Paxlovid and Naproxen: Safety Assessment
Yes, it is safe to take Paxlovid (nirmatrelvir/ritonavir) and naproxen together—there is no clinically significant drug-drug interaction between these medications. 1, 2
Mechanism and Interaction Profile
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that does not rely on CYP3A4 metabolism or P-glycoprotein transport for its elimination, which are the primary pathways affected by ritonavir in Paxlovid 2, 3. The drug-drug interaction concerns with Paxlovid specifically involve:
- CYP3A4 substrates with narrow therapeutic indices (such as immunosuppressants, certain statins, calcium channel blockers, and anticoagulants) 4, 2, 3
- P-glycoprotein substrates that can accumulate to toxic levels when this transporter is inhibited 2, 3
Naproxen does not fall into either of these high-risk categories 1.
Clinical Considerations
No dose adjustment of naproxen is required when co-administered with Paxlovid, and patients can continue their usual NSAID regimen without interruption 1. This is in stark contrast to medications like:
- Tacrolimus (requires discontinuation or microdosing) 4
- Apixaban/rivaroxaban (may require dose reduction or switching to alternative anticoagulation) 5
- Atorvastatin (increased toxicity risk requiring dose adjustment) 2
Practical Management
Continue naproxen at the standard prescribed dose throughout the 5-day Paxlovid treatment course 1. Monitor for standard NSAID-related adverse effects (gastrointestinal symptoms, renal function changes) as you would in any patient, but these are not amplified by the Paxlovid interaction 1.
Focus your drug interaction screening on high-risk medications that patients may be taking concurrently, particularly those metabolized by CYP3A4 or transported by P-glycoprotein, as these represent the true interaction concerns with ritonavir-containing regimens 2, 3.
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