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Alternative Treatment: [top]Pregnancy and Breast-feeding Warnings [top]
Fluticasone and salmeterol caused fetal harm in animal studies, including delayed bone formation, malformations, and fetal death. Because of the potential for serious adverse effects to the fetus, this drug should not be used by pregnant women.
Fluticasone is excreted in animal milk, and it is likely that this occurs in humans. Although fluticasone was not tested, other corticosteroids have been detected in human milk. Because of the potential for serious adverse effects in nursing infants, you should not take fluticasone and salmeterol while nursing.Safety Warnings For This Drug: [top]
FDA Black Box Warning
Long-acting beta2-adrenergic agonists, such as salmeterol, one of the active ingredients in ADVAIR DISKUS, may increase the risk of asthma-related death. Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on other asthma-controller medications (e.g., low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies. Data from a large placebo-controlled US study that compared the safety of salmeterol (SEREVENT® Inhalation Aerosol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,176 patients treated for 28 weeks on salmeterol versus 3 deaths out of 13,179 patients on placebo).1
Do not stop any asthma medication without first consulting your physician. Abruptly stopping a medication may result in acutely deteriorating asthma control.
Additional Precautions for Asthma
Avoid exposure to things that trigger your allergies or asthma, such as animals, bedding, chemicals, cosmetics, drugs, dust, mold, foods, pollens, or smoke. Wearing a mask reduces inhalation of drugs, pollens, and smoke.
Aspirin can trigger asthma in people who are aspirin-allergic, as can beta-blockers. Infections aggravate lung problems. During epidemics of respiratory illnesses, avoid crowded places and wash your hands frequently to help prevent infection. If you have asthma, get a flu vaccination.
Note: The information in this profile addresses the care of asthma that is not serious enough to need emergency treatment.
Fluticasone and salmeterol inhalation powders (ADVAIR DISKUS) combines powders of a steroid called fluticasone (FLOVENT) with a long-acting beta-blocker called salmeterol (SEREVENT). The diskus is used to inhale the powders by mouth. The combination allows a lower dose of fluticasone to be used, reducing steroid exposure and its attendant dangers.2
Fluticasone and salmeterol inhalation powders are approved by the Food and Drug Administration (FDA) for the treatment of chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and for chronic asthma. However the powders are not intended for treatment of acute episodes or rapidly deteriorating asthma.
The inhaled powders decrease the constriction of bronchial smooth muscle and inflammation of the airway, thus opening the airways and making it easier to breathe. This may reduce the need for rescue medications, such as albuterol (PROVENTIL, VENTOLIN) reduce severity of shortness of breath, reduce mortality, improve lung function, improve ability to endure strenuous activity and increase the number of symptom-free days.3, 4, 5
While inhaled steroids reduce the likelihood of systemic effects compared to steroids taken by mouth, the risks are not eliminated. Steroids can damage adrenal glands and potentially reduce bone mineral density.6, 7, 8
High-dose steroids used for longer than six months are more associated with adrenal crisis than those taken at lower doses or for shorter periods.9 Adrenal crisis refers to the suppression of the body’s normal production of steroids by the adrenal glands because of taking steroid drugs. When the drugs are stopped suddenly, the body’s production of cortisone does not return right away and the body is in a “crisis” because of the lack of the normal amounts of cortisone.
Suppression of adrenal glands can cause low blood sugar, unconsciousness, convulsions, coma or death. Onset in adults may start with drowsiness and nausea.
A detachment of the retina, called chorioretinopathy, has been associated with steroid inhalers, especially in women.10
The most frequently reported side effect associated with inhaled corticosteroid use in children with asthma is behavior alteration, according to researchers from the Netherlands. There have been reports of behavioral changes in children associated with ADVAIR DISKUS as well as inhaled fluticasone propionate (FLOVENT DISKUS). The use of intranasal corticosteroids appears to be associated with psychiatric disorders.11
In 2007, Prescire International compared the use of ADVAIR DISKUS, fluticasone product, salmeterol product and placebo product in patients with COPD. According to the article patients treated with ADVAIR DISKUS had an increased risk of pneumonia.12
There also have been 18 reports of skin bruising associated with the use of inhalation and/or intranasal fluticasone products.13
In May 2010, the Medical Letter published an article reviewing the safety of using a long-term corticosteroid inhaler in patients with COPD. Fluticasone and salmeterol inhalation powders [ADVAIR] are approved for use in COPD patients, and the article discusses the efficacy and adverse effect of using this combination treatment. The conclusion by the authors of the Medical Letter was that there is an increased risk of fractures and pneumonia in patients with COPD using a long term inhaled corticosteroid.14
Regulatory actions surrounding ADVAIR DISKUS
2003: In August 2003, the FDA announced that a black-box warning (see above) would be required on the professional product labeling or package inserts for drug products containing salmeterol. This requirement applies to both salmeterol alone and fluticasone and salmeterol together (ADVAIR DISKUS). The FDA has the regulatory authority to require boxed warnings for drugs that have been associated with death or serious injury of patients and may also require them if there is strong evidence from animal experiments that the drugs may be dangerous. A black-box warning is the strongest type of safety warning that the FDA can mandate in a drug's professional product labeling.
The black-box warning was the result of a study known as the Salmeterol Multicenter Asthma Research Trial (SMART). This study, which was terminated early, was initiated by GlaxoSmithKline in 1996 after reports of death had been submitted to the FDA. It was designed to assess the safety of salmeterol because of concerns regarding the safety of regular use of the combination of short- and long-acting beta agonists in the management of asthma after reports of death had been submitted to the FDA. Data revealed by the FDA in July 2005 lead us to conclude that ADVAIR DISKUS should not be used because of the increased risk of asthma deaths with its ingredient salmeterol.
2005: In November 2005, the FDA notified manufacturers of ADVAIR DISKUS to update its existing product label with a new warning and a Medication Guide for patients. The intention of the new warnings was to alert health care professionals and patients that this medicine may increase the chance of severe asthma episodes, and death when those episodes occur. Even though ADVAIR DISKUS decreases the frequency of asthma episodes, the drug may make asthma episodes more severe when they do occur.15
This is one of a limited number of drugs for which the FDA requires an FDA-approved Medication Guide to be dispensed when the prescription is filled. An FDA advisory committee has unanimously recommended that all drugs be accompanied by such Medication Guides but, at present, fewer than 5 percent of drugs are. The other 95 percent of drugs are accompanied by unregulated, often dangerously incomplete information leaflets that are not approved by the FDA.
2006: In March 2006, the FDA officially designated this drug a “last choice” option for the treatment and management of asthma. The regulatory agency released the following guidelines for the use of ADVAIR DISKUS:
Long-acting beta2-adrenergic agonists, such as salmeterol, one of the active ingredients in ADVAIR DISKUS, may increase the risk of asthma-related death. Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on other asthma-controller medications (e.g., low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with two maintenance therapies. ADVAIR DISKUS is not indicated in patients whose asthma can be successfully managed by inhaled corticosteroids along with occasional use of inhaled, short-acting beta2-agonists.15
2010: In February 2010, the FDA updated the safety information on long-acting beta2-adrenergic agonists (LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS. The FDA will now require a risk-management strategy to educate healthcare professionals on the appropriate uses of these drugs and a revised Medication Guide for patients. The FDA made these changes based on studies in pediatric and adult patients using these drugs for asthma. The studies showed that there was an increased risk of severe exacerbation of asthma symptoms leading to hospitalizations as well as death in some patients.16
In June 2010, the FDA posted an updated drug product label detailing the February 2010 safety information update. Read more at www.fda.gov/Safety/MedWatch/SafetyInformation/ucm218833.htm.
The FDA-approved Medication Guide for Advair can be found here.
last reviewed August 31, 2010