Zonisamide: Review of Recent Clinical Evidence for Treatment of Epilepsy

Abstract

Zonisamide is an orally administered antiepileptic drug that was first approved for clinical use in Japan in 1989. Since then, it has been licensed in Korea for a broad spectrum of epilepsies in adults and children, and in the USA for adjunctive therapy of adults with partial seizures, and in Europe for monotherapy of adults with newly diagnosed partial seizures and adjunctive therapy of adults and adolescents and children aged ≥6 years with partial seizures with or without secondary generalization. Zonisamide is a benzisoxazole derivative with a unique chemical structure, predictable dose-dependent pharmacokinetics, and multiple complementary mechanisms of action. Treatment with zonisamide is well tolerated and is not known to be associated with clinically significant drug-drug interactions, including with oral contraceptives or other antiepileptic drugs. There have been >2 million patient-years of experience with zonisamide for treatment of epilepsy, and this drug has International League Against Epilepsy level A evidence for efficacy/effectiveness as initial monotherapy for adults with partial-onset seizures. This review presents the evidence for zonisamide across the spectrum of epilepsy, with emphasis on real-world clinical practice and special populations of patients (children, elderly patients, and women of childbearing age) who are likely to be treated in daily clinical practice.

Evaluation of Medicinal Effects of Isoxazole Ring Isosteres on Zonisamide for Autism Treatment by Binding to Potassium Voltage-Gated Channel Subfamily D Member 2 (Kv 4.2)

“…Zonisamide later received its FDA approval as an adjuvant treatment for partial seizures in 2000. Over the years, the ameliorative effect of this drug in both partial and generalized seizures [2][3][4][5][6][7] as well as several other neurological disorders namely, psychotic conditions [8], Parkinson disease [9][10][11][12][13], neuropathic pain [14] and essential tremor [15] have been investigated. Although the precise mechanism of Zonisamide has not yet fully understood, blockage of voltagegated sodium channels and T-type calcium channels seems to be the principle route of action.…”

Genetic T-type calcium channelopathies

“…Conversely, pharmacological inhibition of T-type currents using pan T-type channel blockers reduces thalamic burst firing and suppresses seizures 87–89. In addition, several pan T-type channel blockers are effective in the treatment of absence seizures in humans90–92 (for recent review see Ref. 81).…”

Pharmacological management of epilepsy

“…It is not known to be associated with clinically significant drug-drug interactions. 22 Zonisamide displays predictable dose-dependent pharmacokinetics, a half-life of 60 hours allowing once or twice daily administration. The most frequently reported adverse effects are somnolence, dizziness and anorexia/ weight loss.…”

“…It is not known to be associated with clinically significant drug-drug interactions. 22 Table 4. Adverse effects associated with AEDs used as adjunctive therapy, second or third line once or twice daily administration.…”