[Originally published: Oct. 11, 2021. Updated: Jan. 5, 2022.]
Note: Since this story about Merck’s molnupiravir was originally published, the Food and Drug Administration has provided emergency use authorizations for pills from both Merck and Pfizer. Scientists continue to study the real-world effectiveness of both. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.
Over the past year, discussions—sometimes heated ones—about ending the COVID-19 pandemic have largely focused on the availability, effectiveness, and safety of vaccines. But in December 2021, the Food and Drug Administration (FDA) issued emergency use authorizations (EUAs) for two pills that patients can take at home in the days after COVID-19 symptoms arise to prevent severe disease and avoid going to the hospital.
Merck applied for authorization first, in October, for a pill called molnupiravir, and many hailed the new drug as a potential game-changer. Pfizer submitted its application in November for a medication called Paxlovid.
“It certainly has the potential to be a really important advance,” said Albert Shaw, MD, PhD, a Yale Medicine infectious diseases specialist, when the Merck application was submitted. “Other COVID-19 treatments, such as remdesivir or monoclonal antibodies against the SARS-CoV-2 virus causing COVID-19, are given intravenously. This is a pill your physician could write a prescription for, that you could pick up in a drugstore.”
An early report showed the Merck drug cut the risk of hospitalization and death to 50% in patients who had mild-to-moderate disease, but a final analysis of the trial reported on in November, before the FDA authorization, showed a reduction in that benefit to 30%. Meanwhile Pfizer reported that its pill (combined with a low dose of ritonavir, an HIV drug) showed 89% efficacy in preventing hospitalization and death in the high-risk patients it studied.
We asked Dr. Shaw and other infectious disease experts to answer commonly asked questions about Merck’s new COVID pill.
1. How does Merck’s COVID-19 pill (molnupiravir) work?
It’s important to note that the pill is meant to be taken after you’ve experienced COVID-19 symptoms. In the clinical trial, molnupiravir was given to study participants in four capsules twice a day for five days—starting within five days after patients experienced the first symptoms of COVID-19.
When the drug enters your bloodstream, it blocks the ability of the SARS-CoV-2 virus to replicate, Dr. Shaw explains.
The coronavirus uses RNA as its genetic material. The structure of molnupiravir resembles the nucleosides (or chemical building blocks) used to make the virus’s RNA. The drug works by incorporating itself into the RNA as it’s being synthesized.
“This results in many mutations, or changes in the RNA genetic code, introduced into the viral RNA,” says Dr. Shaw. “And when this RNA is translated into viral proteins, these proteins contain too many mutations for the virus to function.”
2. Does molnupiravir have any side effects?
Based on the final analysis of Merck's clinical trial, the drug appears to have a clean safety profile, meaning there were no serious side effects in trial volunteers.
Possible side effects of molnupiravir include diarrhea, dizziness, and nausea.
3. Is molnupiravir similar to Tamiflu?
Yes, this new pill is similar—in function, ease of use, and availability—to Tamiflu, the antiviral medication that is used to prevent serious symptoms of flu. There is a key difference, though, says Dr. Shaw. “Tamiflu works through a different mechanism—by interfering with the entry of influenza virus into cells—instead of targeting the reproduction of viral RNA,” he says.
However, Tamiflu can be given in a single dose to prevent infection with the flu, “like a post-exposure prophylaxis [PEP],” says Dr. Meyer, explaining how some people may be prescribed antiviral medications after a potential exposure to a disease, like HIV, to prevent infection. “Molnupiravir has not yet been tested as a PEP against COVID-19,” she says, “but that would be a hope for the future.”
Currently, the FDA has not authorized the use of molnupiravir for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
4. Does molnupiravir prevent infection or severe illness and death?
The goal of the Merck pill is to keep people out of the hospital, explains Dr. Meyer. “We want to prevent severe illness and death in people who are infected with mild-to-moderate COVID, but who are not yet hospitalized,” says Dr. Meyer. The Merck study suggested that molnupiravir would help patients who have at least one risk factor for severe COVID-19 to avoid hospitalization.
5. Who is molnupiravir recommended for?
Molnupiravir is authorized for the treatment of mild-to-moderate COVID-19 in adults 18 and older who are at high risk for progressing to severe COVID-19, including hospitalization or death. It is not authorized for children and teenagers younger than 18 years because it may affect bone and cartilage growth.
6. Will molnupiravir work on virus variants, including Delta and Omicron?
7. Could molnupiravir be a turning point for other COVID-19 treatments?
So far, treatments for COVID-19 have been hard to deliver or not very effective. “We don't have a lot of COVID medications in our arsenal,” Dr. Shaw says. Remdesivir, the only COVID-19 drug treatment fully approved by the FDA, can only be administered intravenously in the hospital. It’s also only for those ages 12 and older, regardless of how severe their symptoms are, and studies suggest it may provide only modest benefit. The Merck and Pfizer pills are the first drugs that can be taken at home, early enough to prevent hospitalization.
“Hopefully, there will be more tools to help us better treat our COVID patients,” Dr. Shaw says.
8. Can pregnant women use molnupiravir ?
Molnupiravir is not recommended for use during pregnancy because findings from animal reproduction studies showed that molnupiravir may cause fetal harm when administered to pregnant individuals. If you have potential to be pregnant, your health care provider should assess whether you are pregnant or not before prescribing molnupiravir. If you are pregnant, the provider should prescribe it only if the potential benefits would outweigh the potential risks and has communicated that to you.
Likewise, breastfeeding is not recommended during treatment with molnupiravir and for four days after the final dose.
Men and women of “reproductive potential” should also use contraception for the duration of treatment and, for women, for four days after the last dose of molnupiravir; men should continue to use contraception for at least three months after the last dose of molnupiravir. More information about side effects of molnupiravir can be found on the FDA site.
9. With molnupiravir authorized, do we still need vaccines?
Both doctors emphasized that even if new COVID-19 drugs are successful in real-world scenarios, vaccination will remain essential for preventing SARS-CoV-2 infection—and for slowing its spread. People who are vaccinated have a much lower chance of getting sick and needing any treatment, they say.
“The vaccine is our first-line tool for preventing hospitalization, and I'm a little concerned that the attention on molnupiravir will draw attention away from vaccination,” says Dr. Meyer. “Some people might say, ‘I'm not getting vaccinated because I'll have access to these medications’—to this pill or to remdesivir or other treatments. But you can’t trade one for the other. If you haven’t done so already, the most important thing is still to get the vaccine."
Note: Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.