Vimpat - Drug Monograph

Introduction

Vimpat (lacosamide) is an anticonvulsant medication approved by the FDA in 2008 for the treatment of partial-onset seizures in patients with epilepsy. It represents a novel class of antiepileptic drugs with a unique dual mechanism of action. Vimpat is available as oral tablets, oral solution, and intravenous injection, providing flexibility in administration across various clinical scenarios.

Mechanism of Action

Lacosamide exerts its antiepileptic effects through two primary mechanisms: 1. Selective enhancement of slow inactivation of voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes and inhibiting repetitive neuronal firing 2. Binding to collapsin response mediator protein-2 (CRMP-2), which may modulate neuronal differentiation and axon guidance

Unlike traditional sodium channel blockers (e.g., carbamazepine, phenytoin) that primarily affect fast inactivation, lacosamide's unique mechanism on slow inactivation provides a differentiated pharmacological profile.

Indications

FDA-approved indications:

• Monotherapy or adjunctive therapy for partial-onset seizures in patients ≥4 years of age
• Adjunctive therapy for primary generalized tonic-clonic seizures in patients ≥4 years of age

Off-label uses (based on clinical evidence):

• Neuropathic pain syndromes
• Diabetic neuropathy
• Fibromyalgia (limited evidence)

Dosage and Administration

• Initial dose: 50 mg twice daily (100 mg/day)
• May increase by 100 mg/day at weekly intervals
• Recommended maintenance dose: 200-400 mg/day divided twice daily
• Maximum recommended dose: 400 mg/day

• Weight-based dosing: 1 mg/kg twice daily initially
• Recommended maintenance dose: 2-12 mg/kg/day (maximum 400 mg/day)

• Renal impairment: Maximum dose 300 mg/day for severe impairment (CrCl ≤30 mL/min)
• Hepatic impairment: Maximum dose 300 mg/day for severe impairment (Child-Pugh Class C)
• Elderly: Consider lower starting doses due to potential decreased renal function
• Pregnancy: Category C - use only if potential benefit justifies potential risk

• Oral: With or without food
• IV: May substitute for oral administration at equivalent dose and frequency
• IV infusion: Over 30-60 minutes

Pharmacokinetics

• Oral bioavailability: ~100%
• Tmax: 1-4 hours post-dose
• Food does not significantly affect absorption

• Volume of distribution: ~0.6 L/kg
• Protein binding: <15%

• Primarily metabolized by CYP2C19 to O-desmethyl metabolite (inactive)
• Minor pathways: CYP2C9 and CYP3A4
• No active metabolites

• Half-life: ~13 hours
• Renal excretion: 95% (40% as unchanged drug, 30% as inactive metabolite)
• Feces: <0.5%

Contraindications

1. Known hypersensitivity to lacosamide or any component of the formulation 2. Second- or third-degree AV block (unless patient has functioning pacemaker) 3. Severe hepatic impairment combined with strong CYP3A4 and CYP2C9 inhibitors

Warnings and Precautions

• Dose-dependent PR interval prolongation
• Risk of atrial fibrillation/flutter, especially in patients with cardiac disease
• Syncope or bradycardia may occur

• Dizziness, ataxia, and coordination difficulties
• May cause cognitive impairment or neuropsychiatric symptoms
• Suicidal behavior and ideation (antiepileptic drug class warning)

• Serious skin reactions including Stevens-Johnson syndrome reported

• Gradual withdrawal recommended (taper over at least 1 week)
• Abrupt discontinuation may increase seizure frequency

• Multiorgan hypersensitivity reactions reported
• May affect ability to drive or operate machinery

Drug Interactions

• Strong CYP2C9 inhibitors (e.g., fluconazole): May increase lacosamide levels
• Strong CYP3A4 inhibitors (e.g., ketoconazole): May increase lacosamide levels
• Strong CYP2C19 inducers (e.g., rifampin): May decrease lacosamide levels
• Other CNS depressants: Additive sedative effects

• Beta-blockers, calcium channel blockers: Potential additive effects on AV conduction
• Digoxin: No significant interaction observed

• No clinically significant interactions with carbamazepine, valproate, levetiracetam, or topiramate

Adverse Effects

• Dizziness (31%)
• Headache (14%)
• Nausea (11%)
• Diplopia (11%)
• Fatigue (9%)

• Prolonged PR interval (dose-dependent)
• Syncope
• Atrial fibrillation/flutter
• Stevens-Johnson syndrome
• Suicidal ideation
• Multiorgan hypersensitivity reactions
• Psychiatric symptoms (agitation, aggression)

Monitoring Parameters

• Comprehensive medical history with focus on cardiac conditions
• ECG (especially in patients with cardiac disease or those taking concomitant medications that affect PR interval)
• Renal and hepatic function tests
• Pregnancy test in women of childbearing potential

• Seizure frequency and characteristics
• ECG monitoring if symptoms of arrhythmia develop
• Neurological assessment for coordination and cognitive effects
• Mood and behavioral changes
• Signs of hypersensitivity reactions

• Routine therapeutic drug monitoring not typically required
• Consider levels in special populations or suspected toxicity (therapeutic range: 1-10 μg/mL)

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• May cause dizziness, drowsiness, or coordination problems - avoid driving or hazardous activities until effects are known
• Rise slowly from sitting/lying position to minimize dizziness
• Avoid alcohol and other CNS depressants
• Report any cardiac symptoms (palpitations, slow heartbeat, fainting)
• Monitor for mood changes, depression, or suicidal thoughts
• Notify healthcare provider if rash develops
• Inform all healthcare providers about Vimpat use, especially before new medications
• Use effective contraception; notify provider if pregnancy is planned or suspected
• Keep all follow-up appointments

• Store at room temperature (15-30°C)
• Oral solution: discard 7 weeks after first opening
• Use medication reminder systems if needed

References

1. FDA Prescribing Information: Vimpat (lacosamide). Revised 2022. 2. Beyreuther BK, et al. Lacosamide: A review of preclinical properties. CNS Drug Reviews. 2007;13(1):21-42. 3. Chung S, et al. Lacosamide: Pharmacology, mechanisms of action and pooled efficacy and safety data in partial-onset seizures. Expert Rev Neurother. 2009;9(1):33-42. 4. Halford JJ, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51(6):958-967. 5. Wechsler RT, et al. Lacosamide: A new approach to target voltage-gated sodium channel slow inactivation. Epilepsy Curr. 2007;7(4):99-101. 6. Epilepsy Foundation. Lacosamide (Vimpat) Medication Guide. 2022. 7. Micromedex Solutions. Lacosamide Drug Information. Truven Health Analytics. 2023. 8. Lexicomp Online. Lacosamide: Drug Information. Wolters Kluwer Health. 2023.