FDA Considers Withdrawal of Asthma Drugs
HealthDay News — A U.S. Food and Drug Administration committee is meeting today to decide whether to take action on three widely used asthma drugs sold under the brand names Advair, Foradil and Serevent.
The expert panel will be considering whether the drugs, which belong to the category of long-acting beta-agonist bronchodilators, should stay on the market, whether they should be relabeled, or whether they should be left for sale as is.
In a statement, the FDA said it is concerned about "severe asthma exacerbations in a small number of patients" using these drugs.
"The objective of today’s meeting is to discuss the implications of recently available data related to the safety of long-acting beta-agonist bronchodilators," added FDA spokeswoman Laura Alvey.
Given the prominence of the drugs in treating the millions of people with asthma, however, completely removing all the drugs from the market seems the least plausible scenario, experts said.
"I continue to use these drugs because they’re so effective and important," said Dr. Adam Wanner, professor of medicine at the University of Miami School of Medicine. "They’re unlikely to be withdrawn. Maybe there will be new labeling."
The committee is considering three products but only two long-acting beta- agonist drugs are at issue: salmeterol xinafoate and formoterol fumarate, both of which are sold in the United States. The former is sold as a single-ingredient product under the brand name Serevent as well as in a combination product (with the corticosteroid fluticasone propionate) under the brand name Advair. The latter product is sold as a single-ingredient product under the trade name Foradil.
Serevent was singled out by Dr. David Graham, the FDA whistleblower, when he discussed the inability of the FDA to protect the nation’s drug supply during the Vioxx hearings.
Although these drugs are indicated for use in patients with asthma as well as chronic obstructive pulmonary disease (COPD), the issues involved here relate only to their use against asthma.
The drugs work by relaxing the smooth muscle in the airways.
"Asthma is a relentless, chronic inflammatory disease. The inflammation results in the smooth muscle of the airways being hyperreactive and they can constrict and narrow the airways," said Dr. Michael Iannuzzi, chief of pulmonary, critical care and sleep medicine at Mount Sinai Medical Center in New York City. "That constriction of the airway results in the symptoms of cough, wheezing, chest tightness and shortness of breath. The beta agonists are bronchodilators that stimulate the smooth muscles of airway to resize."
An enormous number of people worldwide use these drugs.
Roughly 5 percent to 6 percent of the U.S. population suffers from asthma. "You figure that about 60 to 70 percent of those require regular medication and these are essentially the most commonly used medications," Wanner said. "That’s a tremendous number of individuals."
According to the New York Times, Advair was the third best-selling drug in the world in 2004.
"These medications are a staple of treatment and are part of recommendations by national and international groups as to how one treats patients with asthma and COPD," Wanner added.
In a statement, the FDA said it is concerned about "severe asthma exacerbations in a small number of patients" using these drugs.
A post-marketing trial conducted by GlaxoSmithKline, makers of salmeterol, showed a statistically significant increase in asthma-related deaths (four times as many as with a placebo), respiratory-related deaths (about twice as many) and in combined asthma-related deaths or life-threatening experiences (almost twice as many). The exacerbations were particularly pronounced among blacks.
As a result, the trial was stopped early and the company incorporated the preliminary results into the labels of both Serevent and Advair.
Similarly, trials on formoterol conducted by the drug’s maker, Novartis Pharmaceuticals, found exacerbations in people taking the higher dose (24 micrograms, or mcg). As a result, the only dose approved for marketing in the United States is 12 mcg every 12 hours.
In general, Iannuzzi said, the combination product Advair is less of a problem than the single-ingredient products. "When you use the long-acting beta agonists alone, you are running the risk of masking the underlying inflammation by just treating the symptoms and not getting at the cause of the problem," he said.
Even if the drugs were banned, there are alternatives to the long-acting beta agonists. "Those are short-acting beta agonists, especially albuterol," Wanner said.
But these are less convenient, as they have to be used every four to six hours.
And there are other considerations, such as whether there will be enough albuterol to replace the long-acting drugs if the latter are discontinued on short notice.
"There are a lot of implications that the FDA will have to consider," Wanner said.
More information
For more on asthma medications, visit the American Academy of Allergy, Asthma and Immunology.
SOURCES: Adam Wanner, M.D., professor of medicine, University of Miami, Fla.; Michael Iannuzzi, M.D., chief of pulmonary, critical care and sleep medicine, Mount Sinai Medical Center, New York, N.Y.; Laura Alvey, U.S. Food and Drug Administration; July 13, 2005 New York Times; FDA briefing paper.~ASTH~~DRUG~~FDA-~