英文药名：RANMARK SUBCUTANEOUS INJECTION（Denosumab(Genetical Recombination)） 中文药名：重组狄诺塞麦注射液 生产厂家：第一三共有限公司 ランマーク皮下注１２０ｍｇ 类别名称 人抗RANKL单克隆抗体制剂 商標名 RANMARK SUBCUTANEOUS INJECTION 1. 一般名 デノスマブ(遺伝子組換え) Denosumab(Genetical Recombination) 2. 本質 通过CHO细胞转染的cDNA的编码轻链和重链制备的重组抗NF-κB活化受体配体（抗RANKL）人IgG2单克隆抗体。它由448个氨基酸残基是重（γ2链）2分子和轻链组成的215个氨基酸残基（κ链）的糖蛋白的两个分子组成。 3. 分子量 約150,000 审批条件 骨巨细胞瘤 由于临床试验的情况下在日本是非常有限的，上市后，直到一定数量案件的数据被集成，通过实施的所有情况下，使用效果的调查，该药物以及了解病人使用的背景资料，搜集有关这种药物的安全性和有效性的数据在年初，采取必要措施，正确使用此药。 药效药理 狄诺塞麦是人IgG2单克隆抗体，其与人RANKL特异性和高亲和性。 (1) 骨吸収抑制 狄诺塞麦猕猴中的单一皮下给药，尿I型胶原交联的N-端肽是骨吸收标记物减少。另外，通过每月一次的重复皮下给药，在给药期间，减少尿I型胶原交联的N-端肽仍然存在。 （2）抑制骨病变的进展 狄诺塞麦因为它不结合RANKL小鼠中，使用与小鼠骨转移模型OPG-Fc的注）抑制通过结合RANKL鼠标作为替代狄诺塞麦。乳腺癌（溶骨或溶骨和混合型成骨细胞），前列腺癌和非小细胞肺癌（均溶骨的小鼠骨转移模型）OPG-它是管理的FC，骨骼病变因癌症进展已被抑制。 注）OPG-Fc的：骨结合的免疫球蛋白结晶碎片骨 (3) 作用机序 RANKL是作为膜结合或可溶的，并且调节破骨细胞，并通过RANK注）受体表达的前体细胞的表面上破骨细胞形成，功能和存活控制骨吸收一个重要的蛋白。在实体癌的多发性骨髓瘤和骨病变骨转移，破骨细胞，其通过RANKL激活是骨破坏的一个主要因素。狄诺塞麦抑制RANK/ RANKL通路，通过抑制破骨细胞的激活抑制骨吸收），被认为是从癌症抑制骨病变的发展。 在骨巨细胞瘤，RANKL在基质细胞中的肿瘤，RANK对破骨细胞样巨细胞中表达。狄诺塞麦与RANKL结合，由破骨细胞样巨细胞，被认为是抑制骨巨细胞瘤的进展）抑制骨质破坏。 注）排名：受体激活核因子κB 适应病症 1、由于多发性骨髓瘤的骨病变，由于骨病变和固体癌骨转移 2、**骨巨细胞瘤 用法用量 由于多发性骨髓瘤的骨病变，由于骨病变和固体癌骨转移 通常情况下，每四周为120mg的denosumab的（基因重组），成人一次，皮下注射。 **骨巨细胞瘤 狄诺塞麦（基因重组）的第一天为120mg如，8天，15个天29天，然后每4周，皮下给药 包装规格 皮下注射120毫克（1.7毫升），1瓶 生产厂商 第一三共有限公司 附原处方资料：http://www.info.pmda.go.jp/go/pack/3999435A1020_1_11/ RANMARK Subcutaneous Injection（Denosumab (Genetical Recombination) ） RANMARK Subcutaneous Injection 120mg [Giant Cell Tumor of Bone]（ランマーク皮下注120mg［骨巨細胞腫］） Brand name : RANMARK Subcutaneous Injection 120mg [Giant Cell Tumor of Bone] 　Active ingredient: Denosumab (Genetical Recombination) 　Dosage form: injection 　Print on wrapping: RANMARK Subcutaneous Injection 120mg [bone lesion associated with multiple myeloma or bone metastases from solid tumors]（ランマーク皮下注120mg［多発性骨髄腫による骨病変および固形癌骨転移による骨病変］） Brand name : RANMARK Subcutaneous Injection 120mg [bone lesion associated with multiple myeloma or bone metastases from solid tumors] 　Active ingredient: Denosumab (Genetical Recombination) 　Dosage form: injection 　Print on wrapping:  Effects of this medicine This medicine is anti-RANKL antibody which inhibits bone resorption and suppresses progression of bone lesion from tumors. It is usually used to treat bone lesion associated with multiple myeloma or bone metastases from solid tumors. Before using this medicine, be sure to tell your doctor and pharmacist •If you have previously experienced any allergic reactions (itch, rash, etc.) to any medicines. If you have hypocalcemia, renal disorder or a potential to develop hypocalcemia. If you are using "PRALIA Subcutaneous Injection 60mg Syringe." •If you are pregnant, possibly 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>> •In general, administer by subcutaneous injection once every 4 weeks. It may be administered over a long period according to your response to the treatment. Precautions while taking this medicine •In order to prevent hypocalcemia, ingest calcium and vitamin D under the instruction of your doctor. If you have difficulty in taking them orally, consult with your doctor. •Since hypocalcemia may occur without any symptoms, frequent blood test is needed. Keep blood test schedule under the instruction of your doctor. •Necrosis/osteomyelitis of the jaw bone may occur in the patients who are taking medicines for bone lesion including this medicine or similar drugs (Bisphosphonate). These adverse reactions often related to dental treatment such as tooth extraction. Receive adequate explanation about the following points from your doctor or pharmacist. (1) Receive dental checkup as needed, and if possible, receive dental treatment such as tooth extraction prior to taking the medicine, after consultation with your doctor. (2) Maintain your oral hygiene by brushing your teeth while taking this medicine. (3) Receive dental checkup regularly while taking the medicine. (4) Inform your dentist that you are taking the medicine when you see a dentist. (5) Avoid any treatments such as tooth extraction while taking the medicine. If abnormalities in teeth/jaw (jaw pain, loose teeth or swollen gums) occur, see a dentist/oral surgery specialist immediately. Possible adverse reactions to this medicine The most commonly reported adverse reactions include hypocalcemia, fatigue, nausea, joint pain, jaw osteonecrosis, asthenia or diarrhea. If any of these symptoms occur, consult with your doctor or pharmacist. 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. •shaking limbs, muscular weakness, convulsion, numbness, arrhythmia [hypocalcemia] •oral pain, swelling of mouth, redness, loose teeth, numbness of jaw, heavy feeling in jaw, fever, loss of appetite [necrosis of the jaw bone, osteomyelitis of the jaw] •hoarse voice, swelling around eyes/lips, hives, impaired judgment, palpitation, shortness of breath, breathing difficulty, dullness, impaired mind, hot flush, decreased consciousness, lightheadedness [anaphylaxis] •pain of thigh or inguinal region [atypical subtrochanteric and diaphyseal femoral fractures] •chill, high fever, redness with local pain and fever [serious skin infection] 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. DAIICHI SANKYO COMPANY, LIMITEDInjection Revised: 5/2014 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. 2013年9月1日，第一三共株式会社（Daiichi Sankyo）宣布，已向日本卫生劳动福利部（MHLW）提交了基因重组药物RANMARK（denosumab，皮下注射液，120mg）的生产及上市申请（MMA），用于治疗一种罕见疾病——骨巨细胞瘤（GCTB）。 MHLW于今年6月指定denosumab为GCTB的有效治疗药物。 Denosumab是世界首个靶向RANK配体的全人源化单克隆抗体。RANK配体是破骨细胞（osteoclast）形成中的重要调节子。 第一三共于2007年从安进（Amgen）授权获得denosumab在日本的开发及销售权利，并于2012年4月以商品名RANMARK（皮下注射，120mg）在日本市场推出，用于治疗多发性骨髓瘤所致的骨骼并发症以及由实体瘤所致的骨转移。 在2013年6月，第一三共推出PRALIA皮下注射60mg注射器（PRALIA，subcutaneous injection 60mg syringe）。 目前，denosumab处于全球性III期临床开发，用于乳腺癌术后辅助治疗。在日本国内，denosumab处于II期临床开发，用于类风湿性关节炎的治疗