etravirine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antivirals Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) 1115 269055-15-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • etravirine
  • intelence
  • etravirin
  • R-165335
  • TMC-125
HIV-1 reverse transriptase inhibitor; an anti-HIV agent
  • Molecular weight: 435.29
  • Formula: C20H15BrN6O
  • CLOGP: 5.17
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 2
  • TPSA: 120.64
  • ALOGS: -4.41
  • ROTB: 4
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.40 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 6.56 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.727 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.247 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 12.853 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 14.355 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.290 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.820 % High 1
herg hERG pIC50 5.541 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 7.295 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 7.907 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.310 % High 1
kinase-safety-class AAK1,ACVR2A,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK5,CDK6,CDK7,CDK9,CHEK1,CLK4,CSF1R,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FGFR1,FLT3,FYN,GRK1,GRK2,GSK3A,GSK3B,IKBKB,INSRR,IRAK1,IRAK3,ITK,JAK1,JAK2,JAK3,KDR,KIT,LRRK2,LYN,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K2,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAPK1,MAPK10,MAPK7,MAPK9,MARK4,MELK,MET,MINK1,MST1R,MTOR,NTRK1,NTRK2,NUAK1,PAK4,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM3,PRKAA1,PRKCD,PRKDC,SGK1,SIK2,SIK3,SRC,STK10,STK33,STK4,SYK,TBK1,TEK,TGFBR1,TNIK,TTK,TYRO3,UHMK1,ULK1,ULK2,YES1 108
kinase-selectivity-class ACVR2A,ACVR2B,ALK,AURKA,AXL,BRAF,CAMK2D,CDK1,CDK2,CDK9,CSF1R,DDR1,DYRK1B,EIF2AK3,ERBB2,FLT3,GSK3A,JAK1,LRRK2,MAP2K3,MAP2K6,MAP3K21,MAP4K1,MAP4K3,MAPK1,MAPK7,MARK4,MELK,MET,MTOR,PDK1,PDK4,PIK3CD,PIK3CG,PRKDC,SIK2,SIK3,STK33,TEK,TTK,ULK1 41
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.531 High 1
mh-clint Mouse hepatocyte intrinsic clearance 37.068 High 1
mppb Mouse plasma protein binding (% unbound) 0.290 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.687 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.520 % High 1
rh-clint Rat hepatocyte intrinsic clearance 17.179 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 1.650 % High 1
rppb Rat plasma protein binding (% unbound) 0.250 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.649 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 28, 2008 EMA
Jan. 18, 2008 FDA JANSSEN R AND D

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
Enlarged clitoris 217.82 40.58 28 2573 123 90625723
Viral mutation identified 215.20 40.58 39 2562 1986 90623860
Virologic failure 198.74 40.58 37 2564 2187 90623659
Hyperandrogenism 197.17 40.58 25 2576 96 90625750
Foetal exposure during pregnancy 171.08 40.58 59 2542 42916 90582930
Exposure during pregnancy 163.28 40.58 95 2506 238315 90387531
Lipodystrophy acquired 140.42 40.58 26 2575 1488 90624358
Cloacal exstrophy 122.12 40.58 17 2584 149 90625697
Congenital genital malformation 121.42 40.58 17 2584 156 90625690
Abortion spontaneous 115.27 40.58 47 2554 54009 90571837
Bladder agenesis 114.65 40.58 16 2585 143 90625703
Genitalia external ambiguous 113.96 40.58 16 2585 150 90625696
Caudal regression syndrome 111.06 40.58 16 2585 183 90625663
Gastrointestinal disorder congenital 107.39 40.58 15 2586 135 90625711
Anal atresia 105.17 40.58 17 2584 433 90625413
Tethered cord syndrome 104.82 40.58 16 2585 278 90625568
Gastrointestinal malformation 102.20 40.58 15 2586 197 90625649
Meconium stain 102.06 40.58 15 2586 199 90625647
Meningomyelocele 99.14 40.58 17 2584 625 90625221
Exomphalos 94.26 40.58 16 2585 553 90625293
Umbilical cord abnormality 91.37 40.58 16 2585 666 90625180
Premature baby 86.55 40.58 31 2570 25046 90600800
Premature labour 84.11 40.58 26 2575 13350 90612496
Pathogen resistance 82.96 40.58 23 2578 8092 90617754
Drug resistance 73.59 40.58 29 2572 30420 90595426
Immune reconstitution inflammatory syndrome 72.24 40.58 20 2581 6999 90618847
Neural tube defect 71.74 40.58 11 2590 197 90625649
Spina bifida 55.89 40.58 11 2590 869 90624977
Treatment noncompliance 55.86 40.58 28 2573 51699 90574147
Congenital ectopic bladder 54.50 40.58 8 2593 105 90625741
Anencephaly 51.05 40.58 9 2592 389 90625457
Sepsis neonatal 47.17 40.58 9 2592 604 90625242
Amniotic cavity infection 45.26 40.58 10 2591 1386 90624460
Adrenogenital syndrome 43.58 40.58 6 2595 48 90625798
Congenital anomaly 42.70 40.58 13 2588 6334 90619512

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
Lipodystrophy acquired 455.78 23.37 101 5005 3349 42612880
Mitochondrial toxicity 414.88 23.37 89 5017 2526 42613703
Progressive external ophthalmoplegia 401.24 23.37 78 5028 1333 42614896
Eyelid ptosis 336.88 23.37 90 5016 6571 42609658
Virologic failure 245.32 23.37 63 5043 3931 42612298
Diplopia 220.13 23.37 85 5021 20231 42595998
Drug interaction 163.39 23.37 179 4927 266820 42349409
Viral mutation identified 144.86 23.37 40 5066 3291 42612938
Drug resistance 105.37 23.37 60 5046 34188 42582041
Ophthalmoplegia 102.98 23.37 28 5078 2172 42614057
Pathogen resistance 73.43 23.37 33 5073 11417 42604812
Adrenal suppression 67.99 23.37 17 5089 948 42615281
CD4 lymphocytes decreased 65.12 23.37 19 5087 1902 42614327
Immune reconstitution inflammatory syndrome 45.90 23.37 23 5083 10120 42606109
Drug level increased 45.52 23.37 32 5074 26168 42590061
Cytomegalovirus chorioretinitis 45.29 23.37 18 5088 4593 42611636
Fibrous histiocytoma 44.63 23.37 10 5096 346 42615883
Multiple-drug resistance 43.45 23.37 20 5086 7302 42608927
Viral load increased 41.37 23.37 15 5091 2982 42613247
Osteoporosis 35.07 23.37 22 5084 14884 42601345
Heart transplant rejection 34.21 23.37 11 5095 1523 42614706
Renal tubular disorder 34.19 23.37 15 5091 4894 42611335
Blood creatine phosphokinase abnormal 33.20 23.37 8 5098 382 42615847
Dyslipidaemia 33.01 23.37 18 5088 9400 42606829
Hepatic steatosis 32.24 23.37 24 5082 21424 42594805
Drug level decreased 32.04 23.37 18 5088 9959 42606270
Hepatic cirrhosis 31.77 23.37 23 5083 19679 42596550
Hepatitis 29.17 23.37 25 5081 27275 42588954
Hepatitis C 29.11 23.37 17 5089 10116 42606113
Choroiditis 27.18 23.37 9 5097 1366 42614863
Mycobacterium avium complex infection 26.91 23.37 11 5095 3016 42613213
Lipohypertrophy 24.69 23.37 6 5100 297 42615932
Genotype drug resistance test positive 24.28 23.37 8 5098 1196 42615033
Anogenital dysplasia 23.44 23.37 5 5101 137 42616092

FDA Adverse Event Reporting System (Geriatric)

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
Lipodystrophy acquired 547.94 25.03 107 5704 4417 110579071
Progressive external ophthalmoplegia 471.84 25.03 79 5732 1341 110582147
Mitochondrial toxicity 462.51 25.03 88 5723 3157 110580331
Virologic failure 356.21 25.03 76 5735 4876 110578612
Eyelid ptosis 333.88 25.03 87 5724 13240 110570248
Viral mutation identified 324.55 25.03 69 5742 4350 110579138
Diplopia 228.35 25.03 85 5726 41809 110541679
Drug interaction 206.48 25.03 186 5625 499997 110083491
Drug resistance 154.73 25.03 70 5741 56304 110527184
Pathogen resistance 126.85 25.03 44 5767 17628 110565860
Ophthalmoplegia 107.57 25.03 27 5784 3523 110579965
Immune reconstitution inflammatory syndrome 95.97 25.03 35 5776 16191 110567297
Multiple-drug resistance 79.95 25.03 29 5782 13206 110570282
Adrenal suppression 77.66 25.03 18 5793 1678 110581810
Abortion spontaneous 64.85 25.03 33 5778 34249 110549239
Treatment noncompliance 57.73 25.03 40 5771 72950 110510538
Blood HIV RNA increased 53.36 25.03 14 5797 2174 110581314
Exposure during pregnancy 49.35 25.03 52 5759 167372 110416116
CD4 lymphocytes decreased 44.65 25.03 13 5798 2961 110580527
Fibrous histiocytoma 44.30 25.03 10 5801 829 110582659
Renal tubular disorder 43.82 25.03 16 5795 7413 110576075
Hepatitis C 42.18 25.03 18 5793 12555 110570933
Dyslipidaemia 41.15 25.03 19 5792 15946 110567542
Mycobacterium avium complex infection 39.72 25.03 14 5797 5863 110577625
Genotype drug resistance test positive 39.16 25.03 10 5801 1396 110582092
Drug level decreased 35.49 25.03 18 5793 18530 110564958
Hepatic cirrhosis 33.41 25.03 28 5783 67598 110515890
Choroiditis 33.07 25.03 9 5802 1606 110581882
Premature labour 30.33 25.03 13 5798 9159 110574329
Hepatic steatosis 30.05 25.03 23 5788 48808 110534680
Superinfection bacterial 29.54 25.03 9 5802 2392 110581096
Amniotic cavity infection 27.98 25.03 7 5804 900 110582588
Oesophageal candidiasis 27.47 25.03 13 5798 11521 110571967
Lipohypertrophy 27.26 25.03 7 5804 999 110582489
Anogenital dysplasia 26.48 25.03 5 5806 171 110583317
Drug level increased 26.17 25.03 21 5790 47698 110535790

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AG04 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Non-nucleoside reverse transcriptase inhibitors
FDA MoA N0000009948 Non-Nucleoside Reverse Transcriptase Inhibitors
FDA EXT N0000175460 Non-Nucleoside Analog
FDA EPC N0000175463 Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018894 Reverse Transcriptase Inhibitors
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
FDA MoA N0000182140 Cytochrome P450 2C19 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000185504 Cytochrome P450 2C9 Inhibitors
FDA MoA N0000190118 Cytochrome P450 3A Inducers
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35441 antiinfective agent
CHEBI has role CHEBI:53756 HIV-1 reverse transcriptase inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

J05AG Non-nucleoside reverse transcriptase inhibitors 5 drugs
delavirdinedoravirineefavirenznevirapinerilpivirine

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

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526
Chronic type B viral hepatitis contraindication 61977001
Chronic hepatitis C contraindication 128302006
Liver function tests abnormal contraindication 166603001
Peripheral nerve disease contraindication 302226006
Breastfeeding (mother) contraindication 413712001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.78 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Multidrug resistance protein 1 Transporter IC50 5.12 CHEMBL
Canalicular multispecific organic anion transporter 1 Transporter IC50 5.11 CHEMBL
Multidrug resistance-associated protein 1 Transporter IC50 5.07 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 5.22 CHEMBL
Canalicular multispecific organic anion transporter 2 Transporter IC50 5.29 CHEMBL
Reverse transcriptase/RNaseH Enzyme INHIBITOR IC50 9.22 CHEMBL CHEMBL
Gag-Pol polyprotein Polyprotein IC50 9 WOMBAT-PK
Cruzipain Enzyme IC50 5.40 CHEMBL
Reverse transcriptase Enzyme IC50 8 CHEMBL
Reverse transcriptase protein Enzyme IC50 8.89 CHEMBL

External reference:

IDSource
4027244 VUID
N0000179781 NUI
D04112 KEGG_DRUG
4027244 VANDF
C1456409 UMLSCUI
CHEBI:63589 CHEBI
65B PDB_CHEM_ID
CHEMBL308954 ChEMBL_ID
DB06414 DRUGBANK_ID
C451734 MESH_SUPPLEMENTAL_RECORD_UI
12675 IUPHAR_LIGAND_ID
8303 INN_ID
0C50HW4FO1 UNII
193962 PUBCHEM_CID
475969 RXNORM
130981 MMSL
24971 MMSL
348481 MMSL
d07076 MMSL
012527 NDDF
432121008 SNOMEDCT_US
432221004 SNOMEDCT_US
0C50HW4FO1 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Etravirine HUMAN PRESCRIPTION DRUG LABEL 1 10147-0570 TABLET 100 mg ORAL NDA 32 sections
Etravirine HUMAN PRESCRIPTION DRUG LABEL 1 10147-0571 TABLET 200 mg ORAL NDA 32 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 42291-473 TABLET 100 mg ORAL ANDA 25 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 42291-474 TABLET 200 mg ORAL ANDA 25 sections
Intelence HUMAN PRESCRIPTION DRUG LABEL 1 53808-0787 TABLET 100 mg ORAL NDA 31 sections
Intelence HUMAN PRESCRIPTION DRUG LABEL 1 54868-5864 TABLET 100 mg ORAL NDA 30 sections
Intelence HUMAN PRESCRIPTION DRUG LABEL 1 54868-6368 TABLET 200 mg ORAL NDA 30 sections
Intelence HUMAN PRESCRIPTION DRUG LABEL 1 59676-570 TABLET 100 mg ORAL NDA 30 sections
Intelence HUMAN PRESCRIPTION DRUG LABEL 1 59676-571 TABLET 200 mg ORAL NDA 30 sections
Intelence HUMAN PRESCRIPTION DRUG LABEL 1 59676-572 TABLET 25 mg ORAL NDA 30 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 60219-1720 TABLET 25 mg ORAL ANDA 26 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 60219-1721 TABLET 100 mg ORAL ANDA 26 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 60219-1722 TABLET 200 mg ORAL ANDA 26 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 69238-1720 TABLET 25 mg ORAL ANDA 26 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 69238-1721 TABLET 100 mg ORAL ANDA 26 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 69238-1722 TABLET 200 mg ORAL ANDA 26 sections
ETRAVIRINE HUMAN PRESCRIPTION DRUG LABEL 1 69315-285 TABLET 100 mg ORAL ANDA 22 sections
ETRAVIRINE HUMAN PRESCRIPTION DRUG LABEL 1 69315-286 TABLET 200 mg ORAL ANDA 22 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 69452-254 TABLET 100 mg ORAL ANDA 29 sections
etravirine HUMAN PRESCRIPTION DRUG LABEL 1 69452-255 TABLET 200 mg ORAL ANDA 29 sections
ETRAVIRINE HUMAN PRESCRIPTION DRUG LABEL 1 80005-112 TABLET 100 mg ORAL ANDA 22 sections
ETRAVIRINE HUMAN PRESCRIPTION DRUG LABEL 1 80005-113 TABLET 200 mg ORAL ANDA 22 sections