New molecular entity: Lacosamide (Vimpat), an antiepileptic drug, was approved on October 28, 2008, as adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy aged 17 years or older
Lacosamide is an antiepileptic drug that enhances slow inactivation of voltage-gated sodium channels, thereby stabilizing hyperexcitable neuronal membranes and inhibiting repetitive neuronal firing. This agent, available in both tablet and intravenous (IV) form, was approved on October 28, 2008, as adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy aged ≥17 years; the IV injection is approved for use when oral administration is temporarily not feasible.
Efficacy. The efficacy of lacosamide was evaluated in three 12-week, randomized, double-blind, placebo-controlled, multicenter trials in adult patients who had partial-onset seizures with or without secondary generalization and whose seizures were not adequately controlled with 1 to 3 concomitant antiepileptic drugs. Study 1 compared lacosamide 200, 400, and 600 mg/d with placebo; Study 2 compared lacosamide 400 and 600 mg/d with placebo; and Study 3 compared lacosamide 200 and 400 mg/d with placebo. In patients randomized to lacosamide, treatment was initiated at 100 mg/d (50 mg administered twice daily) and was increased weekly by 100 mg/d to the target dose. This titration phase lasted 6 weeks in Studies 1 and 2 and 4 weeks in Study 3; in all 3 trials, this titration was followed by a maintenance phase that lasted 12 weeks. The primary outcome was a reduction in 28-day seizure frequency. This outcome was significantly improved (P<.05) with lacosamide 200 mg/d in Study 3, lacosamide 400 mg/d in Studies 1, 2, and 3, and 600 mg/d in Studies 1 and 2.
Safety. Antiepileptic drugs increase the risk of suicidal behavior and ideation. Lacosamide may cause dizziness and ataxia. Lacosamide treatment has been associated with dose-dependent prolongations in PR interval. Rarely, multiorgan hypersensitivity reactions have been reported in lacosamide-treated patients. The most common adverse reactions reported in lacosamide-treated patients include dizziness, headache, diplopia, and nausea.