Nirmatrelvir and ritonavir, marketed as Paxlovid by Pfizer, are antiviral drugs that inhibit a protease vital to the viral replication of SARS-CoV-2. Paxlovid was FDA-approved based on the EPIC-HR trial, conducted during the Delta variant’s dominance. Patients taking nirmatrelvir-ritonavir had a significantly lower risk of progression to severe Covid-19 or death (5.8% absolute risk reduction; 89% relative risk reduction). All enrolled patients were unvaccinated and considered high risk for progression to severe disease (with one or more risk factors including overweight, smoking, hypertension, etc).
Like many other drugs, Paxlovid has been used off-label beyond its original proven benefits, in the hopes that it might work for lower-risk patients.
However, randomized and observational studies have not shown nirmatrelvir-ritonavir to benefit people of average risk with Covid-19 in the Omicron era:
Concurrent to EPIC-HR was the less well-known EPIC-SR (for “standard risk”) trial, which Pfiz…
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