COVID-19 Oral Antivirals

COVID-19 Oral Antivirals

Reuben Strayer

• The FDA has granted emergency use authorization (EUA) to two new oral antiviral medications targeting SARS-CoV2: Paxlovid (Pfizer) and molnupiravir (Merck).
• Paxlovidcontains both nirmatrelvir (protease inhibitor) and ritonavir (pharmacokinetic booster).
  • A Pfizer press release touts an 88% relative reduction in hospitalization.
  • Data not yet published.
  • Approved for patients > 12 and at least 40 kg.
  • Treatment consists of 2 x 150 mg nirmatrelvir tabs + 1 x 100 mg ritonavir tablets (eg, 3 pills total) given twice daily for 5 days
  • Contraindications
    • Hypersensitivity to either component.
    • Severe renal/hepatic impairment.
    • Ritonavir is a strong P450 enzyme inhibitor (required to increase nirmatrelvir concentrations).

PITFALLS

• • • There are many medications (at least 28) that are contraindicated with Paxlovid therapy including simvastatin, sildenafil and phenytoin.
    • Even more medications include warnings for use with Paxlovid, including warfarin and rivaroxaban, methadone, and a variety of immunomodulators.
• Molnupiraviris a ribonucleoside prodrug.
  • Molnupiravir has demonstrated a 30% relative reduction in hospitalization.
    • Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients | NEJM
  • Approved for patients > 18 years
  • Treatment consists of 4 x 200mg molunpiravir tabs (eg, 800 mg) twice daily for 5 days.

PITFALLS

• • Molnupiravir appears to be a teratogen
    • Avoid in pregnancy.
    • Breastfeeding is not recommended until 4 days after conclusion of course.
    • Men are advised not to cause pregnancy for 3 months after use.
• Both agents appear to be well tolerated.
  • The most common adverse effects are GI upset, malaise, and dizziness, which overlap with the symptoms of COVID.
• Who should get these drugs?
  • Not accounting for scarcity or contraindications, the EUA approval indications are relatively broad:
    • Positive test for SARS-CoV-2
    • Symptomatic for 5 days or fewer
    • High risk for progression to severe disease
    • Does not require hospitalization

PERSPECTIVES

• • The goal is to avoid treating people who would do well regardless, and catch high risk patients in the viral replication phase of their illness, which presumably is when the drugs are effective, prior to the need for hospitalization.
  • Who is at high risk of progression?  The CDC maintains a list of high risk conditions that predispose to severe illness from COVID. It is relatively broad and includes cancer, disease of any major organ (heart, lung, liver, kidney, brain), diabetes, mood disorders like depression, high BMI, pregnancy, smoking or other substance use.
• Priority Recommendations
  • Because these medications are currently scarce, New York State, for example, suggests reserving Paxlovid for patients who are moderately to severely immunocompromised, or, those that are unvaccinated, over 65, with at least 1 additional risk factor for severe illness. 
• The latest NIH guidelines recommend these therapies in order of preference: Paxlovid, sotrovimab, remdesivir, and finally molnupiravir.