FDA Panel Urges Restrictions on 2 Asthma Drugs

FDA Panel Urges Restrictions on 2 Asthma Drugs
Serevent, Foradil Inhalers Should Not Be Used Alone, Experts Urge
By Todd Zwillich
Michael W. Smith, MD

Dec. 11, 2008 - An expert panel said Thursday that the benefits of two inhaler drugs are not worth the risks and should no longer be used to treat asthma.

The vote does not mean the two drugs, Serevent and Foradil, will be pulled from the market. Instead, the panel strongly urged the FDA to tell doctors not to prescribe the drugs to children or adults as a standalone asthma treatment.

The drugs are also widely prescribed for chronic obstructive pulmonary disease. That use was not affected by Thursday's deliberations of a 27-member FDA advisory committee.

At the same time, the experts backed two other popular asthma drugs, saying their benefits outweigh their risks.

Serevent and Foradil are in a class of drugs known as beta-agonists. They help control and prevent airway spasms during asthma attacks. But the drugs have also been associated with a small but significant increase in the risk of hospitalization and death from asthma.

Medical guidelines and the drugs' labeling recommend that beta-agonists only be used in combination with inhaled steroids that cut down on airway inflammation leading to attacks. The combination lowers the risks to a level most experts believed is justified by their benefits.

But studies show that many patients do not use inhaled steroids as directed when taking them separately from beta-agonists. At the same time, patients often feel physical relief from labored breathing when they use their beta-agonist inhaler. The difference can lead to many patients using the beta-agonist alone (called monotherapy), which raises the risk of dangerous side effects, according to FDA analyses presented this week.

"I think the label should be greatly strengthened to say that monotherapy for asthma should basically be contraindicated" for Serevent and Foradil, said Daniel Notterman, MD, a member of the advisory panel from the department of molecular biology at Princeton University.

The rest of the advisors agreed. In a 17-to-10 vote, the panel said the risks of long-term Serevent and Foradil use outweigh the benefits when used alone. The panel cast a similar vote for adolescents with asthma and voted unanimously that the drugs are not worth the risk in children 4 to 11 years old.

"The data is that single use is dangerous," said David Schoenfeld, PhD, a panelist and professor of medicine from Massachusetts General Hospital.

The panel gave broad backing to two other asthma drugs, Advair and Symbicort, in adults. Those products contain a combination of beta-agonist and steroid drugs, thus guaranteeing that patients get both drugs each time they take a puff.

The group was split on whether Advair should be used in children. Thirteen panelists said Advair's benefits outweigh its risks in children, while 11 said they did not. Three abstained.

Experts said they were uneasy with how few studies had been performed showing Advair's safety and efficacy in children.
"I think there's a paucity of data," Notterman said.

Symbicort is generally not used in children.

John Jenkins, MD, who heads FDA's Office of New Drugs, said the agency would consider ordering manufacturers to conduct more safety studies in children, which it can do under new authority granted by Congress.

Ellen Strahlman, MD, the chief medical officer of GlaxoSmithKline, which makes both Advair and Serevent, said the company was pleased with the committee's backing of Advair. But she also said the company was "concerned" that the panel's vote to restrict Serevent could "deny patients needed treatment for optimal care of their asthma."

A statement from Novartis and Schering-Plough said the companies "strongly disagree" with the panel's rejection of Foradil, which they market in a joint venture.

"We believe this opinion is inconsistent with clinical evidence supporting the benefit/risk profile of Foradil in patients not adequately controlled on other asthma-controller treatments," the statement read.

The FDA now has to go back and consider whether to change product labeling or indicated uses for Serevent and Foradil. It will also consider ordering new safety studies, Jenkins said.

Jenkins emphasized that patients currently taking Serevent or Foradil "should not stop taking your asthma medications without talking to your physician."
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SOURCES:

Daniel Notterman, MD, department of molecular biology, Princeton University; member, FDA advisory panel.

David Schoenfeld, PhD, professor of medicine, Massachusetts General Hospital; member, FDA advisory panel.

John Jenkins, MD, director, FDA Office of New Drugs.

Ellen Strahlman, MD, chief medical officer, GlaxoSmithKline.

News release, Novartis Pharmaceuticals Corp. and Schering-Plough