CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-16307825 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 erneutes Vorhofflattern (10003662): Atrial flutter ] (10001484): Aggravation of existing disorder ] (10013718): Drug level decreased ] (10069336): Product substitution issue brand to generic ] 67 DA MO YR (Year) Male 30 06 2016 8-1 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) (cont.) PATIENT DIED INVOLVED OR PROLONGED INPATIENT HOSPITALISATION Results of tests and procedures relevant to the investigation of the patient: 30.06.2016: Amiodaron-Spiegel: 503 µg/l 8 Wochen später: Amiodaron-Spiegel 1650 µg/l Reporter's comments: UAW-Verlauf: initial schwer einstellbares Vorhofflattern. Einstellung auf Cordarex. Hierunter 3 Jahre stabil. Speigel immer im therap. Bereich um 1900 µg/l. Dann Umstellung der Medikamente von Marcumar auf Xarelto wegen Op. und Umstellung von Cordarex auf Amiodarion 200-1 A Pharma II. SUSPECT DRUG(S) INFORMATION 14. SUSPECT DRUG(S) (include generic name) amiodaron 200-1 a pharma 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION 200 Mg 17. INDICATION(S) FOR USE Atrial fibrillation 18. THERAPY DATES (from/to) 19. THERAPY DURATION from 2013 III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) beloc-zok 95 mg from 2013 inspra from 2013 (cont.) þ 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 19.0 (10028596): Myocardial infarction ] Continuing: No [ MedDRA 19.0 (10063919): Bypass surgery ] from FEB-2013 Continuing: Unknown [ MedDRA 19.0 (10059864): Cardiac ablation ] Continuing: No (cont.) IV. SENDER INFORMATION 24a. NAME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 25-AUG-2016 DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-16307825 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 7 7. + 13. Describe Reaction(s) (including relevant tests/lab data) (... continuation...) (aus Kostengründen). Erneutes Vorhofflattern. Überraschenderweise Amiodaron-Spiegel 503 µg/l. Umstellung bei gleicher Dosierung von Amiodaron wieder auf Cordarex 200 mg in Erhaltungsdosis. Sender's comment: Reporter's comments: Nach 8 Wochen dann wieder Spiegel 1650 µg/l. Sehr hohe Compliance des Pat., keine Lebensstiländerung etc. Reaction text as reported MedDRA coding Duration Outcome* Term highlighted Time interval 1** Time interval 2*** erneutes Vorhofflattern [MedDRA 19.0 PT (10003662): Atrial flutter ] (10003662): Atrial flutter ] [MedDRA 19.0 PT (10010264): Condition aggravated ] (10001484): Aggravation of existing disorder ] [MedDRA 19.0 PT (10013718): Drug level decreased ] (10013718): Drug level decreased ] [MedDRA 19.0 PT (10069326): Product substitution issue ] (10069336): Product substitution issue brand to generic ] * 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 Drug level 503 µg/l AUG-2016 Drug level 1650 µg/l 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of amiodaron 200-1 a pharma 2013 A: C: 200Mg Atrial fibrillation
Report Page: 3 of 7 1 A Pharma Drug withdrawn Cumulative dose number (to first reaction) C: Structure dosages number Number of separate dosages Number of units in the interval amiodarone hydrochloride Causality assessment Reaction Source Method Result [ MedDRA 19.0 (10069336): Product substitution issue brand to generic ] possible [ MedDRA 19.0 (10013718): Drug level decreased ] possible [ MedDRA 19.0 (10001484): Aggravation of existing disorder ] [ MedDRA 19.0 (10003662): Atrial flutter ] 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) beloc-zok 95 mg 2013 A: C: 0.5Mg Cardiac arrhythmia
Report Page: 4 of 7 Cululative dose number (to first reaction) Number of separate dosages Number of units in the interval metoprolol succinate 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) inspra 2013 A: C: 25Mg Cardiac failure Cululative dose number (to first reaction) Number of separate dosages Number of units in the interval
Report Page: 5 of 7 eplerenone 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) atorvastatin 2013 A: C: 20Mg Hypercholesterolaemi a Cululative dose number (to first reaction) Number of separate dosages Number of units in the interval atorvastatin 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) xarelto NOV- 2015 A: C: 20Mg
Report Page: 6 of 7 7 Month Cululative dose number (to first reaction) Number of separate dosages Number of units in the interval rivaroxaban 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Continuing Comments [ MedDRA 19.0 (10028596): Myocardial infarction ] No Z.n. Vorderwandinfarkt [ MedDRA 19.0 (10063919): Bypass surgery ] FEB- 2013 Unknown LIMA auf RIVA [ MedDRA 19.0 (10059864): Cardiac ablation ] No Z.n. Kryoablation [ MedDRA 19.0 (10003662): Atrial flutter ] Unknown [ MedDRA 19.0 (10075476): Left atrial appendage occlusion ] Unknown Vorhofohrokklusion (im TEE inkomplett) Report duplicates Duplicate source Duplicate number DE-DCGMA-16170769 Patient past drug therapy Name of drug as reported Indication MedDRA code Reactions MedDRA code cordarex [ MedDRA 19.0 (0): unbekannt ] [ MedDRA 19.0 (0): unbekannt ] 2013 marcumar [ MedDRA 19.0 (0): unbekannt ] [ MedDRA 19.0 (0): unbekannt ] NOV- 2015 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
Report Page: 7 of 7 where the reaction/event occur Serious Date Format of receipt of the most recent information for this report Additional documents Yes 20160825 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? 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 59 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) 84 Height (cm) 175 Last menstrual periode Text for relevant medical history and concurrent conditions