2015年4月29日，CYRAMZA在美国FDA获批，与FOLFIRI方案联合用于转移性结直肠癌的二线治疗。这是FDA对于CYRAMZA的第四项批准。目前，Cyramza（ramucirumab注射液10mg/mL溶液）还可联合FOLFIRI（伊立替康、叶酸和5-氟尿嘧啶）化疗用于贝伐单抗、奥沙利铂和氟嘧啶治疗期间或治疗后出现疾病进展的转移性结直肠癌（mCRC）患者。
CYRAMZA（雷莫芦单抗 ramucirumab）注射剂，供静脉内使用
最初美国批准：2014年
警告：
出血，胃肠道穿孔，伤口愈合不良，请参阅完整的黑框警告的完整处方信息。
出血：CYRAMZA增加出血的风险，和胃肠道出血，包括严重的和有时致命的出血事件。在谁的经验严重出血患者永久停止CYRAMZA。
胃肠道穿孔：永久停止CYRAMZA在谁遇到消化道穿孔的患者。
伤口愈合不良：扣压CYRAMZA手术前并停止CYRAMZA如果患者出现伤口愈合并发症
目前的主要变化
适应证和用途
胃癌  11/2014 
非小细胞肺癌  11/2014 
结直肠癌  04/2015
用法与用量：
推荐剂量和日程安排  04/2015
剂量调整  11/2014 
警告和注意事项：
出血  04/2015
高血压  11/2014 
胃肠道穿孔  04/2015
伤口愈合不良  04/2015
含蛋白尿肾病综合征 04/2015
甲状腺功能低下  04/2015
胚胎 - 胎仔毒性  04/2015
作用机理
Ramucirumab是血管内皮生长因子受体2拮抗剂特异性结合VEGF配体，VEGF-A，VEGF-C和VEGF-D的血管内皮生长因子受体2和块结合。其结果是，ramucirumab抑制VEGF受体2的配体刺激活化，由此抑制配体诱导的增殖，和人内皮细胞的迁移。 Ramucirumab在体内动物模型中抑制血管生成。
适应症和用法
CYRAMZA®是人血管内皮生长因子受体2所示拮抗剂
作为单一药剂或与紫杉醇结合，用于治疗晚期胃癌或胃食管交界处腺癌，与上或事先fluoropyrimidine-或含铂化疗​​后疾病进展。
在与多西他赛的组合，用于治疗转移性非小细胞肺癌的上或基于铂的化疗后疾病进展。患者的EGFR或ALK基因组肿瘤像差应具有对之前接收CYRAMZA这些像差FDA批准的治疗疾病的进展。
与FOLFIRI联合，用于治疗转移性结肠直肠癌的与上或与贝伐单抗，奥沙利铂，和一个氟嘧啶现有治疗后疾病恶化。
用法用量
静脉滴注只。不要给予作为静脉推或推注。
胃癌
CYRAMZA的作为单一药剂或与紫杉醇组合的推荐剂量是8毫克/公斤，每2个星期。
非小细胞肺癌
在10毫克管理CYRAMZA / kg静脉注射于前多西他赛注射21天周期的第一天。
大肠癌
在8毫克/ kg静脉注射，每2周，FOLFIRI给药前管理CYRAMZA。
剂型和规格
注射：
100毫克/ 10毫升（每毫升10毫克）溶液中，单剂量小瓶
500毫克/ 50毫升（每毫升10毫克）溶液中，单剂量小瓶
禁忌症
无
警告和注意事项
动脉血栓栓塞事件（的ATE）：严重，有时甚至是致命的ATE已经报道了在临床试验中。停止CYRAMZA严重的ATE。
高血压：监测血压和治疗高血压。暂停CYRAMZA了严重的高血压。停止CYRAMZA对于无法控制医疗高血压。
与输液有关的反应：监测输液过程中的症状和体征。
伤口愈合不良：扣压CYRAMZA手术前。
患者临床恶化肝硬化：新发或加重的脑病，腹水，或肝肾综合征患者可出现与Child-Pugh分级B或C级肝硬化。
可逆性后部白质脑病综合征：请停止CYRAMZA。
蛋白尿包括肾病综合征：监视蛋白尿。中断CYRAMZA的尿蛋白含量≥2克/ 24小时。永久停止CYRAMZA尿蛋白水平“3克/24小时或为肾病综合征。
甲状腺功能异常：有CYRAMZA治疗期间监测甲状腺功能。
胚胎 - 胎仔风险：可引起胎儿造成伤害。
不良反应
在高于安慰剂≥10％和≥2％的速率在单一试剂CYRAMZA治疗的患者中观察到的最常见的不良反应是高血压和腹泻。
在患者中观察到的最常见的不良反应有CYRAMZA加紫杉醇的≥30％，比安慰剂+紫杉醇为乏力，中性粒细胞减少，腹泻，鼻衄和提高≥2％的速度处理。
在比安慰剂加上多西他赛为白细胞减少，疲劳/虚弱，和口腔炎/粘膜炎症更高≥30％和≥2％的速度与CYRAMZA加多西他赛治疗的患者中观察到的最常见的不良反应。
在≥30％和高于安慰剂≥2％的速度加FOLFIRI与CYRAMZA加FOLFIRI治疗的患者中观察到的最常见的不良反应为腹泻，白细胞减少，食欲减退，鼻衄，口腔炎。
要报告疑似不良反应，请联系礼来公司1-800-LillyRx（1-800-545-5979）或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。
特殊人群中使用
哺乳期：不建议母乳喂养。

CYRAMZA(Ramucirumab)injection
Generic Name: ramucirumab
Dosage Form: intravenous infusion
Ramucirumab is the generic name for the trade name CYRAMZA™.
Drug type:
CYRAMZA™ is a monoclonal antibody, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Inhibitor.
What this drug is used for:
•Treatment of advanced gastric cancer or gastro-esophageal junction adenocarcinoma.
•Non-small cell Lung cancer
•Metastatic Colorectal cancer
Note:
If a drug has been approved for one use, physicians sometimes elect to use this same drug for other problems if they believe it might be helpful.
How this drug is given:
•As an infusion into a vein (intravenous, IV) every 2 weeks.
•Medications may be given just before the infusion to reduce the occurrence of infusion-related symptoms.
•There is no pill form of CYRAMZA™.
•The amount of this medication you will receive depends on many other factors, including your weight and your general health or other health problems. Your doctor will determine your dosage and schedule.
Side effects:
Important things to remember about the side effects of CYRAMZA™:
•Most people do not experience all of the side effects listed.
•Side effects are often predictable in terms of their onset and duration.
•Side effects are almost always reversible and will go away after treatment is complete.
•There are many options to help minimize or prevent side effects.
•There is no relationship between the presence or severity of side effects and the effectiveness of the medication.
The following are possible side effects (occurring in about 10-29%) of patients receiving CYRAMZA™:
•High blood pressure
•Diarrhea
•Headache
A serious but rare side effect of CYRAMZA™ is an increase in the risk of bleeding. Contact your health care provider if any unusual bleeding occurs or if you experience any symptoms of bleeding including lightheadedness, coughing up blood-tinged sputum, nose bleed, or blood in your urine.
Other rare but serious side effects:
•Arterial Thromboembolic Events (blood clots)
•Infusion Related Reaction
•Gastrointestinal perforation
•Impaired Wound Healing
•Clinical Deterioration in Patients with Cirrhosis
•Reversible Posterior Leukoencephalopathy Syndrome
If you have questions about this information ask your health care provider
Not all side effects are listed above. Some that are uncommon are not listed here. You should always inform your health care provider if you experience any unusual symptoms.
When to contact your doctor:
Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:
•Fever of 100.4° F (38° C) or chills (possible signs of infection)
•Shortness of breath, chest pain or discomfort; swelling of your lips or throat
•Any unusual bleeding occurs or any symptoms of bleeding including lightheadedness, coughing up blood-tinged sputum, nose bleed, or blood in your urine.
The following symptoms require medical attention, but are not emergency situations. Contact your health care provider within 24 hours of noticing any of the following:
•Rise in blood pressure or symptoms of high blood pressure such as headache, lightheadedness, visual changes, etc.
•A rash
•Diarrhea (4-6 episodes in a 24-hour period).
•Nausea (interferes with ability to eat and unrelieved with prescribed medication).
•Vomiting (vomiting more than 4-5 times in a 24 hour period).
•Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decrease amount of urine, or dizziness.
•Decreased appetite
•Cough with or without mucus
•Other signs of infection, such as sore throat, pain with urination
Always inform your health care provider if you experience any unusual symptoms.
Precautions:
•Before starting CYRAMZA™treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).
•Do not receive any kind of immunization or vaccination without your doctor's approval while taking CYRAMZA™.
•Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category C (CYRAMZA™ may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus.)
•For both men and women: Do not conceive a child (get pregnant) while taking CYRAMZA™. Barrier methods of contraception, such as condoms, are recommended during treatment and for 3 months after stopping the treatment. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
•Do not breast feed while taking this medication.
Self Care Tips:
•CYRAMZA™ may cause temporary low blood pressure. If you are taking medication to reduce your blood pressure, check with your doctor or nurse as to whether you should take it as usual or not before the infusion.
•You may experience shortness of breath, feel flushed or dizzy during the infusion. You will most likely receive medication before the infusion, and you will be closely monitored during the infusion.
•For flu-like symptoms, keep warm with blankets and drink plenty of liquids. There are medications that can help reduce the discomfort caused by chills.
•Drink 2 to 3 quarts of fluid for the first 48 hours after each infusion, unless you were told to restrict your fluid intake.
•This medication infrequently causes nausea. But if you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals. Sucking on lozenges and chewing gum may also help.
•You may experience drowsiness or dizziness; avoid driving or engaging in tasks that require alertness until your response to the drug is known.
•In general, drinking alcoholic beverages should be avoided. You should discuss this with your doctor.
•Maintain good nutrition.
•If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.
Monitoring and testing:
You will be checked regularly by your health care provider while you are taking CYRAMZA™, to monitor side effects and check your response to therapy. Your blood pressure will be monitored routinely as high blood pressure may be a side effect of CYRAMZA™.
How this drug works:
CYRAMZA™ is classified as a monoclonal antibody. Monoclonal antibodies are a relatively new type of "targeted" cancer therapy.
Antibodies are an integral part of the body's immune system. Normally, the body creates antibodies in response to an antigen (such as a protein in a germ) that has entered the body. The antibodies attach to the antigen in order to mark it for destruction by the immune system.
To make anti-cancer monoclonal antibodies in the laboratory, scientists analyze specific antigens on the surface of cancer cells (the targets). Then, using animal and human proteins, they create a specific antibody that will attach to the target antigen on the cancer cells. When given to the patient, these monoclonal antibodies will attach to matching antigens like a key fits a lock.
Since monoclonal antibodies target only specific cells, they may cause less toxicity to healthy cells. Monoclonal antibody therapy is usually given only for cancers in which antigens (and the respective antibodies) have been identified already.
CYRAMZA™ is a monoclonal antibody that works by targeting and binding with the vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks the activation of VEGF.
When VEGF is overexpressed, it can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply; cancers that can express VEGF are able to grow and metastasize. Drugs such as CYRAMZA™ can inhibit VEGF and control or slow down tumor growth by decreasing the blood supply to the tumor.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6080942-dee6-423e-b688-1272c2ae90d4
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产地国家：美国
原产地英文商品名:
CYRAMZA INJECTION 500mg/50mL(10mg/mL)/vials
原产地英文药品名:
ramucirumab
中文参考商品译名:
CYRAMZA注射液 500毫克/50毫升(10毫克/毫升)/瓶
中文参考药品译名:
雷莫芦单抗
生产厂家中文参考译名:
礼来公司
生产厂家英文名:
Eli Lilly
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产地国家：美国
原产地英文商品名:
CYRAMZA INJECTION  100mg/10mL(10mg/mL)/vials
原产地英文药品名:
ramucirumab
中文参考商品译名:
CYRAMZA注射液 100毫克/10毫升(10毫克/毫升)/瓶
中文参考药品译名:
雷莫芦单抗
生产厂家中文参考译名:
礼来公司
生产厂家英文名:
Eli Lilly