Serevent, Foradil should only be used with another medication, in both children and adults, but Advair is spared in advisers' recommendations
THURSDAY, Dec. 11 (HealthDay News) -- The risks of two widely used asthma drugs outweigh their benefits for both children and adults, a U.S. Food and Drug Administration advisory panel said Thursday.
The health panel targeted GlaxoSmithKline's Serevent and Foradil, made jointly by Novartis AG and Schering-Plough, for restrictions, but it excluded Advair, Glaxo's biggest-selling drug in the class of medications known as long-acting beta-agonists. It also left alone a fourth such drug, AstraZeneca's Symbicort.
The health experts did not say that the use of Serevent and Foradil should be abandoned altogether. Instead, they said the medications' labeling should be reworded to urge doctors to use the drugs along with an inhaled corticosteroid -- as guidelines already recommend.
That may help explain why Advair and Symbicort were spared. Serevent contains just one active ingredient, sameterol, while Foradil contains only formoterol. Advair is a combination of both salmeterol and fluticasone (an inhaled cortocosteroid), while Symbicort contains formoterol and another steroid (budesonide). All of these drugs relax airway muscles, letting asthma patients breathe more easily.
The controversy over these drugs has been going on for several years, with two FDA officials recently calling for banning the use of these drugs for anyone under 17. The results of studies noting a rise in asthma-related deaths by people using the medications have already resulted in a black-box warning that use could "increase the risk of asthma-related death."
The advisory panel voted 10 to 17 on whether the benefits of Serevent outweighed its risk as maintenance therapy for adults, and voted 6 to 21 on the same question for adolescents ages 12 to 17, Dow Jones reported. Foradil received similar votes on the same questions: 9 to 18 for adults and 6 to 21 for adults.
The panelists were unanimous in voting that the benefits of the two drugs did not outweigh risks when used for children ages 11 and younger.
The announcement followed a two-day meeting on the issue by the expert advisory panel. The FDA is not obligated to follow the advice of its advisory panels but usually does so.
Speaking before Thursday's decision, one expert said the problem is not with the drugs, but with their misuse.
"This is an over-interpretation of the risk without adequate consideration of benefit," said Dr. Miles Weinberger, a professor of pediatrics at the University of Iowa. "However, there has been irresponsible marketing of the products, salmeterol and formoterol, and irresponsible prescribing by many physicians."
"Since most patients with chronic asthma can be controlled with inhaled steroids alone, using these more expensive combination formulations as first line is inappropriate but strongly encouraged by marketing practices" of drug makers, Weinberger said.
In the panel's first day of hearings on Wednesday, FDA officials themselves were split over the risks of the drugs.
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, in statements filed with the FDA, said they believe there is adequate evidence that their products are safe and effective when used properly.
"AstraZeneca 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," the company said in its statement.
GlaxoSmithKline said in its statement: "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."
And Novartis noted, "Given the benefits associated with long-acting beta 2-agonist use in asthma, Novartis believes that the benefit-risk ratio is in favor of formoterol use as currently reflected in labeling and treatment guidelines. Long-acting beta 2-agonists, including formoterol, remain an important therapeutic option in the treatment of patients with asthma."
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; Dow Jones
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