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apixaban (Eliquis)

Indications: - prophylaxis for venous thromboembolism after knee replacement or hip replacement [10] - embolic stroke prophylaxis for atrial fibrillation [3,8] - better than warfarin [4,6] - annual risk of death lower than with warfarin (5.2% vs 8.5%) [15] - appears to be direct anticoagulant of choice [19] - prevention & treatment of deep vein thrombosis & venous thromboembolism [7,9,13] - more effective with less major bleeding than rivaroxaban [26] - prevention of venous thromboembolism in patients with cancer [24] - useful for prevention of pulmonary embolism in patients starting chemotherapy (NNT = 17) [24] * safe & effective in the elderly [12] Contraindications: - continued use of apixaban as thromboprophylaxis after hospitalization of medically ill patients [5] - pregnancy - valvular heart disease - morbid obesity (BMI >40 mg/kg) [27] - high-risk antiphospholipid antibody syndrome [14] - osteoporosis (GRS11: due to increased fracture risk relative to warfarin) [27] - ref [38] concludes decreased fracture risk relative to warfarin * apixaban ok in ESRD with close monitoring [14] (see [22,31]) Dose: - DVT prophylaxis - 2.5 mg PO BID - start 12-24 hours after surgery - continue for 10-14 days - DVT treatment - 10 mg BID for 7 days followed by 5 mg BID for 6 months [9] - treatment for 1 year better than 6 months - number needed to treat = 14 to prevent one recurrent DVT [7] - prophylaxis for embolic stroke with atrial fibrillation - 5 mg PO BID - 2.5 mg PO BID age >= 80 years, body weight <= 60 kg, or serum creatinine >= 1.5 mg/dL, (2 of 3) [16] - apixaban beneficial & safe in all weight groups [28] Tabs: 5 mg, 2.5 mg * stop 24-48 hours prior to surgery [27] (see perioperative anticoagulation) Pharmacokinetics: - renal elimination: 25% - metabolized in the liver by CYP3A4 - time to maximum concentration: 3 hours - 1/2life: 9-14 hours - protein binding: 87% [14] Dosage adjustment in renal failure: - 2.5 mg PO BID with serum creatinine >= 1.5 mg/dL AND - body weight <= 60 kg OR age >= 80 years [36] - lack of efficacy with eGFR < 25 mL/min [30] - apixaban with 5-fold higher risk of stroke when underdosed [20] - dabigatran & rivaroxaban not associated with higher risk of stroke when underdosed [20] - in patients with ESRD, apixaban associated with lower risk of major bleeding than warfarin, & with reductions in thromboembolism & mortality (dose 5 mg BID) [22,34] - contraindicated in ESRD [14] (not so) [31,34] - risk of bleeding lower with apixaban dose of 5 mg bid than 2.5 mg bid [31] Monitor: - none required Adverse effects: - less bleeding than enoxaparin or warfarin [21] - annual risk of bleeding 3.3% vs 5.0% for warfarin [15] - number needed to harm = 200 for one case of clinically relevant bleeding [7] - risks of bleeding & thrombosis lower with apixaban than warfarin in patients with ESRD [31] - apixaban with lowest risk of GI bleed among direct oral anticoagulants [17,21,25,35] - lowest risk of GI bleed in patients > 75 years - risk < 1/2 that with rivaroxaban (highest risk) - rates of ischemic stroke, systemic embolism, intracranial hemorrhage & all-cause mortality similar for apixaban, dabigatran, edoxaban, & rivaroxaban in patients with atrial fibrillaton including for patients >= 80 years & those with chronic kidney disease [35] - coadministration of proton pump inhibitor may further decrease risk of upper GI bleed [25] - among Medicare recipients with atrial fibrillation >= 65 years, apixaban is associated with lower risk of major ischemic events & major hemorrhage than rivaroxaban [33] - apixaban 5 mg PO BID may not increase risk of hemorrhagic stroke [23] - doses of apixaban < 10 mg/day associated with increased mortality ~30% relative to warfarin [21] - higher risk of ischemic stroke in nursing home residents than warfarin (RR=1.9), but lower risk of bleeding (RR=0.7) [32] Bleeding: - andexanet reverses factor Xa inhibition - 4 factor prothrombin complex concentrate effective for 70% of hemorrhages [18] Drug interactions: - strong dual inhibitors of CYP3A4 & P-glycoprotein increase levels of apixaban Laboratory: - apixaban in serum/plasma Mechanism of action: - direct inhibitor of factor Xa Notes: - rivaroxaban is also a small molecule inhibitor of factor Xa administered orally - 1st generic FDA-approved Dec 2019 [29] - Manufacturer's website offers free 30 day trial & $10 copay options [37]

Interactions

drug interactions drug adverse effects of direct oral anticoagulants

Related

rivaroxaban (Xarelto)

General

coagulation factor Xa inhibitor direct oral anticoagulant; novel oral anticoagulant (DOAC, NOAC)

Database Correlations

PUBCHEM cid=10182969

References

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