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Phenobarbital Induced Liver Disease

Written by: Dr William Thomas, DVM Dipl.ACVIM(Neurology)

Many dogs taking phenobarbital develop increases in certain liver enzymes, especially alkaline phosphatase (ALP) and aspartate transaminase (AST). These laboratory changes do not indicate or predict the development of significant liver disease and are not indications to stop therapy.(1) Rather these changes probably reflect enzyme induction by phenobarbital.

However, a small percentage of dogs on long-term phenobarbital therapy do develop serious liver disease.(2) The precise incidence of phenobarbital-induced liver disease is unknown, although in one study the rate of death due to liver disease in dogs taking phenobarbital was low (0.8%).(3) Liver toxicity may be more likely when taking multiple anti-seizure drugs with the potential for liver disease or when phenobarbital blood concentrations are greater than 35 mg/ml.(3)

Clinical signs of liver disease include decreased appetite, sedation, incoordination, icterus (yellow-tinged gums and eyes, and ascites (increased fluid within the abdomen). These signs are not specific for liver disease and can be seen with many other disorders. Laboratory evidence of liver disease includes elevations in bile acids, and an increase in serum phenobarbital concentrations despite no increase in dose.(3) Because phenobarbital therapy does not normally cause increases in bile acids, this laboratory test is more specific for liver disease, compared to liver enzymes.

Liver toxicity may be reversible if it is detected early and the phenobarbital is withdrawn. However, this adverse effect can be irreversible and ultimately fatal.((3) Some veterinarians recommend periodic screening with bile acid testing every 6-12 months in order to detect early liver disease, although the benefit of such testing has not been evaluated in controlled clinical trials. In dogs with substantial liver disease, replacement of the phenobarbital with bromide is often considered. Bromide is probably the anti-seizure drug of choice in dogs with liver disease.


1. Muller PB, et al. Effects of long-term phenobarbital treatment on the liver in dogs. Jour Vet Int Med 2000;14:165-171.

2. Dayrell-Hart B, et al. Hepatoxicity of phenobarbital in dogs: 18 cases (1985-1989). Jour Amer Vet Med Assoc 1991;199:1060-1066.

3. Gaskill C, et al. Pancreatitis in epileptic dogs receiving potassium bromide therapy. Proceedings du Congrès Mondial Vétérinaire 1999 (abstract).


WB Thomas DVM
University of Tennessee
Knoxville, TN


Page last update: 12/13/2011

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