Expiration date: 04/2026

Structure and Composition:

Tablets. 1 tab contains active substance: micronized dienogest 2 mg

Excipients: lactose monohydrate - 62.8 mg of potato starch - MCC 36 mg - 18 mg povidone K25 - 8.1 mg talc - 4.05 mg Crospovidone - Magnesium stearate 2.7 mg - 1.35 mg

in a blister made of PVC and aluminum foil 14 pcs. in the cardboard box 2 or, 6 or 12 blisters.

Description pharmaceutical form:

Round white or almost white tablet with a flat surface and bevelled edges, engraved "B" on one side.

Pharmacokinetics:

Absorption. After oral administration of dienogest is rapidly and almost completely absorbed. Cmax in the blood serum component 47 ng / ml, is reached in about 1.5 hours after a single oral administration. The bioavailability is about 91%. Pharmacokinetics of dienogest in a dosage range from 1 mg to 8 characterized by a dose dependent.

Distribution. Dienogest binds to serum albumin and globulin binds to sex hormone-binding (SHBG) and to kortikosteroidsvyazyvayuschim globulin. 10% of the concentration in the blood serum is as free steroid, whereas about 90% of non-specifically associated with albumin. The apparent Vd dienogest is 40 l.

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

Elimination. The concentration of serum dienogest reduced bi-phase. T1 / 2 in the terminal phase is about 9-10 hours after oral dose of 0.1 mg / kg dienogest displayed as metabolites that are released by the kidneys and intestines in a ratio of about 3:. 1. T1 / 2 at their metabolites renal excretion of 14 hours. After oral administration of approximately 86% of dose excreted within 6 days, with most of the output in the first 24 hours, preferably kidneys.

The equilibrium concentration. Pharmacokinetics dienogest is independent of SHBG levels. Serum concentrations of dienogest after daily administration increases approximately 1.24 times, reaching the Css 4 days admission. The pharmacokinetics of dienogest after repeated reception Visanne can be predicted on the basis of pharmacokinetics after a single ingestion.

Description of the pharmacological actions:

Dienogest is a derivative of nortestosterone, marked by anti-androgenic activity of approximately one third of the activity of cyproterone acetate. Dienogest binds to progesterone receptors in 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 affects endometriosis by inhibiting the trophic effects of estrogen against eutopic and ectopic endometrial estrogen production due to a reduction in the ovaries and reducing their concentration in the plasma.

Prolonged use causes initial decidualization endometrial tissue followed by atrophy of endometriotic lesions. Dienogest additional properties such as anti-angiogenic and immunologic effects appear to contribute to its inhibitory effect on cell proliferation.

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

Testimony:

The treatment of endometriosis.

Contraindications:

Visanne The drug should not be used if any of the conditions listed below, some of which are common to all products containing only progestin component. If any of these conditions will develop in patients receiving the drug Visanne, the use of the drug should be discontinued immediately.

• acute thrombophlebitis, venous thromboembolism now
  
• heart disease and arteries, which are based on atherosclerotic vascular disease (including coronary artery disease, myocardial infarction, stroke and transient ischemic attack) in the present or in history
  
• diabetes with vascular complications
  
• severe liver disease at present or in history (in the absence of normalization of liver function tests)
  
• liver tumors (benign or malignant) currently or history
  
• identified or suspected hormone-dependent cancers, including mammary cancer
  
• vaginal bleeding of unknown origin
  
• cholestatic jaundice of pregnant women in history
  
• Hypersensitivity to the active substances or any of the excipients
  
• galactose intolerance, lactase deficiency, glucose-galactose malabsorption
  
• during pregnancy and breastfeeding
  
• childhood and adolescence to 18 years (effectiveness and safety of adolescents have not been established).
  

With care, depression in history, a history of ectopic pregnancy, hypertension, chronic heart failure, migraine with aura, diabetes without vascular complications, hyperlipidemia, deep vein thrombophlebitis in history of venous thromboembolism (sm. section "Special Instructions") .

Application of pregnancy and breastfeeding:

Visanne The drug is contraindicated in pregnant women. If pregnancy occurred during use of Visanne drug, the drug should be discontinued.

Admission Visanne drug during breast-feeding is contraindicated.

Side effect:

Side effects occur more frequently in the first few months of taking the drug Visanne, and over time their number is decreasing. The most common side effects include: vaginal bleeding (including spotting, metrorrhagia, menorrhagia, irregular bleeding), headache, discomfort in the breast, depressed mood and acne.

Table 1 lists adverse drug reactions (ADRs), distributed over the organ system classes. Side effects in each frequency band are presented in order of decreasing frequency. The frequency is defined as "often" (from & ge1 / 100 to <1/10) and "infrequent" (from & ge1 / 1,000 to <1/100).

Drug Interactions:

The influence of other drugs on the drug Visanne

Certain inducers or inhibitors of enzymes (isoenzyme CYP3A)

Progestogens, including dienogest metabolized mainly involving cytochrome P450 3A4 (CYP3A4), located in the intestinal mucosa and in the liver. Accordingly, CYP3A4 inhibitors or inducers may affect the metabolism gestagen preparations.

Increased clearance of hormones, enzymes due to induction can lead to a decrease in therapeutic effect Visanne drug and cause side effects, such as changing the nature of uterine bleeding.

Sexual hormones decrease in clearance due to enzyme inhibition may increase the exposure of dienogest and cause side effects.

- Substances capable of inducing enzymes

May have an interaction with drugs that induce microsomal enzymes (such as cytochrome P450), whereby the clearance of hormones can be increased (to such drug substances include phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, nevirapine, griseofulvin, and preparations containing St. John's wort).

Maximal induction of enzyme, typically not earlier than observed after 2-3 weeks, but may then be stored for at least 4 weeks after cessation of therapy.

The effect of CYP3A4 inducer rifampicin was studied in healthy postmenopausal women. At the same time taking rifampicin with tablets estradiol valerate / dienogest showed a significant decrease in Css and systemic exposure of dienogest. Systemic exposure of dienogest with Css, determined by the value of AUC0-24 h was reduced by 83%.

- Substances capable of inhibiting 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 (such as ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (e.g. nefazodone, fluvoxamine, fluoxetine), and grapefruit juice may increase the concentration of progestin in plasma and cause side effects.

In one study, during which studied the effect of CYP3A4 inhibitors (ketoconazole, erythromycin), the concentration of estradiol valerate and dienogest in plasma at Css were raised. In the case of simultaneous reception with a potent inhibitor ketoconazole value of AUC0-24 h at the equilibrium concentration at the dienogest has increased by 186%. In an application with a moderate CYP3A4 inhibitor erythromycin value of AUC0-24 h in dienogest at Css increased by 62%. The clinical significance of these interactions is not clear.

Effect dienogest other drugs

Based on these in vitro inhibition studies, a clinically significant drug interactions mediated by Visanne with enzymes of the cytochrome P450 metabolism of other drugs is unlikely.

Note: You should read the instructions accompanying drugs for possible interactions.

Interaction with food

Eating a high-fat diet had no effect on the bioavailability of the drug Visanne.

Other interactions

Acceptance of progestogens may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney, plasma concentrations of protein (boosters), such lipid fractions / lipoprotein parameters of carbohydrate metabolism and parameters of coagulation.

Dosage and administration:

Inside. The drug Visanne appointed for 6 months. The decision on further treatment adopted the doctor depending on the clinical picture.

The dosage regimen

Reception of tablets you can start any day of the menstrual cycle. Take one tablet a day without interruption, preferably at the same time every day, if necessary with water or other liquid. Tablets must be taken continuously, regardless of the bleeding of the vagina. After completion of the pills from one package begin taking pills from the next, without making a break in taking the drug.

Omitting the case of tablets and vomiting and / or diarrhea (if it occurs within 3-4 h after administration of the tablet) Visanne drug efficacy may be reduced. When you miss one or more pills a woman should take one tablet as soon as she remembers this, and then the next day to continue taking the tablets at the usual time. Instead of a tablet which is absorbed due to no diarrhea or vomiting should also drink one tablet.

Overdose:

Serious violations were reported in overdose.

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

No specific antidote, symptomatic treatment should be conducted.

Special instructions:

Before you start taking the drug Visanne necessary to exclude pregnancy. While taking the drug if necessary Visanne contraception patients recommended hormonal contraceptive methods (eg barrier).

fertility

According to reports, while taking the drug Visanne most patients ovulation suppression. However, Visanne  is not a contraceptive.

According to available data, the physiological menstrual cycle is restored within 2 months after discontinuation of the drug Visanne.

The question of the application of Visanne drug in women with a history of ectopic pregnancy or a dysfunction of the fallopian tubes should be decided only after careful evaluation of the ratio of expected benefits and possible risks.

Since Visanne  is a preparation with only progestin component, it can be assumed that the special warnings and precautions for use of other drugs of this type are valid in respect of the preparation Visanne, although not all of them are confirmed in the clinical trials of the drug Visanne.

In the presence or worsening of any of the following conditions or risk factors before starting or continuation of Visanne  receiving the drug should carry out an individual assessment of the ratio of benefits and risks.

circulatory disorders

While epidemiological studies have been received is insufficient evidence to support a link between the use of drugs only with a progestin component and an increased risk of myocardial infarction or embolism of cerebral vessels. The risk of cardiovascular events, and cerebrovascular events associated more with increasing age, hypertension and smoking. The risk of stroke in women with hypertension may slightly increase the intake of drugs only with the progestin component.

Epidemiological studies indicate the possibility of a statistically insignificant increase in the risk of venous thromboembolism (deep vein thrombosis, pulmonary embolism) in connection with the use of drugs only with the progestin component. It recognized risk factors for venous thromboembolism (VTE) include relevant family history (VTE in a sibling or a parent at a relatively early age), age, obesity, prolonged immobilization, major surgery or massive trauma. In the event of prolonged immobilization it is recommended to stop taking the drug Visanne  (for elective surgery at least four weeks prior to her) and resume use of the drug only two weeks after the full recovery of motor abilities.

It is necessary to take into account the increased risk of thromboembolism during the postpartum period.

In developing or suspected of arterial or venous thrombosis receiving the drug should be discontinued immediately.

Tumors

A meta-analysis of 54 epidemiological studies showed a slight increase in the relative risk (RR = 1.24) of developing breast cancer in women who have used at the time of the study, oral contraceptives (PC), especially estrogen-progestogen preparations. This increased risk disappears gradually within 10 years after the cessation of the use of combining PC. Because breast cancer is rare in women younger than 40 years, a similar increase in the number of diagnoses in women taking combined PC now or use the combined PC before, is small relative to the total index of the risk of breast cancer. The risk of breast cancer in women using hormonal contraceptives only progestin component may be similar in magnitude to the corresponding risk in connection with the use of combining PC. However, the facts related to drugs only progestin component, based on much smaller populations of women using them and therefore less convincing than for combining the PC data. Establish a causal relationship on the basis of these studies is not possible. This picture is of increased risk may be due to an earlier diagnosis of breast cancer in women taking the PC, the biological action of a PC or a combination of both factors. Malignant breast tumors that are diagnosed in women who had ever used a PC, usually clinically less pronounced than that of women who never used hormonal contraception.

In rare cases, against the background of the use of hormonal substances such as the one contained in the preparation Visanne, noted benign and even more rarely - malignant tumors of the liver. In some cases, these tumors have led to life-threatening intra-abdominal haemorrhage. If a woman taking the drug Visanne, there are severe pain in the upper abdomen, enlarged liver, or there are signs of intra-abdominal bleeding, the differential diagnosis should take into account the probability of having liver cancer.

The changing nature of bleeding

The majority of women receiving the drug Visanne affect the nature of menstrual bleeding.

Against the background of Visanne drug may increase uterine bleeding, for example in women with adenomyosis or uterine leiomyoma. Heavy and prolonged bleeding at the time can lead to anemia (severe in some cases). In such cases, you should consider the abolition of the drug Visanne.

other conditions

Patients with a history of depression need to be closely monitored. If depression recurs to a serious form, the drug should be discontinued.

In general, Visanne, apparently, does not affect blood pressure in women with normal blood pressure. However, if the intake of the drug occurs Visanne persistent clinically significant hypertension, it is recommended to cancel the drug and prescribe antihypertensive treatment.

When relapse cholestatic jaundice and / or cholestatic pruritus, first emerged on the background of pregnancy or previous use of sex steroids, the drug should be abolished Visanne.

Visanne may have little effect on peripheral insulin resistance and glucose tolerance. Women suffering from diabetes, in particular diabetes mellitus in pregnancy history, during reception Visanne preparation needed careful observation.

In some cases there may be chloasma, especially in women with a history of chloasma pregnant. Women who are prone to the development of chloasma, during the administration of the drug Visanne should avoid exposure to the sun or UV radiation.

During the application of the drug may occur Visanne persistent ovarian follicles (often referred to as functional ovarian cysts). Most of these follicles is asymptomatic, although some may be accompanied by pain in the pelvic area.

Lactose

In one tablet of 63 mg is contained Visanne lactose monohydrate. Located on the lactose free diet to patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should be considered contained in the product Visanne amount of lactose.

Additional information but some groups of patients

Children. Visanne is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established in adolescents).

Women in menopause. Not applicable.

Patients with renal failure. No data are available, indicate the need for dose adjustment in patients with kidney disease.