Can Eliquis (apixaban) cause acute renal failure?

Eliquis (Apixaban) and Acute Renal Failure

Eliquis (apixaban) does not typically cause acute renal failure, but it requires dose adjustment in patients with renal impairment and should be used with caution in those with severe kidney dysfunction.

Pharmacokinetics and Renal Clearance

Apixaban has a more favorable pharmacokinetic profile in patients with renal impairment compared to other direct oral anticoagulants (DOACs):

• Only approximately 27% of apixaban is eliminated through renal clearance 1
• This is significantly less than other DOACs (dabigatran: 80%, rivaroxaban: 66%, edoxaban: 50%) 1
• Apixaban undergoes metabolism mainly via CYP3A4 with minor contributions from other cytochrome enzymes 2
• Renal excretion accounts for about 27% of total clearance, with the remainder eliminated through biliary and direct intestinal excretion 2

Renal Considerations with Apixaban

Dose Adjustment in Renal Impairment

• Standard apixaban dosing should be reduced to 2.5 mg twice daily if patients meet ≥2 of the following criteria 3:

  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL (133 μmol/L)

• For patients with severe renal impairment (CrCl 15-29 mL/min), more frequent monitoring of renal function is required 1

Monitoring Recommendations

• Regular assessment of renal function using creatinine clearance (CrCl) with the Cockcroft-Gault equation is recommended 1
• More frequent monitoring is advised in patients with CrCl <30 mL/min 1
• The FDA recommends continuous monitoring of renal function and bleeding risk throughout treatment 1

Evidence on Apixaban and Renal Function

Safety in Renal Impairment

Recent studies suggest apixaban may be safely used in patients with severe renal impairment:

• A retrospective cohort analysis found no significant difference in major bleeding events between patients with preserved renal function versus impaired renal function (CrCl <25 mL/min and/or SCr >2.5 mg/dL) taking apixaban 5 mg or 2.5 mg twice daily 4

• A matched-cohort study comparing apixaban to warfarin in patients with severe renal impairment showed a nonsignificant difference in major bleeding (9.6% vs 17.8%, p=0.149) 5

• A national registry study of patients with severe renal dysfunction (15<eGFR<30 mL/min/BSA) found that reduced-dose apixaban had lower rates of composite endpoints and mortality compared to warfarin, with no significant difference in stroke, systemic embolism, or major bleeding 6

Case Report of Apixaban-Related Nephropathy

While rare, there is a case report of anticoagulant-related nephropathy (ARN) associated with apixaban:

• One reported case showed aggravation of preexisting mild acute kidney injury after initiation of apixaban therapy 7
• The patient developed oligoanuria, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts 7
• This suggests that, in rare cases, apixaban may potentially contribute to ARN similar to what has been previously described with warfarin and dabigatran 7

Clinical Recommendations

1. Monitor renal function regularly in patients taking apixaban, especially those with baseline renal impairment
2. Consider dose reduction to 2.5 mg twice daily in patients meeting specific criteria for renal impairment
3. Be vigilant for signs of worsening renal function after initiating apixaban, particularly in patients with preexisting kidney disease
4. Assess for drug interactions that might affect apixaban metabolism or excretion, especially strong dual inhibitors/inducers of CYP3A4 and P-glycoprotein

Conclusion

While apixaban has a more favorable pharmacokinetic profile in renal impairment compared to other DOACs, it should be used with appropriate dose adjustments and monitoring in patients with kidney dysfunction. Though rare, there is a documented case of possible apixaban-related nephropathy, suggesting clinicians should remain vigilant for changes in renal function after initiating therapy.