What are the dosing considerations for Eliquis (apixaban) in patients with impaired renal function, specifically those with reduced creatinine clearance?

From the Guidelines

Apixaban (Eliquis) dosing requires adjustment in patients with impaired renal function, with a recommended dose of 2.5 mg twice daily for patients with severe renal impairment (creatinine clearance 15-29 mL/min) or those meeting specific criteria such as age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. For patients with end-stage renal disease (creatinine clearance less than 15 mL/min) or on dialysis, the dose is also 2.5 mg twice daily, though clinical experience in this population is limited 1. The following key points should be considered:

• For patients with mild to moderate renal impairment (creatinine clearance 30-80 mL/min), no dose adjustment is typically required unless other risk factors are present 1.
• Dose reduction to 2.5 mg twice daily is recommended if the patient meets two or more of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1.
• Regular monitoring of renal function is essential during treatment, as deterioration may necessitate dose adjustments.
• Apixaban is partially cleared by the kidneys (approximately 27%), which explains why severe renal impairment increases drug exposure and bleeding risk, making these dose adjustments necessary to maintain an appropriate balance between preventing thrombosis and avoiding hemorrhagic complications 1. Key considerations for dosing adjustments include:
• Creatinine clearance levels
• Patient age and weight
• Serum creatinine levels
• Presence of other risk factors It is essential to follow the most recent guidelines and consult with a healthcare professional for personalized dosing recommendations, as the optimal approach may vary depending on individual patient factors 1.

From the FDA Drug Label

The recommended dose of apixaban tablets is 2.5 mg twice daily in patients with at least two of the following characteristics:

• 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 dosing considerations for Eliquis (apixaban) in patients with impaired renal function, specifically those with reduced creatinine clearance, are as follows:

• No dose adjustment is recommended for nonvalvular atrial fibrillation patients unless at least 2 of the following patient characteristics are present: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL.
• For patients with end-stage renal disease (ESRD) on hemodialysis, the systemic exposure to apixaban is 36% higher when compared to subjects with normal renal function. However, no specific dose recommendations are provided for patients with reduced creatinine clearance. 2 2

From the Research

Dosing Considerations for Eliquis (Apixaban) in Patients with Impaired Renal Function

• The dosing of Eliquis (apixaban) in patients with impaired renal function is an important consideration due to the potential for increased risk of bleeding or thrombosis 3, 4, 5, 6.
• Studies have shown that apixaban may be a reasonable alternative to warfarin in patients with severe renal dysfunction, with a lower risk of thrombotic and bleeding events 3.
• In patients with mild renal impairment (creatinine clearance 50-80 mL/min), the risk of bleeding with apixaban is significantly less compared to conventional anticoagulants 4.
• In patients with moderate to severe renal impairment (creatinine clearance <50 mL/min), the risk of bleeding with apixaban is similar to that of conventional anticoagulants 4.
• The efficacy and safety of apixaban compared to warfarin in patients with atrial fibrillation is consistent across different levels of renal function, with apixaban reducing the rate of stroke, death, and major bleeding regardless of renal function 5, 6.

Renal Function and Apixaban Dosing

• The Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations can be used to estimate glomerular filtration rate (GFR) and guide apixaban dosing in patients with impaired renal function 5, 6.
• A decrease in estimated GFR over time is associated with a higher risk of stroke, bleeding, and death in patients with atrial fibrillation, and the beneficial effects of apixaban compared to warfarin are consistent in patients with normal, poor, and worsening renal function 6.
• Alternative dose reduction criteria for apixaban based on age and renal function alone may be valid in patients with atrial fibrillation and chronic kidney disease, particularly when patient weight is not available 7.

Key Findings

• Apixaban may be a reasonable alternative to warfarin in patients with severe renal dysfunction 3.
• The risk of bleeding with apixaban is lower in patients with mild renal impairment and similar in patients with moderate to severe renal impairment compared to conventional anticoagulants 4.
• The efficacy and safety of apixaban compared to warfarin is consistent across different levels of renal function 5, 6.