Erin Y. Akin, DVM, DACVIM (Neurology), Bush Veterinary Neurology Service, Woodstock, Georgia

ArticleLast Updated March 20173 min readPeer Reviewed
featured image

The popularity and use of zonisamide in veterinary patients has rapidly increased in recent years.


Zonisamide is used as an anticonvulsant in dogs and cats.

  • Based on the author’s clinical experience, zonisamide may be effective when used as monotherapy or in conjunction with other anticonvulsants (eg, phenobarbital, potassium bromide, levetiracetam).

  • In some cases, zonisamide may reduce seizure frequency by up to 70% to 80%.1,2

  • Zonisamide is available in generic form, which makes it more affordable than when first introduced.


Zonisamide’s exact mechanism of action is not completely understood.

  • It is known to block sodium channels, suppress inward calcium currents, enhance neuronal inhibition, and weakly inhibit carbonic anhydrase.3

Zonisamide is metabolized by hepatic microsomal enzymes.

  • In dogs, the half-life is ≈15 hours, with steady state reached in 3 to 4 days.4,5

  • In cats, the half-life is ≈33 hours, with steady state expected in ≈1 week.6


In dogs, a starting dosage of 3-5 mg/kg PO q12h is recommended.4,7

  • Concurrent use of phenobarbital may speed up zonisamide clearance, necessitating monitoring and dose adjustments.5

  • When used in combination with phenobarbital, the recommended starting dose for zonisamide is 10 mg/kg PO q12h.

In cats, a starting dose of 5-10 mg/kg PO q24h is recommended, although further research is necessary.8

Rectal dosing of zonisamide for the control of status epilepticus is not recommended.9

  • An IV form is not commercially available.

The author recommends therapeutic monitoring on a case-by-case basis to track trends, but it may not be necessary in all cases.

  • Serum or plasma zonisamide levels should be monitored no earlier than 1 week after initiation of therapy or a dose change.4

  • A serum level of 10-40 µg/mL is targeted based on therapeutic concentrations established in human medicine. 

  • More research is needed to establish a therapeutic range for dogs and cats.


Zonisamide is considered to have a wide margin of safety.

  • In dogs, typically only mild side effects (eg, sedation, lethargy, ataxia, vomiting) are seen.1

  • 50% of cats receiving 20 mg/kg PO q24h for 9 weeks suffered adverse events, including anorexia, diarrhea, vomiting, somnolence, and ataxia.6

Published case reports have documented serious and potentially fatal adverse events, including drug-induced acute liver failure, renal tubular acidosis, and, most recently, erythema multiforme in individual dogs.10-13

Zonisamide may affect thyroid hormone synthesis and circulating levels of thyroid hormone.

  • It is important to establish baseline thyroid function before beginning zonisamide therapy.4

  • In patients receiving zonisamide therapy, the author recommends checking zonisamide levels, CBC, and serum chemistry profile 2 weeks and 3 months after beginning initial therapy and every 6 to 12 months thereafter, depending on patient’s seizure control and clinical status.