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Fluticasone propionate (top) and salmeterol (bottom)
|Salmeterol||Long-Acting Beta2 Agonist|
|Trade names||Advair, Seretide|
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The combination preparation fluticasone/salmeterol is a formulation containing fluticasone propionate and salmeterol xinafoate, used in the management of asthma and chronic obstructive pulmonary disease (COPD). It is marketed by GlaxoSmithKline under various trade names including Advair (in the US and Canada), Seretide (Brazil, India, Australia, Colombia, EU, México, New Zealand, South Africa, South Korea, UK, Estonia), Viani (Germany), Adoair (Japan) and Foxair (South Africa). In India it is marketed by Intas under the trade name 'Quikhale SF'. Annual worldwide sales were approximately US$7 billion in 2009. Patent protection in the US expired in 2010, and European patent protection expired in 2013. However, the availability of a generic form of Advair in the United States may be significantly delayed because the Food and Drug Administration has not determined a standard for the bioequivalence of inhaled steroids in multi-dose inhalers or dry powder inhalers.
Fluticasone, a corticosteroid, is the anti-inflammatory component of the combination, while salmeterol treats constriction of the airways. Together, they relieve the symptoms of coughing, wheezing and shortness of breath.
Advair is available in several dosage strengths, depending on the patient's country, as a DPI (dry powder inhaler). The smallest dosage is 100 μg fluticasone/ 50 μg salmeterol, the intermediate dosage is 250 μg / 50 μg and the highest dosage is 500 μg / 50 μg.
Advair HFA aerosol as a MDI (metered dose inhaler) is available in Canada and the US and now in Australia and New Zealand as Advair HFA 45 μg / 21 μg, Advair HFA 115 μg / 21 μg, and Advair HFA 230 μg / 21 μg. These contain 60 inhalations and are generally prescribed as a 30 day supply (1 inhalation twice a day).
Internationally the fluticasone/salmeterol combination is delivered by a number of devices, including standard aerosol metered dose inhalers (brand name "Evohaler" in Mexico and UK) or dry-powder devices termed "Accuhaler" in Australia and the UK, and "Diskus" in France and the US. These purple disk-shaped containers are about 3.5 inches (8.9 cm) across and about 1 inch thick (2.5 cm). The disc container uses a machined 2 piece long foil ribbon with each unit dose held in small caplet-shaped depressions along the entire dose-count-length. Once the lever is actuated the dose is advanced by peeling away the flat outermost layer exposing the medication that is ready to be inhaled.
The common and minor side effects of this combination are those of its individual drugs. For instance, the use of inhaled corticosteroids is associated with oral candidiasis (commonly known as yeast infection). It is recommended to rinse and gargle with water after inhaling the medication. This decreases the risk of developing a candidiasis infection.
Whilst the use of inhaled steroids and long acting beta-adrenoceptor agonist (LABA) are recommended in asthma guidelines for the resulting improved symptom control, concerns have been raised that salmeterol may increase the small risks of asthma deaths and this additional risk is not reduced with the additional use of inhaled steroids. This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning. Other side effects from this drug combination may include increased blood pressure, change in heart rate, an irregular heartbeat, increased risk of osteoporosis, cataracts, and glaucoma. No increase in bone loss or osteoporosis was noted in one study of 658 patients on high dose Advair (500 μg fluticasone/50 μg salmeterol twice daily), although the 57% dropout rate over three years may have biased the reported outcome.
Although Advair lost US patent protection in 2010, no generic equivalent is imminent in the US. On November 8, 2010, Teva Pharmaceutical Industries said the regulatory hurdles were too high for a US generic. Teva said they would work on a branded competitor that should be ready by 2014 and might receive US approval by 2016. Seroflo, manufactured by Cipla, is a generic form of Advair available outside of the US.
In 2012, Advair was part of a larger civil settlement agreement between GlaxoSmithKline (GSK) and the United States, in which GSK agreed to pay $1.043-billion. The United States alleges that GSK promoted off-label uses of Advair and paid kickbacks to healthcare professionals to sell this drug.
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- Biospace.com 11/8/2010
- "GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data". http://www.justice.gov/opa/pr/glaxosmithkline-plead-guilty-and-pay-3-billion-resolve-fraud-allegations-and-failure-report. Department of Justice: Office of Public Affairs.