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

Stem definitionDrug idCAS RN
systemic antifungal agents, miconazole derivatives 1527 65277-42-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ketoconazole
  • (+/-)-ketoconazole
  • brizoral
  • fungarest
  • fungoral
  • ketoderm
  • ketoisdin
  • ketozoral
  • nizoral
  • nizral
  • panfungol
  • ketoconazol
  • R-41400
Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
  • Molecular weight: 531.43
  • Formula: C26H28Cl2N4O4
  • CLOGP: 3.64
  • LIPINSKI: 1
  • HAC: 8
  • HDO: 0
  • TPSA: 69.06
  • ALOGS: -4.76
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
0.40 g V
0.20 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.01 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 3 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 10.75 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 75 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
June 12, 1981 FDA JANSSEN PHARMS

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
Psoriasis 89.05 13.37 88 8122 78516 46599336
Cortisol increased 51.11 13.37 12 8198 345 46677507
Purpura senile 39.61 13.37 11 8199 624 46677228
Tarsal tunnel syndrome 39.27 13.37 11 8199 644 46677208
Exposure during pregnancy 37.78 13.37 68 8142 108144 46569708
Hypothalamic pituitary adrenal axis suppression 36.94 13.37 8 8202 158 46677694
Adrenal insufficiency 32.21 13.37 23 8187 13101 46664751
Resorption bone increased 29.42 13.37 10 8200 1117 46676735
Vertigo positional 27.54 13.37 12 8198 2618 46675234
Vestibular disorder 27.53 13.37 10 8200 1356 46676496
Abortion spontaneous 25.83 13.37 35 8175 43611 46634241
Drug interaction 23.70 13.37 84 8126 203010 46474842
Pneumonia mycoplasmal 20.09 13.37 7 8203 841 46677011
Blood uric acid decreased 19.06 13.37 6 8204 526 46677326
Drug clearance increased 17.85 13.37 4 8206 93 46677759
Thrombophlebitis superficial 17.67 13.37 11 8199 4992 46672860
Deafness bilateral 17.47 13.37 7 8203 1240 46676612
Toxicity to various agents 16.99 13.37 8 8202 211758 46466094
Nonalcoholic fatty liver disease 16.74 13.37 6 8204 783 46677069
Otitis media 16.71 13.37 10 8200 4230 46673622
Product dose omission issue 16.56 13.37 66 8144 168454 46509398
Hypertrophy 16.17 13.37 5 8205 413 46677439
Otitis media acute 15.97 13.37 6 8204 894 46676958
Haematopoietic neoplasm 14.22 13.37 3 8207 52 46677800
Mixed liver injury 13.94 13.37 8 8202 3135 46674717
Seborrhoeic dermatitis 13.37 13.37 5 8205 736 46677116

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
Therapeutic response unexpected 29.67 13.91 23 8763 8880 29934812
Off label use 29.08 13.91 147 8639 249143 29694549
Prostatic specific antigen increased 27.55 13.91 25 8761 11979 29931713
Seborrhoeic dermatitis 26.43 13.91 11 8775 1282 29942410
Multiple chemical sensitivity 25.77 13.91 4 8782 4 29943688
Colour vision tests normal 25.77 13.91 4 8782 4 29943688
Transient aphasia 24.87 13.91 6 8780 114 29943578
Anaplastic astrocytoma 22.97 13.91 6 8780 159 29943533
Alcohol intolerance 21.09 13.91 7 8779 433 29943259
Toxicity to various agents 21.05 13.91 13 8773 177170 29766522
Rhabdomyolysis 20.03 13.91 52 8734 63528 29880164
Central vision loss 19.65 13.91 4 8782 33 29943659
Psoriasis 19.14 13.91 40 8746 42466 29901226
Guttate psoriasis 17.67 13.91 5 8781 180 29943512
Bone disorder 17.38 13.91 15 8771 6726 29936966
Product use issue 16.99 13.91 40 8746 45976 29897716
Adrenal insufficiency 16.92 13.91 18 8768 10445 29933247
Vitamin E deficiency 16.03 13.91 3 8783 15 29943677
Polyarteritis nodosa 15.79 13.91 5 8781 266 29943426
Tinea pedis 14.59 13.91 7 8779 1139 29942553
Prurigo 14.21 13.91 6 8780 724 29942968
Herpes virus infection 14.16 13.91 9 8777 2535 29941157

Pharmacologic Action:

SourceCodeDescription
ATC D01AC08 DERMATOLOGICALS
ANTIFUNGALS FOR DERMATOLOGICAL USE
ANTIFUNGALS FOR TOPICAL USE
Imidazole and triazole derivatives
ATC G01AF11 GENITO URINARY SYSTEM AND SEX HORMONES
GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
Imidazole derivatives
ATC H02CA03 SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
CORTICOSTEROIDS FOR SYSTEMIC USE
ANTIADRENAL PREPARATIONS
Anticorticosteroids
ATC J02AB02 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOTICS FOR SYSTEMIC USE
ANTIMYCOTICS FOR SYSTEMIC USE
Imidazole derivatives
FDA CS M0002083 Azoles
MeSH PA D058888 14-alpha Demethylase Inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000935 Antifungal Agents
MeSH PA D065692 Cytochrome P-450 CYP3A Inhibitors
MeSH PA D065607 Cytochrome P-450 Enzyme Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006727 Hormone Antagonists
MeSH PA D065606 Metabolic Side Effects of Drugs and Substances
MeSH PA D065088 Steroid Synthesis Inhibitors
FDA EPC N0000175487 Azole Antifungal
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190115 Cytochrome P450 3A5 Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Tinea pedis indication 6020002 DOID:12403
Histoplasmosis indication 12962009 DOID:1731
Hypercortisolism indication 47270006
Candidiasis of skin indication 49883006
Seborrheic dermatitis indication 50563003 DOID:8741
Pityriasis versicolor indication 56454009 DOID:9060
Paracoccidioidomycosis indication 59925007 DOID:12662
Coccidioidomycosis indication 60826002 DOID:13450
Blastomycosis indication 69996000 DOID:12663
Disseminated candidiasis indication 70572005
Candidiasis of mouth indication 79740000 DOID:14262
Tinea corporis indication 84849002
Chromoblastomycosis indication 187079000
Pityriasis simplex indication 200767005
Tinea cruris indication 399029005
Paronychia off-label use 71906005 DOID:13117
Advanced Prostatic Carcinoma off-label use
Torsades de pointes contraindication 31722008
Achlorhydria contraindication 47481007
Prolonged QT interval contraindication 111975006
Disease of liver contraindication 235856003 DOID:409
Telangiectasia disorder contraindication 247479008
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Atrophoderma contraindication 399979006
Peripheral vascular disease contraindication 400047006
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.84 Basic
pKa2 3.5 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
Steroid 17-alpha-hydroxylase/17,20 lyase Enzyme INHIBITOR IC50 7.28 WOMBAT-PK DRUG LABEL
Cytochrome P450 11B1, mitochondrial Enzyme INHIBITOR IC50 6.90 SCIENTIFIC LITERATURE DRUG LABEL
Sodium-dependent serotonin transporter Transporter Ki 6.55 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 4.62 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 5.08 DRUG MATRIX
Histamine H2 receptor GPCR Ki 4.67 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 5.03 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 4.73 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 4.84 DRUG MATRIX
Delta-type opioid receptor GPCR Ki 5.35 DRUG MATRIX
Thromboxane-A synthase Enzyme IC50 5.66 DRUG MATRIX
Substance-K receptor GPCR Ki 5.24 DRUG MATRIX
Sodium/nucleoside cotransporter 1 Transporter Ki 5.82 DRUG MATRIX
Aldehyde oxidase Enzyme IC50 5.46 WOMBAT-PK
Lanosterol 14-alpha demethylase Enzyme app Ki 7.20 WOMBAT-PK
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Enzyme IC50 6.51 WOMBAT-PK
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor WOMBAT-PK
Multidrug resistance protein 1 Transporter Ki 6 WOMBAT-PK
Cytochrome P450 3A4 Enzyme Ki 7 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.72 WOMBAT-PK
Cytochrome P450 11B2, mitochondrial Enzyme INHIBITOR IC50 7.17 SCIENTIFIC LITERATURE
Aromatase Enzyme Ki 6.40 CHEMBL
Cytochrome P450 21 Enzyme IC50 5.05 CHEMBL
Indoleamine 2,3-dioxygenase 1 Enzyme IC50 4.60 CHEMBL
Potassium voltage-gated channel subfamily A member 10 Ion channel BLOCKER IC50 6.30 IUPHAR
Alpha-2A adrenergic receptor GPCR Ki 5.13 DRUG MATRIX
Lanosterol 14-alpha demethylase Enzyme INHIBITOR IC50 7 WOMBAT-PK CHEMBL
Arachidonate 15-lipoxygenase Enzyme IC50 5.27 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 4.90 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 5.21 DRUG MATRIX
Membrane-associated progesterone receptor component 1 Membrane receptor Ki 5.01 DRUG MATRIX
Cytochrome P450 11A1 Enzyme IC50 5.91 CHEMBL
Cytochrome P450 24A1 Enzyme IC50 4.70 CHEMBL
Gonadotropin-releasing hormone receptor GPCR Kd 9.66 CHEMBL
Cytochrome P450 7A1 Enzyme IC50 6.71 CHEMBL
Cytochrome P450 51 Enzyme Ki 7.19 CHEMBL
Cytochrome P450 11B1 Unclassified IC50 6.82 CHEMBL
Cytochrome P450 17A1 Enzyme IC50 6.69 CHEMBL
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial Unclassified IC50 6.44 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 4.45 CHEMBL

External reference:

IDSource
4019271 VUID
N0000147470 NUI
D00351 KEGG_DRUG
4019271 VANDF
C1517666 UMLSCUI
CHEBI:47519 CHEBI
KTN PDB_CHEM_ID
CHEMBL157101 ChEMBL_ID
CHEMBL295698 ChEMBL_ID
D007654 MESH_DESCRIPTOR_UI
DB01026 DRUGBANK_ID
47576 PUBCHEM_CID
2568 IUPHAR_LIGAND_ID
4594 INN_ID
R9400W927I UNII
202692 RXNORM
2701 MMSL
31001 MMSL
4945 MMSL
d00103 MMSL
002903 NDDF
387216007 SNOMEDCT_US
40232005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 0093-3219 CREAM 20 mg TOPICAL ANDA 17 sections
ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 0168-0099 CREAM 20 mg TOPICAL ANDA 16 sections
Ketaconazole HUMAN PRESCRIPTION DRUG LABEL 1 0378-7007 AEROSOL, FOAM 20 mg TOPICAL NDA authorized generic 26 sections
EXTINULL HUMAN PRESCRIPTION DRUG LABEL 1 0378-8136 AEROSOL, FOAM 20 mg TOPICAL NDA 25 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 0713-0671 CREAM 20 mg TOPICAL ANDA 11 sections
Xolegel HUMAN PRESCRIPTION DRUG LABEL 1 16110-080 GEL 20 mg TOPICAL NDA 27 sections
KETOCONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 16590-998 TABLET 200 mg ORAL ANDA 22 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 16714-955 CREAM 20 mg TOPICAL ANDA 18 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 21695-554 CREAM 20 mg TOPICAL ANDA 19 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 21695-555 CREAM 20 mg TOPICAL ANDA 19 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 21695-556 CREAM 20 mg TOPICAL ANDA 19 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 21695-562 TABLET 200 mg ORAL ANDA 23 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 21922-025 CREAM 20 mg TOPICAL ANDA 15 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 33261-739 TABLET 200 mg ORAL ANDA 26 sections
KETOCONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 35573-433 TABLET 200 mg ORAL ANDA 15 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 43063-036 TABLET 200 mg ORAL ANDA 26 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 43063-882 TABLET 200 mg ORAL ANDA 26 sections
Ketodan HUMAN PRESCRIPTION DRUG LABEL 1 43538-530 AEROSOL, FOAM 20 mg TOPICAL ANDA 28 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 45802-465 SHAMPOO, SUSPENSION 20 mg TOPICAL ANDA 18 sections
ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 45802-532 AEROSOL, FOAM 2 g TOPICAL ANDA 27 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 50090-1220 SHAMPOO, SUSPENSION 20 mg TOPICAL ANDA 18 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 50090-1524 CREAM 20 mg TOPICAL ANDA 18 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 50090-1675 CREAM 20 mg TOPICAL ANDA 18 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 50090-1992 TABLET 200 mg ORAL ANDA 26 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 50090-3288 SHAMPOO, SUSPENSION 20.50 mg TOPICAL ANDA 17 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 50090-5265 CREAM 20 mg TOPICAL ANDA 17 sections
Nizoral HUMAN PRESCRIPTION DRUG LABEL 1 50458-680 SHAMPOO 20 mg TOPICAL NDA 20 sections
Nizoral A-D HUMAN OTC DRUG LABEL 1 50580-895 SHAMPOO 10 mg TOPICAL NDA 15 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 51407-279 CREAM 20 mg TOPICAL ANDA 19 sections
Ketoconazole HUMAN PRESCRIPTION DRUG LABEL 1 51672-1298 CREAM 20 mg TOPICAL ANDA 19 sections