Generic: FORMOTEROL FUMARATE
1 INDICATIONS AND USAGE Formoterol fumarate inhalation solution is a long-acting beta 2 -adrenergic agonist (beta 2 -agonist) indicated for: • Long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. ( 1.1 ) Important limitations of use: • Formoterol fumarate inhalation solution is not indicated to treat acute deteriorations of chronic ...
1 INDICATIONS AND USAGE Formoterol fumarate inhalation solution is a long-acting beta 2 -adrenergic agonist (beta 2 -agonist) indicated for: • Long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. ( 1.1 ) Important limitations of use: • Formoterol fumarate inhalation solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease. ( 1.2 , 5.2 ) •Formoterol fumarate inhalation solution is not indicated to treat asthma. ( 1.2 ) 1.1 Maintenance Treatment of COPD Formoterol fumarate inhalation solution is indicated for the long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. 1.2 Important Limitations of Use Formoterol fumarate inhalation solution is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease [ see WARNINGS AND PRECAUTIONS (5.2) ]. Formoterol fumarate inhalation solution is not indicated to treat asthma. The safety and effectiveness of formoterol fumarate inhalation solution in asthma have not been established.
5 WARNINGS AND PRECAUTIONS • LABA as monotherapy (without inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. ( 5.1 ) • Do not initiate formoterol fumarate inhalation solution in acutely deteriorating patients. ( 5.2 ) • Do not use for relief of acute symptoms. Concomitant short-acting beta 2 -agonists can be used as needed for acute relief. ( 5.2 ) • Do not exceed the recommended dose. Excessive use of formoterol fumarate inhalation solution or use in conjunc...
5 WARNINGS AND PRECAUTIONS • LABA as monotherapy (without inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. ( 5.1 ) • Do not initiate formoterol fumarate inhalation solution in acutely deteriorating patients. ( 5.2 ) • Do not use for relief of acute symptoms. Concomitant short-acting beta 2 -agonists can be used as needed for acute relief. ( 5.2 ) • Do not exceed the recommended dose. Excessive use of formoterol fumarate inhalation solution or use in conjunction with other medications containing long-acting beta 2 -agonists, can result in clinically significant cardiovascular effects, and may be fatal. ( 5.3 , 5.5 ) • Life-threatening paradoxical bronchospasm can occur. Discontinue formoterol fumarate inhalation solution immediately. ( 5.4 ) • Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or with sensitivity to sympathomimetic drugs. ( 5.6 , 5.7 ) 5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death The safety and efficacy of formoterol fumarate inhalation solution in patients with asthma have not been established. Formoterol fumarate inhalation solution is not indicated for the treatment of asthma [ see CONTRAINDICATIONS (4) ]. Use of long-acting beta 2 -adrenergic agonists (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 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 vs. 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 long-acting beta 2 -adrenergic agonists, including formoterol fumarate inhalation solution. No study adequate to determine whether the rate of asthma related death is increased in patients treated with formoterol fumarate inhalation solution has been conducted. Clinical studies with formoterol fumarate administered as a dry powder inhaler suggested a higher incidence of serious asthma exacerbations in patients who received formoterol than in those who received placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups. 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 Formoterol fumarate inhalation solution should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. Formoterol fumarate inhalation solution has not been studied in patients with acutely deteriorating COPD. The use of formoterol fumarate inhalation solution in this setting is inappropriate. Formoterol fumarate inhalation solution should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Formoterol fumarate inhalation solution 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 formoterol fumarate inhalation solution, 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 drugs and use them only for symptomatic relief of acute respiratory symptoms. When prescribing formoterol fumarate inhalation solution, the healthcare provider should also prescribe an inhaled, short-acting beta 2 -agonist and instruct the patient 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 formoterol fumarate inhalation solution 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 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 dosage of formoterol fumarate inhalation solution beyond the recommended 20 mcg twice daily dose is not appropriate in this situation. 5.3 Excessive Use and Use with Other Long-Acting Beta 2 -Agonists As with other inhaled beta 2 -adrenergic drugs, formoterol fumarate inhalation solution should not be used more often, at higher doses than recommended, or in conjunction with other medications containing long-acting beta 2 -agonists, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. 5.4 Paradoxical Bronchospasm As with other inhaled beta 2 -agonists, formoterol fumarate inhalation solution can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, formoterol fumarate inhalation solution should be discontinued immediately and alternative therapy instituted. 5.5 Cardiovascular Effects Formoterol fumarate inhalation solution, like other beta 2 -agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic and/or diastolic blood pressure, and/or symptoms. If such effects occur, formoterol fumarate inhalation solution may need to be discontinued. In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, formoterol fumarate inhalation solution, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. 5.6 Coexisting Conditions Formoterol fumarate inhalation solution, like other 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. 5.7 Hypokalemia and Hyperglycemia Beta-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-agonist medications may produce transient hyperglycemia in some patients. Clinically significant changes in serum potassium and blood glucose were infrequent during clinical studies with long-term administration of formoterol fumarate inhalation solution at the recommended dose. 5.8 Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions may occur after administration of formoterol fumarate inhalation solution, as demonstrated by cases of anaphylactic reactions, urticaria, angioedema, rash, and bronchospasm.
6 ADVERSE REACTIONS Long-acting beta 2 -adrenergic agonists, such as formoterol fumarate inhalation solution, as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of asthma-related events. Formoterol fumarate inhalation solution is not indicated for the treatment of asthma [ see WARNINGS AND PRECAUTIONS (5.1) ]. Most common adverse reactions (>2% and more common than placebo) are diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia ( 6.2 ) To...
6 ADVERSE REACTIONS Long-acting beta 2 -adrenergic agonists, such as formoterol fumarate inhalation solution, as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of asthma-related events. Formoterol fumarate inhalation solution is not indicated for the treatment of asthma [ see WARNINGS AND PRECAUTIONS (5.1) ]. Most common adverse reactions (>2% and more common than placebo) are diarrhea, nausea, nasopharyngitis, dry mouth, vomiting, dizziness, and insomnia ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Beta 2 -Agonist Adverse Reaction Profile Adverse reactions to formoterol fumarate inhalation solution are expected to be similar in nature to other beta 2 -adrenergic receptor agonists including: angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, muscle cramps, palpitations, nausea, dizziness, fatigue, malaise, insomnia, hypokalemia, hyperglycemia, and metabolic acidosis. 6.2 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults with COPD The data described below reflect exposure to formoterol fumarate inhalation solution 20 mcg twice daily by oral inhalation in 586 patients, including 232 exposed for 6 months and 155 exposed for at least 1 year. Formoterol fumarate inhalation solution was studied in a 12-week, placebo-and active-controlled trial (123 subjects treated with formoterol fumarate inhalation solution) and a 52-week, active-controlled trial (463 subjects treated with formoterol fumarate inhalation solution). Patients were mostly Caucasians (88%) between 40-90 years old (mean, 64 years old) and had COPD, with a mean FEV1 of 1.33 L. Patients with significant concurrent cardiac and other medical diseases were excluded from the trials. Table 1 shows adverse reactions from the 12-week, double-blind, placebo-controlled trial where the frequency was greater than or equal to 2% in the formoterol fumarate inhalation solution group and where the rate in the formoterol fumarate inhalation solution group exceeded the rate in the placebo group. In this trial, the frequency of patients experiencing cardiovascular adverse events was 4.1% for formoterol fumarate inhalation solution and 4.4% for placebo. There were no frequently occurring specific cardiovascular adverse events forformoterol fumarate inhalation solution (frequency greater than or equal to 1% and greater than placebo). The rate of COPD exacerbations was 4.1% for formoterol fumarate inhalation solutionand 7.9% for placebo. TABLE 1 Number of patients with adverse reactions in the 12-week multiple-dose controlled clinical trial Adverse Reaction Formoterol fumarate inhalation solution 20 mcg Placebo n (%) n (%) Total Patients 123 (100) 114 (100) Diarrhea 6 (4.9) 4 (3.5) Nausea 6 (4.9) 3 (2.6) Nasopharyngitis 4 (3.3) 2 (1.8) Dry Mouth 4 (3.3) 2 (1.8) Vomiting 3 (2.4) 2 (1.8) Dizziness 3 (2.4) 1 (0.9) Insomnia 3 (2.4) 0 0 Patients treated with formoterol fumarate inhalation solution 20 mcg twice daily in the 52-week open-label trial did not experience an increase in specific clinically significant adverse events above the number expected based on the medical condition and age of the patients. 6.3 Postmarketing Experience The following adverse reactions have been reported during post-approval use of formoterol fumarate inhalation solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Anaphylactic reactions, urticaria, angioedema (presenting as face, lip, tongue, eye, pharyngeal, or mouth edema), rash, and bronchospasm.
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.