The impact of legislation on drug substances used off-label in paediatric wards--a nationwide study

Eur J Clin Pharmacol. 2014 Apr;70(4):445-52. doi: 10.1007/s00228-013-1626-1. Epub 2014 Jan 8.

Abstract

Purpose: This nationwide study is aimed at describing to what extent the European Paediatric Regulation has met therapeutic needs in children.

Methods: Data for each drug substance in defined daily doses (DDD) were extracted from the national Danish data base. We evaluated if drug substances were used off-label and whether they had a paediatric investigation plan (PIP). This study did not include drug prescriptions for individual paediatric patients; thus, it was not possible to make use of all off-label categories previously used. Additionally, paediatric standard assortments (SA) were compared to the European survey on paediatric medicinal products.

Results: Thirteen percent of the 100 most used drug substances were determined as being used off-label, four of which had a PIP and one had a full waiver. Only one of the three drug substances used off-label most often, accounting for 85 % of such use, had a PIP. Neonates were included in one-third of PIPs and adolescents in 15. Nineteen out of 21 PIPs had a waiver and 14 PIPs were deferred. In line with the European survey, carbapenems, corticosteroids and proton pump inhibitors were frequent found in SAs.

Conclusion: PIPs only cover a small proportion of the drugs found to be used off-label in this study. Despite waivers granted, drug substances were used nonetheless. Unmet regulatory needs are still considerable in some therapeutic areas in neonates as well as in children.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Drug Approval / legislation & jurisprudence*
  • Drug Labeling / legislation & jurisprudence*
  • Drug Utilization / legislation & jurisprudence*
  • Europe
  • Humans
  • Infant
  • Infant, Newborn
  • Off-Label Use / legislation & jurisprudence*
  • Pediatrics / legislation & jurisprudence*