Eliquis (Apixaban) Dosing in Chronic Kidney Disease
For patients with CKD, use apixaban 5 mg twice daily as the standard dose, reducing to 2.5 mg twice daily ONLY when at least 2 of the following 3 criteria are met: age ≥80 years, body weight ≤60 kg, OR serum creatinine ≥1.5 mg/dL. 1, 2
Dosing Algorithm by Renal Function
Mild to Moderate CKD (CrCl 30-59 mL/min / Stage 3)
- Standard dose: 5 mg twice daily unless ≥2 dose-reduction criteria are met 1, 3
- CrCl 30-59 mL/min alone does NOT trigger dose reduction 2, 3
- Apixaban has only 27% renal clearance, making it safer than dabigatran (80%) or rivaroxaban (35%) in renal impairment 1, 2, 3
Severe CKD (CrCl 15-29 mL/min / Stage 4)
- Reduce to 2.5 mg twice daily 1, 4, 3
- This is based on pharmacokinetic data showing acceptable drug exposure at this dose 5
- Post-hoc analysis from ARISTOTLE trial (269 patients with CrCl 25-30 mL/min) showed apixaban caused 66% less major bleeding than warfarin (HR 0.34,95% CI 0.14-0.80) 5
End-Stage Renal Disease (CrCl <15 mL/min or Dialysis / Stage 5)
- FDA-approved dose: 5 mg twice daily 6
- Reduce to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (only ONE criterion needed in dialysis, not two) 1, 6
- However, recent pharmacokinetic data suggest 5 mg twice daily produces supra-therapeutic levels in dialysis patients, while 2.5 mg twice daily produces levels similar to normal renal function 3
- Critical caveat: Major trials excluded dialysis patients, so evidence is limited to pharmacokinetic modeling 1, 6, 7
The Three Dose-Reduction Criteria
Reduce to 2.5 mg twice daily when ≥2 of these are present: 1, 2
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL (NOT CrCl cutoff)
Common prescribing error: Reducing dose based on a single criterion or perceived bleeding risk rather than meeting formal criteria 2, 3
Monitoring Requirements
- Calculate CrCl using Cockcroft-Gault equation (not eGFR), as this was used in pivotal trials and FDA labeling 1, 2, 4
- Reassess renal function at least annually 1
- Increase monitoring frequency to every 3-6 months if CrCl <60 mL/min or with any acute illness affecting renal function 2, 3
- Monitor for bleeding signs, particularly gastrointestinal, but also rare sites like pleural/pericardial effusions in severe CKD 8
Drug Interactions Requiring Dose Adjustment
- Reduce to 2.5 mg twice daily when using combined P-glycoprotein AND strong CYP3A4 inhibitors (ketoconazole, ritonavir, itraconazole) in patients otherwise receiving 5 mg twice daily 1, 2
- Avoid entirely with strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine) as they reduce apixaban to subtherapeutic levels 1, 2
Comparative Safety Evidence
- Systematic review of 27,007 patients (11 studies) showed apixaban had equivalent efficacy to warfarin for stroke prevention but superior or equivalent safety profile for bleeding in CKD stages 4-5 7
- Retrospective study of 604 patients with advanced CKD showed similar bleeding rates at 3 months (8.3% vs 9.9%, p=0.48), but significantly lower bleeding with apixaban at 6-12 months (1.5% vs 8.4%, p<0.001) 9
- Small study (95 patients) showed no difference in major bleeding between 5 mg and 2.5 mg twice daily in CKD stages 4-5 (9.1% vs 12.3%, p=1.00) 10
Critical Pitfalls to Avoid
- Do not reduce dose based on CrCl alone without meeting ≥2 formal criteria 2, 3
- Do not use eGFR for dosing decisions—always calculate CrCl with Cockcroft-Gault 1, 2, 4
- Do not underdose out of bleeding fear—studies show 9.4-40.4% of prescriptions involve inappropriate dose reduction 2
- Be aware of rare hemorrhagic complications (pleural, pericardial, intracranial) even with guideline-based dosing in severe CKD/ESRD 8
- Recognize that dialysis data is limited—FDA approval based on pharmacokinetic modeling, not clinical trials 6, 7