英文药名：UZEL tablet（Calcium Folinate） 中文药名：亚叶酸钙片 生产厂家：大鵬薬品 ユーゼル錠25mg 药物分类名称 减少叶酸制剂 批准日期：2003年9月 商標名 UZEL tablet 25mg 構造式   一般名 ホリナートカルシウム（Calcium Folinate） （別名：ロイコボリンカルシウム） 化学名 Monocalcium N-(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamate 分子式 C20H21CaN7O7 分子量 511.50 性状 这是一种白色至淡黄色结晶粉末。 微溶于水，几乎不溶于甲醇或乙醇（99.5）。 审批条件 在日本进行一项足够样本量的随机对照试验，以进一步阐明亚叶酸替加氟尿嘧啶治疗结肠直肠癌的有效性和安全性。 药效药理 1.体外测试 已经显示使用浓度为0.006μM的人烟酸盐作为左旋甲苯磺酸盐对人结肠癌细胞（COLO 205）的体外试验增强了氟尿嘧啶的抗肿瘤作用。 2.体内试验（通过伴随给药增强抗肿瘤效果的效果） 对于移植人结肠癌细胞（KM20C，KM12C，Co-3）的裸小鼠，联合使用替加氟（20mg/kg /天）和替加氟/尿嘧啶（20mg/kg/天替加氟） 与抗肿瘤作用相比。 3. 作用机序 具有氟尿嘧啶替加氟的分解抑制作用替加氟尿嘧啶摩尔尿嘧啶是1比氟尿嘧啶前药：4：抗肿瘤剂混有（替加氟尿嘧啶）。左旋门冬酰胺（一种旋光形式的月桂酸酯（I型））通过生物化学调节增强氟尿嘧啶的抗肿瘤作用。抑制：（TS胸苷酸合成酶）加上和，通过抑制胸苷酸合成氟尿嘧啶氟脱氧尿苷TS活性，抑制DNA合成单磷酸酯的活性代谢物（FdUMP的），胸苷酸合成到。左乙酸盐在细胞内被还原成5,10-CH 2 -THF。这种5,10-CH 2 -THF与FdUMP，TS形成强烈的三元复合物，减缓了TS的解离，从而增强了氟尿嘧啶的抗肿瘤作用。因此，联合使用亚叶酸和替加氟/尿嘧啶可增强替加氟降解产物氟尿嘧啶的抗肿瘤作用。 适应病症 Holinato·替加氟·尿嘧啶疗法： 替加氟/尿嘧啶对结直肠癌的抗肿瘤作用 用法与用量 Holinato·替加氟·尿嘧啶疗法： 通常，每天三次（大约每8小时一次），与替加氟/尿嘧啶组合物同时向成人施用75mg作为holinert。 替加氟/尿嘧啶组合的剂量通常分为每日3次（约每8小时）相当于每日剂量300至600mg替加氟（300mg/m 2标准），1餐前后 避免一次口服。 或连续28天每天更多，随后撤回7天。 重复一次。 临床结果 国内外桥接检查（日本44例，国外44例）和国外临床试验对此疗法进行了检查。 （1）国内临床试验1） 在日本的临床试验Horinato-替加氟尿嘧啶治疗结肠直肠癌有效率为36.4％（实施例16/44）。 （2）国外临床试验 1）针对奏在外国的临床试验结直肠癌（桥接研究）效率Horinato-替加氟尿嘧啶疗法为34.1％（实施例15/44）。 2）联合疗法Horinato氟尿嘧啶治疗靶向结肠直肠癌（Horinato注射和氟尿嘧啶注射，5-FU/ LV）和治疗（Horinato，替加氟尿嘧啶疗法，UFT/LV）和开放标签为我们进行了两次设计审查的第三阶段比较测试。 1.等价验证生存率分别作为试验的结果，其主要目的是下面，生存期与UFT/LV和5-FU/LV（见表2）相媲美。 2.优越性验证疾病进展时间分别为与主目标，时间以下测试结果疾病进展显著差异UFT/LV和5-FU /观察LV（表参考文献3）。 包装规格 PTP包装：42片（21片×2），84片（21片×2×2） 制造商 大鵬薬品工業株式会社 注：以上中文不够完整，使用者以原资料为准。 完整说明书附件：http://www.info.pmda.go.jp/go/pack/3929004F2021_1_12/ Calcium Folinate简介 本品是叶酸还原型的甲酰化衍生物，系叶酸在体内的活化形式，作用与叶酸相似，主要用于叶酸拮抗剂(如甲氨蝶呤、乙胺嘧啶、甲氧苄啶等)的解毒剂。当口服叶酸疗效不佳时，也用于口炎性腹泻，妊娠期或婴儿期引起的巨幼细胞性贫血，此类贫血是因二氢叶酸还原酶受抑制，叶酸在体内不能变成四氢叶酸所致，但对维生素B12缺乏性贫血并不适用。CF生化调节使5-FU增效是近年来化疗的一项进展。多数文献报道，CF/5-FU方案对以往未用过5-FU的结肠癌，疗效约30%～50%，对以往用过5-FU的，近期疗效为10%～20%。CF/5-FU方案较单用5-FU的疗效提高1倍。CF/5-FU是结肠癌、胃癌等的基本用药，CF/5-FU加顺铂或VP16、ADM(EPI)、MMC等方案广泛应用于消化道肿瘤中。还可用于预防甲氨蝶呤大剂量引起的严重毒副作用，作为抗癌药辅助用药。 ユーゼル錠25mg：UZEL tablet（Calcium Folinate） Brand name : UZEL tablet 25mg 　Active ingredient: Calcium folinate 　Dosage form: tablet, light yellowish white; (Diameter 8.0mm, thickness 3.5mm) 　Print on wrapping: （front）TC447 25mg, （back）TC447 25mg Effects of this medicine This medicine is a reduced folic acid formulation which has no antitumor effect by itself. The concomitant use of UFT (tegafur-uracil) and UZEL boosts the effectiveness of antitumor effect of UFT (folinate, tegafur-uracil therapy). This folinate / tegafur-uracil therapy can be expected to reduce tumor size and alleviate symptoms. It is commonly used to treat colorectal cancer. Before using this medicine, be sure to tell your doctor and pharmacist •If you ever experienced any allergic reaction (itch, rash etc.) to any medicine. If you present a condition indicative of bone marrow suppression (including leucopenia). If you have diarrhea. If you have an infection. If you have hepatic dysfunction or a history of hepatic dysfunction. If you have renal dysfunction. If you have a heart disease or a history of heart disease. If you have gastrointestinal ulcers or hemorrhage. If you have diabetes or varicella. If you are having radiotherapy. If you have been previously treated with other chemotherapy medicines. •If you are using TS-1, fluoropyrimidine anticancer drug, currently or within the last 7 days. •If you are pregnant or breastfeeding. •If you are taking any other medicinal products. (Some medicines may interact to enhance or diminish medicinal effects. Beware of over-the-counter medicines and dietary supplements as well as other prescription medicines.) Dosing schedule (How to take this medicine) •Your dosing schedule prescribed by your doctor is <<to be written by a healthcare professional>> •General dosage regimen (for adults): UZEL is administered 1 tablet (equivalent to 25mg of Calcium Folinate) 3 times daily (at an interval of approximately 8 hours) together with UFT. Administration should be withheld during one hour before or after meal. Repeat a course of 28 consecutive days (4 weeks) followed by a 7-day (1 week) rest period. Be sure to follow the dosage instructions. •UZEL must not be combined with TS-1, fluoropyrimidine anticancer drug. A minimum washout period of 7 days must be provided when UZEL is used after withdrawal of TS-1. •Proceed with the prescribed schedule of medication starting from the next dose. DO NOT take a double dose to make up for the missed dose. •If you took too much of this medicine (more than ordered), check with your doctor/pharmacist. •Do not change your dose and schedule of your chemotherapy without the instructions of your doctor. Precautions while taking this medicine •During the treatment, laboratory tests (hematological, liver and renal function tests) are performed regularly to detect asymptomatic side effects as early as possible. Be sure to consult your doctor. Possible adverse reactions to this medicine Common side effects are reported as below. If any of them occurs, check with your doctor/pharmacist: diarrhea, stomatitis, anorexia, nausea, vomiting, tasteabnormality, tiredness, pigmentation, rash, itch, abdominal pain. The symptoms described below are rarely seen as initial symptoms of the adverse reactions indicated in brackets. If any of these symptoms occur, stop taking this medicine and see your doctor immediately. •Bleeding tendency, tiredness, sore throat, fever[bone marrow suppression] •Yellowing of the skin, tiredness, yellowing of the whites of the eyes, anorexia[severe hepatic dysfunction] •Diarrhea, severe abdominal pain[severe enteritis] •Unstableness, forgetfulness, trouble speaking[psychoneurologic disorders including leukoencephalopathy or other symptoms] •Olfactory disturbance[anosmia] •Difficult breathing, fever, dry cough[interstitial pneumonia] The above symptoms do not describe all the adverse reactions to this medicine. Consult with your doctor or pharmacist if you notice any symptoms of concern other than those listed above. Storage conditions and other information •Keep the medicine out of the reach of babies, infants and children. Store away from direct light, heat, and humidity. •If you have any left-over medicine, be sure to discard it. TAIHO Pharmaceutical Co.,LTD.Internal Revised: 10/2008 The information on this sheet is based on approvals granted by the Japanese regulatory authority. Approval details may vary by country. Medicines have adverse reactions (risks) as well as efficacies (benefits). It is important to minimize adverse reactions and maximize efficacy. To obtain a better therapeutic response, patients should understand their medication and cooperate with the treatment.