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Xgeva(denosumab)是一种RANK配体(RANKL)抑制剂，由安进公司（Amgen）生产，2010年11月18日批准用于防止已扩散到骨的癌症所造成的骨折，2012年4月26日FDA将会决定是否批准用于预防前列腺癌骨转移。
xgeva（denosumab）注射，皮下使用
最初美国批准：2010
适应症
xgeva是A的秩配体（RANKL）抑制剂，表示为：
预防骨骼相关事件从实体瘤骨转移的患者.
重要的限制：使用Xgeva为预防骨骼相关事件在多发性骨髓瘤患者未标明.
剂量和用法
管理120毫克，每4周皮下注射在上臂，大腿或腹部.
管理作为必要的钙和维生素D，预防或治疗低血钙.
剂型和优势
120 mg/1.7毫升（70毫克/毫升），单次使用的小瓶
禁忌
无
注意事项：
低钙血症：可能会出现严重低钙血症患者接受Xgeva。纠正低血钙开始前Xgeva。监测血钙水平，并适当补充钙和维生素D的所有患者.
可以发生在颚骨坏死患者接受Xgeva。开始Xgeva前进行口腔检查。监测的症状。避免在侵入性牙科手术治疗与Xgeva.
怀孕：可对胎儿造成伤害。提醒女性胎儿的潜在风险
不良反应
在接受Xgeva（每位病人的发病率大于或等于25％）患者最常见的不良反应是疲劳/乏力，低磷血症，恶心.
在1-800-77-AMGEN（1-800-772-6436）或FDA报告疑似不良反应，联系Amgen公司在1-800-FDA-1088或www.fda.gov / medwatch。
在特殊人群中使用
哺乳母亲：停止药物或护理，同时考虑药物对母亲的重要性.
儿科患者：安全性和有效性尚未建立.
肾功能不全：与肌酐清除率小于30 mL / min或接受透析患者在为低钙风险的。适当补充钙和维生素D.
保存：
贮藏在冰箱内在2至8℃(36至46℉)在原始盒内。不要冻结，一旦从冰箱取出，不要暴露在温度25℃/77℉以上或光线，必须在14天内使用。
更新日期：05/2012
XGEVA
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
地诺单抗（denosumab，商品名Xgeva）是一种比唑来膦酸更好的药问世
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。
地诺单抗这一获准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。
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. | 
