What is the appropriate dosing of Eliquis (apixaban) for an 80-year-old patient with atrial fibrillation, impaired renal function, and multiple comorbidities, including diabetes and potential bleeding risks?

Eliquis (Apixaban) 2.5 mg Dosing Guidelines

For an 80-year-old patient with atrial fibrillation and impaired renal function, apixaban 2.5 mg twice daily is indicated if the patient meets at least two of three dose-reduction criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Standard Dosing for Atrial Fibrillation

• The standard dose of apixaban for stroke prevention in atrial fibrillation is 5 mg twice daily 1, 2

• Dose reduction to 2.5 mg twice daily is required when at least TWO of the following three criteria are present: 1, 2

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

• If only one criterion is met, the standard 5 mg twice daily dose should be used 2

• This dose-reduction strategy was validated in the ARISTOTLE trial, where patients meeting these criteria received 2.5 mg twice daily with maintained efficacy and improved safety 1

Renal Function Considerations

For patients with moderate renal impairment (CrCl 15-50 mL/min), no automatic dose adjustment is required unless the patient meets the two-of-three dose-reduction criteria above 1

• Apixaban has the lowest renal clearance (27%) among all direct oral anticoagulants, making it preferable in renal impairment 1, 3
• For severe renal impairment (CrCl 15-29 mL/min), apixaban can be used at standard dosing (5 mg twice daily) or reduced dosing (2.5 mg twice daily) based on the two-of-three criteria 1
• Recent evidence shows that 5 mg twice daily in severe CKD (stage 4/5) is associated with higher bleeding risk without additional stroke protection compared to 2.5 mg twice daily, supporting more conservative dosing in advanced renal disease 4

End-Stage Renal Disease and Dialysis

For patients with ESRD on hemodialysis, the 2023 ACC/AHA/HRS guidelines recommend apixaban 5 mg twice daily, with dose reduction to 2.5 mg twice daily if the patient is ≥80 years old OR weighs ≤60 kg 1, 3

• This differs from the standard two-of-three criteria, as only ONE criterion (age OR weight) is needed for dose reduction in dialysis patients 3
• Pharmacokinetic studies demonstrate that apixaban 2.5 mg twice daily in dialysis patients produces drug exposure comparable to 5 mg twice daily in patients with normal renal function 3
• Observational data from 25,523 dialysis patients showed standard-dose apixaban (5 mg twice daily) was associated with lower stroke/embolism and death compared to reduced-dose apixaban and warfarin, but this must be balanced against bleeding risk 3
• The European Heart Rhythm Association does not recommend routine DOAC use in CrCl <15 mL/min due to limited evidence, highlighting the uncertainty in this population 3

Drug Interactions Requiring Dose Adjustment

When apixaban 5 mg twice daily is combined with dual P-glycoprotein and strong CYP3A4 inhibitors, reduce the dose to 2.5 mg twice daily 1, 2

• Strong dual inhibitors include: ketoconazole, itraconazole, ritonavir, and clarithromycin 1
• If the patient is already receiving 2.5 mg twice daily, avoid concomitant use of these strong inhibitors entirely 1, 2
• Avoid all P-glycoprotein/CYP3A4 inducers (carbamazepine, phenytoin, rifampin, St. John's wort) as they reduce apixaban to subtherapeutic levels 1

Other Indications for 2.5 mg Twice Daily Dosing

For DVT/PE prophylaxis after hip or knee replacement surgery, the dose is 2.5 mg twice daily for all patients, starting 12-24 hours post-surgery 2

• Duration: 35 days for hip replacement, 12 days for knee replacement 2

For reduction in risk of recurrent DVT/PE after completing at least 6 months of initial treatment, the dose is 2.5 mg twice daily 2

Critical Safety Considerations

• Premature discontinuation increases thrombotic risk; if stopping apixaban, provide bridging with another anticoagulant 2
• For elective surgery, discontinue apixaban 48 hours before procedures with moderate-to-high bleeding risk, or 24 hours before low-bleeding-risk procedures 1, 2
• Apixaban affects INR measurements; when transitioning to warfarin, discontinue apixaban and start both parenteral anticoagulation and warfarin simultaneously 2
• Concomitant antiplatelet therapy substantially increases bleeding risk and should be avoided unless absolutely necessary 3
• Activated charcoal can reduce apixaban absorption by 50% if given within 2 hours of ingestion in overdose situations 2
• Andexanet alfa is the FDA-approved reversal agent for life-threatening bleeding 1

Monitoring and Follow-up

• Renal function should be evaluated before initiation and reassessed at least annually, or more frequently when clinically indicated 1
• Use the Cockcroft-Gault method to calculate creatinine clearance for dosing decisions 1
• Monitor for signs of bleeding throughout therapy, particularly in elderly patients and those with multiple comorbidities 5
• In patients with diabetes and bleeding risks, the dose-reduction criteria remain the same; diabetes alone does not warrant dose adjustment 1, 2