What adjustments should be made to a patient's anticoagulation regimen when initiating Paxlovid (nirmatrelvir/ritonavir) while on Eliquis (apixaban) and Pradaxa (dabigatran)?

Management of Paxlovid Initiation in Patients on Pradaxa (Dabigatran)

Temporarily discontinue dabigatran for the entire 5-day course of Paxlovid (nirmatrelvir/ritonavir) due to ritonavir's potent P-glycoprotein inhibition, which significantly increases dabigatran levels and bleeding risk. 1

Mechanism of Drug-Drug Interaction

• Ritonavir is a potent P-glycoprotein (P-gp) inhibitor that rapidly and substantially increases plasma concentrations of dabigatran, which is a P-gp substrate 1
• Unlike apixaban and rivaroxaban (which are primarily metabolized by CYP3A4), dabigatran relies heavily on P-gp for elimination, making this interaction particularly significant 2, 1
• The interaction occurs immediately upon ritonavir administration and persists throughout the 5-day treatment course 1

Specific Management Protocol for Dabigatran

Step 1: Discontinue dabigatran before starting Paxlovid

• Hold dabigatran at least 24-48 hours before initiating Paxlovid in patients with normal renal function (CrCl >50 mL/min) 2, 3
• For patients with CrCl 30-50 mL/min, extend the discontinuation period to 48-72 hours due to predominant renal elimination 2
• Do not administer dabigatran during the entire 5-day Paxlovid course 1

Step 2: Assess thromboembolic risk during the treatment gap

• For patients at very high thromboembolic risk (mechanical heart valves, recent stroke within 3 months, CHA₂DS₂-VASc score ≥5), consider bridging with low-molecular-weight heparin (LMWH) during the 7-day anticoagulation gap 2
• For most patients with non-valvular atrial fibrillation and moderate thromboembolic risk, a 7-day interruption without bridging is acceptable given the short duration 2
• Bridging is generally not recommended for routine cases as the bleeding risk may outweigh benefits for such a brief interruption 2

Step 3: Resume dabigatran after Paxlovid completion

• Wait at least 48-72 hours after the last dose of Paxlovid before restarting dabigatran to allow complete ritonavir clearance 1
• Resume at the patient's previous maintenance dose (typically 150 mg twice daily, or 110 mg twice daily if age ≥80 years, CrCl 30-50 mL/min, or on verapamil) 2

Critical Monitoring Parameters

• Assess renal function (CrCl by Cockcroft-Gault formula) before discontinuing dabigatran, as this determines the appropriate washout period 2
• Monitor for signs of thromboembolism during the anticoagulation gap (new neurological symptoms, limb swelling, chest pain) 2
• After resuming dabigatran post-Paxlovid, counsel patients on bleeding precautions and signs requiring immediate medical attention 2

Common Pitfalls to Avoid

• Do not continue dabigatran at a reduced dose during Paxlovid treatment - the P-gp inhibition is too potent for dose adjustment to be safe 1
• Do not use activated charcoal to mitigate the interaction - this is only useful for recent ingestion (within 2-4 hours), not for ongoing therapy 2
• Do not assume the interaction resolves immediately after stopping Paxlovid - ritonavir's effects on P-gp persist for 2-3 days after the last dose 1
• Do not routinely bridge all patients - assess individual thromboembolic risk as most patients tolerate a brief interruption without bridging 2

Alternative Anticoagulation Considerations

If the patient requires urgent COVID-19 treatment and cannot safely interrupt anticoagulation:

• Consider switching to unfractionated heparin or LMWH for the duration of Paxlovid treatment, which have no significant interaction with ritonavir 2, 1
• Apixaban has less severe interactions with ritonavir compared to dabigatran, but still requires careful management and is not a simple substitute during active treatment 1