baloxavir marboxil 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antivirals	5301	1985606-14-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: baloxavir marboxil xofluza S-033188 S 033188 RG 6152	Baloxavir marboxil is a prodrug that is converted by hydrolysis to baloxavir, the active form that exerts anti-influenza virus activity. Baloxavir inhibits the endonuclease activity of the polymerase acidic (PA) protein, an influenza virus-specific enzyme in the viral RNA polymerase complex required for viral gene transcription, resulting in inhibition of influenza virus replication. The 50% inhibitory concentration (IC50) of baloxavir was 1.4 to 3.1 nM (n=4) for influenza A viruses and 4.5 to 8.9 nM (n=3) for influenza B viruses in a PA endonuclease assay. Viruses with reduced susceptibility to baloxavir have amino acid substitutions in the PA protein. It was investigated as a potential treatment during the early stages of the COVID-19 pandemic but in vitro antiviral activity against SARS-CoV-2 was not confirmed. Molecular weight: 571.55 Formula: C27H23F2N3O7S CLOGP: 2.16 LIPINSKI: 1 HAC: 10 HDO: 0 TPSA: 97.85 ALOGS: -4.14 ROTB: 6 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

baloxavir marboxil
xofluza
S-033188
S 033188
RG 6152

Baloxavir marboxil is a prodrug that is converted by hydrolysis to baloxavir, the active form that exerts anti-influenza virus activity. Baloxavir inhibits the endonuclease activity of the polymerase acidic (PA) protein, an influenza virus-specific enzyme in the viral RNA polymerase complex required for viral gene transcription, resulting in inhibition of influenza virus replication. The 50% inhibitory concentration (IC50) of baloxavir was 1.4 to 3.1 nM (n=4) for influenza A viruses and 4.5 to 8.9 nM (n=3) for influenza B viruses in a PA endonuclease assay. Viruses with reduced susceptibility to baloxavir have amino acid substitutions in the PA protein. It was investigated as a potential treatment during the early stages of the COVID-19 pandemic but in vitro antiviral activity against SARS-CoV-2 was not confirmed.

Molecular weight: 571.55
Formula: C27H23F2N3O7S
CLOGP: 2.16
LIPINSKI: 1
HAC: 10
HDO: 0
TPSA: 97.85
ALOGS: -4.14
ROTB: 6

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
40	mg	O

ADMET properties:

Property	Value	Reference
S (Water solubility)	0.02 mg/mL	Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company
Jan. 7, 2021	EMA	ROCHE REGISTRATION GmbH
Oct. 24, 2018	FDA	GENENTECH INC
Feb. 23, 2018	PMDA	Shionogi & Co., Ltd.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
No adverse event	141.54	48.44	39	570	41366	63447047
Melaena	52.66	48.44	17	592	30348	63458065

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
No adverse event	88.02	46.47	26	487	22901	34933517

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
No adverse event	91.50	41.62	29	976	37163	79706220
Pneumonia	62.21	41.62	57	948	660189	79083194
Anaphylactic reaction	61.93	41.62	27	978	83716	79659667
Abnormal behaviour	52.37	41.62	19	986	36402	79706981
Loss of consciousness	52.05	41.62	30	975	167913	79575470
Colitis ischaemic	50.56	41.62	15	990	15344	79728039
Rhabdomyolysis	50.50	41.62	25	980	103106	79640277
Delirium febrile	46.09	41.62	6	999	75	79743308
Erythema multiforme	44.31	41.62	14	991	17637	79725746

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	J05AX25	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Other antivirals
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Influenza	indication	6142004	DOID:8469
Coronavirus infection	off-label use	186747009

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	2.75	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
20MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	DISCN	TABLET	ORAL	10633397	April 27, 2036	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
20MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	DISCN	TABLET	ORAL	10633397	April 27, 2036	METHOD FOR TREATING INFLUENZA
40MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	RX	TABLET	ORAL	10633397	April 27, 2036	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
40MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	RX	TABLET	ORAL	10633397	April 27, 2036	METHOD FOR TREATING INFLUENZA
80MG	XOFLUZA	GENENTECH INC	N210854	March 18, 2021	RX	TABLET	ORAL	10633397	April 27, 2036	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
80MG	XOFLUZA	GENENTECH INC	N210854	March 18, 2021	RX	TABLET	ORAL	10633397	April 27, 2036	METHOD FOR TREATING INFLUENZA
2MG/ML	XOFLUZA	GENENTECH INC	N214410	Nov. 23, 2020	RX	FOR SUSPENSION	ORAL	10633397	April 27, 2036	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
2MG/ML	XOFLUZA	GENENTECH INC	N214410	Nov. 23, 2020	RX	FOR SUSPENSION	ORAL	10633397	April 27, 2036	METHOD FOR TREATING INFLUENZA
20MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	DISCN	TABLET	ORAL	11306106	Aug. 9, 2037	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
20MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	DISCN	TABLET	ORAL	11306106	Aug. 9, 2037	METHOD FOR TREATING INFLUENZA
40MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	RX	TABLET	ORAL	11306106	Aug. 9, 2037	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
40MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	RX	TABLET	ORAL	11306106	Aug. 9, 2037	METHOD FOR TREATING INFLUENZA
80MG	XOFLUZA	GENENTECH INC	N210854	March 18, 2021	RX	TABLET	ORAL	11306106	Aug. 9, 2037	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
80MG	XOFLUZA	GENENTECH INC	N210854	March 18, 2021	RX	TABLET	ORAL	11306106	Aug. 9, 2037	METHOD FOR TREATING INFLUENZA
2MG/ML	XOFLUZA	GENENTECH INC	N214410	Nov. 23, 2020	RX	FOR SUSPENSION	ORAL	11306106	Aug. 9, 2037	METHOD FOR POST-EXPOSURE PROPHYLAXIS OF INFLUENZA
2MG/ML	XOFLUZA	GENENTECH INC	N214410	Nov. 23, 2020	RX	FOR SUSPENSION	ORAL	11306106	Aug. 9, 2037	METHOD FOR TREATING INFLUENZA

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
20MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	DISCN	TABLET	ORAL	Oct. 24, 2023	NEW CHEMICAL ENTITY
40MG	XOFLUZA	GENENTECH INC	N210854	Oct. 24, 2018	RX	TABLET	ORAL	Oct. 24, 2023	NEW CHEMICAL ENTITY
80MG	XOFLUZA	GENENTECH INC	N210854	March 18, 2021	RX	TABLET	ORAL	Oct. 24, 2023	NEW CHEMICAL ENTITY
2MG/ML	XOFLUZA	GENENTECH INC	N214410	Nov. 23, 2020	RX	FOR SUSPENSION	ORAL	Oct. 24, 2023	NEW CHEMICAL ENTITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Polymerase acidic protein	Enzyme		PA_I34A1	INHIBITOR	IC50	8.85		DRUG LABEL	DRUG LABEL

External reference:

ID	Source
505CXM6OHG	UNII
C4688747	UMLSCUI
CHEMBL4297503	ChEMBL_ID
124081896	PUBCHEM_CID
DB13997	DRUGBANK_ID
D11021	KEGG_DRUG
10491	INN_ID
11748	IUPHAR_LIGAND_ID
017822	NDDF
782500006	SNOMEDCT_US
4037950	VANDF
1985605-59-1	SECONDARY_CAS_RN
2099995	RXNORM
294671	MMSL
35334	MMSL
d09012	MMSL
C000628402	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50090-4102	TABLET, FILM COATED	20 mg	ORAL	NDA	31 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50090-4104	TABLET, FILM COATED	40 mg	ORAL	NDA	31 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-583	GRANULE, FOR SOLUTION	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-583	GRANULE, FOR SOLUTION	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-583	GRANULE, FOR SOLUTION	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-583	GRANULE, FOR SOLUTION	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-828	TABLET, FILM COATED	20 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-828	TABLET, FILM COATED	20 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-860	TABLET, FILM COATED	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-860	TABLET, FILM COATED	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-860	TABLET, FILM COATED	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-860	TABLET, FILM COATED	40 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-877	TABLET, FILM COATED	80 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-877	TABLET, FILM COATED	80 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-877	TABLET, FILM COATED	80 mg	ORAL	NDA	32 sections
Xofluza	HUMAN PRESCRIPTION DRUG LABEL	1	50242-877	TABLET, FILM COATED	80 mg	ORAL	NDA	32 sections