Asthma Drugs Salmeterol (SEREVENT), Salmeterol with Fluticasone (ADVAIR), and Formoterol (FORADIL)

On Nov. 18, 2005, the Food and Drug Administration requested that additional new safety warnings be added to the professional product labels for the popular asthma drugs salmeterol (SEREVENT), salmeterol with fluticasone (ADVAIR), and formoterol (FORADIL). The new warnings concern the possibility that these drugs may increase the chance of severe asthma attacks and asthma-related death.

The FDA will also require that a Medication Guide be distributed with each new and refill prescription for these drugs. A Medication Guide is FDA-approved, scientifically accurate drug information that is written specifically for patients. The FDA has the regulatory authority to require that pharmacists distribute Medication Guides for drugs that present a significant public health risk.  

Salmeterol and formoterol belong to the family of asthma drugs known as long-acting beta-agonist bronchodilators. Note that this is a different family than asthma drugs such as albuterol (PROVENTIL, VENTOLIN) and metaproterenol (ALUPENT), which are short-acting beta-agonist bronchodilators. The new warnings do not apply to the short-acting beta-agonist bronchodilators. Fluticasone is an anti-inflammatory corticosteroid, or steroid, and in combination with salmeterol is sold as Advair. The warning also does not apply to fluticasone when it is used by itself.

The FDA made the following recommendations about the use of salmeterol, formoterol, and Advair:

• These drugs should not be the first ones prescribed to treatment for asthma.
• These drugs should not be used by themselves to treat asthma.  
• These drugs should always be used with another asthma treatment drug and only after the other asthma treatment, such as a low-to-medium dose inhaled corticosteroid, has not controlled the asthma.  

GlaxoSmithKline of Research Triangle Park, N.C., sells both of the salmeterol-containing products. Salmeterol by itself was dispensed over 2.1 million times in U.S. pharmacies in 2004 with sales exceeding $200 million. The combination product, Advair, is what Wall Street calls a “blockbuster.” More than 16.1 million Advair prescriptions were sold in the U.S. in 2004; sales topped $2.1 billion for the year.

Formoterol is produced by the Schering Corp. of Kenilworth, N.J. It is not a top seller and sales figures for 2004 are not available.

We listed salmeterol as a DO NOT USE drug in January 2003. We did so because the FDA announced that a large safety study had been terminated early due to the fact that data from the trial suggested an increased risk of life-threatening asthma episodes or asthma-related deaths with the use of the drug (see Worst Pills, Best Pills News March 2003).

The terminated safety study was called the Salmeterol Multi-center Asthma Research Trial, or SMART for short. This study was initiated by GlaxoSmithKline in 1996. It was designed to assess the safety of salmeterol because concerns existed regarding the safety of the regular use of both short- and long-acting beta agonists in the management of asthma.  

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.

What You Can Do

Do not stop any asthma medication without first consulting your physician. Abruptly stopping a medication may result in acutely deteriorating asthma control.

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

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