Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 14/2014

Open Access 01-09-2014 | Review Article

Clinical Use of Rivaroxaban: Pharmacokinetic and Pharmacodynamic Rationale for Dosing Regimens in Different Indications

Authors: Toby Trujillo, Paul P. Dobesh

Published in: Drugs | Issue 14/2014

Login to get access

Abstract

Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily dose is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery, the long-term prevention of stroke in patients with non-valvular atrial fibrillation, and the long-term secondary prevention of recurrent VTE. Twice-daily dosing is required in the acute phase of treatment in patients with VTE and in the combination of rivaroxaban with standard single or dual antiplatelet therapy for secondary prevention after acute coronary syndrome events. This article reviews the empirical and clinical rationale supporting the dose regimens of rivaroxaban in each clinical setting.
Literature
1.
2.
3.
4.
5.
6.
7.
Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e44S–88S.PubMedCrossRefPubMedCentral
8.
9.
Wong PC, Pinto DJ, Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis. 2011;31:478–92.PubMedCrossRefPubMedCentral
10.
Perzborn E, Roehrig S, Straub A, Kubitza D, Misselwitz F. The discovery and development of rivaroxaban, an oral, direct Factor Xa inhibitor. Nat Rev Drug Discov. 2011;10:61–75.PubMedCrossRef
11.
Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct Factor Xa inhibitor. Clin Pharmacol Ther. 2005;78:412–21.PubMedCrossRef
12.
Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. 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;61:873–80.PubMedCrossRef
13.
Kubitza D, Becka M, Roth A, Mueck W. The influence of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban—an oral, direct Factor Xa inhibitor. J Clin Pharmacol. 2013;53:249–55.PubMedCrossRef
14.
Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs and humans. Drug Metab Dispos. 2009;37:1056–64.PubMedCrossRef
15.
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;76:455–66.PubMedCrossRefPubMedCentral
16.
Mueck W, Becka M, Kubitza D, Voith B, Zuehlsdorf M. Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban—an oral, direct Factor Xa inhibitor—in healthy subjects. Int J Clin Pharmacol Ther. 2007;45:335–44.PubMedCrossRef
17.
Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin. 2008;24:2757–65.PubMedCrossRef
18.
Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol. 2007;47:218–26.PubMedCrossRef
19.
Jiang J, Hu Y, Zhang J, Yang J, Mueck W, Kubitza D, Bauer RJ, Meng L, Hu P. Safety, pharmacokinetics and pharmacodynamics of single doses of rivaroxaban—an oral, direct Factor Xa inhibitor—in elderly Chinese subjects. Thromb Haemost. 2010;103:234–41.PubMedCrossRef
20.
Zhao X, Sun P, Zhou Y, Liu Y, Zhang H, Mueck W, Kubitza D, Bauer RJ, Zhang H, Cui Y. Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects. Br J Clin Pharmacol. 2009;68:77–88.PubMedCrossRefPubMedCentral
21.
Graff J, von Hentig N, Misselwitz F, Kubitza D, Becka M, Breddin HK, Harder S. Effects of the oral, direct Factor Xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity. J Clin Pharmacol. 2007;47:1398–407.PubMedCrossRef
22.
23.
Kubitza D, Becka M, Mueck W, Halabi A, Maatouk H, Klause N, Lufft V, Wand DD, Philipp T, Bruck H. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2010;70:703–12.PubMedCrossRefPubMedCentral
24.
Kubitza D, Roth A, Becka M, Alatrach A, Halabi A, Hinrichsen H, Mueck W. 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;76:89–98.PubMedCrossRefPubMedCentral
25.
Kubitza D, Becka M, Zuehlsdorf M, Mueck W. 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;46:549–58.PubMedCrossRef
26.
Stampfuss J, Kubitza D, Becka M, Mueck W. The effect of food on the absorption and pharmacokinetics of rivaroxaban. Int J Clin Pharmacol Ther. 2013;51:549–61.PubMedCrossRef
27.
Kubitza D, Becka M, Roth A, Mueck W. Absence of clinically relevant interactions between rivaroxaban—an oral, direct Factor Xa inhibitor—and digoxin or atorvastatin in healthy subjects. J Int Med Res. 2012;40:1688–707.PubMedCrossRef
28.
Kubitza D, Becka M, Schwers S, Voith B. Investigation of pharmacodynamic and pharmacokinetic interactions between rivaroxaban and enoxaparin in healthy male subjects. Clin Pharmacol Drug Dev. 2013;2:270–7.CrossRef
29.
Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Rivaroxaban (BAY 59-7939)—an oral, direct Factor Xa inhibitor—has no clinically relevant interaction with naproxen. Br J Clin Pharmacol. 2007;63:469–76.PubMedCrossRefPubMedCentral
30.
Kubitza D, Becka M, Mueck W, Schwers S. Effect of co-administration of rivaroxaban and clopidogrel on bleeding time, pharmacodynamics and pharmacokinetics: a phase I study. Pharmaceuticals (Basel). 2012;5:279–96.PubMedCrossRefPubMedCentral
31.
Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban—an oral, direct Factor Xa inhibitor—are not affected by aspirin. J Clin Pharmacol. 2006;46:981–90.PubMedCrossRef
32.
Lang D, Freudenberger C, Weinz C. In vitro metabolism of rivaroxaban—an oral, direct Factor Xa inhibitor—in liver microsomes and hepatocytes of rat, dog and man. Drug Metab Dispos. 2009;37:1046–55.PubMedCrossRef
33.
Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:381S–453S.PubMedCrossRef
34.
Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW Jr. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e278S–325S.PubMedCrossRefPubMedCentral
35.
Wilke T, Muller S. Non-adherence in outpatient thromboprophylaxis after major orthopedic surgery: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2010;10:691–700.PubMedCrossRef
36.
Turpie AGG, Fisher WD, Bauer KA, Kwong LM, Irwin MW, Kälebo P, Misselwitz F, Gent M, ODXIa-Knee Study Group. BAY 59-7939: an oral, direct Factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. J Thromb Haemost. 2005;3:2479–86.PubMedCrossRef
37.
Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Muehlhofer E, Dierig C, Misselwitz F, Kälebo P, ODIXa-HIP Study Investigators. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation. 2006;114:2374–81.PubMedCrossRef
38.
Eriksson BI, Borris L, Dahl OE, Haas S, Huisman MV, Kakkar AK, Misselwitz F, Kälebo P, ODIXa-HIP Study Investigators. Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost. 2006;4:121–8.PubMedCrossRef
39.
Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Misselwitz F, Muehlhofer E, Kälebo P. Dose-escalation study of rivaroxaban (BAY 59-7939)—an oral, direct Factor Xa inhibitor—for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Res. 2007;120:685–93.PubMedCrossRef
40.
Mueck W, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Kälebo P, Muelhofer E, Misselwitz F, Eriksson BI. Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Haemost. 2008;100:453–61.PubMed
41.
Mueck W, Eriksson BI, Bauer KA, Borris L, Dahl OE, Fisher WD, Gent M, Haas S, Huisman MV, Kakkar AK, Kälebo P, Kwong LM, Misselwitz F, Turpie AGG. Population pharmacokinetics and pharmacodynamics of rivaroxaban—an oral, direct Factor Xa inhibitor—in patients undergoing major orthopaedic surgery. Clin Pharmacokinet. 2008;47:203–16.PubMedCrossRef
42.
Turpie AGG, Lassen MR, Eriksson BI, Gent M, Berkowitz SD, Misselwitz F, Bandel TJ, Homering M, Westermeier T, Kakkar AK. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost. 2011;105:444–53.PubMedCrossRef
43.
Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W, RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765–75.PubMedCrossRef
44.
Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S, RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372:31–9.PubMedCrossRef
45.
Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AGG, RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776–86.PubMedCrossRef
46.
Turpie AGG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD, RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373:1673–80.PubMedCrossRef
47.
Eriksson BI, Kakkar AK, Turpie AGG, Gent M, Bandel TJ, Homering M, Misselwitz F, Lassen MR. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Jt Surg Br. 2009;91:636–44.CrossRef
48.
Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK, Mottier D, Oger E, Samama MM, Spannagl M, VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756–64.PubMed
49.
Heit JA, Cohen AT, Anderson FA, on behalf of the VTE Impact Assessment Group. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood (ASH Annual Meeting Abstracts). 2005;106. (Abstract 910).
50.
Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Zamorano JL, Andreotti F, Ascherman M, Athanassopoulos G, De Sutter J, Fitzmaurice D, Forster T, Heras M, Jondeau G, Kjeldsen K, Knuuti J, Lang I, Lenzen M, Lopez-Sendon J, Nihoyannopoulos P, Perez Isla L, Schwehr U, Torraca L, Vachiery JL. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29:2276–315.PubMedCrossRef
51.
Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. 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:e419S–94S.PubMedCrossRefPubMedCentral
52.
Buller HR, Lensing AW, Prins MH, Agnelli G, Cohen A, Gallus AS, Misselwitz F, Raskob G, Schellong S, Segers A. 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;112:2242–7.PubMedCrossRef
53.
Agnelli G, Gallus A, Goldhaber SZ, Haas S, Huisman MV, Hull RD, Kakkar AK, Misselwitz F, Schellong S, ODIXa-DVT Study Investigators. 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;116:180–7.PubMedCrossRef
54.
Fiessinger JN, Huisman MV, Davidson BL, Bounameaux H, Francis CW, Eriksson H, Lundström T, Berkowitz SD, Nyström P, Thorsén M, Ginsberg JS, THRIVE Treatment Study Investigators. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA. 2005;293:681–9.PubMedCrossRef
55.
van Gogh Investigators, Büller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M, Pillion G, Piovella F, Prins MH, Raskob GE. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med. 2007;357:1094–104.PubMedCrossRef
56.
Mueck W, Lensing AW, Agnelli G, Decousus H, Prandoni P, Misselwitz F. 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;50:675–86.PubMedCrossRef
57.
The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.CrossRef
58.
59.
The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97.CrossRef
60.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–245.PubMedCrossRef
61.
Camm AJ, Kirchhof P, Lip GYH, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH, Vahanian A, Auricchio A, Bax J, Ceconi C, Dean V, Filippatos G, Funck-Brentano C, Hobbs R, Kearney P, McDonagh T, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas PE, Widimsky P, Vardas PE, Agladze V, Aliot E, Balabanski T, Blomstrom-Lundqvist C, Capucci A, Crijns H, Dahlof B, Folliguet T, Glikson M, Goethals M, Gulba DC, Ho SY, Klautz RJ, Kose S, McMurray J, Perrone Filardi P, Raatikainen P, Salvador MJ, Schalij MJ, Shpektor A, Sousa J, Stepinska J, Uuetoa H, Zamorano JL, Zupan I. Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369–429.PubMedCrossRef
62.
Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006;114:119–25.PubMedCrossRef
63.
Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D’Agostino RB, Larson MG, Kannel WB, Benjamin EJ. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290:1049–56.PubMedCrossRef
64.
Bae JP, Dobesh PP, Klepser DG, Anderson JD, Zagar AJ, McCollam PL, Tomlin ME. Adherence and dosing frequency of common medications for cardiovascular patients. Am J Manag Care. 2012;18:139–46.PubMed
65.
Halperin JL, Executive Steering Committee SPORTIF III and V Study Investigators. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with non-valvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J. 2003;146:431–8.PubMedCrossRef
66.
Executive Steering Committee of behalf of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet. 2003;362:1691–8.CrossRef
67.
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KAA, Califf RM, ROCKET AF Investigators. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011;365:883–91.PubMedCrossRef
68.
Mueck W, Schwers S, Stampfuss J. Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. Thromb J. 2013;11:10.PubMedCrossRefPubMedCentral
69.
Grech ED, Ramsdale DR. Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction. Br Med J. 2003;326:1259–61.CrossRef
70.
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.PubMedCrossRef
71.
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.PubMedCrossRef
72.
Théroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992;327:141–5.PubMedCrossRef
73.
Merlini PA, Bauer KA, Oltrona L, Ardissino D, Cattaneo M, Belli C, Mannucci PM, Rosenberg RD. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation. 1994;90:61–8.PubMedCrossRef
74.
Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med. 2005;143:241–50.PubMedCrossRef
75.
Andreotti F, Testa L, Biondi-Zoccai GG, Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J. 2006;27:519–26.PubMedCrossRef
76.
Mega JL, Braunwald E, Mohanavelu S, Burton P, Poulter R, Misselwitz F, Hricak V, Barnathan ES, Bordes P, Witkowski A, Markov V, Oppenheimer L, Gibson CM. ATLAS ACS-TIMI 46 study group. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet. 2009;374:29–38.PubMedCrossRef
77.
Xu XS, Moore K, Burton P, Stuyckens K, Mueck W, Rossenu S, Plotnikov A, Gibson M, Vermeulen A. Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndromes. Br J Clin Pharmacol. 2012;74:86–97.PubMedCrossRefPubMedCentral
78.
Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA, Goto S, Murphy SA, Plotnikov AN, Schneider D, Sun X, Verheugt FW, Gibson CM, ATLAS ACS 2-TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9–19.PubMedCrossRef
79.
Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, Cohen A, Davidson B, Decousus H, Raskob GE, Berkowitz SD, Wells PS, On behalf of the EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11:21.PubMedCrossRefPubMedCentral
80.
Camm AJ, Lip GYH, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Vardas P, Al Attar N, Alfieri O, Angelini A, Blomstrom-Lundqvist C, Colonna P, De Sutter J, Ernst S, Goette A, Gorenek B, Hatala R, Heidbuchel H, Heldal M, Kristensen SD, Kolh P, Le Heuzey JY, Mavrakis H, Mont L, Filardi PP, Ponikowski P, Prendergast B, Rutten FH, Schotten U, Van Gelder IC, Verheugt FW. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33:2719–47.PubMedCrossRef
Metadata
Title
Clinical Use of Rivaroxaban: Pharmacokinetic and Pharmacodynamic Rationale for Dosing Regimens in Different Indications
Authors
Toby Trujillo
Paul P. Dobesh
Publication date
01-09-2014
Publisher
Springer International Publishing
Published in
Drugs / Issue 14/2014
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-014-0278-5

Other articles of this Issue 14/2014

Drugs 14/2014 Go to the issue

Letter to the Editor

Comment on “Treat-to-Target in Spondyloarthritis: Implications for Clinical Trial Designs”

R&D Insight Report

Ataluren: First Global Approval

Review Article

New Directions for Rabbit Antithymocyte Globulin (Thymoglobulin®) in Solid Organ Transplants, Stem Cell Transplants and Autoimmunity

Review Article

Turning a Molecule into a Medicine: the Development of Indacaterol as a Novel Once-Daily Bronchodilator Treatment for Patients with COPD

Adis Drug Evaluation

Omalizumab: A Review of Its Use in Patients with Chronic Spontaneous Urticaria

Adis Drug Evaluation

OnabotulinumtoxinA (Botox®): A Review of its Use in the Treatment of Urinary Incontinence in Patients with Multiple Sclerosis or Subcervical Spinal Cord Injury