Description
Film-coated pills. Femoston mini - anti-menopausal combination low-dose hormonal agent. Estradiol hemihydrate, which is part of the drug Femoston mini, when dissolved goes into 17-β-estradiol, identical to human endogenous estradiol, which is the most active estrogen. Estradiol compensates for the lack of estrogen in the body in postmenopausal women and reduces the severity of menopausal symptoms. When prescribing the drug Femoston mini, the reduction in the frequency of "hot flashes" of moderate and severe degree was statistically significant compared with placebo starting from 4 weeks of therapy. The number of moderate and severe hot flashes further decreased at week 13 before discontinuation of therapy. Didrogesterone is a progestogen that is effective when taken orally and has activity similar to parenterally administered progesterone. Because estrogens promote endometrial proliferation, hormone replacement therapy (HRT) only estrogen increases the risk of endometrial hyperplasia and cancer. Inclusion of dydrogesterone significantly reduces the risk of endometrial hyperplasia in women with a preserved uterus increased by estrogen. During clinical studies, it was shown that the drug Femoston mini provides relief from the symptoms associated with the lack of estrogen and the nature of bleeding. Easing of the menopausal symptoms was achieved during the first weeks of treatment.
Active ingredients
Didrogesterone + Estradiol
Release form
Pills
Composition
Active ingredients: didrogesteron - 2.5 mg, estradiol hemihydrate - 0.517 mg. Excipients: lactose monohydrate, hypromellose (HPMC 2910), corn starch, colloidal silicon dioxide, magnesium stearate. Film coating: Yellow 1 film coating (macrogol 3350, polyvinyl alcohol, talc, titanium dioxide, iron dye yellow oxide - E172).
Indications
Hormone replacement therapy of disorders caused by estrogen deficiency in postmenopausal women (no earlier than 12 months after the last menstruation).
Precautionary measures
Before use, consult with your doctor. The drug is available on prescription.
Use during pregnancy and lactation
Contraindicated in pregnancy and lactation.
Dosage and administration
The drug is taken orally daily, in continuous mode, 1 tablet per day (preferably at the same time of day), regardless of the meal. Patients who make the transition from another continuous sequential or cyclic mode of the drug should finish the current cycle, and then go to the drug Femoston mini. Patients who are not receiving drugs for HRT or are switching from continuous use of combination drugs for HRT may start taking Femoston mini on any day. If the patient missed a pill, it must be taken within 12 hours after the usual time of admission, otherwise missed the pill 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 bleeding. To start and continue therapy for postmenopausal disorders, you should take the smallest effective dose for the shortest period of time. Didrogesterone 5 mg and estradiol 1 mg per tablet depending on the time after menopause and the severity of symptoms. m combined drug for hormone therapy Femoston mini in women with natural menopause can be started no earlier than 12 months after the last menstruation. Women whose menopause is due to surgery can start taking the drug right away (prescribed by a doctor in case of symptoms).
Side effects
In clinical trials, patients receiving therapy with the estradiol / didrogesterone combination most often encountered: headache, abdominal pain, tension, breast tenderness, and back pain. In clinical studies (n = 4929), the following undesirable effects were observed with the development frequency indicated below (number of registered cases / number of patients): very often - 1/10, often from 1/100 to <1/10, infrequently - from 1 / 1000 to <1/100, rarely from 1/10000 to <1/1000, very rarely - <1/10000. Infections and invasions - often. Vaginal candidiasis - often.Neoplasms: benign, malignant and unspecified - rare. An increase in leiomyoma size is infrequent. Immune system disorders: hypersensitivity is rare. Mental disorders: depression, nervousness - often. Change libido-infrequent. Nervous system disorders: headache - very often, migraine, dizziness - often. Heart disorders: myocardial infarction - rarely. Vascular disorders: venous thromboembolism, arteritis, varicose veins - infrequently. Disorders of the gastrointestinal tract: abdominal pain - very often, nausea, vomiting, flatulence, dyspepsia - often. Disorders of the liver and biliary ducts: impaired liver function, sometimes in combination with jaundice, asthenia, malaise, gallbladder disease - rarely. Violations of the skin and subcutaneous tissues: allergic reactions such as urticaria, skin rash and itching, vascular purpura, angioedema - often. Disorders of the musculoskeletal and connective tissue: pain in the back (lower back) - very often. Disorders of the genital organs and breast: tension / tenderness of the mammary glands - infrequently. Menstrual disorders (including "bloody" postmenopausal bleeding, metrorrhagia, menorrhagia, oligo / amenorrhagia, irregular menstruation, dysmenorrhea), abdominal pain, change in vaginal secretion, breast enlargement, premenstrual syndrome - often General disorders: asthenic conditions (weakness, malaise, fatigue), peripheral edema. Other: weight gain, weight loss - infrequent Other side effects caused by the treatment of the combination of estrogen and progestogen (including estradiol / didrogesterone): benign, malignant and unspecified neoplasms: estrogen dependent benign and malignant neoplasms, including endometrial cancer, ovarian cancer. Increasing the size of progestogen-dependent neoplasms, including meningiomas. From the side of blood and lymphatic system: hemolytic anemia. On the part of the immune system: systemic lupus erythematosus. Metabolism: hypertriglyceridemia.On the part of the nervous system: the risk of dementia in women who start using drugs for hormone therapy after the age of 65, chorea, provoking epileptic seizures. From the organ of vision: intolerance to contact lenses, increased curvature of the cornea. Since the cardiovascular system: arterial thromboembolism. On the part of the gastrointestinal tract: pancreatitis (in patients with hypertriglyceridemia). On the part of the skin and subcutaneous tissues: chloasma and / or melasma, which may persist after discontinuation of the drug, erythema multiforme, erythema nodosum. From the musculoskeletal system and connective tissue: cramps in the muscles of the lower extremities. On the part of the genitourinary system: urinary incontinence. Disorders of the reproductive system and mammary glands: fibrocystic mastopathy, cervical erosion. Congenital and hereditary disorders: deterioration of concurrent porphyria. Laboratory indicators: elevated thyroid hormone levels.
Overdose
Estradiol and didrogesteron - substances with low toxicity. Symptoms: in case of an overdose, symptoms such as nausea, vomiting, exertion of the mammary glands, dizziness, pain in the abdomen, drowsiness / weakness and "withdrawal" bleeding may develop. Treatment: symptomatic.
Interaction with other drugs
The effectiveness of the drug Femoston mini may be reduced in the following cases: the metabolism of estrogen and progestogen can be enhanced while taking microsomal liver enzymes (P450 2B6, 3A4, 3A5, 3A7) with inducing agents: anticonvulsant (phenobarbital, carbamazepine, anti-convulsant) and anticonvulsant (antibiotic), carbamazepine, and anti-convulsants (antibiotics), anti-convulsants, carbamazepine, and anti-convulsants (anticoagulant) , rifabutin, nevirapine, efavirenz), ritonavir and nelfinavir, although known as strong inhibitors of CYP 450 3A4, A5, A7, when used simultaneously with sex hormones can enhance their metabolism, drugs p Hypericum perforatum containing St. John's wort can enhance estrogen and progestogen metabolism through CYP 450 3A4, increased estrogen and progestogen metabolism can clinically manifest a decrease in the effect of using the drug and the appearance of bloody discharge from the vagina. Estrogens can influence the metabolism of other drugs. .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 action, such as tacrolimus and cyclosporin A (CYP 450 3A4, 3A3), fentanyl (CYP 450 3A4) and theophylline (CYP 450 1A2), since this type of interaction may lead to an increase in concentration in blood plasma of the above drugs to toxic levels. In this regard, it may be necessary to carefully monitor the medication for a long period of time and, possibly, reduce the dose of tacrolimus, fentanyl, cyclosporin A and theophylline.
Contraindications: hypersensitivity to the components of the drug, diagnosed or suspected breast cancer, diagnosed or suspected estrogen-dependent malignant tumors (for example, endometrial cancer), diagnosed or suspected progestogen-dependent tumors (for example, meningioma), hemorrhage from a vaginal discharge of an unclear etiology, untreated hyperplasma, (arterial and venous) and thromboembolism at present or in history (including thrombosis, thrombotic deep veins, pulmonary thromboembolism, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders), acute or chronic liver disease now or in history (before normalization of functional liver function tests), including malignant tumors of the liver, porphyria, multiple or pronounced factors arterial or venous thrombosis associated with congenital or acquired predisposition, such as protein C deficiency, protein S deficiency, en deficiency titrombin III, the presence of antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant), angina pectoris, prolonged immobilization, severe obesity (body mass index more than 30 kg / m2), vascular diseases of the brain or coronary arteries, transient ischemic attacks, complicated valvular lesions heart apparatus, atrial fibrillation, pregnancy and breastfeeding period, galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome, meningioma, jaundice and / or impaired f liver function, uncontrolled arterial hypertension, first appeared on the background of the use of drugs for HRT migraine-like headache.The drug is prescribed only if there are symptoms that adversely affect the quality of life. Therapy should continue until the benefits of taking the drug outweigh the risk of side effects. The experience of using the drug in women over 65 is limited. Medical examination Before prescribing or resuming therapy with Femoston mini, you must collect a full 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 that require observance of precautionary measures. During treatment with the drug Femoston mini, it is recommended to conduct periodic examinations, the frequency and nature of which is determined individually, but not less than 1 time in 6 months. It is advisable to conduct instrumental methods of research (for example, mammography) for additional examination of the mammary glands. Women should be informed about possible changes in the mammary glands, which are required to inform the attending physician. The use of estrogen can affect the results of the following laboratory tests: determination of glucose tolerance, the study of the functions of the thyroid gland 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 patients use only estrogen depends on the dose and duration of treatment and increases from 2 to 12 times compared with no treatment, the risk may remain elevated for 10 years after discontinuation of therapy. The use of combined drugs for hormone therapy in continuous mode in women with a preserved uterus can prevent the increased estrogen risk of hyperplasia and endometrial cancer. For the purpose of timely diagnosis, it is advisable to conduct an ultrasound screening, if necessary - to conduct a histological (cytological) examination. Bloodstained from the vagina. In the first months of drug treatment, "breakthrough" bleeding and / or scanty bleeding from the vagina can occur. If such bleeding occurs some time after the start of therapy or continues after stopping treatment, their cause should be established. It is possible to conduct a biopsy of the endometrium 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 1st degree of relationship at a young age, as well as with the usual miscarriage in history, it is necessary to conduct a study of hemostasis. If the patient is taking anticoagulants, it is necessary to carefully consider the appointment of the drug Femoston mini in terms of the "benefit / risk" ratio. Until a thorough assessment of the factors for the possible development of thromboembolism or the start of anticoagulant therapy is completed, Femoston mini is not prescribed. When a thrombophilic condition is detected in a family member and / or in the case of the severity or severity of the defect (for example, lack 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 prescription of 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 about the possible role of varicose veins in the development of VTE. To prevent VTE after surgery in all postoperative patients, it is necessary to consider the issue of preventive measures. To prevent VTE in the event of prolonged immobilization after surgery, large surgery, surgery on the lower limbs, in the pelvic region or neurosurgical operation, an extensive injury, the drug is stopped and resumed only after the full mobility of the woman is restored. In the case of planned surgery, the drug is discontinued 4-6 weeks before surgery. If VTE develops already after the start of therapy, the drug should be discontinued, and patients should be informed that they should immediately contact their doctor if they have any potentially thromboembolic symptom (for example, pain or swelling of the lower extremities, sudden pain chest, shortness of breath). Mammary cancer.The data available to date indicate an increase in the risk of breast cancer in women taking HRT with combined (estrogen + progestogen) drugs and also, possibly, only estrogen. The risk depends on the duration of the reception of HRT. HRT with combined (estrogen + progestogen) drugs A randomized, placebo-controlled study (the results of the Initiative for Women's Health (WH1) study) and epidemiological studies have shown an increased risk of developing breast cancer in women taking HRT with combined (estrogen + progestogen) drugs. The increase is noticeable after about three years of therapy. Estrogen therapy. In the WHI study, there was no increase in the risk of breast cancer in women with a 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 a diagnosis of breast cancer, while this risk was significantly lower than that of women taking HRT with combined (estrogen + progestogen) drugs. The increase in risk becomes noticeable after several years of using HRT drugs, but after cessation of therapy returns to the initial level for several (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. Prolonged use (at least 5-10 years) of estrogen in monotherapy mode for HRT is associated with a slight increase in the risk of developing ovarian cancer. Data from several studies, including WHI, indicate that combined HRT may increase the risk of developing this pathology in the same or somewhat less degree. Risk of ischemic stroke. Estrogen / progestogen combination therapy or estrogen-only therapy is associated with a 1.5-fold increase in the relative risk of ischemic stroke. The risk of hemorrhagic stroke when using drugs for HRT does not increase. The relative risk does not depend on the age or time of menopause, however, the initial risk is highly dependent on age, so the overall risk of stroke in women receiving HRT will increase with age. Coronary heart disease (CHD).In randomized controlled clinical trials, no evidence was obtained of the protective effect of HRT against myocardial infarction in women with / without coronary artery disease who received HRT with combined (estrogen + progestogen) drugs or estrogen alone. HRT combined (estrogen + progestogen) drugs. The relative risk of coronary artery disease during the use of HRT combined (estrogen + progestogen) drugs slightly increased. Due to the fact that the absolute risk of coronary artery disease is highly dependent on age, the number of additional cases of coronary artery disease due to HRT use 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, while taking drugs for hormone therapy in very rare cases, the concentration of triglycerides in the blood plasma can be significantly increased, which contributes to the development of pancreatitis. Estrogens increase the concentration of thyroxin-binding globulin, which leads to an overall increase in the concentration of circulating thyroid hormones, as measured by the determination of iodine associated with plasma proteins, the concentration of thyroxin (T4) - chromatographic or radioimmunoassay or triiodothyronine (T3) - radioimmunoassay. The capture test for labeled triiodothyronine shows an elevated level of thyroxin-binding globulin. The levels of free T4 and T3 remain unchanged. The concentration of other binding proteins in the blood plasma, for example, transcortin, sex hormone binding globulin, may 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 systems, α-1-antitrypsin, ceruloplasmin). The use of HRT does not improve cognitive function. There are reports of an increased risk of dementia in women who have started using HRT (combined or estrogen-containing) after 65 years of age. The drug Femoston mini is not a contraceptive.
