What is lacosamide?

Lacosamide: An Antiepileptic Medication

Lacosamide is an antiepileptic medication with a novel mechanism of action that selectively enhances slow inactivation of voltage-gated sodium channels, primarily indicated for the treatment of partial-onset seizures in adults with epilepsy. 1

Mechanism of Action and Pharmacology

• Unlike traditional sodium channel blockers, lacosamide works through a unique mechanism:
  • Selectively enhances slow inactivation of voltage-gated sodium channels 2, 3
  • Stabilizes hyperexcitable neuronal membranes
  • Inhibits neuronal firing
  • May interact with collapsin-response mediator protein 2 (CRMP-2), potentially mediating neuronal plasticity 4

Pharmacokinetic Properties

• Rapid absorption with maximum plasma concentrations reached within 0.5-4 hours
• High oral bioavailability (100%) for doses up to 800mg
• Food does not affect bioavailability
• Terminal half-life of approximately 13 hours in young adults (14-16 hours in elderly)
• Low protein binding (<15%)
• Multiple elimination pathways with primarily renal excretion
• Low pharmacokinetic variability between individuals 3

Clinical Uses

• FDA-approved indications:

  • Adjunctive therapy for partial-onset seizures in adults with epilepsy, with or without secondary generalization 1
  • Available in both oral and intravenous formulations 5

• Available dosage forms:

  • Oral tablets: 50mg, 100mg, 150mg, and 200mg 6
  • Intravenous solution

Dosing

• Recommended dose range: 200-400mg per day, administered twice daily 4
• Bioequivalence established between oral tablet and oral syrup formulations
• Intravenous administration provides similar bioavailability to oral tablets when given as 30-60 minute infusions 5

Efficacy

• Clinical trials have demonstrated significant efficacy as adjunctive therapy:
  • 34% of patients achieved ≥50% reduction in seizure frequency at 200mg/day
  • 40% of patients achieved ≥50% reduction in seizure frequency at 400mg/day
  • Compared to 23% with placebo 5

Safety and Adverse Effects

• Generally well-tolerated with most adverse events being mild to moderate

• Most common adverse effects:

  • Dizziness
  • Vertigo
  • Nausea
  • Headache 4

• Important cardiac consideration:

  • Small dose-related increases in PR interval have been observed
  • Requires caution in patients with cardiac conduction disorders 2, 1

Drug Interactions

• Does not induce or inhibit cytochrome P450 enzymes
• Does not affect known drug transporter systems
• No clinically significant drug-drug interactions have been identified 4, 3

Special Considerations

• Classified as a Schedule V controlled substance in the United States 2
• May have effects on driving performance, requiring appropriate patient counseling 2
• Despite studies in painful diabetic peripheral neuropathy (DPN), lacosamide was not approved for this indication by either the FDA or European Medicines Agency 2

Emerging Uses

• While primarily approved for adults, limited data suggests potential efficacy for status epilepticus in pediatric populations, though this remains an off-label use 7