What is the recommended oral (PO) dosing of Eliquis (apixaban) for a patient with atrial fibrillation, considering factors such as age, weight, renal function, and bleeding risk?

Apixaban (Eliquis) Oral Dosing

Standard Dosing for Atrial Fibrillation

The standard dose of apixaban is 5 mg orally twice daily for most patients with nonvalvular atrial fibrillation, with dose reduction 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, 2, 3

Dose Reduction Criteria (Must Meet ≥2 of 3)

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

Critical: Meeting only ONE criterion does NOT warrant dose reduction—this is the most common prescribing error with apixaban. 3, 4

Renal Function Considerations

Moderate Renal Impairment (CrCl 30-59 mL/min)

• Use standard 5 mg twice daily dosing unless the patient meets ≥2 dose-reduction criteria 2, 3
• Apixaban has only 27% renal clearance, making it safer in renal impairment compared to other DOACs 3, 5
• Calculate creatinine clearance using the Cockcroft-Gault equation, NOT eGFR, as this is what FDA labeling and clinical trials used 2, 3

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

• Use 2.5 mg twice daily with caution 3
• Apixaban demonstrated less bleeding than warfarin even in patients with CrCl 25-30 mL/min 5

End-Stage Renal Disease on Hemodialysis

• Start with 5 mg twice daily, reducing to 2.5 mg twice daily ONLY if age ≥80 years OR body weight ≤60 kg 2, 1
• Note: This is based on pharmacokinetic data, not clinical trial evidence 2

Contraindication

• Do NOT use apixaban in patients with CrCl <15 mL/min who are NOT on dialysis 2

Other Indications and Dosing

DVT/PE Treatment

• 10 mg twice daily for first 7 days, then 5 mg twice daily 1

DVT/PE Recurrence Prevention

• 2.5 mg twice daily after at least 6 months of treatment 1

Hip/Knee Replacement Prophylaxis

• 2.5 mg twice daily starting 12-24 hours post-surgery 1
• Duration: 35 days for hip replacement, 12 days for knee replacement 1

Administration and Monitoring

Missed Dose

• Take as soon as possible on the same day 1
• Resume twice-daily schedule 1
• Never double the dose 1

Monitoring Requirements

• No routine coagulation monitoring (INR) required 2, 3
• Assess renal function before starting and at least annually 2
• Monitor more frequently (every 3-6 months) if CrCl <60 mL/min or declining renal function 3
• Monitor for bleeding symptoms, particularly gastrointestinal in elderly patients 2

Switching Between Anticoagulants

From Warfarin to Apixaban

• Discontinue warfarin and start apixaban when INR <2.0 2, 1
• No bridging therapy needed 2

From Apixaban to Warfarin

• Discontinue apixaban and begin both parenteral anticoagulant AND warfarin at the time of next scheduled apixaban dose 2, 1
• Continue parenteral anticoagulant until INR reaches therapeutic range 2, 1

From Other DOACs to Apixaban

• Simply discontinue the other DOAC and start apixaban at the time the next dose would have been due 2, 1

Perioperative Management

Low Bleeding Risk Procedures

• Hold for 1 day if CrCl >25 mL/min 3

High Bleeding Risk Procedures

• Hold for 2 days if CrCl >25 mL/min 3
• Consider holding for additional 1-3 days if CrCl <25 mL/min 3

Resumption

• Restart as soon as adequate hemostasis established 1
• No bridging generally required 1

Drug Interactions

Avoid or Adjust

• Avoid combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir)—if necessary, reduce 5 mg twice daily to 2.5 mg twice daily 2
• Avoid rifampin and other strong CYP3A4 inducers 2

Safe Combinations

• Proton pump inhibitors do NOT significantly interact with apixaban 3
• When combining with antiplatelet therapy, clopidogrel is preferred over aspirin 2

Critical Pitfalls to Avoid

Underdosing Error

• 9.4-40.4% of apixaban prescriptions involve inappropriate dose reduction based on single criterion or perceived bleeding risk 3
• The ARISTOTLE trial demonstrated that patients with only 1 dose-reduction criterion receiving 5 mg twice daily had similar efficacy and safety compared to those with no criteria 4

Renal Function Assessment

• Always use Cockcroft-Gault equation for CrCl calculation, not eGFR or serum creatinine alone 2, 3
• Serum creatinine ≥1.5 mg/dL is a dose-reduction criterion, but this does NOT automatically mean dose reduction unless combined with another criterion 3

Special Populations

• No dose adjustment needed for mild hepatic impairment (Child-Pugh A) 1
• Apixaban NOT recommended in severe hepatic impairment (Child-Pugh C) 1
• Dosing recommendations cannot be provided for moderate hepatic impairment (Child-Pugh B) due to limited data 1