What is the recommended dosing for Vimpat (lacosamide) in adults with partial-onset seizures?

Vimpat (Lacosamide) Dosing for Partial-Onset Seizures

For adults with partial-onset seizures, initiate lacosamide at 50 mg twice daily (100 mg/day) and titrate to the recommended maintenance dose of 100-200 mg twice daily (200-400 mg/day) based on response and tolerability, with no loading dose recommended for non-emergent situations. 1

Standard Maintenance Dosing

Recommended therapeutic dosing ranges from 200-400 mg/day administered in two divided doses:

• Initial dose: 50 mg twice daily (100 mg/day) 2, 3
• Target maintenance doses:
  • 100 mg twice daily (200 mg/day) 3, 4
  • 200 mg twice daily (400 mg/day) 3, 4
  • Maximum studied dose: 300 mg twice daily (600 mg/day) 3, 5

Titration should occur over 4-6 weeks to reach target maintenance dose, as this approach minimizes adverse events. 3, 5

Efficacy by Dose

All three dosages (200,400, and 600 mg/day) demonstrated significant efficacy compared to placebo:

• 200 mg/day: 34% of patients achieved ≥50% seizure reduction (vs 23% placebo) 2, 3
• 400 mg/day: 40% of patients achieved ≥50% seizure reduction with superior tolerability compared to 600 mg/day 2, 3
• 600 mg/day: Highest efficacy but associated with increased adverse events and discontinuation rates 3, 5

The 400 mg/day dose represents the optimal balance between efficacy and tolerability for most patients. 3, 4

Loading Dose Considerations

Loading doses for lacosamide have not been studied and are not recommended for routine use. 6, 1 The American College of Emergency Physicians guidelines explicitly state that while both oral and IV formulations are available and safe, loading dosage strategies lack evidence. 6, 1

For non-emergent situations, standard maintenance dosing should be initiated without a loading dose. 1

Route of Administration

Both oral and intravenous formulations are available and bioequivalent:

• Oral tablets and syrup are bioequivalent 2, 7
• IV infusions (15,30, or 60 minutes) provide similar bioavailability to oral administration at the same dose 2, 7
• IV lacosamide can serve as short-term replacement for oral therapy when needed 2, 7

The tolerability profile of IV lacosamide is consistent with oral administration, though local injection site reactions (discomfort, pain, irritation, erythema) may occur. 6, 7

Critical Safety Considerations

Abrupt discontinuation must be avoided as withdrawal seizures can occur with sudden cessation of lacosamide. 6, 1 This emphasizes the importance of consistent dosing and gradual tapering if discontinuation is necessary.

Most common adverse events are dose-related and include:

• Dizziness (30.6% vs 8.2% placebo) 5
• Nausea (11.4% vs 4.4% placebo) 5
• Diplopia (10.5% vs 1.9% placebo) 5
• Headache 7

These adverse events are predominantly mild to moderate in severity and occur more frequently during titration than maintenance phases. 5, 7 Slower titration over 4-6 weeks minimizes these effects. 3, 5

Discontinuation rates due to adverse events are dose-dependent:

• 200 mg/day: 8.1% 5
• 400 mg/day: 17.2% 5
• 600 mg/day: 28.6% 5

Small dose-related increases in PR interval have been observed, warranting caution in patients with cardiac conduction abnormalities. 6

Onset of Efficacy

Therapeutic benefit is evident by the first week of treatment, with sustained efficacy demonstrated up to 8 years in long-term studies. 3, 7 This early onset supports the standard titration approach without loading.

Concomitant Antiepileptic Drug Use

Lacosamide demonstrates efficacy regardless of concomitant AED regimen, with most patients (84.4%) taking 2-3 concurrent AEDs. 3, 5 Lacosamide has minimal drug-drug interactions due to low plasma protein binding and renal excretion. 4

Discontinuation rates varied by concomitant AED:

• Carbamazepine: 15.3% (vs 3.9% placebo) 5
• Lamotrigine: 19.2% (vs 4.3% placebo) 5
• Levetiracetam: 10.1% (vs 3.9% placebo) 5