World Journal of Pediatrics

, Volume 14, Issue 6, pp 528–540 | Cite as

Two decades of off-label prescribing in children: a literature review

  • Shamala BalanEmail author
  • Mohamed Azmi Ahmad Hassali
  • Vivienne S. L. Mak
Review Article



In the past two decades, many legislative and regulatory initiatives were taken globally to improve drug use in children. However, children are still found to be prescribed with off-label drugs. This study was conducted to provide an overview of the worldwide trend in off-label prescribing in children from the year 1996 to 2016.

Data sources

The articles published in PubMed, MEDLINE and Google Scholar were searched using text words: off-label, unlicensed, paediatric and children. Additional articles were identified by reviewing the bibliography of the retrieved articles. Full-text articles published in English which reported on the prevalence of off-label prescribing in children between January 1996 and December 2016 were included.


A total of 101 studies met the inclusion criteria. Off-label prescribing definition included four main categories: age, indication, dose and route of administration. The three most common reference sources used in the studies were summary of product characteristics, national formularies and package inserts. Overall, the off-label prescribing rates in children ranged from 1.2 to 99.7%. The most common category of off-label prescribing in children was dose and age.


This review highlighted that off-label prescribing in children was found to be highly prevalent throughout the past two decades, persistently in the neonatal intensive care units. This suggests that besides legislative and regulatory initiatives, behavioural, knowledge aspects and efforts to integrate evidence into practice related to off-label prescribing also need to be evaluated and consolidated as part of the concerted efforts to narrow the gaps in prescribing for children.


Children Dose Indication Off-label Pediatric 


Author contributions

SB contributed in the conception of the review, acquisition of review articles, analysis and interpretation of data for the review and writing of the review. MAAH and VM provided the supervision, critical revision of intellectual content of the review and final approval of the version to be published.


No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Compliance with ethical standards

Ethical approval

This literature review is exempted from ethical review as it involves the use of existing data or records that contains only de-identifiable data about human beings.

Conflict of interest

All the authors of this study declare that they have no competing interest.

Supplementary material

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Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2018

Authors and Affiliations

  1. 1.Discipline of Social and Administrative Pharmacy, School of Pharmaceutical SciencesUniversity Sains MalaysiaGelugorMalaysia
  2. 2.Center for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical SciencesMonash UniversityMelbourneAustralia

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