Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.
Active Ingredient / Synonyms
Baloxavir marboxil | Baloxavir marboxil |
Baloxavir marboxil is a medication developed by Shionogi Co., a Japanese pharmaceutical company, for treatment of influenza A and influenza B. The drug was approved for use in Japan in February 2018 and is in late phase trials in the United States as of early 2018. Roche, which makes Tamiflu, has acquired the license to sell Xofluza internationally, but it may not be until 2019 that it could be available in the United States [L1481]. Interestingly, a study has determined that administering Baloxavir marboxil with neuraminidase inhibitors leads to a synergistic effect in influenza treatment [L1480].
Influenza A and B virus infection [L1473, L1475].
Mechanism of Action
This drug is a CAP endonuclease inhibitor [L1473]. The influenza endonuclease is an essential subdomain of the viral RNA polymerase enzyme. CAP endonuclease processes host pre-mRNAs to serve as primers for viral mRNA and therefore has been a common target for studies of anti-influenza drugs. Viral gene transcription is primed by short-capped oligonucleotides that are cleaved from host cell pre mRNA by endonuclease activity. Translation of viral mRNAs by the host ribosome requires that they are capped at the 5' end, and this is achieved in cells infected with influenza virus by a “cap-snatching” mechanism, whereby the endonuclease cleaves 5′ caps from host mRNA which then act as primers for transcription.The N-terminal domain of PA subunit (PAN) has been confirmed to accommodate the endonuclease activity residues, which is highly preserved among subtypes of influenza A virus and is able to fold functionally [L1478]. Translation of viral mRNAs by the host ribosome requires that they are capped at the 5' end, and this is achieved in cells infected with influenza virus by a “cap-snatching” mechanism, whereby the endonuclease cleaves 5′ caps from host mRNA which then act as primers for transcription. The endonuclease domain binds the N-terminal half of PA (PAN) and contains a two-metal (Mn2+) active site that selectively cleaves the pre-mRNA substrate at the 3′ end of a guanine [L1477]. The administration of a CAP endonuclease inhibitor, such as Baloxavir marboxil, prevents the above process from occurring, exhibiting its action at the beginning of the pathway before CAP endonuclease may exert its action [L1475].
This medication, also known as _S-033188_, inhibits an enzyme required for viral replication, thus rapidly treating flu virus infection [L1475] and alleviating the symptoms associated with infection. A single dose of S-033188 was superior to placebo in relieving influenza symptoms and superior to both oseltamivir and placebo drug in virologic outcomes. The safety profile of S-033188 (Baloxavir marboxil) compared favorably with that of oseltamivir, thus making it a suitable option for treatment of the flu virus, in one single dose [L1475].
Baloxavir marboxil (S-033188) is a prodrug that is hydrolyzed in vivo to its metabolite, _S-033447_, the active form that selectively inhibits cap-dependent endonuclease, a key enzyme involved in the initiation of mRNA synthesis of influenza viruses [L1479].
Adverse effects of this medication include headache and diahrrea as well as increased ALT and AST (liver transaminases). These adverse effects were found, in one study, to occur at a rate of 1-4%, with higher occurrence in the subgroup receiving 40mg of the drug [L1479].
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