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

Stem definitionDrug idCAS RN
antivirals RNA polymerase (NS5B) inhibitors 4914 1132935-63-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • dasabuvir sodium monohydrate
  • dasabuvir
  • dasabuvir sodium
  • exviera
  • ABT-333
Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome. In a biochemical assay, dasabuvir inhibited a panel of genotype 1a and 1b NS5B polymerases. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor.
  • Molecular weight: 493.58
  • Formula: C26H27N3O5S
  • CLOGP: 4.07
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 104.81
  • ALOGS: -5.79
  • ROTB: 5

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
0.50 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 2.13 L/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 5.70 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 20, 2014 EMA AbbVie Ltd
Dec. 19, 2014 FDA ABBVIE 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
Jaundice 505.83 22.88 188 7695 28657 46649522
Blood bilirubin increased 365.52 22.88 156 7727 34028 46644151
Hyperbilirubinaemia 355.54 22.88 112 7771 10326 46667853
Hepatic failure 271.92 22.88 126 7757 33290 46644889
Ascites 210.73 22.88 109 7774 36475 46641704
Hepatic encephalopathy 144.62 22.88 57 7826 10100 46668079
Hepatocellular carcinoma 141.99 22.88 41 7842 2798 46675381
Hepatic cirrhosis 133.04 22.88 61 7822 15671 46662508
Asthenia 95.27 22.88 180 7703 310895 46367284
Anaemia 88.35 22.88 156 7727 255623 46422556
Vomiting 81.85 22.88 212 7671 452582 46225597
Nausea 79.91 22.88 275 7608 687179 45991000
Drug ineffective 69.61 22.88 15 7868 677823 46000356
Pruritus 68.84 22.88 136 7747 242216 46435963
Yellow skin 61.37 22.88 20 7863 2044 46676135
Haemoglobin decreased 61.23 22.88 91 7792 128858 46549321
Child-Pugh-Turcotte score increased 60.02 22.88 10 7873 44 46678135
Ocular icterus 57.36 22.88 22 7861 3618 46674561
Renal impairment 56.25 22.88 66 7817 74306 46603873
Bilirubin conjugated increased 56.12 22.88 20 7863 2678 46675501
Chromaturia 49.19 22.88 31 7852 14988 46663191
Fatigue 44.30 22.88 211 7672 608486 46069693
Hepatorenal syndrome 43.74 22.88 15 7868 1793 46676386
Encephalopathy 41.94 22.88 39 7844 33550 46644629
Varices oesophageal 40.73 22.88 16 7867 2803 46675376
Decreased appetite 40.29 22.88 96 7787 193740 46484439
Portal vein thrombosis 39.19 22.88 15 7868 2452 46675727
Oesophageal varices haemorrhage 36.96 22.88 12 7871 1211 46676968
Off label use 35.74 22.88 10 7873 379831 46298348
Upper gastrointestinal haemorrhage 34.56 22.88 26 7857 16712 46661467
Acute hepatic failure 32.94 22.88 24 7859 14697 46663482
Hepatic cancer 32.56 22.88 14 7869 3083 46675096
Blood bilirubin unconjugated increased 30.47 22.88 8 7875 382 46677797
Insomnia 30.35 22.88 78 7805 164846 46513333
Hepatitis C 28.41 22.88 16 7867 6302 46671877
Renal failure 27.71 22.88 60 7823 113534 46564645
Pain 26.49 22.88 25 7858 476923 46201256
Drug hypersensitivity 25.71 22.88 5 7878 243820 46434359

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
Blood bilirubin increased 339.32 21.80 179 8481 36457 29907361
Jaundice 243.21 21.80 138 8522 32348 29911470
Ascites 230.31 21.80 138 8522 35783 29908035
Hepatocellular carcinoma 195.31 21.80 81 8579 9529 29934289
Hepatic cirrhosis 188.16 21.80 92 8568 15907 29927911
Hepatic failure 188.13 21.80 119 8541 33924 29909894
Hyperbilirubinaemia 148.68 21.80 80 8580 16862 29926956
Hepatic encephalopathy 144.42 21.80 74 8586 14118 29929700
Renal impairment 123.06 21.80 136 8524 84048 29859770
Fatigue 95.20 21.80 253 8407 320420 29623398
Yellow skin 64.97 21.80 24 8636 2069 29941749
Anaemia 60.29 21.80 163 8497 207829 29735989
Ocular icterus 59.42 21.80 25 8635 3039 29940779
Hepatitis C 55.52 21.80 39 8621 13166 29930652
Encephalopathy 53.91 21.80 56 8604 32149 29911669
Oesophageal varices haemorrhage 52.91 21.80 23 8637 3028 29940790
Asthenia 51.17 21.80 160 8500 221130 29722688
Blood bilirubin unconjugated increased 50.10 21.80 15 8645 671 29943147
Haemoglobin decreased 49.86 21.80 105 8555 113993 29829825
Portal hypertension 47.66 21.80 23 8637 3850 29939968
Drug interaction 44.91 21.80 143 8517 199425 29744393
Insomnia 44.42 21.80 89 8571 93247 29850571
Distributive shock 42.35 21.80 13 8647 633 29943185
Hepatitis C RNULL increased 39.84 21.80 11 8649 367 29943451
Gastric varices haemorrhage 39.14 21.80 10 8650 246 29943572
Alanine aminotransferase increased 35.52 21.80 71 8589 74205 29869613
Child-Pugh-Turcotte score increased 34.05 21.80 7 8653 62 29943756
Bilirubin conjugated increased 32.69 21.80 17 8643 3334 29940484
Vomiting 29.05 21.80 133 8527 219685 29724133
Nausea 27.70 21.80 163 8497 296794 29647024
Chromaturia 26.65 21.80 26 8634 13839 29929979
Varices oesophageal 26.43 21.80 15 8645 3494 29940324
Hepatic lesion 25.24 21.80 14 8646 3122 29940696
Alpha 1 foetoprotein increased 25.17 21.80 9 8651 706 29943112
Immunosuppressant drug level increased 24.82 21.80 16 8644 4686 29939132
Acute on chronic liver failure 24.34 21.80 6 8654 127 29943691
Death 23.72 21.80 42 8618 357241 29586577
Drug ineffective 23.52 21.80 39 8621 340348 29603470
Irritability 23.35 21.80 31 8629 23019 29920799
Arteriovenous malformation 22.61 21.80 8 8652 609 29943209
Hepatorenal syndrome 22.40 21.80 12 8648 2499 29941319
Headache 22.36 21.80 108 8552 182198 29761620

Pharmacologic Action:

SourceCodeDescription
ATC J05AP09 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
ATC J05AP52 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA EPC N0000191257 Hepatitis C Virus Non-Nucleoside NS5B Palm Polymerase Inhibitor
FDA MoA N0000191258 RNULL Replicase Inhibitors
FDA MoA N0000191272 UGT1A1 Inhibitors
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:85180 nonstructural protein 5b 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 8.38 acidic
pKa2 9.01 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

None

External reference:

IDSource
D10553 KEGG_DRUG
1456607-55-8 SECONDARY_CAS_RN
4034028 VANDF
C3850285 UMLSCUI
CHEBI:85182 CHEBI
CHEMBL3137312 ChEMBL_ID
56640146 PUBCHEM_CID
CHEMBL3544985 ChEMBL_ID
DB09183 DRUGBANK_ID
C588260 MESH_SUPPLEMENTAL_RECORD_UI
11270 IUPHAR_LIGAND_ID
9741 INN_ID
DE54EQW8T1 UNII
1597381 RXNORM
30778 MMSL
31899 MMSL
d08322 MMSL
015829 NDDF
015830 NDDF
714104000 SNOMEDCT_US
714105004 SNOMEDCT_US
716018007 SNOMEDCT_US
725851005 SNOMEDCT_US

Pharmaceutical products:

None