Compare COVID-19 Oral Antivirals

You'll be asked about the new COVID-19 oral antivirals nirmatrelvir/ritonavir (Paxlovid) and molnupiravir.

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

Nirmatrelvir/ritonavir is for age 12 and up...molnupiravir is for 18 and up. Either is started within 5 days of symptoms...and used bid for 5 days. Patients don't currently have to pay for them.

Advise using the COVID-19 Therapeutics Locator to help find stock.

If a patient is admitted while taking these meds, it's okay to complete the course. But it's too soon to say if continuing improves outcomes...and you'll likely need to use the patient's home supply.

Efficacy. Early evidence suggests that nirmatrelvir/ritonavir prevents hospitalization in about 1 in 18 high-risk unvaccinated adults with mild to moderate COVID-19.

This is similar to the efficacy of the monoclonal antibody sotrovimab or a 3-day course of outpatient IV remdesivir.

Molnupiravir prevents hospitalization in about 1 in 35.

Recommend nirmatrelvir/ritonavir first. If it's not available, go to sotrovimab...or remdesivir if needed. Save molnupiravir for when others aren't an option.

Considerations. Assess nirmatrelvir/ritonavir interactions before continuing it in-house...since ritonavir is a strong CYP3A4 inhibitor. For example, stop it if you are starting amiodarone.

Also stop nirmatrelvir/ritonavir for patients with an eGFR under 30 mL/min/1.73 m2...and reduce doses for eGFR 30 to 59 mL/min/1.73 m2.

Generally discontinue molnupiravir for a positive pregnancy test.

If a patient with reproductive potential needs molnupiravir, educate 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 (2-1-22)
  • 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/ (2-1-22)
  • https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-paxlovid-drug-drug-interactions/ (2-1-22)
Hospital Pharmacist's Letter. February 2022, No. 380201



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