Asthma Drug Combo Could Be Dangerous

Medications used for long-term control of asthma -- known as long-acting beta agonists -- are among the most widely prescribed asthma medications. But now there are new concerns that too many patients are taking them.

Drugs such as Advair, Serevent, and Foradil are beta-agonist bronchodilators that are used to relax smooth muscles in the airways. Late last year, the FDA announced that the packaging for these drugs would have to carry new 'black box' warnings that the medications may increase the risk of severe, potentially life-threatening asthma flares in some people.

The regulatory agency also recommended that use of the drugs be restricted to patients whose asthma is not adequately controlled with inhaled corticosteroids alone -- the cornerstone of asthma-control therapy.

But long-acting beta agonists (LABA) are still aggressively marketed to both the public and primary care doctors who are often unaware of the safety concerns, asthma specialist Miles Weinberger, MD, tells WebMD.

"These drugs are being used too much and patients who are on them are often not monitored as they should be," he says.

Advair and Serevent, both manufactured by GlaxoSmithKline, contain the active ingredient salmeterol. In a study funded by the drug company, asthma-related deaths were slightly more common in patients on salmeterol than among patients on a placebo. GlaxoSmithKline is a WebMD sponsor.

The overall number of asthma deaths was small, however, with 13 deaths among 13,176 patients who took salmeterol for seven months. But the findings led to the FDA action.
Side Effects of Drug Combo

Writing in today's New England Journal of Medicine, Weinberger and colleague Mutasim Abu-Hasan, MD, reported on two of their own patients with severe asthma who had life-threatening reactions on a combination treatment with a long-acting bronchodilator and an inhaled steroid.

Both patients were adolescent boys who were admitted to the Children's Hospital of Iowa following severe asthma attacks while on the combination treatment.

Treadmill exercise tests revealed that both patients experienced profound constriction of their airways within minutes of beginning exercise while on the combination therapy, despite pretreatment with the inhaler medication albuterol. This short-acting beta-agonist medication is used prior to exercise to prevent exercise-induced symptoms and provides quick relief of asthma symptoms.

When the long-acting asthma medication was replaced with another asthma treatment, the boys' asthma control improved, as did their response to the medications used to treat an acute attack -- or quick relief therapy.

Weinberger says most patients whose asthma cannot be controlled with a low-dose inhaled steroid do benefit from adding a long-acting bronchodilator to their daily maintenance treatment.

But he adds that it is increasingly clear that there is a small subgroup of patients for whom the combination treatment has a negative, rather than positive, effect.

"We do not want to unduly alarm people but instead help spread the word that patients should talk to their physicians if they are using Advair, or another inhaled asthma medication that contains salmeterol, and feel that it worsens symptoms instead of making them better," he says.

Follow Patients Closely

In both cases highlighted by Weinberger and Abu-Hasan, treatment with the long-acting drug appeared to render quick-relief therapy ineffective. But GlaxoSmithKline spokeswoman Mary Anne Rhyne tells WebMD that the clinical evidence shows that the vast majority of patients on a long-acting beta agonist remain responsive to treatment with albuterol.

"There will always be some patients who are not responsive to any medicines, but it is very difficult to draw conclusion from the brief case reports outlined in Dr. Weinberger's letter," she says.

Rhyne agrees that patients on long-acting brochodilators should be monitored very closely by their doctors, as should patients on any therapy for moderate to severe asthma.

"Advair has been proven safe and effective for millions of patients," she says. "But it is not right for everyone. Asthma can be a deadly disease and severe problems can come on quite quickly, so it is important that patients tell their physicians about symptoms and their responses to medication."

SOURCES: Weinberger, M. and Abu-Hasan, M. The New England Journal of Medicine, Aug. 24, 2006; vol 355: pp 852-853. Miles Weinberger, MD, professor of pediatrics, director, allergy and pulmonary division, University of Iowa, Iowa City. WebMD Medical News: "Death Risk Warning for Asthma Drugs." Martinez, F.D. The New England Journal of Medicine, Dec. 22, 2006; vol 353: pp 2637-2639. Mary Anne Rhyne, spokeswoman, GlaxoSmithKline.