Lagevrio (Molnupiravir) vs. Paxlovid: How Do They Compare for COVID-19

COVID-19 is a contagious viral illness that spread worldwide during 2020. As a response to this, scientists and researchers made many medical breakthroughs to help combat it.

In late December 2021, the FDA authorized two oral COVID treatments: Lagevrio (generic name: molnupiravir) and Paxlovid (generic name: nirmatrelvir / ritonavir). They were the first oral medications to come to market to help prevent mild to moderate COVID from worsening. But Lagevrio and Paxlovid have a number of differences to know about. And it can be easy to confuse them.

What is Paxlovid?

Paxlovid is manufactured by Pfizer and is a combination of two antiviral pills: nirmatrelvir and ritonavir. It was the first oral medication to receive FDA emergency use authorization (EUA) for treating mild to moderate COVID. And in May 2023, it became the first oral antiviral to be fully FDA approved for the illness.

Paxlovid is approved for adults with mild to moderate COVID symptoms. It's also authorized for children ages 12 and older who weigh at least 88 pounds (40 kg). Paxlovid is currently only recommended for people at high risk of developing severe COVID. High-risk people include older adults and those with certain medical conditions.

How does Paxlovid work to treat COVID?

The two medications in Paxlovid, nirmatrelvir and ritonavir, work together to help treat COVID. They both belong to the same class of medications: protease inhibitors.

Nirmatrelvir stops the virus that causes COVID from copying itself. The virus relies on an enzyme (protein) in our bodies called protease to copy itself. Nirmatrelvir temporarily stops this enzyme from working so the virus can't use it to multiply.

Ritonavir helps slow the breakdown of nirmatrelvir. This helps nirmatrelvir stay in the body at higher levels for a longer period of time. In other words, ritonavir helps make nirmatrelvir more effective against COVID than it would be on its own.

What is Lagevrio (molnupiravir)?

Lagevrio is the brand name for the medication molnupiravir. It's also an oral antiviral pill authorized to treat mild to moderate COVID. This medication, manufactured by Merck, received EUA shortly after Paxlovid. Lagevrio is authorized for adults ages 18 and older that are at high risk of developing severe COVID. However, you should only take it if other treatments are unavailable or inappropriate. And unlike Paxlovid, Lagevrio isn't fully FDA approved for use.

How does Lagevrio work for COVID?

Lagevrio is a nucleoside analog antiviral. It also stops the COVID virus from copying itself, but it does this in a different way than Paxlovid.

Lagevrio looks like the genetic building blocks that the COVID virus uses to copy itself. So when you take the medication, the virus mistakenly inserts Lagevrio into its genetic material. When this happens, the virus can't copy itself.

What are the dosages for Paxlovid and Lagevrio?

Paxlovid and Lagevrio have several similarities when it comes to how they are administered.

Both Paxlovid and Lagevrio should be started within 5 days of when a person first starts experiencing COVID symptoms. Both COVID pills can be taken with or without food. It's also important to finish taking every dose of the medication prescribed to you to help the treatment be as effective as possible.

Where Paxlovid and Lagevrio dosages vary is in the number of pills you take at one time.

Paxlovid dosage

Paxlovid comes as a prepackaged carton containing 30 tablets. For each dose, you'll take 2 nirmatrelvir tablets and 1 ritonavir tablet. The 3 tablets should be taken by mouth twice daily for 5 days. Swallow the pills whole. Don't split, chew, or crush them.

Lagevrio dose

A Lagevrio prescription comes with 40 capsules. Take 4 capsules by mouth twice daily (every 12 hours) for 5 days. The capsules should be swallowed whole. Don't open or crush the capsules.

How effective are Paxlovid and Lagevrio for treating COVID?

Probably the most notable difference between Paxlovid and Lagevrio is how effective they are.

In its initial clinical trials, Paxlovid was nearly 90% effective at preventing hospital stays or death due to COVID in high-risk people. Other studies suggest that the benefits of Paxlovid are especially evident for older adults.

On the other hand, Lagevrio lowered the risk of COVID hospital stays or death by about 30% in high-risk people in initial studies. This difference in effectiveness may be one of the reasons that Lagevrio is FDA authorized to use only if other treatments aren't available or appropriate.

It's important to note that these levels of effectiveness were recorded when study participants started Paxlovid or Lagevrio within 5 days of first feeling symptoms. The medications' effectiveness is lower if the medications are started after this timeframe. This data was also collected before the Omicron variant became predominant.

What is the Paxlovid rebound effect?

In late April 2022, some reports emerged of people experiencing a return (or rebound) of their COVID symptoms after finishing their Paxlovid prescription. Media outlets have referred to this as "Paxlovid rebound." Keep in mind that rebound symptoms are not a side effect of Paxlovid, and they can also happen with Lagevrio. It isn't recommended to take a second course of medication if this happens.

For some people, the symptoms are mild. But others find their rebound symptoms are worse than their original symptoms. It's important to note that there are currently no reported cases of deaths with rebound symptoms after taking Paxlovid. With rebound symptoms, it's also possible to test positive again after testing negative at the end of a 5-day Paxlovid treatment.

In initial clinical trials, between 2% and 3% of people who took Paxlovid experienced rebound symptoms. Further studies suggest this may happen to between 10% and 16% of people after finishing the medication.

It's important to note that COVID rebound can also happen if you don't take any COVID pills. Studies suggest that similar amounts of people experience COVID rebound symptoms, regardless of whether they received treatment. But if you have a weakened immune system, you may be more likely to experience COVID rebound in general.

What are the known side effects of Paxlovid and Lagevrio?

Side effects for both Paxlovid and Lagevrio were mild for most people in clinical trials.

Common Paxlovid side effects include:

• Changes in taste ("Paxlovid mouth")

• Diarrhea

• High blood pressure

• Muscle aches

The most reported side effects of Lagevrio are:

• Diarrhea

• Nausea

• Dizziness

What are the serious side effects of Paxlovid and Lagevrio?

As with any medication, Paxlovid and Lagevrio have risks of more serious side effects. Each medication's risks are unique, which could be a reason why a healthcare professional may pick one COVID pill over the other.

Serious side effects associated with Paxlovid

Paxlovid can have effects on both the liver and kidneys. It's possible the medication could damage these organs, especially if you have preexisting conditions.

If you have severe liver problems, taking Paxlovid is not recommended. If you have kidney problems, you may need a different dose of Paxlovid. Depending on your personal risks, a healthcare professional may also choose to avoid prescribing it.

As mentioned above, Paxlovid contains two protease inhibitors, a type of medication that is often used to treat HIV. Paxlovid may cause HIV to become resistant to other medications in people who aren't being fully treated for the condition. If you have HIV, discuss whether Paxlovid is the best choice for you with your prescriber.

Serious side effects associated with Lagevrio

Lagevrio shouldn't be taken if you're pregnant. Animal studies suggest that Lagevrio may harm unborn babies or cause a miscarriage. If you are sexually active and able to get pregnant, you should use reliable birth control while taking Lagevrio and for 4 days after your last dose.

There's also concern that Lagevrio may affect sperm. Experts are unsure if this could affect a future pregnancy. As an extra precaution, it's recommended for men who are sexually active with a woman who can become pregnant to use condoms while taking Lagevrio. They should also continue using condoms for at least 3 months after their last dose.

Lagevrio also shouldn't be taken by people who are under 18 years old. This is because the medication may affect bone and cartilage development in younger people. Discuss the best COVID treatment option for your child or teen with their pediatrician.

Can you take Paxlovid if you're pregnant?

Experts currently recommend Paxlovid as the preferred treatment during pregnancy if you're not hospitalized with COVID. But it's best to discuss this with your prenatal care team, as everyone's risks are unique.

Research suggests that Paxlovid, unlike Lagevrio, is likely safe to take if you're pregnant. A small study found no increased rates of birth defects or complications in women who took this COVID pill while pregnant. However, larger studies are needed to confirm this.

There are many known risks when it comes to having COVID during pregnancy. These include a higher risk of getting very sick and an increased risk of preterm birth (having a baby before week 37 of pregnancy). And Paxlovid may help lower the risk of COVID-related complications.

What interactions do Paxlovid and Lagevrio have?

Paxlovid interacts with many medications. Some interactions make Paxlovid less effective, and others make it too plentiful in your body.

The following list includes some of the most notable interactions. But there are many other medications that may be unsafe to combine with Paxlovid. Discuss all medications and over-the-counter (OTC) products you take with a healthcare professional.

Some of Paxlovid's interactions include:

• Certain medications that treat heart rhythm problems, such as amiodarone (Pacerone)

• Certain medications used to control seizures, such as carbamazepine (Tegretol)

• Certain statin cholesterol medications, such as simvastatin (Zocor)

• Colchicine (Colcrys)

• Ergot medications, such as dihydroergotamine mesylate (Migranal)

• Lurasidone (Latuda)

• Sildenafil (Revatio) when used to treat pulmonary arterial hypertension (PAH)

• St. John's wort, an OTC herbal product

Currently, Lagevrio isn't known to interact with any medications. This is still being studied and may change as more information becomes available. Always discuss all your existing medications with a healthcare professional before starting a new medication.

How much do Paxlovid and Lagevrio cost?

The cost of Paxlovid and Lagevrio will depend on whether you have insurance and if you qualify for savings opportunities from the manufacturers.

Paxlovid's average cost for a 5-day treatment course is $1561.00. Many insurance plans, including Medicare, cover Paxlovid. If you have commercial insurance, a manufacturer copay card can help lower your costs. Paxlovid may cost as little as $0 when using this savings card. If you're uninsured, you may be eligible for the medication's patient assistance program, which offers the medication free of cost.

The average cost for 5 day's worth of Lagevrio is $876.69. Similar to Paxlovid, many insurance plans, including Medicare, cover Lagevrio. If you have commercial insurance, you may be eligible to pay as little as $10 for the medication using a savings card from the manufacturer. A patient assistance program is also available for Lagevrio.

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