BREZTRI AEROSPHERE® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol
- BREZTRI is contraindicated in patients who have a hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or product excipients
- BREZTRI is not indicated for treatment of asthma. Long-acting beta2-adrenergic agonist (LABA) monotherapy for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When a LABA is used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Available data do not suggest an increased risk of death with use of LABA in patients with COPD
- BREZTRI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition
- BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute symptoms; treat with an inhaled short-acting beta2-agonist
- BREZTRI should not be used more often than recommended; at higher doses than recommended; or in combination with LABA-containing medicines, due to risk of overdose. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs
- Oropharyngeal candidiasis has occurred in patients treated with orally inhaled drug products containing budesonide. Advise patients to rinse their mouths with water without swallowing after inhalation
- Lower respiratory tract infections, including pneumonia, have been reported following ICS. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap
- Due to possible immunosuppression, potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
- Particular care is needed for patients transferred from systemic corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI
- Hypercorticism and adrenal suppression may occur with regular or very high dosage in susceptible individuals. If such changes occur, consider appropriate therapy
- Caution should be exercised when considering the coadministration of BREZTRI with long-term ketoconazole and other known strong CYP3A4 Inhibitors. Adverse effects related to increased systemic exposure to budesonide may occur
- If paradoxical bronchospasm occurs, discontinue BREZTRI immediately and institute alternative therapy
- Anaphylaxis and other hypersensitivity reactions (eg, angioedema, urticaria or rash) have been reported. Discontinue and consider alternative therapy
- Use caution in patients with cardiovascular disorders, especially coronary insufficiency, as formoterol fumarate can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles
- Decreases in bone mineral density have been observed with long-term administration of ICS. Assess initially and periodically thereafter in patients at high risk for decreased bone mineral content
- Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur, so use with caution. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI long term. Instruct patients to contact a healthcare provider immediately if symptoms occur
- Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if symptoms occur
- Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually responsive to sympathomimetic amines
- Be alert to hypokalemia or hyperglycemia
- Most common adverse reactions in a 52-week trial (incidence ≥ 2%) were upper respiratory tract infection (5.7%), pneumonia (4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza (2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough (2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial, adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle spasms (3.3%)
- BREZTRI should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these may potentiate the effect of formoterol fumarate on the cardiovascular system
- BREZTRI should be administered with caution to patients being treated with:
- Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)
- Adrenergic drugs (may potentiate effects of formoterol fumarate)
- Xanthine derivatives, steroids, or non-potassium sparing diuretics (may potentiate hypokalemia and/or ECG changes)
- Beta-blockers (may block bronchodilatory effects of beta-agonists and produce severe bronchospasm)
- Anticholinergic-containing drugs (may interact additively). Avoid use with BREZTRI
- Use BREZTRI with caution in patients with hepatic impairment, as budesonide and formoterol fumarate systemic exposure may increase. Patients with severe hepatic disease should be closely monitored
INDICATION
BREZTRI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
LIMITATIONS OF USE
Not indicated for the relief of acute bronchospasm or for the treatment of asthma.
Please see full BREZTRI Prescribing Information, including Patient Information.
You may report side effects related to AstraZeneca products.
Notes
Asthma
Asthma is a prevalent, chronic respiratory disease affecting as many as 262 million people worldwide,2 including over 25 million in the US.3 When uncontrolled, inflammation and muscle tightening in the airway (bronchoconstriction) may cause wheezing, breathlessness, chest tightness, coughing, and even death.2,4 Many patients remain uncontrolled despite the availability of standard of care medicines and continue to experience significant limitations on lung function and reduced quality of life.5,6
KALOS and LOGOS Phase III trials
KALOS and LOGOS were replicate confirmatory, randomised, double-blind, double-dummy, parallel group, multi-centre, 24-to-52-week variable length Phase III trials to assess the efficacy and safety of BREZTRI Aerosphere (320/28.8/9.6μg and 320/14.4/9.6μg) compared with two fixed-dose, dual-combination therapies of budesonide, an ICS, and formoterol fumarate, a LABA: Symbicort pressurised metered-dose inhaler (pMDI) and PT009 (in an Aerosphere formulation).1,7,8 KALOS and LOGOS included approximately 4,300 randomised patients.
The trial design was optimised to evaluate the 320/28.8/9.6μg dose of BGF. The primary efficacy endpoints for the two individual trials were the change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24 and trough FEV1 over 12-24 weeks and over 24 weeks.1,7,8 The primary endpoints and treatment comparisons in the KALOS and LOGOS trials differed according to regulatory submission approaches. The full results published in The Lancet Respiratory Medicine report the pooled analysis of KALOS and LOGOS results for BREZTRI compared with the ICS/LABA treatment groups combined, and includes comparisons of BREZTRI to individual comparators arms measured across both trials in the supplement.
In addition to the two registrational trials (KALOS and LOGOS), two qualifying trials, LITHOS and VATHOS, also met their primary endpoints.9,10 LITHOS and VATHOS included approximately 1,000 randomised patients.
BREZTRI/TRIXEO Aerosphere
Budesonide/glycopyrronium/formoterol fumarate (BGF), approved under the brand name BREZTRI Aerosphere in Japan, China and the US, and TRIXERO Aerosphere in the EU, is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a long-acting muscarinic antagonist (LAMA), with budesonide, an ICS, and delivered via the Aerosphere pMDI. BREZTRI/TRIXEO Aerosphere (320/14.4/9.6μg) is approved to treat adults with COPD in more than 80 countries worldwide including the US, EU, China, Japan, and was prescribed to more than 5.5 million patients globally in 2024.11
AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the Company.
AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca. The contents of AstraZeneca’s website do not form part of this document and no one should rely on such websites or the contents thereof in reading this document.
Media Inquiries
|
Fiona Cookson |
+1 212 814 3923 |
|
|
US Media Mailbox: usmediateam@astrazeneca.com
References
1. Papi A, et al. Budesonide–glycopyrronium–formoterol fumarate dihydrate in uncontrolled asthma (KALOS and LOGOS): twin multicentre, double-blind, double-dummy, parallel-group, randomised, phase 3 trials. Lancet Respir. Med. 2026; https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(25)00457-6/abstract [Last accessed: February 2026]
2. Global Asthma Network. The Global Asthma Report 2022. [Online]. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2022.pdf. [Last accessed: February 2026].
3. U.S. Centers for Disease Control and Prevention (CDC). Most Recent National Asthma Data. [Online]. Available at: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. [Last accessed: February 2026].
4. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372.
5. Davis J, et al. Burden of asthma among patients adherent to ICS/LABA: A real-world study. J Asthma. 2019 Mar;56(3):332-340.
6. Buhl R, et al. One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med. 2020 Feb: 162:105859.
7. Clinicaltrials.gov. Study to Assess PT010 in Adult and Adolescent Participants with Inadequately Controlled Asthma (KALOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT04609878?limit=25&term=KALOS&rank=1. [Last accessed: February 2026].
8. Clinicaltrials.gov. Study to Assess PT010 in Adult and Adolescent Participants with Inadequately Controlled Asthma (LOGOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT04609904?limit=25&term=LOGOS&rank=4 [Last accessed: February 2026].
9. Clinicaltrials.gov. A 12-week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler in Participants with Inadequately Controlled Asthma (LITHOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT05755906?limit=25&term=LITHOS&rank=1. [Last accessed: February 2026].
10. Clinicaltrials.gov. A 24-Week Efficacy and Safety Study to Assess Budesonide and Formoterol Fumarate Metered Dose Inhaler in Adult and Adolescent Participants with Inadequately Controlled Asthma (VATHOS) [Online]. Available at: https://clinicaltrials.gov/study/NCT05202262?limit=25&term=VATHOS&rank=1. [Last accessed: February 2026].
11. AstraZeneca Data on File. 2025. REF-270910.
