UF researchers report mixed results in safety study of drugs seen as possible COVID-19 therapeutics

Joshua Brown, Pharm.D., Ph.D., said the goal of the study was to verify that these potential treatments don’t cause more problems than they cure. Photo Credit: Jesse Jones

Press release from UF Health

University of Florida College of Pharmacy researchers studying the safety of two classes of drugs touted as potential therapeutics for COVID-19 report mixed results.

Their analysis of 13.3 million reports from the Food and Drug Administration’s Adverse Event Reporting System showed antimalarial drugs hydroxychloroquine and chloroquine were not associated with the risk of abnormal heart rhythm either on their own or when prescribed with the antibiotic azithromycin. Azithromycin on its own, however, was associated with this safety concern.

The FDA has warned individuals not to use the antimalarial drugs outside of the hospital due to hearth rhythm concerns, and the National Institute of Allergy and Infectious Diseases recommended against doctors using the antimalarials with azithromycin for the same reason.

Interest in treating COVID-19 patients with azithromycin and the antimalarial drugs rose in March when a small clinical study in France reported promising results. However, medical professionals have long cautioned against prescribing the two drugs together, due to safety concerns and a lack of evidence.

“Multiple ongoing trials are currently investigating the efficacy of antimalarials and azithromycin for COVID-19, but safety concerns are often not resolved in these small-scale clinical studies,” said lead author Joshua Brown, Pharm.D., Ph.D., an assistant professor of pharmaceutical outcomes and policy at the College of Pharmacy. “Our study’s goal was to verify that these potential treatments don’t cause more problems than they cure. As an example, recently, Brazilian authorities have halted one of the first clinical trials using these medications together because of safety concerns.”

The safety concerns are primarily centered on the risk of abnormal heart rhythm, specifically drug-induced QT interval prolongation, which can lead to tachycardias such as torsades de pointes and sudden cardiac death. Previous studies have not shown if the adverse effect is caused by the two classes of drugs interacting or if it’s azithromycin’s effect alone.

“What also needs to be considered is that the existing data, our study included, are based in patients using the medications to manage chronic disease like rheumatoid arthritis or to treat minor upper respiratory infections,” Brown said. “The risk profile could be much higher in patients with severe COVID-19 who are critically ill or have comorbid conditions and may be using these medications at a higher than normal dose.”

Brown noted that the UF study in no way determines whether or not hydroxychloroquine or azithromycin are effective for treating COVID-19. Both drugs have demonstrated antiviral and immunosuppressive activity in test tube studies. These results have led to widespread hope for COVID-19 prevention and treatment, but real-world evidence among COVID-19-positive patients has yet to prove this.

The study was conducted by Brown; Amir Sarayani, Pharm.D., M.P.H.; Carl Henriksen and Brian Cicali. Their study was published in the journal Research in Social & Administrative Pharmacy.