Is zonisamide effective as sole antiepileptic therapy in dogs and what dosing do I use?

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Zonisamide (ZNS) is effective as monotherapy for canine idiopathic epilepsy (IE), with 55–76% of dogs achieving ≥50% seizure frequency reduction and 55% achieving complete seizure freedom. The standard oral dose is 5–10 mg/kg PO q12h, targeting a trough serum concentration of 10–40 μg/mL.128 Efficacy data support ZNS as a first-line option. In dogs with newly diagnosed IE, 76% achieved ≥50% reduction in seizure frequency and 55% achieved seizure freedom on ZNS monotherapy; the mean effective dose in responders was 4.8 mg/kg q12h (range 2.7–8.6 mg/kg q12h), with mean trough plasma concentrations of 18.9 μg/mL (range 8.0–48.0 μg/mL).2 An earlier study reported 60% of dogs as favorable responders (≥50% reduction in monthly seizure frequency) at a mean dose of 7.92 mg/kg q12h.1 The published dose range is 2.7–15 mg/kg PO q12h across studies, with the MSD Veterinary Manual citing 5–10 mg/kg PO q12h as the standard clinical range.128 Steady state is achieved within approximately 1 week.8 The half-life in dogs is 18–28 hours, supporting twice-daily dosing.5 A critical pharmacokinetic interaction exists with phenobarbital (PB): dogs receiving concurrent PB require nearly twice the ZNS dose to achieve and maintain therapeutic serum concentrations, due to cytochrome P450 induction by PB.5 ZNS co-administration does not meaningfully alter levetiracetam extended-release pharmacokinetics.6 Adverse effects are generally mild and transient. In the largest monotherapy trial, 13% of dogs experienced reduced activity, decreased appetite, vomiting, hindlimb weakness, soft stools, or constipation, all of which were mild and temporary, with no relevant changes on laboratory testing.2 Idiosyncratic reactions — including neutropenia, erythema multiforme, and acute hepatopathy — are reported but uncommon; severe acute hepatopathy has been described in individual cases.3 Experimental dosing at 75 mg/kg/day (approximately 5× the recommended clinical dose) produced persistent increases in ser