Article Text

Download PDFPDF

P17 Licensed, unlicensed or off-label? A snapshot of medicines used in neonatal intensive care
  1. Thomas Wyllie
  1. University Hospital of UK


Background Medicines in the UK are licensed for use by the MHRA. The term ‘unlicensed’ describes medicines without a marketing authorisation in the UK.1 whereas an off-label medicine is a licensed product used outside of the terms of its licensing, i.e., for a different age/population, dose or route.1 The use of unlicensed medicines presents many challenges, including inconsistent supply, high cost and lack of information together with increased risk of medication errors and adverse drug reactions.1 2 Despite these significant drawbacks, the dearth of products licensed for the neonatal population necessitates the routine use of these medicines.1 Various studies have shown that the use of unlicensed and off-label medicines is common in a neonatal intensive care setting: in the UK in 1999,2 and more recently in Brazil3 and Norway.4

Aim Prospectively record the license status of medicines prescribed on a tertiary neonatal unit to determine the relative numbers of licensed, off-label and unlicensed medicines administered.

Method Medication prescription charts were reviewed for a four-week period on a tertiary regional neonatal unit. Each medicine prescribed was recorded and the license status determined, taking into account the indication, patient characteristics and formulation used. Information was gathered on the number of different drugs used and the number of patients that they were prescribed for.

Results Over the study period a total of 72 distinct medications were prescribed 404 times for 68 patients. Of the 404 prescriptions analysed during the study period, just over half (53%) were licensed medicines being used within their licensed indication. 31% were licensed medicines being used off-label and 15% were unlicensed medicines. 43% of the 72 medicines used were licensed but being used off-label. 36% were licensed medicines being used within their licensed indication and 21% of medicines were unlicensed. Of the licensed medicines being used off-label, the most common reason was that the indication/age was not covered by the summary of product characteristics (SPC). However, the detail given in the SPCs varied greatly and it was often challenging to determine whether specific uses were within the license. The top 3 most commonly prescribed medicines (gentamicin, benzylpenicillin and caffeine citrate) accounted for 29% of all prescriptions recorded and were all being used within their license.

Conclusion This study found that the majority (64%) of medicines used in neonatal intensive care during the study period were unlicensed or off-label, similar to other recent work in neonates.3 However, when analysed by the number of prescription events, the majority of these (53%) were licensed. This was mainly due to a small number of licensed drugs which are used often, including antibiotics and caffeine citrate. A licensed form of caffeine citrate was released in 2012, which may partly explain why the proportion is higher in this study than Conroy et al in 1999 2 who found only 35.4% of prescriptions were licensed. While this is a trend in the right direction, more work is needed to license medicines specifically for this vulnerable group of patients.


  1. Rawlence E, Lowey A, Tomlin S, et al. Is the provision of paediatric oral liquid unlicensed medicines safe?. Arch Dis Child Educ Pract Ed 2018;103:310.

  2. Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 1999;80:F142–145.

  3. Costa HT, Costa TX, Martins RR, et al. Use of off-label and unlicensed medicines in neonatal intensive care. PloS One 2018;13:e0204427.

  4. Teigen A, Wang S, Truong BT, et al. Off-label and unlicensed medicines to hospitalised children in Norway. J Pharm Pharmacol 2017;69:432–438.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.