FDA Relegates ADVAIR and SEREVENT to Last Choice Status for Asthma Treatment

The Food and Drug Administration-approved professional product labels for the asthma drugs Advair and Serevent now state that these drugs should only be used when nothing else works to control asthma symptoms. Salmeterol, a component of these two widely-prescribed asthma drugs, is associated with an increased risk of asthma-related death. The change became effective on March 2, 2006.

Salmeterol was approved by the FDA in 1994 to treat asthma, and later approval was extended for the treatment of chronic obstructive pulmonary disease (COPD). The drug belongs to a family of asthma medications known as long acting beta2-receptor agonists. Drugs such as albuterol (PROVENTIL, VENTOLIN), metaproterenol (ALUPENT) and pirbuterol (MAXAIR) are short-acting beta agonists. This new safety labeling change does not apply to these drugs.

Salmeterol is produced by GlaxoSmithKline of Research Triangle, NC. In 2005, there were almost 20 million prescriptions dispensed in U.S. pharmacies for salmeterol (SEREVENT) and salmeterol with fluticasone (ADVAIR). Combined sales approached $3.0 billion.

We listed salmeterol as a DO NOT USE drug in the March 2003 Worst Pills, Best Pills News after a study know as the Salmeterol Multi-center Asthma Research Trial, or SMART for short, was prematurely terminated study because of an excess of asthma related deaths in patients receiving salmeterol. This study was initiated by GlaxoSmithKline in 1996. It was designed to assess the safety of salmeterol because of concerns regarding the safety of regular use of short- and long-acting beta agonists in the management of asthma. We also designated ADVAIR as a DO NOT USE drug after we learned more details concerning the SMART study.

The labeling change will appear under the “Approved Uses” section of the professional product label. The new section in the label of ADVAIR will read:

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. 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.

The new section in the label of salmeterol contains similar warnings.

In addition to the new labeling changes, the FDA now requires that a Medication Guide be distributed with each and refill prescription for salmeterol-containing products. Since 1998, the FDA has had the regulatory authority to require Medication Guides for drugs that present significant public health concerns. The purpose of Medication Guides is to give patients enough information to decide if they wish to use, or continue use, a particular drug. At this time there are about 80 drugs that require Medication Guides.

The full text of the Advair Medication Guide can be found online at the FDA's web site.  Anyone receiving a prescription for either of these drugs should receive a copy of the FDA-approved Medication Guide.

A black box warning was added to the professional product labeling for salmeterol-containing products on Aug. 14, 2003 and was subsequently strengthened (see Worst Pills, Best Pills News November 2003 and September 2005 ). A black box warning is the strongest type of warning that the FDA can request from a manufacturer and the usual standard used by the FDA for requesting such a warning is death in patients.

The most up-to-date black box warning for salmeterol with fluticasone appears at the beginning of this article.

What You Can Do

Do not stop these asthma medications without first consulting the healthcare provider who prescribed the drugs.    

You should not use salmeterol (SEREVENT) or the combination of salmeterol with the steroid fluticasone (ADVAIR) as your only treatment of your asthma.  

You should read the FDA-approved Medication Guide before filling a new prescription for a salmeterol containing product or a refill prescription for a salmeterol containing product. If you do not have access to the Internet, ask your pharmacist for a copy of the Medication Guide.

You should report any increased need for a short-acting beta agonist to your healthcare provider. This is a sign of deteriorating asthma control.