Apixaban Dosing in Renal Impairment
For patients with impaired renal function, apixaban dosing should be reduced to 2.5 mg twice daily in patients with severe renal impairment (CrCl 15-29 mL/min), while it is not recommended for patients with end-stage renal disease (CrCl <15 mL/min) who are not on dialysis. 1, 2, 3
Dosing Recommendations Based on Renal Function
| Renal Function | Apixaban Dosing | Notes |
|---|---|---|
| Normal/Mild impairment (CrCl >50 mL/min) | 5 mg twice daily | Standard dosing |
| Moderate impairment (CrCl 30-50 mL/min) | 5 mg twice daily* | *Reduce to 2.5 mg twice daily if patient has at least 2 of: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL |
| Severe impairment (CrCl 15-29 mL/min) | 2.5 mg twice daily | Approved in Europe for use with reduced dose regimen [2] |
| End-stage CKD (CrCl <15 mL/min) not on dialysis | Not recommended | Limited clinical data [3,1] |
| Dialysis-dependent | Not recommended in Europe; 2.5 mg twice daily may be considered in US | FDA approval differs from European recommendations [2,1] |
Pharmacokinetic Considerations
- Apixaban has the lowest renal clearance (27%) among direct oral anticoagulants, making it potentially preferable in patients with renal impairment 2
- Comparatively, dabigatran has 80% renal elimination, edoxaban 50%, and rivaroxaban 33% 2, 3
- The relative safety of apixaban vs. warfarin has been demonstrated to increase with decreasing renal function 2
Special Considerations
Dose Reduction Criteria
Reduce dose to 2.5 mg twice daily if patient has at least two of the following:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL 1
Monitoring
- Regular assessment of renal function is essential, especially in patients with fluctuating renal function 3
- Monitor for signs of bleeding complications, particularly in elderly patients 3
Drug Interactions
- P-glycoprotein inhibitors (e.g., ketoconazole, verapamil, amiodarone) may increase apixaban plasma concentrations
- P-glycoprotein inducers (e.g., phenytoin, carbamazepine, rifampin) may decrease apixaban to subtherapeutic levels 3
Evidence from Clinical Studies
While landmark trials excluded patients with CrCl <25 mL/min, observational studies suggest:
- Apixaban may be a reasonable alternative to warfarin in patients with severe renal dysfunction 4, 5, 6, 7
- One study found no significant difference in major bleeding events between patients with preserved renal function versus impaired renal function (CrCl <25 mL/min) taking apixaban 5 mg twice daily (4.41% vs. 3.57%, p=0.66) 4
- Another study demonstrated lower risk of thrombotic and bleeding events with apixaban compared to warfarin in patients with CrCl <25 mL/min (HR 0.47; 95% CI 0.25-0.92) 5
Cautions and Contraindications
- Apixaban is not recommended in patients with severe hepatic impairment (Child-Pugh class C) 1
- In patients with end-stage renal disease on dialysis, clinical efficacy and safety data are limited 1
- The European Heart Rhythm Association states that routine use of NOACs in patients with severe renal dysfunction remains to be established 2, 3
Remember that renal function can fluctuate, particularly in elderly patients or those with acute illness, necessitating regular monitoring and potential dose adjustments.