Non-Fatal and Fatal Liver Failure Associated with Valproic Acid.

Introduction: Little is known about hepatotoxicity associated with valproic acid (VPA), a widely used substance in neuropsychiatry. Methods: All reported cases to the German Federal Institute for Drugs and Medical Devices between 1993 and 2009 of VPA-induced serious hepatic side effects were evaluated. Results: A total of 132 cases of serious VPAassociated liver failure were identifi ed. Approximately one third (34.8 %) occurred under VPA monotherapy, while the majority was seen with VPA plus co-medication, most frequently antiepileptics (34.8 %) and benzodiazepines (16.7 %). A subgroup of 34 cases (25.8 %) had a fatal outcome, the largest number reported to date. Of these,32.4 % were under VPA monotherapy and 67.6 % under VPA plus concomitant medication. Within the study period a signifi cant increase in the total number of reported cases and the subgroup of fatal cases was found. Discussion: This first pharmacovigilance study of VPA-associated liver failure indicates a higher rate of non-fatal and fatal liver failure when VPA is given with co-medication as compared to monotherapy. However, co-medication per se does not increase the risk of fatalities. [ABSTRACT FROM AUTHOR]