Vizanna

General characteristics. Structure:

Active agents: Диеногест micronized 2,000 mg
Auxiliary veshchestva:laktoza monohydrate of 62,800 mg, starch of potato 36,000 mg, cellulose of microcrystallic 18,000 mg, povidon-K25 - 8,100 mg, talc - 4,050 mg, кросповидон-2,700 mg, magnesium stearate - 1,350 mg.
Description. Round white or almost white tablets with a flat surface and slanted edges, an engraving "In" on one party.

Pharmacological properties:

Pharmacodynamics. Диеногест the nortestosterona is derivative, being characterized by the anti-androgenic activity making about one third of activity of a tsiproteron of acetate. Диеногест contacts progesterone receptors in a uterus of the person, having only 10% of relative affinity of progesterone. Despite low affinity to progesterone receptors, диеногест it is characterized by powerful progestagenny effect of in vivo. Диеногест has no essential mineralokortikoidny or glucocorticoid activity of in vivo.
Диеногест influences endometriosis by suppression of trophic effects of estrogen concerning an eutopichesky and ectopic endometria, owing to decrease in products of estrogen in ovaries and reduction of their concentration in plasma.
At long use causes an initial detsidualization of fabric of an endometria with the subsequent atrophy of the endometrioid centers. Additional properties of a diyenogest, such as immunological and antiangiogenic effects as it is represented, promote its overwhelming impact on proliferation of cells.
Decrease in mineral density of a bone tissue (MPK), and also significant influence of drug of Vizann on standard laboratory parameters, including the general and biochemical indicators of blood, liver enzymes, lipids and HbAlC is noted. Диеногест moderately reduces production of estrogen in ovaries.

Pharmacokinetics.

• Absorption

After oral administration диеногест it is quickly and almost completely soaked up. The maximum concentration in blood serum making 47 ng/ml is reached approximately in 1,5 h after one-time oral administration. Bioavailability makes about 91%. The pharmacokinetics of a diyenogest in the dose range from 1 to 8 mg is characterized by a dozozavisimost.

• Distribution
Диеногест contacts a seralbumin and does not contact the globulin, connecting sex hormones (G,CSH), and also about the corticosteroid-the connecting globulin (CCG). 10% of the general concentration of substance in blood serum are in a type of a free steroid whereas about 90% are nonspecific connected with albumine.

The seeming volume of distribution of a diyenogest makes 40 l.

• Metabolism

Диеногест it is almost completely metabolized preferential by a hydroxylation with formation of several almost inactive metabolites. Proceeding from results of the researches in vitro and in vivo, the main enzyme participating in metabolism of a diyenogest is CYP3A4. Metabolites are removed very quickly so the prevailing fraction in a blood plasma is not changed диеногест.

Speed of metabolic clearance makes 64 ml/min. of blood serum.

• Elimination

Concentration of a diyenogest in blood serum decreases dvukhfazno. The elimination half-life in a terminal phase makes about 9-10 h. After intake in a dose of 0,1 mg/kg диеногест it is removed in the form of metabolites which are allocated through kidneys and intestines in the ratio about 3: 1. The elimination half-life of metabolites at their excretion kidneys makes 14 h. After oral administration about 86% of the received dose it is removed within 6 days, and the main part is removed in the first 24 hours, preferential by kidneys.

• Equilibrium concentration

The pharmacokinetics of a diyenogest does not depend on the GSPG level. Concentration of a diyenogest after daily reception increases in blood serum approximately by 1,24 times, reaching equilibrium concentration in 4 days of reception. The pharmacokinetics of a diyenogest after multiple dose of Vizanna can be predicted on the basis of pharmacokinetics after one-time reception.

Indications to use:

Treatment of endometriosis

Route of administration and doses:

For intake.
Vizann's drug is appointed to 6 months. The decision on further therapy is made by the doctor depending on a clinical picture.

Scheme of reception
Reception of tablets can be begun in any day of a menstrual cycle.
Accept on one tablet a day without interruption, preferably at the same time every day, if necessary washing down with water or other liquid. A pill needs to be taken continuously regardless of bleedings from a vagina. After completion of reception of tablets from one packaging begin reception of tablets from following, without doing a break in administration of drug.
At the admission of tablets and in case of vomiting and/or diarrhea (if it occurs in limits 3k4 hours after reception of a tablet) efficiency of drug of Vizann can decrease. In case of the admission of one or several tablets the woman should take one pill as soon as she remembers it, and then next day to continue reception of tablets in usual time. Instead of a tablet which was not absorbed owing to vomiting or diarrhea it is also necessary to take one medicine.

Features of use:

Before administration of drug of Vizann it is necessary to exclude pregnancy. During administration of drug of Vizann in need of contraception patients are recommended to apply non-hormonal contraceptive methods (for example, barrier).

Fertility
According to the available data, during administration of drug of Vizann most of patients has a suppression of an ovulation. However Vizanna is not a contraceptive.
According to the available data, the physiological menstrual cycle is recovered within 2 months after the termination of administration of drug of Vizann.
 
The question of use of drug of Vizann for women with an extrauterine pregnancy in the anamnesis or with dysfunction of uterine tubes has to be solved only after careful assessment of a ratio of the expected advantage and possible risk.
As Vizanna represents drug only with a gestagenny component, it is possible to assume that special cautions and precautionary measures when using other drugs of this kind are valid also concerning Vizann's drug though not all from them are confirmed in the course of clinical trials of drug of Vizann.
At existence or aggravation of any of the listed below states or risk factors, before the beginning or continuation of administration of drug of Vizann it is necessary to carry out individual assessment of a ratio of advantage and risk.

Blood circulation disturbances
In the course of the epidemiological researches it was received not enough facts confirming existence of communication between use of drugs only with a gestagenny component and the increased risk of a myocardial infarction or thromboembolism of vessels of a brain. The risk of cardiovascular episodes and disturbances of cerebral circulation is connected more likely with increase in age, an arterial hypertension and smoking. The risk of development of a stroke in women with an arterial hypertension can increase a little against the background of administration of drugs only with a gestagenny component.
Epidemiological researches indicate a possibility statistically not of significant increase in risk of a venous thromboembolism (a deep vein thrombosis, an embolism of a pulmonary artery) in connection with use of drugs only with a gestagenny component. The age, obesity, a long immobilization, extensive surgical intervention or a massive injury belong to the conventional risk factors of development of a venous thromboembolism (VTE) the corresponding family anamnesis (VTE at the brother, the sister or at one of parents at rather early age). In case of a long immobilization it is recommended to stop administration of drug of Vizann (at planned operation, at least, in four weeks prior to it) and to resume drug use only in two weeks after a complete recovery of motive ability.

It is necessary to consider the increased risk of development of a thromboembolism in a puerperal period.
At development or suspicion on development of arterial or venous thrombosis administration of drug should be stopped immediately.

Tumors
Meta-analysis of 54 epidemiological researches revealed small increase in relative risk (the SHOUTING = 1,24) development of a breast cancer in the women using the oral contraceptives (OC) at the time of the research is preferential oestrogenic-gestagennye drugs. This increased risk gradually disappears within 10 years after the termination of use of the combined oral contraceptives. As the breast cancer seldom occurs at women more young than 40 years, some increase in number of similar diagnoses at the women accepting the contraceptives combined peroral at the moment or using the contraceptives combined peroral earlier is small in relation to the general indicator of risk of developing of a breast cancer. The risk of detection of a breast cancer at the women using hormonal contraceptives only with a gestagenny component, perhaps is similar in size to the corresponding risk in connection with use of the combined oral contraceptives. However the facts relating to drugs only with a gestagenny component are based on much populations, smaller on number, of the women using them and therefore are less convincing, than data on the combined oral contraceptives. It is not possible to establish relationship of cause and effect on the basis of these researches. The revealed picture of increase of risk can be caused by earlier diagnosis of a breast cancer at the women accepting the personal computer, biological effect of the personal computer or a combination of both factors. Malignant tumors of a mammary gland which are diagnosed for the women ever using the personal computer, as a rule, are clinically less expressed, than at women who never used hormonal contraception.
In rare instances against the background of use of the hormonelike materials similar to that which contains in Vizann's drug, were noted high-quality, and is even more rare - malignant tumors of a liver. In some cases these tumors led to the intra belly bleeding posing a threat for life. If at the woman accepting Vizann's drug severe pains in an upper part of a stomach take place, the liver is increased or there are symptoms of intra belly bleeding, then at differential diagnosis it is necessary to consider probability of existence of a hepatic tumor.

Change of nature of bleedings

At most of women administration of drug of Vizann influences the nature of menstrual bleedings.
Against the background of use of drug of Vizann uterine bleedings, for example, at women with an adenomyosis or a leiomyoma of a uterus can amplify. Plentiful and enduring bleedings can lead to anemia (in certain cases heavy). In such cases it is necessary to consider a question of drug withdrawal of Vizann.

Other states
Patients with a depression in the anamnesis need careful observation. If the depression recurs in a serious form, drug should be cancelled.
In general, Vizanna, most likely, does not influence arterial pressure at women with normal arterial pressure. However if against the background of administration of drug of Vizann there is persistent clinically significant arterial hypertension, it is recommended to cancel drug and to appoint anti-hypertensive treatment.
At a recurrence of cholestatic jaundice and/or cholestatic itch, for the first time arisen against the background of pregnancy or the previous use of sexual steroids, Vizann's drug needs to be cancelled.
Vizanna can exert insignificant impact on peripheral insulin resistance and tolerance to glucose. The women suffering from a diabetes mellitus, in particular in the presence of a diabetes mellitus of pregnant women in the anamnesis during administration of drug of Vizann need careful observation.
In certain cases can take place of a hloazm, especially at women with hloazmy pregnant women in the anamnesis. To the women inclined to development of a hloazma, during administration of drug of Vizann it is necessary to avoid influence of the sun or ultraviolet radiation.
During use of drug of Vizann there can be persistent follicles of ovaries (which are often called by functional cysts of ovaries). The majority of such follicles has symptomless character though some can be followed by pains in the field of a basin.

Lactose
Contains in one tablet of drug of Vizann 63 mg of lactose of monohydrate. To the patients who are on a delactosed diet with rare inherited disorders, such as intolerance of a galactose, deficit of Lapp lactase or glyukozo-galaktozny malabsorption, it is necessary to consider the lactose volume which is contained in Vizann's drug.
Additional information on some groups of patients
Children
Vizanna is contraindicated to children and teenagers up to 18 years (efficiency and safety of use for teenagers are not established). Women in a postmenopause it is not applied.
Patients with a renal failure
There are no data indicating the need corrections of a dose at patients with diseases of kidneys.

Medical examination
Before the beginning or resuming of administration of drug of Vizann it is necessary to get acquainted in detail with a case history of the patient and to conduct physical and gynecologic examination. Frequency and the nature of such inspections have to be based on the existing norms of medical practice at the necessary accounting of specific features of each patient (but at least 1 time in 3 - 6 months) and have to include measurement of arterial pressure, assessment of a condition of mammary glands, an abdominal cavity and pelvic bodies, including a cytologic research of an epithelium of a neck of uterus.

Influence on ability to drive the car and mechanisms
As a rule, Vizann's drug does not influence ability to driving and work with mechanisms, however patients at whom disturbances of concentration of attention are noted have to be careful.

Side effects:

System and organ class	Often	Infrequently
Hemolymphatic system		Anemia
Metabolism and alimentary disturbances	Increase in body weight	Decrease in body weight Increase in appetite
Nervous system	Headache Migraine Reduced mood Sleep disorder (including sleeplessness) Nervousness Loss of a libido Change of mood	Imbalance of a peripheral nervous system Disturbance of attention Uneasiness Depression Mood swings
Organ of sight		Feeling of a xerophthalmus
Acoustic organ		Ring in ears
Cardiovascular system		Not specified blood circulation disturbance Heartbeat Arterial hypotension
Respiratory system		Asthma
Alimentary system	Nausea Pains in a stomach (including pains in the bottom of a stomach and pain in epigastriums) Meteorism Feeling of a raspiraniye of a stomach Vomiting	Diarrhea Lock Discomfort in a stomach Inflammatory diseases of digestive tract Ulitis
Skin and hypodermic cellulose	Acne Alopecia	Xeroderma Hyperhidrosis Itch Anomalies of growth of hair, including hirsutism and hypertrichosis Onikhoklaziya Dandruff Dermatitis Photosensitivity reactions Pigmentation disturbance
Musculoskeletal system	Dorsodynias	Ostealgias Muscular spasms Extremity pains Heavy feeling in extremities
Urinary system		Infection of uric ways (including cystitis)
Reproductive system and mammary glands	Discomfort in mammary glands (including increase in mammary glands and mammary gland pain) Oothecoma (including a hemorrhagic cyst) Heat inflows Uterine bleedings / bleedings from a vagina (including the smearing allocations, metrorrhagias, menorrhagias, irregular bleedings) Amenorrhea	Vagina candidiasis Dryness in vulvovaginal area (including dryness of mucous) Allocations from generative organs (including allocations from a vagina) Pains in pelvic area Atrophic vulvovaginitis Fibrous and cystous mastopathy Consolidation of mammary glands
The general pathology and states in an injection site	Asthenic state (including fatigue, an adynamy and an indisposition) Irritability	Hypostasis (including a face edema)

 

Interaction with other medicines:

•  Influence of other medicines on Vizann's drug Separate inductors or inhibitors of enzymes (CYP3A isoenzyme)
Gestagena, including диеногест, are metabolized preferential with participation of the system of P450 3A4 cytochrome (CYP3A4) located both in mucous intestines and in a liver. Therefore, inductors or CYP3A4 inhibitors can influence metabolism of gestagenny drugs.
The increased clearance of sex hormones caused by induction of enzymes can lead to decrease in therapeutic effect of drug of Vizann, and also cause side effects, for example, change of nature of uterine bleedings.
Decrease in clearance of sex hormones in connection with inhibition of enzymes can increase exposure of a diyenogest and cause side effects.

- The substances capable to induce enzymes

Interaction with the drugs inducing microsomal enzymes (for example, systems of P450 cytochrome) can take place therefore the clearance of sex hormones can increase (Phenytoinum, barbiturates, Primidonum, carbamazepine, rifampicin and, perhaps, also окскарбазепин, топирамат, фелбамат, not Virapinum, griseofulvin, and also the drugs containing a St. John's Wort belong to such drugs).
The maximum induction of enzymes is, as a rule, noted not earlier than in 2-3 weeks, however then can remain within not less than 4 weeks after the therapy termination.
The effect of the inductor CYP3A4 of rifampicin was studied at healthy women in a postmenopause. At a concomitant use of rifampicin with valerate oestradiol tablets / диеногеста essential decrease in equilibrium concentration and system exposure of a diyenogest was noted. The system exposure of a diyenogest at equilibrium concentration determined by the size AUC(0-24 of the h), was reduced by 83%.

- The substances capable to inhibit enzymes

The known CYP3A4 inhibitors, such as azolny antifungal drugs (for example, кетоконазол, итраконазол, флуконазол), Cimetidinum, verapamil, macroleads (for example, erythromycin, кларитромицин and рокситромицин), diltiazem, inhibitors of proteases (for example, ритонавир, саквинавир, индинавир, нелфинавир), antidepressants (for example, нефазодон, флувоксамин, fluoxetine) and grapefruit juice, can increase concentration of gestagen in a blood plasma and cause side effects.
In one research in the course of which the effect of CYP3A4 inhibitors was studied (a ketokonazola, erythromycin) concentration of oestradiol of valerate and a diyenogest in a blood plasma at equilibrium concentration were increased. In case of a concomitant use with powerful inhibitor ketokonazoly the size AUC(0-24 of the h) at equilibrium concentration at a diyenogest increased for 186%. At simultaneous use with moderate CYP3A4 inhibitor erythromycin the size AUC(0-24 of the h) at a diyenogest at equilibrium concentration increased by 62%. Clinical value of these interactions is not found out.
 
• Influence of a diyenogest on other medicinal substances

Proceeding from these researches of inhibition in vitro, clinically significant interaction of drug of Vizann with the metabolism of other medicinal substances mediated by enzymes of system of P450 cytochrome it is improbable.
Note: for identification of possible interactions it is necessary to study instructions of the accompanying medicines.

• Interaction with foodstuff
Meal with the high content of fats did not influence bioavailability of drug of Vizann.

• Other types of interaction
Reception of gestagen can influence results of some laboratory researches, including biochemical parameters of function of a liver, thyroid gland, adrenal glands and kidneys, plasma concentration of proteins (-carriers), for example, fractions of lipids/lipoproteids, parameters of carbohydrate metabolism and parameters of coagulation.

Contraindications:

Vizann's drug should not be used in the presence of any of the listed below states, a part from which is the general for all drugs containing only a gestagenny component. If any of these states develops against the background of administration of drug of Vizann, use of drug should be stopped immediately.
• Acute thrombophlebitis, venous thromboembolisms now;
• A heart disease and arteries which cornerstone atherosclerotic defeats of vessels (including coronary heart disease, a myocardial infarction, a stroke and the tranzitorny ischemic attack) or the anamnesis are now;
• A diabetes mellitus with vascular defeats;
• A serious illness of a liver now or in the anamnesis (in the absence of normalization of functional trials of a liver);
• Liver tumors (high-quality or malignant) now or in the anamnesis;
• The revealed or suspected hormonedependent malignant tumors, including a breast cancer;
• Bleedings from a vagina of not clear genesis;
• Cholestatic jaundice of pregnant women in the anamnesis;
• Hypersensitivity to active agents or to any of excipients;
• Intolerance of a galactose, deficit of lactase, glyukozo-galaktozny malabsorption;
•  Children's and teenage age up to 18 years (efficiency and safety of use for teenagers are not established).

Use with care
Depression in the anamnesis, an extrauterine pregnancy in the anamnesis, arterial hypertension, chronic heart failure, migraine with aura, a diabetes mellitus without vascular complications, a lipidemia, thrombophlebitis of deep veins in the anamnesis, venous thromboembolisms in the anamnesis (see the section "Special Instructions").

Pregnancy and period of breastfeeding

Pregnancy

Data on use of drug of Vizann for pregnant women are limited. The data obtained in researches on animals and data on use of a diyenogest for women during pregnancy did not reveal specific risk for pregnancy, fetation, childbirth and development of the child after the birth. Pregnant women should not appoint Vizann's drug due to the lack of need of treatment of endometriosis during pregnancy.

Breastfeeding period

Administration of drug of Vizann during breastfeeding is not recommended as researches on animals indicate allocation of a diyenogest with breast milk. The decision on the termination of breastfeeding or on refusal of Vizanna's reception is accepted proceeding from assessment of a ratio of advantage of breastfeeding for the child and advantage of treatment for the woman.

Overdose:

About serious violations at overdose it was not reported. Symptoms which can be noted at overdose: nausea, vomiting, the smearing bloody allocations or a metrorrhagia. There is no specific antidote, it is necessary to carry out symptomatic lecheniyey.

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to apply after a period of validity!

Issue conditions:

According to the recipe

Packaging:

Tablets; on 14 tablets in the blister from PVH/PVDH and aluminum foil. On 2, 6 or 12 blisters together with the application instruction put in a cardboard box.