Dosing of Direct Oral Anticoagulants

Paul Dobesh, PharmD, FCCP, BCPS, discusses the dosing differences among the DOAC agents.

Paul Dobesh, PharmD, FCCP, BCPS: Another difference is dosing. You've got 2 agents, apixaban and dabigatran, that are dosed twice a day. You've got 3 agents that are dosed once a day. Now, we don’t need to talk so much about betrixaban, it's got the 1 indication. What's interesting is that all 4 drugs have a half-life of about 12 hours. A common question that we get is, how can you have a dose that has a 12-hour half-life and only dose it once a day? That doesn't make sense. And I completely get that because for 90% to 95% of the drugs we use in clinical practice, the pharmacokinetics dictate the pharmacodynamics. How long the drug is in the system dictates how long it works, but it's not that way for all drugs. The example, to stick with anticoagulation, is low molecular weight heparin. How many times a day do we give low molecular weight heparin? Once or twice a day. Low molecular weight heparin has a half-life of 4 to 6 hours. Nobody is giving low molecular weight heparin 4 times a day because that's its half-life. Why? Because the pharmacodynamic, the anticoagulant effect, is longer than the kinetic effect, so there is a separation there, and it happens with other drugs.

So for apixaban and dabigatran, they've got 12-hour half-lives, they provide 12 hours of anticoagulation. Their kinetics and dynamics line up. But for both rivaroxaban and edoxaban, once-daily drugs, even with the 12-hour half-life, they clearly provide 24 hours of anticoagulant effect. So that's another difference between some of the agents that people look at when deciding what they're going to do, a twice-daily drug versus a once-daily drug, trying to think of adherence type of issues.

Jessica Kerr, PharmD, CDE: Great. I know that over the years with me being in clinical practice, it used to always be the warfarin clinics and such. When a lot of these newer agents came out, and even until recently, it's hard for many of the clinicians to stay on track with it if this is not really their forte. I think the background that you provided with those and regarding the indication is helpful. And you had great points when you're talking about the dosage forms. Because I think, like you had said, so much of it typically supports each other when we're looking at PK/PD type of parameters for dosing durations and schedules. I think that is helpful to give that background.

Oftentimes when individual agents have shared indications, it is important for us to consider safety that's noted in the clinical trials, as well as perceived barriers to patients. Hopefully for the rest of the talk today we can look at that data, and then Dr Johnson from a clinical standpoint, as well as Dr Dobesh, with your experience, can share with us what you're seeing about how you and your colleagues are actually utilizing these agents.