维耐托克，维耐托克Venclexta Tablets 120x100mg(venetoclax abt-199)

药店国别：无 产地国家：美国 处方药：是 所属类别： 100毫克/片 120片/瓶 包装规格： 100毫克/片 120片/瓶 计价单位：瓶 生产厂家中文参考译名：无 生产厂家英文名：ABBVIE US LLC 原产地英文商品名：VENCLEXTA 100MG BTL 120/EA 原产地英文药品名：VENETOCLAX 中文参考商品译名：VENCLEXTA 100毫克/片 120片/瓶 中文参考药品译名：VENETOCLAX 曾用名：ABT-199

简介

近日，新型抗癌药Venclexta（venetoclax）获FDA批准为首个靶向BCl-2蛋白（急性骨髓性白血病）的药物，是一种每日一次的口服的突破性白血病新药Venclexta是第一个靶向B-细胞淋巴瘤2(BCL-2)蛋白被FDA-批准治疗。 FDA的药品评价和研究中心中血液学和肿瘤室主任Richard Pazdur 说： “这些患者现有一种新，抑制涉及保持肿瘤细胞存活蛋白的靶向治疗，” “对某些用其他治疗没有有利结局的CLL有患者，Venclexta对他们的特殊情况可能提供一个新选择。 ” 突破性治疗，优先审评，加速批准和孤儿药物 批准日期：2016年4月11日 公司：艾伯维与基因泰克公司VENCLEXTA（venetoclax片剂）用于口服 美国最初批准：2016年 最近的重大变化适应症和用法，CLL：05/2019 适应症和用法，AML：11/2018 剂量和用药：05/2019 警告和注意事项，中性粒细胞减少症：11/2018 警告和注意事项，感染：05/2019 作用机制 Venetoclax是一种选择性和口服生物可利用的小分子抑制剂BCL-2，一种抗凋亡蛋白。已经在CLL和AML细胞中证实了BCL-2的过表达，其中它介导肿瘤细胞存活并且与抗性化学治疗相关。 Venetoclax通过直接结合BCL-2蛋白，取代促凋亡蛋白如BIM，触发线粒体外膜透化和半胱氨酸蛋白酶激活，帮助恢复细胞凋亡过程。在非临床研究中，venetoclax在过度表达BCL-2的肿瘤细胞中表现出细胞毒活性。 适应症和用法 VENCLEXTA是一种BCL-2抑制剂，表明： •用于治疗慢性淋巴细胞白血病（CLL）或小淋巴细胞淋巴瘤（SLL）的成年患者。 •与阿扎胞苷或地西他滨或低剂量阿糖胞苷联合用于治疗75岁或以上成人的新诊断的急性髓细胞白血病（AML），或合并症，不能使用强化诱导化疗。 该指示根据响应率在加速批准下获得批准。持续批准该适应症可能取决于确证试验中的临床益处的验证和描述。 剂量和给药 •有关推荐的VENCLEXTA起始剂量和加速剂量，请参阅完整处方信息。 •VENCLEXTA片剂应每日口服一次，用餐和水。不要咀嚼，压碎或破坏药片。 •对肿瘤溶解综合征进行预防。 剂量形式和强度片剂：10mg，50mg，100mg 禁忌症 CLL/SLL患者在开始和缓慢期间同时使用强CYP3A抑制剂是禁忌的。 警告和注意事项 •肿瘤裂解综合症（TLS）：预期TLS;评估所有患者的风险。预防抗高尿酸血症并确保充足的水合作用。随着整体风险的增加，采取更加密集的措施（静脉补液，频繁监测，住院治疗）。 •中性粒细胞减少症：监测血细胞计数和感染迹象;管理适当的。 •感染：监测感染的体征和症状，及时治疗。对3级及以上感染进行治疗，直至消退。 •免疫接种：在VENCLEXTA治疗之前，期间或之后不要使用减毒活疫苗。 •胚胎 - 胎儿毒性：可能导致胚胎 - 胎儿伤害。 建议女性对胎儿的潜在风险具有生殖潜力，并在治疗期间使用有效的感染。 不良反应 在CLL/SLL中，与obinutuzumab或利妥昔单抗或asmonotherapy联合给予VENCLEXTA时最常见的不良反应（≥20％）是中性粒细胞减少，血小板减少，贫血，腹泻，恶心，上呼吸道感染，咳嗽，肌肉骨骼疼痛，疲劳，水肿。 在AML中，与盐酸阿扎胞苷或地西他滨或低剂量阿糖胞苷联合使用时最常见的不良反应（≥30％）为恶心，腹泻，血小板减少，便秘，中性粒细胞减少，发热性中性粒细胞减少，疲劳，呕吐，外周性水肿，发热，肺炎，呼吸困难，出血，贫血，皮疹，腹痛，败血症，背痛，肌痛，头晕，咳嗽，口咽疼痛和低血压。 药物相互作用 •强或中等CYP3A抑制剂或P-gp抑制剂：调整VENCLEXTA的剂量。 •强或中等CYP3A诱导剂：避免共同给药。 •P-gp底物：在VENCLEXTA之前至少服用6小时。用于特定人群 •哺乳期：建议女性不要母乳喂养。 包装提供/存储和处理 VENCLEXTA分配如下包装 片剂 NDC 每包含四个每周泡罩包装： •第1周（14x10mg片剂）CLL/SLL混合片 •第2周（7x50mg片剂） 0074-0579-28 •第3周（7x100mg片剂） •第4周（14x100mg片剂） 包含10毫克片剂 14x10毫克片剂 0074-0561-14包含50毫克片剂 7x50毫克片剂 0074-0566-07单位剂量含10 2x10毫克片剂 0074-0561-11毫克片剂单位剂量含50 1x50毫克片剂 0074-0566-11毫克片剂单位剂量含100 1x100毫克片剂 0074-0576-11毫克片剂100毫克片剂的瓶 120x100毫克片剂 0074-0576-22100毫克片剂的瓶 180x100毫克片剂 0074-0576-34VENCLEXTA 10毫克薄膜包衣片呈圆形，双凸形，浅黄色，一侧有“V”，另一侧有“10”。VENCLEXTA 50毫克薄膜包衣片呈椭圆形，双凸形，米色凹陷，一侧为“V”，另一侧为“50”。VENCLEXTA 100毫克薄膜包衣片呈椭圆形，双凸形，浅黄色凹陷，一侧为“V”，另一侧为“100”。储存温度为86°F（30°C）或以下。

英文版说明

(venetoclax tablets) for oral useInitial U.S. Approval: 2016Important Safety Information & UsesImportant Safety InformationContraindicationConcomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).Tumor Lysis SyndromeTumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients with high tumor burden when treated with VENCLEXTA.In patients with CLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL monotherapy studies. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab. With a 2 to 3 week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.VENCLEXTA poses a risk for TLS at initiation and during the ramp-up phase. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase.Patients should be assessed for TLS risk, including eva luation of tumor burden and comorbidities, and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Reduced renal function further increases the risk. Monitor blood chemistries and manage abnormalities promptly. Interrupt dosing if needed. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases.Concomitant use of VENCLEXTA with strong or moderate CYP3A inhibitors or P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase, and requires dose adjustment due to increases in VENCLEXTA exposure.NeutropeniaIn patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients treated with VENCLEXTA in combination and monotherapy studies.In patients with AML, baseline neutrophil counts worsened in 97% to 100% of patients treated with VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine. Neutropenia can recur with subsequent cycles of therapy.Monitor complete blood counts throughout the treatment period. Interrupt dosing or reduce dose for severe neutropenia. Consider supportive measures including antimicrobials for signs of infection and use of growth factors (e.g.G-CSF).InfectionsFatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients closely for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and higher infection.ImmunizationDo not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be less effective.Embryo-Fetal ToxicityVENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment.Adverse ReactionsIn patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%).In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%) were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and cough (22%).In patients with AML receiving combination therapy with azacitidine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome. The most common adverse reactions (≥30%) of any grade were nausea (58%), diarrhea (54%), constipation (49%), neutropenia (49%), thrombocytopenia (49%), hemorrhage (46%), peripheral edema (46%), vomiting (40%), fatigue (36%), febrile neutropenia (36%), rash (33%), and anemia (30%).In patients with AML receiving combination therapy with decitabine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia, sepsis (excluding fungal), pneumonia (excluding fungal), diarrhea, fatigue, cellulitis, and localized infection. The most common adverse reactions (≥30%) of any grade were febrile neutropenia (69%), constipation (62%), fatigue (62%), thrombocytopenia (54%), abdominal pain (46%), dizziness (46%), hemorrhage (46%), nausea (46%), pneumonia (excluding fungal) (46%), sepsis (excluding fungal) (46%), cough (38%), diarrhea (38%), neutropenia (38%), back pain (31%), hypotension (31%), myalgia (31%), oropharyngeal pain (31%), peripheral edema (31%), pyrexia (31%), and rash (31%).In patients with AML receiving combination therapy with low-dose cytarabine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection. The most common adverse reactions (≥30%) of any grade were nausea (64%), thrombocytopenia (59%), hemorrhage (49%), febrile neutropenia (46%), neutropenia (46%), diarrhea (44%), fatigue (44%), constipation (33%), and dyspnea (31%).Drug InteractionsConcomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Adjust VENCLEXTA dosage and closely monitor patients for signs of VENCLEXTA toxicities. Resume the VENCLEXTA dosage that was used prior to concomitant use of a strong or moderate CYP3A inhibitor or a P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor.Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A.Avoid concomitant use of strong or moderate CYP3A inducers.Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA.Monitor international normalized ratio (INR) closely in patients receiving warfarin.LactationAdvise nursing women to discontinue breastfeeding during treatment with VENCLEXTA.Females and Males of Reproductive PotentialAdvise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for at least 30 days after the last dose.Based on findings in animals, male fertility may be compromised by treatment with VENCLEXTA.