For an adult with asthma currently using Advair Diskus (fluticasone 250 µg/salmeterol 50 µg) 1 puff twice daily, is it appropriate to switch to or add Breztri (budesonide/formoterol/glycopyrrolate) and what are the recommendations?

Do Not Switch to Breztri for Asthma

Breztri is FDA-approved only for COPD, not asthma, and should not be used in this patient. The patient should remain on Advair Diskus or consider alternative asthma-specific therapies if control is inadequate.

Why Breztri is Inappropriate

Breztri (budesonide/glycopyrronium/formoterol) is a triple therapy containing a long-acting muscarinic antagonist (LAMA) specifically designed for COPD maintenance treatment 1. The evidence base for Breztri exclusively involves COPD patients, with pivotal trials demonstrating benefits in reducing COPD exacerbations and improving lung function compared to dual therapy 1. There is no evidence supporting its use in asthma, and it lacks FDA approval for this indication.

The addition of a LAMA (glycopyrrolate) to ICS/LABA therapy is not part of standard asthma management guidelines. Current asthma guidelines recommend ICS/LABA combinations as preferred therapy for moderate-to-severe persistent asthma (Steps 3-4), with LABAs being the preferred adjunctive therapy to ICS in adults 2. Anticholinergics like ipratropium are only recommended for acute exacerbations in asthma, not maintenance therapy 2.

Appropriate Management Options

If Asthma is Well-Controlled on Current Therapy

• Continue Advair Diskus 250/50 mcg twice daily 3
• Reassess control every 3 months; consider step-down if well-controlled for ≥3 consecutive months 4

If Asthma Control is Inadequate

Step-up options within asthma guidelines:

1. Increase ICS dose: Switch to Advair Diskus 500/50 mcg twice daily (high-dose ICS/LABA) 3

2. Consider budesonide/formoterol as alternative ICS/LABA:

   • Switching from fluticasone/salmeterol to budesonide/formoterol combinations has shown improved peripheral airway inflammation and asthma control in some patients 5
   • Budesonide/formoterol 320/9 mcg twice daily provides comparable or superior exacerbation reduction versus salmeterol/fluticasone 6, 7, 8
   • May offer maintenance and reliever therapy option (SMART regimen) where approved 8, 9

3. Add adjunctive therapy:

   • Add leukotriene receptor antagonist (montelukast) to current ICS/LABA 3
   • Note: FDA issued Boxed Warning for montelukast in March 2020 regarding neuropsychiatric events 4

4. Consider biologics for severe asthma (Step 5-6):

   • Omalizumab for allergic asthma in patients ≥12 years requiring high-dose ICS/LABA 2

Critical Safety Consideration

LABAs must never be used as monotherapy in asthma 3, 2. They should only be used in combination with ICS, as LABA monotherapy increases the risk of asthma-related deaths and severe exacerbations 3, 10. This fundamental principle underscores why switching to any therapy must maintain appropriate ICS coverage.

Assessment Before Any Change

Before modifying therapy, verify:

• Adherence to current regimen
• Inhaler technique is correct 11
• Environmental triggers are controlled 4
• Comorbid conditions (GERD, rhinitis, obesity) are managed 4
• SABA use: Using rescue inhaler >2 days/week indicates inadequate control and need for step-up 2, 4

The patient should remain on asthma-specific therapy with appropriate ICS/LABA combinations rather than switching to a COPD medication.