Implications of Potential Heparin Shortage - Episode 5
Comparison of DOACs Available for VTE Prophylaxis
Dr. Manesh R. Patel and Sarah A. Spinler compare and contrast the direct oral anticoagulants betrixaban and rivaroxaban and remark on variables that impact treatment selection.
Manesh R. Patel, MD: Between rivaroxaban and betrixaban, what do you think are the differences between these 2 agents? I mean specifically, is there any difference within indication or half-life? [What] do you think about the presence of these therapies in the practice right now?
Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS, AQ-Cardiology: In general, they’re both approved for the medically ill for prophylaxis. Betrixaban, in terms of looking at its pharmacokinetics, differs quite a bit. It has a very long half-life, more than 24 hours. Rivaroxaban has a half-life somewhere around 9 hours in a healthy volunteer, maybe longer at 13 to 19 hours in patients who are [older]. If you look in terms of administration, rivaroxaban at the 10-mg dose—as opposed to the 20-mg dose like we use for atrial fibrillation—does not require that you have to give it with food or a meal.
Betrixaban you give it with a meal, but it’s not necessarily to increase absorption; it’s to prevent higher absorption. You’re trying to prevent an increase in the Cmax and thus an area under the curve. Betrixaban has drug-drug interactions with P-Glycoprotein inhibitors. Whereas rivaroxaban is certainly limited to a combined P-Glycoprotein inhibitor with a strong CYP3A4 inhibitor. There [are] very few drugs—ketoconazole is 1 of those, but we don’t really use oral ketoconazole anymore—but there [are] probably more P-Glycoprotein inhibitors that would have an interaction with betrixaban that are used more in practice. For instance, carvedilol as an example.
Manesh R. Patel, MD: Oh, yeah.
Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS, AQ-Cardiology: There [are] probably more drug interactions that would require a dosing adjustment. Also, if you look in terms of renal dose adjustment, there’s more of a renal dose adjustment with betrixaban than there is with rivaroxaban.
Manesh R. Patel, MD: Yeah, that’s interesting. And certainly we would say that, so both drugs are indicated. Betrixaban has a much longer half-life, [and] rivaroxaban [is] certainly shorter. You sort of went through the differences in their interactions then. How does the half-life affect how you think about using these in these patients [who] are medically ill?
Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS, AQ-Cardiology: When betrixaban was first approved for extended prophylaxis—again you start in the hospital—I think 1 of the concerns of practitioners was to manage such an invasive procedure. As an example, if you’re having a drug that has a half-life of longer than 24 hours because we don’t monitor or measure any anti-Xa levels in these patients. I think that was 1 of the reasons why—especially in someone [who] may have impaired renal function or something where you would be more concerned about doing those procedures—even in hospital on day 2, they’re both administered as a single daily dose. Whereas at least with rivaroxaban, there’s a little more comfort from using it in the higher doses even in hospitalized patients, and maybe either just holding the dose, then doing the procedure, and then reinstituting the dose, similar to how we use subcutaneous unfractionated heparin in patients in [who] are undergoing highly invasive procedures, you kind of delay the dose.
Manesh R. Patel, MD: Yeah, delay the dose. I often think about rivaroxaban use in the hospital much [as] I think about enoxaparin going in and out of procedures and holding a dose or 2 or delaying a dose after. I often tell people [that] it’s safe to restart when you would restart 1 of those agents, because that’s probably how you’re going to be getting that affect. In the clinical trial data we saw some of that.