Can Paxlovid (nirmatrelvir/ritonavir) be given with Eliquis (apixaban)?

Paxlovid and Eliquis Interaction Management

Paxlovid (nirmatrelvir/ritonavir) should not be administered with Eliquis (apixaban) without appropriate dose adjustment due to increased bleeding risk from significantly elevated apixaban levels caused by ritonavir's strong CYP3A4 and P-glycoprotein inhibition.

Mechanism of Interaction

• Ritonavir, a component of Paxlovid, is a strong inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp) transporters 1
• Apixaban (Eliquis) is a substrate of both CYP3A4 and P-gp, making it vulnerable to significant drug interactions with inhibitors of these pathways 2, 1
• The combination results in increased apixaban blood levels and consequently an elevated risk of bleeding complications 1

FDA Recommendations for Management

• According to the FDA drug label for Paxlovid, combined P-gp and strong CYP3A inhibitors increase blood levels of apixaban and increase the risk of bleeding 1
• Dosing recommendations for co-administration depend on the apixaban dose and require careful adjustment 1
• The FDA advises referring to the apixaban product label for specific dosing modifications when used with strong CYP3A4 inhibitors like ritonavir 1

Clinical Approach to Management

When a patient on Eliquis requires Paxlovid treatment, consider the following options:

1. Dose adjustment approach:

   • Reduce apixaban dose according to the product label recommendations for use with strong CYP3A4/P-gp inhibitors 1
   • Monitor closely for signs of bleeding during the 5-day Paxlovid treatment course 1

2. Alternative anticoagulant approach:

   • Temporarily switch to an alternative anticoagulant with fewer drug interactions during the Paxlovid treatment course 2
   • Low molecular weight heparin may be considered as it has minimal drug interactions with Paxlovid 2

Important Considerations and Monitoring

• The risk of interaction is particularly significant in patients with additional risk factors for bleeding or those with renal impairment 2
• Careful monitoring for signs of bleeding is essential during co-administration 1
• The interaction persists throughout the 5-day course of Paxlovid treatment 3
• Patients should be educated about signs and symptoms of bleeding to report immediately 2

Other Direct Oral Anticoagulants (DOACs) with Paxlovid

• Rivaroxaban (Xarelto): Contraindicated with Paxlovid due to increased bleeding risk 1
• Dabigatran (Pradaxa): Increased bleeding risk; requires dose reduction or avoidance depending on indication and renal function 1
• Edoxaban: Similar concerns as with other factor Xa inhibitors 2

Conclusion

When considering Paxlovid for patients on Eliquis, clinicians must carefully weigh the benefits of COVID-19 treatment against the increased bleeding risk. Appropriate dose adjustment of apixaban or temporary switch to an alternative anticoagulant with close monitoring is essential to minimize bleeding complications while providing effective COVID-19 treatment.