Details of the Drug

General Information of Drug (ID: DMZK0FQ)

Drug Name
Oestradiol valerate and dienogest
Synonyms
Dienogest; 65928-58-7; Dienogestrel; Dienogestum; Dienogestril; Dinagest; Natazia; Endometrion; Visanne; STS-557; STS 557; Dienogestum [Latin]; UNII-46M3EV8HHE; MJR-35; 17alpha-17-Hydroxy-3-oxo-19-norpregna-4,9-diene-21-nitrile; BAY86-5258; BAY 86-5258; 46M3EV8HHE; CHEBI:70708; 17-alpha-Cyanomethyl-17-beta-hydroxy-estra-4,9(10)-dien-3-one; 2-[(8S,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl]acetonitrile; 17-alpha-Cyanomethyl-17-beta-hydroxyestra-4,9(10)-diene-3-one; Natazia (TN)
Indication
Disease Entry ICD 11 Status REF
Contraception QA21 Approved [1]
Endometriosis GA10 Approved [2]
ATC Code
G03DB08: Oestradiol valerate and dienogest
G03DB: Pregnadien derivatives
G03D: PROGESTOGENS
G03: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
G: GENITO URINARY SYSTEM AND SEX HORMONES
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 311.4
Logarithm of the Partition Coefficient (xlogp) 1.8
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Bioavailability
The bioavailability of drug is 0.63% []
Clearance
The clearance of drug is 64 mL/min [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 9 - 10 hours [3]
Metabolism
The drug is metabolized via the CYP3A4 []
Unbound Fraction
The unbound fraction of drug in plasma is 0.1% [4]
Vd
The volume of distribution (Vd) of drug is 40 L [3]
Chemical Identifiers
Formula
C20H25NO2
IUPAC Name
2-[(8S,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl]acetonitrile
Canonical SMILES
C[C@]12CCC3=C4CCC(=O)C=C4CC[C@H]3[C@@H]1CC[C@]2(CC#N)O
InChI
InChI=1S/C20H25NO2/c1-19-8-6-16-15-5-3-14(22)12-13(15)2-4-17(16)18(19)7-9-20(19,23)10-11-21/h12,17-18,23H,2-10H2,1H3/t17-,18+,19+,20-/m1/s1
InChIKey
AZFLJNIPTRTECV-FUMNGEBKSA-N
Cross-matching ID
PubChem CID
68861
ChEBI ID
CHEBI:70708
CAS Number
65928-58-7
UNII
46M3EV8HHE
DrugBank ID
DB09123
TTD ID
D04CBI
INTEDE ID
DR0490
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Gene/Protein Processing [6]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Gene/Protein Processing [6]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Gene/Protein Processing [6]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Gene/Protein Processing [7]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Gene/Protein Processing [8]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Gene/Protein Processing [8]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Protein Interaction/Cellular Processes [7]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Gene/Protein Processing [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Oestradiol valerate and dienogest (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Emapalumab DMZG5WL Moderate Altered metabolism of Oestradiol valerate and dienogest due to Emapalumab alters the formation of CYP450 enzymes. Adaptive immunity immunodeficiency [4A01] [9]
Ag-221 DMS0ZBI Moderate Increased metabolism of Oestradiol valerate and dienogest caused by Ag-221 mediated induction of CYP450 enzyme. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [10]
Pexidartinib DMS2J0Z Major Increased metabolism of Oestradiol valerate and dienogest caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [11]
Eslicarbazepine DMZREFQ Major Increased metabolism of Oestradiol valerate and dienogest caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [12]
Lesinurad DMUR64T Moderate Increased metabolism of Oestradiol valerate and dienogest caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [10]
Brigatinib DM7W94S Major Increased metabolism of Oestradiol valerate and dienogest caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [13]
Calaspargase pegol DMQZBXI Moderate Decreased metabolism of Oestradiol valerate and dienogest caused by Calaspargase pegol mediated hepatotoxicity. Malignant haematopoietic neoplasm [2B33] [14]
LGX818 DMNQXV8 Major Increased metabolism of Oestradiol valerate and dienogest caused by LGX818 mediated induction of CYP450 enzyme. Melanoma [2C30] [13]
Ixekizumab DMXW92T Moderate Altered metabolism of Oestradiol valerate and dienogest due to Ixekizumab alters the formation of CYP450 enzymes. Psoriasis [EA90] [9]
Sarilumab DMOGNXY Moderate Altered metabolism of Oestradiol valerate and dienogest due to Sarilumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [9]
Pitolisant DM8RFNJ Moderate Increased metabolism of Oestradiol valerate and dienogest caused by Pitolisant mediated induction of CYP450 enzyme. Somnolence [MG42] [15]
⏷ Show the Full List of 11 DDI Information of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7654).
3 Bayer Inc: VISANNE (2mg dienogest tablets) Product Monograph
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Progestogens in menopausal hormone therapy. Prz Menopauzalny. 2015 Jun;14(2):134-43.
6 Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line. Chem Biol Interact. 2013 Feb 25;202(1-3):218-25.
7 Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E?production in human endometriotic stromal cells in spheroid culture. Fertil Steril. 2012 Feb;97(2):477-82.
8 Twenty-one day administration of dienogest reversibly suppresses gonadotropins and testosterone in normal men. J Clin Endocrinol Metab. 2002 May;87(5):2107-13. doi: 10.1210/jcem.87.5.8514.
9 Product Information. Cosentyx (secukinumab). Novartis Pharmaceuticals, East Hanover, NJ.
10 Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
11 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
12 Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32. [PMID: 3408633]
13 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
14 Cerner Multum, Inc. "Australian Product Information.".
15 Cerner Multum, Inc. "UK Summary of Product Characteristics.".