Two Asthma Meds May Be Too Risky, FDA Panel Says

One official told the panel members that more than 14,000 people may have died since 1994 after taking the drugs, while another suggested that an even greater number might have died without them, according to The New York Times.

Last week, two FDA officials, who work in the agency's safety division, posted an assessment on the agency Web site, saying asthma sufferers of all ages should not take the medicines. But a third FDA official concluded that Advair and Symbicort are safe for adults, but that all four drugs should no longer be used by children 17 and younger, the Times said.

The panel was reviewing an FDA study of 110 trials that included 60,954 people and found an increase in asthma-related hospitalization, asthma-related intubation, and asthma-related death in asthmatic patients with the use of these drugs. The risk varied, however, depending on the particular drug studied.

For example, there were 20 asthma-related deaths, 16 among people taking long-acting beta agonists compared with four patients not taking these drugs. All the deaths were in patients taking Serevent, the FDA notes.

The increased risk wasn't seen when a long-acting beta agonist was used along with an inhaled corticosteroid, the agency found.

The greatest risk appears to be among children aged 4 to 11; women also appeared to be at greater risk than men.

Weinberger thinks that long-acting beta agonists should be used only in combination with inhaled steroids.

"All trials of the combination of long-acting beta agonists and an inhaled steroid demonstrate substantial additive effect for patients not fully controlled on the inhaled steroid alone," Weinberger said. "The sensible approach is to use the combination products only after inadequate control is observed with an inhaled steroid alone."

For their part, the drugs' manufacturers said they believe there is adequate evidence that their products are safe and effective when used properly.

In a joint statement issued after the panel voted, Novartis and Schering-Plough said both companies "remain confident in the safety and efficacy of Foradil." The statement added, "Novartis and Schering-Plough strongly disagree with the Joint Advisory Committees view that the benefits of Foradil do not outweigh its risks in patients using it according to current product labeling for the maintenance treatment of asthma. We believe this opinion is inconsistent with clinical evidence supporting the benefit/risk profile of Foradil in patients not adequately controlled on other asthma-controller treatments."

In its statement before the vote, AstraZeneca said the company "believes that Symbicort exhibits a favorable benefit-risk profile in patients 6 years of age and older. Symbicort offers an important therapeutic option for asthma patients who cannot be adequately controlled on other asthma controller medications [low- to medium-dose inhaled corticosteroids] or whose disease severity clearly warrants initiation of treatment with two maintenance therapies."

And GlaxoSmithKline said in its statement before the vote: "The combination of salmeterol with an inhaled corticosteroid provides unsurpassed asthma control to patients by improving lung function, preventing daytime and night-time symptoms and decreasing the use of rescue medications. For Advair, there was no evidence of increased risk for asthma-related death, asthma-related hospitalization, asthma-related intubation and all-cause death in any database. Therefore, no regulatory action is necessary for this product."

More information

For more information on asthma, visit the U.S. National Institutes of Health.

SOURCES: Miles Weinberger, M.D., professor, pediatrics, University of Iowa, Iowa City; U.S. Food and Drug Administration briefing documents; 12/11, 2008, prepared statement, Schering-Plough; Dow Jones