What is the recommended dose of Apixaban (apixaban) for patients with varying degrees of impaired renal function?

Apixaban Dosing in Renal Impairment

The standard dose of apixaban is 5 mg twice daily for most patients, with dose reduction to 2.5 mg twice daily required ONLY when patients meet at least 2 of 3 specific criteria: age ≥80 years, body weight ≤60 kg, OR serum creatinine ≥1.5 mg/dL. 1, 2

Standard Dosing Algorithm

For Atrial Fibrillation (Stroke Prevention)

Patients require dose reduction to 2.5 mg twice daily ONLY if they meet ≥2 of the following 3 criteria: 1, 2

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL (133 μmol/L)

If patients meet 0 or 1 criterion, the standard dose of 5 mg twice daily should be used. 3, 4, 5

Renal Function-Specific Guidance

Mild Renal Impairment (CrCl 50-79 mL/min)

• Standard dose of 5 mg twice daily 3, 6
• No automatic dose reduction based on renal function alone 3, 6
• Annual renal function monitoring is sufficient 3

Moderate Renal Impairment (CrCl 30-50 mL/min)

• Standard dose of 5 mg twice daily unless patient meets ≥2 dose-reduction criteria 1, 6
• Apixaban is preferred over other DOACs due to only 27% renal clearance (vs. 80% for dabigatran, 66% for rivaroxaban) 1, 3, 6
• Monitor renal function every 3-6 months 3, 4

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

• Standard dose of 5 mg twice daily can be used 6, 7
• Reduce to 2.5 mg twice daily if patient meets ≥2 dose-reduction criteria 6
• European guidelines support apixaban use in severe CKD with appropriate dosing 6
• More frequent renal monitoring required 3

End-Stage Renal Disease on Dialysis

• 5 mg twice daily is the recommended dose 3, 2
• Reduce to 2.5 mg twice daily if age ≥80 years OR body weight ≤60 kg (note: only 2 criteria apply in dialysis, not the creatinine criterion) 3, 2
• Pharmacokinetic data show 2.5 mg twice daily in dialysis produces similar drug exposure to 5 mg twice daily in normal renal function 6
• Apixaban is preferred over other DOACs in dialysis due to lowest renal clearance 3, 6

Critical Dosing Pitfalls to Avoid

Most Common Prescribing Error

Underdosing based on a single criterion rather than requiring 2 criteria 3, 4

• Studies show 9.4-40.4% of apixaban prescriptions involve inappropriate dose reduction 4
• Clinicians often reduce dose based solely on perceived bleeding risk or isolated renal dysfunction without meeting formal criteria 3, 4
• Patients with only 1 dose-reduction criterion should receive 5 mg twice daily 5, 8

Renal Function Assessment

• Use Cockcroft-Gault equation to calculate creatinine clearance for DOAC dosing 3, 4
• Do not confuse stable CKD with acute renal failure 3
• In acute illness, reassess renal function immediately before continuing apixaban 3

Evidence Supporting Standard Dosing with Single Criterion

The ARISTOTLE trial demonstrated that patients with only 1 dose-reduction criterion who received 5 mg twice daily had similar efficacy (HR 0.94 vs warfarin) and safety (HR 0.68 for major bleeding vs warfarin) compared to those with no criteria 5. This confirms that 5 mg twice daily is safe and appropriate for patients with isolated advanced age, low body weight, or renal dysfunction. 5

Monitoring Requirements

Renal Function Monitoring Frequency

• CrCl ≥60 mL/min: Annual monitoring 3
• CrCl 30-60 mL/min: Every 3-6 months 3, 4
• CrCl <30 mL/min or dialysis: More frequent monitoring 3, 6
• Use formula: CrCl ÷ 10 = minimum months between checks 3

Additional Monitoring Triggers

• Acute illness, infections, or acute heart failure warrant immediate renal reassessment 3
• 29% of patients with heart failure or CKD require dose adjustments during follow-up 4

Drug Interactions Requiring Dose Adjustment

Avoid or use caution with strong P-glycoprotein and CYP3A4 inhibitors: 3, 6

Contraindicated Combinations

• Ketoconazole, itraconazole, verapamil 3

Require Caution/Possible Adjustment

• Amiodarone, dronedarone, quinidine, clarithromycin 3
• Ciclosporin, erythromycin 1

Reduce Apixaban Effectiveness (Avoid)

• Rifampicin, St. John's wort 3

Increase Bleeding Risk (Avoid)

• NSAIDs, COX-2 inhibitors (can worsen renal function and increase bleeding) 3

Special Populations

DVT/PE Treatment and VTE Prophylaxis

• No dose adjustment needed for any degree of renal impairment, including ESRD on dialysis 2
• Standard dosing: 10 mg twice daily for 7 days, then 5 mg twice daily 1
• Extended prophylaxis: 2.5 mg twice daily 1

Cancer Patients

The 2013 NCCN guidelines noted insufficient data in cancer patients (only 2.7% enrolled in AMPLIFY trial), though this reflects older evidence 1. Current practice has evolved, but apixaban should be avoided in severe renal impairment (CrCl <15 mL/min) per manufacturer specifications 1.

Comparative Advantages in Renal Impairment

Apixaban has the lowest renal clearance (27%) among all DOACs: 1, 3, 6

• Dabigatran: 80% renal clearance (contraindicated in ESRD) 6
• Rivaroxaban: 66% renal clearance 6
• Edoxaban: 50% renal clearance (contraindicated in ESRD) 6

When switching from dabigatran, transition to apixaban when CrCl falls below 50 mL/min 6

Clinical Outcomes in Severe Renal Impairment

Real-world registry data in patients with severe renal impairment (eGFR 15-30 mL/min) showed reduced-dose apixaban had significantly lower 1-year composite endpoints (18.4% vs 39.5%, P=0.007) and mortality (15.8% vs 36.8%, P=0.006) compared to warfarin, with no difference in stroke or major bleeding rates 7.