Goodbye, black box warning

Many patients with persistent asthma use an inhaler every day called a maintenance inhaler. The medications in these inhalers are either inhaled corticosteroids (ICS) or a combination of ICS and long-acting beta agonists or LABAs. Those of us who keep a magnifying glass handy may have read the fine print that comes with each inhaler warning that LABAs have been found to increase the risk of asthma-related death. How can a medication used to treat a certain ailment increase the risk of death for that same ailment? That is like saying there is a cough drop that helps your cough but increases your risk of dying from it.

Let me first assure you that this is not the case and that it is safe for patients with asthma to use these inhalers when combined with ICS, and doing so will help control symptoms and decrease the risk of asthma exacerbations. In fact, the LABA/ICS combinations, the medications which carry the black box warning in the U.S., are used extensively in Europe as both maintenance and rescue inhalers for asthma. Despite this, LABA's do not carry such warnings in Europe.

Why was the warning there in the first place? After concerns of asthma-related deaths in patients taking LABAs in the SMART (Salmeterol Multicenter Asthma Research Trial) study, published in 2003, the FDA put the black box warning on all inhalers containing LABAs. The SMART study (since re-named the “Dumb Study” by famed allergist Hal Nelson, MD) was not well designed and did not take into account factors such as asthma severity or whether the patients using LABAs were also using ICS. Over time, as more precise and better designed studies have continued to study inhalers containing LABAs, the benefits and importance of using LABAs in combination with ICS have become more central in the way we treat asthma today. Using any beta agonist too much reduces the production of the receptor it attaches to. Loss of that receptor makes the medication less effective. By also using an ICS, production of that receptor is up-regulated to restore its normal function. After much feedback from allergists and pulmonologists, the FDA finally removed the black box warning on ICS/LABA combination inhalers in 2017.

Of course, if you open a brand new package of Breo, Advair, Symbicort or Dulera today, the black box warning will still be there. But it's officially ok not to worry about it, and one day, when the regulatory agencies give their blessing, that warning will disappear.

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Note: Information contained in this article should not be considered a substitute for consultation with a board-certified allergist to address individual medical needs.

Author

Alnoor A. Malick, MD, FACAAI, FAAAAI Dr. Malick is board-certified in allergy and immunology and oversees the formulation of allergen immunotherapy at The Allergy Clinic. He was nominated by his physician peers and voted by the readers of H Texas Magazine as Best Allergist/Immunologist in Houston five years in a row.