Aclidinium and Formoterol

DUAKLIR PRESSAIR is a combination of aclidinium bromide (an anticholinergic) and formoterol fumarate (a LABA) indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Limitations of Use: DUAKLIR PRESSAIR is not indicated for the relief of acute bronchospasm or for the treatment of asthma. DUAKLIR PRESSAIR is a combination of aclidinium bromide 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.

DUAKLIR PRESSAIR DUAKLIR PRESSAIR contains two bronchodilators: aclidinium a long-acting muscarinic antagonist (also known as an anticholinergic) and formoterol a long-acting beta 2 -adrenergic agonist. Further information regarding these two substances is provided below. The mechanism of action described below for the individual components apply to DUAKLIR PRESSAIR. These drugs represent two different classes of medications (a long-acting antimuscarinic agent and a selective long-acting beta 2 -adrenergic receptor agonist) that have different effects on clinical and physiological indices of COPD. Aclidinium bromide Aclidinium bromide 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.

The recommended dose of DUAKLIR PRESSAIR is one oral inhalation of 400 mcg/12 mcg, twice daily (once in the morning and once in the evening). Do not take more than one inhalation twice daily. • For oral inhalation only. • 400 mcg/12 mcg, twice daily (once in the morning and once in the evening).

Use of a long-acting beta 2 -adrenergic agonist (LABA), including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid is contraindicated in patients with asthma. DUAKLIR PRESSAIR is not indicated for the treatment of asthma. DUAKLIR PRESSAIR is contraindicated in patients with: • Severe hypersensitivity to milk proteins. • Hypersensitivity to aclidinium bromide, formoterol fumarate, or to any component of the product. • Use of a long-acting beta 2 -adrenergic agonist (LABA), including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid is contraindicated in patients with asthma.

• Asthma-related death: Long-acting beta 2 -adrenergic agonists as monotherapy (without an inhaled corticosteroid) for asthma increase 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 medicine containing a LABA because of risk of overdose. • If paradoxical bronchospasm occurs, discontinue DUAKLIR PRESSAIR and institute alternative therapy. • Use with caution in patients with cardiovascular disorders. • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus and ketoacidosis. • Be alert to hypokalemia and hyperglycemia. • 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.

LABAs, such as formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, increase the risk of asthma-related death. DUAKLIR PRESSAIR is not indicated for the treatment of asthma. The following adverse reactions are described in greater detail elsewhere in the labeling: • Paradoxical bronchospasm • Immediate hypersensitivity reactions • Cardiovascular effects • Worsening of narrow-angle glaucoma • Worsening of urinary retention Most common adverse reactions (incidence ≥ 3% and more common than with placebo) include: upper respiratory tract infection, headache and, back pain.

No formal drug interaction studies have been performed with DUAKLIR PRESSAIR. • Use of other adrenergic by any route may potentiate the effect of DUAKLIR PRESSAIR. 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.

Store DUAKLIR PRESSAIR in a dry place at 20°C-25°C (68°F-77°F), excursions permitted to 15-30°C (59-86°F). Do not store the inhaler on a vibrating surface. The PRESSAIR inhaler should be stored inside the sealed bag and only be opened immediately before use.