active ingredient: dienogest;
1 tablet contains 2 mg of dienogest
auxiliary substances: lactose, potato starch, microcrystalline cellulose, povidone K 25, talcum, crospovidone, magnesium stearate.
Basic physico-chemical properties: round tablets 7 mm in diameter with beveled edges, white or almost white, with the displaced letter " B " on one side.
Hormones of sexual glands and the preparations, used with the pathology of the sexual organs. Progestogens.
Code ATX G03DB08.
Dienoguest - nortestosterone derivative with no androgenic and with a specific antiandrogenic activity, which is approximately one third the activity of cyproterone acetate. Dienogest binds to progesterone receptors in the uterus with only 10% relative affinity. Despite the low affinity to progesterone receptors, dienogest has a strong progestogenic effect in vivo . Dienogest does not exhibit significant androgen, mineralocorticoid or glucocorticoid activity in vivo .
Dienogest affects endometriosis, reducing endogenous estradiol production and thus suppressing trophic effects of estradiol on eutopic and ectopic endometrium. In continuous use dienoguest leads to the creation of hypoestrogenia, giperestrogenia endocrine environment causing initial decidualization of endometrial tissue followed by atrophy of endometriotic lesions.
The advantage of the drug Visan compared with placebo was demonstrated in a three-month study involving 198 patients with endometriosis. Pelvic pain associated with endometriosis was measured using a visual analog scale (0-100 mm). After 3 months of therapy with the drug Visan, a statistically significant difference was determined compared to placebo (D = 12.3 mm; 95% CI: 6.4 - 18.1; p<0.0001) and a clinically significant reduction in pain compared to the initial level ( average decrease = 27.4 mm ± 22.9).
After 3 months of treatment, reduction of pelvic pain associated with endometriosis by 50% or more was achieved in 37.3% of patients receiving Visan (placebo: 19.8%) without a corresponding increase in the dose of concomitant painkiller; reduction of pelvic pain associated with endometriosis by 75% or more (also without a corresponding increase in the dose of concomitant painkiller) was achieved in 18.6% of patients receiving Visan (placebo: 7.3%).
An open continuation of this placebo-controlled study showed a continuous reduction in endometriosis-related pelvic pain in the treatment of up to 15 months.
The results of placebo-controlled studies were confirmed by the results obtained in a six-month actively controlled study compared with the gonadotropin-releasing hormone agonist involving 252 patients with endometriosis.
Three studies involving 252 patients receiving dienogest of 2 mg per day showed a significant decrease in endometrioid lesions after 6 months of treatment.
In a small study (n = 8 per dosing group), the use of dienogest at a dose of 1 mg per day revealed a lack of ovulation after 1 month of therapy. Wizan has not been investigated for contraceptive efficacy in large studies.
The level of endogenous estrogen is only moderately suppressed during the treatment of visans.
Currently, the results of long-term studies of bone mineral density (IGC) and the risk of fractures in patients taking the drug Visan are not yet available. IGC was evaluated in 21 adult patients before and after 6 months of treatment of Byzantines. The decrease in the average indicator of IPC was not revealed. In 29 patients treated with leuprolide acetate, the mean reduction of 4.04% ± 4,84, it was noted during the same period (D between groups = 4,29%, 95% CI: 1.93 and-of 6.66, p
There has been no significant impact on standard laboratory parameters, including the results of the analysis of blood, biochemical analysis of blood, the level of liver enzymes, lipid levels and HbA1с, during treatment Visan for 15 months (N = 168).
Safety data for adolescents
The safety of the drug Visan regarding the IPC was investigated during uncontrolled study over 12 months involving 111 patients of the adolescent (12 to
Data from preclinical safety studies
Data from preclinical studies do not indicate the existence of a particular risk for humans on the basis of standard studies of toxicity in multiple intake, genotoxicity, carcinogenic effects and toxic effects on reproductive function. However, it should be taken into account that sex steroids can contribute to the growth of certain hormone-dependent tissues and tumors.
After taking dienogest quickly and completely absorbed. The maximum concentration in serum is achieved within 1.5 hours after a single oral administration and is 47 ng/ml. Bioavailability of dienogest is about 91%. Pharmacokinetics of dienogest depends on the dose in the range of doses 1-8 mg.
Dienoguest is bound to albumin and does not bind globulin, linking sex hormones (SHBG), or globulin that binds GCS (GOK). Only 10% of the total serum dienogest concentration is in the form of a free steroid, and 90% is non - specific to albumin. The apparent volume of the distribution of dienogest is 40 liters.
Dienogest is completely metabolized by the known steroid metabolism methods, with the formation of predominantly endocrinological inactive metabolites. Based on studies in vitro and in vivo CYP3A4-the main enzyme involved in the metabolism of dienogest. These metabolites are very rapidly excreted from the plasma in such a way that the dominant metabolite in the blood plasma is dienogest unchanged.
The rate of clearance of serum is 64 ml/min.
The level of dienogest in serum decreases in two phases with a half-life of 9-10 hours. Dienogest is excreted as metabolites with urine and feces in a ratio of about 3: 1 after oral administration at a dose of 0.1 mg/kg.the half-life of metabolites with urine is about 14 hours. After taking 86% of the dose is excreted from the body within 6 days, most of this amount is excreted in the first 24 hours, mainly with urine.
state of equilibrium
Pharmacokinetics of dienogest does not depend on the level of gspg. With daily intake of serum concentration increases by 1.24 times, reaching an equilibrium state after 4 days of use. Pharmacokinetics of dienogest after repeated use of the drug Visan can budi provided on the basis of the pharmacokinetics of one dose.
Pharmacokinetics in special groups of patients
In patients with impaired renal function the pharmacokinetics of a drug Visan has not been studied.
In patients with hepatic impairment the pharmacokinetics of a drug Visan has not been studied.
Treatment of endometriosis.
The drug viz should not be used in the presence of any of the following conditions or diseases. This information is partly derived from the use of other drugs containing only progestagen. If any of these conditions or diseases occurs for the first time during the use of the drug Visan, the drug should be stopped immediately.
Venous thromboembolism in the active form.
History of arterial or cardiovascular diseases (e.g. myocardial infarction, cerebrovascular event, ischemic heart disease).
Diabetes mellitus with vascular lesions.
Severe liver disease at present or their presence in the history, while liver function indicators are not normal.
Tumors of liver disease (benign or malignant).
Or suspected malignant tumors that are dependent on sex hormones.
Vaginal bleeding of unclear etiology.
Hypersensitivity to the active substance or to any of the components of the drug.
Interaction with other medicinal products and other forms of interaction
Note: in order to identify possible interactions, you should read the instructions for the use of drugs used in conjunction.
The effect of other drugs on Visan
Progestogens, including dienogest, are metabolized primarily by the cytochrome P450 ZA4 (CYP3A4) system located in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 may affect the metabolism of the progestogen. Increased clearance of sex hormones through the induction of enzymes can reduce the therapeutic effect of visans and lead to undesirable effects, such as changes in the nature of menstrual bleeding.
Reducing the clearance of sex hormones due to enzyme suppression can reduce the therapeutic effect of visans and lead to the development of adverse reactions.
Substances that increase the clearance of sex hormones (reduced efficiency by inducing enzymes), for example: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort ( Hypericum perforatum )
The induction of enzymes can be observed after several days of therapy. The maximum induction of enzymes as a whole is manifested in a few weeks.
The induction of enzymes can last up to 4 weeks after the termination of therapy.
The influence of the inductor CYP ZA4 rifampicin was studied in healthy women in the post-menopausal period. The simultaneous use of rifampicin with a tablet form of estradiol valerate/dienogest led to a significant decrease in the equilibrium concentration and systemic effects of dienogest and estradiol. Systemic effects dienogest and estradiol at steady state, measured by AUC (0 - 24h), were decreased by 83% and 44% respectively.
Substances with different effects on the clearance of sex hormones.
Concomitant use of a large number of combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors with sex hormones, combined with combinations of hepatitis C virus inhibitors, can increase or decrease the level of progestin in blood plasma. The cumulative effect of these changes may be clinically significant in some cases.
Substances that reduce the clearance of sex hormones (enzyme inhibitors).
Dienogest is a substrate of cytochrome P450 (CYP) 3A4.
The clinical significance of potential interactions with enzyme inhibitors remains unknown.
Concurrent use of strong inhibitors of CYP3A4 can increase the plasma concentrations of dienogest.
Concurrent use with potent CYP3A4 enzyme inhibitor ketoconazole led to an increase of 2.9 times the AUC (0 - 24 hours) dienogest in the equilibrium state. Simultaneous application with the moderate inhibitor erythromycin resulted in an increase in 1.6 times the AUC (0 - 24 hours) dienogest in the equilibrium state.
Effect of dienogest on other drugs
According to the results of in vitro inhibition studies , clinically significant interaction of dienogest with other drugs, the metabolism of which is mediated by cytochrome P450 enzymes, is unlikely.
Interaction with food products
Meal with a high fat content does not affect the bioavailability of the medication vizan.
Receiving a progestogen may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, kidneys and adrenal glands, levels of the proteins (carriers) in the blood plasma (for example mining and the fraction of lipids/lipoproteins), parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes usually remain within the laboratory norm.
Since Visan is a drug containing only progestagen, it is believed that special warnings and safety measures for the use of progestin preparations also concern Visan, although not all warnings and precautions are based on the relevant results of clinical studies of this particular drug.
If any of the following conditions/risk factors deteriorate or occur for the first time, the risk/benefit ratio must be analyzed individually before starting or continuing the administration of the drug Visan.
Severe uterine bleeding
Uterine bleeding, for example, in women with uterine adenomyosis or uterine leiomyoma may increase with the use of the drug vizan. If bleeding is expressed and does not stop for a long time, it can lead to anemia (in some cases, severe). In this case, you need to consider stopping taking the drug.
Changes in the nature of bleeding
Treatment with the drug Visan affects the nature of menstrual bleeding in most women (see section "Adverse reactions").
Based on the results of epidemiological studies revealed a small amount of data on the existence of a relationship between the use of drugs containing progestagen only, and increased risk of myocardial infarction or cerebral thromboembolism. The risk of cardiovascular and cerebral events is more related to age, hypertension and Smoking. In women with hypertension, the risk of stroke may slightly increase with the use of drugs containing only progestagen.
Some studies indicate the existence of a certain, but not statistically significant increase in the risk of venous thromboembolism (deep vein thrombosis, pulmonary thromboembolism) associated with the use of drugs containing only progestagen. Recognized factors that increase the risk of venous thromboembolism (VTE) include: personal or family history (for example, cases of VTE have siblings or parents at a relatively young age); age; obesity, prolonged immobilization, radical surgery or injury. In the case of prolonged immobilization, it is recommended to stop the use of the drug Visan (with planned operations at least 4 weeks before it) and not restore it before 2 weeks after full rehabilitation.
It is necessary to take into account the increased risk of thromboembolism in the puerperium.
In case of any symptoms of venous and arterial thrombotic diseases or suspicion on them, treatment should be discontinued.
A meta-analysis of 54 epidemiological studies indicate a slight increase in the relative risk (RR = 1,24) of developing breast cancer in women using oral contraceptives (OC), mainly containing estrogen-progestogen. This increased risk gradually disappears during the 10 years after the end of the reception of combined oral contraceptives (COCs). Because breast cancer is rare in women under the age of 40, the increase in the number of breast cancer cases in women who use or recently COC is negligible relative to the overall risk of breast cancer. There is the same risk of breast cancer in women taking preparations containing only progestogen, or a cook. However, the information concerning preparations containing only progestagen is based on a much smaller number of women who use it, and therefore less convincing than the data concerning COC. The results of these studies do not provide evidence of the existence of a causal relationship. The increased risk may be due to both an earlier diagnosis of breast cancer in women using OK, and the biological effects of these drugs, or a combination of both factors. There is a tendency that breast cancer detected in women has ever been taken OK, clinically less pronounced than those who have never used oral contraceptives.
In rare cases, women taking hormonal substances, such as the one that contains the medication vizan, was observed benign and even more rarely - malignant liver tumors, which in some cases led to life-threatening intra-abdominal hemorrhage. In case of complaints of severe epigastric pain, enlarged liver or signs of intra-abdominal hemorrhage in the differential diagnosis should take into account the possible presence of liver tumors in women taking medication vizan.
The changes of mineral bone density (BMD).
The use of the drug Visan adolescents (12 - 18 years) during the period of treatment 12 months was associated with a decrease in the average value of MPT in the lumbar spine (L2 - L4) by 1.2%. After the termination of treatment, the MPT increased again in these patients.
The average relative change from baseline to end of treatment was 1.2% with a range between -6% and 5% (95% CI: -1.70% and -0.78%, n = 103). Repeated measurement 6 months after the end of treatment in the subgroup with low values of ivct showed a tendency to recovery (average relative change from the baseline: -2.3% at the end of treatment and -0.6% 6 months after the end of treatment with a range between - 9% and 6% (DI 95%: -1.20% and 0.06% (n = 60))).
Violation of mineral bone density is of particular importance in adolescence and in early puberty, a critical period of bone growth. Unknown, will reduce peak bone mass and increase the risk of bone fracture in old age, the decline in BMD in this population (see Section "Children" and "Pharmacological properties").
Before starting treatment, the doctor should weigh the benefits of the drug Visan and the possible risks of use for each individual child, taking into account also the presence of significant risk factors for osteoporosis.
The proper use of calcium and vitamin D in the diet or by using supplements is important for healthy bone condition in women of all age categories.
There was no decrease in BMD in adults (see Section "Pharmacodynamic properties").
Patients who are at increased risk of osteoporosis, a careful assessment of risk/benefit should be performed before treatment Visan, because the level of endogenous estrogens is moderately reduced on the background of treatment medication vizan (see "Pharmacological").
As patients with a history of depression should carefully observe and cancel the drug in the development of severe manifestations of depression.
Dienoguest, as a rule, does not affect blood pressure in normotensive women. However, if prolonged clinically expressed hypertension occurs when using the drug, it is recommended to cancel the drug Visan and treat hypertension.
In case of recurrent cholestatic jaundice and/or pruritus, which occurred during pregnancy or previous use of sex hormones, the drug should be discontinued.
Dienogest may have a slight effect on peripheral insulin resistance and glucose tolerance. Women with diabetes mellitus, especially with a history of gestational diabetes, should be carefully examined throughout the use of the drug Visan.
Sometimes it can develop chloasma, especially in women with chloasma pregnant women in history. Women who are prone to chloasma should avoid exposure to direct sunlight or ultraviolet radiation while taking vizan.
The likelihood of ectopic pregnancy in women who use drugs containing only progestagen for contraception is higher than in women taking COC. Therefore, for women with a history of ectopic pregnancy or impaired function of the fallopian tubes, the use of the drug Visan should be decided only after a thorough assessment of the benefit/risk ratio.
During the application of the medication vizan can cause persistence of follicles (often noted as functional ovarian cysts). Most of these follicles are asymptomatic, although some may be accompanied by pain in the pelvic region.
Not used in geriatric practice.
Each Visan tablet contains 62.8 mg of monohydrate lactose. Patients with rare hereditary diseases associated with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose who adhere to a lactose-free diet should take into account the amount of this substance in the tablet of the drug Visan.
Use during pregnancy or breast-feeding.
There are limited data on the use of dienogest pregnant women. Animal studies do not indicate direct or indirect risks to reproductive toxicity (see Section "Pharmacological properties").
Vizan is not recommended for pregnant women, as there is no need to treat endometriosis during pregnancy.
Treatment medication vizan during the period of breast-feeding is not recommended. Unknown, dienogest penetrates into the breast milk of a woman. Data obtained in animal studies indicate the penetration of dienogest into breast milk. A decision should be made to discontinue breastfeeding or discontinue therapy with vizan, taking into account the benefits of breastfeeding for the child and the need for therapy for the woman.
Based on the available data, it can be argued that during the treatment of visans, ovulation is inhibited in most patients. However, the drug viz is not a contraceptive.
If you need contraception, you should additionally apply non-hormonal method of preventing pregnancy (see section"dosage and Administration").
On the basis of the available data, it can be argued that the menstrual cycle returns to normal within 2 months after the termination of treatment of Byzantines.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms.
No influence was observed on the ability to drive vehicles and control mechanisms in patients taking drugs containing dienogest.
Method of application and doses
method of application
For oral administration.
Take 1 tablet daily without interruption in taking the drug at about the same time, drinking a small amount of liquid. Tablets can be taken with or without food.
Tablets should be taken regularly, regardless of menstrual bleeding. As soon as the pill of one pack is over, start taking pills from the next pack without a break in use of the drug.
There is no experience in treating vizan patients with endometriosis for more than 15 months.
The drug can be started on any day of the menstrual cycle.
The use of any hormonal contraceptives should be stopped before starting therapy with the drug vizan. If contraception is necessary, a non-hormonal method of prevention (for example, a barrier method) should be additionally applied.
Skipping drug intake
In the case of missing the pill, vomiting and/or diarrhea (which took place within 3-4 hours after taking the pill), the effectiveness of the drug Visan may decrease. If you skip taking one or more tablets 1 tablet should be taken as soon as the woman remembers about it, and the next take at the usual time. Similarly, the tablet, not absorbed through vomiting or diarrhea, should be replaced by another tablet.
Additional information on application in special groups of patients
There are no relevant indications for the use of the drug Visan patients of this group.
The drug is contraindicated in patients with severe liver disease history (see section "Contraindications").
There is no evidence of the need for dose adjustment for patients with renal insufficiency.
The drug Visan is not indicated for use in children before menarche.
Safety and efficacy of the drug Visan were studied in an uncontrolled study for 12 months in 111 adolescent patients (12 -
The efficacy of the drug Visan was demonstrated in the treatment of endometriosis associated with pelvic pain in adolescents (12-18 years) with a General favorable profile of safety and tolerance of the drug.
The use of the drug Visan in adolescents during treatment for 12 months was associated with a decrease in the average value of bone mineral density (mpkt) in the lumbar spine by 1.2%. After the termination of treatment, the MPT increased again in these patients.
Violation of mineral bone density is particularly important in adolescence and early puberty, a critical period of bone growth. It is not known will reduce peak bone mass and increase the risk of bone fracture in old age, the decline in BMD in this population.
Therefore, the doctor should weigh the benefits of the drug Visan and the possible risks of application for each individual teenager (see Sections "features of application", "Pharmacodynamic properties").
The study of acute toxicity carried out with Dienogest did not indicate the risk of acute adverse reactions in the case of unintentional administration of several daily therapeutic doses. There are no specific antidotes. The use of 20-30 mg of dienogest per day (10-15 times higher than the dose in the tablet drug Visan) for more than 24 weeks were very well tolerated.
Adverse reactions are described according to MedDRA.
Adverse reactions often develop during the first months of administration of the drug Visan and disappear during treatment. There may be changes in the nature of bleeding, such as spotting, irregular bleeding or amenorrhea.
The following adverse reactions were reported during the treatment of Byzantines. Side effects, most commonly reported during the treatment of Byzantines, include headache (9.0%), discomfort in the mammary glands (5.4%), depressed mood (5.1%) and acne (5.1%) .
In addition, the drug Visan affects the nature of menstrual bleeding in most women. The nature of menstrual bleeding was assessed systematically using patient diaries and analyzed using the who method during the 90-day reporting period. During the first 90 days of therapy with vizan, the following bleeding patterns were observed (n = 290, 100%): amenorrhea (1.7%), rare bleeding (27.2%), frequent bleeding (13.4%), irregular bleeding (35 , 2%), prolonged bleeding (38.3%), normal menstrual bleeding, that is, none of the previous categories (19.7%). During the fourth reporting period, the following bleeding patterns were observed (n = 149, 100%): amenorrhea (28.2%), rare bleeding (24.2%), frequent bleeding (2.7%), irregular bleeding (21.5%), prolonged bleeding (4.0%), normal menstrual bleeding, that is, none to one of the previous categories (22,8%). Changes in the nature of menstrual bleeding only occasionally reported as adverse reactions in patients (see the table of adverse reactions).
Table 1 lists the adverse reactions according to the MedDRA classification (MedDRA SOCs) reported during treatment Visan, and their frequency.
Within each group, the side effects are indicated in order of frequency reduction: often (?1/100 to<1/10) and infrequently (?1/1000 to<1/100). The frequency was determined based on the combined data of four clinical trials involving 332 patients (100%).
Adverse reactions, phase III clinical trials, N = 332
Organ systems (MedDRA)zastonecesda
From the blood and lymphatic systems anemia
Metabolism and metabolic disorders weight gain body weight reduction, increased appetite
mental disorders compounded mood, sleep disturbance, nervousness, decreased libido, mood changes anxiety, depression, mood lability
From the nervous systemically pain, millennialmedia autonomic regulation, impaired attention
On the part of the eye dryness
On the part of hearing and vestibular tinnitus
Cardiac non-specific circulatory disorders, tachycardia
From the vessels hypotension
Respiratory system, chest and shortness of breath
From the gastrointestinal tract, abdominal pain, flatulence, bloating, vomiting, constipation, discomfort in the abdomen, inflammation of the gastrointestinal tract, gingivitis
The skin and subcutaneous Khatchatrian, alopeciathe skin, hyperhidrosis, pruritus, hirsutism, oligoclase, dandruff, dermatitis, impaired hair growth, photosensitivity, pigmentation changes
On the part of the musculoskeletal system and connective of danabol in spinball in the bones, muscle cramps, pain in limbs, feeling of heaviness in the limbs
The kidneys and urinary system urinary tract infection
From the reproductive system and mammary salesdiscount the Breasts, ovarian cysts, hot flushes uterine/vaginal bleeding,
including roomselegantly candidiasis, dryness of the vulva and vagina, discharge from genitals, pain in the pelvic area, atrophic vulvovaginitis, breast enlargement, fibrocystic breast disease, breast engorgement
General disorders and local reactivations state rastitelnosti
Was also observed following side effects: persistence of the follicles, increased appetite, hypersensitivity reactions.
Other serious adverse reactions were observed in the application of the steroid sex hormones, a progestogen (see Section "Peculiarities of application"): venous and arterial thromboembolic disorders, arterial hypertension, myocardial infarction, stroke, neoplasms of the mammary glands, tumors of the liver, discomfort in the back, chloasma, cholestatic jaundice, osteoporosis (see below), changes in glucose tolerance or effect on peripheral insulin resistance.
The decrease in mineral bone density
In the course of an uncontrolled clinical trial involving 111 adolescent patients (12 to
The message of suspected adverse reactions
The message of suspected adverse reactions in the period of post-marketing surveillance is very important. This makes it possible to control the use/risk ratio of drugs. Health workers should report suspected adverse reactions.
Does not require any special storage conditions. Store in the original packaging, out of reach of children.
Do not use the product after the expiry date indicated on the package.
For 14 tablets in a blister, 2 blisters in a cardboard box.
Category home away from home
Bayer Weimar GmbH & Co. KG, Germany/Bayer Weimar GmbH & Ko. KG, Germany.
Manufacturer's location and address of the place of business
Dobrinishte 20 99427 Weimar, Germany/
Dobereinerstrasse 20 99427 Weimar, Germany.
VIZAN PILLS 2MG
Specialized hormonal pharmaceuticals used for the treatment of pathologies of the genital organs. Therapeutic efficacy is achieved due to the part of the main active ingredient – dienogest (2 mg), which is characterized by pronounced antiandrogenic activity. It is shown in the presence of obvious foci of endometriosis. Reduces the endogenous production of estradiol, inhibiting its trophic effect on the endometrium. Causes a gradual atrophy of the endometrial lesions.
The drug is intended for oral administration. "Visan" is used every day at the same time, 1 table./day. Tablets are taken regularly and continuously for 6 months. The beginning of therapy may occur on any day of the cycle. In case of admission, the patient should drink the forgotten pill as soon as she remembers it. The purpose of this product should be made by a doctor on the basis of the clinical picture of the disease.
Unacceptable use "of Visana" with:
Diabetes mellitus type, venous thromboembolism, ischemia hearts.
Pathologies of the liver, hormone-dependent tumors.
Hypersensitivity to individual components.