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Roflumilast Tablets (Daliresp®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
An oral selective phosphodiesterase 4 (pde4) inhibi-tor has been approved for the treatment of patients with chronic obstructive pulmonary disease (COPD). Roflumilast is the first drug of this type to be approved for this indication. It is marketed by Forest Pharmaceuticals as Daliresp.
Roflumilast is indicated to reduce the risk of COPD exacerbation in patients with severe COPD associated with chronic bronchitis and a history of exacerbation.1
The recommended dose is 500 mcg orally once daily. The tablet may be taken without regard to meals. Roflumilast is available as 500 mcg tablets.
Roflumilast provides an agent with a different mechanism of action than current treatment options (e.g., inhaled corticosteroids, anticholinergics, and beta agonist). The drug seems to work better in patients with more symptomatic and severe disease.2,3
Roflumilast is contraindicated in individuals with liver impairment. Psychiatric adverse events were reported more frequently with roflumilast compared to placebo (e.g., anxiety, insomnia, depression). Common adverse events include diarrhea, weight loss, nausea, and headache. Concomitant use of roflumilast and CYP 3A4 inhibitors or dual inhibitors of 3A4 and 1A2 should be used with caution as systemic exposure is increased. Use of rifampin, a strong enzyme inducer, is contraindicated.
Roflumilast, as well as its N-oxide metabolite, are selective PDE4 inhibitors. Its clinical effect is believed to be mediated via inhibition of proinflammatory cell function rather than bronchodilation (Gross). Its efficacy was studied in eight randomized trials. Two were dose-selection trials, four were placebo-controlled, 1-year trials assessing the rate of exacerbation, and two were 6-month studies where roflumilast was added onto salmeterol or tiotropium.1,4-6 The primary endpoint in the last two studies was change in prebronchodilator FEV1. Patients randomized to the four exacerbation trials had severe COPD (FEV1 ≤ 50%). In these studies, roflumilast showed a modest improvement in prebronchodilator FEV1 (39 to 58 mL) and 15%-18% reduction in the mean rate of exacerbation/patient/year. When roflumilast was added onto treatment with salmeterol or tiotropium, there were improvements in prebronchodilator FEV1 of 49 mL and 80 mL, respectively.6 The drug appears to be more effective in patients with more severe disease.2,3 The discontinuation rates were 14.8% for roflumilast compared to 9.9% for placebo. The most common adverse events associated with roflumilast were diarrhea, nausea, and weight loss. Roflumilast is associated with an increased risk of psychiatric adverse reactions and possibly suicide ideation.1
COPD is a debilitating lung disease with periodic exacerbation. Pharmacotherapy includes beta agonists, anticholingerics, and inhaled corticosteroids. The goal of treatment is to control symptoms, improve health status, and reduce the frequency and severity of exacerbations.7 Roflumilast is the newest drug for the management of COPD exacerbations, showing a modest reduction in exacerbations of 15%-18% in patients with severe COPD. Roflumilast is not a bronchodilator but did show measurable but modest improvement in FEV1. Patients with severe COPD with a history of exacerbation and chronic bronchitis appear to benefit from roflumilast.
1. Daliresp prescribing Information. Forest Pharmaceuticals. February 2011.
2. Rennard SI, et al. Reduction of exacerbations by the PDE4 inhibitor roflumilast The importance of defining different subsets of patients with COPD. Respir Res 2011;12:18.
3. Ulrik CS, Calverley PM. Roflumilast: Clinical benefit in patients suffering from COPD. Clin Respir J 2010; 4:197-201.
4. Calverley PM, et al. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:154-161.
5. Calverley PM, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: Two randomised clinical trials. Lancet 2009;374:685-694.
6. Fabbri LM, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long-acting bronchodilators: Two randomised clinical trials. Lancet 2009;374:695-703.
7. Global Initiative for Chronic Obstructive Lung Disease. http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=1116.