Long-term azithromycin may increase the rate of relapse and mortality risk and should not be used among patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation (HSCT), according to a news release from the US Food and Drug Administration (FDA).1
Previous studies have suggested that azithromycin, a macrolide antibiotic, may prevent bronchiolitis obliterans, a serious lung condition caused by scarring and inflammation in the lungs associated with increased morbidity and mortality among patients who have undergone HSCT.
For the ALLOZITHRO phase 3 study, researchers randomly assigned 480 patients with hematologic malignancies who underwent HSCT to azithromycin 250 3 times a week or to placebo for 2 years, starting at the time of the conditioning regimen.2The primary outcome of the study was airflow decline-free survival, and secondary end points included overall survival (OS) and the occurrence of bronchiolitis obliterans syndrome.
After 13 months, the study was terminated as researchers found that the rate of relapse among patients receiving azithromycin was 33.5% compared with 22.3% for placebo (P =.002). The 2-year OS rate was 57% and 70% among azithromycin-treated patients and placebo-receiving patients, respectively (P=.02).
The airflow decline-free survival was also worsened among patients who received prophylactic azithromycin.
The authors of the study noted while these findings are limited by early termination, azithromycin may lead to poorer outcomes. Although the precise mechanism by which azithromycin leads to relapse has not been elucidated, the FDA recommends that azithromycin not be used in this patient population.
1. FDA warns about increased risk of cancer relapse with long-term use of azithromycin (Zithromax, Zmax) antibiotic after donor stem cell transplant [news release]. Silver Springs, MD: US Food and Drug Administration; August 3, 2018. https://www.fda.gov/Drugs/DrugSafety/ucm614085.htm. Accessed August 6, 2018.
2. Bergeron A, Chevret S, Granata A, et al. Effect of azithromycin on airflow decline-free survival after allogeneic hematopoietic stem cell transplant: the ALLOZITHRO randomized clinical trial. JAMA. 2017;318(6):557-566.