Weight-Related Considerations for Apixaban (Eliquis)
Weight is not an absolute contraindication to apixaban, but it is one of three dose-reduction criteria that must be evaluated together—specifically, body weight ≤60 kg triggers dose reduction only when combined with at least one other criterion (age ≥80 years or serum creatinine ≥1.5 mg/dL). 1, 2
The "2-of-3" Dose Reduction Algorithm
For atrial fibrillation, reduce apixaban from 5 mg twice daily to 2.5 mg twice daily only when the patient meets at least TWO of the following three criteria: 1, 2
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Meeting only one criterion—including low weight alone—does NOT justify dose reduction. 1, 2 This is the most common prescribing error with apixaban, with studies showing 9.4-40.4% of prescriptions involve inappropriate underdosing based on a single criterion. 2
High Body Weight (Obesity)
For patients weighing >120 kg or BMI >40 kg/m², apixaban can be used with standard dosing, though limited clinical data exist at extreme weights. 1
Pharmacokinetic Evidence in Obesity
- Patients >120 kg show 31% lower peak apixaban concentrations and 23% lower drug exposure compared to reference weight (65-85 kg), but this was deemed clinically insignificant and does not require dose adjustment. 1
- Pooled analysis from ADVANCE-2 and ADVANCE-3 trials showed similar efficacy and safety in patients with BMI ≥30 kg/m² compared to enoxaparin, with no increased thrombotic risk. 1
- Apixaban maintains a predictable pharmacokinetic profile across weight ranges, with only 27% renal clearance making it less dependent on body size than other anticoagulants. 1, 3
Guideline Recommendations for Extreme Weight
The International Society on Thrombosis and Haemostasis (ISTH) suggests DOACs should not be used in patients with BMI >40 kg/m² or weight >120 kg due to limited data, but if used, checking drug-specific peak and trough levels is recommended. 1 However, more recent comprehensive reviews of pharmacokinetic and clinical data suggest obesity does not substantially influence apixaban efficacy or safety. 4
Low Body Weight
Body weight ≤60 kg alone does NOT require dose reduction unless combined with another criterion (age ≥80 or creatinine ≥1.5 mg/dL). 1, 2
- Low body weight (<50 kg) increases apixaban exposure by approximately 27% for peak concentration and 20% for total exposure, but this modest increase does not mandate automatic dose reduction. 5
- The dose reduction algorithm was validated in the ARISTOTLE trial, where patients meeting ≥2 criteria on the reduced dose had similar efficacy and safety to warfarin. 1, 2
Venous Thromboembolism (VTE) Treatment
For VTE treatment, weight-based dose adjustments are NOT recommended—use standard dosing (10 mg twice daily × 7 days, then 5 mg twice daily) regardless of body weight. 6, 7
This differs fundamentally from atrial fibrillation dosing, where the 2-of-3 criteria apply. 6, 7
Critical Pitfalls to Avoid
- Do not reduce apixaban dose based on weight alone, perceived frailty, or bleeding risk without meeting the formal 2-of-3 criteria. 2
- Do not confuse eGFR with creatinine clearance—the dose-reduction criterion is serum creatinine ≥1.5 mg/dL, not a specific eGFR cutoff. 2
- For patients >120 kg, standard dosing is appropriate; do not empirically increase the dose, as this lacks evidence and increases bleeding risk. 1, 4
- Weight is measured in kilograms for the ≤60 kg criterion, not pounds. 1, 2
Monitoring Recommendations
- Renal function should be reassessed at least annually, and every 3-6 months if creatinine clearance <60 mL/min, as changing renal parameters may alter dose requirements. 2
- In patients at extreme weights (>120 kg or <50 kg) with concerns about efficacy or safety, consider measuring apixaban-calibrated anti-Xa levels (expected peak 91-321 ng/mL, trough 41-230 ng/mL), though routine monitoring is not required. 1, 8