Oxcarbazepine, an antiepileptic agent.
BACKGROUND
Epilepsy is a common neurologic condition. Many of the currently approved pharmacologic agents for its treatment are associated with numerous adverse drug reactions and drug interactions.


OBJECTIVE
This review describes the pharmacology and therapeutic use of oxcarbazepine, an analogue of the well-known antiepileptic agent carbamazepine.


METHODS
Articles for review were identified through a search of MEDLINE, International Pharmaceutical Abstracts, and EMBASE for the years 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 animal models of epilepsy that generally predict efficacy in generalized tonic-clonic seizures and partial seizures in humans. The exact mechanism of action of oxcarbazepine is unknown, although as with carbamazepine, it is believed to involve blockade of voltage-gated sodium channels. The pharmacokinetic profile of oxcarbazepine is less complicated than that of carbamazepine, with less metabolism by the cytochrome P450 system, no production of an epoxide metabolite, and lower plasma protein binding. The clinical efficacy and tolerability of oxcarbazepine have been demonstrated in trials in adults, children, and the elderly. In a double-blind, randomized, crossover trial 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 10.4) compared with carbamazepine 200 mg (P = 0.05). A multinational, multicenter, double-blind, placebo-controlled, 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 with placebo (600 mg, 26% reduction; 1200 mg, 40% reduction; 2400 mg, 50% reduction; placebo, 7.6% reduction; all, P < 0.001). A trial in children assessed the efficacy and toxicity of oxcarbazepine (median dose, 31.4 mg/kg/d) as adjunctive therapy for partial seizures. Patients receiving oxcarbazepine experienced a 35% reduction in seizure frequency, compared with a 9% reduction in the placebo group (P < 0.001). The most common adverse effects associated with oxcarbazepine are related to the central nervous system (eg, dizziness, headache, diplopia, and ataxia) and the gastrointestinal system (eg, nausea and vomiting). Compared with carbamazepine, there is an increased risk of hyponatremia with oxcarbazepine. The frequency and severity of drug interactions are less with oxcarbazepine than with carbamazepine or other antiepileptic agents.


CONCLUSIONS
Oxcarbazepine may be considered an appropriate alternative to carbamazepine for the treatment of partial seizures in patients who are unable to tolerate carbamazepine. Its use in nonseizure disorders remains to be examined in large-scale clinical trials, and pharmacoeconomic comparisons of oxcarbazepine with other antiepileptic agents, particularly carbamazepine, are needed.
Kalis
M M
MM
School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston 02115, USA.
Huff
N A
NA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine