What is the safety of long-acting beta agonists in the treatment of asthma?

Updated: Oct 07, 2019
  • Author: John J Oppenheimer, MD; Chief Editor: Michael A Kaliner, MD  more...
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Answer

Answer

The safety of long-acting beta agonists had been questioned because of SMART (the Salmeterol Multicenter Asthma Research Trial). In this study, which involved approximately 25,000 patients, respiratory- and asthma-related deaths were greater in the group that received salmeterol than in the placebo group (although this signal was statistically significant only in African Americans). [26]

A combination of an inhaled corticosteroid and long-acting beta agonist (STAY trial, using budesonide/formoterol [27] ) for maintenance and reliever medication in patients with moderate to severe asthma may lower the risk of severe exacerbations, reduce the need for systemic steroids, and improve symptoms, compared with a fixed maintenance dose of a similar medication or a 4-fold increase in the inhaled corticosteroid dose. [28] In patients with inadequately controlled severe allergic asthma who are receiving high-dose ICS and long-acting beta agonists, omalizumab provided additional clinical benefit. [29]

Elderly patients are more likely to experience adverse effects from asthma medications.

Note:  In December 2008, an advisory panel to the FDA voted to ban 2 long-acting beta agonists (LABAs)---Serevent (salmeterol) and Foradil (formoterol)---as monotherapy (meaning by itself, without inhaled corticosteroids also) for treating asthma in adults and children. [30] This guidance will likely apply to other medications in the same class, such as arformoterol (Brovana).

Serevent and Foradil will remain on the market to treat chronic obstructive pulmonary disorders. The panel also voted to continue allowing the use of Symbicort (formoterol plus budesonide) and Advair (salmeterol plus fluticasone), as these drugs contain LABAs and steroids (as discussed above).

In February 2010, the FDA announced additional safety controls regarding the use of LABAs. As previously announced, these medications should never be used as monotherapy to treat asthma in children or adults. The additional safety controls also institute labeling requirements for manufacturers, including recommendations that LABAs, even as combination therapy, should be used for the shortest possible duration. For more information, see the FDA news release. [31]

In 2017, the FDA removed box warnings about the possibility of asthma-related death from asthma and COPD inhalers delivering fixed-dose combinations of ICS and LABA drugs. The removal comes after an FDA review of four large clinical safety trials which showed no increase in serious asthma-related side effects with the ICS/LABA fixed-dose products than with ICS agents alone. [32]

Go to Use of Metered Dose Inhalers, Spacers, and Nebulizers for complete information on this topic.


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