Version July 2025
Chronic obstructive pulmonary disease: Metered-dose inhaler (budesonide 160 mcg/glycopyrrolate 9 mcg/formoterol 4.8 mcg per actuation): Oral inhalation: 2 inhalations twice daily; maximum dose: 2 inhalations twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
CrCl ≤45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic glycopyrrolate exposure may be increased; use with caution.
End-stage renal disease requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic glycopyrrolate exposure may be increased; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic budesonide and formoterol exposure may be increased in patients with severe impairment; use with caution and monitor closely.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. See individual agents.
1% to 10%:
Gastrointestinal: Diarrhea (2%), oral candidiasis (3%)
Genitourinary: Urinary tract infection (3%)
Infection: Influenza (3%)
Nervous system: Voice disorder (3%)
Neuromuscular & skeletal: Back pain (3%), muscle spasm (3%)
Ophthalmic: Cataract (≤1%)
Respiratory: Cough (3%), pneumonia (2% to 5%), sinusitis (3%), upper respiratory tract infection (6%)
Frequency not defined: Respiratory: Paradoxical bronchospasm
Hypersensitivity to budesonide, glycopyrrolate, formoterol, or any component of the formulation.
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. Do not use this product to transfer patients from oral corticosteroid therapy.
• Asthma-related deaths: The use of long-acting beta-2 agonists (LABAs) as monotherapy has been associated with an increased risk of severe exacerbations and asthma-related deaths (SMART [Nelson 2006]; Walters 2007); additional data from other clinical trials suggest risk of asthma-related hospitalization may also be increased with LABA monotherapy in pediatric and adolescent patients. However, data from large, randomized, double-blind controlled trials do not show a significant increase in risk of serious asthma-related events (including hospitalizations, intubations, and death) in adults, adolescents, and pediatric patients (4 to 11 years of age) when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy (FDA 2017).
• Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents and may be life-threatening; this should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue and institute alternative therapy.
• Hypersensitivity: Immediate hypersensitivity reactions (eg, urticaria, angioedema, rash) have been reported; discontinue if a hypersensitivity reaction occurs and institute alternative therapy.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use, if possible, in patients with ocular herpes; tuberculosis (TB) infection (latent TB) or disease (active TB) of the respiratory tract; or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin or pooled IV immunoglobulin may be indicated; if chickenpox develops, treatment with antiviral agents may be considered. If exposure to measles occurs, prophylaxis with pooled IM immunoglobulin may be indicated.
• Lower respiratory infections: Pneumonia and other lower respiratory tract infections have been reported in patients with COPD following the use of inhaled corticosteroids; monitor COPD patients closely since pneumonia symptoms may overlap symptoms of exacerbations.
• Oral candidiasis: Local oropharyngeal Candida infections may occur; treat appropriately while either continuing or interrupting (if necessary) therapy.
• Serious effects/fatalities: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.
Disease-related concerns:
• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, antiseizure medications, oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, especially coronary insufficiency, arrhythmias, and hypertension; beta-agonists may cause elevation in BP, heart rate, and increase risk of arrhythmias (eg, supraventricular tachycardia, extrasystoles); may also cause ECG changes (eg, flattening of the T wave, QTc prolongation, ST segment depression).
• Diabetes: Use with caution in patients with diabetes mellitus; beta-2 agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.
• Hepatic impairment: Budesonide and formoterol exposure may be increased in patients with severe hepatic impairment; use with caution in patients with severe impairment and monitor closely.
• Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (effect is usually transient).
• Ocular disease: Use with caution in patients with increased intraocular pressure, cataracts, and/or glaucoma; increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use of inhaled corticosteroids. Consider routine eye exams in chronic users.
• Prostatic hyperplasia/bladder neck obstruction: Glycopyrrolate may worsen the symptoms of prostatic hyperplasia and/or bladder neck obstruction (eg, painful urination, difficulty passing urine); use with caution.
• Renal impairment: Use with caution in patients with severe renal impairment, including end-stage renal disease requiring dialysis; systemic exposure to glycopyrrolate may be increased.
• Seizure disorders: Use with caution in patients with seizure disorders.
• Thyrotoxicosis: Use with caution in patients with thyrotoxicosis.
Other warnings/precautions:
• Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening, potentially life-threatening, or acutely deteriorating COPD. Do not exceed the recommended dose. After initiation of therapy, patients should use short-acting bronchodilators only on an as needed basis for acute symptoms.
• Discontinuation of systemic corticosteroids: Withdraw systemic corticosteroid therapy with gradual tapering of dose (eg, patients on prednisone may decrease dose by 2.5 mg weekly during inhaled corticosteroid therapy). Monitor lung function, beta-agonist use, and COPD symptoms, and for signs and symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal.
• Transfer to oral inhaler: When transferring to oral inhaler, previously suppressed allergic conditions (eg, arthritis, rhinitis, conjunctivitis, eczema, eosinophilic conditions) may be unmasked.
Breztri Aerosphere 10.7 g canisters contain 120 inhalations; 5.9 g canisters contain 28 inhalations.
In the United States, each metered dose per actuation contains budesonide 170 mcg, glycopyrrolate 9.6 mcg (equivalent to glycopyrronium 7.7 mcg), and formoterol fumarate 5.1 mcg (equivalent to formoterol 4.4 mcg). However, each actuation of the inhaler delivers budesonide 160 mcg, glycopyrrolate 9 mcg (equivalent to 7.2 mcg glycopyrronium), and formoterol fumarate 4.8 mcg (equivalent to formoterol 4.1 mcg) from the mouthpiece. Dosing is based on the amounts delivered per actuation.
In Canada, each metered dose per actuation contains budesonide 170 mcg, glycopyrrolate 9.6 mcg (equivalent to glycopyrronium 7.7 mcg), and formoterol fumarate dihydrate 5.3 mcg (equivalent to formoterol fumarate 5.1 mcg). However, each actuation of the inhaler delivers budesonide 160 mcg, glycopyrrolate 9 mcg (equivalent to glycopyrronium 7.2 mcg), and formoterol fumarate dihydrate 5 mcg (equivalent to formoterol fumarate 4.8 mcg) from the mouthpiece. Dosing is based on the amounts delivered per actuation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol, Inhalation:
Breztri Aerosphere: Budesonide 160 mcg, glycopyrrolate 9 mcg, and formoterol fumarate 4.8 mcg per actuation (5.9 g, 10.7 g)
No
Aerosol (Breztri Aerosphere Inhalation)
160-9-4.8 mcg/ACT (per gram): $74.53
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol, Inhalation:
Breztri Aerosphere: 160-7.2-5 MCG/ACT (1 ea)
Metered-dose inhaler: For oral inhalation only; administer every morning and evening. Prior to first use, prime inhaler by releasing 4 test sprays into the air; shake well before each spray. Inhaler must be reprimed by releasing 2 test sprays into the air if not used for >7 days, if it has been dropped, or after weekly cleaning. Shake inhaler well before each use. Rinse mouth with water (spit out without swallowing) after each use. Clean inhaler (remove canister out of actuator) 1 time each week by running warm water through the actuator for ~30 seconds then turn actuator upside down and run warm water through it again for ~30 seconds and allow to air dry completely. Discard 3 weeks (28-inhalation cannister) or 3 months (120-inhalation cannister) after removal from the foil pouch or when the counter reads “0”, whichever comes first.
Delivery of dose: Instruct patient to shake well and then place mouthpiece gently between teeth, closing lips around inhaler. Instruct patient to inhale deeply, press the top counter, and hold breath for up to 10 seconds or as long as they comfortably can. Remove mouthpiece from mouth prior to exhalation. Patient should not breathe out through the mouthpiece.
Chronic obstructive pulmonary disease: Maintenance treatment of patients with chronic obstructive pulmonary disease.
Limitations of use: Not indicated for the relief of bronchospasm or for the treatment of asthma.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Atomoxetine: May increase tachycardic effects of Beta2-Agonists. Atomoxetine may increase hypertensive effects of Beta2-Agonists. Risk C: Monitor
Atosiban: Beta2-Agonists may increase adverse/toxic effects of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor
Benzodiazepines: May increase adverse/toxic effects of Corticosteroids (Orally Inhaled). Specifically, the risk of pneumonia may be increased. Risk C: Monitor
Beta-Blockers (Beta1 Selective): May decrease bronchodilatory effects of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor
Beta-Blockers (Nonselective): May decrease bronchodilatory effects of Beta2-Agonists. Risk X: Avoid
Beta2-Agonists (Long-Acting): May increase adverse/toxic effects of Beta2-Agonists (Long-Acting). Risk X: Avoid
Caffeine and Caffeine Containing Products: May increase adverse/toxic effects of Formoterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Formoterol. Risk C: Monitor
Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider Therapy Modification
Cosyntropin: Coadministration of Corticosteroids (Orally Inhaled) and Cosyntropin may alter diagnostic results. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Desmopressin: Corticosteroids (Orally Inhaled) may increase hyponatremic effects of Desmopressin. Risk X: Avoid
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Inhaled Anticholinergic Agents: May increase anticholinergic effects of Inhaled Anticholinergic Agents. Risk C: Monitor
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification
Loop Diuretics: Beta2-Agonists may increase hypokalemic effects of Loop Diuretics. Risk C: Monitor
Loxapine: Agents to Treat Airway Disease may increase adverse/toxic effects of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Risk X: Avoid
Methacholine: Beta2-Agonists (Long-Acting) may decrease therapeutic effects of Methacholine. Management: Hold long-acting beta2 agonists for 36 hours before methacholine use. Risk D: Consider Therapy Modification
Methacholine: Long-acting muscarinic antagonists (LAMAs) may decrease therapeutic effects of Methacholine. Management: Hold long-acting muscarinic antagonists (LAMAs) for at least 7 days before methacholine use. Risk D: Consider Therapy Modification
Monoamine Oxidase Inhibitors: May increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor
Nirmatrelvir and Ritonavir: May increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Theophylline Derivatives: May increase hypokalemic effects of Beta2-Agonists. Beta2-Agonists may increase adverse/toxic effects of Theophylline Derivatives. Specifically, sympathomimetic effects may be increased. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Tobacco (Smoked): May decrease therapeutic effects of Corticosteroids (Orally Inhaled). Risk C: Monitor
Refer to individual monographs.
Budesonide is present in breast milk following oral inhalation; excretion of formoterol and glycopyrrolate are not known.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Refer to individual monographs for additional information.
FEV1, peak flow, and/or other pulmonary function tests; bone mineral density; hypothalamic-pituitary-adrenal axis suppression; BP, heart rate; serum potassium; serum glucose; ocular changes; signs/symptoms of oral or systemic infection.
Budesonide: A corticosteroid that controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes/fibroblasts, and reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.
Formoterol: Relaxes bronchial smooth muscle by selective action on beta-2 receptors with little effect on heart rate; formoterol has a long-acting effect.
Glycopyrrolate: Competitively and reversibly inhibits the action of acetylcholine at muscarinic receptor subtypes 1 to 3 (greater affinity for subtypes 1 and 3) in bronchial smooth muscle thereby causing bronchodilation.
See individual agents.
