Apixaban Dosing in Patients with Impaired Renal Function
The standard dose of apixaban is 5 mg twice daily, with a reduced dose of 2.5 mg twice daily required for patients with at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Standard Dosing Guidelines
Apixaban dosing should follow this algorithm based on renal function:
Normal to Moderate Renal Impairment (CrCl >30 mL/min):
- Standard dose: 5 mg twice daily
- Reduced dose (2.5 mg twice daily) if patient has at least 2 of:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Severe Renal Impairment (CrCl 15-30 mL/min):
- Use with caution
- Same dosing criteria as above (5 mg twice daily or 2.5 mg if meeting reduction criteria)
- More frequent monitoring recommended
End-Stage Renal Disease (ESRD) on Hemodialysis:
- Standard dose: 5 mg twice daily
- Reduced dose (2.5 mg twice daily) if:
- Age ≥80 years OR
- Body weight ≤60 kg
- Note: Clinical trials did not include these patients 1
CrCl <15 mL/min (not on dialysis):
- Limited data available
- No specific dosing recommendations provided in FDA labeling 1
Evidence Quality and Considerations
The FDA-approved dosing recommendations are based on the ARISTOTLE trial, which demonstrated that apixaban was more effective than warfarin for stroke prevention with less bleeding risk 2. However, patients with severe renal impairment (CrCl <25 mL/min) were excluded from this pivotal trial 2.
For ESRD patients on dialysis, the FDA label states that administration of apixaban at the usually recommended dose will result in concentrations similar to those observed in the ARISTOTLE study, but acknowledges that it's unknown whether these concentrations will lead to similar stroke reduction and bleeding risk 1.
Special Considerations
Drug Interactions: Dose adjustments may be needed with medications that are strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole), which require a 50% reduction in apixaban dose 3.
Elderly Patients: Older adults often have higher than expected apixaban concentrations, even at recommended doses 4. This suggests careful monitoring is particularly important in this population.
ESRD Patients: An observational study found that standard-dose apixaban (5 mg twice daily) in ESRD patients on dialysis was associated with lower risks of stroke/systemic embolism and death compared to reduced-dose apixaban or warfarin 5. However, this was not a randomized trial, and the FDA label does not specifically recommend this approach.
Common Pitfalls to Avoid
Inappropriate Dose Reduction: In clinical practice, reduced doses are often prescribed when not indicated by the criteria. A study from AUGUSTUS showed that less than half of patients receiving reduced-dose apixaban actually met dose-reduction criteria 6.
Overlooking Drug Interactions: Failing to adjust dosing when patients are on medications that interact with apixaban's metabolism pathways.
Assuming All DOACs Have Similar Renal Dosing: Unlike dabigatran (which should not be used if CrCl <15 mL/min) 2 or rivaroxaban (which should not be used if CrCl <15 mL/min) 2, apixaban has different recommendations for severe renal impairment.
Hepatic Impairment: No dose adjustment is required for mild hepatic impairment (Child-Pugh A), but apixaban is not recommended in severe hepatic impairment (Child-Pugh C) 1.
By following these evidence-based dosing recommendations and considering patient-specific factors, clinicians can optimize the safety and efficacy of apixaban therapy in patients with impaired renal function.