Efficacy and Tolerability of Lacosamide in the Concomitant Treatment of 130 Patients Under 16 Years of Age with Refractory Epilepsy

Abstract

BackgroundThe safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients.ObjectiveTo assess the efficacy and tolerability of lacosamide in children with refractory epilepsy.Design/MethodsThe trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT®; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1–2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ≥1 other AED. Treatment response to lacosamide was determined by assessing the change in seizure frequency after 3 months of lacosamide therapy. Responders were defined as patients who achieved a seizure frequency reduction of >50%. Tolerability was assessed by the reporting of adverse effects, laboratory testing, and electroencephalography recordings.ResultsLacosamide was dosed at a mean of 6.80 ± 2.39 mg/kg/day. After 3 months of lacosamide therapy, 62.3% of patients achieved a >50% reduction in seizure frequency, with complete seizure suppression being reported in 13.8% of patients. Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events. In ten patients, instability, difficulty walking, an inability to relate to subjective elements, and blurred vision or dizziness were reported. A total of 13 patients discontinued treatment — in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation. The symptoms were markedly different in each patient, preventing determination of a causal factor(s).ConclusionsThe results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy. Further evaluation in a randomized, controlled trial is needed to validate the efficacy in this population and to fully investigate the adverse effects described here. We recommend an initial dose of 1–2 mg/kg/day, uptitrated to 6–9 mg/kg/day over 4–6 weeks.

Efficacy and Tolerability of Lacosamide in the Treatment of Children With Refractory Generalized Epilepsy

“…The use of lacosamide in patients younger than 17 years with partial-onset epilepsy has been studied both retrospectively and prospectively in several centers and has had favorable results (Table 1). 6,7,10 –15 Lacosamide has also been used effectively in children with refractory status epilepticus as demonstrated by multicenter studies performed in Italy. 16,17 However the efficacy of lacosamide in generalized epilepsy both in adults and children appears to be less clear.…”

“…Casas-Fernandez et al 10 published 2 patients with Lennox–Gastaut syndrome who had a ≥50% reduction in focal seizure frequency with the addition of lacosamide. Two of the 4 patients with Lennox–Gastaut syndrome studied by Rastogi and Ng 20 had a greater than 90% reduction in seizure frequency, while the frequency in the other 2 patients was unchanged.…”

The effects of lacosamide in cerebral tuberculoma induced nonconvulsive status epilepticus: case report

“…[5] Lakozamid, Acetamido-N-benzyl-3-methoxypropionamide yapısında bir aminoasit olup etkisini voltaj-kapılı sodyum kanallarının yavaş inaktivasyonunu selektif olarak artırarak gösterir ve nöronların fizyolojik aktivitesinde değişiklik yapmadan patolojik hipereksitabilitesini azaltır. [6][7][8][9] Lineer farmakokinetik özelliği ile %100 oral biyoyararlanıma sahip, proteinlere düşük oranda bağlanan (<%15) fonksiyonelleştirilmiş bir aminoasit bileşimidir. Yarı ömrü 13 saat olup bir-iki saat içerisinde pik kan konsantrasyonuna ulaşır.…”

Lacosamide-induced atrial tachycardia in a child with hypoplastic left-heart syndrome: the importance of assessing additional proarrhythmic risks

“…Lacosamide is a newer antiepileptic drug composed of the functionalised amino-acid acetamido-N-benzyl-3-methoxypropionamide, which was approved for adjunctive therapy for partial onset seizures in epilepsy patients over 16 years of age 1 2 Lacosamide has been demonstrated to achieve its antiepileptic effect by selectively enhancing slow inactivation of voltage-gated sodium channels and interfering with collapsin-response mediator protein 2, reducing the number of sodium channels that can be recruited for subsequent action potentials.…”

“…Early studies have shown that lacosamide has a favourable side effect profile with side effects including dyspepsia, dizziness, headache, nausea, and vomiting 1 2 Cardiac effects are rare but have been documented in larger phase II trials as well as individual case reports and include atrioventricular block, atrial flutter/atrial fibrillation, and sinus node dysfunction 5 …”