【药品名称】
通用名：注射用丝裂霉素
英文名：Mitomycin for Injection
汉语拼音：Zhusheyong Siliemeisu
本品主要成份及其化学名称为：5－氨基－3－氨基甲酰氧甲基－2－甲氧基－2，3－二氢－4，7－吲哚醌骈（1，2）－吡咯烷骈－（9，10）－氮丙啶。
结构式：
分子式：C15H18N4O5
分子量：334.34
【性状】
灰色的冻干粉针剂。
【药理毒理】本品为细胞周期非特异性药物。丝裂霉素对肿瘤细胞的G1期、特别是晚G1期及早S期最敏感，在组织中经酶活化后，它的作用似双功能或三功能烷化剂，可与DNA发生交叉联结，抑制DNA合成，对RNA及蛋白合成也有一定的抑制作用。
大鼠皮下注射200?g/kg，在60日以内引起死亡，组织学上在肝脏、肾脏及骨髓发现有郁血现象。
妊娠10～14日的小鼠，单次静脉注射给药2.0~10.0mg/kg，发现生存胎仔有明显的发育障碍。7.5mg/kg的给药群，有腭裂、尾短小、小颌症、欠趾症等畸形。
【药代动力学】本品主要在肝脏中生物转化，不能通过血脑屏障。T1/2分别为5～10分钟及50分钟，主要通过肾脏排泄。
【适应症】主要适用于胃癌、肺癌、乳腺癌，也适用于肝癌、胰腺癌、结直肠癌、食管癌、卵巢癌及癌性腔内积液。
【用法用量】
1. 静脉注射：每次6～8mg，以氯化钠注射液溶解后静脉注射，每周一次。也可10～20mg一次，每6～8周重复治疗。
2. 动脉注射：剂量与静脉注射同。
3. 腔内注射：每次6～8mg。
4. 联合化疗：FAM（氟尿嘧啶、阿霉素、丝裂霉素）主要用于胃肠道肿瘤。
【不良反应】
1. 骨髓抑制是最严重的毒性，可致白细胞及血小板减少，白细胞减少常发生于用药后28～42日，一般在42～56日恢复。
2. 恶心、呕吐发生于给药后1～2小时，呕吐在3～4内停止，而恶心可持续2～3日。
3. 对局部组织有较强的刺激性，若药液漏出血管外，可引起局部疼痛、坏死和溃疡。
4. 少见的副作用有间质性肺炎、不可逆的肾功能衰竭等。
5. 心脏：本品与阿霉素同时应用可增加心脏毒性，建议阿霉素总量限制在按体表面积450mg/m2以下。
【禁忌】
1. 水痘或带状疱疹患者禁用。
2. 用药期间禁用活病毒疫苗接种和避免口服脊髓灰质炎疫苗。
3. 孕妇及哺乳期妇女禁用。
【注意事项】
丝裂霉素应在有经验的肿瘤化疗医师指导下使用。
1. 用药期间应密切随访血常规及血小板、血尿素氮、肌酐。
2. 在应用丝裂霉素后数月仍应随访血常规及肾功能，特别是接受总量大于60mg的患者，易发生溶血性贫血。
3. 长期应用抑制卵巢及睾丸功能，造成闭经和精子缺乏。
4. 本品局部刺激严重，若药液漏出血管外，可致局部红肿疼痛，以致坏死溃疡。
5. 丝裂霉素一般经静脉给药，也可经动脉注射或腔内注射给药，但不可作肌肉或皮下注射。
6. 应避免注射于静脉外，如静脉注射时有烧灼感或刺痛，应立即停止注射。
7. 由于丝裂霉素有延迟性及累积性骨髓抑制，一般较大剂量应用时两疗程之间间隔应超过6周。
8. 静注时药液漏至血管外应立即停止注射，以1％普鲁卡因注射液局封。
【孕妇及哺乳期妇女用药】本品在动物实验中有致癌及致畸性，在妊娠初期的3个月应避免应用本品，哺乳期不应用丝裂霉素。
【儿童用药】尚不明确。
【老年患者用药】老年患者常有肾功能损害，丝裂霉素应慎用。
【药物相互作用】丝裂霉素与阿霉素同时应用可增加心脏毒性，建议阿霉素的总量限制在按体表面积450mg/m2以下。
【药物过量】尚不明确。
【规格】（1）2mg （2）10mg
【有效期】
【贮藏】遮光，密闭保存。

MUTAMYCIN - mitomycin injection, powder, for solution 
E.R. Squibb & Sons, L.L.C.

Each vial contains:
 Mitomycin .........................  5 mg  20 mg
 Mannitol ..........................  10 mg  40 mg

WARNING

MUTAMYCIN® (also known as mitomycin and/or mitomycin-C) is an antibiotic isolated from the broth of Streptomyces caespitosus which has been shown to have antitumor activity. The compound is heat stable, has a high melting point, and is freely soluble in organic solvents.

ACTION

MUTAMYCIN selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of MUTAMYCIN-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.

In humans, MUTAMYCIN is rapidly cleared from the serum after intravenous administration. Time required to reduce the serum concentration by 50% after a 30 mg bolus injection is 17 minutes. After injection of 30 mg, 20 mg, or 10 mg I.V., the maximal serum concentrations were 2.4 µg/mL, 1.7 µg/mL, and 0.52 µg/mL, respectively. Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other tissues as well. The rate of clearance is inversely proportional to the maximal serum concentration because, it is thought, of saturation of the degradative pathways.

Approximately 10% of a dose of MUTAMYCIN is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases with increasing dose. In children, excretion of intravenously administered MUTAMYCIN is similar.

Animal Toxicology

MUTAMYCIN has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical dose in man, it produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice.

INDICATIONS

MUTAMYCIN is not recommended as single-agent, primary therapy. It has been shown to be useful in the therapy of disseminated adenocarcinoma of the stomach or pancreas in proven combinations with other approved chemotherapeutic agents and as palliative treatment when other modalities have failed. MUTAMYCIN is not recommended to replace appropriate surgery and/or radiotherapy.

CONTRAINDICATIONS

MUTAMYCIN (mitomycin for injection, USP) is contraindicated in patients who have demonstrated a hypersensitive or idiosyncratic reaction to it in the past.

MUTAMYCIN is contraindicated in patients with thrombocytopenia, coagulation disorder, or an increase in bleeding tendency due to other causes.

WARNINGS

Patients being treated with MUTAMYCIN must be observed carefully and frequently during and after therapy.

The use of MUTAMYCIN results in a high incidence of bone marrow suppression, particularly thrombocytopenia and leukopenia. Therefore, the following studies should be obtained repeatedly during therapy and for at least eight weeks following therapy: platelet count, white blood cell count, differential, and hemoglobin. The occurrence of a platelet count below 100,000/mm3 or a WBC below 4,000/mm3 or a progressive decline in either is an indication to withhold further therapy until blood counts have recovered above these levels.

Patients should be advised of the potential toxicity of this drug, particularly bone marrow suppression. Deaths have been reported due to septicemia as a result of leukopenia due to the drug.

Patients receiving MUTAMYCIN should be observed for evidence of renal toxicity. MUTAMYCIN should not be given to patients with a serum creatinine greater than 1.7 mg percent.

Usage in Pregnancy

Safe use of MUTAMYCIN in pregnant women has not been established. Teratological changes have been noted in animal studies. The effect of MUTAMYCIN on fertility is unknown.

PRECAUTIONS

Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received MUTAMYCIN. The onset of this acute respiratory distress occurred within minutes to hours after the vinca alkaloid injection. The total number of doses for each drug has varied considerably. Bronchodilators, steroids and/or oxygen have produced symptomatic relief.

A few cases of adult respiratory distress syndrome have been reported in patients receiving MUTAMYCIN in combination with other chemotherapy and maintained at FIO2 concentrations greater than 50% perioperatively. Therefore, caution should be exercised using only enough oxygen to provide adequate arterial saturation since oxygen itself is toxic to the lungs. Careful attention should be paid to fluid balance and overhydration should be avoided.

Bladder fibrosis/contraction has been reported with intravesical administration (not an approved route of administration), which in rare cases has required cystectomy.

Nursing Mothers

It is not known if mitomycin 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 from mitomycin, it is recommended that nursing be discontinued when receiving mitomycin therapy.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Insufficient data from clinical studies of MUTAMYCIN are available for patients 65 years of age and older to determine whether they respond differently than younger patients. Postmarketing surveillance suggests that elderly patients may be more susceptible than younger patients to injection site reactions (see ADVERSE REACTIONS: Integument and Mucous Membrane Toxicity) and hypersensitivity reactions. In general, caution should be exercised when prescribing to elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

Bone Marrow Toxicity

This was the most common and most serious toxicity, occurring in 605 of 937 patients (64.4%). Thrombocytopenia and/or leukopenia may occur anytime within 8 weeks after onset of therapy with an average time of 4 weeks. Recovery after cessation of therapy was within 10 weeks. About 25% of the leukopenic or thrombocytopenic episodes did not recover. MUTAMYCIN produces cumulative myelosuppression.

Integument and Mucous Membrane Toxicity

This has occurred in approximately 4% of patients treated with MUTAMYCIN. Cellulitis at the injection site has been reported and is occasionally severe. Stomatitis and alopecia also occur frequently. Rashes are rarely reported. The most important dermatological problem with this drug, however, is the necrosis and consequent sloughing of tissue which results if the drug is extravasated during injection. Extravasation may occur with or without an accompanying stinging or burning sensation and even if there is adequate blood return when the injection needle is aspirated. There have been reports of delayed erythema and/or ulceration occurring either at or distant from the injection site, weeks to months after MUTAMYCIN, even when no obvious evidence of extravasation was observed during administration. Skin grafting has been required in some of the cases. Elderly patients may be more susceptible than younger patients to injection site reactions (see PRECAUTIONS: Geriatric Use).

Renal Toxicity

2% of 1,281 patients demonstrated a statistically significant rise in creatinine. There appeared to be no correlation between total dose administered or duration of therapy and the degree of renal impairment.

Pulmonary Toxicity

This has occurred infrequently but can be severe and may be life threatening. Dyspnea with a nonproductive cough and radiographic evidence of pulmonary infiltrates may be indicative of MUTAMYCIN-induced pulmonary toxicity. If other etiologies are eliminated, MUTAMYCIN therapy should be discontinued. Steroids have been employed as treatment of this toxicity, but the therapeutic value has not been determined. A few cases of adult respiratory distress syndrome have been reported in patients receiving MUTAMYCIN in combination with other chemotherapy and maintained at FIO2 concentrations greater than 50% perioperatively.

Hemolytic Uremic Syndrome (HUS)

This serious complication of chemotherapy, consisting primarily of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (≤100,000/mm3), and irreversible renal failure (serum creatinine ≥1.6 mg/dL) has been reported in patients receiving systemic MUTAMYCIN. Microangiopathic hemolysis with fragmented red blood cells on peripheral blood smears has occurred in 98% of patients with the syndrome. Other less frequent complications of the syndrome may include pulmonary edema (65%), neurologic abnormalities (16%), and hypertension. Exacerbation of the symptoms associated with HUS has been reported in some patients receiving blood product transfusions. A high mortality rate (52%) has been associated with this syndrome.

The syndrome may occur at any time during systemic therapy with MUTAMYCIN (mitomycin for injection, USP) as a single agent or in combination with other cytotoxic drugs. Less frequently, HUS has also been reported in patients receiving combinations of cytotoxic drugs not including MUTAMYCIN. Of 83 patients studied, 72 developed the syndrome at total doses exceeding 60 mg of MUTAMYCIN. Consequently, patients receiving ≥60 mg of MUTAMYCIN should be monitored closely for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function.

The incidence of the syndrome has not been defined.

Therapy for the syndrome is investigational.

Cardiac Toxicity

Congestive heart failure, often treated effectively with diuretics and cardiac glycosides, has rarely been reported. Almost all patients who experienced this side effect had received prior doxorubicin therapy.

Acute Side Effects Due to MUTAMYCIN were fever, anorexia, nausea, and vomiting. They occurred in about 14% of 1,281 patients.

Other

Headache, blurring of vision, confusion, drowsiness, syncope, fatigue, edema, thrombophlebitis, hematemesis, diarrhea, and pain. These did not appear to be dose related and were not unequivocally drug related. They may have been due to the primary or metastatic disease processes. Malaise and asthenia have been reported as part of postmarketing surveillance. Bladder fibrosis/contraction has been reported with intravesical administration (see PRECAUTIONS).

DOSAGE AND ADMINISTRATION

MUTAMYCIN should be given intravenously only, using care to avoid extravasation of the compound. If extravasation occurs, cellulitis, ulceration, and slough may result.

Each vial contains either mitomycin 5 mg and mannitol 10 mg, mitomycin 20 mg and mannitol 40 mg, or mitomycin 40 mg and mannitol 80 mg. To administer, add Sterile Water for Injection, 10 mL, 40 mL, or 80 mL respectively. Shake to dissolve. If product does not dissolve immediately, allow to stand at room temperature until solution is obtained.

After full hematological recovery (see guide to dosage adjustment) from any previous chemotherapy, the following dosage schedule may be used at 6 to 8 week intervals:

      20 mg/m2 intravenously as a single dose via a functioning intravenous catheter.

Because of cumulative myelosuppression, patients should be fully reevaluated after each course of MUTAMYCIN, and the dose reduced if the patient has experienced any toxicities. Doses greater than 20 mg/m2 have not been shown to be more effective, and are more toxic than lower doses.

The following schedule is suggested as a guide to dosage adjustment:

Nadir After Prior Dose
Leukocytes/mm3	Platelets/mm3	Percentage of Prior Dose to be Given
>4000	>100,000	100%
3000-3999	75,000-99,999	100%
2000-2999	25,000-74,999	70%
<2000	<25,000	50%

No repeat dosage should be given until leukocyte count has returned to 4000/mm3 and a platelet count to 100,000/mm3.

When MUTAMYCIN is used in combination with other myelosuppressive agents, the doses should be adjusted accordingly. If the disease continues to progress after two courses of MUTAMYCIN, the drug should be stopped since chances of response are minimal.

STABILITY

1. Unreconstituted MUTAMYCIN stored at room temperature is stable for the lot life indicated on the package. Avoid excessive heat (over 40° C, 104° F).
2. Reconstituted with Sterile Water for Injection to a concentration of 0.5 mg per mL, MUTAMYCIN is stable for 14 days refrigerated or 7 days at room temperature.
3. Diluted in various I.V. fluids at room temperature, to a concentration of 20 to 40 micrograms per mL:

   I.V. Fluid	Stability
   5% Dextrose Injection	3 hours
   0.9% Sodium Chloride Injection	12 hours
   Sodium Lactate Injection	24 hours

4. The combination of MUTAMYCIN (5 mg to 15 mg) and heparin (1,000 units to 10,000 units) in 30 mL of 0.9% Sodium Chloride Injection is stable for 48 hours at room temperature.

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 SUPPLIED

MUTAMYCIN® (mitomycin for injection, USP)

      NDC 0015-3001-20—Each vial contains 5 mg mitomycin.

      NDC 0015-3002-20—Each vial contains 20 mg mitomycin.

      NDC 0015-3059-20—Each vial contains 40 mg mitomycin.

注册证号 国药准字J20100139
原注册证号 H20090868
产品名称（中文） 注射用丝裂霉素
产品名称（英文） Mitomycin for Injection
商品名（中文） 
商品名（英文） 
剂型（中文） 注射剂
规格（中文） 10mg
注册证号备注 
包装规格（中文） 每盒1瓶；每盒5瓶
生产厂商（中文） 协和发酵麒麟株式会社 富士工厂
生产厂商（英文） Kyowa Hakko Kirin Co.,Ltd. Fuji Plant
厂商地址（中文） 
厂商地址（英文） 1188 Shimotogari,Nagaizumi-cho,Sunto-gun,Shizuoka,Japan
厂商国家（中文） 日本
厂商国家（英文） Japan
分包装批准文号 国药准字J20100139
发证日期 2010-10-12
有效期截止日 
分包装企业名称 麒麟鲲鹏（中国）生物药业有限公司
分包装企业地址 上海市浦东新区龙东大道970号
分包装文号批准日期 2010-10-12
分包装文号有效期截止日 2014-01-23
产品类别 化学药品
药品本位码 86979089002086
药品本位码备注 
公司名称（中文） 协和发酵麒麟株式会社
公司名称（英文） Kyowa Hakko Kirin Co.,Ltd.
地址（中文） 
地址（英文） 1-6-1 Ohtemachi,Chiyoda-ku,Tokyo,Japan
国家（中文） 日本
国家（英文） Japan