The pharmacovigilance-center FAKOS – Detection of drug induced agranulocytosis, immune thrombocytopenia, hepatitis, pancreatitis, LongQT-Syndrome and Torsade de pointes

Background and Aim: Adverse drug reactions (ADR) are an important cause of morbidity and mortality. The Berlin Pharmacovigilance Center PVZ-FAKOS uses an active surveillance approach to identify hospitalised patients with serious rare, however often drug-induced diseases. Aim of FAKOS is to assess potential drug risks for the following diseases: acute Agranulocytosis (AGR), Immune Thrombocytopenia (ITP), acute Hepatitis (HEP), acute Pancreatitis (PAN), and LongQT Syndrome/Torsade de pointes (LQT/TdP). Materials and Methods: FAKOS recruits patients (age ≥18) with AGR and ITP (2000–2009), HEP and PAN (2002–2009) and LQT/TdP (2008–2009) from all Berlin hospitals. Only patients with idiosyncratic or drug-induced disease of the different disease entities are included. Information on drugs and other exposures is ascertained in a standardized personal interview. For each patient, a drug causality assessment is conducted according to the WHO causality assessment criteria. Results: Whereas most patients with AGR and HEP (>90%) were categorized as possibly drug associated, for 65% of PAN and LQT/TdP and for 40% of ITP. The number of different drugs classified as at least probably causing one of the diseases were N=48 for AGR, N=57 for HEP, N=14 for PAN, N=19 for LQT/TdP and N=26 for ITP. Of those, suspected drugs assessed in >2 cases were for AGR: Metamizole N=10, Clozapine N=10, Methimazole N=6, Sulfasalazine N=5; for HEP: Phenprocoumon N=5, Flupirtine N=5, Simvastatine, Clarithromycine, Ciprofloxacine, Moxifloxacine, Diclofenac and Olanzapine each with N=3; for PAN: Azathioprine N=4, for ITP: Tirofibane N=8; for LQT/TdP: (Levo-)/Methadon N=5. Conclusion: A broad range of drugs has to be considered in patients with unknown etiology of AGR, ITP, HEP, PAN and LQT/TdP. The disease based, active surveillance approach of PVZ-FAKOS with standardized causality assessment potentially overcomes problems of underdetection and underreporting of ADR. Acknowledgement: PVZ-FAKOS is being funded by the Federal Institute for Drugs and Medical Devices, Germany.