What is the recommended dosing of Eliquis (apixaban) when used with Paxlovid (nirmatrelvir and ritonavir)?

Eliquis Dosing with Paxlovid

Reduce Eliquis (apixaban) dose to 2.5 mg twice daily during the 5-day course of Paxlovid (nirmatrelvir/ritonavir), then resume the original dose after completing Paxlovid treatment. 1

Mechanism of Interaction

• Ritonavir is a potent CYP3A4 inhibitor that significantly increases apixaban plasma concentrations, as CYP3A4 is a major metabolic pathway for apixaban 2
• The ritonavir component causes drug-drug interactions during active treatment and for several days after completion 2
• Elevated apixaban exposure increases bleeding risk without providing additional therapeutic benefit 1

Specific Dosing Algorithm

During Paxlovid Treatment (Days 1-5):

• Reduce standard apixaban dose from 5 mg twice daily to 2.5 mg twice daily 1
• If patient is already on reduced-dose apixaban 2.5 mg twice daily, consider holding apixaban during the 5-day Paxlovid course and monitoring closely for thromboembolic risk 1
• Maintain the twice-daily dosing schedule approximately 12 hours apart 3

After Paxlovid Completion:

• Resume original apixaban dose on day 4 after discontinuing Paxlovid, as rivaroxaban modeling shows enzyme activity recovery by this timepoint 1
• Apixaban likely follows similar recovery kinetics given shared CYP3A4 metabolism 1

Critical Monitoring Parameters

• Watch for bleeding signs including unusual bruising, petechiae, gastrointestinal bleeding, hematuria, prolonged bleeding from minor cuts, and intracranial hemorrhage symptoms 3
• Monitor renal function during treatment, as COVID-19 itself can cause acute kidney injury, which would further increase apixaban levels 4
• Assess for dysgeusia and diarrhea, which are common Paxlovid adverse effects that do not require discontinuation 2, 4

Special Population Considerations

Renal Impairment:

• If creatinine clearance is 30-59 mL/min, reduce Paxlovid dose to 150 mg/100 mg nirmatrelvir/ritonavir twice daily 2, 4
• Apixaban dose reduction may need further adjustment based on renal function independent of the drug interaction 3
• Reassess renal function if clinical deterioration occurs during treatment 4

Hepatic Impairment:

• Use Paxlovid with caution in severe liver impairment, as trials excluded these patients 2, 4

Common Pitfalls to Avoid

• Do not add antiplatelet agents (especially aspirin) during this period unless absolutely necessary for acute vascular disease, as this compounds bleeding risk 5, 3
• Do not forget to resume original apixaban dose after Paxlovid completion, as subtherapeutic anticoagulation increases stroke risk 1
• Do not use the Liverpool COVID-19 Drug Interaction Tool as optional—this is explicitly recommended in WHO guidelines for systematic interaction checking 2, 4
• Do not delay Paxlovid initiation due to anticoagulation concerns; the interaction is manageable with dose adjustment, and Paxlovid must be started within 5 days of symptom onset for effectiveness 2, 4

Evidence Quality Note

The dose reduction recommendation is based on PBPK modeling rather than clinical trials, as prospective DDI studies with apixaban and Paxlovid have not been conducted 1. However, the modeling approach is validated and widely accepted for predicting CYP3A4-mediated interactions 1. The ritonavir interaction profile is well-established from decades of HIV treatment experience 2.