Incidence of hepatopathies in dogs administered zonisamide orally: A retrospective study of 384 cases

Background Acute hepatopathy secondary to administration of zonisamide has been reported in 2 dogs, but overall incidence of hepatopathy is unknown. Objective To characterize the incidence of hepatopathy in dogs administered zonisamide PO. Animals Three hundred eighty‐four dogs administered zonisamide PO. Methods Multicenter retrospective study. Medical records were searched for dogs prescribed zonisamide PO and which had follow‐up for at least 3 months (acute exposure) and >3 months (chronic exposure). Reported clinical signs, physical examination findings, and serum biochemical panels were reviewed for possible hepatotoxicosis. Serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activity and albumin concentration were documented for all available cases. Results Acute clinical hepatopathy was found in 2 of 384 treated dogs (0.52%, 95% confidence interval [CI], 0.06‐1.9) after 13‐16 days of zonisamide treatment. One additional dog had elevated serum ALT activity with no clinical signs. Of these 3 dogs, 2 recovered after administration of zonisamide was stopped, and 1 was euthanized because of liver failure. Of the 117 cases chronically administered zonisamide, 10 had an increase in ALP, 6 had an increase in ALT, and 1 had hypoalbuminemia. No clinical signs of liver disease were noted in dogs chronically treated with zonisamide (median, 20 months; range, 5‐94 months). Conclusions and Clinical Importance Acute, potentially life‐threatening hepatopathy associated with oral administration of zonisamide to dogs is estimated to occur in less than 1% of dogs and was observed in the first 3 weeks of treatment. Subclinical abnormalities in ALT and ALP activity were noted in <10% of dogs during chronic administration of zonisamide, with no clinical signs of liver disease noted.