Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Flupirtine has been on the market for about 30 years in several European countries as an analgesic. This use has not resulted in regulatory action concerning hepatotoxicity. WHAT THIS STUDY ADDS • When used in a novel indication, hepatotoxicity was frequent with flupirtine, questioning the general assumption that the safety profile in one indication can be extrapolated to other indications. AIMS To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof‐of‐concept study. METHODS Double‐blind, double‐dummy, three‐armed comparison of flupirtine extended release (400 mg/day, titrated to 600 mg/day), tolterodine extended release (4 mg/day) and placebo for 12 weeks. RESULTS When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine‐exposed patients, the study was prematurely discontinued. Based on study‐end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥6 weeks. CONCLUSIONS Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.