Journal ArticleDOI
Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention.
Wolfgang Mueck,Anthonie W. A. Lensing,Giancarlo Agnelli,Hervé Decousus,Paolo Prandoni,Frank Misselwitz +5 more
TLDR
In this paper, a population pharmacokinetic model was developed using plasma samples from these patients and various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with atrial fibrillation.Abstract:
Background and objective Rivaroxaban is an oral, direct Factor Xa inhibitor, which is at an advanced stage of clinical development for prevention and treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or twice daily) for treatment of acute deep-vein thrombosis (DVT). Population pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these two phase II studies were conducted to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban and the relationship between important patient covariates and model parameters. Exposure simulations in patients with atrial fibrillation (AF) were also performed in order to predict the exposure of rivaroxaban, using modified demographic data reflecting the characteristics of a typical AF population. Methods A population pharmacokinetic model was developed using plasma samples from these patients. Various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with AF. Correlations between plasma rivaroxaban concentrations and the prothrombin time, Factor Xa activity, HepTest® and activated partial thromboplastin time were also described. Results The pharmacokinetics of rivaroxaban in patients with DVT were found to be consistent and predictable across all doses studied. The area under the plasma concentration-time curve (AUC) increased dose dependently. The same total daily doses given once daily achieved higher maximum plasma concentration (C(max)) values (∼20%) and lower trough (minimum) plasma concentration (C(trough)) values (∼60%) than when given twice daily; however, the 5th-95th percentile ranges for these parameters overlapped. Rivaroxaban clearance was moderately influenced by age and renal function, and the volume of distribution was influenced by age, body weight and sex; the effects were within the observed interindividual variability. Simulations in virtual patient populations with AF showed that a rivaroxaban dose of 15 mg once daily in patients with creatinine clearance of 30-49 mL/min would achieve AUC and C(max) values similar to those observed with 20 mg once daily in patients with normal renal function. The prothrombin time correlated almost linearly with plasma rivaroxaban concentrations (≤500 μg/L). Conclusion Population analyses of phase II clinical data indicated that the pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable and were affected by expected demographic factors in patients with acute DVT.read more
Citations
More filters
Journal ArticleDOI
Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism
Barry F. Jacobson,Erich Minar,Jaromir Chlumsky,Peter Verhamme,Phil Wells,Giancarlo Agnelli,Alexander T. Cohen,Scott D. Berkowitz,Bruce L. Davidson,Frank Misselwitz,Gary E. Raskob,Annelise Segers +11 more
TL;DR: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile.
Journal ArticleDOI
The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.
Jan Steffel,Peter Verhamme,Tatjana S. Potpara,Pierre Albaladejo,M Antz,Lien Desteghe,Karl Georg Haeusler,Jonas Oldgren,Holger Reinecke,Roldan-Schilling,Nigel Rowell,Peter Sinnaeve,Ronan Collins,Alan John Camm,Hein Heidbuchel +14 more
TL;DR: Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on antICOagulation.
Journal ArticleDOI
Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.
Hein Heidbuchel,Peter Verhamme,Marco Alings,Matthias Antz,Hans-Christoph Diener,Werner Hacke,Jonas Oldgren,Peter Sinnaeve,A. John Camm,Paulus Kirchhof,Paulus Kirchhof +10 more
TL;DR: The current manuscript is an update of the original Practical Guide, published in June 2013, and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence.
Journal ArticleDOI
European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation
Hein Heidbuchel,Peter Verhamme,Marco Alings,Matthias Antz,Werner Hacke,Jonas Oldgren,Peter Sinnaeve,A. John Camm,Paulus Kirchhof,Paulus Kirchhof +9 more
TL;DR: New oral anticoagulant drugs are an alternative for vitamin K antagonists to prevent stroke in patients with non-valvular atrial fibrillation (AF) and many unresolved questions on how to optimally use these drugs in specific clinical situations remain.
Journal ArticleDOI
Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment
Keith A.A. Fox,Jonathan P. Piccini,Daniel Wojdyla,Richard C. Becker,Jonathan L. Halperin,Christopher C. Nessel,John F. Paolini,Graeme J. Hankey,Kenneth W. Mahaffey,Manesh R. Patel,Daniel E. Singer,Robert M. Califf +11 more
TL;DR: Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin, and there was no evidence of heterogeneity in treatment effect across dosing groups.
References
More filters
Journal ArticleDOI
Prediction of Creatinine Clearance from Serum Creatinine
Donald W. Cockcroft,M H Gault +1 more
TL;DR: A formula has been developed to predict Creatinine clearance from serum creatinine (Scr) in adult males: Ccr = (140 – age) (wt kg)/72 × Scr (mg/100ml) (15% less i).
Journal ArticleDOI
Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.
Alan S. Go,Elaine M. Hylek,Kathleen A. Phillips,Yuchiao Chang,Lori E. Henault,Joe V. Selby,Daniel E. Singer +6 more
TL;DR: It is confirmed that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States.
Journal ArticleDOI
Oral rivaroxaban for symptomatic venous thromboembolism
Rupert Bauersachs,Scott D. Berkowitz,Benjamin Brenner,Harry R. Buller,Hervé Decousus,Alexander Gallus,Anthonie W. A. Lensing,Frank Misselwitz,Martin H. Prins,Gary E. Raskob,Annelise Segers,Peter Verhamme,Phil Wells,Giancarlo Agnelli,Henri Bounameaux,Alexander T. Cohen,Bruce L. Davidson,Franco Piovella,Sebastian Schellong +18 more
TL;DR: Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation.
Journal ArticleDOI
Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
TL;DR: Guyatt et al. as mentioned in this paper presented the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) and provided specific management recommendations for the first 1 or 2 days for most individuals.
Journal ArticleDOI
Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
Clive Kearon,Susan R. Kahn,Giancarlo Agnelli,Samuel Z. Goldhaber,Gary E. Raskob,Anthony J. Comerota +5 more
TL;DR: This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) and indicates that the benefits do or do not outweigh risks, burden, and costs.
Related Papers (5)
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation
Dabigatran versus warfarin in patients with atrial fibrillation
Oral rivaroxaban for symptomatic venous thromboembolism
Rupert Bauersachs,Scott D. Berkowitz,Benjamin Brenner,Harry R. Buller,Hervé Decousus,Alexander Gallus,Anthonie W. A. Lensing,Frank Misselwitz,Martin H. Prins,Gary E. Raskob,Annelise Segers,Peter Verhamme,Phil Wells,Giancarlo Agnelli,Henri Bounameaux,Alexander T. Cohen,Bruce L. Davidson,Franco Piovella,Sebastian Schellong +18 more
Apixaban versus Warfarin in Patients with Atrial Fibrillation
Christopher B. Granger,John H. Alexander,Renato D. Lopes,Elaine M. Hylek,Michael G. Hanna,Hussein R. Al-Khalidi,Jack Ansell,Dan Atar,Alvaro Avezum,M. Cecilia Bahit,Rafael Diaz,J. Donald Easton,Justin A. Ezekowitz,Greg C. Flaker,David A. Garcia,Margarida Geraldes,Bernard J. Gersh,Sergey P. Golitsyn,Shinya Goto,Antonio G. Hermosillo,Stefan H. Hohnloser,John D. Horowitz,Puneet Mohan,Petr Jansky,Basil S. Lewis,Jose Lopez-Sendon,Prem Pais,Alexander Parkhomenko,Jun Zhu,Lars Wallentin +29 more