Baloxavir marboxil

571.55

571.55

606-227-7

505CXM6OHG

C166177

White to yellow

J - Antiinfectives for systemic use

2.24

1.57±0.1 g/cm3(Predicted)

712.8±70.0 °C(Predicted)

Soluble in water

-1.46±0.40(Predicted)

Sealed in dry,Store in freezer, under -20°C

|H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|P273, P391, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Ld50 (oral, rats): >2000 mg/kg [MSDS] **Pregnancy Risk** There are no available data on the use of this drug in pregnant women to predict or inform a drug-associated risk of adverse developmental outcomes. However, there are known risks to the mother and fetus associated with influenza virus infection during pregnancy. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits with oral administration of Baloxavir marboxil at exposures approximately 5 (rats) and 7 (rabbits) times the systemic Baloxavir exposure at the maximum recommended human dose. The estimated background risk of major birth defects and miscarriage for the indicated population is not known at this time. **Breastfeeding** There are no data on the presence of this drug in human breastmilk, the effects on the breastfed infant, or the effects on milk production. Baloxavir and its related metabolites were present in the milk of lactating rats. **Carcinogenicity** Carcinogenicity studies have not been completed with baloxavir marboxil. **Mutagenesis** Baloxavir marboxil and the active metabolite, baloxavir, were not shown to be mutagenic in in-vitro and in in-vivo genotoxicity assays, which included bacterial mutation assays in S. typhimurium and E. coli, micronucleus tests with cultured mammalian cells, and in the rodent micronucleus assay. **Impairment of Fertility** In a fertility and early embryonic development study in rats, doses of baloxavir marboxil at 20, 200, or 1,000 mg/kg/day were given to female animals for 2 weeks before mating, during mating and until day 7 of pregnancy. Male animals were dosed for 4 weeks before mating and throughout mating. There were no measured effects on fertility, mating performance, or early embryonic development at any dose level, resulting in systemic drug exposure (AUC) approximately 5 times the MRHD (maximum recommended human dose).

In clinical trials, there was little evidence that baloxavir caused liver injury, either in the form of serum enzyme elevations or clinically apparent liver disease. A proportion of patients with acute influenza A may have minor serum enzyme elevations during the acute illness, but these are independent of therapy and do not appear to be exacerbated by baloxavir.

92.9 - 93.9 %

For the treatment of influenza A and B virus infection, in patients 12 and older who have been symptomatic for no more than 48 hours. Clinical trials of this drug did not include subjects 65 years of age and older to determine whether they respond in a different way than younger subjects.|FDA Label|Treatment of influenzaXofluza is indicated for the treatment of uncomplicated influenza in patients aged 12 years and above.Post exposure prophylaxis of influenzaXofluza is indicated for post-exposure prophylaxis of influenza in individuals aged 12 years and above. Xofluza should be used in accordance with official recommendations.|Prevention of influenza infection, Treatment of influenza

Baloxavir is an inhibitor of the influenza cap-dependent endonuclease enzyme and is used as therapy of influenza A and B. Baloxavir is given as a single, one-time dose and has not been associated with serum enzyme elevations or with clinically apparent liver injury.

Antiviral Agents

Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease which prevents polymerase function and therefore influenza virus mRNA replication,. It has shown therapeutic activity against influenza A and B virus infections, including strains resistant to current antiviral agents. This drug inhibits an enzyme required for viral replication, thus rapidly treating flu virus infection, and alleviating the symptoms associated with infection. A single dose of this agent was shown to be superior to placebo in relieving influenza symptoms and superior to both oseltamivir and placebo drug in virologic outcomes (marked by decreased viral load). The safety profile of Baloxavir marboxil compared favorably with that of oseltamivir, making it an effective treatment option for treatment of the flu virus, in one single dose,.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

Tmax: 4h|14.7 % of a single dose is excreted in the urine, and 80.1% excreted in the feces|1180 (V/F, L).|10.3 L/h

Baloxavir marboxil is a prodrug that is converted by hydrolysis to baloxavir, the active form that exerts anti-influenza virus activity.

Terminal elimination half-life: 79.1 h.

This drug is a CAP endonuclease inhibitor. 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. Inhibiting the activity of endonuclease can block the transcription of mRNA and inactivate the influenza virus. 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. 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. 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.

(((12aR)-12-((11S)-7,8-difluoro-6,11-dihydrodibenzo(b,E)thiepin-11-yl)-6,8-dioxo-3,4,6,8,12,12ahexahydro-1H-(1,4)oxazino(3,4-C)pyrido(2,1-F)(1,2,4)triazin-7-yl)oxy)methyl methyl carbonate

Human drugs -> Xofluza -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients