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雌莫司汀磷酸钠胶囊(Emcyt, Estracyte,estramustine)

2012-11-10 21:28:33 作者：新特药房来源：中国新特药网天津分站浏览次数：365 文字大小：【大】【中】【小】

简介： 【药物名称】 estramustine (Emcyt, Estracyte)中文通用名称：雌莫司汀磷酸钠英文通用名称：Estramustine Phosphate Sodium其它名称：癌腺治、艾去适、雌氮芥磷酸二钠、雌氮芥磷酸钠、雌二醇氮芥、雌二 ...

关键字：雌莫司汀磷酸钠胶囊晚期前列腺癌

【药物名称】 estramustine (Emcyt, Estracyte)
中文通用名称：雌莫司汀磷酸钠
英文通用名称：Estramustine Phosphate Sodium
其它名称：癌腺治、艾去适、雌氮芥磷酸二钠、雌氮芥磷酸钠、雌二醇氮芥、雌二醇氮芥磷酸钠、雌莫司汀、雌莫司汀磷酸二钠、雌甾醇氮芥、雌甾氮芥、磷雌醇氮芥、磷雌醇氮芥钠、磷雌氮芥、磷雌氮芥钠、磷酸雌二醇氮芥、磷酸雌二醇氮芥钠、磷酸雌莫司汀、依立适、Emcyt、Emecyt、Estracyt、Estramustin Phosphate、Estramustine、Estramustine Phosphate、Estramustine Phosphate Disodium、Estramustinum

【临床应用】
主要用于晚期前列腺癌，特别是对激素治疗无效的患者。

【药理】
1．药效学本药以雌二醇17磷酸酯为载体的一种氮芥类烷化剂，具有烷化剂及雌激素的双重作用。可通过类固醇受体特异性地将药物导入前列腺组织，阻止前列腺癌细胞的有丝分裂，裂解已形成的微管，并阻止微管的再形成，同时促使前列腺癌细胞中谷胱甘肽的排空，从而达到破坏癌细胞的目的。由于本药对肿瘤的作用具有专一性，故可提高疗效，减轻不良反应。使用推荐剂量时，本药对骨髓的抑制极轻，甚至没有骨髓抑制作用，可用于长期治疗。
2．药动学本药口服后吸收良好，吸收率约为75%，药物被浓集于前列腺组织中。给药后，本药迅速脱磷氧基成为雌二醇氮芥(口服时，脱磷氧基作用在胃肠道进行)，大部分再被氧化为雌酮氮芥(雌酮氮芥的血浆半衰期为10-12小时)。部分活性代谢产物蓄积在脂肪组织内，经过进一步代谢而消除。代谢产物大部分从胆道排泄，少量从肾脏排泄，能否经乳汁分泌尚不清楚。

【注意事项】
1．禁忌症
(1)对雌二醇或氮芥类药物过敏者。
(2)严重肝脏或心脏疾病患者。
(3)活动性血栓性静脉炎或血栓栓塞性疾病患者。
2．慎用
(1)有水钠潴留者。
(2)糖尿病患者。
(3)冠心病及高血压患者。
(4)消化性溃疡患者。
(5)脑血管疾病患者。
3．药物对妊娠的影响国内尚缺乏孕妇用药的资料。美国药品和食品管理局(FDA)对本药的妊娠安全性分级为D级。
4．药物对哺乳的影响尚不明确。
5．用药前后及用药时应当检查或监测用药期间应定期检查血常规及肝功能。
【不良反应】
可出现暂时性恶心、呕吐、腹泻，少数患者出现白细胞和血小板减少、肝功能损害、皮疹、水肿、咽痛、血压升高及血栓栓塞。男性可出现乳房增大、性欲减退及勃起不良。

【药物相互作用】
·药物-药物相互作用
1．含钙药物(如含钙的抗酸剂)与本药同服，可降低本药血药浓度。
2．使用本药时接种活疫苗(如轮状病毒疫苗)，将增加活疫苗感染的风险。接受免疫抑制化疗的病人不能接种活疫苗。缓解期白血病病人，至少要停止化疗3个月，才允许接种活疫苗。

•药物-食物相互作用
服药时进食奶制品或其它含钙食物，可降低本药血药浓度。

【给药说明】
1．配制注射液时，予8ml稀释液(不可用氯化钠注射液)缓缓注入本药包装瓶内，不能振荡，以防产生泡沫。
2．静脉注射应使用细针缓慢注射(3-5分钟)，如药液漏出血管外，应立即停止注射。本药也可用于静脉滴注(稀释于5%葡萄糖注射液250ml中)，但滴注时间不能超过3小时。
3．本药口服制剂应于饭前1小时或饭后2小时服用。
4．服用本药时，不得同时服用其它含钙药物，也不得进食其它含钙食物。

【用法与用量】
成人
·常规剂量
·口服给药一次200-300mg，一日2次。连服3-4周后仍无效，则应停药；如病情好转，应按原剂量继续服用3-4月。必要时应根据疗程、疗效和不良反应等适当调整剂量。
·静脉注射用于治疗的开始阶段，一日300mg，连用3周。以后改为口服给药，也可继续静脉注射(一次300mg，一周2次)。

【制剂与规格】
雌莫司汀磷酸钠胶囊 (1)100mg。(2)140mg。
贮法：25℃以下密闭贮存。

注射用雌莫司汀磷酸钠(附稀释液) (1)150mg。(2)300mg。
贮法：25℃以下密闭贮存。

Emcyt
Generic Name: estramustine phosphate sodium
Dosage Form: capsule

Emcyt®
estramustine phosphate sodium
capsules
Emcyt Description
Estramustine phosphate sodium, an antineoplastic agent, is an off-white powder readily soluble in water. Emcyt Capsules are white and opaque, each containing estramustine phosphate sodium as the disodium salt monohydrate equivalent to 140 mg estramustine phosphate, for oral administration. Each capsule also contains magnesium stearate, silicon dioxide, sodium lauryl sulfate, and talc. Gelatin capsule shells contain the following pigment: titanium dioxide.

Chemically, estramustine phosphate sodium is estra-1,3,5(10)-triene-3,17-diol(17β)-,3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate), disodium salt, monohydrate. It is also referred to as estradiol 3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate), disodium salt, monohydrate. Estramustine phosphate sodium has an empiric formula of C23H30Cl2NNa2O6P•H2O, a calculated molecular weight of 582.4, and the following structural formula:

Emcyt - Clinical Pharmacology
Estramustine phosphate (Figure 1) is a molecule combining estradiol and nornitrogen mustard by a carbamate link. The molecule is phosphorylated to make it water soluble.

Estramustine phosphate taken orally is readily dephosphorylated during absorption, and the major metabolites in plasma are estramustine (Figure 2), the estrone analog (Figure 3), estradiol, and estrone.

Prolonged treatment with estramustine phosphate produces elevated total plasma concentrations of estradiol that fall within ranges similar to the elevated estradiol levels found in prostatic cancer patients given conventional estradiol therapy. Estrogenic effects, as demonstrated by changes in circulating levels of steroids and pituitary hormones, are similar in patients treated with either estramustine phosphate or conventional estradiol.
The metabolic urinary patterns of the estradiol moiety of estramustine phosphate and estradiol itself are very similar, although the metabolites derived from estramustine phosphate are excreted at a slower rate.

Indications and Usage for Emcyt

Emcyt Capsules are indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

Contraindications

Emcyt Capsules should not be used in patients with any of the following conditions:

1): Known hypersensitivity to either estradiol or to nitrogen mustard.
2): Active thrombophlebitis or thromboembolic disorders, except in those cases where the actual tumor mass is the cause of the thromboembolic phenomenon and the physician feels the benefits of therapy may outweigh the risks.

Warnings

It has been shown that there is an increased risk of thrombosis, including fatal and nonfatal myocardial infarction, in men receiving estrogens for prostatic cancer. Emcyt Capsules should be used with caution in patients with a history of thrombophlebitis, thrombosis, or thromboembolic disorders, especially if they were associated with estrogen therapy. Caution should also be used in patients with cerebral vascular or coronary artery disease.

Glucose Tolerance—Because glucose tolerance may be decreased, diabetic patients should be carefully observed while receiving Emcyt.

Elevated Blood Pressure—Because hypertension may occur, blood pressure should be monitored periodically.

Precautions

General

Fluid Retention. Exacerbation of preexisting or incipient peripheral edema or congestive heart disease has been seen in some patients receiving therapy with Emcyt Capsules. Other conditions which might be influenced by fluid retention, such as epilepsy, migraine, or renal dysfunction, require careful observation.

Emcyt may be poorly metabolized in patients with impaired liver function and should be administered with caution in such patients.

Because Emcyt may influence the metabolism of calcium and phosphorus, it should be used with caution in patients with metabolic bone diseases that are associated with hypercalcemia or in patients with renal insufficiency. Patients with prostate cancer and osteoblastic metastases are at risk for hypocalcemia and should have calcium levels closely monitored.

Gynecomastia and impotence are known estrogenic effects.

Allergic reactions and angioedema at times involving the airway have been reported.

Information for the Patient

Because of the possibility of mutagenic effects, patients should be advised to use contraceptive measures.

Laboratory Tests

Certain endocrine and liver function tests may be affected by estrogen-containing drugs. Emcyt may depress testosterone levels. Abnormalities of hepatic enzymes and of bilirubin have occurred in patients receiving Emcyt. Such tests should be done at appropriate intervals during therapy and repeated after the drug has been withdrawn for two months.

Food/Drug Interaction

Milk, milk products, and calcium-rich foods or drugs may impair the absorption of Emcyt.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term continuous administration of estrogens in certain animal species increases the frequency of carcinomas of the breast and liver. Compounds structurally similar to Emcyt are carcinogenic in mice. Carcinogenic studies of Emcyt have not been conducted in man. Although testing by the Ames method failed to demonstrate mutagenicity for estramustine phosphate sodium, it is known that both estradiol and nitrogen mustard are mutagenic. For this reason and because some patients who had been impotent while on estrogen therapy have regained potency while taking Emcyt, the patient should be advised to use contraceptive measures.

Adverse Reactions

In a randomized, double-blind trial comparing therapy with Emcyt Capsules in 93 patients (11.5 to 15.9 mg/kg/day) or diethylstilbestrol (DES) in 93 patients (3.0 mg/day), the following adverse effects were reported:

	Emcyt n=93	DES n=93
CARDIOVASCULAR-RESPIRATORY
Cardiac Arrest	0	2
Cerebrovascular Accident	2	0
Myocardial Infarction	3	1
Thrombophlebitis	3	7
Pulmonary Emboli	2	5
Congestive Heart Failure	3	2
Edema	19	17
Dyspnea	11	3
Leg Cramps	8	11
Upper Respiratory Discharge	1	1
Hoarseness	1	0
GASTROINTESTINAL
Nausea	15	8
Diarrhea	12	11
Minor Gastrointestinal Upset	11	6
Anorexia	4	3
Flatulence	2	0
Vomiting	1	1
Gastrointestinal Bleeding	1	0
Burning Throat	1	0
Thirst	1	0
INTEGUMENTARY
Rash	1	4
Pruritus	2	2
Dry Skin	2	0
Pigment Changes	0	3
Easy Bruising	3	0
Flushing	1	0
Night Sweats	0	1
Fingertip—Peeling Skin	1	0
Thinning Hair	1	1
BREAST CHANGES
Tenderness	66	64
Enlargement
Mild	60	54
Moderate	10	16
Marked	0	5
MISCELLANEOUS
Lethargy Alone	4	3
Depression	0	2
Emotional Lability	2	0
Insomnia	3	0
Headache	1	1
Anxiety	1	0
Chest Pain	1	1
Hot Flashes	0	1
Pain in Eyes	0	1
Tearing of Eyes	1	1
Tinnitus	0	1
LABORATORY ABNORMALITIES
Hematologic
Leukopenia	4	2
Thrombopenia	1	2
Hepatic
Bilirubin Alone	1	5
Bilirubin and LDH	0	1
Bilirubin and SGOT	2	1
Bilirubin, LDH and SGOT	2	0
LDH and/or SGOT	31	28
Miscellaneous
Hypercalcemia—Transient	0	1

Overdosage

Although there has been no experience with overdosage to date, it is reasonable to expect that such episodes may produce pronounced manifestations of the known adverse reactions. In the event of overdosage, the gastric contents should be evacuated by gastric lavage and symptomatic therapy should be initiated. Hematologic and hepatic parameters should be monitored for at least 6 weeks after overdosage of Emcyt Capsules.

Emcyt Dosage and Administration

The recommended daily dose is 14 mg per kg of body weight (ie, one 140 mg capsule for each 10 kg or 22 lb of body weight), given in 3 or 4 divided doses. Most patients in studies in the United States have been treated at a dosage range of 10 to 16 mg per kg per day.

Patients should be instructed to take Emcyt Capsules at least 1 hour before or 2 hours after meals. Emcyt should be swallowed with water. Milk, milk products, and calcium-rich foods or drugs (such as calcium-containing antacids) must not be taken simultaneously with Emcyt.

Patients should be treated for 30 to 90 days before the physician determines the possible benefits of continued therapy. Therapy should be continued as long as the favorable response lasts. Some patients have been maintained on therapy for more than 3 years at doses ranging from 10 to 16 mg per kg of body weight per day.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1–8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

How is Emcyt Supplied

White opaque capsules, each containing estramustine phosphate sodium as the disodium salt monohydrate equivalent to 140 mg estramustine phosphate—bottle of 100 (NDC 0013-0132-02).

NOTE

Emcyt Capsules should be stored in the refrigerator at 36° to 46°F (2° to 8°C).