The FDA's new restrictions on some asthma medications.

The latest medical studies explained.
Dec. 17 2008 12:21 PM

Breathing Trouble

The FDA's new restrictions on some asthma medications.

New regulations reduce the treatment palate for asthma. Is that a good thing? Click image to expand.
New regulations reduce the treatment palate for asthma. Is that a good thing?

Question: In a dramatic move, an FDA advisory panel has recommended the elimination or restriction of a group of asthma medicines—long-acting beta-agonists—that many patients with severe asthma have come to depend on. While "controller" drugs like steroids stop the inflammation that leads to asthma attacks, patients use short-acting ("rescue") beta-agonists like albuterol for immediate relief of the tightness and wheezing of acute attacks. For more severe cases of asthma, patients are often given long-acting beta-agonists, like Serevent and Foradil, that relieve the sense of tightness throughout the day (though they aren't intended for use in an acute attack). These are the medications addressed by the FDA panel's nonbinding (but usually followed) recommendations. Why do they want to restrict the use of medicines that seem so effective for treating this chronic disease?

Rationale: The introduction of long-acting beta-agonists, like Serevent and Foradil, was greeted with great enthusiasm. These powerfully effective new drugs substantially improve quality of life for asthma sufferers and cut down on acute flare-ups. Unfortunately, that enthusiasm decreased when a number of studies (recently reviewed in one of the few papers not directly paid for by a drug company) raised serious questions about the safety of these medicines, especially for children and especially for the forms that don't contain a steroid controller medicine in addition to the LABA. Because of these concerns, the advisory panel has recommended that the FDA prohibit the use of LABAs that don't contain controller medications for pediatric patients and to strongly highlight the risks for similar products used by adults. *


Background: During an attack, asthma sufferers have difficulty breathing in and out (especially out) as their air passages increasingly tighten, stiffen, and become plugged with mucus. The mainstay of asthma treatment is a controller medication that stops the harmful process at its beginning. They're generally safe, but they work slowly and don't provide immediate relief. For that, we turn to short-acting beta-2 agonist "rescue" medications. But these drugs have no effect on the inflammation that causes the mess in the first place. Plus, overuse of beta-agonists is itself dangerous: It can weaken their effectiveness and tempt patients to use their controller medications less frequently so the underlying cause of the asthma isn't adequately addressed. Furthermore, beta-agonist medications directly stimulate heart muscles, sometimes leading to dangerous abnormal heart rhythms.

Findings: How risky are LABA medications? The question is hard to answer with certainty, but in two large studies (about 26,000 subjects total), there were almost four times as many deaths in patients treated with LABA medications as in those treated with placebos. In these studies, the risk of death for patients treated with a LABA drug was more than one in 1,000, whereas the risk of an asthma death in patients treated with a placebo was less than one in 4,000. These numbers may seem small, but they are nevertheless alarming, as the period of the studies was relatively short. (One study lasted 12 weeks, the other 28.) It is likely that the risk over time would be greater for typical patients with severe asthma who need a long course of treatment. Adding an inhaled steroid "controller" medication to the LABA mitigated the risk.

Conclusion: Was the panel's decision a wise one? Well, yes—mostly. When uncombined with a steroid, the danger of LABAs, though not huge, is clear, so expecting patients to switch over to the combined form makes sense. The combination forms will be as effective and a little bit safer—and the benefit (in quality of life) for adults with severe asthma is clear. I am a little less convinced that banning even the combination products for children across the board is a good idea. These medications should not be casually used for childhood asthmatics, but some children suffer from an extremely severe form of the disease, resulting in very bad quality of life. It seems to me that the small degree of increased risk is well-balanced by the dramatic improvement these medicines can provide. Still better would be the introduction of new and more effective, yet still very safe, treatments for this difficult disease. Sadly, these are still out of our grasp.

Correction, Dec. 19, 2008: This article originally stated that the FDA decided to prohibit the use of LABAs for pediatric patients and eliminate any products that don't also include a controller medication. An advisory panel has recommended that the FDA prohibit the use of LABAs that don't contain controller medications for pediatric patients and strongly highlight the risks for similar products used by adults. The FDA has not yet acted on these recommendations. ( Return to the corrected sentence.)

Sydney Spiesel is a pediatrician in Woodbridge, Conn., and clinical professor of pediatrics at Yale University's School of Medicine.


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