title: Safety and tolerability of zonisamide in paediatric patients with epilepsy.
abstract: BACKGROUND
  Zonisamide has recently been approved in Europe for the adjunctive treatment of partial seizures (with or without secondary generalisation) in adolescents and children aged ≥6 years.
  
  
  OBJECTIVE
  To further assess the safety of adjunctive zonisamide in paediatric epilepsy patients.
  
  
  METHODS
  A pooled analysis of data from 17 studies (including four randomised, double-blind trials) was conducted. The safety population comprised patients aged ≤16 years receiving at least one dose of study drug. Assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs and electrocardiography.
  
  
  RESULTS
  The analysis included 398 patients treated with zonisamide (<12 years, n = 191; 12-16 years, n = 207). All but seven patients received zonisamide as adjunctive therapy. Mean duration of exposure was 318.7 days (mean dose, 253.1 mg/day). Most TEAEs were of mild or moderate intensity. The most frequently reported treatment-related TEAEs were decreased appetite (15.6%), somnolence (12.1%), fatigue (9.3%), dizziness (6.0%), decreased weight (5.8%), irritability (5.8%) and headache (5.3%). Incidence of serious zonisamide-related TEAEs was low (3.5% overall). TEAEs most commonly leading to discontinuation were lethargy (1.0%) and fatigue (1.0%). TEAEs of decreased weight and decreased appetite occurred in 28 (7.0%) and 78 (19.6%) patients, respectively. Twenty-eight patients had decreased bicarbonate levels, but there were no reports of respiratory alkalosis or metabolic acidosis. No changes in vital signs of clinical concern were observed and there were no reports of clinically significant electrocardiogram abnormalities with zonisamide treatment.
  
  
  CONCLUSIONS
  Zonisamide demonstrated an acceptable safety profile when used as adjunctive treatment in paediatric patients.
authors.affiliation: UCL-Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust, London, and Young Epilepsy, Lingfield, UK. Electronic address: h.cross@ucl.ac.uk.
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.affiliation: APHP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, Paris, France; Inserm, U676, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Auvin
authors.affiliation: Eisai Ltd, Hatfield, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Patten
authors.affiliation: Eisai Ltd, Hatfield, UK.
authors.forename: Luigi
authors.initials: L
authors.lastname: Giorgi
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D010372:Pediatrics; D016896:Treatment Outcome; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide
keywords: Paediatric epilepsy; Partial seizures; Pooled analysis; Safety; Tolerability; Zonisamide