近日,FDA批准新靶向药Verzenio (abemaciclib)用于治疗HR阳性和HER-2阴性晚期乳腺癌或转移性乳腺癌治疗。 乳腺癌为全球妇女高发的恶性肿瘤之一,全球每年新发病例达138.4万,约45.8万患者死于乳腺癌。我国每年约有16.9万女性患乳腺癌,是女性第二位最常见恶性肿瘤。美国国立卫生研究院的国家癌症研究所估计今年美国将有大约252,710名妇女被诊断患有乳腺癌,其中40,610名将死于该疾病。 其中大约72%的乳腺癌患者具有HR阳性和HER2阴性的肿瘤。 Verzenio为乳腺癌患者提供了新的靶向治疗方案,通过阻断某些分子(蛋白激酶-4,蛋白激酶-6),抑制癌细胞生长。它可以作为一种单独的治疗方案,给曾接受内分泌疗法和化疗的患者使用。 批准日期:2017年9月28日;公司:Eli Lilly和公司 VERZENIO™(abemaciclib)片,为口服使用 美国初次批准:2017 作用机制 Abemaciclib是一个细胞周期蛋白[cyclin]-依赖激酶4和6(CDK4和CDK6)的抑制剂。结合至D-细胞周期蛋白上这些激酶被激活。在雌激素受体-阳性(ER+)乳癌细胞系,细胞周期蛋白D1和CDK4/6促进视网膜母细胞瘤蛋白质[retinoblastoma protein(Rb)]的磷酸化,细胞周期进展,和细胞增殖。在体外,连续暴露至abemaciclib抑制Rb磷酸化和阻断细胞周期的从G1至S期进程,导致细胞老化[senescence]和凋亡。在乳腺癌异种移植模型中,每天给予abemaciclib无中断作为一个单药或与抗雌激素组合导致肿瘤大小减小。. 适应证和用途 VERZENIO™是一种激酶抑制剂适用: ●与氟维司群[fulvestrant]联用为有激素受体(HR)-阳性,人表皮生长因子受体2(HER2)-阴性晚期或转移乳癌内分泌治疗有疾病进展妇女的治疗。 ● 作为单药治疗为有HR-阳性,HER2-阴性晚期或转移乳癌内分泌治疗后有疾病进展和在转移情况前化疗成年患者的治疗。 剂量和给药方法 VERZENIO片与无或有食物口服服用. ● 与氟维司群联用推荐的开始剂量:150mg每天2次。 ●作为单药治疗推荐的开始剂量:200mg每天2次。 ● 可能需要根据个体安全性和耐受性给药中断和/或剂量减低。 剂型和规格 片:50mg,100mg,150mg,和200mg。 禁忌证 无。 警告和注意事项 ● 腹泻:在松软便的第一个征象指导患者开始抗腹泻治疗,增加口服液体,和通知他们的卫生保健提供者。 ● 中性细胞减少:VERZENIO治疗的开始前,对头2个月每2周,对下一个2个月每月,和当临床上有适应证时监视完全血细胞计数。 ●肝毒性:曽观察到血清转氨酶水平增加。进行肝功能测试(LFTs)用VERZENIO开始治疗前. 监视LFTs 对头两个月每两州,对下两个月每月,和对临床有适应证时. ●静脉血栓栓塞:监视患者对血栓形成的体征和症状和肺栓塞和药物治疗当医疗上适当时。 胚胎-胎儿毒性:可能致胎儿危害。忠告患者对胎儿潜在风险和使用有效避孕。 不良反应 最常见不良反应(发生率 ≥20%)为腹泻,中性细胞减少,恶心,腹痛,感染,疲乏,贫血,中性细胞减少,食欲减低,呕吐,头痛,和血小板减少。 药物相互作用 ●CYP3A抑制剂:避免同时使用酮康唑[ketoconazole]。减低VERZENIO给药与其他强CYP3A抑制剂的同时使用。 ●CYP3A诱导剂:避免强CYP3A诱导剂的同时使用。 在特殊人群中使用 哺乳:建议不要哺乳喂养。 包装规格/贮存和处置 供应 VERZENIO 50 mg片是椭圆形米色片有“Lilly”凹陷在一侧和“50”在其他侧。 VERZENIO 100 mg片是椭圆形白色至实际白色片剂有“Lilly”凹陷在一侧和“100”在其他侧。 VERZENIO 150 mg片是椭圆形黄色片有“Lilly”凹陷在一侧和“150”在其他侧。VERZENIO 200 mg片为椭圆形米色片有“Lilly”凹陷在一侧和“200”在其他侧。 VERZENIO片被供应在7-天剂量包装规格如下: ●200mg剂量包装(14片) – 每个吸塑包装包含14片(200mg每片)(200mg每天2次)NDC 0002-6216-54 ●150mg剂量包装(14片) – 每个吸塑包装包含14片(150mg每片)(150mg每天2次)NDC 0002-5337-54 ●100mg剂量包装(14片) – 每个吸塑包装包含14片(100mg每片)(100mg每天2次)NDC 0002-4815-54 ●50mg剂量包装(14片) – 每个吸塑包装包含14片(50 mg每片)(50 mg每天2次)NDC 0002-4483-54 贮存和处置 贮存在20°C至25°C(68°F至77°F);外出允许至15°C至30°C(59°F至86°F).
Verzenio (abemaciclib) Tablets VERZENIO Rx Generic Name and Formulations: Abemaciclib 50mg, 100mg, 150mg, 200mg; tabs. Company: Lilly, Eli and Company Select therapeutic use: Breast cancer Indications for VERZENIO: In combination with fulvestrant for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. As monotherapy for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. Adult: Swallow whole. Take at the same time every day. Combination with fulvestrant (see full labeling): initially 150mg twice daily; in pre/perimenopausal women: also treat with a gonadotropin-releasing hormone agonist according to current practice standards. Monotherapy: initially 200mg twice daily. Both: continue until disease progression or unacceptable toxicity. Dose modifications for adverse reactions, concomitant strong CYP3A4 inhibitors: see full labeling. Severe hepatic impairment: reduce frequency to once daily. Children: Not established. Warnings/Precautions: Advise patients to initiate antidiarrheal (eg, loperamide) and increase fluids at first sign of loose stools; discontinue if Grade 3/4 diarrhea occurs or hospitalization required, until resolves to ≤Grade 1, then resume at next lower dose. Monitor CBCs and LFTs prior to initiation and every 2 weeks for the first 2 months, then monthly for the next 2 months, and as clinically indicated. Dose interruption/reduction/discontinuation or delay in starting treatment cycles if Grade 3/4 neutropenia, recurrent Grade 2 or Grade 3/4 transaminase elevation occurs. Monitor for signs/symptoms of venous thromboembolic events; treat appropriately. Severe hepatic impairment (Child-Pugh C). Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during therapy and for at least 3 weeks after last dose. Pregnancy; exclude status prior to initiation. Nursing mothers: not recommended (during and for at least 3 weeks after the last dose). Interactions: Avoid concomitant ketoconazole, grapefruit products. Concomitant other strong CYP3A inhibitors: reduce abemaciclib dose. Avoid concomitant strong CYP3A inducers (eg, rifampin): consider alternative agents. Pharmacological Class: Kinase inhibitor. Adverse Reactions: Diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, thrombocytopenia; venous thromboembolic events, hepatotoxicity. Generic Availability: NO How Supplied: Blister pack—14
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