Moderate in apixaban ↑ concentration Combined P-gp inhibitor and All indications No specific dose adjustment recommended by moderate CYP3A4 inhibitor Concentration may be manufacturer. Use with caution. significantly in patients with ↑ impaired function Combined P-gp inducer and Significant in apixaban ↓ All indications Avoid use strong CYP3A4 inducer concentration Rivaroxaban67 Drug Class Type of interaction Indication Recommendations Combined P-gp inhibitor Significant in ↑ and strong inhibitor of All indications Avoid use rivaroxaban concentration CYP3A4 Moderate in rivaroxaban ↑ concentration CrCl 15 to <80 mL/min: Use only if the potential Combined P-gp inhibitor benefit justifies the potential risk* and/or moderate CYP3A4 Concentration may be All indications inhibitor significantly in patients ↑ CrCl <15 mL/min: Avoid use with impaired renal function Combined P-gp inducer and Significant in ↓ All indications Avoid use strong CYP3A4 inducer rivaroxaban concentration *While increases in rivaroxaban exposure can be expected under such conditions, results from an analysis in the ROCKET AF which allowed concomitant use with combined P-gp and either weak (e.g., amiodarone) or moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, and erythromycin), did not show an increase in bleeding in patients with CrCl 30 to <50 mL/min. Dabigatran68 Drug Class Type of interaction Indication Recommendations CrCl 30-50 mL/min: 75 mg twice daily (dronedarone or systemic ketoconazole)* Atrial Fibrillation Variable in dabigatran ↑ Inhibitors of P-gp concentration CrCl < 30 mL/min: Avoid use Treatment of DVT/PE CrCl < 50 mL/min: Avoid use
Combined P-gp inhibitor and moderate CYP3A4 inhibitor Moderate ↑ in apixaban concentration Concentration may be significantly ↑ in patients with impaired function All indications No specific dose adjustment recommended by manufacturer. Use with caution. Combined P-gp inducer and strong CYP3A4 inducer Significant ↓ in apixaban concentration All indications Avoid use Rivaroxaban67 Drug Class Type of interaction Indication Recommendations Combined P-gp inhibitor and strong inhibitor of CYP3A4 Significant ↑ in rivaroxaban concentration All indications Avoid use Combined P-gp inhibitor and/or moderate CYP3A4 inhibitor Moderate ↑ in rivaroxaban concentration Concentration may be significantly ↑ in patients with impaired renal function All indications CrCl 15 to <80 mL/min: Use only if the potential benefit justifies the potential risk* CrCl <15 mL/min: Avoid use Combined P-gp inducer and strong CYP3A4 inducer Significant ↓ in rivaroxaban concentration All indications Avoid use *While increases in rivaroxaban exposure can be expected under such conditions, results from an analysis in the ROCKET AF which allowed concomitant use with combined P-gp and either weak (e.g., amiodarone) or moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, and erythromycin), did not show an increase in bleeding in patients with CrCl 30 to <50 mL/min. Dabigatran68 Drug Class Type of interaction Indication Recommendations Inhibitors of P-gp Variable ↑ in dabigatran concentration Atrial Fibrillation CrCl 30-50 mL/min: 75 mg twice daily (dronedarone or systemic ketoconazole)* CrCl < 30 mL/min: Avoid use Treatment of DVT/PE CrCl < 50 mL/min: Avoid use
Anticoagulation%20Management%20Service%20Guideline.083017.docx