英文药名：Cyramza(ramucirumab)

中文药名：雷莫芦单抗注射液

生产厂家：礼来公司
药品介绍
注射用CYRAMZA(雷莫芦单抗[ramucirumab])，为静脉输注
美国初次批准：2014
适应证和用途
CYRAMZATM是一种人血管内皮生长因子受体2(VEGFR2)拮抗剂适用为胃癌的治疗。
⑴ 晚期胃癌或胃-食管结合部腺癌，作为单药既往氟嘧啶-或含铂化疗后。
剂量和给药方法
⑴ 给予8mg/kg静脉每2周。
剂型和规格
⑴ 100mg/10mL (10mg每mL)溶液，单次-剂量小瓶。
⑵ 500mg/50mL (10mg每mL)溶液，单次-剂量小瓶。
禁忌证
无。
警告和注意事项
⑴ 动脉血栓事件(ATEs)：在临床试验中曾报道严重，有时致命性ATEs。对严重ATEs终止CYRAMZA。
⑵ 高血压：监视血压和治疗高血压。对严重高血压暂时不给CYRAMZA。对药物不能控制的高血压终止CYRAMZA。
⑶ 输注相关反应：输注期间监视体征和症状。
⑷ 胃肠道穿孔：终止CYRAMZA。
⑸ 损害伤口愈合：手术前不给CYRAMZA。
⑹ 有肝硬变患者中临床恶化：有Child-Pugh B或C肝硬化患者可能发生脑病，腹水，或肝肾综合征新发病或恶化。
⑺ 可逆性后部白质脑病综合征: 终止CYRAMZA。
不良反应
CYRAMZA-治疗患者观察到发生率≥10%和高于安慰剂≥2%最常见不良反应为高血压和腹泻。
特殊人群中使用
⑴ 妊娠：根据其作用机制，CYRAMZA可能致胎儿危害。
⑵ 哺乳母亲：终止哺乳或终止CYRAMZA。

美国FDA批准ramucirumab用于治疗晚期胃癌
2014年4月21日美国食品药品监督管理局(FDA)批准Cyramza(雷莫芦单抗[ramucirumab])治疗患者有晚期胃癌或胃食管结合部腺癌，位于食管和胃连接区的一种形式癌。
胃癌在胃村里组织中形成和大多数影响老年成人。按照美国国立癌症研究所今年估计22,220 美国人将被诊断有胃癌和10,990 人将死于此病。
Cyramza是一种血管生成抑制剂阻断肿瘤血管供应。意向对不能外科切除癌或被用一种氟嘧啶[fluoropyrimidine]-或含铂治疗后已播散(转移) 的患者。
FDA药物评价和研究中心血液学和肿瘤学产品室主任Richard Pazdur，医学博士说：“尽管在过去四十年在美国胃癌率已下降，患者需要新治疗选择，尤其是当他们对其他治疗不再反应时，”“Cyramza是新治疗选择已证实延长患者生命和减慢肿瘤生长。”
在355 例有不可切除或转移胃或胃食道结合部癌参加者一项临床试验评价Cyramza的安全性和有效性。2/3试验参加者接受Cyramza 而剩余参加者接受安慰剂。试验被设计测量参加者死亡前(总生存)生存时间长度。
结果显示用Cyramza治疗参加者经受中位总生存5.2个月与之比较参加者接受安慰剂为3.8个月。此外，用Cyramza参加者与给予安慰剂参加者比较经受肿瘤生长延迟(无进展生存期)。来自第二个临床试验评价Cyramza加紫杉醇[paclitaxel](另一个抗癌药)相比单独紫杉醇的疗效结果也显示总体活存改善。
Cyramza-治疗参加者在临床试验期间经受Common副作用包括腹泻和高血压。
FDA在其优先审评程序下审评Cyramza，该程序对在申请递交时在一种严重情况安全性或有效性显著改善有潜能药物加快审评。Cyramza还授予孤儿产品指定因为它意向治疗一种罕见疾病或条件。
Cyramza由印第安纳波利斯的礼来公司上市。
完整说明书资料下载：http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477lbl.pdf

Lilly's CYRAMZA™ (ramucirumab) Becomes First FDA-Approved Treatment for Advanced Gastric Cancer After Prior Chemotherapy
Indication for CYRAMZA
CYRAMZA as a single agent is indicated for the treatment of patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
IMPORTANT SAFETY INFORMATION FOR CYRAMZA
WARNING: HEMORRHAGE
CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding.
Warnings and Precautions
Hemorrhage 
•CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. In Study 1, which evaluated CYRAMZA as a single agent in advanced gastric cancer, the incidence of severe bleeding was 3.4% for CYRAMZA and 2.6% for placebo. Patients with gastric cancer receiving nonsteroid anti-inflammatory drugs (NSAIDs) were excluded from enrollment in Study 1; therefore, the risk of gastric hemorrhage in CYRAMZA-treated patients with gastric tumors receiving NSAIDs is unknown. Permanently discontinue CYRAMZA in patients who experience severe bleeding.
Arterial Thromboembolic Events
•Serious, sometimes fatal, arterial thromboembolic events (ATEs) including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia occurred in clinical trials including 1.7% of 236 patients who received CYRAMZA as a single agent for gastric cancer in Study 1. Permanently discontinue CYRAMZA in patients who experience a severe ATE.
Hypertension
•An increased incidence of severe hypertension occurred in patients receiving CYRAMZA as a single agent (8%) as compared to placebo (3%). Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every 2 weeks or more frequently as indicated during treatment. Temporarily suspend CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA if medically significant hypertension cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.
Infusion-Related Reactions
•Prior to the institution of premedication recommendations across clinical trials of CYRAMZA, infusion-related reactions (IRRs) occurred in 6 out of 37 patients (16%), including 2 severe events. The majority of IRRs across trials occurred during or following a first or second CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. Monitor patients during the infusion for signs and symptoms of IRRs in a setting with available resuscitation equipment. Immediately and permanently discontinue CYRAMZA for Grade 3 or 4 IRRs.
Gastrointestinal Perforations
•CYRAMZA is an antiangiogenic therapy that can increase the risk of gastrointestinal perforation, a potentially fatal event. Four of 570 patients (0.7%) who received CYRAMZA as a single agent in clinical trials experienced gastrointestinal perforation. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.
Impaired Wound Healing
•CYRAMZA has not been studied in patients with serious or nonhealing wounds. CYRAMZA is an antiangiogenic therapy with the potential to adversely affect wound healing. Withhold CYRAMZA prior to surgery. Resume CYRAMZA following the surgical intervention based on clinical judgment of adequate wound healing. If a patient develops wound healing complications during therapy, discontinue CYRAMZA until the wound is fully healed.
Clinical Deterioration in Child-Pugh B or C Cirrhosis
•Clinical deterioration, manifested by new onset or worsening encephalopathy, ascites, or hepatorenal syndrome, was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis only if the potential benefits of treatment are judged to outweigh the risks of clinical deterioration. Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
•RPLS has been reported at a rate of <0.1% in clinical studies with CYRAMZA. Confirm the diagnosis of RPLS with MRI and discontinue CYRAMZA in patients who develop RPLS. Symptoms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death.
Most Common Adverse Reactions
•The most commonly reported adverse reactions (all grades) occurring in ≥5% of patients receiving CYRAMZA and ≥2% higher than placebo in Study 1 were hypertension (16% vs 8%), diarrhea (14% vs 9%), headache (9% vs 3%), and hyponatremia (6% vs 2%).
•The most common serious adverse events with CYRAMZA in Study 1 were anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated patients vs 8.7% of patients who received placebo.
•Clinically relevant adverse reactions reported in ≥1% and <5% of CYRAMZA-treated patients in Study 1 were: neutropenia (4.7% vs 0.9%), epistaxis (4.7% vs 0.9%), rash (4.2% vs 1.7%), intestinal obstruction (2.1% vs 0%), and arterial thromboembolic events (1.7% vs 0%).
•Across clinical trials of CYRAMZA administered as a single agent, clinically relevant adverse reactions (including Grade ≥3) reported in CYRAMZA-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions. In Study 1, according to laboratory assessment, 8% of CYRAMZA-treated patients developed proteinuria vs 3% of placebo-treated patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in Study 1 was 0.8% and the rate of infusion-related reactions was 0.4%.
•As with all therapeutic proteins, there is the potential for immunogenicity. In clinical trials, 33/443 (7.4%) CYRAMZA-treated patients with post-baseline serum samples tested positive for anti-ramucirumab antibodies using an enzyme-linked immunosorbent assay (ELISA). However, this assay has limitations in detecting anti-ramucirumab antibodies in the presence of ramucirumab; therefore, the incidence of antibody development may not have been reliably determined. Neutralizing antibodies were detected in 1 of the 33 patients who tested positive for anti-ramucirumab antibodies.
Drug Interactions
•No formal drug interaction studies have been conducted.
Use in Specific Populations
•Pregnancy Category C: Based on its mechanism of action, CYRAMZA may cause fetal harm. Advise females of reproductive potential to avoid getting pregnant, including use of adequate contraception, while receiving CYRAMZA and for at least 3 months after the last dose of CYRAMZA. Animal models link angiogenesis, VEGF and VEGF Receptor 2 to critical aspects of female reproduction, embryofetal development, and postnatal development. There are no adequate or well-controlled studies of ramucirumab in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus.
•Nursing Mothers: It is recommended to discontinue nursing or discontinue CYRAMZA due to the potential risks to the nursing infant.
•Females of Reproductive Potential: Advise females of reproductive potential that CYRAMZA may impair fertility.