Can a patient take Eliquis (apixaban) with Paxlovid (nirmatrelvir/ritonavir)?

Can a Patient Take Eliquis with Paxlovid?

Yes, a patient can take Eliquis (apixaban) with Paxlovid (nirmatrelvir/ritonavir), but the apixaban dose must be reduced by 50% if the patient is taking 5 mg or 10 mg twice daily, and the combination should be avoided entirely if the patient is already on the reduced 2.5 mg twice daily dose. 1

Mechanism of Drug Interaction

• Paxlovid contains ritonavir, which is a potent combined P-glycoprotein and strong CYP3A4 inhibitor 1, 2
• Apixaban is both a P-glycoprotein substrate and is metabolized via CYP3A4, making it highly susceptible to this interaction 1
• Ritonavir significantly increases apixaban plasma concentrations by inhibiting both its metabolism and transport, substantially raising bleeding risk 2, 3

Specific Dosing Recommendations

For Patients on Standard Dose Apixaban (5 mg twice daily):

• Reduce apixaban to 2.5 mg twice daily during the entire 5-day course of Paxlovid treatment 1
• Resume the original 5 mg twice daily dose after completing Paxlovid 2

For Patients Already on Reduced Dose Apixaban (2.5 mg twice daily):

• Avoid the combination entirely - the interaction cannot be safely managed with further dose reduction 1
• Consider alternative COVID-19 treatments or temporarily switching to a parenteral anticoagulant (e.g., LMWH) during Paxlovid therapy if clinically appropriate 1

For Patients on Higher Dose Apixaban (10 mg twice daily for acute VTE):

• Reduce to 5 mg twice daily during Paxlovid treatment 1
• This scenario is less common but follows the same 50% dose reduction principle 2

Clinical Monitoring During Concurrent Use

• Monitor closely for bleeding complications including bruising, hematuria, melena, hemoptysis, or any unusual bleeding 2, 3
• Assess baseline renal function, as approximately 27% of apixaban undergoes renal elimination and the interaction may be more pronounced in renal impairment 2
• Be particularly vigilant in elderly patients (>75 years) who have baseline increased bleeding risk 2

Common Pitfalls to Avoid

• Failing to adjust the dose before starting Paxlovid - the dose reduction should begin with the first dose of Paxlovid, not after several days 1
• Forgetting to resume the original apixaban dose after completing the 5-day Paxlovid course, which could lead to inadequate anticoagulation 2
• Attempting to use the combination in patients already on 2.5 mg twice daily - this is explicitly contraindicated 1
• Not considering the patient's indication for anticoagulation - patients with acute VTE or recent stroke may not tolerate any interruption in anticoagulation 1

Alternative Considerations

• If the drug interaction cannot be safely managed, consider alternative COVID-19 treatments such as molnupiravir (which has no significant drug interactions) or monoclonal antibodies if available 3
• For hospitalized patients with acute VTE requiring Paxlovid, temporary switch to LMWH or unfractionated heparin during the 5-day Paxlovid course may be the safest approach 1
• The cardiovascular literature emphasizes that preventing and managing DDIs with nirmatrelvir/ritonavir requires thorough assessment, particularly for drugs with narrow therapeutic indices like anticoagulants 3

Special Population Considerations

• Renal impairment (CrCl 15-29 mL/min): Use extreme caution as both reduced renal clearance and the drug interaction compound bleeding risk 2
• Cancer patients on apixaban for VTE: The interaction management is the same, but consider the higher baseline thrombotic risk in this population 1, 2
• Patients on multiple interacting medications: Ritonavir interacts with numerous cardiovascular and other medications; comprehensive medication review is essential 3