What are the criteria for a low dose of Eliquis (apixaban) in patients with impaired renal function, age 80 or older, or weighing 60kg or less?

Low Dose Apixaban (2.5 mg Twice Daily) Criteria

Apixaban should be reduced to 2.5 mg twice daily only when patients meet at least 2 of the following 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1

The Three-Criteria Dosing Algorithm

The FDA-approved dosing for atrial fibrillation requires simultaneous presence of at least 2 criteria to justify dose reduction 1:

• Age ≥80 years 2, 1
• Body weight ≤60 kg 2, 1
• Serum creatinine ≥1.5 mg/dL 2, 1

Meeting only 1 criterion does NOT warrant dose reduction - the standard 5 mg twice daily dose should be maintained 2, 3.

Critical Dosing Principles

Standard Dose (5 mg Twice Daily) Should Be Used When:

• Zero dose-reduction criteria are met 1
• Only one dose-reduction criterion is met 2, 3
• Patients with isolated moderate renal impairment (CrCl 30-50 mL/min) without meeting ≥2 criteria 2, 4
• Patients with isolated advanced age (≥80 years) without meeting ≥2 criteria 3
• Patients with isolated low body weight (≤60 kg) without meeting ≥2 criteria 3

The ARISTOTLE trial demonstrated that patients with only 1 dose-reduction criterion who received 5 mg twice daily had similar efficacy (HR 0.94 for stroke) and safety (HR 0.68 for major bleeding) compared to warfarin, with no increased risk compared to patients with no criteria 3.

Reduced Dose (2.5 mg Twice Daily) Should Be Used When:

• Two or more dose-reduction criteria are met simultaneously 2, 1
• Example combinations requiring dose reduction:
  • Age ≥80 years + weight ≤60 kg 1
  • Age ≥80 years + serum creatinine ≥1.5 mg/dL 1
  • Weight ≤60 kg + serum creatinine ≥1.5 mg/dL 1
  • All three criteria present 1

Special Population: End-Stage Renal Disease on Hemodialysis

For patients on hemodialysis, the dosing algorithm differs slightly 4:

• Standard dose: 5 mg twice daily for most dialysis patients 4
• Reduced dose: 2.5 mg twice daily if the patient meets either (not both required):
  • Age ≥80 years OR 4
  • Body weight ≤60 kg 4

This represents a more liberal dose-reduction threshold in dialysis patients compared to non-dialysis patients 4.

Common Prescribing Errors to Avoid

The Single-Criterion Error

The most frequent mistake is reducing apixaban dose based on a single criterion 5. Studies show 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing, often driven by clinician concern about renal function or perceived bleeding risk when formal criteria are not met 5.

Do not reduce dose based solely on:

• Perceived bleeding risk without meeting formal criteria 6
• Creatinine clearance alone (unless CrCl <15 mL/min) 2, 4
• Advanced age alone 3
• Low body weight alone 3
• Single elevated serum creatinine alone 3

Renal Function Calculation

Always use the Cockcroft-Gault equation to calculate creatinine clearance - do not use eGFR for apixaban dosing decisions 4, 5. The FDA labeling and clinical trials used Cockcroft-Gault, not eGFR 4.

The serum creatinine threshold of ≥1.5 mg/dL is separate from creatinine clearance calculations and serves as one of the three dose-reduction criteria 2, 1.

Renal Impairment Considerations

Moderate Renal Impairment (CrCl 30-50 mL/min)

Standard dose 5 mg twice daily should be maintained unless the patient meets ≥2 of the three dose-reduction criteria 2, 6. Apixaban has only 27% renal clearance, making it safer in renal impairment compared to dabigatran (80%) or rivaroxaban (66%) 4, 6.

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

Use 2.5 mg twice daily with caution in this population 2. The safety and efficacy have not been fully established, but apixaban may be considered given its low renal clearance 2.

CrCl <15 mL/min (Not on Dialysis)

Apixaban is not recommended in patients with CrCl <15 mL/min who are not on dialysis 2.

Drug Interactions Requiring Dose Adjustment

Reduce to 2.5 mg twice daily when using combined P-glycoprotein and strong CYP3A4 inhibitors in patients otherwise receiving 5 mg twice daily 2, 5:

• Ketoconazole 2, 5
• Itraconazole 2, 5
• Ritonavir 5
• Verapamil (avoid combination) 4

Avoid strong CYP3A4 inducers that decrease apixaban effectiveness 5:

• Rifampin 5
• St. John's wort 4

Monitoring Requirements

Reassess renal function regularly 5:

• Annually if CrCl ≥60 mL/min 4, 6
• Every 3-6 months if CrCl 30-60 mL/min 5, 6
• More frequently if CrCl <30 mL/min or clinical deterioration occurs 4, 5

Use the formula: CrCl divided by 10 equals minimum months between checks for patients with declining renal function 4.

Evidence Supporting the Two-Criteria Requirement

The ARISTOTLE trial specifically evaluated patients with 1 dose-reduction criterion receiving 5 mg twice daily (n=3,966) versus those with no criteria (n=13,356) 3. Patients with 1 criterion had higher baseline risk but showed consistent benefit with 5 mg twice daily compared to warfarin 3:

• Stroke/systemic embolism: HR 0.94 (95% CI 0.66-1.32) 3
• Major bleeding: HR 0.68 (95% CI 0.53-0.87) 3
• No significant interaction between treatment effect and presence of 1 vs. 0 criteria (P=0.36 for efficacy, P=0.71 for bleeding) 3

This evidence strongly supports maintaining the standard 5 mg twice daily dose when only 1 criterion is present 3.