Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures

Abstract

Purpose: Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200-800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures.

Methods: This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2-5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations.

Results: A total of 160 patients received lacosamide 200-800 mg/day, i.v., for 2-5 days, of which 69% received 400-800 mg/day doses. The most common AEs (reported by <or=10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (>or=400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts.

Discussion: This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2-5 days) replacement for patients temporarily unable to take oral lacosamide.

Trial registration: ClinicalTrials.gov NCT00151879.