What is ‘Paxlovid Rebound,’ and Should It Concern Us?

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There's been a lot of news, some of it fear-mongering, about Pfizer's Covid drug Paxlovid. Some people are having their symptoms return after completing the five-day course. Does that mean there is something wrong with the drug, or it's simply a property of the virus? Drs. Henry Miller and Josh Bloom try to provide an answer in Issues & Insights.

Decades ago, a case report (relating the experience with a single patient) was published, which described how a person’s flu symptoms improved after a bowl of chicken soup, but then reappeared. The article was meant as a kind of parody of the old maxim that chicken soup is the best cure for a cold. Pediatricians occasionally see a similar phenomenon when children are treated with an antibiotic for an ear infection; they may then have to prescribe another course of the drug. We’re seeing a similar phenomenon with Paxlovid, an oral two-drug combination regimen that treats COVID-19. One drug is nirmatrelvir, an antiviral, while the second, ritonavir, inhibits the metabolism of the nirmatrelvir, maintaining therapeutic levels.

Although not perfect, Paxlovid is a breakthrough, with efficacy of over 90% in treating mild-to-moderate COVID-19 and preventing hospitalization and death. One drawback, however, is that the ritonavir also affects the metabolism of many other drugs, including anticoagulants, anticonvulsants, antiarrhythmics, anti-hypertensives, and lipid-lowering drugs, which can turn a normal dose into a toxic or ineffective one. Still, it’s a hugely important advance.

However, physicians are seeing an unusual phenomenon in a small number of patients treated with Paxlovid – an improvement of symptoms while taking the drug, only to have them return after completing the five-day course. It has been dubbed “Paxlovid Rebound.” There is not much data on how frequently this occurs, but Pfizer’s application to the FDA for Emergency Use states that “several subjects appeared to have a rebound in SARS-CoV-2 RNA levels around Day 10 or Day 14.” And according to Dr. Mikael Dolsten, Pfizer’s chief scientific officer, “We have access to more than 300,000 Paxlovid treated [patients] in [a large database]. We have reports of this happening in about 0.005% or less [of patients treated].”

# This article by Drs. Henry Miller and Josh Bloom originally appeared on the Issues & Insights website. Reprinted with permission. The entire piece can be read here

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