CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-17219108 I. REACTION INFORMATION 1. PATIENT INITIALS 1a. COUNTRY 2. DATE OF BIRTH 2a. AGE 3. SEX 4-6 REACTION ONSET privacy (10043913): Toe amputation ] Zehennekrosen (10050630): Digital necrosis ] (10075816): Hypercoagulability ] Fingernekrosen re. Hand (10050630): Digital necrosis ] (10003180): Arterial thrombosis limb ] Thrombose der A. brachialis, radialis, ulnaris (10003182): Arterial thrombosis of the arm ] Reporter's comments: DE DA MO YR 56 DA MO YR (Year) Male 12 2014 UAW: V. a. arterieller Thrombosen kleinerer und mittelgroßer Gefäße der oberen und unteren Extremitäten durch Hyperkoagulabilität unter Ciclosporin A-Therapie; seit 12.2014 Zehennekrosen re. u. Amputation bds.; seit 05.2017 Fingernekrosen re. Hand bei art. Thrombose der A. brachialis,- radialis und - ulnaris und interossea -> Thrombektomie am 17.03.2017; erneuter Frühverschluss der re. A. ulnaris u. - radialis; 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) sandimmun II. SUSPECT DRUG(S) INFORMATION 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION "daily dose: 150 " { 75 Mg, 2 in 1 Day } 17. INDICATION(S) FOR USE Renal transplant 18. THERAPY DATES (from/to) 19. THERAPY DURATION from 2014 III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) atorvastatin daily dose: 40 atorvastatin 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 (10038533): Renal transplant ] from 2004 Continuing: No [ MedDRA 20.0 (10061105): Dialysis ] from 1997 to 2004 [ MedDRA 20.0 (10029117): Nephritis ] to 2004 Continuing: No (cont.) IV. SENDER INFORMATION 24a. NAME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 07-JUN-2017 DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-17219108 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 (10020608): Hypercoagulation ] Unknown DEC-2014 (10075816): Hypercoagulability ] [MedDRA 20.0 PT (10043913): Toe amputation ] recovered/resolved with sequel DEC-2014 (10043913): Toe amputation ] Zehennekrosen [MedDRA 20.0 PT (10059385): Extremity necrosis ] recovered/resolved with sequel DEC-2014 (10050630): Digital necrosis ] Fingernekrosen re. Hand [MedDRA 20.0 PT (10059385): Extremity necrosis ] Unknown MAY-2017 (10050630): Digital necrosis ] [MedDRA 20.0 PT (10072564): Peripheral artery thrombosis ] Unknown DEC-2014 (10003180): Arterial thrombosis limb ] Thrombose der A. brachialis, radialis, ulnaris [MedDRA 20.0 PT (10072564): Peripheral artery thrombosis ] (10003182): Arterial thrombosis of the arm ] Unknown MAY-2017 * 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 Angiogram peripheral vorhanden/present NA DEC-2015 GFR 30 ml/min 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of sandimmun 2014 A: daily dose: 150 Renal transplant
Report Page: 3 of 11 C: 75Mg D: 2 11 Month Cumulative dose number (to first reaction) C: Structure dosages number ciclosporin Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10075816): Hypercoagulability ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10043913): Toe amputation ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10050630): Digital necrosis ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10003180): Arterial thrombosis limb ] AkdÄ Global Introspection (WHO GI) possible [ MedDRA 20.0 (10003182): Arterial thrombosis of the arm ] AkdÄ Global Introspection (WHO GI) possible 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) atorvastatin A: daily dose: 40 C: 40Mg
Report Page: 4 of 11 Cululative dose number (to first reaction) atorvastatin 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) amlodipin A: daily dose: 5 Mg millgram(s) every Days C: 5Mg
Report Page: 5 of 11 Cululative dose number (to first reaction) amlodipine 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) prednisolon 2004 A: daily dose: 5 Mg millgram(s) every Days C: 5Mg Renal transplant 10 Year Cululative dose number (to first reaction) prednisolone 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) carvedilol A: daily dose: 25 C: 12.5Mg D: 2
Report Page: 6 of 11 Cululative dose number (to first reaction) carvedilol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) torasemid A: daily dose: 10 C: 10Mg
Report Page: 7 of 11 Cululative dose number (to first reaction) torasemide 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) calciferol A: C: D: E: Cululative dose number (to first reaction) ergocalciferol 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) ass 100 A: daily dose: 100 C: 100Mg
Report Page: 8 of 11 Cululative dose number (to first reaction) acetylsalicylic acid 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) omeprazol A: daily dose: 20 C: 20Mg
Report Page: 9 of 11 Cululative dose number (to first reaction) omeprazole 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) berlinsulin normal A: C: D: E: Cululative dose number (to first reaction) insulin human 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Continuing Comments [ MedDRA 20.0 (10038533): Renal transplant ] 2004 No Z. n. Nierentransplantation bei IgA-Nephritis [ MedDRA 20.0 (10061105): Dialysis ] 1997 2004 [ MedDRA 20.0 (10029117): Nephritis ] 2004 No IgA-Nephritis [ MedDRA 20.0 (10033968): Parathyroidectomy ] No Z. n. totaler Parathyreoidektomie
Report Page: 10 of 11 [ MedDRA 20.0 (10020705): Hyperparathyroidism ] Unknown [ MedDRA 20.0 (10067585): Type 2 diabetes mellitus ] 2006 Unknown [ MedDRA 20.0 (10020772): Hypertension ] Unknown [ MedDRA 20.0 (10028596): Myocardial infarction ] 2014 No [ MedDRA 20.0 (10011099): Coronary disease ] Unknown [ MedDRA 20.0 (10075505): Quintuple coronary bypass ] JAN- 2014 No [ MedDRA 20.0 (10009122): Chronic renal impairment ] Unknown chronische Niereninsuffizienz Stadium 3 Report duplicates Duplicate source Duplicate number DE-DCGMA-17173934 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 20170607 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 44 Physician SENDER INFORMATION (... continuation...)
Report Page: 11 of 11 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 Adult >18.Lj. bis einschl. 65.Lj. Weight (kg) 81 Height (cm) 179 Last menstrual periode Text for relevant medical history and concurrent conditions