Venclexta(Venetoclax Tablets)获FDA批准为突破性白血病新药 近日，美国食品和药物管理局（FDA）已批准Venclexta单药治疗携带17p删除突变（del 17p）以及之前已接受至少一种疗法的慢性淋巴细胞白血病（CLL）患者。Venclexta是一种每日一次的口服药物，适用于采用FDA批准的一款伴随诊断试剂盒Vysis CLL FISH探针试剂盒（雅培生产）确认为存在17p删除突变的CLL患者。 Venclexta是FDA批准的首个B细胞淋巴瘤因子-2（BCL-2）抑制剂，之前FDA已授予其突破性药物认定、优先审查资格、加速审批资格。 Venclexta已获FDA3个突破性药物资格。BCL-2蛋白支持癌细胞的生长，并且在许多CLL患者中过度表达，代表着血液癌症治疗的一个新靶标。Venclexta能够帮助恢复让白血病细胞自我毁灭的自然过程，代表着预后极差且治疗选择十分有限的17p删除突变CLL患者群体中的一种新的治疗方式。 批准日期：2016年4月12日 公司：AbbVie/Roche VENCLEXTA™(venetoclax)片，为口服使用 美国初次批准：2016 作用机制 Venetoclax是BCL-2，一种抗凋亡蛋白的选择性和一种口服生物可利用小-分子抑制剂。曽证实在CLL细胞中BCL-2的过表达，它介导肿瘤细胞生存和被伴随对化疗抗力。Venetoclax通过与BCL-2蛋白直接结合帮助恢复凋亡过程，取代促凋亡蛋白像BIM，触发线粒体外膜通透化和半胱氨酸蛋白酶[caspases]的激活，在非临床研究中，venetoclax曽显示对过表达BCL-2肿瘤细胞细胞毒活性。 适应证和用途 VENCLEXTA是一种BCL-2抑制剂适用为有慢性淋巴细胞性白血病(CLL)通过一个FDA批准测试检测有17p缺失患者的治疗，患者曽接受至少一种以前治疗。 这个适应证是在加快批准下根据总体反应率批准的。继续批准这个适应证可能取决于在验证性试验中证实和临床获益的描述。 剂量和给药方法 ⑴用VENCLEXTA在20 mg每天1次共7天初始治疗，接着通过一个每周启动给药时间表至推荐的每天剂量400 mg。 ⑵VENCLEXTA片应被与一个餐和水口服每天1次。不要不要咀嚼，压碎或破坏片。 ⑶进行对肿瘤溶解综合证预防。 剂型和规格 片：10mg，50mg，100mg 禁忌证 禁忌VENCLEXTA与CYP3A的强抑制剂在初始和启动阶段时同时使用。 警告和注意事项 ⑴ 肿瘤溶解综合证(TLS)：期望TLS：在所有患者评估风险。用抗-高尿酸血症药物预先给药和确保适当水化。 当总体风险增加应用更强措施(静脉水化，频繁监视，住院)。 ⑵中性粒细胞减少：监视血细胞计数和感染的体征：处置如医学上适当。 ⑶免疫接种：VENCLEXTA治疗前，期间，或后不要给予减毒活疫苗。 ⑷胚胎-胎儿毒性：可能致胚胎-胎儿危害。忠告生殖潜能女性对胎儿潜在风险和治疗期间使用有效避孕。 不良反应 最常见不良反应(≥20%)为中性粒细胞减少，腹泻，恶心，贫血，上呼吸道感染，血小板减少,和疲乏。 药物相互作用 ⑴避免VENCLEXTA与中度CYP3A抑制剂，强或中度CYP3A诱导剂，P-gp抑制剂，或狭窄治疗指数P-gp底物的同时使用。 ⑵如必须使用一种中度CYP3A抑制剂或一种P-gp抑制剂，减低VENCLEXTA剂量至少50%。 ⑶如启动阶段后必须使用一种强CYP3A抑制剂，减低VENCLEXTA剂量至少75%。 如必须使用一种狭窄治疗指数P-gp底物，它应在VENCLEXTA前至少6小时前使用。 特殊人群中使用 哺乳：终止哺乳喂养。 包装规格/储存 VENCLEXTA被分配如下： 开始包每包包含四个每周钱包泡罩包装： •1周（14×10毫克片剂） •2周（7×50毫克片剂） •3周（7×100 mg片剂） •4周（14×100 mg片剂） 0074-0579-28 10毫克钱包14×10毫克片剂  0074-0561-14 50毫克钱包7×50毫克片剂   0074-0566-07 10毫克单位剂量2×10毫克片剂 0074-0561-11 50毫克单位剂量1×50毫克片剂 0074-0566-11 100毫克单位剂量1×100mg片 0074-0576-11 100毫克 瓶120×100 mg片剂 0074-0576-22 贮存在或低于86°F(30°C)。 完整使用资料附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b118a40d-6b56-cee3-10f6-ded821a97018 Venetoclax (Venclexta) Tablets •VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. •This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Important Safety Information/Indication Important Safety Information Contraindication •Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated.a Tumor Lysis Syndrome •Tumor lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in previously treated CLL patients with high tumor burden treated with VENCLEXTA. •VENCLEXTA poses a risk for TLS in the initial 5-week 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 evaluation of tumor burden and comorbidities, and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Reduced renal function (CrCl <80 mL/min) 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 and P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase, and may require dose adjustment due to increases in VENCLEXTA exposure. Neutropenia •Grade 3 or 4 neutropenia occurred in 41% (98/240) of patients treated with VENCLEXTA. Monitor complete blood counts throughout treatment. 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). Immunization •Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery. Advise patients that vaccinations may be less effective. Embryo-Fetal Toxicity •VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Adverse Reactions •Serious adverse reactions were reported in 43.8% of patients. The most frequent serious adverse reactions (≥2%) were pneumonia (5%), febrile neutropenia (4.6%), pyrexia (3.3%), autoimmune hemolytic anemia (2.9%), anemia (2.1%), and TLS (2.1%).b •The most common adverse reactions (≥20%) of any grade were neutropenia (45%), diarrhea (35%), nausea (33%), anemia (29%), upper respiratory tract infection (22%), thrombocytopenia (22%), and fatigue (21%).a Drug Interactions •For patients who have completed the ramp-up phase and are on a steady daily dose of VENCLEXTA, reduce the dose by at least 75% when used concomitantly with strong CYP3A inhibitors. Resume the VENCLEXTA dose that was used prior to initiating the CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor. •Avoid concomitant use of moderate CYP3A inhibitors or P-gp inhibitors. If an inhibitor must be used, reduce the VENCLEXTA dose by at least 50%. Monitor patients more closely for signs of VENCLEXTA toxicities. Resume the VENCLEXTA dose that was used prior to initiating the CYP3A inhibitor or 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 narrow therapeutic index P-gp substrates. If these substrates must be used, they should be taken at least 6 hours before VENCLEXTA. •Monitor international normalized ratio (INR) closely in patients receiving warfarin. Lactation •Advise nursing women to discontinue breastfeeding during treatment with VENCLEXTA. Females and Males of Reproductive Potential •Advise 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.