Zonisamide

From Dog

Zonisamide is a sulfonamide derivative that was introduced into the Japanese market in 1989 and received licensure in the US and Europe in 2000 and 2005, respectively.

This drug is an anticonvulsant drug primarily indicated for idiopathic epilepsy in dogs[1].

With blockage of voltage-sensitive sodium channels and T-type calcium channels, zonisamide possesses a unique mode of action among the currently available anticonvulsant drugs. There is evidence that ZNS also exhibits direct effects on synthesis, release and degradation of the neurotransmitters glutamate, gamma aminobutyric acid (GABA), dopamine, serotonin and acetylcholine, thereby promoting synaptic inhibition. Furthermore, ZNS has been ascribed neuroprotective effects[2].

Zonisamide has less efficacy than other drugs such as phenobarbital, diazepam or potassium bromide, but zonisamide monotherapy is effective in some dogs with idiopathic epilepsy[3] with few side-effects at the recommended dose, primariyl transient neurological signs (e.g., transient sedation, ataxia, vomiting) and elevated liver enzymes[4].

However, severe side effects have been reported in some dogs, such as acute renal tubular acidosis[5] and acute idiosyncratic hepatic necrosis have been reported[6]. Side-effects commonly reported at dose of 30 mg/kg or higher[7].

Recommended dose in dogs is 3 - 10 mg/kg orally twice daily[8][9], aimed at reaching a target blood level of 10 - 40 μg/mL.

Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide[10].

References

  1. Thomas WB (2010) Idiopathic epilepsy in dogs and cats. Vet Clin North Am Small Anim Pract 40(1):161-179
  2. Schwartz M et al (2011) Possible drug-induced hepatopathy in a dog receiving zonisamide monotherapy for treatment of cryptogenic epilepsy. J Vet Med Sci 73(11):1505-1508
  3. Chung JY et al (2012) Zonisamide monotherapy for idiopathic epilepsy in dogs. N Z Vet J 60(6):357-359
  4. von Klopmann T et al (2007) Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. J Small Anim Pract 48(3):134-138
  5. Cook AK et al (2011) Renal tubular acidosis associated with zonisamide therapy in a dog. J Vet Intern Med 25(6):1454-1457
  6. Miller ML et al (2011) Apparent acute idiosyncratic hepatic necrosis associated with zonisamide administration in a dog. J Vet Intern Med 25(5):1156-1160
  7. Walker RM et al (1988) Chronic toxicity of the anticonvulsant zonisamide in beagle dogs. Fundam Appl Toxicol 11(2):333-342
  8. Dewey CW et al (2004) Zonisamide therapy for refractory idiopathic epilepsy in dogs. J Am Anim Hosp Assoc 40(4):285-291
  9. Boothe DM & Perkins J (2008) Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs. J Vet Pharmacol Ther 31(6):544-553
  10. Orito K et al (2008) Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs. J Vet Pharmacol Ther 31(3):259-264