Eliquis (Apixaban) Dosing in Renal Impairment
Apixaban can be safely used across most levels of renal function with specific dose adjustments, and should be avoided only in patients with creatinine clearance <15 mL/min or those on dialysis (where data are limited and dosing recommendations are uncertain). 1
Standard Dosing by Indication and Renal Function
For Atrial Fibrillation (Stroke Prevention)
Standard dose is 5 mg twice daily, but reduce to 2.5 mg twice daily if the patient meets at least TWO of the following criteria: 1, 2
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
This dosing strategy applies regardless of renal function level, as long as CrCl is ≥15 mL/min 1
For VTE Treatment/Prophylaxis
No dose adjustment is required for any degree of renal impairment, including severe renal insufficiency (CrCl 15-29 mL/min). 1 The standard dosing remains:
- VTE treatment: 10 mg twice daily for 7 days, then 5 mg twice daily 2
- VTE prophylaxis post-orthopedic surgery: 2.5 mg twice daily 2
Renal Elimination and Pharmacokinetics
Apixaban has the lowest renal dependence among direct oral anticoagulants, with only 27% renal elimination (compared to 80% for dabigatran and 66% for rivaroxaban). 2, 1 The remainder is metabolized primarily via CYP3A4 in the liver. 1
The half-life is approximately 12 hours, which remains relatively stable across renal function levels. 2, 1
Specific Renal Function Categories
Mild Renal Impairment (CrCl 50-80 mL/min)
Moderate Renal Impairment (CrCl 30-49 mL/min)
- For atrial fibrillation: Use the two-criteria rule above to determine if 2.5 mg twice daily is appropriate 1, 2
- For VTE: No dose adjustment required 1
- Monitor renal function 2-3 times per year 2
Severe Renal Impairment (CrCl 15-29 mL/min)
- Apixaban should be avoided in this range according to manufacturer prescribing information 2, 1
- However, pharmacokinetic data suggest it can be used with the standard AF dosing algorithm (2.5 mg twice daily if meeting two criteria) 1
- Clinical trial data excluded patients with CrCl <25 mL/min 2
End-Stage Renal Disease (CrCl <15 mL/min or on Dialysis)
The evidence is conflicting and requires careful interpretation:
FDA labeling states: For AF patients on dialysis, standard dosing (5 mg or 2.5 mg twice daily based on the two-criteria rule) will result in similar concentrations to those in the ARISTOTLE trial, but it is unknown if this translates to similar efficacy and safety 1
Clinical trials excluded these patients 2, 1, so recommendations are based on pharmacokinetic modeling only 1
Observational data suggest: Apixaban may be safer than warfarin in dialysis patients, with lower major bleeding risk and similar stroke prevention 3. Standard-dose apixaban (5 mg twice daily) was associated with better outcomes than reduced-dose (2.5 mg twice daily) in this population 3
Dialysis removes only 14% of apixaban during a 4-hour session 1, so it is not significantly dialyzable
Current guidelines recommend against use in severe renal impairment (CrCl <30 mL/min) 2, though this is based on trial exclusion criteria rather than safety data
Monitoring Requirements
Baseline renal function assessment is mandatory before initiating apixaban. 2 Use the Cockcroft-Gault formula to calculate creatinine clearance, as this was used in clinical trials. 2
Ongoing monitoring frequency: 2
- Annual assessment for patients with normal or mildly impaired renal function
- Every 4-6 months for moderate impairment (CrCl 30-49 mL/min)
- Every 3-4 months for severe impairment if used off-label
Comparison to Other Anticoagulants in Renal Disease
Apixaban has significant advantages over other options in renal impairment: 2, 4, 5
- Versus warfarin: Similar efficacy but lower bleeding risk, particularly in moderate-to-severe CKD 6, 3
- Versus dabigatran: Dabigatran is contraindicated when CrCl <30 mL/min due to 80% renal elimination 2
- Versus rivaroxaban: Rivaroxaban should be avoided when CrCl <30 mL/min and used cautiously at 30-49 mL/min 2
- Versus enoxaparin: LMWH requires dose reduction or is contraindicated when CrCl <30 mL/min 2
Critical Pitfalls to Avoid
Do not use the two-criteria dose reduction rule for VTE treatment/prophylaxis – it only applies to atrial fibrillation. 1 VTE dosing remains standard regardless of age, weight, or creatinine.
Do not assume all DOACs are equivalent in renal disease – apixaban's lower renal dependence makes it the preferred DOAC when renal function is impaired. 2, 5
Avoid concurrent use of strong dual CYP3A4 and P-glycoprotein inhibitors (ketoconazole, itraconazole, ritonavir) as these are contraindicated and can significantly increase apixaban levels. 2, 1
In elderly patients with borderline renal function, reassess frequently – a patient who initially doesn't meet dose reduction criteria may develop worsening renal function requiring dose adjustment. 2
For dialysis patients, if apixaban is used off-label, strongly consider standard 5 mg twice daily dosing rather than empiric dose reduction, as observational data suggest better outcomes with standard dosing. 3