Does lemborexant interact with apixaban (Eliquis)?

Lemborexant and Apixaban Drug Interaction

Lemborexant should be used with caution when co-administered with apixaban due to potential moderate CYP3A4 interactions that could increase apixaban plasma levels and bleeding risk. 1

Mechanism of Interaction

Lemborexant and apixaban interact through shared metabolic pathways:

• Apixaban metabolism: Primarily metabolized by CYP3A4 and is a substrate of P-glycoprotein (P-gp) 2
• Lemborexant profile: Metabolized by CYP3A4 and has been shown to interact with CYP3A4 inhibitors 1, 3

Evidence for Interaction

Studies of lemborexant show:

• When co-administered with moderate CYP3A inhibitors like fluconazole, lemborexant exposure increased 1.4-1.6 fold (Cmax) and 3.7-4 fold (AUC) 1
• Lemborexant does not appear to affect the pharmacokinetics of CYP3A substrates like midazolam 1
• PBPK modeling indicates moderate interactions with moderate CYP3A inhibitors like erythromycin and verapamil 3

For apixaban:

• Apixaban interacts with drugs that inhibit CYP3A4 or P-gp, with combined inhibitors increasing maximum concentration (Cmax) and AUC, potentially increasing bleeding risk 2
• Strong CYP3A4 and P-gp inhibitors significantly increase apixaban plasma levels 4

Clinical Implications

Based on the metabolic profiles and interaction studies:

1. Bleeding risk: The co-administration may potentially increase apixaban levels, though likely to a lesser extent than with strong CYP3A4 inhibitors
2. Monitoring recommendations:
   • Watch for signs of bleeding (unexplained bruising, blood in urine/stool, unusual headaches) 4
   • Monitor renal and hepatic function periodically 4

Management Recommendations

For patients requiring both medications:

• Dosing considerations:

  • Consider using the lower dose of lemborexant (5 mg rather than 10 mg) 1, 3
  • For apixaban, standard dosing can be maintained but with increased vigilance for bleeding signs 2

• Alternatives to consider:

  • If high bleeding risk exists, consider an alternative sleep medication that doesn't interact with CYP3A4
  • For anticoagulation, dabigatran or edoxaban may have fewer CYP3A4-related interactions 2

Pitfalls and Caveats

• Polypharmacy concerns: The risk increases with multiple medications that affect coagulation (NSAIDs, SSRIs, SNRIs) 4
• Individual variability: Pharmacokinetic responses may vary between patients
• Limited direct evidence: No specific studies directly examining lemborexant-apixaban interaction are available; recommendations are based on understanding of metabolic pathways

While this interaction is not as concerning as with strong CYP3A4 inhibitors, prudent monitoring and potential dose adjustments should be considered when using lemborexant and apixaban concurrently.