Are there any interactions between apixaban (direct oral anticoagulant) 5mg twice a day and celery seed extract containing 3-n-butylphthalide?

Potential Interactions Between Apixaban and Celery Seed Extract (3-n-butylphthalide)

There is a potential risk of increased bleeding when combining apixaban with celery seed extract containing 3-n-butylphthalide due to possible pharmacokinetic interactions affecting apixaban metabolism. While no direct studies specifically examine this combination, the interaction mechanism is concerning based on established pharmacological principles.

Mechanism of Potential Interaction

Apixaban's metabolism and potential interactions are well-documented in clinical guidelines:

• Apixaban is metabolized primarily via CYP3A4 (hepatic cytochrome P450 3A4) and is a substrate for P-glycoprotein (P-gp) transport system 1
• Approximately 27% of apixaban is eliminated via renal excretion as unchanged drug 1
• Substances that inhibit CYP3A4 and/or P-gp can increase apixaban plasma concentrations, potentially increasing bleeding risk 1

Celery seed extract containing 3-n-butylphthalide has properties that may interfere with these pathways:

• 3-n-butylphthalide has demonstrated antihypertensive effects 2, which could have additive effects with anticoagulation
• Herbal medicines are frequently underestimated regarding their potential for drug interactions 1
• Plant compounds can inhibit CYP enzymes and/or P-gp transporters

Clinical Implications

The risk of this combination relates to:

1. Increased bleeding risk: If celery seed extract inhibits CYP3A4 or P-gp, it could increase apixaban plasma concentrations beyond therapeutic levels

2. Pharmacodynamic interaction: Celery seed extract has demonstrated blood pressure-lowering effects 2, which could compound cardiovascular effects

3. Lack of monitoring: Unlike warfarin, apixaban doesn't require routine coagulation monitoring, making detection of excessive anticoagulation difficult 3

Recommendations for Management

Given the potential for interaction:

1. Exercise caution with concurrent use of apixaban and celery seed extract containing 3-n-butylphthalide

2. Consider alternative anticoagulants if celery seed extract must be continued:

   • Dabigatran may be preferable as it has less CYP3A4 dependence (primarily eliminated via P-gp) 1

3. Monitor for signs of bleeding if concurrent use cannot be avoided:

   • Unusual bruising
   • Prolonged bleeding from minor cuts
   • Gum bleeding
   • Epistaxis
   • Hemoptysis
   • Hematuria

4. Consider measuring apixaban plasma concentrations if available and if concurrent use is necessary 1

Key Considerations

• Patient education is critical - many patients lack knowledge about potential interactions between over-the-counter products (including supplements) and apixaban 3

• Approximately 33% of patients on apixaban take at least one OTC product with potentially serious interactions 3

• The safety and efficacy of combining apixaban with herbal supplements have not been well established 1

• When making decisions about anticoagulation, always prioritize the prevention of stroke and systemic embolism while minimizing bleeding risk 1

In conclusion, until more specific data becomes available on this particular interaction, caution is warranted when combining apixaban with celery seed extract containing 3-n-butylphthalide due to the theoretical risk of increased bleeding through pharmacokinetic and/or pharmacodynamic interactions.