Drug Profile

Do Not Use: This drug has been associated with an increased death rate. Safer alternatives are available.

Salmeterol is marketed as a single-drug inhaler under the brand name SEREVENT and in combination with the corticosteroid fluticasone propionate marketed under the brand name ADVAIR. Salmeterol belongs to a family of asthma medications known as long-acting beta2-receptor agonists (LABAs or beta-agonists). Salmeterol and formoterol (FORADIL) are the only long-acting beta-agonists marketed in the U.S.

In contrast, drugs such as albuterol (PROVENTIL, VENTOLIN), metaproterenol (ALUPENT) and pirbuterol (MAXAIR) are short-acting beta-agonists.

Studies show...

In 2003, the Food and Drug Administration (FDA)- required a black-box warning (see top of page) for all products containing salmeterol based on the results of a study known as the Salmeterol Multicenter Asthma Research Trial (SMART), which began in 1996 but was terminated early. This study was initiated by GlaxoSmithKline to assess the safety of salmeterol after reports of death submitted to the FDA sparked concerns regarding the safety of regular use of the combination of short- and long-acting beta-agonists to manage asthma.

Unfortunately, information about the SMART study is only fragmentary. GlaxoSmithKline has not published a full description of the study and its outcomes in a medical journal. What is known about the SMART study is contained in a Jan. 23, 2003, FDA announcement and in the new additions to salmeterol’s product label.

A very troubling aspect of the FDA’s announcement was the number of patients in the trial not using an inhaled steroid as the foundation of their asthma treatments. The National Asthma Education and Prevention Program guidelines published in 1997 recommend that patients requiring more medicine than needed for simply treating an acute attack with short-acting beta-agonists should be using regular and adequate doses of an inhaled steroid for optimal management of their asthma. There are a number of inhaled steroids on the market in the U.S., including beclomethasone (BECLOVENT, VANCERIL), budesonide (PULMICORT), flunisolide (AEROBID), fluticasone (FLOVENT) and triamcinolone (AZMACORT).

In May 2013, an article was published in the Journal of the American Medical Association on the association between the risk of cardiovascular events and new use of inhaled long-acting beta-agonist or long-acting anticholinergic medications in patients 66 years and older with COPD. The study found that patients using these medications had a higher risk of cardiovascular events than patients not using either medication. The study also found that there was no significant difference in the risk of cardiovascular events between users of either of the two classes of medication.[1]

Regulatory actions surrounding salmeterol

2003: The FDA announced that it would require a black-box warning (see top of page) on the product label for drug products containing salmeterol. This requirement initially applied to both SEREVENT and the combination of salmeterol with the steroid fluticasone, sold as ADVAIR DISKUS. In 2017, the FDA removed the requirement for the black-box warning in the label for ADVAIR DISKUS, but not for SEREVENT.[2]

2005: The FDA notified manufacturers of fluticasone and salmeterol inhalation powders to update the existing product label with a new warning and a Medication Guide 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 this drug decreases the frequency of asthma episodes, it may make asthma episodes more severe when they do occur.[3]

Products containing salmeterol are required to be dispensed with an FDA-approved Medication Guide. An FDA advisory committee has unanimously recommended that all prescription drugs be accompanied by such Medication Guides, but at present, less than 5 percent of drugs are. The other 95 percent of drugs are accompanied by unregulated, often dangerously incomplete information leaflets not approved by the FDA. Click here to read the Medication Guide for SEREVENT DISKUS.

2006: The FDA officially designated salmeterol as a “last choice” drug for the treatment and management of asthma. The agency released the following guidelines for the use of salmeterol:

Long-acting beta 2-adrenergic agonists, such as salmeterol, the active ingredient in SEREVENT DISKUS, have been associated with an increased risk of severe asthma exacerbations and asthma-related death. FDA has requested that the package insert (labeling) for all long-acting beta 2-adrenergic agonists, including SEREVENT, be revised to provide more information about this possible increased risk. ... SEREVENT DISKUS should only be used as additional therapy in patients who have not adequately responded to other asthma-controller medications, such as low- to medium-dose inhaled corticosteroids.[4]

2010: The FDA updated the safety information on LABAs such as salmeterol — one of the active ingredients in SEREVENT DISKUS. The FDA required a risk-management strategy to educate health care professionals on the appropriate uses of these drugs and a revised Medication Guide for patients. The FDA made these changes based on studies of 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.[5]

2011: The FDA announced that it has asked the drug manufacturers of LABAs to conduct five randomized, double-blind, controlled clinical trials to evaluate the safety of these drugs in the treatment of asthma when used with an inhaled corticosteroid drug (combination therapy) versus when an inhaled corticosteroid drug is used alone (single therapy). The clinical trials began in 2011, and the FDA expects to receive results in 2017.