Baloxavir marboxil

Last updated

Baloxavir marboxil
Baloxavir marboxil.svg
Clinical data
Trade names Xofluza
Other namesBXM (S-033188), BXA (S-033447)
AHFS/Drugs.com Monograph
MedlinePlus a618062
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
  • ({(12aR)-12-[(11S)-7,8-Difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-6,8-dioxo-3,4,6,8,12,12a-hexahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f] [1,2,4]triazin-7-yl}oxy)methyl methyl carbonate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
Formula C27H23F2N3O7S
Molar mass 571.55 g·mol−1
3D model (JSmol)
  • O=C(OCOC(C(C=C1)=O)=C(N1N([C@@H]2C3=CC=CC=C3SCC4=C(F)C(F)=CC=C24)[C@@]5([H])N6CCOC5)C6=O)OC
  • InChI=1S/C27H23F2N3O7S/c1-36-27(35)39-14-38-25-19(33)8-9-31-24(25)26(34)30-10-11-37-12-21(30)32(31)23-15-6-7-18(28)22(29)17(15)13-40-20-5-3-2-4-16(20)23/h2-9,21,23H,10-14H2,1H3/t21-,23+/m1/s1
  • Key:RZVPBGBYGMDSBG-GGAORHGYSA-N

Baloxavir marboxil, sold under the brand name Xofluza, is an antiviral medication for treatment of influenza A and influenza B. [4] It was approved for medical use both in Japan and in the United States in 2018, [7] [8] [9] and is taken as a single dose by mouth. [4] It may reduce the duration of flu symptoms by about a day, but is prone to selection of resistant mutants that render it ineffectual. [10] [ unreliable medical source? ]

Contents

Baloxavir marboxil was developed as a prodrug strategy, with its metabolism releasing the active agent, baloxavir acid (BXA). Baloxavir acid then functions as enzyme inhibitor, targeting the influenza virus' cap-dependent endonuclease activity, used in "cap snatching" by the virus' polymerase complex, a process essential to its life-cycle. [11]

The most common side effects of baloxavir marboxil include diarrhea, bronchitis, nausea, sinusitis, and headache. [12]

The US Food and Drug Administration (FDA) considers baloxavir marboxil to be a first-in-class medication. [13]

Medical uses

Baloxavir marboxil is an influenza medication, an antiviral, [14] [4] for individuals who are twelve years of age or older, [5] [14] that have presented symptoms of this infection for no more than 48 hours. [5] [14] [15] The efficacy of baloxavir marboxil administered after 48 hours has not been tested. [14]

In October 2019, the FDA approved an updated indication for the treatment of acute, uncomplicated influenza in people twelve years of age and older at risk of influenza complications. [4] [9]

In November 2020, the FDA approved an updated indication to include post-exposure prevention of influenza (flu) for people twelve years of age and older after contact with an individual who has the flu. [4] [12]

In August 2022, the FDA approved an updated indication to include post-exposure prevention of influenza (flu) for people five years of age and older after contact with an individual who has the flu. [4] [16]

In the EU, baloxavir marboxil is indicated for the treatment of uncomplicated influenza and for post-exposure prophylaxis of influenza in individuals aged twelve years of age and older. [5]

Available forms

Baloxavir marboxil is available in tablet form and as granules for mixing in water. [12]

Resistance

In 2.2% of baloxavir recipients in the Phase II trial and in about 10% of baloxavir recipients in the Phase III trial, the infecting influenza strain had acquired resistance to the drug, due to variants of the polymerase protein displaying substitutions of isoleucine-38, specifically, the I38T, I38M, or I38F mutations. [17] There is continuing research into and clinical concern over the resistance appearing in recipients, in response to treatment with this drug. [18] [19] [20]

Contraindications

Baloxavir marboxil should not be co-administered with dairy products, calcium-fortified beverages, or laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminum or zinc. [12]

Side effects

Common side effects following the single dose administration of baloxavir marboxil include diarrhea, bronchitis, common cold, headache, and nausea. [4] [15] [7] Adverse events were reported in 21% of people who received baloxavir, 25% of those receiving placebo, and 25% of oseltamivir. [17]

Mechanism of action

Baloxavir marboxil is an influenza therapeutic agent, specifically, an enzyme inhibitor targeting the influenza virus' cap-dependent endonuclease activity, one of the activities of the virus polymerase complex. [21] In particular, it inhibits a process known as cap snatching,[ medical citation needed ] by which the virus derives short, capped primers from host cell RNA transcripts, which it then uses for polymerase-catalyzed synthesis of its needed viral mRNAs. [22] A polymerase subunit binds to the host pre-mRNAs at their 5' caps, then the polymerase's endonuclease activity catalyzes its cleavage "after 10–13 nucleotides".[ medical citation needed ] As such, its mechanism is distinct from neuraminidase inhibitors such as oseltamivir and zanamivir. [22]

Chemistry

Baloxavir marboxil is a substituted pyridone derivative of a polycyclic family, whose chemical synthesis has been reported in a number of ways by the company discovering it, Shionogi and Co. of Japan (as well as others); the Shionogi reports have appeared several times in the Japanese patent literature between 2016 and 2019, providing insight into possible industrial synthetic routes that may be in use. [23] [24] [25] [26] [27]

Baloxavir acid (BXA) or simply baloxavir, the active moiety Baloxavir.svg
Baloxavir acid (BXA) or simply baloxavir, the active moiety

Baloxavir marboxil (BXM) is a prodrug whose active agent, baloxavir acid (BXA) is released rapidly in vivo, as the hydrolysis of baloxavir marboxil is catalyzed by arylacetamide deacetylases in cells of the blood, liver, and lumen of the small intestine. [29] [30] [31] The compound numbers for baloxavir marboxil and baloxavir acid used in publications by Shionogi and others during discovery and development (prior to assignment of a United States Adopted Name (USAN)) were, respectively, S-033188 and S-033447. [32] As reported in a review of the patent literature, the carbonic acid ester (carbonate) moiety of the prodrug—shown in the lower left-hand corner of the image above—was prepared during discovery and development research from a late stage 2-hydroxy-4-pyridone precursor by treatment with chloromethyl methyl carbonate. [29] [33]

History

As of September 2018, in the only report of a Phase III randomized, controlled trial, baloxavir reduced the duration of influenza symptoms of otherwise healthy participants by about one day compared with a placebo treatment group, and comparable with what was seen for an oseltamivir treatment group. [15] On the first day after baloxavir was started in its treatment group of participants, viral loads decreased more than in participants in either the oseltamivir or placebo groups; however, after five days, the effect on viral load of the single dose of baloxavir was indistinguishable from the effect observed following the complete, 5-day regimen of oseltamivir in its treatment group. [17] [ verification needed ]

Baloxavir marboxil was developed for the market by Shionogi Co., a Japanese pharmaceutical company, and Switzerland-based Roche AG. [34] The names under which baloxavir marboxil and baloxavir acid appear in Shionogi research reporting are S-033188 and S-033447, respectively.[ citation needed ]

Society and culture

Japan's Ministry of Health, Labour and Welfare (JMHLW) and the US Food and Drug Administration (FDA) approved baloxavir marboxil based on evidence of its benefits and side effects from two clinical trials in adult and pediatric participants with uncomplicated influenza (Trial 1, 1518T0821 and Trial 2, NCT02954354 [35] ), [4] involving 1119 participants. [15] [36] [ better source needed ][ verification needed ] Both trials included clinical sites and participants in Japan, with Trial 2 adding clinical locations in the United States. [4] [15]

Baloxavir marboxil was approved for sale in Japan in February 2018. [37] [ better source needed ] In October 2018, the FDA approved it for the treatment of acute uncomplicated influenza in people twelve years of age and older who have been symptomatic for no more than 48 hours. [7] [8] The FDA application of baloxavir marboxil was granted priority review in the United States, and approval of Xofluza was granted to Shionogi & Co., Ltd. in October 2018. [7] [8] Specifically, the FDA approved the use of baloxavir marboxil for people at high risk of developing influenza-related complications. [38] In October 2019, the FDA approved an updated indication for the treatment of acute, uncomplicated influenza in people twelve years of age and older at risk of influenza complications. [9] In November 2020, the FDA approved an updated indication to include post-exposure prevention of influenza (flu) for people twelve years of age and older after contact with an individual who has the flu. [12]

Baloxavir marboxil was approved for medical use in Australia in February 2020. [1]

The safety and efficacy of baloxavir marboxil, an antiviral drug taken as a single oral dose, was demonstrated in two randomized controlled clinical trials of 1,832 subjects where participants were assigned to receive either baloxavir marboxil, a placebo, or another antiviral flu treatment within 48 hours of experiencing flu symptoms. [7] In both trials, subjects treated with baloxavir marboxil had a shorter time to alleviation of symptoms compared with subjects who took the placebo. [7] In the second trial, there was no difference in the time to alleviation of symptoms between subjects who received baloxavir marboxil and those who received the other flu treatment. [7]

The safety and efficacy of baloxavir marboxil for post-flu exposure prevention is supported by one randomized, double-blind, controlled trial in which 607 subjects, twelve years of age and older who were exposed to a person with influenza in their household, received either a single dose of baloxavir marboxil or a single dose of a placebo. [12] Of these 607 subjects, 303 received baloxavir marboxil and 304 received the placebo. [12] The trial's primary endpoint was the proportion of subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from day 1 to day 10. [12] Of those who received baloxavir marboxil, 1% of subjects met these criteria, compared to 13% of subjects who received a placebo for the clinical trial. [12]

Baloxavir marboxil was approved for medical use in the European Union in January 2021. [5]

Related Research Articles

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

<span class="mw-page-title-main">Zanamivir</span> Influenza medication

Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and approved in the US in 1999, only for use as a treatment for influenza. In 2006, it was approved for prevention of influenza A and B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is marketed by GlaxoSmithKline under the trade name Relenza as a powder for oral inhalation.

<span class="mw-page-title-main">Oseltamivir</span> Antiviral medication used against influenza A and influenza B

Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid.

<span class="mw-page-title-main">Rimantadine</span> Drug used to treat influenzavirus A infection

Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Rimantadine can mitigate symptoms, including fever. Both rimantadine and the similar drug amantadine are derivates of adamantane. Rimantadine is found to be more effective than amantadine because when used the patient displays fewer symptoms. Rimantadine was approved by the Food and Drug Administration (FDA) in 1994.

<span class="mw-page-title-main">Amantadine</span> Medication used to treat dyskinesia

Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because of widespread drug resistance. It acts as a nicotinic antagonist, dopamine agonist, and noncompetitive NMDA antagonist. The antiviral mechanism of action is antagonism of the influenzavirus A M2 proton channel, which prevents endosomal escape.

Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are a commonly used antiviral drug type against influenza. Viral neuraminidases are essential for influenza reproduction, facilitating viral budding from the host cell. Oseltamivir (Tamiflu), zanamivir (Relenza), laninamivir (Inavir), and peramivir belong to this class. Unlike the M2 inhibitors, which work only against the influenza A virus, NAIs act against both influenza A and influenza B.

<span class="mw-page-title-main">Peramivir</span> Antiviral drug targeting influenza

Peramivir is an antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. It is approved for intravenous administration.

<span class="mw-page-title-main">Influenza treatment</span> Therapy and pharmacy for the common infectious disease

Treatments for influenza include a range of medications and therapies that are used in response to disease influenza. Treatments may either directly target the influenza virus itself; or instead they may just offer relief to symptoms of the disease, while the body's own immune system works to recover from infection.

<span class="mw-page-title-main">Umifenovir</span> Chemical compound

Umifenovir, sold under the brand name Arbidol, is an antiviral medication for the treatment of influenza and COVID infections used in Russia and China. The drug is manufactured by Pharmstandard. It is not approved by the U.S. Food and Drug Administration (FDA) for the treatment or prevention of influenza.

<span class="mw-page-title-main">Nitazoxanide</span> Broad-spectrum antiparasitic and antiviral medication

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Influenza</span> Infectious disease, often just "the flu"

Influenza, commonly known as "the flu" or just "flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<span class="mw-page-title-main">Tecovirimat</span> Antiviral medication

Tecovirimat, sold under the brand name Tpoxx among others, is an antiviral medication with activity against orthopoxviruses such as smallpox and mpox. In 2018 it became the first antipoxviral drug approved in the United States.

<span class="mw-page-title-main">Favipiravir</span> Experimental antiviral drug with potential activity against RNA viruses

Favipiravir, sold under the brand name Avigan among others, is an antiviral medication used to treat influenza in Japan. It is also being studied to treat a number of other viral infections, including SARS-CoV-2. Like the experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.

<span class="mw-page-title-main">Brincidofovir</span> Antiviral drug

Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.

Neuraminidase inhibitors inhibit enzymatic activity of the enzyme neuraminidase (sialidase). These type of inhibitors have been introduced as anti-influenza drugs as they prevent the virus from exiting infected cells and thus stop further spreading of the virus. Neuraminidase inhibitors for human neuraminidase (hNEU) have the potential to be useful drugs as the enzyme plays a role in several signaling pathways in cells and is implicated in diseases such as diabetes and cancer.

<span class="mw-page-title-main">Cap snatching</span>

The first step of transcription for some negative, single-stranded RNA viruses is cap snatching, in which the first 10 to 20 residues of a host cell RNA are removed (snatched) and used as the 5′ cap and primer to initiate the synthesis of the nascent viral mRNA. The viral RNA-dependent RNA polymerase (RdRp) can then proceed to replicate the negative-sense genome from the positive-sense template. Cap-snatching also explains why some viral mRNA have 5’ terminal extensions of 10-20 nucleotides that are not encoded for in the genome. Examples of viruses that engage in cap-snatching include influenza viruses (Orthomyxoviridae), Lassa virus (Arenaviridae), hantaan virus (Hantaviridae) and rift valley fever virus (Phenuiviridae). Most viruses snatch 15-20 nucleotides except for the families Arenaviridae and Nairoviridae and the genus Thogotovirus (Orthomyxoviridae) which use a shorter strand.

<span class="mw-page-title-main">Pimodivir</span> Chemical compound

Pimodivir is an antiviral drug which was developed as a treatment for influenza. It acts as an inhibitor of influenza virus polymerase basic protein 2, and has shown promising results in Phase II clinical trials. However, in late 2021, Janssen announced that the clinical development of pimidivir had been halted due to lack of benefit over standard of care.

<span class="mw-page-title-main">Molnupiravir</span> Antiviral medication

Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID‑19 in those infected by SARS-CoV-2. It is taken by mouth.

<span class="mw-page-title-main">Ensitrelvir</span> COVID-19 SARS-CoV-2 3CL-protease-inhibitor antiviral drug

Ensitrelvir, sold under the brand name Xocova is an antiviral medication used as a treatment for COVID-19. It was developed by Shionogi in partnership with Hokkaido University and acts as an orally active 3C-like protease inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Enisamium iodide</span> Chemical compound

Enisamium iodide is a derivative of isonicotinic acid. Based on its systematic chemical name of N-benzyl-1-methylpyridin-1-ium-4-carboxamide iodide, the shortened name carbabenzpiride is sometimes used. Enisamium iodide is a registered antiviral drug sold in Ukraine, Kazakhstan, Mongolia, Belarus, and other Eastern European countries under the trade names Amizon, Amizon Max, Amizonchik.

References

  1. 1 2 3 "Xofluza Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 2 March 2020. Archived from the original on 13 March 2020. Retrieved 16 August 2020.
  2. ↑ "Xofluza Product information". Health Canada. 25 April 2012. Archived from the original on 12 August 2022. Retrieved 29 May 2022.
  3. ↑ "Summary Basis of Decision (SBD) for Xofluza". Health Canada . 23 October 2014. Archived from the original on 31 May 2022. Retrieved 29 May 2022.
  4. 1 2 3 4 5 6 7 8 9 10 "Xofluza- baloxavir marboxil tablet, film coated". DailyMed. 28 October 2019. Archived from the original on 28 October 2020. Retrieved 9 January 2020.
  5. 1 2 3 4 5 "Xofluza EPAR". European Medicines Agency (EMA). 9 November 2020. Archived from the original on 30 January 2021. Retrieved 25 January 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ↑ "Xofluza Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  7. 1 2 3 4 5 6 7 "FDA approves new drug to treat influenza" (Press release). U.S. Food and Drug Administration (FDA). 24 October 2018. Archived from the original on 24 October 2019. Retrieved 23 October 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. 1 2 3 "Drug Approval Package: Xofluza Film-Coated Tablets (Baloxavir marboxil)". U.S. Food and Drug Administration (FDA). 7 December 2018. Archived from the original on 26 July 2020. Retrieved 10 May 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. 1 2 3 "FDA Approval Package for 210854Orig1s001" (PDF). U.S. Food and Drug Administration (FDA). 16 October 2019. Archived (PDF) from the original on 9 April 2021. Retrieved 30 September 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. ↑ "Baloxavir Marboxil for Uncomplicated Influenza: Mechanism of Action & Side Effects". Huateng Pharma. Archived from the original on 24 February 2021. Retrieved 29 May 2020.
  11. ↑ Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S, Baba K, et al. (December 2018). "In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit". Antiviral Res. 160: 109–117. doi: 10.1016/j.antiviral.2018.10.008 . PMID   30316915.
  12. 1 2 3 4 5 6 7 8 9 "FDA Expands Approval of Influenza Treatment to Post-Exposure Prevention" (Press release). U.S. Food and Drug Administration (FDA). 23 November 2020. Archived from the original on 23 November 2020. Retrieved 23 November 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  13. ↑ New Drug Therapy Approvals 2018 (PDF) (Report). U.S. Food and Drug Administration (FDA). January 2019. Archived from the original on 17 September 2020. Retrieved 16 September 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  14. 1 2 3 4 "Baloxavir Marboxil Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. 19 August 2019. Archived from the original on 7 October 2019. Retrieved 9 January 2020.
  15. 1 2 3 4 5 Food and Drug Administration (23 July 2019). "Drug Trial Snapshot: Xofluza". U.S. Food and Drug Administration (FDA). Archived from the original on 12 December 2019. Retrieved 7 January 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  16. ↑ "Genentech Announces FDA Approval of Xofluza to Treat Influenza in Children Aged Five and Older" (Press release). Genentech. 11 August 2022. Archived from the original on 12 August 2022. Retrieved 11 August 2022– via Business Wire.
  17. 1 2 3 Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. (September 2018). "Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents". N. Engl. J. Med. 379 (10): 913–923. doi: 10.1056/NEJMoa1716197 . PMID   30184455. S2CID   52173453.
  18. ↑ "Roche's flu med Xofluza drives drug resistance and may be a bad choice for kids, study says". FiercePharma. 26 November 2019. Archived from the original on 25 November 2020. Retrieved 8 January 2020.
  19. ↑ "New flu drug drives drug resistance in influenza viruses". EurekAlert (Press release). Archived from the original on 16 January 2021. Retrieved 8 January 2020.
  20. ↑ Imai M, Yamashita M, Sakai-Tagawa Y, Iwatsuki-Horimoto K, Kiso M, Murakami J, et al. (January 2020). "Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets". Nature Microbiology. 5 (1): 27–33. doi:10.1038/s41564-019-0609-0. PMID   31768027. S2CID   208279215.
  21. ↑ Eisfeld AJ, Neumann G, Kawaoka Y (January 2015). "At the centre: influenza A virus ribonucleoproteins". Nature Reviews. Microbiology. 13 (1): 28–41. doi:10.1038/nrmicro3367. PMC   5619696 . PMID   25417656.
  22. 1 2 O'Hanlon R, Shaw ML (April 2019). "Baloxavir marboxil: the new influenza drug on the market". Current Opinion in Virology. 35: 14–18. doi:10.1016/j.coviro.2019.01.006. PMID   30852344. S2CID   73726080.
  23. ↑ WO 2019070059,Okamoto K, Ueno T, Hato Y, Hakogi T, Majima S,"Method for stereoselective preparation of substituted polycyclic pyridone derivative.",published 2019, assigned to Shionogi & Co., Ltd., Japan.
  24. ↑ JPWO 2018030463,Kawai M, Tomita K, Akiyama T, Okano A, Miyagawa M,"Pharmaceutical composition containing polycyclic pyridone derivatives as cap-dependent endonuclease (CEN) inhibitors.",published 2017, assigned to Shionogi and Co., Ltd., Japan.
  25. ↑ JPWO 2017221869,Shibahara S, Fukui N, Maki T,"Polycyclic pyridone derivative, crystal and preparation method thereof.",published 2017, assigned to Shionogi and Co., Ltd., Japan.
  26. ↑ JPWO 2016175224,Kawai M, Tomita K, Akiyama T, Okano A, Miyagawa M,"Preparation of polycyclic pyridone derivatives as cap-dependent endonuclease (CEN) inhibitors and prodrugs thereof.",published 2016, assigned to Shionogi and Co., Ltd., Japan
  27. ↑ CN 108440564,Zhu X, Jiang W,"Process for preparation of substituted polycyclic carbamoylpyridone derivative and its prodrug.",published 2018
  28. ↑ "Baloxavir". PubChem. U.S. National Library of Medicine. CID 124081876. Retrieved 28 July 2021.
  29. 1 2 Hughes DL (June 2019). "Review of the Patent Literature: Synthesis and Final Forms of Antiviral Drugs Tecovirimat and Baloxavir Marboxil". Organic Process Research & Development. 23 (7): 1298–1307. doi:10.1021/acs.oprd.9b00144. S2CID   197172102.
  30. ↑ Yoshino R, Yasuo N, Sekijima M (November 2019). "Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil". Scientific Reports. 9 (1): 17464. Bibcode:2019NatSR...917464Y. doi: 10.1038/s41598-019-53945-1 . PMC   6877583 . PMID   31767949.
  31. ↑ Kawaguchi N, Koshimichi H, Ishibashi T, Wajima T (November 2018). "Evaluation of Drug-Drug Interaction Potential between Baloxavir Marboxil and Oseltamivir in Healthy Subjects". Clinical Drug Investigation. 38 (11): 1053–1060. doi: 10.1007/s40261-018-0697-2 . PMID   30203386.
  32. ↑ Yang J, Huang Y, Liu S (May 2019). "Investigational antiviral therapies for the treatment of influenza". Expert Opinion on Investigational Drugs. 28 (5): 481–488. doi:10.1080/13543784.2019.1606210. PMID   31018720. S2CID   131775842.
  33. ↑ "Baloxavir Marboxil" . Pharmaceutical Substances. Archived from the original on 26 July 2020. Retrieved 8 January 2020.
  34. ↑ Branswell H (27 June 2018). "A flu drug — shown to reduce the duration of symptoms — could upend treatment in U.S." . Stat . Archived from the original on 20 October 2020. Retrieved 28 June 2018.
  35. ↑ "A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza". ClinicalTrials.gov. 3 November 2016. Archived from the original on 21 January 2022. Retrieved 11 August 2022.
  36. ↑ Otake T (24 February 2018). "One-dose flu drug Xofluza gets nod from health ministry". Japan Times Online. Archived from the original on 2 November 2021. Retrieved 8 January 2020.
  37. ↑ "Xofluza (Baloxavir Marboxil) Tablets 10mg/20mg Approved For The Treatment Of Influenza Types A And B In Japan" (Press release). Shionogi & Co., Ltd. 23 February 2018. Archived from the original on 20 January 2021. Retrieved 23 February 2018– via publicnow.com.
  38. ↑ "Genentech Announces FDA Approval of Xofluza (Baloxavir Marboxil) for People at High Risk of Developing Influenza-Related Complications" (Press release). Genentech. 17 October 2019. Archived from the original on 24 October 2019. Retrieved 23 October 2019– via Business Wire.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.