What is the recommended dosing regimen for Breztri (budesonide, glycopyrrolate, and formoterol) in patients with Chronic Obstructive Pulmonary Disease (COPD)?

Recommended Dosing for Breztri in COPD

The recommended dosing regimen for Breztri (budesonide/glycopyrrolate/formoterol) is two inhalations twice daily (morning and evening) delivering a total daily dose of 320/18/9.6 μg of budesonide/glycopyrrolate/formoterol. 1

Mechanism and Formulation

Breztri Aerosphere is a fixed-dose combination triple therapy that combines:

• Budesonide (inhaled corticosteroid/ICS)
• Glycopyrrolate (long-acting muscarinic antagonist/LAMA)
• Formoterol fumarate (long-acting β2-agonist/LABA)

It is delivered via a pressurized metered-dose Aerosphere inhaler using co-suspension delivery technology to ensure consistent medication delivery.

Clinical Evidence Supporting This Dosing

The efficacy of Breztri at this dosing regimen has been established in multiple clinical trials:

• The ETHOS trial demonstrated that Breztri 320/18/9.6 μg twice daily significantly reduced:

  • Moderate to severe COPD exacerbations compared to dual therapies
  • All-cause mortality compared to glycopyrrolate/formoterol (GFF) dual therapy 2

• The KRONOS study showed that Breztri at this dosing improved:

  • Lung function (morning pre-dose trough FEV1)
  • COPD symptoms
  • Health-related quality of life 3

Patient Selection

Breztri is indicated for maintenance treatment of COPD. Real-world data shows it is typically prescribed for patients who:

• Have moderate to very severe COPD
• Experience symptoms and exacerbations despite current therapy
• Have various chronic comorbidities (often cardiopulmonary-related)
• Have a history of COPD exacerbations 4

Administration Guidelines

• Patients should be instructed to:
  • Take exactly two inhalations twice daily (morning and evening)
  • Rinse mouth with water after each use to reduce risk of oral candidiasis
  • Not use with other medications containing LABAs due to risk of overdose 5
  • Not use for acute symptoms (rescue therapy)

Important Precautions

1. Not for Acute Use: Breztri should not be used for relief of acute symptoms. A short-acting beta2-agonist should be prescribed for acute symptom relief 5

2. Deterioration Monitoring: Patients should be monitored for:

   • Increasing use of rescue medications
   • Decreasing effectiveness of treatment
   • Worsening symptoms These may indicate disease deterioration requiring prompt medical attention 5

3. Cardiovascular Effects: As with other beta2-agonists, Breztri can produce clinically significant cardiovascular effects and should be used with caution in patients with cardiovascular disorders 5

4. Other Precautions:

   • Risk of paradoxical bronchospasm
   • Potential for hypokalemia and hyperglycemia
   • Do not exceed recommended dose

Common Pitfalls to Avoid

1. Inappropriate Use as Rescue Medication: Ensure patients understand Breztri is for maintenance therapy only, not for acute symptom relief

2. Concomitant Use with Other LABAs: Avoid prescribing Breztri with other medications containing LABAs to prevent overdose 5

3. Inadequate Monitoring: Failure to monitor for disease deterioration or adverse effects

4. Abrupt Discontinuation: If treatment needs to be discontinued, consider gradual tapering, especially of the inhaled corticosteroid component

5. Ignoring Comorbidities: Be mindful of cardiovascular comorbidities when prescribing, as these are common in COPD patients and may affect tolerability 4

By following these dosing recommendations and precautions, Breztri can effectively help manage COPD symptoms and reduce exacerbations in appropriate patients.