Femoston® mini (Femoston® mini)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDydrogesterone + EstradiolDydrogesterone + Estradiol
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    Abbott Helskea Products BV     Netherlands
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  • Femoston® mini
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    Abbott Helskea Products BV     Netherlands
    • Dosage form: & nbspTfilm-covered abeys.
    Composition:

    Active substances: dydrogesterone - 2.5 mg, estradiol hemihydrate - 0.517 mg (in terms of estradiol - 0.5 mg).

    Excipients: lactose monohydrate - 117.4 mg; hypromellose (HPMC 2910) 2.8 mg; corn starch - 14.7 mg; silicon dioxide colloidal - 1.4 mg; magnesium stearate - 0.7 mg.

    Film sheath: film coating YELLOW 1 (macrogol 3350-20.2%, polyvinyl alcohol 40.0%, talc 14.8%, titanium dioxide (E 171) 20.55%, iron dye oxide yellow (E 172) -4.45% ) - 4.0 mg.

    Description:

    Round, biconvex tablets, covered with a film coating of yellow color, engraved "379" on one side.

    Pharmacotherapeutic group:antimycotics combined (estrogen + progestogen)
    ATX: & nbsp

    G.03.F.A.14   Dydrogesterone and estrogen

    Pharmacodynamics:

    Estradiol

    The estradiol hemihydrate, which is part of the preparation Femoston® mini, dissolves into 17-β-estradiol, identical to the endogenous estradiol of the human being, which is the most active estrogen.

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

    In appointing the drug Femoston® small reductions in "tide" moderate to severe degree it was statistically significant compared with placebo, starting at 4 weeks of therapy. The number of moderate and pronounced hot flushes was further reduced by 13 weeks before the termination of therapy.

    Dydrogesterone

    Dydrogesterone - progestogen effective when taken orally, and having a similar parenterally administered progesterone activity.

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

    In clinical trials, it has been shown that the preparation of Femoston® mini provides relief from symptoms associated with a lack of estrogens and the nature of bleeding. Attenuation of menopausal symptoms was achieved during the first weeks of treatment.

    Pharmacokinetics:

    Estradiol

    Suction

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

    Distribution

    Estradiol (like other estrogens) can be detected both in bound and free state. About 98-99% of the dose of estradiol binds to blood plasma proteins, of which 30-52% - with albumin and about 46-69% - with sex hormone binding globulin (GSHG).

    Metabolism

    After oral administration estradiol is actively metabolized in the liver. The main unconjugated and conjugated metabolites are estrone and estrone sulfate, which have estrogenic activity. Estrone sulfate can undergo intestinal hepatic recirculation.

    Excretion

    Estrone and estradiol are excreted in the kidney conjugated with glucuronic acid. The half-life (T1/2) is 10-16 hours. Estrogens penetrate into breast milk.

    Dependence of the concentration of estradiol on time and dose

    With the daily administration of the drug Femoston® mini, the concentration of estradiol in the blood plasma reaches a constant value after about 5 days. Usually, this indicator is achieved within 8-11 days after the initiation of therapy.

    Dydrogesterone

    Suction

    After oral administration dydrogesterone quickly absorbed.The time value of the maximum concentration (TmOh) for dydrogesterone varies from 30 minutes to 2.5 hours. Bioavailability of dydrogesterone - 28%.

    Distribution

    More than 90% of dydrogesterone and 20a-dihydrodidrogesterone (DHD) bind to blood plasma proteins.

    Metabolism

    After oral administration dydrogesterone quickly metabolized to DGD. The maximum concentration of DGD in the blood plasma is reached approximately 1.5 hours after the administration of the drug. The concentration of DGD in plasma significantly exceeds the initial concentration of dydrogesterone, the ratio of the area under the curve "concentration-time" (AUC) and maximum concentration (CmOh) DGD to dydrogesterone is about 40 and 25, respectively. The half-life is 5-7 hours for dydrogesterone, 14-17 hours for DGD.

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

    Excretion

    Completely dydrogesterone is output after 72 hours. On average, 63% from the adopted dose is excreted by the kidneys. The total plasma clearance is 6.4 l / min.DGD is determined in urine mainly in the form of glucuronic acid conjugate.

    Dependence of dydrogesterone concentration on time and dose

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

    The equilibrium concentration of dydrogesterone was achieved 3 days after the start of the admission.
    Indications:

    Replacement hormone therapy for estrogen deficiency disorders in postmenopausal women (no earlier than 12 months after the last menstrual period).

    Contraindications:

    - Hypersensitivity to the components of the drug.

    - Diagnosed or suspected breast cancer.

    - Diagnosed or suspected estrogen-dependent malignant neoplasms (eg, endometrial cancer).

    - Diagnosed or suspected progestogen-dependent neoplasms (eg, meningioma).

    - Bleeding from the vagina of an unclear etiology.

    - Untreated hyperplasia of the endometrium.

    - Thrombosis (arterial and venous) and thromboembolism at present or in the anamnesis (including thrombosis,deep vein thrombosis; thromboembolism of the pulmonary artery, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders).

    - Acute or chronic liver disease at present or in the anamnesis (before the normalization of indicators of functional liver tests), including malignant liver tumors.

    - Porphyria.

    - Multiple or expressed factors of arterial or venous thrombosis associated with a congenital or acquired predisposition, for example, protein C deficiency, protein deficiency S, insufficiency of antithrombin III, the presence of antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant), stenocardia, prolonged immobilization, severe forms of obesity (body mass index more than 30 kg / m2), cerebrovascular or coronary artery disease, transient ischemic attacks, complicated valvular heart disease, atrial fibrillation.

    - Pregnancy and the period of breastfeeding.

    - Intolerance to galactose, insufficiency of lactase, glucose-galactose malabsorption syndrome.

    - Meningioma.

    The preparation of the drug Femoston® mini should be discontinued if there are any contraindications and / or when the following conditions occur:

    - jaundice and / or liver dysfunction;

    - uncontrolled arterial hypertension;

    - The first to appear on the background of the use of drugs for HRT is migraine headache.

    Carefully:

    Carefully HRT is prescribed to women if any of the listed conditions are diagnosed at the present time, occurred earlier and / or intensified during pregnancy or previous hormonal therapy:

    - Lymomyoma of the uterus, endometriosis.

    - The presence of risk factors for the occurrence of estrogen-dependent tumors (for example, relatives of the first degree of kinship with breast cancer).

    - Arterial hypertension.

    - Benign tumors of the liver.

    - Diabetes mellitus, both in the presence of vascular complications, and in the absence of them.

    - Chololithiasis.

    - Migraine or severe headache.

    - Systemic lupus erythematosus.

    - Hyperplasia of the endometrium in the anamnesis.

    - Epilepsy.

    - Bronchial asthma.

    - Otosclerosis.

    It should be taken into account that these conditions may recur or worsen during therapy with the drug Femoston® mini.

    Precautions should be taken in the following cases:

    - in patients with chronic cardiac and renal insufficiency;

    - in patients with risk factors for thrombosis and thromboembolism in a family history (thromboembolic complications in relatives of the first degree of kinship at a young age), screening should be done by consulting the patient in advance of its limitations (only a part of the thrombophilic defects can be detected by screening) ;

    - in patients receiving anticoagulant therapy, it is necessary to carefully consider the use of the drug Femoston® mini in terms of the "benefit / risk" ratio.

    Pregnancy and lactation:

    The drug is contraindicated in pregnancy and during breastfeeding.

    The results of most epidemiological studies with the analysis of data on the unintentional intake of pregnant estrogen and progestogen combinations, indicate the absence of teratogenic and fetotoxic effects of drugs on the fetus. The available data on the use of estradiol / dydrogesterone by pregnant women are limited.

    If a pregnancy occurs while the treatment with Femoston® is being treated, the mini therapy should be discontinued immediately.

    Dosing and Administration:

    The drug is taken orally daily, in continuous mode, 1 tablet per day (preferably at the same time of day), regardless of food intake.

    Patients making the transition from another continuous sequential or cyclic regimen should complete the current cycle, and then switch to the preparation of Femoston® mini. Patients who do not receive HRT medications or who are taken with a continuous regimen of combination therapy for HRT may start taking Femoston® mini on any given day.

    If the patient missed taking the pill, it must be taken within 12 hours after the usual intake time; otherwise, the missed tablet should not be taken, and the next day it is necessary to take the pill at the usual time. Skipping the drug may increase the likelihood of "breakthrough" uterine bleeding or spotting spotting.

    To start and continue therapy for postmenopausal disorders, the lowest effective dose should be taken for the shortest period of time (see section "Special instructions").

    Continuous combination therapy can be started with the preparation of Femoston®mini or a preparation of the line of Femoston® with 5 mg dydrogesterone and 1 mg estradiol in one tablet, depending on the time after the onset of menopause and the severity of the symptoms.

    Admission of a combined preparation for HRT Femoston® mini in women with natural menopause can begin no earlier than 12 months after the last menstruation.

    Women who have menopause due to surgery can start taking the drug immediately (as directed by the doctor if symptoms occur).

    Application in special clinical groups of patients

    Children

    Indications for the use of the drug Femoston® mini in children are absent.

    Older patients

    The experience of treating women over the age of 65 is absent.

    Impaired renal function

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

    Impaired liver function

    Acute or chronic liver diseases at present or in the anamnesis (before normalization of indicators of functional tests of the liver) are a contraindication to the use of the drug.

    Side effects:

    In clinical studies, the most common cases of patients receiving estradiol / dydrogesterone combination therapy were headache, abdominal pain, mammary tension / tenderness, and back pain.

    In clinical trials (n= 4929), the following adverse events were observed with a developmental frequency indicated below (number of reported cases / number of patients):

    Often -

    ≥ 1/10

    Often -

    from ≥ 1/100 to <1/10

    Infrequently -

    from ≥ 1/1000 to <1/100

    Rarely -

    from ≥ 1/10000 to <1/1000

    Rarely -

    <1/10000

    Infections and invasions

    Candidiasis of the vagina

    Neoplasms: benign, malignant and unspecified

    Increased size of leiomyoma

    Immune system disorders

    Hypersensitivity

    Disorders of the psyche

    Depression, nervousness

    Changing libido

    Disturbances from the nervous system

    Headache

    Migraine, dizziness

    Heart Disease

    Myocardial infarction

    Vascular disorders

    Venous thromboembolism, arteritis, varicose veins

    Disorders from the gastrointestinal tract

    Abdominal pain

    Nausea, vomiting, flatulence

    Dyspepsia

    Disturbances from the liver and bile ducts

    Dysfunction of the liver, sometimes in combination with jaundice, asthenia, malaise, gallbladder disease

    Disturbances from the skin and subcutaneous tissues

    Allergic reactions, such as urticaria, skin rash and itching

    Vascular purpura, angioedema

    Disturbances from musculoskeletal and connective tissue

    Pain in the back (waist)

    Violations of the genitals and mammary gland

    Breast pressure / soreness

    Violations of the menstrual cycle (including "smearing" spotting in postmenopause, metrorrhagia, menorrhagia, oligo- / amenorrhagia, irregular menstruation, dysmenorrhea) pain in the lower abdomen, changes in vaginal secretion

    Breast augmentation, premenstrual-like syndrome

    General disorders

    Asthenic conditions (weakness, malaise, fatigue), peripheral edema

    Other

    Weight gain

    Weight loss

    Other side effects caused by treatment with a combination of estrogen and progestogen (including estradiol / dydrogesterone):

    Benign, malignant and unspecified neoplasms: estrogen-dependent benign and malignant neoplasms, including endometrial cancer, ovarian cancer. Increase in the size of progestogen-dependent neoplasms, including meningiomas.

    On the part of the blood and lymphatic system: hemolytic anemia.

    From the immune system: systemic lupus erythematosus.

    From the side of metabolism: hypertriglyceridemia.

    From the nervous system: the risk of developing dementia in women starting to use drugs for HRT over the age of 65, chorea, provoking epileptic seizures.

    From the side of the organ of vision: intolerance to contact lenses, increased curvature of the cornea.

    From the side of the cardiovascular system: arterial thromboembolism.

    From the gastrointestinal tract: pancreatitis (in patients with hypertriglyceridemia).

    From the skin and subcutaneous tissues: Chloasma and / or melasma, which can persist after discontinuation, erythema multiforme, erythema nodosum.

    From the musculoskeletal system and connective tissue: cramps in the muscles of the lower extremities.

    From the genitourinary system: urinary incontinence.

    Disorders from the reproductive system and mammary glands: fibrocystic mastopathy, cervical erosion.

    Congenital and hereditary disorders: worsening of the course of concomitant porphyria.

    Laboratory indicators: an elevated level of thyroid hormones.

    Overdose:

    Estradiol and dydrogesterone - substances with low toxicity.

    Symptoms

    In case of an overdose, symptoms such as nausea, vomiting, mammary gland tension, dizziness, abdominal pain, drowsiness / weakness and bleeding can be developed.

    Treatment

    Symptomatic.

    Interaction:

    Studies on the interaction with other drugs have not been conducted.

    The effectiveness of the preparation Femoston® mini can be reduced in the following cases:

    - Metabolism of estrogens and progestogens can be enhanced by simultaneous reception with induction drugs of microsomal liver enzymes (P450 2B6, 3A4, 3A5, 3A7): anticonvulsant (phenobarbital, carbamazepine, phenytoin) and antimicrobial agents (rifampicin, rifabutin, nevirapine, efavirenz).

    - Ritonavir and nelfinavir although they are known as strong inhibitors CYP 450 3A4, A5, A7, with simultaneous application with sex hormones can enhance their metabolism.

    - Preparations of plant origin containing St. John's wortHypericum perforatum), can enhance the metabolism of estrogens and progestogens through CYP 450 3A4.

    - The increase in the metabolism of estrogens and progestogens can be clinically manifested by a decrease in the effect of the drug and the appearance of bloody discharge from the vagina.

    Estrogens can affect the metabolism of other medicines:

    Estrogens can affect the metabolism of other drugs through competitive binding to enzymes (CYP 450). This should be taken into account for drugs with a narrow breadth of therapeutic effect, such as tacrolimus and ciclosporin A (CYP 450 3A4, 3A3), fentanyl (CYP 450 3A4) and theophylline (CYP 450 1A2), since this type of interaction can lead to an increase in the concentration in the blood plasma of the above drugs to a toxic level. In this regard, careful monitoring of medication intake over a long period of time and possibly a reduction in the dose of tacrolimus, fentanyl, cyclosporin A, and theophylline may be required.

    Special instructions:

    The drug is prescribed only in the presence of symptoms adversely affecting the quality of life. Therapy should be continued until the benefit of taking the drug exceeds the risk of side effects.

    The experience of using the drug in women over 65 is limited.

    Medical examination

    Before the appointment or resumption of therapy with the drug 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 compliance with precautions. During treatment with the drug Femoston® mini, periodic examinations are recommended, the frequency and nature of which are determined individually, but at least 1 time in 6 months. It is advisable to conduct instrumental research methods (for example, mammography) for additional examination of the mammary glands. Women should be informed of possible changes in the mammary glands, which are required to inform the treating doctor.

    The use of estrogens can affect the results of the following laboratory tests: determinationtolerance to glucose, the study of the functions of the thyroid and liver.

    Hyperplasia and endometrial cancer

    In women with a preserved uterus, the risk of developing hyperplasia and endometrial cancer increases with prolonged estrogen monotherapy. The risk of developing endometrial cancer when only estrogen is used by patients depends on the dose and duration of treatment and is increased 2 to 12 times compared to the absence of treatment; the risk may remain elevated for 10 years after discontinuation of therapy.

    The use of combined drugs for continuous HRT in women with a preserved uterus can prevent increased estrogen risk of hyperplasia and endometrial cancer.

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

    Bloody discharge from the vagina

    In the first months of treatment, the drug may be marked by "breakthrough" bleeding and / or meager spotting from the vagina. If such bleeding occurs some time after the initiation of therapy or continues after discontinuation of treatment,it is necessary to establish their cause. It is possible to conduct an endometrial biopsy to exclude a malignant neoplasm.

    Venous thromboembolism

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

    In the presence of thromboembolic complications in relatives of the first degree of kinship at a young age, as well as with a habitual miscarriage in a history, it is necessary to conduct a study of hemostasis. If the patient is taking anticoagulants, you should carefully consider the use of the drug Femoston® mini in terms of the "benefit / risk" ratio. Before the completion of a thorough assessment of the possible development of thromboembolism or the initiation of anticoagulant therapy, the preparation of Femoston® mini is not prescribed.

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

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

    In most cases, risk factors for VTE include: estrogen use, advanced age, extensive surgical interventions, 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 surgical intervention in all postoperative patients, it is necessary to consider the issue of preventive measures.

    To prevent VTE in the case of prolonged immobilization after surgery, a large operation, lower limb surgery, pelvic or neurosurgical operation, extensive trauma, the drug is stopped and resumed only after the full mobility of the woman is restored. In the case of a planned surgical intervention, the drug is stopped 4 to 6 weeks before the operation.

    If VTE develops after the initiation of therapy, the drug should be discontinued and the patients should be informed that they should immediately consult their doctor if they have any potentially thromboembolic symptoms (eg, tenderness or swelling of the lower limbs, sudden pain in the chest, shortness of breath).

    Mammary cancer

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

    HRT combined (estrogen + progestogen) drugs Randomized placebo-controlled study (results of the study "Women's Health Initiative" (WH1)) and epidemiological studies have shown an increased risk of developing breast cancer in women taking HRT combined (estrogen + progestogen) drugs. The increase is noticeable after approximately three years of therapy.

    Therapy with estrogen

    In the study WHI there was no increased risk of developing breast cancer in women with previous hysterectomy who received HRT only with estrogen.

    The results of observational studies, for the most part, showed a slight increase in the risk of breast cancer diagnosis, and this risk was significantly lower than that of women taking HRT combined (estrogen + progestogen) drugs. The increase in risk becomes noticeable after several years of HRT use, but after the cessation of therapy it returns to the baseline within a few (maximum five) years.

    On the background of HRT, especially HRT combined (estrogen + progestogen) drugs, there is 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. Long-term use (at least 5-10 years) of estrogen in monotherapy with HRT is associated with a slight increase in the risk of ovarian cancer. Data from some studies, including WHI, indicate that combined HRT can increase the risk of developing this pathology to the same or slightly lesser extent.

    The risk of ischemic stroke

    Combined therapy with estrogen and progestogen or estrogen alone is associated with an increase in the relative risk of ischemic stroke by a factor of 1.5. The risk of hemorrhagic stroke with the use of drugs for HRT is not increased. The relative risk does not depend on the age or timing of menopause, but the initial risk depends heavily on age, so the overall risk of stroke in women receiving HRT will increase with age.

    Ischemic heart disease (CHD)

    In the randomized controlled clinical trials, there was no evidence of the protective effect of HRT against myocardial infarction in women with / without IHD who received HRT combined (estrogen + progestogen) drugs or only estrogen.

    HRT combined (estrogen + progestogen) drugs

    The relative risk of coronary heart disease during the use of HRT combined (estrogen + progestogen) drugs slightly increases. Due to the fact that the absolute risk of coronary heart disease greatly depends on age, the number of additional cases of IHD due to taking HRT with combined (estrogen + progestogen) drugs in healthy women of premenopausal age is extremely rare, but increases with age.

    Other states

    Estrogens can cause fluid retention, which can adversely affect the condition of patients with impaired renal and cardiac function.

    In women with hypertriglyceridemia, when taking drugs for HRT in very rare cases, the plasma concentration of triglycerides can significantly increase, which contributes to the development of pancreatitis.

    Estrogens increase the concentration of thyroxine-binding globulin, which leads to a general increase in the concentration of circulating thyroid hormones, as measured by the determination of iodine bound to plasma proteins, thyroxine concentration (T4) -chromatographic or radioimmunoassay or triiodothyronine (T3) - radioimmunoassay. The capture test of labeled triiodothyronine shows an elevated level of thyroxin-binding globulin. Levels of free T4 and T3 remain unchanged. The concentration of other binding proteins in the blood plasma, for example, transcortin, globulin, binding sex hormones, can also increase, which leads to an increase in the concentration of circulating glucocorticosteroids and sex hormones, respectively. Concentrations of free or biologically active hormones do not change.It is possible to increase the concentration of other plasma proteins (renin-angiotensin-aldosterone 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 started using HRT (combined or estrogen-only) after 65 years.

    The drug Femoston® mini is not a contraceptive.

    Effect on the ability to drive transp. cf. and fur:

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

    Form release / dosage:Film-coated tablets, 2.5 mg + 0.5 mg.
    Packaging:

    For 28 tablets in PVC / Al blister.

    For 1, 3 or 10 blisters in a cardboard box together with instructions for use.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    4 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003754
    Date of registration:26.07.2016
    Expiration Date:26.07.2021
    The owner of the registration certificate:Abbott Helskea Products BVAbbott Helskea Products BV Netherlands
    Manufacturer: & nbsp
    Representation: & nbspABBOTT LABORATORIES LLC ABBOTT LABORATORIES LLC Russia
    Information update date: & nbsp30.08.2016
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