title: Prokinetics prescribing in paediatrics: evidence on cisapride, domperidone, and metoclopramide.
abstract: OBJECTIVE
  Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children.
  
  
  METHODS
  We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case-control studies.
  
  
  RESULTS
  The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified.
  
  
  CONCLUSIONS
  These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.
authors.affiliation: *Imperial Clinical Trials Unit, School of Public Health, Imperial College London †Evelina Children's Hospital, Pharmacy Department, King's Health Partners, Guy's and St Thomas' NHS Foundation Trust ‡General and Adolescent Paediatrics Unit, Institute of Child Health, University College London, London §Warwick Medical School, University of Warwick, Coventry ||Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool ¶Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
authors.forename: Shahrul
authors.initials: S
authors.lastname: Mt-Isa
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlin
authors.forename: Alastair
authors.initials: A
authors.lastname: Sutcliffe
authors.forename: Martin
authors.initials: M
authors.lastname: Underwood
authors.forename: Paula
authors.initials: P
authors.lastname: Williamson
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Croft
authors.forename: Deborah
authors.initials: D
authors.lastname: Ashby
mesh_terms: D000293:Adolescent; D000932:Antiemetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D020117:Cisapride / Q000009:adverse effects / Q000627:therapeutic use*; D004294:Domperidone / Q000009:adverse effects / Q000627:therapeutic use*; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008787:Metoclopramide / Q000627:therapeutic use*; D010372:Pediatrics; D010818:Practice Patterns, Physicians'; D006113:United Kingdom
chemical_list: D000932:Antiemetics; D005765:Gastrointestinal Agents; D004294:Domperidone; D008787:Metoclopramide; D020117:Cisapride