2010年6月1日，美国安进公司和美国食品药品管理局(FDA)宣布， Prolia (狄诺赛麦)已获准用于骨折风险高的绝经后女性，作为骨质疏松症的治疗药。该组女性包括长期存在骨质疏松性骨折或有多个骨折危险因素的女性。Prolia也适用于对其他现有的骨质疏松症治疗方法不耐受或无反应的女性。
据该药的处方信息，Prolia可抑制破骨细胞的生成、功能和存活，因此可减少骨的再吸收，增加骨小梁和皮质骨内的骨量和强度。
FDA批准Prolia上市是基于一项为期3年的关键性III期随机、双盲、安慰剂对照试验的研究结果，该试验涉及7,808例患有骨质疏松症的绝经后女性(年龄介于60~91岁)。据治疗后3年的测量结果，与安慰剂对照组相比，Prolia治疗组骨密度增高、骨强度增大，椎骨、髋骨和非脊椎骨折的风险减少。
应用Prolia治疗所报告的最常见不良反应包括：背痛、肢体疼痛、肌肉骨骼痛、胆固醇水平升高和泌尿系统感染。严重的不良反应包括：低钙血症、重度感染和皮肤过敏反应，如皮炎、皮疹和湿疹。Prolia可严重抑制骨转化，这种抑制作用可能会导致颌骨坏死的发生。
Prolia禁用于有低钙血症的患者。在开始应用Prolia治疗之前一定要纠正之前存在的低钙血症。低钙血症可能会因此而恶化，尤其是对于有重度肾功能障碍的患者。所有患者都应该补充足量的钙和维生素D。
Prolia的治疗方案为：Prolia 60 mg，皮下注射，每6个月注射1次，应该由医护人员对患者进行给药。

一般描述：

Prolia(狄诺塞麦denosumab)是一种人IgG2单克隆抗体，对人RANKL(receptor activator of nuclear factor kappa-B ligand，即核因子κB配体受体激活剂)有亲和力和特异性。Denosumab的分子量约为147 kDa和是在遗传工程哺乳动物(中国仓鼠卵巢)细胞中生产。
Prolia是一种消毒，无防腐剂，透明，无色至淡黄色溶液。
每1 mL单次-使用预装注射器的Prolia含60 mg denosumab(60 mg/mL溶液)，4.7%山梨糖醇，17 mM醋酸盐， 0.01% 聚山梨醇20，注射用水(美国药典USP)，和氢氧化钠至pH值5.2。
每1 mL单次-使用Prolia小瓶a含60 mg denosumab(60 mg/mL溶液)，4.7%山梨糖醇，17 mM醋酸盐， 0.01% 聚山梨醇20，注射用水(美国药典USP)，和氢氧化钠至pH值5.2。

制造商：
安进公司，公司

类药物：
破骨细胞抑制剂（RANKL的抑制剂）

活性成分（S）：
denosumab的60mg/mL;为SC注射soln;不含防腐剂。
指示（S）：
在减少脊椎，非脊椎和髋部骨折的发生率与绝经后妇女骨质疏松症：骨折的高风险的定义，为骨质疏松性骨折的历史，或骨折的多种危险因素，或失败或不能耐受其他治疗的患者; 。

药理：
denosumab的是一个人IgG2的单克隆抗体结合到人类受体活化的核因子kappa - B配体（RANKL）。 denosumab的阻止RANKL的交互其对破骨细胞及其前体的的表面的受体，从而抑制破骨细胞形成，功能和生存。这反过来又降低骨吸收和增加骨皮质及骨小梁的质量和强度。

临床试验：
在为期3年的，随机研究涉及7808 60-91岁的妇女与骨密度T值-2.5和-4.0之间的腰椎或全髋关节治疗绝经后骨质疏松症的安全性和疗效的denosumab的评估。所有受试者每天钙和维生素D补充，除每6个月的研究药物或安慰剂。主要疗效变量是新的椎体骨折的发生率在3年;次要疗效变量的髋关节和非脊椎骨折的发生率。

denosumab的显著减少新的椎体骨折的发生率在1，2和3年。处3年以上，发病率在安慰剂组的7.2％相比，在研究药物组2.3％（相对危险降低68％）。髋部骨折的发病率在3年，为denosumab的0.7％（相对危险降低40％）相比，服用安慰剂的患者为1.2％。与非脊椎骨折在今年3的妇女的比例是8.0％，服用安慰剂的患者相比为denosumab的6.5％（相对危险降低20％）。

治疗与denosumab的显着增加骨密度（BMD）的，处3年以上（腰椎，全髋，股骨颈）测量所有站点。 denosumab的停药后，骨密度1年之内恢复到基线水平。

法律分类：
接收

成人：
应该由医疗专业人士。 60mg SC每6个月;注入上臂，大腿或腹部。

儿童：
不推荐。

禁忌（S）：
低钙血症。

警告/注意事项：
在开始之前正确的低钙血症;确保足够的每日钙（≥1000毫克）和Vit.D（≥400IU）的摄入量，ESP。在肾功能不全（肌酐清除率<30mL/min）。监视器钙，磷，镁在易感患者（甲状旁腺功能低下，甲状腺或甲状旁腺手术，吸收障碍，严重肾功能不全透析，）的水平。监测感染，颚骨坏死，骨oversuppression。做基线口试和预防性牙科如果存在颚骨坏死的风险（如拔牙，牙科植入物，口腔外科，癌症，贫血，凝血功能障碍）。保持良好的口腔卫生。免疫抑制。乳胶过敏（预充式注射器）。怀孕（Cat.C）。哺乳母亲：避免（可能会损害乳腺/哺乳期）。

相互作用（S）：
伴随免疫抑制剂（增加感染的风险）。皮质类固醇（颚骨坏死的风险增加）。

不良反应（S）：
痛（背部，下肢或肌肉骨骼），高胆固醇血症，膀胱炎，感染（可能是严重的，例如，蜂窝组织炎，尿路感染，耳，腹部），皮炎，皮疹，湿疹，颚骨坏死，骨转换抑制，加重低钙血症，胰腺炎。

如何提供：
单用小瓶（1毫升）-1
单剂量预充SYR（1ML）-1

最后更新：
2010年6月17日

FDA批准骨科药物Prolia用于癌症患者

9月19日，安进宣布美国FDA批准了Prolia(狄诺塞麦)的2项新适应证。该药以RANK配体——破骨细胞的一个关键调控子——为靶点。本次批准的新适应证为：用于正在接受芳香酶抑制剂辅助治疗的乳腺癌患者，以及正在接受雄激素剥夺治疗的非转移性前列腺癌患者。Prolia的适应证得以扩展是基于2项3期临床试验的数据：一项是为期3年的随机、双盲、安慰剂对照、国际多中心研究，纳入1,468正在接受雄激素剥夺治疗的非转移性前列腺癌患者；另一项是纳入252例正在接受芳香酶抑制剂治疗的绝经后乳腺癌患者。

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原产地英文商品名:
PROLIA 60MG/ML/SYRINGE
原产地英文药品名:
DENOSUMAB
中文参考商品译名:
PROLIA 60毫克/毫升/注射器
中文参考药品译名:
狄诺赛麦
生产厂家中文参考译名:
安进
生产厂家英文名:
AMGEN

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Prolia
Generic Name: denosumab (den OH sue mab)
Brand Names: Prolia
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What is Prolia?
Prolia (denosumab) is a monoclonal antibody that affects the actions of the body's immune system. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.
Prolia is used to treat osteoporosis in postmenopausal women who have high risk of bone fracture.
Prolia may also be used for purposes not listed in this medication guide.
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Important information about Prolia
You should not receive Prolia if you are allergic to denosumab, or if you have low levels of calcium in your blood (hypocalcemia).
Before you receive Prolia, tell your doctor if you have kidney disease (or if you are on dialysis), a weak immune system, a history of hypoparathyroidism or thyroid surgery, a history of intestinal surgery; or if you are allergic to latex.
Serious infections may occur during treatment with Prolia. Call your doctor right away if you have signs of infection such as: severe skin irritation; swelling or redness anywhere on your body; pain or burning when you urinate; severe stomach cramps, diarrhea, or vomiting; ear pain, trouble hearing; cough, feeling short of breath; purple or red spots under your skin; or fever, chills, night sweats, flu symptoms, or weight loss.
Some people using Prolia have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums. You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and a pre-existing dental problem.
If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are receiving Prolia. You may need to stop using the medicine for a short time.
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Before receiving Prolia
You should not receive Prolia if you are allergic to denosumab, or if you have low levels of calcium in your blood (hypocalcemia).
To make sure you can safely use Prolia, tell your doctor if you have any of these other conditions:
kidney disease (or if you are on dialysis);
a weak immune system (caused by disease or by using certain medicines);
a history of hypoparathyroidism (decreased functioning of the parathyroid glands);
a history of thyroid surgery;
a history of surgery to remove part of your intestine; or
if you are allergic to latex.
FDA pregnancy category C. It is not known whether Prolia will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Prolia. It is not known whether denosumab passes into breast milk or if it could harm a nursing baby. However, this medication may slow the production of breast milk. You should not breast-feed while receiving Prolia.
Some people using Prolia have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums. You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and a pre-existing dental problem.
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How is Prolia given?
Prolia is injected under the skin of your stomach, upper thigh, or upper arm. A healthcare provider will give you this injection.
Prolia is usually given once every 6 months. Follow your doctor's instructions.
Your doctor may have you take extra calcium and vitamin D while you are being treated with Prolia. Take only the amount of calcium and vitamin D that your doctor has prescribed.
If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are receiving Prolia. You may need to stop using the medicine for a short time.
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What happens if I miss a dose?
Call your doctor for instructions if you miss an appointment for your Prolia injection.
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What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
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What should I avoid while receiving Prolia?
Follow your doctor's instructions about any restrictions on food, beverages, or activity.
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Prolia side effects
Get emergency medical help if you have any of these signs of an allergic reaction to Prolia: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Serious infections may occur during treatment with Prolia. Call your doctor right away if you have signs of infection such as:
severe itching, burning, rash, or dryness of the skin;
swelling, pain, tenderness, or redness anywhere on your body;
pain or burning when you urinate;
severe stomach cramps, diarrhea, vomiting;
ear pain or drainage, trouble hearing;
fever, chills, night sweats;
cough, feeling short of breath;
pinpoint purple or red spots under your skin; or
flu symptoms, weight loss.
Call your doctor at once if you have a serious side effect such as:
numbness or tingly feeling around your mouth, fast or slow heart rate, muscle tightness or contraction, overactive reflexes; or
severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate.
Less serious Prolia side effects may include:
back pain;
constipation;
pain in your arms or legs; or
muscle or joint pain.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
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What other drugs will affect Prolia?
Tell your doctor about all other medicines you use, especially:
drugs that weaken your immune system (such as cancer medicine or steroids);
cyclosporine (Neoral, Sandimmune, Gengraf);
sirolimus (Rapamune), tacrolimus (Prograf);
basiliximab (Simulect), efalizumab (Raptiva), muromonab-CD3 (Orthoclone);
mycophenolate mofetil (CellCept); or
azathioprine (Imuran), leflunomide (Arava), etanercept (Enbrel).
This list is not complete and other drugs may interact with Prolia. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
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Where can I get more information?
Your doctor or pharmacist can provide more information about Prolia.
Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.