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 beta2-agonist.

COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If INCRUSE ELLIPTA no longer controls symptoms of bronchoconstriction; the patient’s inhaled, short-acting beta2-agonist becomes less effective; or the patient needs more short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting a re-eva luation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of INCRUSE ELLIPTA beyond the recommended dose is not appropriate in this situation.

5.2 Paradoxical Bronchospasm

As with other inhaled medicines, 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.

5.3 Hypersensitivity Reactions

Hypersensitivity reactions may occur after administration of INCRUSE ELLIPTA. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose; therefore, patients with severe milk protein allergy should not use INCRUSE ELLIPTA [see Contraindications (4)].

5.4 Worsening of Narrow-Angle Glaucoma

INCRUSE ELLIPTA should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should 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 physician immediately if any of these signs or symptoms develops.

5.5 Worsening of Urinary Retention

INCRUSE ELLIPTA 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 physician immediately if any of these signs or symptoms develops.

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.

A total of 1,663 subjects with COPD across 8 clinical trials (mean age: 62.7 years; 89% white; 65% male across all treatments, including placebo) received at least 1 inhalation dose of umeclidinium at doses of 62.5 or 125 mcg. In the 4 randomized, double-blind, placebo- or active-controlled, efficacy clinical trials, 1,185 subjects received umeclidinium for up to 24 weeks, of which 487 subjects received the recommended dose of umeclidinium 62.5 mcg. In a 12-month, randomized, double-blind, placebo-controlled, long-term safety trial, 227 subjects received umeclidinium 125 mcg for up to 52 weeks [see Clinical Studies (14)].

The incidence of adverse reactions associated with INCRUSE ELLIPTA in Table 1 is based upon 2 placebo-controlled efficacy trials: one 12-week trial and one 24-week trial.

Other adverse reactions with INCRUSE ELLIPTA observed with an incidence less than 1% but more common than placebo included atrial fibrillation.

In a long-term safety trial, 336 subjects (n = 227 umeclidinium 125 mcg, n = 109 placebo) were treated for up to 52 weeks with umeclidinium 125 mcg or placebo. The demographic and baseline characteristics of the long-term safety trial were similar to those of the efficacy trials described above. Adverse reactions that occurred with a frequency greater than or equal to 1% in subjects receiving umeclidinium 125 mcg that exceeded that in placebo in this trial were: nasopharyngitis, upper respiratory tract infection, urinary tract infection, pharyngitis, pneumonia, lower respiratory tract infection, rhinitis, supraventricular tachycardia, supraventricular extrasystoles, sinus tachycardia, idioventricular rhythm, headache, dizziness, sinus headache, cough, back pain, arthralgia, pain in extremity, neck pain, myalgia, nausea, dyspepsia, diarrhea, rash, depression, and vertigo.

7.1 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 [see Warnings and Precautions (5.4, 5.5), Adverse Reactions (6)].