Background: Worldwide, in the absence of standard pediatric prescribing information,
clinicians often use medicines in children in a dosage form or for an indication that has not been
approved for use. Inadequate clinical trials increase exposure to drugs that lack safety-efficacy data in
pediatric population. Hence, off-label and unlicensed drug use must be regarded as a patient safety-issue
that is known to be associated with increased risks of adverse drug reactions apart from under- or overdosing
due to lack of pharmacokinetic data. This review aims to give an overview of the worldwide
reported rates of off-label and unlicensed drug use in different patient populations in pediatric
settings, with a brief summary of the related adverse drug reactions (ADRs) and a discussion of the
existing regulatory provisions and possible solutions for ensuring safe use of medicines in children.
Method: Literature searches were conducted and we included studies that evaluated unlicensed or
off-label drug use in various pediatric patient populations. The definition of off-label drug use and
unlicensed drug varied between different studies.
Results: Fourteen studies from different countries were included in the review and were grouped as:
studies conducted in the patients admitted in neonatal intensive care units, in pediatric wards, in
hospitalized children and in pediatric outpatient settings. The number of patients studied ranged from
34 in neonatal intensive care units to 355 409 hospitalized children. Many studies reported high rates of
off-label (9% to 78.7%) and unlicensed (0.3% to 35%) drug use in different pediatric patient settings.
Conclusion: Given the prevalence of unlicensed and off-label drug use, the cooperation of various
stakeholders including health professionals, pediatric population and their parents/caregivers,
regulatory authorities, and the pharmaceutical industry is integral to instituting individual measures to
avoid exposing children to unnecessary risks and avoid depriving them of potentially effective
pharmacotherapy. Initiatives to encourage clinical trials for licensing drug use in children by
providing market exclusivity and patent extension could aid in bridging the gap between approval
and contemporary drug prescribing practices. Enforcement of legislations in the drug development
process and subsequent pharmacovigilance could improve the quality of information and
accountability of pharmaceutical industry to support and facilitate drug research in children.