Clinical Considerations for Prescribing Oral Antivirals

This is a checklist of eligibility criteria to consider when prescribing molnupiravir (LAGEVRIO) or nirmatrelvir/ritonavir (Paxlovid) for the treatment of acute COVID-19.

The FDA has issued an emergency use authorization (EUA) for molnupiravir and nirmatrelvir/ritonavir for treating people with COVID-19 who meet the following criteria:

• Are within five days of symptom onset.
• Have symptoms consistent with mild to moderate COVID-19.
• Are at risk for progression to severe COVID-19.
• Are not hospitalized due to COVID-19.
• Are age 12 years and older for nirmatrelvir/ritonavir, or 18 years and older for molnupiravir.

Note: On Feb. 1, 2023, FDA removed the requirement for positive direct SARS-CoV-2 viral testing results prior to prescribing Paxlovid or molnupiravir. While FDA continues to recommend testing be performed to help diagnose COVID-19, FDA also recognizes that in rare instances, prescribers may determine that treatment is appropriate for people at higher risk with negative test results and symptoms of COVID-19, for example following exposure to a household contact with COVID-19. Refer to FDA: Frequently Asked Questions on the Emergency Use Authorization for Paxlovid.

Review prior to prescribing nirmatrelvir/ritonavir (Paxlovid)

• Date of symptom onset (therapy must start within five days of symptom onset).
• Patient's risk of progressing to severe COVID-19 (CDC: Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19).
• Dosing adjustment in patients with renal impairment:
  • Mild impairment (eGFR higher than 60, but lower than 90 ml/min): No change.
  • Moderate impairment (eGFR higher than 30, but lower than 60 ml/min): Reduce regular dose to 150 mg of nirmatrelvir (one 150 mg tablet) with 100 mg of ritonavir (one 100 mg tablet), taken together twice daily for five days.
  • Severe impairment (eGFR lower than 30 ml/min): Not recommended.
• Use in patients with hepatic impairment:
  • Mild to moderate impairment: No dose adjustment needed.
  • Severe impairment (Child-Pugh Class C or higher; score calculator at MDCalc: Child-Pugh Score for Cirrhosis Mortality): Not recommended.
• Review the patient's medication regimen (including over-the-counter medications, herbal supplements, and any recreational drugs) for potentially serious drug interactions, as outlined in the FDA: Fact Sheet for Healthcare Providers: Emergency Use Authorization for Paxlovid and NIH COVID-19 Treatment Guidelines: Ritonavir-Boosted Nirmatrelvir (Paxlovid).
  • Drug classes of particular concern are those that include drugs that are prone to concentration-dependent toxicities, including certain antiarrhythmics, oral anticoagulants, immunosuppressants, anticonvulsants, antineoplastics, and neuropsychiatric drugs.
  • Interactions may be checked using the University of Liverpool COVID-19 Drug Interactions interactive webpage.
  • If patient is taking any medication(s) that are contraindicated for co-administration with Paxlovid:
    • Consider specialist review (e.g., HIV provider, transplant provider, specialist pharmacist) for patients receiving highly specialized therapies, such as immunosuppressants or antineoplastics.
    • Strategies for management of the concomitant medication may include dose adjustment, use of an alternative agent, increased monitoring, or temporary withholding. Note: the dose of Paxlovid should not be adjusted to avoid a drug interaction.
    • In settings where using these management strategies is not feasible, or where the effectiveness of ritonavir-boosted nirmatrelvir may be compromised, consider using alternative COVID-19 therapies.
• For patients ages 12-17 years
  • The same eligibility considerations as above, plus:
    • Confirm weight is more than 40 kg (about 88 lbs).
    • For additional considerations of high-risk pediatric conditions, please refer to the NIH Covid Treatment Guidelines: Therapeutic Management of NonHospitalized Children with COVID-19:  Table 3b: Framework for Assessing Risk of Progression to Severe COVID-19.

FDA: Fact Sheet for Health Care Providers: Emergency Use Authorization for Paxlovid

Review prior to prescribing molnupiravir

• Date of birth (must be at least 18 years).
• Date of symptom onset (therapy needs to start within five days of symptom onset).
• Patient is at high risk of progression to severe COVID-19 (CDC: Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19)
• For females of childbearing potential:
  • Assess whether pregnant or not (based on report of last menstrual period in individual with regular menstrual cycles and using reliable contraception correctly and consistently, or based on a negative pregnancy test).
  • If pregnant:
    • Counsel patient regarding known and potential risks and benefits of molnupiravir use during pregnancy and document that patient is aware.
    • Counsel patient on the pregnancy surveillance program and provide patient name and contact information to Merck, if patient agrees (at 877-888-4231 or Report a pregnancy exposure).
  • If not pregnant, recommend using effective contraception during treatment and for four days after the last dose.
  • If breastfeeding, confirm education has been provided that breastfeeding is not recommended during treatment and for four days after the last dose of molnupiravir. Recommend interrupting breastfeeding or pumping and discarding breast milk during treatment and for four days after the last dose of molnupiravir.
• For males:
  • Confirm education has been provided recommending sexually active individuals with partners of childbearing age use a reliable method of contraception correctly and consistently during treatment and for at least three months after the last dose of molnupiravir.

FDA: Fact Sheet for Health Care Providers: Emergency Use Authorization for Molnupiravir

Information to provide when prescribing

When prescribing treatments for acute COVID-19, consider including specific clinical information in the prescription to ensure the dispensing pharmacist is aware of relevant information:

• Date of symptom onset.
• Any renal or hepatic impairment.
• Attestation that appropriate counseling has been performed and any relevant drug interactions have been assessed.

When prescribing nirmatrelvir/ritonavir (Paxlovid), consider providing an up-to-date medication list (including over-the-counter medications) to patients to bring to the dispensing pharmacy.

Reporting of medication errors and serious adverse events

The prescribing health care provider and/or designee must report to Medwatch: The FDA Safety Information and Adverse Event Reporting Program all medication errors and serious adverse events potentially related to these medications. Reports must be filed within seven calendar days from the health care provider's awareness of the event.