Is it appropriate to decrease Eliquis (apixaban) to 2.5 mg twice daily in an elderly female patient with rheumatoid arthritis, history of blood clots, and chronic kidney disease stage three with worsening anemia?

Apixaban Dose Reduction in CKD Stage 3 with Anemia

No, it is not appropriate to decrease Eliquis to 2.5 mg twice daily in this patient based solely on CKD stage 3 and worsening anemia—dose reduction requires meeting at least 2 of 3 specific criteria: age ≥80 years, body weight ≤60 kg, OR serum creatinine ≥1.5 mg/dL (not just CKD stage 3). 1, 2

Critical Dose-Reduction Criteria Assessment

The decision to reduce apixaban from 5 mg to 2.5 mg twice daily depends on meeting at least 2 of the following 3 criteria 2, 3:

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

You must verify the actual serum creatinine value and body weight in this patient. CKD stage 3 alone (CrCl 30-59 mL/min) does not automatically qualify for dose reduction—the serum creatinine must be ≥1.5 mg/dL specifically. 1, 2

Why CKD Stage 3 Alone Is Insufficient

• Apixaban has only 27% renal clearance, the lowest among all DOACs, making it relatively safe in mild-to-moderate CKD without dose adjustment. 1, 4
• For pulmonary embolism or DVT treatment specifically, standard dosing is 10 mg BID × 7 days, then 5 mg BID, with no renal-based dose adjustments recommended for CrCl >30 mL/min. 1
• The FDA label and guidelines consistently state that dose reduction to 2.5 mg BID requires meeting 2 of 3 criteria, not just impaired renal function alone. 3

Anemia Is Not a Dose-Reduction Criterion

Worsening hemoglobin is not a criterion for apixaban dose reduction. 3 However, it raises two critical clinical concerns:

• Investigate the cause of anemia: In RA patients with CKD, anemia is multifactorial (chronic disease, renal impairment, possible GI bleeding from anticoagulation). 5
• Assess bleeding risk: Worsening anemia may indicate occult bleeding, which warrants evaluation before continuing any anticoagulant dose. 3

Specific Algorithm for This Patient

Step 1: Verify the 3 dose-reduction criteria 2

• Is she ≥80 years old?
• Does she weigh ≤60 kg?
• Is her serum creatinine ≥1.5 mg/dL (not just estimated CrCl)?

Step 2: Count how many criteria are met

• If 0-1 criteria met: Continue 5 mg BID (or standard treatment dosing if treating acute VTE). 1, 2
• If ≥2 criteria met: Reduce to 2.5 mg BID. 2, 3

Step 3: Investigate the anemia 5

• Check for signs of bleeding (stool guaiac, imaging if indicated)
• Assess inflammatory markers (ESR, CRP—strongest predictors of anemia in RA after renal function) 5
• Consider iron studies, B12/folate if not recently checked

Step 4: Calculate creatinine clearance using Cockcroft-Gault equation 1

• Reassess renal function at least annually, or more frequently if CrCl ≤60 mL/min. 1
• If CrCl approaches 15-30 mL/min, apixaban can still be used at 5 mg BID for atrial fibrillation, though data for VTE treatment at this level is limited. 1

Common Pitfalls to Avoid

• Do not reduce dose based on CKD stage alone without checking actual serum creatinine value. CKD stage 3 encompasses a wide range (CrCl 30-59 mL/min), and only serum creatinine ≥1.5 mg/dL counts as a criterion. 2
• Do not confuse atrial fibrillation dosing with VTE treatment dosing. If this patient is being treated for acute DVT/PE, she should be on 10 mg BID × 7 days, then 5 mg BID, regardless of mild-moderate CKD. 1, 3
• Do not ignore drug interactions. If she is on combined P-glycoprotein AND strong CYP3A4 inhibitors (e.g., clarithromycin with ritonavir), dose adjustment may be needed. 1, 3
• Avoid dose reduction in patients already on 2.5 mg BID who are started on combined P-gp/CYP3A4 inhibitors—instead, avoid the combination entirely. 3

Special Considerations for RA and CKD

• RA patients have higher prevalence of both anemia (31.5%) and impaired renal function compared to controls. 5
• Renal function in RA is typically 9.8 mL/min lower than age/sex-matched controls with non-inflammatory conditions. 5
• ESR and CRP are stronger predictors of anemia than renal function in RA, suggesting inflammatory anemia may be the primary driver rather than renal impairment alone. 5

When Warfarin Might Be Preferred

If this patient's renal function deteriorates to CrCl <15 mL/min or she requires dialysis, warfarin may be preferred over apixaban, though emerging data supports apixaban 2.5 mg BID in dialysis patients (producing similar drug exposure to standard dosing in normal renal function). 1, 6, 7, 8