Eliquis (Apixaban) Renal Dosing Guidelines
For patients with renal impairment, Eliquis (apixaban) should be dosed at 5 mg twice daily for most patients with normal to moderate renal impairment, and reduced to 2.5 mg twice daily when specific criteria are met. 1, 2
Standard Dosing Based on Renal Function
| Renal Function | Recommended Apixaban Dose |
|---|---|
| Normal/Mild impairment (CrCl >50 mL/min) | 5 mg twice daily |
| Moderate impairment (CrCl 30-50 mL/min) | 5 mg twice daily* |
| Severe impairment (CrCl 15-30 mL/min) | 5 mg twice daily* |
| End-stage CKD not on dialysis (CrCl <15 mL/min) | Not recommended in most guidelines |
| End-stage CKD on dialysis | Not recommended in most guidelines |
*Dose reduction to 2.5 mg twice daily required if patient meets specific criteria (see below)
Dose Reduction Criteria
Reduce dose to 2.5 mg twice daily if the patient has at least 2 of the following characteristics 1, 2:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
This dose reduction algorithm is based on the FDA-approved prescribing information and is consistently recommended across multiple guidelines.
Important Clinical Considerations
Renal Function Assessment
- Renal function should be evaluated before initiating apixaban
- Use the Cockcroft-Gault method to calculate creatinine clearance
- Reassess renal function when clinically indicated and at least annually
- For patients with moderate renal impairment, more frequent monitoring (2-3 times per year) is recommended 1
Severe Renal Impairment
- While European guidelines (ESC) do not recommend apixaban in patients with CrCl <15 mL/min, the AHA/ACC/HRS guidelines suggest apixaban may be used in severe renal impairment (CrCl 15-30 mL/min) 1
- Apixaban has the lowest renal clearance (27%) among NOACs, making it potentially safer in patients with impaired renal function 1, 3
- The ARISTOTLE trial showed that patients with impaired renal function had the greatest reduction in major bleeding with apixaban compared to warfarin 3
Drug Interactions
- P-glycoprotein inhibitors (ketoconazole, verapamil, amiodarone, dronedarone, quinidine, clarithromycin) may increase apixaban plasma concentrations 1, 4
- P-glycoprotein inducers (phenytoin, carbamazepine, rifampin, St. John's wort) may decrease apixaban to subtherapeutic levels 1
- Concomitant use with these medications may require dose adjustment or avoidance, particularly in patients with renal impairment 1
Common Pitfalls and Caveats
Underdosing: Many clinicians inappropriately reduce the dose of apixaban in patients with renal impairment who don't meet the specific dose reduction criteria, which may lead to inadequate stroke prevention 4
Monitoring limitations: Unlike warfarin, routine INR monitoring is not recommended for apixaban. An elevated INR may occur with apixaban use but doesn't correlate well with anticoagulant effect 5
Renal function calculation: Using different equations (CKD-EPI vs. Cockcroft-Gault) may lead to different estimates of renal function. Guidelines specifically recommend using the Cockcroft-Gault equation for dosing decisions 1
Dialysis patients: Limited data exists for apixaban use in dialysis patients. While some guidelines suggest apixaban 2.5 mg twice daily might be used in these patients, this remains controversial and requires careful consideration 1, 6
Hepatic impairment: Apixaban is not recommended in patients with severe hepatic impairment (Child-Pugh class C) 2
Apixaban has demonstrated favorable outcomes in patients with renal impairment compared to warfarin, with significant reductions in stroke, mortality, and major bleeding across all ranges of renal function 3. The relative risk reduction for major bleeding appears to be greatest in patients with more severe renal impairment.