COVID Early Home Treatment: Paxlovid becomes 1st US-authorized home COVID treatment

U.S. health regulators authorized the first oral pill against COVID-19 in December 2021 (Associated Press), a Pfizer drug that Americans will be able to take at home to head off the worst effects of the virus.

Authorization was based on results from EPIC-HR, a randomized, placebo-controlled treatment trial in adult outpatients with mild-to-moderate COVID who were at high risk for progression to severe disease.

What's New: Paxlovid vs Monoclonal Antibodies: What's the Difference?

The latest (last updated: April 8, 2022) NIH guidelines recommended Paxlovid as the no. 1 preferred therapy for non-hospitalized patients.

The drug, Paxlovid (ritonavir-boosted nirmatrelvir), is a faster, cheaper way to treat early COVID-19 infections, though initial supplies will be extremely limited. All of the previously authorised drugs against the disease require an IV (intravenous) or an injection.

Locations in the USA that may have Paxlovid available can be found at: https://covid-19-therapeutics-locator-dhhs.hub.arcgis.com.

Paxlovid is also no. 8 in this COVID treatment league table:

“The efficacy is high, the side effects are low and it’s oral. It checks all the boxes,” said Dr. Gregory Poland of the Mayo Clinic. “You’re looking at a 90% decreased risk of hospitalization and death in a high-risk group — that’s stunning.”

The Food and Drug Administration authorized Pfizer’s drug for adults and children ages 12 and older with a positive COVID-19 test and early symptoms who face the highest risks of hospitalization. That includes older people and those with conditions like obesity and heart disease. Children eligible for the drug must weigh at least 88 pounds (40 kilograms).

The pills from both Pfizer and Merck are expected to be effective against omicron because they don’t target the spike protein where most of the variant’s worrisome mutations reside.

Pfizer currently has 180,000 treatment courses available worldwide, with roughly 60,000 to 70,000 allocated to the U.S. Federal health officials are expected to ration early shipments to the hardest hit parts of the country. Pfizer said the small supply is due to the manufacturing time — currently about nine months. The company says it can halve production time next year.

The U.S. government has agreed to purchase enough Paxlovid to treat 10 million people. Pfizer says it’s on track to produce 80 million courses globally next year, under contracts with the U.K., Australia and other nations.

Health experts agree that vaccination remains the best way to protect against COVID-19. But with roughly 40 million American adults still unvaccinated, effective drugs will be critical to blunting the current and future waves of infection.

The U.S. is reporting more than 140,000 new infections daily and federal officials warn that the omicron variant could send case counts soaring. Omicron has already whipped across the country to become the dominant strain.

Against that backdrop, experts warn that Paxlovid’s initial impact could be limited.

For more than a year, biotech-engineered antibody drugs have been the go-to treatments for COVID-19. But they are expensive, hard to produce and require an injection or infusion, typically given at a hospital or clinic. Also, laboratory testing suggests the two leading antibody drugs (from Regeneron and Eli Lilly) used in the U.S. aren’t effective against omicron.

Pfizer’s pill comes with its own challenges.

Patients will need a positive COVID-19 test to get a prescription. And Paxlovid has only proven effective if given within five days of symptoms appearing. With testing supplies stretched, experts worry it may be unrealistic for patients to self-diagnose, get tested, see a physician and pick up a prescription within that narrow window.

“If you go outside that window of time I fully expect the effectiveness of this drug is going to fall,” said Andrew Pekosz, a Johns Hopkins University virologist.

The FDA based its decision on company results from a 2,250-patient trial that showed the pill cut hospitalizations and deaths by 89% when given to people with mild-to-moderate COVID-19 within three days of symptoms. Less than 1% of patients taking the drug were hospitalized and none died at the end of the 30-day study period, compared with 6.5% of patients hospitalized in the group getting a dummy pill, which included nine deaths.

Pfizer’s drug is part of a decades-old family of antiviral drugs known as protease inhibitors, which revolutionized the treatment of HIV and hepatitis C. The drugs block a key enzyme which viruses need to multiply in the human body.

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 Sheet, Letter 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 Doesn’t Work for Healthier Patients, Pfizer Says (Time.com - June 2022)

Pfizer Inc. plans to stop enrollment in a study of its COVID-19 drug in patients who aren’t at high risk of severe disease after the pill didn’t help alleviate their symptoms, a major setback for broader use of the treatment.

The New York-based drugmaker said Tuesday that it would stop adding new participants to a highly anticipated study testing Paxlovid in a broader population of COVID patients who are at low risk of hospitalization and death. The decision comes after the study failed to demonstrate that the drug reduced COVID symptoms among relatively healthy patients and wasn’t able to show a statistically significant reduction in hospitalization and death.

Since Paxlovid works by blocking a protease enzyme, should I be concerned about taking digestive enzymes that contain proteases? (ConsumerLab)

No, you should not be concerned. The proteases produced by your body and found in digestive enzyme supplements, which help digest protein in foods, are different from the viral protease (3CL) that is needed by coronaviruses to replicate (Zhang, Science 2020) and is the target of the antiviral protease-inhibitor drug Paxlovid. Taking a supplement that contains proteases to digest food is not likely to affect the course of COVID-19 infection or the activity of antiviral drugs.

The COVID-19 Treatment Guidelines Panel’s Statement on Therapies for High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19  (Last Updated: April 8, 2022)

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

The Panel’s recommendations take into account the efficacies of these drugs and the high prevalence of the Omicron VOC. When resources are limited, therapy should be prioritized for patients who are at the highest risk of progressing to severe COVID-19.

The Panel’s current outpatient treatment recommendations are as follows (in order of preference):

Preferred Therapies

• Paxlovid (nirmatrelvir 300 mg plus ritonavir 100 mg) orally twice daily for 5 days
• Remdesivir 200 mg IV on Day 1 followed by remdesivir 100 mg IV on Days 2 and 3

Alternative Therapies

For use only when neither of the preferred therapies are available, feasible to use, or clinically appropriate. Listed in alphabetical order:

• Bebtelovimab (monoclonal antibody from Eli Lilly)
• Molnupiravir 800 mg orally twice daily for 5 days

Notes: 

• Bebtelovimab is active in vitro against all circulating Omicron subvariants, but there are no clinical efficacy data from placebo-controlled trials that evaluated the use of bebtelovimab in patients who are at high risk of progressing to severe COVID-19. Therefore, bebtelovimab should be used only when the preferred treatment options are not available, feasible to use, or clinically appropriate.
• According to GoodRx Health (Jan 26, 2022): 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% in high risk people.