Visanna, tablets 2 mg 28 pcs

Pharmacodynamics

Dienogest is a derivative of nortestosterone, characterized by antiandrogenic activity of approximately one-third that of cyproterone acetate. Dienogestrone binds to progesterone receptors in the human uterus, having only 10% relative progesterone affinity. Despite its low affinity for progesterone receptors, dienogestrone is characterized by a potent progestagenic effect in vivo. Dienogest has no significant mineralocorticoid or glucocorticoid activity in vivo.

Dienogest affects endometriosis by suppressing the trophic effects of estrogen against eutopic and ectopic endometrium, due to a decrease in estrogen production in the ovaries and a decrease in their plasma concentration.

Long-term use causes initial decidualization of endometrial tissue with subsequent atrophy of endometrioid foci. Additional properties of dienogest, such as immunological and anti-angiogenic effects, appear to contribute to its suppressive effect on cell proliferation.

There was no decrease in bone mineral density and no significant effect of Vizantin on standard laboratory parameters, including general and biochemical blood counts, liver enzymes, lipids, and HbA1C. Dienogest moderately reduces estrogen production in the ovaries.

Pharmacokinetics

Absorption. After oral administration, dienogest is rapidly and almost completely absorbed. The serum Cmax of 47 ng/mL is reached approximately 1.5 h after a single oral dose. Bioavailability is about 91%. Pharmacokinetics of dienogest in the dose range from 1 to 8 mg is dose-dependent.

Distribution. Dienogest binds to serum albumin and does not bind to sex hormone-binding globulin (hSPH) and corticosteroid-binding globulin. 10% of the total serum concentration of the substance is in the form of a free steroid, whereas about 90% is nonspecifically bound to albumin. The apparent Vd of dienogest is 40 liters.

Metabolism. Dienogest is almost completely metabolized mainly by hydroxylation to form several virtually inactive metabolites. Based on in vitro and in vivo studies, the main enzyme involved in the metabolism of dienogest is CYP3A4. Metabolites are excreted very rapidly, so that the predominant fraction in blood plasma is unchanged dienogest. The metabolic clearance rate from serum is 64 ml/min.

Elimination. The serum concentration of dienogest decreases in two phases. T1/2 in the terminal phase is approximately 9-10 hours. After oral administration at a dose of 0.1 mg/kg, dienogest is excreted as metabolites, which are excreted through the kidneys and intestines at a ratio of approximately 3:1. The T1/2 of the metabolites when excreted by the kidneys is 14 hours. After oral administration, approximately 86% of the dose received is excreted within 6 days, with the majority excreted in the first 24 hours, primarily by the kidneys.

The equilibrium concentration. The pharmacokinetics of dienogest is independent of hGH levels. The serum concentration of dienogest after daily administration increases approximately 1.24-fold, reaching Css after 4 days of administration. The pharmacokinetics of dienogest after multiple doses of Visanna can be predicted based on the pharmacokinetics after a single dose.

Indications

Treatment of endometriosis.

Active ingredient

Composition

Active substance:

Dienogest 2 mg.

Auxiliary substances:

Lactose monohydrate,

Potato starch,

Microcrystalline cellulose,

povidone K25,

talk,

crospovidone,

magnesium stearate.

How to take, the dosage

To be taken orally.

The tablets can be started on any day of the menstrual cycle. Take one tablet a day without interruption, preferably at the same time each day, with fluids if necessary.

The pills should be taken continuously regardless of vaginal bleeding. After completing one package, start the next one without interruption of the pills.

The efficacy of Visanna may decrease if the pills are missed, if there is vomiting and/or diarrhea (if this occurs within 3-4 hours of taking the pill). If a woman misses one or more pills, she should take only one pill as soon as she remembers it and then continue taking the pills at the usual time the next day.

The tablet not absorbed due to vomiting or diarrhea should be replaced by taking one additional tablet. There is no corresponding indication for the use of Visanna in elderly patients. There are no data indicating the need for dose adjustment in patients with renal impairment.

Interaction

Selected enzyme inducers or inhibitors (CYP3A isoenzyme):

The gestagens, including dienogest, are metabolized primarily by the cytochrome P450 3A4 (CYP3A4) system, which is localized in both the intestinal mucosa and the liver. Consequently, inducers or inhibitors of CYP3A4 can affect the metabolism of gestagenic drugs. Increased clearance of sex hormones due to induction of enzymes may lead to decreased therapeutic effect of Visanna, and also cause side effects, such as change of uterine bleeding patterns.

Decreased clearance of sex hormones due to enzyme inhibition may increase exposure to dienogest, which may lead to the development of side effects.

The substances that can induce enzymes:

The use of drugs that induce microsomal liver enzymes (such as cytochrome P450 system enzymes) may result in increased clearance of sex hormones. These medications include phenytoin, barbiturates, primidone, carbamazepine, and rifampicin; there are also suggestions for oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin, nevirapine, and St John’s wort medications. Maximum induction of enzymes is usually not noted before 2-3 weeks, but then may persist for at least 4 weeks after discontinuation of therapy.

Substances that can inhibit enzymes:

. Known CYP3A4 inhibitors 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 plasma gestagen concentrations and lead to side effects.

The effect of dienogest on other medications:

Based on data from in vitro inhibition studies, it is unlikely to develop clinically significant interactions of Visanna with metabolism of other drugs involving enzymes of the cytochrome P450 system.

Interaction with food:

The standardized intake of high-fat foods had no effect on the bioavailability of Visanna.

Other interactions:

Gestagen intake may affect some laboratory results, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma protein concentrations such as lipid/lipoprotein fractions, carbohydrate metabolism parameters and clotting parameters. Changes are usually within normal limits.

Special Instructions

Pregnancy should be excluded before starting to take Visansa. During taking Visansa, if contraception is necessary, patients are recommended to use non-hormonal contraceptive methods (e.g., barrier method).

Pregnancies occurring in women using contraceptives with only a gestagen component (e.g., minipills) are more likely to be ectopic compared to pregnancies occurring with combined oral contraceptives. Therefore, the use of Visanna in women with a history of ectopic pregnancies or with tubal dysfunction should be decided only after a careful assessment of the benefit-risk ratio.

Since Visanna is a drug with only a gestagen component, it can be assumed that the specific cautions and precautions for use of other drugs with a gestagen component are also applicable for the use of Visanna, although not all cautions and precautions are based on relevant results in clinical trials of Visanna.

If any of the following conditions or risk factors are present or aggravated, an individual risk-benefit assessment should be performed before starting or continuing to take Visansa.

Contraindications

Side effects

Overdose

Serious abnormalities have not been reported in overdose.

Symptoms that may be seen in overdose: nausea, vomiting, mucous bloody discharge or metrorrhagia.

There is no specific antidote, symptomatic treatment should be given.

Similarities