Utilisation and Off-Label Prescriptions of Respiratory Drugs in Children

Abstract

Respiratory drugs are widely used in children to treat labeled and non-labeled indications but only some data are available quantifying comprehensively off-label usage. Thus, we aim to analyse drug utilisation and off-label prescribing of respiratory drugs focusing on age- and indication-related off-label use. Patients aged ≤18 years documented in the Bavarian Association of Statutory Health Insurance Physicians database (approx. 2 million children) between 2004 and 2008 were included in our study. Annual period prevalence rates (PPRs) per 10,000 children and the proportion of age- and indication-related off-label prescriptions were calculated and stratified by age and gender. Within the study period, highest PPRs were found for the fixed combination of clenbuterol/ambroxol (between 374–575 per 10,000 children) and the inhaled short acting beta-2-agonist salbutamol (between 378–527 per 10,000 children). Highest relative PPR increase was found for oral salbutamol (approx. 39-fold) whereas the most distinct decrease was found for oral long-acting beta-2-agonist clenbuterol (−97%). Compound classes most frequently involved in off-label prescribing were inhaled bronchodilative compounds (91,402; 37.3%) and oral beta-2-agonists (26,850; 22.5%). The highest absolute number of off-label prescriptions were found for inhaled salbutamol (n = 67,084; 42.0%) and oral clenbuterol/ambroxol (fixed combination, n = 18,897; 20.7%). Off-label prescribing due to indication was of much greater relevance than age-related off-label use. Most frequently, bronchodilative compounds were used off-label to treat respiratory tract infections. Highest off-label prescription rates were found in the youngest patients without relevant gender-related differences. Off-label prescribing of respiratory drugs is common especially in young children. Bronchodilative drugs were most frequently used off-label for treating acute bronchitis or upper respiratory tract infections underlining the essential need for a more rational prescribing in this area.

Off-label prescribing for children with chronic diseases in Nigeria; findings and implications

“…The 9.7% rate of prescribing medicine for an off-label use observed in children with epilepsy was substantially lower than 53% reported among children with pharmacoresistant epilepsy prescribed off-label antiepileptic medicines in Italy [33]. Similarly, the rate (10.3%) for children with asthma ( Table 4) was lower than 29.8% reported for respiratory medicines prescribed for off-label use among a general paediatric population in Germany [43]. It was also lower than 34.5% reported for off-label use of anti-allergic medicines prescribed for pre-school children with allergic diseases in Portugal [35].…”

“…This may be one reason why only a small number of off-label prescriptions were received by the patients in our study. Our sample size was also small compared with other studies [33,43]; however, comparable to pre-school children studied by Morais-Almeida and Cabral [35]. Other reasons for the differences seen may include the fact that this study was undertaken in a tertiary referral centre involving trained paediatricians who supervise the prescribing of young physicians undergoing postgraduate training.…”

“…In contrast, only pulmonary medicines for pulmonary conditions, i.e. inhaled bronchodilators, inhaled and oral corticosteroids, mast cell stabilizers, leukotrienes, and xanthines, were evaluated in the German study [43]. Anti-allergic medicines comprising inhaled corticosteroids, nasal and topical corticosteroids, long acting β2 agonists, oral antihistamines, and topical immunomodulators were the medicines evaluated in the off-label prescriptions for allergic diseases among pre-school children in Portugal [35].…”

“…Furthermore, while these studies have defined off-label medicines in relation to deviation from recommended ages, indications and doses [33,35,43], we included non-recommended formulations and routes of administration in our definition of off-label prescription. This may be one reason why only a small number of off-label prescriptions were received by the patients in our study.…”

The IMI PROTECT project: purpose, organizational structure, and procedures

“…However, the supplement also includes descriptive and outcome validation studies and two assessments of the use of instrumental variables as a method for control of confounding. Several manuscripts from the PROTECT project were published prior to the development of this supplement …”