CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-17058924 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 79 DA MO YR (Year) Female 09 2016 idiopathische Leberzirrhose Child A, Ösophagusvarizen Grad II-III, Gastroösophageale Varizen Typ II, Portal-hypertensive Gastropathie; hepatische Enzephalopathie (11/2016) [ MedDRA 20.0 LLT (10019641): Hepatic cirrhosis ] 8-1 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) PATIENT DIED INVOLVED OR PROLONGED INPATIENT HOSPITALISATION Results of tests and procedures relevant to the investigation of the patient: Coeruloplasmin: im Normbereich Reporter's comments: Maßnahme: KH-Aufenthalt und TIPSS am 25.10.2016 II. SUSPECT DRUG(S) INFORMATION 14. SUSPECT DRUG(S) (include generic name) (cont.) hydroxycarbamid 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION "daily dose: 500 Mg millgram(s) every Days" [ 366000 Mg Oral milligram(s) { 500 Mg milligram(s), 1 in 1 Day } ] 17. INDICATION(S) FOR USE Polycythaemia 18. THERAPY DATES (from/to) 19. THERAPY DURATION from SEP-2014 to 2 Year III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) clopidogrel daily dose: 1 Df dosage form every Days 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 DID REACTION REAPPEAR AFTER REINTRODUCTION? YES NO (cont.) 23. OTHER RELEVANT HISTORY (e.g. diagnostics, allergics, pregnancy with last month of period, etc.) [ MedDRA 20.0 (10036057): Polycythaemia vera ] from DEC-2012 Continuing: Unknown [ MedDRA 20.0 (10020775): Hypertension arterial ] Continuing: Unknown [ MedDRA 20.0 (10044390): Transient ischaemic attack ] Continuing: No (cont.) IV. SENDER INFORMATION 24a. ME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 28-APR-2017 DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-17058924 24d. REPORT SOURCE STUDY 25a. REPORT TYPE LITERATURE HEALTH PROFESSIOL INITIAL FOLLOW UP FIL (Cont.) = Continuation on attached sheet(s)
Report Page: 2 of 7 7. + 13. Describe Reaction(s) (including relevant tests/lab data) (... continuation...) Reaction text as reported MedDRA coding Duration Outcome* Term highlighted Time interval 1** Time interval 2*** Start End idiopathische Leberzirrhose Child A, Ösophagusvarizen Grad II-III, Gastroösophageale Varizen Typ II, Portal-hypertensive Gastropathie; hepatische Enzephalopathie (11/2016) [MedDRA 20.0 PT (10019641): Hepatic cirrhosis ] [ MedDRA 20.0 LLT (10019641): Hepatic cirrhosis ] not recovered/not resolved * Outcome of reaction/event at the time of last observation ** Time interval between beginning of suspect drug administration and start of reaction/event *** Time interval between last dose and start of reaction/event Results of tests Date Test Result Unit Normal low range Normal high range More inform. available 08-DEC-2016 Ammonia 198 µg/dl 19-DEC-2016 Aspartate aminotransferase 36 19-DEC-2016 Alanine aminotransferase 24 19-DEC-2016 Gamma-glutamyltransferase 113 U/l <39 12-DEC-2016 Bilirubin total 4.20 mg/dl 0.1 1.2 19-DEC-2016 INR 1.6 19-DEC-2016 Biopsy liver 12- Venous Doppler Mesenterialvenen: Hepatitis viral test unauffällig Alpha-1 anti-trypsin normal/normal Copper normal/normal 07- Computerised tomogram abdomen 07-07- Red blood cell count 5.6 /pl 3.8 5.0 07- Thrombocyte count 445 /nl 150 361 07- Leucocyte count 11.5 /nl 3.7 10.1 07- Haemoglobin 14.4 g/dl 11.6 15.1 07- Haematocrit 0.46 l/l 0.34 0.44 07- INR 1.3 0.8 1.2 07- Aspartate aminotransferase 34 07- Alanine aminotransferase 22 07- Gamma-glutamyltransferase 198 U/l <42
Report Page: 3 of 7 08- Alkaline phosphatase 258 35 104 08- Bilirubin total 1.3 mg/dl <1.2 08- Cholinesterase 5.10 5.32 12.92 Aspartate aminotransferase 38 Alanine aminotransferase 26 Gamma-glutamyltransferase 197 U/l <39 Bilirubin total 1.2 mg/dl 0.1 1.2 Leucocyte count 11.7 10^3 Haemoglobin 13.8 g/dl Haematocrit 42.40 % Red blood cell count 5.27 10^6 Thrombocyte count 367 Tsd/µl 09-JUL-2015 Aspartate aminotransferase 41 U/l 09-JUL-2015 Alanine aminotransferase 36 U/l 09-JUL-2015 Gamma-glutamyltransferase 225 U/l 25-AUG-2014 29-AUG-2014 02-APR-2013 01-JUN-2013 Aspartate aminotransferase 27 01-JUN-2013 Alanine aminotransferase 28 01-JUN-2013 Gamma-glutamyltransferase 166 U/l <40 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug and batch no. Start End Duration Dose * Route(s) of Administration Indication(s) hydroxycarbamid SEP- 2014 SEP- 2016 2 Year A: daily dose: 500 Mg millgram(s) every Days B: 366000Mg milligram(s) C: 500Mg milligram(s) D: 1 E: 1Day Oral Polycythaemia Identification of the country where the drug was obtained Name of holder/applicant Authorization/Application Number Country of authorization/application Pharmaceutical form (Dosage form) Parent route of administration (in case of a parent child/fetus report)
Report Page: 4 of 7 Gestation period at time of exposure Time interval between beginning of drug administration and start of reaction/event 2 Year Time interval between last dose of drug and start of reaction/event Action(s) taken with drug Drug withdrawn Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text B: Cumulative dose number (to first reaction) C: Structure dosages number D: Number of separate dosages E: Number of units in the interval Active drug substance name hydroxycarbamide Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10019641): Hepatic cirrhosis ] AkdÄ Global Introspection (WHO GI) possible 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug and batch no. Start End Duration Dose * Route(s) of Administration Indication(s) atorvastatin A: daily dose: 20 Mg millgram(s) every Days B: C: 20Mg milligram(s) D: 1 E: 1Day Oral Apoplexy Identification of the country where the drug was obtained Name of holder/applicant Authorization/Application Number Country of authorization/application Pharmaceutical form (Dosage form) Parent route of administration (in case of a parent child/fetus report) Gestation period at time of exposure Time interval between beginning of drug administration and start of reaction/event Time interval between last dose of drug and start of reaction/event Action(s) taken with drug Drug withdrawn Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text B: Cumulative dose number (to first reaction) C: Structure dosages number
Report Page: 5 of 7 D: Number of separate dosages E: Number of units in the interval Active drug substance name atorvastatin Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10019641): Hepatic cirrhosis ] AkdÄ Global Introspection (WHO GI) possible 22. Concomitant Drug(s) and Dates of Administration (exclude those used to treat reaction) (... continuation...) Concomitant Drug and batch no. Start End Duration Dose * Route(s) of Administration Indication(s) clopidogrel A: daily dose: 1 Df dosage form every Days B: C: 1Df dosage form D: 1 E: 1Day Oral Apoplexy Identification of the country where the drug was obtained Name of holder/applicant Authorization/Application Number Country of authorization/application Pharmaceutical form (Dosage form) Parent route of administration (in case of a parent child/fetus report) Gestation period at time of exposure Time interval between beginning of drug administration and start of reaction/event Time interval between last dose of drug and start of reaction/event Action(s) taken with drug Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text B: Cululative dose number (to first reaction) C: Structure of separate dosages D: Number of separate dosages E: Number of units in the interval Active drug substance name clopidogrel 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Start End Continuing Comments [ MedDRA 20.0 (10036057): Polycythaemia vera ] DEC- 2012 Unknown [ MedDRA 20.0 (10020775): Hypertension arterial ] Unknown [ MedDRA 20.0 (10044390): Transient ischaemic attack ] No
Report Page: 6 of 7 [ MedDRA 20.0 (10048921): Alcohol use ] Unknown 1 Bier/Woche [ MedDRA 20.0 (10067083): Polyglobulia ] DEC- 2012 Unknown niedriges Serum-Erythropoietin, Thrombozytose, niedriges BSG, Nachw.: heterozy. V617F-JAK-2 Mutation Report duplicates Duplicate source Duplicate number DE-DCGMA-17172598 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 Identification of the country 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? 20170428 Medical report Regulatory authority's case report number Other case identifiers in previous transmissions Was the case medically confirmed, if not initially from health professional? 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 66 Physician SENDER INFORMATION (... continuation...) Type Organisation Health professional Department Street address
Report Page: 7 of 7 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 kein Alkoholkonsum