Mechanism of Action of Intravenous Lacosamide
Intravenous lacosamide works by selectively enhancing slow inactivation of voltage-gated sodium channels, which differs fundamentally from traditional sodium channel blockers that primarily affect fast inactivation. 1, 2
Unique Mechanism of Action
Lacosamide selectively enhances sodium channel slow inactivation, distinguishing it from traditional sodium channel blockers like carbamazepine, oxcarbazepine, lamotrigine, and phenytoin, which primarily affect fast inactivation. 1, 2
This selective enhancement of slow inactivation results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological neuronal function. 2
The mechanism allows lacosamide to control seizure activity while preserving normal neuronal signaling, which contributes to its favorable tolerability profile compared to older sodium channel blockers. 2
Clinical Pharmacology
Lacosamide has a fast absorption rate with minimal or no interaction with cytochrome P-450 isoenzymes, resulting in a low potential for drug-drug interactions. 1, 2
Bioequivalence exists between oral and intravenous formulations, with the bioavailability of oral lacosamide tablets similar to that of 30- or 60-minute intravenous infusions administered at the same dosage. 3
Near steady-state plasma concentrations can be achieved with a single intravenous loading dose followed by oral maintenance therapy, allowing for rapid therapeutic effect. 4
Approved Indications and Dosing
Lacosamide is FDA-approved for treatment of partial-onset seizures in patients 1 month of age and older (both monotherapy and adjunctive therapy), and as adjunctive therapy for primary generalized tonic-clonic seizures in patients 4 years of age and older. 5
For adults (17 years and older), the recommended maintenance dose is 300-400 mg per day, with titration increments of 100 mg per day at weekly intervals. 5
Intravenous loading doses of 200 and 300 mg administered over 15 minutes followed by oral lacosamide are well tolerated in lacosamide-naive patients, though the 400 mg loading dose shows higher frequency of dose-related adverse events. 4
Safety Profile
The most common treatment-emergent adverse events include dizziness, headache, somnolence, nausea, and injection site pain or discomfort, with most being mild to moderate in severity. 6, 3, 7
Most adverse events occur within the first 4 hours following intravenous infusion, with dose-related effects including dizziness, somnolence, and nausea. 4
No clinically relevant changes in ECG parameters, clinical laboratory values, or vital signs have been observed with intravenous lacosamide administration. 4
Critical Clinical Considerations
Abrupt discontinuation of lacosamide can precipitate withdrawal seizures, necessitating gradual tapering when discontinuation is required. 6, 8
Lacosamide has minimal drug-drug interactions as a non-enzyme-inducing antiepileptic drug, making it particularly useful in patients taking multiple concomitant medications. 8, 9
Intravenous lacosamide serves as short-term replacement for oral lacosamide when oral administration is temporarily not feasible, with administration possible as 15-, 30-, or 60-minute infusions. 3, 7