What are alternative medications to Eliquis (apixaban) for anticoagulation?

Alternative Medications to Eliquis (Apixaban)

The primary alternatives to Eliquis for anticoagulation are rivaroxaban, edoxaban, and dabigatran—all direct oral anticoagulants (DOACs) that are recommended as first-line therapy over warfarin for most indications. 1

Direct Oral Anticoagulant (DOAC) Alternatives

The three main DOAC alternatives to apixaban are:

Rivaroxaban (Factor Xa Inhibitor)

• Dosed once daily for most indications, improving convenience 1
• 35% renal elimination, 65% hepatic elimination 1
• Has CYP3A4 and P-glycoprotein interactions 1
• Strongest phase 4 real-world data among DOACs 1
• Approved for pulmonary embolism, deep vein thrombosis, atrial fibrillation, and post-orthopedic surgery prophylaxis 1, 2, 3
• Consider dose reduction after first 6 months for extended anticoagulation 1

Edoxaban (Factor Xa Inhibitor)

• Dosed once daily 1
• 50% renal elimination, 50% hepatic elimination 1
• No CYP3A4 interaction, only P-glycoprotein substrate 1
• Most robust evidence for dose reduction with P-glycoprotein drugs (prespecified in ENGAGE-AF and HOKUSAI trials) 1
• Strongest randomized controlled trial data for cancer-associated thrombosis 1
• Approved for atrial fibrillation, VTE treatment, and post-orthopedic surgery prophylaxis 2, 3, 4

Dabigatran (Direct Thrombin Inhibitor)

• Dosed twice daily for all indications 1, 3
• 80% renal elimination, 20% hepatic elimination 1
• No CYP3A4 interaction, only P-glycoprotein substrate 1
• Stricter prescribing restrictions in moderate-to-severe renal impairment compared to factor Xa inhibitors 3
• Specific reversal agent available (idarucizumab 5g IV) for life-threatening bleeding 1
• Approved for atrial fibrillation, VTE treatment/prevention, and post-orthopedic surgery prophylaxis 1, 2, 3

Choosing Between DOAC Alternatives

When selecting an alternative to apixaban, consider these clinical factors:

Gastrointestinal Bleeding Risk

• Apixaban has the lowest GI bleeding risk among DOACs 1
• If switching due to GI bleeding, consider warfarin or LMWH instead of another DOAC 1
• Avoid edoxaban and rivaroxaban in gastrointestinal cancer with intact primary tumor 1

Renal Function

• Dabigatran requires strictest dose adjustments in renal impairment (contraindicated if CrCl <30 mL/min for atrial fibrillation) 3
• Rivaroxaban and edoxaban have more balanced renal/hepatic elimination 1
• For severe renal dysfunction (eGFR 15-30), apixaban may actually be preferred over warfarin based on registry data showing lower mortality 5

Dosing Convenience

• Rivaroxaban and edoxaban offer once-daily dosing 1, 3
• Dabigatran requires twice-daily dosing for all indications 1, 3
• Single-drug pathways are preferred to minimize dosing confusion 1

Drug Interactions

• Edoxaban has no CYP3A4 interaction and most robust P-glycoprotein interaction data 1
• Rivaroxaban has both CYP3A4 and P-glycoprotein interactions 1
• Review concomitant medications, particularly strong P-glycoprotein and CYP3A4 inhibitors/inducers 6

Cancer Patients

• Edoxaban or rivaroxaban should be considered as alternatives to LMWH for cancer-associated thrombosis 1
• Exception: avoid in gastrointestinal cancer due to increased bleeding risk 1
• Edoxaban has strongest RCT data for cancer-associated thrombosis 1

Traditional Anticoagulant Alternatives

Warfarin (Vitamin K Antagonist)

• Remains an alternative when DOACs are contraindicated 1
• Requires INR monitoring and has multiple drug/food interactions 4
• Mandatory for antiphospholipid antibody syndrome 1
• Reversal with prothrombin complex concentrate (PCC) 25-50 U/kg plus vitamin K 5-10 mg IV 1

Low Molecular Weight Heparin (LMWH)

• Consider when DOACs contraindicated (e.g., severe renal impairment, pregnancy) 1
• NOACs are not recommended during pregnancy or lactation 1
• Requires subcutaneous injection 1

Critical Switching Considerations

When transitioning between anticoagulants:

• Switch directly from one DOAC to another when next dose is due—no overlap, no gap, no bridging 6
• Never overlap DOACs (creates excessive bleeding risk) 6
• Never leave a gap (creates thrombotic risk) 6
• Switching between DOACs without clear indication is not recommended by the European Society of Cardiology 7
• Verify appropriate dosing for the specific indication and patient characteristics 6

Reversal Agents

For life-threatening bleeding:

• Andexanet alfa for apixaban or rivaroxaban 1, 8
• Idarucizumab 5g IV for dabigatran 1
• PCC 25-50 U/kg if specific reversal unavailable or for edoxaban 1, 8

Common Pitfalls to Avoid

• Do not assume all DOACs are interchangeable—they have distinct pharmacologic profiles 1, 3
• Do not use clinical risk scores (PESI/sPESI) derived for non-pregnant patients in pregnancy 1
• Do not forget thromboprophylaxis after PCC administration due to increased thrombotic risk 1
• Assess renal function before any DOAC switch as all require dose adjustment in renal dysfunction 6, 3