Estradiol + Norethisterone - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

"Estrogens, gestagens, their homologues and antagonists"

Included in the formulation

АТХ:

G.03.F.A.01 Norethisterone and estrogen

Pharmacodynamics:

Combined drug, the effect of which is due to its constituent components. Monophasic estrogen-progestogen preparation.

17-beta-estradiol is identical to endogenous estradiol; stimulates the development of the uterus, fallopian tubes, secondary sexual characteristics in their underdevelopment, causes activation of the regeneration and growth of the endometrium in the first phase of the menstrual cycle, the preparation of the endometrium to the action of progesterone, the increase in libido in the middle of the cycle, affects the exchange of fats, proteins and carbohydrates, electrolytes: reduces the concentration of lipids and cholesterol in the blood, regulates nitrogen metabolism; stimulates the production of liver globulins, binding sex hormones, renin, TG and clotting factors. Has moderate central effects: it removes vegetative-vascular and psycho-emotional disorders. It plays an important role in the development of bone tissue and the formation of bone structure, hinders the development of osteoporosis. Increases the excitability of the uterus, in large doses inhibits lactation, improves trophism of the urino-genital organs and skin, has a weak anabolic effect.

Synthetic progestogen - norethisterone provides the transition of the mucous membrane of the uterus from the stage of proliferation into the secretory phase. It reduces the excitability and contractility of the musculature of the uterus and fallopian tubes, stimulates the development of the end elements of the mammary glands. It blocks the secretion of hypothalamic factors releasing LH and FSH in the pituitary gland, inhibits the formation of gonadotropic hormones and inhibits ovulation. It has minor androgenic properties. Attenuation of symptoms with ingestion is achieved within a few weeks.

Not a contraceptive.

Pharmacokinetics:

Active substances are absorbed from the digestive tract. After taking estradiol, the time to reach the maximum concentration of the compound5-8 hours, and its value is 35 pg / ml (21-52 pg / ml). Linkage with proteins: albumins - 61%, globulins - 37%, 1-2% - in unbound form. Half-lifeis 12-14 hours Metabolism in the liver with the formation of estrone, catechol estrogens, estrogen sulfates and glucuronides. It is excreted by the kidneys in the form of metabolites and partially unchanged, a small amount - through the intestine. Estrogens penetrate into breast milk. After oral administration of norethisterone acetate is rapidly absorbed and converted into norethisterone. The time to reach the maximum concentration is 0.5-1.5 hours, with a value- 3.9 ng / ml (1.4-6.8 ng / ml). Linkage with proteins: with albumin - 61%, globulins - 36%. The half-life is 8-11 hours. It is metabolized in the liver with the formation of 5-alpha-dihydro-norethisterone and tetrahydro-norethisterone, which are mainly excreted in the urine in the form of sulfate and glucuronide conjugates.

Indications:

Climacteric disorders in the postmenopausal period (not earlier than 1 year after the onset of menopause): "hot flashes", increased sweating, sleep disorders, irritability, depression, forgetfulness, postmenopausal osteoporosis, degenerative changes in the skin and mucous membranes (nail brittleness, thinning of the skin, education wrinkles, dryness of the mucous membranes of the urogenital organs). Prevention of postmenopausal osteoporosis (belonging to the European or Asian race, short stature, lack of body weight, early menopause, osteoporosis in a family history, insufficient intake of Ca²⁺ with food, hypodynamia, smoking, abuse of ethanol).

ICD-10

IV.E20-E35.E28.3 Primary ovarian failure

XIII.M80-M85.M81.0 Postmenopausal osteoporosis

XIV.N80-N98.N95.1 Menopause and menopause in women

Contraindications:

Hypersensitivity; pregnancy; lactation period; acute or chronic liver disease, liver failure; liver cancer, congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor syndrome), hemangioma; disorders of cerebral circulation (ischemic stroke, hemorrhagic stroke); breast cancer and suspected of it, endometrial cancer, hyperlipoproteinemia; idiopathic jaundice (including during the previous pregnancy); herpes (in the anamnesis); vaginal bleeding, metrorrhagia of unknown origin; IHD, atherosclerosis, heart disease, myocarditis.

Carefully:

Migraine, epilepsy, depression, severe headache, diabetes mellitus, diabetic angiopathy, bronchial asthma, chronic heart failure, otosclerosis, multiple sclerosis, arterial hypertension, hyperlipoproteinemia, idiopathic jaundice (including during the previous pregnancy) thromboembolic disease, liver disease with normal functional tests (including porphyria) and gallbladder, leiomyoma, endometriosis, endometrial hyperplasia, mammary gland fibroadenoma,estrogen-dependent tumors, uterine fibroids, mastopathy, ulcerative colitis, renal failure.

Pregnancy and lactation:

Action category for the fetus by FDA - X. When pregnant or suspected of it, during the lactation period, the drug is contraindicated.

Estrogens can have embryotoxic effects. Studies have shown the relationship of congenital malformations with the use of certain estrogens during pregnancy.

Estrogens penetrate into breast milk, and norethisterone inhibits lactation.

Dosing and Administration:

Inside, 1 tablet per day daily. Treatment is started any day and is conducted without interruption.

Side effects:

In the first months of treatment: sporadic menstrual bleeding, painful mammary tension, nausea, headache, swelling.

After 3 months of treatment - abdominal pain, flatulence, cholelithiasis, changes in sexual desire, candidiasis, thrombosis, thromboembolism, increased blood pressure, dizziness, depression, convulsions, hirsutism, alopecia; skin rash, itching, chloasma, erythema multiforme, erythema nodosum, hemorrhages, arthralgia, myalgia, visual impairment, insomnia, weight gain or loss.

Overdose:

Symptoms: vomiting, nausea.

Treatment: symptomatic.

Interaction:

Barbiturates, antiepileptic drugs (carbamazepine, phenytoin) increase the metabolism of steroid hormones. Antibiotics (ampicillin, rifampicin), changing the microflora of the intestine, reduce the effective concentration.

Means for general anesthesia, narcotic analgesics, anxiolytics, antiepileptic drugs, some antihypertensives, ethanol decrease efficiency.

With a simultaneous appointment, it may be necessary to correct the dosage regimen for hypoglycemic agents.

Special instructions:

Assign only to women who have had the last menstrual cycle at least 1 year ago.

Before the beginning of treatment it is necessary to conduct a thorough medical examination, including measurement of blood pressure, examination of mammary glands and abdominal cavity, gynecological examination to exclude hyperplasia of the endometrium.

During the drug every 6 months, gynecological control (cervical smear and breast examination) should be performed.

Regular monitoring of liver function, blood pressure, urinalysis, blood lipids is necessary.

Treatment ceases immediately if pregnancy occurs, migraine headaches (if they were not present earlier), signs of phlebitis (unusual pain or bloating of the veins on the legs), jaundice, visual disturbances, blood clots, cerebrovascular disorders, when stitching pains of an unclear aetiology during breathing or coughing , with pain and a feeling of restraint in the chest, increased blood pressure, increased episodes of epilepsy, with the detection of liver tumors, 6 weeks before the scheduled surgical intervention, with prolonged immobilization. If menstrual bleeding lasts more than 3 months or first appeared after several months of treatment, diagnostic scraping is performed to exclude malignant neoplasms of the uterus.

Not a contraceptive.

Instructions

Estradiol + Norethisterone (Oestradiolum + Norethisteronum)