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

Stem definitionDrug idCAS RN
antivirals, hepatitis C Virus (HCV) NS5A inhibitors 4899 1256388-51-8

Description:

MoleculeDescription

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:

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

Approvals:

DateAgencyCompanyOrphan
Dec. 4, 2014 EMA
Oct. 10, 2014 FDA GILEAD SCIENCES INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Genome polyprotein Polyprotein INHIBITOR EC50 10.51 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Genome polyprotein Polyprotein INHIBITOR EC50 11.40 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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