Edoxaban Drug Interaction Potential

Pharmacodynamic Interactions
The concurrent use of edoxaban with other anticoagulants, antiplatelet agents, and nonsteroidal anti-inflammatory agents is expected to increase the risk of bleeding in comparison to use of edoxaban alone.

Pharmacokinetic Interactions
The absorption of edoxaban is mediated by P-glycoprotein (P-gp). P-gp inhibitors can increase the absorption of edoxaban, increasing both AUC and Cmax. Conversely, P-gp inducers can reduce the absorption of edoxaban, decreasing AUC and Cmax.

It is possible that administration of edoxaban two hours prior to any P-gp inhibitor or inducer may reduce or eliminate the impact of the interaction, but there is insufficient evidence at this time to make this conclusion definitively

Drug Class  Examples (based on human in vivo data1) Known or Probable Effect US PI Recommendation

UW Medicine

Suggested Management Guidelines2

P-gp inhibitors 

alfentanil, amiodarone*, azithromycin, carvedilol, clarithromycin, cobicistat, conivaptan, cyclosporine*,  diltiazem, dronedarone*, duloxetine, erythromycin*, fenofibrate, grapefruit, all HIV protease inhibitors, itraconazole, ivacaftor, ketoconazole*, lapatinib, lomitapide, mefloquine, nicardipine, nifedipine, posaconazole, progesterone, propafenone, quinidine*, quinine, ranolazine, sunitinib, tacrolimus,tamoxifen, telithromycin, ticagrelor, tolvaptan, vemuranfenib, verapamil*

 

* cited as examples in US PI, with pharmacokinetic data cited

significant increase in edoxaban concentration (AUC and Cmax)

AF: Do not reduce dose of edoxaban

 

VTE Treatment: reduce dose to 30mg

AVOID USE 
P-gp inducers

carbamazepine, dexamethasone, pentobarbital, phenobarbital, rifampin*, St. John's wort, tipranavir

 

* cited as example in US PI, with pharmacokinetic data cited

significant reduction in edoxaban concentration (AUC and Cmax) Avoid use with rifampin AVOID USE

(1) based on human in vivo data, in Cytochrome P450 Enzymes and Transporters Table, from Hansten PD and Horn JR.  The Top 100 Drug Interactions: A Guide to Patient Management, 2014 ed, H&H Publications, Freeland WA

(2) based on probable effects of edoxaban, taking into consideration known characteristics of the precipitant drug according to human in vivo data