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 详细处方信息以本药内容附件文件（201882921180020.pdf）的“原文Priscribing Information”为准
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部分中文Tomudex处方资料（仅供参考）
 

英文药名：

Raltitrexed Injection

商标名称：

Tomudex

药物名称：

雷替曲塞粉针

分子式成分：

N-[5-[N-甲基-N-(2-甲基-4-氧代-3，4-二氢喹唑啉-6-基甲基)氨基]-2-噻吩甲酰基]-L-谷氨酸

制剂规格：

本品为白色冻干粉末，每瓶含雷替曲塞2 mg。

药理毒理

药理学研究表明，雷替曲塞为新一代水溶性胸苷酸合酶抑制剂，该药通过细胞膜外还原型叶酸盐载体系统将本品主动摄入细胞内，而后迅速代谢为多谷氨酸类化合物抑制胸苷酸合酶的活性，并能在细胞内潴留，长时间发挥作用。 它对结肠直肠癌细胞系的抑制作用强于5-氟尿嘧啶，雷替曲塞的IC50长期给药为1.3～3.9nmol/L，短期给药为80nmol/L，而5-氟尿嘧啶与甲酰四氢叶酸合用长期给药IC50为330～5800nmol/L，短期给药为150000nmol/L。体外研究观察到雷替曲塞与5-氟尿嘧啶联合用药有协同作用，这种作用依赖于给药方案和剂量。

对176例晚期结肠直肠癌患者进行的II期临床试验，给予雷替曲塞3 mg/m2，每3周1次，有25.6%产生综合疗效，从治疗到病情进展平均时间为4.2周，存活期平均为11.2月。1300多例晚期结肠直肠癌患者的3项III期临床研究结果表明，雷替曲塞治疗组（每3周1次，每次3mg/m2）与5-氟尿嘧啶加甲酰四氢叶酸治疗组（5-氟尿嘧啶425mg/m2加甲酰四氢叶酸20 mg/m2或5-氟尿嘧啶400 mg/m2加甲酰四氢叶酸200 mg/m2，每天1次，连续5天，每4～5周重复1次），所产生的客观有效率相似，分别为14.3%～19.3%和15.2%～18.1%，中位缓解时间分别为3.1～4.8和3.6～5.3个月，中位生存期分别为9.7～10.9和10.2～12.7个月。

药 动 学

患有不同程度实体瘤的患者给予本品3mg/m2治疗后，药物浓度与时间呈三室模型，Cmax的平均值为833μg/L，AUC为1090μg/L.h，分布相半衰期T1/2为0.8～3 h，最终消除半衰期T1/2γ为8.2～105h，与给药剂量无关。雷替曲塞主要消除途径是以原型药物形式从肾脏排出，患有轻、中度肾功能不全的患者的T1/2明显延长，AUC比正常肾功能患者增加2倍。

适 应 证：

晚期直肠结肠癌的一线治疗。

不良反应

静脉滴注本品后常见副作用为血液毒性包括骨髓抑制，中性粒细胞减少、血小板减少等，胃肠道副作用有恶心、呕吐、腹泻，头痛、失眠、皮疹等现象，一般患者耐受性良好，副作用发生率较低。

相互作用

未见本品与华法林、非甾体抗炎药的相互作用，建议本品不与亚叶酸钙、叶酸和维生素制剂联合用药，以免发生相互作用，与其他细胞毒药物联合用药的安全尚未确立。

用法用量

推荐给药剂量为每次3mg/m2，用25至250ml 0.9%生理盐水或5%葡萄糖稀释后静脉滴注15min以上，每3周重复给药1次。

药物过量

药物服用过量的产生严重的骨髓抑制等血液毒性和胃肠道毒性，应避免使用过量或遵医嘱，药物过量时可每6 h给予亚叶酸钙25 mg/m2。

注意事项

对本品过敏者及有严重并发症者禁用。孕妇及哺辱期妇女禁用。 本能只做单独给药，避免与其它药物混合使用。本品用0.9%生理盐水或5%葡萄糖水溶液稀释后应避光保存，在24小时内使用。轻度和中毒肝损伤患者使用时无需调整本品剂量，但本品部分经粪便排泄，严重肝损伤患者使用时应注意。孕妇及哺辱期妇女禁用本品。儿童患者使用本品的安全性尚未确立，儿童慎用。

老年患者用药

药代动力学研究表明肾肾功能损伤的老年患者血浆清除率降低，可发生体内积蓄，应降低本品的剂量肌苷清除率在55～65 mL/min，应给予推荐剂量的75%，肌苷清除率在25～54 mL/min，应给予推荐剂量的50%，每4周重复给药1次。

English drug name:

Raltitrexed Injection

Trademark name:

Tomudex

Drug name:

Rortezide powder needle

Molecular composition:

N-[5-[N-Methyl-N-(2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)amino]-2-thiophene-yl]- L-glutamic acid

Formulation Specifications:

This product is a white lyophilized powder containing 2 mg of raltitrexed per bottle.

Pharmacology and Toxicology

Pharmacological studies have shown that raltitrexed is a new generation of water-soluble thymidylate synthase inhibitor, which actively ingests the product through the extracellular extracellular folate carrier system and then rapidly metabolizes to polyglutamine. The acid compound inhibits the activity of thymidylate synthase and can be retained in the cells for a long period of time. It inhibits colorectal cancer cell lines more strongly than 5-fluorouracil. The long-term IC50 of raltitrexed is 1.3-3.9 nmol/L, and the short-term dose is 80 nmol/L, while 5-fluorouracil and formyltetrahydrol The IC50 for long-term administration of folic acid is 330 to 5800 nmol/L, and the short-term administration is 150,000 nmol/L. In vitro studies have observed a synergistic effect of raltitrexed in combination with 5-fluorouracil, depending on the dosage regimen and dosage.

A phase II clinical trial of 176 patients with advanced colorectal cancer was given raltitrexed 3 mg/m2 once every 3 weeks, and 25.6% had a combined effect. The average time from treatment to progression was 4.2. Week, the average survival period is 11.2 months. Three phase III clinical trials of more than 1,300 patients with advanced colorectal cancer showed raltitrexed in the treatment group (3 mg/m2 once every 3 weeks) and 5-fluorouracil plus formyltetrahydrofolate treatment group ( 5-fluorouracil 425mg/m2 plus formyltetrahydrofolate 20 mg/m2 or 5-fluorouracil 400 mg/m2 plus formyltetrahydrofolate 200 mg/m2 once daily for 5 days, repeat every 4 to 5 weeks 1 Times), the objective and effective rates were similar, 14.3% to 19.3% and 15.2% to 18.1%, respectively. The median time to remission was 3.1 to 4.8 and 3.6 to 5.3 months, respectively. The median survival time was 9.7 to 10.9. And 10.2 to 12.7 months.

Pharmacokinetics

After treatment with 3 mg/m2 of this product, patients with different degrees of solid tumors showed a three-compartment model with drug concentration and time. The average value of Cmax was 833 μg/L, the AUC was 1090 μg/Lh, and the distribution phase half-life T1/2 was 0.8-3. h, the final elimination half-life T1/2γ is 8.2-105h, regardless of the dose administered. The main elimination route of raltitrex was excreted from the kidney in the form of a prototype drug. The T1/2 was significantly prolonged in patients with mild to moderate renal insufficiency, and the AUC was 2-fold higher than that in patients with normal renal function.

Adaptation:

First-line treatment for advanced colorectal cancer.

Adverse reactions

Common side effects after intravenous infusion of this product are blood toxicity including myelosuppression, neutropenia, thrombocytopenia, etc. Gastrointestinal side effects include nausea, vomiting, diarrhea, headache, insomnia, rash, etc., and patients are generally well tolerated. The incidence of side effects is low.

Interaction

No interaction between this product and warfarin or non-steroidal anti-inflammatory drugs is recommended. It is recommended that this product should not be combined with calcium folinate, folic acid and vitamin preparations to avoid interaction. The safety of combination with other cytotoxic drugs has not yet been safe. establish.

Usage and Usage

The recommended dose is 3 mg/m 2 each time, diluted with 25 to 250 ml of 0.9% physiological saline or 5% glucose, and intravenously infused for 15 minutes or more, and repeated once every 3 weeks.

Overdose

Excessive use of drugs to produce severe bone marrow suppression and other hematological and gastrointestinal toxicity, should avoid excessive or as directed, calcium leucovorin 25 mg / m2 every 6 h.

Notes

Those who are allergic to this product and have serious complications are prohibited. Pregnant women and pregnant women are banned. Instinct is only administered alone, avoiding mixing with other drugs. This product should be stored in darkness after being diluted with 0.9% normal saline or 5% dextrose in water and used within 24 hours. Patients with mild and poisoned liver injury do not need to adjust the dose of this product, but this product is partially excreted by feces, and should be noted when using patients with severe liver injury. Pregnant women and pregnant women are prohibited from using this product. The safety of children using this product has not been established, and children should use it with caution.

Medicine for elderly patients

Pharmacokinetic studies have shown that plasma clearance in elderly patients with renal and renal dysfunction is reduced, and accumulation in the body can occur. The dose of inosine should be reduced at 55-65 mL/min, and the recommended dose should be 75%. The glycosidic clearance rate is 25-54 mL/min, and 50% of the recommended dose should be given, and the drug is administered once every 4 weeks.

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 详细处方信息以本药内容附件文件（201882921180020.pdf）的“原文Priscribing Information”为准
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