What are the indications for reducing Eliquis (apixaban) to 2.5mg twice a day (BID) in patients with atrial fibrillation or venous thromboembolism, particularly those with impaired renal function, age greater than 80 years, low body weight, or elevated serum creatinine?

Indications for Reducing Eliquis (Apixaban) to 2.5mg BID

Reduce apixaban to 2.5mg twice daily when a patient meets at least 2 of the following 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Primary Dose Reduction Criteria for Atrial Fibrillation

The FDA-approved and guideline-endorsed dose reduction algorithm requires the simultaneous presence of at least 2 out of 3 specific characteristics 2:

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

Critical point: Meeting only ONE of these criteria does NOT warrant dose reduction—you must have at least TWO criteria present simultaneously. 1, 4, 2

Severe Renal Impairment as Alternative Criterion

Creatinine clearance 15-29 mL/min alone qualifies for dose reduction to 2.5mg BID, even without meeting the other criteria. 1, 4 This represents an alternative pathway independent of the "2 out of 3" rule above. 5

Important Renal Function Caveats:

• CrCl 30-50 mL/min alone does NOT warrant dose reduction unless the patient also meets at least 2 of the 3 standard criteria. 5
• Use the Cockcroft-Gault formula with actual body weight to calculate creatinine clearance, NOT eGFR. 3, 4
• Patients with end-stage renal disease on hemodialysis should receive 5mg BID, reduced to 2.5mg BID only if they meet age ≥80 years OR weight ≤60 kg (not both required in ESRD). 1, 4

Special Indication: Extended VTE Prevention

For secondary prevention of recurrent DVT/PE after completing at least 6 months of initial treatment, use 2.5mg BID regardless of the above criteria. 1, 4, 2 This lower dose is specifically studied and approved for extended-phase anticoagulation to reduce recurrence risk. 4

Post-Orthopedic Surgery Prophylaxis

For DVT prophylaxis following hip or knee replacement surgery, all patients receive 2.5mg BID. 1, 2 This is the standard dose for this indication, not a "reduced" dose. 2

Common Pitfalls to Avoid

Inappropriate Dose Reduction:

• Do NOT reduce dose based on age ≥80 years alone—this is a frequent error that leads to underdosing and inadequate stroke prevention. 3, 4
• Do NOT reduce dose based on weight ≤60 kg alone—again, you need at least 2 criteria. 3, 4
• Do NOT reduce dose based on CrCl 30-50 mL/min alone—this moderate renal impairment does not warrant reduction unless combined with other criteria. 5

Monitoring Requirements:

• Reassess renal function at least annually and whenever clinically indicated, as fluctuations in kidney function are common and may change dosing requirements. 4, 6
• Reassess body weight periodically, particularly in elderly patients or those with heart failure, as weight changes may affect whether dose reduction criteria are met. 4
• In patients with heart failure and atrial fibrillation, up to 29% may need apixaban dose adjustments during the first 6 months due to fluctuating renal function. 6

Drug Interactions Requiring Consideration

Avoid concomitant use with strong dual inhibitors of both CYP3A4 AND P-glycoprotein (ketoconazol, itraconazol, ritonavir), as these significantly increase apixaban levels. 3 However, these interactions do not themselves constitute reasons for dose reduction—they may warrant avoiding apixaban entirely or choosing an alternative anticoagulant. 3

Context-Specific Dosing: PCI and Dual Antiplatelet Therapy

When apixaban is used in patients with atrial fibrillation undergoing PCI, a 15mg once daily dose (not 2.5mg BID) was studied in the PIONEER AF-PCI trial with concomitant P2Y12 inhibitor use. 1 This is an off-label strategy and represents a different clinical scenario than standard stroke prevention dosing. 1

What Does NOT Require Dose Reduction

• Obesity, including Class 3 obesity (BMI >40): No dose adjustment needed. 3
• Age 75-79 years: Does not meet the age criterion for reduction. 1
• Moderate renal impairment (CrCl 30-50 mL/min) in isolation: Standard 5mg BID dose is appropriate. 5
• Single criterion met: Whether age, weight, or creatinine alone—maintain 5mg BID. 4, 5