View source for Nirmatrelvir/ritonavir

{{Short description|Antiviral combination medication}}
{{Use American English|date=January 2022}}
{{Use dmy dates|date=February 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| type = combo
| image = PF-07321332.svg
| width = 250
| caption = [[Nirmatrelvir]]
| image2 = Ritonavir structure.svg
| width2 = 250
| caption2 = [[Ritonavir]]

<!-- Combo data -->
| component1 = Nirmatrelvir
| class1 = [[Antiviral drug]]
| component2 = Ritonavir
| class2 = [[CYP3A inhibitor]]; [[Antiviral drug]]

<!-- Clinical data -->
| pronounce = 
| tradename = Paxlovid
| Drugs.com = {{drugs.com|monograph|nirmatrelvir}}
| MedlinePlus = a622005
| DailyMedID = Nirmatrelvir and ritonavir
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Paxlovid APMDS">{{cite web | title=Paxlovid APMDS | website=[[Therapeutic Goods Administration]] (TGA) | date=21 January 2022 | url=https://www.tga.gov.au/resources/auspmd/paxlovid | access-date=5 February 2022 | archive-date=5 February 2022 | archive-url=https://web.archive.org/web/20220205215257/https://www.tga.gov.au/apm-summary/paxlovid | url-status=live }}</ref><ref name="AusPAR: nirmatrelvir/ritonavir" />
| pregnancy_category = Not recommended<ref name="Paxlovid AU PI" />
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = J05
| ATC_suffix = AE30
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="Paxlovid AU PI">{{cite web|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2022-PI-01049-1|title=TGA eBS - Product and Consumer Medicine Information Licence|access-date=5 February 2022|archive-date=5 February 2022|archive-url=https://web.archive.org/web/20220205223700/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2022-PI-01049-1|url-status=live}}</ref><ref name="AusPAR: nirmatrelvir/ritonavir">{{cite web | title=AusPAR: nirmatrelvir/ritonavir | website=[[Therapeutic Goods Administration]] (TGA) | date=25 January 2022 | url=https://www.tga.gov.au/auspar/auspar-nirmatrelvirritonavir | access-date=23 March 2022 | archive-date=24 March 2022 | archive-url=https://web.archive.org/web/20220324045903/https://www.tga.gov.au/auspar/auspar-nirmatrelvirritonavir | url-status=live }}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = Rx-only
| legal_CA_comment = <ref name="Paxlovid CA monograph">{{cite web |url=https://pdf.hres.ca/dpd_pm/00073991.PDF |title=Product Monograph: Paxlovid |archive-url=https://web.archive.org/web/20240107060255/https://pdf.hres.ca/dpd_pm/00073991.PDF |archive-date=7 January 2024 | url-status=live }}</ref><ref>{{cite web | title=Summary Basis of Decision (SBD) for Paxlovid | website=[[Health Canada]] | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00577&lang=en | access-date=29 May 2022 | archive-date=12 June 2022 | archive-url=https://web.archive.org/web/20220612043817/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00577&lang=en | url-status=live }}</ref><ref name="Paxlovid details" />
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref name="Paxlovid SmPC" /><ref name="Regulatory approval of Paxlovid">{{cite web | title=Regulatory approval of Paxlovid | website=[[Medicines and Healthcare products Regulatory Agency]] (MHRA) | date=31 December 2021 | url=https://www.gov.uk/government/publications/regulatory-approval-of-paxlovid | access-date=31 December 2021 | archive-date=11 January 2022 | archive-url=https://web.archive.org/web/20220111184003/https://www.gov.uk/government/publications/regulatory-approval-of-paxlovid | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = and emergency use authorization<ref name="Paxlovid FDA label" /><ref name="Paxlovid FDA EUA label" /><ref name="FDA PR 20211222" /><ref name="fda-factsheet" /><ref name="FDA PR 20230525" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Paxlovid EPAR" /><ref name="Paxlovid PI">{{cite web | title=Paxlovid PI | website=Union Register of medicinal products | date=28 January 2022 | url=https://ec.europa.eu/health/documents/community-register/html/h1625.htm | access-date=24 April 2022 | archive-date=16 May 2022 | archive-url=https://web.archive.org/web/20220516151322/https://ec.europa.eu/health/documents/community-register/html/h1625.htm | url-status=live }}</ref><ref>{{cite web | title=COVID-19 medicines | website=European Medicines Agency (EMA) | date=14 October 2024 | url=https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/coronavirus-disease-covid-19/covid-19-medicines | access-date=14 October 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = Rx-only

<!-- Identifiers -->
| CAS_number = 
| CAS_supplemental =
| PubChem = 
| IUPHAR_ligand =
| DrugBank = 
| ChemSpiderID =
| UNII = 
| KEGG = D12269
| ChEBI = 192712
| ChEMBL = 
| synonyms = 
}}

<!-- Definition and medical uses -->
'''Nirmatrelvir/ritonavir''', sold under the brand name '''Paxlovid''', is a co-packaged [[medication]] used as a [[Treatment and management of COVID-19|treatment]] for [[COVID-19|COVID{{nbhyph}}19]].<ref name="Paxlovid SmPC">{{cite web | title=Summary of Product Characteristics for Paxlovid | website=[[Medicines and Healthcare products Regulatory Agency]] (MHRA) | date=31 December 2021 | url=https://www.gov.uk/government/publications/regulatory-approval-of-paxlovid/summary-of-product-characteristics-for-paxlovid | access-date=31 December 2021 | archive-date=31 December 2021 | archive-url=https://web.archive.org/web/20211231171058/https://www.gov.uk/government/publications/regulatory-approval-of-paxlovid/summary-of-product-characteristics-for-paxlovid | url-status=live }}</ref><ref name="Paxlovid FDA EUA label">{{cite web | title=Paxlovid- nirmatrelvir and ritonavir kit | website=[[DailyMed]] | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bdddfba-bd31-44cb-ba9e-23a4e17a4691 | access-date=30 December 2021 | archive-date=31 December 2021 | archive-url=https://web.archive.org/web/20211231050453/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bdddfba-bd31-44cb-ba9e-23a4e17a4691 | url-status=live }}</ref><ref name="Paxlovid FDA label">{{cite web | title=Paxlovid- nirmatrelvir and ritonavir kit | website=DailyMed | date=18 October 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8a99d6d6-fd9e-45bb-b1bf-48c7f761232a | access-date=6 January 2024 | archive-date=26 February 2024 | archive-url=https://web.archive.org/web/20240226072934/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8a99d6d6-fd9e-45bb-b1bf-48c7f761232a | url-status=live }}</ref><ref name="EUA FAQ">{{cite web|date=1 November 2023|title=Frequently Asked Questions on the Emergency Use Authorization for Paxlovid for Treatment of COVID-19|url=https://www.fda.gov/media/155052/download|format=PDF|publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=6 January 2024|archive-date=7 January 2024|archive-url=https://web.archive.org/web/20240107052414/https://www.fda.gov/media/155052/download |url-status=live}} {{PD-notice}}</ref> It contains the [[antiviral medication]]s [[nirmatrelvir]] and [[ritonavir]] and was developed by [[Pfizer]].<ref name="Paxlovid SmPC" /><ref name="Paxlovid FDA label" /> Nirmatrelvir inhibits [[SARS-CoV-2 main protease]], while ritonavir is a strong [[CYP3A inhibitor]], slowing down nirmatrelvir [[metabolism]] and therefore boosting its effect.<ref name="Paxlovid FDA label" /><ref name="pmid36423149" /> It is taken [[by mouth]].<ref name="Paxlovid FDA label" />

<!-- Effects, side effects and mechanism of action -->
In unvaccinated high-risk people with COVID{{nbhyph}}19, nirmatrelvir/ritonavir can reduce the risk of hospitalization or death by 88% if taken within five days of symptom onset.<ref name="NEJM Hammond" /> People who take nirmatrelvir/ritonavir also test negative for COVID{{nbhyph}}19 about two and a half days earlier than people who do not.<ref>{{cite journal | vauthors = Amani B, Amani B | title = Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID-19: A rapid review and meta-analysis | journal = Journal of Medical Virology | volume = 95 | issue = 2 | pages = e28441 | date = February 2023 | pmid = 36576379 | pmc = 9880713 | doi = 10.1002/jmv.28441 }}</ref> [[Side effect]]s of nirmatrelvir/ritonavir include changes in sense of taste ([[dysgeusia]]), [[diarrhea]], high blood pressure ([[hypertension]]), and muscle pain ([[myalgia]]).<ref name="Paxlovid FDA label" />

<!-- History, society, and culture -->
In December 2021, the United States [[Food and Drug Administration]] (FDA) granted nirmatrelvir/ritonavir [[emergency use authorization]] (EUA) to treat COVID{{nbhyph}}19.<ref name="fda-factsheet">{{cite tech report |title=Fact sheet for healthcare providers: Emergency Use Authorization for Paxlovid |number=LAB-1492-0.8 |publisher=[[Pfizer]] |date=22 December 2021 |url=https://www.fda.gov/media/155050/download |format=PDF |archive-url=https://web.archive.org/web/20211223210430/https://www.fda.gov/media/155050/download |archive-date=23 December 2021 |url-status=live}}</ref><ref name="Pfizer PR 20211222">{{cite press release | title=Pfizer Receives U.S. FDA Emergency Use Authorization for Novel COVID-19 Oral Antiviral Treatment | publisher=[[Pfizer]] | date=22 December 2021 | url=https://www.businesswire.com/news/home/20211221005795/en/Pfizer-Receives-U.S.-FDA-Emergency-Use-Authorization-for-Novel-COVID-19-Oral-Antiviral-Treatment | access-date=22 December 2021 | via=Business Wire | archive-date=22 December 2021 | archive-url=https://web.archive.org/web/20211222175027/https://www.businesswire.com/news/home/20211221005795/en/Pfizer-Receives-U.S.-FDA-Emergency-Use-Authorization-for-Novel-COVID-19-Oral-Antiviral-Treatment | url-status=live }}</ref> It was approved in the United Kingdom later that month,<ref name="MHRA PR 20211231">{{cite press release | title = Oral COVID-19 antiviral, Paxlovid, approved by UK regulator | url = https://www.gov.uk/government/news/oral-covid-19-antiviral-paxlovid-approved-by-uk-regulator | publisher = Medicines and Healthcare products Regulatory Agency | date = 31 December 2021 | access-date = 5 January 2022 | archive-date = 11 January 2022 | archive-url = https://web.archive.org/web/20220111235804/https://www.gov.uk/government/news/oral-covid-19-antiviral-paxlovid-approved-by-uk-regulator | url-status = live }}</ref> and in the European Union and Canada in January 2022.<ref name="Paxlovid EPAR">{{cite web | title=Paxlovid EPAR | website=[[European Medicines Agency]] (EMA) | date=24 January 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/paxlovid | access-date=3 February 2022 | archive-date=11 May 2022 | archive-url=https://web.archive.org/web/20220511124118/https://www.ema.europa.eu/en/medicines/human/EPAR/paxlovid | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="Health Canada PR 20220117">{{cite press release | title=Health Canada authorizes Paxlovid for patients with mild to moderate COVID-19 at high risk of developing serious disease | website=[[Health Canada]] | date=17 January 2022 | url=https://www.canada.ca/en/health-canada/news/2022/01/health-canada-authorizes-paxlovidtm-for-patients-with-mild-to-moderate-covid-19-at-high-risk-of-developing-serious-disease.html | access-date=24 April 2022 | archive-date=29 April 2022 | archive-url=https://web.archive.org/web/20220429032614/https://www.canada.ca/en/health-canada/news/2022/01/health-canada-authorizes-paxlovidtm-for-patients-with-mild-to-moderate-covid-19-at-high-risk-of-developing-serious-disease.html | url-status=live }}</ref><ref>{{cite web | title=Paxlovid | website=COVID-19 vaccines and treatments portal | date=17 January 2022 | url=https://covid-vaccine.canada.ca/info/paxlovid-en.html | access-date=25 April 2022 | archive-date=22 April 2022 | archive-url=https://web.archive.org/web/20220422152439/https://covid-vaccine.canada.ca/info/paxlovid-en.html | url-status=live }}</ref> In May 2023, it was approved in the U.S. to treat mild to moderate COVID{{nbhyph}}19 in adults who are at high risk for progression to severe COVID{{nbhyph}}19, including hospitalization or death.<ref name="FDA PR 20230525">{{cite press release | title=FDA Approves First Oral Antiviral for Treatment of COVID-19 in Adults | website=U.S. [[Food and Drug Administration]] (FDA) | date=26 May 2023 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults | access-date=26 May 2023 | archive-date=28 July 2023 | archive-url=https://web.archive.org/web/20230728235258/https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults | url-status=live }} {{PD-notice}}</ref><ref name="EUA FAQ" /> The FDA considers the combination to be a [[first-in-class medication]].<ref>{{cite report | title=New Drug Therapy Approvals 2023 | website=U.S. [[Food and Drug Administration]] (FDA) | date=January 2024 | url=https://www.fda.gov/media/175253/download | format=PDF | access-date=9 January 2024 | archive-url=https://web.archive.org/web/20240110032419/https://www.fda.gov/media/175253/download | archive-date=10 January 2024 | url-status=live }}</ref> In 2022, it was the 164th most commonly prescribed medication in the United States, with more than 3{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Nirmatrelvir; Ritonavir Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/NirmatrelvirRitonavir | access-date = 30 August 2024 }}</ref>
{{TOC limit|3}}

==Medical uses==
In the United States, nirmatrelvir/ritonavir is [[indicated]] for the treatment of mild-to-moderate COVID{{nbhyph}}19 in adults who are at high risk for progression to severe COVID{{nbhyph}}19, including hospitalization or death.<ref name="Paxlovid FDA label" /><ref name="FDA PR 20230525" /> This includes people above 50, people with diabetes, cancer, coronary artery disease, chronic lung diseases, pregnancy, or on immunosuppressant drugs.<ref name="jama224" />

The co-packaged medication is not authorized or suggested for the [[Pre-exposure prophylaxis|pre-exposure]] or [[Post-exposure prophylaxis|post-exposure prevention]] of COVID{{nbhyph}}19.<ref name="FDA PR 20211222">{{cite press release | title=FDA Authorizes First Oral Antiviral for Treatment of COVID-19 | publisher=U.S. [[Food and Drug Administration]] (FDA) | date=22 December 2021 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19 | access-date=22 December 2021 | archive-date=27 December 2021 | archive-url=https://web.archive.org/web/20211227225836/https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19 | url-status=live }} {{PD-notice}}</ref><ref name="FDA PR 20230525" /><ref>{{cite journal | vauthors = Reis S, Metzendorf MI, Kuehn R, Popp M, Gagyor I, Kranke P, Meybohm P, Skoetz N, Weibel S | title = Nirmatrelvir combined with ritonavir for preventing and treating COVID-19 | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 11 | pages = CD015395 | date = November 2023 | pmid = 38032024 | pmc = 10688265 | doi = 10.1002/14651858.CD015395.pub3 }}</ref>

In the European Union, the co-packaged medication is indicated for the treatment of COVID{{nbhyph}}19 in adults who do not require [[Breathing apparatus|supplemental oxygen]] and who are at increased risk for progressing to severe COVID{{nbhyph}}19.<ref name="Paxlovid EPAR" />

If administered within five days of symptom onset in confirmed COVID{{nbhyph}}19 infections, the [[Intrinsic activity|efficacy]] of the co-packaged medication against hospitalization or death in unvaccinated high-risk adults, as of 2022, was about {{Estimate|88|75|94|unit=%|mini=no}}.<ref name="fda-factsheet" /><ref name="NEJM Hammond">{{cite journal | vauthors = Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, Baniecki M, Hendrick VM, Damle B, Simón-Campos A, Pypstra R, Rusnak JM | title = Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19 | journal = The New England Journal of Medicine | volume = 386 | issue = 15 | pages = 1397–1408 | date = April 2022 | pmid = 35172054 | pmc = 8908851 | doi = 10.1056/NEJMoa2118542 | title-link = doi | doi-access = free }}</ref>

===Pregnancy===
The suggestion of the use of co-packaged medication during pregnancy in people who can become pregnant and are not using contraception and for people who are breastfeeding needs further study.<ref name = "Chourasia_2023">{{cite journal | vauthors = Chourasia P, Maringanti BS, Edwards-Fligner M, Gangu K, Bobba A, Sheikh AB, Shekhar R | title = Paxlovid (Nirmatrelvir and Ritonavir) Use in Pregnant and Lactating Woman: Current Evidence and Practice Guidelines-A Scoping Review | journal = Vaccines | volume = 11 | issue = 1 | pages = 107 | date = January 2023 | pmid = 36679952 | pmc = 9866309 | doi = 10.3390/vaccines11010107 | doi-access = free | title-link = doi }}</ref> Given the risk of morbidity, hospitalization and mortality associated with severe COVID{{nbhyph}}19 disease in females and fetuses, nirmatrelvir/ritonavir can provide an important option to reduce the risks associated with acute COVID{{nbhyph}}19 infection in at-risk and unvaccinated patients after careful consideration of the benefits and risks for each patient.<ref name = "Chourasia_2023" /> There is limited human data on the use of nirmatrelvir during pregnancy related to the risk of birth defects, spontaneous abortions (miscarriage), or adverse outcomes.<ref>{{cite journal | vauthors = Loza A, Farias R, Gavin N, Wagner R, Hammer E, Shields A | title = Short-term Pregnancy Outcomes After Nirmatrelvir-Ritonavir Treatment for Mild-to-Moderate Coronavirus Disease 2019 (COVID-19) | journal = Obstetrics and Gynecology | volume = 140 | issue = 3 | pages = 447–449 | date = September 2022 | pmid = 36356238 | pmc = 9377369 | doi = 10.1097/AOG.0000000000004900 }}</ref> There are no human data on the presence of nirmatrelvir in human milk, or its effects on milk production or the infant.<ref>{{cite web |date=11 May 2022 |title=Pregnancy, breastfeeding and fertility while taking Paxlovid |url=https://www.nhs.uk/medicines/paxlovid/pregnancy-breastfeeding-and-fertility-while-taking-paxlovid/ |access-date=16 November 2023 |website=[[National Health Service]] |archive-date=12 November 2023 |archive-url=https://web.archive.org/web/20231112153502/https://www.nhs.uk/medicines/paxlovid/pregnancy-breastfeeding-and-fertility-while-taking-paxlovid/ |url-status=live }}</ref> A temporary reduction in body weight was observed in the offspring of nursing rats.<ref name="fda-factsheet"/> Other observational studies have also demonstrated the safety of ritonavir during pregnancy.<ref>{{cite journal | vauthors = Pasley MV, Martinez M, Hermes A, d'Amico R, Nilius A | title = Safety and efficacy of lopinavir/ritonavir during pregnancy: a systematic review | journal = AIDS Reviews | volume = 15 | issue = 1 | pages = 38–48 | date = 2013 | pmid = 23449228 }}</ref>

==Contraindications==
The medication is contraindicated in those with [[hypersensitivity]] to either of the two main components, and in those with severely reduced kidney or liver function.<ref name="fda-factsheet"/> Co-administration with certain drugs may have serious, sometimes fatal, effects.<ref>{{cite web |title=Ritonavir-Boosted Nirmatrelvir (Paxlovid) |url=https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ritonavir-boosted-nirmatrelvir--paxlovid-/ |publisher=[[National Institutes of Health]] |date=24 February 2022 |access-date=25 April 2022 |archive-url=https://web.archive.org/web/20220423232602/https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ritonavir-boosted-nirmatrelvir--paxlovid-/ |archive-date=23 April 2022 |url-status=live }}</ref>

==Side effects==
Nirmatrelvir/ritonavir has a high potential for potentially serious [[drug interaction]]s due to strong [[CYP3A]] [[enzyme inhibitor|inhibition]] by ritonavir.<ref name="Paxlovid FDA label" /><ref name="pmid36423149" /> The US FDA label, the FDA fact sheet, and the FDA EUA contain a [[boxed warning]] about the CYP3A inhibition.<ref name="Paxlovid FDA label" /><ref name="FDA PR 20230525" />

Adverse events of the co-packaged medication, regardless of causality, observed in the [[Phases of clinical research|phase II-III]] EPIC-HR study included [[dysgeusia]] (6% vs. <&nbsp;1% for [[placebo]]), [[diarrhea]] (3% vs. 2% for placebo), [[hypertension]] (1% vs. <&nbsp;1% for placebo), and [[myalgia]] (1% vs. <&nbsp;1% for placebo).<ref name="Paxlovid FDA label" /><ref name="fda-factsheet"/><ref name="ema-advice"/> In clinical trials, 2% of people discontinued treatment due to side effects with nirmatrelvir/ritonavir while 4% in the placebo group did so.<ref name="Paxlovid FDA label" /> Nirmatrelvir/ritonavir is under investigation, so its side effects have yet to be fully evaluated and may not be completely known.<ref name="pmid36423149" />

Other side effects of nirmatrelvir/ritonavir may include [[hypersensitivity reaction]]s, [[liver toxicity]], and development of [[HIV drug resistance]] in people with uncontrolled or undiagnosed [[HIV infection]].<ref name="Paxlovid FDA label" /><ref name="pmid36423149" /> Hypersensitivity reactions (allergic reactions) may manifest as [[skin rash]], [[hives]], [[difficulty swallowing]], [[difficulty breathing]], [[angioedema]], and/or [[anaphylaxis]].<ref name="Paxlovid FDA label" /><ref name="pmid36423149" /> Liver toxicity may manifest as [[elevated transaminases]] and clinical [[hepatitis]], including symptoms like [[appetite loss]], [[jaundice]] (yellowing of the skin and whites of eyes), [[dark-colored urine]], [[pale-colored stools]], [[itchy skin]], and [[abdominal pain]].<ref name="Paxlovid FDA label" /><ref name="pmid36423149" />

== Interactions ==

Co-administration of nirmatrelvir/ritonavir with certain drugs is contraindicated, including drugs dependent on [[CYP3A]] for removal, for which a raised concentration results in serious reactions, or those with potent CYP3A [[inducer]]s, for which reduced blood concentration of the two main components may result in loss of effect against the virus and possible resistance, among others.<ref name="Paxlovid FDA label" /> Co-administration also affects the concentration of several drugs, sometimes requiring changing the dose or careful monitoring.<ref name="fda-factsheet"/><ref name="ema-advice">{{cite press release |title=EMA issues advice on use of Paxlovid (PF-07321332 and ritonavir) for the treatment of COVID-19: rolling review starts in parallel |url=https://www.ema.europa.eu/en/news/ema-issues-advice-use-paxlovid-pf-07321332-ritonavir-treatment-covid-19-rolling-review-starts|publisher=[[European Medicines Agency]] (EMA) |date=16 December 2021 |archive-date=11 January 2022 |archive-url=https://web.archive.org/web/20220111183944/https://www.ema.europa.eu/en/news/ema-issues-advice-use-paxlovid-pf-07321332-ritonavir-treatment-covid-19-rolling-review-starts |url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Many of these drugs are widely prescribed to people at high risk from COVID{{nbhyph}}19.<ref>{{cite news |title=Pfizer antiviral pills may be risky with other medications |url=https://www.nbcnews.com/health/health-news/pfizer-covid-pills-covid-symptoms-may-risky-drugs-rcna9683 |access-date=4 February 2022 |work=ABC News |date=26 December 2021 |archive-date=3 February 2022 |archive-url=https://web.archive.org/web/20220203171405/https://www.nbcnews.com/health/health-news/pfizer-covid-pills-covid-symptoms-may-risky-drugs-rcna9683 |url-status=live }}</ref> With the extension of the emergency authorization in August 2022, the FDA updated a checklist to help evaluate potential drug interactions and other patient factors before prescribing Paxlovid, including more than 120 drugs that are contraindicated, should be avoided or held from use, or require dose adjustments or special monitoring.<ref>{{cite web |date=26 August 2022 |title=Paxlovid Patient Eligibility Screening Checklist and Drug Interaction Tool |url=https://www.fda.gov/media/158165 |access-date=10 October 2022 |website=U.S. [[Food and Drug Administration]] (FDA) |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010134205/https://www.fda.gov/media/158165 |url-status=live }}</ref><ref name="fda-factsheet" />

Nirmatrelvir/ritonavir is safe to use in combination with [[over-the-counter]] [[analgesic|pain-]] and [[antipyretic|fever-reducing]] medications such as [[paracetamol]] (acetaminophen) and [[ibuprofen]].<ref name="Drugs.com-2022">{{cite web | title = Should I take Paxlovid after a Positive COVID-19 Test? | date = 13 November 2022 | website = drugs.com | url = https://www.drugs.com/insights/paxlovid-after-positive-covid-19-test-3571219/ | access-date = 7 December 2022 | archive-date = 7 December 2022 | archive-url = https://web.archive.org/web/20221207042138/https://www.drugs.com/insights/paxlovid-after-positive-covid-19-test-3571219/ | url-status = live }}</ref>

==Pharmacology==
Nirmatrelvir is responsible for the [[antiviral]] activity against [[SARS-CoV-2]], while ritonavir works by inhibiting the [[metabolization]] of nirmatrelvir in the liver, strengthening its activity.<ref name="Paxlovid FDA label" /><ref name="pmid36423149" />

===Pharmacodynamics===
Nirmatrelvir is a [[SARS-CoV-2 main protease]] (M<sup>pro</sup>, 3CL<sup>pro</sup>, nsp5 protease) [[enzyme inhibitor|inhibitor]] while ritonavir is an [[HIV-1 protease]] [[protease inhibitor (pharmacology)|inhibitor]] and strong [[CYP3A]] [[enzyme inhibitor|inhibitor]].<ref name="Paxlovid FDA label" /><ref name="pmid36423149">{{cite journal | vauthors = Akinosoglou K, Schinas G, Gogos C | title = Oral Antiviral Treatment for COVID-19: A Comprehensive Review on Nirmatrelvir/Ritonavir | journal = Viruses | volume = 14 | issue = 11 | date = November 2022 | page = 2540 | pmid = 36423149 | pmc = 9696049 | doi = 10.3390/v14112540 | doi-access = free | title-link = doi }}</ref> Nirmatrelvir is the main active agent in the formulation, while ritonavir, which inhibits [[HIV-1 protease]], is a strong [[CYP3A inhibitor]]: it inhibits the metabolization of nirmatrelvir in the liver and thereby strengthens or boosts its activity.<ref name="Paxlovid FDA label" /><ref name="pmid36423149" /> Ritonavir is not active against or thought to directly contribute to the medication's antiviral activity against SARS-CoV-2.<ref name="pmid36423149" /><ref name="Paxlovid FDA label" /> Nirmatrelvir/ritonavir works against COVID{{nbhyph}}19 by preventing the [[viral replication|replication]] of SARS-CoV-2, which the SARS-CoV-2 main protease is essential for.<ref name="Paxlovid FDA label" /><ref name="pmid36423149" />

===Pharmacokinetics===

====Absorption====
The [[Tmax (pharmacology)|time to peak]] concentrations of nirmatrelvir combined with ritonavir is 3.00{{nbsp}}hours (range 1.02–6.00{{nbsp}}hours), while that of ritonavir is 3.98{{nbsp}}hours.<ref name="Paxlovid FDA label" /> [[Cmax (pharmacology)|Peak]] concentrations of nirmatrelvir combined with ritonavir following a single dose (300{{nbsp}}mg nirmatrelvir and 100{{nbsp}}mg ritonavir) in healthy individuals are 2.21{{nbsp}}μg/mL while [[area-under-the-curve (pharmacokinetics)|total exposure]] is 23.01{{nbsp}}μg•h/mL.<ref name="Paxlovid FDA label" /> Taking nirmatrelvir/ritonavir with a high-fat meal modestly increases exposure to nirmatrelvir (peak concentrations increased by 15% and total exposure increased by 1.6%) relative to taking them under fasting conditions.<ref name="Paxlovid FDA label" />

====Distribution====
The [[volume of distribution]] (V<sub>z</sub>/F) of nirmatrelvir combined with ritonavir is 104.7{{nbsp}}L while that of ritonavir is 112.4{{nbsp}}L.<ref name="Paxlovid FDA label" /> The [[blood]]-to-[[blood plasma|plasma]] ratio of nirmatrelvir combined with ritonavir is 0.60 while the [[red blood cell|red-blood-cell]]-to-plasma ratio of ritonavir is 0.14.<ref name="Paxlovid FDA label" /> The [[plasma protein binding]] of nirmatrelvir combined with ritonavir is 69% while that of ritonavir is 98 to 99%.<ref name="Paxlovid FDA label" />

====Metabolism====
Nirmatrelvir is mainly a [[substrate (biochemistry)|substrate]] of [[CYP3A]] in terms of its [[metabolism]].<ref name="Paxlovid FDA label" /> But when it is combined with ritonavir, a strong CYP3A4 inhibitor, nirmatrelvir's metabolism is minimal and its [[elimination (pharmacology)|elimination]] instead is mainly via [[kidney|renal]] [[excretion]].<ref name="Paxlovid FDA label" /> Ritonavir is eliminated mainly by [[liver|hepatic]] metabolism, with [[CYP3A4]] the major [[enzyme]] involved and [[CYP2D6]] the minor enzyme.<ref name="Paxlovid FDA label" />

====Elimination====
Nirmatrelvir combined with ritonavir is excreted 35.3% in [[feces]] and 49.6% in [[urine]], while ritonavir is excreted 86.4% in feces and 11.3% in urine.<ref name="Paxlovid FDA label" />

The [[oral clearance]] (CL/F) of nirmatrelvir combined with ritonavir is 8.99 while that of ritonavir is 13.92.<ref name="Paxlovid FDA label" /> The [[elimination half-life]] of nirmatrelvir combined with ritonavir is (mean ± SD) 6.05 ± 1.79{{nbsp}}hours while that of ritonavir is 6.15{{nbsp}}hours.<ref name="Paxlovid FDA label" /> The half-life of nirmatrelvir combined with ritonavir makes the formulation suitable for administration every 12{{nbsp}}hours.<ref name="Paxlovid FDA label" /><ref name="pmid36423149" />

====Specific populations====
The pharmacokinetics of nirmatrelvir/ritonavir based on age or gender have not been assessed.<ref name="Paxlovid FDA label" /> Exposure to nirmatrelvir/ritonavir was numerically lower in Japanese than in Western people, but not to a clinically meaningful extent.<ref name="Paxlovid FDA label" /> Peak concentrations, total exposure, time to peak concentrations, and elimination half-life of nirmatrelvir combined with ritonavir are severity-dependently increased in people with [[renal impairment]],<ref name="Paxlovid FDA label" /> but not increased in people with moderate [[hepatic impairment]].<ref name="Paxlovid FDA label" /> The combination has not been studied in people with severe hepatic impairment.<ref name="Paxlovid FDA label" />

==Research==
Research suggests that nirmatrelvir/ritonavir may minimize the risk of [[long COVID]].<ref name="jama224">{{cite journal | vauthors = Rubin R | title = Paxlovid Is Effective but Underused-Here's What the Latest Research Says About Rebound and More | journal = JAMA | volume = 331 | issue = 7 | pages = 548–551 | date = January 2024 | pmid = 38294771 | doi = 10.1001/jama.2023.28254 }}</ref>

===Rebound===

An additional analysis of the original EPIC-HR clinical trial data ([[Delta variant]]) showed that about 2% of both the treatment and placebo groups experienced a [[Rebound effect |symptomatic rebound]] after the five-day treatment, meaning they felt ill again and tested positive again (antigen test and PCR test) after testing negative.<ref>{{cite journal | vauthors = Anderson AS, Caubel P, Rusnak JM | title = Nirmatrelvir-Ritonavir and Viral Load Rebound in Covid-19 | journal = The New England Journal of Medicine | volume = 387 | issue = 11 | pages = 1047–1049 | date = September 2022 | pmid = 36069818 | doi = 10.1056/NEJMc2205944 | pmc = 9513855 }}</ref> The exact cause is not known, but there is speculation that it is due to reservoirs in tissues that are not reached by the medication, or reinfection. In May 2022, Pfizer suggested repeating the treatment, but the FDA said there was no evidence of benefit.<ref name="bloom">{{cite news |date=3 May 2022 |title=Pfizer Says Patients Who Relapse After Covid Pill Can Repeat Treatment |work=Bloomberg |url=https://www.bloomberg.com/news/articles/2022-05-03/pfizer-says-patients-who-relapse-after-covid-pill-can-take-more |url-status=live |access-date=21 May 2022 |archive-url=https://web.archive.org/web/20220514173915/https://www.bloomberg.com/news/articles/2022-05-03/pfizer-says-patients-who-relapse-after-covid-pill-can-take-more |archive-date=14 May 2022}}</ref><ref>{{cite news |title=FDA Updates on Paxlovid for Health Care Providers |url=https://www.fda.gov/drugs/news-events-human-drugs/fda-updates-paxlovid-health-care-providers |access-date=21 May 2022 |publisher=U.S. [[Food and Drug Administration]] (FDA) |date=4 May 2022 |archive-date=20 May 2022 |archive-url=https://web.archive.org/web/20220520235103/https://www.fda.gov/drugs/news-events-human-drugs/fda-updates-paxlovid-health-care-providers |url-status=live }}</ref>

In June 2022, a US case report of ten people with rebound COVID{{nbhyph}}19 had found viral load during relapse was comparable to levels during an initial infection, and high enough to cause secondary transmission.<ref name="jama">{{cite journal | vauthors = Rubin R | title = From Positive to Negative to Positive Again-The Mystery of Why COVID-19 Rebounds in Some Patients Who Take Paxlovid | journal = JAMA | volume = 327 | issue = 24 | pages = 2380–2382 | date = June 2022 | pmid = 35675094 | doi = 10.1001/jama.2022.9925 | s2cid = 249465757 | title-link = doi | doi-access = free }}</ref> President [[Joe Biden]], First Lady [[Jill Biden]], [[Anthony Fauci]],<ref name="bloom"/> [[Peter Hotez]], and [[Rochelle Walensky]]<ref>{{cite news |date=31 October 2022 |title=CDC Director Rochelle Walensky tests positive for Covid again after taking a course of the antiviral pill Paxlovid |work=NBC |url=https://www.nbcnews.com/news/us-news/cdc-director-tests-positive-covid-paxlovid-rebound-case-rcna54870 |access-date=1 November 2022 |archive-date=1 November 2022 |archive-url=https://web.archive.org/web/20221101021107/https://www.nbcnews.com/news/us-news/cdc-director-tests-positive-covid-paxlovid-rebound-case-rcna54870 |url-status=live }}</ref> are known to have experienced rebound. As of June 2022, Pfizer studied the phenomenon in a new trial it called EPIC-SR (standard risk) while the [[omicron variant]] was circulating.<ref name="jama"/> Both EPIC-HR and EPIC-SR were randomized controlled trials that provide information about COVID{{nbhyph}}19 rebound.<ref name="FDA PR 20230525" /> Data from these trials showed that rebound in SARS-CoV-2 (RNA or virus) shedding or COVID{{nbhyph}}19 symptoms occurred in a subset of participants and happened in both the participants receiving nirmatrelvir/ritonavir and the placebo.<ref name="FDA PR 20230525" /> As of 2023, the FDA found there was no clear association between nirmatrelvir/ritonavir treatment and COVID{{nbhyph}}19 rebound based on data available to them.<ref name="FDA PR 20230525" />

===Resistance===
As of July 2022, no nirmatrelvir/ritonavir [[drug resistant]] SARS-CoV-2 had been observed in clinical context.<ref>{{cite journal |vauthors=Lowe D |date=11 July 2022 |title=Paxlovid Resistance: Is It Just a Matter of Time Now? |journal=In the Pipeline |url=https://www.science.org/content/blog-post/paxlovid-resistance-it-just-matter-time-now |access-date=10 October 2022 |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010143000/https://www.science.org/content/blog-post/paxlovid-resistance-it-just-matter-time-now |url-status=live }}</ref> The engineering of a nirmatrelvir-resistant chimera of [[vesicular stomatitis virus]] (VSV) under laboratory conditions was published without formal peer review in July 2022.<ref>{{cite web |title=SARS-CoV-2 3CLpro mutations confer resistance to Paxlovid (nirmatrelvir/ritonavir) in a VSV-based, non-gain-of-function system |doi=10.1101/2022.07.02.495455 |vauthors=Heilmann E, Costacurta F, Volland A, von Laer D |url=https://www.biorxiv.org/content/10.1101/2022.07.02.495455v1.full |date=4 July 2022 |s2cid=250353628 |access-date=8 November 2023 |archive-date=9 November 2023 |archive-url=https://web.archive.org/web/20231109080525/https://www.biorxiv.org/content/10.1101/2022.07.02.495455v1.full |url-status=live }}</ref> As of November 2022, multiple pathways that could lead to resistance to nirmatrelvir/ritonavir had been demonstrated ''in vitro''.<ref>{{cite journal | vauthors = Iketani S, Mohri H, Culbertson B, Hong SJ, Duan Y, Luck MI, Annavajhala MK, Guo Y, Sheng Z, Uhlemann AC, Goff SP, Sabo Y, Yang H, Chavez A, Ho DD | title = Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir | journal = Nature | pages = 558–564 | date = November 2022 | volume = 613 | issue = 7944 | pmid = 36351451 | doi = 10.1038/s41586-022-05514-2 | pmc = 9849135 | s2cid = 253445215 }}</ref>

==History==
Nirmatrelvir belongs to a family of [[3C-like protease|3C-like]] [[Protease inhibitor (pharmacology)|protease inhibitors]] developed in the late 2010s against [[feline coronavirus]], while ritonavir is an [[antiretroviral]] drug developed in the 1980s and used since the 1990s to inhibit the enzyme that metabolizes other protease inhibitors.

The primary data supporting the US [[Food and Drug Administration]] (FDA) [[emergency use authorization]] for nirmatrelvir/ritonavir were from the EPIC-HR trial, a randomized, double-blind, placebo-controlled clinical trial studying nirmatrelvir/ritonavir for the treatment of non-hospitalized symptomatic adults with a laboratory-confirmed diagnosis of SARS-CoV-2 infection.<ref name="Paxlovid FDA label" /><ref name="FDA PR 20211222" /><ref name="fda_155194">{{cite report | url=https://www.fda.gov/media/155194/download | format=PDF | title=CDER Scientific Review Supporting EUA | publisher=U.S. [[Food and Drug Administration]] (FDA) | date= | access-date=16 February 2022 | archive-date=17 January 2022 | archive-url=https://web.archive.org/web/20220117232334/https://www.fda.gov/media/155194/download | url-status=live }}</ref> Participants were 18 years of age and older with a pre-specified risk factor for progression to severe disease, or were 60{{nbsp}}years and older regardless of pre-specified chronic medical conditions.<ref name="FDA PR 20211222" /> No participants had received a COVID{{nbhyph}}19 vaccine or been previously infected with COVID{{nbhyph}}19.<ref name="FDA PR 20211222" /> The main outcome measured in the trial was the proportion of people who were hospitalized due to COVID{{nbhyph}}19 or died due to any cause during 28{{nbsp}}days of follow-up.<ref name="FDA PR 20211222" /> EPIC-HR started in July 2021, and completed in December 2021.<ref name="NCT04960202">{{ClinicalTrialsGov|NCT04960202|EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19}}</ref> Nirmatrelvir/ritonavir significantly reduced the proportion of people with COVID{{nbhyph}}19-related hospitalization or death from any cause by 88% compared to placebo among participants treated within five days of symptom onset and who did not receive COVID{{nbhyph}}19 therapeutic monoclonal antibody treatment.<ref name="FDA PR 20211222" /> In December 2021, Pfizer also announced that a Phase II/III study of nirmatrelvir/ritonavir showed a reduced risk of hospitalization or death.<ref name="pfizer2">{{cite press release |date=14 December 2021 |title=Pfizer Announces Additional Phase 2/3 Study Results Confirming Robust Efficacy of Novel COVID-19 Oral Antiviral Treatment Candidate in Reducing Risk of Hospitalization or Death |url=https://www.businesswire.com/news/home/20211214005548/en/Pfizer-Announces-Additional-Phase-23-Study-Results-Confirming-Robust-Efficacy-of-Novel-COVID-19-Oral-Antiviral-Treatment-Candidate-in-Reducing-Risk-of-Hospitalization-or-Death |publisher=[[Pfizer]] |via=Business Wire |access-date=25 December 2021 |archive-date=26 December 2021 |archive-url=https://web.archive.org/web/20211226044106/https://www.businesswire.com/news/home/20211214005548/en/Pfizer-Announces-Additional-Phase-23-Study-Results-Confirming-Robust-Efficacy-of-Novel-COVID-19-Oral-Antiviral-Treatment-Candidate-in-Reducing-Risk-of-Hospitalization-or-Death |url-status=live }}</ref>

In August 2021, Pfizer began a [[Phases of clinical research#Phase III|phase II/III trial]] of nirmatrelvir/ritonavir for COVID{{nbhyph}}19 in standard-risk individuals with COVID{{nbhyph}}19 known as EPIC-SR.<ref name="pmid36384743" /><ref name="trials">{{cite web |date=2 September 2021 |title=Pfizer begins dosing in Phase II/III trial of antiviral drug for Covid-19. |url=https://www.clinicaltrialsarena.com/news/pfizer-antiviral-covid-trial/ |website=Clinical Trials Arena |access-date=5 January 2022 |archive-date=5 November 2021 |archive-url=https://web.archive.org/web/20211105141753/https://www.clinicaltrialsarena.com/news/pfizer-antiviral-covid-trial/ |url-status=live }}</ref> Interim results of this trial were announced in December 2021, and final results were released in June 2022.<ref name="pmid36384743" /> Pfizer discontinued enrollment in the study, with the reason given being the very low rate of hospitalization and death in this population.<ref name="Pfizer2022" /> EPIC-SR was another clinical trial that enrolled vaccinated participants with at least one risk factor for progression to severe COVID{{nbhyph}}19.<ref name="FDA PR 20230525" /> Although not statistically significant, among these vaccinated participants, there was a reduction in the risk of COVID{{nbhyph}}19 related hospitalization or death from any cause.<ref name="FDA PR 20230525" />

In December 2021, nirmatrelvir/ritonavir was granted [[emergency use authorization]] by the United States [[Food and Drug Administration]] (FDA) for the treatment of COVID{{nbhyph}}19.<ref name="fda-factsheet"/> In December 2021, the United Kingdom's [[Medicines and Healthcare products Regulatory Agency]] (MHRA) approved the use of nirmatrelvir combined with ritonavir for adults with mild to moderate infection and at high risk of their illness worsening.<ref name="Aripaka">{{cite news|vauthors=Aripaka P|date=31 December 2021|title=Britain approves Pfizer's antiviral COVID-19 pill|work=Reuters|url=https://www.reuters.com/world/uk/britain-approves-pfizer-covid-19-pill-2021-12-31/|access-date=31 December 2021|archive-date=31 December 2021|archive-url=https://web.archive.org/web/20211231114438/https://www.reuters.com/world/uk/britain-approves-pfizer-covid-19-pill-2021-12-31/|url-status=live}}</ref><ref name="MHRA PR 20211231" />

In April 2022, it was announced that the [[PANORAMIC trial]] would start testing the effectiveness of nirmatrelvir/ritonavir for treating COVID{{nbhyph}}19 infections.<ref>{{cite journal |vauthors=Robinson J |title=PANORAMIC trial to enlist 17,500 more patients as researchers add second COVID-19 antiviral |url=https://pharmaceutical-journal.com/article/news/panoramic-trial-enlists-17500-more-patients-as-researchers-add-second-covid-19-antiviral |date=April 2022 |journal=The Pharmaceutical Journal |doi=10.1211/PJ.2022.1.138635 |doi-access=free |title-link=doi |access-date=26 April 2022 |archive-date=25 April 2022 |archive-url=https://web.archive.org/web/20220425051016/https://pharmaceutical-journal.com/article/news/panoramic-trial-enlists-17500-more-patients-as-researchers-add-second-covid-19-antiviral |url-status=live }}</ref>

Nirmatrelvir/ritonavir has been evaluated in the treatment of COVID{{nbhyph}}19 in standard-risk individuals in the EPIC-SR trial.<ref name="pmid36384743">{{cite journal | vauthors = Lee TC, Pogue JM, McCreary EK, Morris AM | title = What is the place in therapy for nirmatrelvir/ritonavir? | journal = BMJ Evid Based Med | volume = 28| issue = 5| pages = 287–290| date = November 2022 | pmid = 36384743 | doi = 10.1136/bmjebm-2022-112064 | s2cid = 253579652 | url = }}</ref><ref name="Pfizer2022" /> This study did not achieve its primary goal of reducing time to sustained alleviation of COVID{{nbhyph}}19 symptoms (treatment: 13{{nbsp}}days (95% CI 12–15 days); placebo: 13{{nbsp}}days (95% CI 11–14 days)).<ref name="pmid36384743" /><ref name="Pfizer2022" /> It also did not find a statistically significant reduction in the risk of hospitalization or death (treatment: 5/576 [0.9%]; placebo: 10/569 [1.8%]; p > 0.05).<ref name="pmid36384743" /><ref name="Pfizer2022" /> Likewise, findings were not statistically significant for reducing hospitalization rates in a subgroup of vaccinated adults with at least one risk factor for severe COVID{{nbhyph}}19 (treatment: 3/361 [0.8%]; placebo: 7/360 [1.9%]; 57% reduction{{snd}}RR 0.43, 95% CI 0.11–1.64).<ref name="pmid36384743" /><ref name="Pfizer2022" /> However, the trial did find a statistically significant 62% decrease in COVID{{nbhyph}}19-related medical visits, similar to the 67% reduction from the EPIC-HR study of high-risk individuals.<ref name="pmid36384743" /><ref name="Pfizer2022" /> Enrollment in EPIC-SR was discontinued due to the low rate of hospitalization and death in this population.<ref name="pmid36384743" /><ref name="Pfizer2022">{{cite web |url=https://www.pfizer.com/news/press-release/press-release-detail/pfizer-reports-additional-data-paxlovidtm-supporting |title=Pfizer Reports Additional Data on Paxlovid Supporting Upcoming New Drug Application Submission to U.S. FDA |date=14 June 2022 |access-date=24 June 2022 |location=New York |archive-date=24 June 2022 |archive-url=https://web.archive.org/web/20220624071817/https://www.pfizer.com/news/press-release/press-release-detail/pfizer-reports-additional-data-paxlovidtm-supporting |url-status=live }}</ref>

In May 2023, nirmatrelvir/ritonavir received FDA approval for the treatment of mild-to-moderate COVID{{nbhyph}}19 in adults who are at high risk for progression to severe COVID{{nbhyph}}19, including hospitalization or death.<ref name="FDA PR 20230525" /> In November 2023, the FDA revised the EUA for nirmatrelvir/ritonavir to authorize EUA- or NDA-labeled nirmatrelvir/ritonavir for the treatment of mild-to-moderate COVID{{nbhyph}}19 in people aged twelve years of age and older weighing at least {{convert|40|kg|lb}}, who are at high risk for progression to severe COVID{{nbhyph}}19, including hospitalization.<ref name="EUA FAQ" /> In March 2024, the FDA revised the EUA for nirmatrelvir/ritonavir to remove the authorization for EUA-labeled nirmatrelvir/ritonavir.<ref name="FDA 20240313" /><ref name="EUA FAQ" />

==Society and culture==
[[File:Paxlovid.jpg|thumb|US packaging for Paxlovid, the branded form of nirmatrelvir/ritonavir, as of 2022]]

===Legal status===
====Canada====

[[Health Canada]] approved the use of the co-packaged medication in January 2022.<ref name="Paxlovid details">{{cite web|title=Paxlovid|url=https://covid-vaccine.canada.ca/paxlovid/product-details|access-date=18 January 2022|website=[[Health Canada]]|date=17 January 2022 |archive-date=18 January 2022|archive-url=https://web.archive.org/web/20220118012129/https://covid-vaccine.canada.ca/paxlovid/product-details|url-status=live}}</ref><ref name="Health Canada PR 20220117" /><ref>{{cite web | title=Paxlovid (nirmatrelvir / ritonavir) | website=[[Health Canada]] | date=1 September 2012 | url=https://covid-vaccine.canada.ca/info/SBD00577-paxlovid-en.html | access-date=30 June 2024 | archive-date=25 February 2024 | archive-url=https://web.archive.org/web/20240225110214/https://covid-vaccine.canada.ca/info/SBD00577-paxlovid-en.html | url-status=live }}</ref><ref>{{cite news |title=Paxlovid, Pfizer's oral COVID-19 pill, approved in Canada|url=https://globalnews.ca/news/8516373/pfizers-paxlovid-covid-antiviral-pill-approved-canada/|access-date=18 January 2022|website=[[Global News]]|archive-date=18 January 2022|archive-url=https://web.archive.org/web/20220118002829/https://globalnews.ca/news/8516373/pfizers-paxlovid-covid-antiviral-pill-approved-canada/|url-status=live}}</ref><ref>{{cite news|vauthors=Weeks C|date=17 January 2022|title=Health Canada approves Pfizer's COVID-19 antiviral pill Paxlovid|work=[[The Globe and Mail]]|url=https://www.theglobeandmail.com/canada/article-health-canada-approves-pfizers-covid-19-antiviral-pill-paxlovid/|access-date=18 January 2022|archive-date=18 January 2022|archive-url=https://web.archive.org/web/20220118014147/https://www.theglobeandmail.com/canada/article-health-canada-approves-pfizers-covid-19-antiviral-pill-paxlovid/|url-status=live}}</ref>

====China====

In February 2022, China approved the medication for the treatment of adults who have mild to moderate COVID{{nbhyph}}19 and are at a high risk of progressing to a severe condition.<ref>{{cite news|date=12 February 2022|title=China conditionally approves Pfizer's Covid treatment pill Paxlovid|url=https://www.theguardian.com/world/2022/feb/12/china-conditionally-approves-pfizer-covid-treatment-pill-paxlovid|access-date=13 February 2022|agency=[[Reuters]]|website=[[The Guardian]]|archive-date=13 February 2022|archive-url=https://web.archive.org/web/20220213003430/https://www.theguardian.com/world/2022/feb/12/china-conditionally-approves-pfizer-covid-treatment-pill-paxlovid|url-status=live}}</ref>

====European Union====

The [[European Medicines Agency]] (EMA) approved the co-packaged medication for the treatment of COVID{{nbhyph}}19 in the EU in January 2022.<ref name="Paxlovid EPAR" /><ref name="Paxlovid PI" />

====Israel====

The [[Ministry of Health (Israel)|Israeli Ministry of Health]] approved the use of the co-packaged medication in December 2021.<ref>{{cite press release|title=The Use of Pfizer's Anti-Viral Drug for the Treatment of COVID-19 Has Been Approved|url=https://www.gov.il/en/departments/news/26122021-01|access-date=28 December 2021|website=Ministry of Health|archive-date=28 December 2021|archive-url=https://web.archive.org/web/20211228152141/https://www.gov.il/en/departments/news/26122021-01|url-status=live}}</ref>

====Japan====

The Japanese [[Ministry of Health, Labour and Welfare]] approved the use of the co-packaged medication for treating adults in February 2022.<ref>{{cite journal |vauthors=Higuchi Y, Kaneda Y, Tanimoto T |title=Japan's COVID-19 treatment strategy: An examination of approved oral medications |journal=Clinical and Translational Science |volume=16 |issue=11 |pages=2075–2077 |date=November 2023 |pmid=37691254 |pmc=10651642 |doi=10.1111/cts.13628}}</ref>

====Singapore====

The Singapore [[Health Sciences Authority]] approved the use of the co-packaged medication for treating adults in February 2022.<ref>{{cite web | vauthors = Chelvan VP |title=Singapore approves Pfizer's Paxlovid pill for COVID-19 treatment in adult patients |url=https://www.channelnewsasia.com/singapore/covid-19-pfizer-pill-paxlovid-treatment-adults-hsa-moh-2477141 |website=CNA |access-date=3 February 2022 |date=3 February 2022 |archive-date=17 February 2022 |archive-url=https://web.archive.org/web/20220217204518/https://www.channelnewsasia.com/singapore/covid-19-pfizer-pill-paxlovid-treatment-adults-hsa-moh-2477141 |url-status=live }}</ref>

====South Korea====

South Korea approved the use of the co-packaged medication in December 2021.<ref>{{cite news|date=27 December 2021|title=S.Korea authorises emergency use of Pfizer's oral coronavirus treatment|work=Reuters|url=https://www.reuters.com/business/healthcare-pharmaceuticals/skorea-emergency-approves-pfizers-oral-coronavirus-treatment-paxlovid-yonhap-2021-12-27/|access-date=28 December 2021|archive-date=11 January 2022|archive-url=https://web.archive.org/web/20220111183946/https://www.reuters.com/business/healthcare-pharmaceuticals/skorea-emergency-approves-pfizers-oral-coronavirus-treatment-paxlovid-yonhap-2021-12-27/|url-status=live}}</ref>

====United Kingdom====

The United Kingdom approved the use of the co-packaged medication in December 2021.<ref name="Paxlovid SmPC" /><ref name="Regulatory approval of Paxlovid" /><ref>{{cite web | title=Paxlovid 150 mg/100 mg film-coated tablets | website=(emc) | date=16 January 2024 | url=https://www.medicines.org.uk/emc/product/13145 | access-date=30 June 2024 | archive-date=27 February 2024 | archive-url=https://web.archive.org/web/20240227191850/https://www.medicines.org.uk/emc/product/13145 | url-status=live }}</ref>

====United States====

In November 2021, Pfizer submitted an application to the US [[Food and Drug Administration]] (FDA) for [[emergency use authorization]] for the co-packaged medication.<ref>{{cite press release | title=Pfizer Seeks Emergency Use Authorization for Novel COVID-19 Oral Antiviral Candidate | publisher=[[Pfizer]] | via=Business Wire | date=16 November 2021 | url=https://www.businesswire.com/news/home/20211116006258/en/ | access-date=17 November 2021 | archive-date=16 November 2021 | archive-url=https://web.archive.org/web/20211116204656/https://www.businesswire.com/news/home/20211116006258/en/ | url-status=live }}</ref><ref>{{cite web|vauthors=Kimball S|date=16 November 2021|title=Pfizer submits FDA application for emergency approval of Covid treatment pill|url=https://www.cnbc.com/2021/11/16/pfizer-plans-to-submit-fda-application-for-emergency-approval-of-covid-treatment-pill-today-ceo-says.html|access-date=17 November 2021|website=[[CNBC]]|archive-date=16 November 2021|archive-url=https://web.archive.org/web/20211116232003/https://www.cnbc.com/2021/11/16/pfizer-plans-to-submit-fda-application-for-emergency-approval-of-covid-treatment-pill-today-ceo-says.html|url-status=live}}</ref><ref>{{cite news | vauthors = Robbins R |date=5 November 2021 |title=Pfizer Says Its Antiviral Pill Is Highly Effective in Treating Covid |work=[[The New York Times]] |url=https://www.nytimes.com/2021/11/05/health/pfizer-covid-pill.html |url-access=registration |access-date=9 November 2021 |issn=0362-4331 |archive-url=https://web.archive.org/web/20211108134000/https://www.nytimes.com/2021/11/05/health/pfizer-covid-pill.html |archive-date=8 November 2021|url-status=live}}</ref> The authorization was granted in December 2021, for people 12 years of age or older who are infected with COVID{{nbhyph}}19 and are at risk.<ref name="FDA PR 20211222" /><ref name="EUA FAQ" /><ref name=Kimball>{{cite news|url=https://www.cnbc.com/2022/05/03/pfizer-paxlovid-prescriptions-to-treat-covid-increased-tenfold-in-us-since-late-february.html|vauthors=Kimball S|date=3 May 2022|title=Paxlovid prescriptions to treat Covid increased tenfold in U.S. since late February, Pfizer says|work=CNBC|access-date=3 May 2022|archive-date=3 May 2022|archive-url=https://web.archive.org/web/20220503190209/https://www.cnbc.com/2022/05/03/pfizer-paxlovid-prescriptions-to-treat-covid-increased-tenfold-in-us-since-late-february.html|url-status=live}}</ref>

In January 2024, the FDA revised the emergency use authorization (EUA) and stated that nirmatrelvir/ritonavir manufactured and labeled in accordance with the EUA currently in U.S. distribution will remain authorized for use through the earlier of the labeled or extended expiration date, or through March 2024.<ref name="FDA 20240313">{{cite web |date=13 March 2024 |title=FDA revises letter of authorization for the emergency use authorization for Paxlovid |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-letter-authorization-emergency-use-authorization-paxlovid |access-date=29 June 2024 |website=U.S. [[Food and Drug Administration]] (FDA) |archive-date=27 May 2024 |archive-url=https://web.archive.org/web/20240527082026/https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-letter-authorization-emergency-use-authorization-paxlovid |url-status=live }} {{PD-notice}}</ref> In March 2024, the FDA revised the emergency use authorization to no longer cover EUA-labeled nirmatrelvir/ritonavir.<ref name="EUA FAQ" /><ref name="FDA 20240313" /> As of March 2024, the FDA emergency use authorization for nirmatrelvir/ritonavir continues to authorize it for the treatment of people 12 years of age and older weighing at least {{convert|40|kg|lb}} who are at high risk for progression to severe COVID-19, including hospitalization or death.<ref name="FDA 20240313" /><ref name="EUA FAQ" /> The emergency use authorization also continues to authorize prescribing of nirmatrelvir/ritonavir by a state-licensed pharmacist to treat mild to moderate COVID-19 in people 12 years of age and older weighing at least {{convert|40|kg|lb}} who are at high risk for progression to severe COVID-19, including hospitalization or death, in accordance with the FDA-approved prescribing information or authorized labeling, as applicable, and subject to certain conditions as detailed in the letter of authorization and the authorized fact sheet for health care providers.<ref name="EUA FAQ" /><ref name="FDA 20240313" /><ref name="Emergency Use Authorization 105">{{cite web | url=https://www.fda.gov/media/155049/download | title=Emergency Use Authorization 105 | date=13 March 2024 | publisher=U.S. [[Food and Drug Administration]] (FDA) | format=PDF | access-date=30 June 2024 | archive-date=22 April 2022 | archive-url=https://web.archive.org/web/20220422151155/https://www.fda.gov/media/155049/download | url-status=live }} {{PD-notice}}</ref>

===Manufacturing===
Pfizer selected its largest oral [[Tablet (pharmacy)|tablet]] factory in [[Freiburg im Breisgau|Freiburg]] as the launch facility for manufacturing the co-packaged medication.<ref name="Schmidt">{{cite news |vauthors=Schmidt B |title=Neues Corona-Medikament von Pfizer wird in Freiburg hergestellt |trans-title=Pfizer corona medicine is being manufactured in Freiburg |language=German |url=https://www.badische-zeitung.de/neues-corona-medikament-von-pfizer-wird-in-freiburg-hergestellt--206901797.html |access-date=15 January 2022 |work=[[Badische Zeitung]] |date=1 December 2021 |archive-date=15 January 2022 |archive-url=https://web.archive.org/web/20220115024153/https://www.badische-zeitung.de/neues-corona-medikament-von-pfizer-wird-in-freiburg-hergestellt--206901797.html |url-status=live }}</ref> Nirmatrelvir, the novel portion of the co-packaged medication, was first developed in the U.S. and was initially manufactured in small amounts in [[Groton, Connecticut]], to support clinical trials,<ref name="Green">{{cite news |vauthors=Green R |title=Pfizer scientists in Groton played a critical role in development of new COVID-19 pill |url=https://www.courant.com/coronavirus/hc-news-coronavirus-pfizer-paxlovid-connecticut-groton-researchers-20211223-hsurttz4lrbt7o4nijvoq5qxui-story.html |work=The Hartford Courant |date=23 December 2021 |access-date=15 January 2022 |archive-date=15 January 2022 |archive-url=https://web.archive.org/web/20220115024158/https://www.courant.com/coronavirus/hc-news-coronavirus-pfizer-paxlovid-connecticut-groton-researchers-20211223-hsurttz4lrbt7o4nijvoq5qxui-story.html |url-status=live }}</ref> but the Freiburg facility was responsible for figuring out how to mass-produce the co-packaged medication on an industrial scale.<ref name="Schmidt" /> Pfizer selected another factory in [[Ascoli Piceno]], Italy, to assist the Freiburg factory with packaging tablets into [[blister pack]]s.<ref name="Paci">{{cite news |vauthors=Paci M |title=Covid, ad Ascoli l'unico stabilimento in Italia che produrrà il farmaco antivirale. Pfizer pensa a cento assunzioni |trans-title=Covid, in Ascoli the only plant in Italy that will produce the antiviral drug. Pfizer thinks to hire one hundred |language=Italian |url=https://www.corriereadriatico.it/ascoli_piceno/covid_farmaco_antivirale_paxlovid_pfizer_prodotto_ascoli_ultime_notizie-6388048.html |work=[[Corriere Adriatico]] |date=17 December 2021 |access-date=15 January 2022 |archive-date=15 January 2022 |archive-url=https://web.archive.org/web/20220115024154/https://www.corriereadriatico.it/ascoli_piceno/covid_farmaco_antivirale_paxlovid_pfizer_prodotto_ascoli_ultime_notizie-6388048.html |url-status=live }}</ref>

===Economics===
In December 2021, the German government ordered one million doses, but by August 2022, wholesalers had delivered only around 43,000 to pharmacies. In Germany, nirmatrelvir/ritonavir has been by prescription through physicians only, and German physicians have been reluctant to prescribe it. Hence, health minister [[Karl Lauterbach]] decided that general practitioners could stock five nirmatrelvir/ritonavir courses in their practice and dispense it directly to patients, that a prescription would be remunerated with 15 euros, and that every nursing home should appoint a vaccination officer as well as a nirmatrelvir/ritonavir officer. As of August 2022 the treatment guidelines German family doctors follow had not been updated since February 2022 and recommended nirmatrelvir/ritonavir only in unvaccinated risk patients, i.e., only a few people.<ref>{{cite news |vauthors=Hackenbroch V |date=25 August 2022 |title=Der Paxlovid-Skandal: Warum verweigern deutsche Ärzte so vielen Patienten den Virenkiller? |language=de |work=Der Spiegel |url=https://www.spiegel.de/wissenschaft/corona-medikament-paxlovid-warum-verweigern-deutsche-aerzte-so-vielen-patienten-den-virenkiller-a-3dcec64c-e45b-4dc7-a534-40488b4f285c |access-date=10 October 2022 |issn=2195-1349 |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010140148/https://www.spiegel.de/wissenschaft/corona-medikament-paxlovid-warum-verweigern-deutsche-aerzte-so-vielen-patienten-den-virenkiller-a-3dcec64c-e45b-4dc7-a534-40488b4f285c |url-status=live }}</ref>

As of April 2022, the U.S. ordered a total of 20 million nirmatrelvir/ritonavir courses.<ref>{{cite press release | title=Fact Sheet: Biden Administration Increases Access to COVID-19 Treatments and Boosts Patient and Provider Awareness | website=The White House | date=26 April 2022 | url=https://www.whitehouse.gov/briefing-room/statements-releases/2022/04/26/fact-sheet-biden-administration-increases-access-to-covid-19-treatments-and-boosts-patient-and-provider-awareness/ | access-date=7 July 2022 | archive-date=6 July 2022 | archive-url=https://web.archive.org/web/20220706183103/https://www.whitehouse.gov/briefing-room/statements-releases/2022/04/26/fact-sheet-biden-administration-increases-access-to-covid-19-treatments-and-boosts-patient-and-provider-awareness/ | url-status=live }}</ref> As of July 2022, the [[United States Department of Health and Human Services]] set up at least 2,200 sites where people can receive nirmatrelvir/ritonavir as soon as they test positive for the virus, including pharmacies, community health centers and long-term care facilities.<ref name=Kimball /> In July 2022, the FDA allowed state-licensed pharmacists to prescribe it to people with COVID{{nbhyph}}19 at high risk of progressing to severe disease.<ref>{{cite journal | vauthors = Stephenson J | title = FDA Authorizes Pharmacists to Prescribe Oral Antiviral Medication for COVID-19 | journal = JAMA Health Forum | volume = 3 | issue = 7 | pages = e222968 | date = July 2022 | pmid = 36219005 | doi = 10.1001/jamahealthforum.2022.2968 | s2cid = 250704928 | doi-access = free | title-link = doi }}</ref>

Throughout 2022, only 10-12% of eligible U.S. adult outpatients received nirmatrelvir/ritonavir.<ref name=jama224 /> Reasons are suspected to be concerns about "rebound, unfamiliarity with the treatment and cost" as well as "confusion around who's at high risk for severe disease".<ref name=jama224 /> In spite of Pfizer's list price of {{US$|1390}} for five days in the US, treatment has been and will be free through the end of 2024 for Medicare or Medicaid beneficiaries and insured persons covering out-of-pocket costs.<ref name=jama224 /><ref>{{cite press release | title=HHS and Pfizer Reach Agreement to Increase Patient Access to Paxlovid | website=U.S. [[Department of Health and Human Services]] (HHS) | date=13 October 2023 | url=https://www.hhs.gov/about/news/2023/10/13/hhs-and-pfizer-reach-agreement-to-increase-patient-access-to-paxlovid.html | access-date=30 June 2024}}</ref>

=== Brand names ===
Nirmatrelvir/ritonavir is sold under the brand name Paxlovid.<ref name="Paxlovid FDA label" /> Primovir and Paxista are generic versions manufactured and distributed in India.<ref name="in-generics">{{cite web |vauthors=Singh AG |title=Indian generics emerge as a life-saver in COVID-hit China |url=https://www.orfonline.org/expert-speak/indian-generics-emerge-as-a-life-saver-in-covid-hit-china/ |access-date=30 December 2022 |website=ORF |archive-date=21 January 2023 |archive-url=https://web.archive.org/web/20230121134614/https://www.orfonline.org/expert-speak/indian-generics-emerge-as-a-life-saver-in-covid-hit-china/ |url-status=live }}</ref><ref>{{cite web |date=26 December 2022 |title=Chinese turn to black market for generic Indian Covid-19 drugs |url=https://www.scmp.com/news/china/politics/article/3204617/chinese-turn-black-market-generic-indian-covid-19-drugs-surge-sweeps-nation |access-date=30 December 2022 |website=South China Morning Post |archive-date=29 December 2022 |archive-url=https://web.archive.org/web/20221229173225/https://www.scmp.com/news/china/politics/article/3204617/chinese-turn-black-market-generic-indian-covid-19-drugs-surge-sweeps-nation |url-status=live }}</ref>

===Comparison to ivermectin===
{{Further|Ivermectin during the COVID-19 pandemic}}

In 2021, it was falsely claimed that nirmatrelvir/ritonavir is a repackaged version of the [[antiparasitic]] drug [[ivermectin]], or that nirmatrelvir/ritonavir is just like ivermectin as both are protease inhibitors.<ref name=csefalvay/><ref name="scimed"/> Ivermectin has been falsely<ref>{{cite web |title=Ivermectin: How false science created a Covid 'miracle' drug |url=https://www.bbc.com/news/health-58170809 |website=BBC News |date=6 October 2021 |access-date=8 November 2022 |archive-date=8 January 2022 |archive-url=https://web.archive.org/web/20220108205355/https://www.bbc.com/news/health-58170809 |url-status=live }}</ref> promoted as a COVID{{nbhyph}}19 therapeutic. Such claims, sometimes using the nickname "Pfizermectin",<ref name="acsh">{{cite web |vauthors=Bloom J |date=2 December 2021 |url=https://www.acsh.org/news/2021/12/02/how-does-pfizers-paxlovid-compare-ivermectin-15967 |title=How Does Pfizer's Paxlovid Compare With Ivermectin? |publisher=American Council on Science and Health |access-date=12 December 2021 |archive-date=15 December 2021 |archive-url=https://web.archive.org/web/20211215100518/https://www.acsh.org/news/2021/12/02/how-does-pfizers-paxlovid-compare-ivermectin-15967 |url-status=live }}</ref> arise from superficial similarities between the mechanism of action of the drugs<ref name=csefalvay>{{cite journal |vauthors=von Csefalvay C |date=27 November 2021 |title=Why Paxlovid is not Pfizermectin |url=https://chrisvoncsefalvay.com/posts/paxlovid/ |url-status=live |access-date=9 January 2022 |website=Chris von Csefalvay: Bits and Bugs |doi=10.59350/576dr-vbd49 |archive-date=9 January 2022 |archive-url=https://web.archive.org/web/20220109142822/https://chrisvoncsefalvay.com/2021/11/27/paxlovid-pfizermectin/ }}</ref> and the claim that Pfizer is suppressing information about the benefits of ivermectin.<ref name="scimed">{{cite web |publisher=[[Science-Based Medicine]] |vauthors=Gorski D |date=15 November 2021 |title=Pfizer's new COVID-19 protease inhibitor drug is not just 'repackaged ivermectin' |url=https://sciencebasedmedicine.org/pfizer-new-covid-19-protease-inhibitor-drug-is-not-just-repackaged-ivermectin/ |access-date=5 January 2022 |archive-date=20 December 2021 |archive-url=https://web.archive.org/web/20211220001619/https://sciencebasedmedicine.org/pfizer-new-covid-19-protease-inhibitor-drug-is-not-just-repackaged-ivermectin/ |url-status=live }}</ref>

== References ==
{{Reflist}}

== External links ==
* {{cite magazine | title=How Pfizer scientists transformed an old drug lead into a COVID-19 antiviral | vauthors = Halford B | date=January 2022 | volume=100 | issue=3 | magazine=Chemical & Engineering News | url=https://cen.acs.org/pharmaceuticals/drug-discovery/How-Pfizer-scientists-transformed-an-old-drug-lead-into-a-COVID-19-antiviral/100/i3 }}
* {{cite magazine | vauthors = Regalado A | title=How Pfizer made an effective anti-covid pill | magazine=MIT Technology Review | date=February 2022 | url=https://www.technologyreview.com/2022/02/04/1044714/pfizer-covid-pill-paxlovid-pandemic/ }}

{{RNA antivirals}}
{{COVID-19 pandemic}}
{{Portal bar | Medicine | Viruses | COVID-19}}
{{Authority control}}

{{DEFAULTSORT:Nirmatrelvir Ritonavir}}
[[Category:Combination antiviral drugs]]
[[Category:COVID-19 drug development]]
[[Category:CYP3A4 inhibitors]]
[[Category:Drugs developed by Pfizer]]
[[Category:SARS-CoV-2 main protease inhibitors]]