DELESTROGEN(estradiol valerate injection, USP)长效雌二醇注射剂-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。
DELESTROGEN(estradiol valerate injection, USP) contains estradiol valerate, a long-acting estrogen in sterile oil solutions for intramuscular use. These solutions are clear, colorless to pale yellow. Formulations (per mL): 10 mg estradiol valerate in a vehicle containing 5 mg chlorobutanol (chloral derivative/preservative) and sesame oil; 20 mg estradiol valerate in a vehicle containing 224 mg benzyl benzoate, 20 mg ben-zyl alcohol (preservative), and castor oil; 40 mg estradiol valerate in a vehicle containing 447 mg benzyl benzoate, 20 mg benzyl alcohol, and castor oil.
Estradiol valerate is designated chemically as estra-1,3,5(10)-triene-3, 17-diol(17β)-, 17-pentanoate. Graphic formula:
INDICATIONS
DELESTROGEN (estradiol valerate injection, USP) is indicated in the:Treatment of moderate to severe vasomotor symptoms associated with the menopause.
Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
Treatment of advanced androgen-dependent carcinoma of the prostate(for palliation only).
DOSAGE AND ADMINISTRATION
When estrogen is prescribed for a postmenopausal woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary (See BOXED WARNINGS and WARNINGS).
For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
Care should be taken to inject deeply into the upper, outer quadrant of the gluteal muscle following the usual precautions for intramuscular administration. By virtue of the low viscosity of the vehicles, the various preparations of DELESTROGEN (estradiol
valerate injection, USP) may be administered with a small gauge needle. Since the 40 mg potency provides a high concentration in a small volume, particular care should be observed to administer the full dose.
DELESTROGEN should be visually inspected for particulate matter and color prior to administration; the solution is clear, colorless to pale yellow. Storage at low temperatures may result in the separation of some crystalline material which redissolves readily on warming.
NOTE: A dry needle and syringe should be used. Use of a wet needle or syringe may cause the solution to become cloudy; however, this does not affect the potency of the material.
Patients should be started at the lowest dose for the indication.
The lowest effective dose of DELESTROGEN has not been determined for any indication. Treated patients with an intact uterus should be monitored closely for signs of endometrial cancer, and appropriate diagnostic measures should be taken to rule our malignancy in the event of persistent or recurring abnormal vaginal bleeding.
See PRECAUTIONS concerning addition of a progestin.
For treatment of moderate to severe vasomotor symptoms, vulvar and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. The usual dosage is 10 to 20 mg DELESTROGEN every four weeks. Attempts to discontinue or taper medication should be made at 3-month to 6-month intervals.
For treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure. The usual dosage is 10 to 20 mg DELESTROGEN every four weeks.
For treatment of advanced androgen-dependent carcinoma of the prostate, for palliation only.
The usual dosage is 30 mg or more administered every one or two weeks.
HOW SUPPLIED
DELESTROGEN(estradiol valerate injection, USP)
Multiple Dose Vials
10 mg/mL (5 mL): NDC 42023-110-01
20 mg/mL (5 mL): NDC 42023-111-01
40 mg/mL (5 mL): NDC 42023-112-01
Storage
Store at room temperature.
Keep out of reach of children.
Prescribing Information as of April 2007. Manufactured and Distributed by: JHP Pharmaceuticals, LLC, Rochester, MI 48307. FDA rev date: 10/11/2007
SIDE EFFECTS
See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
The following additional adverse reactions have been reported with estrogen and/or progestin therapy.
Genitourinary system
Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal can-didiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia;
endometrial cancer.
Breasts
Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
Cardiovascular
Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in 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 persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.
Eyes
Retinal vascular thrombosis; intolerance to contact lenses.
Central Nervous System
Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia.
Miscellaneous
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.
DRUG INTERACTIONS
Drug/Laboratory Test Interactions.
Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased
antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoas-say) or T3 levels by radioimmunoassay. T3 resin uptake
is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.
Other binding proteins may be elevated in serum (i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin(SHBG)) leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
Increased plasma HDL and HDL2cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels.
Impaired glucose tolerance.
Reduced response to metyrapone test.

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部份中文长效雌二醇的戊酸酯处方资料（仅供参考）
药品英文名
Estradiol Valerate
药物剂型
1.注射剂：5mg(1ml)，10mg(1ml)；2.缓释片：1mg；3.片剂：0.5mg，1mg，2mg。
药理作用
本药为雌激素的一种，是长效雌二醇的戊酸酯。雌激素能促使细胞合成DNA、RNA和相应组织内各种不同的蛋白质，并通过减少下丘脑促性腺激素的释放，导致卵泡刺激素(FSH)、黄体生成素(LH)和促黄体分泌素从垂体的释放也减少，从而抑制了排卵。
男性LH分泌减少可使睾丸分泌睾酮降低。
1.卵泡早期发育，协同FSH促进内卵泡膜细胞和颗粒细胞合成细胞膜上LH受体，从而支持LH调节卵泡的分泌功能，促进卵泡发育。
2.子宫内膜上皮细胞和腺细胞增生，促使子宫颈腺体上皮细胞增生，黏液分泌量增加。
3.子宫平滑肌细胞增生肥大，提高子宫平滑肌对催产素的敏感性和收缩力。
4.阴道上皮细胞增生、成熟。
5.女性外生殖器如大小阴唇发育、增大。
6.乳腺管细胞增生，并与黄体酮、催乳素和肾上腺皮质激素协同，促进乳腺发育。
7.青春期决定女性脂肪分布，形成女性状态。
8.钙在骨中的沉着。
9.中胆固醇含量与磷脂的比值下降。
10.水钠潴留。
药动学
本品吸收后经血液和组织液转运到靶细胞，能与血浆蛋白中度或高度结合，转运到雌激素反应组织后，与特异性受体蛋白结合，形成“活化”的复合体，此种复合体具有多种功能。本品口服后生物利用度为3%～5%，吸收迅速，在体内水解为雌二醇（E2)，血雌二醇于服药后3h达峰值浓度，6～8h后出现第二高峰，提示有肠肝循环。血内雌二醇在肠道及肝内迅速代谢为雌酮（E1)及其硫酸盐。E1和E2之间在体内可互相转换，然后进一步代谢为雌三醇、儿茶酚雌激素等。主要以葡萄糖醛酸盐或硫酸盐的形式，自肾脏排泄，少部分自粪便排出。在肝内代谢的雌激素有部分经胆汁排入肠内可再吸收，即肠肝循环。雌激素的吸收、利用、代谢有一定的个体差异，因此用药需因人而异。
适应证
1.纠正雌激素缺乏与雌激素缺乏所引起的症状，如治疗自然或人工绝经的妇女血管舒缩功能不稳定症状、泌尿生殖道萎缩症状、神经精神症状等。
2.绝经后妇女保持骨密度，预防或延缓骨质疏松症的发生；保护心血管系统，减少动脉硬化性心血管病发生的危险。
3.育龄期闭经患者人工诱导月经来潮，防止生殖道萎缩。
4.促进原发闭经性患者乳房、第二性征、生殖道的发育。
5.晚期前列腺癌。
6.与孕激素类药合用，能抑制排卵，可作避孕药。
7.用于退奶。

禁忌证
1.妊娠期间不要使用雌激素，全身用药和阴道用药均可能导致胎儿畸形。因用药后所生女婴有可能出现生殖道异常。有育龄期妇女使用该药后发生阴道癌或宫颈癌的个案报道。
2.雌激素可经乳腺进入乳汁而排出，并可抑制泌乳，故哺乳期妇女禁用。
3.已知或怀疑患有乳腺癌，但用来作为治疗晚期转移性乳腺癌时例外。
4.已知或怀疑患有雌激素依赖性肿瘤(如子宫内膜癌)。
5.急性血栓性静脉炎或血栓栓塞。
6.以前使用雌激素时，曾伴有血栓性静脉炎或血栓栓塞史的患者，但用以治疗晚期乳腺癌及前列腺癌时例外。
7.有胆汁淤积性黄疸史。
8.未明确诊断的阴道不规则流血。
注意事项
1.慎用：
(1)哮喘。
(2)心功能不全。
(3)癫痫。
(4)精神抑郁。
(5)偏头痛。
(6)肾功能不全(雌激素可使水潴留加剧)及肾功能异常。
(7)糖尿病。
(8)良性乳腺疾病。
(9)脑血管疾患。
(10)冠状动脉疾患。
(11)子宫内膜异位症。
(12)胆囊疾患或有胆囊病史，尤其是胆结石。
(13)肝功能异常。
(14)血钙过高，伴有肿瘤或代谢性骨质疾患。
(15)高血压。
(16)妊娠时黄疸或黄疸史。
(17)甲状腺疾患。
(18)子宫肌瘤。
2.应使用本药的最低有效量，时间尽可能缩短，以减少可能发生的不良反应。
3.男性患者以及女性子宫切除后患者，通常采用周期治疗，即用药3周停药1周，相当于自然月经周期中雌激素的变化情况。有子宫的女性，为避免过度刺激，可在月经周期的最后10～14天加用孕激素，模拟自然周期中激素的浓度。
4.长期或大量使用本药者，停药或减量时须逐步进行。
5.促进性征发育应在骨龄大于13岁以后开始，以免引起骨骺早闭。
6.药物对检验值或诊断的影响：
(1)美替拉酮(metyrapone)试验，反应减低。
(2)去甲肾上腺素导致的血小板凝聚力可增加。
(3)碘溴酞钠(BSP)潴留增加。
(4)用血清蛋白结合碘(PBI)测试甲状腺功能，T4的结合增加，T3血清树脂的摄取减低，这是由于血清甲状腺结合球蛋白(TBG)增多所致。至于放射性131I及血清促甲状腺激素(TSH)，并不受雌激素的影响。
7.用药前后及用药时应当检查或监测：
(1)血压。
(2)肝功能。
(3)阴道脱落细胞。
(4)全面体检(每6～12个月1次)，尤其是对子宫内膜的厚度和乳腺的检查。
(5)宫颈刮片检查(每年1次)。
(6)用药前应详细询问病史及全面体检，包括乳腺、盆腔检查及宫颈细胞学检查。
8.长期单纯使用雌激素有增加子宫内膜增生的危险，应加用孕激素拮抗其内膜增殖作用。
不良反应
1.腹部绞痛或胀气、胃纳不佳、恶心、踝及足水肿、乳房胀痛或肿胀及体重增加或减少较常发生，但常在持续用药后可减少发生。
2.少见或罕见的不良反应
(1)乳腺出现小肿块；不规则阴道流血、点滴出血、突破性出血、长期出血不止或闭经；黏稠的白色凝乳状阴道分泌物(继发性念珠菌感染)。
(2)困倦；精神抑郁，严重的或突发的头痛；动作突然失去协调，不自主的动作(舞蹈病)；胸、上腹(胃)、腹股沟或腿痛，尤其是腓肠肌痛，臂或腿无力或麻木；突然言语或发音不清。
(3)尿频或尿痛。
(4)突发的呼吸急促；血压升高。
(5)视力突然下降(眼底出血或血块)；眼结膜或皮肤黄染；皮疹。
3.用药5～10年以上，乳腺癌发病危险略有增加。
4.服药可刺激子宫内膜增生，增加子宫内膜癌的发病危险，每月加用10～12天足量孕激素，即可避免。
用法用量
1.肌内注射：
(1)补充雌激素不足：每次5mg，每4周1次；
(2)前列腺癌：每次30mg，每1～2周1次，按需调整用量；
(3)替代治疗：每次5～10mg，每1～2周1次。平均为每2周5～20mg；
(4)退奶：每次10mg。
2.口服给药：戊酸雌二醇缓释片每天1～2mg，连续20天。戊酸雌二醇片剂用量因人而异。一般剂量为每天1～2mg，饭后随水吞服，连续25～28天。有完整子宫的患者需在服药第15～19天加用孕激素10～14天。停药2周内应有月经样出血数日。可在出血第5天起按同法重复服用。这种方案称为“周期序贯方案”，适用于绝经前妇女及绝经后要求月经来潮的妇女。对绝经后1年以上，不愿有月经的妇女可用“连续联合方案”，即每天同时服雌、孕激素，连续而不间断，初剂量可为戊酸雌二醇片剂每天1mg，需视治疗反应而做必要的调整。
药物相应作用
1.与钙剂合用可增加钙剂的吸收。
2.与三环类抗抑郁药合用时，大量的雌激素可增强抗抑郁药的不良反应，同时降低其应有的效应。3.与卡马西平、苯巴比妥、苯妥英钠、扑米酮、利福平合用时，可减低雌激素的效应，这是由于诱导肝微粒体酶，加快雌激素的代谢所致。
4.与抗凝药合用时，雌激素可降低抗凝药的抗凝效应。故在必须同时用药时，应调整抗凝药用量。
5.与抗高血压药合用时，可减低抗高血压药的作用。
6.与他莫昔芬合用时，可降低他莫昔芬的治疗效果。
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产地国家: 美国
原产地英文商品名:
DELESTROGEN 10MG/ML 5ML/VIAL
原产地英文药品名:
ESTRADIOL VALERATE
中文参考商品译名:
DELESTROGEN 10毫克/毫升 5毫升/瓶
中文参考药品译名:
戊酸雌二醇
生产厂家中文参考译名:
JHP制药有限责任公司
生产厂家英文名:
JHP PHARMACEUTICALS LLC

---------------------------------------------------------------
产地国家: 美国
原产地英文商品名:
DELESTROGEN 20MG/ML 5ML/VIAL
原产地英文药品名:
ESTRADIOL VALERATE
中文参考商品译名:
DELESTROGEN 20毫克/毫升 5毫升/瓶
中文参考药品译名:
戊酸雌二醇
生产厂家中文参考译名:
JHP制药有限责任公司
生产厂家英文名:
JHP PHARMACEUTICALS LLC

---------------------------------------------------------------
产地国家: 美国
原产地英文商品名:
DELESTROGEN 40MG/ML 5ML/VIAL
原产地英文药品名:
ESTRADIOL VALERATE
中文参考商品译名:
DELESTROGEN 40毫克/毫升 5毫升/瓶
中文参考药品译名:
戊酸雌二醇
生产厂家中文参考译名:
JHP制药有限责任公司
生产厂家英文名:
JHP PHARMACEUTICALS LLC