Can a patient with a history of bleeding disorders take Eliquis (apixaban) and Paxlovid (nirmatrelvir/ritonavir) concurrently?

Can a Patient Take Eliquis and Paxlovid Concurrently?

Yes, a patient can take Eliquis (apixaban) and Paxlovid (nirmatrelvir/ritonavir) together, but the apixaban dose must be reduced by 50% during the 5-day Paxlovid treatment course to prevent excessive bleeding risk. 1

Mechanism of Drug Interaction

• Paxlovid contains ritonavir, which is a combined strong inhibitor of both CYP3A4 and P-glycoprotein (P-gp), the two primary pathways responsible for apixaban metabolism and elimination 1
• This dual inhibition significantly increases apixaban blood levels, thereby elevating bleeding risk 1
• The FDA label explicitly states that "combined P-gp and strong CYP3A inhibitors increase blood levels of apixaban and increase the risk of bleeding" 1

Specific Dosing Recommendations

For patients on apixaban 5 mg twice daily:

• Reduce to apixaban 2.5 mg twice daily during the 5-day Paxlovid course 1
• Resume apixaban 5 mg twice daily after completing Paxlovid 1

For patients already on apixaban 2.5 mg twice daily:

• The FDA label recommends referring to the apixaban product label for specific guidance, as further dose reduction may not be feasible 1
• Consider temporarily holding apixaban or switching to an alternative anticoagulation strategy in consultation with cardiology

Critical Timing Considerations

• PBPK modeling demonstrates that rivaroxaban (a similar factor Xa inhibitor) concentrations return to normal range by day 4 post-discontinuation of Paxlovid, correlating with recovery of enzyme activity 2
• This suggests apixaban can safely return to full dose immediately after completing the 5-day Paxlovid course 2

Monitoring Requirements During Concurrent Use

Watch for bleeding signs at every patient contact: 3

• Unusual bruising or petechiae
• Black/tarry stools or blood in urine
• Gum bleeding or nosebleeds lasting >10 minutes
• Headache with visual changes (concern for intracranial hemorrhage)

Consider baseline and follow-up laboratory assessment: 3

• Complete blood count with hemoglobin/hematocrit before starting Paxlovid
• Repeat CBC if any bleeding symptoms develop
• Renal function assessment, as both drugs require dose adjustment in renal impairment 3, 1

Special Populations Requiring Extra Caution

Elderly patients (≥75 years): 3

• Already at increased risk for intracranial and gastrointestinal bleeding with apixaban
• The combination with Paxlovid further amplifies this risk
• Consider more frequent monitoring or alternative COVID-19 treatment if available

Patients with renal impairment: 3, 1

• Apixaban dose may already be reduced to 2.5 mg twice daily if CrCl 15-50 mL/min
• Paxlovid also requires dose reduction if CrCl <60 mL/min
• The interaction becomes more pronounced with declining renal function 2

Patients with history of bleeding disorders: 3

• This combination should be avoided if possible in patients with active bleeding
• Consider alternative COVID-19 therapies such as remdesivir or molnupiravir

Absolute Contraindications to Avoid

Never combine apixaban/Paxlovid with: 3, 4

• Antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor) - creates additive bleeding risk
• NSAIDs (ibuprofen, naproxen, celecoxib) - substantially increases bleeding risk
• SSRIs or SNRIs - additional bleeding risk through platelet dysfunction
• Other anticoagulants - obvious compounding effect

Common Pitfalls to Avoid

Failure to reduce apixaban dose: 1

• The most critical error is continuing full-dose apixaban during Paxlovid treatment
• This can result in apixaban levels 2-3 times higher than intended

Premature resumption of full-dose apixaban: 2

• Wait until Paxlovid course is completely finished before returning to standard apixaban dosing
• Do not resume full dose if patient still has ritonavir in their system

Ignoring renal function: 3, 1

• Both drugs accumulate in renal impairment
• A patient with CrCl 30 mL/min on apixaban 2.5 mg twice daily may need to hold apixaban entirely during Paxlovid

Overlooking concomitant medications: 1

• Review all medications for additional CYP3A4/P-gp inhibitors (clarithromycin, ketoconazole, dronedarone)
• These create triple interactions and may necessitate holding apixaban

Alternative Anticoagulation Strategies

If dose reduction is not feasible or patient is high bleeding risk: 3

• Consider switching to low molecular weight heparin (enoxaparin) during the 5-day Paxlovid course
• LMWH has no significant interaction with ritonavir 3
• Resume apixaban after Paxlovid completion

For patients with contraindications to dose reduction: 1

• Discuss alternative COVID-19 treatments with infectious disease
• Remdesivir (IV) or molnupiravir (oral) have no significant interactions with apixaban