title: Rufinamide from clinical trials to clinical practice in the United States and Europe.
abstract: Rufinamide is a triazole derivative structurally unrelated to other antiepileptic drugs that is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4 years. Originally granted orphan drug status, marketing authorisation was obtained on the basis of a randomised, double-blind, placebo-controlled trial conducted in 138 LGS patients. An open-label extension study subsequently demonstrated that rufinamide's efficacy and tolerability were maintained over the longer term (median duration of treatment, 432 days). Recently published reports from Europe and the United States have described the use of adjunctive rufinamide to treat LGS in clinical practice. These data complement the clinical trial results, by providing information on the efficacy and tolerability of rufinamide when used on an individualised basis in real-world practice, under less tightly restricted conditions in terms of patient population and dosing strategies. A comparison of the data reveals that a "lower and slower" dosing strategy tends to be adopted in clinical practice, in comparison with the clinical trial, which does not appear to compromise efficacy, but may provide improvements in tolerability. Individual case reports provide additional valuable information on how rufinamide is being used to treat different seizure types associated with LGS. Since clinical experience with rufinamide is currently at an early stage, there are still unanswered questions relating to its use, and it is likely that its place in the adjunctive treatment of LGS will evolve as further data emerge.
authors.affiliation: Department of Neurology, Miami Children's Hospital, Miami, Florida 33155, USA. Trevor.Resnick@mch.com
authors.forename: Trevor
authors.initials: T
authors.lastname: Resnick
authors.forename: Alexis
authors.initials: A
authors.lastname: Arzimanoglou
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Brown
authors.forename: Robert
authors.initials: R
authors.lastname: Flamini
authors.forename: Michael
authors.initials: M
authors.lastname: Kerr
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kluger
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kothare
authors.forename: Sunny
authors.initials: S
authors.lastname: Philip
authors.forename: Miranda
authors.initials: M
authors.lastname: Harrison
authors.forename: Milind
authors.initials: M
authors.lastname: Narurkar
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005060:Europe; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy* / Q000503:physiopathology; D065768:Lennox Gastaut Syndrome; D016032:Randomized Controlled Trials as Topic; D012640:Seizures / Q000188:drug therapy*; D013036:Spasms, Infantile / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D014481:United States
chemical_list: D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide