IDStewardship

Nirmatrelvir/ ritonavir (Paxlovid)

Photo of Paxlovid (nirmatrelvir/ ritonavir), source: Pfizer Pharma

Update in April 2024:

  • This page has been updated to reflect a more recent status of nirmatrelvir/ ritonavir, major updates include:
    • EUA content mostly removed from page
    • Note that NIH has stopped updating their COVID-19 guideline to guide drug selection/evidence
    • EPIC-SR study was recently released and has hampered the enthusiasm for a role of nirmatrelvir/ ritonavir, this post by Dr. Sax does a nice job of detailing ‘the rise and fall of Paxlovid’

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.
  •  Commercial approval for nirmatrelvir/ritonavir came in May 2023 for COVID-19
  • “At risk” is a very broad designation and the CDC website is a reference for determining risk
  • Studied in the EPIC-HR study, published in 2022, which concluded: “Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns.”
  • Studied in the EPIC-SR study, published in 2024, which concluded: “The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir–ritonavir and those who received placebo.”
  • Dosing depends on renal function, requires adjustment for eGFR below 60 mL/min
    • 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 for adults with normal renal functionDoses should not be chewed, broken, or crushedNot authorized for more than 5 days duration & must initiate within 5 days of symptom onset
    • Dosing packs shown above are for the renal and non-renal products
    • 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
    • Bad taste or dysgeusia has been very common and may be quite bothersome

RESOURCES

 

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