darunavir Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.15 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1.20 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 20.87 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 37 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
CL (Clearance) 7.81 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.05 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 15 hours Lombardo F, Berellini G, Obach RS

Approvals:

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

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 1523.54 64.41 376 1456 24843 2331410
Foetal exposure during pregnancy 826.98 64.41 173 1659 5079 2351174
Abortion spontaneous 719.29 64.41 184 1648 13261 2342992
Maternal exposure during pregnancy 421.83 64.41 124 1708 14739 2341514
Live birth 311.61 64.41 61 1771 1230 2355023
Premature baby 309.30 64.41 71 1761 3133 2353120
Premature labour 298.81 64.41 64 1768 2042 2354211
Premature delivery 225.46 64.41 55 1777 3145 2353108
Foetal death 214.76 64.41 48 1784 1864 2354389
Foetal growth restriction 209.78 64.41 43 1789 1097 2355156
Immune reconstitution inflammatory syndrome 188.74 64.41 40 1792 1204 2355049
Rash 178.44 64.41 98 1734 59460 2296793
Lipodystrophy acquired 148.40 64.41 26 1806 273 2355980
Stillbirth 139.13 64.41 32 1800 1409 2354844
Hepatocellular injury 137.24 64.41 39 1793 4016 2352237
Abortion induced 129.71 64.41 36 1796 3400 2352853
Caesarean section 128.02 64.41 37 1795 4044 2352209
Congenital naevus 123.94 64.41 17 1815 23 2356230
Treatment noncompliance 121.08 64.41 38 1794 5496 2350757
Spina bifida 116.99 64.41 19 1813 120 2356133
Drug interaction 115.39 64.41 58 1774 29105 2327148
Viral mutation identified 112.06 64.41 20 1812 235 2356018
Sudden infant death syndrome 110.74 64.41 17 1815 70 2356183
Acoustic stimulation tests abnormal 107.11 64.41 15 1817 26 2356227
Low set ears 105.84 64.41 16 1816 58 2356195
Premature rupture of membranes 103.01 64.41 23 1809 883 2355370
Supernumerary nipple 101.66 64.41 13 1819 5 2356248
Drug resistance 101.33 64.41 28 1804 2596 2353657
Anal atresia 96.53 64.41 15 1817 68 2356185
Rash maculo-papular 96.32 64.41 30 1802 4222 2352031
Cloacal exstrophy 94.29 64.41 12 1820 4 2356249
Viral load increased 91.70 64.41 17 1815 250 2356003
Congenital heart valve disorder 90.04 64.41 13 1819 31 2356222
Eosinophilia 88.99 64.41 26 1806 2944 2353309
Bladder agenesis 87.75 64.41 11 1821 2 2356251
Congenital pulmonary valve disorder 86.35 64.41 12 1820 19 2356234
Congenital genital malformation 84.17 64.41 11 1821 7 2356246
Cholestasis of pregnancy 83.40 64.41 14 1818 111 2356142
Oligohydramnios 80.36 64.41 19 1813 941 2355312
Genitalia external ambiguous 80.13 64.41 11 1821 15 2356238
Cerebral ventricle dilatation 76.76 64.41 14 1818 187 2356066
Gastrointestinal disorder congenital 76.74 64.41 10 1822 6 2356247
Ventricular hypertrophy 76.46 64.41 17 1815 639 2355614
Congenital anomaly 75.80 64.41 16 1816 469 2355784
Tethered cord syndrome 75.67 64.41 11 1821 28 2356225
Meningomyelocele 75.28 64.41 12 1820 66 2356187
Dermatitis exfoliative generalised 74.89 64.41 15 1817 337 2355916
Cushing's syndrome 73.33 64.41 17 1815 772 2355481
Meconium stain 72.94 64.41 11 1821 39 2356214
Maternal drugs affecting foetus 71.36 64.41 19 1813 1528 2354725
Skull malformation 70.84 64.41 12 1820 101 2356152
Cardiac murmur 70.13 64.41 19 1813 1632 2354621
Caudal regression syndrome 70.13 64.41 10 1822 21 2356232
Exomphalos 69.89 64.41 11 1821 55 2356198
Neonatal respiratory arrest 68.92 64.41 10 1822 25 2356228
Anaemia 68.79 64.41 44 1788 34748 2321505
Pulmonary valve sclerosis 65.15 64.41 8 1824 0 2356253

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
Foetal exposure during pregnancy 625.78 33.10 176 2952 6183 1737470
Immune reconstitution inflammatory syndrome 581.95 33.10 126 3002 1423 1742230
Lipodystrophy acquired 355.35 33.10 66 3062 307 1743346
Progressive external ophthalmoplegia 260.51 33.10 39 3089 21 1743632
Drug interaction 252.90 33.10 136 2992 27822 1715831
Diarrhoea 239.35 33.10 166 2962 53686 1689967
Mitochondrial toxicity 239.29 33.10 43 3085 159 1743494
Premature baby 202.62 33.10 62 3066 2880 1740773
Eyelid ptosis 194.40 33.10 45 3083 692 1742961
Rash 180.07 33.10 123 3005 38570 1705083
Drug reaction with eosinophilia and systemic symptoms 169.51 33.10 62 3066 5008 1738645
Acute kidney injury 155.14 33.10 108 3020 34836 1708817
Viral load increased 145.21 33.10 34 3094 550 1743103
Nausea 142.99 33.10 120 3008 51076 1692577
Osteoporosis 142.92 33.10 41 3087 1514 1742139
Nephrolithiasis 130.34 33.10 48 3080 3944 1739709
Pyrexia 125.80 33.10 107 3021 46293 1697360
Diplopia 122.63 33.10 41 3087 2529 1741124
Virologic failure 118.86 33.10 27 3101 379 1743274
Renal tubular disorder 117.08 33.10 31 3097 844 1742809
Renal impairment 116.64 33.10 62 3066 12252 1731401
Rash maculo-papular 115.27 33.10 43 3085 3660 1739993
Hypertriglyceridaemia 111.63 33.10 32 3096 1177 1742476
Drug resistance 95.03 33.10 36 3092 3194 1740459
Hepatitis 93.11 33.10 40 3088 4915 1738738
Vomiting 92.84 33.10 83 3045 38232 1705421
Mycobacterium avium complex infection 91.00 33.10 21 3107 317 1743336
Thrombocytopenia 87.76 33.10 63 3065 21186 1722467
Renal failure 81.84 33.10 59 3069 19958 1723695
Dyslipidaemia 81.38 33.10 23 3105 802 1742851
Low birth weight baby 79.73 33.10 23 3105 864 1742789
Osteonecrosis 77.78 33.10 33 3095 3929 1739724
Hyperlipidaemia 73.42 33.10 27 3101 2202 1741451
Stevens-Johnson syndrome 72.73 33.10 30 3098 3327 1740326
Hepatocellular injury 70.43 33.10 29 3099 3202 1740451
Pruritus 69.78 33.10 57 3071 23165 1720488
Headache 68.75 33.10 67 3061 34309 1709344
Blood creatinine increased 68.41 33.10 46 3082 13900 1729753
Foetal growth restriction 67.15 33.10 19 3109 665 1742988
Weight increased 66.83 33.10 42 3086 11315 1732338
Insomnia 66.54 33.10 48 3080 16228 1727425
Myocardial infarction 65.94 33.10 59 3069 27115 1716538
Hemivertebra 64.54 33.10 11 3117 27 1743626
Viral mutation identified 63.22 33.10 16 3112 362 1743291
Genital herpes simplex 61.13 33.10 10 3118 17 1743636
Cholestasis 57.24 33.10 26 3102 3639 1740014
Neuropathy peripheral 56.39 33.10 35 3093 9218 1734435
Weight decreased 56.34 33.10 50 3078 22703 1720950
Blood HIV RNULL increased 56.09 33.10 13 3115 200 1743453
Cushing's syndrome 55.79 33.10 16 3112 588 1743065
Blood cholesterol increased 55.40 33.10 24 3104 3002 1740651
Polydactyly 55.26 33.10 13 3115 214 1743439
Eosinophilia 55.02 33.10 25 3103 3502 1740151
Liver function test abnormal 54.58 33.10 29 3099 5697 1737956
Genital herpes 52.87 33.10 11 3117 99 1743554
Fatigue 52.03 33.10 70 3058 50711 1692942
Congenital mitral valve incompetence 51.99 33.10 9 3119 25 1743628
Treatment noncompliance 51.44 33.10 27 3101 5174 1738479
CD4 lymphocytes decreased 51.35 33.10 14 3114 426 1743227
HIV-associated neurocognitive disorder 51.06 33.10 10 3118 64 1743589
Hepatitis cholestatic 50.99 33.10 18 3110 1303 1742350
Anaemia 50.74 33.10 53 3075 29404 1714249
Embolism 50.00 33.10 17 3111 1100 1742553
Hepatitis B 49.93 33.10 18 3110 1385 1742268
Oesophageal atresia 49.80 33.10 10 3118 74 1743579
Diabetes mellitus 49.49 33.10 29 3099 6879 1736774
Liver disorder 49.40 33.10 27 3101 5609 1738044
Abdominal pain 48.81 33.10 45 3083 21445 1722208
Cytomegalovirus chorioretinitis 48.18 33.10 13 3115 380 1743273
Exposure during pregnancy 47.22 33.10 21 3107 2796 1740857
Syphilis 47.11 33.10 10 3118 100 1743553
Congenital anomaly 47.08 33.10 13 3115 415 1743238
Product use complaint 46.81 33.10 12 3116 286 1743367
Pneumocystis jirovecii pneumonia 46.67 33.10 20 3108 2436 1741217
Blood triglycerides increased 45.57 33.10 20 3108 2580 1741073
Hepatic failure 45.52 33.10 26 3102 5877 1737776
Hypercholesterolaemia 44.83 33.10 16 3112 1196 1742457
Ophthalmoplegia 44.41 33.10 11 3117 227 1743426
Spine malformation 42.69 33.10 8 3120 39 1743614
Immune reconstitution inflammatory syndrome associated Kaposi's sarcoma 42.39 33.10 7 3121 13 1743640
HIV lipodystrophy 41.71 33.10 6 3122 1 1743652
Proteinuria 40.72 33.10 19 3109 2825 1740828
Congenital hydronephrosis 40.38 33.10 9 3119 115 1743538
Malaise 40.17 33.10 47 3081 29518 1714135
Pancreatitis acute 39.78 33.10 21 3107 4066 1739587
Jaundice 39.64 33.10 24 3104 6038 1737615
Superior mesenteric artery syndrome 39.56 33.10 7 3121 23 1743630
Blood bilirubin increased 39.11 33.10 24 3104 6186 1737467
Pancytopenia 38.57 33.10 30 3098 11327 1732326
Anogenital dysplasia 38.48 33.10 7 3121 28 1743625
Drug-induced liver injury 38.38 33.10 19 3109 3218 1740435
Amniotic band syndrome 37.99 33.10 6 3122 7 1743646
Gene mutation 37.93 33.10 9 3119 154 1743499
Maternal drugs affecting foetus 37.86 33.10 14 3114 1157 1742496
Hyperglycaemia 37.82 33.10 22 3106 5143 1738510
Candida infection 37.38 33.10 16 3112 1942 1741711
Asthenia 37.28 33.10 49 3079 34621 1709032
Neutropenia 37.16 33.10 36 3092 18224 1725429
Progressive multifocal leukoencephalopathy 36.68 33.10 15 3113 1624 1742029
Myalgia 35.93 33.10 33 3095 15625 1728028
Hospitalisation 35.62 33.10 30 3098 12670 1730983
Pathogen resistance 35.14 33.10 13 3115 1076 1742577
Hepatitis C 34.90 33.10 17 3111 2779 1740874
Glomerular filtration rate decreased 34.89 33.10 14 3114 1443 1742210
HIV associated nephropathy 34.84 33.10 6 3122 16 1743637
Extraocular muscle paresis 34.15 33.10 7 3121 58 1743595
Hepatic function abnormal 33.83 33.10 23 3105 7051 1736602
Agranulocytosis 33.75 33.10 18 3110 3558 1740095
Blood creatine phosphokinase increased 33.60 33.10 25 3103 8831 1734822
Coccidioidomycosis 33.54 33.10 8 3120 140 1743513
Aspartate aminotransferase increased 33.48 33.10 27 3101 10729 1732924

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