What is the role of lacosamide in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Lacosamide (formerly known as erlosamide, harkoseride, or SPM 927) is an amino acid derivative referred to as functionalized amino acid. The (R)-enantiomer lacosamide has about twice the potency of the racemic mixture. Lacosamide is inactive against clonic seizures induced by bicuculline and picrotoxin but showed efficacy against hippocampal kindled seizures at least as much as other AEDs including phenytoin, carbamazepine, and valproate. [25] Lacosamide was approved in the United States in 2008.

Lacosamide has a novel mechanism of action of modulation of voltage-gated sodium channels by selective enhancement of slow inactivation but without apparent interaction with fast inactivation gating. [26] This effect may be relatively selective for neurons involved in a seizure activity in which the persistence of sodium currents is more pronounced and preserve the function of a relative less active neurons. [27] Lacosamide does not affect AMPA, kainate, NMDA, GABAA, GABAB, or various dopaminergic, serotoninergic, adrenergic, muscarinic, or cannabinoid receptors and does not block potassium or calcium currents. [28]

Upon oral administration, lacosamide has a bioavailability close to 100% and is not affected by food; intravenous infusion of lacosamide has demonstrated bioequivalence with the same dose of oral administration. Peak plasma levels occur approximately 1-4 hours after the dose, and elimination half-life is approximately 13 hours. Lacosamide has minimal protein binding (< 15%) and does not act as an inducer or inhibitor of the cytochrome P-450 (CYP-450) isoenzymes and does not have a significant interaction with other AEDs. [29]

Lacosamide effect on seizures was demonstrated as adjunctive therapy in partial-onset seizures in three 12-week, randomized, double-blind, placebo-controlled, multicenter trials in adult patients. [30, 31, 32] Lacosamide has been used in children with refractory epilepsy of different etiologies [33, 34] and in adults juvenile myoclonic epilepsy [35] with apparently good tolerability and fair efficacy, but controlled studies confirming the findings are lacking. Lacosamide has been used as well in patients in a critical care setting with nonconvulsive status epilepticus given the favorable pharmacokinetics and intravenous route access; [36, 37] however, the safety and efficacy of lacosamide in this situations has not been determined yet.

Lacosamide currently is approved in the United States as monotherapy and as adjunctive therapy for adults and adolescents aged 17 years or older with partial-onset seizures.

The dose regimen and titration is based on clinical response and tolerability. The starting dose for adjunctive therapy is 50 mg BID, and then increased by weekly increments of 50 mg BID up to 100-200 mg BID.

The starting dose for monotherapy is 100 mg BID initially, then increased at weekly intervals by 50 mg BID up to 150-200 mg BID. Alternatively, a 200 mg loading dose may be given, followed 12 hours later by 100 mg BID for 1 week, and then gradually increased at weekly intervals by 50 mg BID up to 150-200 mg BID.

Commonly reported adverse reactions include dizziness, headache, nausea, and diplopia.

Lacosamide has been labeled pregnancy category C because it has produced developmental toxicity (increased embryofetal and perinatal mortality, growth deficit) in rats following administration during pregnancy. No human data is currently available; however, a pregnancy registry is ongoing.

The excellent pharmacokinetic profile and relative good tolerability make this drug easy to use as add-on therapy (it is not approved as initial monotherapy in the United States). Intravenous formulation makes this drug particularly useful in ICU settings. The efficacy of lacosamide in status epilepticus has not been determined.


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