What are the serum creatinine and Glomerular Filtration Rate (GFR) thresholds for initiating Eliquis (apixaban) in a patient with impaired renal function?

Renal Function Thresholds for Initiating Eliquis (Apixaban)

Apixaban can be initiated in patients with creatinine clearance (CrCl) ≥15 mL/min, but dose reduction to 2.5 mg twice daily is required for CrCl 15-29 mL/min or when two of three criteria are met: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Renal Function Assessment Requirements

You must calculate creatinine clearance using the Cockcroft-Gault formula—never rely on serum creatinine alone or eGFR for medication dosing decisions. 3, 2

• The Cockcroft-Gault formula is: CrCl (mL/min) = [(140 - age) × weight (kg)] / [72 × serum creatinine (mg/dL)] × (0.85 if female) 3
• This formula is specifically required because apixaban dosing studies and FDA approval were based on Cockcroft-Gault-derived creatinine clearance values 3
• eGFR (MDRD or CKD-EPI equations) should NOT be used for apixaban dosing decisions, as these provide GFR normalized to body surface area (mL/min/1.73 m²), which leads to dosing errors 3, 2

Specific Dosing Thresholds by Renal Function

CrCl ≥50 mL/min (Mild Renal Impairment)

• Standard dose: 5 mg twice daily 1, 2
• No dose adjustment required based on renal function alone 4

CrCl 30-49 mL/min (Moderate Renal Impairment)

• Standard dose: 5 mg twice daily 1, 2
• Reduce to 2.5 mg twice daily if two of the following criteria are met:
  • Age ≥80 years
  • Weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL 1, 2

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

• Reduced dose: 2.5 mg twice daily 1, 2
• This is approved in Europe and supported by pharmacokinetic data showing apixaban has the lowest renal clearance (27%) among DOACs 1, 2, 4
• Apixaban exposure (AUC) increases by only 44% in severe renal impairment compared to normal function, which is modest compared to other DOACs 4

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

• In the United States: 5 mg twice daily is FDA-approved for chronic, stable dialysis-dependent patients 1, 2
• In Europe: Apixaban use in ESRD is not routinely recommended due to lack of hard endpoint data 1
• Critical caveat: Recent evidence shows plasma levels with 5 mg twice daily may be supra-therapeutic in dialysis patients, and 2.5 mg twice daily produces levels similar to those in patients with normal renal function 1
• Multiple observational studies suggest apixaban may be safer than warfarin in ESRD, but randomized trial data are lacking 5

Critical Monitoring Requirements

Renal function must be reassessed at regular intervals—never assume stable kidney function. 2

• Assess renal function at least annually in all apixaban patients 1, 2
• For CrCl <60 mL/min: Monitor more frequently using the formula (CrCl ÷ 10 = monitoring frequency in months) 2
  • Example: CrCl 30 mL/min = reassess every 3 months
• Reassess renal function during acute illness (infections, heart failure, dehydration) as these can transiently worsen kidney function 2

Common Pitfalls to Avoid

Do not use serum creatinine alone to assess renal function—this significantly underestimates renal insufficiency, especially in elderly patients with reduced muscle mass. 3

• A serum creatinine of 1.2 mg/dL may represent CrCl of 110 mL/min in a young adult but only 40 mL/min in an elderly patient 3
• When serum creatinine significantly increases, GFR has already decreased by at least 40% 3

Avoid combining apixaban with nephrotoxic medications (NSAIDs, COX-2 inhibitors) or other drugs that increase bleeding risk. 2

Be aware that apixaban can cause rare but serious hemorrhagic complications in uncommon sites (pleural, pericardial, intracranial) in patients with severe kidney disease, even with guideline-based dosing. 6

Absolute Contraindication

Apixaban should be avoided in patients with CrCl <15 mL/min who are not on chronic, stable dialysis, as safety and efficacy data are insufficient. 1, 2