Formoterol and Glycopyrrolate

BEVESPI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Limitations of Use: BEVESPI AEROSPHERE is not indicated for the relief of acute bronchospasm or for the treatment of asthma. BEVESPI AEROSPHERE is a combination of glycopyrrolate, an anticholinergic, and formoterol fumarate, a long-acting beta 2 -adrenergic agonist (LABA) 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.

BEVESPI AEROSPHERE BEVESPI AEROSPHERE contains both glycopyrrolate and formoterol fumarate. The mechanism of action described below for the individual components applies to BEVESPI AEROSPHERE. These drugs represent two different classes of medications (an anticholinergic, and a long-acting selective beta 2 -adrenoceptor agonist) that have different effects on clinical physiology and inflammatory indices of COPD. Glycopyrrolate Glycopyrrolate is a long-acting antimuscarinic agent which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations.

• For oral inhalation only. • Maintenance treatment of COPD: 2 inhalations of BEVESPI AEROSPHERE twice daily by oral inhalation. Recommended Dosage and Administration The recommended dosage of BEVESPI AEROSPHERE is glycopyrrolate 18 mcg and formoterol fumarate 9.6 mcg (administered as two inhalations of BEVESPI AEROSPHERE [glycopyrrolate/formoterol fumarate 9 mcg/4.8 mcg]) twice daily in the morning and in the evening by oral inhalation. Do not take more than two inhalations twice daily. Preparation Prime BEVESPI AEROSPHERE before using for the first time. Priming BEVESPI AEROSPHERE is essential to ensure appropriate drug content in each actuation. To prime BEVESPI AEROSPHERE, release 4 sprays into the air away from the face, shaking well before each spray. BEVESPI AEROSPHERE must be re-primed when the inhaler has not been used for more than 7 days.

BEVESPI AEROSPHERE is contraindicated in: • use of a long-acting beta 2 -adrenergic agonist (LABA), including formoterol fumarate, one of the active ingredients in BEVESPI AEROSPHERE, without an inhaled corticosteroid, in patients with asthma. BEVESPI AEROSPHERE is not indicated for the treatment of asthma. • patients with hypersensitivity to glycopyrrolate, formoterol fumarate, or to any component of the product. • Use of a LABA, including formoterol fumarate, one of the active ingredients in BEVESPI AEROSPHERE, without an inhaled corticosteroid is contraindicated in patients with asthma. • Hypersensitivity to glycopyrrolate, formoterol fumarate, or to any component of this product.

• LABA as monotherapy (without an inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. • Do not initiate in acutely deteriorating COPD or to treat acute symptoms. • Do not use in combination with an additional therapy containing a LABA because of risk of overdose. • If paradoxical bronchospasm occurs, discontinue BEVESPI AEROSPHERE and institute alternative therapy. • Use with caution in patients with cardiovascular disorders. • Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a physician immediately if symptoms occur. • Worsening urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a physician immediately if symptoms occur.

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.

No formal drug interaction studies have been performed with BEVESPI AEROSPHERE. • Other adrenergic drugs may potentiate effect: Use with caution. • Xanthine derivatives, steroids, diuretics or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes. Use with caution. • Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non-potassium sparing diuretics may worsen with concomitant beta 2 -agonists. • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol fumarate on cardiovascular system. • Beta-blockers: Use with caution and only when medically necessary. • Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administrations of BEVESPI AEROSPHERE with other anticholinergic-containing drugs.

Store at controlled room temperature 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). For best results, the canister should be at room temperature before use. Exposure to temperatures above 49°C (120°F) may cause bursting. Do not use or store near heat or open flame.