Paxlovid (nirmatrelvir + ritonavir) for early treatment of COVID-19

Paxlovid is the brand name of two medicines (nirmatrelvir + ritonavir). Nirmatrelvir is an antiviral drug that reduces the production of new copies of SARS-CoV-2, the virus that causes COVID-19. Ritonavir is used to slow the breakdown of nirmatrelvir in the body.

Nirmatrelvir was designed to interfere with an enzyme used by SARS-CoV-2. This enzyme is called main protease.

In a clinical trial called Epic-HR, researchers randomly assigned 2,246 people who had recently been infected with SARS-CoV-2 to receive one of the following interventions every 12 hours for five consecutive days:

  • nirmatrelvir 300 mg + ritonavir 100 mg
  • placebo

At the start of the study, participants had recently developed symptoms of COVID-19 and did not require hospitalization. However, they were considered to be at heightened risk for hospitalization or dying from COVID-19. Furthermore, they had not been vaccinated against SARS-CoV-2.

Twenty-eight days after entering the study, the risk of developing severe COVID-19, hospitalization and death was 6% less in people who received Paxlovid compared to people who received placebo. Statistical analysis revealed that the use of Paxlovid resulted in an 89% reduction in the risk of severe disease, hospitalization or death.

Nine people died during the study—all deaths occurred in people who received placebo.

Study details

The average profile of the 2,246 participants was as follows:

  • 51% men, 49% women
  • age – 46 years
  • major ethno-racial groups: White – 72%; Asian – 14%; Indigenous – 9%; Black – 5%

A majority of people had symptoms consistent with COVID-19 for three days or less. All tested positive for SARS-CoV-2.

Participants were enrolled between July 16 and December 9, 2021, at 343 clinics around the world.

At the start of the study, the most common underlying conditions associated with an increased risk for worsening COVID-19 were as follows:

  • a body mass index (BMI) greater than 25 kg/m2 – 81%
  • smoking tobacco – 39%
  • having high blood pressure – 33%

Overall, 61% of participants had two or more of the above characteristics.

Results – effectiveness

The researchers found that the following proportions of people were hospitalized and/or died:

  • Paxlovid – 0.72% (five people were hospitalized and none died)
  • placebo – 6.45% (35 people were hospitalized and nine died)

This difference was statistically significant; that is, not likely due to chance alone. Further analysis indicated that Paxlovid reduced the likelihood of serious issues developing (hospitalization and deaths) by 89% compared to placebo.

Paxlovid had a significant benefit regardless of the following factors:

  • age, BMI, gender, ethno-racial group, underlying conditions, the amount of SARS-CoV-2 produced (viral load)

Paxlovid reduced the average amount of SARS-CoV-2 produced by participants by 10-fold.


Overall, the proportions of people reporting any adverse event were similar—23% in people on Paxlovid and 24% in people on placebo. Note that the term adverse event refers to a range of unfortunate events that can occur during a clinical trial. These include drug side effects, issues caused by the underlying disease process and things that have nothing to do with the study drugs (such as accidents).

In general, people who received Paxlovid reported fewer serious or life-threatening adverse events (4%) than people on placebo (8%). This difference arose because more people on placebo developed adverse events related to COVID-19 (such as pneumonia).

More people who used Paxlovid reported or developed certain side effects as follows:

Altered sense of taste

  • Paxlovid – 6%
  • placebo – 0.3%


  • Paxlovid – 3%
  • placebo – 2%


  • Paxlovid – 1%
  • placebo – 0.8%

According to the researchers, these side effects were mostly mild to moderate and resolved after treatment ended.

Managing potential drug interactions

Many people at high risk for severe COVID-19 symptoms will likely be taking medications to treat underlying conditions (high blood pressure, high cholesterol and so on). Paxlovid contains nirmatrelvir and ritonavir, both of which can affect the body’s ability to break down other drugs. This effect of one drug on another is called a drug interaction. Ritonavir is notorious for its potential to cause drug interactions. Aware of this issue, the researchers suggested that healthcare providers who are concerned about potential drug interactions could do any of the following as clinically appropriate:

  • reduce the dose of the other medicine(s)
  • use a different medicine for the underlying condition
  • increase monitoring for potential side effects
  • have a lab assess blood samples from Paxlovid users to check the level of medications in the blood
  • temporarily discontinue use of the medicine(s) for the underlying condition

—Sean R. Hosein


Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, non-hospitalized adults with COVID-19. New England Journal of Medicine. 2022 Apr 14;386(15):1397-1408.