Baloxavir marboxil
Antiviral for influenza, first-in-class cap-dependent endonuclease inhibitor.
Baloxavir marboxil, known as Xofluza, is an oral antiviral drug for influenza A and B. It was approved in Japan and the United States in 2018. The US Food and Drug Administration considers it a first-in-class medication, and it is available as a generic.
The drug works as a prodrug; the body quickly converts it into the active compound, baloxavir acid. This active form inhibits the influenza virus's cap-dependent endonuclease, a part of the polymerase complex that performs "cap snatching." This process is essential for the virus to produce its own messenger RNA, and the mechanism is distinct from neuraminidase inhibitors like oseltamivir.
For treatment, it is indicated for people twelve and older who have had flu symptoms for no more than 48 hours. In October 2019, the FDA approved it for acute, uncomplicated influenza in those twelve and older at risk of complications. In November 2020, the FDA approved it for post-exposure prevention in people twelve and older after contact with someone who has the flu, and in August 2022, this was expanded to include those five and older. In the EU, it is indicated for treatment and post-exposure prophylaxis in people twelve and older.
Common side effects include diarrhea, bronchitis, nausea, sinusitis, and headache. In clinical trials, adverse events occurred in 21% of those taking baloxavir, compared to 25% for placebo and 25% for oseltamivir. It should not be taken with dairy products, calcium-fortified drinks, or laxatives, antacids, or supplements containing calcium, iron, magnesium, selenium, aluminum, or zinc.
The drug can reduce flu symptom duration by about one to two days in some people. However, resistant mutants can emerge. In a phase II trial, 2.2% of recipients had resistant strains, and in a phase III trial, about 10% did, due to mutations at isoleucine-38 (I38T, I38M, or I38F) in the polymerase protein. This resistance was noted mostly in children studied, and research and clinical concern continue.
Baloxavir marboxil is available as tablets and as granules for mixing in water. Chemically, it is a substituted pyridone derivative of a polycyclic family, developed by Shionogi of Japan. The prodrug is rapidly hydrolyzed by arylacetamide deacetylases in blood, liver, and small intestine cells. Its active form was known as S-033447 during development, and the prodrug as S-033188. The carbonate moiety was p
- field
- Antiviral medication
- known_for
- Treatment of influenza A and B, first-in-class cap-dependent endonuclease inhibitor
- approved_in
- Japan and United States (2018)
- common_side_effects
- Diarrhea, bronchitis, nausea, sinusitis, headache
Quick Facts
- Tradename
- Xofluza
- Drugs.Com
- monograph · baloxavir-marboxil
- Medlineplus
- a618062
- Dailymedid
- Baloxavir marboxil
- Pregnancy Au
- B3
- Routes Of Administration
- By mouth
- Atc Prefix
- J05
- Atc Suffix
- AX25
- Legal Au
- S4
- Legal Ca
- Rx-only
- Cas Number
- 1985606-14-1
- Pubchem
- 124081896
Facts from the source article.
Lore & Background
Baloxavir marboxil was developed as a prodrug strategy, with its metabolism releasing the active agent, baloxavir acid. Baloxavir acid functions as an 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. Its mechanism is distinct from neuraminidase inhibitors such as oseltamivir and zanamivir.
The medication can reduce the duration of flu symptoms by about 1-2 days in some people, but can also develop selection of resistant mutants that render it ineffectual; studies noted this was seen mostly in children. In 2.2% of baloxavir recipients in a phase II trial and in about 10% in a phase III trial, the infecting influenza strain acquired resistance due to variants of the polymerase protein displaying substitutions of isoleucine-38, specifically the I38T, I38M, or I38F mutations.
Baloxavir marboxil was developed for the market by Shionogi Co., a Japanese pharmaceutical company, and Switzerland-based Roche AG. It is available in tablet form and as granules for mixing in water. It 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.
Reader's Guide
Baloxavir marboxil represents a significant advance in influenza treatment as a first-in-class medication targeting the virus's cap-dependent endonuclease, a mechanism distinct from older neuraminidase inhibitors. Its approval in Japan and the United States in 2018 provided a new oral option for acute uncomplicated influenza in people twelve years of age and older, with later approvals expanding to post-exposure prevention. Clinical trials showed it reduced symptom duration by about one day compared to placebo, with a faster initial reduction in viral load than oseltamivir, though after five days the effect was indistinguishable. However, the emergence of resistance, particularly the I38T, I38M, and I38F mutations in the polymerase protein, poses a clinical concern, especially in children. The medication's prodrug design, with rapid conversion to baloxavir acid via arylacetamide deacetylases, and its contraindication with certain minerals and dairy, highlight its unique pharmacological profile. Its legacy includes being a first-in-class agent that expanded therapeutic options for influenza, though ongoing research into resistance patterns remains critical.
Did You Know?
- Baloxavir marboxil is a prodrug whose active agent, baloxavir acid, is released rapidly in vivo by hydrolysis catalyzed by arylacetamide deacetylases.
- Resistance mutations in the influenza polymerase protein, specifically I38T, I38M, or I38F, were observed in about 10% of baloxavir recipients in a phase III trial.
- The medication should not be co-administered with dairy products, calcium-fortified beverages, or supplements containing calcium, iron, magnesium, selenium, aluminum, or zinc.
- Baloxavir marboxil was developed by Shionogi Co. of Japan and Roche AG of Switzerland.
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