警告：此药是一种非常有效的抗癌药物，造成严重的，有时是致命的，严重的副作用包括恶心 ， 呕吐 ， 腹泻 ，肾脏问题，肝脏疾病，或血液的问题。 只有医生遇到这种药物应订明，它应该只考虑在办公室，诊所或医院设置了实验室和/或生命支持设备。

用途：链是用来治疗某些类型的癌症 （例如，癌症胰腺）

如何使用：遵守所有的指示妥善处理，使用和混合流体的正确四。.如果您有任何问题就使用这种药物，咨询您的药剂师。喝大量的液体，而您使用的是这种药物，除非另有指示由您的医生。 .不要让这种药物接触到你的皮肤，它可能损害健康细胞。如果皮肤接触的情况下，清洗受影响的地区立即用肥皂及水彻底。让这个药物的静脉（四）严格按照医生的指示。 剂量是根据您的健康状况和应对治疗。 不超过最大推荐剂量。咨询您的医生或药剂师的细节。使用前，请检查该产品直观的颗粒或变色（解决方案应该会出现苍白的黄金色） 。如果存在，请不要使用液体。了解如何存储和丢弃的针头和医疗用品的安全。
 
不良反应：恶心，呕吐，腹泻，或疼痛/发红/燃烧和肿胀在注射部位可能会发生。 如果这些影响仍然存在或恶化，通知你的医生迅速。 请告知您的医生立即如果上述任何严重的副作用发生：改变尿量，不同寻常的瘀伤或出血，持续喉咙痛或发烧，发冷，不寻常的弱点。请告知您的医生立即如果这些不太可能，但严重的副作用发生：黄眼睛或皮肤，深色尿，精神/情绪变化，腹痛，头晕或异常疲弱，快速脉冲和出汗，增加口渴，视力模糊，混乱。如果您发现其他影响没有在上面列出，请与您的医生或药剂师。

注意事项：请告知您的医生您的病史，尤其是：肾脏问题，肝脏疾病，糖尿病， 放射治疗 ，任何过敏。由于此药物可降低你的免疫系统功能，没有预防接种/疫苗同意的情况下，你的医生，并避免接触的人谁最近收到活疫苗（如口服脊髓灰质炎疫苗） 。使用慎重利器诸如安全剃须刀或钉刀具和避免活动可能增加的机会，得到削减，撞伤，或受伤。这种药物被建议不用于在怀孕 。 向你的医生更多的细节，并讨论可靠形式的控制生育 。 目前尚不清楚这是否药物传递到乳腺癌牛奶。由于潜在风险的婴儿，母乳喂养而使用这种药物，不建议。 向你的医生在母乳喂养。

药物相互作用：请告知您的医生的所有处方药和非处方药你可以使用，特别是：其他癌症的化疗药物（如阿霉素） ，苯妥英钠，非甾体抗炎药（如布洛芬，萘普生） ，氨基糖甙类抗生素（如庆大霉素，妥布霉素） ，两性霉素，环孢素A 。不启动或停止任何药物没有医生或药剂师的批准。

过量：如果过量怀疑，请联络您当地中毒控制中心或急诊室立即。.美国居民可致电美国国家毒物热线1-800-222-1222 。加拿大居民应要求当地中毒控制中心直接联系。过量症状可能包括：改变尿量，深色尿液，眼睛或皮肤变黄。

注：实验室和/或医学检查（例如，血球计数，肝/肾功能试验）将进行经常监测的副作用和应对治疗。保留所有预定医疗任用。

错过剂量：如果你错过的剂量，请与您的医生立即建立一个新的给药时间表。

存储：存储的小瓶在冰箱之间36和46华氏度（ 2至8摄氏度）远离光线和湿度。 .混合后的正确四液，解决了四是稳定的48小时在室温下（ 59和86华氏度或15和30摄氏度）或96小时内冷藏。 丢弃任何未使用部分的小瓶（县） 。

其他名称：链氮霉素 链料霉素
主要成分：
性状：粉针剂,注射剂。
功能主治：主要用于转移性胰岛细胞肿瘤，对功能性和非功能性细胞癌变均有作用。
用法及用量：每体表面积平方米为0.5ｇ，每日１次，连用５日，６周为１疗程；或者每体表面积平方米为１ｇ，每周１次，连用２周。如病人没明显疗效和毒性，可逐步加量，但一次量小于每体表面积平方米为1.5ｇ。
不良反应和注意：氮血症、低磷酸盐血症、无尿、糖尿、肾小管性酸中毒及胃肠道反应。少数病人有肝毒性，罕见有严重血球和血小板数减少。给药前，给药期间，给药后４周应连续进行尿分析、血尿氮、血浆肌酐、血清电解质和肌酸酐清除率的测定以监测肝功能。
规格：粉针剂：１g／支。注射剂：0.2g／支。
生产厂家：
是否医保用药：非医保
是否非处方药：处方

【原产地英文商品名】ZANOSAR-1gm/Vial
【原产地英文药品名】STREPTOZOCIN
【中文参考商品译名】
注：以下产品不同的规格和不同的价格，购买时请用电话咨询为准
·链佐星-1克/瓶
·链佐星-1克无菌粉末/瓶
【生产厂家中文参考译名】法玛西亚-普强公司
【生产厂家英文名】Pharmacia & Upjohn Company

WARNING

ZANOSAR should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.

A patient need not be hospitalized but should have access to a facility with laboratory and supportive resources sufficient to monitor drug tolerance and to protect and maintain a patient compromised by drug toxicity. Renal toxicity is dose-related and cumulative and may be severe or fatal. Other major toxicities are nausea and vomiting which may be severe and at times treatment-limiting. In addition, liver dysfunction, diarrhea, and hematological changes have been observed in some patients. Streptozocin is mutagenic. When administered parenterally, it has been found to be tumorigenic or carcinogenic in some rodents.

The physician must judge the possible benefit to the patient against the known toxic effects of this drug in considering the advisability of therapy with ZANOSAR. The physician should be familiar with the following text before making a judgment and beginning treatment.

DRUG DESCRIPTION
Each vial of ZANOSAR contains 1 g of the active ingredient streptozocin 2 -deoxy - 2 -[[(methylnitrosoamino)carbonyl]amino] - α(and β) - D - glucopyranose and 220 mg citric acid anhydrous. ZANOSAR is available as a sterile, pale yellow, freeze-dried preparation for intravenous administration. The pH was adjusted with sodium hydroxide. When reconstituted as directed, the pH of the solution will be between 3.5 and 4.5. Streptozocin is a synthetic antineoplastic agent that is chemically related to other nitrosoureas used in cancer chemotherapy. Streptozocin is an ivory-colored crystalline powder with a molecular weight of 265.2. It is very soluble in water or physiological saline and is soluble in alcohol. The structural formula is represented below:
 
INDICATIONS
ZANOSAR is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Responses have been obtained with both functional and nonfunctional carcinomas. Because of its inherent renal toxicity, therapy with this drug should be limited to patients with symptomatic or progressive metastatic disease.

DOSAGE AND ADMINISTRATION
ZANOSAR should be administered intravenously by rapid injection or short/prolonged infusion. It is not active orally. Although it has been administered intraarterially, this is not recommended pending further evaluation of the possibility that adverse renal effects may be evoked more rapidly by this route of administration.

Two different dosage schedules have been employed successfully with ZANOSAR.

Daily Schedule - The recommended dose for daily intravenous administration is 500 mg/m2 of body surface area for five consecutive days every six weeks until maximum benefit or until treatment-limiting toxicity is observed. Dose escalation on this schedule is not recommended.

Weekly Schedule - The recommended initial dose for weekly intravenous administration is 1000 mg/m2 of body surface area at weekly intervals for the first two courses (weeks). In subsequent courses, drug doses may be escalated in patients who have not achieved a therapeutic response and who have not experienced significant toxicity with the previous course of treatment. However, A SINGLE DOSE OF 1500 mg/m2 BODY SURFACE AREA SHOULD NOT BE EXCEEDED as a greater dose may cause azotemia. When administered on this schedule, the median time to onset of response is about 17 days and the median time to maximum response is about 35 days. The median total dose to onset of response is about 2000 mg/m2 body surface area and the median total dose to maximum response is about 4000 mg/m2 body surface area.

The ideal duration of maintenance therapy with ZANOSAR has not yet been clearly established for either of the above schedules.

For patients with functional tumors, serial monitoring of fasting insulin levels allows a determination of biochemical response to therapy. For patients with either functional or nonfunctional tumors, response to therapy can be determined by measurable reductions of tumor size (reduction of organomegaly, masses, or lymph nodes).

Reconstitute ZANOSAR with 9.5 mL of Dextrose Injection USP, or 0.9% Sodium Chloride Injection USP. The resulting pale-gold solution will contain 100 mg of streptozocin and 22 mg of citric acid per mL. Where more dilute infusion solutions are desirable, further dilution in the above vehicles is recommended. The total storage time for streptozocin after it has been placed in solution should not exceed 12 hours. This product contains no preservatives and is not intended as a multiple-dose vial.

Caution in the handling and preparation of the powder and solution should be exercised, and the use of gloves is recommended. If the sterile powder of ZANOSAR or a solution prepared from ZANOSAR contacts the skin or mucosae, immedi-ately wash the affected area with soap and water.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED
ZANOSAR is supplied in 1 gram vials (NDC 0009-0844-01). Unopened vials of ZANOSAR should be stored at refrigeration temperatures (2° to 8°C) and protected from light (preferably stored in carton).

REFERENCES

1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs, NIH Publication No. 83-2621. For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402.

2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA. 1985; 2.53(11):1590-1592.

3. National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.

4. Clinical Oncological Society of Australia, Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia, 1983; 1:426-428.

5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA - A Cancer Journal for Clinicians, 1983; (Sept/Oct) 258-263.

6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. AM J. Hosp Pharm, 1990; 47:1033-1049.

7. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines), Am J Health-Syst Pharm, 1996; 53:1669-1685.

Renal: See WARNINGS.

Gastrointestinal: Most patients treated with ZANOSAR have experienced severe nausea and vomiting, occasionally requiring discontinuation of drug therapy. Some patients experienced diarrhea. A number of patients have experienced hepatic toxicity, as characterized by elevated liver enzyme (SGOT and LDH) levels and hypoalbuminemia.

Hematological: Hematological toxicity has been rare, most often involving mild decreases in hematocrit values. However, fatal hematological toxicity with substantial reductions in leukocyte and platelet count has been observed.

Metabolic: Mild to moderate abnormalities of glucose tolerance have been noted in some patients treated with ZANOSAR. These have generally been reversible, but insulin shock with hypoglycemia has been observed.

Genitourinary: Two cases of nephrogenic diabetes insipidus following therapy with ZANOSAR have been reported. One had spontaneous recovery and the second responded to indomethacin.

Post-marketing experience: Spontaneous reports have been received of local inflammation (i.e., edema, erythema, burning, tenderness) following extravasation of the product. In most cases, these events resolved the same day or within a few days.

DRUG INTERACTIONS
ZANOSAR may demonstrate additive toxicity when used in combination with other cytotoxic drugs. Streptozocin has been reported to prolong the elimination half-life of doxorubicin and may lead to severe bone marrow suppression; a reduction of the doxorubicin dosage should be considered in patients receiving ZANOSAR concurrently. The concurrent use of streptozocin and phenytoin has been reported in one case to result in reduced streptozocin cytotoxicity.

Renal Toxicity
Many patients treated with ZANOSAR have experienced renal toxicity, as evidenced by azotemia, anuria, hypophosphatemia, glycosuria and renal tubular acidosis.

Such toxicity is dose-related and cumulative and may be severe or fatal.

Renal function must be monitored before and after each course of therapy. Serial urinalysis, blood urea nitrogen, plasma creatinine, serum electrolytes and creatinine clearance should be obtained prior to, at least weekly during, and for four weeks after drug administration. Serial urinalysis is particularly important for the early detection of proteinuria and should be quantitated with a 24 hour collection when proteinuria is detected. Mild proteinuria is one of the first signs of renal toxicity and may herald further deterioration of renal function. Reduction of the dose of ZANOSAR or discontinuation of treatment is suggested in the presence of significant renal toxicity. Adequate hydration may help reduce the risk of nephrotoxicity to renal tubular epithelium by decreasing renal and urinary concentration of the drug and its metabolites.

Use of ZANOSAR in patients with preexisting renal disease requires a judgment by the physician of potential benefit as opposed to the known risk of serious renal damage.

This drug should not be used in combination with or concomitantly with other potential nephrotoxins.

When exposed dermally, some rats developed benign tumors at the site of application of streptozocin. Consequently, streptozocin may pose a carcinogenic hazard following topical exposure if not properly handled (see DOSAGE AND ADMINISTRATION).

See additional warnings at the beginning of this insert.

PRECAUTIONS
Injection-Site Reactions
ZANOSAR is irritating to tissues. Extravasation may cause severe tissue lesions and necrosis.

Laboratory Tests
Patients who are treated with ZANOSAR must be monitored closely, particularly for evidence of renal, hepatic, and hematopoietic toxicity. Renal function tests are described in the WARNINGS section. Patients should also be monitored closely for evidence of hematopoietic and hepatic toxicities. Complete blood counts and liver function tests should be done at least weekly. Dosage adjustments or discontinuance of the drug may be indicated, depending upon the degree of toxicity noted.

Mutagenesis, Carcinogenesis, Impairment of Fertility
Streptozocin is mutagenic in bacteria, plants, and mammalian cells. When administered parenterally, it has been shown to induce renal tumors in rats and to induce liver tumors and other tumors in hamsters. Stomach and pancreatic tumors were observed in rats treated orally with streptozocin. Streptozocin has also been shown to be carcinogenic in mice.

Streptozocin adversely affected fertility when administered to male and female rats.

Pregnancy Category D
Reproduction studies revealed that streptozocin is teratogenic in the rat and has abortifacient effects in rabbits. When administered intravenously to pregnant monkeys, it appears rapidly in the fetal circulation. There are no studies in pregnant women. ZANOSAR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers
It is not known whether streptozocin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, nursing should be discontinued in patients receiving ZANOSAR.

Geriatric Use
Clinical studies of streptozocin did not include sufficient numbers of patients aged 65 years and older to determine whether there was a difference in either efficacy or toxicity as compared to younger patients. Other reported clinical experience has not identified differences in efficacy or safety between the elderly and younger patient populations. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.