Paxlovid vs. Molnupiravir for COVID-19

 Key takeaways:

• Paxlovid (nirmatrelvir and ritonavir) and molnupiravir are two oral antiviral treatments that are authorized to treat mild to moderate COVID-19. These COVID-19 pills are only recommended for people with a high risk of developing severe illness.

• Both Paxlovid and molnupiravir are taken by mouth twice daily for 5 days. They should both be started within 5 days of first feeling symptoms.

• Studies suggest that Paxlovid can lower the risk of severe COVID-19 for high-risk people by almost 90%. Studies suggest molnupiravir can lower this risk by about 30%.

Nearly 2 years after it began, the COVID-19 pandemic continues to rage on. As the number of cases continues to rise, it’s clear that the fight isn’t over yet. But during this time, many scientific and medical breakthroughs have been made to help combat this illness.

In late December 2021, the FDA authorized two oral COVID-19 treatments: Paxlovid (nirmatrelvir and ritonavir) and molnupiravir. These are the first two oral medications that can help prevent mild or moderate COVID-19 from worsening. But with all the buzz on these COVID-19 pills, it can be easy to confuse them.

Here, we’ll discuss the differences between Paxlovid and molnupiravir when used to treat COVID-19.

What is Paxlovid?

Paxlovid is a combination of two antiviral pills: nirmatrelvir and ritonavir. This medication made by Pfizer was the first oral medication to receive FDA emergency use authorization (EUA) for treating mild to moderate COVID-19.

Paxlovid is authorized for adults and children ages 12 and older that weigh at least 88 pounds (40 kg). Paxlovid is currently only recommended for people at high risk of developing severe COVID-19. High-risk people include older adults and those with certain medical conditions.

How does Paxlovid work for COVID-19?

The two medications in Paxlovid work together to help treat COVID-19. Both nirmatrelvir and ritonavir belong to the same class of medications: protease inhibitors.

Nirmatrelvir stops the virus that causes COVID-19 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 longer. In other words, ritonavir helps make nirmatrelvir more effective against COVID-19 than it would be on its own.

What is molnupiravir?

Molnupiravir is also an oral antiviral pill authorized to treat mild to moderate COVID-19. This medication, manufactured by Merck, received EUA shortly after Paxlovid. Molnupiravir is authorized for adults ages 18 and older that are at high risk of severe COVID-19. However, the FDA has stated it should only be used if no other recommended COVID-19 treatments are available.

How does molnupiravir work for COVID-19?

Molnupiravir is a nucleoside analog. It also stops the COVID-19 virus from copying itself. But it does this in a different way than Paxlovid.

Molnupiravir looks like genetic building blocks that the COVID-19 virus uses to copy itself. So when you take the medication, the virus mistakenly inserts molnupiravir into its genetic material. When this happens, the virus can’t copy itself.

How are Paxlovid and molnupiravir dosed and given?

Paxlovid and molnupiravir have several similarities when it comes to taking each medication. The biggest dose difference lies in how many pills you take at one time.

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

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

Paxlovid and molnupiravir should be started within 5 days of when a person first starts experiencing COVID-19 symptoms. Both COVID-19 pills can be taken with or without food. It’s also important to finish all the medication prescribed to you to help them be as effective as possible.

How effective are Paxlovid and molnupiravir for treating COVID-19?

The effectiveness is probably the most notable difference between Paxlovid and molnupiravir.

In clinical trials, Paxlovid was nearly 90% effective at preventing hospital stays or death due to COVID-19 in high-risk people. Ongoing clinical trials suggest Paxlovid is about 70% effective in people with a standard risk of severe illness.

On the other hand, molnupiravir lowered the risk of COVID-19 hospital stays or death by about 30% in high-risk people. This difference in effectiveness may be one of the reasons the FDA suggests using molnupiravir only if other treatments aren’t available.

It’s important to note that these levels of effectiveness were recorded when study participants started Paxlovid or molnupiravir within 5 days of first feeling symptoms. The medications’ effectiveness is lower if the medications are started after this timeframe.

What are the known side effects of Paxlovid and molnupiravir?

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

Common Paxlovid side effects include:

• Changes in taste

• Diarrhea

• High blood pressure

• Muscle aches

Molnupiravir side effects reported most often include diarrhea, nausea, and dizziness.

What are the serious side effects of Paxlovid and molnupiravir?

As with any medication, Paxlovid and molnupiravir have risks of more serious side effects. Each medication’s risks are unique. These could be a reason why a healthcare provider may pick one COVID-19 pill over the other.

Paxlovid

Paxlovid can be hard on both the liver and kidneys. It’s possible this medication could damage these organs, especially if you already have issues with them. Paxlovid isn’t recommended if you have liver problems. If you have kidney problems, you may need a different dose of Paxlovid. Depending on your personal risks, your healthcare provider may also choose to avoid prescribing it.

Protease inhibitors are often used to treat HIV. As mentioned above, Paxlovid contains two protease inhibitors. This medication may cause HIV to become resistant to other HIV medications if you aren’t being fully treated for the condition. If you have HIV, discuss whether Paxlovid is the best choice for you with your healthcare provider.

Molnupiravir

Molnupiravir shouldn’t be taken if you're pregnant. Animal studies suggest that molnupiravir 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 molnupiravir and for 4 days after your last dose.

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

Molnupiravir also shouldn’t be taken by people under 18 years old. This is because the medication may affect bone and cartilage development in younger people. Discuss the best COVID-19 treatment option for your child or teen with their healthcare provider.

What interactions do Paxlovid and molnupiravir 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 your healthcare provider and pharmacist.

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 (D.H.E. 45, Migranal)

• Forms of birth control that include an estrogen called ethinyl estradiol

• Lurasidone (Latuda)

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

• St. John’s wort — an OTC herbal product

Currently, molnupiravir 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 medications with your healthcare provider before starting a new medication.

How much do Paxlovid and molnupiravir cost?

Definite cost information for Paxlovid and molnupiravir still isn’t available. The original prices reported were around $530 for a course of Paxlovid and about $700 for a round of molnupiravir.

More recently, news reports have stated that Paxlovid will be provided to all U.S. states at no cost. Merck has previously stated the cost of molnupiravir will also be lower than the original price given. But an exact cost hasn’t been confirmed for either.

We’ll know more about their costs as these COVID-19 pills become available. Quantities of Paxlovid and molnupiravir are limited at this time. More courses of the two antiviral treatments will be shipped to the U.S. during 2022.

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

No. This combination hasn’t been studied for any use, including COVID-19. An interaction between Paxlovid and molnupiravir isn’t listed by either Pfizer or Merck. But due to the lack of research about whether this is safe or effective, this combination isn’t suggested.

The bottom line

Paxlovid and molnupiravir are the first two oral medications available for treating mild or moderate COVID-19. Both medications are authorized for high-risk people. They should be started within 5 days of first feeling symptoms.

There are several similarities between Paxlovid and molnupiravir. But the biggest difference lies in how effective they’ve been for COVID-19 in studies. If you’ve recently tested positive for COVID-19, talk to your healthcare provider to see if either COVID-19 pill is an option for you.

References

Associated Press. (2021). Merck asks US FDA to authorize promising anti-COVID pill.

Centers for Disease Control and Prevention. (2021). COVID-19 information for specific groups of people.

Centers for Disease Control and Prevention. (2021). People with certain medical conditions.

Centers for Disease Control and Prevention. (2022). COVID data tracker.

Food and Drug Administration. (2021). Coronavirus (COVID-19) update: FDA authorizes additional oral antiviral for treatment of COVID-19 in certain adults.

Food and Drug Administration. (2021). Emergency use authorization 105.

Food and Drug Administration. (2021). Emergency use authorization 108.

Food and Drug Administration. (2021). Fact sheet for healthcare providers: emergency use authorization for molnupiravir.

Food and Drug Administration. (2021). Fact sheet for healthcare providers: emergency use authorization for Paxlovid.

HIVinfo. (2022). Protease inhibitor (PI).

Merck & Co., Inc. (2021). Fact sheet for healthcare providers: emergency use authorization for molnupiravir.

Merck Sharp & Dohme Corp. (2021). Merck and Ridgeback Biotherapeutics provide update on results from MOVe-OUT study of molnupiravir, an investigational oral antiviral medicine, in at risk adults with mild-to-moderate COVID-19.

Nature. (2021). How antiviral pill molnupiravir shot ahead in the COVID drug hunt.

NBC News. (2021). FDA authorizes first Covid pill, from Pfizer, for emergency use.

Pfizer Inc. (2021). Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death.

Pfizer Inc. (2021). Pfizer’s novel COVID-19 oral antiviral treatment candidate reduced risk of hospitalization or death by 89% in interim analysis of phase 2/3 EPIC-HR study.

Pfizer Inc. (2021). Pfizer receives U.S. FDA emergency use authorization for novel COVID-19 oral antiviral treatment.

Pfizer Inc. (2021). Protease inhibitors to fight COVID-19: stopping the virus’s life cycle.

Reuters. (2021). U.S. to buy 10 mln courses of Pfizer's COVID-19 pill for $5.3 bln.

https://www.goodrx.com/conditions/covid-19/covid-19-pill-paxlovid-molnupiravir

Shanghai confirms 5 local infections

 Shanghai reported two locally transmitted COVID-19 cases and three local asymptomatic cases on Thursday.

All the five people, who have been sent to the Shanghai Public Health Clinical Center, are related to an imported asymptomatic COVID-19 case reported in the city on Tuesday.

They tested positive during screening and quarantine as close or secondary contacts to the imported case, Wu Jinglei, head of the Shanghai Health Commission, said at a press briefing on Thursday.

The two new confirmed cases, both close contacts of the imported case, work at a milk tea store at 228 Yuyuan Road in Jing'an District. They are showing mild symptoms.

SHINE

The 18-year-old female employee has received two shots of the COVID-19 vaccine, while her 17-year-old male colleague, a part-time worker, has not been jabbed.

Another female employee at the store and her sister, who live together, have been diagnosed as asymptomatic cases. They are fully vaccinated.

A 26-year-old unemployed female, another close contact of the imported case, has also been diagnosed as an asymptomatic case. She said she had taken full vaccination overseas.

SHINE

A total of 304 people who had close links with the five people have been put under medical observation. A total of 30,783 people have been screened, with 30,128 results negative.

Health authorities collected 1,626 environmental samples and 34 pieces, mainly at the places they live, have tested positive.

The milk tea store has been elevated to a medium-level risk area. A search on Dianping.com shows the store named "China Fresh Tea" is about 200 meters from the No. 1 exit of the Jing'an Temple Station on Metro Lines 2 and 7.

Jiang Xiaowei / SHINE

The milk tea store on 228 Yuyuan Road has been elevated to a medium-level risk area on Thursday.

Jiang Xiaowei / SHINE

Two-week quarantine

The imported asymptomatic COVID-19 case, the origin of the new cases, is a Chinese studying in the United States, who arrived at Pudong International Airport on December 21.

During the two-week quarantine, the patient tested negative for COVID-19 four times. But in the ensuing seven-day self-health monitoring period, the patient tested positive on the last day without showing symptoms.

All overseas travelers to Shanghai are subject to 14 days of central quarantine and another week of self-health monitoring period.

Authorities reiterated that during the self-health monitoring period, people are not allowed to take public transport, gather for meals or dine in restaurants, and participate in activities such as watching movies, exhibitions or meetings.

Zeng Qun, deputy director of the Shanghai Civil Affairs Bureau, said violators shall bear legal responsibility, get demerits on their credit accounts and will be exposed publicly.

Wu said citizens, especially those above 60 years old and between three and 17 years old, should take COVID-19 vaccines and the booster shots as soon as possible.

Details on how local expats can take the booster shots of the COVID-19 vaccines have not been announced.

About 8.7 million people in Shanghai had received the booster shots as of midnight on Wednesday. A total of 23.5 million people in the city have taken at least one jab, while some 94 percent among them have received two shots, according to Wu.

Elsewhere, north China's Tianjin Municipality on Thursday said it would upgrade its COVID-19 prevention and control measures in risk areas to prevent the virus from spreading.

Vehicles entering and leaving the affected areas will be arranged by local authorities and people outside the risk areas under government control are prohibited from visiting those areas to deliver materials.

The city logged 41 new locally transmitted COVID-19 cases on Wednesday, according to a daily report by the National Health Commission on Thursday.

https://www.shine.cn/news/metro/2201130748/

'COVID is here to stay: countries must decide how to adapt'

 From a pandemic perspective, 2022 seemed poised to begin with a hefty dose of déjà vu, with COVID-19 cases on the rise in many countries in the lead-up to the new year. Meanwhile, a new coronavirus variant seemed poised to overwhelm health-care systems amid fears that vaccines — from first inoculations to boosters, depending on the country — could not be rolled out quickly enough to stem the impending tsunami of infections.

The welcome news that surges of the Omicron variant are associated with less severe disease in adults than are preceding variants of SARS-CoV-2 suggests that some of pandemic modellers’ worst-case scenarios will not come to pass. But life has again been disrupted. Widespread absences due to coronavirus infections have left hospitals in many countries understaffed, forced schoolchildren to return to remote learning, and limited global mobility. And even if a relatively small percentage of those infected require hospitalization, sky-high infection rates across large populations mean that many people will still face life-threatening disease and long-term disability. This is particularly true for the unvaccinated — a group that includes a large proportion of the world’s population, especially children.

For those who had hoped that 2021 would be the year that put the pandemic in the past tense, it was a harsh reminder that it is still very much present. Rather than laying plans to return to the ‘normal’ life we knew before the pandemic, 2022 is the year the world must come to terms with the fact that SARS-CoV-2 is here to stay.

Countries must decide how they will live with COVID-19 — and living with COVID-19 does not mean ignoring it. Each region must work out how to balance the deaths, disability and disruption caused by the virus with the financial and societal costs of measures used to try to control the virus, such as mask mandates and business closures. This balance will vary from one place to another, and with time, as more therapies and vaccines become available — and as new variants emerge.

The emergence of the Omicron variant last November highlighted the ongoing challenges of life with SARS-CoV-2. Some countries were already facing surges in the highly transmissible Delta variant, but vaccines and prior infection conferred relatively high levels of protection against Delta, particularly against severe disease. Many researchers — and a fair few politicians — hoped that future waves would be less disruptive, thanks to the build-up of immunity in populations that would keep viral circulation in check and protect most people from the severe manifestations of disease that drain health-care resources.

It was expected that mutations in the viral genome would slowly chip away at this immunity, particularly its ability to stop viral transmission. But Omicron dealt a swifter and more serious blow to immunity than predicted. It is now clear that SARS-CoV-2 reinfections are more common, and that some of the most widely used COVID-19 vaccines have faltered in the face of the variant. Existing vaccines, developed against an earlier variant, now require a booster to provide substantial levels of protection against infection.

But the news has not all been grim. Vaccines, particularly when boosted, still seem to provide substantial protection against severe disease and death. Early data from animal studies suggest that Omicron might generate a different pathology compared with previous variants, causing greater infection of the upper respiratory tract and less infection in the lungs. Data from several countries suggest that the variant is associated with less severe disease, although whether this is due to the variant itself or widespread pre-existing immunity requires further study.

Countries have charted a variety of courses through the latest surge. Many with the resources have accelerated the distribution of vaccine boosters, but many others do not have this luxury. Some countries have reinstituted lockdowns, whereas others are holding back, waiting to see the extent to which climbing infection rates affect hospitals.

With infection rates soaring around the globe and many countries still unable to access adequate vaccine supplies, more SARS-CoV-2 variants of concern will continue to emerge. And, as Omicron has illustrated, the ability to predict what course those variants will take becomes more difficult as the complexities of viral evolution and pre-existing immunity complicate the models that have previously been used to anticipate the course of the pandemic. Now modellers need to factor in the effects of vaccines, previous infections, waning immunity over time, booster shots and viral variants — and, as the year progresses, they will also have to consider the impact of emerging antiviral treatments.

But what is clear is that the hope that vaccines and prior infection could generate herd immunity to COVID-19 — an unlikely possibility from the start — has all but disappeared. It is widely thought that SARS-CoV-2 will become endemic rather than extinct, with vaccines providing protection from severe disease and death, but not eradicating the virus.

As Omicron and other variants have shown, this only adds to the urgency with which vaccines must be distributed to countries that currently lack supplies. Efforts are under way to bolster vaccine production in countries such as South Africa, which have not historically been centres for vaccine manufacturing. These and other efforts to boost global access to vaccines remain in the best interests of all countries: devastating variants are particularly likely to emerge and seed blazing outbreaks in regions with low vaccination rates, and their spread will be further exacerbated where levels of testing and genomic surveillance are also low.

Fortunately, 2022 is poised to add to our defences against the pandemic. New vaccines — such as protein-based vaccines, which might cost less and have less-stringent storage requirements than mRNA vaccines currently do — will become more widely available. In December, the World Health Organization approved the long-awaited protein vaccine made by Novavax in Gaithersburg, Maryland, for emergency use. Ongoing clinical trials will establish whether upcoming vaccine candidates that target specific coronavirus variants, or that can be inhaled or taken orally rather than injected, will also be useful. Several nasal candidates are in clinical testing, including one from CanSino in Tianjin, China, and another developed by AstraZeneca in Cambridge, UK.

Meanwhile, new antiviral drugs, formulated in tablets that can be easily administered early in the course of infection to reduce the chance of serious disease and death, offer another approach against COVID-19. In the past few months, some countries have authorized the use of two such drugs: molnupiravir, made by Merck in Kenilworth, New Jersey, and Ridgeback Biotherapeutics in Miami, Florida; and Paxlovid, made by Pfizer, based in New York. Data from pivotal clinical trials of other candidates are expected in the coming year.

All of these will expand the world’s capacity to manage SARS-CoV-2 outbreaks. They are cause for hope and optimism, but with a hefty dose of realism: the virus will continue to circulate and change, and governments must continue to rely on the guidance and advice of scientists. We will not always be able to predict the virus’s path, and we must be ready to adapt with it.

Nature 601, 165 (2022)

doi: https://doi.org/10.1038/d41586-022-00057-y

https://www.nature.com/articles/d41586-022-00057-y

If you got Omicron post-vaccination, don't rush out for booster shot

 In just a matter of weeks, hundreds of thousands of Canadians likely became infected with the Omicron variant of the coronavirus.

The unprecedented surge of cases has led to cancelled surgeries, staffing shortages in the health-care system and record-breaking hospitalization rates — alongside plenty of less serious bouts of illness, including among those who've been fully vaccinated against COVID-19.

If you're now one of a growing number of people who've been infected post-vaccination, you might be wondering when it's appropriate to get a booster — or if you need one at all.

"People should still get a booster," Dr. Lynora Saxinger, an infectious diseases specialist and associate professor at the University of Alberta in Edmonton, told CBC News. "I think the harder part is, when is the best time to boost?"

Provincial guidance on that timing varies across the country, ranging from Quebec's suggestion to simply wait until your symptoms go away to a recommendation from Ontario's top doctor to hold off for 30 days.

There's no magic number, but the science behind how our immune system works means you might want to wait weeks or even months after an Omicron infection to reap the benefits of a booster shot.

Don't get a shot while sick

In general, if you're sick, you shouldn't get any type of vaccine, said Alyson Kelvin, a virologist and vaccine researcher at the University of Saskatchewan's Vaccine and Infectious Disease Organization in Saskatoon.

"Your body's immune response to whatever it's fighting is going to be directed toward that pathogen," she explained.

At the same time, your body might not respond as effectively to a vaccine dose, which is meant to trigger your immune system by imitating a threat like the coronavirus. "So this is generally why we should wait some time after being infected to get any vaccine," Kelvin said.

The ideal time to get a booster shot, she said, is when your immune system has calmed down.

Kelvin likened what's happening inside your body to the process of recruiting people for a job: You want highly trained candidates for a specific task, which in this case means fighting off the coronavirus.

"Say you send out a job advertisement, and you get lots of people responding to that job. That's kind of like when you're given an initial vaccine, or you're infected, and your immune response starts to recruit all of these different immune cells," she said.

That's a busy time, but the bulk of those immune cells — or job applicants, shall we say — will eventually tail off. That's when you want another boost to re-engage the immune system, or as Kelvin's analogy goes, another chance to regroup with applicants that are best fitted for the job.

"So definitely, you want to wait till your symptoms clear up, and probably it's beneficial to wait an extra month or a couple of weeks after your initial infection, as you'll have more benefits of that boost," she said.

No need to rush getting a booster post-infection

Other immunologists agreed there's really no urgent need for a booster post-infection.

"I think it's a better idea to wait several months before getting boosted because then the boost will be more effective," said Dr. Jamie Scott, a molecular immunologist and professor emeritus at Simon Fraser University in Burnaby, B.C. "It'll have a stronger effect again because the memory cells will be much more fully developed and the antibody levels will be down."

"I don't think it makes a lot of sense to get a booster soon after you've recovered from an Omicron infection," echoed Deepta Bhattacharya, a professor of immunobiology at the University of Arizona in Tucson.

Preliminary data suggests infections with this variant also protect against getting infected by the once-dominant Delta variant, he said, which reduces your chance of being infected with either version of the virus right away.

And Bhattacharya noted that not rushing out and getting a booster soon after your recovery actually aligns with Canada's unorthodox vaccination approach — to space out doses — throughout the pandemic.

Before vaccine shipments started ramping up, Canada's National Advisory Committee on Immunization issued a bold recommendation to delay second doses well beyond manufacturing guidelines to a maximum of four months.

While the move was controversial at the time, vaccine experts had told CBC News it was rooted in decades of vaccine science and could actually provide more protection than sticking to the tight schedule of clinical trials.

"One of the things Canada has taught us is spacing them out — spacing out your exposures — makes a big difference in the quality and the magnitude of antibodies that you get," Bhattacharya said.

The next phase in protecting people from Omicron and future variants may require developing vaccines tailored to those threats.

"Right now, the boosters that we have are matched to a strain that's long gone — and probably never will be seen again," he said. "So my hope is we'll get some better options down the road."

https://www.cbc.ca/news/health/omicron-covid-vaccinated-booster-1.6312471