General Information

Brovana is specifically indicated for the long term, twice daily maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Brovana is supplied as 2 mL of a sterile solution in unit-dose, low-density polyethylene vials individually overwrapped in foil. It is designed for use as an inhalation solution. The recommended initial dose of the drug is 15 mcg administered twice a day (morning and evening) by nebulization.

Clinical Results

FDA Approval
FDA approval of Brovana was based on the results of two clinical trials. These were identical, 12-week, double-blind, placebo- and active-controlled, randomized, multi-center, parallel group trials. A total of 1,456 subjects were enrolled. Subjects received 15 or 25 mcg of Brovana twice daily, 50 mcg of Brovana once daily or placebo. Both trials included salmeterol inhalation aerosol, 42 mcg twice daily as an active comparator. In both trials Brovana administered at 15 mcg twice daily resulted in significantly greater post-dose bronchodilation (as measured by percent change from study baseline FEV1 at the end of the dosing interval over the 12 weeks of treatment) compared to placebo. At the 25 and 50 mcg doses, Brovana did not demonstrate sufficient enough benefit on a number of endpoints to support the use of higher doses. In addition, when compared to placebo, the subjects treated with Brovana demonstrated improvements in peak expiratory flow rates, supplemental ipratropium and rescue albuterol use.

Ongoing Study Commitments

Sepracor has agreed to conduct a multicenter, randomized, placebo-controlled, large, simple safety trial to evaluate the effects of long term use of Brovana Inhalation Solution in patients with COPD.
Protocol Submission: August 2007
Study Start: December 2007
Final Report Submission: December 2012

Sepracor has agreed to conduct a a safety and tolerability study with one or more doses and one or more dose levels of Brovana Inhalation Solution in children with asthma and/or obstructive airway disease.
Protocol Submission: June 2007
Study Start: September 2007
Final Report Submission: December 2008

Sepracor has agreed to conduct a safety and efficacy study with one or more doses and one or more dose levels of Brovana Inhalation Solution in children with asthma and/or obstructive airway disease presenting with an acute exacerbation.
Protocol Submission: September 2008
Study Start: January 2009
Final Report Submission: May 2011

Side Effects

Adverse events associated with the use of Brovana may include, but are not limited to, the following:

Chest pain

Back pain

Diarrhea

Sinusitis

Leg cramps

Dyspnea

Rash

In addition, Brovana has been seen to cause infrequent yet clinically significant changes in systolic and/or diastolic blood pressure, pulse rate and electrocardiograms. Treatment should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive disorders or thyrotoxicosis; and in patients who are unusually responsive to sympathomimetic amines. Beta-agonist medications may also produce significant hypokalemia in some patients. Brovana is contraindicated in patients with a history of hypersensitivity to arformoterol, racemic formoterol or to any other components of this product.

Mechanism of Action

Brovana is a selective beta2-adrenergic bronchodilator. Beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle. They cause stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased intracellular cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Literature References

Campbell SC, Criner GJ, Levine BE, Simon SJ, Smith JS, Orevillo CJ, Ziehmer BA Cardiac safety of formoterol 12mug twice daily in patients with chronic obstructive pulmonary disease. Pulmonary pharmacology & therapeutics 2006 Jul 11

Cheer SM, Scott LJ Formoterol: a review of its use in chronic obstructive pulmonary disease. American journal of respiratory medicine : drugs, devices, and other interventions. 2002;1(4):285-300

Aalbers R, Ayres J, Backer V, Decramer M, Lier PA, Magyar P, Malolepszy J, Ruffin R, Sybrecht GW Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 2002 May;19(5):936-43.