What is the interaction between Eliquis (apixaban) and quercetin?

Interaction Between Eliquis (Apixaban) and Quercetin

Quercetin may potentially interact with apixaban (Eliquis) through inhibition of P-glycoprotein (P-gp) and BCRP transporters, which could increase apixaban levels and bleeding risk. Caution is advised when using these substances together.

Mechanism of Potential Interaction

• Apixaban (Eliquis) is a substrate for both P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transport systems, as well as cytochrome P450 3A4 (CYP3A4) 1
• Quercetin, a flavonoid commonly found in dietary supplements, has been shown to inhibit P-gp in laboratory studies, which could potentially increase apixaban levels 2, 3
• Inhibition of these transport systems can lead to increased plasma concentrations of apixaban, potentially increasing the risk of bleeding complications 1

Clinical Significance

• While no specific studies directly examine quercetin-apixaban interactions, the European Heart Rhythm Association guidelines classify substances that inhibit P-gp as having potential interactions with direct oral anticoagulants (DOACs) like apixaban 1
• A study found that 20.2% of patients on apixaban were taking dietary supplements with potentially serious interactions daily/most days, highlighting the prevalence of this issue 4
• Approximately 66% of patients were either uncertain or incorrect about potential interactions between their medications and over-the-counter products, including supplements 4

Risk Assessment

• The interaction between quercetin and apixaban would likely be classified as "yellow" (caution needed) according to the European Heart Rhythm Association's color-coding system for drug interactions 1
• The risk may be higher in patients with:
  • Renal impairment (as apixaban is partially eliminated by the kidneys) 1
  • Advanced age (>80 years) 1
  • Low body weight (<60 kg) 1
  • Concomitant use of other medications that affect P-gp or CYP3A4 1

Management Recommendations

• Consider avoiding the combination of high-dose quercetin supplements with apixaban when possible 1, 5
• If quercetin supplementation is desired:
  • Use the lowest effective dose of quercetin 2
  • Monitor for signs of increased anticoagulant effect (bruising, bleeding gums, prolonged bleeding from cuts) 1
  • Consider spacing the administration times (similar to recommendations for other P-gp inhibitors) 1
• For patients requiring anticoagulation who wish to continue quercetin supplementation, alternative anticoagulants less dependent on P-gp transport (such as warfarin with appropriate INR monitoring) could be considered 1, 5

Monitoring Considerations

• No specific laboratory monitoring is routinely recommended for apixaban, which complicates detection of increased drug levels 1
• Be vigilant for signs of bleeding, particularly with high-dose quercetin supplementation (≥1000 mg/day) 2
• Patient education about potential supplement-drug interactions is crucial, as knowledge gaps are common 4

Special Considerations

• Short-term use of low-dose quercetin is less likely to cause significant interactions than long-term or high-dose use 2
• Safety data regarding long-term use (>12 weeks) of high supplemental quercetin doses (≥1000 mg) are currently limited 2
• The interaction potential may be greater when quercetin is combined with other factors that increase apixaban levels, such as renal impairment or concomitant use of other P-gp inhibitors 1