The non-vitamin K oral anticoagulants (NOACs) are used for the treatment of nonvalvular atrial fibrillation (AF), in part because they are seen as more convenient and safer alternatives to warfarin. But NOACs (e.g., rivaroxaban, dabigatran, and apixaban) produce important drug-drug interactions, as noted in a new study from Taiwan. In a retrospective cohort study, the records of more than 91,000 AF patients who had received at least one NOAC were reviewed. There were nearly 5,000 major bleeding events during almost 450,000 person-quarters with NOAC prescriptions. The most common drugs administered concurrently with NOACs were atorvastatin, diltiazem, digoxin, and amiodarone. Of that group, only amiodarone was associated with a significantly higher risk of bleeding. Other drugs that increased bleeding risk were fluconazole, rifampin, and phenytoin. Concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin lowered bleeding rates, while verapamil, diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone produced no effect. The authors suggested that among patients taking NOACs for AF, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin was associated with increased risk of major bleeding. (JAMA 2017;318:1250-1259)