The FDA has issued a warning that azithromycin should not be used to prevent bronchiolitis obliterans syndrome in patients with hematologic malignancies who undergo HSCT.
The US Food and Drug Administration (FDA) has released a safety communication warning that azithromycin (Zithromax, Zmax) should not be used to prevent bronchiolitis obliterans syndrome (BOS) in patients with hematologic malignancies who undergo hematopoietic stem cell transplant (HSCT), as this could increase the risk for relapse or death.
The FDA has issued this statement in light of results from a French clinical trial referred to as ALLOZITHRO, which investigated whether early prophylactic azithromycin could improve airflow decline-free survival 2 years post-HSCT.
The randomized, placebo-controlled, parallel-group trial had been conducted in 19 academic transplant centers throughout France. A total of 480 patients aged 16 years or older who were undergoing HSCT due to hematologic malignancy were enrolled in the study. The participants were randomized to receive 250 mg of azithromycin 3 times weekly for the duration of 2 years (n=243) or to receive placebo for 2 years (n=237), starting at the time of the conditioning regimen. Investigators evaluated the immunomodulating effects of the therapy when used for the long-term prevention of BOS.
The study was terminated on December 26, 2016, just 13 months after recruitment had been completed due to the fact that the independent Data and Safety Monitoring Board (DSMB) found an unanticipated imbalance across the groups in the number of hematological relapses (77 versus 48 patients; adjusted hazard ratio [HR] [95%CI]=1.6 [1.12-2.4] for azithromycin and placebo).
After analyzing data collected through April 26, 2017, investigators found that 2-year survival rates were just 57% in the patients who had been treated with azithromycin compared with a 70% 2-year survival rate noted in those receiving the placebo. As such, the authors of the study concluded that early administration of azithromycin as prophylaxis resulted in worse airflow decline-free survival than a placebo did.
Although azithromycin has been approved for the treatment of many types of infections that affect the lungs, sinuses, skin, as well as other parts of the body, it is not approved for the prevention of BOS.
“Health care professionals should not prescribe long-term azithromycin for prophylaxis of BOS to patients who undergo donor stem cell transplants because of the increased potential for cancer relapse and death,” the FDA recommends in their safety announcement.