A 2-week, prospective, multicenter, randomized, modified-blind, double-dummy, parallel group study to evaluate the efficacy and safety of sequentially dosed BROVANA 15 mcg BID and tiotropium 18 mcg QD vs the individual monotherapies in the treatment of subjects with COPD (n=234).2
The study compared BROVANA (n=76), tiotropium (n=80), and BROVANA + tiotropium dosed sequentially (n=78). The primary comparison was between the BROVANA + tiotropium group vs tiotropium alone. The key secondary analysis was BROVANA + tiotropium vs BROVANA alone. The primary efficacy endpoint was mean change from baseline in FEV1 AUC0-24 at Week 2.2,3
Limitations are related to the 2-week study duration as well as the modified, double-dummy design required for the blinding the study arms.2
Study was not designed to be comparative and should not be interpreted as providing evidence of superiority.
BROVANA is indicated and supplied as a 15 mcg BID monotherapy. This study evaluated 2 monotherapies dosed sequentially.
GOLD does not endorse any specific treatments.
Dosed sequentially. Subjects instructed to use nebulizer first, followed immediately (within 5 minutes) by dry-powder inhaler.
AUC0-24=area under the change from study baseline curve for FEV1 over 24 hours; BID=twice a day; FEV1=forced expiratory volume in 1 second; GOLD=Global Initiative for Chronic Obstructive Lung Disease; QD=once a day.
1. BROVANA [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; 2019.
2. Data on File. Clinical Study Report 091-902. Sunovion Pharmaceuticals Inc.
3. Tashkin DP, Donohue JF, Mahler DA, et al. Effects of arformoterol twice daily, tiotropium, once daily, and their combination in patients with COPD. Respir Med. 2009;103(4):516-524.
4. Global Strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2019 report. Global Initiative for Chronic Obstructive Lung Disease. 2019:1-139.
BROVANA is contraindicated in patients with a history of hypersensitivity to arformoterol, racemic formoterol or to any of the ingredients.
Use of a LABA, including BROVANA, without an inhaled corticosteroid is contraindicated in patients with asthma.
Use of a LABA, including BROVANA, as monotherapy (without inhaled corticosteroids) for asthma increases the risk of serious asthma-related events, including hospitalization, intubation and death. No study adequate to determine whether the rate of asthma-related death is increased in patients treated with BROVANA Inhalation Solution has been conducted. Available data do not suggest an increased risk of death with use of LABAs in patients with COPD.
BROVANA should not be initiated in patients with acutely deteriorating COPD or potentially life-threatening episodes of COPD or used as rescue therapy for acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled short-acting beta2-agonist.
BROVANA should not be used more often, at higher doses than recommended, or in conjunction with other medications containing LABAs as an overdose may result. Patients who have been taking inhaled short-acting beta2-agonists on a regular basis should be instructed to discontinue their regular use and to use them only for symptomatic relief for acute respiratory symptoms. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using BROVANA should not use another medicine containing a LABA for any reason.
Immediate hypersensitivity reactions may occur with BROVANA. If signs occur, discontinue immediately and institute alternative therapy.
As with other inhaled beta2-agonists, BROVANA can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, BROVANA should be discontinued immediately and alternative therapy instituted.
BROVANA, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and/or symptoms. BROVANA should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Beta2-adrenergic agonists may produce significant hypokalemia in some patients.
As with other beta2-agonists, BROVANA, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval because these agents may potentiate the action of adrenergic agonists on the cardiovascular system.
As with other beta2-agonists, BROVANA should be used with caution in patients treated with additional adrenergic drugs, non-potassium-sparing diuretics, and beta-blockers.
BROVANA, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
Overall efficacy of BROVANA was maintained throughout the 12-week trial duration. Some tolerance to the bronchodilator effect of BROVANA was observed after 6 weeks of dosing (at the end of the dosing interval), although the FEV1 improvement remained statistically significant. This was not accompanied by other clinical manifestations of tolerance.
The five most common adverse events reported with frequency ≥2% in patients taking BROVANA, and occurring more frequently than in patients taking placebo, were pain (8% vs 5%), chest pain (7% vs 6%), back pain (6% vs 2%), diarrhea (6% vs 4%), and sinusitis (5% vs 4%).
BROVANA should not be swallowed as the intended effects on the lungs will not be obtained. BROVANA is only for oral inhalation via a standard jet nebulizer connected to an air compressor.
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BROVANA® (arformoterol tartrate) Inhalation Solution is a long-acting beta2- adrenergic agonist (LABA) indicated for the long-term, twice-daily (morning and evening) maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. BROVANA is for use by nebulization only.
Important limitations: BROVANA is not indicated to treat acute deteriorations of COPD and is not indicated to treat asthma.