Four safety trials have concluded that popular combination inhalers — like Advair (fluticasone/salmeterol) and Symbicort (budesonide/formoterol) — are not associated with an increased risk of asthma-related hospitalizations or deaths, undermining previous findings. LABAs (long-acting beta agonists) such as salmeterol and formoterol, and combination products containing them, received a boxed warning in 2003 because findings at the time suggested that LABAs were associated with serious adverse outcomes, including asthma-related hospitalization, intubation and death.
Combination Inhalers Manufacturers to Perform Studies
In 2011, the FDA required the manufacturers of the combination inhalers to perform studies where they compared an inhaled glucocorticoid (corticosteroid) – such as fluticasone or budesonide – plus a LABA (combination therapy) with an inhaled glucocorticoid alone. The analysis included 36,010 patients who participated in the 4 trials. In each trial, patients were randomly assigned to receive a combination therapy (inhaled glucocorticoid plus a LABA) or an inhaled glucocorticoid alone.
The results, details of which were recently published in the New England Journal of Medicine, indicated that there is not a higher risk of severe asthma-related outcomes (endotracheal intubation or death) among patients who receive combination therapy than among those who receive an inhaled glucocorticoid alone.
In December 2017, the results prompted the FDA to remove the “black box” warning from combination products that warned of an increased risk of asthma-related deaths. However, medications that contain just a LABA retain a boxed warning of an increased risk of asthma-related death.
