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

Stem definition	Drug id	CAS RN
proton pump inhibitors, not dependent on acid activation	4993	881681-00-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: vonoprazan vonoprazan fumarate takecab TAK-438	Vonoprazan is a potassium-competitive proton pump blocker which was approved in Japan for the treatment of gastroduodenal ulcer. FDA approved a co-packaged combination of vonoprazan and antibiotics (amoxicillin and clarithromycin) to eradicate Helicobacter pyroli. Its potential to combat cytokine release syndrome (CRS) in patients with severely ill COVID-19 was investigated. Accordingly, it is recommended to use tocilizumabin combination with dexamethasone (or another corticosteroid at an equivalent dose) in certain hospitalized patients who are exhibiting rapid respiratory decompensation caused by COVID-19. Molecular weight: 345.39 Formula: C17H16FN3O2S CLOGP: 2.54 LIPINSKI: 0 HAC: 5 HDO: 1 TPSA: 63.99 ALOGS: -3.85 ROTB: 4 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

vonoprazan
vonoprazan fumarate
takecab
TAK-438

Vonoprazan is a potassium-competitive proton pump blocker which was approved in Japan for the treatment of gastroduodenal ulcer. FDA approved a co-packaged combination of vonoprazan and antibiotics (amoxicillin and clarithromycin) to eradicate Helicobacter pyroli. Its potential to combat cytokine release syndrome (CRS) in patients with severely ill COVID-19 was investigated. Accordingly, it is recommended to use tocilizumabin combination with dexamethasone (or another corticosteroid at an equivalent dose) in certain hospitalized patients who are exhibiting rapid respiratory decompensation caused by COVID-19.

Molecular weight: 345.39
Formula: C17H16FN3O2S
CLOGP: 2.54
LIPINSKI: 0
HAC: 5
HDO: 1
TPSA: 63.99
ALOGS: -3.85
ROTB: 4

Status: OFM

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

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Dec. 26, 2014	PMDA

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
Hepatic function abnormal	87.21	26.00	40	2948	37102	63448932
Interstitial lung disease	70.57	26.00	41	2947	61867	63424167
Platelet count decreased	68.72	26.00	51	2937	116071	63369963
Decreased appetite	56.40	26.00	64	2924	250988	63235046
Anaemia	51.51	26.00	66	2922	293364	63192670
Cardiac failure	45.75	26.00	36	2952	89106	63396928
White blood cell count decreased	33.79	26.00	37	2951	139067	63346967
Renal impairment	33.55	26.00	30	2958	88325	63397709
Cerebral infarction	33.09	26.00	18	2970	23875	63462159
Marasmus	32.56	26.00	7	2981	518	63485516
Familial mediterranean fever	32.08	26.00	5	2983	59	63485975
Neutrophil count decreased	31.57	26.00	24	2964	56382	63429652
Fulminant type 1 diabetes mellitus	27.58	26.00	6	2982	469	63485565
Enterocolitis	26.71	26.00	11	2977	7847	63478187
Liver disorder	26.05	26.00	21	2967	53666	63432368

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
Interstitial lung disease	155.26	23.06	93	3668	65189	34887981
Hepatic function abnormal	94.53	23.06	59	3702	44304	34908866
Cardiac failure	49.87	23.06	55	3706	91193	34861977
Cerebral infarction	49.72	23.06	33	3728	27422	34925748
Renal impairment	44.92	23.06	53	3708	94460	34858710
Pneumonia aspiration	41.36	23.06	35	3726	41868	34911302
Radiation pneumonitis	40.88	23.06	14	3747	2626	34950544
Immune-mediated enterocolitis	40.08	23.06	14	3747	2785	34950385
Adrenal insufficiency	35.82	23.06	21	3740	14026	34939144
Decreased appetite	35.72	23.06	64	3697	166328	34786842
Liver disorder	29.39	23.06	26	3735	32971	34920199
Oesophagitis	29.09	23.06	18	3743	13243	34939927
Malignant neoplasm progression	28.68	23.06	41	3720	88005	34865165
Cholangitis acute	27.53	23.06	8	3753	880	34952290
Adrenocorticotropic hormone deficiency	27.02	23.06	8	3753	939	34952231
Hypergastrinaemia	26.84	23.06	5	3756	75	34953095
Neutrophil count decreased	26.48	23.06	30	3731	51074	34902096
Cholangitis	24.85	23.06	14	3747	8675	34944495
Platelet count decreased	24.31	23.06	45	3716	119672	34833498
Organising pneumonia	23.77	23.06	12	3749	5967	34947203
Pulmonary toxicity	23.46	23.06	12	3749	6135	34947035

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
Interstitial lung disease	220.07	21.56	132	6926	112468	79624862
Hepatic function abnormal	169.96	21.56	96	6962	73011	79664319
Cardiac failure	89.74	21.56	88	6970	154754	79582576
Platelet count decreased	83.14	21.56	94	6964	194570	79542760
Decreased appetite	78.81	21.56	122	6936	342296	79395034
Renal impairment	70.43	21.56	78	6980	157705	79579625
Cerebral infarction	70.03	21.56	46	7012	45630	79691700
Pneumonia aspiration	58.45	21.56	48	7010	66919	79670411
Neutrophil count decreased	53.62	21.56	53	7005	93906	79643424
Liver disorder	49.22	21.56	45	7013	72372	79664958
Immune-mediated enterocolitis	46.06	21.56	17	7041	4813	79732517
Enterocolitis	44.68	21.56	23	7035	14489	79722841
Adrenal insufficiency	44.40	21.56	29	7029	28458	79708872
Malignant neoplasm progression	43.82	21.56	57	7001	135933	79601397
Anaemia	43.76	21.56	111	6947	444904	79292426
Marasmus	41.84	21.56	11	7047	1017	79736313
Radiation pneumonitis	41.81	21.56	15	7043	3918	79733412
Cholangitis	41.51	21.56	21	7037	12755	79724575
Hypergastrinaemia	40.70	21.56	8	7050	198	79737132
Adrenocorticotropic hormone deficiency	38.60	21.56	11	7047	1374	79735956
Cardiac failure acute	36.36	21.56	22	7036	18907	79718423
Disseminated intravascular coagulation	36.19	21.56	28	7030	35814	79701516
Pneumonia bacterial	35.93	21.56	22	7036	19309	79718021
Altered state of consciousness	33.27	21.56	29	7029	43793	79693537
Pulmonary toxicity	32.78	21.56	18	7040	12896	79724434
Immune-mediated hepatic disorder	32.76	21.56	10	7048	1584	79735746
Drug ineffective	32.37	21.56	29	7029	1080884	78656446
Fatigue	31.53	21.56	22	7036	929705	78807625
Hypothyroidism	30.70	21.56	30	7028	52362	79684968
KL-6 increased	30.27	21.56	6	7052	155	79737175
Tumour haemorrhage	30.23	21.56	12	7046	4132	79733198
White blood cell count decreased	29.88	21.56	57	7001	188231	79549099
Fulminant type 1 diabetes mellitus	29.19	21.56	9	7049	1474	79735856
Drug eruption	27.33	21.56	26	7032	43909	79693421
Blood pressure decreased	26.44	21.56	38	7020	99428	79637902
Physical deconditioning	26.24	21.56	9	7049	2061	79735269
Enterocolitis haemorrhagic	25.73	21.56	9	7049	2185	79735145
Myelosuppression	25.35	21.56	24	7034	40272	79697058
Asthenia	25.32	21.56	7	7051	511682	79225648
Erythema multiforme	25.16	21.56	17	7041	17634	79719696
Drug-induced liver injury	24.93	21.56	30	7028	66087	79671243
Ascites	24.83	21.56	32	7026	75530	79661800
Cholangitis acute	24.76	21.56	8	7050	1524	79735806
Pain	24.70	21.56	16	7042	703786	79033544
Organising pneumonia	24.38	21.56	14	7044	10925	79726405
Familial mediterranean fever	23.57	21.56	5	7053	182	79737148
Pyrexia	23.36	21.56	120	6938	678589	79058741
Cerebellar haemorrhage	23.22	21.56	9	7049	2911	79734419

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	A02BC08	ALIMENTARY TRACT AND METABOLISM DRUGS FOR ACID RELATED DISORDERS DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD) Proton pump inhibitors
ATC	A02BD14	ALIMENTARY TRACT AND METABOLISM DRUGS FOR ACID RELATED DISORDERS DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD) Combinations for eradication of Helicobacter pylori
ATC	A02BD15	ALIMENTARY TRACT AND METABOLISM DRUGS FOR ACID RELATED DISORDERS DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD) Combinations for eradication of Helicobacter pylori

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

Disease	Relation	SNOMED_ID	DOID
Duodenal ulcer disease	indication	51868009	DOID:1724
Gastro-esophageal reflux disease with esophagitis	indication	266433003
Gastric ulcer	indication	397825006	DOID:10808
Infection caused by Helicobacter pylori	indication	721730009

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.09	Basic
pKa2	2.72	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
500MG;500MG;EQ 20MG BASE	VOQUEZNA TRIPLE PAK	PHATHOM	N215152	May 3, 2022	DISCN	CAPSULE, TABLET, TABLET	ORAL	May 3, 2027	NEW CHEMICAL ENTITY
500MG;EQ 20MG BASE	VOQUEZNA DUAL PAK	PHATHOM	N215153	May 3, 2022	DISCN	CAPSULE, TABLET	ORAL	May 3, 2027	NEW CHEMICAL ENTITY
500MG;500MG;EQ 20MG BASE	VOQUEZNA TRIPLE PAK	PHATHOM	N215152	May 3, 2022	DISCN	CAPSULE, TABLET, TABLET	ORAL	May 3, 2032	GENERATING ANTIBIOTIC INCENTIVES NOW
500MG;EQ 20MG BASE	VOQUEZNA DUAL PAK	PHATHOM	N215153	May 3, 2022	DISCN	CAPSULE, TABLET	ORAL	May 3, 2032	GENERATING ANTIBIOTIC INCENTIVES NOW

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Potassium-transporting ATPase	Transporter	P20648 P51164	ATP4A_HUMAN ATP4B_HUMAN	INHIBITOR	Ki	8		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE

External reference:

ID	Source
1R5L3J156G	UNII
D10466	KEGG_DRUG
881681-01-2	SECONDARY_CAS_RN
4041456	VANDF
C4080009	UMLSCUI
CHEBI:136048	CHEBI
HKT	PDB_CHEM_ID
CHEMBL2079130	ChEMBL_ID
15981397	PUBCHEM_CID
DB11739	DRUGBANK_ID
CHEMBL2064032	ChEMBL_ID
9535	INN_ID
C552956	MESH_SUPPLEMENTAL_RECORD_UI
11549	IUPHAR_LIGAND_ID
2604576	RXNORM
40790	MMSL
d09874	MMSL
019050	NDDF
019051	NDDF

Pharmaceutical products:

None