What is the dosing and usage of Xarelto (Rivaroxaban) for anticoagulation?

Dosing and Usage of Xarelto (Rivaroxaban) for Anticoagulation

Rivaroxaban dosing varies by indication, with 15 mg twice daily for 3 weeks followed by 20 mg once daily being the standard regimen for venous thromboembolism treatment, and dose adjustments required for renal impairment.

Indications and Standard Dosing

Venous Thromboembolism (VTE) Treatment

• Initial treatment (first 3 weeks): 15 mg twice daily 1
• Continued treatment: 20 mg once daily 1, 2
• Extended treatment (after completing 6-12 months of standard therapy):
  • 20 mg once daily for continued full-dose therapy, or
  • 10 mg once daily for reduced-dose extended therapy (preferred for long-term prevention) 1

Atrial Fibrillation (AF)

• Standard dose: 20 mg once daily with food 1
• With renal impairment (CrCl 15-49 mL/min): 15 mg once daily with food 1

VTE Prophylaxis after Hip/Knee Replacement

• Dose: 10 mg once daily 1
• Duration:
  • Total knee replacement: 2 weeks
  • Total hip replacement: 5 weeks 1

Medical Illness VTE Prophylaxis

• Dose: 10 mg once daily 1

Coronary Artery Disease (CAD)

• Dose: 2.5 mg twice daily (plus aspirin 100 mg once daily) 3

Renal Considerations

• Severe renal impairment (CrCl 15-29 mL/min): 15 mg once daily recommended 1
• End-stage renal disease (CrCl <15 mL/min): Not recommended 1
• Rivaroxaban is approximately one-third cleared by the kidneys, making it less affected by renal impairment than dabigatran (which is 80% renally cleared) 1

Hepatic Considerations

• Avoid in patients with:
  • Child-Pugh B and C liver cirrhosis 1
  • Hepatic disease associated with coagulopathy 1
  • Liver enzymes >2x upper limit of normal with coagulopathy 1

Timing and Administration

• Rivaroxaban reaches peak plasma concentration 2-4 hours after ingestion 4
• Half-life: 5-9 hours in healthy young subjects, 11-13 hours in elderly 4
• For 15 mg and 20 mg doses: Take with food to enhance absorption 4
• For 10 mg dose: Can be taken with or without food 1

Drug Interactions

• Contraindicated with:

  • Strong inhibitors of both CYP3A4 and P-glycoprotein (P-gp) such as:
    • Azole antifungals (ketoconazole, itraconazole)
    • HIV protease inhibitors 1

• Use with caution with:

  • Strong P-gp inducers (rifampicin, St. John's wort) 1

Special Populations

• Elderly patients (>80 years): Standard dosing, but monitor renal function 1
• Pregnancy and breastfeeding: Not recommended due to potential reproductive toxicity and secretion into milk 1
• Children and adolescents (<18 years): Not approved due to lack of clinical data 1

Monitoring

• No routine coagulation monitoring required 4
• If assessment of anticoagulant effect is needed:
  • Standard PT/INR tests are not suitable for monitoring rivaroxaban 1
  • Specific anti-Factor Xa assays with rivaroxaban calibration may be used if available 1

Switching Between Anticoagulants

• When switching from warfarin to rivaroxaban:
  • Discontinue warfarin and start rivaroxaban when INR is below 3.0 5
• When switching from rivaroxaban to warfarin:
  • Overlap rivaroxaban with warfarin until INR ≥2.0 5

Bleeding Management

• Unlike warfarin, vitamin K administration does not reverse rivaroxaban's effects 1
• For severe bleeding:
  • Prothrombin complex concentrate (PCC) may reverse rivaroxaban's effect 1
  • Consider tranexamic acid, although evidence is limited 1

Clinical Pearls

• Rivaroxaban restores therapeutic anticoagulation within 3 hours of administration, unlike warfarin which takes days 1
• Lower risk of intracranial bleeding compared to warfarin, but may have increased risk of gastrointestinal bleeding 1
• For patients with heparin-induced thrombocytopenia, rivaroxaban can be used at 15 mg twice daily until platelet recovery, then 20 mg once daily 1

Remember that therapeutic anticoagulation is restored rapidly (within 3 hours) after taking rivaroxaban, unlike warfarin which has a delayed onset of action 1. This is particularly important when transitioning between anticoagulants or resuming therapy after interruption.