GFR Cut-offs for Eliquis (Apixaban) Dosing
Apixaban can be safely used down to a creatinine clearance of 15 mL/min with appropriate dose adjustments, and is the only DOAC with evidence supporting use in end-stage renal disease on dialysis. 1
Standard Dosing by Renal Function
Normal to Moderate Renal Impairment (CrCl >30 mL/min)
- Standard dose is 5 mg twice daily for CrCl >30 mL/min with no renal-based adjustment required 2, 1
- This applies to both mild (CrCl 50-80 mL/min) and moderate (CrCl 30-50 mL/min) renal impairment 2, 1
Dose Reduction Criteria (Any Level of Renal Function)
- Reduce to 2.5 mg twice daily ONLY if the patient meets at least 2 of the following 3 criteria: 2, 1
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL (133 μmol/L)
Critical point: The serum creatinine criterion (≥1.5 mg/dL) is NOT a GFR cut-off itself—it must be combined with at least one other criterion to trigger dose reduction. 2, 1
Severe Renal Impairment (CrCl 15-29 mL/min)
- Apixaban 5 mg twice daily is the recommended dose for CrCl 15-30 mL/min 1
- Apply the same dose reduction criteria: reduce to 2.5 mg twice daily if ≥2 of the 3 criteria above are met 1
- Apixaban has the lowest renal clearance (27%) among all DOACs, making it the preferred agent in this population 2, 1
- Post-hoc analysis from ARISTOTLE showed apixaban caused significantly less major bleeding (HR 0.34) and major/clinically relevant non-major bleeding (HR 0.35) compared to warfarin in patients with CrCl 25-30 mL/min 3
End-Stage Renal Disease on Dialysis (CrCl <15 mL/min)
- Apixaban 5 mg twice daily can be used in stable hemodialysis patients 1
- Reduce to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (note: only ONE criterion needed in dialysis patients, not two) 1
- Pharmacokinetic data demonstrate that 2.5 mg twice daily in dialysis patients produces drug exposure comparable to 5 mg twice daily in patients with normal renal function 1
- Meta-analysis showed apixaban reduced major bleeding risk by 73% (OR 0.27) compared to warfarin in ESRD patients on dialysis 4
- Real-world data supports lower mortality and composite endpoints with apixaban versus warfarin in severe renal impairment 5
Absolute Contraindication
- CrCl <15 mL/min NOT on dialysis is a relative contraindication due to lack of clinical trial data, though observational evidence suggests safety 6, 7
- The ARISTOTLE trial excluded patients with serum creatinine >2.5 mg/dL or CrCl <25 mL/min 2
Monitoring Requirements
- Calculate creatinine clearance using the Cockcroft-Gault equation (this was used in pivotal trials, not eGFR) 1
- Reassess renal function at least annually, and more frequently (every 3-6 months) if: 1
- CrCl 30-50 mL/min
- Declining renal function
- Clinical deterioration
- Age >75 years
- Acute illness
Key Advantages in Renal Impairment
Apixaban's pharmacokinetic profile makes it uniquely suited for renal impairment: 2, 1
- Only 27% renal clearance (versus 80% for dabigatran, 50% for edoxaban, 33% for rivaroxaban)
- Substantial overlap in drug exposure between patients with CrCl 25-30 mL/min and those with normal renal function when using standard dosing 3
- Lower rates of intracranial hemorrhage across all renal function categories 1
Common Pitfalls to Avoid
- Do NOT reduce the dose based on renal function alone—you must apply the 2-of-3 criteria rule 1
- Do NOT use eGFR for dosing decisions—use Cockcroft-Gault calculated CrCl 1
- Do NOT automatically reduce dose in moderate renal impairment (CrCl 30-50 mL/min)—5 mg twice daily is appropriate unless ≥2 dose reduction criteria are met 2, 1
- Do NOT confuse the dose reduction criteria for dialysis patients (only 1 criterion needed: age ≥80 OR weight ≤60 kg) with non-dialysis patients (≥2 of 3 criteria needed) 1
- Be aware that P-glycoprotein inhibitors and strong CYP3A4 inhibitors/inducers may require additional dose adjustments, particularly in patients with renal impairment 1