What medications affect Eliquis (apixaban)?

Medications That Affect Eliquis (Apixaban)

Apixaban is significantly affected by medications that inhibit or induce CYP3A4 and P-glycoprotein (P-gp) pathways, with strong dual inhibitors increasing bleeding risk and strong inducers potentially reducing anticoagulant efficacy. 1

Key Drug Interactions with Apixaban

Strong CYP3A4 and P-gp Inhibitors

• Significantly increase apixaban levels (99% increase with ketoconazole) 2
• Examples: ketoconazole, ritonavir, clarithromycin
• Recommendations:
  • Reduce apixaban dose by 50% if on 5-10mg twice daily regimen
  • Avoid combination if on 2.5mg twice daily regimen 1
  • Consider alternative medications when possible

Moderate CYP3A4 and P-gp Inhibitors

• Moderately increase apixaban levels (40% increase with diltiazem) 2
• Examples: diltiazem, verapamil, amiodarone, dronedarone, quinidine
• No empiric dose reduction required but monitor for bleeding 1

Strong CYP3A4 and P-gp Inducers

• Significantly decrease apixaban levels, reducing efficacy
• Examples: rifampin, carbamazepine, phenytoin, St. John's wort
• Recommendation: Avoid combination or use with extreme caution 1

Medications That Increase Bleeding Risk

• Antiplatelet agents: aspirin, clopidogrel (consider short duration of combination therapy) 3, 4
• NSAIDs: Long-term use increases bleeding risk 4
• Other anticoagulants: warfarin, heparin (avoid combination) 4
• SSRIs/SNRIs: Increase bleeding risk through platelet effects 4

Clinical Implications and Management

Monitoring Recommendations

• More frequent assessment for bleeding signs when using interacting medications
• Monitor renal and hepatic function periodically
• Watch for signs of bleeding: unexpected bruising, nosebleeds, blood in urine/stool, unusual headaches 3, 4

Special Considerations

1. Renal impairment: Increases apixaban exposure, especially when combined with P-gp inhibitors 4
2. Hepatic impairment: Moderate impairment (Child-Pugh B) does not significantly affect apixaban levels, but caution is advised 1
3. Food interactions: Food does not significantly affect apixaban bioavailability 5

Common Pitfalls and Caveats

• Failure to recognize dual pathway inhibitors: Medications that inhibit both CYP3A4 and P-gp pose the highest risk for increasing apixaban levels
• Overlooking OTC medications: Some over-the-counter medications like NSAIDs can increase bleeding risk
• Inadequate monitoring: Patients on interacting medications require more vigilant monitoring for bleeding
• Abrupt discontinuation: Stopping interacting medications may require reassessment of apixaban dosing

Practical Algorithm for Managing Drug Interactions

1. Assess the interaction type:

   • Strong dual inhibitor → Reduce dose or avoid
   • Strong inducer → Avoid combination
   • Moderate inhibitor → Standard dose with monitoring
   • Bleeding risk enhancer → Consider risk/benefit carefully

2. Evaluate patient-specific factors:

   • Renal function (CrCl <50 mL/min increases risk)
   • Age ≥80 years
   • Body weight ≤60 kg
   • Bleeding history

3. Implement appropriate strategy:

   • Dose adjustment
   • Alternative medication selection
   • Enhanced monitoring
   • Patient education on bleeding signs

Apixaban's multiple elimination pathways (metabolism, biliary excretion, direct intestinal excretion, and renal excretion) make it less susceptible to drug interactions compared to some other anticoagulants, but clinically significant interactions still occur and require careful management 5, 6.