What are the guidelines for dose reduction of Eliquis (apixaban) in patients?

Eliquis (Apixaban) Dose Reduction Guidelines

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

Standard Dosing for Atrial Fibrillation

• Most patients should receive 5 mg orally twice daily as the standard dose for stroke prevention in nonvalvular atrial fibrillation 2
• This standard dose applies even to patients with a single dose-reduction criterion (isolated advanced age, low body weight, or elevated creatinine) 3

Dose Reduction Criteria for Atrial Fibrillation

The reduced dose of 2.5 mg twice daily is indicated only when patients meet at least 2 of these 3 criteria: 1, 2

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

Critical Point on Single Criterion

• Patients with only 1 dose-reduction criterion should receive the standard 5 mg twice daily dose, not the reduced dose 3
• These patients have higher baseline risk of stroke and bleeding compared to those with no criteria, but demonstrate consistent benefit and safety with the 5 mg dose compared to warfarin 3
• The 5 mg dose in patients with a single criterion showed similar relative risk reductions for stroke (HR 0.94 vs 0.77, P for interaction = 0.36) and major bleeding (HR 0.68 vs 0.72, P for interaction = 0.71) compared to those with no criteria 3

Renal Function Considerations

• For creatinine clearance >30 mL/min: no dose adjustment needed unless other dose-reduction criteria are met 1, 4
• For creatinine clearance 15-30 mL/min: the FDA label does not provide specific dosage adjustments 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 (note: only 1 criterion needed in dialysis patients, not 2) 1, 4

Dosing for Venous Thromboembolism

VTE treatment and prophylaxis follow different dosing regimens without the same dose-reduction criteria: 2

• Acute DVT/PE treatment: 10 mg twice daily for 7 days, then 5 mg twice daily 2
• Extended-phase therapy (secondary prevention): 2.5 mg twice daily after completing at least 6 months of treatment 1, 2
• Post-surgical prophylaxis: 2.5 mg twice daily starting 12-24 hours after surgery 2

Common Prescribing Errors to Avoid

Underdosing is the most frequent error, occurring in 9.4-40.4% of apixaban prescriptions: 1

• Do not reduce dose based on a single criterion (age alone, weight alone, or creatinine alone) 1, 3
• Do not reduce dose based on bleeding history or perceived bleeding risk - this is not a validated dose-reduction criterion 1
• Do not reduce dose based on concurrent antiplatelet use - while this increases bleeding risk, it does not justify dose reduction 1
• Do not reduce dose based on frailty, fall risk, or dementia - these are not dose-reduction criteria 1

Drug Interactions Requiring Dose Adjustment

When combined P-gp and strong CYP3A4 inhibitors are used: 2

• For patients on 5 mg or 10 mg twice daily: decrease apixaban dose by 50% 2
• For patients already on 2.5 mg twice daily: avoid coadministration with these inhibitors 2
• Examples include: ketoconazole, itraconazole, ritonavir 2
• Exception: clarithromycin does not require dose adjustment despite being a combined inhibitor 2

Avoid apixaban with combined P-gp and strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's wort) as they significantly decrease apixaban exposure 2

Monitoring and Reassessment

• Evaluate renal function before initiation and at least annually, or when clinically indicated 1
• Use Cockcroft-Gault method for creatinine clearance calculation 1
• Reassess body weight and renal function periodically, as changes may affect dose-reduction criteria status 1