Skip to main content
SpringerLink
Log in

Rivaroxaban: A Review of Its Use in the Treatment of Deep Vein Thrombosis or Pulmonary Embolism and the Prevention of Recurrent Venous Thromboembolism

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Rivaroxaban (Xarelto®), an oral direct factor Xa inhibitor, is approved for the initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as the prevention of recurrent DVT and PE. It is administered at a fixed oral dose and does not require routine coagulation monitoring. In the EINSTEIN-DVT and EINSTEIN-PE trials, in over 8,000 patients with DVT and/or PE, a single-drug approach with rivaroxaban was shown to be noninferior to standard therapy consisting of subcutaneous enoxaparin sodium overlapping with and followed by an oral dose-adjusted vitamin K antagonist (enoxaparin–VKA) with regard to the incidence of symptomatic recurrent venous thromboembolism (VTE) after 3, 6 or 12 months of treatment. Rivaroxaban was generally well tolerated in patients with DVT or PE, with no significant between-group differences in clinically relevant bleeding between the rivaroxaban and enoxaparin–VKA groups. Notably, rivaroxaban was associated with a significantly lower rate of major bleeding compared with enoxaparin–VKA when EINSTEIN-DVT and EINSTEIN-PE data were pooled. Pharmacoeconomic analyses indicated that rivaroxaban may be a cost-effective alternative to enoxaparin–VKA for the treatment of DVT or PE and prevention of recurrent VTE. Extended prophylaxis with rivaroxaban reduced the incidence of symptomatic recurrent VTE to a greater extent than placebo in the EINSTEIN-Extension trial, but was associated with a non-significant increase in the risk of clinically relevant bleeding compared with placebo. In conclusion, rivaroxaban is a reasonable alternative to standard therapy for the treatment of DVT and PE, and as extended thromboprophylaxis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Turpie AG, Esmon C. Venous and arterial thrombosis: pathogenesis and the rationale for anticoagulation. Thromb Haemost. 2011;105(4):586–96.

    Article  CAS  PubMed  Google Scholar 

  2. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(Suppl 2):e419S–94S.

    Google Scholar 

  3. National Institute for Health and Clinical Excellence. CG144 Venous thromboembolic disease: NICE guideline. 2012. http://guidance.nice.org.uk/CG144/NICEGuidance/pdf/English. Accessed 13 Dec 2013.

  4. Cohen AT, Agnelli G, Anderson FA, et al. Venous thromboembolism (VTE) in Europe: the number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98(4):756–64.

    CAS  PubMed  Google Scholar 

  5. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(Suppl 4):S495–501.

    Article  PubMed  Google Scholar 

  6. Prandoni P, Noventa F, Ghirarduzzi A, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism: a prospective cohort study in 1,626 patients. Haematologica. 2007;92(2):199–205.

    Article  PubMed  Google Scholar 

  7. Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Intern Med. 2004;164(1):17–26.

    PubMed  Google Scholar 

  8. Abad Rico JI, Llau Pitarch JV, Paramo Fernandez JA. Topical issues in venous thromboembolism. Drugs. 2010;70(Suppl 2):11–8.

    Article  PubMed  Google Scholar 

  9. Bayer. Xarelto®: EU summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf. Accessed 13 Dec 2013.

  10. National Institute for Health and Clinical Excellence. Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. 2012. http://www.nice.org.uk/nicemedia/live/13805/60040/60040.pdf. Accessed 13 Dec 2013.

  11. Janssen Pharmaceuticals Inc. Xarelto® (rivaroxaban): US prescribing information. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022406s004lbl.pdf. Accessed 13 Dec 2013.

  12. Duggan ST. Rivaroxaban: a review of its use for the prophylaxis of venous thromboembolism after total hip or knee replacement surgery. Am J Card Drugs. 2012;12(1):57–72.

    Article  CAS  Google Scholar 

  13. Duggan ST, Scott LJ, Plosker GL. Rivaroxaban: a review of its use for the prevention of venous thromboembolism after total hip or knee replacement surgery. Drugs. 2009;69(13):1829–51.

    Article  CAS  PubMed  Google Scholar 

  14. Carter NJ, Plosker GL. Rivaroxaban: a review of its use in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Drugs. 2013;73(7):715–39.

    Article  CAS  PubMed  Google Scholar 

  15. Perzborn E, Strassburger J, Wilmen A, et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939: an oral, direct factor Xa inhibitor. J Thromb Haemost. 2005;3(3):514–21.

    Article  CAS  PubMed  Google Scholar 

  16. Tersteegen A, Burkhardt N. Rivaroxaban an oral, direct factor Xa inhibitor binds rapidly to factor Xa [abstract no. P-W-651]. J Thromb Haemost. 2007;5(Suppl):2.

    Google Scholar 

  17. Laux V, Perzborn E, Kubitza D, et al. Preclinical and clinical characteristics of rivaroxaban: a novel, oral, direct factor Xa inhibitor. Semin Thromb Hemost. 2007;33(5):515–23.

    CAS  PubMed  Google Scholar 

  18. Roehrig S, Straub A, Pohlmann J, et al. Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor. J Med Chem. 2005;48(19):5900–8.

    Article  CAS  PubMed  Google Scholar 

  19. Graff J, von Hentig N, Misselwitz F, et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity. J Clin Pharmacol. 2007;47(11):1398–407.

    Article  CAS  PubMed  Google Scholar 

  20. Perzborn E, Harwardt M. Inhibition of thrombin generation in human plasma by rivaroxaban, an oral, direct factor Xa inhibitor [abstract no. PP-MO-184]. J Thromb Haemost. 2009;7(Suppl 2):379.

    Google Scholar 

  21. Gerotziafas GT, Elalamy I, Depasse F, et al. In vitro inhibition of thrombin generation, after tissue factor pathway activation, by the oral, direct factor Xa inhibitor rivaroxaban. J Thromb Haemost. 2007;5(4):886–8.

    Article  CAS  PubMed  Google Scholar 

  22. Agnelli G, Gallus A, Goldhaber SZ, et al. Treatment of proximal deep-vein thrombosis with the oral direct factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients with Acute Symptomatic Deep-Vein Thrombosis) study. Circulation. 2007;116(2):180–7.

    CAS  PubMed  Google Scholar 

  23. Varin R, Mirshahi S, Mirshahi P, et al. Effect of rivaroxaban, an oral direct factor Xa inhibitor, on whole blood clot permeation and thrombolysis: critical role of red blood cells [abstract no. 1064]. 51st ASH Annual Meeting and Exposition; 5-8 Dec 2009; New Orleans, LA.

  24. Kubitza D, Becka M, Voith B, et al. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther. 2005;78(4):412–21.

    Article  CAS  PubMed  Google Scholar 

  25. Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939-an oral, direct factor Xa inhibitor-after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61(12):873–80.

    Article  CAS  PubMed  Google Scholar 

  26. Mueck W, Becka M, Kubitza D, et al. Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban-an oral, direct factor Xa inhibitor-in healthy subjects. Int J Clin Pharmacol Ther. 2007;45(6):335–44.

    Article  CAS  PubMed  Google Scholar 

  27. Mueck W, Lensing AWA, Agnelli G. Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet. 2011;50(10):675–86.

    Article  CAS  PubMed  Google Scholar 

  28. Kubitza D, Becka M, Mueck W, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct factor Xa inhibitor. Br J Clin Pharmacol. 2010;70(5):703–12.

    Article  CAS  PubMed  Google Scholar 

  29. Kubitza D, Roth A, Becka M, et al. Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct factor Xa inhibitor. Br J Clin Pharmacol. 2013;76(1):89–98.

    Article  CAS  PubMed  Google Scholar 

  30. Perzborn E, Lange U. Rivaroxaban: an oral, direct factor Xa inhibitor inhibits tissue factor-mediated platelet aggregation [abstract no. P-W-642]. XXI ISTH Congress; 6–12 Jul 2007; Geneva.

  31. Walenga JM, Prechel M, Jeske WP, et al. Rivaroxaban-an oral, direct factor Xa inhibitor-has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol. 2008;143(1):92–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kubitza D, Mueck W, Becka M. Randomized, double-blind, crossover study to investigate the effect of rivaroxaban on QT-interval prolongation. Drug Saf. 2008;31(1):67–77.

    CAS  PubMed  Google Scholar 

  33. European Medicines Agency. Xarelto-H-C-000944-X-0010: EPAR: Assessment Report—Variation 2011. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000944/WC500120736.pdf. Accessed 13 Dec 2013.

  34. Kubitza D, Becka M, Mueck W, et al. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban-an oral, direct factor Xa inhibitor-are not affected by aspirin. J Clin Pharmacol. 2006;46(9):981–90.

    Article  CAS  PubMed  Google Scholar 

  35. Kubitza D, Becka M, Mueck W, et al. Rivaroxaban (BAY 59-7939)-an oral, direct Factor Xa inhibitor-has no clinically relevant interaction with naproxen. Br J Clin Pharmacol. 2007;63(4):469–76.

    Article  CAS  PubMed  Google Scholar 

  36. Kubitza D, Becka M, Mueck W, et al. Co-administration of rivaroxaban: a novel, oral direct factor Xa inhibitor—and clopidogrel in healthy subjects [abstract no. P1272]. Eur Heart J. 2007;28(Suppl 1):189.

    Google Scholar 

  37. Kubitza D, Becka M, Zuehlsdorf M, et al. Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects. J Clin Pharmacol. 2006;46(5):549–58.

    Article  CAS  PubMed  Google Scholar 

  38. Weinz C, Schwarz T, Kubitza D, et al. Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2009;37(5):1056–64.

    Article  CAS  PubMed  Google Scholar 

  39. Kubitza D, Becka M, Roth A, et al. The influence of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban: an oral, direct factor Xa inhibitor. J Clin Pharmacol. 2013;53(3):249–55.

    Article  PubMed  Google Scholar 

  40. Kubitza D, Becka M, Zuehlsdorf M, et al. Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol. 2007;47(2):218–26.

    Article  CAS  PubMed  Google Scholar 

  41. Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455–66.

    Article  CAS  PubMed  Google Scholar 

  42. Buller HR, Lensing AW, Prins MH, et al. A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the EINSTEIN-DVT dose-ranging study. Blood. 2008;112(6):2242–7.

    Article  CAS  PubMed  Google Scholar 

  43. EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–510.

    Article  Google Scholar 

  44. EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287–97.

    Article  Google Scholar 

  45. Prins MH, Lensing AW, Bauersachs R, et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013. doi:10.1186/1477-9560-11-21.

    Google Scholar 

  46. Prins M, Bamber L, Cano S, et al. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic pulmonary embolism [abstract no. 1163]. 54th ASH Annual Meeting and Exposition; 8–11 Dec 2012; Atlanta, GA.

  47. Prins M, Erkens P, Lensing A. Incidence of recurrent venous thromboembolism in patients following completion of the EINSTEIN DVT and EINSTEIN PE studies [abstract no. OC 79.4]. XXIV Congress of the International Society on Thrombosis and Haemostasis; 29 Jun–4 Jul 2013; Amsterdam.

  48. Prins MH, Bounameaux H, Lensing A, et al. The effect of prerandomization use of therapeutic anticoagulants on the risk of recurrent venous thromboembolism in patients with deep vein thrombosis treated with rivaroxaban [abstract no. P-TH-286]. J Thromb Haemost. 2011;9(Suppl 2):860.

    Google Scholar 

  49. Prins MH, Lensing AWA, Wells P, et al. The relative efficacy of rivaroxaban vs. vitamin K antagonists (VKA) in relation to time in therapeutic range (TTR) in patients with deep vein thrombosis (DVT) [abstract no. P-TH-281]. J Thromb Haemost. 2011;9(Suppl 2):858.

    Google Scholar 

  50. Bamber L, Wang MY, Prins MH, et al. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Thromb Haemost. 2013. doi:10.1160/TH13-03-0243.

    PubMed  Google Scholar 

  51. European Medicines Agency. Xarelto-H-C-944-II-18: EPAR: Assessment Report—Variation 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000944/WC500138505.pdf. Accessed 13 Dec 2013.

  52. Wasserlauf G, Grandi SM, Filion KB, et al. Meta-analysis of rivaroxaban and bleeding risk. Am J Cardiol. 2013;112(3):454–60.

    Article  CAS  PubMed  Google Scholar 

  53. Davidson B, Verheijen S, Lensing A, et al. Risk of bleeding in patients with acute venous thromboembolism treated with rivaroxaban or enoxaparin/VKA and concomitant ASA therapy or NSAIDs: subanalysis from EINSTEIN DVT and PE studies [abstract no. AS 17.1]. XXIV Congress of the International Society on Thrombosis and Haemostasis; 29 Jun–4 Jul 2013; Amsterdam.

  54. Seaman CD, Smith KJ, Ragni MV. Cost-effectiveness of rivaroxaban versus warfarin anticoagulation for the prevention of recurrent venous thromboembolism: a U.S. perspective. Thromb Res. 2013. doi:10.1016/j.thromres.2013.09.015.

    PubMed  Google Scholar 

  55. National Institute for Health and Clinical Excellence. Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism. 2013. http://www.nice.org.uk/nicemedia/live/14192/64274/64274.pdf. Accessed 13 Dec 2013.

  56. Lefebvre P, Coleman CI, Bookhart BK, et al. Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism. J Med Econ. 2013. doi:10.3111/13696998.2013.858634.

    Google Scholar 

  57. Scottish Medicines Consortium. Rivaroxaban 15 mg and 20 mg film-coated tablets (Xarelto®) SMC No. (852/13). 2013. http://www.scottishmedicines.org.uk/files/advice/rivaroxaban_Xarelto_FINAL_FEBRUARY_2013_amended_04.03.13_for_website.pdf. Accessed 13 Dec 2013.

  58. McLeod E, Guillermin A, Hudson R, et al. Cost-effectiveness of rivaroxaban for the treatment of pulmonary embolism and secondary prevention of venous thromboembolism: a UK perspective [abstract no. OC 02.6]. XXIV Congress of the International Society on Thrombosis and Haemostasis; 29 Jun–4 Jul 2013; Amsterdam.

  59. Becattini C, Agnelli G, Emmerich J, et al. Initial treatment of venous thromboembolism. Thromb Haemost. 2006;96(3):242–50.

    CAS  PubMed  Google Scholar 

  60. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(Suppl 2):e44S–88S.

    Google Scholar 

  61. Hutten BA, Lensing AW, Kraaijenhagen RA, et al. Safety of treatment with oral anticoagulants in the elderly. A systematic review. Drugs Aging. 1999;14(4):303–12.

    CAS  PubMed  Google Scholar 

  62. Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484–8.

    Article  CAS  PubMed  Google Scholar 

  63. Gogarten W, Vandermeulen E, Van Aken H, et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol. 2010;27(12):999–1015.

    Article  CAS  PubMed  Google Scholar 

  64. Rosencher N, Llau JV, Mueck W, et al. Incidence of neuraxial haematoma after total hip or knee surgery: RECORD programme (rivaroxaban vs. enoxaparin). Acta Anaesthesiol Scand. 2013;57(5):565–72.

    Article  CAS  PubMed  Google Scholar 

  65. Bayer. Treatment of an acute deep vein thrombosis (DVT) with either rivaroxaban or current standard of care therapy (XALIA) [ClinicalTrials.gov identifier NCT01619007]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/ct2/show/NCT01619007. Accessed 13 Dec 2013.

  66. Thrombosis Research Institute. About GARFIELD VTE. 2013. http://www.tri-london.ac.uk/uploads/files/GARFIELD%20VTE%20Study%20Overview.pdf. Accessed 13 Dec 2013.

  67. Donadini MP, Ageno W, Douketis JD. Management of bleeding in patients receiving conventional or new anticoagulants: a practical and case-based approach. Drugs. 2012;72(15):1965–75.

    Article  CAS  PubMed  Google Scholar 

  68. Fareed J, Sadeghi N, Kahn D, et al. Tissue factor mediated activation of prothrombin complex concentrates (PCCs) is differently inhibited by dabigatran, rivaroxaban and apixaban: potential clinical implications [abstract no. 3410]. 54th ASH Annual Meeting and Exposition; 8–11 Dec 2012; Atlanta, GA.

  69. Godier A, Miclot A, Le Bonniec B, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology. 2012;116(1):94–102.

    Article  CAS  PubMed  Google Scholar 

  70. Gruber A, Marzec UM, Buetehorn U, et al. Reversal of the antihaemostatic effects of rivaroxaban by activated factor VII and activated prothrombin complex in primates [abstract no. 3825]. American Society of Hematology (ASH) 50th Annual Meeting and Exposition; Jun 2009; San Francisco, CA.

  71. Gruber A, Marzec UM, Buetehorn U, et al. Activated factor VII and activated prothrombin complex for reversal of the antihaemostatic effects of rivaroxaban in primates [abstract no. 80]. Br J Haematol. 2009;145(Suppl S1):32.

    Google Scholar 

  72. Hollenbach S, Lu G, Tan S, et al. PRT064445 but not recombinant FVIIa reverses rivaroxaban induced anticoagulation as measured by reduction in blood loss in a rabbit liver laceration model [abstract no. 3414]. 54th ASH Annual Meeting and Exposition; 8–11 Dec 2012; Atlanta, GA.

  73. Perzborn E, Tinel H. Prothrombin complex concentrate reverses the effects of high-dose rivaroxaban in rats [abstract no. PP-MO-183]. XXII ISTH Congress; 11–16 Jul 2009; Boston, MA.

  74. Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573–9.

    Article  CAS  PubMed  Google Scholar 

  75. Levi M, Moore T, Castillejos C, et al. Effects of three-factor and four-factor prothrombin complex concentrates on the pharmacodynamics of rivaroxaban [abstract no. OC 36.5]. XXIV Congress of the International Society on Thrombosis and Haemostasis; 29 Jun–4 Jul 2013; Amsterdam.

  76. Portola Pharmaceuticals. Phase 2 healthy volunteer study to evaluate the ability of PRT064445 to reverse the effects of several blood thinner drugs on laboratory tests [ClinicalTrials.gov identifier NCT01758432]. US National Institutes of Health, ClinicalTrials.gov. 2012. http://clinicaltrials.gov/ct2/show/NCT01758432. Accessed 13 Dec 2013.

  77. Crowther M, Mathur V, Kitt M. A phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of rivaroxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), an antidote for FXa inhibitors [abstract no. 3636]. 55th ASH Annual Meeting and Exposition; 7–10 Dec 2013; New Orleans, LA.

  78. Baglin T, Keeling D, Kitchen S. Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: guidance from the British Committee for Standards in Haematology. Br J Haematol. 2012;159(4):427–9.

    Article  CAS  PubMed  Google Scholar 

  79. Samama MM, Martinoli JL, LeFlem L, et al. Assessment of laboratory assays to measure rivaroxaban: an oral, direct factor Xa inhibitor. Thromb Haemost. 2010;103(4):815–25.

    Article  CAS  PubMed  Google Scholar 

  80. Samama MM, Contant G, Spiro TE, et al. Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls. Thromb Haemost. 2012;107(2):379–87.

    Article  CAS  PubMed  Google Scholar 

  81. Brandjes DP, Heijboer H, Buller HR, et al. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med. 1992;327(21):1485–9.

    Article  CAS  PubMed  Google Scholar 

  82. Fiessinger JN, Huisman MV, Davidson BL, et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA. 2005;293(6):681–9.

    Article  CAS  PubMed  Google Scholar 

  83. Boehringer Ingelheim Limited. Pradaxa: summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf. Accessed 13 Dec 2013.

  84. Boehringer Ingelheim Pharmaceuticals Inc. Pradaxa® (dabigatran etexilate mesylate capsules): US prescribing information. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022512s017lbl.pdf. Accessed 13 Dec 2013.

  85. Bristol-Myers Squibb, Pfizer EEIG. Eliquis® (apixaban) Summary of Product Characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. Accessed 13 Dec 2013.

  86. Daiichi Sankyo Company Ltd. Daiichi Sankyo receives first market approval in Japan for LIXIANA(R) (edoxaban), a direct oral factor Xa inhibitor, for the prevention of venous thromboembolism after major orthopedic surgery [media release]. 22 Apr 2011. http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/005806.html.

  87. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–52.

    Article  CAS  PubMed  Google Scholar 

  88. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.

    Article  CAS  PubMed  Google Scholar 

  89. The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406–15.

    Article  Google Scholar 

  90. Wong PC, Crain EJ, Watson CA, et al. Comparative antithrombotic and antihemostatic effects of the direct factor Xa inhibitors, apixaban and rivaroxaban, and the direct thrombin inhibitors, dabigatran and lepirudin, in rabbit models of venous thrombosis and bleeding time [abstract no. 3025]. 50th American Society of Hematology Annual Meeting and Exposition; 2008 Dec 6–9 2008; San Francisco, CA.

  91. Fox BD, Kahn SR, Langleben D, et al. Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials. BMJ. 2012;345:e7498.

    Article  PubMed Central  PubMed  Google Scholar 

  92. Sardar P, Chatterjee S, Mukherjee D. Efficacy and safety of new oral anticoagulants for extended treatment of venous thromboembolism: systematic review and meta-analyses of randomized controlled trials. Drugs. 2013;73(11):1171–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Celeste B. Burness & Caroline M. Perry

Authors
  1. Celeste B. Burness
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Celeste B. Burness.

Additional information

The manuscript was reviewed by: T.L. Carman, Department of Cardiovascular Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA; A.T. Cohen, Department of Haematological Medicine, King’s College Hospital, London, UK; W. Dietrich, Institute for Research in Cardiac Anesthesia, Munich, Germany; J. Fareed, Departments of Pathology & Pharmacology, Loyola University Chicago, Maywood, IL, USA; J.J. Harenberg, Department of Clinical Pharmacology, University Hospital Mannheim, Mannheim, Germany; A. Squizzato, Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Varese, Italy

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burness, C.B., Perry, C.M. Rivaroxaban: A Review of Its Use in the Treatment of Deep Vein Thrombosis or Pulmonary Embolism and the Prevention of Recurrent Venous Thromboembolism. Drugs 74, 243–262 (2014). https://doi.org/10.1007/s40265-013-0174-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-013-0174-4

Keywords

Search

Navigation