title: Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years.
abstract: OBJECTIVE
  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.
authors: Department of Pharmacology & Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands. martincmichel@yahoo.de
authors: Martin C
authors: MC
authors: Michel
authors: Piotr
authors: P
authors: Radziszewski
authors: Christian
authors: C
authors: Falconer
authors: Daniela
authors: D
authors: Marschall-Kehrel
authors: Koenraad
authors: K
authors: Blot
mesh_terms: D000368:Aged; D000631:Aminopyridines / Q000009:adverse effects*; D000700:Analgesics / Q000009:adverse effects*; D001559:Benzhydryl Compounds / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D003408:Cresols / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects; D010665:Phenylpropanolamine / Q000009:adverse effects; D013577:Syndrome; D000068737:Tolterodine Tartrate; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D000631:Aminopyridines; D000700:Analgesics; D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C034161:flupirtine