Lacosamide Dosing for Adults
For adults with partial-onset seizures, initiate lacosamide at 100 mg/day (50 mg twice daily) and titrate weekly by 100 mg/day increments to a maintenance dose of 200-400 mg/day based on efficacy and tolerability, with 400 mg/day providing the optimal balance of seizure control and side effects. 1, 2, 3
Standard Oral Dosing Regimen
- Starting dose: 100 mg/day administered as 50 mg twice daily 4, 5
- Titration schedule: Increase by 100 mg/day weekly increments 3, 5
- Maintenance dose range: 200-400 mg/day divided into twice-daily dosing 2, 3, 4
- Maximum approved dose: 400 mg/day 4
The 400 mg/day dose demonstrates significant efficacy with median seizure frequency reductions of 37-39% compared to 10-21% for placebo, and achieves 50% responder rates of 38-41% 3, 5. While 600 mg/day has been studied and shows similar efficacy, it is associated with substantially higher discontinuation rates (28.6% vs 17.2% at 400 mg/day) due to dose-related adverse events 2.
Intravenous Loading Dose Option
For patients requiring rapid therapeutic initiation:
- Loading dose: 200-300 mg IV infused over 15 minutes 1
- Maintenance: Begin oral dosing 12 hours after loading dose at one-half the loading dose given twice daily 1
- Avoid 400 mg loading dose: Associated with 16% discontinuation rate within 4 hours due to dizziness, nausea, and vomiting 1
The IV and oral formulations have equivalent tolerability profiles when loading doses are not used 6. Near steady-state plasma concentrations are achieved with a single IV loading dose 1.
Titration Flexibility for Sensitive Patients
- Intermediate doses (e.g., 150 mg/day, 250 mg/day) may be used for one week at each escalation step in patients known to be sensitive to new antiepileptic drugs 4
- Most treatment-emergent adverse events occur during titration rather than maintenance phases 2, 5
Common Dose-Related Adverse Events
The most frequent side effects (≥5% incidence and twice that of placebo) include:
These adverse events are dose-dependent and predominantly mild-to-moderate in severity, with most occurring during titration 2, 3, 5. Severe adverse events are predominantly observed at 600 mg/day 2.
Critical Pitfalls to Avoid
- Do not exceed 400 mg/day in routine practice: The 600 mg/day dose offers minimal additional efficacy benefit but substantially increases adverse events and discontinuation rates 2, 3
- Avoid rapid IV loading doses ≥400 mg: Associated with unacceptable early discontinuation rates 1
- Monitor closely during titration: Most adverse events and discontinuations occur during dose escalation rather than maintenance 2, 5
- Consider concomitant AEDs: Discontinuation rates due to adverse events vary by concomitant therapy (carbamazepine 15.3%, lamotrigine 19.2%, levetiracetam 10.1%) 2
Drug Interactions
Lacosamide does not affect plasma concentrations of concomitantly administered antiepileptic drugs, indicating minimal pharmacokinetic interactions 5.