CIOMS FORM SUSPECT ADVERSE REACTION REPORT I. REACTION INFORMATION 1. PATIENT INITIALS 1a. COUNTRY 2. DATE OF BIRTH 2a. AGE 3. SEX 4-6 REACTION ONSET privacy DA MO YR (10028606): Myocarditis ] (10024283): Leucopenia ] (10016558): Fever ] (10047700): Vomiting ] (10012727): Diarrhea ] (10058267): Troponin increased ] (10058911): General physical condition abnormal ] 42 DA MO YR (Year) Male 11 04 2016 Case narrative including clinical course, therapeutic measures, outcome and additional relevant information: Genaue Beschreibung der UAW-Symptomatik: Leukopenie, Fieber, Erbrechen, Diarrhö, erhöhte Troponinwerte, Verschlechterung des Allgemeinzustandes Frühere Exposition: nein Reexposition: nein Die Behandlung mit Quetiapin ret. (150-0-250) wurde während der Myokarditis fortgeführt. II. SUSPECT DRUG(S) INFORMATION 8-1 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) (cont.) PATIENT DIED 14. SUSPECT DRUG(S) (include generic name) clozapin 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION 250 Mg,1 Day 17. INDICATION(S) FOR USE DE 18. THERAPY DATES (from/to) 19. THERAPY DURATION to 14-APR-2016 III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) geodon from 03-MAR-2016 to 14-APR-2016 quetiapin retard von 750mg abdosiert (cont.) þ 20. 21. INVOLVED OR PROLONGED INPATIENT HOSPITALISATION 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 20.1 (10033872): Paranoid schizophrenia ] Continuing: Unknown [ MedDRA 20.1 (10001584): Alcohol abuse ] to 2014 Continuing: Unknown [ MedDRA 20.1 (10062060): Hyperlipidaemia ] Continuing: Unknown (cont.) IV. SENDER INFORMATION 24a. NAME AND ADRESS OF SENDER AGATE, Arbeitsgemeinschaft Universitätsstr. 84 93053 Regensburg, DE 24c. DATE RECEIVED BY MANUFACTURER 13-NOV-2017 DATE OF THIS REPORT 24b. MFR CONTROL NO. 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 9 7. + 13. Describe Reaction(s) (including relevant tests/lab data) (... continuation...) Maßnahmen nach der UAW: Reduktion;Absetzen;Verlegung;Weiterbehandlung Clozapin abdosiert und danach abgesetzt. Ziprasidon und Biperiden ret. abgesetzt. Quetiapin abdosiert. EKG, Echokardiogramm, Labor (inklusive Troponin und CK) durchgeführt. Patient verlegt nach Innere Medizin/Kardiologie Verlauf: UAW im Abklingen Patient wurde verlegt, er wurde auf eine internistische kardiologische Abteilung aufgenommen. Eine koronare Herzerkrankung wurde ausgeschlossen. Dringender Verdacht auf Myokarditis mit linksführender kardialer Dekompensation. Patient beklagte unter Quetiapin, Promethazin und Ziprasidon das Fortbestehen wahnhafter Symptome (Stimmen hören, Verfolgungsideen) Daraufhin wurde nach Aufklärung eine Behandlung mit Clozapin unter regelmäßiger Blutbild-und EKG-Kontrolle begonnen. Das wahnhafte Erleben war unter Aufdosierung rückläufig. Die restliche neuroleptische Medikation wurde schrittweise reduziert. Unter einer Clozapindosis von 250 mg kam es zur Entwicklung eines gastrointestinalen Infektes mit Diarrhö und Erbrechen. Eine Leukozytenkontrolle ergab einen Abfall in den unteren Referenzbereich. Zudem zeigte sich ein starker CRP-Anstieg. Nachdem Troponin T im Blut anstieg, wurde der Patient bei v.a. medikamenteninduzierter Myokarditis unter Clozapintherapie ins Kiinikum XY verlegt. Dort wurde eine Myokarditis diagnostiziert und antibiotisch behandelt. In der Folge entwickelte der Patient zudem einen Pericarderguss, der ebenfalls u.a. medikamentös behandelt wird. Clozapin wurde abgesetzt. Mögliche Risikofaktoren: nein Alternativerklärungen: ja - weniger wahrscheinlich virale gastrointestinale Injektion mit kardialer Beteiligung Reaction text as reported MedDRA coding Duration Outcome* Term highlighted Time interval 1** Time interval 2*** [MedDRA 20.1 PT (10028606): Myocarditis ] (10028606): Myocarditis ] [MedDRA 20.1 PT (10024384): Leukopenia ] (10024283): Leucopenia ] [MedDRA 20.1 PT (10037660): Pyrexia ] (10016558): Fever ] [MedDRA 20.1 PT (10047700): Vomiting ] (10047700): Vomiting ] [MedDRA 20.1 PT (10012735): Diarrhoea ] (10012727): Diarrhea ] [MedDRA 20.1 PT (10058267): Troponin increased ] (10058267): Troponin increased ]
Report Page: 3 of 9 [MedDRA 20.1 PT (10058911): General physical condition abnormal ] (10058911): General physical condition abnormal ] * 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 12-APR-2016 C-reactive protein 14.37 mg/l 12-APR-2016 Leucocyte count 6630 /nl 13-APR-2016 C-reactive protein 20.91 mg/l 13-APR-2016 Leucocyte count 4690 /nl 13-APR-2016 Troponin T 0.018 µg/l 14-APR-2016 C-reactive protein 27.26 mg/l 14-APR-2016 Troponin T 0.289 µg/l 14-APR-2016 Leucocyte count 6280 /nl 14-APR-2016 QTc 466 ms 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug Duration Dose * Route(s) of clozapin 14-APR- 2016 A: C: 250Mg Drug withdrawn
Report Page: 4 of 9 Cumulative dose number (to first reaction) C: Structure dosages number Number of separate dosages clozapine Causality assessment Reaction Source Method Result [ MedDRA 20.1 (10028606): Myocarditis ] AGATE Global Introspection (WHO GI) probable/likely 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) geodon 03-MAR- 14-APR- 2016 2016 43 Day A: C: 20Mg Drug withdrawn Cululative dose number (to first reaction) Number of separate dosages ziprasidone hydrochloride 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) quetiapin retard A: von 750mg abdosiert
C: 350Mg Report Page: 5 of 9 Cululative dose number (to first reaction) Number of separate dosages quetiapine 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) biperiden 14-APR- 2016 A: C: 2Mg Drug withdrawn
Report Page: 6 of 9 Cululative dose number (to first reaction) Number of separate dosages biperiden 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) promethazin A: Bei Bedarf C: 25Mg E: Cululative dose number (to first reaction) Number of separate dosages promethazine 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) pantoprazol ABZ A: C: 20Mg
Report Page: 7 of 9 Cululative dose number (to first reaction) Number of separate dosages pantoprazole 22. (s) and Dates of (exclude those used to treat reaction) (... continuation...) bezafibrat A: C: 400Mg
Report Page: 8 of 9 Cululative dose number (to first reaction) Number of separate dosages bezafibrate 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Continuing Comments [ MedDRA 20.1 (10033872): Paranoid schizophrenia ] Unknown [ MedDRA 20.1 (10001584): Alcohol abuse ] 2014 Unknown [ MedDRA 20.1 (10062060): Hyperlipidaemia ] Unknown [ MedDRA 20.1 (10061111): Drug abuser ] 2008 Unknown Drogenkonsum (THC,Speed) Report duplicates Duplicate source AGATE, Arbeitsgemeinschaft Arzneimitteltherapie be Duplicate number AN-02-007 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 20171113 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 Yes 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 91 Physician SENDER INFORMATION (... continuation...) Type Health professional
Report Page: 9 of 9 Organisation Department AGATE, Arbeitsgemeinschaft Street address Universitätsstr. 84 City Regensburg Postcode 93053 Country Fax 0941 941 2 Telephone 0941 941 2 E-mail address PATIENT INFORMATION (... continuation...) Investigation number Gestation period Patient age group Adult >18.Lj. bis einschl. 65.Lj. Weight (kg) Height (cm) Last menstrual periode Text for relevant medical history and concurrent conditions