SUSPECT ADVERSE REACTION REPORT



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CIOMS FORM SUSPECT ADVERSE REACTION REPORT DE-BFARM-16211860 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 50 DA MO YR (Year) Female 06 10 starke Magenschmerzen (10042112): Stomach pain ] Angstattacken (10002856): Anxiety attack ] Gelenkschmerzen Knie, Hüfte (10023222): Joint pain ] (10005750): Blood pressure increased ] Konzentrationstörung (10010249): Concentration impaired ] Schwindel und Gangunsicherheit (10013573): Dizziness ] (10013963): Dyspnea ] (10016062): Facial paralysis ] starke Müdigkeit (10016257): Fatigue extreme ] Taubheitsgefühle Gesichtshälfte (10029833): Numbness facial ] Taubheitsgefühl Arm (10049111): Numbness of extremities ] Muskelschwäche (10028350): Muscle weakness ] Übelkeit (10028813): Nausea ] (10033664): Panic attack ] Ohnmachtsgefühl (10066202): Near fainting ] (10014018): Ear noises ] (10044563): Trembling ] Sehstörungen (10047543): Visual disturbance ] 8-12 CHECK ALL APPROPRIATE TO ADVERSE REACTION 7. + 13. DESCRIBE REACTION(S) (including relevant tests/lab data) (cont.) PATIENT DIED þ þ INVOLVED OR PROLONGED INPATIENT HOSPITALISATION INVOLVED PERSISTENCE OR SIGNIFICANT DISABILITY OR INCAPACITY LIFE THREATENING CONGENITAL ANOMALY / BIRTH DEFECT OTHER MEDICALLY IMPORTANT CONDITION II. SUSPECT DRUG(S) INFORMATION 14. SUSPECT DRUG(S) (include generic name) (cont.) norfloxacin 15. DAILY DOSE(S) 16. ROUTE(S) OF ADMINISTRATION "400" Oral 17. INDICATION(S) FOR USE Cystitis 18. THERAPY DATES (from/to) 19. THERAPY DURATION from 10-JUL- III. CONCOMITANT DRUG(S) AND HISTORY 22. CONCOMITANT DRUG(S) AND DATES OF ADMINISTRATION (exclude those used to treat reaction) 20. 21. DID REACTION ABATE AFTER STOPPING DRUG? YES NO NA DID REACTION REAPPEAR AFTER REINTRODUCTION? YES NO NA 23. OTHER RELEVANT HISTORY (e.g. diagnostics, allergics, pregnancy with last month of period, etc.) [ MedDRA 19.0 (10033664): Panic attack ] Continuing: [ MedDRA 19.0 (10007598): Cardiac pacemaker insertion ] from 01-JUL-2014 Continuing: [ MedDRA 19.0 (10000599): Acromegaly ] from 2008 Continuing: (cont.) 24a. NAME AND ADRESS OF SENDER 53175 Bonn, DE IV. SENDER INFORMATION 24c. DATE RECEIVED BY MANUFACTURER DATE OF THIS REPORT 24b. MFR CONTROL NO. DE-BFARM-16211860 24d. REPORT SOURCE 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...) Case narrative including clinical course, therapeutic measures, outcome and additional relevant information: Bericht des Meldenden: Angststörung mit akuten Panikattacken traten erstmals im Jahr auf. Starke Müdigkeit und abnehmende Belastbarkeit wurden zunächst mit der Blaseninfektion in Verbindung gebracht, besserten sich aber nach Abklingen der Infektion nicht. Nach Psychotherapie, Reha in den Jahren 2013 bis 2015 trat zunächst Besserung auf. Im Jahr 2014 trat eine plötzliche Verschlimmerung der Angstattacken mit Zittern und Atemnot auf. Am 01.07.2014 erfolgte eine Implantation eines Herzschrittmachers wegen AV Block. Am 14.7 2014 erfolgte wiederum eine stationäre Aufnahme ins Krankenhaus wegen Schwindel Luftnot und Angstattacken. Anfang 2015 konnte die Psychtherapie erfolgreich beendet werden. Panikattacken mit Depressionen und starken körperlichen Beschwerden traten nicht mehr auf. Erstmalig traten am 19.06.2016 starke Todesängste mit Zittern kalten Extremitäten, hohem Blutdruck, Lähmung der linken Gesichtshälfte und starken Taubheitsgefühl im linken Arm und in den Beinen auf. Starkes Schwanken beim Gehen und Stehen auf. Dies erfolgte am 3. Tag der Therapie mit Ciprofloxaxin, das aufgrund einer Blasenspiegelung am 17.06.2016 durch einen Urologen verordnet wurde. Reaction text as reported MedDRA coding Outcome* Term highlighted Time interval 1** Time interval 2*** Start End Angstattacken [MedDRA 19.0 PT (10002855): Anxiety ] 4 Year 06-OCT- (10002856): Anxiety attack ] Muskelschwäche [MedDRA 19.0 PT (10028372): Muscular weakness ] 2 Year 2014 (10028350): Muscle weakness ] Sehstörungen [MedDRA 19.0 PT (10047571): Visual impairment ] MAR-2015 (10047543): Visual disturbance ] Taubheitsgefühle Gesichtshälfte [MedDRA 19.0 PT (10020937): Hypoaesthesia ] (10029833): Numbness facial ] Gelenkschmerzen Knie, Hüfte [MedDRA 19.0 PT (10003239): Arthralgia ] 4 Year recovered/resolved with sequel (10023222): Joint pain ] Schwindel und Gangunsicherheit [MedDRA 19.0 PT (10013573): Dizziness ] 2 Year JUN-2014 (10013573): Dizziness ] Konzentrationstörung [MedDRA 19.0 PT (10013496): Disturbance in attention ] 2 Year JUN-2014 (10010249): Concentration impaired ]

Report Page: 3 of 7 Übelkeit [MedDRA 19.0 PT (10028813): Nausea ] (10028813): Nausea ] Ohnmachtsgefühl [MedDRA 19.0 PT (10036653): Presyncope ] (10066202): Near fainting ] [MedDRA 19.0 PT (10043882): Tinnitus ] MAR-2015 (10014018): Ear noises ] Taubheitsgefühl Arm [MedDRA 19.0 PT (10020937): Hypoaesthesia ] (10049111): Numbness of extremities ] starke Müdigkeit [MedDRA 19.0 PT (10016256): Fatigue ] 2 Year JUN-2014 (10016257): Fatigue extreme ] starke Magenschmerzen [MedDRA 19.0 PT (10000087): Abdominal pain upper ] (10042112): Stomach pain ] [MedDRA 19.0 PT (10016062): Facial paralysis ] (10016062): Facial paralysis ] [MedDRA 19.0 PT (10013968): Dyspnoea ] (10013963): Dyspnea ] [MedDRA 19.0 PT (10005750): Blood pressure increased ] (10005750): Blood pressure increased ] [MedDRA 19.0 PT (10033664): Panic attack ] (10033664): Panic attack ] [MedDRA 19.0 PT (10044565): Tremor ] (10044563): Trembling ]

Report Page: 4 of 7 * 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 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug and batch no. Start End Dose * Route(s) of Administration Indication(s) norfloxacin 10-JUL- A: 400 B: C: D: E: Oral Cystitis 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 Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text 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 norfloxacin 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug and batch no. Start End Dose * Route(s) of Administration Indication(s) 22-JUN- 2014 A: B: C: D: E: Oral Cystitis Identification of the country where the drug was obtained Name of holder/applicant Authorization/Application Number

Report Page: 5 of 7 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 Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text 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 14. Suspect Drug(s) (including generic name) (... continuation...) Suspect Drug and batch no. Start End Dose * Route(s) of Administration Indication(s) 17-JUN- 2016 A: B: C: D: E: Oral Chronic cystitis 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 Additional information on drug Did reaction reappear after reintroduction? * A: Dosage Text 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

Report Page: 6 of 7 23. Other relevant history (... continuation...) Reactions, Symptoms and Events Start End Continuing Comments [ MedDRA 19.0 (10033664): Panic attack ] [ MedDRA 19.0 (10007598): Cardiac pacemaker insertion ] 01-JUL- 2014 wegen AV Block [ MedDRA 19.0 (10000599): Acromegaly ] 2008 Zustand nach Operation und Bestrahlung [ MedDRA 19.0 (10011814): Cystoscopy ] [ MedDRA 19.0 (10012378): Depression ] Report duplicates Duplicate source Paul-Ehrlich-Institut Duplicate number DE-CADRBFARM-2016012913 Patient past drug therapy Name of drug as reported Indication MedDRA code Reactions MedDRA code Start End opipramol [ MedDRA 19.0 (10033664): Panic attack ] [ MedDRA 19.0 (0): unbekannt ] 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 Deutschland Yes 20160623 No List of documents held by sender Does this case fulfill the local criteria for an expedited report? Regulatory authority's case report number Other case identifiers in previous transmissions Was the case medically confirmed, if not initially from health professional? Yes DE-CADRBFARM-2016012913 Yes 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

Report Page: 7 of 7 45 Deutschland Consumer or other non health professional SENDER INFORMATION (... continuation...) Type Organisation Department Regulatory Authority Street address City Bonn Postcode 53175 Country Deutschland Fax Telephone E-mail address pharmakovigilanz@bfarm.de PATIENT INFORMATION (... continuation...) Investigation number Gestation period Patient age group Adult >18.Lj. bis einschl. 65.Lj. Weight (kg) 96 Height (cm) 174 Last menstrual periode Text for relevant medical history and concurrent conditions