How does Roflumilast (Daxas) help Chronic Obstructive Pulmonary Disease (COPD)?

From the Guidelines

Roflumilast (Daxas) helps Chronic Obstructive Pulmonary Disease (COPD) by reducing moderate and severe exacerbations in patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations, as evidenced by its ability to inhibit the enzyme phosphodiesterase-4 (PDE4) and decrease inflammatory cell activity and the production of inflammatory mediators in the lungs 1.

Key Points

• Roflumilast is typically prescribed at a dose of 500 mcg once daily as an oral tablet for patients with severe COPD who have chronic bronchitis and a history of exacerbations.
• This medication works differently from bronchodilators by targeting the underlying inflammation rather than directly opening airways.
• It decreases the frequency of exacerbations by reducing inflammatory cell activity and the production of inflammatory mediators in the lungs.
• Patients should be aware that roflumilast is not a rescue medication for acute breathing problems but rather a maintenance therapy that works over time to reduce flare-ups.
• Common side effects include diarrhea, weight loss, nausea, and headache, and it should be avoided in underweight patients and used with caution in patients with depression 1.

Clinical Considerations

• Roflumilast should be taken consistently even when symptoms improve, and patients should continue using their other COPD medications as prescribed since roflumilast complements rather than replaces bronchodilators and other treatments.
• Improvement may not be immediately noticeable as the anti-inflammatory effects develop gradually.
• The European Respiratory Society/American Thoracic Society guideline suggests treatment with roflumilast to prevent future exacerbations in patients who have COPD with severe or very severe airflow obstruction, symptoms of chronic bronchitis, and exacerbations despite optimal inhaled therapy 1.

From the FDA Drug Label

Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic-3',5'-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP While the specific mechanism(s) by which roflumilast exerts its therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in lung cells. Roflumilast tablet is a prescription medicine used in adults with severe Chronic Obstructive Pulmonary Disease (COPD) to decrease the number of flare-ups or the worsening of COPD symptoms (exacerbations).

Roflumilast (Daxas) helps Chronic Obstructive Pulmonary Disease (COPD) by:

• Inhibiting phosphodiesterase 4 (PDE4), which leads to an increase in intracellular cyclic AMP in lung cells
• Decreasing the number of flare-ups or exacerbations of COPD symptoms
• Reducing sputum neutrophils and eosinophils by 31% and 42%, respectively, in COPD patients 2 Roflumilast is not a bronchodilator and should not be used for treating sudden breathing problems 2 2

From the Research

Mechanism of Action

• Roflumilast is a selective phosphodiesterase 4 inhibitor that targets inflammatory cells involved in triggering COPD exacerbations 3, 4.
• It is an oral tablet that only needs to be taken once daily, offering an advantage over inhaler therapy 3.

Efficacy

• Roflumilast has been shown to improve lung function and reduce exacerbations in patients with severe COPD, especially those with chronic bronchitis, frequent exacerbations, or who require frequent rescue inhaler therapy 3, 5.
• It has also been found to be effective in reducing moderate and severe exacerbations in patients with moderate-to-severe COPD associated with chronic bronchitis and a history of exacerbations 5, 6.
• The greatest benefit of roflumilast was seen in patients with moderate-to-severe COPD associated with chronic bronchitis, along with a recent history of exacerbations 5.

Safety and Tolerability

• The most common adverse events associated with roflumilast are diarrhea, nausea, and headache 3, 5, 4.
• Weight loss and an increased risk of psychiatric events have also been reported in association with roflumilast use 5, 4.
• Roflumilast is generally well tolerated, but patients who discontinued therapy usually did so during the first few weeks due to gastrointestinal side effects 3.

Patient Subgroups

• The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD, including older adults, those with a higher Charlson comorbidity index, and those with a history of exacerbation 6.
• Roflumilast may provide additional benefits when added to inhaled combination therapy in patients still suffering from frequent exacerbations 7.