Eslicarbazepine acetate is used orally in combination with other anticonvulsant agents in the management of partial-onset seizures in adults.
Efficacy of eslicarbazepine acetate as adjunctive therapy for partial-onset seizures was established in 3 multicenter, randomized, double-blind, placebo-controlled studies of similar design in adult patients with refractory partial-onset seizures (with or without secondary generalization). All 3 studies consisted of an 8-week baseline period followed by a double-blind treatment period consisting of a 2-week titration period and a subsequent 12-week maintenance period. Studies 1 and 2 compared eslicarbazepine acetate dosages of 400 mg, 800 mg, and 1.2 g once daily with placebo, and study 3 compared eslicarbazepine acetate dosages of 800 mg and 1.2 g once daily with placebo. During the 8-week baseline period, patients who were receiving stable dosages of 1-3 anticonvulsants for at least 2 months prior to screening and who had an average of 4 or more partial-onset seizures per 28 days with no seizure-free period exceeding 21 days were randomized to the double-blind treatment period. The median duration of epilepsy in the patients in these studies was 19 years and the median baseline seizure frequency was 8 seizures per 28 days; 69% of patients were receiving 2 concomitantly administered anticonvulsants and 28% were receiving one concomitant anticonvulsant. The most commonly used anticonvulsants were carbamazepine (50%), lamotrigine (24%), valproate (21%), and levetiracetam (18%); patients receiving oxcarbazepine or felbamate were excluded from the studies.
Efficacy of eslicarbazepine acetate was evaluated principally by the standardized seizure frequency over 28 days during the maintenance phase (primary efficacy endpoint) as well as the secondary endpoint of percent reduction in seizure frequency from baseline to the end of the treatment period, based on self-reported patient diaries. Eslicarbazepine acetate 400 mg daily was assessed and not found to be substantially more effective than placebo in reducing seizures in studies 1 and 2. The 800-mg daily dosage of the drug substantially reduced seizure frequency compared with placebo in studies 1 and 2, but not in study 3. In all 3 studies, eslicarbazepine acetate 1.2 g daily was more effective than placebo in reducing seizure frequency.
Results of longer-term, open-label extensions of studies 1 and 2 indicate that reductions in seizure frequency are maintained in patients who continue to receive eslicarbazepine acetate for at least 1 year. Approximately 69-77% of the patients enrolled in these extension studies completed one year of treatment with the drug; the median dosage was 800 mg once daily in both studies. Eslicarbazepine acetate therapy was generally well tolerated, and improvements in quality of life and depressive symptoms were observed in both long-term studies.
Eslicarbazepine is commercially available as the acetate salt, which is rapidly and almost completely reduced by esterases in the liver to the active S-enantiomer, which is called S-licarbazepine or eslicarbazepine.
(See Description.)Oxcarbazepine, another anticonvulsant, also is a prodrug that is metabolized to both the S-enantiomer (active) and R-enantiomer (inactive) of licarbazepine. It has been suggested that the nearly complete conversion of eslicarbazepine acetate to its active metabolite, eslicarbazepine, and the drug's preferential action on the inactivated state of the ion channel potentially may result in improved tolerability (including fewer neurologic adverse effects and a reduced risk of hyponatremia) and anticonvulsant efficacy compared with oxcarbazepine. However, controlled comparative trials between eslicarbazepine acetate and oxcarbazepine have not been conducted to date and are needed to fully evaluate the relative efficacy and tolerability of these 2 structurally related anticonvulsants. The once-daily dosage regimen of eslicarbazepine acetate may help improve patient compliance over many other anticonvulsants, which require more frequent administration.