Budesonideside effects

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

Serious asthma-related events – hospitalizations, intubations, death

Oropharyngeal candidiasis infection

Increased risk of pneumonia in COPD

Immunosuppression and risk of infections

Hypercorticism and adrenal suppression

Paradoxical bronchospasm

Hypersensitivity reactions including anaphylaxis

Cardiovascular effects

Reduction in bone mineral density

Growth effects in pediatric patients

Worsening of narrow-angle glaucoma and cataracts

Worsening of urinary retention 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.

COPD: Most common adverse reactions (incidence ≥ 2%) are upper respiratory tract infection, pneumonia, back pain, oral candidiasis, influenza, muscle spasm, urinary tract infection, cough, sinusitis and diarrhea.

Asthma: Most common adverse reactions (incidence ≥ 2%) are nasopharyngitis, pneumonia, and headache. To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Chronic Obstructive Pulmonary Disease The safety of BREZTRI AEROSPHERE in COPD is based on the safety data from one 52-week exacerbation trial (ETHOS) and one 24-week lung function trial with a 28-week safety extension study, resulting in up to 52 weeks of treatment (KRONOS). In ETHOS and KRONOS, a total of 2783 subjects have received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg. In ETHOS and KRONOS, 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 ETHOS, 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). In KRONOS, 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). The incidence of adverse reactions from the 52-week trial (ETHOS) is presented in Table 2 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 2: Adverse Reactions Occurring at an Incidence of ≥ 2% of Subjects with COPD and More Common in BREZTRI AEROSPHERE Compared to GFF MDI and/or BFF MDI (ETHOS) Adverse Reaction BREZTRI AEROSPHERE 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. 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 123 102 115 Pneumonia 98 61 107 Back pain 67 55 64 Oral candidiasis 65 24 57 Influenza 63 42 61 Muscle spasms 60 19 53 Urinary tract infection 58 60 41 Cough 58 50 51 Sinusitis 56 47 55 Diarrhea 44 37 38 In 24-week data from KRONOS, 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%). Asthma The safety of BREZTRI AEROSPHERE for the maintenance treatment of asthma is based on the pooled safety data from two, 24 to 52-week, clinical trials (KALOS and LOGOS). In the KALOS and LOGOS pooled safety population, a total of 1179 subjects with asthma received at least one dose of BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg. The mean duration of exposure to BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg twice daily was 45 weeks, with 678 (57%) subjects treated for at least 52 weeks. The incidence of adverse reactions (≥ 2%) from the 24 to 52-week trials (KALOS and LOGOS) is presented in Table 3 for subjects treated with BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg or BFF MDI 320 mcg/9.6 mcg.

Table 3: Adverse Reactions with BREZTRI AEROSPHERE with an Incidence of ≥ 2% of Subjects with Asthma and More Common than with BFF MDI (KALOS and LOGOS) Adverse Reaction BREZTRI AEROSPHERE BREZTRI AEROSPHERE=budesonide/glycopyrrolate/formoterol fumarate 320 mcg/36 mcg/9.6 mcg; BFF MDI=budesonide/formoterol fumarate 320 mcg/9.6 mcg; all treatments were administered twice daily. 320 mcg/36 mcg/9.6 mcg N=1179 (%) BFF MDI 320 mcg/9.6 mcg N=1208 (%) Nasopharyngitis 111 101 Pneumonia Consists of pneumonia, pneumonia bacterial, pneumonia fungal, pneumonia mycoplasma, pneumonia pneumococcal, pneumonia viral. 33 27 Headache 26 15 Additional Adverse Reactions Other adverse reactions that have been associated with one or more of the individual components of BREZTRI AEROSPHERE include: gastroesophageal reflux disease, dysphonia, oropharyngeal pain, renal and urinary tract infection, hyperglycemia, anxiety, insomnia, 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.