What is the dosage of Eliquis (apixaban) for patients with Impaired renal function undergoing hemodialysis?

From the Guidelines

For patients with impaired renal function undergoing hemodialysis, the recommended dose of Eliquis (apixaban) is 2.5 mg twice daily, as this dose has been shown to achieve plasma levels similar to those in patients with normal renal function on the respective NOACs 1.

Key Considerations

• The dose reduction is necessary due to the significant impairment of kidney function in hemodialysis patients, despite apixaban being primarily metabolized by the liver, with approximately 27% renally excreted.
• Some clinicians may consider 5 mg twice daily in hemodialysis patients with normal body weight and no other risk factors for bleeding, but this approach carries a higher bleeding risk.
• Apixaban should be taken at consistent times each day, regardless of dialysis schedule, as it is not significantly removed by the dialysis process.
• Blood levels should be monitored periodically, and patients should be assessed regularly for signs of bleeding.
• Any signs of unusual bleeding, such as blood in urine or stool, should prompt immediate medical attention.
• Patients should also inform all healthcare providers about their apixaban use before any procedures or when starting new medications to avoid potential interactions.

Evidence-Based Recommendations

• The 2019 AHA/ACC/HRS guideline recommends a dose of 5.0 or 2.5 mg twice daily for apixaban in patients with CrCl <15 ml/min (dialysis) 1.
• The 2018 European Heart Rhythm Association practical guide suggests that apixaban 2.5 mg twice daily may be used in patients on dialysis, as plasma levels similar to those in patients with normal renal function on the respective NOACs were found 1.
• The ARISTOTLE trial demonstrated that apixaban was significantly better than warfarin, with fewer overall strokes, systemic emboli, and major bleeding events, and the benefit of apixaban was independent of type of AF, risk profile, CHADS 2 or CHA 2DS-VASc score, and whether there was a prior stroke 1.

From the FDA Drug Label

Patients with End-Stage Renal Disease 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 No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis [see Dosage and Administration (2. 1)].

The dosage of Eliquis (apixaban) for patients with impaired renal function undergoing hemodialysis is the usually recommended dose. The recommended dose for most patients is 2.5 mg twice daily for patients with at least two of the following characteristics or 5 mg twice daily for other patients (although the exact usual recommended dose is not specified in the provided text) 2.

From the Research

Dosage of Eliquis (Apixaban) for Patients with Impaired Renal Function Undergoing Hemodialysis

• The dosage of apixaban for patients with impaired renal function undergoing hemodialysis is not explicitly stated in the provided studies, but some studies suggest the following:
  • A single-dose pharmacokinetics study 3 found that apixaban 5 mg resulted in higher area under the curve (AUC0-48) compared to 2.5 mg, although significance could only be reached for dosing pre-dialysis.
  • The same study 3 found that dialysis resulted in significant reduction of drug exposure, and a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0-48.
• Other studies compared the safety and efficacy of apixaban with warfarin or low-molecular weight heparin in patients with severe renal impairment, but did not specifically address the dosage for patients undergoing hemodialysis:
  • A review of the safety and efficacy of apixaban in patients with severe renal impairment 4 found that apixaban may be associated with a lower prevalence of bleeding and thromboembolic events compared to warfarin therapy.
  • A systematic review and meta-analysis 5 found that apixaban was favored over warfarin for treating venous thromboembolism in severe renal failure, reducing venous thromboembolism recurrence and bleeding risk.

Key Findings

• Apixaban may be a cautious consideration in hemodialysis patients until there is further insight into the effect of subsequent, multiple doses on drug accumulation and clinical outcomes 6.
• The safety and efficacy of apixaban in patients with end-stage renal disease (ESRD) undergoing hemodialysis is supported by several studies 6, 4, 5.
• Clinicians should monitor for signs of bleeding throughout the duration of apixaban therapy in patients with ESRD 4.