Download PDF
Journal of Pediatric Epilepsy 2017; 06(02): 103-110
DOI: 10.1055/s-0037-1599190
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effectiveness and Tolerability of Rufinamide in Children and Young People: A Survey of Experience from the United Kingdom

Hui Jeen Tan
1   Department of Paediatric Neurology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
,
Mostafa Awadh
2   Department of Neurology, Ain Shams University Hospital, Cairo, Egypt
3   Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children (Yorkhill), Glasgow, United Kingdom
,
Mary O'Regan
3   Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children (Yorkhill), Glasgow, United Kingdom
,
Timothy R. Martland
1   Department of Paediatric Neurology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
,
Rachel Kneen
4   The Roald Dahl EEG Unit, Department of Neurology, Royal Liverpool Children's (Alder Hey) NHS Foundation Trust, Liverpool, United Kingdom
5   Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
› Author Affiliations
Further Information

Publication History

12 May 2016

21 December 2016

Publication Date:
16 March 2017 (online)

    Permissions and Reprints

Abstract

The purpose of this study was to collate information on the clinical use of rufinamide in a pediatric population with epilepsy. A standardized proforma was sent to a group of pediatric neurologists and pediatricians in the United Kingdom requesting information about patients who were prescribed rufinamide. A total of 76 patients, with a median (range) age of 10.2 (2.8–19.8) years, were included. The patients had heterogeneous epilepsy syndromes, including 30 (39.5%) with Lennox-Gastaut syndrome (LGS), refractory to a minimum of three previous antiepileptic drugs. The median (range) maintenance dose of rufinamide was 25.4 (6.3–60) mg/kg/d. After 3 months of treatment, two (2.6%) of the 76 patients became seizure free, and 21 (27.6%) had ≥ 50% reduction in seizure frequency. The median (range) duration of treatment was 4.2 (0.5–38.4) months. At the last follow-up, 15 (19.7%) of the 76 patients continued with ≥ 50% reduction in seizure frequency; 2 of whom remained seizure free. Eighteen (23.7%) patients had treatment-emergent unwanted effects contributing to its discontinuation in nine (11.8%). In this study of a heterogeneous group of children and young people with medically refractory epilepsy on rufinamide, there was ≥ 50% seizure reduction in 30% at 3 months and 20% at the last follow-up.

Keywords

rufinamide - children - epilepsy
 

  • References

  • 1 McLean MJ, Schmutz M, Pozza M, Wamil A. The influence of rufinamide on sodium currents and action potential firing in rodent neurons. Epilepsia 2005; 46 (Suppl. 08) 296-296
    PubMedGoogle Scholar
  • 2 White HS, Franklin MR, Kupferberg HJ, Schmutz M, Stables JP, Wolf HH. The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models. Epilepsia 2008; 49 (7) 1213-1220
    CrossrefPubMedGoogle Scholar
  • 3 Hakimian S, Cheng-Hakimian A, Anderson GD, Miller JW. Rufinamide: a new anti-epileptic medication. Expert Opin Pharmacother 2007; 8 (12) 1931-1940
    CrossrefPubMedGoogle Scholar
  • 4 Perucca E, Cloyd J, Critchley D, Fuseau E. Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia 2008; 49 (7) 1123-1141
    CrossrefPubMedGoogle Scholar
  • 5 Paediatric Formulary Committee. British National Formulary for Children. London, UK: British Medical Journal Group, Pharmaceutical Press, and Royal College of Paediatrics and Child Health Publications; 2014
    Google Scholar
  • 6 Mohanraj R, Brodie MJ. Measuring the efficacy of antiepileptic drugs. Seizure 2003; 12 (7) 413-443
    CrossrefPubMedGoogle Scholar
  • 7 Biton V, Krauss G, Vasquez-Santana B , et al. A randomized, double-blind, placebo-controlled, parallel-group study of rufinamide as adjunctive therapy for refractory partial-onset seizures. Epilepsia 2011; 52 (2) 234-242
    PubMedGoogle Scholar
  • 8 Brodie MJ, Rosenfeld WE, Vazquez B , et al. Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. Epilepsia 2009; 50 (8) 1899-1909
    CrossrefPubMedGoogle Scholar
  • 9 Elger CE, Stefan H, Mann A, Narurkar M, Sun Y, Perdomo C. A 24-week multicenter, randomized, double-blind, parallel-group, dose-ranging study of rufinamide in adults and adolescents with inadequately controlled partial seizures. Epilepsy Res 2010; 88 (2–3): 255-263
    CrossrefPubMedGoogle Scholar
  • 10 Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008; 70 (21) 1950-1958
    CrossrefPubMedGoogle Scholar
  • 11 Ohtsuka Y, Yoshinaga H, Shirasaka Y, Takayama R, Takano H, Iyoda K. Rufinamide as an adjunctive therapy for Lennox-Gastaut syndrome: a randomized double-blind placebo-controlled trial in Japan. Epilepsy Res 2014; 108 (9) 1627-1636
    CrossrefPubMedGoogle Scholar
  • 12 Dahlin MG, Ohman I. Rufinamide in children with refractory epilepsy: pharmacokinetics, efficacy, and safety. Neuropediatrics 2012; 43 (5) 264-270
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Joseph JR, Schultz RJ, Wilfong AA. Rufinamide for refractory epilepsy in a pediatric and young adult population. Epilepsy Res 2011; 93 (1) 87-89
    CrossrefPubMedGoogle Scholar
  • 14 Kluger G, Kurlemann G, Haberlandt E , et al. Effectiveness and tolerability of rufinamide in children and adults with refractory epilepsy: first European experience. Epilepsy Behav 2009; 14 (3) 491-495
    CrossrefPubMedGoogle Scholar
  • 15 Thome-Souza S, Kadish NE, Ramgopal S , et al. Safety and retention rate of rufinamide in 300 patients: a single pediatric epilepsy center experience. Epilepsia 2014; 55 (8) 1235-1244
    CrossrefPubMedGoogle Scholar
  • 16 Vendrame M, Loddenkemper T, Gooty VD , et al. Experience with rufinamide in a pediatric population: a single center's experience. Pediatr Neurol 2010; 43 (3) 155-158
    CrossrefPubMedGoogle Scholar
  • 17 Coppola G, Zamponi N, Kluger G , et al. Rufinamide for refractory focal seizures: an open-label, multicenter European study. Seizure 2013; 22 (1) 33-36
    CrossrefPubMedGoogle Scholar
  • 18 Moavero R, Cusmai R, Specchio N , et al. Rufinamide efficacy and safety as adjunctive treatment in children with focal drug resistant epilepsy: the first Italian prospective study. Epilepsy Res 2012; 102 (1–2): 94-99
    CrossrefPubMedGoogle Scholar
  • 19 Kim SH, Lee JH, Ryu HW , et al. Short-term efficacy and tolerability of rufinamide adjunctive therapy in children with refractory generalised epilepsy. Epileptic Disord 2013; 15 (1) 49-54
    PubMedGoogle Scholar
  • 20 Coppola G, Grosso S, Franzoni E , et al. Rufinamide in children and adults with Lennox-Gastaut syndrome: first Italian multicenter experience. Seizure 2010; 19 (9) 587-591
    CrossrefPubMedGoogle Scholar
  • 21 Kim SH, Eun SH, Kang HC , et al. Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome. Seizure 2012; 21 (4) 288-291
    CrossrefPubMedGoogle Scholar
  • 22 Kluger G, Glauser T, Krauss G, Seeruthun R, Perdomo C, Arroyo S. Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study. Acta Neurol Scand 2010; 122 (3) 202-208
    CrossrefPubMedGoogle Scholar
  • 23 Lee EH, Yum MS, Ko TS. Effectiveness and tolerability of rufinamide in children and young adults with Lennox-Gastaut syndrome: a single center study in Korea. Clin Neurol Neurosurg 2013; 115 (7) 926-929
    CrossrefPubMedGoogle Scholar
  • 24 Olson HE, Loddenkemper T, Vendrame M , et al. Rufinamide for the treatment of epileptic spasms. Epilepsy Behav 2011; 20 (2) 344-348
    CrossrefPubMedGoogle Scholar
  • 25 von Stülpnagel C, Coppola G, Striano P, Müller A, Staudt M, Kluger G. First long-term experience with the orphan drug rufinamide in children with myoclonic-astatic epilepsy (Doose syndrome). Eur J Paediatr Neurol 2012; 16 (5) 459-463
    CrossrefPubMedGoogle Scholar
  • 26 Häusler M, Kluger G, Nikanorova M. Epilepsy with myoclonic absences—favourable response to add-on rufinamide treatment in 3 cases. Neuropediatrics 2011; 42 (1) 28-29
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Coppola G, Grosso S, Franzoni E , et al. Rufinamide in refractory childhood epileptic encephalopathies other than Lennox-Gastaut syndrome. Eur J Neurol 2011; 18 (2) 246-251
    CrossrefPubMedGoogle Scholar
  • 28 Mueller A, Boor R, Coppola G , et al. Low long-term efficacy and tolerability of add-on rufinamide in patients with Dravet syndrome. Epilepsy Behav 2011; 21 (3) 282-284
    CrossrefPubMedGoogle Scholar
  • 29 Grosso S, Coppola G, Dontin SD , et al. Efficacy and safety of rufinamide in children under four years of age with drug-resistant epilepsies. Eur J Paediatr Neurol 2014; 18 (5) 641-645
    CrossrefPubMedGoogle Scholar
  • 30 Cusmai R, Verrotti A, Moavero R , et al. Rufinamide for the treatment of refractory epilepsy secondary to neuronal migration disorders. Epilepsy Res 2014; 108 (3) 542-546
    CrossrefPubMedGoogle Scholar
  • 31 Kluger G, Haberlandt E, Kurlemann G , et al. First European long-term experience with the orphan drug rufinamide in childhood-onset refractory epilepsy. Epilepsy Behav 2010; 17 (4) 546-548
    CrossrefPubMedGoogle Scholar
  • 32 Kessler SK, McCarthy A, Cnaan A, Dlugos DJ. Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox-Gastaut Syndrome. Epilepsy Res 2015; 112: 18-26
    CrossrefPubMedGoogle Scholar
  • 33 Mourand I, Crespel A, Gelisse P. Dramatic weight loss with rufinamide. Epilepsia 2013; 54 (1) e5-e8
    CrossrefPubMedGoogle Scholar
  • 34 Coppola G, Besag F, Cusmai R , et al. Current role of rufinamide in the treatment of childhood epilepsy: literature review and treatment guidelines. Eur J Paediatr Neurol 2014; 18 (6) 685-690
    CrossrefPubMedGoogle Scholar