Two decades of off-label prescribing in children: a literature review
- 152 Downloads
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.
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.
KeywordsChildren Dose Indication Off-label Pediatric
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
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.
- 13.Man SC, Primejdie DP, Sarkozi IK, Popa A. Off-label and unlicensed prescribing in hospitalized children: prevalence and reasons. Farmacia. 2017;65:460–6.Google Scholar
- 14.Balan S, Hassali MA, Mak VSL. Non-regulatory related factors leading to off-label prescribing in children: a concept map. Res Soc Adm Pharm. 2017;13:1219–21.Google Scholar
- 23.Uchiyama A. Pediatric clinical studies in Japan: regulations and current status. Appl Clin Trials. 2002;11:57.Google Scholar
- 24.Yang Y, Su GC. A comparative study between WHO essential medicines for children and pediatric medicines in the national essential drug list of China. China Pharm. 2011;22:2994–8.Google Scholar
- 28.Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3:77–101.Google Scholar
- 31.Carvalho PR, Carvalho CG, Alievi PT, Martinbiancho J, Trotta EA. Prescription of drugs not appropriate for children in a Pediatric Intensive Care Unit. J Pediatr (Rio J). 2003;79:397–402 (in Portuguese).Google Scholar
- 34.Lifshitz M, Gavrilov V, Grossman Z, Binsthok M, Hornik D, Rosemblum H, et al. Unapproved prescription practices in primary pediatric clinics in Israel: a prospective analysis. Curr Ther Res. 2002;63:830–7.Google Scholar
- 47.Turner S. Unregistered and off-label drug use in paediatric inpatients. Aust J Hosp Pharm. 1999;29:265–8.Google Scholar
- 56.Carvalho CG, Ribeiro MR, Bonilha MM, Fernandes M Jr, Procianoy RS, Silveira RC. Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores. J Pediatr (Rio J). 2012;88:465–70.Google Scholar
- 57.Mesquita M, Godoy G, Cabral MS, Zavala R, Espínola E, Genes L. Prescription of off-label and unlicensed drugs in hospitalized newborns: a multicenter study in five hospitals in Greater Asuncion, Paraguay. Pediatría (Asunción). 2014;41:208–14.Google Scholar
- 59.Ferreira Lde A, Ibiapina Cda C, Machado MG, Fagundes ED. High prevalence of off-label and unlicensed drug prescribing in a Brazilian intensive care unit. Rev Assoc Med Bras. 1992;2012:82–7 (in Portuguese).Google Scholar
- 74.Ariati AL, Kartinah N, Intannia D. Description of the use of off-label drugs in pediatric patients outpatient in Ulin Banjarmasin public hospital period January–December 2013. J Pharmasci. 2015;2:58–64 (in Indonesian).Google Scholar
- 91.Thomas A. The use of unlicensed and off label drugs in Tygerberg Hospital neonatal intensive care unit. Stellenbosch: Stellenbosch University; 2014.Google Scholar
- 101.Okechukwu RC, Aghom OE. Prescription pattern of unlicensed and off-label medicines for children aged 0–5 years in a tertiary hospital and a primary health care centre in Nigeria. S Afr J Bioeth Law. 2009;2:62–6.Google Scholar
- 105.Slažneva J, Kovács L, Kuželová M. Off-label drug use among hospitalized children: identifying extent and nature. Eur Pharm J. 2012;59:621–5.Google Scholar
- 108.Sturkenboom M, Felisi M, Manfredi C, Neubert A, Cantarutti L, Padula R, et al. Paediatric status and off-label use of drugs in children in Italy, United Kingdom and the Netherlands. Pharm Policy Law. 2009;11:51–9.Google Scholar
- 121.Oreagba IA, Omotoso KS, Sonibare AJT, Sonibare T, Oshikoya KA. Off-label prescription for paediatric in- and out-patients at a tertiary hospital in Lagos, Nigeria. W Afr J Pharmacol Drug Res. 2015;30:18–27.Google Scholar
- 122.Bhadiyadara SN, Rana DA, Malhotra SD, Patel VJ. Off-label and unlicensed drug use in paediatric outpatient department—a prospective study at a tertiary care teaching hospital. J Young Pharm. 2015;7:164–70.Google Scholar
- 136.Clarkson A, Conroy S, Burroughs K, Choonara I. Surveillance for adverse drug reactions in children: a paediatric regional monitoring centre. Paediatr Perinat Drug Ther. 2004;6:20–3.Google Scholar
- 139.Rylance GW. Drug availability and dose information for children. J Clin Pharm Ther. 1979;4:153–8.Google Scholar
- 142.Thompson DF, Rains C. A comparison of licensed indications for equivalent drugs in the United Kingdom and the United States. Ther Innov Regul Sci. 1993;27:529–36.Google Scholar
- 147.Ng H, Thomas T. Paediatric Protocols for Malaysian Hospitals. Malaysia: Ministry of Health of Malaysia; 2012.Google Scholar