What is the renal dosing for Eliquis (apixaban) in patients with impaired renal function?

Renal Dosing for Eliquis (Apixaban)

For patients with normal to moderate renal impairment (CrCl ≥30 mL/min), use apixaban 5 mg twice daily; reduce to 2.5 mg twice daily ONLY when at least 2 of 3 criteria are met: age ≥80 years, body weight ≤60 kg, OR serum creatinine ≥1.5 mg/dL. 1, 2

Dosing Algorithm by Renal Function

Normal to Moderate Renal Impairment (CrCl ≥30 mL/min)

• Standard dose: 5 mg twice daily for all patients with CrCl >30 mL/min, regardless of severity of impairment 1, 2
• No dose adjustment based on renal function alone, even with CrCl 30-50 mL/min (moderate impairment) 1
• Reduce to 2.5 mg twice daily only when patient meets at least 2 of these 3 criteria: 1, 2
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

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

• Use 5 mg twice daily as standard dose 1
• Reduce to 2.5 mg twice daily if patient meets ≥2 of the 3 dose-reduction criteria listed above 1
• Apixaban has only 27% renal clearance, making it the preferred DOAC in severe renal impairment 1, 2

End-Stage Renal Disease on Hemodialysis

• FDA-approved dosing: 5 mg twice daily for stable hemodialysis patients 1, 2
• Reduce to 2.5 mg twice daily if age ≥80 years OR body weight ≤60 kg (note: only 1 criterion needed in dialysis, not 2) 1, 3, 2
• Pharmacokinetic data show 2.5 mg twice daily in dialysis produces drug exposure similar to 5 mg twice daily in patients with normal renal function 1, 3
• Observational data from 25,523 US dialysis patients showed standard-dose apixaban (5 mg twice daily) associated with lower stroke, death, and major bleeding compared to reduced-dose apixaban and warfarin 3

End-Stage Renal Disease NOT on Dialysis (CrCl <15 mL/min)

• No established dosing recommendations exist - this population was excluded from clinical trials 1
• Consider warfarin as first-line if time in therapeutic range can be maintained >65-70% 3
• If apixaban used, employ extreme caution with individualized risk-benefit assessment 1

Critical Monitoring Requirements

Renal Function Assessment

• Calculate creatinine clearance using Cockcroft-Gault equation - this method was used in pivotal trials and FDA labeling 1, 2
• Reassess renal function at least annually in stable patients 1
• Reassess every 3-6 months in patients with CrCl <60 mL/min or declining renal function 1
• Reassess every 1-3 months in patients with progressive CKD approaching dialysis 1

Common Prescribing Errors to Avoid

The Single-Criterion Mistake

• The most common error is reducing apixaban dose based on only 1 criterion rather than requiring 2 1, 4
• Studies show 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing 1
• Do NOT reduce dose based solely on: 1
  • Renal function alone (even with CrCl 30-50 mL/min)
  • Age alone (even if ≥80 years)
  • Weight alone (even if ≤60 kg)
  • Perceived bleeding risk without meeting formal criteria

Renal Function Misinterpretation

• CrCl 30-59 mL/min (moderate CKD Stage 3) does NOT trigger dose reduction by itself 1
• Serum creatinine must be ≥1.5 mg/dL to count as 1 criterion, AND patient must meet at least 1 additional criterion 1, 2
• eGFR and CrCl are not interchangeable - always use Cockcroft-Gault CrCl for dosing decisions 1

Drug Interactions Requiring Attention

Avoid or Adjust with Dual P-glycoprotein and Strong CYP3A4 Inhibitors/Inducers

• Concomitant use may require dose adjustment or avoidance, particularly in patients with CKD 1
• Strong dual inhibitors (e.g., ketoconazole, itraconazole, ritonavir) increase apixaban levels 1
• Strong dual inducers (e.g., rifampin, carbamazepine, phenytoin) decrease apixaban levels 1

Bleeding Risk Amplifiers

• Avoid concomitant antiplatelet therapy including low-dose aspirin when possible - substantially elevates bleeding risk in CKD 1
• All anticoagulants carry increased bleeding risk in severe renal impairment, with potential for bleeding at uncommon sites (pleura, pericardium, intracranial space) 1

Pharmacokinetic Rationale

• Apixaban has the lowest renal clearance (27%) among all DOACs compared to dabigatran (80%), rivaroxaban (66%), and edoxaban (50%) 1, 2
• In severe renal impairment (CrCl 15 mL/min), apixaban AUC increases by only 44% compared to normal renal function 5
• Hemodialysis removes minimal apixaban - dialysis clearance is only 18 mL/min 2
• Apixaban 5 mg twice daily produces supratherapeutic levels in dialysis patients, but observational data suggest this may be more effective than reduced dosing 1, 3

Evidence Quality Considerations

• Dosing for CrCl >30 mL/min is based on high-quality RCT data from ARISTOTLE trial (18,201 patients) 1
• No RCTs exist for severe CKD (CrCl <25-30 mL/min) or dialysis patients - recommendations based on pharmacokinetic data and observational studies 1, 3
• European guidelines do not recommend routine DOAC use in CrCl <15 mL/min or dialysis due to limited hard endpoint data 1, 3
• US FDA approval for dialysis patients is based primarily on pharmacokinetic modeling, not clinical outcomes 3