英文药名：Xgeva(denosumab)

中文药名：地诺单抗注射剂

品牌药生产商：Amgen Inc

药品介绍

美国FDA于 11月19日批准地诺单抗（denosumab，商品名Xgeva）用以预防癌症已经转移并且损害骨质的肿瘤患者骨骼相关事件（SREs）。所谓骨骼相关事件包括癌症所致骨折和疼痛。

FDA批准地诺单抗预防癌症相关骨损伤

美国FDA于 11月19日批准地诺单抗（denosumab，商品名Xgeva）用以预防癌症已经转移并且损害骨质的肿瘤患者骨骼相关事件（SREs）。所谓骨骼相关事件包括癌症所致骨折和疼痛。适用人群不包括多发性骨髓瘤或其它血癌患者。

骨转移是癌症患者疼痛和难受的重要原因，影响患者的生活质量。地诺单抗具有与现已获准的减少肿瘤骨骼并发症药物不同的作用机制。

三项随机-双盲的临床研究证实了地诺单抗的安全性和疗效，总共有5723名患者参与研究。这些研究在乳腺癌（研究1）、前列腺癌（研究2）以及多种其它癌症（研究3）患者身上对地诺单抗与唑来膦酸作了比较。

这些研究旨在测定由于癌症，患者最终出现骨折或脊髓压迫，或为控制疼痛需要进行放射或手术治疗间隔的时间。

在乳腺癌或前列腺癌患者中，地诺单抗延迟SREs优于唑来膦酸。前列腺癌患者中SREs延迟时间中位值21个月，唑来膦酸为17个月。乳腺癌患者唑来膦酸使SREs延迟的中位时间为26个月，而地诺单抗没有达到这一水平。

在其它实体瘤患者中，地诺单抗和唑来膦酸使SREs延迟的中位时间不相上下。受试者主要的实体瘤为非小细胞肺癌、多发性骨髓瘤、肾癌以及小细胞肺癌。

地诺单抗最严重的不良反应为低钙血症和颚骨坏死。

今年6月1日FDA批准注射用地诺单抗（denosumab）治疗有高骨折风险的绝经后妇女骨质疏松症，其所用商品名Prolia

批准日期：2010年11月18日；公司：Amgen Inc.

适应证和用途
Xgeva是一种RANK配体(RANKL)抑制剂适用于：
（1）在有实体瘤骨转移患者中骨骼相关事件的预防
使用的重要限制：Xgeva不适用于在多发性骨髓瘤患者中为预防骨骼相关事件

剂量和给药方法
（1）在上臂，上大腿，或腹部皮下注射给予120 mg每4周1次
（2）当需要治疗或预防低钙血症给予钙和维生素D

剂型和规格
（1）120 mg/1.7 mL(70 mg/mL)单次使用小瓶

禁忌证
（1）无

警告和注意事项
（1）接受Xgeva患者中可能发生低钙血症，严重低钙血症。开始Xgeva前纠正低钙血症。监视钙水平和用钙和维生素D适当补充所有患者
（2）接受Xgeva患者中可能发生颚骨坏死。开始Xgeva前进行口腔检查。监视症状。用Xgeva治疗期间避免侵害性牙科手术

不良反应
（1）接受Xgeva患者中最常见不良反应(每例-患者发生率大于或等于25%)是疲劳/虚弱, 低磷酸盐血症,和恶心

为报告怀疑的不良反应，联系Amgen Inc. 公司电话1-800-77-AMGEN(1-800-772-6436)或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.

特殊人群中使用
（1）妊娠：根据动物资料，可能引起胎儿损害。可供利用妊娠监察计划
（2）哺乳母亲：乳腺发育和哺乳可能受损。终止药物或哺乳
（3）儿童患者：未确定安慰性和有效性
（4）肾受损：患者with肌酐清除率低于30 mL/min或接受透析是低钙血症风险。适当补充钙和维生素D

如何供应/贮藏和处理

Xgeva是在单次使用小瓶中供应。

120 mg/1.7 mL     每盒1小瓶    NDC 55513-730-01

贮藏Xgeva在冰箱内在2°C至8°C(36°F至46°F)在原始盒内。不要冻结，一旦从冰箱取出，Xgeva必须不要暴露在温度25°C/77°F以上或直接光线和必须在14天内使用。遗弃Xgeva在14天未使用者。不要用标签有效日期后过期的Xgeva。
 
保护Xgeva避光和热。

避免剧烈震动Xgeva。

Xgeva: osteoclast-targeting agent for malignant fractures
30 August 2011, 9:26am
Xgeva (denosumab) has been launched for the prevention of skeletal events due to bone metastases from solid tumours.

Subcutaneous injection to prevent skeletal events
Denosumab is a fully human monoclonal antibody specific for the RANK ligand, which is essential for the differentiation, function and survival of osteoclasts. Denosumab is already licensed as Prolia to treat bone loss in postmenopausal women and in men with prostate cancer.

Three randomised, double-blind studies assessed the capacity of denosumab, given as a 120mg subcutaneous injection every four weeks, to prevent events such as pathological fracture and spinal cord compression in 5723 patients with advanced malignancies. The studies enrolled patients with breast cancer, prostate cancer, and other solid tumours or multiple myeloma.

Compared with zoledronic acid, denosumab increased the median time to the first skeletal-related event by 8.2 months (from 19.4 months to 27.6 months; p<0.0001). Overall survival and time to pain improvement were similar for the two agents.
Manufacturer:
Amgen, Inc.

Pharmacological Class:
Osteoclast inhibitor (RANKL inhibitor)

Active Ingredient(s):
Denosumab 120mg/vial (70mg/mL); soln for SC inj; preservative-free.
Indication(s):
Prevention of skeletal-related events (SRE) in patients with bone metastases from solid tumors. Not for preventing SRE with multiple myeloma.

Pharmacology:
In patients with solid tumors with osseous metastases, an increase in osteoclast activity is a mediator of bone pathology. This increased osteoclast activity is stimulated by a substance called receptor activator of nuclear factor kappa-B ligand, or RANKL. Denosumab is a monoclonal antibody that binds to human RANKL. It prevents RANKL from interacting with its receptors on the surfaces of osteoclasts and their precursors, thereby inhibiting osteoclast formation, function, and survival.

Clinical Trials:
The safety and efficacy of Xgeva in the prevention of skeletal-related events (eg, pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression) in patients with bone metastases from solid tumors were evaluated in three randomized, double-blind, active-controlled trials that compared this drug to zoledronic acid. In each trial, the main outcome measure was to show noninferiority of time-to-first skeletal-related event (SRE) with denosumab as compared to zoledronic acid. If primary endpoint (noninferiority) was reached, secondary endpoints for Time to First SRE and Time to First and Subsequent SRE were tested for superiority.

Trial 1 enrolled patients with advanced breast cancer and bone metastasis. Trial 2 enrolled adults with bone metastasis from solid tumors, other than prostate or breast cancer, or with multiple myeloma. Trial 3 enrolled patients with castrate-resistant prostate cancer and bone metastasis.

Xgeva delayed the time to first SRE following randomization as compared to zoledronic acid in patients with breast or castrate-resistant prostate cancer with osseous metastases. In patients with bone metastasis due to other solid tumors or lytic lesions due to multiple myeloma, Xgeva was noninferior to zoledronic acid in delaying time to first SRE after randomization.

Overall survival and progression-free survival were similar between arms in all three trials, but mortality was higher with Xgeva in a subgroup of patients with multiple myeloma; therefore, it should not be used in these patients.

Legal Classification:
Rx

Adults:
Give by SC inj into upper arm, upper thigh, or abdomen. 120mg once every 4 weeks.

Children:
Not recommended (interferes with bone growth and dentition).

Warnings/Precautions:
Correct hypocalcemia before starting; ensure adequate daily calcium, magnesium, and Vit.D intake, esp. in renal impairment (CrCl<30mL/min). Monitor calcium, phosphorus, magnesium levels in susceptible patients (eg, severe renal impairment, receiving dialysis). Monitor for osteonecrosis of the jaw. Do baseline oral exam and preventive dentistry before and regularly during therapy. Maintain good oral hygiene. Avoid invasive dental procedures during treatment. Pregnancy (Cat.C). Nursing mothers: avoid (may impair mammary gland development/lactation).

Interaction(s):
Concomitant drugs that can lower calcium levels; monitor.

Adverse Reaction(s):
Fatigue, asthenia, hypophosphatemia, GI upset, dyspnea, osteonecrosis of jaw, severe hypocalcemia.

Notes:
Encourage women who become pregnant during Xgeva treatment to enroll in Amgen’s Pregnancy Surveillance program. To enroll call (800) 77-AMGEN.

How Supplied:
Single-use vial (1.7mL)—1

Last Updated:
8/12/2011