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.
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
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.
- 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.
- 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.
- Baulac M. Introduction to zonisamide. Epilepsy Res. 2006;68(Suppl 2):S3-S9.
- 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.
- 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.
- 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.
- Thomas WB. Idiopathic epilepsy in dogs and cats. Vet Clin North Am Small Anim Pract. 2010;40(1):161-179.
- Smith Bailey K, Dewey CW. The seizuring cat. Diagnostic work-up and therapy. J Feline Med Surg. 2009;11(5):385-394.
- 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.
- 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.
- 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.
- 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.
- Ackermann AL, Frank LA, McEntee MF, May ER. Erythema multiforme associated with zonisamide in a dog. Vet Dermatol. 2015;26(5):391-392, e89.
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