What is Roflumilast (Daxas, phosphodiesterase-4 inhibitor)?

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From the Guidelines

Roflumilast is a phosphodiesterase-4 inhibitor used to reduce the risk of COPD exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. It is typically prescribed as a 500 microgram oral tablet taken once daily, with or without food. Roflumilast works by reducing inflammation in the lungs by preventing the breakdown of cyclic AMP, an important cellular messenger. Unlike bronchodilators or inhaled corticosteroids, roflumilast is not used for immediate symptom relief but rather as a maintenance therapy to prevent COPD flare-ups over time. Common side effects include diarrhea, weight loss, nausea, headache, and back pain. Patients should be monitored for psychiatric adverse effects including insomnia and depression. Roflumilast is typically added to existing COPD treatments when patients continue to experience exacerbations despite using other medications like long-acting bronchodilators, as suggested by the European Respiratory Society/American Thoracic Society guideline 1. The use of roflumilast has been shown to decrease the number of moderate or severe exacerbations per patient-year, as well as the proportion of patients who have an exacerbation, and increase the time to next exacerbation, as demonstrated in a meta-analysis of three trials 1. However, roflumilast also increases adverse events, and patients should be advised of the potential side effects, as noted in the American College of Chest Physicians and Canadian Thoracic Society guideline 1. In patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations, roflumilast improves lung function and reduces moderate and severe exacerbations, as stated in the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 report 1. Overall, roflumilast is a valuable treatment option for patients with severe COPD and a history of exacerbations, and its use should be considered in conjunction with other treatments, such as long-acting bronchodilators, to reduce the risk of exacerbations and improve patient outcomes.

From the FDA Drug Label

The active ingredient in roflumilast tablets is roflumilast. Roflumilast and its active metabolite (roflumilast N-oxide) are selective phosphodiesterase 4 (PDE4) inhibitors. Roflumilast is a selective phosphodiesteride 4 (PDE4) inhibitor. Its chemical name is 3-(Cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy) benzamide. The empirical formula is C17H14Cl2F2N2O3 and the molecular weight is 403.21 2 2 2.

From the Research

Definition and Mechanism of Roflumilast

  • Roflumilast is a selective phosphodiesterase 4 inhibitor 3, 4, 5, 6, 7
  • It is used for the maintenance treatment of severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add-on to bronchodilator treatment 3

Efficacy of Roflumilast

  • Roflumilast improves lung function and reduces exacerbations in patients with severe COPD, especially those with chronic bronchitis, frequent exacerbations, or who require frequent rescue inhaler therapy 3, 4, 7
  • It also improves lung function and reduces exacerbations in patients with moderately severe COPD treated with salmeterol or tiotropium 3, 7
  • Roflumilast has been shown to increase prebronchodilator forced expiratory volume in 1 second (FEV(1)) by 36-88 mL compared to placebo 6

Safety and Tolerability of Roflumilast

  • The most common adverse effects of roflumilast are gastrointestinal upset, headache, and weight loss 3, 4, 6, 7
  • Roflumilast has an acceptable tolerability profile, with 14% of patients discontinuing medication due to adverse events in a pooled analysis of two trials 7
  • Serious adverse events, including suicide-related adverse effects, have been reported in patients taking roflumilast 6

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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