Non-fatal and fatal liver failure associated with valproic acid.
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.
Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany. markus.schmid@uni-ulm.de
M M
MM
Schmid
R W
RW
Freudenmann
F
F
Keller
B J
BJ
Connemann
C
C
Hiemke
M
M
Gahr
W
W
Kratzer
M
M
Fuchs
C
C
Schönfeldt-Lecuona
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000401:mortality; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D001569:Benzodiazepines; D014635:Valproic Acid