Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison

Abstract

The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic-clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as 'improved', i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy.

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

“…Variable monotherapy efficacy for seizure reduction was evaluated in 8 studies for a total of 311 dogs 29, 30, 31, 32, 33, 34, 35. Twenty or more dogs were evaluated in each of 5 studies31, 32, 33, 34, 35 evaluating a total of 289 dogs treated from 5 to 32 months in 3 of the studies31, 32, 35 with undocumented duration in 2 studies29, 33 The cumulative success rate of >50% seizure reduction to improve seizure control was 82% (258/311 dogs), with a cumulative seizure‐free rate of 31% (93/311) and failure rate (no improvement) of 15% (48/311).…”

“…Forty percent of the dogs became seizure‐free during treatment with phenobarbital compared to only 25% with primidone. Furthermore, primidone was less well tolerated in dogs than phenobarbital 30. In a retrospective trial in 65 epileptic dogs, primidone and phenobarbital were reported to exert similar efficacy, but important details of study design were not reported 43.…”

“…The most efficacious and safe therapeutic range reported for dogs is 15–35 μg/mL,26, 30, 58 although efficacy can be seen at lower concentrations. Metabolic tolerance is present when progressive dose increases without concurrent parallel increase in serum drug concentration occurs, most likely because of other drugs that are p450 enzyme inducers or genetic variations.…”

“…Type III: Increased hepatic enzyme activity is more frequent and severe with primidone than with phenobarbital,30, 77, 88 which can be explained by assuming that both intact primidone and its active metabolite phenobarbital affect the liver. As a consequence, primidone is associated with a higher frequency of hepatotoxicity than phenobarbital hepatic necrosis, fibrosis and cirrhosis all have been associated with chronic use of primidone 76, 88, 89.…”

Seizures and epilepsy in cats

“…28 Although there are limited available efficacy data regarding PB in cats, the efficacy of PB in epileptic dogs is reported to be between 60%-80%. 29 The most common adverse effects of PB reported in dogs are sedation, weight gain, increased thirst, increased urination, and increased appetite, most of which resolve within a few weeks of starting treatment. 30 In the author's experience, cats are less likely to develop polyuria and polydipsia when receiving this medication.…”