darunavir Indications/Contra | FAERs | Orange Book | BioActivity |

Stem definitionDrug idCAS RN
HIV protease inhibitors 4143 206361-99-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • darunavir
  • darunavir ethanolate
  • prezista
  • TMC-114
  • TMC 114
  • darunavir ethnolate
An HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS.
  • Molecular weight: 547.67
  • Formula: C27H37N3O7S
  • CLOGP: 2.89
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 3
  • TPSA: 140.42
  • ALOGS: -3.91
  • ROTB: 11

Drug dosage:

DoseUnitRoute
1.20 g O

Approvals:

DateAgencyCompanyOrphan
Feb. 12, 2007 EMA
June 23, 2006 FDA JANSSEN PRODS

FDA Adverse Event Reporting System

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
Foetal exposure during pregnancy 2219.63 43.90 581 5758 22588 4610065
Exposure during pregnancy 1460.50 43.90 454 5885 32517 4600136
Virologic failure 897.27 43.90 181 6158 2048 4630605
Immune reconstitution inflammatory syndrome 823.51 43.90 178 6161 2876 4629777
Premature baby 712.07 43.90 200 6139 9851 4622802
Abortion spontaneous 627.09 43.90 196 6143 13996 4618657
Lipodystrophy acquired 589.55 43.90 108 6231 692 4631961
Rash 446.34 43.90 280 6059 108108 4524545
Drug interaction 446.33 43.90 234 6105 64274 4568379
Maternal exposure during pregnancy 442.78 43.90 158 6181 16935 4615718
Drug resistance 425.29 43.90 128 6211 8008 4624645
Foetal growth restriction 334.74 43.90 83 6256 2483 4630170
Progressive external ophthalmoplegia 280.02 43.90 40 6299 23 4632630
Live birth 275.51 43.90 64 6275 1439 4631214
Diarrhoea 272.35 43.90 237 6102 149948 4482705
Viral load increased 263.64 43.90 58 6281 1011 4631642
Mitochondrial toxicity 259.56 43.90 47 6292 278 4632375
Premature labour 252.45 43.90 65 6274 2267 4630386
Drug reaction with eosinophilia and systemic symptoms 239.14 43.90 91 6248 11622 4621031
Treatment noncompliance 233.22 43.90 90 6249 11937 4620716
Acute kidney injury 225.45 43.90 156 6183 70275 4562378
Viral mutation identified 221.16 43.90 51 6288 1108 4631545
Rash maculo-papular 217.30 43.90 78 6261 8451 4624202
Premature delivery 214.84 43.90 65 6274 4119 4628534
Congenital anomaly 207.23 43.90 55 6284 2161 4630492
Foetal death 204.17 43.90 56 6283 2496 4630157
Nephrolithiasis 190.85 43.90 72 6267 8967 4623686
Hepatocellular injury 189.08 43.90 69 6270 7831 4624822
Pyrexia 183.41 43.90 164 6175 106980 4525673
Low birth weight baby 182.67 43.90 52 6287 2658 4629995
Renal tubular disorder 181.51 43.90 46 6293 1502 4631151
Anaemia 175.48 43.90 135 6204 71425 4561228
Eyelid ptosis 174.12 43.90 47 6292 1970 4630683
Osteoporosis 167.66 43.90 60 6279 6435 4626218
Stillbirth 164.83 43.90 45 6294 1969 4630684
Nausea 162.68 43.90 194 6145 177139 4455514
Cushing's syndrome 161.04 43.90 42 6297 1539 4631114
Cerebral ventricle dilatation 155.35 43.90 33 6306 483 4632170
Renal impairment 152.22 43.90 84 6255 25254 4607399
Cloacal exstrophy 150.47 43.90 21 6318 7 4632646
Spine malformation 146.74 43.90 26 6313 133 4632520
Bladder agenesis 145.20 43.90 21 6318 15 4632638
Spina bifida 145.15 43.90 31 6308 466 4632187
Gastrointestinal disorder congenital 141.96 43.90 21 6318 21 4632632
Eosinophilia 141.43 43.90 54 6285 6939 4625714
Dyslipidaemia 139.17 43.90 38 6301 1663 4630990
Abortion induced 129.38 43.90 44 6295 4053 4628600
Hepatitis 127.88 43.90 59 6280 12146 4620507
Meconium stain 126.20 43.90 21 6318 68 4632585
Maternal drugs affecting foetus 122.93 43.90 42 6297 3923 4628730
Congenital naevus 122.37 43.90 20 6319 56 4632597
Tethered cord syndrome 122.37 43.90 20 6319 56 4632597
Genitalia external ambiguous 119.67 43.90 20 6319 67 4632586
Thrombocytopenia 118.98 43.90 91 6248 47582 4585071
Renal failure 118.98 43.90 86 6253 41283 4591370
Mycobacterium avium complex infection 118.51 43.90 29 6310 817 4631836
Umbilical cord abnormality 118.21 43.90 23 6316 210 4632443
Caudal regression syndrome 114.07 43.90 19 6320 62 4632591
Weight increased 111.97 43.90 79 6260 36502 4596151
Vomiting 111.12 43.90 132 6207 119567 4513086
Skull malformation 110.51 43.90 23 6316 303 4632350
Diplopia 109.91 43.90 44 6295 6407 4626246
Exomphalos 109.77 43.90 22 6317 237 4632416
Oesophageal atresia 109.54 43.90 23 6316 317 4632336
Acoustic stimulation tests abnormal 108.72 43.90 18 6321 56 4632597
Blood HIV RNA increased 106.28 43.90 23 6316 369 4632284
Blood creatinine increased 106.07 43.90 68 6271 26832 4605821
Liver function test abnormal 105.84 43.90 55 6284 14637 4618016
Hypertriglyceridaemia 105.66 43.90 33 6306 2320 4630333
Caesarean section 105.35 43.90 40 6299 5058 4627595
Congenital genital malformation 104.98 43.90 17 6322 44 4632609
Anal atresia 104.13 43.90 21 6318 234 4632419
Gastrointestinal malformation 103.12 43.90 18 6321 83 4632570
Meningomyelocele 102.40 43.90 21 6318 256 4632397
Low set ears 101.70 43.90 20 6319 194 4632459
Cholestasis 101.19 43.90 44 6295 7876 4624777
Polydactyly 99.33 43.90 23 6316 508 4632145
Supernumerary nipple 97.46 43.90 15 6324 24 4632629
Pruritus 96.88 43.90 97 6242 72475 4560178
Diabetes mellitus 94.69 43.90 52 6287 15449 4617204
Sudden infant death syndrome 92.31 43.90 19 6320 236 4632417
Neuropathy peripheral 91.24 43.90 59 6280 23610 4609043
Premature rupture of membranes 89.31 43.90 24 6315 987 4631666
Myocardial infarction 88.96 43.90 78 6261 49298 4583355
Alanine aminotransferase increased 88.46 43.90 62 6277 28311 4604342
Osteonecrosis 87.87 43.90 46 6293 12418 4620235
Hypercholesterolaemia 86.06 43.90 30 6309 2973 4629680
Hepatitis cholestatic 85.91 43.90 29 6310 2609 4630044
Cardiac murmur 85.55 43.90 30 6309 3025 4629628
Renal colic 85.02 43.90 22 6317 780 4631873
Ventricular septal defect 84.86 43.90 28 6311 2347 4630306
Oesophageal candidiasis 80.96 43.90 24 6315 1413 4631240
Headache 80.63 43.90 114 6225 122259 4510394
Hyperlipidaemia 80.44 43.90 33 6306 5112 4627541
Hemivertebra 79.77 43.90 14 6325 67 4632586
Cholestasis of pregnancy 78.86 43.90 15 6324 120 4632533
Weight decreased 78.58 43.90 76 6263 54388 4578265
CD4 lymphocytes decreased 77.95 43.90 21 6318 872 4631781
Product use complaint 75.35 43.90 20 6319 784 4631869
Wrong technique in product usage process 74.52 43.90 60 6279 33714 4598939
Hepatotoxicity 74.25 43.90 36 6303 8263 4624390
Adverse event 74.10 43.90 45 6294 16127 4616526
Stevens-Johnson syndrome 72.88 43.90 36 6303 8603 4624050
Small for dates baby 72.83 43.90 24 6315 2003 4630650
Pathogen resistance 72.57 43.90 26 6313 2790 4629863
Pneumocystis jirovecii pneumonia 72.37 43.90 31 6308 5347 4627306
Congenital heart valve disorder 72.04 43.90 13 6326 75 4632578
Aspartate aminotransferase increased 71.97 43.90 52 6287 24886 4607767
Abdominal pain 70.59 43.90 75 6264 59949 4572704
Insomnia 70.58 43.90 66 6273 45279 4587374
Congenital pulmonary valve disorder 69.93 43.90 12 6327 49 4632604
Pancreatitis acute 69.90 43.90 35 6304 8608 4624045
Blood triglycerides increased 69.37 43.90 30 6309 5295 4627358
Hepatic failure 69.16 43.90 40 6299 13109 4619544
Treatment failure 69.04 43.90 41 6298 14106 4618547
HIV-associated neurocognitive disorder 68.23 43.90 13 6326 105 4632548
Hospitalisation 67.75 43.90 55 6284 31250 4601403
Hyperbilirubinaemia 67.12 43.90 28 6311 4523 4628130
Ventricular hypertrophy 66.79 43.90 21 6318 1508 4631145
Liver disorder 66.65 43.90 39 6300 13059 4619594
Rhabdomyolysis 66.26 43.90 45 6294 19513 4613140
Ichthyosis 66.24 43.90 12 6327 71 4632582
Progressive multifocal leukoencephalopathy 66.13 43.90 27 6312 4130 4628523
Blood iron decreased 65.95 43.90 22 6317 1907 4630746
Death 64.57 43.90 135 6204 198028 4434625
Syphilis 64.12 43.90 13 6326 149 4632504
Amniotic band syndrome 63.14 43.90 11 6328 50 4632603
Jaundice 63.09 43.90 37 6302 12437 4620216
Plagiocephaly 62.68 43.90 13 6326 168 4632485
Oligohydramnios 62.60 43.90 19 6320 1213 4631440
Depression 62.14 43.90 63 6276 47670 4584983
Left ventricular dilatation 61.72 43.90 12 6327 109 4632544
Drug-induced liver injury 61.38 43.90 32 6307 8559 4624094
Dermatitis exfoliative generalised 61.18 43.90 17 6322 793 4631860
Hyperglycaemia 61.02 43.90 35 6304 11287 4621366
Breast disorder 60.57 43.90 15 6324 444 4632209
Lipohypertrophy 60.15 43.90 13 6326 207 4632446
Blood bilirubin increased 60.00 43.90 36 6303 12616 4620037
Pancytopenia 58.76 43.90 46 6293 24807 4607846
Pulmonary valve sclerosis 58.67 43.90 8 6331 1 4632652
Hepatitis B 58.07 43.90 22 6317 2761 4629892
Foetal malnutrition 57.48 43.90 10 6329 45 4632608
Proteinuria 57.00 43.90 28 6311 6608 4626045
Neonatal respiratory arrest 56.29 43.90 10 6329 52 4632601
Adrenal insufficiency 56.18 43.90 22 6317 3018 4629635
Genital herpes simplex 55.97 43.90 10 6329 54 4632599
Product dose omission 55.70 43.90 70 6269 66892 4565761
Product size issue 55.03 43.90 14 6325 463 4632190
Teratogenicity 54.58 43.90 11 6328 122 4632531
Congenital anomaly in offspring 54.39 43.90 10 6329 65 4632588
Micrognathia 53.63 43.90 12 6327 226 4632427
Condition aggravated 53.53 43.90 64 6275 58107 4574546
Neural tube defect 53.49 43.90 11 6328 136 4632517
Pre-eclampsia 53.42 43.90 18 6321 1609 4631044
Ascites 53.39 43.90 33 6306 12192 4620461
Hepatic enzyme increased 53.00 43.90 38 6301 17953 4614700
Sepsis 52.95 43.90 55 6284 42784 4589869
Dermatitis exfoliative 52.77 43.90 21 6318 3005 4629648
Transaminases increased 52.58 43.90 30 6309 9576 4623077
Blood creatine phosphokinase increased 51.75 43.90 35 6304 15064 4617589
Immune reconstitution inflammatory syndrome associated Kaposi's sarcoma 51.53 43.90 8 6331 14 4632639
HIV lipodystrophy 51.23 43.90 7 6332 1 4632652
Gastroschisis 50.61 43.90 11 6328 180 4632473
Gestational diabetes 50.54 43.90 17 6322 1511 4631142
Congenital mitral valve incompetence 50.31 43.90 9 6330 49 4632604
Blood cholesterol increased 49.84 43.90 28 6311 8678 4623975
Pneumonia 49.59 43.90 83 6256 102732 4529921
Congenital musculoskeletal anomaly 48.87 43.90 11 6328 213 4632440
Genotype drug resistance test positive 48.84 43.90 13 6326 515 4632138
Malaise 46.46 43.90 75 6264 90082 4542571
Meningitis cryptococcal 46.40 43.90 13 6326 625 4632028
Fanconi syndrome 46.16 43.90 13 6326 637 4632016
Nervous system disorder 46.06 43.90 24 6315 6407 4626246
Hepatic function abnormal 46.01 43.90 32 6307 14404 4618249
Hepatitis C 45.78 43.90 22 6317 4948 4627705
Pancreatitis 45.43 43.90 34 6305 17144 4615509
Dysphagia 45.24 43.90 40 6299 25491 4607162
Cytomegalovirus chorioretinitis 45.08 43.90 13 6326 694 4631959
Vertigo 44.99 43.90 32 6307 14924 4617729
Fatigue 44.78 43.90 97 6242 145469 4487184
CSF test abnormal 44.65 43.90 10 6329 189 4632464
Musculoskeletal deformity 44.35 43.90 8 6331 46 4632607
Viral load 43.92 43.90 8 6331 49 4632604

Pharmacologic Action:

SourceCodeDescription
ATC J05AE10 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Protease inhibitors
ATC J05AR14 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR22 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
ATC J05AR26 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HIV infections, combinations
FDA EPC N0000175889 Protease Inhibitor
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
FDA MoA N0000182137 Cytochrome P450 2D6 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 D017320 HIV Protease Inhibitors
MeSH PA D011480 Protease Inhibitors
CHEBI has role CHEBI:36044 antiviral drug

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526
Coronavirus infection off-label use 186747009
Hypercholesterolemia contraindication 13644009
Cirrhosis of liver contraindication 19943007 DOID:5082
Hereditary factor VIII deficiency disease contraindication 28293008 DOID:12134
Hereditary factor IX deficiency disease contraindication 41788008 DOID:12259
Hepatic failure contraindication 59927004
Chronic type B viral hepatitis contraindication 61977001
Diabetes mellitus contraindication 73211009 DOID:9351
Hyperglycemia contraindication 80394007 DOID:4195
Chronic hepatitis C contraindication 128302006
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Hypertriglyceridemia contraindication 302870006
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.67 acidic
pKa2 1.64 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 6642245 Nov. 4, 2020 TREATMENT OF HIV-1 INFECTION IN ADULTS WHO HAVE NO PRIOR ANTIRETROVIRAL TREATMENT HISTORY OR ARE VIROLOGICALLY SUPPRESSED ON A STABLE ANTIRETROVIRAL REGIMEN FOR AT LEAST 6 MONTHS
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 7803788 Feb. 2, 2022 TREATMENT OF HIV-1 INFECTION IN ADULTS WHO HAVE NO PRIOR ANTIRETROVIRAL TREATMENT HISTORY OR ARE VIROLOGICALLY SUPPRESSED ON A STABLE ANTIRETROVIRAL REGIMEN FOR AT LEAST 6 MONTHS
800MG PREZCOBIX JANSSEN PRODS N205395 Jan. 29, 2015 RX TABLET ORAL 8148374 Sept. 3, 2029 TREATMENT OF HIV INFECTION USING A COMPOSITION CONTAINING A PHARMACOKINETIC ENHANCER THAT INHIBITS CYTOCHROME P450 MONOOXYGENASE
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 8148374 Sept. 3, 2029 TREATMENT OF HIV-1 INFECTION USING A COMPOSITION CONTAINING A PHARMACOKINETIC ENHANCER THAT INHIBITS CYTOCHROME P450 MONOOXYGENASE IN ADULTS WHO HAVE NO PRIOR ANTIRETROVIRAL TREATMENT HISTORY
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 8148374 Sept. 3, 2029 TREATMENT OF HIV-1 INFECTION USING A COMPOSITION CONTAINING A PHARMACOKINETIC ENHANCER THAT INIBITS CYTOCHROME P450 MONOOXYGENASE IN ADULTS WHO ARE VIROLOGICALLY SUPPRESSED ON A STABLE ANTIRETROVIRAL REGIMEN FOR AT LEAST 6 MONTHS
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 8148374 Sept. 3, 2029 TX OF HIV-1 INFECTION USING A COMPOSITION CONTAINING A PK ENHANCER THAT INHIBITS CYTOCHROME P450 MONOOXYGENATES IN ADULTS WHO HAVE NO PRIOR ANTIRETROVIRAL TX HISTORY OR ARE VIROLOGICALLY SUPPRESSED ON A STABLE ANTIRETROVIRAL REGIMEN FOR AT LEAST 6 MONTHS
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 8754065 Aug. 15, 2032 TREATMENT OF HIV-1 INFECTION IN ADULTS WHO HAVE NO PRIOR ANTIRETROVIRAL TREATMENT HISTORY OR ARE VIROLOGICALLY SUPPRESSED ON A STABLE ANTIRETROVIRAL REGIMEN FOR AT LEAST 6 MONTHS
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL 9296769 Aug. 15, 2032 TREATMENT OF HIV-1 INFECTION IN ADULTS WHO HAVE NO PRIOR ANTIRETROVIRAL TREATMENT HISTORY OR ARE VIROLOGICALLY SUPPRESSED ON A STABLE ANTIRETROVIRAL REGIMEN FOR AT LEAST 6 MONTHS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL July 17, 2020 NEW COMBINATION
800MG SYMTUZA JANSSEN PRODS N210455 July 17, 2018 RX TABLET ORAL Nov. 5, 2020 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Pol polyprotein Enzyme INHIBITOR Ki 10.85 CHEMBL CHEMBL
Gag-Pol polyprotein Polyprotein Ki 9.66 WOMBAT-PK
Protease Enzyme IC50 10.21 CHEMBL

External reference:

IDSource
D000069454 MESH_DESCRIPTOR_UI
4025441 VUID
N0000179778 NUI
C1435444 UMLSCUI
D03656 KEGG_DRUG
33O78XF0BW UNII
635728-49-3 SECONDARY_CAS_RN
424096001 SNOMEDCT_US
d05825 MMSL
460132 RXNORM
4025441 VANDF
423888002 SNOMEDCT_US
011599 NDDF
CHEMBL1323 ChEMBL_ID
017 PDB_CHEM_ID
DB01264 DRUGBANK_ID
CHEBI:367163 CHEBI
8305 INN_ID
CHEMBL1201127 ChEMBL_ID
213039 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 53808-0672 TABLET, FILM COATED 400 mg ORAL NDA 18 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 53808-0773 TABLET, FILM COATED 600 mg ORAL NDA 18 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 54868-5969 TABLET, FILM COATED 400 mg ORAL NDA 19 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 54868-6369 TABLET, FILM COATED 600 mg ORAL NDA 19 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 59676-562 TABLET, FILM COATED 600 mg ORAL NDA 20 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 59676-563 TABLET, FILM COATED 75 mg ORAL NDA 20 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 59676-564 TABLET, FILM COATED 150 mg ORAL NDA 20 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 59676-565 SUSPENSION 100 mg ORAL NDA 20 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 59676-566 TABLET, FILM COATED 800 mg ORAL NDA 20 sections
PREZCOBIX HUMAN PRESCRIPTION DRUG LABEL 2 59676-575 TABLET, FILM COATED 800 mg ORAL NDA 19 sections
Symtuza HUMAN PRESCRIPTION DRUG LABEL 3 59676-800 TABLET, FILM COATED 800 mg ORAL NDA 20 sections
PREZISTA HUMAN PRESCRIPTION DRUG LABEL 1 70518-1483 TABLET, FILM COATED 800 mg ORAL NDA 20 sections