What is the recommended dosing and management strategy for Breztri (budesonide, glycopyrrolate, and formoterol) in a patient with Chronic Obstructive Pulmonary Disease (COPD)?

How to Use Breztri for COPD Management

Breztri (budesonide/glycopyrrolate/formoterol) should be administered as two inhalations twice daily (morning and evening) via the metered-dose Aerosphere inhaler for maintenance treatment of COPD, particularly in patients with moderate to severe disease (FEV₁ <50-60% predicted) who have a history of exacerbations despite optimal bronchodilator therapy. 1, 2

Patient Selection Criteria

Breztri is most appropriate for GOLD Group D patients who meet the following criteria:

• Severe airflow obstruction with FEV₁ <50% predicted 1
• History of exacerbations (≥2 moderate exacerbations per year or ≥1 hospitalization) despite current therapy 3, 4
• Persistent symptoms (moderate to severe dyspnea) despite dual bronchodilator therapy (LABA/LAMA) or dual ICS/LABA therapy 3, 2

Real-world data demonstrates that Breztri is being initiated in patients experiencing symptoms and exacerbations despite current therapy, with 57.9% having evidence of COPD exacerbation in the prior year and 54.3% having required oral corticosteroid fills 4.

Dosing and Administration

Standard dosing: Two inhalations of budesonide 160 mcg/glycopyrrolate 18 mcg/formoterol 9.6 mcg twice daily (morning and evening) 2, 5

Key administration points:

• Delivered via pressurized metered-dose Aerosphere inhaler using co-suspension delivery technology 2
• Not for acute symptom relief - patients must have a separate short-acting beta2-agonist rescue inhaler 6
• When initiating Breztri, discontinue regular use of short-acting beta2-agonists (if used four times daily), reserving them only for acute symptom relief 6

Clinical Efficacy Evidence

Triple therapy with Breztri demonstrates superior outcomes compared to dual therapy:

• Exacerbation reduction: 24% reduction in moderate/severe exacerbations versus dual bronchodilator therapy, with a number needed to treat of 4 patients for one year to prevent one exacerbation 1, 2
• Mortality benefit: 49% reduction in all-cause mortality risk compared to glycopyrrolate/formoterol (hazard ratio 0.51,95% CI 0.33-0.80) 5
• Lung function improvement: Significant improvements in FEV₁ and peak expiratory flow maintained over 52 weeks 2, 7
• Quality of life: Improvements in dyspnea scores, reduced rescue medication requirements, and enhanced health-related quality of life 2, 7

Treatment Pathway Algorithm

For GOLD Group D patients (high symptoms, high exacerbation risk):

1. First-line: Initiate LABA/LAMA dual bronchodilator therapy 8
2. If exacerbations persist on LABA/LAMA: Escalate to triple therapy (Breztri) 8
3. Alternative pathway: Switch from LABA/LAMA to LABA/ICS if initial response inadequate, then add LAMA to create triple therapy 8

For patients already on LABA/ICS who continue to exacerbate:

• Add LAMA component to create triple therapy (Breztri provides all three in single inhaler) 8

For patients with asthma-COPD overlap or elevated blood eosinophils:

• Triple therapy including ICS may be considered as first-line therapy 8

Safety Considerations and Monitoring

Pneumonia risk: ICS-containing regimens increase pneumonia risk with a number needed to harm of 33 patients treated for one year, but this is outweighed by exacerbation reduction benefits in appropriate patients 1, 9

Cardiovascular monitoring: Monitor for tachycardia, hypertension, ECG changes (QTc prolongation, ST segment depression, T wave flattening), particularly in patients with pre-existing cardiovascular disease 6

Metabolic effects: Monitor for hypokalemia and hyperglycemia, though clinically significant changes are infrequent at recommended doses 6

Contraindications for use:

• Do not use for acute deteriorations or as rescue therapy 6
• Do not use in conjunction with other long-acting beta2-agonists 6
• Use with caution in patients with cardiovascular disorders, convulsive disorders, thyrotoxicosis, or diabetes 6

Critical Pitfalls to Avoid

Never add additional ICS therapy (such as Pulmicort) to Breztri - this represents irrational polypharmacy exposing patients to two ICS medications simultaneously without guideline support 9

When transitioning from dual ICS/LABA therapy to Breztri, discontinue the previous ICS-containing regimen rather than continuing both 9

Do not increase dosing beyond two inhalations twice daily if symptoms worsen - instead, re-evaluate the patient and overall COPD treatment regimen 6

Recognize that increasing rescue inhaler use signals disease deterioration requiring prompt medical attention and treatment reassessment, not simply increasing Breztri dose 6

Management of Persistent Exacerbations on Triple Therapy

If patients continue to exacerbate despite Breztri:

• Add roflumilast for patients with FEV₁ <50% predicted, chronic bronchitis phenotype, and history of hospitalization for exacerbation 8, 9
• Add macrolide therapy in former smokers, weighing risk of resistant organism development 8
• Consider ICS withdrawal if adverse effects (particularly pneumonia) outweigh benefits, as data show no significant harm from ICS withdrawal 8
• Evaluate for pulmonary rehabilitation, oxygen therapy, or treatment of comorbidities rather than medication duplication 9

Complementary Non-Pharmacologic Management

All patients on Breztri should receive:

• Smoking cessation counseling if currently smoking 8
• Pulmonary rehabilitation for GOLD Groups B, C, and D patients 8
• Vaccination: Annual influenza vaccine and pneumococcal vaccines (PCV13 and PPSV23 for patients ≥65 years) 8
• Education on inhaler technique and self-management strategies 8