Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain.

Abstract

BACKGROUND:

The 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.

OBJECTIVE:

To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. DesignMethods: The 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.

RESULTS:

Lacosamide 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).

CONCLUSIONS:

The 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.

• Authors: Carlos Casas-Fernández, Antonio Martínez-Bermejo, Miguel Rufo-Campos, Patricia Smeyers-Durá, José L Herranz-Fernández, Salvador Ibáñez-Micó, Jaume Campistol-Plana, Helena Alarcón-Martínez, Jaime Campos-Castelló
• Journal: Drugs in R&D (Drugs R D) Vol. 12 Issue 4 Pg. 187-97 (Dec 01 2012) ISSN: 1179-6901 [Electronic] New Zealand
• PMID: 23193979 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Anticonvulsants
• Lacosamide

Topics

• Acetamides (adverse effects, therapeutic use)
• Adolescent
• Anticonvulsants (adverse effects, therapeutic use)
• Child
• Child, Preschool
• Dose-Response Relationship, Drug
• Epilepsy (drug therapy)
• Female
• Humans
• Infant
• Lacosamide
• Male
• Observation
• Prospective Studies
• Spain
• Treatment Outcome