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Xarelto (rivaroxaban)

Company: Bayer
Approval Status: Approved July 2011
Treatment for: prophylaxis of deep vein thrombosis during knee or hip replacement surgery
Areas: Cardiovascular / Cardiology; Hematology
Possible similar drugs: Xarelto

| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |


General Information

Xarelto (rivaroxaban) is a factor Xa inhibitor that selectively blocks the active site of factor Xa and does not require a cofactor (such as Anti-thrombin III) for activity. Activation of factor X to factor Xa (FXa) via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation.

Xarelto is specifically indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery.

Xarelto is supplied as a tablet for oral administration. The recommended initial dose is 10 mg taken orally once daily with or without food. The initial dose should be taken at least 6 to 10 hours after surgery once hemostasis has been established. For hip replacement surgery a treatment duration of 35 days is recommended. For knee replacement surgery a treatment duration of 12 days is recommended.


Clinical Results

FDA Approval
The FDA approval of Xarelto was based on three trials, RECORD 1, 2, and 3, conducted in 9,011 subjects.
RECORD 1 and 2
These randomized, double-blind studies enrolled 6,727 subjects undergoing elective total hip replacement surgery. The trials compared Xarelto 10 mg once daily starting at least 6 to 8 hours after wound closure versus enoxaparin 40 mg once daily started 12 hours preoperatively. In RECORD 1, the mean exposure duration to active Xarelto and enoxaparin was 33.3 and 33.6, respectively. In RECORD 2, the mean exposure duration to active Xarelto and enoxaparin was 33.5 and 12.4, respectively. After Day 13, oral placebo was continued in the enoxaparin group for the remainder of the double-blind study duration.
RECORD 1 Results
The study met its primary endpoint, demonstrating a 71% relative risk reduction (RRR) (p<0.001) in total VTE (composite of deep vein thrombosis, non-fatal pulmonary embolism and all-cause mortality) for the rivaroxaban arm compared to the enoxaparin arm (1.1% and 3.9%, respectively). The secondary endpoint was also achieved, with a 91% RRR (p<0.001) in major VTE (composite of proximal deep vein thrombosis, non-fatal pulmonary embolism and VTE-related death) observed in the rivaroxaban arm versus the enoxaparin arm (0.2% and 2.1%, respectively). Rivaroxaban also demonstrated a similar rate of major bleeding to enoxaparin (0.3% and 0.1%, respectively, p=0.178).
RECORD 2 Results
Data showed a 76% RRR (p<0.001) in total VTE and an 87% RRR (p<0.001) in major VTE for subjects treated with rivaroxaban compared with those treated with enoxaparin. Rivaroxaban demonstrated a similar rate of major bleeding compared to enoxaparin (0.1% and 0.1%, respectively, p=0.980).
RECORD 3
This randomized, double-blind study enrolled 1,684 subjects undergoing elective total knee replacement surgery. The trial compared Xarelto 10 mg once daily started at least 6 to 8 hours after wound closure versus enoxaparin 40 mg once daily started 12 hours preoperatively. The mean exposure duration to active Xarelto and enoxaparin was 11.9 and 12.5 days, respectively. Subjects treated with Xarelto demonstrated a 48% relative risk reduction in total DVT, pulmonary embolism (PE) and all-cause mortality when compared to enoxaparin (p<0.001). Major VTE occurred in 1.0% of the Xarelto-treated group and in 2.6% of the enoxaparin-treated group (p=0.01) with a relative risk reduction of 62%. Symptomatic VTE occurred in 1.0% of subjects who received Xarelto, compared to 2.5% of those in the enoxaparin group, a relative risk reduction of 60%. Major bleeding rates were 0.6% and 0.5%, and any bleeding rates were 4.9% and 4.8% for the Xarelto and enoxaparin groups, respectively.


Side Effects

Adverse events associated with the use of Xarelto may include, but are not limited to, the following:

  • major bleeding events
  • wound secretion
  • pruritus


Mechanism of Action

Xarelto (rivaroxaban) is a factor Xa inhibitor that selectively blocks the active site of factor Xa and does not require a cofactor (such as Anti-thrombin III) for activity. Activation of factor X to factor Xa (FXa) via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation.


Literature References

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. New England Journal of Medicine 2008 Jun 26;358(26):2765-75

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 Jul 5;372(9632):31-9

Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. New England Journal of Medicine 2008 Jun 26;358(26):2776-86


Additional Information

For additional information regarding Xarelto or the prophylaxis of deep vein thrombosis in patients undergoing knee or hip replacement surgery, please visit the Xarelto web page.




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Xarelto Drug Information

The Xarelto drug information shown above is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.





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