Apixaban Dosing with GFR of 12 mL/min
Apixaban is contraindicated or should be avoided in patients with GFR 12 mL/min who are not on dialysis, as there are no established safety or efficacy data for this population. 1, 2
Critical Context: The GFR 12 Dilemma
A GFR of 12 mL/min represents end-stage renal disease (ESRD, CKD Stage 5) but falls into a dangerous gray zone:
- If NOT on dialysis: No published studies support any apixaban dose (Level of Evidence: C) 1
- If on stable hemodialysis: Apixaban 5 mg twice daily is FDA-approved, reduced to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg 1, 2
The American College of Chest Physicians explicitly recommends individualized decision-making for CrCl <15 mL/min not on dialysis, acknowledging the absence of evidence 1. The European Heart Rhythm Association does not recommend routine NOAC use in CrCl <15 mL/min or dialysis due to limited hard endpoint data 1, 2.
If Patient IS on Stable Hemodialysis
Use apixaban 5 mg twice daily as the starting dose 1, 2:
- Reduce to 2.5 mg twice daily if the patient meets at least ONE of these criteria:
This dosing is based on pharmacokinetic data showing that 2.5 mg twice daily in dialysis patients produces drug exposure comparable to 5 mg twice daily in patients with normal renal function 1, 2. Observational data from 25,523 US dialysis patients showed standard-dose apixaban (5 mg twice daily) was associated with lower risk of stroke/embolism and death compared to reduced-dose apixaban and warfarin 2.
If Patient is NOT on Dialysis
Warfarin is the preferred anticoagulant for patients with CrCl <15 mL/min not on dialysis, targeting TTR >65-70% 1. If apixaban must be considered despite lack of evidence:
- Some clinicians use 2.5 mg twice daily extrapolating from dialysis data, but this is off-label and carries significant risk 1
- The National Comprehensive Cancer Network lists apixaban as contraindicated when creatinine clearance is <25 mL/min 2
Critical Safety Warnings
Bleeding risk is substantially elevated in severe kidney disease, even with guideline-based dosing 1, 3:
- Bleeding can occur at uncommon sites including pleura, pericardium, and intracranial space 1, 3
- A case report documented fatal intracranial hemorrhage in an ESRD patient on apixaban despite appropriate dosing 3
- Apixaban has only 27% renal clearance (lowest among DOACs), but even this limited excretion can result in drug accumulation in ESRD 1, 3
Monitoring Requirements
Renal function must be reassessed every 1-3 months in patients with declining kidney function or pending dialysis 1. Calculate creatinine clearance using the Cockcroft-Gault equation, not eGFR, as this was used in pivotal trials 1, 4.
Drug Interactions to Avoid
Absolutely avoid concomitant use with 1, 2:
- Dual P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir)
- Strong CYP3A4 inducers (rifampin)
- Antiplatelet therapy including low-dose aspirin, which substantially elevates bleeding risk in CKD patients
Common Pitfall
The most common prescribing error is inappropriate dose reduction based on renal function alone when the patient is on dialysis 1. The dose reduction criteria for dialysis patients are age ≥80 years OR weight ≤60 kg—NOT based on meeting 2 of 3 criteria like in non-dialysis patients 1, 2.
Alternative Consideration
Left atrial appendage occlusion should be considered as an alternative to anticoagulation in ESRD patients at high risk of both stroke and bleeding, avoiding the bleeding risks associated with all anticoagulants 2.