Is Paxlovid (nirmatrelvir/ritonavir) contraindicated in patients with deep vein thrombosis (DVT)?

Paxlovid is Not Contraindicated for Patients with Deep Vein Thrombosis, but Requires Careful Medication Review

Paxlovid (nirmatrelvir/ritonavir) is not contraindicated in patients with deep vein thrombosis (DVT), but caution is warranted if the patient is taking certain anticoagulants, particularly direct oral anticoagulants (DOACs) like rivaroxaban, due to significant drug-drug interactions.

Drug Interaction Concerns with Anticoagulants

Mechanism of Interaction

• Ritonavir (component of Paxlovid) is a strong inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp) transporter protein 1
• This inhibition can significantly increase plasma concentrations of medications metabolized through these pathways

Specific Anticoagulant Considerations

1. Direct Oral Anticoagulants (DOACs):

   • Rivaroxaban: Significant interaction with Paxlovid due to CYP3A4 and P-gp inhibition, increasing bleeding risk 1
   • Apixaban: Similar concerns as rivaroxaban
   • Edoxaban and dabigatran: May have fewer interactions but still require caution

2. Other Anticoagulants:

   • Low-molecular-weight heparin (LMWH): Preferred option during Paxlovid treatment
   • Unfractionated heparin (UFH): Alternative with minimal drug interactions
   • Warfarin: Requires close INR monitoring if used with Paxlovid 1

Management Approach for DVT Patients Needing Paxlovid

Step 1: Evaluate Current Anticoagulation

• Identify which anticoagulant the patient is taking for DVT
• Assess duration of therapy and clinical stability of DVT

Step 2: Decision Algorithm

1. If patient is on rivaroxaban or other DOAC:

   • Consider temporary switch to LMWH during Paxlovid treatment course (5 days)
   • Resume DOAC 2-3 days after completing Paxlovid

2. If patient is on LMWH or UFH:

   • Continue current therapy without modification
   • Paxlovid can be administered safely

3. If patient is on warfarin:

   • More frequent INR monitoring during and shortly after Paxlovid treatment
   • Dose adjustments may be necessary based on INR results

Special Considerations

Timing Considerations

• For newly diagnosed DVT requiring both anticoagulation and COVID-19 treatment:
  • Initiate treatment with LMWH rather than DOACs if Paxlovid will be used 2
  • Consider the 5-day duration of Paxlovid in planning anticoagulation strategy

Monitoring Recommendations

• Monitor for signs of bleeding during co-administration
• For patients who must remain on DOACs during Paxlovid treatment:
  • Consider dose reduction based on pharmacist consultation
  • Increase monitoring for bleeding complications

Conclusion

DVT itself is not a contraindication to Paxlovid therapy, but the concomitant use of certain anticoagulants (particularly DOACs) with Paxlovid requires careful medication management. When possible, switching to LMWH during the short course of Paxlovid represents the safest approach for patients with DVT requiring COVID-19 treatment.