What are the recommended Eliquis (apixaban) dosing regimens for stroke prevention in non‑valvular atrial fibrillation, treatment of acute deep‑vein thrombosis (DVT) and pulmonary embolism (PE), extended secondary prevention, and postoperative thromboprophylaxis after hip or knee replacement, including dose reductions based on age ≥ 80 years, body weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL, and renal impairment?

Eliquis (Apixaban) Dosing Recommendations

Stroke Prevention in Nonvalvular Atrial Fibrillation

The standard dose is 5 mg orally twice daily, but reduce to 2.5 mg twice daily if the patient has at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1

• The 5 mg twice daily regimen demonstrated superiority over warfarin in the ARISTOTLE trial, reducing stroke/systemic embolism from 1.60% to 1.27% per year (HR 0.79, P<0.001) with lower major bleeding rates (2.1% vs 3.1%) 2

• Dose reduction criteria are strict: you must have ≥2 of the three criteria (age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) to justify the 2.5 mg twice daily dose 2, 1

• A common prescribing error is reducing the dose when only one criterion is met—this leads to underdosing in 56% of cases where age ≥80 is the sole factor 3

• For patients unsuitable for warfarin therapy, apixaban 5 mg twice daily is superior to aspirin, with the same dose reduction rules applying 2

• Do not use apixaban in patients with creatinine clearance <15 mL/min, as safety and efficacy are not established 2

Treatment of Acute DVT and Pulmonary Embolism

Start with 10 mg orally twice daily for exactly 7 days, then reduce to 5 mg twice daily for the remainder of treatment. 1

• This two-phase dosing regimen provides higher initial anticoagulation during the acute thrombotic phase, then transitions to maintenance therapy 4

• No renal dose adjustment is required for acute VTE treatment, even in patients with renal insufficiency—maintain the standard dosing schedule 5, 6

• The treatment duration depends on whether the VTE was provoked or unprovoked, but the dosing regimen remains constant regardless 1

Extended Secondary Prevention After Initial VTE Therapy

After completing at least 6 months of anticoagulation for VTE, use 2.5 mg orally twice daily for extended prevention of recurrent DVT/PE. 1

• This lower dose balances efficacy in preventing recurrence against bleeding risk during long-term therapy 2

• The decision to extend therapy beyond 6 months should weigh thrombotic risk (unprovoked VTE, active cancer, thrombophilia) against bleeding risk 2

Postoperative Thromboprophylaxis After Hip or Knee Replacement

Give 2.5 mg orally twice daily starting 12-24 hours after surgery, continuing for 35 days after hip replacement or 10-14 days after knee replacement. 2, 7, 1

Hip Replacement Surgery:

• Begin 2.5 mg twice daily at 12-24 hours post-surgery when hemostasis is adequate 7
• Continue for the full 5 weeks (35 days)—inadequate duration is a common pitfall 7
• The ADVANCE-3 trial showed superiority over enoxaparin (1.4% vs 3.9% VTE rate, P<0.001) 2

Knee Replacement Surgery:

• Same 2.5 mg twice daily dose starting 12-24 hours post-surgery 2, 1
• Duration is shorter: 10-14 days 2
• The ADVANCE-2 trial demonstrated superiority over enoxaparin 40 mg daily (15.1% vs 24.4% VTE rate, P<0.0001) 2

Critical Perioperative Considerations:

• If neuraxial anesthesia (spinal/epidural) was used, wait at least 5 hours after catheter removal before giving the first apixaban dose 8
• For patients on chronic apixaban requiring orthopedic surgery, discontinue 48 hours before surgery (standard renal function) or up to 5 days if creatinine clearance 30-50 mL/min or age ≥80 years 8
• Never perform neuraxial anesthesia if residual apixaban may be present—this risks epidural hematoma and permanent paralysis 1
• Bridging with heparin preoperatively is not indicated and increases bleeding risk without reducing thrombotic events 8

Renal Impairment Dosing Adjustments

For atrial fibrillation only: reduce to 2.5 mg twice daily if creatinine clearance 15-29 mL/min AND the patient also meets ≥1 additional dose reduction criterion (age ≥80 or weight ≤60 kg). 1

• Calculate creatinine clearance using Cockcroft-Gault formula—this is mandatory for accurate dosing 8
• Apixaban is contraindicated if creatinine clearance <15 mL/min 2, 1
• Approximately 27% of apixaban clearance is renal, so renal function significantly impacts drug levels 5
• Monitor renal function postoperatively, as surgical stress can acutely worsen kidney function and prolong apixaban half-life 7, 6

Drug Interactions Requiring Dose Modification

Reduce apixaban dose by 50% when combined P-gp and strong CYP3A4 inhibitors are used concomitantly; avoid combined P-gp and strong CYP3A4 inducers entirely. 1

• Strong dual inhibitors requiring dose reduction: ketoconazole, itraconazole, ritonavir, clarithromycin 2, 1
• Strong dual inducers to avoid: rifampin, carbamazepine, phenytoin, St. John's wort 1
• Apixaban has multiple elimination pathways (metabolism, biliary, intestinal, renal), making it less susceptible to single-pathway interactions than other anticoagulants 5

Key Contraindications and Warnings

• Active pathological bleeding is an absolute contraindication 1
• Do not use in patients with prosthetic heart valves—apixaban is not recommended in this population 1
• Avoid in triple-positive antiphospholipid syndrome due to increased thrombotic risk 1
• Severe hepatic impairment is a contraindication 1
• Premature discontinuation increases stroke risk—always provide bridging anticoagulation if stopping apixaban before completing therapy 1