From the Guidelines
For patients experiencing frequent COPD exacerbations despite triple inhaler therapy, the addition of macrolide maintenance therapy, such as azithromycin, is recommended in appropriate patients with a normal QT interval on ECGs, no significant drug interactions, and no evidence of atypical mycobacteria infection, as stated in the 2023 Canadian Thoracic Society guideline 1. This recommendation is based on the most recent and highest quality evidence available. The 2023 Canadian Thoracic Society guideline suggests that macrolide maintenance therapy can be beneficial in reducing exacerbations in patients with COPD who continue to exacerbate despite being on triple inhaler therapy.
- Key considerations for the addition of macrolide maintenance therapy include:
- Normal QT interval on ECGs
- No significant drug interactions with concomitant medications
- No evidence of atypical mycobacteria infection
- Alternative options, such as roflumilast or N-acetylcysteine, may be considered for patients with a chronic bronchitic phenotype and high risk of exacerbations, as suggested by the 2023 Canadian Thoracic Society guideline 1 and supported by previous studies 1.
- The use of biologic therapies, such as mepolizumab or benralizumab, may be considered for patients with elevated blood eosinophils (≥300 cells/μL), although this is not explicitly stated in the provided guidelines.
- Theophylline and systemic oral corticosteroids, such as prednisone, are not recommended for maintenance treatment in COPD due to their potential side effects and lack of benefits, as stated in the 2023 Canadian Thoracic Society guideline 1 and previous studies 1.
From the FDA Drug Label
The effect of roflumilast 500 mcg once daily on COPD exacerbations was evaluated in five 1-year trials (Trials 3,4,5,6 and 9). An additional placebo-controlled 1-year trial (Trial 9) evaluated the effect of roflumilast 500 mcg on COPD exacerbations when added to a fixed-dose combination (FDC) product containing an inhaled corticosteroid and long-acting beta agonist (ICS/LABA).
Medications for frequent COPD exacerbations despite triple inhaler therapy may include roflumilast.
- Roflumilast 500 mcg once daily demonstrated a significant reduction in the rate of moderate or severe exacerbations compared to placebo in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.
- The use of roflumilast as add-on therapy to a fixed-dose combination product containing an inhaled corticosteroid and long-acting beta agonist (ICS/LABA) has been evaluated in a clinical trial 2.
- Patients with severe COPD and a history of exacerbations may benefit from roflumilast as an add-on therapy to reduce the rate of moderate or severe exacerbations.
From the Research
Medications for Frequent COPD Exacerbations
Despite Triple Inhaler Therapy
- Patients with chronic obstructive pulmonary disease (COPD) who experience frequent exacerbations despite maximal inhaled therapy ("triple therapy") may benefit from additional treatments 3.
- Roflumilast, a selective phosphodiesterase 4 inhibitor, 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 4, 5, 6.
- The advantages of roflumilast over inhaler therapy include its oral administration and once-daily dosing, with common adverse effects being gastrointestinal upset, headache, and weight loss 4, 6.
- Patients with elevated blood eosinophil counts (BEC) and frequent exacerbations may be candidates for biologic therapies, such as eosinophil-depleting therapies 3.
- Triple inhaled therapy for COPD, consisting of an inhaled corticosteroid, a long-acting β2-agonist, and a long-acting muscarinic antagonist, is recommended for patients who experience recurrent exacerbations despite treatment with dual bronchodilator or LABA/ICS combination therapy 7.