Vaccine Info

PAXLOVID Oral Antiviral

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Last reviewed
October 21, 2023
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PAXLOVID™ Oral Antiviral

Pfizer Inc. Paxlovid™ (nirmatrelvir, BexovidritonavirPF-07321332) is an Aprroved oral antiviral targeting the SARS-CoV-2 beta coronavirus to prevent COVID-19. Paxlovid is packaged with nirmatrelvir and ritonavir, a strong cytochrome P450 (CYP) 3A4 inhibitor. Nirmatrelvir, a novel main protease (Mpro) inhibitor originating in Pfizer's laboratories, is specifically designed to block the activity of the SARS-CoV-2 Mpro, an enzyme the novel coronavirus needs to replicate. It is an analog of GC373, where the aldehyde covalent cysteine acceptor replaced a nitrile

Paxlovid works intracellularly, inhibiting viral replication at a stage known as proteolysis, which occurs before viral RNA replication. Protease inhibitors bind to a viral enzyme, preventing the virus from replicating in the cell. A study published on March 29, 2023, concluded multiple single amino acid changes in Mpro confer resistance to nirmatrelvir (the active component of Paxlovid). 

Pfizer developed PF-07321332 by modifying PF-07304814 (Lufotrelvir), a covalent inhibitor. PF-07321332 is also a covalent inhibitor, but its warhead is a phosphate prodrug, a hydroxyketone. Paxlovid is co-administration with a low dose of ritonavir, a strong cytochrome P450 (CYP) 3A inhibitor, to slow the metabolism or breakdown of Paxlovid and to remain active in the body for more extended periods at higher concentrations to help combat the virus. In preclinical studies, PF-07321332 did not demonstrate evidence of mutagenic DNA interactions. However, Paxlovid has complex drug-drug interactions, primarily due to the ritonavir component.

Paxlovid became the first orally administered coronavirus-specific investigational protease inhibitor authorized under Emergency Use Authorization (EUA) for certain adults and children by the U.S. Food and Drug Administration (FDA) on December 22, 2021. Then, on January 28, 2022, the European Medicines Agency (EMA) and European Commission granted Pfizer Europe MA EEIG marketing authorization EMEA/H/C/005973 for adults. As a result, effective from Feb. 10, 2022, Paxlovid was added as a first-line treatment option for patients with hospital-onset COVID-19 infection in the United Kingdom (U.K.). The FDA issued its Approval on May 25, 2023.

The World Health Organization (WHO) strongly recommended Paxlovid for mild and moderate COVID-19 patients at the highest risk of hospital admission, calling it the best therapeutic choice for high-risk patients as of April 22, 2022. Paxlovid treatment should be initiated within days of disease symptom onset, says the U.S. NIH and the U.S. Centers for Disease Control and Prevention (CDC) on December 5, 2022. On December 20, 2022, Pfizer Inc.   announced that the U.S. FDA extended the review period for the New Drug Application (NDA) of PAXLOVID, which remains available to eligible U.S. patients under an EUA. On February 1, 2023, the FDA issued a revised EUA #105.

Please see the EUA Prescribing Information available at fda.gov and COVID19oralRx.com. Chemical Formula: C23H32F3N5O4; DrugBank Accession Number DB16691; CAS Number 2628280-40-8; PubChem CID 155903259; Molecular Weight: 499.5. Contact COVID19Therapeutics@hhs.​gov with any questions. To learn more, please visit New York-based Pfizer Inc. at www.Pfizer.com. (NYSE: PFE).

PAXLOVID Availability 2023

As of October 2023, 16,929,933 Paxlovid orders had been placed, and 10,443,892 courses had been administered in the U.S.

Paxlovid (Bexovid, nirmatrelvir, ritonavir) was authorized by about 65 countries, including Australia, Bahrain, Canada, ChinaEuropeIsrael, JapanGreeceSingapore, South AfricaSouth Korea, Switzerland, the United Kingdom, MalaysiaOntario, Quebec, New Brunswick, the Philippines, Taiwan, Malaysia, and Mexico. Pfizer expects a 58% reduction in 2023-distribution-related revenues. On October 13, 2023, the U.S. Department of Health and Human Services (HHS), announced that HHS and Pfizer have reached an agreement that extends patient access to Paxlovid, maximizes taxpayer investment, and begins Paxlovid's transition to the commercial market in November 2023. 

PAXLOVID Price

During the U.S. FDA Emergency Use Authorization, PAXLOVID™, there is no price to the patient; however, there may be related service fees. The original Paxlovid price without insurance was about $530. Additional Paxlovid price and discount information is posted at InstantRx™.

PAXLOVID Rebound

The JAMA Network published a study based in Japan on December 6, 2022, focused on the Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir, which found viral rebound was uncommon in adults with COVID-19 after treatment with nirmatrelvir-ritonavir. A total of 13 studies involving 186,306 patients were identified in the final analysis published on September 30, 2022. This research shows that the overall Odds Ration of rebound among COVID-19 patients in the Paxlovid vs. control group was 0.99 (95% CI, 0.28-3.57; I2 =59%), P =0.99. The U.S. FDA acknowledged cases on May 4, 2022, stating it 'was aware of the reports of some patients developing recurrent COVID-19 symptoms after completing a treatment course of Paxlovid.' 

PAXLOVID Drug Interactions

In its clinical guidance published on October 4, 2023, the U.S. CDC urges health providers to be aware of Paxlovid's potential for drug interactions. The drug carries a boxed warning about significant drug interactions. NIH treatment guidelines urge clinicians to carefully review patients’ medications. As of December 30, 2022, Medscape identifies 44 Paxlovid drug interactions. Pfizer confirms PAXLOVID is contraindicated in patients with a history of clinically significant hypersensitivity reactions to its active ingredients (nirmatrelvir or ritonavir) or any other components of the product and with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. Before prescribing ritonavir-boosted nirmatrelvir, clinicians should carefully review the patient's concomitant medications, including over-the-counter medicines, herbal supplements, and recreational drugs, says the U.S. NIH. The FDA provided additional guidance on June 3, 2022, to help prescribers evaluate potential drug interactions when using Paxlovid therapy for COVID-19. On February 24, 2022, the NIH published 'Ritonavir-boosted nirmatrelvir (Paxlovid) has significant and complex drug-drug interaction potential, primarily due to the ritonavir component of the combination. Clinicians who are not experienced in prescribing ritonavir-boosted drugs should refer to resources such as the EUA fact sheet for ritonavir-boosted nirmatrelvir (Paxlovid) and the Liverpool COVID-19 Drug Interactions website for additional guidance.

PAXLOVID Ingredients

The two active substances of the medicine, PF-07321332 and ritonavir, are available as separate tablets. The EMA confirmed: (1R,2S,5S)-N-((1S)-1-Cyano-2-((3S)-2-oxopyrrolidin-3-yl)ethyl)-3-((2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido) butanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide; ritonavir.

PAXLOVID Dosage

Please see Full EUA Prescribing Information at COVID19oralRx.com.

PAXLOVID Indication

PAXLOVID oral antiviral therapy prevents the SARS-CoV-2 virus from replicating in human host cells.

PAXLOVID Generic

Under the terms of the head license agreement between Pfizer and MPP, announced on November 16, 2021, qualified generic medicine manufacturers worldwide that are granted sub-licenses will be able to supply PF-07321332 in combination with ritonavir to 95 countries, covering up to approximately 53% of the world's population. This agreement was expanded on March 17, 2022, to include 35 companies. Beximco Pharma markets Paxlovid under the brand name Bexovid, initially in Bangladesh. Manila confirmed on March 10, 2022, that it authorized Bexovid for those aged 12 and above.

Paxlovid News 2023

May 2, 2023 - The Company announced Paxlovid revenues were approximately $8 billion, down 58% from 1Q 2022 results.

Paxlovid Clinical Trials

For PAXLOVID data, visit clinicaltrials.gov.