Rivaroxaban Dosing in Adults with Cardiovascular Disease and Renal Impairment
Non-Valvular Atrial Fibrillation
For stroke prevention in non-valvular atrial fibrillation, use rivaroxaban 20 mg once daily with the evening meal in patients with normal renal function (CrCl >50 mL/min), and reduce to 15 mg once daily in patients with moderate renal impairment (CrCl 30-50 mL/min). 1, 2
Renal Function-Based Dosing Algorithm
- CrCl >50 mL/min: 20 mg once daily with food 1
- CrCl 30-50 mL/min: 15 mg once daily with food 1, 2
- CrCl 15-30 mL/min: 15 mg once daily may be considered, though safety data are limited; observe closely for bleeding 1, 2
- CrCl <15 mL/min: Avoid use 1
End-Stage Renal Disease on Dialysis
In patients with ESRD on intermittent hemodialysis, rivaroxaban 15 mg once daily produces similar concentrations to those in the ROCKET AF trial, though clinical outcomes in this population remain uncertain. 2
Deep Vein Thrombosis and Pulmonary Embolism
Initial Treatment Phase
For acute DVT/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 continued treatment. 1
- The 15 mg twice daily loading dose for 21 days is critical for achieving therapeutic anticoagulation rapidly 1
- All doses must be taken with food to ensure adequate absorption 1
Long-Term Secondary Prevention
After completing at least 6 months of initial treatment, consider reducing to rivaroxaban 10 mg once daily (with or without food) for extended secondary prevention of recurrent VTE. 1
- The 10 mg daily dose provides adequate prophylaxis against recurrence while potentially reducing bleeding risk 1
- This reduced dose is appropriate for patients at continued risk of recurrent VTE but lower acute thrombotic burden 1
Renal Impairment Considerations for VTE
- CrCl 30-50 mL/min: Use standard VTE dosing (15 mg twice daily × 21 days, then 20 mg daily) with caution 1
- CrCl 15-30 mL/min: Expected to produce similar concentrations to moderate impairment; observe closely for bleeding 1, 2
- CrCl <15 mL/min: Avoid use 1, 2
Critical Renal Monitoring Requirements
Rivaroxaban undergoes 66% renal elimination, making creatinine clearance assessment mandatory before initiation and during ongoing therapy, particularly in elderly patients where half-life extends from 5-9 hours to 11-13 hours. 1, 3
When to Reassess Renal Function
- Before initiating therapy 2, 3
- After any surgical procedure or acute illness that could affect renal function 1
- Periodically during long-term therapy, especially in patients ≥75 years 1, 2
- When adding medications that may impair renal function 2
High-Risk Populations Requiring Extra Caution
Elderly Patients (≥75 Years)
Elderly patients on rivaroxaban demonstrate higher rates of gastrointestinal and intracranial bleeding compared to younger patients, particularly with the 20 mg daily dose for atrial fibrillation. 1, 2
- Consider the 15 mg dose in patients ≥75 years with CrCl 30-50 mL/min 1, 2
- Monitor more frequently for bleeding signs 1
Patients on Concomitant Medications
Avoid combining rivaroxaban with strong dual P-glycoprotein and CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), as these significantly increase rivaroxaban exposure and bleeding risk. 1
- P-glycoprotein inhibitors alone (e.g., verapamil) require dose adjustment consideration 1
- Combining with corticosteroids creates a 3-6 fold increase in gastrointestinal bleeding risk; add a proton pump inhibitor if combination cannot be avoided 4
- Avoid concurrent NSAIDs, antiplatelet agents, or other anticoagulants unless specifically indicated 1, 4
Dosing Administration Requirements
Food Requirements
- Atrial fibrillation: Take with evening meal 2
- VTE treatment (15 mg and 20 mg doses): Must take with food 1, 2
- VTE secondary prevention (10 mg dose): May take with or without food 1
For Patients Unable to Swallow Tablets
Crush rivaroxaban tablets and mix with applesauce immediately before administration, followed by food. 2
- For nasogastric/gastric feeding tubes: Crush tablet, suspend in small amount of water, administer via tube, then flush 2
- Do not split tablets to achieve partial doses 2
Contraindications and When to Avoid Rivaroxaban
Rivaroxaban is contraindicated in patients with active pathological bleeding, severe hepatic impairment (Child-Pugh B or C), and CrCl <15 mL/min. 4, 2
- Avoid in patients with prosthetic heart valves or hemodynamically significant valvular disease 1
- Do not use in patients with severe renal failure (CrCl <30 mL/min) for VTE prophylaxis post-orthopedic surgery 1
- Contraindicated in patients with history of hypersensitivity to rivaroxaban 2
Missed Dose Management
For Once-Daily Dosing (20 mg, 15 mg, or 10 mg)
If a once-daily dose is missed, take it as soon as remembered on the same day, then resume the regular schedule the next day; do not double the dose. 2
For Twice-Daily Dosing (15 mg BID for acute VTE)
If a twice-daily dose is missed, take the missed dose immediately to ensure 30 mg total daily intake, then continue with regular twice-daily dosing the next day. 2
Special Clinical Scenarios
Transitioning from Warfarin to Rivaroxaban
Discontinue warfarin and start rivaroxaban when INR falls below 3.0 for atrial fibrillation, or below 2.5 for VTE treatment. 2
Transitioning from Rivaroxaban to Warfarin
Continue rivaroxaban and warfarin together until INR reaches therapeutic range (≥2.0), as rivaroxaban affects INR measurements. 2
Perioperative Management
For high hemorrhagic risk procedures (including neuraxial anesthesia), discontinue rivaroxaban for up to 5 days before the procedure in patients without renal failure, with timing adjusted based on creatinine clearance. 1
- CrCl ≥80 mL/min: Stop 24 hours before low-risk procedures, 48 hours before high-risk procedures 1
- CrCl 50-79 mL/min: Stop 48 hours before low-risk procedures, 72 hours before high-risk procedures 1
- CrCl 30-49 mL/min: Stop 48 hours before low-risk procedures, 96 hours before high-risk procedures 1
- CrCl 15-29 mL/min: Stop 96 hours before high-risk procedures 1