Impact of concomitant fluconazole on direct oral anticoagulant bleeding risk

Study Objective The aim of this study was to evaluate the effect on bleeding risk when fluconazole is administered concomitantly with direct oral anticoagulants (DOACs). Design This was a retrospective cohort study including hospitalized adult patients prescribed a DOAC with or without fluconazole. Setting The Ohio State University Wexner Medical Center, a tertiary care academic medical center with more than 1800 beds. Patients Hospitalized patients ages 18-89 years who received apixaban or rivaroxaban with or without fluconazole from October 1, 2016, to September 30, 2021, were included. The minimum duration of DOAC or DOAC with fluconazole therapy was 48 h. Patients were excluded if they received fluconazole Patients who received a DOAC with fluconazole were compared with those receiving a DOAC alone. The primary outcome was a composite of major, clinically relevant nonmajor, and minor bleeding events at 30 days. Measurements and Main Results There were 216 patients included, 108 in the DOAC with fluconazole group and 108 in the DOAC alone group. More patients in the DOAC with fluconazole group experienced bleeding at 30 days compared with the DOAC alone group [35/108 (32%) vs. 21/108 (19%), respectively; p = 0.03]; however, after adjusting for proven confounding variables (hemoglobin and concomitant carvedilol) this was found not to be statistically significant [adjusted odds ratio 1.71, 95% confidence interval 0.85-3.40]. Conclusions Patients receiving a DOAC with fluconazole were not at significantly increased risk for bleeding at 30 days compared with those receiving a DOAC alone after controlling for confounding variables. As an increasing number of patients are prescribed DOACs, the results of this study may inform clinical decision-making on the safety of concomitant DOAC and fluconazole use.

Automated summary

The aim of this study was to evaluate the effect of concomitant use of fluconazole and direct oral anticoagulants (DOACs) on bleeding risk. The study found that patients receiving a DOAC with fluconazole did not have a significantly increased risk for bleeding at 30 days compared to those receiving a DOAC alone after adjusting for confounding variables.