Lacosamide for Partial-Onset Seizures
Recommended Treatment Protocol
Lacosamide is approved as adjunctive therapy for partial-onset seizures in adults and adolescents (16-18 years), with a standard dosing regimen starting at 100 mg twice daily and titrating to a maintenance dose of 200-400 mg/day, divided twice daily. 1
Standard Dosing Regimen
Initial Dosing and Titration
- Start with 100 mg twice daily (200 mg/day) 1
- Increase by 50 mg twice daily (100 mg/day) at weekly intervals 1
- Target maintenance dose: 200-400 mg/day (100-200 mg twice daily) for adjunctive therapy 1
- For monotherapy in partial-onset seizures, the maintenance dose is 300-400 mg/day (150-200 mg twice daily) 1
Accelerated Loading Protocol
For patients requiring faster therapeutic levels, an alternate loading regimen can be used: 1
- Single loading dose of 200 mg 1
- 12 hours later, initiate 100 mg twice daily 1
- Continue weekly titration by 50 mg twice daily increments as needed 1
- This loading approach requires medical supervision due to increased risk of CNS and cardiovascular adverse effects 1
Formulation Options
Oral vs. Intravenous Administration
- Both oral and IV formulations are bioequivalent and have consistent tolerability profiles 2, 1
- IV lacosamide is approved for temporary conversion from oral therapy when oral administration is not feasible 1, 3
- The 30- or 60-minute IV infusion provides similar bioavailability to oral tablets at the same dosage 3
- Adverse effects are mild to moderate with both routes, including dizziness, headache, back pain, somnolence, and injection site pain with IV administration 2
Efficacy Data
Seizure Reduction Outcomes
- Lacosamide 400 mg/day produces a median 37.3-37.8% reduction in seizure frequency compared to 20.8% with placebo 4
- Responder rates (≥50% seizure reduction) are 38-41% with lacosamide 400-600 mg/day versus 18% with placebo 4
- Particularly effective for secondarily generalized tonic-clonic seizures, with median reductions of 59.4% at 400 mg/day and 93.0% at 600 mg/day 4
- Doses above 400 mg/day provide minimal additional benefit but substantially higher adverse event rates 1
Safety Profile and Adverse Effects
Common Adverse Events
- Dizziness (30.6%), nausea (11.4%), and diplopia (10.5%) are the most common drug-related adverse effects 5
- These adverse effects are dose-related and occur predominantly during titration rather than maintenance 5
- Most adverse events are mild to moderate in severity 2, 5
- Severe adverse events are predominantly observed with the 600 mg/day dose 5
Cardiovascular Considerations
- Small dose-related increases in PR interval have been observed 6
- Monitor for cardiac conduction abnormalities, particularly in patients with pre-existing cardiac disease 6
Neurological Effects
- Lacosamide may impair driving ability due to CNS effects 6
- Patients must be counseled about potential driving impairment, especially during initiation or dose changes 6
- Cognitive-related adverse events show similar odds ratios to placebo at 200-400 mg/day doses 5
Special Population Dosing Adjustments
Renal Impairment
- No adjustment needed for mild to moderate renal impairment 1
- For severe renal impairment (CrCl <30 mL/min) or end-stage renal disease: reduce maximum dose by 25% 1
- Following 4-hour hemodialysis: consider dosage supplementation up to 50% 1
Hepatic Impairment
- For mild or moderate hepatic impairment: reduce maximum dose by 25% 1
- Not recommended in severe hepatic impairment 1
Pregnancy Management
- Pregnant women with well-controlled seizures should continue lacosamide, as seizure recurrence risks outweigh potential medication risks 7
- Seizure control is critical for reducing maternal and fetal morbidity and mortality 7
- Abrupt discontinuation can precipitate breakthrough seizures with significant risks to mother and fetus 7
- Maintain current dosage rather than tapering if seizures remain controlled throughout pregnancy 7
Drug Interactions
Concomitant AED Considerations
- Lacosamide has no major drug interactions and exhibits linear kinetics 8
- Discontinuation rates due to adverse events vary by concomitant AED: carbamazepine (15.3%), lamotrigine (19.2%), levetiracetam (10.1%) 5
- Dose reduction may be necessary in patients with renal or hepatic impairment taking strong CYP3A4 or CYP2C9 inhibitors 1
Conversion to Monotherapy
Transitioning from Adjunctive Therapy
- When converting from a single AED to lacosamide monotherapy, achieve therapeutic lacosamide dosage first 1
- Maintain therapeutic lacosamide dose for at least 3 days before beginning AED withdrawal 1
- Gradually withdraw the concomitant AED over at least 6 weeks 1
Discontinuation Protocol
Tapering Recommendations
- When discontinuing lacosamide, taper gradually over at least 1 week 1
- Abrupt discontinuation may precipitate seizures 6
Common Pitfalls to Avoid
- Failing to provide medical supervision during loading dose administration increases risk of CNS and cardiovascular adverse reactions 1
- Using doses above 400 mg/day routinely—this provides minimal additional efficacy with substantially higher adverse event rates 1
- Not warning patients about driving impairment, particularly during treatment initiation 6
- Abruptly discontinuing lacosamide in pregnancy, which precipitates breakthrough seizures carrying higher risks than continuing medication 7
- Changing to another AED during pregnancy when seizures are already well-controlled introduces unnecessary risks 7