What are the potential interactions between apixaban (anticoagulant) 5mg twice a day and sage extract containing 2.5% rosmarinic acid?

Potential Interaction Between Apixaban and Sage Extract

There is a potential risk of increased bleeding when combining apixaban 5mg twice daily with sage extract containing 2.5% rosmarinic acid due to possible pharmacodynamic interactions, though direct evidence is limited. 1

Mechanism of Potential Interaction

Apixaban is metabolized through several pathways:

• Primary metabolism via CYP3A4 (hepatic clearance)
• Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters
• Approximately 27% renal excretion and 73% biliary/intestinal excretion 1

Sage extract containing rosmarinic acid may interact with apixaban through:

1. Potential inhibition of P-gp transporters, which could increase apixaban plasma levels
2. Possible antiplatelet effects that could enhance the anticoagulant effect of apixaban

Risk Assessment

The 2018 European Heart Rhythm Association practical guide classifies herbal supplements as having potential interactions with NOACs that require caution, particularly when combined with other factors that might increase bleeding risk 1.

Key considerations:

• Apixaban has significant potential for drug-drug interactions, either with CYP3A/P-gp modulators or with substances that may impair hemostasis 2
• Many patients taking apixaban also take over-the-counter products with potentially serious interactions (33% of patients in one study) 3
• Herbal supplements with anticoagulant or antiplatelet properties may have additive effects with apixaban

Recommendations for Management

1. Monitor for signs of increased bleeding risk:

   • Bruising
   • Gum bleeding
   • Prolonged bleeding from minor cuts
   • Dark urine or stool
   • Epistaxis

2. Consider alternatives:

   • If sage extract is being used for medicinal purposes, discuss alternative treatments with fewer potential interactions
   • If continued use is necessary, separate administration times (take sage extract at least 2 hours before or after apixaban)

3. Dose adjustment considerations:

   • Standard apixaban dosing should be maintained unless there are multiple interacting factors present
   • If multiple interacting factors are present (e.g., advanced age, renal impairment, low body weight plus sage extract), closer monitoring is warranted 1

Clinical Pitfalls to Avoid

1. Don't assume herbal supplements are harmless: Many patients fail to disclose supplement use to healthcare providers, assuming they are safe because they are "natural" 3

2. Avoid multiple interacting substances: The risk increases substantially when multiple products with potential interactions are used concurrently 1

3. Be aware of bleeding risk factors: The combination may be particularly risky in patients with:

   • History of GI bleeding
   • Renal impairment
   • Advanced age
   • Concomitant use of antiplatelet drugs
   • Recent surgery

4. Don't stop anticoagulation without medical advice: The risk of thrombotic events from stopping apixaban may outweigh the potential interaction risk 1

While direct evidence specifically addressing sage extract with apixaban is limited, the general approach to managing potential herb-drug interactions with anticoagulants should be applied with caution, focusing on monitoring for signs of bleeding and considering the overall risk-benefit profile for the individual patient.