Can you take Yupelri (revefenacin) and Incruse (umeclidinium) together?

Concurrent Use of Yupelri and Incruse is Not Recommended

You should not use Yupelri (revefenacin) and Incruse (umeclidinium) together because both are long-acting muscarinic antagonists (LAMAs), and combining two drugs from the same class with identical mechanisms of action provides no additional benefit while increasing the risk of anticholinergic side effects. 1

Why This Combination Should Be Avoided

Same Mechanism of Action

• Both revefenacin and umeclidinium are LAMAs that work by blocking muscarinic receptors (M1-M5) in the airways to produce bronchodilation 2, 3
• Revefenacin is a potent and selective muscarinic antagonist with similar affinity for different muscarinic receptor subtypes, with particular selectivity for M3 receptors 2, 3
• Umeclidinium is also a LAMA approved for COPD maintenance therapy, functioning through the same anticholinergic pathway 4, 5

Guideline Recommendations Against Dual LAMA Therapy

• The FDA label for Yupelri explicitly states: "Do not use other medicines that contain an anticholinergic for any reason" and specifically lists umeclidinium as an anticholinergic medicine that should not be used concurrently 1
• The 2023 Canadian Thoracic Society COPD guidelines recommend LAMA monotherapy or LAMA/LABA dual therapy, but never mention combining two LAMAs 6
• Drug combinations with similar mechanisms of action should be avoided, as two drugs from the same class should not be administered together 6

Increased Risk Without Benefit

• Using two LAMAs simultaneously would expose patients to redundant anticholinergic effects without additional bronchodilation 1
• The risk of anticholinergic adverse effects increases, including worsening glaucoma, urinary retention, and other systemic anticholinergic side effects 1
• No clinical evidence supports improved efficacy with dual LAMA therapy compared to single LAMA therapy 6

What to Do Instead

If Current LAMA Monotherapy is Insufficient

• Add a long-acting beta-agonist (LABA) to create LAMA/LABA dual therapy, which is supported by strong evidence for reducing exacerbations and improving lung function 6
• The 2023 Canadian Thoracic Society guidelines recommend LAMA/LABA dual therapy as initial maintenance therapy for patients with moderate to high symptom burden and impaired lung function (FEV₁ <80% predicted) 6
• LAMA/LABA combinations have complementary mechanisms of action where the LABA provides additional bronchodilation through beta-2 receptor stimulation 6, 5

Switching Between LAMAs

• If a patient is not responding adequately to one LAMA, consider switching to a different LAMA rather than adding a second one 6
• Individual differences in response mean switching between different LAMAs may be worthwhile if the first drug produces a poor response 6
• Revefenacin delivered via nebulizer may be suitable for patients with conditions that impair proper use of traditional handheld inhalers like Incruse 2

For Patients Requiring Intensified Therapy

• Consider triple therapy (LAMA/LABA/ICS) for patients at high risk of exacerbations, though this increases pneumonia risk 6, 7
• Evaluate for pulmonary rehabilitation, oxygen therapy, or treatment of comorbidities rather than medication duplication 7

Common Clinical Pitfalls to Avoid

• Never combine two LAMAs thinking it will provide "double the bronchodilation" - this represents irrational polypharmacy with only increased side effect risk 1
• Always verify that patients are not already on another anticholinergic medication before prescribing a new LAMA 1
• When transitioning between LAMAs, discontinue the previous LAMA rather than continuing both 1
• Remember that revefenacin is specifically formulated for nebulizer use and cannot be used in handheld inhalers, while umeclidinium is a dry powder inhaler - this delivery system difference does not justify using both 2