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

Stem definitionDrug idCAS RN
antivirals 4805 1051375-16-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • dolutegravir sodium
  • tivicay
  • dolutegravir
  • GSK 1349572
  • S-349572
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.
  • Molecular weight: 419.39
  • Formula: C20H19F2N3O5
  • CLOGP: 0.05
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 99.18
  • ALOGS: -3.66
  • ROTB: 3

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
50 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Aug. 12, 2013 FDA VIIV HLTHCARE

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
Exposure during pregnancy 585.78 26.40 272 5098 107940 46572752
Abortion spontaneous 512.29 26.40 191 5179 43455 46637237
Foetal exposure during pregnancy 440.45 26.40 156 5214 30591 46650101
Maternal exposure during pregnancy 436.63 26.40 219 5151 102330 46578362
Virologic failure 386.78 26.40 80 5290 1975 46678717
Blood HIV RNULL increased 234.44 26.40 44 5326 643 46680049
Stillbirth 195.51 26.40 58 5312 6433 46674259
Live birth 184.73 26.40 62 5308 10268 46670424
Immune reconstitution inflammatory syndrome 176.09 26.40 52 5318 5673 46675019
Pathogen resistance 164.57 26.40 50 5320 6010 46674682
Congenital umbilical hernia 152.91 26.40 29 5341 449 46680243
Abortion induced 131.25 26.40 48 5322 10212 46670480
Foetal death 131.05 26.40 46 5324 8697 46671995
Treatment noncompliance 109.89 26.40 58 5312 29673 46651019
Ectopic kidney 93.72 26.40 15 5355 78 46680614
Birth mark 85.78 26.40 16 5354 225 46680467
Drug resistance 85.02 26.40 41 5329 17327 46663365
Viral mutation identified 79.73 26.40 22 5348 1877 46678815
Hydrops foetalis 79.64 26.40 16 5354 338 46680354
Premature baby 77.47 26.40 39 5331 18073 46662619
Premature delivery 72.96 26.40 40 5330 22029 46658663
Pre-eclampsia 65.24 26.40 27 5343 7967 46672725
Product size issue 60.27 26.40 13 5357 392 46680300
Foetal growth restriction 59.81 26.40 24 5346 6543 46674149
Viral load increased 58.05 26.40 16 5354 1359 46679333
Drug interaction 49.81 26.40 86 5284 203008 46477684
Premature separation of placenta 45.78 26.40 14 5356 1714 46678978
Macrocephaly 45.40 26.40 8 5362 80 46680612
Antiviral drug level below therapeutic 41.95 26.40 7 5363 49 46680643
Genotype drug resistance test positive 40.70 26.40 10 5360 540 46680152
Congenital skin dimples 40.38 26.40 8 5362 157 46680535
Polydactyly 39.12 26.40 9 5361 366 46680326
Endometritis decidual 37.05 26.40 6 5364 34 46680658
Drug-induced liver injury 36.05 26.40 27 5343 25341 46655351
Potassium wasting nephropathy 34.23 26.40 6 5364 58 46680634
Ectopic pregnancy 32.70 26.40 12 5358 2570 46678122
Hyperbilirubinaemia 31.96 26.40 18 5352 10420 46670272
Encephalomalacia 31.42 26.40 8 5362 500 46680192
Mental disability 30.67 26.40 6 5364 110 46680582
Generalised anxiety disorder 29.78 26.40 10 5360 1650 46679042
Total bile acids increased 29.50 26.40 6 5364 135 46680557
Gestational diabetes 29.26 26.40 15 5355 7204 46673488
Umbilical hernia 28.47 26.40 11 5359 2713 46677979
Ultrasound uterus abnormal 28.11 26.40 5 5365 53 46680639
Social avoidant behaviour 28.03 26.40 11 5359 2828 46677864
Pubertal failure 26.50 26.40 4 5366 13 46680679

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
Immune reconstitution inflammatory syndrome 490.33 16.04 170 11662 8931 29931715
Blood HIV RNULL increased 430.00 16.04 102 11730 1314 29939332
Virologic failure 422.98 16.04 119 11713 3100 29937546
Foetal exposure during pregnancy 243.74 16.04 162 11670 36709 29903937
Congenital umbilical hernia 193.24 16.04 42 11790 353 29940293
Birth mark 155.38 16.04 32 11800 201 29940445
Viral mutation identified 110.86 16.04 41 11791 2585 29938061
Viral load increased 103.95 16.04 40 11792 2814 29937832
Drug resistance 79.65 16.04 65 11767 20068 29920578
CD4 lymphocytes decreased 78.93 16.04 30 11802 2040 29938606
Suicidal ideation 75.87 16.04 82 11750 36032 29904614
Hepatitis C 75.19 16.04 53 11779 13152 29927494
Drug-induced liver injury 74.47 16.04 64 11768 21210 29919436
Drug level decreased 73.86 16.04 39 11793 5766 29934880
Treatment noncompliance 65.06 16.04 64 11768 25189 29915457
Hyperferritinaemia 54.27 16.04 15 11817 364 29940282
HIV infection 52.37 16.04 21 11811 1647 29938999
Insomnia 51.81 16.04 114 11718 93222 29847424
Meningitis cryptococcal 51.74 16.04 22 11810 2002 29938644
Mycobacterial infection 48.33 16.04 20 11812 1701 29938945
Drug interaction 46.22 16.04 178 11654 199390 29741256
Viraemia 44.63 16.04 17 11815 1162 29939484
Portal fibrosis 44.27 16.04 13 11819 394 29940252
Pathogen resistance 43.84 16.04 32 11800 8378 29932268
Faeces pale 40.92 16.04 17 11815 1460 29939186
Syphilis 40.64 16.04 12 11820 371 29940275
Acute hepatitis C 39.70 16.04 10 11822 167 29940479
Immune reconstitution inflammatory syndrome associated tuberculosis 39.41 16.04 12 11820 413 29940233
Chylothorax 38.48 16.04 13 11819 627 29940019
Hepatitis A 38.09 16.04 12 11820 463 29940183
Hepatotoxicity 37.72 16.04 41 11791 18104 29922542
Fibrous histiocytoma 37.35 16.04 9 11823 124 29940522
Enterovirus infection 35.58 16.04 12 11820 576 29940070
Sleep disorder 35.47 16.04 46 11786 24433 29916213
Glomerular filtration rate decreased 35.38 16.04 32 11800 11330 29929316
Lipodystrophy acquired 34.52 16.04 20 11812 3540 29937106
Cytomegalovirus chorioretinitis 33.40 16.04 19 11813 3249 29937397
Osteoporosis 33.14 16.04 30 11802 10633 29930013
Depressed mood 31.15 16.04 36 11796 16993 29923653
Polydactyly 30.17 16.04 13 11819 1222 29939424
Lymphadenopathy 29.53 16.04 42 11790 24334 29916312
Anogenital warts 29.20 16.04 10 11822 503 29940143
Ocular icterus 29.14 16.04 17 11815 3047 29937599
Renal failure 28.94 16.04 114 11718 128852 29811794
Venolymphatic malformation 28.69 16.04 6 11826 41 29940605
Hypotension 27.92 16.04 23 11809 200542 29740104
Fall 27.69 16.04 19 11813 181853 29758793
Pneumonia 27.41 16.04 57 11775 334249 29606397
Hepatic enzyme decreased 26.94 16.04 6 11826 57 29940589
Hepatitis cholestatic 26.15 16.04 23 11809 7849 29932797
Abnormal dreams 25.55 16.04 23 11809 8092 29932554
Suicide attempt 25.23 16.04 49 11783 36648 29903998
Lung transplant rejection 25.21 16.04 10 11822 762 29939884
Anogenital dysplasia 25.05 16.04 7 11825 177 29940469
Hepatomegaly 25.00 16.04 25 11807 10022 29930624
Blood creatinine increased 24.87 16.04 86 11746 91289 29849357
Renal impairment 24.46 16.04 81 11751 84103 29856543
Renal hypoplasia 24.24 16.04 6 11826 93 29940553
Genotype drug resistance test positive 24.04 16.04 12 11820 1577 29939069
Talipes 23.44 16.04 12 11820 1663 29938983
Opportunistic infection 23.19 16.04 11 11821 1293 29939353
Cardiac failure congestive 23.16 16.04 3 11829 84404 29856242
Hepatic necrosis 23.13 16.04 16 11816 3847 29936799
Lactic acidosis 23.08 16.04 43 11789 31170 29909476
Neuropsychiatric symptoms 21.83 16.04 8 11824 491 29940155
Renal tubular disorder 21.56 16.04 17 11815 4989 29935657
Malabsorption 21.52 16.04 12 11820 1975 29938671
Congenital skin dimples 21.42 16.04 6 11826 153 29940493
Lymphoma 21.26 16.04 23 11809 10098 29930548
Anal cancer stage 0 20.92 16.04 4 11828 16 29940630
Mycobacterium avium complex infection 20.53 16.04 13 11819 2698 29937948
Iodine uptake increased 20.51 16.04 3 11829 0 29940646
Nephropathy toxic 20.31 16.04 23 11809 10616 29930030
Headache 20.15 16.04 132 11700 182174 29758472
Psychiatric decompensation 20.10 16.04 10 11822 1305 29939341
Drug abuse 20.09 16.04 4 11828 82068 29858578
Osteonecrosis 19.83 16.04 28 11804 16107 29924539
Therapy cessation 19.70 16.04 27 11805 15110 29925536
Polymicrogyria 19.57 16.04 4 11828 24 29940622
Blood HIV RNULL 18.92 16.04 4 11828 29 29940617
Cerebral dysgenesis 18.80 16.04 4 11828 30 29940616
Trisomy 21 18.64 16.04 7 11825 460 29940186
Chromaturia 18.45 16.04 25 11807 13840 29926806
Head lag abnormal 18.43 16.04 3 11829 3 29940643
Product use complaint 18.32 16.04 9 11823 1143 29939503
Hepatitis fulminant 18.31 16.04 14 11818 3927 29936719
Hypovolaemic shock 17.71 16.04 17 11815 6483 29934163
Platelet count decreased 17.63 16.04 10 11822 106119 29834527
Genital herpes 17.58 16.04 7 11825 539 29940107
Hepatic enzyme increased 17.51 16.04 40 11792 33454 29907192
Fat redistribution 17.41 16.04 5 11827 140 29940506
Cell death 17.30 16.04 11 11821 2300 29938346
Haemoglobin decreased 17.24 16.04 12 11820 114086 29826560
Congenital pigmentation disorder 17.22 16.04 3 11829 6 29940640
Congenital anomaly 17.15 16.04 9 11823 1313 29939333
Hyperphagia 17.06 16.04 9 11823 1326 29939320
Hemiparaesthesia 16.81 16.04 4 11828 52 29940594
Acute hepatic failure 16.77 16.04 22 11810 11805 29928841
Coccidioidomycosis 16.52 16.04 7 11825 631 29940015
Depression 16.41 16.04 75 11757 90362 29850284
Chlamydial infection 16.23 16.04 5 11827 179 29940467
Therapy change 16.08 16.04 11 11821 2598 29938048
Transplant rejection 16.06 16.04 19 11813 9187 29931459

Pharmacologic Action:

SourceCodeDescription
ATC J05AJ03 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Integrase inhibitors
ATC J05AR13 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR21 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR25 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR27 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
FDA MoA N0000000127 HIV Integrase Inhibitors
MeSH PA D019380 Anti-HIV Agents
MeSH PA D000890 Anti-Infective Agents
MeSH PA D044966 Anti-Retroviral Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D019428 HIV Integrase Inhibitors
MeSH PA D019429 Integrase Inhibitors
FDA EPC N0000175887 Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
FDA MoA N0000191423 Multidrug and Toxin Extrusion Transporter 1 Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.24 acidic
pKa2 12.47 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 50MG BASE;300MG DOVATO VIIV HLTHCARE N211994 April 8, 2019 RX TABLET ORAL April 8, 2022 NEW COMBINULLTION
EQ 50MG BASE;300MG DOVATO VIIV HLTHCARE N211994 April 8, 2019 RX TABLET ORAL Aug. 6, 2023 TO REPLACE THE CURRENT ANTIRETROVIRAL REGIMEN IN THOSE WHO ARE VIROLOGICALLY SUPRESSED (HIV-1 RNULL LESS THAN 50 COPIES PER ML) ON A STABLE ANTIRETROVIRAL REGIMEN WITH NO HISTORY OF TREATMENT FAILURE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Integrase Enzyme INHIBITOR IC50 8.13 SCIENTIFIC LITERATURE CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane other Ki 7.15 CHEMBL

External reference:

IDSource
D10066 KEGG_DRUG
1051375-19-9 SECONDARY_CAS_RN
4032640 VANDF
C3253985 UMLSCUI
CHEBI:76007 CHEBI
DLU PDB_CHEM_ID
CHEMBL1229211 ChEMBL_ID
CHEMBL1213165 ChEMBL_ID
DB08930 DRUGBANK_ID
C562325 MESH_SUPPLEMENTAL_RECORD_UI
54726191 PUBCHEM_CID
7365 IUPHAR_LIGAND_ID
9261 INN_ID
DKO1W9H7M1 UNII
1433867 RXNORM
205031 MMSL
29613 MMSL
30505 MMSL
d08117 MMSL
015174 NDDF
015175 NDDF
713464000 SNOMEDCT_US
713465004 SNOMEDCT_US
714767001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tivicay HUMAN PRESCRIPTION DRUG LABEL 1 49702-226 TABLET, FILM COATED 10 mg ORAL NDA 25 sections
Tivicay HUMAN PRESCRIPTION DRUG LABEL 1 49702-227 TABLET, FILM COATED 25 mg ORAL NDA 25 sections
Tivicay HUMAN PRESCRIPTION DRUG LABEL 1 49702-228 TABLET, FILM COATED 50 mg ORAL NDA 25 sections
Triumeq HUMAN PRESCRIPTION DRUG LABEL 3 49702-231 TABLET, FILM COATED 50 mg ORAL NDA 26 sections
Juluca HUMAN PRESCRIPTION DRUG LABEL 2 49702-242 TABLET, FILM COATED 50 mg ORAL NDA 28 sections
Dovato HUMAN PRESCRIPTION DRUG LABEL 2 49702-246 TABLET, FILM COATED 50 mg ORAL NDA 29 sections
Tivicay PD HUMAN PRESCRIPTION DRUG LABEL 1 49702-255 TABLET, FOR SUSPENSION 5 mg ORAL NDA 25 sections
Tivicay HUMAN PRESCRIPTION DRUG LABEL 1 53808-1130 TABLET, FILM COATED 50 mg ORAL NDA 25 sections
Dolutegravir HUMAN PRESCRIPTION DRUG LABEL 1 65015-353 TABLET, FOR SUSPENSION 10 mg ORAL Export only 1 sections
Tivicay HUMAN PRESCRIPTION DRUG LABEL 1 67296-1818 TABLET, FILM COATED 50 mg ORAL NDA 25 sections
Tivicay HUMAN PRESCRIPTION DRUG LABEL 1 70518-1487 TABLET, FILM COATED 50 mg ORAL NDA 25 sections