title: Evaluation of unlicensed and off-label antiepileptic drugs prescribed to children: Brazilian Regulatory Agency versus FDA.
abstract: BACKGROUND
  Epileptic seizures are neurological disorders common in children; 4 to 10% of under 16-year olds have suffered at least one seizure. Antiepileptic drugs represent the basis of treatment for the majority of patients, but many of the drugs prescribed to pediatrics are used unlicensed and off-label.
  
  
  OBJECTIVE
  To analyze the prevalence of use of unlicensed and off-label antiepileptic drugs, by the pediatric population, according to the Food and Drug Administration and the Brazilian National Health Surveillance Agency. Setting General Hospital of the Faculty of Medicine at Ribeirão Preto, Brazil.
  
  
  METHODS
  A cross-sectional, retrospective and observational study was carried out. The daily prescriptions of children up to 12 years of age were collected for the analysis of antiepileptic drug use. Data of the registration number, sex, age, reason hospitalized, unit where hospitalized, drug prescribed, dosage, route and administration frequency were collected.
  
  
  METHODS
  Antiepileptic drugs prescribed for children were classified as unlicensed and off-label according to the term of the product's license registered in the Food and Drug Administration and the Brazilian National Health Surveillance Agency.
  
  
  RESULTS
  Of the 6,637 pediatric patients identified during the study period, 583 (9.0%) received at least one antiepileptic drug. The most used antiepileptic drugs were phenobarbital, phenytoin, carbamazepine, valproic acid and clonazepam. As expected, the number of pharmaceutical dosage form classified as unlicensed or off-label was high in both agencies, but distinct between the two. The number of patients (n = 287) using unlicensed drugs was similar in the two agencies, but the use of off-label drugs was higher according to the analysis carried out by the North American agency (40.5%).
  
  
  CONCLUSIONS
  Old-generation antiepileptic drugs are widely prescribed to children. The results found for the use of off-label drugs demonstrate the absence of uniformity in action between the agencies and a lack of integration between the studies carried out. Although legislation on the licensing of drugs aims to protect the patients from drugs that have not been scientifically evaluated, the scarcity of data about the safety of the therapeutic resources obliges the doctors to prescribe unlicensed and off-label antiepileptic drugs to the pediatric population.
authors: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/no., Campus Universitário da USP, Ribeirão Preto, SP 14040-903, Brazil.
authors: Anna Paula de Sá
authors: AP
authors: Borges
authors: Marília Silveira de Almeida
authors: MS
authors: Campos
authors: Leonardo Régis Leira
authors: LR
authors: Pereira
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D017277:Drug Approval / Q000331:legislation & jurisprudence; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D056687:Off-Label Use / Q000706:statistics & numerical data*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000927:Anticonvulsants