Stronger Warnings Urged on Asthma Drugs
FDA Panel Recommends Clearer Warning on Risks for Children Using Advair and Serevent
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.
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
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
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
"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