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

CLINICAL APPLICATIONS

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.

MECHANISM OF ACTION & PHARMACOKINETICS

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

PROTOCOL

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.

ADVERSE EVENTS & CAUTIONS

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.
References and author information Show
References
  1. Dewey CW, Guiliano R, Boothe DM, et al. Zonisamide therapy for refractory idiopathic epilepsy in dogs. J Am Anim Hosp Assoc. 2004;40(4):285-291.
  2. von Klopmann T, Rambeck B, Tipold A. Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. J Small Anim Pract. 2007;48(3):134-138.
  3. Baulac M. Introduction to zonisamide. Epilepsy Res. 2006;68(Suppl 2):S3-S9. 
  4. Boothe DM, Perkins J. Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs. J Vet Pharmacol Ther. 2008;31(6):544-553.
  5. Orito K, Saito M, Fukunaga K, et al. Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs. J Vet Pharmacol Ther. 2008;31(3):259-264.
  6. Hasegawa D, Kobayashi M, Kuwabara T, Ohmura T, Fujita M, Orima H. Pharmacokinetics and toxicity of zonisamide in cats. J Feline Med Surg. 2008;10(4):418-421. 
  7. Thomas WB. Idiopathic epilepsy in dogs and cats. Vet Clin North Am Small Anim Pract. 2010;40(1):161-179.
  8. Smith Bailey K, Dewey CW. The seizuring cat. Diagnostic work-up and therapy. J Feline Med Surg. 2009;11(5):385-394.
  9. Brewer DM, Cerda-Gonzalez S, Dewey CW, Boothe D, Van Horne K. Pharmacokinetics of single-dose rectal zonisamide administration in normal dogs. J Vet Intern Med. 2015;29(2):603-606.
  10. Schwartz M, Muñana KR, Olby NJ. Possible drug-induced hepatopathy in a dog receiving zonisamide monotherapy for treatment of cryptogenic epilepsy. J Vet Med Sci. 2011;73(11):1505-1508.
  11. Miller ML, Center SA, Randolph JF, Lepherd ML, Cautela MA, Dewey CW. Apparent acute idiosyncratic hepatic necrosis associated with zonisamide administration in a dog. J Vet Intern Med. 2011;25(5):1156-1160.
  12. Cook AK, Allen AK, Espinosa D, Barr J. Renal tubular acidosis associated with zonisamide therapy in a dog. J Vet Intern Med. 2011;25(6):1454-1457.
  13. Ackermann AL, Frank LA, McEntee MF, May ER. Erythema multiforme associated with zonisamide in a dog. Vet Dermatol. 2015;26(5):391-392, e89.
Author

Erin Y. Akin

DVM, DACVIM (Neurology) Bush Veterinary Neurology Service, Woodstock, Georgia

Erin Y. Akin, DVM, DACVIM (Neurology), works at Bush Veterinary Neurology Service in Woodstock, Georgia. She earned her DVM from Auburn University and completed a rotating internship in small animal medicine and surgery in Florida and a neurology residency at Mississippi State University, where she remained as a clinical instructor for 1 year before entering private practice. Dr. Akin’s professional interests include intervertebral disk disease and Chiari-like malformations.

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