What medications should be avoided while taking Eliquis (apixaban)?

Medications to Avoid While Taking Eliquis (Apixaban)

Critical Drug Interactions Requiring Avoidance

Avoid combining Eliquis with strong dual CYP3A4 and P-gp inhibitors (such as ketoconazole, itraconazole, ritonavir) if you are taking the 2.5 mg twice daily dose, and reduce your dose by 50% if taking 5 mg or 10 mg twice daily doses. 1

Absolutely avoid strong CYP3A4 and P-gp inducers including rifampin, carbamazepine, phenytoin, and St. John's wort, as these significantly reduce apixaban levels and increase your risk of stroke and blood clots. 1

High-Risk Medication Categories

NSAIDs and Pain Medications

• Avoid all NSAIDs (ibuprofen, naproxen, etc.) as they significantly increase bleeding risk - the British Society of Gastroenterology specifically warns against this combination 2
• Use acetaminophen (Tylenol) instead for pain management, as it does not increase bleeding risk 2
• Chronic NSAID use with apixaban increases major bleeding rates substantially 1

Antiplatelet Agents

• Avoid combining with aspirin unless absolutely necessary - concomitant aspirin use increases bleeding risk from 1.8% to 3.4% per year 1
• Avoid dual antiplatelet therapy (aspirin plus clopidogrel) - the APPRAISE-2 trial was terminated early due to bleeding rates of 5.9% per year with apixaban versus 2.5% with placebo 1
• Avoid prasugrel and ticagrelor unless specifically directed by your cardiologist 3

Other Anticoagulants

• Never combine with warfarin, heparin, enoxaparin, or other anticoagulants unless specifically transitioning between medications under physician supervision 1
• Avoid thrombolytic agents (clot-busting drugs) 1

Antibiotics Requiring Caution or Avoidance

Avoid Completely

• Rifampin - dramatically reduces apixaban levels, increasing clot risk 4, 1
• Nafcillin - reduces apixaban effectiveness over time 4

Use With Caution and Monitoring

• Erythromycin (moderate CYP3A4 inhibitor) - requires closer bleeding monitoring 4
• Trimethoprim-sulfamethoxazole - may affect kidney function, compounding risk 4

Generally Safe Antibiotics

• Penicillins, cephalosporins, fluoroquinolones, azithromycin, doxycycline, and metronidazole can be used without dose adjustment 4
• Clarithromycin is safe despite being a strong dual inhibitor - no dose adjustment needed per FDA labeling 1, 4

Antiarrhythmic Drugs

Moderate P-gp Inhibitors

• Amiodarone, dronedarone, verapamil - these moderately increase apixaban levels but can be used with caution 3
• Consider administering apixaban 2 hours before these medications to minimize interaction 3
• Monitor closely for bleeding, especially in patients over 75 years or with kidney impairment (CrCl 30-50 mL/min) 3, 4

Quinidine

• Moderately increases apixaban exposure through P-gp inhibition 3
• Use with enhanced bleeding monitoring 3

Antidepressants and Psychiatric Medications

• SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) increase bleeding risk through effects on platelet function 1
• Avoid combination when possible or monitor closely for bleeding signs 3

Herbal Supplements and Natural Products

• St. John's wort - strongly induces CYP3A4 and P-gp, dramatically reducing apixaban levels 1
• Berberine - inhibits CYP3A4 and increases apixaban levels, raising bleeding risk 5
• Consider switching to edoxaban (minimally metabolized by CYP3A4) if berberine is necessary 5

High-Risk Patient Populations Requiring Extra Caution

Elderly patients (>75 years), those with kidney impairment (CrCl 30-50 mL/min), and patients weighing <50 kg face compounded bleeding risk with any interacting medication. 4, 5

• In these populations, even moderate CYP3A4/P-gp inhibitors can cause clinically significant bleeding 3, 4
• Renal impairment significantly exacerbates drug accumulation, particularly with P-gp inhibitors 3
• Consider baseline and periodic kidney function monitoring 3

Cancer Therapy Interactions

Contraindicated Combinations

• Alectinib, brigatinib, capmatinib, ceritinib, entrectinib, lorlatinib - these potent P-gp/BCRP inhibitors are contraindicated or require significant dose adjustments 3
• Consider switching to low molecular weight heparin during cancer therapy if these agents are necessary 3

Safer Alternatives

• Erlotinib and gefitinib can be used safely with apixaban 3
• Edoxaban represents the safest DOAC option with most cancer therapies due to minimal CYP3A4 metabolism 3, 4, 5

Monitoring and Management Strategies

• Monitor for bleeding signs including unusual bruising, blood in urine/stool, prolonged bleeding from cuts, or unexplained bleeding throughout therapy with any potentially interacting medication 2, 4
• Assess kidney function before initiating any interacting medication and monitor for deterioration 4, 5
• Consider PPI prophylaxis to reduce gastrointestinal bleeding risk when combining with NSAIDs or antiplatelet agents, though this does not eliminate systemic bleeding risk 3, 2
• Screen for concurrent antiplatelet or NSAID use before prescribing any new medication 4

Common Pitfalls to Avoid

• Do not assume "natural" supplements are safe - many have significant interactions 5, 1
• Do not use INR or aPTT to monitor apixaban levels - these tests are not reliable for DOACs 6
• Do not combine multiple drugs affecting hemostasis without careful risk-benefit assessment 1
• Do not forget that even mild kidney impairment (CrCl <50 mL/min) significantly increases interaction risk 3, 4