BREZTRI (Page 3 of 10)

5.15 Worsening of Urinary Retention

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. Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

5.16 Coexisting Conditions

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.

5.17 Hypokalemia and Hyperglycemia

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.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling.

Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions (5.1)]
Oropharyngeal candidiasis infection [see Warnings and Precautions (5.4)]
Increased risk of pneumonia in COPD [see Warnings and Precautions (5.5)]
Immunosuppression and risk of infections [see Warnings and Precautions (5.6)]
Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8)]
Paradoxical bronchospasm [see Warnings and Precautions (5.10)]
Hypersensitivity reactions including anaphylaxis [see Contraindications (4) and Warnings and Precautions (5.11)]
Cardiovascular effects [see Warnings and Precautions (5.12)]
Reduction in bone mineral density [see Warnings and Precautions (5.13)]
Worsening of narrow-angle glaucoma and cataracts [see Warnings and Precautions (5.14)]
Worsening of urinary retention [see Warnings and Precautions (5.15)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of BREZTRI AEROSPHERE is based on the safety data from one 52-week exacerbation trial (Trial 1) and one 24-week lung function trial with a 28-week safety extension study, resulting in up to 52 weeks of treatment (Trial 2). In Trials 1 and 2, a total of 2783 subjects have received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg [see Clinical Studies (14)].

In Trials 1 and 2, subjects received one of the following treatments: BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg, glycopyrrolate and formoterol fumarate [GFF MDI 18 mcg/9.6 mcg], or budesonide and formoterol fumarate [BFF MDI 320 mcg/9.6 mcg]. Each treatment was administered twice daily.

In Trial 1, a 52-week, randomized, double-blind clinical trial, a total of 2144 subjects with COPD received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (mean age: 64.7 years, 84.9% Caucasian, 59.7% male across all treatments) [see Clinical Studies (14)].

In Trial 2, a 24-week, randomized, double-blind clinical trial, with a 28-week long-term safety extension resulting in up to 52 weeks of treatment, a total of 639 subjects received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (mean age: 65.2 years, 50.1% Caucasian, 71.2% male across all treatments) [see Clinical Studies (14)].

The incidence of adverse reactions from the 52-week trial (Trial 1) is presented in Table 1 for subjects treated with BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg, GFF MDI 18 mcg/9.6 mcg, or BFF MDI 320 mcg/9.6 mcg.

Table 1: Adverse reactions occurring at an incidence of ≥ 2% of subjects and more common in BREZTRI AEROSPHERE compared to GFF MDI and/or BFF MDI (Trial 1)
*
BREZTRI AEROSPHERE = budesonide/glycopyrrolate/formoterol fumarate 320 mcg/18 mcg/9.6 mcg; GFF MDI = glycopyrrolate/formoterol fumarate 18 mcg/9.6 mcg; BFF MDI = budesonide/formoterol fumarate 320 mcg/9.6 mcg; all treatments were administered twice daily.

Adverse Reaction

BREZTRI AEROSPHERE *

320 mcg/18 mcg/9.6 mcg

N=2144 (%)

GFF MDI *

18 mcg/9.6 mcg

N=2125 (%)

BFF MDI *

320 mcg/9.6 mcg

N=2136 (%)

Upper Respiratory Tract Infection

123 (5.7)

102 (4.8)

115 (5.4)

Pneumonia

98 (4.6)

61 (2.9)

107 (5.0)

Back pain

67 (3.1)

55 (2.6)

64 (3.0)

Oral candidiasis

65 (3.0)

24 (1.1)

57 (2.7)

Influenza

63 (2.9)

42 (2.0)

61 (2.9)

Muscle spasms

60 (2.8)

19 (0.9)

53 (2.5)

Urinary tract infection

58 (2.7)

60 (2.8)

41 (1.9)

Cough

58 (2.7)

50 (2.4)

51 (2.4)

Sinusitis

56 (2.6)

47 (2.2)

55 (2.6)

Diarrhea

44 (2.1)

37 (1.7)

38 (1.8)

In 24-week data from Trial 2, adverse reactions that occurred in subjects treated with BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (n=639) at an incidence of ≥ 2% included dysphonia (3.1%) and muscle spasms (3.3%).

Additional Adverse Reactions

Other adverse reactions that have been associated with one or more of the individual components of BREZTRI AEROSPHERE include: hyperglycemia, anxiety, insomnia, headache, palpitations, nausea, hypersensitivity, depression, agitation, restlessness, nervousness, tremor, dizziness, angina pectoris, tachycardia, cardiac arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia, and extrasystoles), throat irritation, bronchospasm, dry mouth, bruising, urinary retention, chest pain, sign or symptoms of systemic glucocorticoid steroid effects (e.g., hypofunctional adrenal gland), and abnormal behavior.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.