Product labeling drug interaction recommendations for direct factor Xa inhibitors40-45,49-52
| Regulatory agency . | Rivaroxaban . | Apixaban . | Edoxaban . | Betrixaban . |
|---|---|---|---|---|
| Pharmacokinetic inducer interactions | ||||
| United States | Avoid p-gp and strong CYP3A4 inducers | Avoid p-gp and strong CYP3A4 inducers | Avoid rifampin | Not addressed |
| Canada | Generally avoid p-gp and strong CYP3A4 inducers | Generally avoid p-gp and strong CYP3A4 inducers | Generally avoid p-gp inducers | Not approved for use |
| Europe | Avoid CYP3A4 inducers unless the patient is closely observed for signs and symptoms of thrombosis | Use p-gp/CYP3A4 inducers with caution in AF and VTE orthopedic surgery prophylaxis indications | Use p-gp inducers with caution | Not approved for use |
| Do not use p-gp/CYP3A4 inducers in acute VTE treatment indication | ||||
| Pharmacokinetic inhibitor interactions | ||||
| United States | Avoid use of combined p-gp/strong CYP3A4 inhibitors | If taking apixaban 5 or 10 mg twice daily, reduce apixaban dose by 50% when used with p-gp and strong CYP3A4 inhibitors; avoid use of combined p-gp/strong CYP3A4 inhibitors if taking apixaban 2.5 mg twice daily | AF: no dose adjustment for concomitant p-gp inhibitors | Reduce initial and maintenance betrixaban dose by 50% when used with p-gp inhibitors |
| Do not use rivaroxaban in patients with CrCl 15 to <80 mL/min who are receiving concomitant combined p-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk | VTE: reduce edoxaban dose to 30 mg once daily with verapamil, quinidine, azithromycin, clarithromycin, erythromycin, oral itraconazole, or oral ketoconazole | |||
| Canada | Systemic ketoconazole and ritonavir are contraindicated with rivaroxaban | Combined p-gp/strong CYP3A4 inhibitors systemic are contraindicated | Reduce edoxaban dose to 30 mg once daily with cyclosporine, dronedarone, erythromycin, ketoconazole, or quinidine | Not approved for use |
| Europe | Azole antifungals and HIV protease inhibitors are not recommended with rivaroxaban | p-gp/strong CYP3A4 inhibitors are not recommended | Reduce edoxaban dose to 30 mg daily with cyclosporine, dronedarone, erythromycin, or ketoconazole | Not approved for use |
| Avoid use of dronedarone with rivaroxaban | ||||
| Regulatory agency . | Rivaroxaban . | Apixaban . | Edoxaban . | Betrixaban . |
|---|---|---|---|---|
| Pharmacokinetic inducer interactions | ||||
| United States | Avoid p-gp and strong CYP3A4 inducers | Avoid p-gp and strong CYP3A4 inducers | Avoid rifampin | Not addressed |
| Canada | Generally avoid p-gp and strong CYP3A4 inducers | Generally avoid p-gp and strong CYP3A4 inducers | Generally avoid p-gp inducers | Not approved for use |
| Europe | Avoid CYP3A4 inducers unless the patient is closely observed for signs and symptoms of thrombosis | Use p-gp/CYP3A4 inducers with caution in AF and VTE orthopedic surgery prophylaxis indications | Use p-gp inducers with caution | Not approved for use |
| Do not use p-gp/CYP3A4 inducers in acute VTE treatment indication | ||||
| Pharmacokinetic inhibitor interactions | ||||
| United States | Avoid use of combined p-gp/strong CYP3A4 inhibitors | If taking apixaban 5 or 10 mg twice daily, reduce apixaban dose by 50% when used with p-gp and strong CYP3A4 inhibitors; avoid use of combined p-gp/strong CYP3A4 inhibitors if taking apixaban 2.5 mg twice daily | AF: no dose adjustment for concomitant p-gp inhibitors | Reduce initial and maintenance betrixaban dose by 50% when used with p-gp inhibitors |
| Do not use rivaroxaban in patients with CrCl 15 to <80 mL/min who are receiving concomitant combined p-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk | VTE: reduce edoxaban dose to 30 mg once daily with verapamil, quinidine, azithromycin, clarithromycin, erythromycin, oral itraconazole, or oral ketoconazole | |||
| Canada | Systemic ketoconazole and ritonavir are contraindicated with rivaroxaban | Combined p-gp/strong CYP3A4 inhibitors systemic are contraindicated | Reduce edoxaban dose to 30 mg once daily with cyclosporine, dronedarone, erythromycin, ketoconazole, or quinidine | Not approved for use |
| Europe | Azole antifungals and HIV protease inhibitors are not recommended with rivaroxaban | p-gp/strong CYP3A4 inhibitors are not recommended | Reduce edoxaban dose to 30 mg daily with cyclosporine, dronedarone, erythromycin, or ketoconazole | Not approved for use |
| Avoid use of dronedarone with rivaroxaban | ||||
AF, atrial fibrillation; CrCl, creatinine clearance; VTE, venous thromboembolism.