Flupirtine-induced liver injury--seven cases from the Berlin Case-control Surveillance Study and review of the German spontaneous adverse drug reaction reporting database.

Purpose: The hepatotoxic potential of the analgesic flupirtine has attracted increased attention over the past years. Recently, risk minimisation measures such as maximum treatment duration of 2 weeks have been requested by the European Medicines Agency (EMA). This study was conducted to further elucidate the clinical pattern of flupirtine-induced liver injury (FILI).

Methods: Seven FILI patients were ascertained in all Berlin hospitals in the Berlin Case-control Surveillance Study (FAKOS) between 2002 and 2011. Furthermore, we reviewed the severe cases of flupirtine-associated hepatotoxicity included in the adverse drug reaction database of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany from between 1991 and 2012.

Results: All seven FILI patients of FAKOS were hospitalised. Six of them were female, mean age was 58 [corrected] years, and the most common symptoms were fatigue and jaundice. Three patients developed acute liver failure (ALF). Discontinuation of flupirtine invariably led to clinical and laboratory improvement. Review of the BfArM cases (n = 248) showed female sex predominance and high prevalence of jaundice and ALF. Time to onset of symptoms was less than 2 weeks in 9 % of the patients with respective data.

Conclusions: Our results corroborate previous findings on FILI's clinical pattern and on its potentially severe course. Although the hepatotoxic risk might be higher after the first 2 weeks of treatment, earlier onset of severe FILI cannot be ruled out. Postauthorisation safety studies are needed to evaluate EMA's risk minimisation measures and to quantify flupirtine's risk according to its duration of use.