中文通用名称: 戊酸雌二醇
英文通用名称: Estradiol Valerate
其它名称: 雌二醇戊酸酯,补乐,Progynon,Progynova,Oestradiol Valerate,Femogex,Delestrogen

DELESTROGEN ® (estradiol valerate injection, USP) contains estradiol valerate, in the intramuscular injection of long-term use of estrogen sterile oil solutions. These solutions are clear, colorless to pale yellow. Recipe (per ml): 10 mg containing 5 mg estradiol valerate chlorobutanol (chloral derivative / preservative), sesame oil vehicle; 20 mg of estradiol valerate in the presence of benzyl benzoate 224 mg, 20 mg of this vehicle - zyl alcohol (preservative), and castor oil, 40 mg, 447 mg of estradiol valerate in the presence of benzyl benzoate, benzyl alcohol 20 mg, and castor oil vehicle.

Estradiol valerate chemical designated as estra - 1,3,5 (10) - triene - 3,17 - diol (17β) -, 17 pentanoate. Graphic formula:

Indications
DELESTROGEN (estradiol valerate injection, USP) is indicated:

Treatment of moderate to severe vasomotor symptoms associated with menopause.
Treatment of vulvar and vaginal atrophy with moderate to severe symptoms of menopause. When the prescription symptoms of vulvar and vaginal atrophy treatment only, topical vaginal products should be considered.
Treatment for hypogonadism hypoestrogenism, castration or primary ovarian failure.
The treatment of advanced hormone-refractory prostate cancer (for relief only).

DOSAGE AND ADMINISTRATION
When estrogen is a provision in postmenopausal women the uterus, progesterone should be started to decrease, the risk of endometrial cancer. Women without a uterus does not need progestin. Use of estrogen, alone or in combination with progestin, should be the lowest effective dose and shortest duration of treatment goals and risks for individual women is consistent. Patients should be re-assessed in the clinical appropriate (such as 3 months to 6 months intervals) to determine whether still requires regular treatment (see Boxed Warning and Warnings). Women who have uterine, appropriate diagnostic methods such as endometrial sampling that should be taken out of the diagnosis of persistent or recurring abnormal vaginal bleeding malignant cases.

Should be noted that injection, the outer quadrant of the gluteal muscle following the usual precautions deep intramuscular injection. Low viscosity of the vehicle by virtue of this DELESTROGEN (estradiol valerate injection, USP) and the preparatory work, managed a small needle. Since the effect of 40 mg provided a high concentration in a small volume, special attention should be observed, and managing the dose.

DELESTROGEN visual inspection should be particulate matter and color prior to administration; solution is clear, colorless to pale yellow. Storage at low temperatures may cause some warming crystal materials redissolves easily separated.

Note: The dry needles and syringes should be used. A wet needle or syringe may cause solution to use to become muddy, but this does not affect the material's effectiveness.

Patients should start at the lowest dose of signs. DELESTROGEN lowest effective dose for any signs yet to be determined. The treatment of patients with an intact uterus should be closely monitored signs of endometrial cancer and appropriate diagnostic measures should be taken out of persistent or recurring abnormal vaginal bleeding fatalities. See Notes on progesterone increase.

For the treatment of moderate to severe vasomotor symptoms, vulvar and vaginal atrophy associated with menopause, the lowest dose and regimen that will control and drug therapy should be selected as soon as possible to stop symptoms. Usually 10 to 20 mg dosage DELESTROGEN every four weeks. Try to stop or taper medication should be made within 3 months 6 months interval.
Women hypoestrogenism for hypogonadism, castration or primary ovarian failure treatment. Usually 10 to 20 mg dosage DELESTROGEN every four weeks.
For the treatment of advanced hormone refractory prostate cancer palliative care only. Usually a dose of 30 mg or more of the management of one or two weeks each.

How to provide
DELESTROGEN ® (estradiol valerate injection, USP)

Multi-dose vials

10 mg / ml (5 ml): North District Council 42023-110-01
20 mg / ml (5 ml): North District Council 42023-111-01
40 mg / ml (5 ml): North District Council 42023-112-01

Storage
Store at room temperature.

Do not let children.

April 2007 provides for the information. Manufacturers and distributors: JHP Pharmaceuticals, Rochester, MI 48307. FDA's pastor Date: 10/11/2007

Side effects
See boxed warning, warnings and precautions.

Because clinical trials are conducted under widely different conditions, adverse reaction rates observed in a drug can not be directly compared in clinical trials of another drug and the rate of clinical trials may not reflect the rates observed in practice. Adverse reactions from clinical trials information does, however, to identify drug use that seems to approximate the rate of adverse events and the basis.

The following additional adverse reactions have been reported with estrogen and / or progesterone treatment.

Genitourinary system
Vaginal bleeding pattern and abnormal withdrawal bleeding or flow changes; breakthrough bleeding, spotting, dysmenorrhea, uterine fibroids the size of the increase; vaginitis, including vaginal can, didiasis, changes in cervical secretion and changes in cervical ectropion, ovarian cancer, endometrial hyperplasia, endometrial cancer.

Breast
Tenderness, swelling, pain, nipple discharge, galactorrhea, fibrocystic breast changes; breast cancer.

Cardiovascular
Deep and superficial venous thrombosis; pulmonary embolism, thrombosis, myocardial infarction, stroke, high blood pressure.

Gastrointestinal
Nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, enlargement of hepatic hemangiomas.

Skin
Chloasma or melasma, which may continue during withdrawal, erythema multiforme, erythema nodosum, hemorrhagic eruption; scalp hair loss, hirsutism, itching, rash.

Eyes
Retinal vascular thrombosis; can not tolerate contact lenses.

Central nervous system
Headache, migraine, dizziness, mental depression, chorea, nervousness, mood disorders, irritability, seizures, dementia.

Miscellaneous
Increase or decrease in weight; reduced carbohydrate tolerance; deterioration of porphyrin; edema; arthalgias, leg cramps, changes in libido, urticaria, angioedema, allergic / allergic reaction; hypocalcemia, aggravation of asthma; increase in triglycerides.

Drug Interactions
Drug / laboratory test interaction.
Accelerated prothrombin time, partial thromboplastin time, platelet aggregation time, increased platelet count; II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII - X of the complex, the second to VII - X of the complex factors that increase β-thromboglobulin 1996-04-03 antifactor Xa and antithrombin Ⅲ lower level, lower antithrombin Ⅲ activity, fibrinogen and fibrinogen activity levels increase; increase in fiber plasminogen antigen and activity.
Increase in thyroid binding globulin (TBG) levels, thereby increasing the total circulating thyroid hormone levels as a measure of protein binding iodine (PBI) T4 levels (by column or radioimmunoas, for example) or T3 levels by radioimmunoassay. T3 resin uptake decreased, reflecting the increase of TBG. Concentration of free T4 and free T3 remain unchanged. Patients with thyroid replacement therapy may require higher doses of thyroid hormone.
Other binding proteins may be elevated in serum (ie, corticosteroid binding globulin (CBG) is the sex hormone binding globulin (SHBG)), which leads to increased total circulating corticosteroids and sex hormones, respectively. Free hormone concentrations may be reduced. Other plasma proteins may be increased (angiotensinogen / renin substrate, α-1 - antitrypsin, ceruloplasmin).
Increased plasma concentrations of HDL subfractions and HDL2cholesterol, lower low-density lipoprotein cholesterol concentration, increased triglyceride levels.
Impaired glucose tolerance.
Metyrapone reduced response to the test.

[药品名]戊酸雌二醇

[英文名]EStradLol Valerate
中文同义词: 氨氯地平苯磺酸盐;雌二醇戊酸酯;3-羟基雌甾-1,3,5(10)-三烯-17b-醇 17-戊酸酯;戊酸雌二醇
英文名称: Estradiol valerate
英文同义词: 3,5(10)-triene-3,17-diol(17-beta)-estra-17-pentanoate;atladiol;b-estradiol17-valerate;deladiol;delahormoneunimatic;delestrogen;delestrogen4x;dura-estradiol
CAS号: 979-32-8
分子式: C23H32O3
分子量: 356.5
熔点  144°C
[性状]白色结晶性粉末，无臭，熔点145℃-150℃。不溶于水，易溶于乙醇、丙酮、氯仿，微溶于植物油。
[作用与用途]为长效雌二醇衍生物，肌注后缓慢释放，作用维持时间2—4周。临床用于卵巢功能不全、闭经、更年期综合征、退奶及前列腺癌等。与乙酸孕酮或庚炔诺酮组成复方，能抑制排卵，作为每月一次的长效避孕针。

描述
DELESTROGEN ®（戊酸雌二醇注射液，美国药典）包含戊酸雌二醇，在肌肉注射使用无菌油解长效雌激素。

适应症和用法
DELESTROGEN ®的适应症是：
1。治疗中度至重度血管收缩与更年期相关症状。
2。治疗中度至外阴和阴道萎缩的更年期症状严重。当处方的外阴及阴道萎缩症状的治疗只，外用阴道产品应予以考虑。
3。治疗因性腺功能减退hypoestrogenism，去势或原发性卵巢功能衰竭。
4。治疗晚期激素非依赖性前列腺癌（为缓解只）。

雌激素增加子宫内膜癌的风险

关闭所有的妇女服用雌激素的临床监测是重要的。适当的诊断方法，包括子宫内膜取样时指出，应采取排除在确诊持续或反复出现异常阴道出血的恶性案件。没有任何证据表明，“自然”雌激素会导致不同的比同等剂量的人工合成的雌激素雌激素子宫内膜癌的风险状况使用。 （见警告，恶性肿瘤，子宫内膜癌）。
心血管及其他风险
雌激素和孕激素不应该用于预防心血管疾病。 （见警告，心血管疾病。）妇女健康倡议（WHI）这项研究报告在5年的心肌梗死，中风，浸润性乳腺癌，肺栓塞，与绝经后妇女发生深度静脉血栓（50至79岁）的风险增加以口服共轭与安宫黄体酮（MPA的2.5毫克），相对于安慰剂相结合雌激素（CE认证0.625毫克）治疗。 （见临床药理学，临床研究。）
妇女健康倡议记忆的研究（WHIMS的），一个WHI的次研究，报告增加发展中国家在65岁以上的老年人在4以口服结合雌激素加甲孕酮治疗绝经后妇女可能患有痴呆症多年相对于安慰剂的风险。目前还不清楚这一发现是否适用于较年轻妇女停经后妇女或单独服用雌激素治疗。 （见临床药理学，临床研究。）其他剂量的口服安宫黄体酮与雌激素结合，和其他组合雌激素和孕激素和剂型没有在WHI的研究和临床试验的可比数据的情况下，这些风险应假设是相似的。由于这些风险，雌激素与孕激素或不应该规定最低有效剂量及治疗时间最短的目标和个别妇女的风险是一致的。 
 

禁忌
DELESTROGEN不应该用于女性具有下列条件之一：
1。未确诊的异常生殖器出血
2。已知，怀疑或历史的乳腺癌
3。已知或怀疑雌激素依赖性肿瘤
4。主动深静脉血栓形成，肺栓塞或对这些条件的历史
5。主动或近期（例如在过去的一年，）动脉血栓栓塞性疾病（如中风，心肌梗死）。
6。肝功能障碍或疾病。
7。 DELESTROGEN不应该用于治疗过敏其成分。
8。已知或怀疑怀孕。有没有在怀孕DELESTROGEN迹象。似乎有很少或没有增加出生缺陷风险所生谁使用口服避孕药无意中从妊娠早期雌激素和孕激素的妇女儿童。

警告
见盒装警告

在无人反对的雌激素的妇女谁拥有使用与子宫内膜癌的风险增加。

1。心血管疾病
雌激素和雌激素/孕激素治疗一直伴随着一个如心肌梗死和中风，以及静脉血栓和肺栓塞（静脉血栓或栓塞）心血管事件的危险性增加。如果这些发生或任何涉嫌，雌激素，应立即停止。
对动脉血管疾病（如高血压，糖尿病，吸烟，高胆固醇，肥胖）和/或静脉血栓栓塞（如个人或家庭的VTE史，肥胖史，系统性红斑狼疮）的危险因素，应适当管理。
如果可行，应停止雌激素至少4至6周前与血栓栓塞的风险增加相关的类型，手术或在固定时间延长。

 2。恶性肿瘤
答：子宫内膜癌
在无人反对的雌激素的妇女使用的是完整的子宫已与子宫内膜癌的风险增加。该报告在无人反对的雌激素子宫内膜癌的风险是用户约2 - 12倍大于非使用者，并似乎对雌激素治疗时间和剂量依赖性。大多数研究显示没有显着增加的风险与雌激素使用不到一年的关联。最大的风险显然与长时间使用，增加风险为15 - 24倍五至十年以上，这种风险已被证明至少8至15岁的雌激素治疗后，坚持已停止。
所有参加临床雌激素/孕激素组合的妇女的监测至关重要。适当的诊断方法，包括子宫内膜取样时指出，应采取排除在确诊持续或反复出现异常阴道出血的恶性案件。没有任何证据表明，雌激素的结果在不同的自然比人工合成的雌激素剂量相当于子宫内膜雌激素的风险状况使用。添加孕激素与雌激素疗法已被证实可以降低子宫内膜增生的风险，这可能是子宫内膜癌的前兆。

乳腺癌
对绝经后妇女雌激素和孕激素的使用有报道增加乳腺癌的风险。最重要的随机临床试验提供了关于此问题的信息是妇女健康倡议（WHI）这项使用CE / MPA（见临床药理学，临床研究）亚组。从观测研究的结果通常与WHI的临床试验报告的一致，没有患乳腺癌的雌激素或孕激素不同，剂量，给药途径或风险显着变化。
雌激素和孕激素的使用有报道导致在需要进一步的评估乳房X光摄影异常增加。所有妇女应接受由医疗保健机构每年进行乳房检查和每月的乳房自我检查。此外，应安排乳房摄影检查病人的年龄，风险因素，在此之前乳房X光检查结果为基础。

3。痴呆
在妇女健康行动记忆的研究（WHIMS的），4,532名一般健康的65岁以上的绝经后妇女进行了研究，其中35％是70至74岁，18％为75岁或以上。在平均随访4年，40名妇女正在接受使用CE / MPA
（1.8％，2,229例）和安慰剂组21名妇女（0.9％组，n = 2,303）接受可能患有痴呆症的诊断。对于使用CE / MPA与安慰剂的相对风险为2.05（95％信赖区间1.21 - 3.48），并为与不WHIMS的绝经前妇女使用激素类似的历史。在对使用CE / MPA与安慰剂可能患有痴呆症的绝对风险为每10,000名妇女，45年比22例，绝对过剩的风险CE / MPA的每23万名妇女，年案件。目前还不清楚这些发现是否适用于较年轻的绝经后妇女。 （见临床药理学，临床研究和注意事项，老年使用。）
目前还不清楚这些发现是否适用于雌激素的治疗。

4。胆囊疾病
一个2 - 4倍，在需要接受胆囊据报道手术绝经后妇女雌激素疾病的风险增加。

5。高钙血症
雌激素可能导致乳腺癌和骨转移患者严重高钙血症。如果高钙血症发生时，应停止用药，并采取适当措施以降低血清钙水平。

6。视觉异常
视网膜血管血栓形成据报道，在接受雌激素的患者。停止服药之前检查是否有突然的部分或完全丧失视力，或眼球突出，复视，或偏头痛突然发作。如果检查发现视乳头水肿或视网膜血管病变，雌激素应该永久地停止。

不良反应

泌尿生殖系统：阴道出血模式的变化和不正常的撤退性出血或流动;突破性出血，点滴出血，痛经，子宫肌瘤的大小增加;阴道炎，阴道念珠菌等，在宫颈分泌量的变化;变化宫颈外翻，卵巢癌;子宫内膜增生;子宫内膜癌。乳房：触痛，肿大，疼痛，乳头溢液，溢乳，乳腺纤维囊性改变;乳腺癌。心血管系统：深，浅静脉血栓形成;肺动脉栓塞;血栓，心肌梗死，中风，血压升高。胃肠道：恶心，呕吐，腹部绞痛，腹胀，胆汁淤积性黄疸，胆囊疾病发病率上升，胰腺炎，肝血管瘤的扩大。皮肤：黄褐斑或黄褐斑，这可能会持续停药时，多形性红斑，结节性红斑，出血疹;头皮脱发，多毛，瘙痒，皮疹。眼睛：视网膜血管血栓形成;不能耐受隐形眼镜。中枢神经系统：头痛，偏头痛，眩晕，精神抑郁，舞蹈病，神经质，情绪障碍，烦躁不安，癫痫发作，痴呆。杂项：增加或减少重量;减少碳水化合物宽容，卟啉症恶化;水肿; arthalgias，腿抽筋，改变性欲，荨麻疹，血管性水肿，过敏性/过敏性反应;低钙血症，哮喘发作;增加甘油三酯。