Index of drugs

Hormone replacement therapy (HRT) to treat the symptoms of estrogen deficiency in postmenopausal women. Prevention of osteoporosis following menopause in women who are at risk of bone fractures when medicines used to prevent osteoporosis are contraindicated or are not well tolerated by the patient. There are only limited experiences regarding the treatment of women over 65 years of age.

The packaging consists of 9 tables. yellow containing 2 mg estradiol valerate and 12 tablets. brown containing 2 mg estradiol valerate and 0.15 mg levonorgestrel. The tablets contain lactose and sucrose.

A two-phase combined preparation containing a natural female sex hormone: estradiol valerate and a synthetic gestagen derivative of 19-nortestosterone: levonorgestrel. The preparation relieves the symptoms associated with estradiol deficiency in menopausal women and reduces bone resorption. Cyclic application with levonorgestrel allows to eliminate the mitogenic effect of estrogens on the endometrium, which reduces the risk of hyperplasia and endometrial cancer. Estradiol valerate is absorbed rapidly and completely after oral administration. C_max occurs after 2-4 h. It is metabolised mainly in the liver. Estradiol and its metabolites are excreted in the urine within 48 hours in a form conjugated to sulfuric and glucuronic acid, some are eliminated in the faeces. Cyproteron acetate is absorbed quickly and completely after oral administration. C_max occurs after 1-2 h after a single administration. It is mainly excreted in the form of metabolites in urine and faeces. T_0,5 is 10-24 hours.

Hypersensitivity to the components of the preparation. Active or metastatic breast cancer or suspicion of this cancer. Estrogen-dependent cancer or suspicion of such cancer (especially endometrial cancer). Bleeding from the genital tract of unexplained etiology. Untreated hyperplasia of the endometrium. I have an idiopathic or existing venous thromboembolism (especially deep vein thrombosis, pulmonary embolism). Active or recent occurrences of arterial thromboembolism (especially angina pectoris, myocardial infarction). Severe liver disease currently or in the past, as long as the liver function parameters have not returned to normal. Porphyria.

In each patient, the benefits and risks of using HRT should be carefully evaluated at least once a year. The patient requires close observation if any of the following conditions are present, occurred in the past and / or exacerbated during pregnancy or previous hormonal treatment (relapse or worsening): leiomyomas (myoma) or endometriosis, thrombotic disorders history of embolism or the presence of risk factors, risk factors for estrogen-dependent tumors, e.g. breast cancer in first-degree relatives, hypertension, liver disease (eg liver adenoma), diabetes mellitus, gallstones, migraine or (severe) headache, lupus systemic lupus erythematosus, endometrial hyperplasia, epilepsy, asthma, otosclerosis, fibrocystic cystic fibrosis, congenital severe metabolic disorders, sickle cell disease. Stop treatment immediately if there are contraindications or if you develop: jaundice, hepatic dysfunction, marked increase in blood pressure, sudden changes in vision, pregnancy or migraine-type headache for the first time. The risk of hyperplasia and endometrial cancer increases when only estrogens are used for a long time. The additional use of progestogen for at least 12 days in the cycle in a woman with a preserved uterus significantly reduces this risk. In the first months of treatment, you may experience periodic bleeding and spotting. If they appear after a certain time from the start of therapy, or they persist despite its cessation, their cause should be determined, which may require a biopsy of the endometrium to exclude malignant changes in the endometrium.An increased risk of breast cancer in women using the estrogen / progestogen combination as part of long-term HRT has been demonstrated. Increased risk occurs within a few years and increases with the duration of treatment, and returns to baseline within a few (at most five) years after discontinuation of therapy. HRT, especially combination therapy with estrogen and progestogen, increases the density of mammography images, which may hamper the radiographic detection of breast cancer. HRT is associated with an increased relative risk of venous thromboembolism (VTE). The occurrence of these disease events is more likely in the first year of HRT. If the patient or her family has had thromboembolism or habitual miscarriages, the possible tendency to thrombosis should be excluded. The use of HRT in such patients should be considered contraindicated, unless thorough analysis of thrombotic factors or initiation of anticoagulant therapy is performed. In women who are already taking anticoagulants, the benefit-risk balance should be considered carefully when using HRT. If prolonged immobilization is expected due to planned surgery, especially in the abdominal cavity or orthopedic surgery of the lower limbs, temporarily discontinuation of HRT should be considered, if possible 4-6 weeks before the procedure. Do not return to using HRT before returning to full mobility. If VTE develops after initiation of therapy, the preparation should be discontinued. When using continuous therapy with conjugated estrogens and medroxyprogesterone acetate (MPA), a potentially increased risk of cardiovascular disease was demonstrated in the first year of use and no overall benefit. An increased risk of ischemic stroke has been observed. In women after hysterectomy, long-term (at least 5-10 years) use of estrogen alone in HRT is associated with an increased risk of ovarian cancer. It is not known whether long-term HRT of complex products is associated with a different degree of risk than for those containing only estrogen. Estrogens may lead to fluid retention, therefore patients with cardiac or renal dysfunction should be supervised, especially end-stage renal disease. Women with hypertriglyceridemia should be closely monitored due to the risk of a significant increase in triglycerides leading to pancreatitis. Estrogens increase the concentration of thyroxine binding globulin (TBG), leading to an increase in the total amount of circulating thyroid hormones. Free T concentrations₄ and T₃ they remain unchanged. Other plasma binding proteins, such as corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG), may increase, leading to increased circulating corticosteroids and sex steroids. The concentrations of free or biologically active hormones remain unchanged. Concentrations of other proteins in the plasma may be elevated (angiotensinogen, alpha-1-antitrypsin, ceruloplasmin). Due to the lactose and sucrose content, the preparation should not be used in patients with rare hereditary galactose intolerance, fructose intolerance, in the case of lactase deficiency (Lapp type), sucrase deficiency - isomaltase or malabsorption of glucose-galactose.

Do not use during pregnancy and breast-feeding.

Common: headache, migraine, hypertension, breast cancer (benign mastopathy), breast pain. Uncommon: respiratory infections / bronchitis, hypersensitivity reactions, mood disorders (including anxiety disorders and depressive moods), memory disorders, dizziness, visual disturbances, tachycardia, palpitations, varicose veins (including hemorrhoids), circulatory disorders, nausea, vomiting, flatulence, abdominal pain, constipation, dyspeptic symptoms, cholangitis, cholecystitis, hepatic dysfunction, acne, seborrhea, pruritus, abnormal bleeding (including intracycular bleeding), mastitis, vaginitis, hyperplasia cervical / cervical dysplasia, endometrial hyperplasia, vulvar and vaginal discomfort, breast cancer, hot flushes, weakness, swelling and leg heaviness, pelvic pain, increased blood Glucose, anemia, weight changes , bilirubinemia. Rare: libido changes, sleep disorders, thrombosis, thrombophlebitis, hypotension, hair loss. In addition, there may be: estrogen-dependent benign and malignant tumor, e.g. endometrial cancer, venous thromboembolism, i.e.deep vein throat or pelvic vein thrombosis, pulmonary embolism, myocardial infarction and stroke, gallbladder disease, gallbladder disease, dementia, chloasma, erythema multiforme, erythema nodosum, vascular purpura.

Orally. Patients who have not previously used HRT can be started on any day. In patients who start taking the product after prior use of continuous combined HRT, treatment should be started on the day following the end of the treatment cycle with the current formulation. Patients who change treatment with another type of cyclic HRT should be started on the day following the expected discontinuance of the drug. One yellow table is accepted. daily for the first 9 days, then 1 brown tabl. daily for the Next 12 days. After the 21-day cycle of taking tablets, a 7-day break should be made. The withdrawal bleeding usually occurs during a 7-day break. The next pack of the preparation should be started after a 7-day break, regardless of whether or not bleeding has occurred. If you forget to take a tablet, take it within the next 12 hours. If this is not possible, continue taking the medicine without using the forgotten tablet at the usual time the next day. If you forget to take your tablet, it increases the likelihood of bleeding or staining.
The tablets should be taken whenever possible at the same time, swallowed whole with liquid, to avoid gastrointestinal discomfort it is recommended to take the product in the evening.