A panel of advisors to the US Food and Drug Administration (FDA) recommended that the agency ban the marketing of 2 popular asthma drugs that have been associated with an increased risk of rare but serious adverse events and, in some cases, death.
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Asthma treatments containing long-acting β-agonists alone are associated with an increased risk of rare but serious adverse events.
The panel was charged with assessing the risks and benefits of certain asthma treatments, specifically the long-acting β-agonist (LABA) drugs formoterol and salmeterol and combination products containing both a LABA and an inhaled corticosteroid (formoterol plus budesonide and salmeterol plus fluticasone). Previously, the FDA’s Office of Drug Safety and the agency’s pulmonary and allergy drug products division had made contradictory recommendations concerning LABAs.
The panel, which consisted of members from 3 committees that advise the FDA on drug safety, pediatric issues, and pulmonary and allergy drugs, recommended that the agency ban the marketing of products containing a LABA only (formoterol or salmeterol) as asthma treatments in all age groups. However, they also recommended the continued sale of combination products (formoterol plus budesonide for adults and adolescents or salmeterol plus fluticasone for all ages) for treating this disorder, noting that these drugs appeared to be less risky.
The agency typically follows the recommendations offered by its advisory committees.
“What we have come to learn is that LABAs, when used alone, are associated with more deaths [among asthma patients],” said Marsha D. Rappley, MD, dean of the College of Human Medicine at Michigan State University in East Lansing. Rappley serves as chair of the FDA's pediatric advisory committee.
As part of its deliberations, the committee reviewed a new FDA meta-analysis of data from 110 clinical trials of LABA products used to treat asthma; these trials included more than 60 000 patients taking formoterol, salmeterol, formoterol plus budesonide, salmeterol plus fluticasone, or a non-LABA therapy (http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4398b1-01-FDA.pdf). Overall, the LABAs were associated with a greater risk of asthma-related death, asthma-related intubation, or asthma-related hospitalization. However, this trend was only significant for salmeterol, which is not surprising because of the majority of the patients included in the analysis (more than 43 000) were involved in trials of salmeterol. Use of salmeterol plus fluticasone was not associated with an increased risk of adverse events.
Of the 20 asthma-related deaths documented in the trials, 16 were among patients taking LABAs, while only 4 were using non-LABA therapies. All 16 deaths were among patients taking salmeterol.
Rappley noted that overall data collected on this class of drugs since the 1990s have consistently shown a small increased risk of rare but serious asthma-related events associated with LABAs, particularly LABA-only products.
It is not clear why taking LABA drugs alone may cause asthma-related events. Some scientists have hypothesized that because LABA drugs, which widen airways, provide patients an immediate sense of relief, patients with separate LABA and corticosteroid inhalers may fail to use the corticosteroid, leading to uncontrolled inflammation.
“Our recommendation is that the combined agent is clearly the wiser choice,” Rappley said.
Although prior to the panel's meeting several medical organizations expressed objections to the idea of a complete ban on LABA products for use in asthma patients, the split decision seems to have won support from some. Thomas B. Casale, MD, executive vice president of the American Academy of Allergy, Asthma, and Immunology and chief of allergy and immunology at Creighton University in Omaha, Neb, said the academy supports the committee's recommendations, which are consistent with the National Institutes of Health's (NIH’s) guidelines on the treatment of asthma. In addition, he warned that patients who hear about the ban should not abruptly change their treatment regimen, but should instead discuss any possible changes with their physician.
Rappley also emphasized the importance of following the NIH's guidelines. The guidelines recommend asthma patients first receive a low-dose inhaled corticosteroid; then, if their asthma remains uncontrolled, they should they receive additional medications.
“The committee reviewed data that indicated asthma medications are being prescribed in ways that don't follow the guidelines and that place adults and children with asthma at risk,” she said.
Accordingly, the panel recommended that the agency, medical organizations, and the manufacturers of LABA products work to educate physicians about the importance of following the guidelines. They also said that large trials designed specifically to assess the risks and benefits of combination LABA-inhaled corticosteroid products are needed.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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