New Warnings Required for Long-acting Beta Agonists, Says FDA

Asthma Medications Linked to Hospitalizations, Deaths

February 24, 2010 05:25 pm Hannah DeClerk

Manufacturers of certain asthma medications must include new warnings on their package labels, according to a recent news release from the FDA. The warnings will state that long-acting beta agonists, or LABAs, should never be used alone to treat asthma in children or adults but may be used in combination with another asthma controller medication.

The Feb. 18 news release( said the new requirements are based on FDA analyses of postmarketing clinical trials, which demonstrated that use of LABAs is associated with an increased risk of severe exacerbation of asthma symptoms, leading to hospitalization and death in some patients.

LABAs relax the muscles that surround the airways and lungs, allowing patients to breathe more easily and reducing symptoms such as wheezing and shortness of breath. However, the medications are effective against asthma only when combined with an asthma controller, such as an inhaled corticosteroid. Consequently, their use is contraindicated without concomitant use of a controller medication.

LABA asthma products include the single-agent medications salmeterol (Serevent, marketed by GlaxoSmithKline) and formoterol (Foradil, marketed by Novartis AG) and the combination medications Advair (contains salmeterol; marketed by GlaxoSmithKline) and Symbicort (contains formoterol; marketed by AstraZeneca), which also contain inhaled corticosteroids. Although LABAs are approved to treat both asthma and COPD, the new recommendations apply only to the use of LABAs to treat asthma.

Manufacturers of these products also will be required to take other steps to reduce overall use of the products, including the creation of a risk evaluation and management strategy to educate both health care professionals and patients about how LABAs can be used safely. In addition, the manufacturers will have to conduct additional studies to evaluate the safety of LABAs when used in combination with inhaled corticosteroids.

The FDA warnings( also state that long-term use of LABAs should be restricted only to patients whose asthma cannot be adequately controlled on asthma controller medications and that they should be used only as long as required to achieve symptom control. Patients then should be maintained on an asthma controller drug. Pediatric and adolescent patients who require an LABA in addition to an inhaled corticosteroid should use a combination product containing both medications to ensure compliance.

Family physician Mark Ebell, M.D., associate professor of epidemiology in the department of public health at the University of Georgia, Athens, and a respiratory health specialist, called the FDA's action "a welcome announcement."

"Evidence has been accumulating for several years that use of long-acting beta agonists without concomitant use of an anti-inflammatory is dangerous and is associated with significantly increased mortality," said Ebell, who also is deputy editor for evidence-based medicine for American Family Physician. "Family physicians should never use these agents alone in any of their patients."

However, one family physician member of the National Heart, Lung, and Blood Institute's National Asthma Education and Prevention Program expert panel that developed the 2007 guidelines for the diagnosis and management of asthma shared a different viewpoint.

Barbara Yawn, M.D., director of research at Olmsted Medical Center in Rochester, Minn., and adjunct professor of family and community health at the University of Minnesota there, told AAFP News Now that she sees the FDA's move as potentially problematic.

"I am scared that these warnings will frighten patients from taking the medications when needed," Yawn said. "I am worried that people who need it will not get it.

"Certainly, LABAs play a critical role in management for people with poorly controlled asthma. There is also no question that they have been overused in the past. It is much easier to do it this way (use LABAs inappropriately) because patients get better faster. It is important that we, as family physicians, do not overprescribe."

Yawn explained that she uses a stepwise approach to therapy that relies on careful assessment of her patients' asthma status. Family physicians must never prescribe LABAs as the first step, she said. Instead, FPs should start with an anti-inflammatory and, if their patients are still having symptoms despite taking their medication properly, move to the next step.

"I think that the FDA is trying to say that (health care professionals) have not looked at the risks and have overprescribed," said Yawn. "The risk becomes a bigger problem if the physician has not taken the appropriate steps."

The FDA said it will work with public and private partners under the agency's ongoing Safe Use Initiative( to study LABA-prescribing practices. The agency also will seek input on the design of the additional studies requested during a public advisory committee meeting scheduled for next month.