What is the recommended dose of apixaban (a direct oral anticoagulant) for an adult patient with atrial fibrillation or venous thromboembolism, considering factors such as age, weight, serum creatinine level, and renal function?

Apixaban Dosing for Atrial Fibrillation and Venous Thromboembolism

Standard Dosing Algorithm

For atrial fibrillation, prescribe apixaban 5 mg orally twice daily for most patients, reducing to 2.5 mg twice daily ONLY when the patient meets at least 2 of these 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2, 3

Key Dosing Principles

• The standard dose is 5 mg twice daily for patients with 0 or 1 dose-reduction criteria 1, 2
• The reduced dose is 2.5 mg twice daily when at least 2 of the 3 criteria are met 1, 2, 3
• Meeting only 1 criterion does NOT justify dose reduction—this is the most common prescribing error, with studies showing 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing 1, 4

The Three Dose-Reduction Criteria

1. Age ≥80 years 1, 2, 3
2. Body weight ≤60 kg 1, 2, 3
3. Serum creatinine ≥1.5 mg/dL 1, 2, 3

Renal Function Considerations

Calculating Renal Function

• Always use the Cockcroft-Gault equation to calculate creatinine clearance (CrCl), not eGFR, as this is what FDA labeling and clinical trials used 1
• Reassess renal function at least annually, and every 3-6 months if CrCl <60 mL/min 1, 2

Dosing by Renal Function Category

Mild to Moderate CKD (CrCl 30-59 mL/min):

• Use standard 5 mg twice daily unless ≥2 dose-reduction criteria are met 1
• CrCl alone does NOT trigger dose reduction 1
• Apixaban has only 27% renal clearance, making it safer than other DOACs in renal impairment 1

Severe CKD (CrCl 15-29 mL/min):

• Use 2.5 mg twice daily 1, 2
• This automatically meets dose-reduction criteria regardless of age or weight 2

End-Stage Renal Disease on Hemodialysis:

• Start with 5 mg twice daily 1, 2, 3
• Reduce to 2.5 mg twice daily ONLY if age ≥80 years OR weight ≤60 kg (note: only ONE criterion needed in dialysis patients, not two) 1, 2

CrCl <15 mL/min NOT on dialysis:

• Apixaban is contraindicated 3

Critical Pitfalls to Avoid

Common Dosing Errors

• Do NOT reduce the dose based on a single criterion (e.g., age 82 alone, or CrCl 45 alone)—this is inappropriate underdosing 1, 4
• Do NOT reduce the dose based on perceived bleeding risk without meeting formal criteria 1
• Do NOT use eGFR for dosing decisions—always calculate CrCl using Cockcroft-Gault 1
• Do NOT confuse serum creatinine ≥1.5 mg/dL with CrCl cutoffs—these are separate parameters 1

Evidence Supporting Standard Dosing with One Criterion

• 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 4
• Patients with isolated renal dysfunction, advanced age, or low body weight show consistent benefits with 5 mg twice daily 4

Venous Thromboembolism Dosing

Treatment of DVT/PE:

• 10 mg orally twice daily for the first 7 days 3
• Then 5 mg orally twice daily thereafter 3

Reduction in Risk of Recurrent DVT/PE:

• 2.5 mg orally twice daily after at least 6 months of treatment 3

VTE Prophylaxis After Hip/Knee Replacement:

• 2.5 mg orally twice daily starting 12-24 hours post-surgery 3
• Duration: 35 days for hip replacement, 12 days for knee replacement 3

Drug Interactions Requiring Dose Adjustment

• Reduce to 2.5 mg twice daily when using combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir, itraconazole) in patients otherwise receiving 5 mg twice daily 1, 2
• Avoid use with rifampin and other strong CYP3A4 inducers 1

Switching Between Anticoagulants

From Warfarin to Apixaban:

• Discontinue warfarin and start apixaban when INR drops below 2.0 2, 3
• No bridging therapy needed 2

From Apixaban to Warfarin:

• Discontinue apixaban and begin both parenteral anticoagulant AND warfarin at the time of the next scheduled apixaban dose 3
• Continue parenteral anticoagulant until INR reaches therapeutic range 3

From Other DOACs to Apixaban:

• Simply discontinue the other DOAC and start apixaban at the time the next dose would have been due 3

Perioperative Management

Low Bleeding Risk Procedures:

• Hold apixaban for 1 day (24 hours) before procedure 1, 2

High Bleeding Risk Procedures:

• Hold apixaban for 2 days (48 hours) before procedure 1, 2
• Consider holding for additional 1-3 days if CrCl <25 mL/min 1, 2

Monitoring Requirements

• No routine coagulation monitoring (INR) is required 1, 2
• Monitor clinically for signs of bleeding or thromboembolism 2
• Reassess renal function at least annually, more frequently if CrCl <60 mL/min 1, 2