Zonisamide
Zonisamide is a benzisoxazole-derivative, sulfonamide-based **anticonvulsant** used primarily in veterinary medicine as an 'add-on' drug for refractory idiopathic epilepsy, or as a first-line monotherapy in dogs and cats. * **Clinical Pearl**: Because it undergoes less hepatic metabolism than phenobarbital, it is often preferred in patients where avoiding hepatotoxicity is a priority. * It has a favorable pharmacokinetic profile in small animals, with a half-life of approximately 15 hours in dogs (allowing twice-daily dosing) and 33 hours in cats (allowing once-daily dosing). * Unlike humans, zonisamide exhibits linear pharmacokinetics in dogs at standard doses.
Mechanism: The exact mechanism of action is multifactorial and not completely elucidated: * Blocks **voltage-gated sodium channels** and reduces transient inward currents โ stabilizes neuronal membranes and suppresses neuronal hypersynchronization. * Inhibits **T-type voltage-gated calcium channels**. * Acts as a weak **carbonic anhydrase inhibitor**. * *Note*: Unlike diazepam or phenobarbital, it does **not** appear to potentiate GABAergic activity.
Dosing by species
- Epilepsy (anecdotal) ยท 5 mg/kg PO every 12-24 hours ยท PO ยท q12-24h ยท Most commonly utilized anecdotal dose.
- Refractory to phenobarbital ยท 5-10 mg/kg PO once daily ยท PO ยท q24h ยท Long half-life makes once daily dosing likely appropriate.
- Epilepsy ยท 10-20 mg/kg PO once daily ยท PO ยท q24h
- Epilepsy ยท 5-10 mg/kg ยท PO ยท q24h ยท Long-term ยท Longer half-life in cats allows for once-daily dosing.
- Refractory epilepsy (with phenobarbital) ยท 5-10 mg/kg PO q12h ยท PO ยท q12h ยท The high end of the dose range is needed when used in combination with phenobarbital due to microsomal enzyme induction.
- Monotherapy ยท Initially at 5 mg/kg PO twice daily (q12h) ยท PO ยท q12h
- Add-on with phenobarbital ยท 10 mg/kg PO q12h ยท PO ยท q12h
- Initial monotherapy ยท 3-5 mg/kg PO q12h ยท PO ยท q12h
- Add-on agent ยท 10 mg/kg PO q12h ยท PO ยท q12h
- Epilepsy ยท 5-10 mg/kg PO q12h ยท PO ยท q12h ยท Gradual adaptation in dosing is recommended. Reduce phenobarbital doses by 25% at the time of starting zonisamide.
- Epilepsy (monotherapy or adjunctive) ยท 5-10 mg/kg ยท PO ยท q12h ยท Long-term ยท Start at 5 mg/kg q12h. If the dog is concurrently receiving phenobarbital, start at 10 mg/kg q12h due to induced metabolism.
Routes of administration
Contraindications
- Hypersensitivity to zonisamide
- Hypersensitivity to sulfonamide drugs
- Pregnancy (known teratogen in dogs)
- Hypersensitivity to sulfonamides
- Severe hepatic impairment
Adverse effects
- Sedation (usually transient)
- Ataxia
- Inappetence / Anorexia
- Vomiting
- Diarrhea
- Somnolence
- Keratoconjunctivitis sicca (KCS) - theoretical risk due to sulfonamide structure
- Polyarthropathy or blood dyscrasias - theoretical risk due to sulfonamide structure
- Sedation
- Anorexia
- Keratoconjunctivitis sicca (KCS)
- Hepatotoxicity (rare)
- Metabolic acidosis
Drug interactions
- Phenobarbital ยท Increases the clearance of zonisamide. Repeated phenobarbital dosing decreases the bioavailability, peak concentrations, half-life, and AUC of zonisamide. This effect can persist up to 10 weeks after phenobarbital discontinuation. Higher zonisamide doses are typically required. ยท moderate
- Ketoconazole ยท May inhibit the hepatic metabolism of zonisamide, potentially increasing serum concentrations. ยท minor
Monitoring
- Clinical efficacy (seizure frequency and severity)
- Serum zonisamide concentrations (suggested therapeutic range in dogs: 10-40 mcg/mL)
- Adverse effects (sedation, ataxia, GI upset)
- Schirmer tear test (monitor for KCS due to sulfonamide structure)
- Serum zonisamide concentrations (therapeutic target typically 10-40 ยตg/mL)
- Schirmer Tear Test (STT) periodically
- Liver enzymes and bilirubin
- Complete Blood Count (CBC)
Overdose
The LD50 of zonisamide in dogs is reportedly 1 gram/kg. In human overdoses, reported effects include **coma, bradycardia, hypotension, and respiratory depression**. **Treatment**: * GI evacuation if ingestion was recent. * Supportive and symptomatic therapy. * Because of the drug's long half-life, supportive care may be required for several days.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.