Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures AUTHORS: Nathan B. Fountain, Gregory Krauss, Jouko Isojarvi, Deanne Dilley, Pamela Doty, and G. David Rudd JOURNAL: Epilepsia FULL REFERENCE: Epilepsia. 2013 Jan; 54(1) : 58-65 • First trial (Phase IIIb, multicenter, open-label) to examine feasibility of administering a single loading dose of adjunctive lacosamide in lacosamide-naive patients with uncontrolled partial-onset seizures • Participants were enrolled into one of four sequential cohorts (n=25 each). Following completion of the first cohort, a data monitoring committee (DMC) determined if it was acceptable to enroll new patients into a subsequent cohort. If reached, the fourth (final) cohort was to repeat the loading dose determined to be the highest dose with clinically acceptable safety results • Primary outcome variables were treatment-emergent adverse events (TEAEs) and patient withdrawals due to TEAEs • The DMC determined that loading doses of lacosamide 200 and 300 mg* administered over 15 min were tolerated best, and the 300 mg* dose was selected as the infusion dose for the repeat cohort (n=50 for the 300 mg cohort) • Ninety-three of the 100 enrolled patients in the Safety Set completed the 7-day trial; of the 7 who discontinued prematurely due to TEAEs, 4 opted to enter the open-label extension trial • Most TEAEs occurred within 4 h of infusion start and are reasonably attributed to the infusion, either from the rapidity of infusion or the dose. In the 4–12 h interval, the overall incidence of TEAEs was <5% for all events, suggesting that the events occurring early were related to infusion and were time limited • TEAEs reported during this trial were consistent in nature with those reported in the double-blind, placebo-controlled trials; however, incidence of CNS adverse reactions such as dizziness may be higher after a loading dose • Results of this trial supported the approval of the following addition to the SPC of lacosamide Lacosamide treatment may also be initiated with a single loading dose of 200 mg, followed approximately 12 hours later by a 100 mg twice daily (200 mg/day) maintenance dose regimen. A loading dose may be initiated in patients in situations when the physician determines that rapid attainment of lacosamide steady state plasma concentration and therapeutic effect is warranted. It should be administered under medical supervision with consideration of the potential for increased incidence of central nervous system adverse reactions. Administration of a loading dose has not been studied in acute conditions such as status epilepticus *The maximum approved loading dose of lacosamide is 200 mg