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

Compound

One Femoston 1/5 tablet contains estradiol and dydrogesterone in concentrations of 1 and 5 mg, respectively.
The auxiliary components used are: lactose in the form of monohydrate, methylhydroxypropylcellulose, anhydrous colloidal silicon dioxide, corn starch, macrogol 400, magnesium stearate, iron dyes (yellow oxide E172 and red E172), titanium dioxide (E171), Opadry orange. Femoston Conti 1/5 tablets have a similar composition.

Femoston 1/10 white tablets use estradiol . Substance concentration - 1 mg/tab. Each gray Femoston tablet contains estradiol and dydrogesterone estradiol per 10 mg dydrogesterone ).

Femoston 2/10 pink tablets contain estradiol at a concentration of 2 mg/tablet. Light yellow tablets contain estradiol and dydrogesterone estradiol per 10 mg dydrogesterone ). Auxiliary components: lactose in the form of monohydrate, hypromellose, magnesium stearate, corn starch, colloidal silicon dioxide, Opadry (white, gray, pink and yellow, respectively).

Release form

The dosage form of the drug is film-coated, round, biconvex tablets with a diameter of 0.7 cm. The tablets differ in color depending on the concentration of the active substance/substances; each of them is marked “379” on one side.

Femoston 1/5 tablets have the letter “S” engraved on the other side. Tablets are available in calendar packs of 28 pieces.

Tablets with a higher concentration of active substances are packaged in calendar packs as follows:

• 14 white tablets 1 mg + 14 gray tablets 1 mg + 10 mg (Femoston 1/10);
• 14 pink tablets 2 mg + 14 light yellow tablets 2 mg + 10 mg (Femoston 2/10).

Pharmacodynamics and pharmacokinetics

Femoston is a combined hormonal drug used to eliminate the symptoms of estrogen deficiency and treat DUB - dysfunctional uterine bleeding .

The estradiol contained in the drug is identical to endogenous estradiol . The drug is used to replenish estrogen after the onset of menopause and effectively treats vegetative and psychoemotional disorders associated with menopause , accompanied by:

• hyperhidrosis;
• tides;
• involution of the mucous membranes and skin, and especially the mucous membranes of the urogenital tract (in particular, the vaginal mucosa, due to which a woman begins to experience discomfort during sexual intercourse);
• increased nervous excitability;
• headaches and dizziness;
• sleep disorders;
• loss of bone mass or osteoporosis (especially if certain risk factors are noted - long-term treatment with glucocorticosteroids in the recent past, early onset of menopause , asthenic type of build, smoking, etc.).

Estradiol also helps reduce the concentration of total cholesterol and low-density lipoproteins, while simultaneously increasing the concentration of high-density lipoproteins.

The action of the gestagenic component of the drug - dydrogesterone - is aimed at stimulating the onset of the secretory phase of the endometrial cycle, and also reduces the risk of carcinogenesis and endometrial hyperplasia associated with the influence of estrogen .

Dydrogesterone does not have androgenic estrogenic , glucocorticosteroid or anabolic effects . To ensure the maximum preventive effect of hormone replacement therapy (HRT), treatment is recommended to begin as early as possible after the onset of menopause .

After taking p/os, estradiol is easily absorbed. Biotransformation of the substance occurs in the liver ; the metabolic are estrone and estrone in the form of sulfate . Estradiol and estrone glucuronides are eliminated from the body primarily in the urine.

Dydrogesterone is also rapidly absorbed from the digestive tract after oral administration. The substance is completely biotransformed, the main product of metabolism is 20-dihydrodydrogesterone. Metabolites excreted mainly through urine.

The half-life of dydrogesterone is from 5 to 7 hours, its main metabolite is from 14 to 17 hours, the substances are completely eliminated after 72 hours.

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.

Indications for use

The use of Femoston is indicated for hormone replacement therapy to eliminate phenomena caused by estrogen deficiency in postmenopausal .

The medicine is prescribed no earlier than six months after the last menstrual bleeding.

Prophylactic use of the drug is advisable to prevent the development of osteoporosis after the onset of menopause . The drug is prescribed to women who have an increased risk of fractures and who are contraindicated in the use of other medications intended to prevent bone loss.

Contraindications

The drug is not prescribed:

• women who have been diagnosed with malignant estrogen- or progestogen-dependent tumors , as well as if these diseases are suspected;
• patients with diagnosed or suspected breast cancer ;
• with vaginal bleeding of unspecified origin;
• with untreated hyperplasia (pathological growth) of the endometrium ;
• venous thromboembolism detected at the moment or noted in the anamnesis (including DVT and PE);
• if the patient has certain thrombophilic disorders (including thrombophilia associated with deficiency of antithrombin , coagulation protein C or its cofactor - protein S );
• for thromboembolic arterial diseases , including angina pectoris or myocardial infarction (both in the active stage and in cases where the disease was suffered in the recent past);
• in case of active liver , and also if the patient’s liver biochemical parameters ;
• with porphyrin disease ;
• if you are aware of individual intolerance to estradiol , dydrogesterone or auxiliary components of Femoston;
• children and adolescents under 18 years of age;
• during pregnancy (both established and suspected pregnancy);
• during lactation.

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.

Side effects

The category of side effects that often occur in connection with the use of Femoston includes: pain (headaches, in the abdomen, in the pelvic area), nausea, migraine attacks, flatulence, leg cramps, increased sensitivity and/or tenderness of the mammary glands, metrorrhagia, the appearance of bloody vaginal bleeding after menopause, asthenia, decrease/increase in body weight.

With a frequency of 1/1000-1/100 during clinical studies, the following phenomena occurred:

• vaginal candidiasis;
• depression;
• an increase in the size of uterine fibroids ;
• change in libido ;
• increased nervousness;
• DVT, PE;
• dizziness;
• gallbladder disease ;
• backache;
• allergic reactions on the skin, accompanied by itching, hives , rashes;
• dysmenorrhea;
• ulcerative defects on the cervix;
• the appearance of cervical discharge;
• peripheral edema.

In rare cases (with a frequency of 1/10000-1/1000), drug therapy was accompanied by:

• intolerance to contact lenses;
• functional liver , which often manifest themselves in the form of asthenia , malaise, abdominal pain, jaundice ;
• increased curvature of the cornea;
• enlargement of the mammary glands;
• premenstrual tension syndrome.

In isolated cases, the drug can provoke the development of chorea , hemolytic anemia, stroke, myocardial infarction, vascular purpura, vomiting, erythema nodosum or multimorphic, melanopathy or chloasma (often persisting even after discontinuation of the drug), angioedema , hypersensitivity reactions, worsening of porphyrin disease .

In addition, in connection with treatment with estrogen-progestagen drugs, women sometimes develop neoplasms (benign, malignant or of unknown etiology), the size of progestogen-dependent tumors fibrocystic lesions of the mammary glands appear of triglycerides in the blood plasma and the concentration of thyroid hormones increase ; arterial hypertension , acute arterial , peripheral vascular disease, varicose , dyspepsia , pancreatitis (against the background of pre-existing hypertriglyceridermia), systemic lupus erythematosus , cystitis-like syndrome , urinary incontinence develop epilepsy worsens , signs of dementia .

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.

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® 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® 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.

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.

Femoston tablets, instructions for use

Most often, Femoston is taken on days strictly determined by the attending physician, taking into account the characteristics of a particular menstrual cycle . In the absence of menstrual bleeding, the tablets should be taken on the expected days when they should begin. With amenorrhea observed throughout the year, taking the drug can be started at any time.

Instructions for use Femoston 1/5

The drug is intended for continuous use: tablets are taken p/os, one per day (optimally at the same time), without reference to meal times. The duration of one cycle is 4 full weeks (1 package No. 28 is designed for one cycle). There is no need to take a break between cycles.

To relieve the symptoms of menopause, the drug is started with the minimum effective dose. Treatment begins with the appointment of Femoston 1/5. Taking into account the time of onset of menopause, the severity of the accompanying symptoms and the effectiveness of therapy, adjustments can be made to the dosage regimen.

If it is necessary to switch from another drug containing estrogen and progestogen components for sequential (or cyclic) use, the patient should complete the full four-week course and only after that switch to treatment with Femoston 1/5 (reception can be started on any day). There is no break between cycles.

The regimen for using Femoston 1/5 Conti is similar to that described above.

Instructions for use Femoston 1/10

Femoston 1/10 tablets should be taken regardless of meal time. The estrogen contained in the drug is intended for continuous daily use during the first two weeks of the cycle.

The progestogen component is added in the last 14 days of each four-week course.

Treatment begins with taking white tablets according to the following scheme: 1 tablet 1 time per day (at the same time) during the first 2 weeks of the cycle. Next, following the instructions on the package, they begin to take gray tablets (also, one per day).

There is no need to take breaks between 28-day cycles.

Sequential combined HRT begins with the prescription of Femoston 1/10, and then, if necessary, the dose is adjusted taking into account the clinical results of therapy.

To switch from a similar drug, you should complete the full cycle of treatment and only then start taking Femoston 1/10 tablets. You can do this any day.

Instructions for use Femoston 2/10

The estrogen component of the drug should be taken continuously, the progestogen component is administered from the 15th day of the 28-day cycle.

This means that in the first 2 weeks of the cycle the patient should take 1 pink tablet per day, and starting from the 15th day, following the instructions on the drug packaging, switch to taking yellow tablets.

Usually the starting dose of estradiol is 1 mg, so sequential combined HRT begins with Femoston 1/10 and, if necessary, moves to a higher dose over time.

Switching from other drugs to Femoston 2/10 is carried out only after completing a full four-week cycle (on any day).

How to take Femoston correctly if you miss the next dose?

If a woman misses the next dose of the drug, the tablet should be taken as quickly as possible. If more than 12 hours have passed since the missed dose, then the course is continued by taking the next tablet from the package (you do not need to drink the missed one).

Taking a double dose to compensate for a missed dose is not advisable, since it is associated with an increased risk of breakthrough bleeding and the appearance of spotting vaginal discharge.

How should patients of different age groups take the drug?

There is no sufficient experience with the use of Femoston for the treatment of patients over 65 years of age.

There are no indications for prescribing the drug to children and adolescents.

Femoston® conti

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 an assessment of the benefit-risk ratio. 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 HRT 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 prescribing or resuming therapy with Femoston® conti, 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.

During treatment with Femoston® conti, 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.

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

Endometrial hyperplasia

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

In women with a preserved uterus, HRT with estrogens alone 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, may prevent the estrogen-increased risk of endometrial hyperplasia and cancer.

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 treatment with 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 is a family history of thrombosis/thromboembolism in first-degree relatives aged less than 50 years, as well as a history of recurrent miscarriage, it is necessary to conduct a hemostasis study (screening reveals only some of the disorders of the blood coagulation system). If the patient is taking anticoagulants, a careful assessment of the benefit-risk ratio should be carried out when using Femoston® conti. Until a thorough assessment of the factors for the possible development of thromboembolism or the initiation of anticoagulant therapy is completed, Femoston® conti is not prescribed.

If a thrombophilic condition is detected in a family member and/or in the case of the seriousness or severity of the defect (for example, antithrombin III deficiency, protein S or C deficiency, as well as a combination of defects), Femoston® conti is contraindicated.

Since patients with diagnosed thrombophilic conditions have an increased risk of developing venous thromboembolism, the use of Femoston® conti, which increases this risk, is contraindicated.

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, it is recommended to stop taking Femoston-conti 4-6 weeks before, and treatment should not be resumed until the woman’s mobility 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 they experience any possible symptoms of thrombosis/thromboembolism (for example, tenderness or swelling of the lower extremities, sudden chest pain, shortness of breath).

Mammary cancer

In women receiving long-term HRT using estrogen alone or in combination with estrogen and progestogen, 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 for more than 5 years, the risk of developing breast cancer can increase up to 2 times.

Combination therapy with estrogen and progestogen

Results from a randomized, placebo-controlled trial (Women's Health Initiative (WHI)) and epidemiological studies have shown an increased risk of breast cancer in women taking combined estrogen and progestogen HRT. This increase becomes noticeable after approximately three years of therapy.

Estrogen-only therapy

According to the WHI study, there was no increased risk of breast cancer in women with a previous hysterectomy who received estrogen-only HRT.

Most observational studies showed a small increase in the risk of breast cancer, although this risk was markedly lower in women taking combined estrogen and progestogen therapy.

The increase in risk becomes noticeable after several years of using HRT drugs, and after stopping therapy it returns to the original level within several (maximum five) years.

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 obtained from a large meta-analysis suggest a small increase in the risk of developing ovarian cancer for women receiving HRT as estrogen monotherapy or combination therapy with estrogens and progestogens.

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 monotherapy.

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.

Estrogen-only therapy

Based on data from randomized controlled trials, there was no increased risk of coronary artery disease in women with a previous hysterectomy who received estrogen monotherapy.

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, as measured by determination of plasma protein-bound iodine, thyroxine (T4) concentration - chromatographic or radioimmunoassay, or triiodothyronine (T3) - radioimmunoassay. A labeled triiodothyronine uptake test shows elevated levels 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 be increased, 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® conti is not a contraceptive.

Overdose

Cases of overdose with Femoston have not been recorded.

Both estrogen and progestogen components of the tablets belong to the category of low-toxic substances.

Theoretically, an overdose can provoke an increase in the severity of side effects such as nausea, vomiting, dizziness, drowsiness.

It is unlikely that an overdose may require any specific symptomatic treatment (including overdose in children).

Interaction

Drug interaction studies with Femoston have not been conducted.

However, it is known that some drugs may affect the effectiveness of estrogens and progesterones .

Thus, anticonvulsants (for example, phenytoin or phenobarbital ) and antimicrobial (including nevirapine , rifampicin or efavirenz enzymes of the cytochrome P450 system involved in drug metabolism .

Ritonavir and nelvinavir , which are potent inhibitors of CYP 3A4, A5 and A7 isoenzymes, in combination with steroid hormones , promote the activation of these cytochromes.

Herbal remedies based on St. John's wort (Hypericum perforatum) can stimulate the biotransformation of estrogens and progestogens due to the ability to influence the CYP 3A4 isoenzyme.

There is evidence that the more active metabolism of estrogens and progestogens provokes a decrease in the clinical effectiveness of these substances and affects the profile of uterine bleeding.

In turn, estrogens can disrupt the process of biotransformation of other substances due to competitive suppression of cytochromes of the P450 system , which take part in the processes of biotransformation of active drug substances.

This should be remembered when prescribing estrogens in combination with drugs that have a narrow therapeutic index, including fentanyl , tacrolimus , theophylline , cyclosporine .

Such combinations can cause an increase in the plasma concentration of these substances to a toxic level. Therefore, there may be a need for careful monitoring of the drug over an extended period of time, as well as a reduction in the dose of cyclosporine, tacrolimus, theophylline and fentanyl .

Femoston Mini tablets PPO 2.5 mg+0.5 mg No. 28

Compound

Active ingredients: dydrogesterone - 2.5 mg; estradiol - 0.5 mg. Excipients: lactose monohydrate - 117.4 mg, hypromellose (HPMC 2910) - 2.8 mg, corn starch - 14.7 mg, colloidal silicon dioxide - 1.4 mg, magnesium stearate - 0.7 mg.

Pharmacokinetics

• Estradiol

Suction

The absorption of estradiol depends on the particle size; micronized estradiol is easily absorbed from the gastrointestinal tract.

The table below presents the pharmacokinetic parameters of estradiol (E2), estrone (E1) and estrone sulfate (E1S) for each dose of micronized estradiol. Data are presented as mean (SD).

Distribution
Estradiol (like other estrogens) can be found in both bound and free states. About 98-99% of a dose of estradiol is bound to plasma proteins, of which 30-52% is bound to albumin and about 46-69% is bound to sex hormone-binding globulin (SHBG).

When taking Femoston® mini daily, the concentration of estradiol in the blood plasma reaches a constant value after about 5 days. Typically, this indicator is achieved within 8-11 days after the start of therapy.

Estrogens are excreted in breast milk.

Metabolism

After oral administration, estradiol is actively metabolized. The main unconjugated and conjugated metabolites are estrone and estrone sulfate, which have estrogenic activity, either directly or after conversion to estradiol. Estrone sulfate may undergo enterohepatic recirculation.

Removal

Estrone and estradiol are excreted in a state conjugated with glucuronic acid by the kidneys. T1/2 is 10-16 hours.

• Dydrogesterone

Suction

After oral administration, dydrogesterone is rapidly absorbed. The Tmax value for dydrogesterone varies from 30 minutes to 2.5 hours. The absolute bioavailability of dydrogesterone is 28%.

The table below presents the pharmacokinetic parameters of dydrogesterone (D) and 20α-dihydrodydrogesterone (DHD). Data are presented as mean (SD).

Distribution
More than 90% of dydrogesterone and 20α-dihydrodydrogesterone (DHD) are bound to plasma proteins.

Comparison of the kinetics of single and multiple doses (from 2.5 to 10 mg) shows that the pharmacokinetic properties of dydrogesterone and DHD do not change when taking multiple doses.

Css of dydrogesterone is achieved 3 days after starting the drug.

Metabolism

After oral administration, dydrogesterone is rapidly metabolized to DHD. Cmax of DHD in blood plasma is achieved approximately 1.5 hours after taking the drug. The concentration of DHD in the blood plasma significantly exceeds the initial concentration of dydrogesterone; the ratios of the AUC and Cmax values ​​of DHD to dydrogesterone are about 40 and 25, respectively.

A common characteristic feature of all dydrogesterone metabolites is the preservation of the 4,6-dien-3-one configuration of the original substance and the absence of 17α-hydroxylation, which determines the absence of estrogenic and androgenic activities.

Removal

T1/2 is 5-7 hours for dydrogesterone, 14-17 hours for DGD. Dydrogesterone is completely eliminated after 72 hours. On average, 63% of the dose taken is excreted by the kidneys. Total plasma clearance - 6.4 l/min. DHD is detected in urine primarily as a glucuronic acid conjugate.

Indications for use

Hormone replacement therapy for disorders caused by estrogen deficiency in postmenopausal women (no earlier than 12 months after the last menstruation).

Contraindications

• diagnosed or suspected breast cancer;
• diagnosed or suspected estrogen-dependent malignancies (for example, endometrial cancer);
• diagnosed or suspected progestogen-dependent neoplasms (for example, meningioma);
• bleeding from the vagina of unknown etiology;
• untreated endometrial hyperplasia;
• thrombosis (arterial and venous) and thromboembolism currently or in history (including thrombosis, deep vein thrombosis; pulmonary embolism, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders);
• acute or chronic liver diseases currently or in history (before normalization of liver function tests), incl. malignant liver tumors;
• porphyria;
• multiple or pronounced factors of arterial or venous thrombosis, angina pectoris, prolonged immobilization, severe forms of obesity (BMI more than 30 kg/m2), diseases of the cerebral vessels or coronary arteries, transient ischemic attacks, complicated lesions of the valvular apparatus of the heart, atrial fibrillation;
• identified hereditary or acquired predisposition to arterial or venous thrombosis/thromboembolism (for example, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant));
• pregnancy;
• breastfeeding period;
• galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
• hypersensitivity to dydrogesterone, estradiol and/or to any excipient in the drug.

Taking Femoston ® mini should be stopped immediately if contraindications are identified and/or if the following conditions occur:

• jaundice and/or liver dysfunction;
• uncontrolled arterial hypertension;
• migraine-like headache that first appeared during the use of drugs for HRT;
• pregnancy.

Carefully

The use of drugs for HRT, incl. Femoston ® mini requires precautions in the presence of any of the following diseases/conditions and risk factors:

• uterine leiomyoma, endometriosis;
• the presence of risk factors for the occurrence of estrogen-dependent tumors (for example, 1st degree relatives with breast cancer);
• arterial hypertension;
• benign liver tumors;
• diabetes mellitus, both in the presence of vascular complications and in their absence;
• cholelithiasis;
• migraine or severe headache;
• systemic lupus erythematosus;
• history of endometrial hyperplasia;
• epilepsy;
• bronchial asthma;
• otosclerosis.

It should be taken into account that these diseases/conditions and risk factors may recur or intensify during therapy with Femoston® mini. Precautions must be taken in the following cases:

• in patients with chronic heart and kidney failure;
• in patients with risk factors for the development of thrombosis and thromboembolism in a family history (thrombosis or thromboembolic complications in first-degree relatives aged less than 50 years (such patients should be screened, having previously been notified that screening can only identify part of thrombophilic disorders));
• in patients receiving anticoagulant therapy, it is necessary to carefully evaluate the benefit-risk ratio of using Femoston® mini.

Directions for use and doses

The drug is taken orally, daily for 28 days, continuously, 1 tablet/day (preferably at the same time of day), regardless of meals.

When switching from another continuous sequential or cyclic regimen of taking the drug, you should finish the current cycle and then switch to Femoston® mini.

Patients not receiving drugs for HRT or switching from a continuous regimen of combined drugs for HRT can start taking Femoston® mini on any day.

If the patient misses the next dose, the tablet must be taken within 12 hours after the usual dosing time; otherwise, you should not take the missed tablet; you should take your tablet the next day at your usual time. Skipping a dose may increase the likelihood of breakthrough uterine bleeding or spotting.

To initiate and continue HRT treatment for disorders caused by estrogen deficiency, the combination of dydrogesterone + estradiol should be used at the lowest effective dose and for the shortest period of time (see section "Special Instructions"). Continuous combination therapy can be started with Femoston® mini, depending on the time after menopause and the severity of symptoms of estrogen deficiency.

Taking the combined drug for HRT Femoston® mini in women with natural menopause can begin no earlier than 12 months after the last menstruation. Women whose menopause is due to surgery can start taking the drug immediately (as prescribed by a doctor if symptoms are present).

There are no indications for the use of Femoston® mini in children.

There is no experience with the use of the drug in women over 65 years of age.

Estrogens can cause fluid retention in the body, so patients with impaired renal function should be under medical supervision.

Acute or chronic liver diseases currently or in history (before normalization of liver function tests) are a contraindication to the use of the drug.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Best before date

4 years. Do not use after the expiration date.

special instructions

The drug is prescribed only in the presence of symptoms that adversely affect the quality of life. 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 HRT 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 prescribing or resuming therapy with Femoston® mini, 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. During treatment with Femoston® mini, 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 conduct instrumental research methods (for example, mammography) for additional examination of the mammary glands. Women should be informed about possible changes in the mammary glands, which should be reported to their doctor.

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

Hyperplasia and endometrial cancer

In women with a preserved uterus, the risk of developing endometrial hyperplasia and cancer increases with long-term estrogen monotherapy. The risk of developing endometrial cancer when patients use estrogen only 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 continuous use of combined HRT drugs in women with a preserved uterus, may prevent the risk of endometrial hyperplasia and cancer increased by estrogen.

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

Bloody vaginal discharge

In the first months of treatment with 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. This phenomenon is most likely during the first year of HRT.

If there is a family history of thrombosis/thromboembolism in first-degree relatives aged less than 50 years, as well as a history of recurrent miscarriage, it is necessary to conduct a hemostasis study (screening reveals only some of the disorders of the blood coagulation system).

If the patient is taking anticoagulants, the benefit-risk ratio should be carefully assessed when using Femoston® mini. Until a thorough assessment of the factors for the possible development of thromboembolism or the initiation of anticoagulant therapy is completed, Femoston® mini is not prescribed.

If a thrombophilic condition is detected in a family member and/or in the case of the seriousness or severity of the defect (for example, antithrombin III deficiency, protein S or C deficiency, as well as a combination of defects), Femoston® mini is contraindicated.

Since patients with diagnosed thrombophilic conditions have an increased risk of developing venous thromboembolism, the use of Femoston® mini, which increases this risk, is contraindicated.

In most cases, risk factors for developing VTE include: estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI>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.

To prevent VTE in case of prolonged immobilization after surgery, major surgery, surgery on the lower extremities, pelvic area or neurosurgical operation, major trauma, the drug is stopped and resumed only after the woman has restored full mobility. In case of planned surgery, the drug should be stopped 4-6 weeks before surgery.

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 possible symptoms of thrombosis/thromboembolism occur (eg, tenderness or swelling of the lower extremities, sudden pain in the chest, shortness of breath).

Mammary cancer

Currently available data indicate an increased risk of developing breast cancer in women receiving HRT with combined (estrogen + progestogen) drugs and also, possibly, only estrogens. The risk depends on the duration of HRT use.

HRT with combined (estrogen + poogestagen) drugs. A randomized placebo-controlled trial (the Women's Health Initiative (WHI) study) and epidemiological studies have shown an increased risk of breast cancer in women receiving combined (estrogen + progestogen) HRT. The increase is noticeable after approximately 3 years of therapy.

Estrogen therapy. In the WHI study, there was no increased risk of breast cancer in women with a previous hysterectomy who received estrogen-only HRT. The results of observational studies, for the most part, showed a slight increase in the risk of being diagnosed with breast cancer, while this risk was noticeably lower than in women receiving combined HRT (estrogen + progestogen) drugs.

The increase in risk becomes noticeable after several years of use of HRT drugs, but after stopping therapy it returns to the original level within a few (maximum five) years.

Against the background of HRT, especially HRT with combined (estrogen + progestogen) drugs, there is an increase in the density of breast tissue during mammography, which can complicate the diagnosis of breast cancer.

Ovarian cancer

Ovarian cancer is much less common than breast cancer. Epidemiological data obtained from a large-scale meta-analysis indicate a small increase in the risk of developing ovarian cancer in women receiving HRT, both combined drugs and drugs containing estrogen alone. According to studies, the risk of developing ovarian cancer increases with a duration of therapy of more than 5 years, and after its cessation it gradually decreases.

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 using HRT drugs. The relative risk is not affected by age or timing of menopause, but 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)

In randomized controlled clinical trials, there was no evidence of a protective effect of HRT against myocardial infarction in women with or without coronary artery disease who received HRT with combined (estrogen + progestogen) drugs or estrogen alone.

HRT with combined (estrogen + progestogen) drugs. The relative risk of coronary heart disease during the use of HRT with combined (estrogen + progestagen) drugs increases slightly. Because the absolute risk of coronary heart disease is highly dependent on age, the number of additional cases of coronary artery disease due to combined hormone therapy (estrogen + progestogen) in healthy premenopausal women is very small, but it 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.

In women with hypertriglyceridemia, while taking drugs for HRT, in very rare cases, the concentration of triglycerides in the blood plasma can significantly increase, 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, as measured by determination of plasma protein-bound iodine, thyroxine (T4) concentration - chromatographic or radioimmunoassay, or triiodothyronine (T3) - radioimmunoassay. A labeled triiodothyronine uptake test shows elevated levels of thyroxine-binding globulin. Free T4 and T3 levels remain unchanged. Plasma concentrations of other binding proteins (eg, transcortin, sex hormone binding globulin) may also increase, resulting in increased concentrations of circulating glucocorticoids 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 (renin-angiotensin 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® mini is not a contraceptive.

Description

Antimenopausal agent (estrogen + progestogen).

Dosage form

Yellow, film-coated tablets, round, biconvex, engraved “379” on one side; cross-sectional appearance of the tablets: white, rough surface.

Use in children

There are no indications for the use of Femoston® mini in children.

Action

• Estradiol

Estradiol hemihydrate, which is part of the drug Femoston® mini, when dissolved, turns into 17-β-estradiol, identical to endogenous human estradiol, which is the most active estrogen.

Estradiol replenishes estrogen deficiency in the body in postmenopausal women and reduces the severity of menopausal symptoms.

• Dydrogesterone

Dydrogesterone is a progestogen that is effective when taken orally and has similar activity to parenterally administered progesterone.

Because estrogens promote endometrial proliferation, estrogen-only hormone replacement therapy (HRT) increases the risk of endometrial hyperplasia and cancer. The inclusion of dydrogesterone significantly reduces the risk of developing endometrial hyperplasia, increased under the influence of estrogen, in women with a preserved uterus.

Information obtained during clinical studies

Effect on the severity of menopausal symptoms

When prescribing Femoston® mini, a reduction in menopausal symptoms was achieved during the first weeks of treatment: the reduction in the frequency of moderate and severe hot flashes was statistically significant compared to placebo, starting from the 4th week of therapy. The number of moderate and severe hot flashes further decreased until therapy was stopped at 13 weeks.

Effect on the severity of symptoms associated with estrogen deficiency and bleeding patterns

Clinical studies have shown that Femoston® mini provides relief from symptoms associated with estrogen deficiency and bleeding patterns. In two studies, amenorrhea (absence of bleeding or spotting) was observed in 91% and 88% of women, respectively, within 10-12 months of starting treatment. Irregular bleeding or spotting occurred in 10% and 21% of women, respectively, during the first 3 months of treatment and in 9% and 12% within 10-12 months of treatment.

Side effects

In clinical studies in patients receiving therapy with the combination of estradiol + dydrogesterone, the most common symptoms were headache, abdominal pain, breast tenderness/tenderness and back pain.

In clinical studies (n=4929), the following undesirable effects were observed with the incidence indicated below (number of reported cases/number of patients): very common (≥1/10); often (from ≥1/100 to <1/10); uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000).

Infectious and parasitic diseases: often - vaginal candidiasis.

Benign, malignant and unspecified neoplasms: uncommon - increase in the size of fibroids.

From the blood and lymphatic system: rarely - hemolytic anemia*.

On the part of the immune system: rarely - hypersensitivity to the active and auxiliary substances in the drug.

Mental disorders: often - depression, nervousness; infrequently - changes in libido.

From the nervous system: very often - headache; often - migraine, dizziness; rarely - meningioma*.

On the part of the organ of vision: rarely - increased corneal curvature*, intolerance to contact lenses*.

From the cardiovascular system: infrequently - venous thromboembolism*, arteritis, peripheral vascular disease, varicose veins; rarely - myocardial infarction.

From the digestive system: very often - abdominal pain; often - nausea, vomiting, flatulence; infrequently - dyspepsia.

From the liver and biliary tract: infrequently - impaired liver function (sometimes in combination with jaundice, asthenia, malaise), gallbladder disease.

From the musculoskeletal system: very often - pain in the back (lower back); rarely - muscle cramps of the lower extremities*.

From the genital organs and mammary glands: very often - tension/pain in the mammary glands; often - menstrual irregularities (including spotting in postmenopause, metrorrhagia, menorrhagia, oligo-/amenorrhea, irregular menstruation, dysmenorrhea), pain in the lower abdomen, changes in vaginal secretion; uncommon - breast enlargement, premenstrual-like syndrome.

General disorders and disorders at the injection site: often - asthenic conditions (weakness, malaise, fatigue), peripheral edema.

Laboratory and instrumental data: often - increase in body weight; infrequently - weight loss.

* Adverse effects obtained from spontaneous reports were included in the frequency of “rare”.

Other adverse reactions caused by the use of a combination of estrogen and progestogen (including estradiol + dydrogesterone)

Benign, malignant and unspecified neoplasms: estrogen-dependent benign and malignant neoplasms, incl. endometrial cancer and ovarian cancer; an increase in the size of progestogen-dependent neoplasms, incl. meningiomas.

From the immune system: systemic lupus erythematosus.

Metabolism: hypertriglyceridemia, worsening of concomitant porphyria.

From the nervous system: risk of developing dementia, chorea, provoking epilepsy attacks.

Vascular disorders: arterial thromboembolism.

From the digestive system: pancreatitis (in patients with hypertriglyceridemia).

From the skin and subcutaneous tissues: erythema multiforme.

From the kidneys and urinary tract: urinary incontinence, cystitis.

From the genital organs and mammary gland: fibrocystic mastopathy, cervical erosion.

Laboratory and instrumental data: increased concentration of thyroid hormones in blood plasma.

Use during pregnancy and breastfeeding

The use of Femoston® mini during pregnancy and breastfeeding is contraindicated.

If pregnancy occurs while taking the drug, you should immediately stop using it.

The results of most epidemiological studies analyzing data on the unintentional use of combinations of estrogens and progestogens by pregnant women indicate the absence of teratogenic and fetotoxic effects of the drugs. Available data on the use of estradiol/dydrogesterone in pregnant women are limited.

The drug Femoston® mini is not used in women of reproductive age.

Interaction

Reduced effectiveness of Femoston® mini

The metabolism of estrogen and progestogen can be enhanced when taken simultaneously with drugs that induce microsomal liver enzymes of the cytochrome P450 system (isoenzymes CYP2B6, 3A4, 3A5, 3A7): anticonvulsants (phenobarbital, carbamazepine, phenytoin) and antimicrobial drugs (rifampicin, rifabutin, nevirapine, efavirenz) .

Ritonavir and nelfinavir, although known as strong inhibitors of CYP3A4, A5, A7, when used simultaneously with sex hormones, can enhance their metabolism.

Herbal preparations containing St. John's wort (Hypericum perforatum) may enhance the metabolism of estrogen and progestogen through the CYP3A4 isoenzyme.

Increased metabolism of estrogen and progestogen can be clinically manifested by a decrease in the effect of the drug and a change in the intensity of bleeding from the vagina.

The effect of estrogens on the metabolism of other drugs

Estrogens can affect the metabolism of other drugs through competitive binding with isoenzymes of the cytochrome P450 (CYP) system. This must be taken into account for drugs with a narrow therapeutic action, such as tacrolimus and cyclosporine A (CYP3A4, 3A3), fentanyl (CYP3A4) and theophylline (CYP1A2), because this type of interaction can lead to an increase in the plasma concentration of the above drugs to a toxic level. This may require careful monitoring of medications over a long period of time and possibly a reduction in the dose of tacrolimus, fentanyl, cyclosporine A and theophylline.

No studies have been conducted to study interactions with other drugs.

Overdose

Estradiol and dydrogesterone are substances with low toxicity.

Symptoms: nausea, vomiting, breast tension, dizziness, abdominal pain, drowsiness/weakness, withdrawal bleeding may occur.

Treatment: symptomatic therapy.

The information above also applies in cases of unintentional overdose in children due to accidental use of the drug.

Impact on the ability to drive vehicles and operate machinery

Care should be taken when operating vehicles and machinery, taking into account the risk of adverse reactions from the nervous system.

Analogs

Level 4 ATX code matches:
Klimonorm

The generic (structural analogue) of Femoston ⅕ is the drug Femoston Conti 1/5.

Drugs with a similar mechanism of action: Divina , Klimonorm , Kliogest , Trisequence .

Klimonorm or Femoston - which is better?

The decision about which drug from the group of combined estrogen-gestagen agents should be chosen is made by the doctor based on the data received from the patient about the period of age-related hormonal changes.

It is believed that in the drug Klimonorm the progestin component is present in the most optimal concentration, which allows effective control of the cycle and provides the necessary level of protection of the endometrium from the hyperplastic effect of estrogens .

At the same time, it is possible to maintain the beneficial effects caused by the influence of estrogens on the state of the cardiovascular system and lipid metabolism . In addition, levonorgestrel Klimonorm potentiates the effect of estradiol , aimed at the treatment and prevention of osteoporosis .

Another important feature of levonorgestrel is its almost 100% bioavailability, thanks to which it is possible to maintain the stability of the drug’s effects.

Moreover, the severity of the effects remains unchanged regardless of the woman’s nutritional characteristics, the presence of diseases of the digestive tract , as well as the activity of the liver system , which plays a key role in the processes of first-pass metabolism of xenobiotics .

The bioavailability of dydrogesterone , which is part of Femoston, is 28%, and therefore its effects are subject to fluctuations (both inter- and inter-individual).

Angelique or Femoston - which is better?

Experts believe that there is not much difference between these means. The main difference between the drug Angelique and Femoston is that it contains drospirenone progestational .

During pregnancy

The use of Femoston is contraindicated if it is known for sure that the woman is pregnant, as well as if there is reason to suspect pregnancy. The drug is also contraindicated for women who are breastfeeding.

In some cases, the medicine is prescribed during pregnancy planning. The indications are:

• conditions caused by estrogen and manifested by insufficiency of the first phase (that is, conditions in which by the end of the first (follicular) phase of the menstrual cycle the thickness of the endometrial layer does not exceed 7-8 mm);
• infertility caused by hormonal imbalance.

Too thin an endometrium can cause disruption of the luteal phase and, as a result, a woman cannot become pregnant.

Most often, at the planning stage, doctors recommend taking Femoston 2/10.

The concentration of estradiol in tablets intended for use during the first 2 weeks of the cycle is such that the drug, unlike contraceptives, does not suppress ovulation , while simulating the first phase of the menstrual cycle and stimulating the division and growth of endometrial .

Taking tablets containing estradiol supplemented with dydrogesterone, in turn, ensures secretory transformation of the inner layer of the uterus , which is necessary for normal implantation of the egg in the event of its fertilization and pregnancy. Thus, Femoston 2/10 allows you to normalize the disrupted menstrual cycle .

When planning pregnancy, Femoston 2/10 is taken from the first day of the menstrual cycle, one tablet per day for 4 full weeks. You should not stop treatment before the entire package is completed, as this can provoke a hormonal imbalance, manifested by breakthrough bleeding of varying degrees of intensity and leaving no chance of pregnancy.

Women who take Femoston when planning a pregnancy should further strengthen the luteal (second) phase of the cycle, therefore, from the 14th day of treatment, the patient is prescribed to take the drug in combination with Duphaston (or its analogue).

Dydrogesterone is present as gestagenic component in Duphaston , and this makes it possible to enhance the positive effect of therapy on the female body and the condition of the endometrium .

Duphaston is taken one tablet twice a day for a full two weeks.

Is it possible to get pregnant while taking the drug?

Pregnancy that occurs during the use of Femoston is an exception. As a rule, the chances of becoming pregnant after taking the drug for several cycles are considered more realistic, and this usually occurs after stopping treatment.

In extremely rare cases, it is possible to use the product against the background of an already existing pregnancy, when a woman needs endometrial . However, such a decision can only be made by a qualified specialist.

Femoston® 2 (Femoston® 2)

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 an assessment of the benefit-risk ratio. 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 HRT in cases of premature menopause is limited. Because of 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® 2, 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® 2, 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, may prevent 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® 2 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® 2 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 line of relationship) taking Femostonk 2 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® 2 4-6 weeks before and not resume 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 developing 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 monotherapy.

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 be increased, 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® 2 is not a contraceptive.

Femoston reviews

A considerable number of reviews about Femoston 1/5 Conti have been left on the forums. Like reviews of Femoston 2/10 or 1/10, they are quite contradictory. As a rule, in reviews, women describe their experience of using the product during menopause or when planning pregnancy .

Those who were satisfied with the treatment note as the advantages of the drug that it is quite well tolerated and rarely causes side effects, quickly normalizes the condition, relieving the unpleasant symptoms of the onset of menopause , and improves overall well-being, has a positive effect on the condition of the skin, and restores the cycle in case of its violations, easy to use.

Negative reviews are associated with the occurrence of undesirable side effects (depression, rash, excess weight, swelling, decreased activity, joint pain, etc.), as well as the lack of the expected effect.

Turning to doctors' reviews of Femoston 1/10, 2/10 or 1/5, which are based on the results of clinical studies, we can conclude that the drug is a highly effective remedy for the treatment and prevention of conditions that have developed as a result of premature ovarian .

Moreover, all patients showed good tolerability of the tablets. Studies have made it possible to establish a pronounced positive effect of therapy on the general well-being of women and, in particular, on the blood lipid profile .

Against the background of the treatment, a significant increase in the rate of maximum oxygen consumption and an increase in the bone-protective effect of the estrogen component of Femoston by dydrogesterone were also established.

Thus, doctors confirm the need for early initiation and differentiated choice of hormone replacement therapy in women with “switched off” ovarian function .

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 price, where to buy

Price Femoston 1/5 in Russian pharmacies from 870 rubles. You can buy Femoston Conti 1/5 for an average of 900 rubles. Price Femoston 2/10 - from 790, Femoston 1/10 - from 795 rubles.

In Ukraine, the price of Femoston 1/10 is from 438 UAH, the price of Femoston 2/10 is from 520 UAH. The cost of the drug with a dosage of 1 mg + 5 mg is from 445 UAH.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

ZdravCity

• Femoston 2 tab.
  p/o captivity. 2mg+10mg No. 28 Abbott Biologicals B.V. NL 1149 rub. order
• Femoston 1/5 conti tablets p.p.o. 28 pcs. Abbott Biologicals B.V.

  RUB 1,149 order

• Femoston Mini tablets p.p.o. 2.5 mg+0.5 mg 28 pcs. Abbott Biologicals B.V.

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• Femoston 1 tab. p/o captivity. 1mg+10mg No. 28 Abbott Biologicals B.V. NL

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Pharmacy Dialogue

• Femoston 1 tablet No. 28Abbot

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• Femoston conti tablets 1mg/5mg No. 28Abbot Biologicals

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• Femoston 2 tablets No. 28Abbot

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• Femoston mini tablets 2.5mg+0.5mg No. 28Abbot

  RUB 1,159 order

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Pharmacy24

• Femoston Conti 1mg+5 mg No. 28 tablets Abbott Biologicals B.V., Netherlands
  444 UAH.order
• Femoston 1 mg/10 mg No. 56 tablets Abbott Biologicals B.V., Netherlands

  816 UAH order

• Femoston Conti Mini 0.5 mg/2.5 mg No. 28 tablets Abbott Biologicals B.V., Netherlands

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• Femoston 1mg+10mg No. 28 tablets Abbott Biologicals B.V., Netherlands

  439 UAH. order

• Femoston 2 mg+10 mg No. 28 tablets Abbott Biologicals B.V., Netherlands

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PaniPharmacy

• Femoston tablets Femoston tablets 2mg+10mg No. 28 Netherlands, Solvay Biologicals

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• Femoston conti tablets Femoston conti tablets 1mg+5mg No. 28 Netherlands, Solvay Biologicals

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• Femoston tablets Femoston tablets 1mg+10mg No. 28 Netherlands, Abbott Biologicals

  433 UAH order

• Femoston tablets Femoston tablets 1mg+10mg No. 56 Netherlands, Abbott Biologicals

  795 UAH. order

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