Salmeterol Have Black Box Warning Citing An Increase In Asthma Related Deaths. The labels of three GlaxoSmithKline asthma products containing salmeterol now have boxed warnings citing a “small but significant increase in asthma-related deaths,” based on recommendations from the Food and Drug Administration.
The interim results of a study of approximately 29,000 asthma patients in the Salmeterol Multi-Center Asthma Research Trial (SMART) showed more asthma-related deaths and life-threatening asthmatic episodes among African American patients taking salmeterol than among those taking a placebo.
The products with label changes are Serevent Inhalation Aerosol, Serevent Diskus, and Advair Diskus (fluticasone propionate and salmeterol inhalation powder). Serevent Diskus is approved for treatment of asthma in patients aged 4 years and older, while both Serevent Inhalation Aerosol and Advair Diskus are approved for patients aged 12 years and older.
Patients Currently Taking The Medications Should Not Stop Immediately
The “Dear Healthcare Professional” letter included with the products states that patients currently taking these medications should not stop suddenly this may lead to life-threatening asthmatic episodes due to uncontrolled asthma. In addition, the letter reminds physicians that patients taking asthma products as their only asthma therapy should add an inhaled corticosteroid to their treatment regimens.
However, the warning implies a much broader problem than exists, Dr. Harold Nelson, professor of medicine at the National Jewish Medical and Research Center, Denver, told this newspaper. The adverse outcomes occurred in patients who were not only African American, but who were not taking inhaled corticosteroids. Those taking inhaled corticosteroids concurrently with salmeterol had no adverse effects, regardless of ethnicity.
In a 28-week safety study, asthma patients aged 12 years and older were given either 42 [micro]g of salmeterol or a placebo twice daily. Although the study was meant to include approximately 60,000 patients, it was stopped at the halfway point due to evidence of increased risk of asthma-related deaths among patients who received salmeterol: 13 deaths among 13,174 patients, compared with 4 asthma-related deaths among 13,179 patients who received placebo. Approximately 17% of the study subjects were African American.
The SMART study did not include outcome analyses based on demographic traits, but a later subgroup analysis showed a statistically significant increase in the number of asthma-related deaths among African American patients who received salmeterol compared with those who received placebo (eight vs. one). In addition, a weakness of the SMART study is that the only information about concomitant medication is the form that patients filled out at the beginning of the study, Dr. Nelson noted.
However, the FDA maintains that the benefits of salmeterol outweigh the risks when patients with asthma and chronic obstructive pulmonary disease use the medication properly and that includes taking inhaled corticosteroids concomitantly.