The Food and Drug Administration has eliminated the boxed warning for risk of asthma-related death from the labels of products containing both an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), the agency announced.
In 2011, the FDA required companies manufacturing fixed-dose LABA-ICS combination products to conduct 26-week clinical safety trials to evaluate the risks of serious adverse asthma-related events in patients treated with these drugs. Specifically, the companies had to compare the risks of taking a LABA in combination with an ICS with the risks of taking an ICS alone.
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The removal of the boxed warning follows the FDA’s review of these trials, which found that treating asthma with LABAs in combination with ICS did not result in patients experiencing significantly more serious asthma-related side effects and asthma-related deaths, compared with those being treated with an ICS alone, according to the FDA announcement. “Results of subgroup analyses for gender, adolescents 12-18 years, and African Americans are consistent with the primary endpoint results,” the statement added.
“These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone,” the FDA said in the statement.
The trials also demonstrated that using the combination reduced asthma exacerbations, compared with using ICS alone, and that most of the exacerbations “were those that required at least 3 days of systemic corticosteroids” – information that is being added the product labels, according to the FDA.
The products that will no longer carry this boxed warning in their labels include AstraZeneca’s budesonide/formoterol fumarate dihydrate (Symbicort) and GlaxoSmithKline’s fluticasone furoate/vilanterol (Breo Ellipta) and fluticasone propionate/salmeterol (Advair Diskus and Advair HFA).
The FDA also approved updates to the Warnings and Precautions section of labeling for the ICS/LABA class, which now includes a description of the four trials. Information on the efficacy of the drugs, found in the trials, has been added to the Clinical Studies section of the labels as well.
In a related safety announcement, the FDA stated the following: “Using LABAs alone to treat asthma without an ICS to treat lung inflammation is associated with an increased risk of asthma-related death. Therefore, the Boxed Warning stating this will remain in the labels of all single-ingredient LABA medicines, which are approved to treat asthma, chronic obstructive pulmonary disease (COPD), and wheezing caused by exercise. The labels of medicines that contain both an ICS and LABA also retain a Warning and Precaution related to the increased risk of asthma-related death when LABAs are used without an ICS to treat asthma.