Outpatient COVID-19 Treatment Options

Full update March 2023

Use this algorithm to help identify the most appropriate outpatient COVID-19 treatment. To qualify, patients generally MUST be ≥12 years old AND weigh ≥88 pounds (40 kg), but exceptions are noted below.^3,4-9

Identify patients who qualify for outpatient COVID-19 treatment.

1. Has the patient been tested for COVID-19?
   •   If YES, and test is positive, continue to the next question.
   •   If no, encourage testing to ensure appropriate use of available treatment options. (Canadian product labeling requires positive result for outpatient COVID-19 treatments).^7,8
2. Does the patient have COVID-19 symptoms that started 7 days ago or less (note some products may only allow for use within 5 days of symptom onset)?^3,4,7-9
   •   If YES, continue to the next question.
   •   If no, the patient does not qualify for outpatient treatment of COVID-19.
3. Is the patient considered high risk of progression to severe disease, hospitalization, or death (e.g., immunocompromised, comorbidities [diabetes, heart disease, lung disease])? For conditions that may increase risk go to https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html (US). In Canada, a scoring system to estimate hospitalization risk is available at http://www.bccdc.ca/Health-Professionals-Site/Documents/COVID-treatment/ClinicalPracticeGuide_Therapeutics_MildModerateCOVID.pdf (Canada).
   •   If YES, continue to the next section to determine the most appropriate treatment.
   •   If no, the patient does not qualify for outpatient treatment of COVID-19.

Determine the most appropriate treatment (presented in order of preference per NIH guidelines) (In Canada, refer to your jurisdiction’s guidelines for management of COVID-19.^10,11 British Columbia COVID Therapeutics Committee guidance is available at http://www.bccdc.ca/Health-Professionals-Site/Documents/COVID-treatment/ClinicalPracticeGuide_Therapeutics_MildModerateCOVID.pdf). If one treatment is deemed inappropriate, continue down to the next treatment option.^1,2

•    Paxlovid (nirmatrelvir co-packaged with ritonavir)^3,7 (authorized for ≥18 years old [Canada]⁷)
  1. Has the patient had COVID-19 symptoms for 5 days or less?
     •   If YES, continue to the next question.
     •   If no, the patient does not qualify for Paxlovid.
  2. Are the patient’s concomitant medications safe to use with Paxlovid? Screen for drug interactions. Paxlovid is contraindicated with certain medications, examples include amiodarone, clopidogrel, lurasidone, phenytoin, simvastatin. Consider using the Liverpool COVID-19 Drug Interactions website: https://www.covid19-druginteractions.org/ or referring to Paxlovid authorization documents to screen for drug interactions.
     •   If YES, continue to the next question.
     •   If no, the patient does not qualify for Paxlovid unless contraindicated meds can be temporarily held (e.g., simvastatin). If contraindicated meds can be held, continue to the next question.
  3. Is the patient’s liver function appropriate for treatment with Paxlovid (i.e., normal liver function, Child Pugh Class A or B)?
     •   If YES, continue to the next question.
     •   If no, the patient does not qualify for Paxlovid (i.e., not recommended in Child Pugh Class C).^3,7
  4. Is the patient’s eGFR ≥30 mL/min/1.73m²?
     •   If YES, the patient qualifies for Paxlovid, continue to the next question for dosing.
     •   If no, the patient does not qualify for Paxlovid (i.e., not recommended if GFR <30 mL/min/1.73m²).^3,7
  5. Is the patient’s eGFR ≥60 mL/min/1.73m²?
  •   If YES, , the recommended dose is nirmatrelvir 300 mg (two 150 mg tablets) and ritonavir 100 mg PO (taken together) every 12 hours for 5 days.
  •   If no (i.e., eGFR is ≥30 and <60 mL/min/1.73m2), the recommended dose is nirmatrelvir 150 mg (one tablet) and ritonavir 100 mg PO (taken together) every 12 hours for 5 days. If the special dose pack for moderate kidney impairment is not available, see dispensing instructions at https://www.fda.gov/media/155072/download (US) or https://recalls-rappels.canada.ca/en/alert-recall/paxlovid-nirmatrelvir-and-ritonavir-dosing-and-dispensing-renal-impairment-risk (Canada).
•    Veklury (remdesivir)^8,9
  1. Has the patient had symptoms for 7 days or less?
     •   If YES, continue to the next question.
     •   If no, the patient does not qualify for remdesivir.
  2. Can logistical issues be addressed to allow for administration of remdesivir? (Requires three consecutive days of infusions and administration in an area capable of monitoring for and treating possible hypersensitivity reactions.)
     •   If YES, patients who weigh ≥40 kg (and, in Canada, are ≥12 years old) qualify for remdesivir 200 mg IV on day one, followed by remdesivir 100 mg IV on days two and three. In the US only, patients who are ≥28 days old and who weigh 3 kg to <40 kg qualify for remdesivir 5 mg/kg IV on day one, followed by remdesivir 2.5 mg/kg/dose IV on days two and three.
     •   If no, the patient does not qualify for remdesivir.
•   Lagevrio (molnupiravir)⁴ (US only [Note: ONLY authorized for patients ≥18 years old])
  1. Are all other outpatient COVID-19 treatment options UNAVAILABLE or NOT appropriate?
     •   If YES, continue to the next question.
     •   If no, the patient does not qualify for molnupiravir.
  2. Has the patient had symptoms for 5 days or less?
     •   If YES, continue to the next question.
     •   If no, the patient does not qualify for molnupiravir.
  3. Is the patient pregnant? (A pregnancy test is recommended if the patient has irregular menstrual cycles, is unsure of the first day of their last cycle, or is not using reliable contraception correctly.)
     •   If NO, the patient qualifies for molnupiravir 800 mg (four 200 mg capsules) PO bid for 5 days.
     •   If yes, the patient does not generally qualify for molnupiravir. Pregnant people may choose to try molnupiravir after a documented, informed discussion with the prescriber. (Note: there is a molnupiravir pregnancy surveillance program.)
  4. Is the patient breastfeeding?
     •   If YES, the patient should avoid breastfeeding during molnupiravir therapy and for 4 days after the last dose. Continue to next question.
     •   If no, continue to the next question.
  5. Is the patient of childbearing potential or sexually active with someone of childbearing potential?
     •   If YES, counsel patients as appropriate:
       •   for female patients with child-bearing potential: advise that reliable contraception is recommended during treatment and for 4 days after the last dose of molnupiravir.
       •   for male patients with partner of child-bearing potential: advise to use a reliable method of contraception during and for 3 months after the last dose of molnupiravir.
•   COVID-19 specific “MAbs” (CANADA only [No “MAbs” are currently authorized for COVID-19 TREATMENT in the US.])⁶
  1. Are all COVID-19 antivirals options unavailable or NOT appropriate?
     •   If yes, contact your local health authority for guidance; current COVID-19 strains are highly resistant, and benefit may not outweigh risk. Also see our algorithm, “MAbs” for COVID-19: Patient Assessment.
     •   If no, use appropriate antiviral.

Suggested resources to assess local COVID-19 treatment availability in the US

•   Product availability can be found at https://covid-19-therapeutics-locator-dhhs.hub.arcgis.com/.
•    Check with your local health department or local pharmacies.

US oral antiviral reimbursement information

•   When submitting prescription claims, use Professional Service Code (440-E5) value of “PE” for patient education to account for the unique dispensing requirements associated with COVID-19 oral antivirals.⁵
•   Follow pharmacy policy on the incentive value to submit for the “PE” professional service code.⁵
•   National Community Pharmacy Association has guidance for dispensing and reimbursement at https://ncpa.org/sites/default/files/2022-01/COVID-19_antivirals_billing_for_NCPA_members.pdf.⁵

Abbreviations: bid = twice daily; eGFR = estimated glomerular filtration rate; IV = intravenously; “MAb” = monoclonal antibody; PO = orally.

References

1. National Institutes of Health. Table 2a. Therapeutic management of nonhospitalized adults with mild to moderate COVID-19 who do not require supplemental oxygen. Updated December 28, 2022. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-adults/clinical-management-of-adults-summary/?utm_source=site&utm_medium=home&utm_campaign=highlights. (Accessed February 7, 2023).
2. National Institutes of Health. Table 3a. Therapeutic management of nonhospitalized children with COVID-19. December 28, 2022. https://www.covid19treatmentguidelines.nih.gov/tables/therapeutic-management-of-nonhospitalised-children/. (Accessed February 7, 2023).
3. FDA. Fact sheet for healthcare providers: emergency use authorization for Paxlovid. February 2023. https://www.fda.gov/media/155050/download. (Accessed February 7, 2023).
4. FDA. Fact sheet for healthcare providers: emergency use authorization for Lagevrio (molnupiravir) capsules. February 2023. https://www.fda.gov/media/155054/download. (Accessed February 7, 2023).
5. National Community Pharmacy Association. COVID-19 antivirals dispensing and reimbursement. April 15, 2022. https://ncpa.org/sites/default/files/2022-01/COVID-19_antivirals_billing_for_NCPA_members.pdf. (Accessed February 7, 2023).
6. British Columbia Centre for Disease Control. Clinical practice guide for the use of therapeutics in mild-moderate COVID-19. January 10, 2023. http://www.bccdc.ca/Health-Professionals-Site/Documents/COVID-treatment/ClinicalPracticeGuide_Therapeutics_MildModerateCOVID.pdf. (Accessed February 8, 2023).
7. Product monograph for Paxlovid. Pfizer Canada. Kirkland, QC H9J 2M5. December 2022.
8. Product monograph for Veklury. Gilead Sciences Canada. Mississauga, ON L5N 2W3. April 2022.
9. Product information for Veklury. Gilead Sciences. Foster City, CA 94404. December 2022.
10. NIH. Therapeutic management of nonhospitalized adults with COVID-19. December 28, 2022. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/nonhospitalized-adults--therapeutic-management/. (Accessed February 15, 2023).
11. Government of Canada. Considerations for the use of nirmatrelvir/ritonavir (brand name Paxlovid) to treat COVID-19. June 22, 2022. https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/guidance-documents/considerations-nirmatrelvir-ritonavir-paxlovid.html. (Accessed February 7, 2023).

Cite this document as follows: Clinical Resource, Outpatient COVID-19 Treatment Options. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber’s Letter. March 2023. [390307]

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