Contraindications Associated With Combining Amiodarone and Rivaroxaban

Direct-acting oral anticoagulants (DOACs) have revolutionized the prevention of stroke in patients with atrial fibrillation. While both direct thrombin inhibitors and Xa-inhibitors are approved for this indication, only the latter is used commonly in clinical practice. Within the Xa-inhibitor class, both rivaroxaban and apixaban are prescribed frequently, and have demonstrated superior safety to warfarin-based anticoagulation.

Rivaroxaban and apixaban differ primarily in their pharmacokinetic properties. While both drugs are renally cleared, rivaroxaban depends more heavily on CYP3A4 and P-GP for hepatic metabolism and renal clearance, which can increase its susceptibility to drug-drug interactions. Knowing what the drug interactions are is salient as patients with AFib are frequently prescribed antiarrhythmic medications with significant drug interactions (eg, amiodarone). In this installment of Talking Therapeutics, we discuss a new paper evaluating the potential clinical ramifications of the drug-drug interaction between amiodarone and rivaroxaban.

Talking Point: Definite Signal for Harm

This single-center prospective study stratified patients into 2 groups: those receiving rivaroxaban without amiodarone (rivaroxaban group) and those receiving rivaroxaban and amiodarone (combination group). The primary outcome was the first occurrence of any International Society on Thrombosis and Hemostasis (ISTH) bleeding over 3 months. Results were provided for ISTH major, clinically relevant nonmajor (CRNM), and minor bleeding.

The primary outcome, any ISTH bleeding, occurred in 26.0% in the combination group and 10.4% in the rivaroxaban group (hazard ratio, 2.76; 95% confidence interval, 1.55-4.93). Major bleeding only occurred in one patient in the rivaroxaban group. CRNM bleeding and minor bleeding were also significantly higher in the combination group. The rivaroxaban dose did not impact these results, but bleeding was higher in the combination group in patients with chronic kidney disease and not increased in those without.

Talking Point: Consider Avoiding This Combo

The results of this study suggest that patients taking rivaroxaban with amiodarone are at an increased risk for significant bleeding. This risk appears to be most pronounced in those with concomitant AFib and chronic kidney disease.

Fortunately, apixaban has demonstrated safety in patients with kidney disease, and it is likely less susceptible to the amiodarone drug interaction than rivaroxaban. Clinicians should, therefore, consider substituting apixaban for rivaroxaban in patients with AFib who are also taking amiodarone, particularly if the patient also has chronic kidney disease.