FDA Panel Asks: Are Asthma Drugs Safe?
Serevent, Symbicort, Foradil Safety Focus of Triple FDA Panel Meeting
By
Daniel J. DeNoon
WebMD Health News
Reviewed By
Louise Chang, MD
Dec. 9, 2008 - Are the commonly prescribed asthma drugs Serevent,
Symbicort, and Foradil safe?
That's the question facing a three-way meeting of the FDA's advisory panels
on asthma, drug safety, and
pediatrics.
Analysis of data pulled from clinical trials shows that patients taking
Serevent, Symbicort, or Foradil have a small increased risk of asthma-related
hospitalization. This is especially true for kids 4 to 11.
The same analysis shows that patients taking Serevent have a small but
significantly increased risk of asthma-related death.
A fourth related drug, Advair, did not increase these
risks. Advair is a combination of an inhaled corticosteroid and the long-acting
beta agonist (LABA) Serevent. Symbicort is a combination of a different inhaled
corticosteroid and a different LABA, Foradil.
Nobody is suggesting the drugs don't help a lot of children and adults with
asthma. But do the drugs benefits outweigh their risks? The drugs already carry
the FDA's top-level "black box" warning -- but are more warnings or
restrictions needed? That's what the panel must decide in their two-day joint
meeting, scheduled for Dec. 10-11.
Inhaled asthma drugsinclude:
- Inhaled short-acting beta-agonists, often called rescue inhalers, which
open the airways to fight the bronchial spasms that make it hard to breathe.
These drugs are taken only as needed.
- Inhaled corticosteroids, which
fight lung inflammation. These drugs are taken every day for long-term asthma control.
- Inhaled long-acting beta-agonists, LABAs, which open the airways to prevent
bronchial spasms for long-term asthma
control. These drugs are taken every day to prevent asthma attacks.
- Intal and Tilade, which are another class of inhaled anti-inflammatory
drugs. They are not steroids. Intal and Tilade are not under safety
review.
When Serevent was first introduced, doctors didn't fully appreciate how
important it was to fight inflammation as well as bronchial spasms. In early
trials of the drug, fewer than half of patients took a corticosteroid along
with Serevent.
In the early 1990s, a U.K. trial suggested there might be too many deaths
among patients taking Serevent. This didn't stop the FDA from approving the
drug -- but after a series of nagging adverse-event reports, Serevent maker GSK
agreed to conduct a large safety study.
That study, the SMART trial, was ended early when patients taking Serevent
turned out to have a small but significant increase in asthma-related deaths
compared to patients taking a placebo. This led to the black-box warning on all
LABA-containing drugs.
In more recent years, doctors have stressed the use of either the
combination inhalers or the concurrent use of both steroid and LABA inhalers.
Use of LABA inhalers has gone way up, but the rate of serious asthma attacks
requiring hospitalization and the rate of asthma-related deaths have both gone
down.
So why sell Serevent alone? GSK says it should stay on the market because
doctors may wish to used a different dose of steroid than the one in the Advair
combination product, or patients may need a different steroid than the one used
in Advair.
But troubling questions remain for the joint FDA panel to resolve:
- Why, if combination products are safer, does there still seem to be a
significant increase in asthma-related problems with Symbicort?
- Do LABA drugs do something to make asthma worse in some patients, or is it
just that people who have LABA problems aren't getting their inflammation under
control with corticosteroids?
- Why do LABA-related adverse events seem to be more frequent in children
under age 12?
- If single-agent LABA drugs remain on the market, what is the best way to
ensure patient safety?
- Are there subgroups of patients for whom the risks of LABA drugs outweigh
their benefits?
The joint panel's 27 voting members are scheduled to vote on Dec. 11,
although the final questions they'll be deciding have not been announced.
SOURCES: FDA: "Long-Acting Beta-Agonists and Adverse Events Meta-Analysis,"
Nov. 12, 2008. GlaxoSmithKline, sponsor briefing information, "Benefit Risk Assessment
of Salmeterol for the Treatment of Asthma in Adults and Children," FDA
Joint Pulmonary/Allergy Drugs, Drug Safety and Risk Management, and Pediatric
Advisory Committee meeting, Dec. 10-11, 2008. Novartis, Foradil briefing document, Nov. 4, 2008. AstraZeneca Briefing Materials, "Review of the Benefits and Risks of
Formoterol-Containing Products," Nov. 3, 2008. WebMD Health News: "Death-Risk Warning for Asthma Drugs."
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