Can Paxlovid (nirmatrelvir/ritonavir) and Tamiflu (oseltamivir) be taken together?

Concurrent Use of Paxlovid and Tamiflu

Paxlovid (nirmatrelvir/ritonavir) and Tamiflu (oseltamivir) should not be taken together due to a significant drug interaction that could lead to oseltamivir toxicity.

Mechanism of Interaction

The interaction between Paxlovid and Tamiflu occurs due to:

• Ritonavir (component of Paxlovid) is a potent inhibitor of the renal anionic pathway through which oseltamivir is excreted 1
• This inhibition can reduce oseltamivir clearance by approximately 50% 2
• The reduced clearance results in approximately twofold increase in plasma levels of oseltamivir carboxylate (the active metabolite) 2

Clinical Implications

This interaction has several important clinical consequences:

• Elevated oseltamivir levels may increase the risk of adverse effects including:

  • Nausea and vomiting (already common with oseltamivir, occurring in approximately 10% of adults) 2
  • Potential neuropsychiatric events (self-injury or delirium) that have been reported with oseltamivir 2
  • Other oseltamivir-related toxicities

• The FDA and CDC guidelines note that drugs affecting the renal anionic pathway can significantly impact oseltamivir pharmacokinetics 2

Management Options

If a patient has both COVID-19 and influenza requiring treatment:

1. Prioritize treatment based on severity and risk factors:

   • For high-risk patients with COVID-19, Paxlovid has shown an 89% reduction in hospitalization and death 3
   • For influenza, consider alternative antiviral options if Paxlovid is deemed necessary

2. Alternative influenza treatments if using Paxlovid:

   • Zanamivir (Relenza): Administered by inhalation and has no known significant drug interactions 2
   • Peramivir: Intravenous option for influenza in adults and children 2
   • Baloxavir: Oral option for people ≥12 years 2

3. If oseltamivir must be used with Paxlovid:

   • Consider dose reduction of oseltamivir by approximately 50% 1
   • Monitor closely for signs of oseltamivir toxicity including nausea, vomiting, and neuropsychiatric symptoms 2

Special Considerations

• Renal impairment: The interaction may be more pronounced in patients with kidney disease 4
• Pediatric patients: Limited data exists on this interaction in children, requiring extra caution 2
• Elderly patients: May be at higher risk for adverse effects from this interaction due to age-related changes in drug metabolism and clearance 5

Common Pitfalls to Avoid

1. Overlooking the interaction: Many providers may not be aware of this specific drug interaction
2. Assuming all influenza antivirals interact similarly: Zanamivir has no known significant drug interactions and may be a safer alternative 2
3. Failing to monitor for toxicity: If both medications must be used, close monitoring for oseltamivir adverse effects is essential

The evidence clearly indicates that concurrent use of Paxlovid and Tamiflu should be avoided when possible due to the significant pharmacokinetic interaction that could lead to oseltamivir toxicity.