Arformoterol Tartrate Inhalation Solution (Brovana™)
Pharmacology Update
Arformoterol Tartrate Inhalation Solution (Brovana™)
By William T. Elliot, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.. Drs. Elliott and Chan report no financial relationship to this field of study.
Arformoterol (R,R-formoterol) is a single isomer form of racemic (RR, SS) formoterol approved for the treatment of chronic obstructive pulmonary disease (COPD). This isomer shows high selectivity for the Beta 2-adrenergic receptor relative to Beta 1-adrenergic receptors. Arformoterol is administered twice a day and is characterized as a long-acting beta2 agonist (LABA). It is marketed by Sepracor, Inc as Brovana.
Indications
Arformoterol is indicated for maintenance therapy of bronchoconstriction in patients with COPD,including chronic bronchitis, and emphysema.1
Dosage
The recommended dose is 15 mcg administered twice daily (morning and evening) by nebulization using a standard jet nebulizer connected to an air compressor.
Arformoterol is supplied as 2 ml vials each containing 15 mcg of arformoterol.
Potential Advantages
Arformoterol has greater selectivity for Beta 2 adrenergic receptors than the other isomers or the racemic mixture. The inactive (S,S) isomer has been reported to paradoxically increase airway reactivity.
Potential Disadvantages
Arformoterol requires administration through a nebulizer machine. As with other long-acting beta agonist, arformoterol may increase the risk of asthma-related deaths. Decrease in bronchodilatory effect (tachyphylaxis) has been observed after 6 weeks of therapy.1
Comments
Arformoterol is the first long-acting beta agonist to be approved as a solution for administration by a nebulizer machine. Efficacy of the 15 mcg dose was demonstrated in two, 12-week, double-blind, placebo-and-active controlled, randomized parallel groups studies in the United States (n = 581). Eighty percent of these study subjects had bronchodilator reversibility as defined by a 10% or greater response in FEV1 to albuterol. Arformoterol at 15 mcg twice daily significantly improved bronchodilation (FEV1) compared to placebo.1 Over the first 6 hours the placebo-subtracted change in FEV1 was approximately 0.2L. Effect was maintained over 12 weeks; however, the difference declined to 0.15L. Peak effect occurs at 1-3 hours. Even though salmeterol was included as an active comparator, comparative data were not reported. Adverse events that exceeded placebo included pain (8% vs. 5%), back pain (6% vs. 2%), diarrhea (6% vs. 4%), dyspnea, rash, leg cramps (each 4% vs. 2%), and flu-like syndrome (3% vs. 1%). Dose-related events included asthenia, fever, bronchitis, COPD, headache, vomiting, hyperkalemia, leukocytosis, nervousness, and tremor.1 Currently there are no published clinical studies on arformoterol. The product is expected to be available the 2nd quarter of 2007 and cost is not available at the time of this review.
Clinical Implications
COPD is the fourth most common cause of death in the U.S.3 In 2004, 11.4 million U.S. adults were estimated to have the disease. Bronchodilators are the mainstay of therapy. These include short-acting beta2 agonists, anticholinergics (ipratropium, tiotropium), and long acting beta2 agonists. While none of these affect disease progression, they reduce symptoms, increase exercise capacity, reduce the number and severity of exacerbations, and improve quality of life.4 There are no published comparative trials among different LABAs. Arformoterol is the first LABA approved as a solution for nebulization for the treatment of COPD. Clinical benefits directly related to the pure (R,R) isomer remains to be determined.
References
1. Brovana Product Information. Sepracor, Inc. October 2006.
2. Anonymous. Drugs R&D. 2004;5:25-27.
3. American Lung Association. http://www.lungusa.org/Accessed 12/25/06.
4. Celli BR, et al. Eur Respir. 2004;23:932-946.
Arformoterol (R,R-formoterol) is a single isomer form of racemic (RR, SS) formoterol approved for the treatment of chronic obstructive pulmonary disease (COPD).Subscribe Now for Access
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