FDA Authorizes Emergency Use of Oral Antiviral Paxlovid for Mild to Moderate COVID-19

The Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for Paxlovid (nirmatrelvir tablets co-packaged with ritonavir tablets for oral use) for the treatment of mild to moderate COVID-19 in patients 12 years of age and older weighing at least 40kg with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Paxlovid consists of nirmatrelvir and low-dose ritonavir. Nirmatrelvir inhibits the viral replication of SARS-CoV-2 by blocking the activity of the SARS-CoV-2-3CL protease. Coadministration with low-dose ritonavir slows the metabolism of nirmatrelvir and prolongs its activity. 

The EUA was supported by data from the phase 2/3 EPIC-HR study (ClinicalTrials.gov Identifier: NCT04960202), which compared the efficacy and safety of Paxlovid to placebo in patients with laboratory-confirmed diagnosis of SARS-CoV-2 infection within a 5-day period with mild to moderate symptoms. Final trial results showed that Paxlovid significantly reduced the risk of COVID-19-related hospitalization or death from any cause within 3 and 5 days of symptom onset. There were no deaths reported in the Paxlovid arm and 12 deaths in the placebo arm.

The most common adverse reactions reported with Paxlovid were dysgeusia, diarrhea, hypertension, and myalgia. Paxlovid is not recommended for patients with severe renal (eGFR <30mL/min) or hepatic impairment (Child-Pugh Class C). Additionally, coadministration with potent CYP3A inducers, as well as drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions, is contraindicated.

The authorized dose for Paxlovid is 300mg of nirmatrelvir (two 150mg tablets) with 100mg of ritonavir (one 100mg tablet) for a total of 3 tablets taken together orally twice daily for 5 days. The treatment course should be initiated as soon as a diagnosis of COVID-19 has been made, and within 5 days of symptom onset. Prescriptions should specify the numeric dose of each active ingredient within Paxlovid.

Paxlovid is supplied in cartons containing 30 tablets divided in 5 daily-dose blister cards; each daily blister card contains 4 nirmatrelvir tablets (150mg each) and 2 ritonavir tablets (100mg each) and indicates which tablets need to be taken in the morning and evening.

Paxlovid is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19; for use as preexposure or postexposure prophylaxis for prevention of COVID-19; or for use for longer than 5 consecutive days.

Additional information on the use of Paxlovid can be found in the fact sheet.

“This breakthrough therapy, which has been shown to significantly reduce hospitalizations and deaths and can be taken at home, will change the way we treat COVID-19, and hopefully help reduce some of the significant pressures facing our healthcare and hospital systems,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “Pfizer stands ready to begin delivery in the US immediately to help get Paxlovid into the hands of appropriate patients as quickly as possible.”

The Company plans to file a New Drug Application with the FDA for full regulatory approval in 2022.

References

1. Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19. News release. US Food and Drug Administration. Accessed December 22, 2021. https://www.prnewswire.com/news-releases/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-for-treatment-of-covid-19-301449970.html.
2. Pfizer receives US FDA Emergency Use Authorization for novel COVID-19 oral antiviral treatment. News release. December 22, 2021.  https://www.businesswire.com/news/home/20211221005795/en/Pfizer-Receives-U.S.-FDA-Emergency-Use-Authorization-for-Novel-COVID-19-Oral-Antiviral-Treatment.
3. Paxlovid fact sheet for health care providers. Accessed December 22, 2021. https://www.fda.gov/media/155050/download.