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Zonisamide: its pharmacology, efficacy and safety in clinical trials
Author(s) -
Brodie M. J.,
BenMenachem E.,
Chouette I.,
Giorgi L.
Publication year - 2012
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.12016
Subject(s) - zonisamide , tolerability , medicine , adverse effect , adjunctive treatment , epilepsy , placebo , carbamazepine , atomoxetine , anesthesia , anticonvulsant , randomized controlled trial , pharmacology , methylphenidate , attention deficit hyperactivity disorder , psychiatry , topiramate , alternative medicine , pathology
Zonisamide is a benzisoxazole derivative, chemically unrelated to other antiepileptic drugs, that appears to have multiple mechanisms of action, including inhibition of N a + channels and reduction of T ‐type C a 2+ currents. It is currently licensed in E urope and the USA for adjunctive treatment of partial seizures in adults, and in Europe as monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy. Zonisamide displays predictable, dose‐dependent pharmacokinetics and has a half‐life of ~60 h, allowing once‐ or twice‐daily administration. It has a low potential for interactions with other medications, including oral contraceptives. The clinical efficacy of adjunctive zonisamide therapy has been established in four pivotal, phase III , randomized, double‐blind, placebo‐controlled trials, which together included approximately 850 patients, aged 12–77 years, with refractory partial epilepsy. In all four trials, zonisamide 300–600 mg/day resulted in significant reductions in median total seizure rates vs placebo, and zonisamide was generally well tolerated; the most frequently reported adverse events being somnolence, dizziness and anorexia/weight loss. Subanalysis of the primary E uropean trial indicated that zonisamide was effective when administered as first‐line adjunctive treatment, and a long‐term extension to the same trial demonstrated that the efficacy and safety/tolerability of adjunctive zonisamide was sustained for up to 36 months. Once‐daily monotherapy with zonisamide (200–500 mg/day) has been shown to be non‐inferior to, and as well tolerated as, twice‐daily monotherapy with controlled‐release carbamazepine (400–1200 mg/day) in adults with newly diagnosed partial epilepsy. Zonisamide has also been shown to have favourable long‐term retention rates, an important indication of its overall effectiveness.