英文药名：Lysodren（Mitotane Tablets） 中文药名：米托坦片、解腺瘤片、解腺瘤、密妥坦 给药说明 米托坦（双氯苯二氯乙烷0，p'-DDD）为杀虫剂滴滴涕（DDT）一类化合物。它能选择性地使肾上腺皮质束状带及网状带细胞萎缩、坏死，但不影响球状带，故醛固酮分泌不受影响。用药后血、尿中氢化可的松及其代谢物迅速减少。主要用于不可切除的皮质癌、切除后复发癌以及皮质癌术后辅助治疗。可有厌食、恶心、腹泻、皮疹、嗜眠、头痛、眩晕、乏力、中枢抑制及运动失调等反应 分类名称 一级分类：抗肿瘤药物 二级分类：激素类 三级分类：    药品英文名 Mitotane   药品别名 氯苯二氯乙烷、邻对滴滴涕、二氯苯二氯乙烷、解腺瘤、Lysodren、O,P-DDD   药物剂型 1.胶囊：0.5g，1g；2.片剂：0.5g。   药理作用 O，P′-DDD为细胞抑制剂和杀虫剂。Haller等于1945年合成DDD(滴滴滴，二氯二苯二氯乙烷，氯苯二氯乙烷)，是一种和DDT(滴滴涕，二氯二苯三氯乙烷)同类化合物。20世纪40年代末Nelson和Woodard在用DDD喂饲狗的实验中发现此药可导致严重的肾上腺皮质萎缩，但在早期临床试验中未发现它对人的肾上腺有作用。Gueto和Brown在1958年的研究中发现工业用DDD是由二种同分异构体P，P-DDD(对，对滴滴滴)和O，P-DDD(邻对滴滴滴)组成的混合物，实验发现O，P′-DDD对肾上腺皮质有毒性作用，而DDD的主要成分P，P′-DDD则无此作用。Bergenstal等1960年首先报道了O，P′-DDD治疗转移性肾上腺皮质癌的临床试验。对狗的研究发现O，P′-DDD能选择性地对肾上腺皮质细胞的线粒体产生直接细胞毒作用，使皮质束状带及网状带细胞萎缩、坏死，但不影响球状带，所以醛固酮分泌不受影响；对ACTH分泌没有影响，但可阻断ACTH对肾上腺皮质的刺激作用，可加速肾上腺皮质激素在周围组织中的灭活。 用药后尿中氢化可的松及代谢产物迅速减少。至于对O，P′-DDD选择性作用于肾上腺皮质细胞的机制还不清楚。在动物实验中，O，P′-DDD可使狗肾上腺的皮质肿瘤伴功能亢进的尿中增高的皮质激素降到很低的水平，并可使肿瘤明显缩小。   药动学 口服后给药量的40%～60%由胃肠道吸收。一次给药3～4h后血中药物浓度达高峰。给药剂量10%～25%以可溶于水的代谢物随尿排出，60%以原形从粪便中排出。分布广泛，主要贮存于脂肪组织中，停药10周后仍可在血中测出药物。   适应证 对不能手术切除或有远处转移的肾上腺皮质癌有效。客观有效率为34%～61%，中位缓解期6～7个月。对功能性肾上腺皮质癌，可使皮质功能亢进症状缓解，肿瘤缩小，延长生命。此外，也可用于肾上腺皮质增生或肿瘤所致的库欣综合征（皮质醇增多症)。   禁忌证 1.对本品过敏者禁用。 2.孕妇、哺乳妇女禁用。   注意事项 1.肝病患者慎用。 2.毒副作用严重者出现肾上腺皮质萎缩、坏死，用药期间为避免肾上腺皮质功能不足，可适当补充糖皮质激素。   不良反应 1.主要为胃肠道反应，发生率79%，其中厌食24%，恶心39%，呕吐37%，腹泻31%。 2.神经肌肉毒性49%，其中中枢神经抑制(嗜睡等)32%，头晕15%，头痛5%，精神错乱3%，肌肉震颤3%，疲乏12%。 3.皮肤病变15%，包括皮疹12%。 4.眼毒性3%，包括视物模糊、复视、晶状体混浊、视网膜病变等。 5.泌尿生殖系统毒性2%，包括血尿、蛋白尿、出血性膀胱炎等。 6.心血管毒性2%，可有高血压、直立性低血压、面部潮红等。 7.严重时肾上腺皮质萎缩、坏死。 8.其他8%，高热、全身疼痛等。   用法用量 1.每天6～15mg/kg，分3～4次口服，从小剂量开始逐渐增大到最大耐受量，其变化范围每天2～16g，一般每天8～10g。2.如出现不良反应，则减少剂量，直到确定最大耐受量，治疗应持续到出现临床效果，有效后改为每天2～4g，4～8周为1个疗程。如服用最大耐受量3个月仍无效，则停止治疗。治疗应在熟悉此药的医师指导下进行。   药物相应作用 本品与华法林之间存在相互作用。   专家点评 本品口服方便，适用于肾上腺皮质癌的治疗。中性缓解期6～7个月，对功能性肾上腺皮质癌，可使皮质功能亢进症状缓解，肿瘤缩小，延长生命。 Lysodren Generic Name: mitotane Dosage Form: tablet Lysodren® (mitotane tablets, USP) Lysodren Description Lysodren® (mitotane tablets, USP) is an oral chemotherapeutic agent. It is best known by its trivial name, o,p′-DDD, and is chemically, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane. The chemical structure is shown below: Lysodren is a white granular solid composed of clear colorless crystals. It is tasteless and has a slight pleasant aromatic odor. It is soluble in ethanol, isooctane, and carbon tetrachloride. It has a molecular weight of 320.05. Inactive ingredients in Lysodren tablets are: avicel, Polyethylene Glycol 3350, silicon dioxide, and starch. Lysodren is available as 500 mg scored tablets for oral administration. Lysodren - Clinical Pharmacology Lysodren can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. Its biochemical mechanism of action is unknown. Data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex. The administration of Lysodren alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-β-hydroxycortisol. Data in adrenal carcinoma patients indicate that about 40% of oral Lysodren is absorbed and approximately 10% of the administered dose is recovered in the urine as a water-soluble metabolite. A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues. Following discontinuation of Lysodren, the plasma terminal half-life has ranged from 18 to 159 days. In most patients blood levels become undetectable after 6 to 9 weeks. Autopsy data have provided evidence that Lysodren is found in most tissues of the body; however, fat tissues are the primary site of storage. Lysodren is converted to a water-soluble metabolite. No unchanged Lysodren has been found in urine or bile. Indications and Usage for Lysodren Lysodren is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Contraindications Lysodren (mitotane tablets, USP) should not be given to individuals who have demonstrated a previous hypersensitivity to it. Warnings Lysodren should be temporarily discontinued immediately following shock or severe trauma, since adrenal suppression is its prime action. Exogenous steroids should be administered in such circumstances, since the depressed adrenal may not immediately start to secrete steroids. Lysodren should be administered with care to patients with liver disease other than metastatic lesions from the adrenal cortex, since the metabolism of Lysodren may be interfered with and the drug may accumulate. All possible tumor tissues should be surgically removed from large metastatic masses before Lysodren administration is instituted. This is necessary to minimize the possibility of infarction and hemorrhage in the tumor due to a rapid cytotoxic effect of the drug. Long-term continuous administration of high doses of Lysodren may lead to brain damage and impairment of function. Behavioral and neurological assessments should be made at regular intervals when continuous Lysodren treatment exceeds 2 years. A substantial percentage of the patients treated show signs of adrenal insufficiency. It therefore appears necessary to watch for and institute steroid replacement in those patients. However, some investigators have recommended that steroid replacement therapy be administered concomitantly with Lysodren. It has been shown that the metabolism of exogenous steroids is modified and consequently somewhat higher doses than normal replacement therapy may be required. Precautions General Adrenal insufficiency may develop in patients treated with Lysodren, and adrenal steroid replacement should be considered for these patients. Since sedation, lethargy, vertigo, and other CNS side effects can occur, ambulatory patients should be cautioned about driving, operating machinery, and other hazardous pursuits requiring mental and physical alertness. Drug Interactions Lysodren has been reported to accelerate the metabolism of warfarin by the mechanism of hepatic microsomal enzyme induction, leading to an increase in dosage requirements for warfarin. Therefore, physicians should closely monitor patients for a change in anticoagulant dosage requirements when administering Lysodren to patients on coumarin-type anticoagulants. In addition, Lysodren should be given with caution to patients receiving other drugs susceptible to the influence of hepatic enzyme induction. Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic and mutagenic potentials of Lysodren (mitotane tablets, USP) are unknown. However, the mechanism of action of this compound suggests that it probably has less carcinogenic potential than other cytotoxic chemotherapeutic drugs. Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Lysodren. It is also not known whether Lysodren can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Lysodren should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from mitotane, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Clinical studies of Lysodren did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient 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. Adverse Reactions A very high percentage of patients treated with Lysodren have shown at least one type of side effect. The main types of adverse reactions consist of the following: Gastrointestinal disturbances, which consist of anorexia, nausea or vomiting, and in some cases diarrhea, occur in about 80% of the patients. Central nervous system side effects occur in 40% of the patients. These consist primarily of depression as manifested by lethargy and somnolence (25%), and dizziness or vertigo (15%). Skin toxicity has been observed in about 15% of the cases. These skin changes consist primarily of transient skin rashes which do not seem to be dose related. In some instances, this side effect subsided while the patients were maintained on the drug without a change of dose. Infrequently occurring side effects involve the eye (visual blurring, diplopia, lens opacity, toxic retinopathy); the genitourinary system (hematuria, hemorrhagic cystitis, and albuminuria); cardiovascular system (hypertension, orthostatic hypotension, and flushing); and some miscellaneous effects including generalized aching, hyperpyrexia, and lowered protein bound iodine (PBI). Overdosage No proven antidotes have been established for Lysodren overdosage. Lysodren Dosage and Administration The recommended treatment schedule is to start the patient at 2 g to 6 g of Lysodren per day in divided doses, either 3 or 4 times a day. Doses are usually increased incrementally to 9 g to 10 g per day. If severe side effects appear, the dose should be reduced until the maximum tolerated dose is achieved. If the patient can tolerate higher doses and improved clinical response appears possible, the dose should be increased until adverse reactions interfere. Experience has shown that the maximum tolerated dose (MTD) will vary from 2 g to 16 g per day, but has usually been 9 g to 10 g per day. The highest doses used in the studies to date were 18 g to 19 g per day. Treatment should be instituted in the hospital until a stable dosage regimen is achieved. Treatment should be continued as long as clinical benefits are observed. Maintenance of clinical status or slowing of growth of metastatic lesions can be considered clinical benefits if they can clearly be shown to have occurred. If no clinical benefits are observed after 3 months at the maximum tolerated dose, the case would generally be considered a clinical failure. However, 10% of the patients who showed a measurable response required more than 3 months at the MTD. Early diagnosis and prompt institution of treatment improve the probability of a positive clinical response. Clinical effectiveness can be shown by reduction in tumor mass; reduction in pain, weakness or anorexia; and reduction of symptoms and signs due to excessive steroid production. A number of patients have been treated intermittently with treatment being restarted when severe symptoms have reappeared. Patients often do not respond after the third or fourth such course. Experience accumulated to date suggests that continuous treatment with the maximum possible dosage of Lysodren is the best approach. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-4 To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing Lysodren tablets. Lysodren tablets should not be crushed. Personnel should avoid exposure to crushed and/or broken tablets. If contact with broken tablets occurs, wash immediately and thoroughly. More information is available in the references listed below. How is Lysodren Supplied。 STORAGE Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. 商品名（製造・販売会社） オペプリム（ヤクルト、アベンティスファーマ） 殺虫剤DDTによく似た物質です。副腎皮質を壊死させたり、副腎皮質が過剰に作り出すステロイドホルモンを抑える作用があります。副腎皮質から生じたがんに対する縮小効果、副腎の過剰なホルモン分泌によって起こるクッシング症候群などに対する治療効果を示します。 安万特制药 適応となるがん 副腎がん 主な副作用 最も注意が必要なのは血栓症で、心筋梗塞や脳梗塞などを引き起こすことがあります。そのほか、肝機能の低下や乳房のはれ・痛み、吐き気、嘔吐、倦怠感などがみられることもあります。また、性機能の低下や肛門周囲のかゆみ・灼熱間などが起こる場合もあります。 使用上の注意点 利尿剤・降圧剤スピロノラクトンはミトタンの作用を妨げることがあり、また睡眠剤や麻酔剤であるペントバルビタールと併用すると、睡眠作用を弱めることがあります。 附件： 201041202150140.pdf ---------------------------------------------- 注，以下产品不同规格和不同价格，购买时请以电话咨询为准！ ---------------------------------------------- 原产地英文商品名: LYSODREN 500mg/tab 100tabs/bottle 原产地英文药品名: MITOTANE 中文参考商品译名: LYSODREN 500毫克/片 100片/瓶 中文参考药品译名: 米托坦 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: BRISTOL MYERS SQUIBB ---------------------------------------------- 原产地英文商品名: LYSODREN 500mg/tab 30tabs/bottle 原产地英文药品名: MITOTANE 中文参考商品译名: LYSODREN 500毫克/片 30片/瓶 中文参考药品译名: 米托坦 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: BRISTOL MYERS SQUIBB ---------------------------------------------- 原产地英文商品名: LYSODREN 500mg/tab 10tabs/bottle 原产地英文药品名: MITOTANE 中文参考商品译名: LYSODREN 500毫克/片 10片/瓶 中文参考药品译名: 米托坦 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: BRISTOL MYERS SQUIBB