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.
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
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.
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.