戊酸雌二醇片(补佳乐)说明书（Estradiol Valerate Tablets (progynova).）

戊酸雌二醇片(补佳乐)（Estradiol Valerate Tablets (progynova).） 戊酸雌二醇片(补佳乐)说明书(Estradiol Valerate Tablets (progynova).) [drug name] general name: Estradiol Valerate Tablets Name of commodity: progynova English Name: Progynova (EstradiolValerateTabletes) Pinyin Name: wusuancierchunpian [ingredients] the main component of this product is estradiol valerate. Its chemical name is 3 hydroxy steroidal -1,3,5 (10), three ene, -17 beta alcohol, -17- valerate. [character] this product is a pale yellow sugar coated tablet, which is white after removing sugar coating. [indications] postmenopausal symptoms of menopause or after ovariectomy, estrogen disease after castration and non cancer radioactive deficiency symptoms, such as hot flashes, paroxysmal sweating, sleep disorders, depression, irritability, headache and dizziness, or for the improvement of cervical mucus. [Specification] 1mg [usage] after the meal, the daily 1mg water swallow, or compliance may increase or decrease, according to each cycle sequential therapy, after 21 days of treatment, should be discontinued at least a week. The dosage is adjusted according to the individual, one tablet per day. According to the clinical situation, adjust the individual dose: generally, breast swell, irritability and other feelings, show that the dose is too high. If the selected dose has not been alleviated, symptoms of estrogen deficiency must be increased by dosage. 1, Estradiol Valerate Tablets 1 mg can be given according to the following treatment program: (1) interrupted treatment (periodic) for 20-25 consecutive days, interrupted all treatment for 5-6 days, in this interval will occur withdrawal bleeding. (2) continuity without any interruption of treatment. For women who have undergone hysterectomy, a significant rebound if symptoms of estrogen deficiency occur during the withdrawal interval suggest that it may be suitable for continuous, non cyclical treatment. For women who do not have the uterus removed, each cycle must be treated with progesterone for at least 12 days to prevent estrogen induced endometrial hyperplasia. 2. The sequential treatment with progesterone must be carried out according to the following protocols: (1) if continuous treatment is recommended, progestin should be taken at least 12 days a month. (2) if treatment is given intermittently, progestin treatment should be given at least for the last 12 days of estrogen treatment. Thus, no hormonal treatment is administered during the interval of withdrawal of each cycle. In these two cases, bleeding may occur after cessation of progesterone therapy. The pros and cons should be assessed periodically (every 6 months) to adjust or abandon treatment when needed. [adverse reactions] except listed in [contraindications] any of the following conditions should not begin with hormone replacement therapy (HRT). If there is any of the following conditions in the HRT in the process of treatment, should be discontinued immediately: pregnancy and lactation, undiagnosed vaginal bleeding, known or suspected breast cancer, known or suspected sex hormones affect precancerous or malignant tumors, existing or previous history of liver tumors (benign or malignant) and severe acute liver disease, arterial thromboembolism (such as myocardial infarction, stroke), the activity of deep vein thrombosis and thromboembolic disease, Or have a history of these diseases, severe hypertriglyceridemia, etc., and are known to be allergic to any component of Estradiol Valerate Tablets or to the heart that causes it [notice] if any of the following conditions or risk factors exists or worsens, individual pros and cons should be analysed before starting or continuing the HRT. 1 、 venous thromboembolism Randomized controlled studies and epidemiological studies have shown that hormone replacement therapy (HRT) increases the relative risk of developing venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary thromboembolism. Therefore there are VTE risk factors in women with hormone replacement therapy (HRT) should consult with patients to carefully weigh the pros and cons. Accepted VTE risk factors include personal history, family history (immediate relatives have occurred at a relatively early age, VTE may indicate a genetic predisposition) and severe obesity. The risk of VTE also increases with age. The possible role of varicose veins in VTE is inconclusive. The risk of VTE may be temporarily increased by prolonged immobilization, larger elective or post-traumatic surgery, or severe trauma. Depending on the circumstances and braking time, the HRT should be temporarily disabled. If symptoms of thrombosis or thrombosis are suspected, immediate treatment should be discontinued. 2. Arterial thromboembolism Two large clinical trials of the use of equine estrogen (CEE) and medroxyprogesterone acetate suggest that the risk of coronary artery disease (CHO) may increase in the first year of treatment and will not be beneficial thereafter. A large-scale clinical trial using CEE alone showed a potential reduction in the incidence of CHD among women aged 50-59, but there was no overall benefit in all studies. Among the two large clinical trials of CEE alone or in combination with MPA, the risk rate for stroke as a secondary indicator was observed to be 30-40%. It is not possible to determine whether the results of other HRT products or non oral routes of administration can be observed. 3. Endometrial carcinoma Prolonged use of unopposed estrogen increases the risk of endometrial hyperplasia or endometrial cancer. Studies have shown that the addition of appropriate progestin in the treatment can eliminate the increased risk. 4 breast cancer Clinical observation shows that women who have been treated with HRT for several years have been found to have an increased risk of breast cancer. These findings may be due to early diagnosis, a promotive effect on preexisting tumor growth, or a combined effect of the two. More than 50 epidemiological studies have shown that most of the studies involved an overall relative risk assessment of breast cancer between 1-2. Treatment duration increased, relative risk increased. For pure estrogen products, relative risks may be reduced or centered. Two large randomized controlled clinical trials using CEE and CEE in combination with MPA showed that after 6 years of HRT treatment, the risk was evaluated at 0.77 (95%, CI:0.59-1.01) or 1.24 (95%, CI:1.01-1.54). It is not known whether other HRT products have similar risk increases. Similar risk increases were observed in the diagnosis of breast pain, such as delayed natural menopause, alcohol consumption, obesity, etc. the risk of increased risk disappeared after a few years of HRT treatment. Most of the studies have been reported, Patients who have been treated with HRT at present or in the near future have a higher rate of tumor differentiation than those who have not been treated with HRT. The data of extra mammary diffusion are not conclusive. HRT enhances the intensity of mammography imaging in some cases, which may have adverse effects on radiographic testing of breast cancer. 5. Ovarian cancer An epidemiological study found that long-term (over 10 years) receiving hormone replacement therapy (ERT) women at risk of ovarian cancer increased slightly, but a meta-analysis of 15 studies found no increased risk for women undergoing ERT. Therefore, the effect of ERT on ovarian cancer is unknown. 6. Liver tumor Using hormones, such as those contained in Estradiol Valerate Tablets, benign liver tumors are observed in rare cases, even in rare cases of liver malignancies. In individual cases, these tumors cause life-threatening intraperitoneal bleeding. Liver tumors should be considered in differential diagnosis if upper abdominal pain, hepatomegaly or signs of intraabdominal hemorrhage are present. 7. Gallbladder diseases Estrogen is known to increase gallstone formation. Some women develop gallbladder disease during estrogen treatment. 8, dementia Limited clinical evidence using CEE as a pretreatment suggests that hormone therapy is more likely to increase the risk of dementia in women over the age of 65 or 65. In other studies, hormone therapy may have decreased the risk of early menopause. It is uncertain whether other HRT products have similar findings. 9, other circumstances (1) prompt treatment should be discontinued immediately if the first migraine or frequent and unusually severe headache or other threatened clinical manifestations of cerebral vascular obstruction is present. (2) the general relationship between the use of HRT and the incidence of clinical hypertension has not been established. It has been reported that women who use HRT have slightly elevated blood pressure, but are clinically rare. In general, however, if individual cases of persistent hypertension with clinical significance are used during HRT, HRT should be considered. (3) non severe liver dysfunction, including hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, should be closely monitored and liver function should be checked regularly. Once the deterioration of hepatic function occurs, HRT should be stopped. (4) for the first time during pregnancy or previous use of sex steroid hormones occurred during cholestatic jaundice or cholestatic pruritus, such as relapse, must immediately stop HRT. (5) women with moderate elevated triglycerides need special monitoring. The use of HRT in women may increase triglyceride levels, thus contributing to the risk of acute pancreatitis. (6) although HRT may have an impact on peripheral insulin resistance and glucose tolerance, diabetes mellitus patients usually do not need to change their treatment regimen when using HRT. However, diabetic women who use HRT should be carefully monitored. (7) some patients can have adverse effects of estrogen stimulation when using HRT, such as abnormal uterine bleeding. Endometrial examination should be performed when frequent or persistent abnormal bleeding occurs during treatment. (8) under the influence of estrogen, the volume of myoma of uterus may increase. If this condition is observed, treatment should be discontinued. (9) if endometriosis is activated during treatment, it is recommended to discontinue treatment. (10) if a suspect is suspected to have prolactin, it should be excluded before starting treatment. (11) occasional melasma, especially in women with a history of melasma. Women with melasma tend to avoid exposure to sunlight or ultraviolet radiation during use of HRT. (12) there are reports of possible or worsening conditions in the use of HRT. Although related to the use of HRT evidence is not conclusive, the women should still be carefully monitored in an HRT: benign breast disease, asthma, epilepsy, migraine, porphyria, otosclerosis, systemic lupus erythematosus, small chorea. [pregnant and lactating women] HRT does not apply to pregnant or lactating women. Steroid hormone used for large-scale epidemiological studies of contraception and hormone replacement therapy, using this kind of hormone before pregnancy women, the risk of birth defects in newborns did not increase during early pregnancy accident taking these drugs no teratogenic effects. A small amount of sex hormone can be secreted in human milk. [child medication] Estradiol Valerate Tablets is not for children. [elderly medication] no special recommended dosage for the elderly. [drug interactions] prolonged use of liver enzymes to induce drugs can speed up the elimination of sex hormones and may reduce their clinical efficacy. Some binding substances (such as acetaminophen) competitively inhibit binding systems, which may increase the bioavailability of estradiol. The dosage of oral antidiabetic drugs or insulin varies in individual cases. Rapid intake of alcohol during the use of HRT can lead to elevated levels of estradiol in the blood circulation. [drug overdose] acute toxicity studies did not suggest that accidental use of multiple daily doses of drugs had the risk of acute adverse reactions. [toxicology] toxicology research: 1 carcinogenicity Toxicological studies of repeated administration, including the results of tumorigenic studies, did not show specific risks associated with human use. However, it must be borne in mind that sex hormones promote the growth of certain hormone dependent tissues and tumors. 2 、 fetal toxicity / teratogenicity Studies on the reproductive toxicology of estradiol valerate do not suggest potential teratogenicity. Since the use of estradiol valerate does not result in a non physiological estradiol valerate plasma concentration, the formulation does not indicate a risk to the dry fetus. 3, mutagenicity The in vitro and in vivo studies of 17 beta estradiol did not indicate the potential for mutagenicity. Pharmacological action: Progynova containing estrogen estradiol valerate, is a precursor of human natural estrogen 17 beta estradiol, estradiol has pharmacological effect, normal development can promote and regulate the female reproductive organs and secondary sex characteristics. The use of Estradiol Valerate Tablets does not inhibit ovulation, and basically does not affect the production of endogenous hormones. During menopause, the decrease and eventual disappearance of ovarian estradiol results in an unstable body temperature, Cause with sleep disorders and sweating hot flashes, and accompanied by vaginal dryness, dyspareunia and urinary incontinence symptoms of urogenital atrophy. Often mentioned but less specific part of menopause syndrome symptoms such as angina pectoris, complained of palpitation, irritability, nervousness, fatigue, inattention, forgetfulness, loss of libido and muscle pain. Hormone replacement therapy (HRT) can alleviate many of the symptoms of estrogen deficiency in postmenopausal women. Using an appropriate amount of estrogen HRT, such as Estradiol Valerate Tablets, can reduce bone resorption and delay or prevent postmenopausal bone loss. When the HRT was discontinued, the rate of bone loss was similar to that in premenopausal women. There is no evidence that HRT restores bone mass to pre menopausal levels. HRT also has a positive effect on skin collagen content and skin thickness, and can delay the development of skin wrinkles. In recent years, a number of published studies have suggested that there may be a causal relationship between postmenopausal oral HRT and reduction in cardiovascular disease in women. However, there is still no evidence of a causal relationship between HRT and cardiovascular disease in postmenopausal women. Moreover, the effect of added progestin on this assumed benefit is unknown. HRT changed the fat mass spectrum. It lowers total cholesterol and LDL cholesterol, and increases HDL cholesterol and triglyceride levels. This metabolic effect can, in part, be counteracted by the addition of progesterone. For women with complete uterus, it is recommended that in an estrogen replacement, such as Estradiol Valerate Tablets, plus a progestin, at least 10 days per cycle. This reduces the risk of endometrial hyperplasia and associated risk of adenocarcinoma in these women. It has not been shown that the use of a progestin in an estrogen replacement can interfere with the effectiveness of estrogen in approved indications. The observational study and the women's Health Initiative (WHI) show that the incidence of colon cancer is lower in postmenopausal women treated with combination of equine estrogen and medroxyprogesterone acetate (MPA) for HRT. No similar risk reduction was observed in the women's Health Initiative (WHI) study using equine estrogen alone. It is not known whether other HRT products have similar findings. [pharmacokinetics] 1. Absorption: estradiol valerate absorbs rapidly and completely. In the process of absorption and passage through the liver for the first time, steroid esters are broken down into estradiol and valerate. At the same time, estradiol, estrone, estradiol for further metabolism of three alcohol and estrone sulfate. Only about 3% of estradiol was bioavailable after oral administration of estradiol valerate. Food does not affect the bioavailability of estradiol. 2. Distribution: the highest serum concentration of estradiol reached hours after taking medicine, usually about 4-9 hours. Serum estradiol levels dropped to about 8pg/ml within 24 hours after taking the medicine. Estradiol binds to albumin and sex hormone binding globulin (SHBG). The unbound estradiol in serum is about 1-1.5%, and the part associated with SHBG is 30-40%. The apparent volume of estradiol after single intravenous administration was about 1L/kg. 3. Metabolism: after exogenous administration of estradiol valerate, the metabolism of the drug follows the pathway of biotransformation of endogenous estradiol. Estradiol is metabolized mainly in the liver, but also outside the liver, Such as intestinal, kidney, skeletal muscle and target organ metabolism. These processes include estrone, three female alcohol, catechol estrogen and these compounds sulfate and glucuronide conjugates formed, the estrogenic activity of these substances is significantly reduced, or even no estrogenic activity. 4. Excretion: the total serum clearance of estradiol showed a high degree of variability after single intravenous administration, ranging from 10-30ml/min/kg. A certain amount of estradiol metabolites can be secreted into the bile, enter the enterohepatic circulation. The final estradiol metabolite is excreted mainly from the urine in the form of salts and glucuronide. 5, the steady state: after multiple dosing was observed, serum estradiol levels than single dose of about 2 times. The mean concentration of estradiol was between 15pg/ml (lowest level) and -30pg/ml (highest level). Estrone as metabolites with a low estrogen activity, serum concentration of about 8 times. Estrone sulfate concentration of about 150 times higher. 2-3 days after discontinuation of Estradiol Valerate Tablets, recovery of estradiol and estrone concentration to the level before the treatment. [storage] keep under 30 degrees celsius. Keep all the medicines in good order so that the children do not touch them.