More info
Active ingredients
Dienogest
Release form
Pills
Composition
Active ingredient: Dienogest Concentration of active ingredient (mg): 2 mg
Pharmacological effect
Dienogest is a derivative of nortestosterone, characterized by antiandrogenic activity, which constitutes about one third of the activity of cyproterone acetate. Dienogest binds to progesterone receptors in the human uterus, possessing 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 does not have significant mineralocorticoid or glucocorticoid activity in vivo. Dienogest affects endometriosis by suppressing the trophic effects of estrogens on eutopic and ectopic endometrium, due to a decrease in the production of estrogens in the ovaries and a decrease in their plasma concentration. atrophy of endometrial foci. Additional properties of dienogest, such as immunological and anti-angiogenic effects, appear to contribute to its overwhelming effect on cell proliferation. No decrease in bone mineral density (ppc), as well as a significant effect of the drug on the standard laboratory parameters, including general and biochemical blood parameters , liver enzymes, lipids and hba1c. Dienogest moderately reduces the production of estrogen in the ovaries.
Pharmacokinetics
AbsorptionAfter oral administration, dienogest is rapidly and almost completely absorbed. Cmax in serum, 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 The dienogest is associated with serum albumin and is not associated with sex hormone-binding globulin (GSPH), as well as with corticosteroid-binding globulin (GHG). 10% of the total concentration of the substance in the serum is in the form of a free steroid, whereas about 90% is nonspecificly bound to albumin. The apparent Vd of the dienogest is 40 liters. The pharmacokinetics of the dienogest does not depend on the level of SHBG. The concentration of dienogest in the serum after daily intake increases by about 1.24 times, reaching an equilibrium concentration after 4 days of intake.The pharmacokinetics of dienogest after repeated administration of Visanne can be predicted on the basis of pharmacokinetics after a single administration. MetabolismDenogest 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, CYP3A4 is the main enzyme involved in the metabolism of dienogest. Metabolites are excreted very quickly, so that the predominant fraction in the blood plasma is unchanged dienogest. The rate of metabolic clearance from serum is 64 ml / min. Excretion The concentration of dienogest in serum 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 in the form of metabolites, which are released through the kidneys and intestines in a ratio of about 3: 1. T1 / 2 metabolites during their excretion by the kidneys is 14 hours. After oral administration, approximately 86% of the received dose is excreted within 6 days, with the main part excreted in the first 24 hours, mostly by the kidneys.
Indications
Treatment of endometriosis
Contraindications
The drug Vizann should not be used in the presence of any of the following conditions, some of which are common to all drugs that contain only the progestogen component. If any of these conditions develop on the background of taking the drug Vizann, use of the drug should be stopped immediately. Acute thrombophlebitis and venous thromboembolism at present; Diseases of the heart and arteries based on atherosclerotic vascular lesions (including coronary heart disease, myocardial myocardium, stroke, and transient ischemic attack) currently or in history; Diabetes mellitus with vascular lesions; Severe liver disease in the present or in history normalization of functional liver tests); Liver tumors (benign or malignant) currently or in history; Identified or suspected hormone-dependent malignant tumors, including breast cancer; Vaginal bleeding of unknown origin; Cholestatic jaundice of pregnant women in anamnesis; Increased sensitivity to active substances or to any of the excipients; Galactose intolerance, lactase deficiency, glucose-galactose malabsorption; Children and adolescents under 18 years of age (effective ivnost and safety of adolescents have not been established).
Precautionary measures
The drug should be stored out of the reach of children at a temperature not higher than 30 ° C.
Use during pregnancy and lactation
Data on the use of the drug Visanne in pregnant women is limited. The data obtained in animal studies and data on the use of dienogest in women during pregnancy did not reveal a specific risk for pregnancy, fetal development, childbirth, and child development after birth. The drug Visanne should not be prescribed to pregnant women in the absence of the need to treat endometriosis during pregnancy. The administration of the drug Vizann during the breastfeeding period is not recommended, because animal studies indicate the allocation of dienogest with breast milk. Decision on the termination of breastfeeding or refusal to take Visanne is taken based on an assessment of the ratio of the benefits of breastfeeding for the child and the benefits of treatment for the woman.
Dosage and administration
For oral administration. The drug Visanne appointed for 6 months. The decision on further therapy is made by the doctor depending on the clinical picture. Intake schedule You can start taking the pills on any day of the menstrual cycle. Take one tablet per day without a break, preferably at the same time every day, if necessary with a glass of water or other liquid. Tablets must be taken continuously, regardless of bleeding from the vagina. After completion of taking the pills from one pack, start taking the pills from the next one, without taking a break in taking the drug. When skipping pills and in the case of vomiting and / or diarrhea (if it occurs within 3-4 hours after taking the pill), the effectiveness of the drug Bezanne may decrease. If one or more pills are missed, a woman should take one pill as soon as she remembers, and then continue taking the pills the next day at the usual time. Instead of a pill that was not absorbed due to vomiting or diarrhea, you should also drink one pill.
Side effects
Side effects occur more often in the first months of taking the drug Bezanne, and over time their number decreases. The most frequent side effects include: bleeding from the vagina (including spotting, metrorrhagia, menorrhagia, irregular bleeding), headache, discomfort in the mammary glands, decreased mood and acne. Table 1 lists the undesirable drug reactions (NLR), divided into classes of organs.Side effects in each frequency group are presented in decreasing order of frequency. Frequency is determined by how often (from ≥1 / 100 to less than 1/10) and infrequently (from ≥1 / 1000 to less than 1/100).
Overdose
No serious violations in overdose were reported. Symptoms that may occur with an overdose: nausea, vomiting, spotting, or metrorrhagia. There is no specific antidote; symptomatic treatment should be carried out.
Interaction with other drugs
Separate inducers or inhibitors of enzymes (CYP3A isoenzyme) Gestagens, incl. dienogest, are metabolized mainly with the participation of CYP3A4, located both in the intestinal mucosa and in the liver. Consequently, inducers or inhibitors of CYP3A4 can affect the metabolism of progestin drugs. Increased clearance of sex hormones due to the induction of enzymes can lead to a decrease in the therapeutic effect of the Vizann drug, as well as cause side effects, such as a change in the nature of uterine bleeding. Decrease in the clearance of sex hormones in communication with enzyme inhibition may increase the exposure of dienogest and cause side effects. Substances capable of inducing enzymes With drugs that induce microsomal enzymes (for example, cytochrome P450 systems), as a result, the clearance of sex hormones may increase (such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin and, possibly, also oxcarbazepine, topiramate, felbamath, glumempath, topiramate, rifampic, and rifampicin, and, possibly, also oxcarbazepine, topiramate, felbamp, imitation, rifampicin, and, possibly, also, oxcarbazepine, topiramate, felbamp, imitation, and rifampicin. griseofulvin, as well as 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 can persist for at least 4 weeks after cessation of therapy. Effect in uktora CYP3A4 rifampicin was studied in healthy postmenopausal women. While taking rifampicin with estradiol valerate / dienogest pills, a significant decrease in the equilibrium concentration and systemic exposure of dienogest was observed. Systemic exposure of dienogest at an equilibrium concentration, determined by the AUC value (0-24 h), was reduced by 83%. Substances that can inhibit enzymes Known inhibitors of CYP3A4, such as azole antifungal drugs (for example, ketoconazole,Itraconazole, fluconazole), cimetidine, verapamil, macrolides (for example, erythromystatics, aphrases, aryan, rhytonavir, indinavir, nelfinavir), diltiazem, protease inhibitors (for example, ritonavir, saquinavir, indinavir, nelfinavir); can increase the concentration of gestagens in the blood plasma and cause side effects. In one study, during which the effect of CYP3A4 inhibitors (ketoconazole, erythromycin) was studied, the concentration of estradiol valerate and dienogest in the blood plasma at equal waist concentrations were increased. In the case of simultaneous administration with a potent ketoconazole inhibitor, the AUC value (0–24 h) at an equilibrium concentration in dienogest increased by 186%. With simultaneous use with a moderate inhibitor of CYP3A4 erythromycin, the AUC value (0-24 h) in dienogest at an equilibrium concentration increased by 62%. The clinical significance of these interactions has not been clarified. The effect of dienogest on other drugs Based on in vitro inhibition data, the clinically significant interaction of Vizann with cytochrome P450 mediated metabolism of other drugs is unlikely. Note: to identify possible interactions, you should read the instructions of related drugs Food interactions High fat intake does not affect bioavailability Other types of interactions: Acceptance of gestagens may affect the results of some laboratory tests, including biochemical parameters of the liver, thyroid, adrenal glands and kidneys, plasma concentrations of proteins (carriers), for example, lipid / lipoprotein fractions, carbohydrate metabolism parameters and coagulation parameters .
special instructions
Before you start taking the drug Visanne pregnancy must be excluded. During the taking of the Vizann drug, if necessary, contraception patients are recommended to use non-hormonal contraceptive methods (eg, barrier). Fertility According to the available data, ovulation suppression occurs in most patients while taking the Vizann drug. 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 using Vizann in women with a history of ectopic pregnancy or with impaired function of the fallopian tubes should be resolved only after a thorough assessment of the ratio of expected benefit and possible risk. Because Visanne is a drug only with the gestagen component, it can be assumed that special precautions and precautions when using other drugs of this type But they are also valid for the Vizann drug, although not all of them are confirmed during the clinical trials of the Vizann drug. If any of the conditions or risk factors listed below are present or aggravated, an individual assessment of the benefit-risk ratio should be carried out before starting or continuing to take the Vizann drug. Circulatory disorders In the process of epidemiological studies, insufficient evidence was obtained confirming the existence of a link between the use of drugs with the progestin component only. entom and an increased risk of myocardial infarction or embolism of cerebral vessels. The risk of cardiovascular episodes and disorders of cerebral circulation is associated, rather, with increasing age, hypertension and smoking. The risk of stroke in women with arterial hypertension may slightly increase while taking drugs with the gestagen component only. Epidemiological studies indicate the possibility of a statistically insignificant increase in the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) due to the use of drugs with only the gestagen component . The generally accepted risk factors for venous thromboembolism (VTE) include an appropriate family history (VTE with a brother, sister, or one parent at a relatively early age), age, obesity, prolonged immobilization, extensive surgical intervention, or massive trauma. In the case of prolonged immobilization, it is recommended to stop taking the Vizann drug (during a planned operation, at least four weeks before it) and resume use of the drug only two weeks after full recovery of the motorabilities. It should take into account the increased risk of thromboembolism in the postpartum period. If you develop or suspect the development of arterial or venous thrombosis, the drug should be stopped immediately. , used at the time of the study, oral contraceptives (PC), mainly estrogen-progestin drugs. This increased risk gradually disappears within 10 years after stopping the use of combined oral contraceptives. Since breast cancer is rare in women younger than 40 years, a slight increase in the number of such diagnoses in women who are currently taking oral oral contraceptives or have used oral oral contraceptives earlier is not large compared to the overall risk of breast cancer. The risk of breast cancer in women who use hormonal contraceptives with only the gestagen component may be similar in magnitude to the corresponding risk associated with the use of combined oral contraceptives. However, the facts relating to drugs with only the gestagen component are based on much smaller populations of women using them and are therefore less convincing than data on combined oral contraceptives. Establishing a causal relationship based on these studies is not possible. The revealed risk increase picture may be due to an earlier diagnosis of breast cancer in women taking PC, the biological effect of PC, or a combination of both factors. Malignant tumors of the breast, which are diagnosed in women who have ever used PC, are usually less clinically pronounced than in women who have never used hormonal contraception. In rare cases, when using hormonal substances like the one found in the preparation Visanne, benign, and even more rarely - malignant liver tumors were noted. In some cases, these tumors led to life threatening intra-abdominal bleeding.If a woman taking a drug Visanne, there are severe pain in the upper abdomen, liver is enlarged or signs of intra-abdominal bleeding are present, then the differential diagnosis should take into account the probability of having a hepatic tumor. Changing the nature of bleeding Visanne affects the nature of menstrual bleeding in most women. On the background of the use of the drug Visanne uterine bleeding may increase, for example, in women with adenomyosis or uterine leiomyoma. Abundant and prolonged bleeding can lead to anemia (in some cases severe). In such cases, consideration should be given to the abolition of the drug Bezanne. Other conditions Patients with a history of depression need careful observation. If depression recurs in serious form, the drug should be discontinued. In general, Visanne does not appear to affect blood pressure in women with normal blood pressure. However, if persistent, clinically significant arterial hypertension occurs while taking Viezanne, it is recommended to stop the drug and prescribe antihypertensive treatment. have a minor effect on peripheral insulin resistance and glucose tolerance. Women with diabetes, especially those with a history of diabetes in pregnancy, while taking the drug Vizann, need careful monitoring. In some cases, chloasma can occur, especially in women with chloasma in pregnancy. Women who are prone to developing chloasma should avoid exposure to the sun or ultraviolet radiation while they are taking Viezanne. During Vizann's use, persistent ovarian follicles (often called functional ovarian cysts) may occur. Most of these follicles are asymptomatic, although some may be accompanied by pain in the pelvic region. Lactose One tablet of the Vizann drug contains 63 mg of lactose monohydrate.Patients with rare hereditary disorders, such as galactose intolerance, lactase deficiency lapp or glucose-galactose malabsorption, who are on a lactose-free diet, should take into account the volume of lactose included in the preparation. the need for dose adjustment in patients with kidney disease. Medical examination Before starting or resuming the administration of the drug Visanne a patient’s history should be reviewed in detail and a physical and gynecological examination should be carried out. The frequency and nature of such examinations should be based on existing standards of medical practice, taking into account the individual characteristics of each patient (but not less than once every 3-6 months) and should include measurement of blood pressure, assessment of the mammary glands, abdominal cavity and pelvic organs, including cytological examination of the cervical epithelium. Use in pediatricsVizanna contraindicated in children and adolescents under 18 years of age (efficacy and safety of use in adolescents have not been established) .The effect on the ability to drive uw vehicles and management mehanizmamiKak usually Visan drug does not affect the ability to control the car and work with mechanisms, but patients who have observed violations of concentration, must be careful.