Direct Oral Anticoagulants (DOAs) Comparison

Mechanism of Action (MOA) of DOAs

I made this table to compare the direct oral anticoagulants, so now I’m sharing with you.

	Pradaxa (dabigatran)	Xarelto (rivaroxaban)	Eliquis (apixaban)	Savaysa (edoxaban)
FDA Approved	10/2010	7/2011	12/2012	1/2015
Indications	NVAF VTE ppx, DVT/PE tx & prevention	NVAF VTE ppx, DVT/PE tx & prevention, DVT ppx post hip/knee replacement surgery	NVAF VTE ppx, DVT/PE tx & prevention, DVT ppx post hip/knee replacement surgery	NVAF VTE ppx, DVT/PE tx
Target (as inhibitor)	Thrombin	Factor Xa	Factor Xa	Factor Xa
Half-life (hrs)	7 – 17	5-9	8-15	10-14
Dosing & Frequency	150mg twice daily (NVAF) 150mg twice daily following 5-10 days of initial tx with parenteral anticoagulation (VTE tx)	(Bioavailability ~100% WITH FOOD) -20 mg once daily with evening meal (NVAF) -15 mg BID with food x21 days then 20mg QD with food (DVT/PE tx) -10 mg QD (x35 days post hip/x12 days post knee replacement)	-5 mg BID (NVAF) – 10 mg BID x7 days then 5 mg QD (DVT/PE tx) -2.5 mg BID (DVT/PE maintenance following initial tx) -2.5 mg BID (x35 days post hip/x12 days post knee replacement)	-60mg once daily in patients with CrCl>50 to <= 95 ml/min (NVAF) -60mg once daily; 30mg if CrCl 15-50 ml/min or BW <= 60kg (VTE tx)
Metabolism	– Hepatically metabolized from prodrug (dabigatran dexilate) to dabigatrin (active form) then hepatic glucuronidized – 80% renal excretion	– CYP3A4 metabolized -66% renal secretion	– CYP3A4 metabolized -25% renal secretion -P-gp substrate	-P-gp substrate -50% renal secretion
Renal adjustment	Yes 75mg BID if CrCl 15-30ml/min (NVAF) Avoid if CrCl <15 ml/min (NVAF) Avoid if CrCl <30 ml/min (VTE)	Yes 15mg QD with eveningmeal if Crcl 15-50 ml/min Avoid if CrCl <15 ml/min (NVAF) Avoid if CrCl <30 ml/min (VTE)	Yes Avoid if CrCl <15 ml/min (NVAF) Avoid if CrCl <30 ml/min (VTE)	Yes Avoid if CrCl >95 ml/min or CrCl < 15 ml/min
Antidote	Praxbind (idarucizumab): FDA-approved 10/2015	None/4F-PCC Betrixaban (andexanet alpha) submitted for FDA approval 12/18/2015	None/4F-PCC Betrixaban (not FDA approved yet)	None/4F-PCC Betrixaban (not FDA approved yet)
Drug interactions	-Avoid strong P-gp inducers; inhibitors if CrCl <30. -Caution with antiplatelets -Drugs that increase gastric pH (H2RBs/PPIs) could reduce efficacy –> take at least 2 hrs before antacids	-Avoid strong P-gp and CYP3A4 inhibitors. -Avoid strong CYP3A4 inducers. -Avoid concurrent use with anticoagulants -Caution with antiplatelets	-Reduce dose to 2.5mg BID with strong P-gp and CYP3A4 inhibitors. -Avoid both strong P-gp and CYP3A4 inducers. -Caution with anticoagulants and antiplatelets	-P-gp strong inhibitors and inducers -Avoid rifampin

Regarding other anticoagulants, a MUST KNOW for the Naplex exam is Lovenox dosing. Study by heart doses based on different conditions (age, STEMI, UA/NSTEMI, VTE ppx) and recognize them to calculate the dose correctly. Remember that lovenox dosing is based on TBW (total body weight), and it is given SQ (know how to give a Lovenox subcutaneously. Do you rub after giving the shot?).

I took the CPhA Anticoagulation Certificate training course this year to strengthen my skills. This is an excellent course to review and keep myself updated with the new anticoagulants.