Off-label use of medicines in children: can available evidence avoid useless paediatric trials? The case of proton pump inhibitors for the treatment of gastroesophageal reflux disease

Eur J Clin Pharmacol. 2009 Feb;65(2):209-16. doi: 10.1007/s00228-008-0560-0. Epub 2008 Sep 17.


Purpose: In some cases of drug therapy, the available evidence might be sufficient to extend the indications to children without further clinical studies.

Methods: We reviewed the available evidence for one of the categories of drugs most frequently used off-label in children: proton pump inhibitors (PPIs) used for the treatment of gastroesophageal reflux disease (GERD). A classification of the appropriateness of off-label use of PPIs in children with GERD was also performed.

Results: Of the five PPIs evaluated, only omeprazole has a paediatric indication in Europe. Overall, 19 clinical trials were retrieved and evaluated on the basis of pharmacokinetics, efficacy and safety data. The off-label use of omeprazole, esomeprazole and lansoprazole in children was evaluated as appropriate given the consistent available evidence retrieved in literature.

Conclusion: This study demonstrates the existence of a large body of clinical evidence on the use of PPIs in children. Regulatory agencies and ethical committees should cope with this issue for ethical reasons to avoid unnecessary trial replication.

Publication types

  • Evaluation Study

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics
  • 2-Pyridinylmethylsulfinylbenzimidazoles / therapeutic use
  • Child
  • Clinical Trials as Topic*
  • Databases, Bibliographic
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Administration Schedule
  • Drug Utilization Review*
  • Esomeprazole
  • European Union
  • Gastroesophageal Reflux / drug therapy*
  • Government Agencies / legislation & jurisprudence
  • Government Agencies / standards
  • Humans
  • Isomerism
  • Lansoprazole
  • Multicenter Studies as Topic
  • Omeprazole / pharmacokinetics
  • Omeprazole / therapeutic use
  • Pediatrics
  • Proton Pump Inhibitors / pharmacokinetics
  • Proton Pump Inhibitors / therapeutic use*
  • United States
  • United States Food and Drug Administration / legislation & jurisprudence
  • United States Food and Drug Administration / standards


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Proton Pump Inhibitors
  • Lansoprazole
  • Omeprazole
  • Esomeprazole