From the Guidelines
Azithromycin can be safely coadministered with Xarelto (rivaroxaban) in most patients without significant interactions or the need for dose adjustments. When considering the effect of azithromycin on patients taking Xarelto, it's crucial to evaluate the potential for drug interactions that could impact morbidity, mortality, and quality of life. The primary concern with coadministering azithromycin and rivaroxaban is the potential for increased bleeding risk due to azithromycin's mild inhibition of P-glycoprotein, a transporter protein that rivaroxaban is a substrate of 1. However, this interaction is considered minimal compared to other antibiotics like clarithromycin or erythromycin, which are strong inhibitors of CYP3A4 and can significantly increase rivaroxaban plasma concentrations.
Key points to consider:
- Azithromycin does not substantially affect the CYP3A4 enzyme system that metabolizes rivaroxaban, reducing the risk of significant drug interactions 1.
- The combination of azithromycin and rivaroxaban may pose a theoretical minimal risk of increased bleeding due to potential mild inhibition of P-glycoprotein, but this is not as pronounced as with other macrolide antibiotics 1.
- Patients should remain vigilant for unusual bleeding or bruising while taking both medications, although the combination is generally considered safer than alternatives.
- Patients with severe kidney disease, liver disease, or those taking multiple medications should exercise additional caution and may require closer monitoring when these medications are combined.
In the context of real-life clinical practice, prioritizing morbidity, mortality, and quality of life outcomes suggests that azithromycin can be a relatively safe choice for patients on Xarelto, provided that healthcare providers are informed and patients are monitored appropriately. This recommendation is based on the most recent and highest quality evidence available, which indicates a low risk of significant interactions between azithromycin and rivaroxaban 1.
From the Research
Effect of Azithromycin on Xarelto (Rivaroxaban)
- The effect of azithromycin on patients taking Xarelto (rivaroxaban) is not directly addressed in the provided studies, but some information can be inferred from the available data.
- A study published in 2020 2 compared the risk of hospitalization with hemorrhage among older adults taking clarithromycin vs azithromycin and direct oral anticoagulants, including rivaroxaban. The results showed that coprescribing clarithromycin vs azithromycin with a DOAC was associated with a higher risk of hospital admission with major hemorrhage.
- Although this study does not directly examine the effect of azithromycin on rivaroxaban, it suggests that azithromycin may be a safer option than clarithromycin when coprescribed with DOACs like rivaroxaban.
- Another study published in 2013 3 investigated the effect of azithromycin on anticoagulation-related outcomes in geriatric patients receiving warfarin, not rivaroxaban. The results showed that the addition of azithromycin to a stable warfarin regimen resulted in a significant change in the international normalized ratio (INR) and warfarin dosage alteration without an increase in bleeding.
- A review of rivaroxaban use in clinical practice 4 highlights the importance of considering drug interactions when prescribing rivaroxaban, but does not specifically address the interaction with azithromycin.
- Two case reports 5, 6 describe rare adverse effects of rivaroxaban, including spontaneous hemothorax and thrombocytopenia, but do not involve azithromycin.
Key Findings
- Azithromycin may be a safer option than clarithromycin when coprescribed with DOACs like rivaroxaban, based on a study comparing the risk of hospitalization with hemorrhage among older adults 2.
- The effect of azithromycin on rivaroxaban is not directly addressed in the provided studies, and more research is needed to fully understand this interaction.