Apixaban Renal Dosing Recommendations
Atrial Fibrillation
For atrial fibrillation, use apixaban 5 mg twice daily as the standard dose, reducing to 2.5 mg twice daily ONLY when patients meet at least 2 of these 3 criteria: age ≥80 years, body weight ≤60 kg, OR serum creatinine ≥1.5 mg/dL. 1, 2, 3
Standard Dosing Algorithm
- Standard dose: 5 mg twice daily for patients with 0 or 1 dose-reduction criteria 1, 2, 3
- Reduced dose: 2.5 mg twice daily when ≥2 of the following are present simultaneously 1, 2, 3:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Renal Function-Specific Guidance
- CrCl >30 mL/min: No dose adjustment needed based on renal function alone unless other dose-reduction criteria are met 4, 1, 5
- CrCl 15-29 mL/min (severe CKD): Use 2.5 mg twice daily 1, 5
- End-stage renal disease on dialysis: FDA recommends 5 mg twice daily, reduced to 2.5 mg twice daily only if age ≥80 years OR weight ≤60 kg (note: only ONE criterion needed in dialysis, not two) 1, 3
Critical Calculation Requirements
- Always calculate creatinine clearance using the Cockcroft-Gault equation with actual body weight, not eGFR, as this method was used in pivotal trials and FDA labeling 1, 2
- Reassess renal function at least annually, or every 3-6 months if CrCl <60 mL/min 1, 2
Common Pitfalls to Avoid
The most frequent prescribing error is inappropriate dose reduction based on a single criterion rather than requiring two. Studies show 9.4-40.4% of apixaban prescriptions involve underdosing, often driven by clinician concern about renal function or perceived bleeding risk when formal criteria are not met 2, 6. Apixaban has only 27% renal clearance, making it relatively safer in renal impairment compared to dabigatran (80%) or rivaroxaban (35%) 4, 2.
Venous Thromboembolism (VTE)
Acute Treatment Phase
- Initial 7 days: 10 mg twice daily 1, 3
- After 7 days: 5 mg twice daily for completion of treatment (minimum 3-6 months) 1, 3
- No dose adjustment for renal impairment during acute treatment phase 5, 3
Extended Secondary Prevention
- After completing ≥6 months of treatment: 2.5 mg twice daily for extended-phase anticoagulation to reduce recurrence risk 1, 5, 3
Postoperative Prophylaxis (Hip/Knee Replacement)
Use 2.5 mg twice daily for all patients regardless of renal function. 5, 3
Duration of Therapy
Drug Interactions Requiring Dose Adjustment
Reduce apixaban from 5 mg to 2.5 mg twice daily when using combined P-glycoprotein AND strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, itraconazole) 1, 2
Avoid apixaban entirely with strong CYP3A4 inducers (e.g., rifampin) as they significantly reduce apixaban levels 2
Perioperative Management
- Low bleeding risk procedures: Hold for 24 hours if CrCl >25 mL/min 2
- High bleeding risk procedures: Hold for 48 hours if CrCl >25 mL/min 2, 3
- CrCl <25 mL/min: Consider holding for an additional 1-3 days, especially for high bleeding risk procedures 2
- Restart as soon as adequate hemostasis is established 3
Special Populations
Severe Renal Impairment (CrCl 15-29 mL/min)
The decision between 5 mg and 2.5 mg twice daily depends on meeting the standard dose-reduction criteria 1, 5. Clinical data suggest apixaban may be safer than warfarin even in advanced CKD stages 4-5, though rare hemorrhagic complications can occur 1, 7, 8.
Dialysis Patients
Clinical trials did not enroll dialysis patients, but FDA guidance permits use based on pharmacokinetic data showing similar drug concentrations to those in the ARISTOTLE trial 3. Use 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg 1, 3.