What is the appropriate dosing of Eliquis (apixaban) for a patient with chronic kidney disease (CKD) and a deep vein thrombosis (DVT) in the right arm?

Apixaban Dosing for DVT in a Patient with CKD

Yes, apixaban (Eliquis) is an appropriate and preferred anticoagulant for treating upper extremity DVT in patients with chronic kidney disease, with dosing determined by the severity of renal impairment. 1, 2

Initial Treatment Phase (First 7 Days)

• Start with apixaban 10 mg orally twice daily for the first 7 days of DVT treatment, regardless of CKD stage, unless contraindicated by severe renal impairment 2
• This higher initial dose applies to upper extremity DVT just as it does for lower extremity DVT 1

Maintenance Phase (After 7 Days)

The dosing after the initial 7 days depends critically on the patient's creatinine clearance (CrCl):

For CKD Stage 1-3 (CrCl >30 mL/min):

• Continue with apixaban 5 mg orally twice daily 2
• No dose adjustment needed for mild to moderate CKD 1, 3

For CKD Stage 4 (CrCl 15-30 mL/min):

• Use apixaban 5 mg orally twice daily as the standard dose 2, 4
• Post-hoc analysis from the ARISTOTLE trial demonstrated that apixaban caused significantly less major bleeding (HR 0.34) and major or clinically relevant nonmajor bleeding (HR 0.35) compared to warfarin in patients with CrCl 25-30 mL/min 4
• Pharmacokinetic data shows only a 36% increase in drug exposure at this level of renal function, which remains within acceptable ranges 4, 5

For CKD Stage 5 (CrCl <15 mL/min) or Dialysis:

• This is a critical decision point requiring extreme caution 2, 6
• The FDA label states that patients with severe CKD (CrCl <25 mL/min) or on dialysis were excluded from major trials 1, 2
• Limited pharmacokinetic data suggests 5 mg twice daily may be used in end-stage renal disease on stable hemodialysis, with reduction to 2.5 mg twice daily if age ≥80 years OR weight ≤60 kg 1, 3
• However, warfarin may be safer than apixaban in end-stage renal disease given the lack of robust trial data and case reports of severe hemorrhagic complications including pleural, pericardial, and intracranial bleeding 6

Extended/Secondary Prevention (After 6 Months)

• After completing at least 6 months of full-dose anticoagulation, consider reducing to apixaban 2.5 mg orally twice daily for extended secondary prevention 1
• This reduced dose provides effective VTE prevention with potentially lower bleeding risk 1
• The decision for extended therapy depends on whether the DVT was provoked or unprovoked 1

Key Monitoring Requirements

• Assess renal function (CrCl) before initiating apixaban using the Cockcroft-Gault equation 3, 2
• Reassess renal function at least annually, and more frequently (every 3-6 months) if CrCl ≤60 mL/min 3
• Monitor for bleeding complications, particularly in patients with CKD stage 4 or worse 3, 7
• If CrCl declines to <15 mL/min during treatment, strongly consider switching to warfarin 6

Drug Interactions in CKD

• Reduce apixaban dose by 50% if coadministered with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) 2
• Avoid apixaban entirely if already on 2.5 mg twice daily and these inhibitors are needed 2

Critical Pitfalls to Avoid

• Do not use the atrial fibrillation dosing criteria (age ≥80, weight ≤60 kg, SCr ≥1.5 mg/dL) for VTE treatment - these only apply to stroke prevention in AF, not DVT/PE 1, 2
• Do not assume apixaban is safe in dialysis patients - while it has the lowest renal clearance (27%) among DOACs, accumulation still occurs and bleeding risk is substantial 6, 5
• Upper extremity DVT requires the same full treatment doses as lower extremity DVT - do not underdose 1

Comparative Evidence

• Retrospective studies in advanced CKD show apixaban has equivalent efficacy but superior safety compared to warfarin, with significantly lower major bleeding rates at 6-12 months (1.5% vs 8.4%, p<0.001) 7
• However, these studies excluded the most severe CKD patients, and case reports demonstrate catastrophic bleeding can occur in ESKD 6