What is the dosing regimen for Eliquis (apixaban) in patients with pulmonary embolism (PE), including considerations for dose adjustments in those with impaired renal function?

Apixaban Dosing for Pulmonary Embolism

For acute PE treatment, initiate apixaban at 10 mg orally twice daily for 7 days, then reduce to 5 mg twice daily for at least 3 months—no parenteral anticoagulation bridge is required. 1, 2, 3

Standard Dosing Regimen

Acute Phase (Days 1-7)

• 10 mg orally twice daily for the first 7 days 1, 2, 3
• This higher initial dose ensures rapid therapeutic anticoagulation during the acute phase 2
• Unlike dabigatran or edoxaban, apixaban does NOT require initial parenteral anticoagulation (heparin/LMWH) before starting 1, 2
• Treatment can be initiated immediately upon PE diagnosis 2

Maintenance Phase (After Day 7)

• 5 mg orally twice daily starting on day 8 1, 2, 3
• Continue for minimum 3 months 1, 2, 3
• For unprovoked PE or ongoing risk factors, consider extended anticoagulation beyond 3 months 1, 2

Extended Secondary Prevention (After ≥6 months)

• 2.5 mg orally twice daily may be used for extended prevention after completing at least 6 months of initial therapy 2, 3
• This reduced dose is specifically for recurrence prevention, not acute treatment 3

Dose Adjustments for Renal Impairment

Creatinine Clearance ≥30 mL/min

• No dose adjustment required for PE treatment 3
• Use standard dosing: 10 mg twice daily × 7 days, then 5 mg twice daily 3

Creatinine Clearance 15-29 mL/min

• Use with caution—limited data available 2, 3
• The FDA label does not provide specific dose reduction recommendations for PE treatment in this range 3
• Consider alternative anticoagulation if CrCl <30 mL/min 2

Creatinine Clearance <15 mL/min or Dialysis

• Avoid apixaban—insufficient data and significantly increased drug exposure 3, 4
• Consider unfractionated heparin or other alternatives 1

Special Populations Requiring Consideration

Patients with Multiple Risk Factors

The dose adjustment criteria used for atrial fibrillation (age ≥80 years, weight ≤60 kg, serum creatinine ≥1.5 mg/dL) do NOT apply to PE treatment dosing 3, 4

• For PE, maintain standard dosing (10 mg twice daily × 7 days, then 5 mg twice daily) regardless of age or weight 3
• The only exception is severe renal impairment as noted above 2, 3

Drug Interactions: Combined P-gp and Strong CYP3A4 Inhibitors

When coadministered with ketoconazole, itraconazole, or ritonavir:

• Reduce dose by 50%: Give 5 mg twice daily (instead of 10 mg) during days 1-7, then 2.5 mg twice daily for maintenance 3
• This applies only when receiving the 5 mg or 10 mg twice daily doses 3

Critical Safety Considerations

Bleeding Risk with Lead-In Therapy

• Do NOT administer parenteral anticoagulation before starting apixaban for PE—this increases bleeding risk without benefit 2
• Recent data shows that patients who received parenteral anticoagulation followed by shortened apixaban lead-in had higher bleeding rates (18.5% vs 5.1%) 5
• Complete the full 7-day lead-in period at 10 mg twice daily—shortening this duration may increase bleeding risk 2, 5

Efficacy and Safety Profile

• Major bleeding with apixaban: 0.6% vs conventional therapy (enoxaparin/warfarin): 1.8% 1, 2
• Combined major and clinically relevant non-major bleeding: 4.3% with apixaban vs 9.7% with conventional therapy 1, 2
• Recurrent VTE rates are non-inferior to conventional therapy 1, 6

Common Pitfalls to Avoid

1. Do not bridge with heparin/LMWH when starting apixaban—this is unnecessary and increases bleeding risk 2
2. Do not continue 10 mg twice daily beyond 7 days—this increases bleeding without additional efficacy 2, 3
3. Do not apply atrial fibrillation dose-reduction criteria (age/weight/creatinine) to PE treatment 3, 4
4. Do not use in severe renal impairment (CrCl <30 mL/min)—consider alternative anticoagulation 2, 3
5. Do not double doses if a dose is missed—take as soon as remembered on the same day and resume twice-daily schedule 3

Monitoring Requirements

• No routine coagulation monitoring required (unlike warfarin) 2
• Apixaban has predictable anticoagulant effects without need for INR monitoring 2
• Assess renal function at baseline and periodically, especially in elderly patients or those with borderline renal function 3