Identification
NameDienogest
Accession NumberDB09123
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
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
BAY 86-5258
Dienogestril
Dienogestum
Endometrion
External IDs M 18575 / MJR-35 / STS 557 / ZK 37659
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VisanneTablet2.00 mgOralBayer2011-10-25Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NataziaTabletOralBayerNot applicableNot applicableCanada
Categories
UNII46M3EV8HHE
CAS number65928-58-7
WeightAverage: 311.425
Monoisotopic: 311.188529049
Chemical FormulaC20H25NO2
InChI KeyAZFLJNIPTRTECV-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][[email protected]@]12CC[[email protected]@](O)(CC#N)[[email protected]@]1(C)CCC1=C3CCC(=O)C=C3CC[[email protected]@]21[H]
Pharmacology
Indication

Indicated for use as the treatment of endometriosis alone and as a contraceptive in combination with ethinylestradiol.

Structured Indications
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 [4]. 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 [A16570], 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 [5]. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue [4]. It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism [A16570].

TargetKindPharmacological actionActionsOrganismUniProt ID
Progesterone receptorProteinyes
agonist
HumanP06401 details
Androgen receptorProteinyes
antagonist
HumanP10275 details
Related Articles
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 [4]. 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 [4].

Protein binding

Dienogest is 90% nonospecifically bound to albumin. It displays no binding to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG) [4].

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 [4].

Half life

Elimination half-life of dienogest is around 9-10 hours. The half-life of urinary metabolites excretion is 14 hours [4].

Clearance

The metabolic clearance rate from serum (Cl/F) is 64 mL/min [4].

Toxicity

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 [5]. 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 [5]. Dienogest does not display genotoxic potential.

Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
2,4-thiazolidinedioneThe therapeutic efficacy of Thiazolidinedione can be decreased when used in combination with Dienogest.Investigational
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Dienogest.Approved
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Dienogest.Approved, Investigational
AcenocoumarolDienogest may decrease the anticoagulant activities of Acenocoumarol.Approved
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Dienogest.Withdrawn
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Dienogest.Approved
AcitretinThe therapeutic efficacy of Dienogest can be decreased when used in combination with Acitretin.Approved
AdapaleneThe therapeutic efficacy of Dienogest can be decreased when used in combination with Adapalene.Approved
AICA ribonucleotideThe therapeutic efficacy of Aicar can be decreased when used in combination with Dienogest.Experimental
AlitretinoinThe therapeutic efficacy of Dienogest can be decreased when used in combination with Alitretinoin.Approved, Investigational
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Dienogest.Approved
AmiodaroneThe serum concentration of Dienogest can be increased when it is combined with Amiodarone.Approved, Investigational
AmobarbitalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Amobarbital.Approved, Illicit
AncrodThe therapeutic efficacy of Ancrod can be decreased when used in combination with Dienogest.Investigational
Antithrombin III humanThe therapeutic efficacy of Antithrombin III human can be decreased when used in combination with Dienogest.Approved
ApixabanThe therapeutic efficacy of Apixaban can be decreased when used in combination with Dienogest.Approved
AprepitantThe serum concentration of Dienogest can be decreased when it is combined with Aprepitant.Approved, Investigational
ArdeparinThe therapeutic efficacy of Ardeparin can be decreased when used in combination with Dienogest.Approved, Withdrawn
ArgatrobanThe therapeutic efficacy of Argatroban can be decreased when used in combination with Dienogest.Approved, Investigational
ArtemetherThe serum concentration of Dienogest can be decreased when it is combined with Artemether.Approved
AtazanavirThe serum concentration of Dienogest can be increased when it is combined with Atazanavir.Approved, Investigational
BalaglitazoneThe therapeutic efficacy of Balaglitazone can be decreased when used in combination with Dienogest.Investigational
BarbexacloneThe therapeutic efficacy of Dienogest can be decreased when used in combination with Barbexaclone.Experimental
BarbitalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Barbital.Illicit
BecaplerminThe therapeutic efficacy of Becaplermin can be decreased when used in combination with Dienogest.Approved, Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Dienogest.Approved, Investigational
BexaroteneThe therapeutic efficacy of Dienogest can be decreased when used in combination with Bexarotene.Approved, Investigational
BexaroteneThe serum concentration of Dienogest can be decreased when it is combined with Bexarotene.Approved, Investigational
BivalirudinThe therapeutic efficacy of Bivalirudin can be decreased when used in combination with Dienogest.Approved, Investigational
BoceprevirThe serum concentration of Dienogest can be increased when it is combined with Boceprevir.Withdrawn
BosentanThe serum concentration of Dienogest can be decreased when it is combined with Bosentan.Approved, Investigational
BuforminThe therapeutic efficacy of Buformin can be decreased when used in combination with Dienogest.Withdrawn
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Dienogest.Approved
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Dienogest.Approved
CarbamazepineThe serum concentration of Dienogest can be decreased when it is combined with Carbamazepine.Approved, Investigational
CastanospermineThe therapeutic efficacy of Castanospermine can be decreased when used in combination with Dienogest.Experimental
CeritinibThe serum concentration of Dienogest can be increased when it is combined with Ceritinib.Approved
CertoparinThe therapeutic efficacy of Certoparin can be decreased when used in combination with Dienogest.Approved
ChlorpropamideThe therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Dienogest.Approved
CholestyramineThe serum concentration of Dienogest can be decreased when it is combined with Cholestyramine.Approved
CiglitazoneThe therapeutic efficacy of Ciglitazone can be decreased when used in combination with Dienogest.Experimental
Citric AcidThe therapeutic efficacy of Citric Acid can be decreased when used in combination with Dienogest.Nutraceutical, Vet Approved
ClarithromycinThe serum concentration of Dienogest can be increased when it is combined with Clarithromycin.Approved
ClobazamThe serum concentration of Dienogest can be decreased when it is combined with Clobazam.Approved, Illicit
CobicistatThe serum concentration of Dienogest can be increased when it is combined with Cobicistat.Approved
ColesevelamThe serum concentration of Dienogest can be decreased when it is combined with Colesevelam.Approved
ColestipolThe serum concentration of Dienogest can be decreased when it is combined with Colestipol.Approved
Conestat alfaDienogest may increase the thrombogenic activities of C1 Esterase Inhibitor (Recombinant).Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Dienogest.Approved, Investigational
Dabigatran etexilateThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Dienogest.Approved
DabrafenibThe serum concentration of Dienogest can be decreased when it is combined with Dabrafenib.Approved
DalteparinThe therapeutic efficacy of Dalteparin can be decreased when used in combination with Dienogest.Approved
DanaparoidThe therapeutic efficacy of Danaparoid can be decreased when used in combination with Dienogest.Approved, Withdrawn
DarexabanThe therapeutic efficacy of Ym150 can be decreased when used in combination with Dienogest.Investigational
DarunavirThe serum concentration of Dienogest can be decreased when it is combined with Darunavir.Approved
DeoxyspergualinThe therapeutic efficacy of Deoxyspergualin can be decreased when used in combination with Dienogest.Investigational
DesirudinThe therapeutic efficacy of Desirudin can be decreased when used in combination with Dienogest.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Dienogest.Approved
DextranThe therapeutic efficacy of Dextran can be decreased when used in combination with Dienogest.Approved, Vet Approved
Dextran 40The therapeutic efficacy of Dextran 40 can be decreased when used in combination with Dienogest.Approved
Dextran 70The therapeutic efficacy of Dextran 70 can be decreased when used in combination with Dienogest.Approved
Dextran 75The therapeutic efficacy of Dextran 75 can be decreased when used in combination with Dienogest.Approved
DicoumarolDienogest may decrease the anticoagulant activities of Dicoumarol.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Dienogest.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Dienogest.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Dienogest.Approved, Investigational
DulaglutideThe therapeutic efficacy of Dulaglutide can be decreased when used in combination with Dienogest.Approved
Edetic AcidThe therapeutic efficacy of Edetic Acid can be decreased when used in combination with Dienogest.Approved, Vet Approved
EdoxabanThe therapeutic efficacy of Edoxaban can be decreased when used in combination with Dienogest.Approved
EfavirenzThe serum concentration of Dienogest can be decreased when it is combined with Efavirenz.Approved, Investigational
EmpagliflozinThe therapeutic efficacy of Empagliflozin can be decreased when used in combination with Dienogest.Approved
EnoxaparinThe therapeutic efficacy of Enoxaparin can be decreased when used in combination with Dienogest.Approved
EnzalutamideThe serum concentration of Dienogest can be decreased when it is combined with Enzalutamide.Approved
Eslicarbazepine acetateThe serum concentration of Dienogest can be decreased when it is combined with Eslicarbazepine acetate.Approved
Ethyl biscoumacetateDienogest may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
ExenatideThe therapeutic efficacy of Exenatide can be decreased when used in combination with Dienogest.Approved, Investigational
FelbamateThe serum concentration of Dienogest can be decreased when it is combined with Felbamate.Approved
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Dienogest.Approved
FluindioneDienogest may decrease the anticoagulant activities of Fluindione.Investigational
FondaparinuxThe therapeutic efficacy of Fondaparinux can be decreased when used in combination with Dienogest.Investigational
Fondaparinux sodiumThe therapeutic efficacy of Fondaparinux sodium can be decreased when used in combination with Dienogest.Approved, Investigational
FosamprenavirThe serum concentration of the active metabolites of Fosamprenavir can be reduced when Fosamprenavir is used in combination with Dienogest resulting in a loss in efficacy.Approved
FosaprepitantThe serum concentration of Dienogest can be decreased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Dienogest can be decreased when it is combined with Fosphenytoin.Approved
GabexateThe therapeutic efficacy of Gabexate can be decreased when used in combination with Dienogest.Investigational
GlibornurideThe therapeutic efficacy of Glibornuride can be decreased when used in combination with Dienogest.Withdrawn
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Dienogest.Approved
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Dienogest.Approved
GlipizideThe therapeutic efficacy of Glipizide can be decreased when used in combination with Dienogest.Approved
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Dienogest.Approved
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Dienogest.Approved
GriseofulvinThe therapeutic efficacy of Dienogest can be decreased when used in combination with Griseofulvin.Approved, Vet Approved
GusperimusThe therapeutic efficacy of Gusperimus can be decreased when used in combination with Dienogest.Investigational
HeparinThe therapeutic efficacy of Heparin can be decreased when used in combination with Dienogest.Approved, Investigational
HexobarbitalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Hexobarbital.Approved
Human C1-esterase inhibitorDienogest may increase the thrombogenic activities of C1 Esterase Inhibitor (Human).Approved
IdelalisibThe serum concentration of Dienogest can be increased when it is combined with Idelalisib.Approved
IdraparinuxThe therapeutic efficacy of idraparinux can be decreased when used in combination with Dienogest.Investigational
IndinavirThe serum concentration of Dienogest can be increased when it is combined with Indinavir.Approved
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Dienogest.Approved
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Dienogest.Approved
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Dienogest.Approved
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Dienogest.Approved
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Dienogest.Approved
Insulin PorkThe therapeutic efficacy of Insulin Pork can be decreased when used in combination with Dienogest.Approved
IsotretinoinThe therapeutic efficacy of Dienogest can be decreased when used in combination with Isotretinoin.Approved
ItraconazoleThe serum concentration of Dienogest can be increased when it is combined with Itraconazole.Approved, Investigational
KetoconazoleThe serum concentration of Dienogest can be increased when it is combined with Ketoconazole.Approved, Investigational
LamotrigineThe serum concentration of Dienogest can be decreased when it is combined with Lamotrigine.Approved, Investigational
LepirudinThe therapeutic efficacy of Lepirudin can be decreased when used in combination with Dienogest.Approved
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Dienogest.Approved
LiraglutideThe therapeutic efficacy of Liraglutide can be decreased when used in combination with Dienogest.Approved
LopinavirThe serum concentration of Dienogest can be decreased when it is combined with Lopinavir.Approved
LumacaftorThe serum concentration of Dienogest can be decreased when it is combined with Lumacaftor.Approved
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Dienogest.Approved
MethohexitalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Methohexital.Approved
MethylphenobarbitalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Methylphenobarbital.Approved
MetreleptinThe serum concentration of Dienogest can be decreased when it is combined with Metreleptin.Approved
MifepristoneThe therapeutic efficacy of Dienogest can be decreased when used in combination with Mifepristone.Approved, Investigational
MiglitolThe therapeutic efficacy of Miglitol can be decreased when used in combination with Dienogest.Approved
MiglustatThe therapeutic efficacy of Miglustat can be decreased when used in combination with Dienogest.Approved
MitiglinideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Dienogest.Approved, Investigational
MitotaneThe serum concentration of Dienogest can be decreased when it is combined with Mitotane.Approved
Mycophenolic acidThe serum concentration of Dienogest can be decreased when it is combined with Mycophenolic acid.Approved
NadroparinThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Dienogest.Approved
NafamostatThe therapeutic efficacy of Nafamostat can be decreased when used in combination with Dienogest.Approved, Investigational
NateglinideThe therapeutic efficacy of Nateglinide can be decreased when used in combination with Dienogest.Approved, Investigational
NefazodoneThe serum concentration of Dienogest can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Dienogest can be decreased when it is combined with Nelfinavir.Approved
NevirapineThe serum concentration of Dienogest can be decreased when it is combined with Nevirapine.Approved
OleandrinAnvirzel may decrease the cardiotoxic activities of Dienogest.Experimental
OtamixabanThe therapeutic efficacy of Otamixaban can be decreased when used in combination with Dienogest.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Dienogest.Approved
OxcarbazepineThe serum concentration of Dienogest can be decreased when it is combined with Oxcarbazepine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Dienogest.Approved, Vet Approved
PentobarbitalThe serum concentration of Dienogest can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
Pentosan PolysulfateThe therapeutic efficacy of Pentosan Polysulfate can be decreased when used in combination with Dienogest.Approved
PerampanelThe serum concentration of Dienogest can be decreased when it is combined with Perampanel.Approved
PhenforminThe therapeutic efficacy of Phenformin can be decreased when used in combination with Dienogest.Approved, Withdrawn
PhenindioneDienogest may decrease the anticoagulant activities of Phenindione.Approved
PhenobarbitalThe serum concentration of Dienogest can be decreased when it is combined with Phenobarbital.Approved
PhenprocoumonDienogest may decrease the anticoagulant activities of Phenprocoumon.Approved
PhenytoinThe serum concentration of Dienogest can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe therapeutic efficacy of Pioglitazone can be decreased when used in combination with Dienogest.Approved, Investigational
PosaconazoleThe serum concentration of Dienogest can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PramlintideThe therapeutic efficacy of Pramlintide can be decreased when used in combination with Dienogest.Approved, Investigational
PrimidoneThe serum concentration of Dienogest can be decreased when it is combined with Primidone.Approved, Vet Approved
Protein CThe therapeutic efficacy of Protein C can be decreased when used in combination with Dienogest.Approved
Protein S humanThe therapeutic efficacy of Protein S human can be decreased when used in combination with Dienogest.Approved
ProtocatechualdehydeThe therapeutic efficacy of Protocatechualdehyde can be decreased when used in combination with Dienogest.Approved
PrucaloprideThe serum concentration of Dienogest can be decreased when it is combined with Prucalopride.Approved
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Dienogest.Approved, Investigational
ReviparinThe therapeutic efficacy of Reviparin can be decreased when used in combination with Dienogest.Approved
RifabutinThe serum concentration of Dienogest can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Dienogest can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Dienogest can be decreased when it is combined with Rifapentine.Approved
RitonavirThe serum concentration of Dienogest can be increased when it is combined with Ritonavir.Approved, Investigational
RivaroxabanThe therapeutic efficacy of Rivaroxaban can be decreased when used in combination with Dienogest.Approved
RosiglitazoneThe therapeutic efficacy of Rosiglitazone can be decreased when used in combination with Dienogest.Approved, Investigational
SaquinavirThe serum concentration of Dienogest can be decreased when it is combined with Saquinavir.Approved, Investigational
SaxagliptinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Dienogest.Approved
SecobarbitalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Secobarbital.Approved, Vet Approved
SelegilineThe serum concentration of Selegiline can be increased when it is combined with Dienogest.Approved, Investigational, Vet Approved
SitagliptinThe therapeutic efficacy of Sitagliptin can be decreased when used in combination with Dienogest.Approved, Investigational
St. John's WortThe serum concentration of Dienogest can be decreased when it is combined with St. John's Wort.Nutraceutical
SugammadexThe serum concentration of Dienogest can be decreased when it is combined with Sugammadex.Approved
SulodexideThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Dienogest.Approved, Investigational
TelaprevirThe serum concentration of Dienogest can be decreased when it is combined with Telaprevir.Withdrawn
TelithromycinThe serum concentration of Dienogest can be increased when it is combined with Telithromycin.Approved
ThalidomideDienogest may increase the thrombogenic activities of Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Thiamylal.Approved, Vet Approved
ThiopentalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Thiopental.Approved, Vet Approved
TipranavirThe serum concentration of Dienogest can be increased when it is combined with Tipranavir.Approved, Investigational
TolazamideThe therapeutic efficacy of Tolazamide can be decreased when used in combination with Dienogest.Approved
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Dienogest.Approved
TopiramateThe serum concentration of Dienogest can be decreased when it is combined with Topiramate.Approved
Tranexamic AcidDienogest may increase the thrombogenic activities of Tranexamic Acid.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Dienogest.Approved, Investigational
TretinoinThe therapeutic efficacy of Dienogest can be decreased when used in combination with Tretinoin.Approved, Investigational, Nutraceutical
TroglitazoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Dienogest.Withdrawn
UlipristalThe therapeutic efficacy of Dienogest can be decreased when used in combination with Ulipristal.Approved
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Dienogest.Approved, Investigational
VogliboseThe therapeutic efficacy of Voglibose can be decreased when used in combination with Dienogest.Approved, Investigational
VoriconazoleThe serum concentration of Dienogest can be increased when it is combined with Voriconazole.Approved, Investigational
WarfarinDienogest may decrease the anticoagulant activities of Warfarin.Approved
XimelagatranThe therapeutic efficacy of Ximelagatran can be decreased when used in combination with Dienogest.Approved, Investigational, Withdrawn
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:21792339 ]
  2. 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. [PubMed:26327902 ]
  3. 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. [PubMed:23113924 ]
  4. Bayer Inc: VISANNE (2mg dienogest tablets) Product Monograph [Link]
  5. Bayer Inc: VISANNE (2mg dienogest tablets) Product Information [Link]
External Links
ATC CodesG03AB08 — Dienogest and estradiolG03DB08 — DienogestG03FA15 — Dienogest and estrogenG03AA16 — Dienogest and ethinylestradiol
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (24.1 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableContraception / Oral Contraceptives (OC) / Ovulation Inhibition / Pharmacology, Clinical1
1CompletedNot AvailablePharmacodynamics1
2CompletedTreatmentEndometriosis1
2Not Yet RecruitingPreventionEndometriosis / Ovarian Reserve1
2RecruitingTreatmentAnorexia Nervosa (AN)1
2, 3SuspendedTreatmentEndometriosis1
3CompletedPreventionOral Contraceptives (OC)1
3CompletedTreatmentContraception1
3CompletedTreatmentEndometriosis4
3CompletedTreatmentMetrorrhagia3
3CompletedTreatmentPrimary Dysmenorrhoea1
3RecruitingTreatmentPremenstrual Syndrome1
4Not Yet RecruitingTreatmentUterine Leiomyomas1
4RecruitingOtherContraception1
4RecruitingPreventionEndometriosis1
4RecruitingTreatmentInfertilities1
4Unknown StatusTreatmentUterine Leiomyomas1
Not AvailableActive Not RecruitingNot AvailableEndometriosis2
Not AvailableActive Not RecruitingTreatmentEndometriosis / Infertilities1
Not AvailableCompletedNot AvailableEndometriosis1
Not AvailableNot Yet RecruitingTreatmentEndometriosis1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
TabletOral2.00 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6133251 No1996-10-252016-10-25Us
US8071577 No2006-05-132026-05-13Us
US8153616 No2008-01-302028-01-30Us
US6884793 No1996-10-252016-10-25Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)210-218Bayer Product Monograph
water solubilityPractically insolubleBayer Product Monograph
Predicted Properties
PropertyValueSource
Water Solubility0.0761 mg/mLALOGPS
logP3.37ALOGPS
logP2.31ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)13.78ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area61.09 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity90.19 m3·mol-1ChemAxon
Polarizability35.4 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-0019000000-8b6511db078a7ef4a6d7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0093000000-b1ea74e40f8e85986825View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0390000000-58a5bd49692ab6bd5ef9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00dl-0950000000-d53345d5771b7bff2baeView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0910000000-6c64873dce18fb49e840View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-1910000000-5dd58f138435ec0555a4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-0009000000-f354babe14ff8cd78da5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-0109000000-aa4e4dd10536f9ed7fb4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-0924000000-0a4b5e59ffb5fd090a1aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0btl-1910000000-baa05a6be42e71aa9634View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4u-2900000000-d615a57fc7b003b3df8dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05ox-3900000000-17cbf8436dfbbec977c2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassOxosteroids
Direct ParentOxosteroids
Alternative Parents3-oxosteroids / 17-hydroxysteroids / Cyclohexenones / Tertiary alcohols / Cyclic alcohols and derivatives / Nitriles / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents3-oxosteroid / Hydroxysteroid / 17-hydroxysteroid / Oxosteroid / Cyclohexenone / Cyclic alcohol / Tertiary alcohol / Ketone / Cyclic ketone / Carbonitrile
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptorsaliphatic nitrile, 3-oxo Delta(4)-steroid, 17beta-hydroxy steroid, steroid hormone (CHEBI:70708 )

Targets

Kind
Protein
Organism
Human
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 isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial ...
Gene Name:
PGR
Uniprot ID:
P06401
Uniprot Name:
Progesterone receptor
Molecular Weight:
98979.96 Da
References
  1. 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. [PubMed:18061638 ]
Kind
Protein
Organism
Human
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 factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Uniprot Name:
Androgen receptor
Molecular Weight:
98987.9 Da
References
  1. 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. [PubMed:18061638 ]

Enzymes

Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
References
  1. 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. [PubMed:26327902 ]
  2. Bayer Inc: VISANNE (2mg dienogest tablets) Product Monograph [Link]
Drug created on September 23, 2015 10:17 / Updated on September 01, 2017 12:02