Non-fatal and fatal liver failure associated with valproic acid.

Abstract

Little is known about hepatotoxicity associated with valproic acid (VPA), a widely used substance in neuropsychiatry.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.A total of 132 cases of serious VPA-associated liver failure were identified. 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 significant increase in the total number of reported cases and the subgroup of fatal cases was found.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.

• Authors: M M Schmid, R W Freudenmann, F Keller, B J Connemann, C Hiemke, M Gahr, W Kratzer, M Fuchs, C Schönfeldt-Lecuona
• Journal: Pharmacopsychiatry (Pharmacopsychiatry) Vol. 46 Issue 2 Pg. 63-8 (Mar 2013) ISSN: 1439-0795 [Electronic] Germany
• PMID: 22915484 (Publication Type: Journal Article)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Anticonvulsants
• Benzodiazepines
• Valproic Acid

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anticonvulsants (adverse effects)
• Benzodiazepines (adverse effects)
• Chemical and Drug Induced Liver Injury (epidemiology, mortality)
• Child
• Child, Preschool
• Drug Therapy, Combination (adverse effects, mortality)
• Female
• Germany (epidemiology)
• Humans
• Infant
• Male
• Middle Aged
• Pharmacovigilance
• Valproic Acid (adverse effects)