Lacosamide is an amino acid-related compound that has been studied in both pain syndromes and partial seizures. The drug was approved in Europe and the USA in 2008 for the treatment of partial seizures.
Activity resides in the R(–) enantiomer. Two effects relevant to the mechanism of action of lacosamide as an antiseizure drug have been described. Lacosamide enhances slow inactivation of voltage-gated Na+ channels (in contrast to the prolongation of fast inactivation shown by other AEDs). It also binds to the collapsin-response media-tor protein, CRMP-2, thereby blocking the effect of neurotrophic factors such as BDNF and NT3 on axonal and dendritic growth.
Lacosamide is approved as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in patients with epilepsy who are age 16–17 years and older. Clinical trials include three multicenter, randomized placebo-controlled studies with more than 1300 patients. Treatment was effective at both 200 and 400 mg/d. Adverse effects were dizziness, headache, nausea, and diplopia. In the open-label follow-up study, at dosages ranging from 100 to 800 mg/d, many patients continued lacos-amide treatment for 24 to 30 months. The drug is typically administered twice daily, beginning with 50 mg doses and increas-ing by 100 mg increments weekly. An intravenous formulation provides short-term replacement for the oral drug.
Oral lacosamide is rapidly and completely absorbed in adults, with no food effect. Bioavailability is nearly 100%. The plasma concen-trations are proportional to dosage up to 800 mg orally. Peak concentrations occur from 1 to 4 hours after oral dosing, with an elimination half-life of 13 hours. There are no active metabolites and protein binding is minimal. Lacosamide does not induce or inhibit cytochrome P450 isoenzymes, so drug interactions are negligible.