Visanne, pills 2mg, 28pcs

Composition

Active ingredient:

dienogest 2 mg.

Auxiliary substances:

lactose monohydrate,

potato starch,

microcrystalline cellulose,

povidone K 25,

talc,

crospovidone,

magnesium stearate.

Pharmacological action

Pharmacodynamics

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

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

With prolonged use, it causes initial decidualization of endometrial tissue, followed by atrophy of endometrioid foci. Additional properties of dienogest, such as immunological and anti-angiogenic effects, seem to contribute to its suppressive effect on cell proliferation.

There was no decrease in bone mineral density, as well as a significant effect of the drug Visanne on standard laboratory parameters, including general and biochemical parameters of blood, liver enzymes, lipids and HbA1c. Dienogest moderately reduces the production of estrogens in the ovaries.

Pharmacokinetics

Absorption. After oral use, dienogest is rapidly and almost completely absorbed. Serum cmax of 47 ng / ml is reached approximately 1.5 hours after a single oral dose. Bioavailability is about 91%. The pharmacokinetics of dienogest in the dose range from 1 to 8 mg is characterized by dose dependence.

Distribution. Dienogest binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin. 10% of the total concentration of the substance in the blood serum is in the form of a free steroid, while about 90% is non-specifically associated with albumin. The apparent Vd of dienogest is 40 l.

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

Elimination. The concentration of dienogest in the blood serum decreases biphasically. T1 / 2 in the terminal phase is approximately 9-10 hours. After oral use at a dose of 0.1 mg / kg, dienogest is excreted as metabolites that are excreted through the kidneys and intestines in a ratio of approximately 3: 1. T1/2 of metabolites with their excretion by the kidneys is 14 hours. After oral use, approximately 86% of the dose received is eliminated within 6 days, with the majority being eliminated in the first 24 hours, mainly by the kidneys.

Equilibrium concentration. The pharmacokinetics of dienogest are independent of SHBG levels. The concentration of dienogest in the blood serum after daily use increases approximately 1.24 times, reaching Css after 4 days of use. The pharmacokinetics of dienogest after repeated use of Visanne can be predicted based on the pharmacokinetics after a single dose.

Indications

Treatment of endometriosis.

Contraindications

• Individual intolerance to the components of Visanne,
• acute thrombophlebitis,
• atherosclerosis,
• myocardial infarction,
• stroke,
• diabetes mellitus with vascular complications,
• severe liver diseases.

Side effects

• Possible allergic reactions,
• vaginal bleeding,
• headache,
• discomfort in the mammary glands,
• decreased mood,
• acne.

Interaction

Individual inducers or inhibitors of enzymes (CYP3A isoenzyme):

Progestins, including dienogest, are mainly metabolized with the participation of the cytochrome P450 3A4 (CYP3A4) system, localized both in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 may affect the metabolism of progestogenic drugs. Increased clearance of sex hormones due to the induction of enzymes can lead to a decrease in the therapeutic effect of Visanne, as well as cause side effects, for example, a change in the nature of uterine bleeding.

Decreased sex hormone clearance due to enzyme inhibition may increase dienogest exposure, which may lead to side effects.

Substances capable of inducing enzymes:

The use of drugs that induce microsomal liver enzymes (for example, cytochrome P450 enzymes) can lead to an increase in the clearance of sex hormones. These drugs include: phenytoin, barbiturates, primidone, carbamazepine and rifampicin; there are also suggestions for oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin, nevirapine and preparations containing St. John’s wort. The maximum induction of enzymes, as a rule, is noted not earlier than in 2-3 weeks, but then it can persist for at least 4 weeks after discontinuation of therapy.

Substances that can inhibit enzymes:

Known CYP3A4 inhibitors, such as azole antifungal drugs (for example, ketoconazole, itraconazole, fluconazole), cimetidine, verapamil, macrolides (for example, erythromycin, clarithromycin and roxithromycin), diltiazem, protease inhibitors (for example, ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (for example, nefazodone, fluvoxamine, fluoxetine) and grapefruit juice, may increase the concentration of progestogens in blood plasma and lead to the development of side effects.

Effect of dienogest on other medicinal substances:

Based on data from in vitro inhibition studies, it is unlikely that a clinically significant interaction of Visanne with the metabolism of other drugs involving cytochrome P450 enzymes will occur. Interaction with food products:

A standardized high-fat meal had no effect on the bioavailability of Visanne.

Other types of interaction:

The use of progestogens may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma protein concentrations, such as lipid/lipoprotein fractions, carbohydrate metabolism parameters, and clotting parameters. Changes usually do not exceed the limits of normal values.

How to take, course of use and dosage

For oral use.

You can start taking pills on any day of your menstrual cycle. Take one tablet a day without a break, preferably at the same time every day, if necessary, with a liquid.

Tablets should be taken continuously, regardless of vaginal bleeding. After completing one package, start taking the next one without a break in taking tablets.

The effectiveness of Visanne may be reduced by skipping pills, vomiting and / or diarrhea (if this occurs within 3-4 hours after taking the pill). If you miss one or more pills, the woman should take only one pill as soon as she remembers, and then continue taking the pills at the usual time the next day.

A tablet that is not absorbed due to vomiting or diarrhea should be replaced with an additional tablet. There is no corresponding indication for the use of Visanne in elderly patients. There are no data indicating the need for dose adjustment in patients with renal insufficiency.

Overdose

No serious overdose violations were reported.

Symptoms that may occur with an overdose: nausea, vomiting, spotting or metrorrhagia.

There is no specific antidote, and symptomatic treatment should be performed.

Special instructions

Before taking Visanne, it is necessary to exclude pregnancy. While taking Visanne, if contraception is necessary, patients are recommended to use non-hormonal contraceptive methods (for example, the barrier method).

If a pregnancy occurs in women who use contraceptives with only a progestogen component (for example, minipil), it is more likely to be ectopic, compared to pregnancy that occurs while taking combined oral contraceptives. Therefore, the question of using Visanne in women with a history of ectopic pregnancy or with impaired fallopian tube function should be decided only after a thorough assessment of the benefits and risks.

Since Visanne is a drug with only a progestogenic component, it can be assumed that special warnings and precautions for the use of other drugs with a progestogenic component are also applicable for the use of Visanne, although not all warnings and precautions are based on relevant results in the course of clinical studies of Visanne.

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

Form of production

Tablets

Storage conditions

Store at a temperature not exceeding 30°C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Dienogest

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For women, For adults as prescribed by a doctor

Indications

Endometriosis