Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years
Version of Record online: 5 APR 2012
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 73, Issue 5, pages 821–825, May 2012
How to Cite
Michel, M. C., Radziszewski, P., Falconer, C., Marschall-Kehrel, D. and Blot, K. (2012), Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years. British Journal of Clinical Pharmacology, 73: 821–825. doi: 10.1111/j.1365-2125.2011.04138.x
- Issue online: 5 APR 2012
- Version of Record online: 5 APR 2012
- Accepted manuscript online: 2 NOV 2011 04:02AM EST
- Received; 27 June 2011; Accepted; 25 October 2011; Accepted Article Published Online; 2 October 2011
- overactive bladder syndrome
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.
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.