What are the recommended doses of Rivaroxaban (Xarelto) for anticoagulation in different clinical conditions?

Rivaroxaban Dosing by Clinical Indication

Venous Thromboembolism (DVT/PE) Treatment

For acute DVT or PE treatment, initiate rivaroxaban at 15 mg twice daily with food for the first 21 days, then transition to 20 mg once daily with food for the remaining treatment duration. 1, 2

Initial Treatment Phase

• 15 mg twice daily with food for 21 days 1, 2
• This loading dose achieves rapid therapeutic anticoagulation without requiring bridging therapy 1

Continuation Phase

• 20 mg once daily with food after the initial 21 days 1, 2
• Minimum treatment duration is 3 months for most patients 1

Extended/Secondary Prevention

After completing at least 6 months of standard anticoagulation, patients at continued risk for recurrent VTE should receive 10 mg once daily (with or without food) for extended prophylaxis. 3, 2, 4

• The 10 mg once daily dose is specifically for extended treatment beyond 6 months 3, 2, 4
• This reduced dose demonstrated superior efficacy compared to aspirin (1.2% vs 4.4% recurrence rate) with minimal bleeding risk (0.4% major bleeding) 4
• Extended therapy should continue indefinitely for unprovoked VTE unless bleeding risk becomes unacceptable 3
• 20 mg once daily may also be used for extended treatment if higher intensity anticoagulation is preferred 3, 2

Atrial Fibrillation (Stroke Prevention)

For nonvalvular atrial fibrillation, use 20 mg once daily with food in patients with normal renal function. 1, 2

Renal Dose Adjustments

• 15 mg once daily if creatinine clearance (CrCl) is 15-49 mL/min 1, 2
• This dose reduction is critical as rivaroxaban exposure increases 44-64% in renal impairment 2
• Avoid use if CrCl <15 mL/min 2

Orthopedic Thromboprophylaxis

For DVT prophylaxis after hip or knee replacement surgery, use 10 mg once daily (with or without food). 1, 2

• Start 6-10 hours after surgery 1
• Duration: 2 weeks for total knee replacement 1
• Duration: 5 weeks for total hip replacement 1

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

For patients with CAD or PAD, use rivaroxaban 2.5 mg twice daily (with or without food) in combination with aspirin 75-100 mg once daily. 1, 2

• This "vascular dose" reduces major cardiovascular events 1, 2
• Do not use higher doses for this indication 2

Acute Coronary Syndrome with Atrial Fibrillation

When patients require anticoagulation for both ACS and atrial fibrillation, use the full VTE treatment dose (20 mg once daily), not the reduced AF dose studied in PIONEER-AF. 1

• The 15 mg dose used in PIONEER-AF is insufficient for VTE treatment 1
• After initial triple therapy (up to 1 week), transition to dual therapy with rivaroxaban plus single antiplatelet agent 1
• 15 mg once daily may be considered if high bleeding risk (HAS-BLED ≥3) outweighs thrombotic risk during concomitant antiplatelet therapy 1

Pediatric Dosing

For pediatric VTE treatment, dosing is weight-based and varies by age group. 1, 2

Weight-Based Dosing Table

• <12 kg: Three times daily dosing with oral suspension only (doses range from 0.8-3 mg per dose) 1
• 12-29.9 kg: 5 mg twice daily 1
• 30-49.9 kg: 15 mg once daily 1
• ≥50 kg: 20 mg once daily (adult dosing) 1

Important Pediatric Considerations

• Not studied in infants <6 months who were <37 weeks gestation at birth, had <10 days oral feeding, or weighed <2.6 kg 2
• Tablets and oral suspension cannot be substituted on a milligram-to-milligram basis 1

Critical Renal Impairment Considerations

Rivaroxaban dosing must be adjusted based on creatinine clearance to prevent drug accumulation and bleeding. 1, 2

Renal Function Categories

• CrCl ≥50 mL/min: Standard dosing 2
• CrCl 30-49 mL/min: Reduce to 15 mg once daily for AF; observe closely for bleeding in VTE treatment 1, 2
• CrCl 15-29 mL/min: Use 15 mg once daily for AF only; observe closely and evaluate any signs of bleeding 2
• CrCl <15 mL/min: Avoid use 1, 2

End-Stage Renal Disease on Dialysis

• 15 mg once daily achieves similar concentrations to those in ROCKET AF, though clinical outcomes in dialysis patients are unknown 2
• One case report demonstrated that 10 mg daily in severe renal failure (CrCl 32 mL/min) was insufficient to prevent ischemic stroke 5

Elderly Patients

In elderly patients (≥60 years) with VTE, consider 10 mg once daily for long-term treatment to reduce bleeding risk while maintaining efficacy. 6

• A real-world study of 576 elderly patients showed 10 mg once daily had significantly lower bleeding rates (3.7% vs 14.7%) compared to higher doses, with similar VTE recurrence rates (4.5% vs 5.7%) 6
• Age is an independent risk factor for bleeding on rivaroxaban 6
• Both thrombotic and bleeding event rates increase with age 2

Contraindications and Precautions

Do not use rivaroxaban in patients with active pathological bleeding, severe hepatic disease with coagulopathy, or concomitant use of combined P-gp and strong CYP3A4 inhibitors. 1, 2

Absolute Contraindications

• Active pathological bleeding 2
• Severe hypersensitivity reaction 2
• Hepatic disease associated with coagulopathy (Child-Pugh B or C) 1, 2
• Concomitant systemic azole antimycotics or HIV protease inhibitors 1

Special Populations to Avoid

• Pregnancy (crosses placenta, potential reproductive toxicity) 1
• Breastfeeding (secreted in milk) 1
• Prosthetic heart valves 2
• Triple positive antiphospholipid syndrome 2

Drug Interactions

Avoid combining rivaroxaban with drugs that are both strong CYP3A4 inhibitors and P-glycoprotein inhibitors, as this significantly increases rivaroxaban exposure. 1, 2

Contraindicated Combinations

• Ketoconazole, itraconazole (azole antifungals) 1
• HIV protease inhibitors 1
• Ciclosporin, tacrolimus 1

Use with Caution

• Amiodarone, verapamil (P-gp inhibitors) 1
• Clarithromycin, quinidine 1
• Concomitant antiplatelet agents increase bleeding risk 1, 6
• Aspirin is an independent risk factor for bleeding 6

Periprocedural Management

For procedures, pause rivaroxaban 24 hours before low-risk bleeding procedures and 48 hours before high-risk bleeding procedures. 1

• Resume therapeutic anticoagulation within 3 hours of taking a dose 1
• Additional parenteral anticoagulation is recommended during PCI regardless of last DOAC dose 1

Monitoring

Routine monitoring of rivaroxaban levels is not required, but PT and aPTT should not be used to assess anticoagulant effect. 1

• Neither PT nor aPTT reliably measures rivaroxaban activity 1
• Reassess patients on extended anticoagulation at least annually for bleeding risk, treatment burden, and continued indication 3

Bleeding Management

For major bleeding on rivaroxaban, hold the drug and consider 4-factor prothrombin complex concentrate (PCC) or andexanet alfa. 1

• Andexanet alfa is FDA-approved for life-threatening hemorrhage in adults on rivaroxaban 1
• Consider activated charcoal if last dose was within 2 hours 1
• No pediatric studies exist for andexanet alfa 1