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

To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof-of-concept study. 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. 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. Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.