Apixaban: A Novel Oral Inhibitor of Factor Xa

Edith Nutescu, Pharm.D., FCCP

Disclosures

Am J Health Syst Pharm. 2012;69(13):1113-1126. 

In This Article

Pharmacology and Monitoring

Pharmacology

Apixaban is an oral, direct, selective factor Xa inhibitor.[23] In vitro, apixaban is potent and selective, with an equilibrium dissociation constant of 0.08 nm for human factor Xa. It also inhibits clot-bound factor Xa in vitro.[23,24] Apixaban has been shown to be effective in the prevention of experimental venous and arterial thrombosis at doses that preserved hemostasis in rabbits.[25] Results from additional studies have shown that bleeding times were lower with apixaban compared with dabigatran at equivalent antithrombotic doses[26] and that the combination of apixaban and aspirin or of apixaban, aspirin, and clopidogrel reduced the formation of occlusive arterial thromboses without excessive increases in bleeding time in rabbits.[27]

Monitoring

When tested in human plasma, apixaban produced concentration-dependent increases in the activated partial thromboplastin time (aPTT), modified pro-thrombin time, and Heptest.[27] The modified prothrombin time and the Heptest (Heptest Laboratories, St. Louis, MO) appear to be 10- to 20-fold more sensitive than the aPTT or prothrombin time for assessing the anticoagulant effect of apixaban; however, commercially available tests for prothrombin time or the International Normalized Ratio (INR) are not appropriate for monitoring factor Xa inhibitors as these values are highly variable and inconsistent. Results from a study using human plasma samples to which bovine factor Xa had been added and evaluated using a Rotachrom assay (Diagnostica Stago, Parsippany, NJ) indicated that apixaban 100 ng/mL resulted in an approximately 45% decrease in factor Xa activity, and apixaban 1000 ng/mL inhibited factor Xa activity by about 90%.[28]

Apixaban does not require routine laboratory monitoring in the majority of patients. However, like other novel anticoagulants, there may be special patient circumstances or clinical scenarios where knowing the patient's anticoagulant status may be beneficial or necessary (e.g., serious bleeding into critical organs, potential overdose, emergency surgery).[28,29]

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