abiraterone acetate Indications/Contra | FAERs | Orange Book | BioActivity |

Stem definitionDrug idCAS RN
antiandrogens 4176 154229-18-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • abiraterone acetate
  • zytiga
  • CB-7630
  • CB7630
Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 alpha-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17alpha-hydroxy derivatives by 17alpha-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17,20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. Abiraterone acetate decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of abiraterone acetate on serum testosterone levels.
  • Molecular weight: 391.56
  • Formula: C26H33NO2
  • CLOGP: 6.11
  • LIPINSKI: 1
  • HAC: 3
  • HDO: 0
  • TPSA: 39.19
  • ALOGS: -5.59
  • ROTB: 3

Drug dosage:

DoseUnitRoute
1 g O

Approvals:

DateAgencyCompanyOrphan
Sept. 5, 2011 EMA
April 28, 2011 FDA JANSSEN BIOTECH

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
Death 1434.50 38.33 743 5870 151581 3227665
Prostatic specific antigen increased 1378.96 38.33 265 6348 1618 3377628
Prostate cancer 790.67 38.33 190 6423 3630 3375616
Hypokalaemia 522.32 38.33 183 6430 13622 3365624
Prostate cancer metastatic 501.31 38.33 97 6516 608 3378638
Fatigue 457.77 38.33 318 6295 106922 3272324
Disease progression 402.47 38.33 193 6420 32066 3347180
Hospitalisation 257.99 38.33 124 6489 20601 3358645
Hot flush 251.24 38.33 91 6522 7410 3371836
Drug ineffective 245.97 38.33 229 6384 115861 3263385
Decreased appetite 231.36 38.33 146 6467 41344 3337902
Anaemia 216.12 38.33 155 6458 54178 3325068
Product use complaint 205.70 38.33 40 6573 257 3378989
Pneumonia 201.84 38.33 165 6448 69978 3309268
Dysphagia 198.32 38.33 102 6511 19549 3359697
Asthenia 194.22 38.33 157 6456 65508 3313738
Hypertension 193.68 38.33 127 6486 38339 3340907
Cardiac failure 193.25 38.33 101 6512 20004 3359242
Thrombocytopenia 191.23 38.33 122 6491 35146 3344100
Drug dose omission 179.25 38.33 121 6492 38311 3340935
Oedema peripheral 176.72 38.33 115 6498 34246 3345000
Hepatic function abnormal 176.36 38.33 79 6534 11148 3368098
Urinary tract infection 173.84 38.33 110 6503 31218 3348028
Nausea 171.65 38.33 199 6414 129446 3249800
Oedema 165.02 38.33 82 6531 14598 3364648
Dehydration 156.98 38.33 106 6507 33543 3345703
Dyspnoea 156.60 38.33 170 6443 102764 3276482
Platelet count decreased 156.24 38.33 98 6515 27370 3351876
Atrial fibrillation 152.94 38.33 92 6521 23849 3355397
Muscular weakness 147.87 38.33 85 6528 20256 3358990
Blood alkaline phosphatase increased 146.02 38.33 68 6545 10485 3368761
Vomiting 145.14 38.33 153 6460 89378 3289868
Diarrhoea 132.54 38.33 157 6456 104191 3275055
Therapy cessation 131.12 38.33 47 6566 3702 3375544
Metastases to bone 128.63 38.33 44 6569 3017 3376229
Incorrect dose administered 128.19 38.33 68 6545 13846 3365400
Liver function test abnormal 127.26 38.33 66 6547 12835 3366411
Bone pain 123.06 38.33 59 6554 9702 3369544
Haematuria 121.97 38.33 59 6554 9893 3369353
Malaise 121.13 38.33 120 6493 65057 3314189
Product size issue 119.94 38.33 26 6587 302 3378944
Constipation 111.09 38.33 83 6530 30729 3348517
Dizziness 110.27 38.33 123 6490 76389 3302857
Back pain 108.12 38.33 89 6524 37916 3341330
Diabetes mellitus 108.10 38.33 58 6555 12075 3367171
Fluid retention 107.98 38.33 51 6562 8107 3371139
General physical health deterioration 101.04 38.33 67 6546 20522 3358724
Pleural effusion 99.20 38.33 64 6549 18715 3360531
Off label use 97.65 38.33 98 6515 53879 3325367
Fall 97.64 38.33 102 6511 58781 3320465
Pain 96.20 38.33 111 6502 71446 3307800
Wrong technique in product usage process 95.73 38.33 60 6553 16691 3362555
Peripheral swelling 95.26 38.33 59 6554 16073 3363173
Adverse event 91.20 38.33 51 6562 11506 3367740
Alanine aminotransferase increased 85.87 38.33 64 6549 23576 3355670
Myocardial infarction 85.10 38.33 83 6530 44050 3335196
Cardiac disorder 78.01 38.33 49 6564 13670 3365576
Inappropriate schedule of drug administration 75.40 38.33 48 6565 13705 3365541
Aspartate aminotransferase increased 74.09 38.33 56 6557 21057 3358189
Hyperglycaemia 70.42 38.33 39 6574 8629 3370617
Sepsis 70.20 38.33 65 6548 32308 3346938
Liver disorder 69.64 38.33 41 6572 10182 3369064
Renal failure 67.32 38.33 64 6549 32876 3346370
Acute kidney injury 66.55 38.33 77 6536 49606 3329640
Metastases to liver 65.50 38.33 29 6584 3967 3375279
Pain in extremity 65.46 38.33 76 6537 49136 3330110
Hepatic enzyme increased 63.58 38.33 43 6570 13582 3365664
Hepatotoxicity 62.38 38.33 31 6582 5500 3373746
Blood glucose increased 61.06 38.33 48 6565 19107 3360139
Spinal cord compression 60.74 38.33 19 6594 980 3378266
Acute coronary syndrome 60.53 38.33 26 6587 3306 3375940
Prescribed underdose 58.88 38.33 21 6592 1627 3377619
Hyperkalaemia 58.39 38.33 38 6575 11256 3367990
Arthralgia 57.13 38.33 79 6534 60782 3318464
Weight decreased 56.79 38.33 64 6549 40047 3339199
Interstitial lung disease 55.50 38.33 40 6573 13976 3365270
Pulmonary embolism 54.73 38.33 53 6560 27835 3351411
Blood potassium decreased 52.84 38.33 29 6584 6301 3372945
Adrenal insufficiency 52.13 38.33 20 6593 1901 3377345
Urinary retention 50.60 38.33 30 6583 7542 3371704
Blood urine present 49.14 38.33 22 6591 3088 3376158
Metastasis 48.31 38.33 18 6595 1579 3377667
Chest pain 48.25 38.33 59 6554 40216 3339030
Metastases to spine 47.39 38.33 14 6599 594 3378652
Pulmonary oedema 47.17 38.33 34 6579 11877 3367369
Malignant neoplasm progression 47.05 38.33 40 6573 17753 3361493
Hyponatraemia 45.96 38.33 40 6573 18319 3360927
Urinary tract obstruction 45.38 38.33 14 6599 689 3378557
Cerebrovascular accident 44.39 38.33 53 6560 35235 3344011
Cardiac failure congestive 42.90 38.33 48 6565 29774 3349472
Weight increased 41.86 38.33 45 6568 26695 3352551
Pyrexia 41.50 38.33 80 6533 81035 3298211
Hypocalcaemia 41.36 38.33 24 6589 5797 3373449
Swelling 40.78 38.33 38 6575 19006 3360240
Transaminases increased 40.35 38.33 25 6588 6799 3372447
Prostatic specific antigen abnormal 40.04 38.33 8 6605 60 3379186
Muscle spasms 39.89 38.33 44 6569 26859 3352387
Confusional state 39.69 38.33 52 6561 37946 3341300
Cushing's syndrome 38.67 38.33 14 6599 1132 3378114

Pharmacologic Action:

SourceCodeDescription
ATC L02BX03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ENDOCRINE THERAPY
HORMONE ANTAGONISTS AND RELATED AGENTS
Other hormone antagonists and related agents
FDA MoA N0000182632 Cytochrome P450 17A1 Inhibitors
FDA EPC N0000182633 Cytochrome P450 17A1 Inhibitor
FDA MoA N0000182137 Cytochrome P450 2D6 Inhibitors
FDA MoA N0000187062 Cytochrome P450 2C8 Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D065607 Cytochrome P-450 Enzyme Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006727 Hormone Antagonists
MeSH PA D006730 Hormones, Hormone Substitutes, and Hormone Antagonists
MeSH PA D065606 Metabolic Side Effects of Drugs and Substances
MeSH PA D065088 Steroid Synthesis Inhibitors
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:35610 antineoplastic agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Malignant tumor of prostate indication 399068003 DOID:10283
Hyperbilirubinemia contraindication 14783006 DOID:2741
Hypertensive disorder contraindication 38341003 DOID:10763
Hypokalemia contraindication 43339004
Body fluid retention contraindication 43498006
Chronic heart failure contraindication 48447003
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.68 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
250MG ZYTIGA JANSSEN BIOTECH N202379 April 28, 2011 RX TABLET ORAL 8822438 Aug. 24, 2027 USE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
250MG ZYTIGA JANSSEN BIOTECH N202379 April 28, 2011 RX TABLET ORAL 8822438 Aug. 24, 2027 USE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAD RECEIVED PRIOR DOCETAXEL CHEMOTHERAPY
250MG ZYTIGA JANSSEN BIOTECH N202379 April 28, 2011 RX TABLET ORAL 8822438 Aug. 24, 2027 USE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC HIGH-RISK CASTRATION-SENSITIVE PROSTATE CANCER
500MG ZYTIGA JANSSEN BIOTECH N202379 April 14, 2017 RX TABLET ORAL 8822438 Aug. 24, 2027 USE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
500MG ZYTIGA JANSSEN BIOTECH N202379 April 14, 2017 RX TABLET ORAL 8822438 Aug. 24, 2027 USE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO HAD RECEIVED PRIOR DOCETAXEL CHEMOTHERAPY
500MG ZYTIGA JANSSEN BIOTECH N202379 April 14, 2017 RX TABLET ORAL 8822438 Aug. 24, 2027 USE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC HIGH-RISK CASTRATION-SENSITIVE PROSTATE CANCER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
250MG ZYTIGA JANSSEN BIOTECH N202379 April 28, 2011 RX TABLET ORAL Feb. 7, 2021 ABIRATERONE ACETATE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC HIGH-RISK CASTRATION-SENSITIVE PROSTATE CANCER
500MG ZYTIGA JANSSEN BIOTECH N202379 April 14, 2017 RX TABLET ORAL Feb. 7, 2021 ABIRATERONE ACETATE IN COMBINATION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC HIGH-RISK CASTRATION-SENSITIVE PROSTATE CANCER

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Steroid 17-alpha-hydroxylase/17,20 lyase Enzyme INHIBITOR IC50 8.54 CHEMBL IUPHAR
Cytochrome P450 3A4 Enzyme IC50 5.57 CHEMBL
Cytochrome P450 11B1, mitochondrial Enzyme IC50 5.79 CHEMBL
Cytochrome P450 11B2, mitochondrial Enzyme IC50 5.76 CHEMBL
Cytochrome P450 17A1 Enzyme IC50 7.90 CHEMBL

External reference:

IDSource
4030721 VUID
N0000182731 NUI
C2607886 UMLSCUI
6745 IUPHAR_LIGAND_ID
D09701 KEGG_DRUG
1100071 RXNORM
27860 MMSL
013721 NDDF
4030721 VANDF
N0000182731 NDFRT
699679004 SNOMEDCT_US
702874007 SNOMEDCT_US
N0000191971 NDFRT
CHEMBL254328 ChEMBL_ID
CHEMBL271227 ChEMBL_ID
9821849 PUBCHEM_CID
EM5OCB9YJ6 UNII
7375 INN_ID
154229-19-3 SECONDARY_CAS_RN
C089740 MESH_SUPPLEMENTAL_RECORD_UI
DB05812 DRUGBANK_ID
D000069501 MESH_DESCRIPTOR_UI
CHEBI:68639 CHEBI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Zytiga HUMAN PRESCRIPTION DRUG LABEL 1 57894-150 TABLET 250 mg ORAL NDA 19 sections
Abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 57894-155 TABLET 250 mg ORAL NDA AUTHORIZED GENERIC 18 sections
Zytiga HUMAN PRESCRIPTION DRUG LABEL 1 57894-184 TABLET, FILM COATED 250 mg ORAL NDA 19 sections
Zytiga HUMAN PRESCRIPTION DRUG LABEL 1 57894-195 TABLET, FILM COATED 500 mg ORAL NDA 19 sections
Abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 57894-199 TABLET, FILM COATED 500 mg ORAL NDA 18 sections