PMID- 28284045
OWN - NLM
STAT- MEDLINE
DCOM- 20170417
LR  - 20171116
IS  - 1532-2688 (Electronic)
IS  - 1059-1311 (Linking)
VI  - 47
DP  - 2017 Apr
TI  - Dosing considerations for rufinamide in patients with Lennox-Gastaut syndrome: 
      Phase III trial results and real-world clinical data.
PG  - 25-33
LID - S1059-1311(17)30126-7 [pii]
LID - 10.1016/j.seizure.2017.02.008 [doi]
AB  - PURPOSE: 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.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Kothare, Sanjeev
AU  - Kothare S
AD  - 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.
FAU - Kluger, Gerhard
AU  - Kluger G
AD  - 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.
FAU - Sachdeo, Rajesh
AU  - Sachdeo R
AD  - Jersey Shore University Medical Center, 1945 NJ-33, Neptune, NJ 07753, USA. 
      Electronic address: drsachdeo@gmail.com.
FAU - Williams, Betsy
AU  - Williams B
AD  - Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, 
      Woodcliff Lake, NJ 07677, USA. Electronic address: Betsy_Williams@eisai.com.
FAU - Olhaye, Omar
AU  - Olhaye O
AD  - Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, 
      Woodcliff Lake, NJ 07677, USA. Electronic address: Omar_Olhaye@eisai.com.
FAU - Perdomo, Carlos
AU  - Perdomo C
AD  - Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, 
      Woodcliff Lake, NJ 07677, USA. Electronic address: Carlos_Perdomo@eisai.com.
FAU - Bibbiani, Francesco
AU  - Bibbiani F
AD  - Eisai Global Neuroscience Business Unit, Eisai Inc., 100 Tice Boulevard, 
      Woodcliff Lake, NJ 07677, USA. Electronic address: Francesco_Bibbiani@eisai.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170217
PL  - England
TA  - Seizure
JT  - Seizure
JID - 9306979
RN  - 0 (Anticonvulsants)
RN  - 0 (Triazoles)
RN  - WFW942PR79 (rufinamide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anticonvulsants/*administration & dosage/adverse effects
MH  - Child
MH  - Child, Preschool
MH  - Clinical Trials, Phase III as Topic
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Humans
MH  - Lennox Gastaut Syndrome/*drug therapy
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
MH  - Triazoles/*administration & dosage/adverse effects
MH  - Young Adult
OTO - NOTNLM
OT  - Antiepileptic drug
OT  - Dosing
OT  - Epilepsy
OT  - Lennox-Gastaut syndrome
OT  - Rufinamide
EDAT- 2017/03/12 06:00
MHDA- 2017/04/18 06:00
CRDT- 2017/03/12 06:00
PHST- 2016/08/12 00:00 [received]
PHST- 2017/01/13 00:00 [revised]
PHST- 2017/02/16 00:00 [accepted]
PHST- 2017/03/12 06:00 [pubmed]
PHST- 2017/04/18 06:00 [medline]
PHST- 2017/03/12 06:00 [entrez]
AID - S1059-1311(17)30126-7 [pii]
AID - 10.1016/j.seizure.2017.02.008 [doi]
PST - ppublish
SO  - Seizure. 2017 Apr;47:25-33. doi: 10.1016/j.seizure.2017.02.008. Epub 2017 Feb 17.