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Asthma Editorial Off-label Use of Drugs in Childhood Asthma António J Cabral 1,2 and Mário Morais-Almeida 3,4 1. Specialist in Paediatrics, Funchal Central Hospital, Madeira; 2. Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal; 3. Head of the Allergy Center, CUF Descobertas Hospital and CUF Infante Santo Hospital, Lisbon, Portugal; 4. CINTESIS – Center for Research in Health Technologies and Information Systems – Faculty of Medicine, University of Porto, Porto, Portugal Abstract 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. Keywords Off-label, asthma, children, paediatric regulation Disclosure: António J Cabral and Mário Morais-Almeida have no conflicts of interest to declare. No funding was received in the publication of this editorial. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 28 July 2015 Published Online: 17 August 2015 Citation: European Respiratory and Pulmonary Diseases, 2015;1(1):16–7 Correspondence: Mário Morais-Almeida, Allergy Center, CUF-Descobertas Hospital, 1998-018 Lisbon, Portugal. E: mmoraisalmeida@netcabo.pt 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 therapy- resistant 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 indication 1 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 16 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 While off-label use can be justified, it involves obtaining informed consent from the parents or guardian. In addition, while this information is important for patient and caregiver adherence, it is frequently omitted. The majority of paediatricians do not seek informed consent, or inform the parents or guardian that they were prescribing an off-label medicine, and only one-third admits to informing a child’s general practitioner of this prescription. 11 One must consider why off-label use in children is so common. It is mainly due to lack of clinical research. 12 Pharmaceutical companies see little benefit with only a few drugs representing a large enough economic interest. This particular population demands specific medical techniques and appropriate equipment that can be difficult to execute or even authorise. Lastly, there are ethical implications due to potential risks that hinder clinical trials. 13 In an effort to oppose this course, EMA released the Paediatric Regulation (EC no. 1902/2006), in order to ensure high-quality research in the development of medicines for children and, over time, have the majority of drugs used in children specifically authorised for such use. This would guarantee the availability of better information on these medicines. To achieve this, a Paediatric Committee was set up that required companies to submit data in accordance with an appropriate Tou c h ME d ica l ME d ia