What are the criteria for dose reduction of apixaban (eliquis) in patients?

Apixaban Dose Reduction Criteria

For stroke prevention in atrial fibrillation, reduce apixaban from 5 mg twice daily to 2.5 mg twice daily only when the patient meets at least 2 of the following 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 μmol/L). 1

Atrial Fibrillation Dosing Algorithm

Standard Dose (5 mg twice daily)

• Use this dose for all patients who meet 0 or only 1 of the dose-reduction criteria 1
• Patients with a single criterion (isolated advanced age, low weight, or renal dysfunction) show consistent safety and efficacy with the standard 5 mg dose compared to warfarin 2

Reduced Dose (2.5 mg twice daily)

Apply dose reduction ONLY when ≥2 of these criteria are present simultaneously: 1, 3

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL (133 μmol/L)

Special Renal Considerations

• For creatinine clearance 15-29 mL/min: use 2.5 mg twice daily regardless of other criteria 1
• For end-stage renal disease on hemodialysis: use 5 mg twice daily, reduced to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (not both required) 1, 3
• For severe renal impairment not on dialysis (CrCl <15 mL/min): no FDA-approved dosing recommendation exists 1

Venous Thromboembolism Dosing

Acute Treatment Phase

• Initial 7 days: 10 mg twice daily 1, 4
• After 7 days: 5 mg twice daily 1, 4
• No dose reduction criteria apply during acute DVT/PE treatment 1

Extended/Secondary Prevention Phase

• After completing at least 6 months of anticoagulation: 2.5 mg twice daily 3, 4
• This reduced dose is used for all patients in the extended treatment phase regardless of age, weight, or renal function 1

Drug Interaction Adjustments

Combined P-gp and Strong CYP3A4 Inhibitors

• For patients on 5 mg or 10 mg twice daily: reduce dose by 50% when coadministered with ketoconazole, itraconazole, or ritonavir 4
• For patients already on 2.5 mg twice daily: avoid coadministration with these inhibitors 4
• Exception: clarithromycin does not require dose adjustment despite being a combined inhibitor 4

Combined P-gp and Strong CYP3A4 Inducers

• Avoid concomitant use with rifampin, carbamazepine, phenytoin, or St. John's wort, as these decrease apixaban exposure and increase thrombotic risk 4

Critical Pitfalls to Avoid

Inappropriate Dose Reduction

• Do not reduce the dose if only 1 criterion is present 1, 2
• Research shows that approximately 43% of patients receiving reduced dose apixaban in clinical practice do not meet the appropriate criteria 5
• Patients with isolated advanced age, low weight, or renal dysfunction receiving standard dose apixaban have similar safety and efficacy compared to those without these characteristics 2

Monitoring Requirements

• Assess renal function (using Cockcroft-Gault method) before initiation and at least annually 3
• Reassess body weight and renal function periodically, as changes may affect dose-reduction criteria status 3
• The combination of criteria matters more than individual thresholds 6

Clinical Context Considerations

• In patients with atrial fibrillation and recent acute coronary syndrome or PCI, appropriately reduced dose apixaban shows lower bleeding risk and similar ischemic outcomes compared to warfarin 5
• The types or combinations of dose reduction criteria do not significantly impact effectiveness or safety when on-label dosing is used 6