Baloxavir marboxil

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Baloxavir marboxil
Baloxavir marboxil.svg
Clinical data
SynonymsS-033188/S-033447
ATC code
Identifiers
CAS Number
PubChem CID
UNII
KEGG
Chemical and physical data
FormulaC27H23F2N3O7S
Molar mass571.55 g·mol−1
3D model (JSmol)

Baloxavir marboxil (trade name Xofluza) is an antiviral medication for treatment of influenza A and influenza B FDA-approved in October 2018 and given as a single dose by mouth. It may reduce the duration of flu symptoms by about a day. It was developed by Shionogi Co., a Japanese pharmaceutical company, and Roche AG.[1]

Mechanism of action[edit]

Baloxavir marboxil is an influenza therapeutic agent (cap-dependent endonuclease inhibitor), characterized by taking a single dose by mouth. The pharmacodynamics of baloxavir marboxil are such that it inhibits the cap-dependent endonuclease activity of the influenza polymerase. It inhibits the process known as cap snatching, which is a mechanism exploited by viruses to hijack the host mRNA transcription system to allow synthesis of viral RNAs. It acts unlike neuraminidase inhibitors such as oseltamivir (Tamiflu) and zanamivir (Relenza) which inhibit the liberation of viruses from the infected cell surface.[2]

Efficacy[edit]

As of 2019 in the only published phase 3 RCT of otherwise healthy outpatients to date, baloxavir reduced the duration of symptoms by about one day compared to placebo, which was the same as oseltamivir. On the first day after baloxavir was started the viral load decreased more than with either placebo or oseltamivir. However, after 5 days of oseltamivir the effect of a single dose of baloxavir was indistinguishable.[3]

In mice, baloxavir and oseltamivir have been shown to be synergistic and there is no significant pharmacokinetic interaction.[4]

Side effects[edit]

Common side effects are diarrhea and bronchitis.[5] Adverse events were reported in 21% of people who received baloxavir, 25% of those receiving placebo, and 25% of oseltamivir.[3]

Resistance[edit]

In 2.2% of baloxavir recipients in the phase 2 trial and in about 10% of baloxavir recipients in the phase 3 trial the influenza strain became resistant. This was due to polymerase acidic protein variants with I38T/M/F substitutions.[3]

Approval[edit]

Baloxavir marboxil was approved for sale in Japan in February 2018.[6] On October 24, 2018 the U.S. FDA approved it for the treatment of acute uncomplicated influenza in people 12 years of age and older who have been symptomatic for no more than 48 hours.[5]

References[edit]

  1. ^ "Flu drug, taken in single dose, could upend treatment if approved in U.S." STAT. 27 June 2018.
  2. ^ Dias, Alexandre; Bouvier, Denis; Crépin, Thibaut; McCarthy, Andrew A.; Hart, Darren J.; Baudin, Florence; Cusack, Stephen; Ruigrok, Rob W. H. (2009). "The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit". Nature. 458 (7240): 914–918. doi:10.1038/nature07745. ISSN 0028-0836.
  3. ^ a b c Hayden FG, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018; 379:913–23.
  4. ^ Fukao K, et al. Combination treatment with the cap-dependent endonuclease inhibitor baloxavir marboxil and a neuraminidase inhibitor in a mouse model of influenza A virus infection. J Antimicrob Chemother. 2018 Nov 21. doi: 10.1093/jac/dky462. PMID 30476172.
  5. ^ a b "FDA approves new drug to treat influenza". 24 October 2018 – via www.fda.gov.
  6. ^ "XOFLUZA (Baloxavir Marboxil) Tablets 10mg/20mg Approved For The Treatment Of Influenza Types A And B In Japan". 23 February 2018 – via www.publicnow.com.