FDA Drops Boxed Warning on LABA/ICS Asthma/COPD Meds

Megan Brooks


December 21, 2017

A review of postmarket safety studies by the US Food and Drug Administration (FDA) has found no significant increase in risk for serious asthma-related outcomes when a long-acting β-agonist (LABA) is used in conjunction with an inhaled corticosteroid (ICS) to treat asthma

The review of four clinical safety trials shows that treating asthma with LABAs in combination with ICS "does not result in significantly more serious asthma-related side effects than treatment with ICS alone," the FDA said December 20 in an updated drug safety communication.

The four trials involved a total of 41,297 patients with asthma treated with a LABA/ICS combination medicine for 6 months. Three trials included patients aged 12 years and older, and one involved children aged 4 to 11 years.

LABA/ICS combinations did not significantly increase the risk for asthma-related hospitalizations, need for intubation, or asthma-related deaths compared with ICS alone, the FDA said.  The trials also showed that ICS/LABA combination products were more effective in decreasing asthma attacks (the need to use oral corticosteroids) compared with ICS alone.

In 2011, the FDA required manufacturers of LABAs to conduct these postmarket trials to evaluate the safety of LABAs when used with an ICS. 

On the basis of the outcomes of these studies, the FDA has removed the boxed warning about asthma-related death from the drug labels of products that contain both an ICS and LABA. In addition, a description of the four trials has been added to the labels. 
"As part of our commitment to protecting the health of patients, the FDA continues to monitor drugs after they're approved," Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, said in a statement. The FDA's approval to remove the boxed warning from LABAs used in combination with ICS "shows that data from the post-market studies we require give the agency actionable safety information on approved drug products," she added.

The FDA notes that using a LABA alone to treat asthma without an ICS is associated with an increased risk for asthma-related death. Therefore, the boxed warning stating this will remain on the labels of all single-ingredient LABA products, which are approved to treat asthma, chronic obstructive pulmonary disease (COPD), and exercise-induced asthma. Labels of products that contain both an ICS and a LABA also retain a warning related to the increased risk for asthma-related death when LABAs are used without an ICS to treat asthma, the FDA said.

Table. FDA-Approved ICS/LABA Combination Products

Brand Name Generic Names
Advair Diskus Fluticasone (ICS)/salmeterol (LABA)
Advair HFA Fluticasone/salmeterol
Airduo RespiClick Fluticasone/salmeterol
Breo Ellipta Fluticasone/vilanterol (LABA)
Dulera Mometasone (ICS)/formoterol (LABA)
Symbicort Budesonide (ICS)/formoterol


Adverse events or side effects related to the use of these products should be reported to the FDA's MedWatch Safety Information and Adverse Event Reporting Program. 

For more news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.