The prescribing of off-label and unauthorised medicines to children is still widespread in Europe, accounting for 45%-60% of total prescriptions in both inpatient and outpatient care, says a new report from the European Medicines Agency (EMA).
The study findings show the highest rates of use are in very young children and in children with very severe conditions. It also notes that the therapeutic classes that are used most frequently off-label or without a marketing authorisation are: antiarrhythmics, antihypertensives (renin-angiotensin inhibitors and beta-blockers) proton pump inhibitors and H2-receptor antagonists, antiasthmatics, and antidepressants (mainly selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants), contraceptives (in adolescents), and antibiotics (in very young children).
The survey was conducted to support the development of the EMA’s Paediatric Committee (PDCO)’s inventory of paediatric needs, a list which describes the different therapeutic areas where research into and develop of medicnes for children is particularly needed. This applies to both off-patent medicines and new products, including authorised drugs and those current under development.
However, the data made available to the EMA for the study was ‘very scarce,” with only 22 - 20 European Union (EU) and two non-EU - countries out of the 30 invited to participate actually submitting data, says the Agency. Moreover, a lack of heterogeneity made inter-company comparisons impossible and there was poor distinction between different types of drug use in children (authorised, unauthorised and off-label), which was further confused by the lack of common terminology in the different EU countries, it adds.
Data from the UK was obtained by using the British National Formulary for Children (BNFC). As expert clinical advisers are used in the UK to advise on use of unlicensed medicines and off-label uses, there was no estimation of the nation’s existing use (both authorised and unauthorised/off-label) of paediatric medicines, says the report.
One important reason for off-label and unauthorised drug use in children is the current lack of age-appropriate formulations, including form and strength, and this produced some surprising results in the study, such as the high off-label use of many antiasthmatics, despite the high paediatric incidence of this condition, says the EMA.
Nor was the exercise able to provide sufficient safety information - only Austria submitted some safety data - but many publications have established that adverse effects are more frequent, more serious and more underreported when medicines are used unauthorised or off-label, says the report. The Paediatric Regulation is expected to improve the situation by ensuring that new products are meeting paediatric needs through the Paediatric Investigation Plans (PIPs) agreed by the PDCO but, says the EMA, in the meantime “a number of easy-to-reach solutions could be proposed at least to make existing medicines available to all member states and existing information to all prescribers for the sake of European children.”