Clinical evaluation of combination drug therapy in dogs with epilepsy

Idiopathic epilepsy is diagnosed in dogs that experience chronic spontaneous seizure activity but do not show neurological abnormalities in the period between seizures. Imepitoin, an anti-epileptic drug used for canine idiopathic epilepsy treatment, has a high efficacy for the treatment of generalised seizures and an improved safety profile compared to phenobarbital. However, imepitoin currently has no specific add-on therapy label for combination treatment with other anti-epileptic drugs. This study aimed to determine the safety and efficacy of combination treatment of imepitoin with phenobarbital in dogs that showed drug resistance to previous treatment. In total 34 dogs were enrolled in the study: 16 in cohort A, 11 in cohort B and seven in cohort C. In cohort A, dogs not responding to phenobarbital (with or without add-on treatment of potassium bromide or levetiracetam) were treated add-on with imepitoin, starting at 10 mg/kg twice daily and increasing up to 30 mg/kg twice daily. In cohort B, the only difference to cohort A was that the starting dose of imepitoin was reduced to 5 mg/kg twice daily. In cohort C, animals not responding to imepitoin at more than 20 mg/kg twice daily were treated with phenobarbital starting at 0.5 mg/kg twice daily. The add-on treatment resulted in a reduction in monthly seizure frequency in all three cohorts. A reduction of more than 50 per cent of seizures was achieved in 36 to 42 per cent of all animals, without significant difference between the cohorts. The lower starting dose of 5 mg/kg twice daily imepitoin was better tolerated and increasing to an average of 15 mg/kg twice daily was sufficient in cohort A and B. In cohort C, a mean add-on dose of 1.5 mg/kg twice daily phenobarbital was sufficient to achieve a clinically meaningful effect. Neither imepitoin nor phenobarbital add-on treatment was capable of suppressing cluster seizure activity. The authors conclude that combination treatment of imepitoin and phenobarbital is well tolerated in dogs with drug-resistant epilepsy.