英文药名：PRALIA Subcutaneous Injection（Denosumab(Genetical Recombination)）

中文药名：重组狄诺塞麦注射器

生产厂家：第一三共有限公司

プラリア皮下注60ｍｇシリンジ

类别名称
人抗RANKL单克隆抗体制剂
商標名
PRALIA SUBCUTANEOUS INJECTION SYRINGE
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。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
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，通过反复每月一次的皮下给药，在给药期间，减少尿I型胶原交联的N-端肽持续
2. 效果对骨密度
嵌合RANKL表达不是转基因小鼠每周一次狄诺塞麦在为10mg/kg的剂量（人RANKL敲除在小鼠中），该狄诺塞麦绑定，当给药3个星期重复皮下，血清TRAP 5b的浓度是骨吸收标记9显著减少，骨质密度增加）。另外，每月一次剂量在25或50mg /kg的所述狄诺塞麦去势猕猴，和16个月的重复皮下给药，骨密度和松质骨和皮质骨的骨强度增加，并且在骨量和骨强度呈正相关
3. 对骨折愈合
人类RANKL敲股骨闭合性骨折受到狄诺塞麦每周鼠标的一次10mg/ kg剂量的两倍时，反复皮下给药21或42天，愈伤组织的重塑骨强度已被推迟骨折部位减少事实并非如此。
4. 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12是一个重要的蛋白是）。狄诺塞麦抑制RANK/ RANKL通路13通过抑制破骨细胞的形成抑制骨吸收）。其结果是，增加骨量的皮质骨和松质骨被认为是提高骨强度。
注）排名：受体激活核因子κB
适应病症
骨质疏松症
用法与用量
每半年一次，以60毫克为狄诺塞麦（基因重组）对于成年人来说，皮下注射
包装规格
皮下注射：60毫克的注射器（1毫升），1本

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/3999435G1023_1_05/
PRALIA Subcutaneous Injection（Denosumab (genetical recombination)）
PRALIA Subcutaneous Injection 60mg Syringe（プラリア皮下注60mgシリンジ） 
Brand name : PRALIA Subcutaneous Injection 60mg Syringe
　Active ingredient: Denosumab (genetical recombination)
　Dosage form: injection
　Print on wrapping: 
Effects of this medicine
This medicine is anti-RANKL antibody which inhibits bone loss and increases bone density to prevent bone fracture.
It is usually used to treat osteoporosis.
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 an allergy to natural rubber (latex), hypocalcemia, renal disorder or a potential to develop hypocalcemia.
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 6 months. It may be administered over a long period according to your response to the treatment.
Precautions while taking this medicine
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.
In order to prevent hypocalcemia, ingest calcium and vitamin D everyday 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.
Possible adverse reactions to this medicine
The most commonly reported adverse reactions include hypocalcemia, back pain, hypertension, eczema or joint pain. 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: 1/2014
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