Stronger Warnings Urged on Asthma Drugs

FDA Panel Recommends Clearer Warning on Risks for Children Using Advair and Serevent

Medically Reviewed by Louise Chang, MD on November 28, 2007
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Nov. 28, 2007 -- An advisory panel recommended stronger warnings for a pair of popular asthma drugs Wednesday, saying they should alert doctors and patients that the drugs could increase risks of dangerous side effects in children.

The two drugs, Serevent and Advair, already carry "black box" warnings that the active ingredient salmeterol may increase the risk of asthma-related death. But experts said Wednesday those warnings don't go far enough to caution that the drugs could pose risks in children.

"The potential risks in children specifically are not well-addressed, and we would like to see that changed," said Marsha Rappley, MD, chairwoman of the agency's advisory committee on pediatric drugs.

Additional Scrutiny

Agency officials previously told the committee that they are considering beefing up safety warnings for the drugs. The agency also says it is beginning to probe whether the two drugs are safe enough for use as childhood asthma treatments.

"We conclude that salmeterol may have an unfavorable risk-benefit ratio in the treatment of pediatric asthma. We recommend a more thoroughgoing, formal risk-benefit analysis," agency safety officers told the panel in a written brief.

Salmeterol works by relaxing the smooth muscle of the airways, making it easier for patients to breathe.

But a study of 26,000 patients published last year showed patients over 12 years old taking the drug are more likely to die from asthma-related causes as patients taking a placebo. Respiratory-related deaths or life-threatening events were four times as likely among African-Americans taking salmeterol vs. placebo.

Asthma Study Halted

Early results caused the study to be halted in 2003 and led to new warnings for salmeterol-containing drugs. FDA officials presented data Wednesday estimating that the drug may lead to one extra death for every 700 patients who use it for a year.

GlaxoSmithKline, which makes both drugs, said that estimate was inflated. Company scientists said more than 10,000 patients per year would die of asthma if the estimate were accurate. They also presented data that children taking the drug had no increased risk of death but were twice as likely as those taking placebo to be hospitalized.

Fewer than 4,000 U.S. patients die from asthma each year, according to the CDC.

Serevent contains salmeterol alone. Advair combines salmeterol with an inhaled steroid.

"The safety profile is favorable when it's used in accordance with the prescribing information," said C. Elaine Jones, PhD, GlaxoSmithKline's head of respiratory regulatory affairs.

But experts said Wednesday the warnings should more clearly state the risks for children.

"It's very hard for a clinician to know what to do with it, to use it, to explain it to a patient," said Jesse Joad, MD, a professor of pediatrics from the University of California, Davis, and a committee member.

Experts also said studies showing no benefit for salmeterol should be included in its labeling. They also cautioned that risks are greater in African-American children.

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SOURCES: Marsha Rappley, MD, Michigan State University; chairwoman, FDA Pediatric Drugs Advisory Committee. Memorandum on 1-year Post-Pediatric Exclusivity Postmarketing Adverse Event Review, FDA, presented Nov. 28, 2007. Chest, 2006; vol 129: pp 15-26. Jesse Joad, MD, professor of pediatrics, University of California, Davis; member, FDA panel. C. Elaine Jones, PhD, respiratory regulatory affairs, GlaxoSmithKline. WebMD Medical News: "Asthma Drug May Be Deadlier for Blacks."WebMD Medical News: "Death Risk Warning for Asthma Drugs."

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