Dienogest is nortestosterone derivative, marked antiandrogenic activity of approximately one third of the activity of cyproterone acetate. Dienogest binds to progesterone receptors in the human uterus, having only 10% of the relative affinity of progesterone. Despite low affinity for progesterone receptors, dienogest is characterized by a strong progestagenic effect in vivo. Dienogest does not have significant glucocorticoid or mineralocorticoid activity in vivo.
Dienogest effect on endometriosis by inhibiting the trophic effects of estrogen with regard eutopic and ectopic endometrial, due to the reduction of estrogen production by the ovaries and reducing their concentration in the plasma.
With prolonged use causes initial decidualization of endometrial tissue with subsequent atrophy of endometriotic lesions. Additional properties of dienogest such as immunological and angiogenic effects appear to contribute to its inhibitory effect on cell proliferation.
There was no decrease in bone mineral density, as well as a significant impact on the drug Visan standard laboratory parameters, including general and biochemical blood counts, liver enzymes, lipids and HbA1C. Dienogest moderately reduces the production of estrogen in the ovaries.
Absorption. After oral administration of dienogest is rapidly and almost completely absorbed. Cmax in the blood serum component 47 ng / ml, achieved after about 1.5 hours after a single oral administration. The bioavailability is about 91%. Pharmacokinetics of dienogest in a dose range from 1 mg to 8 characterized by a dose dependent.
Distribution. Dienogest binds to serum albumin and does not bind to globulin, sex hormone binding (SHBG), as well as kortikosteroidsvyazyvayuschim globulin. 10% of the concentration in the blood serum is as free steroid, whereas about 90% of non-specifically associated with albumin. Apparent Vd dienogest is 40 l.
Metabolism. Dienogest almost completely metabolized mainly by hydroxylation to form several substantially inactive metabolites. Based on in vitro studies and in vivo, the primary enzyme involved in the metabolism of dienogest is CYP3A4. Metabolites are excreted very quickly so that the dominant faction in the plasma is unchanged dienogest. The metabolic clearance rate from the blood serum of 64 ml / min.
Elimination. The concentration in serum decreases dwuhfazno dienogest. T1 / 2 in the terminal phase is about 9-10 hours. After oral administration at a dose of 0.1 mg / kg dienogest is displayed in the form of metabolites that are released by the kidneys and intestines in a ratio of about 3: 1. T1 / 2 at their metabolites excretion by the kidneys at 14 hrs. After oral administration of approximately 86% of the administered dose excreted within 6 days, with most of the output in the first 24 hours, preferably kidneys.
The equilibrium concentration. The pharmacokinetics of dienogest are not dependent on the SHBG level. serum concentration dienogest after daily administration increases by about 1.24 times, reaching 4 days Css reception. Pharmacokinetics after multiple dose dienogest Visan can be predicted on the basis of the pharmacokinetics after a single administration.
Bayer Pharma AG, Germany
Adults are prescribed by a doctor, for women
The active ingredient is:
Treatment of endometriosis.
- Individual intolerance of components Visan,
- acute thrombophlebitis,
- diabetes with vascular complications,
- severe liver disease.
- Allergic reactions,
- bleeding from the vagina,
- discomfort in the breast,
- depressed mood,
How to accept, acceptance rate and dosage
Pills can start on any day of the menstrual cycle. Take one tablet per day without interruption, preferably at the same time each day, if necessary with some liquid.
Tablets must be taken continuously, regardless of vaginal bleeding. After the completion of one package begin receiving the next without tablet-free interval.
Visan efficiency may decrease with passage of tablets, vomiting and / or diarrhea (if it occurs within 3-4 hours after ingestion of the tablet). When you miss one or more pills, women should take only one tablet as soon as she remembers this, and then the next day to continue taking the tablets at the usual time.
Due to unabsorbed vomiting or diarrhea tablet should be replaced additional reception of one tablet. There is an appropriate indication for the use of Visan in elderly patients. There is no evidence pointing to the need for dose adjustment in patients with renal insufficiency.
Store at a temperature not higher than 30 ° C.
Keep out of the reach of children.
Individual inductors or enzyme inhibitors (isoenzyme CYP3A):
Progestins including dienogest, metabolized mainly involving cytochrome P450 3A4 (CYP3A4), localized in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 may affect the metabolism gestagen preparations. Increased clearance of hormones, enzymes due to induction can lead to a decrease in therapeutic effect Visan and cause side effects, such as changing the nature of uterine bleeding.
Reduced clearance of sex hormones in connection with the inhibition of enzymes may increase the exposure of dienogest, which may lead to the development of side effects.
Substances capable of inducing enzymes:
The use of drugs that induce microsomal liver enzymes (e.g., cytochrome P450 enzyme system) can lead to increased clearance of sex hormones. These medicines include: phenytoin, barbiturates, primidone, carbamazepine and rifampicin; also has assumptions regarding oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin, nevirapine and preparations containing St. John’s wort. Maximal enzyme induction is generally observed not earlier than 2-3 weeks, but may then persist for at least 4 weeks following discontinuation of therapy.
Substances capable of inhibiting enzymes:
Known inhibitors of CYP3A4, such as azole antifungals (e.g., ketoconazole, itraconazole, fluconazole), cimetidine, verapamil, macrolides (e.g., erythromycin, clarithromycin and roxithromycin), diltiazem, protease inhibitors (e.g., ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (e.g., nefazodone, fluvoxamine, fluoxetine) and grapefruit juice may increase the concentration of progestogens in plasma and lead to the development of side effects.
Effect on dienogest other medicinal substances:
From the data inhibition in vitro studies, it is unlikely development Visan clinically significant interaction with the metabolism of other drugs with the cytochrome P450 enzyme system.
Interaction with food:
A standardized meal with high-fat diet had no effect on the bioavailability of Visan.
Receiving progestogens can affect the results of some laboratory tests, including biochemical parameters of the liver, thyroid, adrenals and kidneys, plasma protein concentration, e.g., fractions of lipids / lipoproteins, carbohydrate metabolism parameters and coagulation parameters. Changes do not usually go beyond the normal range.
Before taking Visan necessary to exclude pregnancy. During reception Visan recommended hormonal contraceptive methods, if necessary patients contraception (e.g., barrier method).
If pregnancy occurred in women using birth control pills only progestin component (eg, minipill) greater than the probability of ectopic localization, compared with pregnancy that occurred in patients receiving combined oral contraceptives. Therefore, the application of Visan in women with ectopic pregnancy history or a dysfunction of the fallopian tubes should be decided only after careful evaluation of the benefits and risks.
Since Visan is a preparation with only progestin component, it can be assumed that the special warnings and precautions for use of other drugs with the progestin component, are also applicable for use Visan, although not all of the warnings and precautions are based on respective findings in the clinical studies Visan .
With or aggravation of any of the following conditions or risk factors, or continuation before receiving Visan should conduct an individual assessment of the risk / an advantage.
Serious violations of overdose have been reported.
Symptoms that can be marked with an overdose: nausea, vomiting, spotting or metrorrhagia.
No specific antidote, symptomatic treatment should be conducted.