Azithromycin (multiple brands) should not be used to prevent bronchiolitis obliterans syndrome (BOS) in patients with hematologic malignancies who undergo hematopoietic stem cell transplant (HSCT), owing to an increased risk for relapse and death, the US Food and Drug Administration (FDA) said today in a safety communication.
The alert stems from the French ALLOZITHRO trial, which was investigating the efficacy of long-term azithromycin in preventing BOS after allogeneic HSCT. The trial was terminated early after an increased risk for relapses was seen in patients taking azithromycin compared with placebo, Pfizer, the manufacturer of the azithromycin drug Zithromax, said in a letter to clinicians.
Cancer relapse was observed in 77 patients (32.9%) receiving azithromycin vs 48 patients (20.8%) receiving placebo (adjusted hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.12 - 2.4).
There were 95 deaths in the azithromycin group vs 66 in the placebo group. The 2-year survival rate was 56.6% in azithromycin group compared to 70.1% in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1 - 2.0).
"In the first few months of the trial, the death rate was about equal between those receiving azithromycin and placebo. However, an imbalance occurred subsequently and continued until the 2-year time point when the study was stopped," Pfizer said.
"Although it is not clear how azithromycin could have contributed to the observed higher rate of hematological relapses, in the study, it is concluded that long-term azithromycin exposure following HSCT may include risks that exceed the anticipated benefits," Pfizer said.
The FDA said it is currently reviewing additional data and will report their conclusions and recommendations when their review is complete.
Cancer patients who undergo stem cell transplants from donors are at risk for BOS. Although azithromycin is approved to treat many types of infections affecting the lungs, sinuses, skin, and other parts of the body, it is not currently approved for prevention of BOS. There are no known effective antibiotic treatments for prophylaxis of BOS, and clinicians should not use azithromycin for this purpose, the FDA said.
It encourages healthcare providers to report side effects involving azithromycin and other drugs to the FDA MedWatch program.
Cite this: FDA: Don't Use Azithromycin for Lung Condition in Cancer Patients - Medscape - Aug 03, 2018.