Betrixaban Drug Interaction Potential

Pharmacodynamic Interactions

The concurrent use of betrixaban with other anticoagulants, antiplatelet agents, and nonsteroidal antiinflammatory agents is expected to increase the risk of bleeding in comparison to use of betrixaban alone

Pharmacokinetic interactions

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

It is possible that administration of betrixaban 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, nilotinib, posaconazole, progesterone, propafenone, quinidine, quinine, ranolazine, sunitinib, tacrolimus, tamoxifen, telithromycin, ticagrelor, tolvaptan, vemuranfenib, verapamil**

* cited as examples in US PI

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

significant increase in betrixaban concentration (AUC and Cmax)

 

  • If CrCl > 30 ml/min, give 80mg x1 then 40mg daily*
  • If CrCl<30 ml/min, avoid use

* based on clinical trial evidence

  • if CrCl > 30ml/min, give 80mg x1 then 40mg daily
  • If CrCl < 30 ml/min, AVOID USE
P-gp inducers carbamazepine, dexamethasone, penobarbital, phenobarbital, rifampin, St John's wort, tipranavir significant redufction in betrixaban concentration (AUC and Cmax) Not addressed 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 probably effects of betrixaban, taking into consideration known characteistics of the precipitant drug according to human in vivo data