CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-17182698 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 [ MedDRA 20.0 LLT (10012735): Diarrhoea ] [ MedDRA 20.0 LLT (10028813): Nausea ] [ MedDRA 20.0 LLT (10047700): Vomiting ] [ MedDRA 20.0 LLT (10000952): Acute on chronic renal failure ] 67 DA MO YR (Year) Male 01 05 2017 8-12 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) PATIENT DIED þ INVOLVED OR PROLONGED INPATIENT HOSPITALISATION Reporter's comments: Maßnahme und Verlauf: Infusionstherapie, Azidosetherapie. Am Morgen des 2.5..2017 plötzlicher Herztod mit frustraner Reanimation. INVOLVED PERSISTENCE OR SIGNIFICANT DISABILITY OR INCAPACITY LIFE THREATENING CONGENITAL ANOMALY / BIRTH DEFECT OTHER MEDICALLY IMPORTANT CONDITION 14. SUSPECT DRUG(S) (include generic name) entresto 24 mg/26 mg II. SUSPECT DRUG(S) INFORMATION 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION "daily dose: 2 Df dosage form " [ 14 Df dosage form { 1 Df dosage form, 2 in 1 Day } ] 17. INDICATION(S) FOR USE Cardiac failure 18. THERAPY DATES (from/to) 19. THERAPY DURATION from 25-APR-2017 III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) metformin daily dose: 1700 isosorbid mononitrat daily dose: 40 (cont.) 20. 21. 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 (10048858): Ischaemic cardiomyopathy ] Continuing: No [ MedDRA 20.0 (10049694): Left ventricular dysfunction ] Continuing: No [ MedDRA 20.0 (10074572): Multiple vessel coronary artery disease ] Continuing: No (cont.) IV. SENDER INFORMATION 24a. NAME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 04-MAY-2017 DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-17182698 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 11 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 (10012735): Diarrhoea ] fatal 01-MAY-2017 [ MedDRA 20.0 LLT (10012735): Diarrhoea ] [MedDRA 20.0 PT (10028813): Nausea ] fatal 01-MAY-2017 [ MedDRA 20.0 LLT (10028813): Nausea ] [MedDRA 20.0 PT (10047700): Vomiting ] fatal 01-MAY-2017 [ MedDRA 20.0 LLT (10047700): Vomiting ] [MedDRA 20.0 PT (10069339): Acute kidney injury ] fatal 01-MAY-2017 [ MedDRA 20.0 LLT (10000952): Acute on chronic renal failure ] * 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 01-MAY-2017 Sodium 135 mmol/l 135 146 01-MAY-2017 Potassium 5.35 mmol/l 3.5 5.1 01-MAY-2017 Calcium 2.38 mmol/l 2.05 2.75 01-MAY-2017 Bilirubin total 45.9 µmol/l 0 17 01-MAY-2017 Urea 16.43 mmol/l 2.8 8 01-MAY-2017 Creatinine 291 µmol/l 20 100 01-MAY-2017 Cystatin C 3.13 mg/l 0.6 1.3 01-MAY-2017 SGOT 16.81 µkat/l 0 0.68 01-MAY-2017 SGPT 10.21 µkat/l 0 0.68 01-MAY-2017 GGT 3.27 µkat/l <=1.07 01-MAY-2017 Creatine kinase 10.98 µkat/l 0 3.2 01-MAY-2017 Creatine kinase MB 1.13 µkat/l <=0.42 01-MAY-2017 Myoglobin blood 1341 ng/ml 2 64 01-MAY-2017 Troponin I 7.12 ng/ml 0 0.04 01-MAY-2017 TSH 8.15 mu/l 0.34 5.6 01-MAY-2017 C-reactive protein 25.4 mg/l 0 10 01-MAY-2017 Leucocyte count 18.1 Gpt/l 4 10
Report Page: 3 of 11 01-MAY-2017 Haemoglobin 7.89 mmol/l 8.7 11.2 01-MAY-2017 Platelet count 318 Gpt/l 150 420 01-MAY-2017 Quick's test 24 % 70 120 01-MAY-2017 INR 2.90 NA 0.85 1.25 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of entresto 24 mg/26 mg 25-APR- 2017 Cumulative dose number (to first reaction) C: Structure dosages number sacubitril/valsartan Causality assessment 7 Day A: daily dose: 2 Df dosage form every Days 14Df dosage form C: 1Df dosage form D: 2 Cardiac failure Reaction Source Method Result [ MedDRA 20.0 (10000952): Acute on chronic renal failure ] AkdÄ Global Introspection (WHO GI) possible 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of spironolacton A: daily dose: 50 Cardiac failure
Report Page: 4 of 11 C: 50Mg D: 1 Cumulative dose number (to first reaction) C: Structure dosages number spironolactone 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of torem A: daily dose: 20 C: 10Mg D: 2 Cardiac failure
Report Page: 5 of 11 Cumulative dose number (to first reaction) C: Structure dosages number torasemide 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) metformin A: daily dose: 1700 C: 850Mg D: 2 Diabetes mellitus Cululative dose number (to first reaction) metformin 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) isosorbid mononitrat A: daily dose: 40 C: 40Mg
Report Page: 6 of 11 D: 1 Indication: AP-Beschwerden. Cululative dose number (to first reaction) isosorbide mononitrate 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) beta-acetyldigoxin A: daily dose: 0.2 C: 0.2Mg D: 1 Atrial fibrillation
Report Page: 7 of 11 Cululative dose number (to first reaction) beta-acetyldigoxin 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) inegy 10 mg/40 mg A: C: D: E: Hyperlipoproteinaemia Cululative dose number (to first reaction) simvastatin ezetimibe 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) allopurinol A: C: 300Mg D: E:
Report Page: 8 of 11 Cululative dose number (to first reaction) allopurinol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) eliquis A: daily dose: 10 C: 5Mg D: 2 Atrial fibrillation Cululative dose number (to first reaction)
Report Page: 9 of 11 apixaban 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) metoprolol A: daily dose: 190 C: 95Mg D: 2 Atrial fibrillation Cululative dose number (to first reaction) metoprolol 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Continuing Comments [ MedDRA 20.0 (10048858): Ischaemic cardiomyopathy ] No [ MedDRA 20.0 (10049694): Left ventricular dysfunction ] No LVEF von 20-25% [ MedDRA 20.0 (10074572): Multiple vessel coronary artery disease ] No 3-Gefäß-KHK [ MedDRA 20.0 (10009119): Chronic renal failure ] Unknown Report duplicates Duplicate source Duplicate number
Report Page: 10 of 11 DE-DCGMA-17173578 Patient death Date of death 02-MAY- 2017 Was autopsy done? Unknown Patient death cause MedDRA version for reported cause(s) of death [ MedDRA 20.0 (10049418): Sudden cardiac death ] 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 Yes 20170504 No List of documents held by sender Does this case fulfill the local criteria for an expedited 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? No 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 14 Physician SENDER INFORMATION (... continuation...) Type Organisation Health professional Department Street address
Report Page: 11 of 11 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) 98 Height (cm) 175 Last menstrual periode Text for relevant medical history and concurrent conditions