Eliquis (Apixaban): Comprehensive Clinical Guide
Indications
Apixaban is FDA-approved for three primary indications:
- Stroke prevention in nonvalvular atrial fibrillation – reduces stroke and systemic embolism risk in patients with AF 1
- Venous thromboembolism (VTE) treatment and prevention – treats DVT/PE and prevents recurrence after initial therapy 1
- VTE prophylaxis after orthopedic surgery – prevents DVT/PE following hip or knee replacement 1, 2
Important contraindication: Apixaban is not recommended for patients with prosthetic heart valves or triple-positive antiphospholipid syndrome 1
Dosing Regimens
Atrial Fibrillation (Stroke Prevention)
Standard dose: 5 mg orally twice daily 1
Reduced dose (2.5 mg twice daily) requires meeting ≥2 of the following 3 criteria:
Critical dosing principle: Do not reduce the dose based on a single criterion, perceived frailty, or isolated moderate CKD—this is the most common prescribing error with apixaban 4
Renal Function-Specific Dosing for Atrial Fibrillation
| Creatinine Clearance | Recommended Dose | Notes |
|---|---|---|
| >30 mL/min | 5 mg twice daily | Unless ≥2 dose-reduction criteria met [4] |
| 15-29 mL/min | 2.5 mg twice daily | All patients, regardless of age/weight [4] |
| <15 mL/min or dialysis | 5 mg twice daily | Reduce to 2.5 mg if age ≥80 OR weight ≤60 kg (only 1 criterion needed) [4,1] |
Calculate creatinine clearance using the Cockcroft-Gault equation, not eGFR—this is what the FDA label and clinical trials used 4
VTE Treatment
- Initial 7 days: 10 mg orally twice daily 1
- Maintenance therapy: 5 mg orally twice daily 1
- Extended prophylaxis (after 6 months): 2.5 mg orally twice daily 4
Important: The "2-of-3" dose-reduction criteria for atrial fibrillation do not apply to VTE treatment 4
Post-Surgical VTE Prophylaxis
Contraindications
Absolute contraindications:
- Active pathological bleeding 1
- Severe hypersensitivity to apixaban 1
- Prosthetic heart valves 1
- Triple-positive antiphospholipid syndrome 1
Relative contraindications/cautions:
- Severe hepatic impairment (transaminases >2× ULN or bilirubin >1.5× ULN) 4
- Creatinine clearance <15 mL/min (warfarin preferred unless dialysis-dependent) 4
Drug Interactions Requiring Dose Adjustment
Combined P-glycoprotein AND Strong CYP3A4 Inhibitors
Reduce apixaban from 5 mg to 2.5 mg twice daily when using:
Strong CYP3A4 Inducers
Avoid apixaban entirely with:
These agents reduce apixaban levels by >50%, rendering it ineffective 4
Monitoring Recommendations
Routine laboratory monitoring:
- No INR monitoring required (unlike warfarin) 3, 4
- Renal function: Check creatinine clearance at least annually 4
- Increased monitoring frequency: Every 3-6 months if CrCl <60 mL/min or during acute illness 4
Use Cockcroft-Gault equation for all renal assessments—eGFR and CrCl are not interchangeable and can lead to dosing errors 4
Perioperative Management
Elective Surgery
Discontinuation timing based on bleeding risk:
| Procedure Risk | CrCl >30 mL/min | CrCl 15-30 mL/min |
|---|---|---|
| Low bleeding risk | Stop 24 hours before [5] | Stop 48 hours before [5] |
| High bleeding risk | Stop 48 hours before [5] | Stop 72-96 hours before [5] |
| Neuraxial anesthesia | Stop 48-72 hours before [5] | Stop 72-96 hours before [5] |
Critical safety point: Do not use bridging anticoagulation with heparin or LMWH when stopping apixaban—this significantly increases bleeding risk without reducing thrombotic events 5, 6
Resumption After Surgery
- Low bleeding risk procedures: Resume 6-24 hours post-procedure once hemostasis confirmed 5
- High bleeding risk procedures: Resume 48-72 hours post-procedure 5
- After epidural catheter removal: Wait at least 2 hours before first apixaban dose 5
Special Populations
Pregnancy and Lactation
Apixaban is not recommended during pregnancy or breastfeeding—no adequate human data exist, and animal studies suggest potential reproductive toxicity 3
If pregnancy occurs while on apixaban, switch to LMWH immediately 3
Chronic Kidney Disease
Apixaban has the lowest renal clearance (27%) among DOACs, compared to dabigatran (80%) and rivaroxaban (66%), making it the safest option in renal impairment 3, 4, 7
For CKD Stage 4 (CrCl 15-29 mL/min): Use 2.5 mg twice daily for all patients—this is mandatory regardless of age or weight 4
For dialysis patients: FDA permits 5 mg twice daily, reduced to 2.5 mg if age ≥80 or weight ≤60 kg (only one criterion required) 4
High Fall Risk
Apixaban is preferred over warfarin in patients at high fall risk because it reduces intracranial hemorrhage by 49% (0.24% vs 0.47%/year) compared to warfarin 4
The absolute stroke risk from untreated AF exceeds the intracranial bleed risk from falls, making anticoagulation net beneficial 4
Switching Between Anticoagulants
From Warfarin to Apixaban
Stop warfarin and start apixaban when INR drops below 2.0—this avoids overlapping anticoagulation and reduces bleeding risk 4
From Dabigatran to Apixaban
Discontinue dabigatran and begin apixaban at the next scheduled dabigatran dose—no overlap, no gap, no bridging required 6
From Rivaroxaban to Apixaban
Stop rivaroxaban after the last dose and start apixaban at the next scheduled time—no washout needed given rivaroxaban's 5-9 hour half-life 4
Reversal Agents
Andexanet alfa is FDA-approved for reversal of apixaban in life-threatening bleeding 3
Dosing:
- Low-dose regimen: 400 mg bolus + 4 mg/min infusion × 120 min (if last apixaban dose <8 hours ago or dose ≤5 mg) 3
- High-dose regimen: 800 mg bolus + 8 mg/min infusion × 120 min (if last dose ≥8 hours ago or dose >5 mg) 3
Alternative: 4-factor prothrombin complex concentrate (PCC) 50 units/kg if andexanet unavailable 3
Common Pitfalls to Avoid
Underdosing based on single criterion – 9.4-40.4% of apixaban prescriptions involve inappropriate dose reduction based on age, renal function, or perceived bleeding risk alone 4
Using eGFR instead of Cockcroft-Gault CrCl – these are not interchangeable and lead to dosing errors 4
Bridging with heparin during interruptions – increases bleeding without reducing thrombosis 5, 6
Performing neuraxial procedures without adequate drug clearance – can cause catastrophic spinal epidural hematoma 5, 1
Assuming all DOACs are interchangeable – apixaban has unique dosing algorithms and renal clearance profiles 4