Impact of the US Food and Drug Administration Warning for Increased Risk of Aortic Aneurysms or Dissections on Fluoroquinolone Prescribing Trends

Background: The United States Food and Drug Administration (FDA) issued a warning in December 2018 for an increased risk of aortic dissection (AD) or aortic aneurysms (AA) associated with fluoroquinolone (FQ) antibiotic use. The warning specifically targeted patients at increased risk of developing AD or AA such as the elderly or patients with hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease, and history of aneurysms.

Objectives: To evaluate the impact of the safety warning on prescribing trends of FQs.

Methods: We used a 25% sample of IQVIA PharMetrics® Plus for Academics health plan data from 2018-2019, which includes billing records for a large sample of commercially insured beneficiaries with a subset of Medicare Advantage / Cost or Managed Medicaid in the US, 18 to 84 years of age. Both populations had to be continuously enrolled for a 1-year pre-(Jan. 2018-Dec. 2018) or post-(Jan. 2019-Dec. 2019) warning period. The targeted population included beneficiaries with a diagnosis claim for at least one high-risk condition, and/or are ≥65 years old. The non-targeted population included beneficiaries who have no evidence of a high-risk diagnosis claim and are < 60 years of age. We calculated monthly prescription rates for all FQ claims (e.g. levofloxacin, ciprofloxacin) and evaluated changes in trends before and after the warning period using an interrupted time series (ITS) analysis in the targeted population, and separately in a non-targeted population. We also ran an ITS analysis using cephalosporins. Cephalosporins are a different antibiotic class with a similar prescribing profile to FQs, are not known to have a causal effect on AD or AA, and thus their prescribing trends should not be affected by the warning. Joinpoint regression, which searches for natural breakpoints without prespecified hypotheses, was also conducted.

Results: The targeted population included 409,646 beneficiaries in the pre-warning period and 376,685 in the post-warning period. In the pre-warning period, there was a negative trend in the monthly rate of FQ prescriptions per 1,000 beneficiaries in both the targeted (coefficient:-0.23, 95% CI -0.39, -0.06) and non-targeted populations (-0.07, 95% CI -0.12, -0.03). In the targeted population, the FDA warning was not associated with a level change or monthly trend change in FQ use. There were no level or slope differences in cephalosporin prescription rates. There were no changes in FQ or cephalosporin use in the non-targeted population. On joinpoint regression, no breakpoints were identified in the entire study period.

Conclusions: The FDA warning was not associated with an immediate or sustained decline in FQ use one year following the warning.