What are the considerations for transitioning a patient from Trelegy (fluticasone furoate, umeclidinium, and vilanterol) and Duoneb (ipratropium bromide and albuterol sulfate) to Yupelri (revefenacin) for Chronic Obstructive Pulmonary Disease (COPD) management?

Transitioning from Trelegy and DuoNeb to Yupelri

Do not transition from Trelegy to Yupelri—this would represent a significant step-down in therapy that eliminates essential COPD medications (ICS and LABA) while duplicating anticholinergic coverage, and concurrent use of both medications is contraindicated due to duplicate LAMA therapy. 1

Why This Transition is Inappropriate

Duplication of Anticholinergic Therapy

• The American Thoracic Society explicitly recommends avoiding concurrent use of Trelegy and Yupelri because both contain long-acting muscarinic antagonists (umeclidinium in Trelegy, revefenacin in Yupelri), which increases the risk of adverse effects without additional clinical benefit 1
• The FDA labeling for Yupelri warns against using other anticholinergic medicines including umeclidinium for any reason 2
• Anticholinergic side effects include worsening narrow-angle glaucoma, urinary retention (especially with prostatic hyperplasia), and paradoxical bronchospasm 2

Loss of Critical Triple Therapy Components

• Trelegy provides complete triple therapy (LABA + LAMA + ICS) in a single once-daily inhaler, while Yupelri provides only LAMA therapy 1
• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines state that triple therapy should be delivered as a single regimen, not duplicated across multiple devices, and adding a second LAMA to existing triple therapy has no supporting evidence 1
• Switching from Trelegy to Yupelri would eliminate fluticasone furoate (ICS) and vilanterol (LABA), leaving the patient with only anticholinergic coverage 3

Recommended Management Algorithm

If Patient is Currently on Both Medications

• The American College of Chest Physicians recommends discontinuing Yupelri immediately, as the umeclidinium component in Trelegy provides adequate LAMA coverage 1
• Continue Trelegy as the sole maintenance therapy, which provides complete triple therapy in a single once-daily inhaler 1
• Reassess symptom control after 2-4 weeks 1

If Considering Switching from Trelegy to Yupelri

• Do not make this switch—it represents inappropriate de-escalation of therapy 1
• If the patient cannot afford Trelegy or has device-related issues, consider alternative triple therapy regimens or step-down to dual therapy (LABA/LAMA or LABA/ICS) based on exacerbation history and eosinophil count, but do not switch to LAMA monotherapy 1, 4

Role of DuoNeb in This Regimen

• DuoNeb (ipratropium/albuterol) is a short-acting combination used for acute symptom relief, not maintenance therapy 5
• If the patient is using DuoNeb regularly for maintenance (not just rescue), this suggests inadequate control on current maintenance therapy 5
• The short-acting anticholinergic (ipratropium) in DuoNeb can be continued as needed for acute symptoms, but regular scheduled use suggests the need to optimize maintenance therapy, not switch to different maintenance therapy 5

Device and Adherence Considerations

Advantages of Trelegy Over Yupelri

• The European Respiratory Society notes that Trelegy's once-daily Ellipta device offers superior convenience compared to nebulized Yupelri, which requires daily nebulizer setup and cleaning 1
• Dry powder inhalers like Ellipta have lower error rates (10-40%) compared to metered-dose inhalers (76% error rate) 5, 1
• Inhaler technique must be demonstrated at prescription and checked at every follow-up visit to improve adherence and reduce errors 5, 1

When Nebulizer Therapy is Appropriate

• The British Thoracic Society guidelines state that nebulizers should only be supplied to patients who have been assessed fully by a respiratory physician, after ensuring optimal use of metered-dose and dry powder inhalers has been attempted 5
• Most patients with COPD can be treated with bronchodilators delivered by metered-dose inhalers with spacers or dry powder devices 5
• Home nebulizer therapy is reserved for patients with severe disease who may benefit from high-dose bronchodilator treatment after formal assessment 5

Safety Monitoring if Patient Remains on Trelegy

Pneumonia Risk with ICS

• The American College of Chest Physicians reports that Trelegy contains fluticasone furoate (ICS), which carries a 4% increased risk of pneumonia compared to bronchodilators alone 1
• This risk is acceptable when triple therapy is indicated (severe COPD with frequent exacerbations or blood eosinophils ≥150-200 cells/µL) 1
• Monitor for signs of pneumonia: new or worsening dyspnea, fever, increased sputum production or purulence 1

Anticholinergic Burden

• The American Thoracic Society recommends reviewing concurrent anticholinergic medications (including those for overactive bladder, antihistamines with anticholinergic properties) to avoid additive anticholinergic burden 1
• Watch for urinary retention symptoms (difficulty passing urine, painful urination) and glaucoma symptoms (eye pain, blurred vision, visual halos) 2

Beta-Blocker Interactions

• The British Thoracic Society recommends avoiding beta-blocking agents (including ophthalmic preparations) in all COPD patients on bronchodilator therapy, as they can antagonize the vilanterol component in Trelegy 1

When to Reassess Therapy

Signs of Inadequate Control

• If Trelegy no longer controls symptoms of bronchoconstriction, the patient's short-acting beta2-agonist becomes less effective, or the patient needs more inhalations than usual, these are markers of disease deterioration requiring re-evaluation 2
• If symptoms remain uncontrolled after 2-4 weeks on optimized therapy, consider pulmonary rehabilitation, oxygen therapy assessment, or evaluation for comorbidities rather than adding duplicate therapy 1
• Increasing the daily dose beyond recommended levels or adding duplicate anticholinergic therapy is not appropriate 2