CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-17183827 I. REACTION INFORMATION 1. PATIENT INITIALS 1a. COUNTRY 2. DATE OF BIRTH 2a. AGE 3. SEX 4-6 REACTION ONSET privacy (10012671): Diabetic ketoacidosis ] hyperglykämische Entgleisung (10020635): Hyperglycaemia ] (10028813): Nausea ] rez. Fieber (10016558): Fever ] (10047700): Vomiting ] (10048709): Urosepsis ] Results of tests and procedures relevant to the investigation of the patient: Glukose-Werte im Tagesverlauf zwischen 300 und 140 -> schwer einstellbar Reporter's comments: DA MO YR 38 DA MO YR (Year) Female 04 05 2017 Maßnahmen: Metformin abgesetzt, Überwachung zur Azidose- und Hyperglykämiebehandlung. Infektbehandlung mit Cefuroxim, Ciprofloxacin und später Piperazillin und Tazobactam. 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) synjardy 850 mg/5 mg 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION 17. INDICATION(S) FOR USE Type 2 diabetes mellitus DE 18. THERAPY DATES (from/to) 19. THERAPY DURATION to APR-2017 1 Year III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) metformin from APR-2017 daily dose: 1700 Mg millgram(s) every Days (cont.) 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 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 (10067585): Type 2 diabetes mellitus ] Continuing: Unknown [ MedDRA 20.0 (10018210): Gestational diabetes mellitus ] Continuing: Unknown [ MedDRA 20.0 (10048880): Smoker ] Continuing: Unknown (cont.) IV. SENDER INFORMATION 24a. ME AND ADRESS OF SENDER 10623 Berlin, DE 24c. DATE RECEIVED BY MANUFACTURER 17- DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-17183827 24d. REPORT SOURCE STUDY 25a. REPORT TYPE LITERATURE HEALTH PROFESSIOL INITIAL FOLLOW UP FIL (Cont.) = Continuation on attached sheet(s)
Report Page: 2 of 6 7. + 13. Describe Reaction(s) (including relevant tests/lab data) (... continuation...) Sonstiges: Das Absetzen von Synjardy erfolgte 1 Monat zuvor wg. einer vergleichbaren Symptomatik. Wg. einem Infekt hat sich die Symptomatik wohl verschlechtert, eine eindeutige Zuordnung ist nicht möglich. Metformin wurde bis zur stat. Aufnahme weiter eingenommen. Sender's comment: Reporter's comments: Sonstiges: Ein Diabetes mellitus Typ 1 als Ursache der Ketoazidose ist unwahrscheinlich (Negative Antikörperbefund, C-Peptid unauffällig). Telefonische Rücksprache mit Meldendem: Keine andere Ursache für Ketoazidose gefunden, daher trotz ungewöhnlichem Zeitverlauf Synjardy als ursächlich angeschuldigt. Reaction text as reported MedDRA coding Duration Outcome* Term highlighted Time interval 1** Time interval 2*** Start End [MedDRA 20.0 PT (10012671): Diabetic ketoacidosis ] (10012671): Diabetic ketoacidosis ] hyperglykämische Entgleisung [MedDRA 20.0 PT (10020635): Hyperglycaemia ] (10020635): Hyperglycaemia ] [MedDRA 20.0 PT (10028813): Nausea ] (10028813): Nausea ] rez. Fieber [MedDRA 20.0 PT (10037660): Pyrexia ] (10016558): Fever ] [MedDRA 20.0 PT (10047700): Vomiting ] (10047700): Vomiting ] [MedDRA 20.0 PT (10048709): Urosepsis ] (10048709): Urosepsis ] * Outcome of reaction/event at the time of last observation ** Time interval between beginning of suspect drug administration and start of reaction/event *** Time interval between last dose and start of reaction/event Results of tests Date Test Result Unit Normal low range Normal high range More inform. available Glucose 477
Report Page: 3 of 6 05- Glucose 348 06- Glucose 250 07- Glucose 270 > 80 05-40 07-40 08-15 10-15 11- negativ/negative HbA1C 12.4 % Creatinine 1.0 mg/dl Creatinine bei Entlassung: 0.66 mg/dl Blood potassium 3.3 mmol/l Haemoglobin initial: 12.2 Haemoglobin bei Entlassung: 8.6 Glucose urine Glukosurie 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug and batch no. Start End Duration Dose * Route(s) of Administration Indication(s) synjardy 850 mg/5 mg APR- 2017 1 Year A: B: C: D: E: Type 2 diabetes mellitus Identification of the country where the drug was obtained Name of holder/applicant Authorization/Application Number Country of authorization/application Pharmaceutical form (Dosage form) Parent route of administration (in case of a parent child/fetus report) Gestation period at time of exposure Time interval between beginning of drug administration and start of reaction/event Time interval between last dose of drug and start of reaction/event Action(s) taken with drug 34 Day Drug withdrawn * A: Dosage Text Additional information on drug Did reaction reappear after reintroduction?
Report Page: 4 of 6 B: Cumulative dose number (to first reaction) C: Structure dosages number D: Number of separate dosages E: Number of units in the interval Active drug substance name empagliflozin metformin Causality assessment Reaction Source Method Result [ MedDRA 20.0 (10012671): Diabetic ketoacidosis ] [ MedDRA 20.0 (10020635): Hyperglycaemia ] [ MedDRA 20.0 (10028813): Nausea ] [ MedDRA 20.0 (10016558): Fever ] [ MedDRA 20.0 (10047700): Vomiting ] [ MedDRA 20.0 (10048709): Urosepsis ] 22. Concomitant Drug(s) and Dates of Administration (exclude those used to treat reaction) (... continuation...) Concomitant Drug and batch no. Start End Duration Dose * Route(s) of Administration Indication(s) metformin APR- 2017 A: daily dose: 1700 Mg millgram(s) every Days B: C: 850Mg milligram(s) D: 2 E: 1Day Type 2 diabetes mellitus Identification of the country where the drug was obtained Name of holder/applicant Authorization/Application Number Country of authorization/application Pharmaceutical form (Dosage form) Parent route of administration (in case of a parent child/fetus report) Gestation period at time of exposure Time interval between beginning of drug administration and start of reaction/event 34 Day Time interval between last dose of drug and start of reaction/event Action(s) taken with drug Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text B: Cululative dose number (to first reaction)
Report Page: 5 of 6 C: Structure of separate dosages D: Number of separate dosages E: Number of units in the interval Active drug substance name metformin 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Start End Continuing Comments [ MedDRA 20.0 (10067585): Type 2 diabetes mellitus ] Unknown Diabetes mellitus Typ 2 bei Z.n. Schwangerschaftsdiabetes während 3 von 3 Schwangerschaften [ MedDRA 20.0 (10018210): Gestational diabetes mellitus ] Unknown [ MedDRA 20.0 (10048880): Smoker ] Unknown 2-3 Zig/die Report duplicates Duplicate source Duplicate number DE-DCGMA-17173720 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 Identification of the country where the reaction/event occur Serious Date Format of receipt of the most recent information for this report Additional documents Yes 20170517 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 64 Physician
Report Page: 6 of 6 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 Adult >18.Lj. bis einschl. 65.Lj. Weight (kg) 67 Height (cm) 160 Last menstrual periode Text for relevant medical history and concurrent conditions kein Alkohol, keine Allergien bekannt