From the Guidelines
Apixaban dose reduction is recommended when a patient's glomerular filtration rate (GFR) falls below 30 mL/min, specifically for patients with a GFR of 15-29 mL/min, the standard dose of 5 mg twice daily should be reduced to 2.5 mg twice daily, as indicated in the 2024 ESC guidelines for the management of atrial fibrillation 1. The dose adjustment is also necessary if a patient meets two or more of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 μmol/L), regardless of their GFR, as stated in the 2024 ESC guidelines 1. For patients with end-stage renal disease on dialysis (GFR <15 mL/min), apixaban should be used with caution at the reduced dose of 2.5 mg twice daily, though clinical data is limited in this population. Key factors to consider for dose reduction include:
- GFR <30 mL/min
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL (133 μmol/L) The dose reduction is necessary because impaired kidney function leads to decreased clearance of apixaban, potentially causing drug accumulation and increasing the risk of bleeding complications, as noted in the 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation 1. Regular monitoring of renal function is essential for patients on apixaban to ensure appropriate dosing as kidney function may change over time.
From the FDA Drug Label
The recommended dose is 2.5 mg twice daily in patients with at least two of the following characteristics [see Dosage and Administration (2.1)]: • age greater than or equal to 80 years • body weight less than or equal to 60 kg • serum creatinine greater than or equal to 1. 5 mg/dL
The dose of Apixaban should be reduced in patients with impaired renal function, as measured by serum creatinine greater than or equal to 1.5 mg/dL, in combination with other characteristics such as age and body weight. However, the exact Glomerular Filtration Rate (GFR) level at which the dose should be reduced is not directly specified in the label. 2
From the Research
Apixaban Dose Reduction Criteria
The decision to reduce the dose of Apixaban in patients with impaired renal function is based on several factors, including the patient's Glomerular Filtration Rate (GFR).
- According to the study 3, patients with moderate renal impairment (eGFR 31.3-67.2 mL/min/1.73 m²) had significantly higher apixaban trough concentrations than patients with normal renal function.
- The study 3 suggests that a dose reduction may be considered for patients with moderately reduced renal function to achieve similar exposure as in patients with normal renal function.
- The study 4 states that dose adjustment is based on age, weight, and serum creatinine in non-valvular atrial fibrillation (NVAF), and that pharmacokinetic studies demonstrated increased apixaban exposure in patients with advanced renal impairment.
- However, the study 5 found that apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes.
- The study 6 defined mild renal impairment as creatinine clearance of 50 to 80 ml/min and moderate to severe renal impairment as creatinine clearance <50 ml/min, and found that the risk of bleeding with apixaban in patients with mild renal impairment was significantly less compared with conventional anticoagulants.
- The study 7 found that apixaban dosing is frequently inconsistent with labeling, and that factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level.
Renal Function and Apixaban Dosing
- The studies suggest that patients with renal impairment, particularly those with moderate to severe renal impairment, may require dose reduction to minimize the risk of bleeding.
- The exact level of impaired renal function at which the dose of apixaban should be reduced is not clearly defined, but the studies suggest that a GFR of less than 50 mL/min/1.73 m² may be a threshold for considering dose reduction 3, 6.
- However, the study 5 found that apixaban at any dose is effective and safe in patients with renal impairment, and that dose reduction may not be necessary in all cases.