Introduction
Dinosen Tablet 2 mg 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.
Uses
Dinosen Tablet 2 mg is an oral progestin used for the treatment of endometriosis as monotherapy or contraception in combination with ethinylestradiol.
Indicated for use as the treatment of endometriosis alone and as a contraceptive in combination with ethinylestradiol.
Associated Conditions
Pharmacodynamics
Dinosen Tablet 2 mg 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 . Dinosen Tablet 2 mg 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 . 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 .
Mechanism of Action
Dinosen Tablet 2 mg 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. Dinosen Tablet 2 mg 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 [A16570].
Absorption
Dinosen Tablet 2 mg 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 .
Volume of Distribution
The apparent volume of distribution (Vd/F) of dienogest is 40 L .
Protein Binding
Dinosen Tablet 2 mg is 90% nonospecifically bound to albumin. It displays no binding to sex hormone binding globulin (SHBG) or corticoid binding globulin (CBG) .
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 .
Half Life
Elimination half-life of dienogest is around 9-10 hours. The half-life of urinary metabolites excretion is 14 hours .
Clearance
The metabolic clearance rate from serum (Cl/F) is 64 mL/min .
Toxicity
Oral LD50 in mouse is 4 mg/kg . 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 . Dinosen Tablet 2 mg does not display genotoxic potential.
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.
Dosage
In the event of missed tablet(s), the woman should take 2 mg only, as soon as she remembers, and should then continue the next day to take the tablet at her usual time. A tablet not absorbed due to vomiting or diarrhea should likewise be replaced by 2 mg.
