Can a patient be on Trelegy (fluticasone furoate, umeclidinium, and vilanterol) and Yupelri (revefenacin) simultaneously for Chronic Obstructive Pulmonary Disease (COPD) management?

Concurrent Use of Trelegy and Yupelri

No, a patient should not be on both Trelegy and Yupelri simultaneously due to duplication of anticholinergic therapy, which increases the risk of adverse effects without additional clinical benefit.

Rationale for Avoiding Concurrent Use

Drug Class Overlap

• Trelegy contains umeclidinium, a long-acting muscarinic antagonist (LAMA), combined with fluticasone furoate (inhaled corticosteroid) and vilanterol (long-acting β2-agonist) in a single inhaler 1
• Yupelri (revefenacin) is also a long-acting muscarinic antagonist delivered via nebulizer
• Using both medications simultaneously results in dual LAMA therapy, which provides no evidence-based benefit and increases anticholinergic side effects (dry mouth, urinary retention, constipation, potential cardiovascular effects)

Guideline-Based Approach to COPD Therapy

For patients with severe COPD requiring triple therapy, the combination of LABA + LAMA + ICS should be delivered as a single regimen, not duplicated across multiple devices 2, 3

• Triple therapy with umeclidinium/fluticasone furoate/vilanterol (Trelegy) is specifically designed for severe COPD patients with frequent exacerbations (≥2 per year) or those with FEV1 <50% predicted 4
• Adding a second LAMA (Yupelri) to existing triple therapy has no supporting evidence and violates the stepwise approach recommended by GOLD guidelines 2, 3

Clinical Decision Algorithm

If Patient is Currently on Both Medications:

1. Discontinue Yupelri immediately - the umeclidinium component in Trelegy provides adequate LAMA coverage 3
2. Continue Trelegy as the sole maintenance therapy - it provides complete triple therapy in a single once-daily inhaler 1, 4
3. Reassess symptom control after 2-4 weeks - if symptoms remain uncontrolled, consider pulmonary rehabilitation, oxygen therapy assessment, or evaluation for comorbidities rather than adding duplicate therapy 3

If Considering Which Agent to Initiate:

• For severe COPD with exacerbation history: Choose Trelegy - provides triple therapy (LAMA/LABA/ICS) in a single device with once-daily dosing, which improves adherence 4, 5
• For patients requiring only LAMA monotherapy: Choose either umeclidinium alone OR revefenacin (Yupelri), but never both 3

Important Safety Considerations

Beta-blocking agents (including ophthalmic preparations) should be avoided in all COPD patients on bronchodilator therapy 2, 3

• The vilanterol component in Trelegy is a β2-agonist that can be antagonized by beta-blockers
• Concurrent anticholinergic medications (including those for overactive bladder, antihistamines with anticholinergic properties) should be reviewed to avoid additive anticholinergic burden

Pneumonia Risk with ICS-Containing Regimens

• Trelegy contains fluticasone furoate (ICS), which carries a 4% increased risk of pneumonia compared to bronchodilators alone 2
• This risk is acceptable when triple therapy is indicated (severe COPD with frequent exacerbations or blood eosinophils ≥150-200 cells/µL) 3
• Monitor for signs of pneumonia: new or worsening dyspnea, fever, increased sputum production or purulence 3

Device and Adherence Factors

Trelegy's once-daily Ellipta device offers superior convenience compared to nebulized Yupelri, which requires daily nebulizer setup and cleaning 4, 6

• 76% of COPD patients make critical errors with metered-dose inhalers, but dry powder inhalers like Ellipta have lower error rates (10-40%) 3
• Inhaler technique must be demonstrated at prescription and checked at every follow-up visit 2, 3
• Once-daily dosing with Trelegy improves adherence compared to twice-daily regimens or nebulized therapy requiring multiple daily treatments 6, 7