What considerations should be taken when switching a patient with Chronic Obstructive Pulmonary Disease (COPD) from Trelegy (fluticasone furoate, umeclidinium, and vilanterol) to Breztri (budesonide, glycopyrrolate, and formoterol)?

Switching from Trelegy to Breztri in COPD

Both Trelegy (fluticasone furoate/umeclidinium/vilanterol) and Breztri (budesonide/glycopyrrolate/formoterol) are effective triple therapy options for COPD, but recent real-world evidence suggests Trelegy may provide superior outcomes with 12% lower exacerbation rates and 11% lower mortality risk compared to Breztri 1.

Key Medication Differences

Corticosteroid Component:

• Trelegy contains fluticasone furoate (a higher potency ICS), while Breztri contains budesonide (a lower potency ICS) 2, 1
• Budesonide in Breztri delivers a lower total daily corticosteroid dose, which may be advantageous for minimizing systemic corticosteroid exposure 3

Bronchodilator Components:

• Both contain a LABA/LAMA combination, but with different specific agents (umeclidinium/vilanterol vs. glycopyrrolate/formoterol) 2, 4
• Formoterol in Breztri has a faster onset of action compared to vilanterol, which may benefit patients requiring more rapid symptom relief 2

Dosing Regimen:

• Trelegy: once daily administration 4
• Breztri: twice daily administration 2

Clinical Scenarios Favoring Switching to Breztri

Consider switching from Trelegy to Breztri when:

• Pneumonia risk is elevated: Patients with recurrent pneumonia or high pneumonia risk may benefit from the lower ICS dose in Breztri, as ICS-containing regimens increase pneumonia risk by approximately 4% 5, 6
• Systemic corticosteroid effects are problematic: Patients experiencing adrenal suppression, bone mineral density loss, cataracts, or other ICS-related adverse effects may benefit from budesonide's lower systemic exposure 3, 2
• Faster-acting bronchodilation is needed: Formoterol's rapid onset may provide better acute symptom control for patients requiring quick relief 2
• Patient preference for twice-daily dosing: Some patients prefer splitting doses throughout the day for more consistent symptom control 2

Clinical Scenarios Favoring Remaining on Trelegy

Maintain Trelegy therapy when:

• Exacerbation control is optimal: Real-world data from 44,542 Medicare patients demonstrated Trelegy users had significantly lower annualized moderate-severe exacerbation rates (0.80 vs 0.91 per patient-year; rate ratio 0.88, p<0.001) 1
• Mortality reduction is a priority: Trelegy showed 11% lower all-cause mortality risk at 12 months compared to Breztri (5.6% vs 6.4%; HR 0.89, p=0.020) 1
• Once-daily dosing improves adherence: Single daily administration may enhance treatment adherence and efficacy 4
• Patient is well-controlled without adverse effects: If the patient has achieved good symptom control and exacerbation prevention without significant side effects, switching is not indicated 5

Practical Switching Algorithm

Step 1: Assess Current Disease Control

• Document exacerbation frequency in the past 12 months 5
• Evaluate symptom burden using validated tools (CAT score, mMRC dyspnea scale) 5
• Review FEV1 and blood eosinophil counts (≥300 cells/μL suggests greater ICS benefit) 5, 3

Step 2: Identify Reasons for Switching

• Evaluate for ICS-related adverse effects: pneumonia history, bone density concerns, cataracts, oral candidiasis 2
• Assess adherence issues with once-daily dosing 4
• Consider cost and insurance coverage factors 1

Step 3: Execute the Switch

• Direct switch without washout period: Transition immediately from Trelegy to Breztri 160/9/4.8 mcg (2 inhalations twice daily) 2
• No dose titration required: Breztri is initiated at full therapeutic dose 2
• Patient education critical: Emphasize twice-daily dosing schedule and proper inhaler technique with the metered-dose inhaler device 2

Step 4: Monitor Post-Switch

• Reassess symptoms and exacerbation frequency at 4-6 weeks and 3 months post-switch 7
• Monitor for worsening dyspnea, increased rescue inhaler use, or exacerbations 7
• Evaluate for paradoxical bronchospasm, which requires immediate discontinuation 2

Critical Safety Considerations

Both medications carry similar warnings:

• Never use as monotherapy for asthma (LABA without ICS increases asthma-related death risk) 2
• Do not combine with additional LABA-containing medications due to overdose risk 2
• Monitor for cardiovascular effects (tachycardia, hypertension, arrhythmias) in patients with cardiac disease 2
• Assess for worsening narrow-angle glaucoma and urinary retention with anticholinergic component 2
• Rinse mouth after each use to reduce oral candidiasis risk 2

Breztri-specific precautions:

• Avoid strong CYP3A4 inhibitors (ritonavir, ketoconazole, clarithromycin) as they increase budesonide systemic exposure 2
• Monitor bone mineral density at baseline and periodically, especially in high-risk patients 2

Common Pitfalls to Avoid

Do not switch if:

• Patient has asthma-COPD overlap syndrome requiring higher ICS doses 5, 7
• Blood eosinophils are ≥300 cells/μL and patient is well-controlled on Trelegy (higher ICS dose provides greater benefit) 5, 3
• Patient has demonstrated excellent adherence and outcomes on once-daily Trelegy 1

Avoid these errors:

• Switching during an acute exacerbation (wait until patient is stable) 2
• Failing to educate on twice-daily dosing schedule, leading to missed doses 2
• Not monitoring for increased exacerbations post-switch, which may indicate inadequate ICS dose 7, 1
• Combining Breztri with other LABA or LAMA medications 2

When to Revert to Trelegy

Consider switching back to Trelegy if:

• Patient experiences ≥2 moderate-severe exacerbations within 12 months after switching to Breztri 7
• Symptom control deteriorates significantly despite proper Breztri use 7
• Adherence issues emerge with twice-daily dosing 4
• Patient develops features suggesting asthma-COPD overlap requiring higher ICS doses 7