What are the potential interactions between apixaban (anticoagulant) and bergamot?

Potential Interactions Between Apixaban and Bergamot

Bergamot may potentially increase apixaban plasma levels through inhibition of CYP3A4 and P-glycoprotein pathways, which could increase bleeding risk, though caution is warranted due to limited direct evidence.

Mechanism of Potential Interaction

Apixaban's metabolism and elimination involve two key pathways that can be affected by bergamot:

1. CYP3A4 Metabolism: Apixaban is partially metabolized by CYP3A4 in the liver 1

   • Bergamot contains bergamottin, a furanocoumarin that has been shown to inhibit CYP3A4 2, 3
   • Inhibition of CYP3A4 can lead to increased apixaban plasma concentrations

2. P-glycoprotein (P-gp) Transport: Apixaban is a substrate for P-gp transporters 1

   • Bergamottin in bergamot may also inhibit P-gp function
   • P-gp inhibition can increase apixaban absorption and reduce elimination

Clinical Significance

The 2022 guidelines on drug interactions affecting oral anticoagulants 1 highlight that:

• Combined P-gp and CYP3A4 inhibitors increase maximum concentration (Cmax) and AUC of apixaban, increasing bleeding risk
• Strong inhibitors of both pathways should be avoided with apixaban
• When strong CYP3A4 inhibitors cannot be avoided with apixaban, dose reduction is recommended:
  • 50% dose reduction for patients on 5-10 mg twice daily regimens
  • Not recommended for patients already on 2.5 mg twice daily regimen

Bergamot-Specific Considerations

While direct studies on bergamot-apixaban interactions are limited:

• Bergamottin in bergamot has been shown to inhibit CYP3A4 in studies, though with less potency than grapefruit juice 2
• In animal studies, bergamottin significantly increased plasma levels of CYP3A4 substrates 3
• The concentration of bergamottin in bergamot products varies considerably, making the interaction potential unpredictable

Risk Assessment and Recommendations

Based on the pharmacokinetic properties and interaction potential:

1. Avoid regular consumption of bergamot products (including bergamot oil, bergamot-containing supplements, Earl Grey tea) while taking apixaban

2. Monitor for signs of increased anticoagulant effect if bergamot exposure occurs:

   • Unusual bruising
   • Prolonged bleeding from minor cuts
   • Nosebleeds
   • Blood in urine or stool

3. Consider alternatives:

   • Non-bergamot citrus fruits or teas without bergamot oil
   • If bergamot is being used for therapeutic purposes, discuss alternative options with healthcare provider

Special Considerations

• Patients at higher bleeding risk should be particularly cautious about bergamot consumption
• Patients with renal impairment may be at greater risk as apixaban clearance is already reduced
• Patients taking multiple interacting medications should be aware that effects may be additive

Clinical Monitoring

Unlike warfarin, apixaban does not require routine coagulation monitoring. However, if significant bergamot consumption occurs:

• Increased vigilance for bleeding signs is warranted
• Patient education about potential interaction is essential
• Consider temporary dose adjustment if significant exposure cannot be avoided

This guidance aligns with the general principle that strong inhibitors of CYP3A4 and P-gp should be avoided or used with caution in patients taking apixaban to minimize bleeding risk while maintaining anticoagulant efficacy.