Bleeding events among patients concomitantly treated with direct oral anticoagulants and macrolide or fluoroquinolone antibiotics

Abstract

Fluoroquinolones and macrolides may, due to a potential drug‐drug interaction, increase the concentration of any concomitantly administered direct oral anticoagulant (DOAC) and thereby increase the risk of severe bleeding. However, clinical evidence for such an effect is scarce. The present study aimed to evaluate the association between the use of fluoroquinolones or macrolides and bleeding events in patients with concomitant DOAC use. This was a nationwide cohort study including 19 288 users of DOACs in 2008‐2018 using information from Swedish national health registers. We compared the incidence of bleeding events associated with use of fluoroquinolones or macrolides using doxycycline as a negative control. Cox regression was used to calculate crude and adjusted hazard ratios (aHRs) in time windows of various length of follow‐up after the start of antibiotic use. The incidence rates for fluoroquinolones and macrolides ranged from 12 to 24 and from 12 to 53 bleeding events per 100 000 patients in the investigated time windows. The aHRs (95% confidence interval) for use of fluoroquinolones and macrolides were 1.29 (0.69‐2.44) and 2.60 (0.74‐9.08) at the concomitant window, 1.31 (0.84‐2.03) and 1.79 (0.75‐4.29) at 30 days, and 1.34 (0.99‐1.82) and 1.28 (0.62‐2.65) at 150 days, respectively. With regard to fluoroquinolones, the present study suggests that the risk of bleeding when combined with DOACs, if any, is small. Codispensation of macrolides in patients on DOACs was not associated with an increased risk of bleeding. However, due to the small number of macrolide users, the results must be interpreted with caution.

Low-dose azithromycin prophylaxis in patients with atrial fibrillation and chronic obstructive pulmonary disease

“…Beyond the cardiovascular safety profile, another source of possible concerns for macrolides use in AF patients with COPD is the possible presence of drug interactions. Indeed, macrolides are a well-known class of CYP3A4 and p-glycoprotein inhibitors and may perturbate the plasma concentration of both vitamin-K antagonists and NOACs [23]. In our study, we showed that not only the risk of cardiovascular events, but also the hemorrhagic risk was reduced in azithromycin users, and this was irrespective of the type of oral anticoagulant (warfarin or NOACs).…”

Antibiotic–Drug Interactions in the Intensive Care Unit: A Literature Review

“…Among this group of antibiotics, delafloxacin did not demonstrate any clinically significant impact on the QT/QTc interval in several studies [34,35] According to the latest studies, fluoroquinolones and DOAC (direct oral anticoagulants) may moderately increase the risk of bleeding by increasing systemic levels of DOAC. Investigators Tatsuya Yagi and Buster Mannheimer specify that 26 out of 9783 patients (0.27%) had bleeding events in the concomitant use window and 0.6% in the extended window of 30 days [36].…”