What is the typical dosing regimen for Eliquis (apixaban) twice daily (bid)?

Eliquis (Apixaban) Twice Daily Dosing

The standard dose of Eliquis is 5 mg orally twice daily for most patients with atrial fibrillation, with dose reduction to 2.5 mg twice daily required when patients meet at least two of three specific criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1

Standard Dosing by Indication

Atrial Fibrillation (Stroke Prevention)

• 5 mg orally twice daily is the recommended dose for most patients with nonvalvular atrial fibrillation 1, 2
• Reduced dose of 2.5 mg twice daily is required when patients have at least 2 of the following characteristics 1, 3, 4:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) Treatment

• Initial therapy: 10 mg orally twice daily for the first 7 days 1, 3
• Maintenance therapy: 5 mg orally twice daily after the initial 7-day period 1, 5

VTE Prophylaxis After Hip or Knee Replacement

• 2.5 mg orally twice daily starting 12-24 hours after surgery 1, 4, 6
• Duration: 35 days for hip replacement, 12 days for knee replacement 1

Reduction in Risk of Recurrent DVT/PE

• 2.5 mg orally twice daily after completing at least 6 months of initial treatment 1

Critical Dosing Adjustments

Drug Interactions Requiring Dose Reduction

• Reduce dose by 50% when coadministered with combined P-glycoprotein (P-gp) AND strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) 1, 4
• Avoid coadministration entirely if patient is already on 2.5 mg twice daily with these inhibitors 1

Renal Impairment Considerations

• No dose adjustment needed for normal to moderate renal impairment (CrCl >30 mL/min) 2
• For severe renal impairment (CrCl 25-30 mL/min), standard dosing appears safe based on pharmacokinetic data, though this population was excluded from major trials 7
• End-stage renal disease on hemodialysis: Use 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years OR body weight ≤60 kg 2

Perioperative Management

Preoperative Interruption

For low bleeding risk procedures:

• Stop apixaban 2 days before surgery (skip 2 doses) in patients with normal/mild renal impairment 2
• Stop 3 days before surgery (skip 4 doses) in patients with moderate renal impairment (CrCl 30-50 mL/min) 2

For high bleeding risk procedures (neurosurgery, spinal anesthesia):

• Stop apixaban 3 days before surgery (skip 4 doses) in patients with normal/mild renal impairment 2, 3
• Stop 4 days before surgery (skip 6 doses) in patients with moderate renal impairment 2
• Consider 3-5 days interruption for very high-risk neuraxial procedures 4

Postoperative Resumption

• Low bleeding risk surgery: Resume full dose 24 hours after surgery 2
• High bleeding risk surgery: Resume full dose 48-72 hours after surgery 2, 4
• Consider reduced dose (2.5 mg twice daily) for first 2-3 days in high-risk patients, then advance to full dose 2
• Bridging anticoagulation is NOT generally required during the brief interruption period 4, 1

Important Clinical Considerations

Compliance and Missed Doses

• Strict adherence is critical due to rapid offset of action—missing even one dose creates a period without thromboembolic protection 2
• If a dose is missed, take it as soon as possible on the same day; do not double the next dose 1
• FDA black box warning emphasizes that premature discontinuation increases thrombotic risk 1

Common Pitfalls to Avoid

• Inappropriate dose reduction: Approximately 43-57% of patients receiving reduced-dose apixaban in clinical practice do not meet dose-reduction criteria, which may expose them to unnecessary thrombotic risk 8, 9
• Neuraxial anesthesia timing: Never perform spinal/epidural procedures without adequate apixaban discontinuation time, especially in elderly patients or those with renal impairment 4, 1
• Switching anticoagulants: When transitioning from warfarin, start apixaban only when INR <2.0; when switching to warfarin, use parenteral bridging as apixaban affects INR measurements 1

Evidence Quality

The ARISTOTLE trial demonstrated that apixaban 5 mg twice daily reduced stroke/systemic embolism by 21%, major bleeding by 31%, and all-cause mortality by 11% compared to warfarin in patients with atrial fibrillation 3, 2