From the Guidelines
Eliquis (apixaban) dosing for patients with impaired renal function should be adjusted based on the presence of specific criteria, including age ≥80 years, body weight ≤60 kg, or serum creatinine ≥133 mmol/L, with a reduced dose of 2.5 mg twice daily if at least two of these criteria are met.
Key Considerations for Renal Dosing
- The standard dose of Eliquis (apixaban) is 5 mg twice daily for patients with nonvalvular atrial fibrillation, but this may need to be reduced in patients with impaired renal function 1.
- For patients with impaired renal function, the dose reduction criteria include age ≥80 years, body weight ≤60 kg, or serum creatinine ≥133 mmol/L, with a reduced dose of 2.5 mg twice daily if at least two of these criteria are met 1.
- The medication should be used with caution in severe renal impairment (creatinine clearance 15-29 mL/min) as drug exposure increases, but the exact dose adjustment for this population is not specified in the guidelines 1.
- Renal function should be assessed before initiating therapy and periodically during treatment, as declining renal function may necessitate dose adjustments to prevent bleeding complications.
Comparison with Other Guidelines
- The 2023 ACC/AHA/ACCp/HRS guideline for the diagnosis and management of atrial fibrillation also recommends dose adjustments for apixaban based on renal function, but the specific criteria differ slightly, with a recommended dose reduction to 2.5 mg twice daily if at least two of the following are present: serum creatinine ≥1.5 mg/dL, age ≥80 years, or body weight ≤60 kg 1.
- However, the most recent and highest-quality study, the 2024 ESC guidelines for the management of atrial fibrillation, recommends the dose reduction criteria of age ≥80 years, body weight ≤60 kg, or serum creatinine ≥133 mmol/L, with a reduced dose of 2.5 mg twice daily if at least two of these criteria are met 1.
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 Patients with End-Stage Renal Disease on Dialysis Clinical efficacy and safety studies with apixaban did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of apixaban at the usually recommended dose [see Dosage and Administration (2. 1)] will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study [see Clinical Pharmacology (12. 3)]. Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery, and Treatment of DVT and PE and Reduction in the Risk of Recurrence of DVT and PE No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis [see Dosage and Administration (2. 1)].
The renal dosing recommendations for Eliquis (apixaban) indications in patients with impaired renal function are as follows:
- For patients with nonvalvular atrial fibrillation, the recommended dose is 2.5 mg twice daily if they have at least two of the following characteristics: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL.
- For patients with end-stage renal disease (ESRD) on dialysis, no dose adjustment is recommended, but it is not known whether the concentrations of apixaban will lead to similar stroke reduction and bleeding risk as seen in the ARISTOTLE study.
- For patients with renal impairment, including those with ESRD on dialysis, no dose adjustment is recommended for prophylaxis of deep vein thrombosis following hip or knee replacement surgery, and treatment of DVT and PE and reduction in the risk of recurrence of DVT and PE. 2
From the Research
Renal Dosing Recommendations for Eliquis (Apixaban)
The renal dosing recommendations for Eliquis (apixaban) in patients with impaired renal function are as follows:
- Apixaban can be used in patients with severe renal impairment, but the dosage may need to be adjusted based on the patient's creatinine clearance (CrCl) 3, 4, 5.
- For patients with a CrCl of < 15 mL/min or those receiving dialysis, the U.S. Food and Drug Administration approval of apixaban is based on pharmacokinetic data, as clinical trials excluded patients with a CrCl of < 25 mL/min or a serum creatinine concentration (SCr) of > 2.5 mg/dL 3.
- Studies have shown that apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment, with similar rates of major bleeding and thrombotic events 3, 5, 6.
- The safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease have been evaluated in a meta-analysis, which found that apixaban was associated with a lower risk of major bleeding compared to warfarin, and was found to be relatively effective with no excess risk of thromboembolic events 6.
- A study evaluating the effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban found that decreasing renal function resulted in modestly increased apixaban exposure, but did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR, suggesting that dose adjustment of apixaban is not required on the basis of renal function alone 7.
Key Findings
- Apixaban can be used in patients with severe renal impairment, but the dosage may need to be adjusted based on the patient's CrCl 3, 4, 5.
- Apixaban appears to be a reasonable alternative to warfarin in patients with severe renal impairment, with similar rates of major bleeding and thrombotic events 3, 5, 6.
- The use of apixaban in patients with advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD) is associated with a lower risk of major bleeding compared to warfarin, and is found to be relatively effective with no excess risk of thromboembolic events 6.