FDA近日批准了一种新的骨质疏松治疗药物狄诺塞麦上市，狄诺塞麦为单克隆抗体类生物制剂，对RANK配合体具有靶向性灭活作用。RANK配合体是骨吸收过程中必需的信号物质，狄诺塞麦通过对其的灭活作用而延缓骨吸收进程，从而能有效地降低骨折风险。狄诺塞麦是首个被批准用于骨质疏松症的“生物学疗法”，主要用于预防绝经期妇女骨质疏松相关性骨折。

狄诺塞麦使用人群：
伴有骨质疏松症并处于骨折高风险人群的绝经期女性（如先前有骨质疏松相关性骨折或伴有多种骨折风险因素）；

伴有骨质疏松症且对先前治疗方案无效的患者；

不能耐受其他抗骨质疏松药物治疗的患者。

不同于通过口服或皮肤贴剂而起效的抗骨质疏松药物，狄诺塞麦需要注射使用。不过，该药物的注射周期为6个月，即1年只需要注射2次。

狄诺塞麦临床研究
狄诺塞麦开展了为期3年的随机、双盲、安慰剂对照性临床研究，共选取了7808名60～91岁的绝经期妇女。
 
结果显示，狄诺塞麦治疗组骨折平均发生率为2%，而安慰剂对照组为7%。此外，狄诺塞麦治疗组受试者的骨密度也显著高于安慰剂对照组。因此，狄诺塞麦可有效降低受试者脊柱、髋骨以及其他部位的骨折发生率。其在试验过程中所表现出的对骨折风险性的降低作用也是显而易见的。

由于骨质疏松症发病率很高，已经严重影响到公众的健康，而狄诺塞麦是一个很有潜力的治疗骨质疏松药物，它的上市为骨折高风险的绝经期妇女提供了一种新选择。

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。

1.适应证：
Prolia是一种 RANK配体(RANKL)抑制剂，适用于：治疗有骨质疏松高危骨折的绝经后妇女(1.1)。

2.剂量和给药方法：
1) 应由卫生保健专业人员给予Prolia(2.1)。
2)每6个月在上臂、上大腿、或腹部皮下注射给予60 mg (2.1)。
3)指导患者每天服用钙1000 mg和每天至少400 IU维生素D (2.1)。

3.剂型和规格：
1)单次使用预装注射器在1 mL溶液中含60 mg (3)。
2)单次使用小瓶在1 mL溶液中含60 mg (3)。

4.禁忌证：
4.1低钙血症
预先存在低钙血症必须纠正开始用Prolia治疗前[见警告和注意事项(5.1)].

5. 警告和注意事项：
1)低钙血症：开始用Prolia前必须纠正。特别是肾损伤患者可能恶化。充分补充患者钙和维生素D(5.1)。
2)严重感染包括皮肤感染：可能发生，包括那些导致住院。忠告患者如他们发生感染的征象或症状，包括蜂窝织炎，寻求及时就医(5.2)。
3)皮肤反应：曾报道皮炎、皮疹、和湿疹。如发生严重症状考虑停止Prolia(5.3)。
4)颚骨坏死：用Prolia曾报道。监查症状(5.4)。
5)骨更新抑制：曾显示显著抑制。监查骨过度抑制的后果(5.5)。

6.不良反应：
最常见不良反应(> 5%和比安慰剂更常见)：背痛、四肢疼痛、高胆固醇血症、肌肉骨骼疼痛、和膀胱炎。在临床试验中曾报道胰腺炎

7.在特殊人群中的使用：
妊娠：根据动物资料, 可能引起胎儿损害。可获得妊娠监察计划
哺乳母亲：可能损害乳腺发育和哺乳。停止药物或哺乳
儿童患者：未确定安全性和有效性。
肾损伤：肾损伤患者无需调整剂量。肌酐清除率< 30 mL/min或接受透析患者处在低钙血症风险，补充钙和维生素D和考虑监测血清钙。

【原产地英文药品名】DENOSUMAB
【中文参考商品译名】
注：以下产品不同规格和不同的价格，购买时请以电话咨询为准！
·PROLIA 60毫克/毫升/注射器 4注射器/盒
·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

Prolia(狄诺塞麦denosumab)

Prolia
Generic Name: denosumab (den OH sue mab)
Brand Names: Prolia

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.

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.

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.

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.

What happens if I miss a dose?
Call your doctor for instructions if you miss an appointment for your Prolia injection.

What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving Prolia?
Follow your doctor's instructions about any restrictions on food, beverages, or activity.

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; orflu 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; orsevere 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.

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.

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.