5. Off-label use across specific patient groups

5.1. Paediatric population

Specifically, paediatric prescriptions are frequently off-label as many medicines were not tested for use in children and not authorised for use in children. There is however broad consensus that children deserve access to medicines that have been specifically developed and researched for their use in young patients.

Regulation (EC) No 1901/2006/EC, the Paediatric Regulation (see also lesson 2, section 3.3 Paediatric medicines), came into force in the European Union (EU) on 26 January 2007. It was seen as a response to the absence of sufficient numbers of suitable, authorised medicines for children. The regulation was adopted to “ensure that medicines are regularly researched, developed and authorised to meet the therapeutic needs of children”. Its objectives were to:

  • facilitate the development and availability of medicines for children aged 0 to17 years of age;
  • ensure that medicines for the treatment of children are subject to ethical research of high quality and are appropriately authorised for use in the paediatric population;
  • improve the available information on the use of medicines in various paediatric populations.
  • achieve this without unnecessary trials in children or delaying the authorisation of medicines for adults

It applies to both, “nationally” (MRP, DCP, national) as well as to centrally authorised medicines.

In their Report on the survey of all paediatric uses of medicinal products in Europe 2010, three years after the coming into force of the paediatric regulation, the EMA summarised their findings on off-label use in the paediatric population: “Prescriptions of off-label and unauthorised medicines for children is widespread throughout the European Union (between 45-60% of the total number of prescriptions from this survey, confirming the results from previous publications). Both hospitalised children and out-patients are frequently treated with medicines used outside the terms of their marketing authorisation”.

A 2017 EC-commissioned study on off-label use of medicines in the EU (‘Study on off-label use of medicinal products in the European Union’) suggested that in children 0-18 years of age the prevalence of off-label use was still widespread, in hospital settings with a mean of  33,8 ± 15,5 SD and outpatient settings with a mean of  40,8 ± 28,1 SD. The authors concluded that, so far, the introduction of the Paediatric Regulation did not seem to have led to a lower prevalence of off-label use[1]

The most common examples for off-label use in children are medicines prescribed:

  • at a different dose or frequency, (many medicines used in children were prescribed and administered based on physicians’ own experience rather than on the results of clinical research)
  • in a different formulation or an alternative route of administration (absence of suitable formulations and routes of administration; paediatricians had to adapt the dosage and form of medicines authorised for adults, for example, by using only a portion of a tablet for adults after dissolving)
  • in this age group for which it had not been authorised
  • for a different indication than that which was authorised

This carries the risk of either lack of efficacy or poses safety problems in children, the latter perhaps of lesser concern in adults but possibly important and serious in children.

A single prescription can be categorised as off-label use in several different categories, of which the most common are shown in Table 3. In earlier studies, a medicine’s use was classified as off-label if the dose, dosing frequency, or the age/weight of the patient was not in agreement with the particulars in the SmPC. In more recent studies, the most prominent reasons for off-label use were a total lack of information in the SmPC about paediatric use of the medicine and the use of a non-approved dose in relation to age or weight.

Table 3. Off-label categories in Paediatrics.

Off-label category



Medicine not recommended in the SmPC below a certain age.


Medicine not recommended in the SmPC for children below a certain weight.

Absence of paediatric information

No mention at all in the SmPC regarding paediatric use.

Lack of paediatric clinical data

Stated lack of evidence of efficacy and safety in paediatric patients in the SmPC.


Statement in the SmPC that the medicine is contraindicated in children.


Medicine prescribed for indications outside of those listed in the SmPC.

Route of administration

Medicine administered by a route not described in the SmPC.

[1] 32 studies on off-label use (including data from 16 EU Member States) in various paediatric populations in the hospital setting showed a range of 13-69% of the investigated prescriptions being off-label. In 40 studies (including data from 12 Member States) in the outpatient setting, a wider range of 2-100% was found.