BREZTRI is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

FOR PATIENTS WITH COPD,
CHOOSE BREZTRI1-3

BREZTRI is not indicated for the relief of acute bronchospasm or for the treatment of asthma.

BREZTRI significantly reduced the annual rate of moderate or severe COPD exacerbations vs LAMA/LABA (RR=0.76; 95% CI: 0.69, 0.83; P<0.0001) and ICS/LABA (RR=0.87; 95% CI: 0.79, 0.95; P=0.0027) in a 52-week study.1†‡ Annual rate estimate: BREZTRI 1.08; LAMA/LABA 1.42; ICS/LABA 1.24.1

In a 52-week study in patients with ≥1 exacerbation within the last year,†

THE ONLY TRIPLE THERAPY§ VS ICS/LABA TO SHOW A SIGNIFICANT REDUCTION IN COPD HOSPITALIZATIONS2,4,5*

*Hospitalization for a severe COPD exacerbation.‡

20% Reduction in COPD Hospitalization
20% Reduction in COPD Hospitalization

REDUCTION VS ICS/LABA2,4

(rate ratio=0.80; 95% CI: 0.66, 0.97; P=0.02)2ǁ

STUDY 1

Reduction in severe exacerbations2‡

16% reduction vs LAMA/LABA (rate ratio=0.84; 95% CI: 0.69, 1.03; P=0.09)2

Annual rate estimate: BREZTRI 0.13 (n=2137); ICS/LABA 0.16 (n=2131); LAMA/LABA 0.15 (n=2120).2

Significant reduction in moderate or severe exacerbations‡

24% reduction vs LAMA/LABA (rate ratio=0.76; 95% CI: 0.69, 0.83; P<0.0001)

13% reduction vs ICS/LABA (rate ratio=0.87; 95% CI: 0.79, 0.95; P=0.0027)

Annual rate estimate: BREZTRI 1.08 (n=2137); LAMA/LABA 1.42 (n=2120); ICS/LABA 1.24 (n=2131).

†Study 1: Patients (N=8588) with ≥1 moderate or severe exacerbation(s) in the year prior to screening.

BREZTRI is administered as 2 inhalations twice daily.

‡Moderate exacerbations were defined as those leading to treatment with systemic corticosteroids and/or antibiotics, and severe exacerbations were defined as those resulting in hospitalization or death.

§Fixed-dose combination: ICS/LAMA/LABA.

ǁBased on predefined Type-1 error control plan.

RR=rate ratio.

BREZTRI demonstrated a significant improvement in FEV1 AUC0-4 vs ICS/LABA (116 mL; P<0.0001) and an improvement in mean change from baseline in morning pre-dose trough FEV1 vs LAMA/LABA (13 mL; P=0.2375) in a 24-week study.1,3

In a 24-week study where the majority of patients did not have a history of exacerbations within the last year,6*

THE ONLY TRIPLE THERAPY† VS LAMA/LABA TO PREVENT MODERATE OR SEVERE EXACERBATIONS1,3,5‡

52% Reduction in Exacerbation
52% Reduction in Exacerbation

REDUCTION VS LAMA/LABA1,3

(rate ratio=0.48; 95% CI: 0.37, 0.64; unadjusted P<0.0001)1,3§

STUDY 2

Reduction in moderate or severe exacerbations1,3‡

18% reduction vs ICS/LABA (rate ratio=0.82; 95% CI: 0.58, 1.17; P=0.2792)1,3

Annual rate estimate: BREZTRI 0.46 (n=639); ICS/LABA 0.56 (n=314); LAMA/LABA 0.95 (n=625).3

Difference in severe exacerbationsǁ (other endpoint)7‡

BREZTRI vs LAMA/LABA (rate ratio=0.36; 95% CI: 0.18, 0.70)

BREZTRI vs ICS/LABA (rate ratio=0.85; 95% CI: 0.34, 2.13)

Annual rate estimate: BREZTRI 0.05 (n=639); ICS/LABA 0.05 (n=314); LAMA/LABA 0.13 (n=625).

*Study 2: Patients (N=1896) were not required to have a history of moderate or severe exacerbations in the year prior to screening.

BREZTRI is administered as 2 inhalations twice daily.

†Fixed-dose combination: ICS/LAMA/LABA.

‡Moderate exacerbations were defined as those leading to treatment with systemic corticosteroids and/or antibiotics, and severe exacerbations were defined as those resulting in hospitalization or death.

§P value is considered unadjusted due to nonsignificant results higher in the testing hierarchy.

ǁResults are descriptive only.

BREZTRI IS THE ONLY TRIPLE THERAPY* THAT CONTAINS BUDESONIDE1,5

*Fixed-dose combination: ICS/LAMA/LABA.

Study 1 Design1,2

Study 1 was a 52-week, Phase 3, randomized, double-blind, parallel-group, multicenter study of 8588 patients with moderate to very severe COPD that compared BREZTRI MDI 320/18/9.6 (n=2157) with budesonide/glycopyrrolate/formoterol fumarate MDI 160/18/9.6 (n=2137), glycopyrrolate/formoterol fumarate MDI 18/9.6 (n=2143), and budesonide/formoterol fumarate MDI 320/9.6 (n=2151), each administered twice daily. Patients were current or former smokers with a smoking history of ≥10 pack-years, aged 40-80 years, with symptomatic COPD despite receiving 2 or more inhaled maintenance therapies, and a history of ≥1 moderate or severe exacerbation(s) in the previous year. The primary endpoint was the estimated annual rate of moderate or severe COPD exacerbations. Secondary endpoints included the estimated annual rate of severe COPD exacerbations and time to all-cause mortality over 52 weeks.

MDI=metered-dose inhaler; BID=twice daily.

Study 2 Design1,3,6,7

Study 2 was a 24-week, Phase 3, randomized, double-blind, parallel-group, multicenter study of 1896 patients with moderate to very severe COPD that compared BREZTRI MDI 320/18/9.6 (n=639) with glycopyrrolate/formoterol fumarate MDI 18/9.6 (n=625), budesonide/formoterol fumarate MDI 320/9.6 (n=314), and budesonide/formoterol fumarate DPI 400/12 (n=318), each administered twice daily. Patients were current or former smokers with a smoking history of ≥10 pack-years, aged 40-80 years, with symptomatic COPD despite receiving 2 or more inhaled maintenance therapies. Patients were not required to have a history of moderate or severe exacerbations in the previous year. The primary endpoints were FEV1 area under the curve from 0-4 hours (FEV1 AUC0-4) at Week 24 for BREZTRI compared to budesonide/formoterol fumarate and change from baseline in morning pre-dose trough FEV1 at Week 24 for BREZTRI compared to glycopyrrolate/formoterol fumarate MDI. Secondary endpoints included the rate of moderate or severe COPD exacerbations and other endpoints included the rate of severe exacerbations.

DPI=dry powder inhaler; MDI=metered-dose inhaler.

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IMPORTANT SAFETY INFORMATION

  • 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 Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products by clicking here.

IMPORTANT SAFETY INFORMATION

  • 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 Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products by clicking here.

Read More