2011年3月25日美国食品与药物管理局（FDA）批准治疗转移性黑瘤素的易普利姆玛注射剂（50mg/10mL，200mg/10mL）于3月25日获FDA批准。Yervoy是一种单克隆抗体，能有效阻断细胞毒性T细胞抗原-4（CTLA-4），半衰期为12天。Yervoy的作用机制可能是帮助人体免疫系统识别、瞄准并攻击黑色素瘤癌细胞。

Yervoy是一种单克隆抗体，已知可阻断细胞毒性T淋巴细胞抗原或CTLA-4等分子。CTLA-4可能在减缓或关闭人体免疫系统中发挥作用，影响免疫系统攻击癌细胞的能力。Yervoy可能通过让机体免疫系统识别、瞄准、攻击黑色素瘤细胞发挥作用。该药物通过经静脉给药。

通过一项纳入676例黑色素瘤患者的国际研究，确立了Yervoy的安全性和有效性。这些患者的疾病已扩散或者无法手术切除。这项研究旨在衡量总生存，从该治疗开始直到患者死亡的时间。经随机分组的患者接受Yervoy加上一种被称为gp100的试验性肿瘤疫苗治疗，或是只接受Yervoy治疗，或是只接受疫苗治疗。那些接受了Yervoy与疫苗组合治疗或者单独使用Yervoy治疗的患者，平均生存时间约10个月，而那些只接受试验性疫苗的患者平均生存时间为6.5个月。

与使用Yervoy相关的自身免疫反应所导致的常见副作用包括疲乏、腹泻、皮疹、内分泌不足（腺体或激素）和肠炎（结肠炎）。严重的、甚至是致命的自身免疫反应可见于12.9%经Yervoy治疗的患者。当发生严重副作用时，应停用Yervoy，并开始皮质类固醇治疗。并非所有患者都对这种治疗产生反应。在某些情况下，有些产生反应的患者在几周时间内也并没有看到任何改善。

由于存在与Yervoy相关的罕见和严重的副作用，该疗法被“风险评估和减低策略”（Risk Evaluation and Mitigation Strategy）批准，以告知医疗专业人员这些严重的风险。药物治疗指南也将同时提供给患者，以告知他们治疗的潜在副作用。

“晚期黑色素瘤是毁灭性的，只有极少的治疗方案可提供给患者，而且以前，这些方案中没有一个能延长患者的生命”，FDA药物评价和研究中心肿瘤药品办公室主任Pazdur博士说。“Yervoy是第一个被FDA批准、并能清楚显示转移性黑色素瘤患者用药后可延长生存时间的治疗方法。”

黑色素瘤是皮肤疾病导致死亡的首要原因。根据美国国家癌症研究所的数据，2010年，在美国，估计有68130例新诊断的黑色素瘤病例，约8700人死于这种疾病。

YERVOYTM（ipilimumab）注射，静脉滴注

最初美国批准：2011

E.R.施贵宝和儿子，L.L.C.

适应症
YERVOY是人类的细胞毒性T淋巴细胞抗原4（CTLA-4）阻断抗体表明为不可切除或转移性黑色素瘤的治疗。
 
剂量和用法
YERVOY 3毫克/千克超过90分钟，每3周静脉注射管理，共有4个剂量。
永久停止对严重不良反应。
 
剂型和优势
50 mg/10毫升（5毫克/毫升）
200 mg/40毫升（5毫克/毫升）
 
禁忌
没有。
 
注意事项：
免疫介导的不良反应：永久停止剧烈反应。隐瞒温和的免疫介导的不良反应的剂量，直到返回到基线，改善轻微的严重性，或完整的决议，和病人接受小于7.5毫克强的松或相当于每天。管理严重，持久，或经常性的免疫介导的反应，全身大剂量的皮质类固醇。

免疫介导的肝炎：评估每个剂量YERVOY前的肝功能化验。
免疫介导的内分泌：监测甲状腺功能试验和临床化学各剂量之前。每次访视评估，内分泌失调的症状和体征。研究所激素替代疗法的需要。
 
不良反应
最常见的不良反应（≥5％），乏力，腹泻，皮肤瘙痒，皮疹，和结肠炎。
 
在特殊人群中使用
妊娠：根据动物实验数据，YERVOY可能会对胎儿造成伤害。
哺乳母亲：终止哺乳或，停止YERVOY。
 
如何供应/贮存和处置

YERVOY可得到以下：

贮存YERVOY在冰箱在2°C至8°C(36°F至46°F)。不要冻结。避光保护小瓶。

日期：03/2011

Yervoy: monoclonal antibody for the treatment of skin cancer
BMS has launched Yervoy (ipilimumab) in the UK for advanced unresectable or metastatic melanoma following prior therapy.

PHARMACOLOGY

Ipilimumab is a fully human monoclonal antibody that indirectly enhances T-cell mediated responses by blocking the inhibitory signal of cytotoxic T-lymphocyte antigen-4 (CTLA-4). This results in T-cell activation, proliferation and lymphocyte infiltration into tumours, leading to tumour cell death.1

CLINICAL STUDIES
A randomised, double-blind, multicentre phase III study (n=676) to establish the efficacy of ipilimumab was conducted using an experimental melanoma peptide vaccine (gp100) as control. Patients with unresectable stage III/IV melanoma were randomised to receive ipilimumab, ipilimumab plus vaccine or vaccine alone (3:1:1). Ipilimumab, alone or in combination with the peptide, produced a significantly longer median overall survival of approximately 10 months compared with 6.4 months for patients receiving gp100 monotherapy (p<0.001). There was no significant difference in overall survival between the two ipilimumab groups.2

The most common adverse events were immune-related reactions, which occurred in approximately 60% of the treatment groups and 32% of the control group. Although ipilimumab-related adverse events can be severe, long-lasting or both, most are reversible with treatment. A total of 14 deaths related to study drugs were reported (with 7 from immune-related adverse events).2

Medication name
Generic name: Ipilimumab - Injection
Pronunciation: (IP-i-LIM-ue-mab)
Brand name(s): Yervoy
Warning
This medication can cause serious (sometimes fatal) side effects in many parts of the body. These effects can occur during treatment with ipilimumab, but can also occur months after the last dose of this medication.Get medical help right away if you experience any of the following serious side effects: diarrhea, mucus or blood in your stool, stomach pain, yellowing of skin/eyes, dark urine, unusual bleeding/bruising, unusual weakness, mouth sores, numbness/tingling in hands/feet, persistent headache, feeling cold all the time, weight gain, mental/mood changes, change in sex drive, unusual change in the amount of urine, dizziness, eye pain/redness, vision changes, fever.
Uses
Ipilimumab is used to treat adults with melanoma (skin cancer) that has spread or cannot be removed by surgery. It works by changing the action of your own immune system, directing it to attack skin cancer cells. Unfortunately, other body parts may also be affected (see Warning section). Ipilimumab is a type of medication called a monoclonal antibody.
How to use
Read the Medication Guide and Patient Wallet Card provided by your pharmacist before you start using ipilimumab and each time you get a refill. If you have any questions, ask your doctor or pharmacist. Carry the Patient Wallet Card with you at all times. Show the card to all of your health care providers to let them know that you are being treated with ipilimumab.This medication is given by injection into a vein by a health care professional. It should be injected slowly over 90 minutes. It is usually given every 3 weeks for up to 4 doses, or as directed by your doctor. The dosage is based on your medical condition, weight and response to treatment.Your doctor may prescribe other medications to help with serious side effects if they occur, or your doctor may delay your dose. If the side effects lessen, then treatment with ipilimumab may continue. The goal is to complete 4 doses of ipilimumab within 16 weeks.Use this medication regularly to get the most benefit from it. It may help to mark your calendar with a reminder.Tell your doctor if your condition does not improve or if it worsens.
Precautions
Before using ipilimumab, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of organ transplant.This medication may worsen certain types of immune system disorders (autoimmune type). Before using this medication, tell your doctor or pharmacist if you have any of the following disorders, among others: certain bowel diseases (Crohn's disease, ulcerative colitis), Guillain-Barre syndrome, lupus, sarcoidosis.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication is not recommended for use during pregnancy. It may harm an unborn baby. Discuss the risks and benefits with your doctor. If you become pregnant or think you may be pregnant, tell your doctor immediately.It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.
Drug interactions
Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
Side effects
See also Warning section.Tiredness, nausea, or vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication have serious side effects.A very serious allergic reaction to this drug is unlikely. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Missed dose
For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule.
Overdose
If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.
Notes
Laboratory and/or medical tests (such as liver function tests, thyroid function test) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
Medical alert
Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (US) or 1-800-668-1507 (Canada).
Storage
Not applicable. This medication is given in a clinic and will not be stored at home.
Photos by medication strength
Click the "Photos" link to see sample photographs for a specific medication strength.
Common strengths
Yervoy 200 mg/40 mL (5 mg/mL) IV

Yervoy 50 mg/10 mL (5 mg/mL) IV

Important note
HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

Information last revised April 2011 Copyright(c) 2011 First DataBank, Inc.

Intravenous
Solution

ipilimumab|
Metastatic Malignant Melanoma|
Selected from NATIONAL DRUG DATA FILE (NDDF) data included with permission and copyrighted by First DataBank, Inc., 2012. This copyrighted material has been downloaded from a licensed data provider.

The above information is intended to supplement, not substitute for, the expertise and judgment of your health care professional. You should consult your health care professional before taking any drug, changing your diet, or commencing or discontinuing any course of treatment.