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Extent, reasons and consequences of off-labeled and unlicensed drug prescription in hospitalized children: a narrative review

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Abstract

Background

Off-label and unlicensed prescriptions pose a severe safety concern among the pediatric population. We aimed to summarize the up-to-date evidence on the extent, reasons, and consequences of off-label and unlicensed drugs in hospitalized pediatric patients.

Methods

We systematically searched PubMed, EMBASE, SCOPUS, Web of Science and Google Scholar between 1990 and 2020 in which the last search was conducted on 12 February 2021. We included studies with the following inclusion criteria: (1) observational studies in design; (2) target population was hospitalized pediatric patients whether admitted in the intensive care unit or in the general ward; (3) study reporting the prevalence of off-label, unlicensed prescriptions or both; and (4) published in English.

Results

A total of 47 studies were eligible for inclusion. The proportion of off-label and unlicensed prescriptions ranged from 7.4% to 99.5% and 0.1% to 74.4%, respectively. The most frequent category of off-label prescriptions was prescription outside the age range, with the most commonly reported reason for off-label prescriptions being the lack of information specifically for pediatrics on the drug information leaflets. The consequences of off-label and unlicensed prescriptions ranged from minor and bearable skin reactions to debilitating renal failure, risking deaths.

Conclusions

Off-label and unlicensed prescriptions are extensive and require progressively meditative interventions. However, the pediatric population is currently a “therapeutic orphan”. Unless adequate pediatric clinical trials and licensed drugs become available, off-label and unlicensed drug prescription should not entirely be banned but rather promoted in an organized manner.

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Acknowledgements

We acknowledge assistance in the PubMed search, from Dr. Joel Swai (ORCID: 0000-0001-5363-3977); Department of Nephrology and Rheumatology, The Third Xiangya Hospital of Central South University, Changsha, China.

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Authors and Affiliations

  1. Xiangya School of Public Health, Central South University, Changsha, 410078, China

    Wasim Shuib, Xin-Yin Wu & Fang Xiao

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  1. Wasim Shuib
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Contributions

SW contributed to study designing, data search, data extraction, and manuscript drafting. WXY contributed to data search, data extraction, and manuscript drafting. XF contributed to data extraction and manuscript drafting. All authors revised the intellectual content of the manuscript critically, and read and approved the final version of the manuscript.

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Correspondence to Fang Xiao.

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Shuib, W., Wu, XY. & Xiao, F. Extent, reasons and consequences of off-labeled and unlicensed drug prescription in hospitalized children: a narrative review. World J Pediatr 17, 341–354 (2021). https://doi.org/10.1007/s12519-021-00430-3

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