)
Report Page: 7 of 12 ramipril 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) hct A: C: 25Mg milligram(s) Cululative dose number (to first reaction) hydrochlorothiazide 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) allopurinol A: C: 100Mg milligram(s)
Report Page: 8 of 12 Cululative dose number (to first reaction) allopurinol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) memantin A: C: 20Mg milligram(s) Cululative dose number (to first reaction) memantine 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...)
Report Page: 9 of 12 dekristol A: C: Cululative dose number (to first reaction) colecalciferol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) spiriva A: C:
Report Page: 10 of 12 Cululative dose number (to first reaction) tiotropium bromide 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) salbutamol A: C: Cululative dose number (to first reaction) salbutamol 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Continuing Comments [ MedDRA 20.0 (10007661): Cardioversion ] No Z.n. Kardioversion bei VHF [ MedDRA 20.0 (10003658): Atrial fibrillation ] Unknown
Report Page: 11 of 12 [ MedDRA 20.0 (10008611): Cholecystectomy ] No Z.n. Cholezystektomie [ MedDRA 20.0 (10012267): Dementia ] No [ MedDRA 20.0 (10020775): Hypertension arterial ] No [ MedDRA 20.0 (10024119): Left ventricular failure ] No [ MedDRA 20.0 (10003417): Arthrosis multiple ] No [ MedDRA 20.0 (10050867): Hip prosthesis user ] 2009 No Z.n. Hüft-TEP rechts Report duplicates Duplicate source Duplicate number DE-DCGMA-16172240 Parent Parent identification Date of birth Age LMP Weight(kg) Height(cm) Sex Text for relevant medical history and concurrent conditions 0 ADMINISTRATIVE AND IDENTIFICATION INFORMATION Safetyreportversion 1 where the reaction/event occur Serious Date Format of receipt of the most recent information for this report Additional documents List of documents held by sender Does this case fulfill the local criteria for an expedited report? Yes 20170330 Yes Laboratory findings, Medical report Yes Regulatory authority's case report number Other case identifiers in previous transmissions Was the case medically confirmed, if not initially from health professional? Yes Primary source(s) of information Reporter postcode Reporter country Qualification Literature reference(s) Study name Sponsor study number Study type in which the reaction(s)/event(s) were observed 76 Physician SENDER INFORMATION (... continuation...) Type Organisation Health professional
Report Page: 12 of 12 Department Street address City Berlin Postcode 10623 Country Fax +49 / (0)30 4004 / 56555 Telephone +49 / (0)30 4004 / 56500 E-mail address phv@akdae.de PATIENT INFORMATION (... continuation...) Investigation number Gestation period Patient age group Elderly >65.Lj. Weight (kg) Height (cm) Last menstrual periode Text for relevant medical history and concurrent conditions