What is the recommended apixaban (Eliquis) dosing schedule for an adult with acute pulmonary embolism, including adjustments for age, weight, serum creatinine, and renal function?

Apixaban Dosing for Acute Pulmonary Embolism

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

Initial Treatment Phase (Days 1-7)

• Administer apixaban 10 mg orally twice daily for the first 7 days to achieve rapid therapeutic anticoagulation during the acute phase 2, 3, 1
• Begin treatment immediately upon diagnosis without any parenteral anticoagulation lead-in (unlike dabigatran or edoxaban which require 5-10 days of heparin) 2, 3, 4
• The initial dose should be taken 12-24 hours after diagnosis is confirmed 1

Maintenance Phase (Day 8 Onward)

• After 7 days, reduce to 5 mg orally twice daily and continue for at least 3 months 2, 3, 4, 1
• For unprovoked PE or ongoing risk factors, extended anticoagulation beyond 3 months is typically necessary 3, 4
• After completing at least 6 months of full-dose therapy, consider reducing to 2.5 mg twice daily for long-term secondary prevention 3, 1

Dose Adjustments Based on Patient Characteristics

Standard dosing (10 mg twice daily → 5 mg twice daily) applies to acute PE treatment regardless of age, weight, or renal function during the initial treatment period. 1

Renal Function Considerations

• No dose reduction is required for acute PE treatment based on renal function alone, even in moderate renal impairment 1, 5
• Use with caution in severe renal impairment (creatinine clearance <30 mL/min or <15 mL/min) 2, 4
• Apixaban exposure increases by approximately 44% in severe renal impairment, but this does not typically require dose adjustment during acute treatment 5
• Patients with chronic kidney disease may have prolonged apixaban half-life (>10 days after last dose in some cases) 6

Age, Weight, and Creatinine Criteria

The 2.5 mg twice daily dose reduction criteria apply ONLY to atrial fibrillation, NOT to acute PE treatment. 2, 1

• For atrial fibrillation (not PE), reduce to 2.5 mg twice daily if patient has ≥2 of the following: age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL 2, 1
• Do not apply these reduction criteria during the initial 3-6 months of acute PE treatment 3, 1
• After 6 months of full-dose therapy for PE, the 2.5 mg twice daily dose may be considered for extended secondary prevention 3, 1

Efficacy and Safety Profile

• Apixaban demonstrated non-inferiority to enoxaparin/warfarin for acute VTE with recurrent VTE rates of 2.3% vs 2.7% 2, 3
• Major bleeding occurred in only 0.6% with apixaban compared to 1.8% with conventional therapy (relative risk 0.31, P<0.001 for superiority) 2, 3, 4
• The composite of major bleeding and clinically relevant non-major bleeding was significantly lower with apixaban (4.3% vs 9.7%) 2, 4

Critical Pitfalls to Avoid

Dosing Errors

• Never administer parenteral anticoagulation before starting apixaban for acute PE—this increases bleeding risk without added benefit 3, 4, 7
• Never continue the 10 mg twice daily dose beyond 7 days—this increases bleeding risk 3, 4
• Never reduce to 2.5 mg twice daily during the initial 3-6 months of treatment—this causes underdosing and increases recurrent VTE risk 3, 4
• Do not double the dose if a dose is missed; take the next scheduled dose 1

Inappropriate Dose Reductions

• Do not reduce the dose based on perceived bleeding risk alone during acute treatment—this leads to treatment failure 3, 4
• Do not apply atrial fibrillation dose reduction criteria (age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) to acute PE treatment 3, 1
• Patients with bleeding risk factors (P2Y12 inhibitors, P-glycoprotein inhibitors, advanced age, elevated creatinine) may have higher bleeding rates, but dose reduction during acute treatment is not recommended 7

Drug Interactions

• Apixaban interacts with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin), which may require dose adjustment 3, 1
• Avoid concomitant use of other anticoagulants or antiplatelet agents unless specifically indicated 2

Perioperative Management

• Discontinue apixaban at least 48 hours before elective surgery with moderate-to-high bleeding risk 1
• Discontinue at least 24 hours before procedures with low bleeding risk 1
• Bridging anticoagulation is not generally required during the 24-48 hour interruption 1
• Restart apixaban when adequate hemostasis is established 1
• In patients with chronic kidney disease, apixaban may remain detectable for >10 days after the last dose, potentially delaying surgical interventions 6

Monitoring

• No routine coagulation monitoring (INR, aPTT) is required with apixaban 3, 4
• Apixaban-calibrated anti-Xa assays may be useful in specific circumstances: severe renal insufficiency, medication adherence assessment, perioperative planning, extremes of body weight, or advanced age 6
• Regular clinical assessment for signs of bleeding or recurrent thromboembolism is recommended 3