Index of drugs

Hormone replacement therapy (HRT) - treatment of symptoms caused by estrogen deficiency in postmenopausal women who have had at least one year from the end of menstruation. Prevention of osteoporosis in postmenopausal women who have an increased risk of fractures and who can not tolerate other medicines used for the prevention of osteoporosis or for which they are contraindicated. Experience in the treatment of women over 65 years is limited.

1 tabl powl. contains 2 mg estradiol (as estradiol semihydrate) and 1 mg norethisterone acetate. The preparation contains lactose.

The product is intended for continuous hormone replacement therapy (HRT), containing 17β-estradiol - identical to human endogenous estradiol and norethisterone acetate - synthetic progestagen. Supplementing estrogen deficiency reduces the symptoms associated with menopause, and estrogens also prevent bone loss during menopause or after ovariectomy. The content of progestagens in the preparation reduces the risk of endometrial hyperplasia in women with a preserved uterus. The disappearance of the menopausal period occurs within the first few weeks of treatment. The preparation is used in continuous combined HRT to avoid withdrawal bleeding associated with the use of sequential HRT. After oral administration, micronized 17β-estradiol is rapidly absorbed from the gastrointestinal tract. As a result of the first pass, it is metabolized mainly in the liver and other internal organs. C_max in plasma occurs within 6 h. T_0,5 it is about 18 h. It is associated with SHBG (37%) and albumin (61%), and only about 1-2% remains in unbound form. Estrogens are secreted in the bile, hydrolysed and re-absorbed (enterohepatic circulation) and excreted mainly in the urine in inactive form. After oral administration of norethisterone acetate, it is rapidly absorbed and converted to norethisterone (NET). Then as a result of the first pass metabolism in the liver and other internal organs, reaching C_max in plasma in 1 h. Final T_0,5 NET is about 10 hours. It is associated with SHBG (36%) and albumin (61%). Metabolites are mainly excreted in the urine in the form of sulphates or glucuronides.

Hypersensitivity to the active substances or to any of the excipients. Diagnosis, history or suspicion of breast cancer. Diagnosis, presence or suspicion of estrogen-dependent malignant tumors (eg endometrial cancer). Undiagnosed bleeding from the genital tract. Untreated endometrial hyperplasia. Current or current venous thromboembolism (deep venous thrombosis, pulmonary embolism). Known disorders with a tendency to thrombosis (eg protein C deficiency, S protein or antithrombin). Active or past thromboembolic disorders of the arteries (eg ischemic heart disease, myocardial infarction). acute liver disease or a history of liver disease until liver function test results return to normal. Porphyria.

HRT should be started when the patient has symptoms of menopause that adversely affects her quality of life. In all cases, the benefit / risk should be evaluated at least once a year and HRT continued, as long as the benefits of treatment outweigh the risks of using it. If any of the following conditions are present in the patient, have recently appeared and / or increased during pregnancy or prior hormonal treatment, the patient needs careful observation. It should be taken into account that these conditions may recur or worsen with treatment with: myoma (fibroids) or endometriosis; risk factors for thromboembolic events; risk factors for the development of estrogen-dependent tumors (eg breast cancer in first-degree relatives); hypertension; liver diseases (e.g. liver adenoma); diabetes with or without vascular complications; cholelithiasis; migraine or (severe) headaches; systemic lupus erythematosus; endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis. It is recommended to stop taking the medicine immediately if any of the contraindications occur and in the following cases: jaundice or liver problems; significant increase in blood pressure; the appearance of migraine-type headaches, pregnancy. In women with a preserved uterus, the risk of hyperplasia and endometrial cancer increases with the use of estrogen alone for a long time.After treatment, the risk may remain elevated for 10 years after the end of treatment. The use of cyclically progestogens for at least 12 days per month / 28 days cycle or continuous complex estrogen-progestagen therapy in women with a preserved uterus, prevents excessive risk associated with the use of estrogen monotherapy in HRT. Bleeding and spotting may occur during the first months of treatment. If bleeding or spotting persists after the first months of treatment, occurs after some time after starting treatment or persists after its completion, the cause of bleeding should be accurately diagnosed by performing an endometrial biopsy to exclude cancer. Evidence suggests an increased risk of breast cancer in women using complex estrogen-progestagen and possibly also estrogen-only HRT. The risk depends on how long HRT is used. Increased risk is observed after several years of treatment, but within a few years after the end of treatment (usually up to 5 years), it returns to baseline. HRT, especially complex estrogen-progestagen treatments, increases breast density in the mammogram image and may adversely affect the radiological detection of breast cancer. Long-term use (at least 5-10 years) of only estrogen preparations in HRT was associated with a slightly increased risk of ovarian cancer. Some studies suggest that long-term use of combined HRT may carry a similar or slightly reduced risk. The use of HRT is associated with a 1,3- to 3-fold greater risk of developing venous thromboembolism (VTE), e.g. deep venous thrombosis or pulmonary embolism. The probability of occurrence of this type of events is greater in the first year of using HRT than in the later period. Risk factors for VTE are: Systemic use of estrogen, older age, major surgical procedures, long-term immobilization, obesity (body mass index> 30 kg / m² pc.), pregnancy or postnatal period, systemic lupus erythematosus (SLE) and cancer. There is no consensus on the effect of varicose veins on the course of VTE. In post-operative patients, prophylactic treatment should be considered to prevent VTE. If long-term immobilization is associated with planned surgery, periodic discontinuation of HRT for 4-6 weeks before surgery is recommended. Resumption of treatment should occur after the patient is fully started. In women without VTE in an interview, but with VTE in a first-degree relative interview at a young age, screening may be proposed after careful consideration of its limitations (only part of the disorder is detected during screening). If a disorder with a type of propensity to thrombosis, other than VTE, has been identified in family members or if the disorder is severe (eg, antithrombin deficiency, protein S or protein C, or a combination of these disorders) HRT is contraindicated. In women who use chronically anticoagulant therapy, careful consideration of the benefit-risk balance of HRT is required. If VTE develops after initiation of treatment, the drug should be discontinued. Patients should be advised of the need to immediately contact a physician in case of symptoms that may indicate the development of VTE (ie painful swelling of the lower limb, sudden pain in the chest, shortness of breath). The relative risk of coronary heart disease when using estrogen-progestagen combined HRT is slightly increased (the risk increases with age). Complex estrogen-progestagen and estrogen only, applied systemically, are associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with the age or time of menopause. However, as the risk of stroke is strongly related to age, the overall risk of stroke in women using HRT increases with age. Estrogens can increase fluid retention in the body, which means that patients with circulatory insufficiency or renal failure require special control. Women who have been diagnosed with hypertriglyceridemia should be closely monitored during the use of estrogens or preparations in HRT due to the rare cases of significantly increased plasma triglyceride levels leading to pancreatitis.Estrogens cause an increase in thyroid hormone binding globulin (TBG) leading to increased total circulating thyroid hormone concentration, measured by parameters such as protein-bound Iodine (PBI), T4 (assessed by column or radioimmunoassay) or T3 (evaluated by radioimmunoassay ). T3 uptake on the resin is reduced, reflecting the increase in TBG. The concentration of unbound T3 and T4 remains unchanged. Increased plasma concentrations of other binding proteins, e.g. corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG), lead to increased levels of circulating corticosteroids and sex hormones, respectively. The concentration of unbound or biologically active hormones remains unchanged. The concentration of other plasma proteins may be increased (substrates of the angiotensinogen / renin system, α-1-antitrypsin and ceruloplasmin). HRT does not affect the improvement of cognitive functions. There are data on the probable risk of dementia in women who start using continuous or estrogen-only HRT over the age of 65. The preparation contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

The product is not recommended during pregnancy and breast-feeding. If pregnancy is detected during treatment, treatment should be discontinued immediately.

Very common: breast pain and tenderness, bleeding from the genital tract. Common: genital candidosis, vaginitis, fluid retention, depression or worsening of depression, headache, migraine or worsening of migraine, nausea, abdominal pain, bloating, abdominal discomfort, back pain, leg cramps, swelling or breast enlargement, enlargement of the fibroids or their reappearance or uterine fibroids, peripheral edema, weight gain. Uncommon: hypersensitivity reactions, nervousness, superficial thrombophlebitis, bloating, winds, alopecia, hirsutism or acne, pruritus, urticaria, ineffectiveness of the drug. Rare: thrombophlebitis, pulmonary embolism. After placing the medicine on the market (frequency unknown or very rare): benign and malignant tumors, including cysts and polyps (eg endometrial cancer), generalized hypersensitivity reactions (eg anaphylactic reaction, anaphylactic shock), insomnia, anxiety, decrease or increase libido, dizziness, stroke, visual impairment, exacerbation of hypertension, exacerbation of hypertension, myocardial infarction, dyspepsia, vomiting, gallbladder disease, cholelithiasis, seborrhea, angioneurotic edema, endometrial hyperplasia, vulval and vaginal pruritus, weight loss, increased pressure arterial blood. Other side effects reported in the use of estrogen-progestagen treatment: skin and subcutaneous tissue disorders: alopecia, chloasma, erythema multiforme, erythema nodosum, vascular purpura; probably dementia over the age of 65. A 2-fold increased risk of breast cancer has been reported in women using estrogen-progestagen complex therapy for more than 5 years. Any increased risk in women using estrogen-only therapy is significantly lower than in those using complex estrogen-progestagen treatments. The level of risk depends on the length of use of HRT. In women with a preserved uterus, the use of estrogen-only HRT is not recommended due to the increased risk of endometrial cancer. The addition of a progestogen to estrogen-only treatment for at least 12 days in a cycle prevents this increased risk. Long-term intake of estrogen-only or combined estrogen-progestagen HRT was associated with a slightly increased risk of ovarian cancer. The use of HRT is associated with a 1,3- to 3-fold increase in the risk of VTE, e.g. deep venous thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the 1st year of use of HRT. The risk of coronary heart disease is slightly increased in those using complex estrogen-progestagen HRT over the age of 60 years. Estrogen and estrogen-progestagen only treatment is associated with a 1.5-fold increase in the relative risk of ischemic stroke. The risk of hemorrhagic stroke is not increased during HRT use.The relative risk does not depend on the age or time of use of HRT. The total risk of stroke in women using HRT increases with age.

Orally. Patients with a preserved uterus: 1 tablet per day (preferably at the same time of day), in continuous therapy. The lowest effective dose should be used and for the shortest possible time. In women with amenorrhea and non-users of HRT or women who change treatment with another formulation used in continuous combined HRT, treatment with Kliogest can be started on any day. In women who change the treatment regimen from sequential HRT, the use of the preparation should be started immediately after stopping the withdrawal bleeding. If the patient forgot to take the tablet, she should do it as soon as possible within the Next 12 hours. If more than 12 hours have passed, she should throw away the unwrapped tablet. Skipping the dose may increase the likelihood of bleeding or spotting.