Aclidinium - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • 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.

Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if symptoms occur.

5.1 Serious Asthma-Related Events-Hospitalizations, Intubations, Death • The safety and efficacy of DUAKLIR PRESSAIR in patients with asthma have not been established.

DUAKLIR PRESSAIR is not indicated for the treatment of asthma. [see Contraindications ] . • Use of LABA as monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated with an increased risk of asthma-related death.

Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients.

These findings are considered a class effect of LABA monotherapy.

When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. • A 28-week, placebo-controlled, U.S. trial comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol vs 3/13,179 in subjects treated with placebo; relative risk: 4.37 [95% CI: 1.25, 15.34]).

The increased risk of asthma-related death is considered a class effect of LABAs, including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR. • No trial adequate to determine whether the rate of asthma-related deaths is increased in subjects treated with DUAKLIR PRESSAIR has been conducted. • Available data do not suggest an increased risk of death with use of LABA in patients with COPD.

5.2 Deterioration of Disease and Acute Episodes DUAKLIR PRESSAIR should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition.

DUAKLIR PRESSAIR has not been studied in patients with acutely deteriorating COPD.

The use of DUAKLIR PRESSAIR in this setting is inappropriate.

DUAKLIR PRESSAIR is intended as twice daily maintenance treatment for COPD and should not be used for the relief of acute symptoms, i.e., as rescue therapy for treatment of acute episodes of bronchospasm.

DUAKLIR PRESSAIR 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.

When beginning treatment with DUAKLIR PRESSAIR, patients who have been taking oral or inhaled, short-acting beta 2 -agonists on a regular basis (e.g., four times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute respiratory symptoms.

When prescribing DUAKLIR PRESSAIR, the healthcare provider should also prescribe an inhaled, short-acting beta 2 -agonist and instruct the patient on how it should be used.

Increasing inhaled beta 2 -agonist use is a signal of deteriorating disease for which prompt medical attention is indicated.

COPD may deteriorate acutely over a period of hours or chronically over several days or longer.

If DUAKLIR PRESSAIR 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, a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once.

Increasing the daily dose of DUAKLIR PRESSAIR beyond the recommended dose is not appropriate in this situation.

5.3 Excessive Use of DUAKLIR PRESSAIR and Use with Other Long-Acting Beta 2 Agonists As with other inhaled drugs containing beta-agonists, DUAKLIR PRESSAIR should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result.

Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

Patients using DUAKLIR PRESSAIR should not use another medicine containing a LABA for any reason [see Drug Interactions ] .