Quinolones FDA Label Changes Resulted in Prescribing Decline

By Lisa Rapaport

April 22, 2021

(Reuters Health) - A move by the U.S. Food and Drug Administration (FDA) in 2016 to remove systemic quinolones' indication for acute uncomplicated urinary tract infection, acute sinusitis, and acute exacerbation of COPD reduced, but didn't eliminate, prescribing for these indications, a new study suggests.

Researchers examined records from Medicare and the IBM MarketScan Commercial Claims on quinolones prescribing trends for these three indications before and after the FDA label change on the drugs in May 2016. They looked at three periods: January 2015 to April 2016 (before the FDA change), April to May 2016 (immediate effect of the change), and May 2016 to November 2018 (after the change).

As of January 2015, quinolones accounted for 41.6% of acute UTIs treated with antibiotics, 8.3% of acute sinusitis cases, and 31.9% of acute exacerbations of COPD. Researchers found quinolones prescribing trends for these three indications essentially flat before the FDA label change in May 2016.

The month of the FDA label change, researchers found an immediate reduction in prescribing for UTIs (-7.2%) and less-pronounced declines for acute sinusitis (-1.2%) and COPD exacerbations (-2.6%).

By the end of the study period, however, quinolones were still used for 19.2% of acute UTIs treated with antibiotics as well as 2.9% of acute sinusitis cases and 14.6% of COPD exacerbations.

"The alternative treatments for these three indications have been approved decades ago and are well-known and accepted in the clinical community, so, I think the issue is really the diffusion of information about quinolone risk and its unfavorable risk-benefit for treatment of uncomplicated infections," said senior study author Almut Winterstein, director of the Center for Drug Evaluation at the University of Florida in Gainesville.

Guidelines had limited effectiveness in communicating this, which triggered the regulatory action by the FDA in 2016, Winterstein said by email.

"Drug label changes also rely on communication to affect prescribing behavior, and I was therefore doubtful whether the removal of indications had the desired effect," Winterstein said. "I was pleased to see that it did."

The study also found that declines in quinolones prescribing occurred in tandem with increased prescribing of first-line recommended alternative therapies such as nitrofurantoin for uncomplicated UTIs, amoxicillin for acute sinusitis, and macrolides for COPD exacerbations.

Utilization of second-line agents, such as tetracyclines for COPD exacerbations, also increased as quinolones prescribing declined, according to the report in JAMA Internal Medicine.

One limitation of the study is the lack of a control group uninfluenced by the FDA label change for quinolones, the study team notes. Another limitation is that they were unable to examine use of another antibiotic unaffected by the label change because this move would indirectly impact prescribing of alternatives, the authors point out.

However, it's logical that the biggest change was seen for uncomplicated acute UTIs because this involved the most prescriptions before the label change, said Dr. Chien-Chang Lee, an associate professor of emergency medicine at National Taiwan University Hospital who wasn't involved in the study.

"Uncomplicated UTIs had higher prevalence of quinolone prescriptions, and hence larger room for improvement," Dr. Lee said by email. "Only a small proportion of patients with acute sinusitis or acute exacerbations of COPD used quinolones, and these patients may have some specific indications for quinolone such as allergy to penicillin, or resistant strains to cephalosporin or penicillin."

SOURCE: https://bit.ly/3na9adj JAMA Internal Medicine, online April 19, 2021.