Adverse drug reactions of botulinum neurotoxin type A in children with cerebral palsy: a pharmaco-epidemiological study in VigiBase.
The aim of this study was to assess the risk of adverse drug reactions (ADRs) with botulinum neurotoxin type A (BoNT-A) in children with cerebral palsy (CP) using the World Health Organization global individual case safety report (ICSR) database, VigiBase.



We extracted all children ICSRs for ADRs with BoNT-A used as anti-spastic drug in CP recorded between 1995 and 2015 in VigiBase. We also performed a case/non-case method (disproportionality analysis) to assess the link between exposure to BoNT-A and each ADR of interest in children and adults, calculating reporting odds ratios (RORs).



In VigiBase, 162 ICSRs were registered. They involved mainly males (n=95, 59%) and mean (SD) age was 7 years 11 months (4y 4mo). The most frequent ADR was dysphagia (27 ICSRs, 17%) followed by asthenia and muscular weakness (25 ICSRs each, 16%). Nineteen ICSRs (12%) were lethal. There was a significant association between BoNT-A and death in children (ROR=11.1 95%, confidence interval [CI] 7.0-17.7) but not in adults.



In children with CP, most ADRs seem to be linked to a systemic spread of BoNT-A. Our study suggests a higher risk of ADRs with BoNT-A in children than in adults.
Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire, Toulouse, France.
Jeanne
J
Montastruc
Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire, Toulouse, France.
Philippe
P
Marque
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'informations sur le Médicament, CIC INSERM 1436, INSERM U 1027, Faculté de Médecine et Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Florence
F
Moulis
Service de Médecine Physique et de Réadaptation, Centre Hospitalier Universitaire, Toulouse, France.
Véronique
V
Bourg
Centre Paul Dottin ASEI, Soins de suite et de réadaptation pédiatriques spécialisés, Toulouse, France.
Valérie
V
Lambert
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'informations sur le Médicament, CIC INSERM 1436, INSERM U 1027, Faculté de Médecine et Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Geneviève
G
Durrieu
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'informations sur le Médicament, CIC INSERM 1436, INSERM U 1027, Faculté de Médecine et Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Jean-Louis
JL
Montastruc
Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'informations sur le Médicament, CIC INSERM 1436, INSERM U 1027, Faculté de Médecine et Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
François
F
Montastruc
D000293:Adolescent; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D002547:Cerebral Palsy / Q000188:drug therapy* / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology*; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D012189:Retrospective Studies
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A