Glycopyrrolate And Formoterol Fumarate

5 WARNINGS AND PRECAUTIONS • LABA as monotherapy (without an inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. ( 5.1 ) • Do not initiate in acutely deteriorating COPD or to treat acute symptoms. ( 5.2 ) • Do not use in combination with an additional therapy containing a LABA because of risk of overdose. ( 5.3 , 7.1 ) • If paradoxical bronchospasm occurs, discontinue BEVESPI AEROSPHERE and institute alternative therapy. ( 5.4 ) • Use with caution in patients with cardiovascular disorders. ( 5.6 ) • 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. ( 5.7 ) • 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. ( 5.8 ) • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. ( 5.9 ) • Be alert to hypokalemia and hyperglycemia. ( 5.10 ) 5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death • The safety and efficacy of BEVESPI AEROSPHERE in patients with asthma have not been established. BEVESPI AEROSPHERE is not indicated for the treatment of asthma [see Contraindications (4) ] . • 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 US 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; RR 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 BEVESPI AEROSPHERE. • No trial adequate to determine whether the rate of asthma-related deaths is increased in patients treated with BEVESPI AEROSPHERE 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 BEVESPI AEROSPHERE should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. BEVESPI AEROSPHERE has not been studied in patients with acutely deteriorating COPD. The use of BEVESPI AEROSPHERE in this setting is inappropriate. BEVESPI AEROSPHERE should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. BEVESPI AEROSPHERE 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 BEVESPI AEROSPHERE, patients who have been taking 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 medicines and use them only for symptomatic relief of acute respiratory symptoms. When prescribing BEVESPI AEROSPHERE, 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 BEVESPI AEROSPHERE no longer controls the symptoms of bronchoconstriction, or the patient’s inhaled, short-acting beta 2 -agonist becomes less effective, or the patient needs more inhalations of 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 dosage of BEVESPI AEROSPHERE beyond the recommended dose is not appropriate in this situation. 5.3 Avoid Excessive Use of BEVESPI and Avoid Use with Other Long-Acting Beta 2 -Agonists As with other inhaled medicines containing beta 2 -agonists, BEVESPI AEROSPHERE 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 medicines. Patients using BEVESPI AEROSPHERE should not use another medicine containing a LABA for any reason [see Drug Interactions (7.1) ]. 5.4 Paradoxical Bronchospasm As with other inhaled medicines, BEVESPI AEROSPHERE can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with BEVESPI AEROSPHERE, it should be treated immediately with an inhaled, short-acting bronchodilator, BEVESPI AEROSPHERE should be discontinued immediately, and alternative therapy should be instituted. 5.5 Hypersensitivity Reactions including Anaphylaxis Immediate hypersensitivity reactions have been reported after administration of glycopyrrolate or formoterol fumarate, the components of BEVESPI AEROSPHERE. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of tongue, lips, and face), urticaria, or skin rash, BEVESPI AEROSPHERE should be stopped at once and alternative treatment should be considered. 5.6 Cardiovascular Effects Formoterol fumarate, like other beta 2 -agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms [see Clinical Pharmacology (12.2) ] . If such effects occur, BEVESPI AEROSPHERE may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression, although the clinical significance of these findings is unknown. Therefore, BEVESPI AEROSPHERE should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. 5.7 Worsening of Narrow-Angle Glaucoma BEVESPI AEROSPHERE 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 should any of these signs or symptoms develop. 5.8 Worsening of Urinary Retention BEVESPI AEROSPHERE 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 should any of these signs or symptoms develop. 5.9 Coexisting Conditions BEVESPI AEROSPHERE, like all medications containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Doses of the related beta 2 -agonist albuterol, when administered intravenously, have been reported to aggravate pre-existing diabetes mellitus and ketoacidosis. 5.10 Hypokalemia and Hyperglycemia Beta 2 -agonist medications may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects [see Clinical Pharmacology (12.2) ] . The decrease in serum potassium is usually transient, not requiring supplementation. Beta 2 -agonist medicines may produce transient hyperglycemia in some patients. In two clinical trials of 24-weeks and a 28-week safety extension study evaluating BEVESPI AEROSPHERE in subjects with COPD, there was no evidence of a treatment effect on serum glucose or potassium.