Clarify the Role of Antivirals for Outpatient Flu and COVID-19 Treatment

We’re getting questions about how to treat COVID-19 and influenza.

Don’t feel compelled to recommend an antiviral for COVID-19 or flu in most healthy patients. Advise fluids, rest, etc.

But know when to consider treating COVID-19 or flu with antivirals.

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COVID-19. Advise treatment for patients at high risk of developing severe COVID-19 (diabetes, obesity, etc)...even if symptoms are mild.

Point out risk of death increases with age...starting at around 50 and jumping again at 65. These patients see the most benefit from meds.

Recommend oral nirmatrelvir/ritonavir (Paxlovid) for most at-risk outpatients age 12 and up...within 5 days of symptom onset.

Explain that nirmatrelvir/ritonavir still seems effective at preventing hospitalization and death...even with circulating variants.

Expect to see no-cost, EUA-labeled nirmatrelvir/ritonavir starting to be phased out at the end of 2023...with the price tag of nearly $1,400/course shifting to payers.

Watch for nirmatrelvir/ritonavir interactions...most can be managed. Bookmark an interaction checker, such as

And keep in mind these top meds to avoid...salmeterol (Advair, etc), rivaroxaban (Xarelto), and strong CYP3A4 inducers (phenytoin, etc).

Save remdesivir (Veklury) for patients who can’t take nirmatrelvir/ritonavir. Remdesivir is for adults and kids down to 28 days old, but it’s a daily infusion for 3 days and often isn’t practical.

Reserve oral molnupiravir (Lagevrio) as a last resort. It’s less effective than other options...and only for patients age 18 and up.

Influenza. Stick with oseltamivir (Tamiflu) for most high-risk outpatients (immunocompromised, pregnant, etc)...severely ill patients (pneumonia, asthma or COPD exacerbation, etc)...and hospitalized patients. Evidence is lacking with baloxavir (Xofluza) in these situations.

But consider oseltamivir OR baloxavir for NONsevere flu in other outpatients with risks (diabetes, heart disease, etc). Data suggest that baloxavir works as well as oseltamivir in these cases.

Educate that oseltamivir or baloxavir only reduces flu symptoms by about a day...if started within 48 hours of symptom onset.

And patients at high risk of complications (age over 65, diabetes, etc) are most likely to benefit from a flu antiviral.

Point out that baloxavir is one dose...and causes less GI upset than oseltamivir. But baloxavir costs about $150/dose...oseltamivir caps cost about $40 for 5 days.

Clarify that flu antivirals aren’t effective against SARS-CoV-2...and vice versa...even though many flu and COVID-19 symptoms overlap.

It’s okay to combine antivirals to treat both COVID-19 and flu.

Continue to emphasize flu and COVID-19 vaccination, handwashing, staying home if sick, etc.

Compare other antivirals (zanamivir, etc) for flu treatment and prevention in our resource, Antivirals for Influenza. Use our algorithm, Outpatient COVID-19 Treatment Options, to help recommend a med.

Key References

  • CDC. Interim Clinical Considerations for COVID-19 Treatment in Outpatients. October 4, 2023. (Accessed October 13, 2023.)
  • NIH. COVID-19 Treatment Guidelines. Clinical Management of Adults. October 10, 2023. (Accessed October 16, 2023.)
  • CDC. Influenza Antiviral Medications:  Summary for Clinicians. September 27, 2023. (Accessed October 2, 2023.)
  • Medication pricing by Elsevier, accessed Oct 2023.
Pharmacist's Letter. November 2023, No. 391103


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