CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-17338368 I. REACTION INFORMATION 1. PATIENT INITIALS 1a. COUNTRY 2. DATE OF BIRTH 2a. AGE 3. SEX 4-6 REACTION ONSET privacy DE [ MedDRA 20.0 LLT (10008641): Cholestatic liver disease ] [ MedDRA 20.0 LLT (10014481): Elevated liver enzymes ] Results of tests and procedures relevant to the investigation of the patient: 08.2017: HSV 1/2-IgM: negativ Coxsackie-IgA, - IgM, - IgG: negativ DA MO YR 75 DA MO YR (Year) Male 08 08 2017 8-1 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) PATIENT DIED þ INVOLVED OR PROLONGED INPATIENT HOSPITALISATION INVOLVED PERSISTENCE OR SIGNIFICANT DISABILITY OR INCAPACITY LIFE THREATENING CONGENITAL ANOMALY / BIRTH DEFECT OTHER MEDICALLY IMPORTANT CONDITION 14. SUSPECT DRUG(S) (include generic name) tilidin comp. 50/4 mg ret. II. SUSPECT DRUG(S) INFORMATION 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION "daily dose: 1 Df dosage form every Day" [ 16 Df dosage form { 1 Df dosage form, 1 in 1 Day } ] 17. INDICATION(S) FOR USE Post herpetic neuralgia 18. THERAPY DATES (from/to) 19. THERAPY DURATION from 24-JUL-2017 to 11-19 Day III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) ramipril daily dose: 5 Mg every Day ramipril daily dose: 5 Mg every Day (cont.) 20. 21. 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 (10041019): Sliding hiatal hernia ] Continuing: Unknown [ MedDRA 20.0 (10076492): Antral gastritis ] Continuing: Unknown [ MedDRA 20.0 (10076726): Subarachnoid hematoma ] from 2010 Continuing: No (cont.) IV. SENDER INFORMATION 24a. ME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 11-SEP-2017 DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-17338368 24d. REPORT SOURCE þ STUDY 25a. REPORT TYPE LITERATURE HEALTH PROFESSIOL þ INITIAL FOLLOW UP FIL (Cont.) = Continuation on attached sheet(s)
Report Page: 2 of 14 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*** [MedDRA 20.0 PT (10008635): Cholestasis ] recovering/resolving 08- [ MedDRA 20.0 LLT (10008641): Cholestatic liver disease ] [MedDRA 20.0 PT (10060795): Hepatic enzyme increased ] recovering/resolving 08- [ MedDRA 20.0 LLT (10014481): Elevated liver enzymes ] * 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 16- SGOT 36 U/l <50 Normal high range More inform. available 12- SGOT 72 U/l <50 17-JUL-2017 SGOT 22 U/l <50 17-JUL-2017 SGPT 27 U/l <50 11- SGPT 133 U/l <50 16- SGPT 68 U/l <50 16- GGT 844 U/l <60 11- GGT 1352 U/l <60 17-JUL-2017 GGT 35 U/l <60 16- Bilirubin 1.5 mg/dl <1.1 Hepatitis A IgM HBsAg HBsAg Hepatitis B antibody Hepatitis C antibody Epstein-Barr virus IgM antibody negative CMV IgM antibody Herpes simplex test vorhanden/present Coxsackie virus serology test 14. Suspect Drug(s) (including generic name) (... continuation...)
Report Page: 3 of 14 Suspect Drug Duration Dose * Route(s) of tilidin comp. 50/4 mg ret. 24-JUL- 2017 11-AUG- 2017 19 Day A: daily dose: 1 Df dosage form every Day 16Df dosage form C: 1Df dosage form Post herpetic neuralgia 16 Day Drug withdrawn Cumulative dose number (to first reaction) C: Structure dosages number naloxone hydrochloride tilidine hydrochloride Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10008641): Cholestatic liver disease ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10014481): Elevated liver enzymes ] AkdÄ Global Introspection (WHO GI) possible 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of metamizol 17-JUL- 2017 11-AUG- 2017 26 Day A: daily dose: 1500 Mg every 2 Day 16500Mg C: 500Mg D: 3 E: 2Day Post herpetic neuralgia
Report Page: 4 of 14 23 Day Drug withdrawn Cumulative dose number (to first reaction) C: Structure dosages number metamizole Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10008641): Cholestatic liver disease ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10014481): Elevated liver enzymes ] AkdÄ Global Introspection (WHO GI) possible 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of aciclovir 03-JUL- 2017 7 Day A: daily dose: 4000 Mg every Day 148000Mg C: 800Mg D: 5
Report Page: 5 of 14 37 Day Cumulative dose number (to first reaction) C: Structure dosages number aciclovir Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10008641): Cholestatic liver disease ] 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...) ramipril A: daily dose: 5 Mg every Day C: 5Mg
Report Page: 6 of 14 ramipril 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) pantoprazol A: daily dose: 40 Mg every Day C: 40Mg pantoprazole 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) pregabalin A: daily dose: 100 Mg every Day C: 50Mg D: 2
Report Page: 7 of 14 pregabalin 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) metamizol A: daily dose: 3 G gram(s) every Day C: 1G gram(s) D: 3
Report Page: 8 of 14 metamizole 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) ass A: daily dose: 100 Mg every Day C: 100Mg acetylsalicylic acid 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) zopiclon A: daily dose: 3.75 Mg every Day C: 3.75Mg
Report Page: 9 of 14 zopiclone 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) salbutamol A: daily dose: 0.36 Mg every 2 Day C: 0.12Mg D: 3 E: 2Day Respiratory (inhalation)
Report Page: 10 of 14 salbutamol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) vardenafil A: b. Bedarf C: 5.93Mg D: E: vardenafil 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) colecalciferol A: daily dose: 1 Iu international unit(s) every Week C: 1.000Iu international unit(s) E: 1Week
Report Page: 11 of 14 colecalciferol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) vitamin b12 A: daily dose: 1 Df dosage form every 3 Day C: 1Df dosage form E: 3Day
Report Page: 12 of 14 cyanocobalamin 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) folsaeure A: daily dose: 1 Df dosage form every 3 Day C: 1Df dosage form E: 3Day folic acid 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) vitamin b6 A: daily dose: 1 Df dosage form every 3 Day C: 1Df dosage form E: 3Day
Report Page: 13 of 14 pyridoxine hydrochloride 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Continuing Comments [ MedDRA 20.0 (10041019): Sliding hiatal hernia ] Unknown [ MedDRA 20.0 (10076492): Antral gastritis ] Unknown [ MedDRA 20.0 (10076726): Subarachnoid hematoma ] 2010 No Report duplicates Duplicate source Duplicate number DE-DCGMA-17174910 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 Yes
Report Page: 14 of 14 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? 20170911 Yes 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 29 Physician SENDER INFORMATION (... continuation...) Type Organisation Health professional 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) 63.8 Height (cm) 166 Last menstrual periode Text for relevant medical history and concurrent conditions