Oxcarbazepine: current status and clinical applications

Oxcarbazepine (OXC) was introduced in 1990 and is now registered in 54 countries worldwide as monotherapy, as add-on treatment for partial seizures, with or without secondarily generalised seizures, and primary generalised tonic-clonic seizures. OXC and its active metabolite, monohydroxy derivative (MHD), block voltage-dependent sodium channels and may effect potassium and calcium channels. In animal models of epilepsy, OXC and MHD have efficacy similar to that of CBZ. There is no evidence for clinically important teratogenicity, mutagenicity or carcinogenicity. OXC has no effect on serum concentrations of hepatically metabolised anti-epileptic drugs (AEDs) and no clinically important interactions with common non-AEDs, other than hormonal contraceptives. MHD has low protein binding and linear pharmacokinetics. Adverse effects (AEs) are usually related to the central nervous system. Approximately three-quarters of patients who experience adverse effects with CBZ improve when switched to OXC, without loss of seizure control. The incidence of rash appears to be less than that expected with CBZ. While hyponatraemia may occur more often with OXC than with CBZ, it is rarely symptomatic. OXC is an effective and safe drug for the treatment of partial-onset and primary generalised tonic-clonic seizures. Placebo- and low-dose controlled double-blind monotherapy studies prove that OXC has anticonvulsant activity and that therapeutic dosages may be obtained with a 24 h titration in hospitalised patients, if necessary. Comparative double-blind trials show that OXC has similar efficacy to VPA, CBZ and PHT, but has advantages compared to those agents in terms of pharmacokinetics, side-effects and tolerability.