What is the difference between Breztri (budesonide/glycopyrrolate/formoterol) and Symbicort (budesonide/formoterol) for a patient with chronic obstructive pulmonary disease (COPD) or asthma?

Breztri vs Symbicort for COPD

For patients with COPD, Breztri (budesonide/glycopyrrolate/formoterol) is superior to Symbicort (budesonide/formoterol) because the addition of the long-acting muscarinic antagonist (LAMA) glycopyrrolate provides significantly better lung function, reduces exacerbations more effectively, and improves symptoms compared to dual ICS/LABA therapy alone. 1, 2

Key Compositional Differences

Breztri contains three active components delivered via metered dose inhaler 2:

• Budesonide 320 μg (inhaled corticosteroid)
• Glycopyrrolate 14.4 μg (long-acting muscarinic antagonist/LAMA)
• Formoterol 10 μg (long-acting beta-2 agonist/LABA)

Symbicort contains two active components 3, 4:

• Budesonide 320-400 μg (inhaled corticosteroid)
• Formoterol 10-12 μg (long-acting beta-2 agonist/LABA)

The critical difference is that Breztri provides triple therapy (ICS/LAMA/LABA) while Symbicort provides only dual therapy (ICS/LABA). 1, 2

When to Choose Breztri Over Symbicort

Primary Indications for Breztri

Use Breztri for patients with:

• FEV1 <60% predicted with ≥2 moderate exacerbations or ≥1 severe exacerbation requiring hospitalization in the past year 5, 2
• Persistent symptoms despite dual bronchodilator therapy (LAMA/LABA) or ICS/LABA combination 1, 5
• GOLD category D disease (high symptom burden with frequent exacerbations) 5

Evidence Supporting Breztri's Superiority

The KRONOS trial demonstrated that Breztri 2:

• Significantly improved morning pre-dose trough FEV1 by 69 mL compared to Symbicort (p<0.0001)
• Reduced annual moderate-to-severe exacerbation rates by 47% compared to dual LAMA/LABA therapy (rate ratio 0.53, p=0.0005)
• Provided these benefits even in patients without airway reversibility and eosinophil counts <300 cells/mm³, proving the advantage extends beyond typical ICS-responsive phenotypes

Triple inhaled therapy improves lung function, symptoms, and health status compared to ICS/LABA combinations, with evidence showing reduced exacerbations versus dual therapy. 1

When Symbicort May Be Appropriate

Consider Symbicort for patients with:

• FEV1 >60% predicted with <2 exacerbations per year 5
• GOLD category B or C disease (either high symptoms with low exacerbation risk, or low symptoms with moderate exacerbation risk) 1, 5
• Adequate symptom control on dual ICS/LABA therapy without need for escalation 5
• Asthma-COPD overlap syndrome where ICS/LABA may be preferred initial therapy 5

Critical Safety Considerations

Pneumonia Risk

Both medications carry increased pneumonia risk due to the ICS component 1, 5:

• ICS-containing regimens increase pneumonia risk by approximately 4% (odds ratio 1.38-1.48) 1, 5
• Risk is particularly elevated in patients who are older, have BMI <25 kg/m², smoke currently, or have severe airflow limitation 1

Contraindications for ICS-Containing Therapy

Avoid both Breztri and Symbicort in patients with: 5

• Active or indolent atypical mycobacterial infection
• Recurrent pneumonia without frequent exacerbations
• History of tuberculosis requiring careful risk-benefit assessment

Monitoring Requirements

For both medications, assess regularly for 5:

• Oral candidiasis, hoarseness, and dysphonia
• Signs of pneumonia (fever, productive cough, chest pain)
• Blood eosinophil counts to identify patients most likely to benefit from ICS component (≥300 cells/μL suggests greater ICS benefit)

Treatment Algorithm

Step 1: Determine disease severity and exacerbation history 1, 5

• Measure FEV1 and document exacerbations in past 12 months
• Assess symptom burden using validated tools (CAT score, mMRC dyspnea scale)

Step 2: Check blood eosinophil count 5

• Eosinophils ≥300 cells/μL predict better ICS response
• Eosinophils <100 cells/μL suggest limited ICS benefit

Step 3: Apply treatment selection criteria:

Choose Breztri if: 1, 5, 2

• FEV1 <60% predicted AND ≥2 moderate or ≥1 severe exacerbations per year
• Persistent symptoms despite optimized dual therapy
• GOLD category D disease

Choose Symbicort if: 1, 5

• FEV1 >60% predicted with <2 exacerbations per year
• Step-up from LABA monotherapy in moderate disease
• Asthma-COPD overlap requiring ICS/LABA as initial combination

Step 4: Reassess at 3 months 5

• If inadequate response on Symbicort with continued exacerbations, escalate to Breztri
• If stable on Breztri but eosinophils <100 cells/μL and no exacerbations for 12 months, consider de-escalation (though withdrawal increases exacerbation risk)

Common Pitfalls to Avoid

Never use ICS monotherapy in COPD - both budesonide components must be combined with long-acting bronchodilators. 5

Do not prescribe Symbicort for severe COPD with frequent exacerbations - these patients require triple therapy with Breztri from the outset rather than sequential step-up. 1, 5

Avoid withdrawing ICS in patients with eosinophils ≥300 cells/μL - this significantly increases moderate-to-severe exacerbation risk. 5

Do not overlook proper inhaler technique - ensure patients can effectively use the specific delivery device, as technique failures reduce medication effectiveness regardless of which agent is prescribed. 5

Breztri is not indicated for asthma - it is FDA-approved only for COPD maintenance treatment, whereas Symbicort has indications for both asthma and COPD. 6