When is it appropriate to use Paxlovid (nirmatrelvir/ritonavir) and Tamiflu (oseltamivir) together in a patient with suspected or confirmed COVID-19 and influenza co-infection?

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Using Paxlovid and Tamiflu Together in COVID-19 and Influenza Co-infection

When a patient has confirmed or suspected co-infection with both COVID-19 and influenza, administer oseltamivir (Tamiflu) and nirmatrelvir/ritonavir (Paxlovid) concurrently according to standard treatment guidelines for each infection, without modification of either therapy. 1

When to Suspect and Test for Co-infection

  • Test for influenza co-infection using PCR or rapid testing of nasopharyngeal secretions when influenza is clinically suspected in any COVID-19 positive patient, as documented co-infection rates range from 0.5-2% in most studies, though some report up to 4.5% in certain populations. 1, 2

  • The most common symptoms in co-infected patients include fever (85.71%), cough (82.14%), and dyspnea (60.71%), which are indistinguishable from COVID-19 alone. 3

  • Co-infected patients may experience more severe clinical conditions compared to those with COVID-19 alone, making early identification and treatment critical. 3

Treatment Approach

Concurrent Antiviral Therapy

  • For confirmed influenza co-infection, start oseltamivir or baloxavir according to standard influenza treatment guidelines while continuing COVID-19 specific therapies concurrently without dose modification. 1

  • Paxlovid has demonstrated a 39% reduction in hospitalization risk (95% CI 36-41%) and 61% reduction in death risk (95% CI 55-67%) in COVID-19 patients, with particular benefit in those aged 65+ years. 4

  • The combination does not require special dosing adjustments, as oseltamivir does not have clinically significant interactions with nirmatrelvir/ritonavir. 5

Drug Interaction Management

  • Before initiating Paxlovid, review all concurrent medications for potential CYP3A interactions with ritonavir, as this is the most critical safety consideration. 5

  • Out of 190 commonly prescribed drugs, 57 require no special measures with brief, low-dose ritonavir treatment, while 15 require dose modification, 8 can be temporarily discontinued, and 9 contraindicate ritonavir use. 5

  • Empirical antiviral therapy should be rapidly de-escalated based on microbiology test results and clinical response to avoid unnecessary drug exposure. 6

Additional Management Considerations

  • Consider empirical antibiotics if bacterial superinfection cannot be ruled out, as bacterial co-infection occurs in approximately 40% of viral respiratory infections requiring hospitalization. 1

  • Maintain any bispecific antibody or immunosuppressive dosing during influenza treatment if the patient is already on such therapies. 1

  • Follow standard isolation protocols for both infections until clinical resolution. 1

Prevention Strategy

  • Influenza vaccination is strongly recommended for all COVID-19 patients and their close contacts to reduce the risk of co-infection and simplify clinical management. 1

  • This preventive approach is particularly important given that co-infection can lead to more severe disease without necessarily prolonging hospital stay. 3

References

Guideline

Management of Influenza in COVID-19 Positive Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Oral Drugs Against COVID-19.

Deutsches Arzteblatt international, 2022

Guideline

Co-infection with Other Viruses in COVID-19 Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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