Should a patient taking Paxlovid (nirmatrelvir/ritonavir) and Eliquis (apixaban) hold Eliquis or monitor while on Paxlovid?

Managing Apixaban During Paxlovid Treatment

Patients taking Eliquis (apixaban) should temporarily reduce their dose by 50% while on Paxlovid (nirmatrelvir/ritonavir) therapy and monitor closely for signs of bleeding.

Mechanism of Interaction

The interaction between Paxlovid and Eliquis occurs because:

• Ritonavir (component of Paxlovid) is a strong inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp) transporters 1
• Apixaban is metabolized primarily by CYP3A4 and is a substrate for P-gp transporters
• This interaction can significantly increase apixaban plasma concentrations, potentially increasing bleeding risk

Management Algorithm

1. For patients on standard apixaban dosing (5mg twice daily):

   • Reduce dose to 2.5mg twice daily during Paxlovid treatment
   • Resume normal dosing 3 days after completing Paxlovid

2. For patients already on reduced apixaban dosing (2.5mg twice daily):

   • Consider temporarily switching to an alternative anticoagulant not metabolized by CYP3A4
   • If switching is not feasible, maintain 2.5mg twice daily with enhanced monitoring

3. Monitoring recommendations during co-administration:

   • Watch for signs of bleeding (bruising, nosebleeds, blood in urine/stool)
   • Monitor for symptoms of increased anticoagulant effect (dizziness, weakness)
   • Consider checking renal function before and during treatment

Evidence Analysis

The evidence strongly suggests that direct oral anticoagulants (DOACs) like apixaban have significant interactions with CYP3A4 inhibitors like ritonavir. The European Society of Cardiology guidelines highlight that anticoagulants can have more bleeding complications in older adults and require careful monitoring when used with CYP3A4 inhibitors 2.

Studies examining drug interactions with Paxlovid have identified anticoagulants, including apixaban, as medications with expected drug-drug interactions 3. Real-world evidence shows that ritonavir's strong inhibition of CYP3A4 enzymes can lead to increased plasma concentrations of medications metabolized through this pathway 1.

Important Considerations

• Duration of interaction: The inhibitory effect of ritonavir may persist for 3-5 days after discontinuation
• Patient-specific factors: Bleeding risk may be higher in elderly patients, those with renal impairment, or patients on multiple medications
• Alternative approaches: For patients at very high bleeding risk, consider consulting with a hematologist about temporary use of alternative anticoagulants with fewer interactions

Common Pitfalls to Avoid

1. Complete discontinuation of anticoagulation: This could increase thrombotic risk, especially in high-risk patients
2. Failure to recognize bleeding signs: Educate patients about monitoring for bleeding symptoms
3. Overlooking other interacting medications: Many patients on anticoagulants take multiple medications that may have additional interactions with Paxlovid
4. Inadequate follow-up: Ensure proper transition back to regular dosing after Paxlovid completion

By following this structured approach, clinicians can effectively manage the interaction between Eliquis and Paxlovid while maintaining therapeutic anticoagulation and minimizing bleeding risk.