Factor Xa inhibitor.
Apixaban 2.5mg, 5mg; tablets.
To reduce risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF).
Apixaban is an oral, reversible, and selective active site inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. It has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development.
Evidence for the efficacy and safety of Eliquis was derived from ARISTOTLE, a multinational, double-blind study in patients with nonvalvular AF comparing the effects of Eliquis and warfarin on the risk of stroke and non-CNS systemic embolism. Eliquis was superior to warfarin in the primary efficacy endpoint of stroke or systemic embolism, with a 21% relative risk reduction beyond warfarin (1.27%/year vs 1.60%/year, HR=0.79, p=0.01). Superiority to warfarin was primarily attributable to a reduction in hemorrhagic stroke and ischemic stroke that converted to hemorrhagic stroke. Purely ischemic strokes occurred with similar rates on both drugs. Eliquis was superior to warfarin for the primary safety endpoint of major bleeding, with a 31% relative risk reduction (2.13%/year versus 3.09%/year, HR=0.69, p<0.0001).
In AVERROES, the primary objective of the study was to determine if Eliquis was superior to aspirin for reducing the risk of stroke or systemic embolism in AF patients thought not to be candidates for warfarin. AVERROES was stopped early on the basis of a prespecified interim analysis showing a significant reduction in stroke and systemic embolism for Eliquis compared to aspirin that was associated with a modest increase in major bleeding.
5mg twice daily. If any two of the following: age ≥80 years; body weight ≤60kg, serum creatinine ≥1.5mg/dL: 2.5mg twice daily. Concomitant strong dual inhibitors of CYP3A4 and P-gp (eg, ketoconazole, itraconazole, ritonavir, clarithromycin): 2.5mg twice daily; if already on 2.5mg twice daily, coadministration should be avoided. Switching from warfarin: discontinue warfarin, start Eliquis when INR is <2. Switching from Eliquis to warfarin: discontinue Eliquis and begin both parenteral anticoagulant and warfarin at the time the next dose of Eliquis would have been taken, discontinue parenteral anticoagulant when INR reaches acceptable range. Switching between Eliquis and anticoagulants other than warfarin: discontinue one being taken and begin the other at next scheduled dose. Discontinue at least 48 hours prior to surgery with moderate-to-high risk of bleeding or 24 hours for procedures with low risk of bleeding. Moderate hepatic impairment: dosing recommendation cannot be provided. Severe hepatic impairment: not recommended.
Active pathological bleeding.
Increased risk of stroke if discontinued without adequate continuous anticoagulation. Prosthetic heart valve: not recommended. Labor & delivery. Pregnancy (Category B). Nursing mothers: not recommended.
See Adult dose. Potentiated by dual inhibitors of CYP3A4 and P-gp. Antagonized by concomitant strong dual inducers of CYP3A4 and P-gp (eg, rifampin, carbamazepine, phenytoin, St. John’s wort); avoid. Increased risk of bleeding with concomitant aspirin, antiplatelet agents, fibrinolytics, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, NSAIDs.