FORMULARY-

ZONISAMIDE

Zonisamide blocks voltage-dependent sodium and calcium channels, enhances actions of GABA and may reduce presynaptic glutamate release (Mac Donald 2002). Furthermore an increase in dopamine and serotonin levels in striatal and hippocampal structures are reported (Kaneko and others 1993, Okada and others 1995). It is metabolised primarily by hepatic microsomal enzymes, and the half-life in dogs is about 15 hours (Matsumoto and others 1983, Thomas 2003).  Consequently, the elimination half-life is dramatically shorter in dogs already receiving drugs that stimulate hepatic microsomal enzymes than in dogs who are not receiving such drugs.

Indications

Adjunct therapy for canine seizures refractory to standard medication.

 

Dose

An initial dose rate of 10 mg/kg BID is recommended if used as an add-on of drugs requiring hepatic metabolism (e.g., phenobarbital) – Lower dose of 5 mg/kg BID can be used in dogs not concurrently receiving drugs that induce hepatic microsomal enzymes.  Trough serum zonisamide concentration should be checked after around 1 week of zonisamide treatment aiming for a serum concentration of 10-40 ug/ml.

 

Side effects

Zonisamide appears to be safe - few side-effects are reported in dogs, although mild ataxia and sedation may occur when treatment is started and vomiting and loss of appetite have been reported in some dogs (Dewey and others, 2004).

 

Has caused kidney stones in some people.

 

At a dose of 75 mg/kg bodyweight (four times the recommended dose) slight changes in blood count and an increase of liver weight were observed in one study (Walker and others 1988).

References:

Boothe D M, Pers J, Dewekiny C. (2005) Clinical pharmacokinetics and safety of the anticonvulsant zonisamide in healthy dogs following single and multiple dosing. In: Proceedings of the 23rd ACVIM forum, Baltimore, USA. pp 858

 

Budsberg, S.C. (2004) Zonisamide therapy for refractory idiopathic epilepsy in dogs. Journal of the AmericanAnimalHospital Association 40, 285-291 - PubMed -

 

Dewey C W, Guiliano R, Boothe D M, Berg J M, Kortz G D, Joseph R J, Budsberg S C (2004) Zonisamide therapy for refractory idiopathic epilepsy in dogs. Journal of the AmericanAnimalHospital Association 40, 285-291-PubMed-

 

Hamada K, Song H K, Ishida S, Yagi K, Seino M (2001) Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling rats. Epilepsia 42, 1379-1386 - PubMed -

 

Juergens, U. (1987) Simultaneous determination of zonisamide and nine other anti-epileptic drugs and metabolites in serum. Journal of Chromatography 385, 233-240 - PubMed -

 

Kaneko S, Okada M, Hirano T (1993) Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels in vivo, and carbamazepine does not antagonize adenosine effect in vitro: mechanisms of blockade of seizure spread. Japanese Journal of Psychiatry and Neurology 47, 371-373 - PubMed -

 

Mac Donald R L (2002) Zonisamide. In: Antiepileptic drugs. 5th edn. Eds: R H Levy, R H Mattson, B S Meldrum, E Perucca. Lippincott Williams and Wilkens, Philadelphia. pp 867-898

 

Matsumoto K, Miyazaki H, Fujii T, Kagemoto A, Maeda T, Hashimoto M (1983) Absorption, distribution and excretion of 3-(sulfamoyl[14C]methyl)-1,2-benziosoxazole (AD-810) in rats, dogs and monkeys and of AD-810 in men. Drug Research 33, 961-968 - PubMed -

 

Okada M, Kaneko S, Hirano T (1995) Effects of zonisamide on dopaminergic system. Epilepsy Research 22, 193-205 - PubMed -

 

Thomas, W.B. (2003) Seizures and narcolepsy. In: A practical guide to canine and feline neurology. Ed C.W. Dewey. Iowa State Press, Ames. ISBN 0-8138-1249-6; pp 193-212

 

Von Klopmann T, Rambeck B, Tipold A (2007) Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. J Small Anim Pract 48 (3), 134-8. PMID: 17355603 - PubMed -

 

Walker R M, DiFonzo C J, Barsoum N J, Smith G S, Macallum G E (1988) Chronic toxicity of the anticonvulsant zonisamide in beagle dogs. Fundamental and applied Toxicology 11, 333-342 - PubMed -

 

 

 

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