Nirmatrelvir/ritonavir#Rebound

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. This includes people above 50, people with diabetes, cancer, coronary artery disease, chronic lung diseases, pregnancy, or on immunosuppressant drugs.

The co-packaged medication is not authorized or suggested for the pre-exposure or post-exposure prevention of COVID{{nbhyph}}19.{{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=dead }} {{PD-notice}}{{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 }}

In the European Union, the co-packaged medication is indicated for the treatment of COVID{{nbhyph}}19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID{{nbhyph}}19.

If administered within five days of symptom onset in confirmed COVID{{nbhyph}}19 infections, the 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}}.{{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 }}

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.{{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 }} 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. 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.{{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 }} There are no human data on the presence of nirmatrelvir in human milk, or its effects on milk production or the infant.{{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 }} A temporary reduction in body weight was observed in the offspring of nursing rats. Other observational studies have also demonstrated the safety of ritonavir during pregnancy.{{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 }}

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. Co-administration with certain drugs may have serious, sometimes fatal, effects.{{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 }}

Nirmatrelvir/ritonavir has a high potential for potentially serious drug interactions due to strong CYP3A inhibition by ritonavir. The US FDA label, the FDA fact sheet, and the FDA EUA contain a boxed warning about the CYP3A inhibition.

Adverse events of the co-packaged medication, regardless of causality, observed in the phase II-III EPIC-HR study included dysgeusia (6% vs. < 1% for placebo), diarrhea (3% vs. 2% for placebo), hypertension (1% vs. < 1% for placebo), and myalgia (1% vs. < 1% for placebo). In clinical trials, 2% of people discontinued treatment due to side effects with nirmatrelvir/ritonavir while 4% in the placebo group did so. Nirmatrelvir/ritonavir is under investigation, so its side effects have yet to be fully evaluated and may not be completely known.

Other side effects of nirmatrelvir/ritonavir may include hypersensitivity reactions, liver toxicity, and development of HIV drug resistance in people with uncontrolled or undiagnosed HIV infection. Hypersensitivity reactions (allergic reactions) may manifest as skin rash, hives, difficulty swallowing, difficulty breathing, angioedema, and/or anaphylaxis. 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.

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 inducers, for which reduced blood concentration of the two main components may result in loss of effect against the virus and possible resistance, among others. Co-administration also affects the concentration of several drugs, sometimes requiring changing the dose or careful monitoring.{{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. Many of these drugs are widely prescribed to people at high risk from COVID{{nbhyph}}19.{{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 }} 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.{{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 }}

Nirmatrelvir/ritonavir is safe to use in combination with over-the-counter pain- and fever-reducing medications such as paracetamol (acetaminophen) and ibuprofen.{{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 }}

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.

Nirmatrelvir is a SARS-CoV-2 main protease (M^pro, 3CL^pro, nsp5 protease) inhibitor while ritonavir is an HIV-1 protease inhibitor and strong CYP3A inhibitor.{{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 }} 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. Ritonavir is not active against or thought to directly contribute to the medication's antiviral activity against SARS-CoV-2. Nirmatrelvir/ritonavir works against COVID{{nbhyph}}19 by preventing the replication of SARS-CoV-2, which the SARS-CoV-2 main protease is essential for.

The 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. 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 total exposure is 23.01{{nbsp}}μg•h/mL. 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.

The volume of distribution (V_z/F) of nirmatrelvir combined with ritonavir is 104.7{{nbsp}}L while that of ritonavir is 112.4{{nbsp}}L. The blood-to-plasma ratio of nirmatrelvir combined with ritonavir is 0.60 while the red-blood-cell-to-plasma ratio of ritonavir is 0.14. The plasma protein binding of nirmatrelvir combined with ritonavir is 69% while that of ritonavir is 98 to 99%.

Nirmatrelvir is mainly a substrate of CYP3A in terms of its metabolism. But when it is combined with ritonavir, a strong CYP3A4 inhibitor, nirmatrelvir's metabolism is minimal and its elimination instead is mainly via renal excretion. Ritonavir is eliminated mainly by hepatic metabolism, with CYP3A4 the major enzyme involved and CYP2D6 the minor enzyme.

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.

The oral clearance (CL/F) of nirmatrelvir combined with ritonavir is 8.99 while that of ritonavir is 13.92. 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. The half-life of nirmatrelvir combined with ritonavir makes the formulation suitable for administration every 12{{nbsp}}hours.

The pharmacokinetics of nirmatrelvir/ritonavir based on age or gender have not been assessed. Exposure to nirmatrelvir/ritonavir was numerically lower in Japanese than in Western people, but not to a clinically meaningful extent. 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, but not increased in people with moderate hepatic impairment. The combination has not been studied in people with severe hepatic impairment.

Research suggests that nirmatrelvir/ritonavir may minimize the risk of long COVID.{{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 = February 2024 | pmid = 38294771 | doi = 10.1001/jama.2023.28254 }} A 2025 recent report indicates that Paxlovid may benefit certain long COVID patients, though it remains unclear which individuals are most likely to respond.{{Cite news | vauthors = Belluck P |date=2025-01-06 |title=Paxlovid Improved Long Covid Symptoms in Some Patients, Researchers Report |url=https://www.nytimes.com/2025/01/06/health/paxlovid-long-covid.html |access-date=2025-01-11 |work=The New York Times |language=en-US |issn=0362-4331}} A study examined 13 long COVID patients who underwent extended treatment with the antiviral drug.{{cite journal | vauthors = Cohen AK, Jaudon TW, Schurman EM, Kava L, Vogel JM, Haas-Godsil J, Lewis D, Crausman S, Leslie K, Bligh SC, Lizars G, Davids JD, Sran S, Peluso M, McCorkell L | title = Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series | journal = Communications Medicine | volume = 4 | issue = 1 | pages = 261 | date = January 2025 | pmid = 39762640 | pmc = 11704346 | doi = 10.1038/s43856-024-00668-8 }} The results were mixed: nine patients experienced some improvement, but only five reported lasting effects, while four saw no improvement. The findings highlight the ongoing uncertainty surrounding effective treatments for long COVID, nearly five years into the pandemic. Although some patients recover naturally or respond to various therapies, no universally effective treatment has been identified.

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 symptomatic rebound after the five-day treatment, meaning they felt ill again and tested positive again (antigen test and PCR test) after testing negative.{{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 }} 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.{{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}}{{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=dead }}

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.{{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 }} President Joe Biden, First Lady Jill Biden, Anthony Fauci, Peter Hotez, and Rochelle Walensky{{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 }} 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. Both EPIC-HR and EPIC-SR were randomized controlled trials that provide information about COVID{{nbhyph}}19 rebound. 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. 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.

As of July 2022, no nirmatrelvir/ritonavir drug resistant SARS-CoV-2 had been observed in clinical context.{{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 }} The engineering of a nirmatrelvir-resistant chimera of vesicular stomatitis virus (VSV) under laboratory conditions was published without formal peer review in July 2022.{{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 }} As of November 2022, multiple pathways that could lead to resistance to nirmatrelvir/ritonavir had been demonstrated in vitro.{{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 }}

Nirmatrelvir belongs to a family of 3C-like 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.{{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=dead }} 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. No participants had received a COVID{{nbhyph}}19 vaccine or been previously infected with COVID{{nbhyph}}19. 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. EPIC-HR started in July 2021, and completed in December 2021.{{ClinicalTrialsGov|NCT04960202|EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19}} 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. In December 2021, Pfizer also announced that a Phase II/III study of nirmatrelvir/ritonavir showed a reduced risk of hospitalization or death.{{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 }}

In August 2021, Pfizer began a phase II/III trial of nirmatrelvir/ritonavir for COVID{{nbhyph}}19 in standard-risk individuals with COVID{{nbhyph}}19 known as EPIC-SR.{{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 }} Interim results of this trial were announced in December 2021, and final results were released in June 2022. Pfizer discontinued enrollment in the study, with the reason given being the very low rate of hospitalization and death in this population. EPIC-SR was another clinical trial that enrolled vaccinated participants with at least one risk factor for progression to severe COVID{{nbhyph}}19. 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.

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. 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.{{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}}

In April 2022, it was announced that the PANORAMIC trial would start testing the effectiveness of nirmatrelvir/ritonavir for treating COVID{{nbhyph}}19 infections.{{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 |url-access=subscription }}

Nirmatrelvir/ritonavir has been evaluated in the treatment of COVID{{nbhyph}}19 in standard-risk individuals in the EPIC-SR trial.{{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 = }} 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)). 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). 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). 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. Enrollment in EPIC-SR was discontinued due to the low rate of hospitalization and death in this population.{{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 }}

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. 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. In March 2024, the FDA revised the EUA for nirmatrelvir/ritonavir to remove the authorization for EUA-labeled nirmatrelvir/ritonavir.

File:Paxlovid.jpg

Health Canada approved the use of the co-packaged medication in January 2022.{{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}}{{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 }}{{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}}{{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}}

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.{{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}}

The European Medicines Agency (EMA) approved the co-packaged medication for the treatment of COVID{{nbhyph}}19 in the EU in January 2022.

The Israeli Ministry of Health approved the use of the co-packaged medication in December 2021.{{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}}

The Japanese Ministry of Health, Labour and Welfare approved the use of the co-packaged medication for treating adults in February 2022.{{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}}

The Singapore Health Sciences Authority approved the use of the co-packaged medication for treating adults in February 2022.{{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 }}

South Korea approved the use of the co-packaged medication in December 2021.{{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}}

The United Kingdom approved the use of the co-packaged medication in December 2021.{{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 }}

In November 2021, Pfizer submitted an application to the US Food and Drug Administration (FDA) for emergency use authorization for the co-packaged medication.{{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 }}{{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}}{{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}} The authorization was granted in December 2021, for people aged twelve years of age or older who are infected with COVID{{nbhyph}}19 and are at risk.{{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}}

In January 2024, the FDA revised the emergency use authorization (EUA) and stated that nirmatrelvir/ritonavir manufactured and labeled in accordance with the EUA under US distribution would remain authorized for use through the earlier of the labeled or extended expiration date, or through March 2024.{{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}} In March 2024, the FDA revised the emergency use authorization to no longer cover EUA-labeled nirmatrelvir/ritonavir. As of November 2024, the FDA emergency use authorization for nirmatrelvir/ritonavir continues to authorize it for the treatment of 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-19, including hospitalization or death.{{Cite web | archive-url=https://web.archive.org/web/20211222191953/https://www.fda.gov/media/155051/download | title=Fact sheet for patients, parents, and caregivers | archive-date=2021-12-22 | url=https://www.fda.gov/media/155051/download}} 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 aged twelve 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.{{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=dead }} {{PD-notice}}

Pfizer selected its largest oral tablet factory in Freiburg as the launch facility for manufacturing the co-packaged medication.{{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 }} Nirmatrelvir, the novel portion of the co-packaged medication, was developed in the US and was initially manufactured in small amounts in Groton, Connecticut, to support clinical trials,{{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 }} but the Freiburg facility was responsible for figuring out how to mass-produce the co-packaged medication on an industrial scale. Pfizer selected another factory in Ascoli Piceno, Italy, to assist the Freiburg factory with packaging tablets into blister packs.{{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 }}

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.{{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 }}

As of April 2022, the US had ordered 20 million nirmatrelvir/ritonavir courses.{{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://bidenwhitehouse.archives.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 }} As of July 2022, the United States Department of Health and Human Services had set up at least 2,200 sites where people could receive nirmatrelvir/ritonavir as soon as they tested positive for the virus, including pharmacies, community health centers and long-term care facilities. 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.{{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 }}

Throughout 2022, only 10-12% of eligible US adult outpatients had received nirmatrelvir/ritonavir. 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". Paxlovid treatment was free through the end of 2024, for Medicare and Medicaid beneficiaries and insured persons covering out-of-pocket costs.{{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 | archive-url=https://web.archive.org/web/20231013211342/https://www.hhs.gov/about/news/2023/10/13/hhs-and-pfizer-reach-agreement-to-increase-patient-access-to-paxlovid.html | url-status=dead | archive-date=13 October 2023 | access-date=30 June 2024}} Paxlovid continues to be free for some Medicare and Medicaid beneficiaries through the end of 2025, via the US Government Patient Assistance Program.{{cite web | last=Patel | first=Urvi | title=2025 Paxlovid U.S. Government Patient Assistance Program | website=AHCA/NCAL | date=8 January 2025 | url=https://www.ahcancal.org/News-and-Communications/Blog/Pages/2025-Paxlovid-U-S--Government-Patient-Assistance-Program.aspx | access-date=25 January 2025}}

Pfizer reported revenue of {{US$|1.279 billion}} for Paxlovid in 2023.{{cite web | title=Pfizer's year in review | website=Pfizer 2023 Annual Report | date=31 December 2023 | url=https://www.pfizer.com/sites/default/files/investors/financial_reports/annual_reports/2023/ | access-date=30 December 2024}}

Nirmatrelvir/ritonavir is sold under the brand name Paxlovid. Primovir and Paxista are generic versions manufactured and distributed in India.{{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 }}{{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 }}

{{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. Ivermectin has been falsely{{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 }} promoted as a COVID{{nbhyph}}19 therapeutic. Such claims, sometimes using the nickname "Pfizermectin",{{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 }} arise from superficial similarities between the mechanism of action of the drugs{{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/ |doi-access=free }} and the claim that Pfizer is suppressing information about the benefits of ivermectin.{{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 }}

{{Reflist}}

• {{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