Rivaroxaban (Xarelto) Dosing for Atrial Fibrillation
For patients with atrial fibrillation, prescribe rivaroxaban 20 mg once daily with the evening meal if creatinine clearance (CrCl) is >50 mL/min, or 15 mg once daily with the evening meal if CrCl is 30-50 mL/min. 1, 2, 3
Standard Dosing Algorithm
Calculate CrCl using the Cockcroft-Gault equation before initiating therapy—this is what FDA labeling and the ROCKET AF trial used for dosing decisions. 2
- CrCl >50 mL/min: Rivaroxaban 20 mg once daily with the evening meal 1, 2, 3
- CrCl 30-50 mL/min (moderate renal impairment): Rivaroxaban 15 mg once daily with the evening meal 1, 2, 3, 4
- CrCl 15-30 mL/min (severe renal impairment): Rivaroxaban 15 mg once daily is expected to achieve similar concentrations as moderate renal impairment, but observe closely for bleeding 3
- CrCl <15 mL/min: Avoid rivaroxaban 3
Critical Administration Requirements
Rivaroxaban must be taken with the evening meal to ensure adequate absorption and consistent anticoagulant effect. 2 This is non-negotiable—taking it without food significantly reduces bioavailability.
Renal Function Monitoring
Reassess renal function at least annually in stable patients, or 2-3 times per year in patients with moderate renal impairment (CrCl 30-50 mL/min). 1, 2 This is critical because renal function can fluctuate, particularly in elderly patients or those with heart failure, potentially requiring dose adjustments.
Evidence Supporting Dose Adjustment in Renal Impairment
The ROCKET AF trial demonstrated that patients with CrCl 30-50 mL/min receiving rivaroxaban 15 mg once daily achieved serum concentrations and clinical outcomes similar to those with better renal function receiving 20 mg once daily. 3, 4 The dose-adjusted rivaroxaban showed consistent efficacy (HR 0.84; 95% CI 0.57-1.23) and similar bleeding rates compared to warfarin in this population. 4
Common Pitfalls to Avoid
Do not reduce the dose based solely on age ≥80 years or low body weight—these are not validated dose reduction criteria for rivaroxaban (unlike apixaban). 2 The only validated reason to use 15 mg is renal impairment with CrCl 30-50 mL/min.
Do not use eGFR for dosing decisions—always calculate CrCl using Cockcroft-Gault, as this is what the FDA label and clinical trials used. 2
Never prescribe rivaroxaban without food—absorption is significantly impaired without a meal. 2
Drug Interactions Requiring Dose Adjustment or Avoidance
Avoid concomitant use with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin), particularly in patients with chronic kidney disease. 1, 2 These can significantly increase rivaroxaban levels and bleeding risk.
Avoid use with strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine) as they significantly reduce rivaroxaban levels and may compromise efficacy. 2
End-Stage Renal Disease on Dialysis
For patients with end-stage renal disease on intermittent hemodialysis, rivaroxaban 15 mg once daily will result in concentrations similar to those in ROCKET AF, but clinical efficacy and safety have not been established in this population. 3 Consider warfarin as the preferred option in dialysis patients given the lack of prospective data. 1
Contraindications
Rivaroxaban is contraindicated in patients with prosthetic heart valves or hemodynamically significant valvular disease. 2