Femoston( estradiol, dydrogesterone)

Femoston( estradiol, dydrogesterone) analogs:

Femoston( estradiol, dydrogesterone) instruction:

Active substance of Femoston

Forms of release of Femoston

Tablets covered with a film sheath No. 28 No. 84( 28x3) - Combination: film-coated tablets, 1 mg No. 14 + film-coated tablets, 1 mg / 10mg No. 14 in blisters No. 1 No. 3

To whom is shown Femoston

  • Replacement hormone therapy for elimination of symptoms due to estrogen deficiency in postmenopausal women.
  • Prevention of osteoporosis in postmenopausal women with a high risk of fracture in case of intolerance or contrai
    ndications for the use of other medications for the prevention of osteoporosis.

How to use Femoston

Method of administration and dose.

Take one tablet that contains 1 or 2 mg of estradiol once a day, daily for the first 14 days of the 28-day cycle;the next 14 days - one tablet per day, which contain 1 or 2 mg of estradiol and 10 mg of dydrogesterone. At the end of the 28-day cycle, you should immediately begin a new cycle. It is necessary to take one tablet daily internally in the sequence that is marked on the package. Treatment should be continuous.

To begin and continue treatment for postmenopausal symptoms, it is necessary to prescribe the minimum effective dose for a minimum period of time.

Treatment of postmenopausal symptoms

It is usually necessary to start treatment with the drug Femoston, which contains 1 mg of estradiol and 10 mg of dydrogesterone. Depending on the clinical effect, in the future, the dose can be selected individually.

If the symptoms associated with estrogen deficiency do not decrease, the dose can be increased by prescribing a drug that contains 2 mg of estradiol and 10 mg of dydrogesterone.

Osteoporosis prevention

With hormone replacement therapy for the prevention of osteoporosis in the postmenopausal period, it is necessary to take into account the expected effects on bone mass, which are dose-dependent, as well as individual tolerability of treatment.

Femoston can be used regardless of the intake of food.

Features of the application.

For the treatment of postmenopausal symptoms, HRT should be started only if there are symptoms that adversely affect the quality of life. In all cases, a thorough risk and benefit analysis must be conducted at least annually, and HRT should be continued only if the benefit exceeds the risk.

Medical examination / observation

Before starting or resuming hormone replacement therapy, you need to find out a complete personal and family history. Physical examination( including examination of the pelvic organs and mammary glands) should be done on the basis of history, contraindications, and taking into account warnings when used.

It is recommended to conduct regular examinations during treatment, the frequency and volume of which is determined individually.

Women should be informed of any changes in the mammary gland that need to be reported to a doctor or nurse. Examination with mammography should be done in accordance with existing practice, modified according to individual needs.

Diseases in which it is necessary to monitor the status of patients

In the presence of each of the diseases noted below, currently, in the past and / or their worsening during pregnancy or previous hormone therapy, patients should be closely monitored. It must be borne in mind that these diseases can recur or their course worsen during treatment with Femoston.

These include:

  • uterine fibroids or endometriosis;
  • thromboembolic disease in the past or the presence of risk factors for thromboembolism( see below);
  • presence of risk factors for the occurrence of estrogen-dependent tumors, for example, the first degree of hereditary propensity to breast cancer;
  • arterial hypertension;
  • liver disease( eg, liver adenoma);
  • diabetes mellitus with or without vascular complications;
  • cholelithiasis;
  • migraine or( severe) headache;
  • systemic lupus erythematosus;
  • endometrial hyperplasia in the anamnesis( see below);
  • epilepsy;
  • bronchial asthma;
  • otosclerosis.

Reasons for immediate cessation of therapy:

  • occurrence of jaundice or impaired liver function;
  • significant increase in blood pressure;
  • appearance of a first-time headache by type of migraine;
  • pregnancy.

Endometrial hyperplasia

When treated with estrogen alone, the risk of hyperplasia and endometrial cancer increases for a long time. The addition of progestogen treatment for at least 12 days of the cycle in women with a preserved uterus significantly reduces this risk.

Bleeding

During the first months of treatment, breakthrough uterine bleeding or clotting can occur. If such occur in treatment after some time or last after its cancellation, it is necessary to find out their cause, which may include an endometrial biopsy to exclude malignant neoplasms of the endometrium.

Venous thromboembolism

HRT is associated with a higher relative risk of venous thromboembolism( VTE), ie, deep vein thrombosis or pulmonary embolism. The emergence of such a condition is likely likely during the first year of HRT, than later.

The presence of such past violations in the past in a patient or family members, severe obesity( body mass index> 30 kg / m2) and systemic lupus erythematosus( SLE) are recognized as common risk factors for developing BTW.There is no consensus on the role of varicose veins in the development of VTE.In patients with BTU in the history or those who have conditions that are accompanied by increased blood clotting, the risk of BTU is elevated. HRT may increase this risk.

In the presence of thromboembolism in a patient's history or a history of a family history, as well as with recurrent spontaneous abortions, a survey should be conducted to exclude the tendency to thrombosis. Before the completion of a thorough assessment of the factors of thrombophilia or the onset of anticoagulant therapy, the use of HRT in such patients should be contraindicated.

Women who are already taking anticoagulants need a thorough analysis of the risk-benefit ratio of HRT use.

The risk of BTW may temporarily increase with prolonged immobilization, significant trauma or extensive surgery. Usually, in the postoperative period, serious attention needs to be given to preventive measures to prevent VTE after operations. If prolonged immobilization is planned after surgical intervention, namely after operations on the abdominal organs or orthopedic operations on the lower limbs, consideration should be given to the possibility of temporary discontinuation of HRT 4 to 6 weeks before surgery.

Treatment should not be started again until the woman's motor activity is fully restored. If venous thromboembolism develops after the initiation of therapy, the drug should be withdrawn.

Patients should be warned about the need to consult a doctor immediately if there is a potential symptom of thromboembolism( eg, painful leg swelling, sudden pain, chest pain, dyspnea).

Coronary artery disease of the heart

No evidence of a positive effect on the cardiovascular system of continuous combination therapy with conjugated estrogens and MPA has been obtained in randomized controlled trials. In two large clinical trials, the WHI and HERS( Heart and Estrogen / progestin Replacement Study) demonstrated a possible increased risk of cardiovascular disease during the first year of treatment and a lack of a positive overall effect.

For other drugs that are used for HRT, there are only limited data from randomized controlled trials in which effects on cardiovascular morbidity or mortality have been studied. Therefore, it is not known whether these results also apply to other HRT preparations.

Stroke

In a large randomized clinical trial( Whi-study) as a secondary result, an increased risk of ischemic stroke in healthy women was observed during the use of continuous combination therapy with conjugated estrogens and MPA.

For women who do not receive HRT, it is estimated that the incidence of stroke that occurs over a 5-year period will be approximately 3 per 1000 women aged 50-59 years and 11 per 1000 women aged 60-69 years. It is estimated that for women who take conjugated estrogens and IPA for 5 years, the number of additional cases will range from 0 to 3( best estimate = 1) per 1000 patients aged 50-59 years and 1 to 9( best estimate= 4) per 1,000 patients aged 60-69 years. It is not known whether the increased risk of stroke also affects other drugs for HRT.

Ovarian cancer

Long-term( at least 5-10 years) use of HRT preparations that contain only estrogens in women with a deleted uterus was associated with an increased risk of ovarian cancer in several epidemiological studies. It is unclear whether there will be a risk of long-term use of combined HRT and only preparations that contain estrogens.

Other conditions

Estrogens can cause fluid retention, and therefore, the condition of patients who have impaired heart or kidney function should be closely monitored. The condition of patients with the final stage of renal failure should be carefully monitored, because it is expected that the level of circulating active ingredients of Femoston will be increased.

Women with existing hypertriglyceridemia should be closely monitored during replacement therapy with estrogen or hormone replacement therapy because in these women, single cases of a significant increase in plasma triglyceride levels were observed in estrogen therapy, leading to pancreatitis.

Estrogens increase the level of thyroxin-binding globulin( TSH), leading to an increase in the concentration of circulating total thyroid hormones, which is determined by the level of protein-bound iodine, thyroxine( in column or radioimmunoassay analysis) or triiodothyronine( by radioimmunoassay).The capture of triiodothyronine is reduced, indicating an elevated level of TSH.The concentrations of free triiodothyronine and thyroxine do not change.

The levels of other binding proteins in the serum of the corticosteroid-binding globulin and globulin that binds the sex hormones can increase, which leads to an increase in the concentration of circulating corticosteroids and sex hormones, respectively. Concentrations of free or biologically active hormones do not change. Concentrations of other plasma proteins( angiotensinogen / substrate of renin, antitrypsin, ceruloplasmin) may increase.

There is no conclusive evidence of improvement in cognitive function. In the WHI study, some data were obtained on the increased risk of dementia in women who received continuous combination therapy with CKE and MPA after 65 years of age. It remains unknown whether this also applies to younger women in the postmenopausal period or other HRT preparations.

Patients with rare hereditary diseases - galactose intolerance, Lappease lactase deficiency or glucose-galactose malabsorption syndrome, - should not take this medication.

The experience of treating women over 65 is limited.

The ability to influence the reaction rate when driving vehicles or other mechanisms. Femoston does not affect the ability to drive and work with machines and mechanisms.

Use during pregnancy and lactation.

Femostone is not indicated for use during pregnancy.

When a pregnancy occurs during treatment with Femoston, the drug should be discontinued immediately.

Femostone is not indicated for use during lactation.

Side effects of Femoston

There are reports of such side effects of Femoston therapy:

  • frequent( 1-10%): headache, migraine, nausea, pain, in the abdomen, flatulence, convulsions, lower limbs, pain in the mammary glands, breakthrough bleeding, clotting, pelvic pain, asthenia, weight reduction or weight gain;
  • infrequent( & lt; 1%): vaginal candidiasis, increased uterine fibroids, depression, changes in libido, nervousness, dizziness, venous thromboembolism, gallbladder disease, allergic skin reactions, rashes, urticaria, itching, pain, back, erosion changescervical and cervical secretions, dysmenorrhea, peripheral edema;
  • rare( & lt; 0.1%): intolerance to contact lenses, increased corneal curvature, impaired function, liver, which can sometimes be accompanied by asthenia, malaise, jaundice and pain, abdominal, breast enlargement, syndrome similar to premenstrual tension syndrome;
  • is very rare( <0.01%): hemolytic anemia, chorea, myocardial infarction, stroke, vomiting, chloasma and melanosis of the skin that can remain after drug discontinuation, polymorphic erythema, nodal erythema, vascular purpura, angioedema, worsening of strokeporphyria, hypersensitivity reactions.

Breast cancer

According to the results of a large number of epidemiological studies and one randomized, placebo-controlled study( Women Health Initiative -whi), the overall risk of breast cancer increases with the increase in the duration of hormone replacement therapy( HRT) in women who receivethis treatment, or those with HRT in the recent past.

For estrogen alone, the results of the relative risk assessment( BP) in the reanalysis of 51 epidemiological studies( in which HRT alone estrogen alone was performed in more than 80% of all cases of HRT) and the MWS( Million Women Study) are similar and are 1,35( 95% confidence interval -I: 1.21-1.49) and 1.30( 95% CI: 1.21-1.40), respectively.

With respect to combined HRT( estrogen plus progestogen), several epidemiological studies have reported a higher overall risk of breast cancer than with estrogen alone. In the MWS study, it was demonstrated that, in comparison with individuals who never received HRT, the use of combined progestogen plus estrogen of different types of HRT was associated with a higher risk of breast cancer( BP = 2.00, 95% DI: 1, 88-2,12) than when using only estrogens( BP = 1.30, 95% CI: 1.21-1.40) or tibolone( BP = 1.45, 95% CI: 1.25-1,68).

In the WHI study, in all patients, the risk was 1.24( 95% CI: 1.01-1.54) after 5.6 years of combined HRT( progestogen plus estrogen) HRT( conjugated equine estrogens - ELE and methylprogesterone acetate - MPA)in comparison with placebo.

The absolute risks calculated in the MWS and WHI studies are presented below:

Based on data on the average incidence of breast cancer in developed countries, the MWS study found the following:

is expected that breast cancer will be diagnosed in about 32 out of every 1000 womenat the age of 50 to 64, who do not receive HRT;

per 1000 women who recently received or receive HRT cases during the relevant period will be:

  • for those who receive estrogen replacement therapy
    • from 0 to 3( best estimate = 1.5) with 5 years of
    • administered from 3 to 7( best estimate = 5) for 10 years.
  • for those who receive combined( estrogen plus progestogen) HRT,
    • from 5 to 7( best estimate = 6) with 5 years
    • applied from 18 to 20( best estimate = 19) when applied for 10 years

Bthe WHI study found that after 5-6 years of follow-up, 8 cases of invasive breast cancer per 10,000 women-years will be diagnosed in a combination of estrogen-progestagenic HRT( CLA and MPA) in women aged 50 to 79 years.

According to study statistics, it was found that:

  • for 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 HRT "estrogen + progestogen"( EML and MPA), the number of additional cases will be from 0 to 9( best estimate = 4) when applied for 5 years. The number of additional cases of breast cancer in women who use HRT is similar to that in women who started HRT, regardless of their age at the onset of use( 45 to 65 years).

Other adverse reactions reported in connection with estrogen / progestogen therapy:

  • estrogen-dependent neoplasms, both benign and malignant, eg endometrial cancer;
  • venous thromboembolism, that is, deep vein thrombosis of the lower limb or pelvis and pulmonary embolism, is more common among women that receive HRT than among those who do not receive it;
  • possible dementia.
  • Endometrial cancer
  • In women with an intact uterus, the risk of hyperplasia and endometrial cancer increases with the duration of monotherapy with estrogens.
  • According to epidemiological studies, the best risk assessment indicates that in women who do not take HRT, it is expected that endometrial cancer will be diagnosed in about 5 out of every 1,000 between the ages of 50 and 65 years. Depending on the duration of treatment and the dose of estrogen, an increased risk of endometrial cancer, among those taking only estrogen, is 2-12 times greater than those who do not take it. Progestogen supplementation with estrogen monotherapy significantly reduces this increased risk.

To whom is contraindicated Femoston

  • Diagnosed in the past or suspected breast cancer
  • diagnosed in the past or suspected estrogen-dependent malignant tumors( eg, endometrial cancer);
  • vaginal bleeding of unexplained genesis;
  • untreated endometrial hyperplasia;
  • has venous thromboembolism( deep vein thrombosis, pulmonary thromboembolism) or idiopathic venous thromboembolism in the past;
  • active or recent thromboembolic diseases of the arteries( eg, angina pectoris, myocardial infarction);
  • acute liver disease, as well as the presence of liver disease in the past, if the liver function indicators are not normalized;
  • known hypersensitivity to active substances or to any of the inactive components of the drug;
  • porphyria;
  • is a pregnancy that is diagnosed or suspected.

Interaction of Femostone

Metabolism of estrogens can be enhanced by the simultaneous use of substances that activate enzymes( especially enzymes of the cytochrome P450 system) that participate in the metabolism of drugs. These substances include anticonvulsants( eg, phenobarbital, carbamazepine, phenytoin), antimicrobial agents( eg rifampicin, rifabutin) and antiviral agents( eg, nevirapine, efavirenz).

Despite the fact that ritonavir and nelvinavir are known as potent inhibitors, when used simultaneously with steroid hormones, they, on the contrary, activate the marked enzymes.

Herbal preparations, of which the Hypericum perforatum is a component, can enhance the metabolism of estrogens and progestogens. This can lead to a weakening of their effect and a change in the profile of uterine bleeding.

There is no information on the interaction of dydrogesterone with other medicinal products.

Overdose of Femoston

Both estradiol and dydrogesterone are substances with low toxicity.

Theoretically, overdose can cause symptoms such as nausea, vomiting, drowsiness and dizziness. It is unlikely that an overdose will require any specific symptomatic treatment. This also applies to accidental overdoses in children.