Chronic Obstructive Pulmonary Disease
Roflumilast is used to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Roflumilast is not a bronchodilator and is not indicated for the relief of acute bronchospasm. The effects of roflumilast on COPD exacerbations when added to a fixed-combination preparation containing a long-acting β2-adrenergic agonist and orally inhaled corticosteroid have not been established.
Safety and efficacy of roflumilast have been evaluated in 8 randomized, double-blind, placebo- and active-controlled studies in adults 40 years of age or older with COPD. Data from two 6-month, placebo-controlled, dose-selection studies in patients with COPD of varying severity (forced expiratory volume in 1 second [FEV1] 30-80% of predicted) resulted in a roflumilast dosage of 500 mcg once daily being selected, based mainly based on improvements in lung function (e.g., FEV1) observed with this dosage compared with roflumilast 250 mcg once daily.
The effect of roflumilast 500 mcg once daily on COPD exacerbations has been evaluated in four 1-year, placebo-controlled studies in patients with severe COPD (FEV1 50% of predicted or less). In the first 2 studies, roflumilast did not substantially reduce the rate of moderate (defined as requiring systemic corticosteroids and/or antibiotics) or severe (defined as resulting in hospitalization and/or death) COPD exacerbations compared with placebo. However, based on results of exploratory analyses of these studies, some patients with severe COPD associated with chronic bronchitis and COPD exacerbations within the previous year appeared to have a greater reduction in the incidence of COPD exacerbations compared with the overall study population. In 2 subsequent studies in patients with severe COPD associated with chronic bronchitis who had at least one COPD exacerbation in the previous year and a history of smoking (20 pack-years or more), roflumilast reduced the incidence of moderate (defined as requiring systemic corticosteroids) or severe (defined as resulting in hospitalization and/or death) exacerbations compared with placebo. In addition, in patients receiving concomitant long-acting β2-adrenergic agonists or short-acting antimuscarinics in these studies, the reduction in moderate or severe COPD exacerbations with roflumilast was similar to that observed in the overall study populations.
While roflumilast is not a bronchodilator, the previous four 1-year studies also evaluated the effect of roflumilast on lung function (as determined by change in pre- or post-bronchodilator FEV1). In these studies, roflumilast 500 mcg once daily improved lung function compared with placebo. In addition, in two 6-month comparative studies in patients with moderate or severe COPD (FEV1 40-70% of predicted) receiving either roflumilast (500 mcg once daily) or placebo as add-on therapy to treatment with salmeterol or tiotropium, roflumilast improved lung function (as determined by mean change in prebronchodilator FEV1) compared with placebo.
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