title: Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Roflumilast is a newly approved phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and a history of exacerbations.
  
  
  OBJECTIVE
  The objective of this article is to review the pharmacology, clinical efficacy, and tolerability of roflumilast in the treatment of COPD.
  
  
  METHODS
  Articles were identified using MEDLINE (1966-August 1, 2011) and EMBASE (1947-August 1, 2011). Searches were conducted using the terms roflumilast and COPD. Included in the search were all English-language clinical trials that were randomized, had durations of >6 weeks, and studied the effects of roflumilast on the forced expiratory volume in 1 second (FEV(1)) or rates of exacerbations in patients with COPD. Abstracts from the annual meetings of the American Thoracic Society, American College of Chest Physicians, and European Respiratory Society were also searched to identify relevant publications. In addition, all pertinent studies evaluating the pharmacokinetics and pharmacodynamics of roflumilast were included.
  
  
  RESULTS
  A total of 6 clinical trials (4 publications) evaluating the efficacy of roflumilast were identified and included. For the treatment of COPD, roflumilast was associated with a significant improvement in lung function (increase in FEV(1) of 36-88 mL) when compared with placebo. Roflumilast also reduced the rate of exacerbations in subsets of patients with chronic cough and a history of exacerbations. Overall, health-related quality of life was not significantly affected. Adverse effects were common in clinical trials, with 9% to 16% of patients discontinuing therapy as a result. The most frequently reported adverse effects were gastrointestinal issues, headache, and weight loss. Suicide-related adverse effects have occurred in 5 patients receiving roflumilast and 1 patient receiving placebo.
  
  
  CONCLUSIONS
  Roflumilast significantly improved FEV(1) in clinical trials but had inconsistent reductions in the rates of exacerbations. Comparative studies with recommended therapies for COPD, particularly inhaled corticosteroids, are needed to better assess the role of roflumilast in the management of COPD.
authors.affiliation: Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, Alabama, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Pinner
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Hamilton
authors.forename: Anthony
authors.initials: A
authors.lastname: Hughes
mesh_terms: D000631:Aminopyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001549:Benzamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast