Efficacy and Tolerability of Rufinamide in Epileptic Children Younger Than 4 Years

Abstract

Background: Rufinamide, a triazole derivative, is a new-generation antiseizure medication with a novel mechanism of action. We evaluated the efficacy and safety of rufinamide treatment in children with epilepsy younger than 4 years at our center. Methods: In this retrospective study, we included children younger than 4 years who had pharmacologically resistant epilepsy and were treated with rufinamide at Boston Children’s Hospital between June 2010 and June 2018. Safety and efficacy of rufinamide treatment were assessed immediately prior to initiation of rufinamide and at the last follow-up visit. Responders were defined as patients who had greater than 50% reduction in seizure frequency on follow-up as compared to baseline. Results: We reviewed records of 128 children and included 103 with complete information. Patients consisted of 60 boys (58%), with a median age of 20 months (interquartile range 13-28, range 2-36). Median treatment duration was 15 months, and median rufinamide dosage at the last follow-up was 42 mg/kg/d (interquartile range 34-56). At the last follow-up, seizure frequency decreased (450 vs 90, P<.001) and overall seizure reduction was 54%. Fifty-one patients (49.5%) were responders with 94% seizure reduction, including 20 (19.4%) who achieved seizure freedom. Treatment retention rate at 12 months was 63%. Thirty patients (29%) developed adverse events and 41 patients (39.8%) discontinued rufinamide because of adverse events (15; 14.5%) and lack of efficacy (26; 25%). Conclusion: Rufinamide is effective in reducing seizure frequency in pediatric epilepsy patients younger than 4 years, and overall well tolerated.

Pharmacologic and Dietary Treatments for Epilepsies in Children Aged 1–36 Months

“…The study performed a prestudy/poststudy of 103 infants (median age 20 months at treatment initiation) treated with rufinamide (median dose 42 mg/kg/d at the last follow-up, which occurred at median of 15 months). 33 At a median of 15 months of treatment, 19% (20/103) were seizure-free, and 50% (51/103) experienced ≥50% reduction in seizure frequency. The median percentage reduction in seizures was 54% (from ∼167/mo at baseline to 90/mo at follow-up).…”

THETA as an Efficient Cu-Binding Ligand for Manual and Automated “Click” Synthesis: the Rufinamide Case

“…3,4 Rufinamide was approved by the FDA in 2008, as an adjunctive treatment for severe epilepsy disorders, and in 2015, its approval for pediatric patients followed. 5 At present, rufinamide is one of only 7 drugs approved for Lennox−Gastaut syndrome treatment. 6 The synthesis of rufinamide has served as a testing ground for modern organic synthesis technologies, including flow chemistry, 7−9 mechanochemistry 10−12 and automated synthesis.…”

“…However, this transformation has not been adequately reflected in the number of approved medications. So far, the only approved small molecule drug featuring the 1,2,3-triazole structure is rufinamide {1-[(2,6-difluorophenyl)methyl]-1 H -1,2,3-triazole-4-carboxamide}, 6 (Figure ), an anticonvulsant used in the treatment of Lennox–Gastaut syndrome, a rare and severe epilepsy that typically manifests at an early age. , Rufinamide was approved by the FDA in 2008, as an adjunctive treatment for severe epilepsy disorders, and in 2015, its approval for pediatric patients followed . At present, rufinamide is one of only 7 drugs approved for Lennox–Gastaut syndrome treatment …”