What common medications interact with Eliquis (apixaban)?

Common Medications That Interact with Eliquis (Apixaban)

Eliquis interacts primarily with drugs that affect CYP3A4 and P-glycoprotein (P-gp) pathways, as well as medications that increase bleeding risk through pharmacodynamic effects. 1

Strong CYP3A4 and P-gp Inhibitors (Require Dose Reduction or Avoidance)

If you're taking Eliquis 5 mg or 10 mg twice daily, reduce the dose by 50% when combined with:

• Ketoconazole
• Itraconazole
• Ritonavir

If you're already on Eliquis 2.5 mg twice daily, avoid these drugs entirely. 1

Exception: Clarithromycin does not require dose adjustment despite being a strong inhibitor, based on pharmacokinetic data. 1 However, real-world evidence shows clarithromycin was associated with higher hospitalization rates for major bleeding compared to azithromycin in DOAC users. 2

Strong CYP3A4 and P-gp Inducers (Avoid Completely)

Avoid these medications as they significantly reduce Eliquis levels and increase stroke risk:

• Rifampin (reduces apixaban exposure by ~50%) 2
• Carbamazepine
• Phenytoin
• St. John's wort 1

Medications That Increase Bleeding Risk (Use with Caution)

These drugs don't change Eliquis levels but increase bleeding through additive effects:

Antiplatelet Agents

• Aspirin - increases bleeding from 1.8% to 3.4% per year 1
• Clopidogrel and other P2Y12 inhibitors
• Dual antiplatelet therapy with Eliquis increases major bleeding to 5.9% per year 1

NSAIDs

• Ibuprofen - taken daily/most days by 1.8% of patients, occasionally by 28.5% 3
• Naproxen
• Chronic NSAID use significantly increases bleeding risk 1

Other Common Medications

• Selective serotonin reuptake inhibitors (SSRIs) - impair hemostasis 4
• Heparin and other anticoagulants 1
• Fibrinolytics 1

Moderate CYP3A4 Inhibitors (Generally No Dose Adjustment Needed)

The ARISTOTLE trial post-hoc analysis found no difference in outcomes with moderate inhibitors, so empiric dose reduction is not recommended. 2 However, individual clinical judgment is warranted with:

• Erythromycin
• Fluconazole (may increase clinically relevant non-major bleeding) 5
• Diltiazem
• Amiodarone

Over-the-Counter Products

A critical but often overlooked category - 33% of patients take at least one potentially interacting OTC product daily: 3

• Dietary supplements - taken daily by 20.2% of patients 3
• Aspirin - 14.7% take daily, with 64.7% of these also consuming other interacting OTC products 3
• NSAIDs - frequently used without patient awareness of interaction risks 3

Important caveat: Approximately 66% of patients are uncertain or incorrect about the bleeding risk from combining NSAIDs with apixaban, highlighting a major education gap. 3

Antibiotics Requiring Special Attention

While data are limited for apixaban specifically, concern exists for:

• Macrolides (clarithromycin, erythromycin) - CYP3A4/P-gp inhibitors 6
• Azole antifungals (fluconazole, ketoconazole) 6
• Common antibiotics like amoxicillin, cephalosporins, and metronidazole have hemorrhagic events reported in databases, though causality is unclear 6

Medications WITHOUT Significant Interactions

Levetiracetam - despite some professional organization warnings, observational data show no apparent interaction with apixaban concentrations. 7

Clinical Pitfalls to Avoid

1. Don't forget OTC products - patients often don't recognize these as "real medications" and fail to report them 8
2. Acetaminophen is safe - this is the preferred analgesic for patients on Eliquis
3. Moderate inhibitors don't need dose adjustment - resist the urge to empirically reduce doses 2
4. Patient education is critical - most patients lack knowledge about potential interactions and believe providers are solely responsible for identifying them 8