What is the renal dosing for Eliquis (apixaban) in patients with impaired renal function?

Renal Dosing for Eliquis (Apixaban)

For patients with renal impairment, apixaban (Eliquis) dosing should be adjusted based on the degree of renal dysfunction, with 2.5 mg twice daily recommended for patients with severe renal impairment who meet specific criteria. 1

Dosing Recommendations by Renal Function Category

Normal to Mild Renal Impairment

• Standard dose of 5 mg twice daily for patients with normal renal function or mild impairment 1
• No dose adjustment needed for creatinine clearance (CrCl) >30 mL/min 1

Moderate Renal Impairment

• Standard dose of 5 mg twice daily for patients with moderate renal impairment (CrCl 30-50 mL/min) 1
• Reduce to 2.5 mg twice daily if the patient has at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1

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

• No specific recommendation was provided in the 2014 AHA/ACC/HRS guidelines 1
• However, European guidelines indicate apixaban can be used in severe CKD with dose reduction 1
• Apixaban has the lowest renal clearance (27%) among direct oral anticoagulants, making it potentially preferable in patients with severe renal impairment 1
• A retrospective study showed no significant difference in major bleeding between apixaban and warfarin in patients with severe renal impairment (9.6% vs 17.8%, p=0.149) 2

End-Stage Renal Disease (ESRD) Not on Dialysis

• No recommendation was provided in the guidelines for patients with ESRD not on dialysis 1
• Caution is advised due to limited clinical data in this population 1

End-Stage Renal Disease on Dialysis

• According to FDA labeling, apixaban 5 mg twice daily can be used in patients with ESRD on stable hemodialysis, with dose reduction to 2.5 mg twice daily if the patient is ≥80 years of age or body weight is ≤60 kg 1, 3
• However, pharmacokinetic studies suggest that apixaban 2.5 mg twice daily in hemodialysis patients results in drug exposure comparable to the standard 5 mg twice daily dose in patients with preserved renal function 4
• The 5 mg twice daily dose led to supratherapeutic levels in hemodialysis patients and should be avoided 4
• Hemodialysis has limited impact on apixaban clearance, removing only about 4% of the drug during a session 5

Important Considerations

Monitoring Renal Function

• Renal function should be evaluated before initiation of apixaban 1
• Reassessment should occur at least annually and when clinically indicated 1
• Creatinine clearance should be calculated using the Cockcroft-Gault method 1

Drug Interactions

• P-glycoprotein inhibitors (ketoconazole, verapamil, amiodarone, dronedarone, quinidine, clarithromycin) may increase apixaban plasma concentrations 1, 3
• Concomitant use of dual P-glycoprotein and strong CYP3A4 inducers or inhibitors may require dosing adjustment or avoidance, particularly in patients with CKD 1

Bleeding Risk

• Patients with severe renal impairment have increased bleeding risk with all anticoagulants 1
• A case report described spontaneous pleural, pericardial, and intracranial hemorrhages in a patient with ESKD receiving apixaban, highlighting the need for vigilant monitoring 6
• The RENAL-AF trial found clinically relevant bleeding events were approximately 10-fold more frequent than stroke or systemic embolism among hemodialysis patients on anticoagulation 7

Clinical Decision Algorithm

1. Calculate creatinine clearance using Cockcroft-Gault method
2. Assess for additional risk factors (age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL)
3. Select appropriate dose:
   • CrCl >30 mL/min with 0-1 risk factors: 5 mg twice daily
   • CrCl >30 mL/min with ≥2 risk factors: 2.5 mg twice daily
   • CrCl 15-29 mL/min: Consider 2.5 mg twice daily (limited evidence)
   • ESRD on dialysis: 2.5 mg twice daily (based on pharmacokinetic data)
4. Monitor renal function regularly and adjust dose as needed
5. Evaluate for drug interactions that may affect apixaban levels

By following these guidelines and considering individual patient factors, appropriate dosing of apixaban can be achieved to balance stroke prevention and bleeding risk in patients with renal impairment.