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

Stem definition	Drug id	CAS RN
Hepatitis Virus C (HVC) protease inhibitors	4812	923604-59-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: olysio TMC-435 TMC435350 simeprevir simeprevir sodium	Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS. Molecular weight: 749.94 Formula: C38H47N5O7S2 CLOGP: 5.45 LIPINSKI: 3 HAC: 12 HDO: 2 TPSA: 156.89 ALOGS: -5.39 ROTB: 7 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

olysio
TMC-435
TMC435350
simeprevir
simeprevir sodium

Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.

Molecular weight: 749.94
Formula: C38H47N5O7S2
CLOGP: 5.45
LIPINSKI: 3
HAC: 12
HDO: 2
TPSA: 156.89
ALOGS: -5.39
ROTB: 7

Status: OFM

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

Drug dosage:

Dose	Unit	Route
0.15	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ
S (Water solubility)	0.00 mg/mL	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
May 14, 2014	EMA
Nov. 22, 2013	FDA	JANSSEN PRODS

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
Platelet count decreased	786.23	38.65	301	4414	115821	63368486
Anaemia	585.05	38.65	325	4390	293105	63191202
White blood cell count decreased	471.06	38.65	221	4494	138883	63345424
Blood bilirubin increased	390.96	38.65	134	4581	37006	63447301
Neutrophil count decreased	278.13	38.65	117	4598	56289	63428018
Haemoglobin decreased	223.50	38.65	137	4578	145348	63338959
Hyperbilirubinaemia	167.78	38.65	53	4662	11261	63473046
Haemolytic anaemia	152.49	38.65	48	4667	10077	63474230
Hepatitis C	113.82	38.65	33	4682	5241	63479066
Hepatocellular carcinoma	111.22	38.65	27	4688	2167	63482140
Pruritus	101.47	38.65	129	4586	361324	63122983
Pyrexia	93.29	38.65	142	4573	470336	63013971
Photosensitivity reaction	86.91	38.65	35	4680	14959	63469348
Off label use	86.90	38.65	168	4547	674294	62810013
Remission not achieved	52.49	38.65	9	4706	122	63484185
Decreased appetite	45.60	38.65	73	4642	250979	63233328
Hepatic failure	45.55	38.65	30	4685	35626	63448681
Hepatic function abnormal	44.43	38.65	30	4685	37112	63447195
Jaundice	43.28	38.65	27	4688	29224	63455083
Hepatic encephalopathy	41.18	38.65	19	4696	11263	63473044
Sunburn	41.04	38.65	13	4702	2775	63481532

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
Platelet count decreased	553.02	28.77	300	5268	119417	34831946
White blood cell count decreased	397.78	28.77	224	5344	95221	34856142
Blood bilirubin increased	357.83	28.77	156	5412	38140	34913223
Anaemia	313.65	28.77	273	5295	233062	34718301
Hepatitis C	293.26	28.77	94	5474	9736	34941627
Hepatocellular carcinoma	262.22	28.77	81	5487	7428	34943935
Off label use	179.08	28.77	271	5297	419253	34532110
Hyperbilirubinaemia	174.62	28.77	74	5494	16769	34934594
Haemoglobin decreased	150.47	28.77	136	5432	120636	34830727
Neutrophil count decreased	144.78	28.77	94	5474	51010	34900353
Photosensitivity reaction	142.07	28.77	56	5512	10538	34940825
Drug ineffective	88.18	28.77	211	5357	456540	34494823
Jaundice	76.59	28.77	53	5515	31829	34919534
Remission not achieved	71.93	28.77	13	5555	106	34951257
Pruritus	67.36	28.77	97	5471	141884	34809479
Haemolytic anaemia	61.32	28.77	31	5537	10448	34940915
Sunburn	52.50	28.77	17	5551	1806	34949557
Hepatic failure	49.00	28.77	42	5526	34489	34916874
Treatment failure	47.23	28.77	47	5521	46650	34904713
Genotype drug resistance test positive	46.97	28.77	14	5554	1131	34950232
Pyrexia	46.68	28.77	137	5431	332876	34618487
Hepatitis C RNA increased	43.66	28.77	10	5558	285	34951078
Viral load increased	43.35	28.77	16	5552	2511	34948852
Ascites	41.87	28.77	44	5524	46527	34904836
Hepatic encephalopathy	41.44	28.77	27	5541	14658	34936705
Bilirubin conjugated increased	39.34	28.77	16	5552	3255	34948108
Thought blocking	39.15	28.77	8	5560	131	34951232
Rash	35.37	28.77	96	5472	222656	34728707
Choroiditis	33.65	28.77	11	5557	1204	34950159
Hyperuricaemia	33.55	28.77	19	5549	8024	34943339

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
Platelet count decreased	1387.40	30.73	600	8990	194064	79540734
White blood cell count decreased	909.39	30.73	444	9146	187844	79546954
Anaemia	872.92	30.73	581	9009	444434	79290364
Blood bilirubin increased	700.00	30.73	272	9318	65960	79668838
Neutrophil count decreased	417.07	30.73	210	9380	93749	79641049
Hepatitis C	400.13	30.73	117	9473	11808	79722990
Haemoglobin decreased	377.43	30.73	267	9323	221852	79512946
Hepatocellular carcinoma	372.19	30.73	104	9486	8917	79725881
Hyperbilirubinaemia	320.99	30.73	118	9472	24400	79710398
Haemolytic anaemia	208.42	30.73	79	9511	17741	79717057
Pruritus	152.68	30.73	211	9379	394437	79340361
Photosensitivity reaction	142.01	30.73	63	9527	21064	79713734
Pyrexia	140.18	30.73	273	9317	678436	79056362
Jaundice	113.61	30.73	74	9516	53275	79681523
Remission not achieved	106.26	30.73	21	9569	388	79734410
Hepatic failure	88.51	30.73	67	9523	61145	79673653
Off label use	78.77	30.73	263	9327	906952	78827846
Hepatic encephalopathy	67.86	30.73	40	9550	24126	79710672
Hepatitis C RNA increased	64.94	30.73	14	9576	402	79734396
Bilirubin conjugated increased	62.72	30.73	24	9566	5515	79729283
Rash	60.39	30.73	179	9411	578179	79156619
Pain	58.08	30.73	8	9582	703794	79031004
Hyperuricaemia	56.96	30.73	28	9562	11771	79723027
Ascites	56.87	30.73	57	9533	75505	79659293
Sunburn	55.89	30.73	20	9570	3813	79730985
Decreased appetite	54.23	30.73	124	9466	342294	79392504
Insomnia	48.24	30.73	97	9493	245073	79489725
Malaise	47.66	30.73	148	9442	489721	79245077
Aspartate aminotransferase increased	47.25	30.73	70	9520	138571	79596227
Hepatorenal syndrome	46.64	30.73	18	9572	4231	79730567
Hepatic function abnormal	44.06	30.73	49	9541	73058	79661740
Red blood cell count decreased	42.56	30.73	43	9547	57470	79677328
Viral load increased	37.83	30.73	14	9576	2934	79731864
Hepatic cirrhosis	37.24	30.73	32	9558	34874	79699924
Thought blocking	37.03	30.73	8	9582	232	79734566
Choroiditis	35.30	30.73	11	9579	1370	79733428
Alanine aminotransferase increased	33.96	30.73	66	9524	162504	79572294
Liver disorder	32.85	30.73	42	9548	72375	79662423
Injection site dermatitis	32.29	30.73	5	9585	19	79734779
Incorrect product administration duration	31.40	30.73	19	9571	12003	79722795

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	J05AP05	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D011480	Protease Inhibitors
FDA MoA	N0000182138	Cytochrome P450 1A2 Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000182638	HCV NS3/4A Protease Inhibitors
FDA EPC	N0000182639	Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA	N0000190108	Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA MoA	N0000193845	Bile Salt Export Pump Inhibitors
FDA MoA	N0000193960	Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA	N0000193965	Sodium Taurocholate Co-transporting Polypeptide Inhibitors

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

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.35	acidic
pKa2	6.66	Basic
pKa3	3.5	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
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8349869	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8741926	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8754106	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9040562	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9353103	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9623022	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9856265	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8148399	Sept. 5, 2029	METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Cathepsin S	Enzyme	P25774	CATS_HUMAN		IC50	6.10	CHEMBL
Hepatitis C virus serine protease, NS3/NS4A	Enzyme		A3EZI9_9HEPC D2K2A8_9HEPC	INHIBITOR	Ki	9.30	CHEMBL	CHEMBL
Genome polyprotein	Polyprotein		POLG_HCVH	INHIBITOR	Ki	9.44	SCIENTIFIC LITERATURE	DRUG LABEL
Nonstructural protein NS3-4A	Unclassified		A0A0K1CY61_9HEPC		Ki	9.44	CHEMBL
Polyprotein	Polyprotein		Q6GYR8_9HEPC	INHIBITOR	Ki	9.44	IUPHAR
Genome polyprotein	Unclassified		A3EZJ3_9HEPC		Ki	9.30	CHEMBL

External reference:

ID	Source
D10081	KEGG_DRUG
4032900	VANDF
CHEBI:134743	CHEBI
30B	PDB_CHEM_ID
CHEMBL501849	ChEMBL_ID
7367	IUPHAR_LIGAND_ID
9432	INN_ID
1241946-89-3	SECONDARY_CAS_RN
DB06290	DRUGBANK_ID
9WS5RD66HZ	UNII
1482790	RXNORM
207569	MMSL
29896	MMSL
d08182	MMSL
015309	NDDF
015310	NDDF
708823009	SNOMEDCT_US
714167009	SNOMEDCT_US
C2605855	UMLSCUI
D000069616	MESH_DESCRIPTOR_UI
CHEMBL3137358	ChEMBL_ID
24873435	PUBCHEM_CID

Pharmaceutical products:

None