Oxcarbazepine, an antiepileptic agent

Background: Epilepsy is a common neurologic condition. Many of the currentl y approved pharmacologic agents for its treatment are associated with numer ous adverse drug reactions and drug interactions. Objective: This review describes the pharmacology and therapeutic use of ox carbazepine, an analogue of the well-known antiepileptic agent carbamazepin e. Methods: Articles for review were identified through a search of MEDLINE (R), International Pharmaceutical Abstracts (R), and EMBASE((R)) for the ye ars 1980 through 2000. The terms used individually and in combination were oxcarbazepine, carbamazepine, epilepsy, and seizures. Results: Oxcarbazepine and its: primary metabolite have been effective in a nimal models of epilepsy that generally predict efficacy in generalized ton ic-clonic seizures and partial seizures in humans. The exact mechanism of a ction of oxcarbazepine is unknown, although as with carbamazepine, it is be lieved to involve blockade of voltage-gated sodium channels. The pharmacoki netic profile of oxcarbazepine: is less complicated than that of carbamazep ine, with less metabolism by the cytochrome P450 system, no production of a n epoxide metabolite, and lower plasma protein binding. The clinical effica cy and tolerability of oxcarbazepine have been demonstrated in trials in ad ults, children, and the elderly. In a double-blind, randomized, crossover t rial in adults, oxcarbazepine 300 mg was associated with a decrease in the mean frequency of tonic seizures (21.4 vs 30.5 seizures during steady-state periods) and tonic-clonic seizures (8.2 vs 10.3) compared with carbamazepi ne 200 mg (P = 0.05). A multinational, multicenter, double-blind, placebo-c ontrolled, randomized, 28-week trial assessed the efficacy and tolerability of oxcarbazepine at doses of 600, 1200, and 2400 mg as adjunctive therapy in patients with uncontrolled partial seizures. All 3 oxcarbazepine groups demonstrated a reduction in seizure frequency per 28-day period compared wi th placebo (600 mg, 26% reduction; 1200 mg, 40% reduction; 2400 mg, 50% red uction; placebo, 7.6% reduction; all, P < 0.001). A trial in children asses sed the efficacy and toxicity of oxcarbazepine (median dose, 31.4 mg/kg/d) as adjunctive therapy for partial seizures. Patients receiving oxcarbazepin e experienced a 35% reduction in seizure frequency, compared with a 9% redu ction in the placebo group (P < 0.001). The most common adverse effects ass ociated with oxcarbazepine are related to the central nervous system leg, d izziness, headache, diplopia, and ataxia) and the gastrointestinal system l eg, nausea and vomiting). Compared with carbamazepine, there is an increase d risk of hyponatremia with oxcarbazepine. The frequency and severity of dr ug interactions are less with oxcarbazepine than with carbamazepine or othe r antiepileptic agents. Conclusions: Oxcarbazepine may be considered an appropriate alternative to carbamazepine for the treatment of partial seizures in patients who are una ble to tolerate carbamazepine. Its use in nonseizure disorders remains to b e examined in large-scale clinical trials, and pharmacoeconomic comparisons of oxcarbazepine with other antiepileptic agents, particularly carbamazepi ne, are needed.