Inhaled antifungal therapy: benefits, challenges, and clinical applications

Disease due to pulmonary infection with Aspergillus, and other emerging opportunistic fungi remains a significant unmet need. Existing antifungal medicines are predominantly dosed either orally or systemically, but because of limited exposure to the lung lumen, adverse events, and problematic drug-drug interactions, inhaled treatment could provide an attractive option.

This review summarizes 1) the limitations of current antifungal therapy, 2) the beneficial effects of inhaled antifungal agents, 3) the clinical development of inhaled antifungal triazoles (repurposed with an innovative inhalation system or a novel inhaled agent) for the treatment of pulmonary fungal infections, and 4) the difficulties and challenges of inhaled antifungal agent development. Regrettably, details of novel inhaled devices or formulations were not covered.

Inhaled antifungal treatment could provide an attractive option by shifting the risk benefit ratio of treatment favorably. Preclinical and clinical studies with inhaled antifungal agents (off-label use) are encouraging so far. New inhaled antifungal triazoles are well tolerated in early clinical studies and warrant further clinical development. However, challenges remain and many unaddressed issues including required preclinical studies, appropriate clinical design, pharmacokinetics, delivery system(s) and regulatory process need to be resolved. Early communication with regulatory authorities is therefore recommended.