Molnupiravir vs. Paxlovid: Which Is Better for COVID-19?

Medically reviewed by Erika Prouty, PharmD

Lagevrio (molnupiravir) and Paxlovid (nirmatrelvir and ritonavir) are prescription medications used to treat COVID-19. Though both have similar uses, they differ in several ways.

Lagevrio is available under the Food and Drug Administration's (FDA) emergency use authorization (EUA). Paxlovid, on the other hand, has received full approval from the FDA to treat mild-to-moderate COVID-19 in high-risk people.

This article will discuss the similarities and differences between Lagevrio and Paxlovid for treating COVID-19, including how well they work against the virus, dosage recommendations, side effects, and more.

What Is Lagevrio and How Does It Work?

Lagevrio is an antiviral medication that is used to slow the progression of the virus for those diagnosed with mild to moderate COVID-19. It is typically used in high-risk people for severe disease or hospitalization.

The medication is activated once it is swallowed and absorbed by the body. It works by stopping the virus from multiplying further to a more severe or complicated infection of COVID-19.

What Is Paxlovid and How Does It Work?

Paxlovid is a combination of two antiviral medications used to stop the progression of COVID-19  from becoming more severe.

The two medications work together. Nirmatrelvir prevents the virus from multiplying, and ritonavir helps block enzymes that break down nirmatrelvir so that it lasts longer to reduce the spread of the virus throughout the body.

How Effective Are Lagevrio and Paxlovid?

In clinical trials, Paxlovid has been demonstrated to be about 90% effective in reducing the risk of severe COVID-19 and death, with no safety concerns reported.

Paxlovid has been used in many studies with over 180,000 individuals. It has also been found to be safe and effective for children aged 12 and older weighing at least 40 kilograms (kg), or 88 pounds.

Although relatively safe, Paxlovid has not been studied in those with severe liver problems. Additionally, its benefits in unvaccinated people at low risk of severe disease and vaccinated people at high risk are unknown.

Lagevrio, on the other hand, appears to be less effective than Paxlovid–reducing the risk of hospitalization or death by 31% in nonhospitalized people compared with a placebo in clinical studies.

However, in a secondary analysis, hospitalized patients treated with Lagevrio were less likely to need respiratory interventions, such as mechanical ventilation.

These two medications have not been studied in head-to-head comparative trials.

Dosage: How Much Paxlovid and Lagevrio Should I Take?

Paxlovid

For mild to moderate COVID-19, healthcare providers may prescribe Paxlovid at 300 milligrams of nirmatrelvir and 100 milligrams of ritonavir tablets twice daily for five days.

For the best results, start Paxlovid immediately after your COVID-19 diagnosis and within five days of symptom onset.

If hospitalization is required after initiating treatment, your healthcare provider will determine whether or not you should continue the five-day course.

If you happen to miss a dose of your Paxlovid within eight hours of your usual time of when you take it, take it as soon as you remember. Resume your usual time of administration.

However, if you miss the dose eight hours after your usual dose, do not take the missed dose. Instead, wait until your next scheduled dose. Do not take double the dose to make up for a missed dose.

Lagevrio

For mild to moderate COVID-19, take one 800-milligram capsule every 12 hours for five days.

Like Paxlovid, take it as soon as you have been diagnosed and within five days of feeling symptoms. If you are hospitalized within five days of starting treatment, your healthcare provider will decide whether you should stop your medication.

If you miss a dose within 10 hours of the usual time you take it, then you can take that dose and continue your original regimen with no issues.

If you happen to forget to take your medication and more than 10 hours have passed, then skip that dose and take your medication the following day and continue your regular schedule. Do not take double the dose at any point while taking this medication.

Side Effects

Like all medications, Paxlovid and Lagevrio can cause side effects and reactions.

More common side effects experienced with Paxlovid include:

• Bitter or metallic taste

• Diarrhea

• Hypertension (elevated blood pressure)

• Nausea or vomiting

• Stomach pain

Sometimes, more severe side effects of Paxlovid may occur. These can include:

• Allergic and hypersensitivity reactions

• Liver disease or complications

• Risk of HIV-1 drug resistance: Using an antiviral medication such as ritonavir can increase the risk of medications not being effective in treating an undiagnosed HIV-1 infection. It is best to get tested before starting an antiviral therapy.

More common side effects experienced with Lagevrio include:

• Diarrhea

• Nausea

• Dizziness

Severe side effects can include a potential allergic reaction, which may cause a skin rash, hives, or severe swelling of the face or throat.

Who Shouldn't Take Paxlovid vs. Lagevrio?

When deciding which treatment is best for you, other factors apart from efficacy may come into play. Certain health conditions or circumstances may prevent you from taking one of these medications over the other.

You should not take Paxlovid if you:

• Are younger than 12

• Weigh less than 40 kg (88 pounds)

• Have severe kidney impairment

• Have severe liver problems

• Are hospitalized with COVID-19

• Are trying to prevent COVID-19

You should not take Lagevrio if you:

• Are under 18

• Are hospitalized with COVID-19

• Are trying to prevent COVID-19 infection

• Are pregnant
  

Drug Interactions

Many drugs interact with others, with some being more severe and potentially causing side effects or affecting how well the drug works.

Always let your primary healthcare provider or pharmacist know about all the medications you are taking to prevent any serious interactions. The following lists are medications that could potentially interact with these medications.

Drugs that may interact with Paxlovid include:

• Certain prostate medications, such as Uroxatral (alfuzosin) and Minipress (prazosin)

• Certain heart medications, such as ranolazine, Pacerone (amiodarone), and Corlanor (ivabradine)

• Antipsychotics, such as Latuda (lurasidone) and Abilify (aripiprazole)

• Anti-gout medications, such as Colcrys (colchicine)

• Ergot derivatives, such as Migranal (dihydroergotamine) and Ergomar (ergotamine)

• Cholesterol-reducing medications, such as Altoprev (lovastatin) or Zocor (simvastatin)

• Medications that lower the immune system, such as Lupkynis (voclosporin)

• Migraine medications, such as Relpax (eletriptan)

• PDE5 inhibitors, such as Revatio (sildenafil), when used for pulmonary arterial hypertension

• Sedatives, such as Halcion (triazolam) or oral Nayzilam (midazolam)

• Other medications, including Addyi (flibanserin), Samsca (tolvaptan), Kerendia (finerenone), and Movantik (naloxegol)

There is no sufficient evidence to conclude any drug interactions exist with Lagevrio.

Ask your healthcare team before starting your prescribed treatment for a complete list of all existing interactions.

Summary

You may be prescribed either Paxlovid or Lagrevio if you've been diagnosed with mild to moderate COVID-19 and are at high risk of severe disease. Generally, Paxlovid is considered more effective and is often the first choice, but Lagevrio may be given if other treatments are unavailable or cannot be used.

These medications should be started as soon as possible after a COVID-19 diagnosis.

While Lagevrio is still available under EUA, the FDA granted Paxlovid full approval for treating mild to moderate COVID-19. You can only get these treatments through a prescription from a healthcare provider permitted to prescribe them.

Do not take more than the prescribed amount, and if you have rebound side effects or COVID-19 symptoms, reach out to your primary healthcare provider for more information on other therapy.

Frequently Asked Questions

How much do Paxlovid and Lagevrio cost?

As an emergency-use medication, Lagevrio is currently available at no cost. The only cost would be getting the prescribed medication through a healthcare provider visit, depending on the insurance cost. Although its retail price is not available yet, it is estimated Lagevrio could cost about $700.

Without insurance, Paxlovid will cost about $530 after the free supply ends. However, what you pay out of pocket will depend on your insurance coverage.

Can you take Paxlovid and Lagevrio together for COVID-19?

Although preliminary studies have evaluated the combination of Paxlovid and Lagevrio, there is not enough evidence to suggest that the combination would resolve mild to moderate disease any better than one medication.

Can you take Paxlovid or Lagevrio while pregnant?

Paxlovid is relatively safe to take while pregnant. No published studies have reported an increased risk of major birth defects. Additionally, there is more maternal and fetal risk associated with untreated COVID-19 in pregnancy. Still, talk to your healthcare provider if you have been diagnosed with COVID-19 and are pregnant.

Lagevrio, on the other hand, is not recommended for use during pregnancy. Individuals of childbearing potential should use effective contraception (e.g., condoms, birth control pills) consistently during treatment and for four days after the last dose. The medication can cause fetal harm.

The author would like to recognize and thank Jaycob Mathew Peña for contributing to this article.