DOAC [11, 13–15, 45] |
Interactions [16]a |
Expected effect/outcome |
Management strategiesb |
Dabigatran (Pradaxa) |
P-gp inducers: carbamazepine, dexamethasone, doxorubicin, nefazodone, phenobarbital, phenytoin, prazosin, rifampin, St. John's wort, tenofovir, tipranavir, vinblastine |
Reduction in serum dabigatran AUC and C max, which may lead to decreased efficacy |
Avoid use |
|
P-gp inhibitors: alfentanil, amiodarone, atorvastatin, azole antimycotics, carvedilol, cyclosporine, diltiazem, dipyridamole, dronedarone, duloxetine, HIV protease inhibitors, fenofibrate, lovastatin, macrolide antibiotics, mefloquine, nicardipine, nifedipine, progesterone, propafenone, propranolol, quinidine, quinine, tacrolimus, tamoxifen, ticagrelor, tolvaptan, verapamil |
Increase in serum dabigatran AUC and C max, which may lead to increased bleeding |
Avoid use with azoles, dronedarone, tacrolimus All other P-gp inhibitors may be used with caution (given 2 h after dabigatran) Decrease dabigatran dose or avoid use when multiple P-gp inhibitors are co-administered Avoid use with any P-gp inhibitor if CrCl < 50 mL/min |
Apixaban (Eliquis) |
Dual strong CYP3A4 and P-gp inducers: carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort |
Significant reduction in serum apixaban AUC and C max, which may lead to decreased efficacy |
Avoid use |
|
Dual strong CYP3A4 and P-gp inhibitors: azole-antimycotics and HIV protease inhibitors |
Significant increase in serum apixaban AUC and C max, which may lead to increased bleeding |
Generally avoid, but can still be used with a 50% dose reduction for doses of 5 mg and 10 mg |
|
Non-strong CYP3A4 and P-gp inducers: aprepitant, armodafinil, bosentan, clobazam, delafloxacin, echinacea, efavirenz, etravirine, lesinurad, modafinil, nafcillin, pioglitazone, prednisone, rufinamide, topiramate |
Decrease in serum apixaban concentration to a lesser extent vs. strong dual inducers and may decrease efficacy |
No dose adjustment needed; use with caution |
|
Non-strong CYP3A4 and P-gp inhibitors: amiodarone, atorvastatin, cilostazol, ciprofloxacin, clindamycin, chloramphenicol, cyclosporine, diltiazem, dronedarone, fluoxetine, imatinib, imipramine, isoniazid, lovastatin, macrolide antibiotics, simvastatin, ranolazine, verapamil |
Increase in serum apixaban concentration to a lesser extent vs. strong dual inhibitors and may increase bleeding risk |
No dose adjustment needed; use with caution |
Rivaroxaban (Xarelto) |
Dual strong CYP3A4 and P-gp inducers: carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort |
Significant reduction in serum rivaroxaban AUC and C max, which may lead to decreased efficacy |
Avoid |
|
Dual strong CYP3A4 and P-gp inhibitors: azole-antimycotics and HIV protease inhibitors |
Significant increase in serum rivaroxaban AUC and C max, which may lead to increased bleeding |
Avoid |
|
Non-strong CYP3A4 and P-gp inducers: aprepitant, armodafinil, bosentan, clobazam, delafloxacin, echinacea, efavirenz, etravirine, lesinurad, modafinil, nafcillin, pioglitazone, prednisone, rufinamide, topiramate |
Decrease in serum rivaroxaban concentration to a lesser extent vs. strong dual inducers and may decrease efficacy |
No dose adjustment needed; use with caution |
|
Non-strong CYP3A4 and P-gp inhibitors: amiodarone, atorvastatin, cilostazol, ciprofloxacin, clindamycin, chloramphenicol, cyclosporine, diltiazem, dronedarone, fluoxetine, imatinib, imipramine, isoniazid, lovastatin, macrolide antibiotics, simvastatin, ranolazine, verapamil |
Increase in serum rivaroxaban concentration to a lesser extent vs. strong dual inhibitors and may increase bleeding risk |
Avoid in patients with CrCl < 80 mL/min; use with caution in patients with normal renal function |
Edoxaban (Savaysa) |
P-gp inducers: carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, St. John's wort |
Significant reduction in serum edoxaban AUC and C max, which may lead to decreased efficacy |
Avoid |
|
P-gp inhibitors: see dabigatran |
Significant increase in serum edoxaban AUC and C max, which may lead to increased bleeding |
AF: no dose adjustment; DVT/PE: 50% dose reduction (i.e., 30 mg daily) if co-administered with verapamil, quinidine, macrolide antibiotics, or azole antimycotics |
Betrixaban (Bevyxxa) |
P-gp inducers: carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, St. John's wort |
Reduction in serum betrixaban AUC and C max, which may lead to decreased efficacy |
Avoid use |
|
P-gp inhibitors: see dabigatran |
Significant increase in serum betrixaban AUC and C max, which may lead to increased bleeding |
50% dose reduction (i.e., 80 mg initially then 40 mg daily); avoid in patients with CrCl < 30 mL/min |
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