What is the role of Lacosamide (generic name) in treating partial-onset seizures?

Lacosamide for Partial-Onset Seizures

Lacosamide is an effective adjunctive antiepileptic drug for partial-onset seizures, available in both oral and intravenous formulations, with demonstrated efficacy in reducing seizure frequency by approximately 37-38% compared to placebo. 1

Mechanism and Pharmacology

• Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, distinguishing it from other sodium channel blockers 2, 3
• The drug is renally excreted, minimally protein-bound, and has no clinically relevant drug-drug interactions 3
• This favorable pharmacokinetic profile makes it suitable for patients on multiple concomitant antiepileptic drugs 2

Efficacy Data

• In randomized controlled trials, lacosamide 400 mg/day and 600 mg/day reduced seizure frequency by 37.3% and 37.8% respectively, compared to 20.8% for placebo 1
• Responder rates (≥50% seizure reduction) were 38.3% for 400 mg/day and 41.2% for 600 mg/day, versus 18.3% for placebo 1
• Particularly impressive reductions occurred in secondarily generalized tonic-clonic seizures: 59.4% reduction with 400 mg/day and 93.0% with 600 mg/day, compared to 14.3% for placebo 1
• Meta-analysis confirms lacosamide increases the 50% responder rate with a relative risk of 1.68 (95% CI 1.36-2.08) 4
• Long-term efficacy is sustained for up to 8 years of treatment 2

Dosing Strategy

Oral Initiation

• Start at 50 mg twice daily (100 mg/day total) 5
• Increase by 50 mg twice daily (100 mg/day total) at weekly intervals 5
• Target maintenance dose is 200-400 mg daily in divided doses 6, 5
• The 400 mg/day dose provides optimal balance of efficacy and tolerability; 600 mg/day may benefit select patients with refractory seizures 1

Intravenous Administration

• Both oral and IV formulations are available and demonstrate equivalent safety profiles 6
• IV lacosamide can be infused over 15-30 minutes as short-term replacement for oral dosing 7, 2
• Infusion durations as short as 15 minutes are safe for 2-5 days of treatment 7
• The tolerability profile of IV lacosamide is consistent with oral administration 6, 7

Critical Safety Monitoring

Cardiovascular Concerns

• Obtain baseline ECG before initiating lacosamide, as dose-related PR interval prolongation occurs 5, 8
• Monitor for cardiac conduction abnormalities, particularly in patients with pre-existing cardiac disease 5
• Small dose-related increases in PR interval have been documented 8

Renal Considerations

• Dose adjustment is required in severe renal disease due to renal excretion 5

Common Adverse Effects

• Most frequent adverse events are dizziness, headache, nausea, and somnolence 6, 7, 2
• Adverse events are dose-related, occurring more frequently with doses ≥400 mg/day 7
• Discontinuation due to adverse events occurs at a rate 3.13 times higher than placebo (95% CI 1.94-5.06) 4
• Injection site reactions with IV administration are rare and include discomfort, pain, irritation, and erythema 2

Special Populations

Pregnancy

• Pregnant women with well-controlled epilepsy should continue lacosamide, as seizure control takes priority over theoretical medication risks 9
• Discontinuation risks breakthrough seizures, which pose greater maternal and fetal harm than continuing medication 9
• Regular monitoring throughout pregnancy is essential to assess seizure control 9
• Maintain current dosage if seizures remain controlled rather than attempting to taper 9

Driving and CNS Effects

• Counsel patients about potential driving impairment, particularly during initiation or dose changes 8
• Lacosamide may impair driving ability due to central nervous system effects 8

Critical Pitfalls to Avoid

• Never abruptly discontinue lacosamide, as withdrawal seizures can occur despite its pharmacokinetic properties 5, 8
• When tapering is necessary, reduce by 2 mg decrements at 1-2 week intervals 5
• Do not use oral tablets for loading in the emergency department, as absorption is unreliable; loading dosages have not been adequately studied 6
• Failing to obtain baseline ECG before initiation misses the opportunity to identify pre-existing conduction abnormalities 5
• Changing antiepileptic medications during pregnancy when seizures are well-controlled introduces unnecessary risks 9

Role in Emergency Department Management

• Lacosamide is not recommended for acute seizure management or loading in the ED setting 6
• Loading dosages have not been studied for seizure recurrence prevention 6
• When resuming chronic therapy in the ED is appropriate, both oral and IV formulations are safe options 6
• The drug is indicated specifically for partial-onset seizures, not for acute convulsive status epilepticus 6