Lacosamide (Vimpat) Indication in Adults with Partial-Onset Seizures
Lacosamide is indicated as adjunctive therapy for the treatment of partial-onset seizures in adults with epilepsy, with or without secondary generalization. 1
Mechanism and Pharmacological Profile
Lacosamide is a functionalized amino acid that exerts its antiepileptic effect through a unique mechanism:
- Selectively enhances slow inactivation of voltage-gated sodium channels 2
- Available in both oral (tablets, solution) and intravenous formulations
- Has favorable pharmacokinetic characteristics:
- Rapid absorption with high oral bioavailability
- Linear and dose-proportional pharmacokinetics
- Low plasma protein binding
- Primarily renal elimination
- Low potential for drug-drug interactions 2
Efficacy Evidence
Lacosamide has demonstrated significant efficacy as adjunctive therapy in adults with partial-onset seizures:
- Increases 50% responder rate by 68% compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]) 3
- Median percent reduction in seizure frequency:
- 33.3% for 200 mg/day (p < 0.01)
- 36.8% for 400 mg/day (p < 0.001)
- 39.4% for 600 mg/day 4
- Sustained efficacy demonstrated in long-term extension studies up to 8 years 5
Dosing and Administration
- Oral and IV formulations are bioequivalent, allowing direct conversion between routes without titration 2
- Typical dosing:
- Starting dose: Usually initiated at lower doses and titrated up
- Target dose range: 200-400 mg/day (maximum approved dose)
- Administration: Twice daily dosing 5
Safety and Tolerability
The most common adverse events with lacosamide (occurring in ≥5% and at least twice the rate of placebo) include:
- Dizziness (30.6% vs 8.2% placebo)
- Nausea (11.4% vs 4.4% placebo)
- Diplopia/double vision (10.5% vs 1.9% placebo) 6
Most adverse events are:
- Dose-related (higher incidence with 600 mg/day)
- Mild to moderate in intensity
- More common during titration than maintenance phase
- Rarely related to rash, weight changes, or psychiatric disturbances 6
Important Clinical Considerations
Discontinuation rates due to adverse events increase with dose:
- 8.1% at 200 mg/day
- 17.2% at 400 mg/day
- 28.6% at 600 mg/day 6
Small dose-related increases in PR interval have been observed, requiring caution in patients with cardiac conduction disorders 1
When used with other antiepileptic drugs, discontinuation rates vary:
- With carbamazepine: 15.3% (vs 3.9% placebo)
- With lamotrigine: 19.2% (vs 4.3% placebo)
- With levetiracetam: 10.1% (vs 3.9% placebo) 6
Place in Therapy
Lacosamide is positioned as an adjunctive therapy for partial-onset seizures when initial monotherapy is inadequate. Its unique mechanism of action makes it a valuable addition to existing treatment regimens, particularly when patients have failed other antiepileptic medications.
Practical Prescribing Points
- Initiate at lower doses and titrate gradually to minimize adverse effects
- Monitor for neurological side effects, particularly dizziness and diplopia
- Consider potential interactions with concomitant antiepileptic drugs
- Both oral and IV formulations can be used interchangeably based on clinical need
- Avoid abrupt discontinuation which can precipitate withdrawal seizures
Lacosamide offers a valuable option for patients with partial-onset seizures who have not achieved adequate seizure control with other antiepileptic medications, with a generally favorable safety profile and the convenience of both oral and IV administration options.