Delivery of inhaled drugs for infants and small children: a commentary on present and future needs.

Although the manufacture of inhaled medications is a multibillion dollar industry, virtually no pharmaceutical drug/device combination has been approved for inhalation across the range of pediatric patient ages and sizes. The clinician who treats neonates, infants, or toddlers is often faced with the dilemma of prescribing inhaled medications that may be disease appropriate but have not been approved for use in patients in these age categories. Their use is thus technically "off label," with limited empirical data to guide both dose and device selection. This dilemma requires the prescribing physician to go beyond the limitations of the product label, often without benefit of appropriately designed clinical trials, in an attempt to select safe and effective doses for use with these smallest of patients. The vast majority of drugs approved for inhalation were studied by using aerosol devices designed for older children and adults using a mouthpiece interface, which may not be practical for use in infants and patients aged <4 years. The selection of the most age-appropriate device and interface is critical for the effective administration of the prescribed therapy. In the absence of industry-sponsored clinical trials in neonates, infants, and toddlers, in vitro and in vivo strategies may help guide age-appropriate dosing, device, and interface selection to better inform clinical practice. In this commentary, the challenges in developing and prescribing effective formulations for aerosol delivery across the range of pediatric ages and sizes are explored, with guidance for device and interface selection. Recommendations for future collaborative sharing of in vitro models and age-specific breathing patterns between academic and industry researchers could help regulators and clinicians better understand the impact age and size have on pulmonary drug delivery.