产地国家：美国 处方药：是 所属类别： 240毫克/片 112片/盒 包装规格： 240毫克/片 112片/盒 计价单位：盒 生产厂家英文名：Genentech, Inc 原产地英文商品名：Zelboraf  240mg/tab  112tabs/bottle 原产地英文药品名：vemurafenib 中文参考商品译名：Zelboraf  240毫克/片 112片/瓶 中文参考药品译名：威罗菲尼

简介：

近日，美国食品和药品监督管理局批准Zelboraf(vemurafenib)上市，本品用于治疗后期(转移)或不可切除黑色素瘤，最危险的皮肤癌类型患者。Zelboraf是特别适用于治疗肿瘤表达基因突变被称BRAFV600E黑色素瘤患者。在用FDA批准的诊断黑色素瘤该突变检验阴性患者中尚未研究药物。FDA的药物评价和研究中心肿瘤药品办公室主任Richard Pazdur, M.D.说“对有后期黑色素瘤患者今年是重要一年。Zelboraf是证实改善总生存的第二个被批准新抗癌药物”。“3月我们批准了Yervoy(ipilimumab)，为后期黑色素瘤另一个新治疗，接受药物后也显示延长患者生存。”批准日期：2011年8月17日 公司：Genentech, IncZELBORAF(威罗菲尼[vemurafenib])片剂用于口服初始美国批准：2011年最近的重大变化适应症和用法，Erdheim-Chester病：11/2017剂量和给药，强CYP3A4诱导剂的剂量修改：04/2017警告和注意事项，新的原发性恶性肿瘤：10/2017警告和注意事项，Dupuytren的挛缩和足底筋膜纤维瘤病：09/2017 作用机制：Vemurafenib是一种低分子量，口服可用的BRAF丝氨酸苏氨酸激酶的突变形式的抑制剂，包括BRAF V600E。因此，Vemurafenib在相似浓度下抑制体外其他激酶如CRAF，ARAF，野生型BRAF，SRMS，ACK1，MAP4K5和FGR。包括V600E在内的BRAF基因中的一些突变导致组成型活化的BRAF蛋白，其可在缺乏通常生长所需的生长因子的情况下引起细胞增殖。Vemurafenib在具有突变的BRAF V600E的黑素瘤的细胞和动物模型中具有抗肿瘤作用。 适应症：ZELBORAF®是一种激酶抑制剂，适用于治疗患有BRAF V600E突变的不可切除或转移性黑色素瘤患者，如FDA批准的检测。ZELBORAF®适用于治疗患有BRAF V600突变的Erdheim-Chester病患者。 使用限制：ZELBORAF不适用于治疗野生型BRAF黑色素瘤患者。 剂量和用量：在开始用ZELBORAF治疗之前，确认肿瘤标本中存在BRAF V600E突变。推荐剂量：960毫克口服，每日两次，间隔约12小时，有或没有用餐。 剂量形式：片剂，240mg 禁忌症：无 警告和注意事项： 新的原发性皮肤恶性肿瘤：在开始治疗前进行皮肤病学评估，在治疗期间每2个月进行一次皮肤病学评估，在停止使用ZELBORAF后进行6个月。切除治疗并继续治疗，无需调整剂量。 新的非皮肤鳞状细胞癌：在开始治疗前和治疗期间定期评估新的非皮肤SCC的症状或临床体征。 其他恶性肿瘤：监测接受ZELBORAF的患者是否接受其他恶性肿瘤的体征或症状。 BRAF野生型黑素瘤中的肿瘤促进：BRAF抑制剂可以增加细胞增殖。 严重的过敏反应：过敏性休克和嗜酸性粒细胞药物不良反应和全身症状(DRESS综合征)：停止Zelboraf严重的过敏反应。 严重的皮肤病反应：Stevens-Johnson综合征和毒性表皮坏死松解症：停止ZELBORAF用于严重的皮肤病反应。 QT延长：在治疗前和治疗期间监测心电图和电解质。保留ZELBORAF的QTc为500 ms或更高。纠正电解质异常并控制QT间期延长的心脏危险因素。 肝毒性：在开始ZELBORAF之前测量肝酶和胆红素，并在治疗期间每月监测一次。 光敏性：建议患者避免阳光照射。 严重的眼科反应：监测葡萄膜炎的体征和症状。 胚胎胎儿毒性：可导致胎儿伤害。告知女性胎儿的潜在风险并使用有效的避孕措施。 辐射敏化和辐射回收：已报告严重病例。 肾功能衰竭：在开始ZELBORAF之前测量血清肌酐并在治疗期间定期监测。 Dupuytren的挛缩和足底纤维瘤病：应通过减少剂量，中断治疗或停止治疗来控制事件。 不良反应：黑色素瘤最常见的不良反应(≥30%)是关节痛，皮疹，脱发，疲劳，光敏性反应，恶心，瘙痒和皮肤乳头状瘤。Erdheim-切斯特疾病：最常见的不良反应(> 50%)是关节痛，皮疹maculo-丘疹，脱发，疲劳，心电图QT间期延长，和皮肤乳头状瘤。 药物相互作用：避免同时使用强力CYP3A4抑制剂或诱导剂给予ZELBORAF。CYP1A2底物：ZELBORAF可以增加CYP1A2底物的浓度。避免同时使用ZELBORAF与CYP1A2底物，治疗窗口狭窄。如果无法避免共同给药，请密切监测毒性并考虑CYP1A2底物的剂量减少。 用于特定人群：哺乳期，服用ZELBORAF时不要母乳喂养。 包装：ZELBORAF(vemurafenib)以240毫克薄膜包衣片供应，其中VEM一侧凹陷。 单瓶120支，单瓶112 储存：在室温20°C-25°C(68°F-77°F)下储存;15°C和30°C(59°F至86°F

英文版说明书：

FDA aproves Zelboraf (vemurafenib) and companion diagnostic for BRAF mutation-positive metastatic melanoma, a deadly form of skin cancerU.S. Food and Drug Administration (FDA) approved Zelboraf (vemurafenib) for the treatment of BRAF V600E mutation-positive, inoperable or metastatic melanoma, as determined by an FDA-approved test.The FDA today also approved the cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche to identify patients eligible for treatment.Zelboraf is the first and only FDA-approved personalized medicine shown to improve survival in people with BRAF V600E mutation-positive metastatic melanoma, demonstrating the benefits of Roche’s personalized healthcare approach. It is designed to target and inhibit some mutated forms of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.“The FDA approval of Zelboraf marks a major step forward in personalizing the treatment of metastatic melanoma, a devastating disease that until this year had limited approved treatment options,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We will continue to study this medicine with a goal of further improving outcomes for people with melanoma and other cancers that are driven by BRAF mutations.”Zelboraf should be used only in people whose inoperable or metastatic melanoma carries a BRAF V600E mutation, which can be determined by the FDA-approved cobas BRAF Mutation Test.“The cobas BRAF Mutation Test has improved sensitivity, accuracy and speed compared to other commonly used, unapproved detection methods,” said Paul Brown, head of Roche Molecular Systems. “With a personalized medicine now available, all people diagnosed with inoperable or metastatic melanoma should be tested to help determine the best options for treatment.”Zelboraf will be available in the United States within two weeks of approval. Roche has also submitted new drug applications for Zelboraf in the EU, Switzerland, Australia, New Zealand, Brazil, India, Mexico and Canada. While Roche seeks regulatory approval of Zelboraf in other countries, a global Expanded Access Program (EAP) is available for people with previously treated or untreated BRAF V600 mutation-positive metastatic melanoma.Zelboraf Efficacy in BRAF V600E Mutation-Positive Metastatic MelanomaThe FDA approval of Zelboraf is based on results from two clinical studies (BRIM3 and BRIM2) in people with BRAF V600E mutation-positive, inoperable or metastatic melanoma as determined by the cobas BRAF Mutation Test.BRIM3 is a global, randomized, open-label, controlled, multicenter, Phase III study that compared Zelboraf to dacarbazine chemotherapy, a standard of care, in 675 patients with previously untreated BRAF V600E mutation-positive, unresectable (inoperable) or metastatic melanoma. The endpoints of BRIM3 were overall survival (OS) and investigator-assessed progression-free survival (PFS). Other endpoints included confirmed investigator-assessed overall response rate. BRIM2 is a global, single-arm, multicenter, open-label Phase II study that enrolled 132 patients with previously treated BRAF V600E mutation-positive, unresectable or metastatic melanoma. The primary endpoint of BRIM2 was confirmed overall response rate as assessed by independent review.BRIM3: Previously Untreated BRAF V600E Mutation-Positive Unresectable or Metastatic MelanomaIn BRIM3, the risk of death was reduced by 56 percent for people who received Zelboraf compared to those who received chemotherapy (hazard ratio [HR]=0.44, p<0.0001). At the time of the analysis, median overall survival of patients receiving Zelboraf had not been reached and was 7.9 months for those receiving chemotherapy.People who received Zelboraf also had a 74 percent reduced risk of the disease getting worse or dying (PFS) compared to those who received chemotherapy (HR=0.26, p<0.0001). Median PFS was 5.3 months for those who received Zelboraf compared to 1.6 months for those who received chemotherapy.The confirmed investigator-assessed response rate (those who experienced tumor shrinkage) in people who received Zelboraf was 48.4 percent (1 percent complete responses and 47.4 percent partial responses) compared to 5.5 percent (partial responses) for those who received chemotherapy (p<0.0001).BRIM2: Previously Treated BRAF V600E Mutation-Positive, Unresectable or Metastatic MelanomaIn BRIM2, Zelboraf shrank tumors in 52 percent of trial participants.Zelboraf safetyThe safety profile of Zelboraf in BRIM3 was generally consistent with that previously reported in prior clinical studies. The most common Grade 3 or higher adverse events seen in more people receiving Zelboraf compared to those receiving chemotherapy were a common type of skin cancer, cutaneous squamous cell carcinoma (cSCC) including keratoacanthomas (18 percent vs. <1 percent), rash, liver function abnormalities, joint pain and sensitivity to the sun. In cases of cSCC, the lesions were generally removed and the patients continued with treatment.The safety profile of Zelboraf in BRIM2 was generally consistent with that observed in the Phase I study. The most common (Grade 3 or greater) adverse events were cSCC (26 percent), abnormal liver function, joint pain/arthritis and rash. In cases of cSCC, the lesions were generally removed and the patients continued with treatment.About Metastatic Melanoma and BRAFWhen melanoma is diagnosed early, it is generally a curable disease. However, when it spreads to other parts of the body, it is the deadliest and most aggressive form of skin cancer. A person with metastatic melanoma typically has on average a short life expectancy that is measured in months. The American Cancer Society estimates there will be more than 70,000 new cases of melanoma and nearly 8,800 melanoma deaths this year in the United States.The BRAF protein is a key component of the RAS-RAF pathway involved in normal cell growth and survival. Mutations that keep the BRAF protein in an active state may cause excessive signaling in the pathway, leading to uncontrolled cell growth and survival. These mutations of the BRAF protein are thought to occur in an estimated half of all melanomas and eight percent of solid tumors.About BRAF V600 Mutation TestingThe cobas 4800 BRAF V600 Mutation Test is a polymerase chain reaction-based diagnostic test developed by Roche. This FDA-approved test was clinically validated in the BRIM2 and BRIM3 studies to identify tumors that carry the BRAF V600E mutation. The test has several advantages compared to Sanger sequencing, a commonly used method, including greater sensitivity and reliability for detecting mutations and quicker results, allowing doctors to know whether a person with metastatic melanoma is eligible for treatment with Zelboraf.About ZelborafZelboraf is an oral, small molecule, kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAF V600E mutation.