warnings and cautions
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 medication containing LABA because of risk of overdose. ( 5.3 , 7.1 ) If paradoxical bronchospasm occurs, discontinue UTIBRON NEOHALER immediately and institute alternative therapy. ( 5.4 ) Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, sensitivity to sympathomimetic drugs, diabetes mellitus, and ketoacidosis. ( 5.6 , 5.7 , 7.1 ) Worsening of narrow-angle glaucoma or urinary retention may occur. Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction and instruct patients to contact their healthcare provider immediately if symptoms occur. ( 5.8 , 5.9 ) Be alert to hypokalemia and hyperglycemia. ( 5.10 ) 5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death The safety and efficacy of UTIBRON NEOHALER in patients with asthma have not been established. UTIBRON NEOHALER 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 a 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. study comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol versus 3/13,179 in patients 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 the LABAs, including indacaterol, one of the ingredients in UTIBRON NEOHALER. No study adequate to determine whether the rate of asthma-related death is increased in patients treated with UTIBRON NEOHALER 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 UTIBRON NEOHALER should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD. UTIBRON NEOHALER has not been studied in patients with acutely deteriorating COPD. The initiation of UTIBRON NEOHALER in this setting is not appropriate. UTIBRON NEOHALER should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. UTIBRON NEOHALER 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 UTIBRON NEOHALER, patients who have been taking oral or inhaled, short-acting beta 2 -agonists on a regular basis (e.g., 4 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 UTIBRON NEOHALER, 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 UTIBRON NEOHALER no longer controls the symptoms of bronchoconstriction; the patient's inhaled, short-acting beta 2 -agonist becomes less effective; or the patient needs more inhalation 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 dose of UTIBRON NEOHALER beyond the recommended dose is not appropriate in this situation. 5.3 Avoid Excessive Use of UTIBRON NEOHALER and Avoid Use With Other Long-Acting Beta2-Adrenergic Agonists As with other inhaled drugs containing beta 2 -adrenergics, UTIBRON NEOHALER 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 UTIBRON NEOHALER 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, UTIBRON NEOHALER can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with UTIBRON NEOHALER, it should be treated immediately with an inhaled, short-acting bronchodilator; UTIBRON NEOHALER should be discontinued immediately and alternative therapy instituted. 5.5 Hypersensitivity Reactions, Including Anaphylaxis Immediate hypersensitivity reactions have been reported after administration of indacaterol or glycopyrrolate, the components of UTIBRON NEOHALER. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of tongue, lips, and face), anaphylaxis, urticaria, or skin rash, UTIBRON NEOHALER should be discontinued immediately and alternative therapy instituted. UTIBRON NEOHALER should be used with caution in patients with severe hypersensitivity to milk proteins. 5.6 Cardiovascular Effects Indacaterol, 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. If such effects occur, UTIBRON NEOHALER may need to be discontinued. In addition, beta-adrenergic agonists have been reported to produce ECG 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, UTIBRON NEOHALER should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. 5.7 Coexisting Conditions UTIBRON NEOHALER, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to sympathomimetic amines. Doses of the related beta 2 -agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. 5.8 Worsening of Narrow-Angle Glaucoma UTIBRON NEOHALER 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 their healthcare provider immediately should any of these signs or symptoms develop. 5.9 Worsening of Urinary Retention UTIBRON NEOHALER 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 their healthcare provider immediately should any of these signs or symptoms develop. 5.10 Hypokalemia and Hyperglycemia Beta 2 -adrenergic agonists may produce significant hypokalemia in some patients, 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. Inhalation of high doses of beta 2 -adrenergic agonists may produce increases in plasma glucose. In patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment [see Drug Interactions ( 7.2 )] , which may increase the susceptibility for cardiac arrhythmias. In 2 clinical trials of 12-weeks duration evaluating UTIBRON NEOHALER in subjects with COPD, there was no evidence of a treatment effect on serum glucose or potassium.