Toxic hepatopathy and intrahepatic cholestasis associated with phenytoin administration in combination with other anticonvulsant drugs in three dogs
Bunch, S.E.; Conway, M.B.; Center, S.A.; Castleman, W.L.; Baldwin, B.H.; Hornbuckle, W.E.; Tennant, B.C.
Journal of the American Veterinary Medical Association 190(2): 194-198
1987
ISSN/ISBN: 0003-1488 PMID: 3818433 Document Number: 294931
Intrahepatic cholestasis was observed in 3 dogs with seizure disorders during treatment with high doses of phenytoin in combination with either phenobarbital or primidone. Clinical signs included depression, vomiting, and jaundice. Results of serum biochemical testing indicated hyperbilirubinaemia, hypoalbuminaemia, and high activities of alanine transaminase, alkaline phosphatase, and gamma -glutamyltransferase. All 3 dogs died and had histological lesions of intrahepatic cholestasis, believed to be the result of metabolic hepatocellular failure. The syndrome observed in dogs treated with phenytoin in combination with either primidone or phenobarbital appeared to represent an adverse hepatic reaction in dogs that is distinct clinically and morphologically from hepatic cirrhosis that has been previously associated with long-term primidone treatment.