Introduction
Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate) is a triple-combination inhalation aerosol indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). This fixed-dose combination product contains an inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta2-agonist (LABA) in a single pressurized metered-dose inhaler using co-suspension delivery technology.
Mechanism of Action
Breztri Aerosphere combines three pharmacologically active components with distinct mechanisms of action:
Budesonide: A synthetic corticosteroid that exerts potent anti-inflammatory effects by inhibiting multiple inflammatory cells and mediators. It reduces airway inflammation through genomic effects mediated by glucocorticoid receptor binding. Glycopyrronium: A long-acting muscarinic antagonist that competitively inhibits acetylcholine at muscarinic receptors (primarily M3) in airway smooth muscle, leading to bronchodilation. Formoterol Fumarate: A long-acting beta2-adrenergic agonist that stimulates intracellular adenylate cyclase, increasing cyclic AMP concentrations, resulting in relaxation of bronchial smooth muscle and bronchodilation.The co-suspension technology allows consistent delivery of all three components regardless of the number of doses remaining in the canister.
Indications
Breztri Aerosphere is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including:
- Chronic bronchitis
- Emphysema
It is specifically approved for patients who require a combination of budesonide (ICS) with both glycopyrronium (LAMA) and formoterol (LABA) for adequate symptom control.
Dosage and Administration
Recommended dosage: Two inhalations twice daily (morning and evening, approximately 12 hours apart) Strength: Each inhalation delivers budesonide 160 mcg/glycopyrronium 9 mcg/formoterol fumarate 4.8 mcg Administration:- Prime before first use or if not used for more than 7 days
- Shake well before each use
- Rinse mouth with water after inhalation without swallowing
- Not for relief of acute symptoms
- Maximum recommended dose: 2 inhalations twice daily
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution in severe impairment
- Geriatric patients: No dosage adjustment required
- Not recommended for use in children
Pharmacokinetics
Absorption:- Budesonide: Systemic bioavailability approximately 34% of metered dose
- Glycopyrronium: Peak plasma concentrations within 5 minutes
- Formoterol: Systemic exposure low due to extensive first-pass metabolism
- Budesonide: Volume of distribution ~300 L, 85-90% protein bound
- Glycopyrronium: Volume of distribution ~510 L, minimal protein binding
- Formoterol: 50% protein bound
- Budesonide: Extensive hepatic metabolism via CYP3A4
- Glycopyrronium: Minimal hepatic metabolism
- Formoterol: Extensive hepatic metabolism via multiple pathways
- Budesonide: Feces (66%) and urine (20%), terminal half-life ~3 hours
- Glycopyrronium: Feces (78%) and urine (11%), terminal half-life ~17 hours
- Formoterol: Feces (60%) and urine (32%), terminal half-life ~10 hours
Contraindications
- Hypersensitivity to any component of Breztri Aerosphere
- Patients with asthma (without concomitant ICS use)
- Primary treatment of status asthmaticus or acute episodes of COPD requiring intensive measures
Warnings and Precautions
Paradoxical bronchospasm: May occur with immediate increase in wheezing after dosing Cardiovascular effects: May produce clinically significant cardiovascular effects in some patients Immunosuppression: Potential increased risk of infections Systemic corticosteroid effects: May occur with high doses over prolonged periods Glaucoma and cataracts: Regular ophthalmological examinations recommended Hypokalemia and hyperglycemia: May occur with beta-agonist components Coexisting conditions: Use with caution in patients with cardiovascular disorders, convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosisDrug Interactions
Strong CYP3A4 inhibitors (ketoconazole, ritonavir): May increase budesonide systemic exposure Beta-blockers: May block bronchodilator effects and produce severe bronchospasm Diuretics: May potentiate ECG changes and hypokalemia MAO inhibitors and tricyclic antidepressants: May potentiate cardiovascular effects Other anticholinergic-containing drugs: May increase anticholinergic adverse effectsAdverse Effects
Most common adverse reactions (≥2% incidence):- Upper respiratory tract infection (8.1%)
- Pneumonia (5.5%)
- Headache (3.8%)
- Back pain (2.8%)
- Oral candidiasis (2.7%)
- Dysphonia (2.5%)
- Diarrhea (2.4%)
- Pneumonia
- Acute exacerbations of COPD
- Cardiovascular events
- Paradoxical bronchospasm
Monitoring Parameters
- Pulmonary function tests (FEV1)
- Symptom control and exacerbation frequency
- Signs and symptoms of pneumonia
- Oropharyngeal examination for candidiasis
- Blood glucose levels in diabetic patients
- Electrolyte levels (particularly potassium)
- Cardiovascular status
- Ophthalmological examinations
- Growth velocity in pediatric patients (if used off-label)
- Bone mineral density with long-term use
Patient Education
- Use regularly as prescribed, not for acute symptom relief
- Demonstrate proper inhaler technique
- Rinse mouth after each use to prevent oral candidiasis
- Do not stop therapy abruptly
- Report any worsening symptoms, chest pain, palpitations, or signs of infection
- Keep regular follow-up appointments
- Inform all healthcare providers about all medications being taken
- Store at room temperature, do not puncture or incinerate
- Use spacer device if recommended by healthcare provider
- Have a short-acting bronchodilator available for rescue therapy
References
1. FDA Prescribing Information: Breztri Aerosphere (2020) 2. Martinez FJ, et al. Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler in COPD: The ETHOS Trial. Am J Respir Crit Care Med. 2020;202(4):571-584. 3. Rabe KF, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35-48. 4. Global Initiative for Chronic Obstructive Lung Disease. 2023 Report. 5. Lipson DA, et al. Once-Daily Single-Inhaler Triple Versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671-1680. 6. ClinicalTrials.gov: KRONOS and ETHOS study results 7. Drug Interaction Facts: Facts & Comparisons