Formoterolside effects

The following adverse reactions are described in greater detail elsewhere in the labeling:

Paradoxical bronchospasm

Hypersensitivity reactions including Anaphylaxis

Cardiovascular effects

Worsening of narrow-angle glaucoma

Worsening of urinary retention Most common adverse reactions (incidence ≥2% and more common than with placebo) include: urinary tract infection and cough. 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 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 clinical program for BEVESPI AEROSPHERE included 4,911 subjects with COPD in two 24-week lung function trials, one long-term safety extension study of 28 weeks, and 10 other trials of shorter duration. A total of 1,302 subjects have received at least 1 dose of BEVESPI AEROSPHERE. The safety data described below are based on the two 24-week trials and the one 28-week long-term safety extension trial. Adverse reactions observed in the other trials were similar to those observed in these confirmatory trials. 24-Week Trials The incidence of adverse reactions with BEVESPI AEROSPHERE in Table 1 is based on reports in two 24-week, placebo-controlled trials (Trials 1 and 2; n=2,100 and n=1,610, respectively). Of the 3,710 subjects, 56% were male and 91% were Caucasian. They had a mean age of 63 years and an average smoking history of 51 pack-years, with 54% identified as current smokers. At screening, the mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV 1 ) was 51% (range: 19% to 82%) and the mean percent reversibility was 20% (range: -32% to 135%). Subjects received one of the following treatments: BEVESPI AEROSPHERE, glycopyrrolate 18 mcg, formoterol fumarate 9.6 mcg, or placebo twice daily or active control. Table 1 - Adverse Reactions with BEVESPI AEROSPHERE ≥2% Incidence and More Common than with Placebo in Subjects with Chronic Obstructive Pulmonary Disease Adverse Reaction BEVESPI AEROSPHERE (n=1036) % Glycopyrrolate 18 mcg BID (n=890) % Formoterol Fumarate 9.6 mcg BID (n=890) % Placebo (n=443) % Respiratory, thoracic, and mediastinal disorders Cough 4.0 3.0 2.7

2.7 Infections and infestation

Urinary tract infection 2.6 1.8 1.5 2.3 Other adverse reactions defined as events with an incidence of >1% but less than 2% with BEVESPI AEROSPHERE but more common than with placebo included the following: arthralgia, chest pain, tooth abscess, muscle spasms, headache, oropharyngeal pain, vomiting, pain in extremity, dizziness, anxiety, dry mouth, fall, influenza, fatigue, acute sinusitis, and contusion. Long-Term Safety Extension Trial In a 28-week long-term safety extension trial, 893 subjects who successfully completed Trial 1 or Trial 2 were treated for up to an additional 28 weeks for a total treatment period of up to 52 weeks with BEVESPI AEROSPHERE, glycopyrrolate 18 mcg, formoterol fumarate 9.6 mcg administered twice daily or active control. Because the subjects continued from Trial 1 or Trial 2 into the safety extension trial, the demographic and baseline characteristics of the long-term safety extension trial were similar to those of the placebo-controlled efficacy trials described above. The adverse reactions reported in the long-term safety trial were consistent with those observed in the 24-week placebo-controlled trials.

Additional Adverse Reactions: Other adverse reactions that have been associated with the component formoterol fumarate include: hypersensitivity reactions, hyperglycemia, sleep disturbance, agitation, restlessness, tremor, nausea, tachycardia, palpitations, cardiac arrhythmias (atrial fibrillation, supraventricular tachycardia, and extrasystoles).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post approval use of BEVESPI AEROSPHERE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In postmarketing experience with BEVESPI AEROSPHERE, hypersensitivity and urinary retention have been reported.