Can Paxlovid and Oseltamivir Be Taken Together?
Yes, Paxlovid (nirmatrelvir/ritonavir) and oseltamivir (Tamiflu) can be safely co-administered without dose adjustments, as they have distinct metabolic pathways that do not interact. 1
Pharmacokinetic Basis for Safety
The safety of this combination is rooted in their completely separate metabolic profiles:
Oseltamivir is metabolized by hepatic esterases (not CYP3A4) and approximately 80% is excreted renally via glomerular filtration and tubular secretion through the anionic pathway. 1 This means ritonavir's potent CYP3A4 inhibition—which causes numerous dangerous drug interactions with Paxlovid—does not affect oseltamivir metabolism. 2, 3
Oseltamivir is not a substrate, inhibitor, or inducer of P-glycoprotein, eliminating another potential interaction pathway with Paxlovid. 1 This is critical because nirmatrelvir functions as both a substrate and inhibitor of P-gp transporter protein. 2
The CDC confirms oseltamivir has minimal drug interaction risk overall, with the only documented clinically significant interaction being probenecid (not Paxlovid). 4, 1 Probenecid reduces oseltamivir carboxylate clearance by approximately 50% through competition for renal tubular secretion. 4, 1
Guideline Recommendations
The Advisory Committee on Immunization Practices (ACIP) and American College of Physicians identify no contraindications to combination use of influenza antiviral drugs with Paxlovid. 1 While they note no published data exist on safety or efficacy of this specific combination, the pharmacokinetic rationale strongly supports safety.
The Infectious Diseases Society of America states neither Paxlovid nor Tamiflu requires dose modification when used together. 1
Clinical Management Considerations
When co-administering these medications, monitor the following:
Renal function monitoring is necessary for both drugs. 1 For oseltamivir, reduce the dose to 75 mg once daily if creatinine clearance is 10-30 mL/min. 5, 1
Administer oseltamivir with food to minimize gastrointestinal side effects (nausea, vomiting), which are the most common adverse events. 4, 1 This does not affect absorption.
Initiate oseltamivir within 48 hours of influenza symptom onset for maximum benefit. 4, 1
Important Caveats
While this combination is safe from a drug-drug interaction standpoint, be vigilant about Paxlovid's extensive interactions with other medications the patient may be taking:
Ritonavir strongly inhibits CYP3A4 and P-gp, creating dangerous interactions with anticoagulants (warfarin, rivaroxaban), calcium channel blockers, statins, immunosuppressants (tacrolimus), antiarrhythmics, and antipsychotics. 2, 6 Review the patient's complete medication list before prescribing Paxlovid.
Consult package inserts for the most detailed drug interaction information for both medications. 4