Zonisamide: veterinary dose and monograph

At a glance

Drug class

Veterinary drug

Also known as

Zonegran, Zonisep, Zalep

Species with doses

Dogs and Cats

General dose range

5–10 mg/kg PO q12h — check the species tables for the indication

Routes

PO

Last reviewed

1 October 2026

Indications

• Canine idiopathic epilepsy — add-on for refractory seizures or monotherapy
• Feline epilepsy (less common; dose conservatively)
• Seizure management when phenobarbital/bromide are unsuitable or insufficient

Zonisamide dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

Dogs

• Epilepsy (monotherapy or add-on): Papich 5e and Plumb’s p.1185: monotherapy start 5 mg/kg PO q12h (3–5 mg/kg — Mariani); with phenobarbital 10 mg/kg q12h (enzyme induction). Consider reducing phenobarbital 25% when starting (Podell). Sulfonamide — watch for KCS, hepatotoxicity and renal tubular acidosis.

Cats

• Epilepsy: Papich 5e: 5 mg/kg PO q12h or 10 mg/kg q24h, adjusted by monitoring. Plumb’s p.1185: 5 mg/kg q12–24h (Munana); 5–10 mg/kg once daily (Bailey & Dewey); 10–20 mg/kg once daily (Martin-Jimenez). Anorexia is a common problem.

Contraindications

Sulfonamide hypersensitivity (it is a sulphonamide derivative — keratoconjunctivitis sicca, blood dyscrasias and hepatopathy reported with sulfonamides). Significant hepatic impairment (canine hepatic metabolism). Pregnancy (teratogenic in lab animals). Known hypersensitivity.

Species-specific warnings

Cats: Use conservative once-daily dosing in cats and watch for inappetence and sedation; data are more limited than in dogs.

Adverse effects

• Sedation, ataxia (often transient)
• Inappetence, GI upset
• Rare idiosyncratic hepatotoxicity (dogs)
• Rare: KCS, blood dyscrasias, renal tubular acidosis (sulfonamide class)

Drug interactions

• Phenobarbital and other hepatic enzyme inducers: increase zonisamide clearance — higher doses needed (and changing phenobarbital alters zonisamide levels)
• Other CNS depressants: additive sedation
• Other sulfonamides: shared idiosyncratic risks
• Carbonic-anhydrase inhibitors: additive (acid-base/urolith) effects

Pregnancy and lactation

Teratogenic in laboratory animals — avoid in pregnancy unless seizure control is essential (uncontrolled epilepsy is itself dangerous).

Monitoring

• Seizure frequency/severity (efficacy)
• Serum zonisamide levels where available (especially when combined with phenobarbital)
• Liver enzymes (idiosyncratic hepatotoxicity) and CBC periodically
• Sedation/ataxia and appetite; never stop abruptly (taper)

Toxicity and overdose

Generally well tolerated; overdose causes sedation, ataxia and GI upset. The notable idiosyncratic risks (as a sulfonamide) are hepatotoxicity (dogs) and, rarely, blood dyscrasias, KCS and renal tubular acidosis. Hepatotoxicity, though uncommon, can be serious — monitor.

Management: No specific antidote. Supportive — fluids, manage sedation/ataxia; monitor liver values. Decontaminate large recent ingestions. For idiosyncratic hepatotoxicity: discontinue and provide hepatoprotection (SAMe, silybin). Effects resolve with clearance (long half-life means slow).

Clinical pearls

• A well-tolerated, twice-daily anticonvulsant — good as add-on for refractory epilepsy or as monotherapy/first-line in dogs
• If the patient is also on phenobarbital, expect to use higher zonisamide doses (enzyme induction) and re-check levels when phenobarbital changes
• Remember it is a SULFONAMIDE — watch for the (rare) sulfonamide idiosyncrasies: hepatopathy, KCS, blood dyscrasias
• Monitor liver values; taper rather than stop suddenly to avoid breakthrough seizures

Mechanism of action

A broad anticonvulsant that blocks voltage-gated sodium and T-type calcium channels (stabilising hyperexcitable neuronal membranes and limiting seizure spread), with additional modulation of GABAergic/glutamatergic transmission and weak carbonic-anhydrase inhibition. The net effect raises the seizure threshold and reduces seizure propagation.

Formulations and products

• 25 mg capsule
• 50 mg capsule
• 100 mg capsule
• Zonisep — 25 / 50 / 100 mg capsule, Capsule (human-label)
• Zonegran — 25 / 50 / 100 mg capsule, Capsule (human-label)

Storage

Capsules: 15–30 °C, dry, protect from light and moisture.

Before you use this dose

Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

Other hormones, emergency drugs, supplements and other drugs

• Vincristine
• Vitamin AD3E Injection
• Vitamin E / Selenium
• Yohimbine

Frequently asked questions