Drug Interactions With Non–Vitamin K Oral Anticoagulants

To the Editor An increased risk of major bleeding was found for the concurrent use of NOACs and amiodarone, fluconazole, rifampin, and phenytoin.¹ Rifampin and phenytoin are not inhibitors of P-glycoprotein and CYP3A4, as stated by the authors, but instead are strong inducers.² Rifampin has been shown to decrease plasma levels of apixaban, dabigatran, and rivaroxaban by more than 50% in healthy volunteers.³ Therefore, the finding that rifampin and phenytoin were associated with an increased risk of major bleeding was unexpected. Moreover, results were not consistent across the different NOACs and sites of bleeding. For instance, the concomitant use of rifampin was associated with a significantly reduced risk of intracranial hemorrhage.