Paxlovid vs Remdesivir vs Monoclonal Antibody: A Comparative Analysis (2023)

Paxlovid vs Remdesivir vs Monoclonal Antibody, what's the difference? If you are confused about the recommendations made by different professional groups for the COVID-19 pandemic, you've come to the right place.  

Most people with COVID-19 will experience a mild illness, and they’ll be able to take care of themselves at home. But some—especially those with underlying health conditions—could benefit from one of several COVID-19 treatments. Some of these are available in pill form and others are given intravenously or by injection—and all of them must be prescribed by a health care provider.

As of the week ending August 5, 2023, the Omicron EG.5 variant and XBB sub-variants represent more than 70% of the SARS-CoV-2 variants currently circulating in the United States, according to the CDC. 

In this article, we will do a roundup and cover 3 popular anti-viral treatments i.e. Remdesivir, Paxlovid and Monoclonal Antibodies.

Paxlovid and COVID-19

How to Get Paxlovid Without a Medical Doctor

In March 2022, the Biden administration launched the Test to Treat initiative. The initiative’s goal was to allow people to be tested for COVID-19 at pharmacies or health centers that have an on-site clinic, like CVS MinuteClinic. If you had a positive test, you’d then receive an antiviral prescription at the pharmacy before leaving the building.

While well-intentioned, there were many roadblocks that made the Test to Treat initiative difficult to roll out. One big barrier was the fact that most pharmacies don’t have clinics in the same building. In late May 2022, there were only about 2,500 Test to Treat locations in the entire U.S. This left many Americans still struggling to get a prescription from their healthcare providers in enough time to benefit from Paxlovid.

In response to this, the FDA updated Paxlovid’s EUA in July 2022. This change allows pharmacists to prescribe Paxlovid directly to people who have tested positive for COVID-19. This means that you might be able to head over to your local pharmacy for the medication without having to make other stops along the way. Keep in mind that not all pharmacies may offer this service.

To get Paxlovid from your pharmacist, you must bring the following documents with you to the pharmacy:
  • Your current health records, which must be less than a year old (either electronic or printed records are fine)
  • Your most recent liver and kidney function tests, which must be less than a year old
  • A complete list of all medications that you take, including any over-the-counter (OTC) medications, vitamins, and supplements
If you don’t have all of this information available, or your records aren’t recent enough, there may be a delay in getting Paxlovid. A pharmacist can reach out to your provider by phone to get this information, but that takes time. In this case, pharmacist-prescribed Paxlovid might not be much faster than seeing your healthcare provider or visiting a Test to Treat location.

How much will Paxlovid cost? 

The U.S. will pay about $500 for each course of Pfizer’s treatment, which consists of three pills taken twice a day for five days. Two of the pills are Paxlovid and the third is a different antiviral that helps boost levels of the main drug in the body.

New Paxlovid Dose Pack Author​ized by FDA

On April 14, 2022, the U.S. Food and Drug Administration (FDA) revised the Emergency Use Authorization (EUA) for the COVID-19 oral antiviral therapeutic Paxlovid to authorize an additional dose pack presentation with appropriate dosing for patients with moderate renal impairment within the scope of the EUA. As a result, Paxlovid will soon be available in two package presentations:
  1. ​The standard packaging that is currently in distribution: 300 mg nirmatrelvir;100 mg ritonavir - Each carton contains 30 tablets divided in 5 daily-dose blister cards. Each blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
  2. The new packaging option that will be in distribution later this month: 150 mg nirmatrelvir; 100 mg ritonavir - Each carton contains 20 tablets divided in 5 daily-dose blister cards. Each blister card contains 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
The updated provider Fact SheetLetter of Authorization, and Dear Healthcare Provider Letter​ are available for reference.

Precaution: PAXLOVID is not recommended (the appropriate dose has not been determined) in patients with severe renal impairment (<30 mL/min). (Source)

Paxlovid Rebound

In late May 2022, the CDC issued a health advisory about “COVID-19 rebound” after Paxlovid treatment. The CDC described it as “a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative.”

At the same time, the CDC wrote, “a brief return of symptoms may be part of the natural history of [coronavirus] infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”

The CDC said there is no evidence for more treatment in rebound cases, though people should isolate again for at least 5 days so they won’t pass COVID-19 to others.

People who have a rebound after taking Paxlovid can report their cases to Pfizer’s adverse event reporting page.

Paxlovid's Contraindications and Drug Interactions

Pfizer anti-COVID pill's interaction with common drugs will narrow its benefit, experts say | National Post:

The buzz around PAXLOVID™ has largely obscured one major downside of this treatment. Ritonavir can interact dangerously with a slew of commonly used medications, pumping up the potency of blood thinners, heart-arrhythmia therapies, epilepsy drugs and others. And the patients targeted for its use – those most at risk of serious COVID disease because of age and other health issues – are also the people most likely to be taking those “contraindicated” medications. 

In some cases, the interactions could be managed, but it’s clear the problem will limit the pool of potential recipients, experts say. “It has a utility, it has a use,” said Dr. Gerald Evans, head of the Infectious Diseases Division of the Queen’s University medical school. “(But) I certainly would not call it a game-changer.” “A patient on blood thinners could end up with spontaneous bleeding in the gastrointestinal tract or brain”, noted Evans. 

“Someone taking pills for hypertension might see their blood pressure fall so much they pass out”, said Dr. Andrew Hill, a pharmacology researcher at the U.K.’s Liverpool University. “There are all kinds of ways that PAXLOVID™ could cause serious harm,” he said. 

Ritonavir is also used in HIV treatments, so there is a wealth of knowledge about those potential drug interactions. The U.S. Food and Drug Administration (FDA) product monograph for PAXLOVID™ lists over 100 drugs that it says should not be taken with the COVID pills, or whose use ought to be carefully monitored. The figure below lists a few of these drugs as well as liver enzymes whose functions are impacted by Ritonavir.

See Sections 4 and 7 of the FACT SHEET FOR HEALTHCARE PROVIDERS and a publication on JAMA by Ross et al. Pharmacists as prescribers may be a problem since they are not authorized to manage, deprescribe and be responsible for the OTHER drugs.

Remdesivir (Veklury)

What is it? The antiviral treatment remdesivir, sold under the brand name Veklury, was the first COVID-19 therapy to get full FDA approval. Although originally used in COVID-19 patients only after they were hospitalized, new data suggests it can be helpful in outpatients who become infected and who are at high risk for severe disease. 

The U.S. Food and Drug Administration (FDA) on July 14, 2023 approved Veklury, also known as remdesivir, to treat COVID-19 in people with severe renal impairment, including dialysis.

Remdesivir is an antiviral medication that targets the RNA in viruses to prevent replication. The FDA first authorized remdesivir for emergency use in May 2020 to treat people with severe COVID-19. 

When it was authorized:

Full approval was granted in October 2020. (It was first authorized in May 2020 for critically ill patients who were being treated with oxygen for COVID-19.) The authorization was later expanded to include other groups, and it was authorized to treat non-hospitalized patients in January 2022.

Who can get it: Fully approved for children and adults who are at high risk for severe disease. Infants and children must be at least 28 days old, weigh over 6.5 pounds or more, and be either hospitalized or at high risk for severe illness.

How you take it: Via injection or IV and administered only in a health care setting by a health care professional. For outpatients, the treatment is a three-day course of infusions that must be initiated within seven days of symptom onset.

Side effects: Nausea is the most common side effect. Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed following treatment. There is insufficient data on the safety of using remdesivir in pregnant women or women who are breastfeeding; patients should speak with their health care provider.

A March 2022 study in Frontiers identified a significant association between AKI (acute kidney injury) and remdesivir in COVID-19 patients using data from the Vaccine Adverse Event Reporting System, especially in older male patients and those aged 65 and older.

A May 2021 pharmacovigilance analysis found that “compared with the use of chloroquine, hydroxychloroquine, dexamethasone, sarilumab, or tocilizumab, the use of remdesivir was associated with an increased reporting of kidney disorders.”

As part of the same analysis, researchers assessed 5,532 reports related to COVID-19 patients from the WHO’s database, identifying 434 cases related to kidney disorders, including 327 reported with remdesivir.

Remdesivir treatment was discontinued shortly after kidney disorder onset, with a median treatment duration of three days. In 316 cases, no other drug was suspected in the onset of kidney disorders. Reactions were serious in 301 cases (92 percent), and 15 patients died. Acute kidney injury presented in 295 cases, with tubular necrosis in eight cases.

“Our findings, based on postmarketing real-life data from >5000 COVID-19 patients, support that kidney disorders, almost exclusively AKI, represent a serious, early, and potentially fatal adverse drug reaction of remdesivir,” the study concluded. “These results are consistent with findings from another group.”

Although the researchers said further data was needed to confirm the safety signal, they urged physicians to be aware of the potential risk of kidney problems and to perform “close kidney monitoring” when prescribing remdesivir.

How it works: Administered intravenously to patients who are in the hospital or in an ambulatory setting, the drug inserts itself into new viral genes to block replication of the virus, shortening the time it takes seriously ill patients to recover. A number of experts believe that the drug may work best early in the course of an infection.

How well it works: 87% reduction in risk of hospitalization in non-hospitalized patients given a three-day course, according to a study published in The New England Journal of Medicine in December 2021.

What else you should know: For hospitalized patients, research in early 2020 showed that the therapy reduced length of stay (the number of days in the hospital) from 15 days to 12. However, questions have been raised about remdesivir’s trial results for hospitalized patients. 

This is one of two NIH-preferred therapies (after Paxlovid) for COVID-19.

More information: Gilead remdesivir fact sheet for patients.

Bebtelovimab (Monoclonal Antibody)

Bebtelovimab is an US FDA-authorized investigational monoclonal antibody treatment that was developed by Eli Lilly. 

Is bebtelovimab effective against omicron? Data showing bebtelovimab’s efficacy against Omicron and its BA.2 subvariant prompted the FDA to authorize the drug through an EUA. 

However, a lab study published in December 2022 (NEJM) using the live-virus neutralization assay revealed that most of the monoclonal antibodies (including bebtelovimab) may not be effective against BQ.1.1 or XBB in the clinical setting. The latest NIH Treatment guidelines (Dec 28, 2022) have also removed Bebtelovimab from the recommendations for "Non-hospitalized Adults With Mild to Moderate COVID-19 Who Do Not Require Supplemental Oxygen".

monoclonal antibodies
Credit: Design Cells/SPL

The COVID-19 Treatment Guidelines Panel’s Statement on Therapeutic Management of Non-hospitalized Adults With Mild to Moderate COVID-19 Who Do Not Require Supplemental Oxygen (Last Updated: July 21, 2023)

This statement contains the Panel’s recommendations for treating these non-hospitalized patients using the currently available therapies.

For Patients Who Are at High Risk of Progressing to Severe COVID-19 (R)
Preferred therapies. Listed in order of preference:
  • Ritonavir-boosted nirmatrelvir (Paxlovid)
  • Remdesivir
Alternative therapy. For use ONLY when neither of the preferred therapies are available, feasible to use, or clinically appropriate. Listed in alphabetical order:
  • Molnupiravir
Note: Bebtelovimab was recommended in the previous version but now has been removed.

Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB | NEJM (Dec 2022)

A lab study published in December 2022 (NEJM) using the live-virus neutralization assay revealed that most of the monoclonal antibodies may not be effective against BQ.1.1 or XBB in the clinical setting.

Overall, the study data also revealed that the three antiviral drugs remdesivir, molnupiravir, and nirmatrelvir (Paxlovid) may still have therapeutic value against the omicron subvariants BQ.1.1 and XBB.

According to the authors:

"...These results suggest that imdevimab–casirivimab, tixagevimab–cilgavimab, sotrovimab, and bebtelovimab may not be effective against BQ.1.1 or XBB in the clinical setting...These results suggest that remdesivir, molnupiravir, and nirmatrelvir are efficacious against both BQ.1.1 and XBB in vitro..."

Emergency warning signs

Individuals are reminded to seek immediate medical attention (go to a hospital’s emergency department) if they develop emergency warning signs of COVID-19 such as:
  • Difficulty breathing
  • Persistent pain or pressure in the chest
  • Bluish lips or face
  • New confusion or inability to arouse
Hospital's emergency department is open 24/7. Do not wait till the next morning.

Key Takeaways

If you are experiencing symptoms of COVID-19 and think you are eligible for a treatment, you can visit the government Test-to-Treat Locator. You can use the site to search for places near you where you can fill a COVID-19 prescription or identify sites that provide testing, medical care, and COVID-19 medications.

The important key takeaway is 'early' treatment. As anti-virals, Paxlovid, Remdesivir and Molnupiravir all need to be given early (within five days of symptoms appearing) for better effectiveness.

That said you should never attempt to self medicate without the guidance of a licensed medical provider. If you are not a medical doctor, you are likely to find the above information overwhelming and complicated. The aim of this article is to empower you with a better understanding of the options available and to discuss the options with your medical doctor.


Information provided in this article 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 trusted health care provider with any questions you have regarding a medical condition.  


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