Roflumilast in the management of chronic obstructive pulmonary disease.

Purpose: The pharmacology, pharmacokinetics, efficacy, and safety of roflumilast-the first in a new class of agents for managing chronic obstructive pulmonary disease (COPD)-are reviewed.

Summary: Roflumilast (Daliresp, Forest Pharmaceuticals) is an oral phosphodiesterase-4 (PDE-4) inhibitor that targets inflammatory cells involved in triggering COPD exacerbations. The only PDE-4 inhibitor approved by the Food and Drug Administration, roflumilast is available in 500-μg tablets to be administered once daily. In six placebo-controlled trials involving nearly 4500 patients with COPD of varying severity, the use of roflumilast was associated with reduced COPD exacerbations and improved lung function, as determined by spirometry, with the greatest benefits observed in patients with severe COPD who had chronic bronchitis and a history of frequent exacerbations; clinical efficacy was demonstrated in patients receiving roflumilast alone as well as those receiving concomitant inhaled long-acting β2-agonist (LABA) therapy. The most common adverse events in clinical trials of roflumilast were diarrhea, nausea, and headache. Weight loss and an increased risk of psychiatric events have also been reported in association with roflumilast use. As roflumilast is rapidly converted to its active metabolite via cytochrome P-450 (CYP) isoenzymes, coadministration with strong CYP inducers is not recommended. Research to better define roflumilast's role in COPD management, including a study to determine whether it confers additive benefits when used in combination with standard inhaled therapies other than LABAs, is ongoing.

Conclusion: Roflumilast is a safe and effective option for controlling COPD exacerbations in a defined subset of patients for whom the available treatment alternatives are very limited.