Managing Eliquis (Apixaban) During Paxlovid Treatment
Temporarily switch to low molecular weight heparin (LMWH) for the 5-day Paxlovid course, or if continuing apixaban is necessary, reduce the dose by 25% during treatment. 1
Understanding the Drug Interaction
The ritonavir component of Paxlovid is a potent CYP3A4 and P-glycoprotein inhibitor, and since apixaban is metabolized through both of these pathways, co-administration significantly increases apixaban blood levels and bleeding risk. 1, 2 This interaction occurs rapidly due to ritonavir's mechanism and persists throughout the treatment course. 2
Primary Management Strategy: Switch to LMWH (Preferred)
The safest approach is switching to LMWH during the 5-day Paxlovid treatment course, which eliminates the drug interaction entirely and provides reliable anticoagulation without dose adjustment concerns. 1
- Resume apixaban 2-3 days after completing Paxlovid to allow ritonavir's inhibitory effects to dissipate. 1
- This strategy is particularly important for high-risk patients (see below). 1
Alternative Strategy: Dose Reduction of Apixaban
If switching to LMWH is not feasible, reduce apixaban by 25% during the 5-day Paxlovid course. 1
- For patients on apixaban 5 mg twice daily: reduce to 3.75 mg twice daily (or consider 2.5 mg twice daily for maximum safety)
- For patients on apixaban 2.5 mg twice daily: this already-reduced dose presents higher risk; strongly consider LMWH switch instead
- Important caveat: Dose reduction mitigates but does not eliminate the interaction risk. 1
Safest DOAC Alternative: Edoxaban
If switching DOACs is preferred over LMWH, edoxaban represents the safest DOAC option with Paxlovid, demonstrating minimal clinically significant interactions and never requiring dose adjustment with ritonavir-containing regimens. 1
High-Risk Patients Requiring Extra Caution
Exercise particular caution and strongly favor LMWH switching in: 1
- Patients >75 years of age 1
- Those with concurrent antiplatelet therapy 1
- Patients with renal impairment (apixaban levels further affected) 2, 3
- Those with additional bleeding risk factors 1
Monitoring Requirements
Monitor closely for bleeding signs throughout the 5-day Paxlovid course and for 2-3 days after completion: 1
- Unusual bruising or bleeding 1
- Blood in urine or stool 1
- Prolonged bleeding from cuts 1
- Severe headache or dizziness 1
- Coughing up blood or coffee-ground emesis 1
Critical Pitfalls to Avoid
Do not simply continue apixaban at the same dose without intervention—the interaction is clinically significant and documented to cause toxicity with ritonavir-boosted regimens. 2, 3 The short 5-day course does not eliminate risk, as ritonavir causes potent and rapid CYP3A4 inhibition. 2 Multiple case reports and studies have confirmed enhanced toxicity risk of anticoagulants with concurrent paxlovid administration. 3