Long-acting beta-2-adrenoceptor agonists and anticholinergic drugs: Drug utilisation and off-label use in paediatric patients living in Bavaria (Germany)

Background: Respiratory drugs are widely used in children, however only few data are available regarding the extent and type of off-label prescriptions. Thus, we aim to analyse drug utilisation and off-label prescriptions of long-acting beta-2-agonists (LABA), ipratropium and tiotropium (including fixed combination drugs). Methods: In this study, all patients documented in the Bavarian Association of Statutory Health Insurance Physicians database which covers 85% of the population (approximately 2 million children) between 2004 and 2008 and aged ≤18 years were included. Annual period prevalence rates (PPRs) per 10,000 children were calculated. Off-label prescriptions due to 'age', 'indication', and 'age &indication' were identified on a compound-level using the respective summary of product characteristics (SPC). For each compound, the fraction of off-label prescription was calculated and stratifications according to the type of off-label prescriptions, age and sex were performed. Cochrane Armitage test was used to analyse trends over time. Results: Between 2004 and 2008, highest PPRs were found for ipratropium (between 81.1 and 103.7 per 10,000 children) and the fixed combination salmeterol/fluticasone (between 54.7 and 72.1 per 10,000 children) whereas for tiotropium, lowest PPRs were found (between 0.3 and 0.5 per 10,000 children). Over time, a significant increase of PPRs was found for fixed combinations of LABA/inhaled corticosteroids compared to a significant decrease for ipratropium, tiotropium and single compound LABA. The highest proportion (but the lowest absolute number) of off-label prescriptions was found for tiotropium (99%, n = 96). For ipratropium- containing compounds, somewhat lower rates (but higher absolute numbers) of off-label prescriptions were found (ipratropium: 50.0%, approximately 10,000; ipratropium/fenoterol [fixed combination]: 43.1%, approximately 1,700). For all compounds, off-label prescriptions due to non-labelled indications were most important in youngest children. Main off-label indications were acute bronchitis and upper respiratory tract infections. Except for tiotropium, off-label prescriptions due to age only were less important. Conclusions: For selected drugs used in respiratory indications, offlabel prescribing is of major importance in particular in very young children. Clinical studies focussing on common off-label indications might help to improve an evidence-based treatment in the paediatric population.