Remdesivir vs. Paxlovid - Compare COVID-19 Antiviral Treatments

Remdesivir vs. Paxlovid: How These COVID-19 Treatments Compare

Remdesivir and Paxlovid are two antiviral medications that have emerged as important tools for treating COVID-19.

Remdesivir was one of the first COVID-19 treatments to receive emergency use authorization from the FDA. Originally developed to treat hepatitis C, remdesivir inhibits viral replication and has been shown to shorten recovery time in hospitalized patients.

Paxlovid is a newer antiviral COVID-19 treatment made by Pfizer. It consists of nirmatrelvir and ritonavir, two medications that work together to stop the virus from replicating. Clinical trials have found Paxlovid highly effective at preventing hospitalization and death when given shortly after the onset of symptoms.

Understanding the key differences between remdesivir and Paxlovid can help inform treatment decisions. This article provides an in-depth comparison of these two antiviral medications for COVID-19.

Mechanisms of Action

Remdesivir and Paxlovid work in different ways to fight SARS-CoV-2, the virus that causes COVID-19.

Remdesivir

Remdesivir is a prodrug, meaning it is an inactive compound that transforms into its active form inside the body. It belongs to a class of antiviral drugs called nucleotide analogues.

Once inside cells, remdesivir is converted to its active form, called remdesivir triphosphate. This molecule mimics some of the building blocks of RNA.

When SARS-CoV-2 copies its RNA genetic material, remdesivir gets incorporated into the new viral RNA strands. This inserts errors into the virus’s genome, preventing it from properly replicating.

Paxlovid

Paxlovid combines two antiviral medications – nirmatrelvir and ritonavir.

Nirmatrelvir blocks the activity of a SARS-CoV-2 enzyme called protease. This enzyme allows new viral particles to separate and mature after being assembled.

By inhibiting protease, nirmatrelvir prevents the virus from proliferating in the body.

Ritonavir acts to boost and prolong the effects of nirmatrelvir. It inhibits enzymes that would break down nirmatrelvir, allowing the drug to remain active for longer.

Together, nirmatrelvir and ritonavir reduce viral load and stop SARS-CoV-2 from replicating.

Effectiveness

Clinical trials have found both remdesivir and Paxlovid effective for treating COVID-19, but in different ways.

Remdesivir

Remdesivir has been studied in hospitalized patients with COVID-19 pneumonia. Results show that it modestly shortens recovery time in this population:

• A 5-day course reduced recovery time from 15 days to 10 days in one study.
• Another trial found patients recovered 4 days faster with remdesivir compared to placebo.

Based on these findings, remdesivir was granted emergency use authorization by the FDA for treatment of hospitalized COVID-19 patients in May 2020.

However, remdesivir does not appear to affect mortality risk. Multiple studies found no statistically significant difference in death rates between patients given remdesivir versus standard care.

Paxlovid

Clinical trials evaluated Paxlovid in non-hospitalized adults at high risk of severe COVID-19, such as the elderly and those with chronic conditions. Results showed:

• Paxlovid cut hospitalization and death rates by around 90% when started within 3–5 days of symptoms appearing.
• Only 0.8% of patients receiving Paxlovid were hospitalized, compared to 6.3% given placebo.
• There were zero deaths among those treated with Paxlovid, versus 9 deaths in the placebo group.

Based on its ability to prevent COVID-19 hospitalization and death, the FDA issued an emergency use authorization for Paxlovid in December 2021.

Overall, Paxlovid appears more effective than remdesivir when given shortly after symptom onset. However, the two drugs have not been directly compared in clinical trials.

Treatment Course

Remdesivir and Paxlovid involve different treatment courses:

Remdesivir

Remdesivir is given intravenously (IV) to hospitalized patients. The standard dosing regimen is:

• 200 mg IV on day 1
• 100 mg IV daily for 4 days

The full course takes 5 days. Patients with severe COVID-19 may be treated for up to 10 days.

Paxlovid

Paxlovid is taken orally in pill form. The treatment course is:

• 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days

Patients take 3 pills in the morning and 3 pills 12 hours later. The 5-day course involves a total of 30 pills.

Paxlovid must be started within 5 days of symptom onset for maximum effectiveness.

Side Effects

The side effect profiles of remdesivir and Paxlovid differ somewhat.

Remdesivir

In clinical trials, the most common side effects of remdesivir included:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Elevated liver enzymes
• Rash

Serious side effects like respiratory failure and acute kidney injury have occurred in some patients, although it’s unclear if remdesivir was the cause.

Remdesivir may cause severe allergic reactions in some people. Patients receive premedications like steroids and antihistamines prior to each infusion to reduce this risk.

Paxlovid

The most common side effects of Paxlovid are altered sense of taste and diarrhea. Other possible side effects include:

• Vomiting
• Headache
• Muscle pain
• High blood pressure
• Back pain

Ritonavir can interact with many medications. Paxlovid cannot be taken along with certain blood thinners, statins, antidepressants, and anti-seizure and anti-arrhythmia drugs.

Cost and Availability

The costs and availability of remdesivir compared to Paxlovid also differ.

Remdesivir

Remdesivir is administered intravenously in the hospital. The drug itself is covered under government emergency programs, but patients may face costs for IV administration and hospitalization.

Remdesivir is approved for use in adults and children ages 12 years and older who weigh at least 88 pounds (40 kg).

Paxlovid

Paxlovid is free to patients under the U.S. government COVID-19 treatment program. For those without insurance, Pfizer offers the drug for free under its patient assistance program.

Paxlovid is authorized for use in adults and children ages 12 years and older who weigh at least 88 pounds (40 kg). It has not yet been approved for younger children.

Due to initially limited supply, Paxlovid was prioritized for those at highest risk of COVID-19 complications in the first months after its authorization. However, availability has increased significantly since early 2022.

Key Differences Between Remdesivir and Paxlovid

To summarize, here are some of the key differences between these two COVID-19 antiviral treatments:

Mechanisms

• Remdesivir mimics the RNA building blocks of SARS-CoV-2, inserting errors into viral genomes.
• Paxlovid blocks viral protease needed for replication and uses ritonavir to remain active longer.

Use

• Remdesivir is given intravenously to hospitalized patients.
• Paxlovid is taken orally for 5 days soon after symptom onset.

Effectiveness

• Remdesivir may shorten recovery but doesn’t affect mortality.
• Paxlovid dramatically reduces hospitalization and death in high-risk patients.

Side Effects

• Remdesivir may cause nausea, elevated liver enzymes, and allergic reactions.
• Paxlovid sometimes causes altered taste and diarrhea.

Age

• Remdesivir is authorized for adults and children 12+ years weighing over 88 lbs (40 kg).
• Paxlovid is authorized for adults and children 12+ years weighing over 88 lbs (40 kg). Not yet approved for younger kids.

In general, remdesivir is given to sicker, hospitalized patients to shorten recovery time, while Paxlovid is used in higher-risk outpatients to prevent hospitalization and death.

Who Should Get Remdesivir or Paxlovid?

Treatment guidelines help identify which COVID-19 patients are most appropriate for remdesivir versus Paxlovid.

Remdesivir

Current guidelines recommend remdesivir for:

• Hospitalized COVID-19 patients on supplemental oxygen
• Hospitalized patients not on oxygen with high risk factors for disease progression

Remdesivir may provide modest benefit for these patients but does not appear to reduce mortality.

Paxlovid

Paxlovid is recommended for high-risk individuals who test positive for COVID-19 but are not hospitalized, including:

• Unvaccinated seniors ages 65+ years
• People with medical conditions like heart disease, diabetes, obesity, and weakened immune systems
• Those with moderate-severe immune-compromising conditions

Paxlovid provides major reductions in hospitalization and death for these higher-risk groups when started quickly after symptom onset.

Other Considerations

Some other factors may inform treatment decisions, such as:

• Supply availability
• Route of administration
• Risk of drug interactions
• Patient preferences

Providers also consider evolving real-world evidence and the emergence of new variants when deciding to use antiviral therapies.

Future Outlook

Remdesivir and Paxlovid have played pivotal roles in COVID-19 treatment. However, new antivirals continue to emerge.

Other antiviral medications like molnupiravir have received authorization for certain patient groups. Some experts believe combination antiviral therapy may offer advantages in the future.

Researchers are also working on next-generation drugs that may improve on current options. For example, new protease inhibitors are in development to overcome potential resistance.

As the pandemic situation evolves, treatment guidelines will continue to adapt. But remdesivir and Paxlovid are likely to remain important tools in the fight against COVID-19.

Prompt antiviral treatment can help prevent severe COVID-19 outcomes. Stay up to date on the latest therapeutic options and get assessed rapidly if you develop symptoms.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional before starting any new treatment regimen.