Dosage form:
Transdermal gel, solution for intramuscular injection of [oil], nasal spray, tablets, coated tablets, Transdermal therapeutic system Vivelle-Dot Patch.
Pharmacological action Vivelle Dot (Estradiol):
Estrogenic drug – 17-beta-estradiol is identical to endogenous estradiol (formed in the body of women, from menarche until menopause), produced by the ovaries. In the cells of organs that are targeted by hormones, estrogens are complexed with specific receptors (found in various organs – the uterus, vagina, urethra, breast, liver, hypothalamus, pituitary) receptor-ligand complex interacts with estrogen-effector elements genome and specific intracellular proteins, inducing the synthesis of m-RNA, protein, and release of cytokines and growth factors. It has a feminizing effect on the body. Stimulates the development of the uterus, fallopian tubes, vagina, stroma and ducts of mammary glands, pigmentation of the nipples and genitals, the formation of secondary sexual characteristics of female type, growth and closure of the epiphyses of long bones. Facilitates timely and regular rejection of endometrial bleeding, in high concentrations causes hyperplasia of the endometrium, inhibits lactation, inhibits bone resorption and stimulates the synthesis of a number of transport proteins (thyroxine binding globulin, transcortin, transferrin, protein, sex hormone binding) and fibrinogen. It has a procoagulant effect, increases the synthesis in the liver vitamin K-dependent coagulation factors (II, VII, IX, X), reduces the concentration of antithrombin III. Increases blood levels of T4, Fe, Cu2 +, etc. It has anti-atherosclerotic effect, increases the concentration of HDL, reduces – and LDL cholesterol (TG concentration increases). Modulates sensitivity to progesterone receptors and the regulation of sympathetic tone of smooth muscles, stimulates the transition to intravascular tissue and causes a compensatory delay in Na + and water. In large doses, prevents the degradation of endogenous catecholamines, competing for the active receptors for catechol-O-methyltransferase. After menopause, the body produces only a small amount of estradiol (from estrone, located in the liver and adipose tissue). Reducing the concentration of estradiol produced by the ovaries is accompanied by many women and thermoregulatory vasomotor instability (“hot flashes” of blood to the face), sleep disturbances, and progressive atrophy of the urogenital tract. As a result of estrogen deficiency osteoporosis (primarily the spine). It is known that oral administration of estrogen causes an increase in protein synthesis (including renin), which leads to increased blood pressure. Estradiol in the form of transdermal patch is affixed to the skin. The control membrane provides a gradual and continuous release of estradiol from the reservoir to the active substance through the adhesive layer on the skin. Because of the lack of effect of “first pass” through the liver TTS provides high efficiency by using smaller doses of the drug. TTS delivers estradiol into the bloodstream unchanged and maintains its concentrations in plasma during therapy at a constant level, an adequate level in the early or middle phase of the follicle.
Indications Vivelle Dot (Estradiol):
Estrogen deficiency in menopause and surgical menopause on the non-malignant neoplasms after radiation castration, primary and secondary amenorrhea, gipomenoreya, oligomenorrhea, dysmenorrhea, secondary estrogen deficiency. Hirsutism in polycystic ovary syndrome, vaginitis (in girls and in old age), gipogenitalizme, infertility, uterine inertia, prolonged pregnancy, to suppress lactation, virilny hypertrichosis in women. Postmenopauzny osteoporosis. Breast cancer and breast cancer, prostate cancer, urogenital disorders (dyspareunia, atrophic vulvovaginitis, urethritis, trigonometric), alopecia in giperandrogenemii. As a drug that stimulates hematopoiesis in men with acute radiation injury.
Contraindications Vivelle Dot (Estradiol):
Hypersensitivity, pregnancy, malignancy or estrogenzavisimye suspicion on them, unusual or undiagnosed genital or uterine bleeding, thrombophlebitis or thromboembolic disease in the active phase (except for the treatment of breast and prostate). C carefully. Thrombophlebitis, thrombosis or thromboembolism (in patients receiving estrogens in history), hyperlipoproteinemia familial, pancreatitis, endometriosis, gallbladder disease in history (especially cholelithiasis), severe hepatic failure, jaundice (including history during previous pregnancy) hepatic porphyria, leiomyoma, hypercalcemia associated with bone metastases from breast cancer. Only to treat breast and prostate cancer: the disease or coronary cerebral vessels, active thrombophlebitis or thromboembolic disorders (high doses of estrogen used to treat, increase the risk of myocardial infarction, pulmonary vascular thrombosis).
Side effects Vivelle Dot (Estradiol):
For women: tenderness, sensitivity, and increase the size of the mammary glands, amenorrhea, bleeding “breakthrough”, menorrhagia, intermenstrual “spotting” vaginal secretions, breast cancer, increased libido. In men, pain and sensitivity of the breast, gynecomastia, decreased libido. Peripheral edema, obstruction of the gallbladder, hepatitis, pancreatitis. Intestinal or biliary colic, flatulence, anorexia, nausea, diarrhea, dizziness, headache (including migraine), intolerance to contact lenses, vomiting (mainly central origin, mainly in large doses). In the treatment of breast and prostate cancer (advanced): embolism, thrombosis. When using TTS: irritation and redness kozhi.Peredozirovka. Symptoms include nausea, vomiting, and in some cases – metrorrhagia. Treatment: removal of the drug, symptomatic therapy aimed at maintaining vital functions.
Dosage and administration Vivelle Dot (Estradiol):
Inside, without chewing, with a small amount of liquid to 2 mg / day for 21 days, followed by a break for 7 days, and then continue treatment. The duration of treatment up to 6 months, after which the survey is conducted to decide whether to continue replacement estrogen therapy. Women with a uterus removed, or in menopausal women, treatment can be started any day. When you save your menstrual cycle begin to receive the first pill with a 5 day cycle (cycle 1 day = 1 day of menstruation). V / m, in a 0.1% solution of estradiol dipropionate in oil: in primary amenorrhoea with hypoplasia of the genital organs and secondary sexual characteristics – 1-2 mg daily or every other day for 1-2 months or more, to increase the palpable uterus, after this – in Progesterone / m, 5 mg daily for 6-8 days. If necessary, repeat courses of hormone therapy. In secondary amenorrhea – 1 mg daily for 15-16 days, followed by administration of progesterone or pregnina within 6-8 days. If persistent clinical effect is not present, repeat the treatment. In the hypo-and oligomenorrhea, dysmenorrhea, infertility due to ovarian hypofunction and hypoplasia of the uterus – to 0.5-1 mg for 15-16 days after the end of menstruation and then, if indicated – Progesterone or pregnin within 6-8 days. Treatment can be repeated several times in the same period, after the end of menstruation. In pathological phenomena associated with menopause and with surgical removal of ovaries – at 0.5-1 mg daily or every 1-2 days, rates of 10-15 injections. With the resumption of symptoms, repeat the treatment. Doses should be chosen strictly individually, depending on the phase of menopause, severity of illness. With the weakness in labor and post-term pregnancy – a / m, with 4-5 mg 2-3 hours prior to the introduction of rodostimuliruyuschih drugs. As gemostimuliruyuschego drugs while reducing the number of counts below 2 thousand / microliter of blood (usually from 10-20 days after exposure in severe lesions and 15-18 days – when the lighter lesions) – 1 mg every 1-2 days. The treatment course is 10 injections (if necessary – up to 15 injections). TTS is attached to a clean, dry and intact skin of the body (lumbar region, abdomen), 2 times a week. Treated with transdermal 50 mg, followed by individual titration (the emergence of a sense of tension in the breast or intermediate bleeding is a sign of increased dosage to be reduced). If after 2-3 weeks of the signs and symptoms of estrogen deficiency are not cropped, it should increase the dose. TTS is applied cyclically: after 3 weeks of treatment (6 applications) – an interval of 7 days, during which possible metrorrhagia. Continuous, noncyclic therapy is prescribed for women after hysterectomy or in cases where the symptoms of estrogen deficiency again strongly manifested during the 7-day interval. Subsequent treatment with progestins should be as follows: a continuous application of TTS is recommended to additionally prescribe progestin (medroxyprogesterone acetate 10 mg, 5 mg of norethisterone, norethisterone acetate 5 mg or 20 mg dydrogesterone during the first 10-12 days of each month). When cyclic transdermal application is recommended in addition, in the last 10-12 days of therapy, estradiol, progestin taken so that the fourth week of each cycle of therapy remained free of any hormone. In both cases, after the 10-12-day progestogen therapy begins bleeding. The gel is used 1 times a day, morning or evening, at 1.5 mg (2.5 g of gel or 1-2 doses) – applied a thin layer to clean skin on the abdomen, lumbar region, shoulders and forearms. The area of application should be equal in magnitude to 1.2 palms. The gel should be absorbed in less than 2-3 minutes. If he remains on the surface of the skin for more than 5 minutes, then the drug was applied to the skin surface is too small. Gel administered continuously or in cycles. Dose and duration of therapy is determined individually.
Special instructions Vivelle Dot (Estradiol):
Treatment should be preceded by a thorough gynecological examination, which is long-term therapy should be repeated at least 1 time per year. In the course of treatment requires regular monitoring of liver function and blood pressure, and diabetes mellitus – the concentration of glucose in the blood. Estradiol therapy must be combined with progestogens. Prolonged treatment with estradiol increases the risk of developing breast cancer and endometrial cancer (depending on the duration of treatment and dose of estrogen). Hyperplasia (atypical glandular or) often precedes endometrial cancer. The combination of estrogen with progestogen has a protective effect on the endometrium. Treatment should be discontinued for 4-6 weeks before the planned surgery. It is not a contraceptive and does not protect against pregnancy. When the irregular menstrual flow after treatment (in women with an intact uterus) should be a diagnostic curettage to rule out malignancy of the uterus. The use of estradiol should be stopped immediately in case of deep vein thrombosis, thromboembolism, etc. localization, the appearance of jaundice, the gain or the appearance of previously unavailable migrenepodobnyh pain, sudden vision impairment, a significant increase in blood pressure. TTC can not attach to the skin of the breast and 2 times in a row on the same area of skin. On the attached TTS should not get sunlight. Avoid getting the gel on the mammary glands and mucous membranes of the vulva and vagina.
Interaction Vivelle Dot (Estradiol):
Improves the effectiveness of lipid-lowering drug. Attenuates the effects of male sex hormones, hypoglycemic, diuretic, antihypertensive drugs, and anticoagulants. Reduces glucose tolerance (may require adjustment of dosage regimen of hypoglycemic drugs). Barbiturates, anxiolytic drugs (tranquilizers), narcotic analgesics, drugs for general anesthesia, some antiepileptic drugs (carbamazepine, phenytoin), inducers of liver enzymes accelerate the metabolism of estradiol. Plasma concentration decreases with the simultaneous use of phenylbutazone and some antibiotics (ampicillin, rifampicin), which is associated with a change in the microflora in the gut. Folic acid and thyroid medications enhance the action of estradiol.
