Nirmatrelvir/ritonavir

Nirmatrelvir/ritonavir
Nirmatrelvir
Ritonavir
Combination of
NirmatrelvirAntiviral drug
RitonavirCYP3A inhibitor; Antiviral drug
Clinical data
Trade namesPaxlovid
AHFS/Drugs.comMonograph
MedlinePlusa622005
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
KEGG
ChEBI

Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID‑19.[8][11][10][18] It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer.[8][10] Nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir is a strong CYP3A inhibitor, slowing down nirmatrelvir metabolism and therefore boosting its effect.[10][19] It is taken by mouth.[10]

In unvaccinated high-risk people with COVID‑19, nirmatrelvir/ritonavir can reduce the risk of hospitalization or death by 88% if taken within five days of symptom onset.[20] People who take nirmatrelvir/ritonavir also test negative for COVID‑19 about two and a half days earlier than people who do not.[21] Side effects of nirmatrelvir/ritonavir include changes in sense of taste (dysgeusia), diarrhea, high blood pressure (hypertension), and muscle pain (myalgia).[10]

In December 2021, the United States Food and Drug Administration (FDA) granted nirmatrelvir/ritonavir emergency use authorization (EUA) to treat COVID‑19.[13][22] It was approved in the United Kingdom later that month,[23] and in the European Union and Canada in January 2022.[15][24][25] In May 2023, it was approved in the U.S. to treat mild to moderate COVID‑19 in adults who are at high risk for progression to severe COVID‑19, including hospitalization or death.[14][18] The FDA considers the combination to be a first-in-class medication.[26] In 2022, it was the 164th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[27][28]

Medical uses

In the United States, nirmatrelvir/ritonavir is indicated for the treatment of mild-to-moderate COVID‑19 in adults who are at high risk for progression to severe COVID‑19, including hospitalization or death.[10][14] This includes people above 50, people with diabetes, cancer, coronary artery disease, chronic lung diseases, pregnancy, or on immunosuppressant drugs.[29]

The co-packaged medication is not authorized or suggested for the pre-exposure or post-exposure prevention of COVID‑19.[12][14][30]

In the European Union, the co-packaged medication is indicated for the treatment of COVID‑19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID‑19.[15]

If administered within five days of symptom onset in confirmed COVID‑19 infections, the efficacy of the co-packaged medication against hospitalization or death in unvaccinated high-risk adults, as of 2022, was about 88% (95% CI, 75–94%).[13][20]

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.[31] Given the risk of morbidity, hospitalization and mortality associated with severe COVID‑19 disease in females and fetuses, nirmatrelvir/ritonavir can provide an important option to reduce the risks associated with acute COVID‑19 infection in at-risk and unvaccinated patients after careful consideration of the benefits and risks for each patient.[31] 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.[32] There are no human data on the presence of nirmatrelvir in human milk, or its effects on milk production or the infant.[33] A temporary reduction in body weight was observed in the offspring of nursing rats.[13] Other observational studies have also demonstrated the safety of ritonavir during pregnancy.[34]

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.[13] Co-administration with certain drugs may have serious, sometimes fatal, effects.[35]

Side effects

Nirmatrelvir/ritonavir has a high potential for potentially serious drug interactions due to strong CYP3A inhibition by ritonavir.[10][19] The US FDA label, the FDA fact sheet, and the FDA EUA contain a boxed warning about the CYP3A inhibition.[10][14]

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).[10][13][36] In clinical trials, 2% of people discontinued treatment due to side effects with nirmatrelvir/ritonavir while 4% in the placebo group did so.[10] Nirmatrelvir/ritonavir is under investigation, so its side effects have yet to be fully evaluated and may not be completely known.[19]

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.[10][19] Hypersensitivity reactions (allergic reactions) may manifest as skin rash, hives, difficulty swallowing, difficulty breathing, angioedema, and/or anaphylaxis.[10][19] 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.[10][19]

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 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.[10] Co-administration also affects the concentration of several drugs, sometimes requiring changing the dose or careful monitoring.[13][36] Many of these drugs are widely prescribed to people at high risk from COVID‑19.[37] 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.[38][13]

Nirmatrelvir/ritonavir is safe to use in combination with over-the-counter pain- and fever-reducing medications such as paracetamol (acetaminophen) and ibuprofen.[39]

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.[10][19]

Pharmacodynamics

Nirmatrelvir is a SARS-CoV-2 main protease (Mpro, 3CLpro, nsp5 protease) inhibitor while ritonavir is an HIV-1 protease inhibitor and strong CYP3A inhibitor.[10][19] 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.[10][19] Ritonavir is not active against or thought to directly contribute to the medication's antiviral activity against SARS-CoV-2.[19][10] Nirmatrelvir/ritonavir works against COVID‑19 by preventing the replication of SARS-CoV-2, which the SARS-CoV-2 main protease is essential for.[10][19]

Pharmacokinetics

Absorption

The time to peak concentrations of nirmatrelvir combined with ritonavir is 3.00 hours (range 1.02–6.00 hours), while that of ritonavir is 3.98 hours.[10] Peak concentrations of nirmatrelvir combined with ritonavir following a single dose (300 mg nirmatrelvir and 100 mg ritonavir) in healthy individuals are 2.21 μg/mL while total exposure is 23.01 μg•h/mL.[10] 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.[10]

Distribution

The volume of distribution (Vz/F) of nirmatrelvir combined with ritonavir is 104.7 L while that of ritonavir is 112.4 L.[10] 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.[10] The plasma protein binding of nirmatrelvir combined with ritonavir is 69% while that of ritonavir is 98 to 99%.[10]

Metabolism

Nirmatrelvir is mainly a substrate of CYP3A in terms of its metabolism.[10] 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.[10] Ritonavir is eliminated mainly by hepatic metabolism, with CYP3A4 the major enzyme involved and CYP2D6 the minor enzyme.[10]

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.[10]

The oral clearance (CL/F) of nirmatrelvir combined with ritonavir is 8.99 while that of ritonavir is 13.92.[10] The elimination half-life of nirmatrelvir combined with ritonavir is (mean ± SD) 6.05 ± 1.79 hours while that of ritonavir is 6.15 hours.[10] The half-life of nirmatrelvir combined with ritonavir makes the formulation suitable for administration every 12 hours.[10][19]

Specific populations

The pharmacokinetics of nirmatrelvir/ritonavir based on age or gender have not been assessed.[10] Exposure to nirmatrelvir/ritonavir was numerically lower in Japanese than in Western people, but not to a clinically meaningful extent.[10] 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,[10] but not increased in people with moderate hepatic impairment.[10] The combination has not been studied in people with severe hepatic impairment.[10]

Research

Research suggests that nirmatrelvir/ritonavir may minimize the risk of long COVID.[29]

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 symptomatic rebound after the five-day treatment, meaning they felt ill again and tested positive again (antigen test and PCR test) after testing negative.[40] 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.[41][42]

In June 2022, a US case report of ten people with rebound COVID‑19 had found viral load during relapse was comparable to levels during an initial infection, and high enough to cause secondary transmission.[43] President Joe Biden, First Lady Jill Biden, Anthony Fauci,[41] Peter Hotez, and Rochelle Walensky[44] 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.[43] Both EPIC-HR and EPIC-SR were randomized controlled trials that provide information about COVID‑19 rebound.[14] Data from these trials showed that rebound in SARS-CoV-2 (RNA or virus) shedding or COVID‑19 symptoms occurred in a subset of participants and happened in both the participants receiving nirmatrelvir/ritonavir and the placebo.[14] As of 2023, the FDA found there was no clear association between nirmatrelvir/ritonavir treatment and COVID‑19 rebound based on data available to them.[14]

Resistance

As of July 2022, no nirmatrelvir/ritonavir drug resistant SARS-CoV-2 had been observed in clinical context.[45] The engineering of a nirmatrelvir-resistant chimera of vesicular stomatitis virus (VSV) under laboratory conditions was published without formal peer review in July 2022.[46] As of November 2022, multiple pathways that could lead to resistance to nirmatrelvir/ritonavir had been demonstrated in vitro.[47]

History

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.[10][12][48] Participants were 18 years of age and older with a pre-specified risk factor for progression to severe disease, or were 60 years and older regardless of pre-specified chronic medical conditions.[12] No participants had received a COVID‑19 vaccine or been previously infected with COVID‑19.[12] The main outcome measured in the trial was the proportion of people who were hospitalized due to COVID‑19 or died due to any cause during 28 days of follow-up.[12] EPIC-HR started in July 2021, and completed in December 2021.[49] Nirmatrelvir/ritonavir significantly reduced the proportion of people with COVID‑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‑19 therapeutic monoclonal antibody treatment.[12] In December 2021, Pfizer also announced that a Phase II/III study of nirmatrelvir/ritonavir showed a reduced risk of hospitalization or death.[50]

In August 2021, Pfizer began a phase II/III trial of nirmatrelvir/ritonavir for COVID‑19 in standard-risk individuals with COVID‑19 known as EPIC-SR.[51][52] Interim results of this trial were announced in December 2021, and final results were released in June 2022.[51] Pfizer discontinued enrollment in the study, with the reason given being the very low rate of hospitalization and death in this population.[53] EPIC-SR was another clinical trial that enrolled vaccinated participants with at least one risk factor for progression to severe COVID‑19.[14] Although not statistically significant, among these vaccinated participants, there was a reduction in the risk of COVID‑19 related hospitalization or death from any cause.[14]

In December 2021, nirmatrelvir/ritonavir was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID‑19.[13] 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.[54][23]

In April 2022, it was announced that the PANORAMIC trial would start testing the effectiveness of nirmatrelvir/ritonavir for treating COVID‑19 infections.[55]

Nirmatrelvir/ritonavir has been evaluated in the treatment of COVID‑19 in standard-risk individuals in the EPIC-SR trial.[51][53] This study did not achieve its primary goal of reducing time to sustained alleviation of COVID‑19 symptoms (treatment: 13 days (95% CI 12–15 days); placebo: 13 days (95% CI 11–14 days)).[51][53] 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).[51][53] 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‑19 (treatment: 3/361 [0.8%]; placebo: 7/360 [1.9%]; 57% reduction – RR 0.43, 95% CI 0.11–1.64).[51][53] However, the trial did find a statistically significant 62% decrease in COVID‑19-related medical visits, similar to the 67% reduction from the EPIC-HR study of high-risk individuals.[51][53] Enrollment in EPIC-SR was discontinued due to the low rate of hospitalization and death in this population.[51][53]

In May 2023, nirmatrelvir/ritonavir received FDA approval for the treatment of mild-to-moderate COVID‑19 in adults who are at high risk for progression to severe COVID‑19, including hospitalization or death.[14] 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‑19 in people aged twelve years of age and older weighing at least 40 kilograms (88 lb), who are at high risk for progression to severe COVID‑19, including hospitalization.[18] In March 2024, the FDA revised the EUA for nirmatrelvir/ritonavir to remove the authorization for EUA-labeled nirmatrelvir/ritonavir.[56][18]

Society and culture

US packaging for Paxlovid, the branded form of nirmatrelvir/ritonavir, as of 2022

Canada

Health Canada approved the use of the co-packaged medication in January 2022.[7][24][57][58][59]

China

In February 2022, China approved the medication for the treatment of adults who have mild to moderate COVID‑19 and are at a high risk of progressing to a severe condition.[60]

European Union

The European Medicines Agency (EMA) approved the co-packaged medication for the treatment of COVID‑19 in the EU in January 2022.[15][16]

Israel

The Israeli Ministry of Health approved the use of the co-packaged medication in December 2021.[61]

Japan

The Japanese Ministry of Health, Labour and Welfare approved the use of the co-packaged medication for treating adults in February 2022.[62]

Singapore

The Singapore Health Sciences Authority approved the use of the co-packaged medication for treating adults in February 2022.[63]

South Korea

South Korea approved the use of the co-packaged medication in December 2021.[64]

United Kingdom

The United Kingdom approved the use of the co-packaged medication in December 2021.[8][9][65]

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.[66][67][68] The authorization was granted in December 2021, for people 12 years of age or older who are infected with COVID‑19 and are at risk.[12][18][69]

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.[56] In March 2024, the FDA revised the emergency use authorization to no longer cover EUA-labeled nirmatrelvir/ritonavir.[18][56] 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 40 kilograms (88 lb) who are at high risk for progression to severe COVID-19, including hospitalization or death.[56][18] 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 40 kilograms (88 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.[18][56][70]

Manufacturing

Pfizer selected its largest oral tablet factory in Freiburg as the launch facility for manufacturing the co-packaged medication.[71] 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,[72] but the Freiburg facility was responsible for figuring out how to mass-produce the co-packaged medication on an industrial scale.[71] Pfizer selected another factory in Ascoli Piceno, Italy, to assist the Freiburg factory with packaging tablets into blister packs.[73]

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.[74]

As of April 2022, the U.S. ordered a total of 20 million nirmatrelvir/ritonavir courses.[75] 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.[69] In July 2022, the FDA allowed state-licensed pharmacists to prescribe it to people with COVID‑19 at high risk of progressing to severe disease.[76]

Throughout 2022, only 10-12% of eligible U.S. adult outpatients received nirmatrelvir/ritonavir.[29] 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".[29] In spite of Pfizer's list price of US$1,390 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.[29][77]

Brand names

Nirmatrelvir/ritonavir is sold under the brand name Paxlovid.[10] Primovir and Paxista are generic versions manufactured and distributed in India.[78][79]

Comparison to ivermectin

Further information: 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.[80][81] Ivermectin has been falsely[82] promoted as a COVID‑19 therapeutic. Such claims, sometimes using the nickname "Pfizermectin",[83] arise from superficial similarities between the mechanism of action of the drugs[80] and the claim that Pfizer is suppressing information about the benefits of ivermectin.[81]

References

  1. ^ "Paxlovid APMDS". Therapeutic Goods Administration (TGA). 21 January 2022. Archived from the original on 5 February 2022. Retrieved 5 February 2022.
  2. ^ a b "AusPAR: nirmatrelvir/ritonavir". Therapeutic Goods Administration (TGA). 25 January 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022.
  3. ^ a b "TGA eBS - Product and Consumer Medicine Information Licence". Archived from the original on 5 February 2022. Retrieved 5 February 2022.
  4. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  5. ^ "Product Monograph: Paxlovid" (PDF). Archived (PDF) from the original on 7 January 2024.
  6. ^ "Summary Basis of Decision (SBD) for Paxlovid". Health Canada. 23 October 2014. Archived from the original on 12 June 2022. Retrieved 29 May 2022.
  7. ^ a b "Paxlovid". Health Canada. 17 January 2022. Archived from the original on 18 January 2022. Retrieved 18 January 2022.
  8. ^ a b c d "Summary of Product Characteristics for Paxlovid". Medicines and Healthcare products Regulatory Agency (MHRA). 31 December 2021. Archived from the original on 31 December 2021. Retrieved 31 December 2021.
  9. ^ a b "Regulatory approval of Paxlovid". Medicines and Healthcare products Regulatory Agency (MHRA). 31 December 2021. Archived from the original on 11 January 2022. Retrieved 31 December 2021.
  10. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an "Paxlovid- nirmatrelvir and ritonavir kit". DailyMed. 18 October 2023. Archived from the original on 26 February 2024. Retrieved 6 January 2024.
  11. ^ a b "Paxlovid- nirmatrelvir and ritonavir kit". DailyMed. Archived from the original on 31 December 2021. Retrieved 30 December 2021.
  12. ^ a b c d e f g h "FDA Authorizes First Oral Antiviral for Treatment of COVID-19" (Press release). U.S. Food and Drug Administration (FDA). 22 December 2021. Archived from the original on 27 December 2021. Retrieved 22 December 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  13. ^ a b c d e f g h i Fact sheet for healthcare providers: Emergency Use Authorization for Paxlovid (PDF) (Technical report). Pfizer. 22 December 2021. LAB-1492-0.8. Archived from the original on 23 December 2021.
  14. ^ a b c d e f g h i j k "FDA Approves First Oral Antiviral for Treatment of COVID-19 in Adults". U.S. Food and Drug Administration (FDA) (Press release). 26 May 2023. Archived from the original on 28 July 2023. Retrieved 26 May 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  15. ^ a b c d "Paxlovid EPAR". European Medicines Agency (EMA). 24 January 2022. Archived from the original on 11 May 2022. Retrieved 3 February 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  16. ^ a b "Paxlovid PI". Union Register of medicinal products. 28 January 2022. Archived from the original on 16 May 2022. Retrieved 24 April 2022.
  17. ^ "COVID-19 medicines". European Medicines Agency (EMA). 14 October 2024. Retrieved 14 October 2024.
  18. ^ a b c d e f g h "Frequently Asked Questions on the Emergency Use Authorization for Paxlovid for Treatment of COVID-19" (PDF). U.S. Food and Drug Administration (FDA). 1 November 2023. Archived from the original on 7 January 2024. Retrieved 6 January 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  19. ^ a b c d e f g h i j k l Akinosoglou K, Schinas G, Gogos C (November 2022). "Oral Antiviral Treatment for COVID-19: A Comprehensive Review on Nirmatrelvir/Ritonavir". Viruses. 14 (11): 2540. doi:10.3390/v14112540. PMC 9696049. PMID 36423149.
  20. ^ a b Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. (April 2022). "Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19". The New England Journal of Medicine. 386 (15): 1397–1408. doi:10.1056/NEJMoa2118542. PMC 8908851. PMID 35172054.
  21. ^ Amani B, Amani B (February 2023). "Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID-19: A rapid review and meta-analysis". Journal of Medical Virology. 95 (2): e28441. doi:10.1002/jmv.28441. PMC 9880713. PMID 36576379.
  22. ^ "Pfizer Receives U.S. FDA Emergency Use Authorization for Novel COVID-19 Oral Antiviral Treatment" (Press release). Pfizer. 22 December 2021. Archived from the original on 22 December 2021. Retrieved 22 December 2021 – via Business Wire.
  23. ^ a b "Oral COVID-19 antiviral, Paxlovid, approved by UK regulator" (Press release). Medicines and Healthcare products Regulatory Agency. 31 December 2021. Archived from the original on 11 January 2022. Retrieved 5 January 2022.
  24. ^ a b "Health Canada authorizes Paxlovid for patients with mild to moderate COVID-19 at high risk of developing serious disease". Health Canada (Press release). 17 January 2022. Archived from the original on 29 April 2022. Retrieved 24 April 2022.
  25. ^ "Paxlovid". COVID-19 vaccines and treatments portal. 17 January 2022. Archived from the original on 22 April 2022. Retrieved 25 April 2022.
  26. ^ New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
  27. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  28. ^ "Nirmatrelvir; Ritonavir Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  29. ^ a b c d e Rubin R (January 2024). "Paxlovid Is Effective but Underused-Here's What the Latest Research Says About Rebound and More". JAMA. 331 (7): 548–551. doi:10.1001/jama.2023.28254. PMID 38294771.
  30. ^ Reis S, Metzendorf MI, Kuehn R, Popp M, Gagyor I, Kranke P, et al. (November 2023). "Nirmatrelvir combined with ritonavir for preventing and treating COVID-19". The Cochrane Database of Systematic Reviews. 2023 (11): CD015395. doi:10.1002/14651858.CD015395.pub3. PMC 10688265. PMID 38032024.
  31. ^ a b Chourasia P, Maringanti BS, Edwards-Fligner M, Gangu K, Bobba A, Sheikh AB, et al. (January 2023). "Paxlovid (Nirmatrelvir and Ritonavir) Use in Pregnant and Lactating Woman: Current Evidence and Practice Guidelines-A Scoping Review". Vaccines. 11 (1): 107. doi:10.3390/vaccines11010107. PMC 9866309. PMID 36679952.
  32. ^ Loza A, Farias R, Gavin N, Wagner R, Hammer E, Shields A (September 2022). "Short-term Pregnancy Outcomes After Nirmatrelvir-Ritonavir Treatment for Mild-to-Moderate Coronavirus Disease 2019 (COVID-19)". Obstetrics and Gynecology. 140 (3): 447–449. doi:10.1097/AOG.0000000000004900. PMC 9377369. PMID 36356238.
  33. ^ "Pregnancy, breastfeeding and fertility while taking Paxlovid". National Health Service. 11 May 2022. Archived from the original on 12 November 2023. Retrieved 16 November 2023.
  34. ^ Pasley MV, Martinez M, Hermes A, d'Amico R, Nilius A (2013). "Safety and efficacy of lopinavir/ritonavir during pregnancy: a systematic review". AIDS Reviews. 15 (1): 38–48. PMID 23449228.
  35. ^ "Ritonavir-Boosted Nirmatrelvir (Paxlovid)". National Institutes of Health. 24 February 2022. Archived from the original on 23 April 2022. Retrieved 25 April 2022.
  36. ^ a b "EMA issues advice on use of Paxlovid (PF-07321332 and ritonavir) for the treatment of COVID-19: rolling review starts in parallel" (Press release). European Medicines Agency (EMA). 16 December 2021. Archived from the original on 11 January 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  37. ^ "Pfizer antiviral pills may be risky with other medications". ABC News. 26 December 2021. Archived from the original on 3 February 2022. Retrieved 4 February 2022.
  38. ^ "Paxlovid Patient Eligibility Screening Checklist and Drug Interaction Tool". U.S. Food and Drug Administration (FDA). 26 August 2022. Archived from the original on 10 October 2022. Retrieved 10 October 2022.
  39. ^ "Should I take Paxlovid after a Positive COVID-19 Test?". drugs.com. 13 November 2022. Archived from the original on 7 December 2022. Retrieved 7 December 2022.
  40. ^ Anderson AS, Caubel P, Rusnak JM (September 2022). "Nirmatrelvir-Ritonavir and Viral Load Rebound in Covid-19". The New England Journal of Medicine. 387 (11): 1047–1049. doi:10.1056/NEJMc2205944. PMC 9513855. PMID 36069818.
  41. ^ a b "Pfizer Says Patients Who Relapse After Covid Pill Can Repeat Treatment". Bloomberg. 3 May 2022. Archived from the original on 14 May 2022. Retrieved 21 May 2022.
  42. ^ "FDA Updates on Paxlovid for Health Care Providers". U.S. Food and Drug Administration (FDA). 4 May 2022. Archived from the original on 20 May 2022. Retrieved 21 May 2022.
  43. ^ a b Rubin R (June 2022). "From Positive to Negative to Positive Again-The Mystery of Why COVID-19 Rebounds in Some Patients Who Take Paxlovid". JAMA. 327 (24): 2380–2382. doi:10.1001/jama.2022.9925. PMID 35675094. S2CID 249465757.
  44. ^ "CDC Director Rochelle Walensky tests positive for Covid again after taking a course of the antiviral pill Paxlovid". NBC. 31 October 2022. Archived from the original on 1 November 2022. Retrieved 1 November 2022.
  45. ^ Lowe D (11 July 2022). "Paxlovid Resistance: Is It Just a Matter of Time Now?". In the Pipeline. Archived from the original on 10 October 2022. Retrieved 10 October 2022.
  46. ^ Heilmann E, Costacurta F, Volland A, von Laer D (4 July 2022). "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. S2CID 250353628. Archived from the original on 9 November 2023. Retrieved 8 November 2023.
  47. ^ Iketani S, Mohri H, Culbertson B, Hong SJ, Duan Y, Luck MI, et al. (November 2022). "Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir". Nature. 613 (7944): 558–564. doi:10.1038/s41586-022-05514-2. PMC 9849135. PMID 36351451. S2CID 253445215.
  48. ^ CDER Scientific Review Supporting EUA (PDF) (Report). U.S. Food and Drug Administration (FDA). Archived from the original on 17 January 2022. Retrieved 16 February 2022.
  49. ^ Clinical trial number NCT04960202 for "EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19" at ClinicalTrials.gov
  50. ^ "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" (Press release). Pfizer. 14 December 2021. Archived from the original on 26 December 2021. Retrieved 25 December 2021 – via Business Wire.
  51. ^ a b c d e f g h Lee TC, Pogue JM, McCreary EK, Morris AM (November 2022). "What is the place in therapy for nirmatrelvir/ritonavir?". BMJ Evid Based Med. 28 (5): 287–290. doi:10.1136/bmjebm-2022-112064. PMID 36384743. S2CID 253579652.
  52. ^ "Pfizer begins dosing in Phase II/III trial of antiviral drug for Covid-19". Clinical Trials Arena. 2 September 2021. Archived from the original on 5 November 2021. Retrieved 5 January 2022.
  53. ^ a b c d e f g "Pfizer Reports Additional Data on Paxlovid Supporting Upcoming New Drug Application Submission to U.S. FDA". New York. 14 June 2022. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  54. ^ Aripaka P (31 December 2021). "Britain approves Pfizer's antiviral COVID-19 pill". Reuters. Archived from the original on 31 December 2021. Retrieved 31 December 2021.
  55. ^ Robinson J (April 2022). "PANORAMIC trial to enlist 17,500 more patients as researchers add second COVID-19 antiviral". The Pharmaceutical Journal. doi:10.1211/PJ.2022.1.138635. Archived from the original on 25 April 2022. Retrieved 26 April 2022.
  56. ^ a b c d e "FDA revises letter of authorization for the emergency use authorization for Paxlovid". U.S. Food and Drug Administration (FDA). 13 March 2024. Archived from the original on 27 May 2024. Retrieved 29 June 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  57. ^ "Paxlovid (nirmatrelvir / ritonavir)". Health Canada. 1 September 2012. Archived from the original on 25 February 2024. Retrieved 30 June 2024.
  58. ^ "Paxlovid, Pfizer's oral COVID-19 pill, approved in Canada". Global News. Archived from the original on 18 January 2022. Retrieved 18 January 2022.
  59. ^ Weeks C (17 January 2022). "Health Canada approves Pfizer's COVID-19 antiviral pill Paxlovid". The Globe and Mail. Archived from the original on 18 January 2022. Retrieved 18 January 2022.
  60. ^ "China conditionally approves Pfizer's Covid treatment pill Paxlovid". The Guardian. Reuters. 12 February 2022. Archived from the original on 13 February 2022. Retrieved 13 February 2022.
  61. ^ "The Use of Pfizer's Anti-Viral Drug for the Treatment of COVID-19 Has Been Approved". Ministry of Health (Press release). Archived from the original on 28 December 2021. Retrieved 28 December 2021.
  62. ^ Higuchi Y, Kaneda Y, Tanimoto T (November 2023). "Japan's COVID-19 treatment strategy: An examination of approved oral medications". Clinical and Translational Science. 16 (11): 2075–2077. doi:10.1111/cts.13628. PMC 10651642. PMID 37691254.
  63. ^ Chelvan VP (3 February 2022). "Singapore approves Pfizer's Paxlovid pill for COVID-19 treatment in adult patients". CNA. Archived from the original on 17 February 2022. Retrieved 3 February 2022.
  64. ^ "S.Korea authorises emergency use of Pfizer's oral coronavirus treatment". Reuters. 27 December 2021. Archived from the original on 11 January 2022. Retrieved 28 December 2021.
  65. ^ "Paxlovid 150 mg/100 mg film-coated tablets". (emc). 16 January 2024. Archived from the original on 27 February 2024. Retrieved 30 June 2024.
  66. ^ "Pfizer Seeks Emergency Use Authorization for Novel COVID-19 Oral Antiviral Candidate" (Press release). Pfizer. 16 November 2021. Archived from the original on 16 November 2021. Retrieved 17 November 2021 – via Business Wire.
  67. ^ Kimball S (16 November 2021). "Pfizer submits FDA application for emergency approval of Covid treatment pill". CNBC. Archived from the original on 16 November 2021. Retrieved 17 November 2021.
  68. ^ Robbins R (5 November 2021). "Pfizer Says Its Antiviral Pill Is Highly Effective in Treating Covid". The New York Times. ISSN 0362-4331. Archived from the original on 8 November 2021. Retrieved 9 November 2021.
  69. ^ a b Kimball S (3 May 2022). "Paxlovid prescriptions to treat Covid increased tenfold in U.S. since late February, Pfizer says". CNBC. Archived from the original on 3 May 2022. Retrieved 3 May 2022.
  70. ^ "Emergency Use Authorization 105" (PDF). U.S. Food and Drug Administration (FDA). 13 March 2024. Archived from the original on 22 April 2022. Retrieved 30 June 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  71. ^ a b Schmidt B (1 December 2021). "Neues Corona-Medikament von Pfizer wird in Freiburg hergestellt" [Pfizer corona medicine is being manufactured in Freiburg]. Badische Zeitung (in German). Archived from the original on 15 January 2022. Retrieved 15 January 2022.
  72. ^ Green R (23 December 2021). "Pfizer scientists in Groton played a critical role in development of new COVID-19 pill". The Hartford Courant. Archived from the original on 15 January 2022. Retrieved 15 January 2022.
  73. ^ Paci M (17 December 2021). "Covid, ad Ascoli l'unico stabilimento in Italia che produrrà il farmaco antivirale. Pfizer pensa a cento assunzioni" [Covid, in Ascoli the only plant in Italy that will produce the antiviral drug. Pfizer thinks to hire one hundred]. Corriere Adriatico (in Italian). Archived from the original on 15 January 2022. Retrieved 15 January 2022.
  74. ^ Hackenbroch V (25 August 2022). "Der Paxlovid-Skandal: Warum verweigern deutsche Ärzte so vielen Patienten den Virenkiller?". Der Spiegel (in German). ISSN 2195-1349. Archived from the original on 10 October 2022. Retrieved 10 October 2022.
  75. ^ "Fact Sheet: Biden Administration Increases Access to COVID-19 Treatments and Boosts Patient and Provider Awareness". The White House (Press release). 26 April 2022. Archived from the original on 6 July 2022. Retrieved 7 July 2022.
  76. ^ Stephenson J (July 2022). "FDA Authorizes Pharmacists to Prescribe Oral Antiviral Medication for COVID-19". JAMA Health Forum. 3 (7): e222968. doi:10.1001/jamahealthforum.2022.2968. PMID 36219005. S2CID 250704928.
  77. ^ "HHS and Pfizer Reach Agreement to Increase Patient Access to Paxlovid". U.S. Department of Health and Human Services (HHS) (Press release). 13 October 2023. Retrieved 30 June 2024.
  78. ^ Singh AG. "Indian generics emerge as a life-saver in COVID-hit China". ORF. Archived from the original on 21 January 2023. Retrieved 30 December 2022.
  79. ^ "Chinese turn to black market for generic Indian Covid-19 drugs". South China Morning Post. 26 December 2022. Archived from the original on 29 December 2022. Retrieved 30 December 2022.
  80. ^ a b von Csefalvay C (27 November 2021). "Why Paxlovid is not Pfizermectin". Chris von Csefalvay: Bits and Bugs. doi:10.59350/576dr-vbd49. Archived from the original on 9 January 2022. Retrieved 9 January 2022.
  81. ^ a b Gorski D (15 November 2021). "Pfizer's new COVID-19 protease inhibitor drug is not just 'repackaged ivermectin'". Science-Based Medicine. Archived from the original on 20 December 2021. Retrieved 5 January 2022.
  82. ^ "Ivermectin: How false science created a Covid 'miracle' drug". BBC News. 6 October 2021. Archived from the original on 8 January 2022. Retrieved 8 November 2022.
  83. ^ Bloom J (2 December 2021). "How Does Pfizer's Paxlovid Compare With Ivermectin?". American Council on Science and Health. Archived from the original on 15 December 2021. Retrieved 12 December 2021.

Read other articles:

Gereja Yesuit, Mannheim

Gereja YesuitGereja Paroki Santo Igantius dari Loyola dan Santo Fransiskus XaveriusJerman: Jesuitenkirchecode: de is deprecated Gereja Yesuit, MannheimLokasiMannheimNegara JermanDenominasiGereja Katolik RomaSejarahDedikasiYesuitArsitekturStatusgereja parokiStatus fungsionalAktifTipe arsitekturGereja Gereja Yesuit (Jerman: Jesuitenkirchecode: de is deprecated ) yang bernama resmi Gereja Santo Igantius dari Loyola dan Santo Fransiskus Xaverius adalah sebuah gereja paroki Katolik yang terle...

 

 

Björn Stenvers

Björn Stenvers (* 25 Mei 1972 di Arnhem) adalah CEO Eye Care Foundation dan pendiri akademi museum. Kehidupan Sebelumnya, ia adalah direktur Fonds de dotation des Dewan Museum Internasional. Hingga 2016 ia adalah direktur Foundation of the Museums of Amsterdam, yang juga ia dirikan. Björn adalah satu-satunya peserta internasional dalam program kepresidenan untuk para menteri Akademi Ekonomi dan Layanan Publik Rusia di bawah Presiden Federasi Rusia (RANEPA, Forum Gaidar) di mana dia juga men...

 

 

دوري جزر فارو الممتاز 1952

يفتقر محتوى هذه المقالة إلى الاستشهاد بمصادر. فضلاً، ساهم في تطوير هذه المقالة من خلال إضافة مصادر موثوق بها. أي معلومات غير موثقة يمكن التشكيك بها وإزالتها. (نوفمبر 2019) دوري جزر فارو الممتاز 1952 تفاصيل الموسم دوري جزر فارو الممتاز  البلد الدنمارك  البطل نادي كلاكسفيك...

Article 18 de la Constitution de la Cinquième République française

Article 18 de la Constitution du 4 octobre 1958 Données clés Présentation Pays France Langue(s) officielle(s) Français Type Article de la Constitution Adoption et entrée en vigueur Législature IIIe législature de la Quatrième République française Gouvernement Charles de Gaulle (3e) Promulgation 4 octobre 1958 Publication 5 octobre 1958 Entrée en vigueur 5 octobre 1958 Article 17 Article 19 modifier L’article 18 de la Constitution de la Ve République est un article de la Co...

 

 

Distrik Matsumae, Hokkaido

Wilayah Distrik Matsumae di Subprefektur Oshima. Matsumae (松前郡code: ja is deprecated , Matsumae-gun) adalah sebuah distrik yang berada di wilayah Subprefektur Oshima, Hokkaido, Jepang. Per 31 Januari 2024, distrik ini memiliki estimasi jumlah penduduk sebesar 9.468 jiwa dan kepadatan penduduk sebesar 19,70 orang per km2. Distrik ini memiliki luas wilayah sebesar 480,53 km2. Kota kecil dan desa Fukushima Matsumae Geografi Wilayah distrik ini berada di ujung selatan Semenanjung Matsu...

 

 

Christophe Noppe

Cet article est une ébauche concernant un coureur cycliste belge. Vous pouvez partager vos connaissances en l’améliorant (comment ?). Pour plus d’informations, voyez le projet cyclisme. Christophe NoppeChristophe Noppe (2022)InformationsNaissance 29 novembre 1994 (29 ans)AudenardeNationalité belgeÉquipe actuelle CofidisÉquipes non-UCI 2012DJ-Matic Kortrijk2014EFC-Omega Pharma-Quick Step2015-2016EFC-EtixxÉquipes UCI 2017-2019Sport Vlaanderen-Baloise2020-2022Arkéa-Samsic20...

تشيب كيل

تشيب كيل معلومات شخصية الميلاد 10 مارس 1949 (75 سنة)  أتلانتا  مواطنة الولايات المتحدة  الحياة العملية المدرسة الأم جامعة تينيسي  المهنة لاعب كرة قدم كندية  الرياضة كرة القدم الكندية  تعديل مصدري - تعديل   تشيب كيل (بالإنجليزية: Chip Kell)‏ هو لاعب كرة قدم كندية أمر�...

 

 

Simona de Silvestro

Simona de SilvestroSimona de Silvestro in May 2010.Kebangsaan SwissLahir1 September 1988 (1988-09) (usia 35)Thun, SwitzerlandKarier Kejuaraan SupercarsNo. mobil78Tim saat iniNissan MotorsportGelar juara0Start28Menang0Podium0Posisi pole0Klasemen 201724th (1131 pts) Simona de Silvestro (lahir 1 September 1988) merupakan seorang pembalap mobil profesional asal Swiss. Ia telah malang melintang membalap di beberapa ajang seperti di Seri IndyCar, FIA Formula E dan V8 Supercars. Ia juga sempat ...

 

 

Trinity Catholic School

Academy in Leamington Spa, Warwickshire, EnglandTrinity Catholic SchoolAddressGuy's Cliffe AvenueLeamington Spa, Warwickshire, CV32 6NBEnglandCoordinates52°17′46″N 1°33′06″W / 52.2960°N 1.5517°W / 52.2960; -1.5517InformationTypeAcademyReligious affiliation(s)Roman CatholicLocal authorityWarwickshireTrustOur Lady of the Magnificat MACDepartment for Education URN148362 TablesOfstedReportsPrincipalBridget MorrisGenderMixedAge11 to 18Enrolment615 (201...

William McBryar

William McBryarLieutenant William McBryarLahir(1861-02-14)14 Februari 1861Elizabethtown, Carolina UtaraMeninggal8 Maret 1941(1941-03-08) (umur 80)Philadelphia, PennsylvaniaTempat pemakamanArlington National CemeteryPengabdianAmerika SerikatDinas/cabangAngkatan Darat Amerika SerikatLama dinas1887–1900, 1905PangkatLetnan SatuPerang/pertempuranPeperangan Apache Kampanye Cherry Creek Perang Spanyol–Amerika Perang Filipina–AmerikaPenghargaanMedal of Honor William McBryar (14 Februa...

 

 

Sander Greenland

American statistician and epidemiologist Sander GreenlandGreenland in 2018Born (1951-01-16) January 16, 1951 (age 73)NationalityAmericanAlma materUniversity of California, Los AngelesUniversity of California, BerkeleyScientific careerFieldsStatisticsEpidemiologyInstitutionsUniversity of California, Los AngelesDoctoral advisorRaymond Neutra Sander Greenland (born January 16, 1951) is an American statistician and epidemiologist with many contributions to statistical and epidemiologic ...

 

 

Tey (regina)

TeyLa regina Tey rappresentata in una cappella ad Akhmin. Disegno di Karl Richard Lepsius.Regina consorte d'Egitto, Grande Sposa RealeIn carica1323 a.C. –1319 a.C. PredecessoreAnkhesenamon(Grande sposa reale di Tutankhamon) SuccessoreMutnodjemet(Grande sposa reale di Horemheb) Mortedopo il 1319 a.C.? Luogo di sepolturaTomba KV23 nella Valle dei Re DinastiaXVIII dinastia ConsorteAy FigliMutnodjemet, Nakhtmin Nefertiti ReligioneReligione egizia Tey (... – Tebe, dopo il 1319 a.C.)...

Diisobutyl phthalate

Diisobutyl phthalate Names Preferred IUPAC name Bis(2-methylpropyl) benzene-1,2-dicarboxylate Other names Diisobutyl phthalateDi-iso-butyl phthalateDi(i-butyl)phthalateDiisobutyl ester of phthalic acid1,2-benzenedicarboxylic acidBis(2-methylpropyl)esterDi(isobutyl) 1,2-benzenedicarboxylateIsobutyl-O-phthalateDIBPDiBPPalatinol IC Identifiers CAS Number 84-69-5 Y 3D model (JSmol) Interactive image ChEBI CHEBI:79053 Y ChemSpider 6524 Y ECHA InfoCard 100.001.412 EC Number 201-553-...

 

 

الإخوان المسلمون في السودان

هذه المقالة مكتوبة من وجهة نظر مُعجَب أو مُشجِّع، وهي لا تعرِض وجهة نظر محايدة. فضلاً، أَزِل ألفاظ الإعجاب والتباهي من متنها، لتتوافق مع دليل الأسلوب في ويكيبيديا. (نقاش) تحتاج هذه المقالة إلى الاستشهاد بمصادر إضافية لتحسين وثوقيتها. فضلاً ساهم في تطوير هذه المقالة بإضافة �...

 

 

Nyanyian Malam

Artikel ini tidak memiliki referensi atau sumber tepercaya sehingga isinya tidak bisa dipastikan. Tolong bantu perbaiki artikel ini dengan menambahkan referensi yang layak. Tulisan tanpa sumber dapat dipertanyakan dan dihapus sewaktu-waktu.Cari sumber: Nyanyian Malam – berita · surat kabar · buku · cendekiawan · JSTOR Artikel ini perlu dikembangkan agar dapat memenuhi kriteria sebagai entri Wikipedia.Bantulah untuk mengembangkan artikel ini. Jika tidak...

Metra Electric District

Metra Electric District Estación Calle 59LugarUbicación Chicago, IllinoisDescripciónTipo Tren de cercaníasSistema MetraInicio MillenniumFin University Park, South Chicago y Blue IslandCaracterísticas técnicasLongitud 31 millas (49,89 km)Estaciones 49Ancho de vía 4 pies 8,5 plg (1435 mm)Propietario MetraExplotaciónEstado OperacionalPasajeros 34,000 (promedio en 2014)[1]​Operador MetraEsquema ¿? 0.00 Millenium 0,8 millas (1,29 km) Calle Va...

 

 

2020年夏季奧林匹克運動會波蘭代表團

2020年夏季奥林匹克运动会波兰代表團波兰国旗IOC編碼POLNOC波蘭奧林匹克委員會網站olimpijski.pl（英文）（波兰文）2020年夏季奥林匹克运动会（東京）2021年7月23日至8月8日（受2019冠状病毒病疫情影响推迟，但仍保留原定名称）運動員206參賽項目24个大项旗手开幕式：帕维尔·科热尼奥夫斯基（游泳）和马娅·沃什乔夫斯卡（自行车）[1]闭幕式：卡罗利娜·纳亚（皮划艇）&#...

 

 

Michigan's at-large congressional district

Michigan's at-large congressional districtObsolete districtCreated183719131963Eliminated184319151965Years active1837-18431913-19151963-1965 Michigan's at-large congressional district may refer to a few different occasions when a statewide at-large district was used for elections to the United States House of Representatives from Michigan. Prior to Michigan's admittance as a state of the Union in 1837, congressional delegates for Michigan Territory were elected from Michigan Territory's at-la...

Bakuage Sentai Boonboomger

Bakuage Sentai Boomboonger⁠GenreTokusatsuSuper SentaiFiksi pahlawan superKomediDramaFiksi IlmiahPembuatTV AsahiToei CompanyNegara asalJepangBahasa asliBahasa JepangJmlh. episode9ProduksiProduserTakehiro OkawaKeisuke ShibatakaReijin KujiKoichi YadaDurasi24–25 MenitRumah produksiTV AsahiToei CompanyToei AgencyRilis asliJaringanANN (TV Asahi, ABC, metele, KBC, HTB)Rilis3 Maret 2024 (2024-03-03) Bakuage Sentai Boonboomger (爆上戦隊ブンブンジャー Bakuage Sentai Bunbunjā) adal...

 

 

مستحاثة

مستحاثةمعلومات عامةصنف فرعي من جسم مادي طبيعي الأسباب fossilization (en) يدرسه الإحاثةpalaeoxylology (en) طريقة التصنيع fossilization (en) تعديل - تعديل مصدري - تعديل ويكي بيانات تحتاج هذه المقالة إلى الاستشهاد بمصادر إضافية لتحسين وثوقيتها. فضلاً ساهم في تطوير هذه المقالة بإضافة استشهادات من مصا�...