Asthma is among the most common illnesses in childhood and may require off-label drug use for adequate symptom control. Several studies have assessed that this use is common mainly due to a lack of clinical research. The leading concerns are the increased risk of adverse drug reactions and prescription errors. However, off-label prescriptions are not necessarily incorrect. The European Medicines Agency released the Paediatric Regulation to promote research in the medicines for children; yet, recent data suggest only a minor impact.
Off-label, asthma, children, paediatric regulation
António J Cabral and Mário Morais-Almeida have no conflicts of interest to declare. No funding was received in the publication of this editorial.
July 28, 2015 Accepted
August 17, 2015
Mário Morais-Almeida, Allergy Center, CUF-Descobertas Hospital, 1998-018 Lisbon, Portugal. E: firstname.lastname@example.org
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Asthma is among the most common respiratory illnesses in childhood and frequently requires the use of long-term control medication. Even though less than half of the children represent true therapyresistant asthma, they may require off-label use for adequate symptom control. Many drugs used in the treatment of allergic diseases are not appropriately studied in the paediatric population, especially in infants and younger children. Nonetheless, their off-label use, that is, use outside the formal indications authorised by the regulatory authorities, in a different age group dose, or indication1 is common in many paediatric illnesses, such as allergic disease, in up to 37 % of paediatric outpatients and in up to 62 % of children treated in paediatric hospital wards.2 This brings to light many health concerns, such as increased risk of adverse drug reactions and prescription errors – namely dosage errors, particularly in younger children and infants.3 However, off-label prescriptions are not necessarily incorrect,4 and may even be appropriate when there is no alternative treatment, when the likely benefits outweigh the potential risks or when conventional treatments are unable to achieve control of the disease.5 New therapeutic uses may also be described, and data on the efficacy and safety of the drug being used may be collected.6
Several studies have assessed the paediatric use of drugs through cohort and cross-sectional studies. A population-based cohort study carried out in primary care units in Holland evaluated the prescribing of respiratory drugs in 2,502 children in which 37 % of all prescriptions were off-label, and 39 % in this group were prescriptions for asthma.7 Data from the Task force in Europe for Drug Development for the Young (TEDDY), comparing the use of anti-asthmatic drugs in children in Holland, Italy and the UK, established that off-label use of beta2- agonists and inhaled corticosteroids (ICS) is frequent.8 A study carried out in Portugal in preschool children showed that 35 % of prescriptions for allergic disease were considered off-label, and this occurred most frequently in children under the age of 2 (74 %).9 This study also revealed that off-label use may vary with national regulatory authorities with examples given for nasal mometasone, whose use in rhinitis, a very prevalent asthma comorbidity, is allowed in the US by the Food and Drug Administration (FDA) from 2 years old, while in Europe it is only approved for children 6 years or older. In addition, levocitirizine is approved by the FDA from 6 months old while the European Medicines Agency (EMA) maintains its use only over the age of 2.10
1. Gazarian M, Kelly M, McPhee JR, et al., Off-label use of
medicines: consensus recommendations for evaluating
appropriateness, Med J Aust, 2006;185:544–8.
2. Pandolfini C, Bonati M, A literature review on off-label drug
use in children, Eur J Pediatr, 2005;164:552–8.
3. Choonara I, Conroy S, Unlicensed and off-label drug use in
children: implications for safety, Drug Saf, 2002;25:1–5.
4. Collier J, Paediatric prescribing: using unlicensed drugs
and medicines outside their licensed indications, Br J Clin
5. Committee on Drugs, American Academy of Pediatrics, uses
of drugs not described in the package insert (off-label uses),
6. Bennett WM, Off-label use of approved drugs: therapeutic
opportunity and challenges, J Am Soc Nephrol,
7. ‘t Jong GW, Eland IA, Sturkenboom MC, et al., Unlicensed
and off-label prescription of respiratory drugs to children,
Eur Respir J, 2004;23:310–3.
8. Sen EF, Verhamme KM, Neubert A, et al., Assessment of
pediatric asthma drug use in three European countries; a
TEDDY study, Eur J Pediatr, 2011;170:81–92.
9. Morais-Almeida M, Cabral AJ, Off-label prescribing for allergic
diseases in pre-school children, Allergol Immunopathol
10. Silva D, Ansotegui I, Morais-Almeida M, Off-label prescribing
for allergic diseases in children, World Allergy Organ J,
11. McLay JS, Tanaka M, Ekins-Daukes S, et al., A prospective
questionnaire assessment of attitudes and experiences of
off label prescribing among hospital based paediatricians,
Arch Dis Child, 2006;91:584–7.
12. Meadows M, Drug research and children, FDA Consum,
13. Steinbrook R, Testing medications in children, N Engl J Med,
14. Dunne J, The European Regulation on medicines for
paediatric use, Paediatr Respir Rev, 2007;8:177–83.
15. Lindell-Osuagwu L, Hakkarainen M, Sepponen K, et al.,
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,
16. Global Strategy for Asthma Management and Prevention.
Available at: http://www.ginasthma.org (accessed on
26 July 2015).
17. National Asthma Education and Prevention Program, Third
expert panel on the diagnosis and management of asthma.
Expert panel report 3: guidelines for the diagnosis and
management of asthma. Available at: http://www.ncbi.nlm.
nih.gov/books/NBK7232/ (accessed on 26 July 2015).
18. Cabral A, Morais-Almeida M, Inhaled long acting beta
agonists prescription for asthma in pre-school children,
Allergy, 2014;69(Suppl. 99):520–1 (abstract).
Off-label, asthma, children, paediatric regulation