What are the implications of using Apixaban (Eliquis) in patients undergoing Hemodialysis (HD)?

From the Guidelines

Eliquis (apixaban) should be used with caution in patients on hemodialysis, with a recommended dose of 2.5 mg twice daily, as it may offer advantages over warfarin, including more predictable anticoagulation and potentially lower bleeding risk. When prescribing Eliquis for hemodialysis patients, consider other dose-reduction criteria such as age ≥80 years, body weight ≤60 kg, or concomitant use of strong CYP3A4 and P-glycoprotein inhibitors, which may warrant further dose adjustments 1. Regular monitoring for signs of bleeding is essential, and the medication should be taken at consistent times each day, regardless of dialysis schedule. According to the latest systematic review and meta-analysis, apixaban was associated with a significantly lower risk of major bleeding compared to warfarin in patients on dialysis 1.

Some key points to consider when using Eliquis in hemodialysis patients include:

• The dose of Eliquis should be reduced to 2.5 mg twice daily, as recommended by the American Heart Association/American College of Cardiology guidelines 1
• Hemodialysis patients often have multiple risk factors that increase bleeding risk, including altered pharmacokinetics due to kidney dysfunction 1
• Regular monitoring for signs of bleeding is essential, and the medication should be taken at consistent times each day, regardless of dialysis schedule 1
• Compared to warfarin, Eliquis may offer advantages for hemodialysis patients, including more predictable anticoagulation, fewer drug interactions, and potentially lower bleeding risk, though individual patient factors should guide the final choice of anticoagulant 1.

It is also important to note that the use of NOACs, including Eliquis, in patients on dialysis is still being studied, and the results of ongoing trials, such as the RENAL-AF and AXADIA trials, may provide further guidance on the safety and efficacy of these medications in this population 1.

From the FDA Drug Label

Patients with End-Stage Renal Disease on Dialysis Clinical efficacy and safety studies with apixaban did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of apixaban at the usually recommended dose [see Dosage and Administration (2. 1)] will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study [see Clinical Pharmacology (12. 3)].

Hemodialysis in ESRD subjects: Systemic exposure to apixaban administered as a single 5 mg dose in ESRD subjects dosed immediately after the completion of a 4-hour hemodialysis session (post-dialysis) is 36% higher when compared to subjects with normal renal function (Figure 3)

Eliquis on Hemodialysis:

• The recommended dose for patients with at least two of the following characteristics is 2.5 mg twice daily:
  • age greater than or equal to 80 years
  • body weight less than or equal to 60 kg
  • serum creatinine greater than or equal to 1.5 mg/dL
• No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis.
• Systemic exposure to apixaban is 36% higher in ESRD subjects dosed immediately after hemodialysis and 17% higher when dosed 2 hours prior to a 4-hour hemodialysis session.
• The dialysis clearance of apixaban is approximately 18 mL/min.
• The systemic exposure of apixaban is 14% lower on dialysis when compared to not on dialysis. 2 2

From the Research

Eliquis (Apixaban) on Hemodialysis

• Apixaban is currently the only oral direct factor Xa inhibitor approved for treatment and prevention of venous thromboembolism (VTE) in patients on hemodialysis 3.
• Studies have shown that apixaban can be safely used in patients with end-stage renal disease (ESRD) on hemodialysis, with a lower risk of bleeding and thromboembolic events compared to warfarin therapy 4, 5.
• The optimal dosing of apixaban in patients on hemodialysis is still uncertain, with varying dosing patterns observed in clinical practice 3.
• A single-dose pharmacokinetics study found that apixaban exposure in patients on maintenance hemodialysis is dependent on both drug dose and timing of intake relative to the hemodialysis procedure 6.
• Drug level monitoring may be a useful tool to increase patient safety and guide dosing decisions in patients on hemodialysis 7.
• A national cohort study found that apixaban was associated with a lower risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding compared to warfarin in patients with ESKD on dialysis 5.

Key Findings

• Apixaban is a safe and effective treatment option for patients with ESRD on hemodialysis 4, 5.
• Dosing patterns for apixaban in patients on hemodialysis vary widely in clinical practice 3.
• Timing of apixaban intake relative to hemodialysis procedure affects drug exposure 6.
• Drug level monitoring may help guide dosing decisions and improve patient safety 7.
• Apixaban is associated with a lower risk of bleeding compared to warfarin in patients with ESKD on dialysis 5.