Clarify the Role of Paxlovid or Molnupiravir for COVID-19

New oral antivirals will raise questions about treating COVID-19.

Recommend Paxlovid (nirmatrelvir/ritonavir) first-line for most outpatients with mild to moderate COVID-19, since it seems more effective...and molnupiravir when other options aren't available.

Eligibility. Educate that these meds are for patients with a positive COVID-19 test who are at high risk of developing severe illness (age 65 or older, diabetes, etc)...regardless of vaccination status.

Paxlovid is for age 12 and up...molnupiravir is for 18 and up.

While supply is tight, be familiar with local criteria...such as limiting use to immunocompromised or the highest-risk unvaccinated patients. To help find stock, use the govt COVID-19 Therapeutics Locator.

Emphasize starting within 5 days of symptoms. Explain either med is bid for 5 days...and patients don't currently have to pay for them.

Reinforce that neither oral antiviral is for postexposure prophylaxis yet...or to have on hand "just in case."

Efficacy. Early evidence suggests Paxlovid prevents hospitalization or death in about 1 in 18 high-risk unvaccinated adults with mild to moderate COVID-19.

Molnupiravir prevents hospitalization in about 1 in 35.

Keep other treatments in mind too. Paxlovid's efficacy seems similar to a single infusion of the monoclonal antibody sotrovimab...or IV remdesivir, which is now a 3-day outpatient option.

Considerations. Watch for a laundry list of drug interactions with Paxlovid...since it contains the strong CYP3A4 inhibitor ritonavir.

For example, avoid Paxlovid with phenytoin...and advise holding some statins. But continue other ritonavir-containing meds.

Stay alert for a lower Paxlovid dose in patients with an eGFR of 30 to 59 mL/min/1.73 m2. They should get just ONE nirmatrelvir tab bid, instead of 2 tabs bid...but the ritonavir dose won't change.

In this case, discard one AM and PM tab of nirmatrelvir from all 5 blister cards...and cover empty blisters with the manufacturer stickers.

Generally avoid molnupiravir during pregnancy.

If a patient with reproductive potential needs molnupiravir, counsel to use reliable contraception during use and for 4 days afterward in women...and at least 3 MONTHS afterward in men.

Get our algorithm, Outpatient COVID-19 Treatment Options, for step-by-step eligibility...and more dosing specifics and precautions.

Key References

  • https://www.fda.gov/media/155050/download (1-26-22)
  • N Engl J Med. 2021 Dec 16. doi: 10.1056/NEJMoa2116044
  • https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-high-risk-nonhospitalized-patients/ (1-26-22)
  • https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-patient-prioritization-for-outpatient-therapies/ (1-26-22)
  • https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-paxlovid-drug-drug-interactions/ (1-26-22)
Pharmacist's Letter. February 2022, No. 380201



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