What is lacosamide?

Lacosamide: A Comprehensive Overview

Lacosamide is an antiepileptic medication that works by selectively enhancing slow inactivation of voltage-gated sodium channels, used primarily for treating partial-onset seizures in adults and children, available in both oral and intravenous formulations. 1

Mechanism of Action and Pharmacology

Lacosamide functions through a unique mechanism compared to other antiepileptic drugs:

• Selectively enhances slow inactivation of voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes and inhibiting repetitive neuronal firing 1, 2
• May interact with collapsin-response mediator protein 2 (CRMP-2), potentially mediating neuronal plasticity 1
• Has a molecular formula of C₁₃H₁₈N₂O₃ and molecular weight of 250.30 2
• Available as a white to light yellow powder that is sparingly soluble in water 2

Formulations and Administration

Lacosamide is available in multiple formulations:

• Oral tablets
• Oral solution (10 mg/mL)
• Intravenous infusion
• Bioequivalence established between oral tablet and oral solution formulations 1
• Recommended dosage: 200-400 mg per day, administered twice daily 1

Clinical Indications

Lacosamide is FDA-approved for:

• Adjunctive therapy for partial-onset seizures in people 1 month of age and older 2
• Adjunctive therapy with other medicines to treat primary generalized tonic-clonic seizures in people 4 years of age and older 2

Efficacy

Clinical trials have demonstrated significant efficacy as adjunctive therapy:

• 34% of patients achieved ≥50% reduction in seizure frequency at 200mg/day 1
• 40% of patients achieved ≥50% reduction in seizure frequency at 400mg/day 1
• 23% of patients achieved ≥50% reduction with placebo 1
• Doses above 400 mg/day do not appear to confer additional benefit in group analyses 2

Pharmacokinetics

Lacosamide has favorable pharmacokinetic properties:

• Complete absorption after oral administration with approximately 100% bioavailability 2
• Maximum plasma concentrations occur 1-4 hours post-dose 2
• Elimination half-life of approximately 13 hours 2
• Steady state plasma concentrations achieved after 3 days of twice daily administration 2
• Dose-proportional pharmacokinetics (100-800 mg) with low inter- and intra-subject variability 2
• Does not induce or inhibit cytochrome P450 enzymes, resulting in fewer drug-drug interactions than older antiseizure medications 1

Common Side Effects

The most common adverse events include:

• Central nervous system effects: dizziness, headache, drowsiness/somnolence, vertigo, and ataxia 1
• Visual disturbances: diplopia (double vision) 1
• Gastrointestinal effects: nausea and vomiting 1
• Administration-related effects: injection site pain (with IV formulation) 1

Cardiac Effects and Precautions

Lacosamide has dose-dependent effects on cardiac conduction:

• PR interval prolongation and risk of atrioventricular block, particularly in:
  • Elderly patients
  • Patients with pre-existing cardiac conduction disorders
  • Patients taking other medications affecting cardiac conduction
  • Patients with renal impairment 1
• Baseline ECG and periodic cardiac assessment recommended for at-risk patients 1
• May cause irregular heartbeat or fainting; cardiac arrest has been reported in rare cases 2

Special Considerations

Controlled Substance Status

• Classified as a Schedule V controlled substance in the United States 1
• Can be abused or lead to drug dependence 2
• May produce euphoria-type responses, particularly at higher doses 2

Suicidal Behavior and Ideation

• Like other antiepileptic drugs, lacosamide may increase the risk of suicidal thoughts or behavior 2
• Mental health monitoring recommended for signs of depression or suicidal ideation 1

Discontinuation

• Should not be stopped abruptly without medical supervision 2
• Sudden discontinuation may cause seizures that will not stop (status epilepticus) 2

Driving and Operating Machinery

• May cause dizziness, double vision, sleepiness, or problems with coordination and walking 2
• Patients should be counseled on potential effects on driving performance 1

Overdose Management

In case of overdose:

• No specific antidote exists 2
• Standard decontamination procedures should be followed 2
• Supportive care including monitoring of vital signs and observation of clinical status 2
• Hemodialysis may be indicated (reduces systemic exposure by 50% in 4 hours) 2
• Contact a Certified Poison Control Center for management guidance 2

Lacosamide represents an important option in the antiepileptic armamentarium with its unique mechanism of action, favorable pharmacokinetic profile, and established efficacy for partial-onset seizures.