Indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

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

Use of long-acting beta₂-adrenergic agonists (LABA) as monotherapy [without inhaled corticosteroid (ICS)] for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma related hospitalization in pediatric and adolescent patients. 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 AEROSPHERE should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. BREZTRI AEROSPHERE has not been studied in patients with acutely deteriorating COPD. The use of BREZTRI AEROSPHERE in this setting is not appropriate.When beginning treatment with BREZTRI AEROSPHERE, patients who have been taking inhaled, short-acting beta_2-agonists on a regular basis (e.g., four times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute respiratory symptoms.

When prescribing BREZTRI AEROSPHERE, the healthcare provider should also prescribe an inhaled, short acting beta₂-agonist and instruct the patient on how it should be used. Increasing inhaled beta₂-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated.COPD may deteriorate acutely over a period of hours or chronically over several days or longer.

If BREZTRI AEROSPHERE no longer controls symptoms, or the patient’s inhaled, short-acting beta₂– agonist becomes less effective or the patient needs more inhalations of short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting, re-evaluate the patient and the COPD treatment regimen at once. The daily dosage of BREZTRI AEROSPHERE should not be increased beyond the recommended dose.

As with other inhaled drugs containing beta₂-adrenergic agents, BREZTRI AEROSPHERE should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

Patients using BREZTRI AEROSPHERE should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.

In patients with severe renal impairment (creatinine clearance of ≤30 mL/min/1.73 m²) or end-stage renal disease requiring dialysis, BREZTRI AEROSPHERE should only be used if the expected benefit outweighs the potential risk.

BREZTRI AEROSPHERE contains budesonide, an ICS. Localized infections of the mouth and pharynx with Candida albicans have occurred in subjects treated with orally inhaled drug products containing budesonide. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with BREZTRI AEROSPHERE continues.

Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap.

Patients who are using drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure.

ICS should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer from systemic corticosteroids to less systemically available ICS. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although BREZTRI AEROSPHERE may provide control of COPD symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does not provide the mineralocorticoid activity that is necessary for coping with these emergencies.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to BREZTRI AEROSPHERE.

Transfer of patients from systemic corticosteroid therapy to BREZTRI AEROSPHERE may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).

As with other inhaled therapies, BREZTRI AEROSPHERE can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs following dosing with BREZTRI AEROSPHERE, it should be treated immediately with an inhaled, short-acting bronchodilator; BREZTRI AEROSPHERE should be discontinued immediately and alternative therapy should be instituted.

Formoterol fumarate, like other beta₂-agonists, 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 (BMD) have been observed with long-term administration of products containing ICS.

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with COPD following the long-term administration of ICS or with use of inhaled anticholinergics. BREZTRI AEROSPHERE should be used with caution in patients with narrow-angle glaucoma.

BREZTRI AEROSPHERE, like all therapies containing an anticholinergic, should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of prostatic hyperplasia or bladder-neck obstruction (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder neck obstruction.

BREZTRI AEROSPHERE, like all therapies containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Doses of the related beta₂-adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Beta-adrenergic agonists may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation.

Beta₂-agonist therapies may produce transient hyperglycemia in some patients.

Exceeding the recommended dosage or co-administration with a strong cytochrome P450 3A4 (CYP3A4) inhibitor may result in HPA dysfunction.

Caution should be exercised when considering the co-administration of BREZTRI AEROSPHERE with long-term ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to budesonide may occur.

Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate the hypokalemic effect of beta₂-adrenergic agonists such as formoterol, a component of BREZTRI AEROSPHERE.

The hypokalemia and/or ECG changes that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta₂-agonists, especially when the recommended dose of the beta₂-agonist is exceeded.

BREZTRI AEROSPHERE, as with other beta₂-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval because the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval may be associated with an increased risk of ventricular arrhythmias.

Beta-adrenergic receptor antagonists (beta-blockers) and BREZTRI AEROSPHERE may interfere with the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta₂-agonists, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of BREZTRI AEROSPHERE with other anticholinergic-containing drugs.

There are no adequate and well-controlled studies with BREZTRI AEROSPHERE or with two of its individual components, glycopyrrolate or formoterol fumarate, in pregnant women to inform a drug associated risk; however, studies are available for the other component, budesonide. Animal studies: structural abnormalities, was embryocidal, and reduced fetal weights. 

Because of the potential for beta-agonist interference with uterine contractility, use of BREZTRI AEROSPHERE during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.

Budesonide, like other ICS, is present in human milk.

GoToSource

• Use in patients under 18 years of age. GoToSource

Pneumonia, paradoxical bronchospasm, urinary retention, tremor, hyperglycemia (high blood sugar), hypokalemia (low blood potassium level), candidiasis (fungal infection ), increased bone density and fractures, cataracts, adrenal suppression (adrenal glands don’t make enough of the hormone cortisol) and mycobacterial infections. GoToSource

Increased cardiovascular risk. GoToSource

Increased glaucoma risk. GoToSource

No major injury lawsuits reported.