Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

Table 2

Edoxaban Drug-Drug and Supplement Interactions [17, 22–29].

(a)

Interacting drugs	Effect	Clinical Implications
Rivaroxaban, apixaban, dabigatran	Enhanced bleeding via additional antithrombotic effects	Avoid combination
Enoxaparin, dalteparin, tinzaparin, fondaparinux, Unfractionated Heparin, warfarin		Avoid combination
Streptokinase, alteplase, reteplase, urokinase, TNK-tPA		Avoid combination
PAR antagonist (atopaxar, vorapaxar)		Avoid combination
GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)		Avoid combination
ADP receptor antagonists (cangrelor, clopidogrel, elinogrel, prasugrel, ticagrelor)		Monitor therapy
Thromboxane inhibitors:aspirin		Monitor therapy: aspirin < 100 mg is safe
Non-Steroidal Anti-inflammatory Agents: naproxen		Monitor therapy: naproxen < 500 mg per day is safe
Cyclooxygenase inhibitor (COX-2)		Monitor therapy
Cilostazol, dipyridamole, ticlopidine		Monitor therapy
Rifampin	Decrease efficacy via P-gp induction	Avoid combination
Carbamazepine, phenobarbital, primidone,		Monitor therapy
St. John’s Wort (Hypericum Perforatum)		Monitor therapy
Tipranavir		Monitor therapy
Verapamil, trandolapril, quinidine	Enhanced bleeding via P-gp inhibition	Decrease the dose of edoxaban to 30 mg daily for VTE treatment.; No dose adjustment required for atrial fibrillation (AF); (i) Verapamil: AUC of edoxaban by 52.7%; (ii) Quinidine: AUC of edoxaban by 76.7%
Diltiazem		Dose reduction may be necessary for treatment of Venous Thromboembolism (VTE); and monitor therapy
Azithromycin, clarithromycin, erythromycin, amoxicillin, ketoconazole, itraconazole		Decrease the dose of edoxaban to 30 mg daily for VTE treatment.; No dose adjustment required for AF
Posaconazole		Dose reduction may be necessary for VTE
Lansoprazole, omeprazole		Decrease the dose of edoxaban to 30 mg daily for VTE treatment.; No dose adjustment required for AF
Amiodarone (oral administration at 600 to 1600 mg per day: causes inhibition of intestinal P-gp efflux pump inhibition), dronaderone		Dose reduction may be necessary for treatment of VTE; and monitor therapy; (i) Amiodarone: ↑ AUC of edoxaban by 39.8%; (ii) Dronaderone ↑ AUC of edoxaban by 84.5%
Propafenone
Atorvastatin, lovastatin, simvastatin, niacin, ezetimibe, amlodipine, carvedilol, nicardipine, nifedipine, ralonazine
Bosutinib, cabozantinib, crizitinib, lapatinib, nilotinib, regorafenib, pazopanib, sorafenib, tamoxifen, vemurafenib,
Canagliflozin, metformin		Dose reduction may be necessary for treatment of VTE; and monitor therapy
Cobicistat, elvitegravir, emtricitabine, tenofovir, ritonavir, lopinavir, saquinavir, aimprevir, nelfinavir, lepidasvir, sofosbuvir, etravirine, draunavir, telaprivir, cyclosporine, eliglustat, enzalutamide, iloperidone, paliperidone, ivacaftor, mefloquine, mifepristone, pirfenidone, ulipristal, testosterone
Grapefruit
Tolvaptan

(b)

Interacting dietary supplements	Effect	Clinical Pearls
Thrombolytic activity: Nattokinase	Enhanced bleeding
Decrease/inhibit platelet aggregation: caffeine, fish oil, fenugreek, flax seed, garlic, ginko, gingeng (panax, Siberian), willow bark, vitamin E (greater than 800 units per day), turmeric, resveratrol
Anticoagulants: gamma Linolenic acid, glucosamine, melatonin,		Avoid combination
Warfarin derivatives: Alfalfa, celery seed, chamomile, dandelion, dong quai, horseradish, licorice root, horse chestnut, parsley, red clover, sweet clover, wild carrot, wild lettuce, nettle, passion flower, horseradish, cassia