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Paxlovid (nirmatrelvir/ ritonavir)

Photo of Paxlovid (nirmatrelvir/ ritonavir)

Background photo source: Pfizer

Last updated 22 December 2021. Information on this topic is rapidly changing and may render the following incomplete or inaccurate. 

KEY POINTS

  • Nirmatrelvir (PF-07321332) plus ritonavir (Norvir, RTV) is a combination therapy that has a brand name of Paxlovid. It is a SARS-CoV-2 protease inhibitor antiviral medication. The lay public refer to it as “the Pfizer COVID pill”.
    • Nirmatrelvir blocks the activity of the SARS-CoV-2-3CL protease, an enzyme that the coronavirus needs to replicate
    • Mechanism of action occurs during viral replication stage of proteolysis
    • Cross-resistance is not expected between nirmatrelvir and anti-SARS-CoV-2 monoclonal antibodies or remdesivir based on their different mechanisms of action
    • Ritonavir (Norvir, RTV) acts as a “booster” to increase nirmatrelvir drug levels, it slows the metabolism of nirmatrelvir so higher drug levels of nirmatrelvir can be achieved
  • Nirmatrelvir/ritonavir was given an FDA Emergency Use Authorization on 22 December 2021 for adults and children (age 12 years and older weighing at least 40 kg) with mild to moderate COVID-19 symptoms and who are at high risk for progression to severe COVID-19.
    • “At risk” is a very broad designation and the CDC website is a reference for determining risk
    • Not authorized for use as pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP)
    • Not authorized to initiate in hospitalized patients with severe or critical COVID-19
      • Can be continued if admitted during course of therapy and prescriber feels is warranted
    • Is authorized for the treatment of patients hospitalized with mild-to-moderate COVID-19, such as patients admitted for monitoring of drug-drug interactions
    • Is authorized for patients hospitalized for conditions other than COVID-19, provided the terms of the authorization are otherwise met
    • Serious adverse effects (e.g., hospitalization, death) are required to be reported to FDA MedWatch
    • Must provide patient with Patient Fact Sheet (can give electronically)
  • Information on national allocation of Paxlovid can be found here
    • “An initial 65,000 courses of Paxlovid will be made available for shipment to states and territories and will begin arriving at dispensing sites during the first week of January.”
  • Studied in the EPIC-HR study (treatment of early COVID disease, including breakthrough infections in vaccinated persons) and EPIC-PEP study (post-exposure prophylaxis after exposure to SARS-CoV-2 by a household member)
  • The approved dose is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg of ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days
    • Doses should not be chewed, broken, or crushed
    • Not authorized for more than 5 days duration & must initiate within 5 days of symptom onset
    • Requires dose adjustment for eGFR 30 to less than 60 mL/min, avoid if eGFR is below 30 mL/min
    • Not recommended in patients with severe hepatic impairment
    • Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card. Each carton contains 30 tablets divided in 5 daily-dose blister cards. Each daily blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each) and indicates which tablets need to be taken in the morning and evening.
    • Should be stored at room temperature
  • Ritonavir has many drug-drug and drug-herbal interactions of clinical importance which may limit capacity to use nirmatrelvir/ritonavir
  • Warnings include: hepatotoxicity and HIV-1 resistance
  • Potential side effects include: dysgeusia, diarrhea, hypertension, and myalgia
  • Pfizer reports that in preclinical studies nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions
  • Expected that the cost of Paxlovid to the Federal Government will be about $700 per course (similar to molnupiravir from Merck)

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