Switching from Apixaban (Eliquis) to Rivaroxaban (Xarelto)
Direct Switching Protocol
Stop apixaban and start rivaroxaban at the next scheduled dose time—no washout period or bridging anticoagulation is required. 1, 2 Given apixaban's half-life of approximately 12 hours, the drug will be largely cleared by the time the first rivaroxaban dose is due, making overlap unnecessary and avoiding gaps in anticoagulation coverage. 3
Dose Selection Based on Indication and Renal Function
For Atrial Fibrillation
Calculate creatinine clearance using the Cockcroft-Gault equation with actual body weight before initiating rivaroxaban. 4, 2 This is the method used in pivotal trials and FDA labeling, and it is not interchangeable with eGFR. 4, 5
| Creatinine Clearance | Rivaroxaban Dose | Administration |
|---|---|---|
| >50 mL/min | 20 mg once daily | With evening meal [4,2] |
| 30-50 mL/min | 15 mg once daily | With evening meal [4,2] |
| 15-29 mL/min | 15 mg once daily (use with caution) | With evening meal [4,2] |
| <15 mL/min | Avoid use [4,2] | — |
Rivaroxaban must be taken with food—specifically the evening meal—to ensure adequate absorption and consistent anticoagulant effect. 4 This is a critical difference from apixaban, which can be taken with or without food. 5
For Venous Thromboembolism (DVT/PE)
For acute VTE treatment, rivaroxaban dosing differs from atrial fibrillation: 2
- Initial 21 days: 15 mg twice daily with food
- After 21 days: 20 mg once daily with food (if CrCl >50 mL/min) or 15 mg once daily with food (if CrCl 30-50 mL/min)
For extended VTE prophylaxis after 6 months of treatment: 10 mg once daily with food 2
Key Pharmacokinetic Differences
Rivaroxaban has significantly higher renal clearance (approximately 66%) compared to apixaban (27%), making renal function monitoring more critical. 4, 5, 6 This means rivaroxaban carries a narrower safety margin in patients with declining kidney function. 5, 6
Reassess renal function at least annually in stable patients, or every 3-6 months in patients with CrCl <60 mL/min. 4, 7 In patients with heart failure or fluctuating renal function, even more frequent monitoring may be warranted, as 35% of such patients require rivaroxaban dose adjustments during follow-up. 7
Drug Interactions Requiring Adjustment or Avoidance
Avoid rivaroxaban with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin), particularly in patients with chronic kidney disease. 4 These agents can significantly increase rivaroxaban levels and bleeding risk.
Avoid rivaroxaban with strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's wort), as they reduce rivaroxaban plasma concentrations to subtherapeutic levels. 4
Special Populations and Contraindications
Rivaroxaban is contraindicated in patients with CrCl <15 mL/min or on dialysis. 4, 2 In contrast, apixaban has FDA approval for use in dialysis patients at 5 mg twice daily (reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg). 5, 8 If your patient is approaching end-stage renal disease, switching from apixaban to rivaroxaban would be inappropriate.
For patients with gastric or gastroesophageal tumors, apixaban may be safer than rivaroxaban due to lower gastrointestinal bleeding risk. 1 The NCCN panel postulates apixaban is preferable to rivaroxaban in this setting (category 2B recommendation). 1
Rivaroxaban is contraindicated in patients with prosthetic heart valves or hemodynamically significant valvular disease. 4
Common Pitfalls to Avoid
Do not reduce rivaroxaban dose based solely on age ≥80 years or low body weight—these are not validated dose-reduction criteria for rivaroxaban. 4 The only validated reason to use 15 mg rivaroxaban in atrial fibrillation is moderate renal impairment (CrCl 30-49 mL/min). 4
Do not forget to counsel patients to take rivaroxaban with food. 4, 2 Missing this instruction can result in 30-50% lower drug absorption and inadequate anticoagulation.
Do not use eGFR for dosing decisions—always calculate CrCl with Cockcroft-Gault using actual body weight. 4, 5 Using eGFR can lead to significant dosing errors.
In patients with fluctuating renal function (heart failure, acute illness), rivaroxaban may require more frequent dose adjustments than apixaban due to its higher renal dependence. 7, 6 Consider whether this switch is truly necessary or if continuing apixaban would be safer.
Bleeding Management Considerations
Both rivaroxaban and apixaban can be reversed with andexanet alfa in life-threatening bleeding. 9 However, given their relatively short half-lives (5-9 hours for rivaroxaban, 12 hours for apixaban), supportive care while the drug is metabolized may be sufficient in many cases. 9, 3
Prothrombin complex concentrates can be used off-label if andexanet alfa is unavailable. 9, 3