Brovana - General Information
Brovana is a bronchodilator. It works by relaxing muscles in the airways to improve breathing. Brovana inhalation is used to prevent bronchoconstriction in people with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.
Pharmacology of Brovana
Brovana, the (R,R)-enantiomer of formoterol, is a selective long-acting beta2-adrenergic receptor agonist (beta2-agonist) that has two-fold greater potency than racemic formoterol (which contains both the (S,S) and (R,R)-enantiomers). The (S,S)-enantiomer is about 1,000-fold less potent as a beta2-agonist than the (R,R)-enantiomer.
Brovana for patients
Patients should be instructed to read the accompanying Medication Guide with each new prescription and refill. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be given the following information:
- Patients should be informed that long-acting beta2-adrenergic agonists may increase the risk of asthma-related death.
- BROVANA is not indicated to relieve acute respiratory symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting, beta2-agonist (the health-care provider should prescribe the patient with such medication and instruct the patient in how it should be used). Patients should be instructed to seek medical attention if their symptoms worsen, if BROVANA treatment becomes less effective, or if they need more inhalations of a short-acting beta2-agonist than usual. Patients should not inhale more than one dose at any one time. The daily dosage of BROVANA should not exceed one vial (15 mcg) by inhalation twice daily (30 mcg total daily dose).
- Patients should be informed that treatment with beta2-agonists may lead to adverse events which include palpitations, chest pain, rapid heart rate, tremor, or nervousness.
- Patients should be instructed to use BROVANA by nebulizer only and not to inject or swallow this inhalation solution.
- Patients should protect BROVANA single-use low-density polyethylene (LDPE) vials from light and excessive heat. The protective foil pouches should be stored under refrigeration between 2°C and 8°C (36°-46°F). They should not be used after the expiration date stamped on the container. Patients should be instructed that once the foil pouch is opened, the contents of the vial should be used immediately and to discard any vial if the solution is not colorless.
- The drug compatibility (physical and chemical), efficacy and safety of BROVANA when mixed with other drugs in a nebulizer have not been established.
- Women should be advised to contact their physician if they become pregnant or if they are nursing.
- It is important that patients understand how to use the BROVANA appropriately and how it should be used in relation to other medications to treat COPD they are taking.
If additional adrenergic drugs are to be administered by any route, they should be used with caution because the pharmacologically predictable sympathetic effects of BROVANA may be potentiated.
When paroxetine, a potent inhibitor of CYP2D6, was co-administered with BROVANA at steady-state, exposure to either drug was not altered. Dosage adjustments of BROVANA are not necessary when the drug is given concomitantly with potent CYP2D6 inhibitors.
Concomitant treatment with methylxanthines (aminophylline, theophylline), steroids, or diuretics may potentiate any hypokalemic effect of adrenergic agonists.
The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the co-administration of beta-agonists with non-potassium sparing diuretics.
BROVANA, as with other beta2-agonists, 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 the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. The concurrent use of intravenously or orally administered methylxanthines (e.g., aminophylline, theophylline) by patients receiving BROVANA has not been completely evaluated. In two combined 12-week placebo controlled trials that included BROVANA doses of 15 mcg twice daily, 25 mcg twice daily, and 50 mcg once daily, 54 of 873 BROVANA -treated subjects received concomitant theophylline at study entry. In a 12-month controlled trial that included a 50 mcg once daily BROVANA dose, 30 of the 528 BROVANA -treated subjects received concomitant theophylline at study entry. In these trials, heart rate and systolic blood pressure were approximately 2-3 bpm and 6-8 mm Hg higher, respectively, in subjects on concomitant theophylline compared with the overall population.
Beta-adrenergic receptor antagonists (beta-blockers) and BROVANA may interfere with the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
BROVANA (arformoterol tartrate) Inhalation Solution is contraindicated in patients with a history of hypersensitivity to arformoterol, racemic formoterol or to any other components of this product.
Additional information about Brovana
Brovana Indication: For the long term, twice daily maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Mechanism Of Action: While it is recognized that beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, data indicate that there are also beta2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including arformoterol, are at least in part attributable to 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. In vitro tests show that arformoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Brovana also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-response.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Arformoterol
Drug Category: Bronchodilator Agents; Adrenergic beta-Agonists
Drug Type: Small Molecule; Approved
Absorption: Not Available
Toxicity (Overdose): A death was reported in dogs after a single oral dose of 5 mg/kg (approximately 4500 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis). As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose.
Protein Binding: The binding of arformoterol to human plasma proteins in vitro was 52-65% at concentrations of 0.25, 0.5 and 1.0 ng/mL of radiolabeled arformoterol.
Biotransformation: Arformoterol was almost entirely metabolized following oral administration of 35 mcg of radiolabeled arformoterol in eight healthy subjects. Direct conjugation of arformoterol with glucuronic acid was the major metabolic pathway. O-Desmethylation is a secondary route catalyzed by the CYP enzymes CYP2D6 and CYP2C19.
Half Life: In COPD patients given 15 mcg inhaled arformoterol twice a day for 14 days, the mean terminal half-life of arformoterol was 26 hours.
Dosage Forms of Brovana: Aerosol, metered Respiratory (inhalation)
Capsule Respiratory (inhalation)
Chemical IUPAC Name: N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide
Chemical Formula: C19H24N2O4
Arformoterol on Wikipedia: Not Available
Organisms Affected: Humans and other mammals