27．环磷酰胺
出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第109页（8766字）
【中文释文】：
〔适应证〕
白血病，尤其是慢性淋巴细胞性白血病与髓性白血病。恶性淋巴瘤。异型球蛋白血症，如浆细胞瘤。瓦尔登斯特伦巨球蛋白血症。恶性实体瘤，尤其是卵巢癌与乳腺癌、支气管小细胞癌、成神经细胞瘤、精原细胞瘤、尤文肉瘤。化疗敏感性肿瘤的术后辅助治疗。
“自身免疫性疾病”，包括类风湿性关节炎、牛皮癣性关节炎、红斑狼疮、硬皮病、重症肌无力、自身免疫溶血性贫血、冷凝集病、肾病综合征、器官移植。
〔禁忌证〕
育龄男女病人在接受治疗期间及其后3个月内必须采取避孕措施。下列情况禁用环磷酰胺：对本药过敏、严重的骨髓抑制、怀孕头3个月。在怀孕后期除非维持生命所必须，才可使用本品。
〔副作用〕
多数人对环磷酰胺有较好耐受性。偶然情况下，尤其是大剂量使用本品时，会出现恶心、呕吐或头痛。给予止吐剂可阻止消化道反应的发生。有时会出现脱发，停药后几周会长出新发。在应用环磷酰胺治疗期间必须定期复查外周血象。白细胞的显着减少多发生在应用大剂量治疗时。必要时应减小剂量或延长给药间期，甚至停药。环磷酰胺引起的白细胞减少很容易逆转。只有在严重的白细胞减少时才有必要输血和应用γ-球蛋白，及时应用抗生素和抗真菌药非常重要，特别是在应用大剂量环磷酰胺化疗时。
应用本品时，如果预先骨髓无损伤，环磷酰胺对血小板与红细胞的生成仅有轻微影响。偶尔会发生膀胱反应，因此需定期检测尿沉渣计数。为预防膀胱炎，在服药时或服药后即刻需大量饮水，并采取措施增加尿液排出。对于用药剂量超过(含)10mg／kg的病人及其他高危病人(在应用环磷酰胺及其类似药物早期即出现膀胱炎者、真骨盆区接受放疗者及泌尿道有损害者)应给予巯乙磺酸纳(Mesna)等药物以保护膀胱。如果缺乏必要的预防措施，发生膀胱炎或血尿时，应立即停止使用环磷酰胺。
在治疗开始时肝、肾功能正常的病人，其肝、肾功能不受损伤。
不能排除对免疫系统的抑制作用，尤其是在重复应用本品时。
性腺可能会受损伤。有可能发生过敏反应，但这种过敏反应无特异性。
〔与其它药物的相互作用〕
环磷酰胺与降糖药同用可增强降血糖作用。环磷酰胺与别嘌呤醇同用时骨髓抑制作用加强。环磷酰胺因降低假胆碱酯酶水平而使琥珀酰胆碱活性增强，有可能引起较长时间呼吸暂停。
〔用法与用量〕
起始治疗：通常采用静脉注射。本品亦可肌肉注射、胸膜腔内注射、腹膜腔内注射，以及淋巴管内注射和鞘内注射。病情缓解后，采用环磷酰胺包衣片口服维持治疗。用药剂量必须个体化，根据病人全身情况及白细胞水平调整用药。
推荐起始治疗剂量为：
1．每天静脉注射3～6mg／kg(200～400mg)。
2．大剂量间歇治疗，10～15mg／kg(500～1000mg)，间隔2～5d。
3．大剂量间歇治疗，20～40mg／kg，间隔10～20d。
环磷酰胺应在上午服用，并应大量饮水。维持治疗剂量为口服50～200mg／d(1～4包衣片)。临床医师可向本公司索取详细资料。
〔注射液的配制〕
为配制环磷酰胺的生理盐水溶液，请分别将100mg环磷酰胺溶于5ml注射用水，200mg本品溶于10ml注射用水，500mg本品溶于25ml注射用水，1g本品溶于50ml注射用水，切勿用生理盐水作溶剂!溶液须现配现用。本品加水后用力振荡0．5～1min后即溶解，如未立即溶解，请静置数分钟至完全溶解。
〔注意事项〕
在开始治疗前，必须排除泌尿道梗阻情况，控制感染及纠正电解质平衡紊乱。
肝肾功能受损的病人在用药期间应仔细观察病情。对严重肾功能衰竭病人应减少环磷酰胺的剂量。
环磷酰胺为可透析性。
服药期间注意口腔保健。
贮存本品不得超过30℃，最好低于25℃。
请将本品置于儿童接触不到的地方!
〔生产厂家〕
德国ASTA Medica AG
(附本品别名：癌得星，环磷氮芥，安道生，Syklofosfamid，Cyolophosphamide，β-518，CTX，Cytoxan，cyclostin)．
【外文释文】：
Indications for use
Leukaemias，especially chronic lymphatic and myeloid leukaemia．Malignant lymphomas．Paraproteinaemias，e．g．plasmacytoma．Waldenstrom’s disease．Malignant solid tumours especially carcinoma of the ovaries or breast，small-cell bronchial carcinoma，neuroblastoma，seminoma，Ewing’s sarcoma．Post-operative adjuvant treatment of chemosensitive tumours．
“Autoimmune diseases”including rheumatoid arthritis(=progressive chronic plyarthritis)，arthropathia psoriatica，lupus erythematosus，sclerodermia，myasthenia gravis，autoimmune haemolytic anaemia，cold agglutination diseases，nephrotic syndrome．Organ transplantations．
Contraindications
Patients of both sexes in the reproductive age should take contraceptives during therapy and for the following 3 months．Endoxan should not be taken in cases of：known hypersensitivity to Cyclophosphamide，severe bone marrow depression，in the first three months of pregnancy，in the second half of pregnancy in cases of vital indication only．
Side effects：
The general and local tolerance of Endoxan is good．Only occasionally，especially with the use of higher doses，have nausea，vomiting or headaches been observed．To prevent nausea and vomiting it is advisable to give an antiemotic．Hairloss sometimes occurs；there is new hair growth after a few weeks．The blood count must be monitored regularly during treatment with Endoxan．A fairly marked fall in the leucocytes mainly occurs with the administration of high doses．If necessary the dosage must be reduced or the interval between treatments increased or in certain circumstances treatment will have to be stopped．Leukopenia after Endoxan is readily reversible．Only in cases of severe leukopenia blood transfusions and the administration of gamma-globulin possibly are indicated．Timely antibiotic or antimycotic protection is important，especially when high doses are given．
Thrombopoiesis and erythropoiesis are only slightly affected provided that there is no preexisting bone-marrow damage．Occasionally reactions involving the bladder are observed． The urinary sediment should therefore be monitored regularly．To prevent cystitis it is recommended that large quantities of fluid should be taken during or immediately after the administration of Endoxan and measures should be taken to increase the urine excretion．With doses of 10 mg／kg or more and in high-risk patients(previous cystitis during earlier treatment with Endoxan or similar drugs，previous irradiation of the small pelvis and in preexisting urinary tract damage)Mesna(Uromitexan)should always be given to protect the bladder．If there is no or only inadequate prophylaxis，and cystitis or blood in the urine occur，the treatment with Endoxan should be discontinued immediately．
Hepatic and renal function is not impaired if it is normal at the start of treatment．
Suppression of the immune response cannot be excluded，especially after the repeated administration of Endoxan．
The function of the gonads may be impaired．Hypersensitivity reactions may occur，butare not typical for Endoxan．
Interactions with other drugs
When antidiabetic drugs are given concomitantly with Endoxan the reduction in the blood sugar level may be potentiated．If Endoxan and allopurinol are given concomitantly there may be an increase in bone-marrow depression．The fall in the pseudocholinesterase level during treatment with Endoxan leads to a potentiation of the action of suxamethonium．Fairly prolonged apnoea is therefore possible．
Administration and dosage
Initial treatment：Generally by intravenous injections．Endoxan-Asta may also be injected i．m．，i．pl．and i．p．as well as intralymphatically and intrathecally．After satisfactory remission has occurred，maintenance therapy with coated tablets is recommended．Dosage must be strictly individual，taking into consideration the general state of the patient and his W．B．C．Initial treatment is recommended with(a)Daily i．v．injections of 3 to 6mg／kg body weight(200-400 mg)or(b)Massive-intermittent therapy-10-15 mg／kg body weight(500-1000mg)，with therapy-free intervals of 2 days or 5 days，or(c)Massive-intermittent therapy-20-40 mg／kg body weight，with therapy-free intervals of 10-20 days．Endoxan should be given in the morning with liberal amounts of liquids，during and immediately after administrations．For continuation or maintenance therapy，50-200 mg／d may be given orally(1-4 ctd．tablets)．For further details see the brochure“Endoxan Basic Scientific Information”which is available to doctors on request．
Preparation of solutions
To prepare the solution of Endoxan in physiological saline，100 mg of Endoxan are dissolved in 5 ml of aqua ad injctabilia(bidist．water)，200 mg in 10ml，500mg in 25ml，1g in 50ml respectively．Do not use physilological saline as a solvent!The solutions should be used as soon as possible after preparation．The substance dissolves readily when the vial is shaken vigorously for 0．5-1 minute after injection of the solvent．If complete dissolution is not achieved immediately，allow the solution to stand for some minutes until it is thoroughly clear．
Store drugs out of children’s reach!
Attention：Before the onset of therapy，all conditions of hampered urinary flow in the efferent urinary passages should be excluded，possible infections have to be cured，and disturbances of the electrolyte balance should be corrected，if necessary．
The patients must be monitored particularly carefully if there is impaired renal or hepatic function．According to investigations available，the dose of Endoxan needs to be reduced in severe cases of renal failure．Endoxan is dialysable．
Careful oral hygiene is important．
Store at a temperature not exceeding 30℃，preferably below 25℃。
Presentation： Coated tablets 50，200，500，1000
Vials of 100mg 10and 50 Vial of 500mg 1
Vials of 200mg 10and 50 Vial of 1g 1
These presentations are not available in all countries．
Manufacturer
ASTA Medica AG
Frankfurt am main
Germany Allemagne Alemania