title: Dosing considerations for rufinamide in patients with Lennox-Gastaut syndrome: Phase III trial results and real-world clinical data.
abstract: OBJECTIVE
  Lennox-Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, rufinamide dosing and titration may differ from the trial setting. Here, rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies.
  
  
  METHODS
  Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared.
  
  
  RESULTS
  Results demonstrated that a rapid titration schedule (7 or 14 days) of rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic-atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study - somnolence, vomiting, and pyrexia - occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings.
  
  
  CONCLUSIONS
  A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of rufinamide in LGS.
authors.affiliation: Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Medical Center, 223 East 34th Street, New York, NY 10016, USA. Electronic address: sanjeev.kothare@nyumc.org.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kothare
authors.affiliation: Neuropaediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Centre for Children and Adolescents, Schoen Klinik Vogtareuth Krankenhausstrasse, 20 D-83569 Vogtareuth, Germany; Paracelsus Medical University Salzburg, Salzburg, Austria. Electronic address: GKluger@Schoen-Kliniken.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kluger
authors.affiliation: Jersey Shore University Medical Center, 1945 NJ-33, Neptune, NJ 07753, USA. Electronic address: drsachdeo@gmail.com.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sachdeo
authors.affiliation: Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Electronic address: Betsy_Williams@eisai.com.
authors.forename: Betsy
authors.initials: B
authors.lastname: Williams
authors.affiliation: Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Electronic address: Omar_Olhaye@eisai.com.
authors.forename: Omar
authors.initials: O
authors.lastname: Olhaye
authors.affiliation: Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Electronic address: Carlos_Perdomo@eisai.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Electronic address: Francesco_Bibbiani@eisai.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bibbiani
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D065768:Lennox Gastaut Syndrome / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide
keywords: Antiepileptic drug; Dosing; Epilepsy; Lennox–Gastaut syndrome; Rufinamide