Effect of concurrent use of rivaroxaban or apixaban with amiodarone on international normalised ratio: a retrospective observational study

The clearance of rivaroxaban and apixaban is mediated via cytochrome P450 3A4 (CYP3A4) and Permeability-glycoprotein (P-gp) at varying extents. Amiodarone, a weak CYP3A4 and moderate P-gp inhibitor, has the potential to reduce the clearance of these factor Xa (FXa) inhibitors. The real-world impact of this drug-drug interaction is unclear. Although international normalised ratio (INR) is not an accurate measure of FXa inhibitor effect, changes in INR may indicate changes in the impact of FXa inhibitors. To determine what effect the addition of amiodarone has on INR in patients concurrently prescribed rivaroxaban or apixaban in clinical practice. This retrospective observational study identified patients with atrial fibrillation prescribed rivaroxaban or apixaban from April 2017 to December 2022. INRs were analysed in patients prescribed rivaroxaban or apixaban with or without concomitant amiodarone. One hundred and forty-seven patients were included in the study and were separated into the following cohorts: patients prescribed apixaban alone, rivaroxaban alone, apixaban with amiodarone, or rivaroxaban with amiodarone. Mean INRs were greater for patients prescribed apixaban with amiodarone compared to those prescribed apixaban only (1.56 vs. 1.29, respectively) but not for patients prescribed rivaroxaban with amiodarone compared to patients prescribed rivaroxaban only (1.57 vs. 1.61, respectively). Four patients prescribed apixaban with amiodarone had INRs greater than or equal to 3. Our real-world data support literature suggesting that the amiodarone apixaban interaction is real and that there is a large inter-individual variability in the magnitude of this interaction. Further research analysing other coagulation markers (i.e. anti-Xa activity) is warranted to identify at-risk cohorts.