apixaban (Eliquis)
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Indications
- prophylaxis for venous thromboembolism after knee replacement or hip replacement[10]
- embolic stroke prophylaxis for atrial fibrillation[3][8]
- 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])
Dosage
- DVT prophylaxis
- DVT treatment
- prophylaxis for embolic stroke with atrial fibrillation
- 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)
Dosage adjustment in renal failure
- 2.5 mg PO BID with serum creatinine >= 1.5 mg/dL AND
- 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]
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]
Monitor
- none required
Adverse effects
- less bleeding than enoxaparin or warfarin[21]
- 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]
- lowest risk of GI bleed in patients > 75 years
- 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]
- 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
- drug interaction(s) of oral anticoagulants with selective serotonin reuptake inhibitor (SSRI)
- drug interaction(s) of apixaban with NSAIDs
- drug interaction(s) of aspirin, P2Y12 inhibitors & anticoagulants
Laboratory
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]
More general terms
Additional terms
References
- ↑ Lassen MR et al Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009 Aug 6; 361:594. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19657123
- ↑ Lassen MR et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010 Dec 23; 363:2487. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21175312
Hylek E. Therapeutic potential of oral factor Xa inhibitors. N Engl J Med 2010 Dec 23; 363:2559 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21175319 - ↑ 3.0 3.1 Connolly SJ et al. for the AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011 Feb 10 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21309657 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1007432
- ↑ 4.0 4.1 Granger CB et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011 Aug 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21870978
Mega JL. A new era for anticoagulation in atrial fibrillation. N Engl J Med 2011 Aug 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21870977 - ↑ 5.0 5.1 Goldhaber SZ et al Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients N Engl J Med, November 13, 20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22077144 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1110899
- ↑ 6.0 6.1 Lopes RD et al. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: A secondary analysis of a randomised controlled trial. Lancet 2012 Oct 2 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23036896 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60986-6/fulltext
Vassiliou VS and Flynn PD Apixaban in atrial fibrillation: Does predicted risk matter? Lancet 2012 Oct 2 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23036897 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61673-0/fulltext - ↑ 7.0 7.1 7.2 7.3 Agnelli G et al Apixaban for Extended Treatment of Venous Thromboembolism. N Engl J Med. December 8, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23216615 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1207541
- ↑ 8.0 8.1 FDA News Release: Dec. 28, 2012 FDA approves Eliquis to reduce the risk of stroke, blood clots in patients with non-valvular atrial fibrillation. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333634.htm
- ↑ 9.0 9.1 9.2 Agnelli G et al Oral Apixaban for the Treatment of Acute Venous Thromboembolism. N Engl J Med. July 1, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23808982 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1302507
Cushman M Treating Acute Venous Thromboembolism: Shift with Care. N Engl J Med. July 1, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23808983 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1307413 - ↑ 10.0 10.1 Bristol-Myers Press Release. March 14, 2014 U.S. FDA Approves Eliquis (apixaban) To Reduce The Risk Of Blood Clots Following Hip Or Knee Replacement Surgery. http://news.bms.com/press-release/us-fda-approves-eliquis-apixaban-reduce-risk-blood-clots-following-hip-or-knee-replace
- ↑ Highlights of Prescribing Information http://packageinserts.bms.com/pi/pi_eliquis.pdf
- ↑ 12.0 12.1 Sardar P et al. New oral anticoagulants in elderly adults: Evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 2014 May; 62:857 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24786913 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/jgs.12799/abstract
- ↑ 13.0 13.1 Husten L, Sadoughi S, Sofair A Physician's First Watch, Aug 25, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Bristol-Myers Squibb U.S. FDA Approves Eliquis (apixaban) for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), and for the Reduction in the Risk of Recurrent DVT and PE Following Initial Therapy. http://news.bms.com/press-release/us-fda-approves-eliquis-apixaban-treatment-deep-vein-thrombosis-dvt-and-pulmonary-embo - ↑ 14.0 14.1 14.2 14.3 14.4 Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2022.
- ↑ 15.0 15.1 15.2 Larsen TB et al Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2016;353:i3189 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27312796 Free full text <Internet> http://www.bmj.com/content/353/bmj.i3189
- ↑ 16.0 16.1 Alexander JH et al. Apixaban 5 mg twice daily and clinical outcomes in patients with atrial fibrillation and advanced age, low body weight, or high creatinine: A secondary analysis of a randomized clinical trial. JAMA Cardiol 2016 Jul 27 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27463942 <Internet> http://cardiology.jamanetwork.com/article.aspx?articleid=2537380
- ↑ 17.0 17.1 Abraham NS et al. Gastrointestinal safety of direct oral anticoagulants: A large population-based study. Gastroenterology 2016 Dec 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28043907
- ↑ 18.0 18.1 Majeed A, Agren A, Holmstrom M et al. Management of rivaroxaban or apixaban associated major bleeding with prothrombin complex concentrates: A cohort study. Blood 2017 Aug 23 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28835439 <Internet> http://www.bloodjournal.org/content/early/2017/08/23/blood-2017-05-782060
- ↑ 19.0 19.1 Lopez-Lopez JA, Sterne JAC, Thom HHZ et al Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ 2017;359:j5058 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29183961 Free full text <Internet> http://www.bmj.com/content/359/bmj.j5058
Ball J. Which anticoagulant for stroke prevention in atrial fibrillation? BMJ 2017;359:j5399 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29183874 <Internet> http://www.bmj.com/content/359/bmj.j5399 - ↑ 20.0 20.1 20.2 Yao X, Shah ND, Sangaralingham LR et al Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Renal Dysfunction. J Am Coll Cardiol. 2017 Jun 13;69(23):2779-2790. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28595692
Pokorney SD, Peterson ED, Piccini JP. When Less Is Not More. J Am Coll Cardiol. 2017 Jun 13;69(23):2791-2793. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28595693 - ↑ 21.0 21.1 21.2 21.3 Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ 2018;362:k2505 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29973392 https://www.bmj.com/content/362/bmj.k2505
- ↑ 22.0 22.1 22.2 Siontis KC, Zhang X, Eckard A et al. Outcomes associated with apixaban use in end-stage kidney disease patients with atrial fibrillation in the United States. Circulation 2018 Jun 28 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29954737 <Internet> http://circ.ahajournals.org/content/early/2018/06/22/CIRCULATIONAHA.118.035418
- ↑ 23.0 23.1 Huang WY, Singer DE, Wu YL et al Association of Intracranial Hemorrhage Risk With Non-Vitamin K Antagonist Oral Anticoagulant Use vs Aspirin Use. A Systematic Review and Meta-Analysis. JAMA Neurol. Published online August 13, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30105396 https://jamanetwork.com/journals/jamaneurology/fullarticle/2696416
- ↑ 24.0 24.1 24.2 Carrier M, Abou-Nassar K, Mallick R et al Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. Dec 3, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30511879 https://www.nejm.org/doi/full/10.1056/NEJMoa1814468
- ↑ 25.0 25.1 25.2 Ray WA, Chung CP, Murray KT et al Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA. 2018;320(21):2221-2230 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30512099 https://jamanetwork.com/journals/jama/fullarticle/2717474
- ↑ 26.0 26.1 Dawwas GK, Brown J, Dietrich E, Park H. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: A retrospective population-based cohort analysis. Lancet Haematol 2019 Jan; 6:e20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30558988 https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30191-1/fulltext
Dawwas GK, Leonard CE, Lewis JD et al. Risk for recurrent venous thromboembolism and bleeding with apixaban compared with rivaroxaban: An analysis of real-world data. Ann Intern Med 2021 Dec 7; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34871048 https://www.acpjournals.org/doi/10.7326/M21-0717 - ↑ 27.0 27.1 27.2 27.3 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 28.0 28.1 Hohnloser SH, Fudim M, Alexander JH et al. Efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation and extremes in body weight: Insights from the ARISTOTLE trial. Circulation 2019 May 14; 139:2292. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30773022
- ↑ 29.0 29.1 FDA News Release. Dec 23, 2019 FDA approves first generics of Eliquis https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-eliquis
- ↑ 30.0 30.1 A Pocket Guide to the 2019 Beer's Criteria. American Geriatrics Society.
- ↑ 31.0 31.1 31.2 31.3 31.4 Hanni C, Petrovitch E, Ali M et al. Outcomes associated with apixaban vs warfarin in patients with renal dysfunction. Blood Adv 2020 Jun 9; 4:2366 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32463871 Free PMC article https://ashpublications.org/bloodadvances/article/4/11/2366/457796/Outcomes-associated-with-apixaban-vs-warfarin-in
- ↑ 32.0 32.1 Alcusky M et al. Comparative safety and effectiveness of direct-acting oral anticoagulants versus warfarin: A national cohort study of nursing home residents. J Gen Intern Med 2020 Aug; 35:2329. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32291717 PMCID: PMC7403286 https://link.springer.com/article/10.1007/s11606-020-05777-3
- ↑ 33.0 33.1 Ray WA, Chung CP, Stein CM et al. Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation. JAMA 2021 Dec 21; 326:2395-2404. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34932078 PMCID: PMC8693217 (available on 2022-06-21) https://jamanetwork.com/journals/jama/fullarticle/2787319
- ↑ 34.0 34.1 34.2 Ellenbogen MI et al. Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study. J Hosp Med 2022 Oct; 17:809 PMID: https://www.ncbi.nlm.nih.gov/pubmed/359295 https://shmpublications.onlinelibrary.wiley.com/doi/10.1002/jhm.12926
- ↑ 35.0 35.1 35.2 Lau WCY, Torre CO et al Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation. A Multinational Population-Based Cohort Study. Annals of Internal Medicine. 2022. Nov 1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36315950 https://www.acpjournals.org/doi/10.7326/M22-0511
- ↑ 36.0 36.1 Yasuda S, Kaikita K, Akao M et al. Antithrombotic therapy for atrial fibrillation with stable coronary disease. N Engl J Med 2019 Sep 2; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31475793 https://www.nejm.org/doi/10.1056/NEJMoa1904143
- ↑ 37.0 37.1 NEJM Knowledge+ Hematology
- ↑ 38.0 38.1 Sugiyama T An update on hip fracture risk associated with anticoagulant therapy: warfarin versus direct oral anticoagulants. Expert Opinion on Drug Safety. 2020 19(10):1219-1220 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32795203