INCRUSE ELLIPTA is an inhalation powder drug product for delivery of umeclidinium (an anticholinergic) to patients by oral inhalation. Umeclidinium bromide has the chemical name 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-azoniabicyclo[2.2.2]octane bromide and the following chemical structure: Umeclidinium bromide is a white powder with a molecular weight of 508.5, and the empirical formula is C 29 H 34 NO 2 •Br (as a quaternary ammonium bromide compound). It is slightly soluble in water. INCRUSE ELLIPTA is a light grey and light green plastic inhaler containing a foil blister strip. Each blister on the strip contains a white powder blend of micronized umeclidinium bromide (74.2 mcg equivalent to 62.5 mcg of umeclidinium), magnesium stearate (75 mcg), and lactose monohydrate (to 12.5 mg). The lactose monohydrate contains milk proteins. After the inhaler is activated, the powder within the blister is exposed and ready for dispersion into the airstream created by the patient inhaling through the mouthpiece. Under standardized in vitro test conditions, INCRUSE ELLIPTA delivers 55 mcg of umeclidinium per dose when tested at a flow rate of 60 L/min for 4 seconds. In adult subjects with obstructive lung disease and severely compromised lung function (COPD with forced expiratory volume in 1 second/forced vital capacity [FEV 1 /FVC] <70% and FEV 1 <30% predicted or FEV 1 <50% predicted plus chronic respiratory failure), mean peak inspiratory flow through the ELLIPTA inhaler was 67.5 L/min (range: 41.6 to 83.3 L/min). The actual amount of drug delivered to the lung will depend on patient factors, such as inspiratory flow profile. incruse-ellipta-spl-graphic-01.jpg

INCRUSE ELLIPTA is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). INCRUSE ELLIPTA is an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

Inhalation powder: 62.5 mcg umeclidinium per actuation. Inhalation powder: 62.5 mcg of umeclidinium per actuation.

The recommended dosage of INCRUSE ELLIPTA for maintenance treatment of COPD is 1 actuation (umeclidinium 62.5 mcg) once daily by oral inhalation. • INCRUSE ELLIPTA should be used at the same time every day. Do not use INCRUSE ELLIPTA more than 1 time every 24 hours. • No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment . • For oral inhalation only. • Maintenance treatment of COPD: 1 actuation of INCRUSE ELLIPTA once daily administered by oral inhalation.

• Do not initiate in acutely deteriorating COPD. Do not use to treat acute symptoms. • If paradoxical bronchospasm occurs, discontinue INCRUSE ELLIPTA and institute alternative therapy. • Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur. • Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a healthcare provider immediately if symptoms occur. 5.1 Deterioration of Disease and Acute Episodes INCRUSE ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD. INCRUSE ELLIPTA has not been studied in subjects with acutely deteriorating COPD. The initiation of INCRUSE ELLIPTA in this setting is not appropriate. INCRUSE ELLIPTA should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. INCRUSE ELLIPTA has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta 2 -agonist. If INCRUSE ELLIPTA no longer controls symptoms of bronchoconstriction; the patient’s inhaled, short-acting beta 2 -agonist becomes less effective; or the patient needs more short-acting beta 2 -agonist than usual, these may be markers of deterioration of disease. In this setting re-evaluate the patient and the COPD treatment regimen at once. Increasing the daily dose of INCRUSE ELLIPTA beyond the recommended dose is not appropriate in this situation

Paradoxical Bronchospasm As with other inhaled therapies, INCRUSE ELLIPTA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with INCRUSE ELLIPTA, it should be treated immediately with an inhaled, short-acting bronchodilator; INCRUSE ELLIPTA should be discontinued immediately; and alternative therapy should be instituted

Hypersensitivity Reactions, including Anaphylaxis Hypersensitivity reactions such as anaphylaxis, angioedema, pruritus, rash, and urticaria may occur after administration of INCRUSE ELLIPTA. Discontinue INCRUSE ELLIPTA if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use INCRUSE ELLIPTA

Worsening of Narrow-Angle Glaucoma INCRUSE ELLIPTA should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should also be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develop

Worsening of Urinary Retention INCRUSE ELLIPTA, 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 urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develop.

Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of INCRUSE ELLIPTA with other anticholinergic-containing drugs

Anticholinergics There is potential for an additive interaction with concomitantly used anticholinergic medicines. Therefore, avoid coadministration of INCRUSE ELLIPTA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects .