What are the dosages of rivaroxaban for adults with varying renal function?

Rivaroxaban Dosing by Indication and Renal Function

Atrial Fibrillation (Stroke Prevention)

For stroke prevention in atrial fibrillation, rivaroxaban dosing is determined solely by creatinine clearance: 20 mg once daily with food for CrCl ≥50 mL/min, and 15 mg once daily with food for CrCl 15-49 mL/min. 1

Standard Dosing Algorithm

• CrCl ≥50 mL/min: 20 mg once daily with the evening meal 1, 2
• CrCl 15-49 mL/min: 15 mg once daily with the evening meal 1, 2
• CrCl <15 mL/min: Avoid use (no clinical data available) 1

Critical Renal Function Considerations

• Calculate creatinine clearance using the Cockcroft-Gault equation, as this was used in pivotal trials 3, 4
• Rivaroxaban has approximately 33% renal clearance, making dose adjustment essential in renal impairment 3, 5
• Monitor renal function annually in patients with preserved function, but increase to 2-3 times per year in patients with CrCl 30-50 mL/min 3, 4
• The 15 mg dose for moderate renal impairment (CrCl 30-49 mL/min) was validated in the ROCKET AF trial and showed consistent efficacy and safety compared to the 20 mg dose in patients with normal renal function 2

Important Administration Requirements

• Both the 15 mg and 20 mg doses MUST be taken with food to ensure adequate absorption (bioavailability increases from 66% to 80-100%) 6, 3
• The 10 mg dose can be taken with or without food 1

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Venous Thromboembolism (DVT/PE) Treatment

For acute DVT or PE treatment, use 15 mg twice daily with food for 21 days, then transition to 20 mg once daily with food for maintenance therapy.

Acute Treatment Phase (First 21 Days)

• 15 mg orally twice daily with food for 21 days 3, 1, 7
• This higher initial dose provides a strong antithrombotic effect during the acute phase 7

Maintenance Phase (After 21 Days)

• 20 mg once daily with food for at least 6 months 3, 1, 7
• This regimen was validated in the EINSTEIN trials 1, 7

Extended Secondary Prevention (After 6 Months)

• Consider dose reduction to 10 mg once daily for extended secondary prevention of recurrent VTE 6, 3
• The 10 mg dose can be taken with or without food 1
• This lower dose for extended prophylaxis is supported by the American Society of Hematology 2020 guidelines 6

Renal Impairment Adjustments for VTE

• CrCl ≥50 mL/min: Use standard dosing (15 mg twice daily × 21 days, then 20 mg once daily) 1
• CrCl 30-49 mL/min: Use standard dosing with close monitoring 1
• CrCl 15-29 mL/min: Use standard dosing but observe closely for signs of bleeding (limited clinical data) 1, 8
• CrCl <15 mL/min: Avoid use 1

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Coronary Artery Disease (CAD) and Peripheral Artery Disease (PAD)

For reduction of major cardiovascular events in CAD or PAD, use rivaroxaban 2.5 mg twice daily in combination with aspirin.

Standard Dosing

• 2.5 mg orally twice daily (with or without food) plus aspirin 75-100 mg once daily 1
• This regimen was validated in the COMPASS and VOYAGER trials 1

Renal Impairment Considerations

• CrCl ≥30 mL/min: Use standard 2.5 mg twice daily dose 1
• CrCl 15-29 mL/min: Use 2.5 mg twice daily (expected to give similar exposure to moderate renal impairment) 1
• CrCl <15 mL/min: Limited data; patients were excluded from trials 1

End-Stage Renal Disease on Dialysis

• 2.5 mg twice daily may be used in ESRD on hemodialysis (will result in concentrations similar to moderate renal impairment, though clinical outcome data are lacking) 1

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DVT Prophylaxis After Hip or Knee Replacement

For post-operative DVT prophylaxis, use 10 mg once daily starting 6-10 hours after surgery.

Standard Dosing

• 10 mg once daily (with or without food) 1
• Duration: 12 days after knee replacement, 35 days after hip replacement 1

Renal Impairment Adjustments

• CrCl ≥30 mL/min: Use standard 10 mg once daily 1
• CrCl 15-29 mL/min: Use 10 mg once daily with close monitoring for bleeding 1, 8
• CrCl <15 mL/min: Avoid use 1

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Critical Warnings and Drug Interactions

Absolute Contraindications

• Avoid rivaroxaban with strong dual inhibitors of both CYP3A4 and P-glycoprotein (e.g., ketoconazole, ritonavir, itraconazole, conivaptan) as these cause significant drug accumulation 3, 5
• Avoid in moderate to severe hepatic impairment (Child-Pugh B or C) or any hepatic disease with coagulopathy 1

Common Pitfalls

• Do NOT use 15 mg daily for VTE maintenance therapy in patients with normal renal function—this underdoses patients and increases recurrence risk; the correct maintenance dose is 20 mg daily 3
• Do NOT confuse the atrial fibrillation dose (15-20 mg once daily) with the VTE acute treatment dose (15 mg twice daily) 3, 1
• Rivaroxaban is not dialyzable due to high plasma protein binding (>90%) 1, 5

Monitoring Requirements

• Baseline renal function assessment is mandatory before initiating therapy 3, 4
• Reassess renal function at least annually, or every 3-6 months in elderly patients or those with CrCl <60 mL/min 3, 4
• No routine INR monitoring is required 2