Adding a LABA to Yupelri (Revefenacin)
For a patient with severe emphysema/COPD already on Yupelri (revefenacin, a LAMA), add a long-acting beta-agonist (LABA) such as formoterol or salmeterol to create dual bronchodilator therapy. This LAMA/LABA combination provides superior symptom control, lung function improvement, and exacerbation prevention compared to LAMA monotherapy in patients with severe disease 1, 2.
Rationale for LABA Addition
Dual bronchodilator therapy with LAMA/LABA is the evidence-based escalation strategy for patients with severe COPD who remain symptomatic on single-agent therapy. The combination demonstrates:
- Greater improvements in lung function (FEV1) compared to LAMA monotherapy, with sustained bronchodilation throughout the 24-hour dosing interval 2, 3
- Superior symptom relief and dyspnea reduction versus single bronchodilators, particularly important in severe emphysema 1, 2
- Similar or better exacerbation prevention compared to LAMA alone, without the pneumonia risk associated with inhaled corticosteroids 2, 1
Specific LABA Options for Nebulized Delivery
Since Yupelri is administered via nebulizer, formoterol fumarate inhalation solution is the preferred LABA addition because:
- Physicochemical compatibility has been demonstrated when revefenacin and formoterol are mixed in the same nebulizer, maintaining stability for up to 25 hours at room temperature 4
- Nebulized formoterol allows patients to continue with their preferred delivery method, potentially improving adherence 5, 6
- Once-daily or twice-daily dosing options are available depending on symptom burden 4
Clinical Trial Evidence Supporting This Approach
The FDA label for Yupelri specifically notes that 37% of patients in pivotal trials were taking LABA or ICS/LABA therapy concomitantly with revefenacin throughout the study, demonstrating the safety and appropriateness of this combination 7. These patients showed:
- Mean trough FEV1 improvements of 146-147 mL versus placebo at Day 85 7
- Peak FEV1 improvements of 129-133 mL within the first 2 hours after dosing 7
- Greater improvements in more severe patients when LABA was added to revefenacin 3
When to Consider Triple Therapy Instead
Do not routinely add an inhaled corticosteroid (ICS) unless specific criteria are met:
- Blood eosinophils ≥300 cells/μL with history of frequent exacerbations (≥2 moderate or ≥1 severe per year) 1, 8
- Asthma-COPD overlap syndrome documented by history or testing 9
- Persistent exacerbations despite LAMA/LABA therapy in former smokers 1, 8
The pneumonia risk with ICS (number needed to harm = 33) must be weighed against exacerbation benefit (number needed to treat = 4), making ICS inappropriate for most emphysema patients without these specific indications 8.
Practical Implementation
Administer both medications via the same nebulizer session:
- Mix revefenacin 175 mcg (one unit-dose vial) with formoterol fumarate inhalation solution in the nebulizer cup 4
- Deliver once daily at the same time each day to maintain consistent bronchodilation 7, 6
- Continue short-acting beta-agonists (albuterol) for rescue use as needed 7
Monitoring and Safety
Reassess at 2-4 weeks for:
- Improvement in dyspnea scores (mMRC or CAT) 10
- Reduction in rescue medication use 7
- Absence of anticholinergic side effects (dry mouth, urinary retention, narrow-angle glaucoma symptoms) 7, 6
If symptoms persist despite LAMA/LABA therapy, then consider escalation to triple therapy with ICS addition based on eosinophil count and exacerbation history 1, 8.