How do Paxlovid and molnupiravir compare for COVID-19?

Key Points

• Paxlovid (nirmatrelvir and ritonavir) and Lagevrio (molnupiravir) are two oral treatment options for mild-to-moderate coronavirus disease 2019 (COVID-19) in people who are at high risk for severe COVID-19 disease.
• Both Paxlovid and Lagevrio are taken by mouth twice a day for 5 days, and should be started within 5 days of COVID-19 symptoms beginning.
• Paxlovid can be used in adults and children ages 12 years and older who weigh at least 40 kg, while Lagevrio can only be used in adults.
• CDC guidelines recommend Paxlovid as a first-choice treatment option, while Lagevrio should be taken by people who cannot take alternative COVID-19 treatment options.

Paxlovid (nirmatrelvir and ritonavir) and Lagevrio (molnupiravir) are oral antiviral medications used to treat certain people with mild-to-moderate COVID-19. Both medications aim to reduce the severity of illness and prevent hospitalization. However, there are some key differences between them.

What is Paxlovid?

Paxlovid is an oral treatment option for mild-to-moderate COVID-19. It contains two medications, nirmatrelvir and ritonavir, that should be taken together at the same time. It is FDA approved in adults who are at high risk for severe COVID-19. Children 12 years and older who weigh at least 40 kg (88 lbs) may also take Paxlovid under the FDA’s Emergency Use Authorization.

Paxlovid is not approved for use as pre-exposure prophylaxis or post-exposure prophylaxis to prevent COVID-19, nor is it approved to treat long COVID.

What is Lagevrio?

Lagevrio, which contains the antiviral molnupiravir, is also an oral treatment option for mild-to-moderate COVID-19. It is authorized under the FDA’s Emergency Use Authorization for adults who are at high risk for severe COVID-19, and who cannot take alternative treatment options.

Lagevrio is only authorized for use in adults. It is not authorized for people younger than 18 years old. Similar to Paxlovid, Lagevrio should not be used for pre-exposure or post-exposure prophylaxis for the prevention of COVID-19.

How do Paxlovid and Lagevrio work?

Paxlovid and Lagevrio are both antiviral medications, but they work differently to treat COVID-19.

Paxlovid contains two medications: nirmatrelvir and ritonavir. These medications work together to fight COVID-19.

• Nirmatrelvir is a protease inhibitor. It blocks a protein in SARS-CoV-2 and prevents it from processing proteins that are required for the virus to multiply and spread in your body.
• Ritonavir is also a protease inhibitor, but doesn’t directly treat COVID-19. Instead, it blocks enzymes in your liver that break down nirmatrelvir. This keeps it around in your blood longer.

Lagevrio contains an antiviral medication called molnupiravir. It works by increasing mutations in viral genetic material. This prevents the SARS-CoV-2 virus from multiplying.

How are Paxlovid and Lagevrio given?

Both Paxlovid and Lagevrio are available as pills that are taken by mouth. Paxlovid is packaged with two different tablets, nirmatrelvir and ritonavir. Lagevrio is available as capsules that contain 200 mg of molnupiravir.

The usual dose of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) taken with 100 mg ritonavir (one 100 mg tablet) by mouth twice a day for 5 days. The dose may be lower in people with kidney problems. Both tablets can be taken with or without food.

The usual dose of Lagevrio is 800 mg (four 200 mg capsules) by mouth every 12 hours for 5 days. It can be taken with or without food. Additionally, Lagevrio can be given through a nasogastric tube, orogastric tube, gastrostomy tube, and gastrojejunostomy tube.

Paxlovid and Lagevrio work best when taken within 5 days of the onset of COVID-19 symptoms.

Related questions

• Paxlovid side effects: 8 key things to know
• How fast does Paxlovid work?
• Can you take Paxlovid twice if COVID rebounds?

How do side effects compare between Paxlovid and Lagevrio?

The most common side effects reported by patients taking Paxlovid during clinical trials were:

• Altered taste (5% vs. 1% placebo)
• Diarrhea (3% vs. 2% placebo)

Other side effects that were reported after Paxlovid was authorized under Emergency Use Authorization include anaphylaxis, severe skin reactions, headache, high blood pressure, stomach pain, nausea, vomiting, and feeling unwell. It is not known how common these reported side effects are in the general population.

During clinical trials of Lagevrio, the most common side effects reported were:

• Diarrhea (2% vs. 2% placebo)
• Nausea (1% vs. 1% placebo)
• Dizziness (1% vs. 1% placebo)

Vomiting, anaphylaxis, hives, rash, and itching are some side effects that patients reported after Lagevrio was authorized.

Serious warnings

The labeling for both Paxlovid and Lagevrio contains warnings of more serious, but rare, side effects.

Paxlovid has a risk of serious problems due to drug interactions. It can also cause severe allergic reactions, liver problems, and development of resistance to HIV protease inhibitors in people with uncontrolled or undiagnosed HIV-1 infection. The risk for liver problems may be higher in people who already have pre-existing liver disease. Tell your prescriber if you notice signs of liver problems, such as yellowing of the skin or whites of the eyes, dark urine, or stomach pain.

Lagevrio carries warnings for potential harm to babies when taken during pregnancy, risk of severe allergic reactions, and bone and cartilage problems. When given to pregnant animals at doses higher than in humans, researchers observed development problems in babies. Because there isn’t enough information to know if Lagevrio is safe in human pregnancy, it is recommended to use effective birth control while taking it and for 4 days after the last dose.

Does Paxlovid or Lagevrio work better for COVID-19?

Early clinical trials showed that Paxlovid was more effective for reducing hospitalization or death associated with COVID-19 in high-risk patients. This is one reason Lagevrio is authorized for use only in patients who cannot take Paxlovid.

• In the EPIC-HR clinical trial that included almost 2,000 people, Paxlovid reduced hospitalization or death associated with COVID-19 by 86% in adults compared to patients taking a placebo. People included in the study had not been infected with COVID-19 before, nor did they have any COVID-19 vaccination.
• In another clinical trial called EPIC-SR, vaccinated patients who took Paxlovid had a lower risk of hospitalization or death compared to those taking a placebo (not statistically significant).
• In the MOVe-OUT trial that included about 1,400 people, Lagevrio reduced the risk of hospitalization or death by 30% compared to placebo.
• A more recent study showed Lagevrio helps clear the COVID-19 virus faster than standard care in patients infected with the Omicron variant.
• A cohort study of around 69,000 patients infected with SARS-CoV-2 Omicron subvariants who were at high risk of severe COVID-19 showed that both Paxlovid and Lagevrio reduced hospitalizations and deaths. Paxlovid and Laevrio reduced the risk of death by 84% and 77%, respectively.

This is not all the information you need to know about Paxlovid (nirmatrelvir and ritonavir) and Lagevrio (molnupiravir) for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.