Off-label and unlicensed medicine use

Overview & Definition

A registrar on a neonatal unit is asked to start caffeine citrate for apnoea of prematurity. The box is not licensed for the baby's gestational age and the strength on the ward is a pharmacy-made solution. The registrar hesitates. This leaf owns that moment — off-label and unlicensed medicine use — and the reasoning that turns it from a worry into a defensible, child-centred decision. The broader medication-safety and pharmacovigilance theory lives on its own leaves; this page is about the licence. [1] [5]

Hold three words apart, because examiners live in the gaps between them. A licensed (sometimes called on-label) medicine is used within all the terms of its marketing authorisation — the approved age or weight band, the approved indication, route, dose and formulation. An off-label medicine is a licensed product used outside one or more of those terms: the right drug, in a child of the wrong age, or for an unapproved indication, route or dose, or in a formulation that differs from the licensed one. An unlicensed medicine has no valid marketing authorisation for that product or formulation in the country at all — a pharmacy-made "special", an imported product, something extemporaneously compounded, or an investigational product in a clinical trial. [1] [6]

The reason this distinction matters clinically is that each category carries a different governance load. A licensed medicine comes with a regulator-vetted dose range, a tested formulation, and a post-marketing safety database. The moment you step outside the licence you take personal responsibility for the dose, evidence, formulation quality and the monitoring — because the regulator's safety net no longer covers that exact use. The rest of this page is about discharging that responsibility well. [7] [5]

References12Show ledgerHide ledger

1. [1]Conroy S Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. BMJ, 2000.PMID 10625257
2. [2]'t Jong GW A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital. Pediatrics, 2001.PMID 11694685
3. [3]'t Jong GW Unlicensed and off-label prescription of respiratory drugs to children. Eur Respir J, 2004.PMID 14979509
4. [4]Neubert A The impact of unlicensed and off-label drug use on adverse drug reactions in paediatric patients. Drug Saf, 2004.PMID 15471510
5. [5]Cuzzolin L Off-label and unlicensed prescribing for newborns and children in different settings: a review of the literature and a consideration about drug safety. Expert Opin Drug Saf, 2006.PMID 16907660
6. [6]Kimland E Off-label drug use in pediatric patients. Clin Pharmacol Ther, 2012.PMID 22472984
7. [7]Frattarelli DA Off-label use of drugs in children. Pediatrics, 2014.PMID 24567009
8. [8]Bellis JR Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of inpatients in a pediatric hospital. BMC Med, 2013.PMID 24229060
9. [9]Nir-Neuman H Unlicensed and Off-Label Medication Use in Pediatric and Neonatal Intensive Care Units: No Change Over a Decade. Adv Ther, 2018.PMID 29949042
10. [10]Lindell-Osuagwu L Prescribing for off-label use and unauthorized medicines in three paediatric wards in Finland, the status before and after the European Union Paediatric Regulation. J Clin Pharm Ther, 2014.PMID 24329556
11. [11]Sohn M National trends in off-label use of atypical antipsychotics in children and adolescents in the United States. Medicine (Baltimore), 2016.PMID 27281081
12. [12]Aurich B c4c: Paediatric pharmacovigilance: Methodological considerations in research and development of medicines for children - A c4c expert group white paper. Br J Clin Pharmacol, 2022.PMID 34699077