Rivaroxaban for thromboprophylaxis in patients undergoing major orthopedic surgery.
OBJECTIVE
To review the pharmacology, pharmacokinetics, and clinical efficacy/safety profile of rivaroxaban to inform health-care professionals of this new agent for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery.


METHODS
A literature search was performed in PubMed/MEDLINE (1966-March 2010), International Pharmaceutical Abstracts (1970-March 2010), and EMBASE (1990-March 2010), limited to publications in English, using the search terms BAY 59-7939, rivaroxaban, factor Xa inhibitor, hip replacement, and/or knee replacement to identify literature sources. References from retrieved articles were evaluated to identify relevant literature. Unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidance, and advisory committee briefing packets.


METHODS
All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of rivaroxaban for the prevention of VTE in patients undergoing major orthopedic surgery were included, with preference for clinical data.


RESULTS
Rivaroxaban use was significantly more effective for thromboprophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR), compared to enoxaparin for the composite incidence of deep vein thrombosis, nonfatal pulmonary embolism, all-cause mortality, and the rate of major VTE; bleeding events occurred at statistically similar rates. In Phase 3 studies, rivaroxaban 10 mg was administered orally 6-8 hours post-surgery and post-hemostasis. Thereafter, administration was once daily for 35 days in THR and 10-14 days in TKR.


CONCLUSIONS
Rivaroxaban has demonstrated comparable safety and superior efficacy to the commonly used low-molecular-weight heparin, enoxaparin. Ongoing and future clinical trials will allow clinicians to further assess the efficacy, safety, and pharmacoeconomics of rivaroxaban.
Melillo
Stephanie N
SN
Biogen Idec/Massachusetts College of Pharmacy and Health Sciences, School of Pharmacy-Worcester-Manchester, Worcester, MA 01608, USA. stephanie.melillo@mcphs.edu
Scanlon
James V
JV
Exter
Benjamin P
BP
Steinberg
Michael
M
Jarvis
Courtney I
CI
D000818:Animals; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage* / Q000737:chemistry; D019637:Orthopedic Procedures / Q000009:adverse effects*; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban