本妥昔单抗冻干粉注射剂Adcetris 50mg(brentuximab vedotin)

药店国别： 产地国家：美国 处方药：是 所属类别： 50毫克/瓶 包装规格： 50毫克/瓶 计价单位：瓶 生产厂家中文参考译名： 生产厂家英文名：SeattleGenetics 原产地英文商品名：ADCETRIS FOR INJECTION 50MG/VIAL 原产地英文药品名：brentuximab vedotin 中文参考商品译名：ADCETRIS冻干粉注射剂 50毫克/瓶 中文参考药品译名：本妥昔单抗

简介

新型抗癌药Adcetris+化疗获FDA扩展批准一线用于III期或IV经典型霍奇金淋巴瘤近日，FDA批准Adcetris(brentuximab vedotin)与化疗联合用于治疗既往未治疗的III或IV期经典型霍奇金淋巴瘤(cHL)成人患者。今天的批准代表了40年前引入晚期霍奇金淋巴瘤初始治疗方案以来的一次改进，FDA药物评价与研究中心血液学及肿瘤学产品办公室代理主任兼FDA肿瘤优化中心主任Pazdur博士称。这次的批准证明了我们在治疗上批准先进产品，为处方医生及患者带来不同治疗选择的承诺。 批准日期：2018年3月20日; 公司：Seattle Genetics, Inc.ADCETRIS(本妥昔单抗[brentuximab vedotin])注射，用于静脉内使用 美国初步批准：2011年 警告：多发性多发性白血病(PML)会出现完整的处方信息以提供完整的装箱警告。在接受ADCETRIS的患者中可能发生导致PML和死亡的JC病毒感染。最近的主要变化适应症和用法，原发性皮肤间变性大细胞淋巴瘤和表达CD30的蕈样肉芽肿。 警告和注意事项 胃肠道并发症 作用机制 CD30是肿瘤坏死因子受体家族的成员。CD30在sALCL细胞表面和cHL中的Hodgkin Reed-Sternberg(HRS)细胞上表达，并且在健康组织和细胞上具有有限的表达。体外数据表明，通过CD30-CD30L结合的信号传导可能影响细胞存活和增殖。Brentuximab vedotin是一种ADC。该抗体是针对CD30的嵌合IgG1。小分子MMAE是一种微管破坏剂。 MMAE通过接头共价连接到抗体上。 非临床数据表明ADCETRIS的抗癌活性归因于ADC与表达CD30的细胞的结合，随后是ADC-CD30复合物的内化以及通过蛋白水解切割释放MMAE。MMAE与微管蛋白的结合破坏细胞内的微管网络，随后诱导细胞周期停滞和细胞的凋亡性死亡。此外，体外数据为抗体依赖性细胞吞噬作用(ADCP)提供了证据。 适应症和用法 ADCETRIS是一种CD30定向的抗体 - 药物偶联物，用于治疗成人患者：作为自体造血干细胞移植(auto-HSCT)巩固后的复发或进展的高风险的古典霍奇金淋巴瘤(cHL)。自体造血干细胞移植失败后或在非自体造血干细胞移植候选患者中至少有两种先前的多药物化疗方案失败后的典型霍奇金淋巴瘤。至少一种先前的多药物化疗方案失败后全身性间变性大细胞淋巴瘤(sALCL)。根据整体回应率，加速批准了sALCL指示。对这种适应症的持续批准可能取决于在验证性试验中对临床获益的验证和描述原发性皮肤间变性大细胞淋巴瘤(pcALCL)或表达CD30的蕈样肉芽肿患者(MF)曾接受过全身治疗。 剂量和给药 每3周仅以30分钟的时间静脉输注。推荐剂量为1.8mg/kg，最高为180mg。减少轻度肝损伤患者的剂量。 剂型和强度用于注射： 在单剂量小瓶中的50mg冻干粉末。 禁忌症 由于肺毒性伴随使用博来霉素。 警告和注意事项 周围神经病：监测患者的神经病变并相应地进行剂量调整。 过敏反应和输液反应：如果输液反应发生，则中断输液。如果发生过敏反应，请立即停止输注。 血液学毒性：在每次剂量的ADCETRIS之前监测全血计数。密切监测患者发热。如果3或4级中性粒细胞减少症发展，考虑剂量延迟，减量，停药或随后剂量的G-CSF预防。 严重感染和机会性感染：密切监测患者是否出现细菌，真菌或病毒感染。 肿瘤溶解综合征：密切监测迅速增殖的肿瘤或高肿瘤负荷的患者。 肝毒性：监测肝酶和胆红素。 肺毒性：监测患者是否出现新的或恶化的症状。 严重的皮肤病反应：如果出现史蒂文斯 - 约翰逊综合征或中毒性表皮坏死松解症，请停止使用。 消化道并发症：监测患者新的或恶化的症状。 胚胎-胎儿毒性：可能导致胎儿伤害。建议女性对胎儿有潜在风险的生殖潜能，并避免怀孕。 不良反应 最常见的不良反应(≥20%)是外周感觉神经病变，疲劳，恶心，腹泻，中性粒细胞减少症，上呼吸道感染和发热。 药物相互作用 伴随使用强CYP3A4抑制剂或诱导剂或P-gp抑制剂有可能影响暴露于单甲基auristatin E(MMAE)。在特定人群中使用中度或重度肝损害或严重肾损害：MMAE暴露和不良反应增加。避免使用。 包装提供/储存和处理提供 用于注射的ADCETRIS(brentuximab vedotin)作为无菌，白色至灰白色不含防腐剂的冻干饼或粉末供应于单独装箱的单剂量小瓶中：50mg brentuximab vedotin。 存储 将瓶保存在2-8°C(36-46°F)的原装纸箱内以免受光照。特殊处理ADCETRIS是一种抗肿瘤产品。 遵循特殊处理和处置程序。

英文版说明书

ADCETRIS IndicationsADCETRIS® (brentuximab vedotin) is indicated for the treatment of:•Previously untreated Stage III/IV classical Hodgkin lymphoma (cHL)Adult patients with previously untreated Stage III/IV cHL in combination with chemotherapy•cHL post-auto-HSCT consolidationAdult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation•Relapsed cHLAdult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates•Relapsed sALCLAdult patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen•Relapsed pcALCL or CD30-expressing MFAdult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapyImportant Safety InformationBOXED WARNINGPROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.Contraindication— ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).Warnings and Precautions— •Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.•Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.•Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Administer G-CSF primary prophylaxis starting with Cycle 1 for previously untreated patients who receive ADCETRIS in combination with chemotherapy for Stage III/IV cHL. Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.•Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.•Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.•Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment. •Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.•Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.•PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.•Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during eva luation and until symptomatic improvement.•Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.•Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic eva luation and treat appropriately.•Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.Adverse Reactions— Most Common (≥20%) Adverse Reactions: Neutropenia, anemia, peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia.Drug Interactions— Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).Use in Specific Populations— Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.