FEMOSTON 2/10 instructions for use, description of the medicinal product FEMOSTON 2/10: contraindications, side effects, dosages, composition - tablets, coating. shell in the directory of medicinal

Pharmacological properties of the drug Femoston

Pharmacodynamics. combined estrogen-progestin drug. Estradiol Estradiol is chemically and biologically identical to the natural human sex hormone estradiol. Among ovarian hormones, it has the highest activity. Estradiol causes cyclic changes in the uterus, cervix and vagina and ensures the maintenance of tone and elasticity of the genitourinary tract. Estradiol also plays an important role in the preservation of bone tissue, ensuring the prevention of osteoporosis and fractures. Oral intake of estrogens has a positive effect on lipid metabolism, has a beneficial effect on the autonomic nervous system and an indirect positive effect on the psycho-emotional sphere. Dydrogesterone Dydrogesterone is an orally effective progestogen whose effects are comparable to those of parenterally administered progesterone. In the context of hormone replacement therapy, dydrogesterone promotes complete secretory transformation of the uterine endometrium, thus preventing the risk of developing estrogen-induced endometrial hyperplasia and/or carcinoma, without excluding androgenic side effects. Due to the fact that estrogens stimulate endometrial growth, estrogen monotherapy increases the risk of developing endometrial hyperplasia and cancer. The use of progestogen in therapy reduces the estrogen-induced risk of developing endometrial hyperplasia in women with a preserved uterus. Clinical trial data Reduction of symptoms of estrogen deficiency and improvement of bleeding profile Reduction in the severity of menopausal symptoms was achieved during the first weeks of treatment. Regular menstrual-like reactions (average duration 5 days) when using Femoston, which contains 2 mg estradiol and 10 mg dydrogesterone, were observed in approximately 90% of women. Menstruation usually began on the day of taking the last tablet of the progestogen phase. Breakthrough uterine bleeding and/or spotting was reported in approximately 10% of women. During the first year of therapy, amenorrhea (absence of bleeding or spotting) was observed in 5–15% of women per cycle. Regular menstrual-like reactions when using the drug Femoston, which contains 1 mg of estradiol and 10 mg of dydrogesterone, were observed in 75–80% of women. The day of the onset of menstruation, its duration, as well as the number of women with periodic menstrual-like reactions were the same as with the use of the drug Femoston, which contains 2 mg estradiol and 10 mg dydrogesterone, but there were more women with no menstruation (10–25% per 1 cycle). Prevention of osteoporosis Estrogen deficiency during menopause is associated with increased bone turnover and decreased bone mass. The effect of estrogens on bone mineral density is dose-dependent. The protective effect of estrogens only occurs during their use. After stopping hormone replacement therapy (HRT), the rate of bone loss is the same as in women who did not receive this therapy. Data from the WHI (Women's Health Initiative) study and objective analysis of studies suggest that current HRT, primarily in healthy women, either as monotherapy or in combination with a progestogen, reduces the risk of hip, vertebral and other types of fractures that occur due to osteoporosis. HRT may also prevent fractures in women with low bone density and/or known osteoporosis, but data on this are limited. After two years of treatment with Femoston, which contains 2 mg estradiol and 10 mg dydrogesterone, bone mineral density (BMD) in the lumbar spine increased by 6.7% ± 3.9%. During treatment, BMD in the lumbar spine increased or remained unchanged in 94.4% of women. In women who took the drug Femoston, which contains 1 mg of estradiol and 10 mg of dydrogesterone, BMD in the lumbar spine increased by 5.2% + 3.8%. BMD in the lumbar spine increased or remained unchanged during treatment in 93.0% of women. Femoston affects BMD of the femur. After two years of therapy with 1 mg estradiol, BMD of the femoral neck increased by 2.7% ± 4.2%, by 3.5% ± 5.0% in the trochanteric area and by 2.7% ± 6.7% in the Ward triangle . After two years of treatment with estradiol at a dose of 2 mg, these figures were 2.6% ± 5.0%; 4.6% ± 5.0% and 4.1% ± 7.4%, respectively. BMD in three areas of the femur increased or remained unchanged after treatment with estradiol at a dose of 1 and 2 mg in 67–78% and 71–88% of women, respectively. Pharmacokinetics. Estradiol After oral administration, micronized estradiol is rapidly absorbed and extensively metabolized. The main unconjugated and conjugated metabolites are estrone and estrone sulfate. These metabolites have estrogenic activity both directly and after their conversion to estradiol. Estrone sulfate may be subject to enterohepatic metabolism. The main compounds found in urine are the glucuronides of estrone and estradiol. Estrogens pass into breast milk. Dydrogesterone After oral administration, approximately 63% of dydrogesterone is excreted in the urine. The drug is completely eliminated after 72 hours. Dydrogesterone is completely metabolized in the body. The main metabolite of dydrogesterone is 20-α-dihydrodydrogesterone (DHD), which is found primarily in urine as a glucuronic acid conjugate. A common feature of all metabolites is that they retain the 4,6-dien-3-one configuration and the absence of hydroxylation reaction under the action of 17α-hydroxylase. This explains the lack of estrogenic and androgenic effects of dydrogesterone. After oral administration of dydrogesterone, the concentration of DHD in the blood plasma significantly exceeds the level of the parent substance. Dydrogesterone is rapidly absorbed. The time to reach maximum concentration for dydrogesterone and DGD varies between 0.5–2.5 hours. The half-lives for dydrogesterone and DGD are 5–7 and 14–17 hours, respectively. Unlike progesterone, dydrogesterone is not excreted in the urine in the form of pregnanediol. Thus, it remains possible to analyze the formation of endogenous progesterone based on the measurement of pregnanediol excretion.

Use of the drug Femoston

To initiate and maintain treatment of postmenopausal symptoms, the minimum effective dose should be prescribed for the minimum period of time. Femoston is taken daily in the first 14 days of a 28-day cycle, 1 tablet containing 1 or 2 mg of estradiol, and in the remaining 14 days - daily, 1 tablet containing 1 mg of estradiol and 10 mg of dydrogesterone or 2 mg of estradiol and 10 mg of dydrogesterone. After the end of the 28-day cycle, a new cycle should begin. Treatment must be continuous. The tablets should be taken in the order indicated on the package. Treatment of postmenopausal symptoms Usually begins with taking the drug Femoston, containing 1 mg of estradiol and 10 mg of dydrogesterone. Depending on the clinical effect, the dose is then selected individually. If the severity of symptoms associated with estrogen deficiency does not decrease, the dose can be increased by prescribing a drug that contains 2 mg of estradiol and 10 mg of dydrogesterone. Prevention of osteoporosis When hormone replacement therapy is used, it is necessary to take into account individual tolerance to treatment and that the expected effect of the drug on bone tissue is dose-dependent. Femoston Conti 1 tablet 1 time per day daily, without breaks, regardless of meals. Prevention of osteoporosis When hormone replacement therapy is used, it is necessary to take into account individual tolerance to treatment and that the expected effect of the drug on bone tissue is dose-dependent.

Instructions for use FEMOSTON® 2/10 (FEMOSTON® 2/10)

Before prescribing or resuming HRT, it is necessary to collect a complete medical and family history, conduct a general and gynecological examination in order to identify possible contraindications and conditions requiring precautions. During treatment with Femoston® 2/10, it is recommended to conduct periodic examinations (the frequency and nature of the examinations are determined individually). In addition, it is advisable to conduct breast examination (including mammography) in accordance with accepted standards, taking into account clinical indications.

Risk factors for thrombosis and thromboembolism during HRT are a history of thromboembolic complications, severe forms of obesity (body mass index more than 30 kg/m2) and systemic lupus erythematosus. There is no generally accepted opinion regarding the role of varicose veins in the development of thromboembolism.

The risk of developing deep vein thrombosis of the lower extremities may temporarily increase with prolonged immobilization, major trauma, or surgery. In cases where prolonged immobilization is necessary after surgery, temporary cessation of HRT should be considered 4-6 weeks before surgery.

When deciding on HRT in patients with recurrent deep vein thrombosis or thromboembolism receiving anticoagulant treatment, the benefits and risks of HRT must be carefully assessed.

If thrombosis develops after starting HRT, Femoston® 2/10 should be discontinued.

The patient should be informed of the need to consult a doctor if the following symptoms occur:

painful swelling of the lower extremities, sudden loss of consciousness, dyspnea, blurred vision.

After consultation with the doctor, the patient should stop taking the drug if jaundice appears or deterioration of liver function, a pronounced increase in blood pressure, a newly diagnosed migraine-like attack, pregnancy, or the manifestation of any contraindication.

There is research data demonstrating a slight increase in the incidence of breast cancer detection in women receiving HRT for a long time (more than 10 years). The likelihood of being diagnosed with breast cancer increases with the duration of treatment and returns to normal 5 years after stopping HRT.

Patients who have previously received HRT using only estrogen drugs should be especially carefully examined before starting treatment with Femoston® 2/10 in order to identify possible endometrial hyperstimulation.

Breakthrough uterine bleeding and mild menstrual-like bleeding may occur in the first months of treatment with the drug. If, despite dose adjustment, such bleeding does not stop, the drug should be discontinued until the cause of the bleeding is determined. If bleeding recurs after a period of amenorrhea or continues after discontinuation of treatment, its etiology should be determined. This may require an endometrial biopsy.

The patient should inform the doctor about the medications she is currently taking or was taking before prescribing Femoston® 2/10.

The use of estrogens may affect the results of the following laboratory tests:

determination of glucose tolerance, study of thyroid and liver functions.

To treat symptoms of estrogen deficiency in postmenopausal women, HRT is prescribed only if symptoms of estrogen deficiency negatively affect quality of life. A thorough assessment of the benefits and disadvantages of HRT should be carried out regularly, at least once a year, and treatment should only be continued if the benefits of therapy outweigh the disadvantages.

Femoston® 2/10 is not a contraceptive. Perimenopausal patients are advised to use non-hormonal contraceptives.

Impact on the ability to drive vehicles and operate machinery

Femoston® 2/10 does not have or has an insignificant effect on the ability to drive vehicles and operate machinery.

Contraindications to the use of Femoston

Hypersensitivity to the components of the drug; diagnosed or suspected breast cancer, endometrial carcinoma and other hormone-dependent tumors diagnosed or suspected; vaginal bleeding of unknown etiology; untreated endometrial hyperplasia; history of acute deep vein thrombosis, pulmonary embolism or idiopathic venous thromboembolism; arterial thromboembolism, including recent ones (for example, angina pectoris, myocardial infarction); acute and chronic liver diseases, as well as their history in the absence of normalization of functional state indicators; porphyria; established or suspected pregnancy.

Femoston® (Femoston®)

Before prescribing or resuming HRT, it is necessary to collect a complete medical and family history, conduct a general and gynecological examination in order to identify possible contraindications and conditions requiring precautions. During treatment with Femoston®, it is recommended to conduct periodic examinations (the frequency and nature of the examinations are determined individually). In addition, it is advisable to conduct breast examination (including mammography) in accordance with accepted standards, taking into account clinical indications.

Risk factors for thrombosis and thromboembolism while taking HRT are a history of thromboembolic complications, severe forms of obesity (body mass index more than 30 kg/m2) and systemic lupus erythematosus. There is no generally accepted opinion regarding the role of varicose veins in the development of thromboembolism.

When deciding on HRT in patients with recurrent deep vein thrombosis or thromboembolism receiving anticoagulant treatment, the benefits and risks of HRT must be carefully assessed.

If thrombosis develops after starting HRT, Femoston® should be discontinued.

The patient should be informed of the need to consult a doctor if the following symptoms occur: painful swelling of the lower extremities, sudden loss of consciousness, dyspnea, blurred vision.

Patients who have previously received HRT using only estrogen drugs should be especially carefully examined before starting treatment with Femoston® in order to identify possible endometrial hyperstimulation.

Femoston® is not a contraceptive. Perimenopausal patients are advised to use non-hormonal contraceptives.

The patient should inform the doctor about the medications she is currently taking or was taking before prescribing Femoston®.

The use of estrogens may affect the results of the following laboratory tests: determination of glucose tolerance, study of thyroid and liver functions.

Impact on the ability to drive vehicles and operate machinery

Femoston® does not affect the ability to drive vehicles or operate machinery.

Side effects of the drug Femoston

Common (1–10%): headache, migraine, nausea, abdominal pain, flatulence, leg cramps, breast pain, breakthrough bleeding, spotting, pelvic pain, asthenia, weight loss or gain. Uncommon (≤1%): vaginal candidiasis, increased size of uterine fibroids, depression, changes in libido, irritability, dizziness, venous thromboembolism, gallbladder disease, allergic skin reactions, rash, urticaria, itching, back pain, changes in cervical erosion and amount of cervical secretion, dysmenorrhea, peripheral edema. Rarely (≤0.1%): intolerance to contact lenses, increased corneal curvature, liver dysfunction, which may be accompanied by asthenia, malaise, jaundice and abdominal pain, breast enlargement, premenstrual-like syndrome. Very rare (≤0.01%): hemolytic anemia, hypersensitivity reactions, chorea, myocardial infarction, stroke, vomiting, chloasma and melasma, which may persist after drug discontinuation, erythema multiforme, erythema nodosum, vascular purpura, angioedema, deterioration with porphyria. Breast cancer According to the results of a large number of epidemiological studies and one randomized, placebo-controlled trial (Women Health Initiative - WHI), the overall risk of breast cancer increases with the duration of hormone replacement therapy (HRT) in women who receive this treatment, or who have undergone HRT in the recent past. For estrogen-only HRT, the relative risk (RR) estimate from a re-analysis of data from 51 epidemiological studies (in which estrogen-only HRT was given to more than 80% of all HRT cases) and the Million Women Study (MWS) epidemiological study is similar at 1.35 (95% confidence interval - CI: 1.21-1.49) and 1.30 (95% CI: 1.21-1.40), respectively. Regarding combined HRT (estrogen plus progestogen), several epidemiological studies have reported a higher overall risk of breast cancer than estrogen monotherapy. The MWS study demonstrated that, compared with patients who had never received HRT, use of different types of combined (progestogen plus estrogen) HRT was associated with a higher risk of breast cancer (RR = 2.00, 95% CI: 1 .88-2.12) than with estrogen alone (RR = 1.30, 95% CI: 1.21-1.40) or tibolone (RR = 1.45; 95% CI: 1.25-1. 68). In the WHI study, the risk in all patients was 1.24 (95% CI: 1.01-1.54) after 5.6 years of combined (progestogen plus estrogen) HRT (conjugated equine estrogens - CLE and methylprogesterone acetate - MPA) in comparison with placebo. The absolute risks calculated in the MWS and WHI studies are presented below: Based on the average incidence of breast cancer in developed countries, the MWS study found that approximately 32 out of 1000 women over 50 years of age can be expected to be diagnosed with breast cancer up to 64 who are not receiving HRT; per 1000 women who have recently received or are receiving HRT, the number of additional cases during the corresponding period would represent for those receiving estrogen replacement therapy only 0 to 3 (best estimate = 1.5) if used for 5 years; from 3 to 7 (best score = 5) when used for 10 years; for those receiving combined (estrogen plus progestogen) HRT 5 to 7 (best estimate = 6) when used for 5 years; 18 to 20 (best estimate = 19) when used for 10 years. The WHI study found that after 5.6 years of follow-up in women aged 50 to 79 years, combined estrogen-progestogen HRT (CPE and MPA) would result in an additional 8 cases of invasive breast cancer diagnosed per 10,000 woman-years. According to study statistics, it was found that: per 1000 women in the placebo group, approximately 16 cases of invasive breast cancer would be diagnosed after 5 years; per 1000 women who received combined estrogen + progestogen HRT (CLE and MPA), the number of additional cases will be from 0 to 9 (best estimate = 4) when used for 5 years. The number of additional cases of breast cancer in women who use HRT is similar to that of women who start HRT, regardless of their age at start of use (45 to 65 years). Other adverse reactions reported in association with estrogen/progestogen therapy:

estrogen-dependent neoplasms, both benign and malignant, for example, endometrial cancer, ovarian cancer;
venous thromboembolism, that is, deep vein thrombosis of the lower extremities or pelvis and pulmonary embolism, is more common among women who receive HRT than among those who do not;
arterial thromboembolism;
an increase in the size of neoplasms caused by progestogen (for example, meningioma);
dementia.

Endometrial cancer In women with an intact uterus, the risk of endometrial hyperplasia and cancer increases with the duration of estrogen monotherapy. According to epidemiological studies, the best estimate of risk is that in women who do not take HRT, endometrial cancer can be expected to be diagnosed in approximately 5 in 1000 cases at ages 50 and 65 years. Depending on the duration of treatment and dose of estrogen, the risk of developing endometrial cancer among those taking estrogen alone is 2 to 12 times greater than among those not taking it. Adding a progestogen to estrogen monotherapy significantly reduces this increased risk.

Femoston® 1 (Femoston® 1)

The drug is prescribed only in the presence of symptoms that adversely affect the quality of life. All patients receiving HRT at least once a year require a benefit/risk assessment. Therapy should be continued until the benefits of taking the drug outweigh the risk of adverse reactions. Experience with the drug in women over 65 years of age is limited.

Information about the risks associated with 3HT in cases of premature menopause is limited. Due to the lower absolute risk in younger women, their benefit/risk ratio may be more favorable than in older women.

Medical examination

Before starting or resuming taking Femoston® 1, it is necessary to collect a complete medical and family history and conduct a general and gynecological examination (including the mammary glands) of the patient in order to identify possible contraindications and conditions requiring precautions. While taking Femoston® 1, it is recommended to conduct periodic examinations, the frequency and nature of which are determined individually, but not less than once every 6 months. It is advisable to perform mammography for additional examination of the mammary glands. Women should be informed about those possible changes in the mammary glands that need to be reported to their doctor.

If there is a family history of thrombosis or thromboembolism in first-degree relatives under the age of 50 years while taking the drug for HRT, careful medical supervision is necessary.

The use of estrogens may affect the results of the following laboratory tests: determination of glucose tolerance, study of thyroid and liver functions.

Reasons for immediate discontinuation of therapy:

Therapy should be discontinued if contraindications are established, as well as in the following cases:

-Jaundice or deterioration of liver function

- Significant increase in blood pressure

-Onset of migraine-type headaches

-Pregnancy

Hyperplasia and endometrial cancer

The risk of developing endometrial hyperplasia and cancer when using HRT drugs containing only estrogen depends on the dose and duration of treatment and increases from 2 to 12 times compared to patients not receiving therapy; the risk may remain elevated for 10 years after stopping therapy.

In women with a preserved uterus, the use of HRT drugs containing only estrogen is not recommended due to the increased risk of developing endometrial cancer. Cyclic use of progestogen (at least 12 days of a 28-day cycle), or use of a continuous combined HRT regimen in women with a preserved uterus, prevents the increased risk of endometrial hyperplasia and cancer associated with estrogen use.

For the purpose of timely diagnosis, it is advisable to conduct ultrasound (US) screening and, if necessary, conduct a histological (cytological) examination.

Bloody vaginal discharge

In the first months of taking the drug, there may be bleeding and/or scanty spotting from the vagina. If such bleeding appears some time after the start of therapy or continues after cessation of treatment, its cause should be determined. An endometrial biopsy may be performed to rule out malignancy.

Venous thromboembolism

HRT is associated with a 1.3-3-fold risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The development of this phenomenon is most likely during the first year of HRT.

If there are thromboembolic complications in first-degree relatives at a young age, as well as with a history of recurrent miscarriage, it is necessary to conduct a hemostasis study (during screening, only some disorders of the blood coagulation system are detected). If the patient is taking anticoagulants, it is necessary to carefully consider the prescription of Femoston® 1 from the point of view of the benefit/risk ratio. Until a thorough assessment of the factors for the possible development of thromboembolism or the initiation of anticoagulant therapy is completed, Femoston 1 is not prescribed.

If a hereditary or acquired predisposition to arterial or venous thrombosis is identified (for example, hyperhomocysteinemia, protein C deficiency, protein S deficiency, antithrombin III deficiency, etc., as well as their combination) and/or the presence of such conditions in the family history (in relatives 1st degree of relationship) taking Femoston® 1 is contraindicated due to the increased risk of thrombosis and thromboembolism, including venous.

In most cases, risk factors for developing VTE include: estrogen use, older age, major surgery, prolonged immobilization, obesity (body mass index > 30 kg/m2), pregnancy or the postpartum period, systemic lupus erythematosus and cancer. There is no consensus on the possible role of varicose veins in the development of VTE.

To prevent VTE after surgery, prophylactic measures should be considered in all postoperative patients.

In case of prolonged immobilization after surgery, you should stop taking Femoston® 1 4-6 weeks before and not resume taking the drug until the woman’s motor activity is completely restored.

If VTE develops after initiation of therapy, the drug should be discontinued and patients should be informed that they should contact their physician immediately if any of the symptoms indicating possible thrombosis or thromboembolism occur (for example, pain or swelling of the lower extremities, sudden chest pain, shortness of breath).

Mammary cancer

In women who have been receiving HRT for a long time containing only estrogen or combined (estrogen + progestogen) drugs, the incidence of breast cancer diagnosis increases, which returns to the original level within 5 years after cessation of therapy.

The increase in risk depends on the duration of HRT use. In women taking combined HRT drugs for more than 5 years, the risk of developing breast cancer can increase up to 2 times.

Combination therapy with estrogen and progestogen

The results of a randomized placebo-controlled trial (Women's Health Initiative (WHI)) and epidemiological studies showed an increased risk of developing breast cancer in women taking combined drugs for HRT (estrogen + progestogen). This increase becomes noticeable after approximately three years of therapy.

While taking HRT medications, there may be an increase in the density of breast tissue during mammography, which can make it difficult to diagnose breast cancer.

Ovarian cancer

Ovarian cancer is much less common than breast cancer. Epidemiological data from a large meta-analysis suggest a small increase in the risk of ovarian cancer for women receiving combined or estrogen-only HRT.

These studies (increased risk) become more apparent when therapy lasts more than five years, and after discontinuation, the risk gradually decreases over time. Findings from a number of other studies, including the WHI, indicate that combined HRT is associated with a similar or slightly lower risk of ovarian cancer.

Risk of ischemic stroke

Combination therapy with estrogen and progestogen or therapy with estrogen alone is associated with a 1.5-fold increase in the relative risk of ischemic stroke. The risk of hemorrhagic stroke does not increase when receiving HRT.

The relative risk does not depend on age, time of menopause, or duration of therapy. However, the baseline risk is highly dependent on age, so the overall risk of stroke in women taking HRT will increase with age.

Coronary heart disease (CHD)

Randomized controlled clinical trials provided no evidence of a protective effect of HRT against myocardial infarction in women with or without CAD who received combined estrogen and progestogen HRT or estrogen alone.

Combination therapy with estrogen and progestogen

The relative risk of coronary heart disease during the use of combined estrogen and progestogen HRT is slightly increased. Because the absolute risk of CAD is highly dependent on age, the number of additional cases of CAD due to combined HRT use in healthy premenopausal women is very small, but increases with age. The risk is slightly higher in women over 60 years of age.

Other states

Estrogens can cause fluid retention, which may adversely affect patients with impaired renal or cardiac function. This group of patients should be under medical supervision. Patients with hypertriglyceridemia while taking HRT medications should also be under medical supervision, because There are reports of very rare cases of significant increases in the concentration of triglycerides in the blood plasma, which contributes to the development of pancreatitis.

Estrogens increase the concentration of thyroxine-binding globulin, which leads to an overall increase in the concentration of circulating thyroid hormones (measured by determination of iodine bound to plasma proteins), the concentration of thyroxine (T4) - chromatographic or radioimmunoassay, or triiodothyronine (T3) - radioimmunoassay. The labeled triiodothyronine uptake test shows an increased concentration of thyroxine-binding globulin. The concentrations of free hormones T3 and T4 usually do not change. Plasma concentrations of other binding proteins (eg, transcortin and sex hormone binding globulin) may also increase, resulting in increased concentrations of circulating corticosteroids and sex hormones.

The concentrations of free or biologically active hormones do not change. It is possible to increase the concentration of other plasma proteins (angiotensinogen/renin system, α-1-antitrypsin, ceruloplasmin).

The use of HRT does not improve cognitive function. There are reports of an increased risk of developing dementia in women who start using HRT (combined or estrogen-containing only) after 65 years.

Femoston® 1 is not a contraceptive.

Special instructions for the use of Femoston

Hormone replacement therapy should only be started if there are symptoms that adversely affect quality of life. In all cases, a careful risk-benefit analysis should be carried out at least annually, and treatment should only be continued if the benefit outweighs the risk. Before prescribing hormone replacement therapy or its resumption, it is necessary to conduct a thorough general and gynecological examination of the patient, study her individual and family history to identify possible contraindications and risk factors. During the treatment period, regular examinations are recommended, the frequency and scope of which are determined individually, with mandatory examination of the mammary glands and/or mammography, modified if necessary. Diseases for which monitoring of the patient’s condition is necessary: uterine fibroids or endometriosis; history of thromboembolic disease or the presence of risk factors for thromboembolism (see below); the presence of risk factors for the occurrence of estrogen-dependent tumors, for example, the first degree of hereditary predisposition to breast cancer; AH (arterial hypertension); liver diseases (for example, liver adenoma); diabetes mellitus with or without vascular complications; cholelithiasis; migraine or (severe) headache; systemic lupus erythematosus; history of endometrial hyperplasia (see below); epilepsy; BA; otosclerosis. You should stop using the drug : if a contraindication to use is identified, as well as if jaundice or liver dysfunction develops, a significant increase in blood pressure, the appearance (for the first time) of a migraine-type headache, or pregnancy. Endometrial hyperplasia. When treated only with estrogen drugs for a long time, the risk of developing endometrial hyperplasia and cancer increases. Adding a progestogen to treatment for at least 12 days of the cycle in women with a preserved uterus significantly reduces this risk. Bleeding. Sometimes, in the first months of treatment, breakthrough uterine bleeding or spotting may occur. If they occur after some time during treatment or are noted after discontinuation of the drug, it is necessary to find out their cause (endometrial biopsy to exclude malignant neoplasms). Venous thromboembolism. Hormone replacement therapy increases the risk of developing venous thromboembolism (VTE), that is, deep vein thrombosis or pulmonary embolism. The occurrence of this condition is most likely during the first year of treatment. Risk factors for the development of VTE are a history of thromboembolism in the patient or her family members, severe obesity (body mass index 30 kg/m2) and systemic lupus erythematosus. If there is a history of thromboembolism, as well as with repeated spontaneous abortions, it is necessary to conduct an examination to exclude a tendency to thrombus formation. Until a thorough evaluation of thrombophilia factors is completed or anticoagulant therapy is initiated, the use of hormone replacement therapy in such patients should be considered contraindicated. In women taking anticoagulants, it is necessary to conduct a careful analysis of the risk/benefit ratio of using hormone replacement therapy. The risk of thromboembolism increases with prolonged immobilization, significant trauma, or extensive surgery. As for all patients in the postoperative period, special attention should be paid to preventive measures to prevent thromboembolic complications after surgery. If prolonged immobilization is planned after surgery, such as abdominal surgery or lower extremity orthopedic surgery, temporary cessation of hormone replacement therapy should be considered 4–6 weeks before surgery. Treatment should not be resumed until the woman’s motor activity is completely restored. If VTE develops after initiation of therapy, the drug must be discontinued. Patients should be warned to seek immediate medical attention if potential symptoms of thromboembolism (eg, painful swelling of the leg, sudden chest pain, shortness of breath) occur. Disease of the coronary arteries of the heart. In randomized controlled trials, there was no evidence of a positive effect on the cardiovascular system with continuous combination therapy of conjugated estrogens and MPA. Two large clinical trials, WHI and HERS (Heart and Estrogen/progestin Replacement Study), demonstrated a possible increased risk of cardiovascular disease during the first year of treatment and a lack of overall benefit. For other drugs used for HRT, there is only limited data from randomized controlled trials examining effects on cardiovascular disease or mortality. Therefore, it is unknown whether these results also apply to other HRT drugs. Stroke. In a large randomized clinical trial (WHI study), the secondary outcome was that the risk of ischemic stroke increased in healthy women during continuous combination therapy with conjugated estrogens and MPA. For women who do not receive HRT, the incidence of stroke over a 5-year period is estimated to be approximately 3 per 1000 women aged 50–59 years and 11 per 1000 women aged 60–69 years. It is estimated that for women who take conjugated estrogens and MPA for 5 years, the number of additional cases will occur in the range of 0 to 3 (best estimate = 1) per 1000 patients aged 50–59 years and from 1 to 9 (best estimate = 4) per 1000 patients aged 60–69 years. It is not known whether the increased risk of stroke also applies to other HRT drugs. Ovarian cancer. Long-term (at least 5–10 years) use of estrogen-only hormone replacement therapy in women with a hysterectomy has been associated with an increased risk of ovarian cancer. It is not known whether the risk will differ between long-term use of combined HRT and drugs that contain only estrogens. Other states. Estrogens may cause fluid retention, and patients with cardiac or renal impairment should be closely monitored. The condition of patients with end-stage renal failure requires constant monitoring, since it is possible that the level of circulating active ingredients of Femoston may increase. Women with hypertriglyceridemia should be closely monitored during hormone replacement therapy, as isolated cases of significant increases in plasma TG levels have been observed during estrogen treatment, leading to the development of pancreatitis. Estrogens increase the level of thyroxine-binding globulin, resulting in an increase in the concentration of circulating total thyroid hormones, which is determined by the level of protein-bound iodine, thyroxine (by column analysis or radioimmunoassay), or triiodothyronine (by radioimmunoassay). Triiodironine uptake is reduced, indicating increased levels of thyroxine-binding globulin. The concentrations of free triiodothyronine and thyroxine do not change. Serum levels of other binding proteins, corticosteroid binding globulin and sex hormone binding globulin, may be increased, resulting in increased concentrations of circulating corticosteroids and sex hormones, respectively. The concentrations of free or biologically active hormones do not change. Concentrations of other plasma proteins (angiotensinogen/renin substrate, alpha-I antitrypsin, ceruloplasmin) may increase. There is no convincing evidence of improvement in cognitive function. The WHI study found evidence of an increased risk of dementia in women receiving continuous combination estrogen and progesterone therapy after the age of 65 years. It remains unknown whether this also applies to younger postmenopausal women or other hormone replacement therapy drugs. Patients with rare hereditary diseases - galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome - should not take this drug. Experience in treating women over 65 years of age is limited. Use during pregnancy and lactation. Femoston is not indicated for use during pregnancy. If pregnancy occurs during treatment with Femoston, the drug should be stopped immediately. Femoston is not recommended for use during breastfeeding. Children. Due to insufficient data on the safety and effectiveness of Femoston in children under 18 years of age, the drug is not recommended for this age group of patients. The drug Femoston does not affect the ability to drive vehicles or operate machines and mechanisms.

Instructions for use FEMOSTON® 1/10 (FEMOSTON® 1/10)

Before prescribing or resuming HRT, it is necessary to collect a complete medical and family history, conduct a general and gynecological examination in order to identify possible contraindications and conditions requiring precautions. During treatment with Femoston® 1/10, it is recommended to conduct periodic examinations (the frequency and nature of the examinations are determined individually). In addition, it is advisable to conduct breast examination (including mammography) in accordance with accepted standards, taking into account clinical indications.

When deciding on HRT in patients with recurrent deep vein thrombosis or thromboembolism receiving anticoagulant treatment, the benefits and risks of HRT must be carefully assessed.

If thrombosis develops after starting HRT, Femoston® 1/10 should be discontinued.

The patient should be informed of the need to consult a doctor if the following symptoms occur:

painful swelling of the lower extremities, sudden loss of consciousness, dyspnea, blurred vision.

Patients who have previously received HRT using only estrogen drugs should be especially carefully examined before starting treatment with Femoston® 1/10 in order to identify possible endometrial hyperstimulation.

The patient should inform the doctor about the medications she is currently taking or was taking before prescribing Femoston® 1/10.

The use of estrogens may affect the results of the following laboratory tests:

determination of glucose tolerance, study of thyroid and liver functions.

Femoston® 1/10 is not a contraceptive. Perimenopausal patients are advised to use non-hormonal contraceptives.

Impact on the ability to drive vehicles and operate machinery

Femoston® 1/10 does not affect the ability to drive vehicles and operate machinery.

Interactions of the drug Femoston

The metabolism of estrogens can be enhanced when used simultaneously with substances that activate enzymes (cytochrome P450 systems) that are involved in the metabolism of drugs. These substances include anticonvulsants (eg, phenobarbital, carbamazepine, phenytoin) and antimicrobials (eg, rifampicin, rifabutin, nevirapine, efavirens). Ritonavir and nelvinavir, when used simultaneously with steroid hormones, activate the above enzymes. Herbal preparations, the component of which is St. John's wort (Hypericum perforatum), increase the metabolism of estrogens and progestogens, which can lead to a weakening of their effect and a change in the profile of uterine bleeding. There is no information on the interaction of dydrogesterone with other drugs.