Apixaban Renal Dosing
For patients with renal impairment, apixaban requires dose reduction 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—renal impairment alone does NOT trigger dose reduction. 1, 2, 3
Standard Dosing Algorithm by Renal Function
Normal to Moderate Renal Impairment (CrCl >30 mL/min)
- Standard dose is 5 mg twice daily for patients with CrCl >30 mL/min, including those with moderate renal impairment (CrCl 30-59 mL/min), unless the patient meets ≥2 dose-reduction criteria 1, 2, 3
- Calculate creatinine clearance using the Cockcroft-Gault equation, not eGFR, as this method was used in pivotal trials and FDA labeling 1, 2
- Apixaban has only 27% renal clearance, making it the safest direct oral anticoagulant in renal impairment compared to dabigatran (80%) or rivaroxaban (66%) 1, 2, 3
Severe Renal Impairment (CrCl 15-29 mL/min)
- Reduce to 2.5 mg twice daily for patients with CrCl 15-29 mL/min 2
- This dose reduction applies regardless of whether other dose-reduction criteria are met 2
End-Stage Renal Disease on Hemodialysis
- FDA-approved dose is 5 mg twice daily for stable hemodialysis patients 2, 3
- Reduce to 2.5 mg twice daily if age ≥80 years OR body weight ≤60 kg (note: only ONE criterion needed in dialysis patients, not two) 1, 2, 3
- Pharmacokinetic data show that 2.5 mg twice daily in dialysis patients produces drug exposure comparable to 5 mg twice daily in patients with normal renal function 2, 4
CrCl <15 mL/min Not on Dialysis
- No established dosing recommendations exist for patients with CrCl <15 mL/min who are not on dialysis 2
- Clinical trials excluded these patients, and dosing must be individualized with extreme caution 2, 3
The Three-Criteria Dose Reduction Algorithm
Reduce apixaban to 2.5 mg twice daily when ≥2 of these criteria are present: 1, 3
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Critical Pitfall: Inappropriate Underdosing
- The most common prescribing error is reducing the dose based on a single criterion rather than requiring two, with studies showing 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing 1
- Clinicians often incorrectly reduce the dose based on perceived bleeding risk or isolated renal dysfunction when formal criteria are not met 1
- Do not reduce the dose based solely on CrCl, eGFR, or bleeding risk without meeting the formal two-criteria threshold 1
Monitoring Requirements
- Reassess renal function at least annually in all patients on apixaban 1, 2
- Increase monitoring frequency to every 3-6 months if CrCl <60 mL/min or if clinical deterioration occurs 1, 2
- In patients with declining renal function or CKD stage 4-5, monitor every 1-3 months as 29% require dose adjustments during follow-up 1, 2
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 concomitant use with strong CYP3A4 inducers (rifampin) as they significantly reduce apixaban levels 1
Special Considerations in Severe Renal Impairment
Bleeding Risk
- All anticoagulants carry increased bleeding risk in severe renal impairment, with bleeding potentially occurring at uncommon sites (pleura, pericardium, intracranial space) 2, 5
- Despite guideline-based dosing, vigilant monitoring is essential for rare but serious hemorrhagic complications 5
Evidence Quality
- Dosing recommendations for CrCl >30 mL/min are based on high-quality RCT data from the ARISTOTLE trial with 18,201 patients 2
- No randomized controlled trials exist for severe CKD (CrCl <25-30 mL/min) or dialysis patients—recommendations are based on pharmacokinetic and observational data only 2, 6
- Observational data suggest apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment, with similar safety profiles 6