ledipasvir Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antivirals, hepatitis C Virus (HCV) NS5A inhibitors	4899	1256388-51-8

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: ledipasvir GS-5885	an inhibitor of the HCV NS5A protein, which is required for viral replication Molecular weight: 889.02 Formula: C49H54F2N8O6 CLOGP: 6.71 LIPINSKI: 3 HAC: 14 HDO: 4 TPSA: 174.64 ALOGS: -5.36 ROTB: 12 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

ledipasvir
GS-5885

an inhibitor of the HCV NS5A protein, which is required for viral replication

Molecular weight: 889.02
Formula: C49H54F2N8O6
CLOGP: 6.71
LIPINSKI: 3
HAC: 14
HDO: 4
TPSA: 174.64
ALOGS: -5.36
ROTB: 12

Status: ONP

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

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	4	Hosey CM, Chan R, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Dec. 4, 2014	EMA
Oct. 10, 2014	FDA	GILEAD SCIENCES INC

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
Headache	1996.54	21.31	1406	12694	476946	46195016
Fatigue	1602.89	21.31	1363	12737	607334	46064628
Hepatocellular carcinoma	694.15	21.31	163	13937	2676	46669286
Hepatitis C	591.66	21.31	169	13931	6149	46665813
Insomnia	241.32	21.31	272	13828	164652	46507310
Genotype drug resistance test positive	201.72	21.31	44	14056	506	46671456
Nausea	159.27	21.31	510	13590	686944	45985018
Hepatic encephalopathy	130.60	21.31	63	14037	10094	46661868
Product dose omission issue	125.40	21.31	200	13900	168320	46503642
Hepatitis C virus test positive	121.97	21.31	24	14076	158	46671804
Ascites	107.95	21.31	89	14011	36495	46635467
Oesophageal varices haemorrhage	102.32	21.31	30	14070	1193	46670769
Hepatic cancer recurrent	80.34	21.31	14	14086	41	46671921
Diarrhoea	78.72	21.31	355	13745	559247	46112715
Dyspepsia	75.36	21.31	98	14002	68374	46603588
Hepatitis B reactivation	71.53	21.31	24	14076	1490	46670472
Rheumatoid arthritis	57.12	21.31	4	14096	240211	46431751
Hepatic cirrhosis	56.52	21.31	43	14057	15689	46656273
Drug hypersensitivity	52.76	21.31	6	14094	243819	46428143
Hepatic cancer	51.61	21.31	23	14077	3074	46668888
Treatment failure	46.52	21.31	93	14007	92994	46578968
Product use complaint	41.97	21.31	17	14083	1795	46670167
Glomerular filtration rate decreased	39.90	21.31	31	14069	11663	46660299
Toxicity to various agents	39.44	21.31	8	14092	211758	46460204
Liver transplant	34.14	21.31	16	14084	2401	46669561
Maternal exposure during pregnancy	32.91	21.31	86	14014	102463	46569499
Hepatic failure	32.41	21.31	45	14055	33371	46638591
Neutropenia	32.30	21.31	3	14097	143201	46528761
Portal vein thrombosis	30.79	21.31	15	14085	2452	46669510
Pruritus	29.60	21.31	148	13952	242204	46429758
Alopecia	28.02	21.31	110	13990	162304	46509658
Irritability	26.61	21.31	38	14062	28908	46643054
Cryoglobulinaemia	26.28	21.31	8	14092	362	46671600
Renal impairment	24.49	21.31	63	14037	74309	46597653
Off label use	24.19	21.31	49	14051	379792	46292170

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
Headache	3086.04	18.82	1727	17757	180579	29752415
Fatigue	3061.34	18.82	2103	17381	318570	29614424
Hepatitis C	1897.26	18.82	584	18900	12621	29920373
Hepatocellular carcinoma	1112.75	18.82	361	19123	9249	29923745
Treatment failure	495.65	18.82	298	19186	34381	29898613
Genotype drug resistance test positive	386.13	18.82	106	19378	1483	29931511
Drug ineffective	370.29	18.82	731	18753	339656	29593338
Insomnia	308.47	18.82	340	19144	92996	29839998
Hepatitis C virus test positive	206.62	18.82	50	19434	407	29932587
Nausea	192.91	18.82	522	18962	296435	29636559
Product dose omission issue	173.32	18.82	253	19231	91378	29841616
Hepatic cirrhosis	167.17	18.82	113	19371	15886	29917108
Ascites	145.27	18.82	146	19338	35775	29897219
Viral mutation identified	127.40	18.82	52	19432	2574	29930420
Liver transplant	120.79	18.82	51	19433	2751	29930243
Hepatitis B reactivation	103.21	18.82	46	19438	2831	29930163
Hypotension	90.19	18.82	12	19472	200553	29732441
Oesophageal varices haemorrhage	88.22	18.82	42	19442	3009	29929985
Dyspepsia	85.48	18.82	102	19382	30227	29902767
Hepatic cancer recurrent	82.38	18.82	23	19461	343	29932651
Toxicity to various agents	78.70	18.82	11	19473	177172	29755822
Pneumonia	63.15	18.82	75	19409	334231	29598763
Hepatic encephalopathy	61.60	18.82	60	19424	14132	29918862
Hepatic cancer	60.72	18.82	43	19441	6505	29926489
Febrile neutropenia	57.09	18.82	3	19481	106690	29826304
Abdominal discomfort	52.50	18.82	105	19379	48686	29884308
Focal segmental glomerulosclerosis	52.36	18.82	25	19459	1802	29931192
Intentional dose omission	51.80	18.82	23	19461	1402	29931592
Irritability	51.40	18.82	69	19415	22981	29910013
Off label use	46.91	18.82	56	19428	249234	29683760
Diarrhoea	45.89	18.82	372	19112	333731	29599263
Glomerular filtration rate decreased	45.54	18.82	46	19438	11316	29921678
General physical health deterioration	40.34	18.82	8	19476	99936	29833058
White blood cell count decreased	40.22	18.82	4	19480	83943	29849051
Hepatic failure	39.94	18.82	76	19408	33967	29899027
Dyspnoea	36.74	18.82	104	19380	333191	29599803
Hepatitis C RNULL positive	36.33	18.82	11	19473	221	29932773
Malignant neoplasm progression	33.21	18.82	4	19480	72283	29860711
Drug abuse	32.22	18.82	7	19477	82065	29850929
Pyrexia	31.61	18.82	93	19391	294396	29638598
Influenza like illness	29.82	18.82	57	19427	25548	29907446
Complications of transplanted lung	29.67	18.82	9	19475	182	29932812
Ectopic kidney	29.25	18.82	7	19477	54	29932940
Disease progression	29.04	18.82	8	19476	79866	29853128
Chronic hepatitis C	28.06	18.82	11	19473	489	29932505
Fall	28.05	18.82	47	19437	181825	29751169
Alpha 1 foetoprotein increased	27.47	18.82	12	19472	703	29932291
Therapy cessation	27.36	18.82	41	19443	15096	29917898
Laryngomalacia	26.54	18.82	9	19475	263	29932731
Constipation	26.53	18.82	144	19340	112762	29820232
Neutropenia	26.18	18.82	27	19457	128513	29804481
Completed suicide	25.05	18.82	17	19467	99475	29833519
Cryoglobulinaemia	25.03	18.82	9	19475	314	29932680
Drug hypersensitivity	24.65	18.82	7	19477	68512	29864482
Myalgia	24.64	18.82	107	19377	76560	29856434
Dry mouth	24.35	18.82	49	19435	22801	29910193
Tachycardia	23.95	18.82	9	19475	73730	29859264
Migraine	23.45	18.82	35	19449	12839	29920155
Abnormal dreams	22.36	18.82	27	19457	8088	29924906
Extra dose administered	22.34	18.82	17	19467	2869	29930125
Plasma cell myeloma	22.15	18.82	4	19480	53458	29879536
Pancytopenia	22.13	18.82	14	19470	85038	29847956
Respiratory failure	21.80	18.82	20	19464	100622	29832372
Cardiac failure	21.34	18.82	14	19470	83404	29849590
Erythema	21.20	18.82	12	19472	77439	29855555
Hepatic fibrosis	21.15	18.82	18	19466	3562	29929432
Hypoxia	21.13	18.82	3	19481	47851	29885143
Virologic failure	20.70	18.82	17	19467	3202	29929792
Ammonia increased	20.43	18.82	19	19465	4222	29928772
Deep vein thrombosis	20.30	18.82	7	19477	60494	29872500
Tinnitus	20.21	18.82	37	19447	16051	29916943
Coronary artery disease	20.00	18.82	4	19480	49708	29883286
Gait disturbance	19.88	18.82	12	19472	74765	29858229
Product use complaint	19.30	18.82	11	19473	1141	29931853

Pharmacologic Action:

Source	Code	Description
ATC	J05AP51	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
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA EPC	N0000191256	Hepatitis C Virus NS5A Inhibitor
CHEBI has role	CHEBI:36044	anti-virus drug
CHEBI has role	CHEBI:64924	hepatitis c protease inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.48	acidic
pKa2	13.1	acidic
pKa3	13.41	acidic
pKa4	13.92	acidic
pKa5	6.07	Basic
pKa6	5.39	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
45MG;200MG	HARVONI	GILEAD SCIENCES INC	N205834	Aug. 28, 2019	RX	TABLET	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
90MG;400MG	HARVONI	GILEAD SCIENCES INC	N205834	Oct. 10, 2014	RX	TABLET	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
90MG;400MG	HARVONI	GILEAD SCIENCES INC	N205834	Oct. 10, 2014	RX	TABLET	ORAL	April 7, 2024	TREATMENT OF PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER OR WEIGHING AT LEAST 35 KG WITH CHRONIC HEPATITIS C VIRUS GENOTYPE 1, 4, 5, OR 6 INFECTION WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS
90MG;400MG	HARVONI	GILEAD SCIENCES INC	N205834	Oct. 10, 2014	RX	TABLET	ORAL	Oct. 7, 2024	PEDIATRIC EXCLUSIVITY
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 INFECTION WITH DECOMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 OR 4 INFECTION WHO ARE LIVER TRANSPLANT RECIPIENTS WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS BETWEEN 3 YEARS OF AGE AND 12 YEARS OF AGE OR WEIGHING 35 KG WITH CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 1, 4, 5, OR 6 INFECTION WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 INFECTION WITH DECOMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 OR 4 INFECTION WHO ARE LIVER TRANSPLANT RECIPIENTS WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS BETWEEN 3 YEARS OF AGE AND 12 YEARS OF AGE OR WEIGHING 35 KG WITH CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 1, 4, 5, OR 6 INFECTION WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Genome polyprotein	Polyprotein		POLG_HCVH	INHIBITOR	EC50	10.51		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Genome polyprotein	Polyprotein		POLG_HCVBK	INHIBITOR	EC50	11.40		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE

External reference:

ID	Source
D10442	KEGG_DRUG
4033796	VUID
N0000191095	NUI
4033796	VANDF
C3852655	UMLSCUI
CHEBI:85089	CHEBI
CHEMBL2374220	ChEMBL_ID
DB09027	DRUGBANK_ID
C586541	MESH_SUPPLEMENTAL_RECORD_UI
11271	IUPHAR_LIGAND_ID
9796	INN_ID
013TE6E4WV	UNII
66621102	PUBCHEM_CID
1591922	RXNORM
30602	MMSL
d08295	MMSL
015709	NDDF
712517005	SNOMEDCT_US
714387002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1801	TABLET, FILM COATED	90 mg	ORAL	NDA	36 sections
Harvoni Access	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1802	TABLET, FILM COATED	90 mg	ORAL	Export only	31 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1803	TABLET, FILM COATED	45 mg	ORAL	NDA	36 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1804	PELLET	45 mg	ORAL	NDA	36 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1805	PELLET	33.75 mg	ORAL	NDA	36 sections
Ledipasvir and Sofosbuvir	HUMAN PRESCRIPTION DRUG LABEL	2	72626-2601	TABLET, FILM COATED	90 mg	ORAL	NDA AUTHORIZED GENERIC	35 sections