XARELTO® (rivaroxaban) tablets Prophylaxis of DVT Following Hip or Knee Replacement Surgery The combined analysis of the RECORD 1-3 clinical efficacy studies did not show an increase in bleeding risk for patients with CrCl 30 to 50 mL/min and reported a possible increase in total venous thromboemboli in this population. Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with CrCl 30 to 50 mL/min. Avoid the use of XARELTO in patients with CrCl <30 mL/min. Reduction of Risk of Major Cardiovascular Events in Patients with Chronic CAD or PAD Patients with Chronic Kidney Disease not on Dialysis Patients with a CrCl <15 mL/min at screening were excluded from COMPASS, and limited data are available for patients with a CrCl of 15-30 mL/min. In patients with CrCl ≤30 mL/min, a dose of 2.5 mg XARELTO twice daily is expected to give an exposure similar to that in patients with moderate renal impairment [see Clinical Pharmacology (12.3) in Full Prescribing Information], whose efficacy and safety outcomes were similar to those with preserved renal function. Patients with End-Stage Renal Disease on Dialysis No clinical outcome data is available for the use of XARELTO with aspirin in patients with ESRD on dialysis since these patients were not enrolled in COMPASS. In patients with ESRD maintained on intermittent hemodialysis, administration of XARELTO 2.5 mg twice daily will result in concentrations of rivaroxaban and pharmacodynamic activity similar to those observed in moderate renal impaired patients in the COMPASS study [see Clinical Pharmacology (12.2, 12.3) in Full Prescribing Information]. It is not known whether these concentrations will lead to similar CV risk reduction and bleeding risk in patients with ESRD on dialysis as was seen in COMPASS. Hepatic Impairment In a pharmacokinetic study, compared to healthy subjects with normal liver function, AUC increases of 127% were observed in subjects with moderate hepatic impairment (Child-Pugh B). The safety or PK of XARELTO in patients with severe hepatic impairment (Child-Pugh C) has not been evaluated [see Clinical Pharmacology (12.3) in Full Prescribing Information]. Avoid the use of XARELTO in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy. OVERDOSAGE Overdose of XARELTO may lead to hemorrhage. Discontinue XARELTO and initiate appropriate therapy if bleeding complications associated with overdosage occur. Rivaroxaban systemic exposure is not further increased at single doses >50 mg due to limited absorption. The use of activated charcoal to reduce absorption in case of XARELTO overdose may be considered. Due to the high plasma protein binding, rivaroxaban is not dialyzable [see Warnings and Precautions and Clinical Pharmacology (12.3) in Full Prescribing Information]. Partial reversal of laboratory anticoagulation parameters may be achieved with use of plasma products. An agent to reverse the anti-factor Xa activity of rivaroxaban is available. Product of Germany Finished Product Manufactured by: Janssen Ortho LLC Gurabo, PR 00778 or Bayer AG 51368 Leverkusen, Germany Manufactured for: Janssen Pharmaceuticals, Inc. Titusville, NJ 08560 Licensed from: Bayer HealthCare AG 51368 Leverkusen, Germany
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