Dienogest

311.422

311.42

1312995-182-4

46M3EV8HHE

C87238

G03DB08|G - Genito urinary system and sex hormones

61.1

1.96

Pale Yellow Solid

1.2±0.1 g/cm3

210-2140C

549.0±50.0 °C at 760 mmHg

285.8±30.1 °C

1.589

Practically insoluble in water

-20°C Freezer

LD50 oral in mouse: 4gm/kg

D25 -290° (c = 0.5 in pyridine)

NONH for all modes of transport

RC8899500

P280

H361

|Danger|H351 (87.1%): Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P260, P263, P264, P270, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 31 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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. 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. Dienogest does not display genotoxic potential.

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

Indicated for use as the treatment of endometriosis alone and as a contraceptive in combination with ethinylestradiol.|Prevention of pregnancy|Excessive, frequent and irregular menstruation, Contraception|Contraception, Inappropriate diet and eating habits, Treatment of acne vulgaris|Treatment of endometriosis

Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use . It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate. 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. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder. Dienogest displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα. 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.

Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. (See all compounds classified as Hormone Antagonists.)|Oral contraceptives which owe their effectiveness to hormonal preparations. (See all compounds classified as Contraceptives, Oral, Hormonal.)|Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079) (See all compounds classified as Antineoplastic Agents, Hormonal.)|Chemical substances or agents with contraceptive activity in males. Use for male contraceptive agents in general or for which there is no specific heading. (See all compounds classified as Contraceptive Agents, Male.)

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. The stable concentrations of the drug are reached after two days of initial treatment.|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.|The apparent volume of distribution (Vd/F) of dienogest is 40 L.|The metabolic clearance rate from serum (Cl/F) is 64 mL/min.

Dienogest undergoes complete metabolism that is mainly mediated by CYP3A4. The metabolites are pharmacologically inactive and rapidly eliminated from the plasma.

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

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

17 alpha-cyanomethyl-17 beta-hydroxy-13 beta-methylgona-4,9-dien-3-one

Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients