Table 5:
Important DOAC-drug interactions and management recommendations
| DOAC | Precipitant Drug | Nature of Interaction | Recommendations | Clinical Significance |
|---|---|---|---|---|
| All DOACs | Apalutamide | Strong CYP3A4 induction164 | Avoid Combination1–4 | Major |
| Carbamazepine | Strong CYP3A4 induction1–4 | Avoid Combination1–4 | Major | |
| Enzalutamide | Strong CYP3A4 induction79 | Avoid Combination1–4 | Major | |
| Phenytoin | Strong CYP3A4 induction1–4 | Avoid Combination1–4 | Major | |
| Rifampin | Strong CYP3A4 induction123 | Avoid Combination1–4 | Major | |
| Ritonavir | Strong P-gp inhibition and Strong CYP3A4 inhibition163 | Avoid Combination1–4 | Major | |
| St John's Wort | Strong CYP3A4 induction1–4 | Limit St. John's Wort to less than 4g/day167 | Minor | |
| Grapefruit Juice | Strong CYP3A4 inhibition | Minimize grapefruit juice intake107 to < 200cc | Minor | |
| Apixaban | Dronedarone | Strong P-gp inhibition and moderate CYP3A4 inhibition2 | Monitor for bleeding | Minor |
| Cyclosporine | Strong P-gp inhibition and CYP3A4 inhibition2 | Combination is ok, monitor for bleeding168 | Minor | |
| Itraconazole | Strong P-gp inhibition and moderate CYP3A4 inhibition2 | Consider alternative, decrease dose by 50% if unavoidable2 | Major | |
| Ketoconazole | Strong P-gp inhibition and moderate CYP3A4 inhibition2 | Consider alternative, decrease dose by 50% if unavoidable2 | Major | |
| Nefazodone | Strong CYP3A4 inhibition13 | Ok if no other PK inhibitor is present, otherwise requires 50% apixaban dose reduction.2 | Minor | |
| Posaconazole | Strong CYP3A4 inhibition163 | Ok if no other PK inhibitor is present, otherwise requires 50% apixaban dose reduction 2 | Minor | |
| Protease inhibitors : Cobicistat Indinavir Nelfinavir Saquinavir |
Strong CYP3A4 inhibition163 | Ok if no other PK inhibitor is present, otherwise requires 50% apixaban dose reduction 2 | Minor | |
| Tyrosine kinase inhibitors | Strong CYP3A4 inhibition | Ok if no other PK inhibitor is present, otherwise requires 50% apixaban dose reduction.2 | Minor | |
| Verapamil | Strong P-gp inhibition and moderate CYP3A4 inhibition | Ok if no other PK inhibitor | Minor | |
| Voriconazole | Strong CYP3A4 inhibition2, 13 | Ok if no other PK inhibitor is present, otherwise requires 50% apixaban dose reduction.2 | Minor | |
| Dabigatran | Amiodarone | P-gp inhibition129 | Administer amiodarone 2 hours after dabigatran1 | Minor |
| Cyclosporine | Strong P-gp inhibition108 | Avoid use169 | Major | |
| Dronedarone | P-gp inhibition129 | Administer dronedarone 2 hours after dabigatran if CrCl is ≥ 50 mL/min1, decrease dose to 75mg PO BID in patients with CrCl < 50mL/min if unavoidable1, avoid if < 30 mL/min | Major | |
| Ketoconazole | Strong P-gp inhibition108 | Consider alternative, decrease dose to 75mg PO BID in patients with CrCl < 50mL/min if unavoidable1, avoid if < 30 mL/min | Major | |
| Lapatanib | Strong P-gp inhibition108 | Not studied, avoid combination1 | Major | |
| Ticagrelor | P-gp inhibition1 | Administer ticagrelor 2 hours after dabigatran1 | Minor | |
| Verapamil | P-gp inhibition129 | Administer dabigatran 2 hours before verapamil.170 | Minor | |
| Edoxaban | Cyclosporine | Strong P-gp inhibition108 | Ok unless another P-gp inhibitor is present. Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min 3, 135 | Major |
| Dronedarone | Strong P-gp inhibition108 | Administer dronedarone 2 hours after edoxaban. Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min 3, 135 | Major | |
| Itraconazole | Strong P-gp inhibition108 | Ok unless another P-gp inhibitor is present. Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min 3, 135 | Major | |
| Ketoconazole | Strong P-gp inhibition108 | Ok unless another P-gp inhibitor is present. Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min 3, 135 | Major | |
| Lapatinib | Strong P-gp inhibition108 | Ok unless another P-gp inhibitor is present. Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min3, 135 | Major | |
| Quinidine | Strong P-gp inhibition108 | Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min3, 134, 135 | Major | |
| Verapamil | Strong P-gp inhibition108 | Reduce dose of edoxaban by 50% if anticoagulation is for venous thromboembolism or CrCl is < 50 mL/min 3, 132, 135 | Minor | |
| Rivaroxaban | Amiodarone | Weak CYP3A4 and P-gp inhibition (PI) | Monitor for bleeding | Minor |
| Cyclosporine | Strong P-gp inhibition and CYP3A4 inhibition4 | Ok unless CrCl is < 50 mL/min4, 171 | Minor | |
| Dronedarone | Strong P-gp inhibition and moderate CYP3A4 inhibition4 | Ok unless CrCl is < 80 mL/min, otherwise consider alternative | Major | |
| Itraconazole | Strong P-gp inhibition and moderate CYP3A4 inhibition4 | Avoid combination4 | Major | |
| Ketoconazole | Strong P-gp inhibition and moderate CYP3A4 inhibition4 | Avoid combination4 | Major | |
| Lapatanib | Strong P-gp inhibition108 | Not studied, avoid combination4 | Major | |
| Nefazodone | Strong CYP3A4 inhibition13 | Ok if no other PK inhibitor is present, otherwise avoid combination.4 | Minor | |
| Posaconazole | Strong CYP3A4 inhibition163 | Ok if no other PK inhibitor is present, otherwise avoid combination.4 | Minor | |
| Protease inhibitors : Cobicistat Indinavir Nelfinavir Saquinavir |
Strong CYP3A4 inhibition163 | Ok if no other PK inhibitor is present, otherwise avoid combination4 | Major | |
| Tyrosine kinase inhibitors | Strong CYP3A4 inhibition4 | Ok if no other PK inhibitor is present, otherwise consider alternative4 | Major | |
| Verapamil | Strong P-gp inhibition and moderate CYP3A4 inhibition4 | Ok unless CrCl is < 80mL/min, otherwise use diltiazem4 | Minor | |
| Voriconazole | Strong CYP3A4 inhibition13 | Ok if no other PK inhibitor is present, otherwise avoid combination.4 | Minor |