What is the recommended dose of Eliquis (apixaban) for a patient with moderate to severe impaired renal function, indicated by an estimated glomerular filtration rate (eGFR) of 36?

Apixaban Dosing for eGFR 36

For a patient with an eGFR of 36 mL/min, the standard dose of apixaban is 5 mg twice daily, but this should be reduced to 2.5 mg twice daily only if the patient meets at least two of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Dosing Algorithm for Moderate Renal Impairment

An eGFR of 36 mL/min falls into the moderate-to-severe renal impairment category (CKD stage 3b), which corresponds to a creatinine clearance typically in the 30-50 mL/min range. 3, 1

Step 1: Determine Base Dose

• Start with 5 mg twice daily as the default dose for patients with CrCl 30-50 mL/min 3, 1, 2
• No automatic dose reduction is required based solely on renal function at this level 1, 4

Step 2: Apply Dose Reduction Criteria

Reduce to 2.5 mg twice daily ONLY if ≥2 of the following are present: 2

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

If only one criterion is met, maintain the 5 mg twice daily dose. 1, 5

Rationale for This Approach

Pharmacokinetic Advantages

• Apixaban has the lowest renal clearance (27%) among all direct oral anticoagulants, making it the preferred choice in renal impairment 1, 4
• The remaining 73% is metabolized via non-renal pathways (primarily CYP3A4), providing a safety margin in kidney disease 4
• This low renal dependence allows for safe use across a broad range of renal function 5

Evidence Base

• The ARISTOTLE trial demonstrated that apixaban was more effective than warfarin in preventing stroke and reducing mortality across all levels of renal function, including patients with eGFR ≤50 mL/min 6
• Major bleeding reduction was actually greatest in patients with impaired renal function (eGFR ≤50 mL/min), with a hazard ratio of 0.50 compared to warfarin 6
• Real-world registry data in patients with severe renal dysfunction (eGFR 15-30 mL/min) showed reduced-dose apixaban had lower mortality and composite endpoints compared to warfarin 7

Critical Monitoring Requirements

Renal Function Assessment

• Calculate creatinine clearance using the Cockcroft-Gault equation, as this was the method used in pivotal trials 1, 5
• Reassess renal function at least annually, or every 3-6 months in patients with declining kidney function 1, 5
• More frequent monitoring (every 2-3 months) is warranted if eGFR continues to decline toward 30 mL/min 5

Drug Interactions to Avoid

• Avoid concomitant use of dual P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) in patients already on 2.5 mg twice daily 2
• If the patient is on 5 mg twice daily and requires these inhibitors, reduce the dose by 50% 2
• Avoid concomitant antiplatelet therapy (including low-dose aspirin) as this substantially increases bleeding risk in CKD patients 1

Common Pitfalls and How to Avoid Them

Pitfall #1: Automatic Dose Reduction Based on Renal Function Alone

• Do not automatically reduce to 2.5 mg twice daily just because eGFR is <50 mL/min 1, 4
• The dose reduction criteria require at least 2 of 3 factors, not renal function alone 2

Pitfall #2: Using the Wrong Renal Function Calculation

• Use Cockcroft-Gault for dosing decisions, not MDRD or CKD-EPI, as regulatory guidance and trial data are based on creatinine clearance 3, 1
• There can be significant discrepancies between these methods for the same patient 3

Pitfall #3: Overlooking Body Weight

• Body weight ≤60 kg is a critical dose reduction criterion but is often missing from electronic health records 8
• Always obtain an accurate weight measurement before finalizing the dose 8

Pitfall #4: Ignoring Bleeding at Uncommon Sites

• In severe kidney disease, bleeding can occur at unusual locations including pleura, pericardium, and intracranial space 9
• Maintain high clinical suspicion for hemorrhagic complications even with guideline-based dosing 9

Comparison to Other Anticoagulants

• Rivaroxaban requires dose reduction to 15 mg daily at CrCl 30-49 mL/min and is not recommended below 30 mL/min 3, 4
• Dabigatran requires dose reduction at CrCl 30-50 mL/min and is contraindicated below 30 mL/min in Europe 3, 5
• Edoxaban is contraindicated in end-stage renal disease and should not be used 1
• Warfarin requires 20% lower doses in severe CKD and has more labile INR control, with increased risk of vascular calcification 3

If Renal Function Continues to Decline

• If eGFR falls to 15-29 mL/min: Consider reducing to 2.5 mg twice daily regardless of other factors, though FDA labeling for atrial fibrillation still permits the dose reduction algorithm 3, 4
• If patient progresses to dialysis: The dose is 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg (note: only ONE criterion needed for dialysis patients) 1, 2