What is the role of lacosamide in seizure prevention?

Role of Lacosamide in Seizure Prevention

Lacosamide is an effective adjunctive therapy for partial-onset seizures, with both oral and intravenous formulations showing good tolerability and efficacy in reducing seizure frequency when added to existing antiepileptic drug regimens. 1, 2

Mechanism of Action and Efficacy

• Lacosamide is a novel antiepileptic medication that works by selectively enhancing slow inactivation of voltage-gated sodium channels, a different mechanism than traditional sodium channel blockers 3
• Clinical trials demonstrate significant efficacy as adjunctive therapy, with 200-400 mg/day doses showing 35-36% median reduction in seizure frequency compared to 20.5% with placebo 2
• The 50% responder rate (proportion of patients experiencing ≥50% reduction in seizures) was 40.5% for lacosamide 400 mg/day, significantly higher than placebo (25.8%) 2
• Both oral and intravenous formulations have similar bioavailability, allowing for flexibility in administration 4

Clinical Applications

• Lacosamide is primarily indicated as adjunctive therapy for partial-onset seizures in adults 1
• It has become increasingly used as an add-on treatment for patients whose seizure disorder is not controlled by monotherapy 1
• The drug has demonstrated efficacy when combined with both traditional sodium channel-blocking antiepileptics (carbamazepine, lamotrigine, oxcarbazepine, phenytoin) and other classes of antiepileptic drugs 5
• In patients not taking traditional sodium channel blockers, lacosamide showed a pronounced dose-related seizure reduction, suggesting potential synergistic effects with certain drug combinations 5

Administration and Dosing

• Available in both oral and intravenous formulations with bioequivalence between routes 4
• Typical dosing ranges from 200-400 mg/day for adults 2
• In emergency settings, IV lacosamide can be administered at rates up to 60 mg/kg with good tolerability 6
• The tolerability profile of IV lacosamide is consistent with oral administration 1

Safety Profile

• Most common adverse effects include dizziness, headache, nausea, somnolence, and injection site pain (with IV formulation) 1, 2
• Adverse effects are generally dose-related but mild to moderate in severity 2
• Small dose-related increases in PR interval have been reported, requiring cardiac monitoring in some patients 1
• Lacosamide has minimal protein binding and few clinically relevant drug-drug interactions 3
• In the United States, lacosamide is classified as a Schedule V controlled substance 1

Special Considerations

• Lacosamide is preferred over older antiepileptic drugs like phenytoin, phenobarbital, and carbamazepine due to its better side effect profile and fewer drug interactions 1
• It should not be abruptly discontinued due to risk of withdrawal seizures 1
• While primarily studied in adults, emerging data suggests efficacy in pediatric populations with status epilepticus, with a loading dose of approximately 10 mg/kg showing efficacy and safety 6

Limitations and Considerations

• Despite approval for epilepsy treatment, lacosamide was not approved for the treatment of painful diabetic peripheral neuropathy despite extensive studies in this area 1
• A clinical trial investigating lacosamide for seizure prevention in patients with malignant glioma (NCT01432171) was terminated early, highlighting the need for more definitive randomized trials in specific populations 1