What is the recommended dosing of Eliquis (apixaban) for a patient with impaired renal function pending dialysis initiation?

Eliquis (Apixaban) Dosing in Chronic Kidney Disease Pending Dialysis Initiation

For patients with chronic kidney disease pending dialysis initiation (CrCl <15 mL/min or ESRD not yet on dialysis), apixaban 2.5 mg twice daily is the recommended dose based on pharmacokinetic data, though clinical outcome data in this population are limited. 1, 2

Dosing Algorithm by Renal Function Status

Pre-Dialysis ESRD (CrCl <15 mL/min, not yet on dialysis)

• Use apixaban 2.5 mg twice daily as the standard dose for patients with CrCl <15 mL/min who are not yet on dialysis 1, 2
• This dosing is based on pharmacokinetic modeling showing that 2.5 mg twice daily in severe renal impairment produces drug exposure comparable to 5 mg twice daily in patients with normal renal function 1, 3
• Apixaban has the lowest renal clearance (27%) among all direct oral anticoagulants, making it the preferred DOAC in severe renal impairment 4, 1, 2

Once Dialysis is Initiated (ESRD on hemodialysis)

• Start with 5 mg twice daily as the standard dose for stable hemodialysis patients 4, 1, 3, 5
• Reduce to 2.5 mg twice daily if the patient meets at least one of these criteria: age ≥80 years OR body weight ≤60 kg 4, 1, 3, 5
• This FDA-approved dosing for dialysis patients is based on pharmacokinetic data showing that standard dosing in hemodialysis produces similar drug concentrations to those in the ARISTOTLE trial 5

Critical Monitoring Requirements

Renal Function Assessment

• Calculate creatinine clearance using the Cockcroft-Gault method, as this was used in pivotal trials 4, 1
• Reassess renal function at least annually and more frequently when clinical deterioration occurs 1
• In patients pending dialysis, monitor renal function every 1-3 months given the dynamic nature of declining kidney function 4

Bleeding Risk Surveillance

• Bleeding can occur at uncommon sites (pleura, pericardium, intracranial space) in severe kidney disease, even with guideline-based dosing 6
• Monitor for progressive dyspnea or chest pain, which may indicate hemorrhagic pleural or pericardial effusions before more catastrophic bleeding occurs 6
• All anticoagulants carry substantially increased bleeding risk in severe renal impairment 4, 3

Drug Interactions Requiring Dose Adjustment or Avoidance

• Avoid concomitant use of dual P-glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) or inducers (e.g., rifampin, carbamazepine), particularly in CKD patients 4, 1, 2
• Avoid concomitant antiplatelet therapy including low-dose aspirin, as this substantially elevates bleeding risk in CKD patients 4, 3

Evidence Quality and Guideline Consensus

Strength of Evidence

• The 2014 AHA/ACC/HRS guidelines state there are no published studies supporting a dose for end-stage CKD not on dialysis (Level of Evidence: C) 4
• The 2018 CHEST guidelines recommend individualized decision-making for CrCl <15 mL/min not on dialysis (Ungraded consensus-based statement) 4
• FDA approval for ESRD is based primarily on pharmacokinetic data rather than clinical outcome trials 3, 5

Comparative Safety Data

• A 2017 retrospective study of 146 patients with severe renal impairment (CrCl <25 mL/min or on dialysis) showed no significant difference in major bleeding between apixaban and warfarin (9.6% vs 17.8%, p=0.149) 7
• A 2020 multicenter study of 861 patients with CrCl <25 mL/min demonstrated lower combined thrombotic and bleeding events with apixaban versus warfarin (HR 0.47,95% CI 0.25-0.92) 8

Common Pitfalls to Avoid

• Do not use dabigatran or rivaroxaban in patients with CrCl <30 mL/min due to their higher renal clearance (80% and 66% respectively) 4, 2
• Do not use edoxaban in ESRD or dialysis patients—it is absolutely contraindicated due to 50% renal excretion 3
• Do not restart apixaban at standard doses if the patient develops ESRD while on therapy; reassess dosing based on dialysis status 6
• Do not assume warfarin is safer—warfarin carries increased bleeding risk and may cause calciphylaxis in ESRD patients 3

Alternative Anticoagulation Strategy

• Warfarin remains an alternative if well-managed with time in therapeutic range (TTR) >65-70%, though it did not reduce deaths or strokes in recent meta-analyses of dialysis patients 4, 3
• Left atrial appendage occlusion should be considered in patients at high risk of both stroke and bleeding who cannot tolerate any anticoagulation 3