What is the dosing of Eliquis (apixaban) in severe renal impairment?

Dosing of Eliquis (Apixaban) in Severe Renal Impairment

For patients with severe renal impairment (creatinine clearance 15-29 mL/min), Eliquis (apixaban) should be dosed at 2.5 mg twice daily. 1, 2

Understanding Apixaban's Renal Clearance Profile

Apixaban has the lowest renal clearance (25%) among the NOACs, making it a preferred option for patients with compromised kidney function 1. This pharmacokinetic property provides a more favorable safety profile compared to other anticoagulants in patients with renal impairment.

Dosing Algorithm for Apixaban in Renal Impairment

1. Normal to Mild Renal Impairment (CrCl ≥30 mL/min):

   • Standard dose: 5 mg twice daily
   • Reduce to 2.5 mg twice daily if patient has at least 2 of the following:
     • Age ≥80 years
     • Body weight ≤60 kg
     • Serum creatinine ≥1.5 mg/dL

2. Severe Renal Impairment (CrCl 15-29 mL/min):

   • 2.5 mg twice daily 1, 2

3. End-Stage Renal Disease (CrCl <15 mL/min) or Dialysis:

   • Limited clinical data available
   • FDA label indicates that in ESRD patients on hemodialysis, 5 mg twice daily can be used, reduced to 2.5 mg twice daily if age ≥80 years or body weight ≤60 kg 2
   • European guidelines are more cautious and do not recommend routine use in this population 1

Evidence Supporting Apixaban in Severe Renal Impairment

Research demonstrates that apixaban has a more favorable safety profile in patients with renal impairment compared to warfarin:

• A meta-analysis showed that bleeding risk with apixaban is significantly lower in mild renal impairment and similar in moderate to severe renal impairment compared to conventional anticoagulants 3

• Clinical studies have found no significant difference in major bleeding events between patients with preserved renal function and those with impaired renal function (CrCl <25 mL/min) receiving apixaban 4, 5

• Pharmacokinetic studies show that decreasing renal function results in only modestly increased apixaban exposure (44% increase in AUC∞ with severe impairment) 6

• A registry study found that apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment, with lower rates of composite endpoints and mortality 7

Important Clinical Considerations

• Regular monitoring of renal function is essential in patients on apixaban with renal impairment 1

• Apixaban has demonstrated a reduction in major hemorrhage compared to warfarin across different levels of renal function 1

• Unlike some other NOACs, apixaban's dose reduction criteria are based on multiple factors (age, weight, and serum creatinine), not solely on renal function 2

• Patients with severe renal dysfunction were largely excluded from pivotal NOAC trials, so clinical experience in this population continues to evolve 1

Potential Pitfalls and Caveats

• Avoid using estimated GFR for dosing decisions; instead, use creatinine clearance calculated by the Cockcroft-Gault equation 1

• Be vigilant for drug interactions, particularly with P-glycoprotein inhibitors or CYP3A4 inhibitors, which may increase apixaban levels 2

• For patients transitioning between anticoagulants, appropriate overlap periods should be considered based on the specific agents involved

• In patients requiring procedures, apixaban should be discontinued 3-4 days before high bleeding risk surgeries in those with moderate renal impairment 1

By following these evidence-based recommendations, clinicians can optimize anticoagulation therapy with apixaban in patients with severe renal impairment while minimizing bleeding risks and maintaining efficacy for stroke prevention.