Climara patch 3.9 mg 12.5 square cm 4 pcs
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Active ingredients
Estradiol
Release form
Patch
Composition
Active ingredient: estradiol hemihydrate 3, 9 mg / 12, 5 kV cm or 7, 8 mg / 25 kV cm smog adjuvants: (poly (acrylamide-to-isooctylacrylate-to-vinyl acetate 5: 75: 20) - 99, 9/99 , 9 mg; ethyl oleate - 19, 25/19, 25 mg; isopropyl myristate - 9, 65/9, 65 mg; glycerol monododecanoate - 4, 8/4, 8 mg; PE film (LDPE) - 12, 5/25 cm2 Basic Volume: 1 g Active ingredient concentration (mg): 3, 9 mg / 7, 8 mg
Pharmacological effect
Estrogenic drug. It is a patch attached to the skin, containing 17β-estradiol. 17β-estradiol is identical to the endogenous estradiol produced by the ovaries. A decrease in ovarian function, accompanied by a decrease in estrogen production, leads to the development of the menopausal syndrome, which is characterized by vasomotor autonomic and organic symptoms. Conducting HRT is aimed at reducing these symptoms. Of all the physiological estrogens, estradiol is the most active and has the highest affinity for estrogen receptors. . After diffusion across the cell membrane, estradiol binds with high affinity to estrogen receptors. After estradiol activation, the hormone receptor complex moves into the nucleus, where it binds to a specific DNA sequence (hormone-sensitive elements), enhancing the transcription of regulated genes. All estrogen-induced proteins are not known (their number ranges from 50 to 100). After menopause, the production of estradiol in women decreases significantly. The remaining estradiol is mainly synthesized from precursors that are produced in the adrenal cortex by flavoring from androstenedione and, to a lesser extent, from testosterone using the aromatase enzyme, with the formation of estrone and estradiol, respectively. Estrone is converted to estradiol by the enzyme 17-hydroxysteroid dehydrogenase. Both enzymes are found in the liver and in adipose and muscle tissue. The estradiol / estrone ratio in postmenopausal women is approximately 0.2 compared to> 1 in premenopausal women. Menopausal disorders can be compensated for by estrogen replacement therapy with average transdermal doses between 25 μg and 100 μg of estradiol per day.estrogen doses needed to reduce menopausal complaints have a dose-dependent stimulating effect on mitosis and proliferation of the endometrium. Estrogen monotherapy increases the incidence of endometrial hyperplasia and thus, the risk of myometrial carcinoma. In order to prevent endometrial hyperplasia in women with a preserved uterus, sequential administration of gestagen for 10-14 days is recommended.
Pharmacokinetics
Absorption After the skin application of the Climara, estradiol is well absorbed through the skin. Transdermal administration allows you to avoid high fluctuations of estradiol and its metabolites in serum, as is observed after oral replacement therapy with estradiol and, accordingly, to avoid liver loading with a large amount of estradiol and its metabolites due to high presystemic metabolism (first-pass effect) after ingestion. Thus, after the transdermal administration of estradiol, there is no effect on protein synthesis in the liver. In the weekly application of the Climara, an even and constant profile of estradiol and estrone in the serum is achieved within the desired range. The absolute value of the serum estradiol level is directly proportional to the area of the patch. The average Css of estradiol in serum is approximately 35 pg / ml (patch of 12.5 cm2) and 70 pg / ml (patch of 25 cm2). About 61% of estradiol binds non-specifically to serum albumin and about 37% specifically to the globulin that binds sex steroids. The apparent Vd of estradiol after a single IV administration is approximately 1 l / kg. With repeated weekly application of the patch, neither estradiol nor estrone is cumulated. Accordingly, the equilibrium serum level of both hormones corresponds to the level observed after a single application. Metabolism After transdermal administration, the conversion of estradiol into estrone and conjugates remains in the physiological limits observed in the early follicular phase in the reproductive period of life, with a ratio of estradiol / estrone levels in serum about 1.A non-physiologically high level of estrone as a result of intensive metabolism during the first passage through the liver during oral HRT by estradiol, reflected by an estradiol / estrone ratio lower than 0.1, is not observed. but also extrahepatic, for example, in the intestines, kidneys, skeletal muscles and target organs. These processes include the formation of estrone, estriol, catechol estrogens and their conjugates - sulfates and glucuronides, which have distinctly lower estrogenic properties or even do not have them. min / kg Some of the estradiol metabolites are excreted in the bile and undergo a so-called enterohepatic circulation. Ultimately, estradiol metabolites are mainly excreted in the form of sulfates and glucuronides in the urine.
Indications
Hormone replacement therapy for disorders caused by natural or surgical menopause (only in case of non-cancer diseases): vasomotor symptoms (hot flashes, sweating), sleep disorders, atrophic processes. Prevention of postmenopausal osteoporosis.
Contraindications
Hypersensitivity, breast tumors, endometriosis, liver tumors, sex steroid hormone-dependent tumors, vaginal bleeding of unknown etiology, thromboembolic processes (thrombophlebitis, thrombosis), pregnancy, breast-feeding.
Precautionary measures
Do not exceed recommended doses.
Use during pregnancy and lactation
During pregnancy and lactation, HRT is not carried out. In extensive epidemiological studies, there was no increased risk of developmental defects in children born to women who received hormonal contraceptives or HRT before pregnancy, or teratogenic effects, when drugs were taken out of negligence in the early stages of pregnancy. the amount of sex steroids can be excreted in breast milk.
Dosage and administration
Treatment of symptoms of menopausal syndrome.Treatment begins with the smallest dose of Klimara plaster. If necessary, you can use a more highly dosed patch. After dose selection, the lowest effective dosage of the patch should be used to relieve symptoms. Prevent osteoporosis. Treatment to prevent postmenopausal bone loss should be started immediately after menopause. Long-term treatment based on an individual approach is recommended. Treatment should be carried out either in continuous or in a cyclical mode. When switching from long-term continuous or cyclic therapy: treatment should begin the next day after the end of the previous treatment regimen. Estrogen-only therapy is used if the woman has had a hysterectomy. In women with an intact uterus, a progestogen should be added to treatment with Climar for 10–14 days each month. When using a patch that releases more than 50 μg of the hormone / day, no protective effect on the endometrium was detected by adding progestogens. The plaster should be attached weekly in a continuous mode, each used patch should be removed after 7 days, after which the fresh patch should be attached to another location. Patches may also be recommended for cyclic treatment. In this case, the patch is attached weekly for 3 consecutive weeks, followed by a 7-day interval without attaching the patch to the next course of treatment. Normally, bleeding normally develops 2–3 days after stopping the reception of the gestagens. The method of attaching the patch. After removing the protective film, the Klimara patch is attached with an adhesive side to a clean, dry skin area along the spine or buttocks. Climara should not be attached in the area of the mammary glands or close to them. The area chosen for fixing the patch should not be fat, damaged or irritated, you should also avoid the waist area, because by rubbing with tight clothing, the plaster may come off. Sticking the patch on those areas of the skin where the patch can move in a sitting position should be avoided. The patch should be attached immediately after opening the package and removing the protective film.The plaster should be firmly pressed with the palm to the place of fixation for about 10 s. It is necessary to make sure that there is good contact with the skin, especially at the edges. If the patch does not fit snugly, for better adhesion it is necessary to press on it. Place of application should be changed with an interval of at least 1 week between applications. If the patch is attached correctly, the patient can wash in the bath or shower, as usual. However, the plaster can peel off the skin under the action of very hot water or in a sauna. Untimely replacement or loss of plaster. If the patch is peeled off before the end of the 7-day course of treatment, you can try to glue it again. If necessary, you can glue the new patch for the remaining days of the 7-day interval of application. If the patient forgot to change the patch in time, the replacement should be made as soon as possible after the fact of the omission has been established. A new patch should be used after the end of the normal 7-day treatment period.
Side effects
Information on the incidence of adverse events with the use of the drug Climar (MedDRA - Medical Dictionary of Regulatory Activity) is reflected below. The information is based on data from clinical studies. The most frequent adverse reactions reported during clinical trials were skin irritation at the site of application and pain in the mammary gland (> 10%). Local symptoms at the site of application are mostly mild and include redness, itching, burning and vesicle formation. On the side of the gastrointestinal tract: often (≥1 / 100 and <1/10) - abdominal pain, bloating, nausea. General and local reactions: often (≥1 / 100 and <1/10) - swelling at the site of the plaster. On the side of the musculoskeletal system, connective tissue: infrequently (≥1 / 1000 and <1/100) - muscle cramps On the side of the nervous system : often (≥1 / 100 and <1/10) - headache, dizziness; infrequently (≥1 / 1000 and <1/100) - migraine. From the reproductive system, mammary glands: often (≥1 / 100 and <1/10) - engorgement of the mammary glands, change in the nature of breakthrough bleeding and spotting vaginal discharge; infrequently (≥1 / 1000 and <1/100) - an increase in mammary glands. Other: often (≥1 / 100 and <1/10) - changes in body weight. Other adverse effects have been reported during estrogen replacement therapy, but their connection with the use of Klimara’s drug can neither be refuted,nor proven. Congenital hereditary genetic diseases: worsening of symptoms of concomitant porphyria. On the side of the gastrointestinal tract: vomiting. On the side of the liver: cholestatic jaundice. Mental disorders: changes in libido. On the part of the reproductive system, mammary glands: change in the size of uterine leiomyoma, changes in cervical secretion Skin and subcutaneous tissues: chloasma or melasma, which can persist after discontinuation of the drug, allergic contact dermatitis, post-inflammatory pruritus, generalized exanthema. Women with hereditary forms of angioedema, exogenous estrogens can cause or worsen the symptoms of angioedema (see "Special Instructions").
Overdose
With the application of climax, an overdose is unlikely. Symptoms: nausea, vomiting; in some cases, withdrawal bleeding. Treatment: removal of the patch, symptomatic therapy. The specific antidote is unknown.
Interaction with other drugs
With long-term simultaneous use of the drug Klimara with inducers of microsomal liver enzymes (for example, derivatives of hydantoin, barbiturates, primidone, carbamazepine, rifampicin, and also, apparently, with oxcarbamazepine, topiramate, felbamate and possible increase of the clearance of the stomach, . The maximum induction of enzymes in general does not manifest itself for 2–3 weeks, but may then persist for at least 4 weeks after cessation of drug therapy. Considerable alcohol consumption during HRT may lead to an increase in circulating estradiol.
special instructions
Before treatment, in the process or reappointment of HRT, a woman is recommended to undergo a thorough general medical and gynecological examination, including examination of the pelvic organs (with cytological examination of the cervical mucus), abdominal cavity, mammary glands, blood pressure monitoring, examination of the coagulation system and blood lipid spectrum. In patients with diabetes mellitus, blood glucose monitoring is required (at least 1 time per year). Hormonal contraception should be discontinued at the onset of HRT,if necessary, the patient should be recommended non-hormonal contraception. If any of the conditions / risk factors mentioned below are present or progressing, then the potential risk and expected benefits of Klimara therapy should be considered in each case before the onset or continuation of HRT. Cardiovascular diseases -vascular system. A number of epidemiological studies have revealed some increase in the incidence of venous thromboembolism (VTE), for example, deep vein thrombosis or pulmonary artery thromboembolism in women who received hormone replacement therapy. If HRT is recommended for women with VTE risk factors, the risk / benefit ratio of the therapy should be carefully weighed. The risk factors for VTE include an individual and family history (the development of VTE in direct relatives at a relatively young age may indicate a genetic predisposition), as well as a pronounced obesity. The risk of VTE also increases with age. There is no single point of view regarding the possible role of varicose veins in the development of VTE. The risk of VTE increases with prolonged immobilization, serious surgery or extensive trauma. Depending on the etiology of the disease and the duration of immobilization, the possibility of temporary cessation of HRT should be considered. Treatment should be stopped immediately if there are symptoms of thromboembolism or suspicion of them. Endometrial cancer. With prolonged exposure to estrogen increases the risk of endometrial hyperplasia or carcinoma. Studies have confirmed that supplemental administration of gestagens reduces the risk of endometrial hyperplasia and / or endometrial cancer. Breast cancer. A meta-analysis of 51 epidemiological studies demonstrated that there is a slightly increased risk of developing breast cancer diagnosed in women who received HRT for 5 years. The observed increase in risk may be due to an earlier diagnosis of breast cancer, the biological effects of HRT, or a combination of both factors. The relative risk increases with the duration of treatment. This is comparable to the increased risk of breast cancer observed in women every year delayed natural menopause.The increased risk gradually disappears after the end of treatment during the first 5 years after discontinuation of HRT. Breast cancer, diagnosed in women receiving HRT, compared with those who have not used HRT, less likely to metastasize. Liver tumors. In extremely rare cases, benign or even more rarely, malignant tumors of the liver were observed after the use of hormonal preparations such as Climar. In rare cases, these tumors lead to life-threatening intra-abdominal bleeding. The main symptoms of a liver tumor are pain in the epigastric region, an enlarged liver and / or symptoms of intra-abdominal bleeding. Gallbladder disease. Estrogens increase the lithogenicity of bile. In some cases, predisposition to gallbladder diseases increases during estrogen therapy. Other conditions. Treatment should be stopped immediately if migraine or unusually severe headaches develop for the first time, or other symptoms occur that are possible precursors of cerebral circulation disorders. If, despite changes in the site of application, according to the recommendations, repeated persistent irritation of the skin is observed (for example, persistent erythema or itching at the site of application) TTC should be discontinued. The overall relationship between HRT and the development of clinical hypertension is not established. but. Despite the fact that a slight increase in blood pressure is described in women who received HRT, a clinically significant increase in blood pressure with such treatment is extremely rare. However, if persistent, clinically significant hypertension develops in individual cases during HRT, discontinuation of HRT should be considered. Sexual steroids can be poorly metabolized in patients with reduced liver function. When carrying out HRT with TTS, the active substance is not metabolized in the liver during the first passage through the liver, in such cases HRT should be prescribed with caution. Relapse of cholestatic jaundice or cholestatic itch that developed earlier during pregnancy or during previous use of sex steroids requires immediate termination of HRT. In some patients receiving HRT, unwanted manifestations of estrogen stimulation, such as abnormal uterine bleeding, may develop. Frequent or persistent abnormal uterine bleeding during treatment is an indication for endometrial examination. Uterine myomas may increase in size under the influence of estrogens.If this is observed, then treatment should be discontinued. If endometriosis is exacerbated during treatment, discontinuation of therapy is recommended. If a prolactin is suspected, diagnosis should be ruled out before the start of therapy. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to UV radiation during HRT. The following conditions occur or worsen during HRT: epilepsy, benign breast disease, asthma, migraine, porphyria, otosclerosis, SLE, minor chorea . Although their relationship with HRT is not definitively proven, in such cases, women receiving HRT should be under close observation. Laboratory tests. Preparations for HRT may affect the results of some laboratory tests, including liver function tests, thyroid, adrenal and kidney function parameters, plasma transport protein levels, for example, corticosteroid-binding globulin and lipid and lipoprotein fractions, carbohydrate metabolism parameters, coagulation parameters and fibrinolysis. Effect on ability to drive motor vehicles and control mechanisms. No influence was observed.