What is the action of intravenous (IV) lacosamide in treating partial-onset seizures?

Mechanism of Action of Intravenous Lacosamide

Lacosamide exerts its antiepileptic effect through selective enhancement of slow inactivation of voltage-gated sodium channels, a mechanism distinct from traditional sodium channel blockers like phenytoin, carbamazepine, and lamotrigine that primarily affect fast inactivation. 1, 2, 3

Unique Pharmacologic Mechanism

• Lacosamide is a functionalized amino acid that selectively enhances slow inactivation of voltage-gated sodium channels, differentiating it from conventional antiepileptic drugs 1, 2, 3
• Traditional sodium channel blockers (carbamazepine, oxcarbazepine, lamotrigine, phenytoin) primarily affect fast inactivation, whereas lacosamide's action on slow inactivation represents a novel therapeutic approach 3
• This selective mechanism allows lacosamide to stabilize hyperexcitable neuronal membranes and prevent excessive repetitive firing without significantly affecting normal neuronal function 1

Clinical Pharmacology and Bioavailability

• The intravenous formulation demonstrates bioequivalence to oral lacosamide when administered at the same dosage, with 30- or 60-minute infusions producing similar plasma concentrations to oral tablets 1
• Lacosamide exhibits fast absorption, minimal interaction with cytochrome P450 isoenzymes, and low potential for drug-drug interactions, making it particularly suitable for patients on multiple concomitant medications 3, 2
• Near steady-state plasma concentrations can be achieved with a single intravenous loading dose, allowing for rapid therapeutic effect 4

Approved Indications and Administration

• Lacosamide IV is FDA-approved for treatment of partial-onset seizures in patients 1 month of age and older, and as adjunctive therapy for primary generalized tonic-clonic seizures in patients 4 years and older 5
• The IV formulation serves as short-term replacement (2-5 days) when oral administration is temporarily not feasible 6, 3
• Infusion durations as short as 15 minutes have been demonstrated safe for doses of 200-800 mg/day, with no increase in adverse events compared to longer infusion times 6

Dosing Strategy and Titration

• For non-emergent situations, initiate lacosamide at 100 mg/day (50 mg twice daily) and increase in weekly increments of 100 mg/day to target maintenance dose of 200-400 mg/day 7, 5
• Loading doses are not recommended for routine use according to American College of Emergency Physicians guidelines, though research demonstrates that IV loading doses of 200-300 mg over 15 minutes followed by oral maintenance are well tolerated 7, 4
• The 400 mg loading dose showed higher frequency of dose-related adverse events (dizziness, nausea, vomiting) with 16% discontinuation rate, making 200-300 mg loading doses preferable when rapid initiation is needed 4

Safety Profile and Adverse Effects

• Most treatment-emergent adverse events are mild to moderate in severity, with dizziness being the most common treatment-related adverse event 1, 2
• Common adverse effects (≥10% incidence) include diplopia, dizziness, headache, nausea, and somnolence 2, 6
• Injection-site events (discomfort, pain, irritation, erythema) are rare and not linked to infusion doses or rates 2, 6
• Small dose-related increases in PR interval have been observed, warranting caution in patients with cardiac conduction abnormalities 7

Critical Safety Warnings

• Abrupt discontinuation must be avoided as withdrawal seizures can occur with sudden cessation 7, 8
• No clinically relevant changes in ECG parameters, laboratory values, or vital signs were observed in clinical trials, though cardiac conduction monitoring remains prudent 4
• The tolerability profile of IV lacosamide is consistent with oral formulations, with most adverse events occurring within the first 4 hours following infusion 4

Comparative Advantages

• Lacosamide has minimal drug-drug interactions as a non-enzyme-inducing antiepileptic drug, making it safer than older agents when combined with other medications including steroids and cytotoxic agents 8, 9
• Limited effect of age and gender on plasma levels simplifies dosing across patient populations 3
• Both oral and IV formulations provide flexibility in clinical management, with demonstrated efficacy sustained for up to 8 years in long-term studies 2