What is the recommended dosing of apixaban (Eliquis) for patients with impaired renal function, specifically chronic kidney disease (CKD)?

Apixaban Dosing in Chronic Kidney Disease

For patients with CKD, apixaban dosing depends critically on both the indication (atrial fibrillation vs. VTE) and the severity of renal impairment, with dose reduction to 2.5 mg twice daily required for atrial fibrillation patients meeting specific criteria, while VTE treatment maintains standard dosing regardless of renal function until end-stage disease. 1

Dosing by CKD Stage and Indication

Mild to Moderate CKD (CrCl 30-89 mL/min)

For atrial fibrillation:

• Standard dose is 5 mg twice daily UNLESS the patient meets at least 2 of 3 dose-reduction criteria: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1
• If 2 or more criteria are met, reduce to 2.5 mg twice daily 2, 3
• Clinical decision-making for mild CKD (Stage II, CrCl 60-89 mL/min) should match patients without CKD 2
• For moderate CKD (Stage III, CrCl 30-59 mL/min), label-adjusted dosing is appropriate 2

For VTE (pulmonary embolism or deep vein thrombosis):

• Standard dosing: 10 mg twice daily for 7 days, then 5 mg twice daily 3
• No renal-based dose adjustments are recommended for VTE treatment in mild-moderate CKD 3, 1

Severe CKD (CrCl 15-30 mL/min)

For atrial fibrillation:

• Apixaban 2.5 mg twice daily can be used with caution based on pharmacokinetic data 2
• The 2018 CHEST guidelines suggest apixaban is a viable option at this stage 2
• Post-hoc analysis from ARISTOTLE showed apixaban 5 mg twice daily (or 2.5 mg if dose-reduction criteria met) caused significantly less major bleeding (HR 0.34) and major/clinically relevant nonmajor bleeding (HR 0.35) compared to warfarin in patients with CrCl 25-30 mL/min 4

For VTE:

• No dose adjustment recommended per FDA labeling, though data are limited 1

Key pharmacokinetic consideration: Apixaban has only 27% renal clearance—the lowest among DOACs—making it theoretically preferable in advanced CKD 2, 3

End-Stage Renal Disease (CrCl <15 mL/min or on Dialysis)

For atrial fibrillation:

• In the United States only, apixaban 5 mg twice daily is FDA-approved for patients on hemodialysis 2, 1
• However, recent pharmacokinetic data show 5 mg twice daily produces supra-therapeutic levels in dialysis patients 2, 5
• Apixaban 2.5 mg twice daily produces plasma levels similar to those in patients with normal renal function on standard dosing 2, 5
• European guidelines do not approve apixaban for ESRD, recommending well-managed warfarin (TTR >65-70%) instead 2
• The 2018 CHEST guidelines suggest individualized decision-making for ESRD patients 2

For VTE:

• No dose adjustment recommended per FDA labeling, though clinical trial data excluded ESRD patients 1

Critical safety concern: Case reports document severe hemorrhagic complications (pleural, pericardial, intracranial) in ESRD patients receiving apixaban, even at guideline-based doses 6

Monitoring Requirements

Assess renal function using Cockcroft-Gault equation before initiating apixaban and reassess: 2, 3

• At least annually for all patients
• More frequently (every 3-6 months) if CrCl ≤60 mL/min
• With any acute illness that may affect renal function

Drug Interactions Requiring Dose Adjustment or Avoidance

Avoid or adjust apixaban with dual P-glycoprotein AND strong CYP3A4 inhibitors (e.g., ketoconazole plus ritonavir) 3

Use caution with single P-glycoprotein inhibitors (verapamil, amiodarone, dronedarone, clarithromycin), particularly in CKD, as they may increase apixaban levels 3

Common Pitfalls to Avoid

Do not confuse atrial fibrillation dosing with VTE dosing: The dose-reduction criteria (age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) apply ONLY to atrial fibrillation, not VTE treatment 3, 1

Do not assume standard dosing is safe in ESRD: Despite FDA approval of 5 mg twice daily for dialysis patients in the US, emerging evidence suggests 2.5 mg twice daily may be safer 2, 5

Do not use estimated GFR (eGFR): Renal function assessment for NOAC dosing should use creatinine clearance via Cockcroft-Gault, not eGFR 2

Monitor for bleeding at uncommon sites: In advanced CKD/ESRD, apixaban-related bleeding can manifest as pleural effusions, pericardial effusions, or intracranial hemorrhage, not just gastrointestinal bleeding 6

Comparative Advantage in CKD

Apixaban demonstrates superior net clinical benefit compared to warfarin across the CKD spectrum: 7, 8, 4

• In stage III CKD, apixaban reduced stroke by 68% compared to aspirin without increasing major bleeding 7
• Apixaban and rivaroxaban are preferred over dabigatran in stage III CKD due to lower renal clearance 8
• The relative safety advantage of apixaban versus warfarin increases as renal function declines 2, 4