Identification
- Summary
Dienogest is an oral progestin used for the treatment of endometriosis as monotherapy or contraception in combination with ethinylestradiol.
- Brand Names
- Natazia, Visanne
- Generic Name
- Dienogest
- DrugBank Accession Number
- DB09123
- Background
Dienogest is an orally-active semisynthetic progestogen which also possesses the properties of 17α-hydroxyprogesterone. It is a derivative of 19-nortestosterone and has antiandrogenic properties. It is primarily used as a contraceptive in combination with ethinylestradiol, or in other combination form pills approved in United States and Europe however it is not available in the US by itself. In Europe, Australia, Malaysia, Singapore and Japan, dienogest single therapy is an approved treatment for endometriosis to alleviate painful symptoms of endometriosis and reduce endometriotic lesions 1. Dienogest is commonly marketed as Visanne, Natazia and Qlaira.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Dienogest (DB09123)
- Weight
- Average: 311.425
Monoisotopic: 311.188529049 - Chemical Formula
- C20H25NO2
- Synonyms
- 17-alpha-Cyanomethyl-17-beta-hydroxy-estra-4,9(10)-dien-3-one
- 17alpha-17-Hydroxy-3-oxo-19-norpregna-4,9-diene-21-nitrile
- Dienogest
- Dienogestril
- Dienogestum
- Endometrion
- External IDs
- BAY 86-5258
- M 18575
- MJR-35
- STS 557
- ZK 37659
Pharmacology
- Indication
Indicated for use as the treatment of endometriosis alone and as a contraceptive in combination with ethinylestradiol.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Menorrhagia Combination Product in combination with: Estradiol valerate (DB13956) •••••••••••• Management of Pain •••••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use 2 . It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate 5. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. 1mg/kg of dienogest also directly inhibits ovulation 2. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder 1. Dienogest displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ 4, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα 3. It has no glucocorticoid or mineralocorticoid effects. In combined oral contraceptive pills (COCP) with ethinyloestradiol, dienogest conjuction therapy effectively reduces the symptoms of acne and hirsutism, as well as improving excessively heavy or prolonged menstrual bleeding 2.
- Mechanism of action
Dienogest acts as an agonist at the progesterone receptor (PR) with weak affinity that is comparable to that of progesterone but has a very potent progestagenic effect in the endometrium, causing endometrial atrophy after prolonged use 2. It promotes antiproliferative, immunologic and antiangiogenic effects on endometrial tissue. Dienogest reduces the level of endogenous production of oestradiol and thereby suppressing the trophic effects of oestradiol on both the eutopic and ectopic endometrium 6. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue 5. It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism 4.
Target Actions Organism AProgesterone receptor agonistHumans AAndrogen receptor antagonistHumans - Absorption
Dienogest is rapidly absorbed following oral administration, with 91% bioavailability. The peak plasma concentration of 47 ng/mL is reached at about 1.5 hours after single ingestion of 2 mg 5. The stable concentrations of the drug are reached after two days of initial treatment 2.
- Volume of distribution
The apparent volume of distribution (Vd/F) of dienogest is 40 L 5.
- Protein binding
Dienogest is 90% nonospecifically bound to albumin. It displays no binding to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG) 5.
- Metabolism
Dienogest undergoes complete metabolism that is mainly mediated by CYP3A4. The metabolites are pharmacologically inactive and rapidly eliminated from the plasma.
- Route of elimination
The ratio of renal elimination to fecal elimination of dienogest is 3:1, where dienogest is predominantly excreted in the form of inactive metabolites. Most of orally administered drug is excreted in the urine within the first 24 hours of ingestion 5.
- Half-life
Elimination half-life of dienogest is around 9-10 hours. The half-life of urinary metabolites excretion is 14 hours 5.
- Clearance
The metabolic clearance rate from serum (Cl/F) is 64 mL/min 5.
- Adverse Effects
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Oral LD50 in mouse is 4 mg/kg MSDS. In a long-term carcinogenicity study involving rats and mice, exposure of 10 times the dose of maximum recommended clinical dose of dienogest resulted in increased incidences of pituitary adenomas, fibroepithelial mammary tumours, stromal polyps of the uterus and malignant lymphoma 6. These tumors are thought to arise from marked species differences in the optimal oestrogen:progestogen ratio for reproductive function. In rat liver foci assay, dienogest did not induce tumor promotion activity 6. Dienogest does not display genotoxic potential.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Dienogest which could result in a higher serum level. Abametapir The serum concentration of Dienogest can be increased when it is combined with Abametapir. Abciximab The risk or severity of adverse effects can be increased when Dienogest is combined with Abciximab. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Dienogest. Aceclofenac Aceclofenac may decrease the excretion rate of Dienogest which could result in a higher serum level. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of dienogest, which may increase its serum concentration.
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of dienogest and may reduce its serum concentration.
- Take at the same time every day.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aspen-dienogest Tablet 2 mg Oral Aspen Pharmacare Canada Inc. 2020-04-14 Not applicable Canada 
M-dienogest Tablet 2 mg Oral Mantra Pharma Inc Not applicable Not applicable Canada Visanne Tablet 2 mg Oral Bayer 2011-10-25 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Jamp Dienogest Tablet 2 mg Oral Jamp Pharma Corporation 2020-12-10 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ARIORA 1MG/2MG Dienogest (2 mg) + Estradiol valerate (1 mg) Tablet Oral 2017-01-01 Not applicable Germany 
ARIORA 1MG/2MG Dienogest (2 mg) + Estradiol valerate (1 mg) Tablet Oral 2017-01-01 Not applicable Germany BELLAFACE® Dienogest (2 mg) + Ethinylestradiol (0.03 mg) Tablet, film coated Oral LABORATORIO FRANCO COLOMBIANO - LAFRANCOL S.A.S. 2009-01-15 Not applicable Colombia 
BELLAFACE® SUAVE Dienogest (2 mg) + Ethinylestradiol (20 mcg) Tablet, coated Oral LABORATORIO FRANCO COLOMBIANO - LAFRANCOL S.A.S. 2014-06-13 Not applicable Colombia BELLANEW® Dienogest (2 mg) + Estradiol hemihydrate (1.5 mg) Tablet, coated Oral LABORATORIO FRANCO COLOMBIANO - LAFRANCOL S.A.S. 2019-03-11 Not applicable Colombia
Categories
- ATC Codes
- G03AB08 — Dienogest and estradiol
- G03AB — Progestogens and estrogens, sequential preparations
- G03A — HORMONAL CONTRACEPTIVES FOR SYSTEMIC USE
- G03 — SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- G03DB — Pregnadien derivatives
- G03D — PROGESTOGENS
- G03 — SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- G03FA — Progestogens and estrogens, fixed combinations
- G03F — PROGESTOGENS AND ESTROGENS IN COMBINATION
- G03 — SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Adrenal Cortex Hormones
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Combination Contraceptives (with Estrogen and derivatives)
- Contraceptive Agents, Female
- Contraceptive Agents, Hormonal
- Contraceptive Agents, Male
- Contraceptives, Oral
- Contraceptives, Oral, Hormonal
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Estranes
- Estrenes
- Fused-Ring Compounds
- Genito Urinary System and Sex Hormones
- Gonadal Hormones
- Gonadal Steroid Hormones
- Hormonal Contraceptives for Systemic Use
- Hormone Antagonists
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hyperglycemia-Associated Agents
- Pregnadien Derivatives
- Progestin Contraceptives
- Progestins
- Progestogens and Estrogens, Sequential Preparations
- Reproductive Control Agents
- Sex Hormones and Modulators of the Genital System
- Steroids
- Testosterone Congeners
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Oxosteroids
- Direct Parent
- Oxosteroids
- Alternative Parents
- 3-oxosteroids / 17-hydroxysteroids / Cyclohexenones / Tertiary alcohols / Cyclic alcohols and derivatives / Nitriles / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- 17-hydroxysteroid / 3-oxosteroid / Alcohol / Aliphatic homopolycyclic compound / Carbonitrile / Carbonyl group / Cyclic alcohol / Cyclic ketone / Cyclohexenone / Hydrocarbon derivative
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- aliphatic nitrile, 3-oxo Delta(4)-steroid, 17beta-hydroxy steroid, steroid hormone (CHEBI:70708)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 46M3EV8HHE
- CAS number
- 65928-58-7
- InChI Key
- AZFLJNIPTRTECV-FUMNGEBKSA-N
- 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
- IUPAC Name
- 2-[(10S,11S,14R,15S)-14-hydroxy-15-methyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-1,6-dien-14-yl]acetonitrile
- SMILES
- [H][C@@]12CC[C@@](O)(CC#N)[C@@]1(C)CCC1=C3CCC(=O)C=C3CC[C@@]21[H]
References
- General References
- Schindler AE: Dienogest in long-term treatment of endometriosis. Int J Womens Health. 2011;3:175-84. doi: 10.2147/IJWH.S5633. Epub 2011 Jul 6. [Article]
- Binkowska M, Woron J: Progestogens in menopausal hormone therapy. Prz Menopauzalny. 2015 Jun;14(2):134-43. doi: 10.5114/pm.2015.52154. Epub 2015 Jun 22. [Article]
- Hayashi A, Tanabe A, Kawabe S, Hayashi M, Yuguchi H, Yamashita Y, Okuda K, Ohmichi M: Dienogest increases the progesterone receptor isoform B/A ratio in patients with ovarian endometriosis. J Ovarian Res. 2012 Nov 1;5(1):31. doi: 10.1186/1757-2215-5-31. [Article]
- Sasagawa S, Shimizu Y, Kami H, Takeuchi T, Mita S, Imada K, Kato S, Mizuguchi K: Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids. 2008 Feb;73(2):222-31. Epub 2007 Oct 22. [Article]
- Bayer Inc: VISANNE (2mg dienogest tablets) Product Monograph [Link]
- Bayer Inc: VISANNE (2mg dienogest tablets) Product Information [Link]
- FDA Approved Drug Products: Natazia (estradiol valerate and dienogest) tablets for oral use [Link]
- External Links
- PubChem Compound
- 68861
- PubChem Substance
- 310265039
- ChemSpider
- 62093
- 22968
- ChEBI
- 70708
- ChEMBL
- CHEMBL1201864
- ZINC
- ZINC000004215629
- Wikipedia
- Dienogest
- MSDS
- Download (24.1 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Other Contraception 1 4 Completed Treatment Endometrial Diseases / Endometrial Polyps 2 4 Completed Treatment Primary Dysmenorrhoea 1 4 Recruiting Treatment Endometriosis 1 4 Recruiting Treatment Endometriosis of Uterus 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, coated Oral 200000 mg Tablet Oral Tablet, coated Oral 2 mg Tablet, film coated Oral Tablet Oral Tablet, film coated Oral 2 MG/0.03MG Tablet Oral 2.000 mg Tablet, film coated Oral 2 MG Tablet, film coated Oral Kit Oral Kit; tablet, film coated Oral Tablet Oral 3.0000 mg Tablet, film coated Oral 1 mg Tablet, coated Oral Tablet, delayed release Oral Tablet, sugar coated Oral Tablet Oral 2 mg Tablet Oral 200000 mg Tablet Oral 2.00 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6133251 No 2000-10-17 2016-10-25 US 
US8071577 No 2011-12-06 2026-05-13 US US8153616 No 2012-04-10 2028-01-30 US US6884793 No 2005-04-26 2016-10-25 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 210-218 Bayer Product Monograph water solubility Practically insoluble Bayer Product Monograph - Predicted Properties
Property Value Source Water Solubility 0.0761 mg/mL ALOGPS logP 3.37 ALOGPS logP 2.31 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 13.78 Chemaxon pKa (Strongest Basic) -3.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 61.09 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 90.19 m3·mol-1 Chemaxon Polarizability 35.4 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 173.45528 predictedDeepCCS 1.0 (2019) [M+H]+ 175.81328 predictedDeepCCS 1.0 (2019) [M+Na]+ 182.89122 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- Sasagawa S, Shimizu Y, Kami H, Takeuchi T, Mita S, Imada K, Kato S, Mizuguchi K: Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids. 2008 Feb;73(2):222-31. Epub 2007 Oct 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Zinc ion binding
- Specific Function
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
- Gene Name
- AR
- Uniprot ID
- P10275
- Uniprot Name
- Androgen receptor
- Molecular Weight
- 98987.9 Da
References
- Sasagawa S, Shimizu Y, Kami H, Takeuchi T, Mita S, Imada K, Kato S, Mizuguchi K: Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids. 2008 Feb;73(2):222-31. Epub 2007 Oct 22. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
Drug created at September 23, 2015 16:17 / Updated at April 26, 2024 00:46