# Zonisamide: veterinary dose and monograph

> Zonisamide is a veterinary drug. Sulfonamide-based anticonvulsant used in dogs (and cats) for idiopathic epilepsy — as add-on therapy for refractory seizures or increasingly as monotherapy/first-line because it is relatively well tolerated, dosed twice daily, and has a… Indications include 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. This monograph lists 2 reference doses for dogs and cats, each with route, frequency and source.

Source: https://vetmasterji.com/drugs/zonisamide · Last reviewed: 2026-10-01

## 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

*Zonisamide doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Epilepsy (monotherapy or add-on) | 5–10 mg/kg | PO | q12h | — |

- 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

*Zonisamide doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Epilepsy | 5–10 mg/kg | PO | q24h | — |

- 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

> **Caution:** 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

> **Caution:** 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.

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## Frequently asked questions

### What is the dose of Zonisamide for dogs?

Reference doses for Zonisamide in dogs: 5–10 mg/kg PO q12h (Epilepsy (monotherapy or add-on)). Confirm against the label and the patient before use.

### What is the dose of Zonisamide for cats?

Reference doses for Zonisamide in cats: 5–10 mg/kg PO q24h (Epilepsy). Confirm against the label and the patient before use.

### When should Zonisamide not be used?

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.

### What are the side effects of Zonisamide in animals?

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

## Sources

- Plumb's Veterinary Drug Handbook
- Merck Veterinary Manual, 11th edition
- Papich, Papich Handbook of Veterinary Drugs, 5th edition

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VetMasterJi is a clinical decision-support and education platform for veterinary professionals and students. It does not provide veterinary advice, diagnosis or treatment for specific animals. All drug doses, calculators and differentials are references that must be independently verified before clinical use; the attending registered veterinarian remains solely responsible for every clinical decision.