Off-label and unlicensed drug use in children population

Therapie. 2018 Apr;73(2):135-149. doi: 10.1016/j.therap.2018.02.002. Epub 2018 Feb 16.


Introduction: Off-label (OL) and unlicensed (UL) drug use is widely developed in the pediatric population according to previous reviews published in the early 2010s. The present study is a narrative review of the literature of OL-UL drug use from 2013.

Methods: We performed a literature search of research articles assessing OL-UL drug use in children (<18 years-old) published in Medline® from January 2013 until May 2017.

Results: Twenty-seven studies were included. OL drug use was defined by inappropriate age, indication, dosage or way of administration according to the summary of product characteristics in >80% of studies. UL drug used was defined by the use of drugs not licensed in the country or modifications of licensed drugs in >70% of studies. Among in- and out-patients, the frequency of patients exposed to at least one OL-UL drug ranged from 36.3 to 97.0% and from 18.6 to 40.2%, respectively. Drug use was categorized as OL mostly due to inappropriate age, dosage or indication. OL-UL drug use was the most prevalent in newborns (mainly preterms) and pre-school children (aged 2-5years). Various drugs were involved, depending on patients' age. Polypharmacy and long hospital stays were risk factors for OL-UL drug use. Whether OL-UL drug use leads to a higher incidence of adverse drug reactions is a controversial finding.

Conclusions: OL-UL drug use is frequent in children. A standardized definition of OL-UL drug use is needed to better assess its frequency, risk factors and impact.

Keywords: Children; Off-label drug use; Unlicensed drug use.

Publication types

  • Review

MeSH terms

  • Humans
  • Off-Label Use*
  • Pediatrics*
  • Practice Patterns, Physicians'*