英文药名：INLYTA（Axitinib tabs） 中文药名：阿西替尼片 生产厂家：美国辉瑞 药品介绍 美国食品药品监督管理局批Inlyta(axitinib)治疗晚期肾癌(肾细胞癌)对这类型癌对另外药物不反应的患者。 肾细胞癌是一种类型肾癌开始是在肾中非常小管衬里中。Inlyta通过阻断肿瘤生长和癌进展起作用的某些蛋白被称为激酶发挥作用。 Inlyta是一种药物患者每天用2次。 FDA 药物评价和研究中心的血液学和肿瘤产品室主任Richard Pazdur, M.D. 说“这是自2005来对转移或晚期肾细胞癌的治疗曾被批准的第7个药物。”“总的来说，在前所未有的水平，在这段时间内的药物开发已显著改变转移肾癌治疗的范式，和提供患者多种治疗选择。” 最近治疗肾癌被批准药物包括索拉非尼[sorafenib](2005)，舒尼替尼[sunitinib](2006)，驮瑞塞尔[temsirolimus](2007)，依维莫司[everolimus](2009)，贝伐单抗 [bevacizumab](2009)和帕唑帕尼[pazopanib] (2009)。 在一项723例用一种既往全身治疗或治疗后疾病有进展患者中进行的单个随机化，开放，多中心临床研究评价Inlyta的安全性和有效性。研究被设计成测量无进展生存，患者生存无癌症进展的时间。结果显示中位无进展生存时间6.7 个月与之比较用标准治疗(索拉非尼)为4.7个月。 在临床研究中在大于20%患者观察到的最常见副作用是腹泻，高血压，疲乏，食欲减低，恶心，失声(发音障碍)，手足综合征(手指-足底erythrodysesthesia)，体重减轻，呕吐, 虚弱(乏力)和便秘。 有高血压患者服用Inlyta前应很好控制。有些患者用Inlyta经受出血问题，在有些病例中是致命性的。有未治疗脑肿瘤或胃肠道出血患者不应用Inlyta。 作用机制 Axitinib曾显示在治疗血浆浓度时抑制酪氨酸激酶受体包括血管内皮生长因子受体(VEGFR)-1，VEGFR-2，和VEGFR-3。这些受体与病理性血管生成，肿瘤生长，和癌进展中有牵连。在体外和小鼠模型中axitinib抑制VEGF-介导内皮细胞增殖和生存。肿瘤异种移植小鼠模型中 Axitinib显示抑制肿瘤生长和VEGFR-2的磷酸化。 适应证和用途 INLYTA 是一种激酶抑制剂适用于一种既往全身治疗失败后晚期肾细胞癌的治疗。 剂量和给药方法 （1）开始剂量为5 mg口服每天2次。可根据个体安全性和耐受性调整剂量。 （2）约间隔12小时给予INLYTA剂量有或无食物。 （3）INLYTA应与一杯水整片吞服。 （4）如需要强CYP3A4/5抑制剂，减低INLYTA 剂量约半量. （5）对中度肝受损患者，减低开始剂量约半量。 剂型和规格 1mg和5mg片。 禁忌证 无。 警告和注意事项 （1）曾观察到高血压包括高血压危象。开始INLYTA前应充分控制血压。需要监视和治疗高血压。尽管使用抗高血压药物，对持续高血压减低INLYTA剂量。(5.1) （2）曾观察到动脉和静脉血栓事件和可能致死。对这些事件风险增加患者慎用。 （3）曾报道出血事件, 包括致命性事件。尚未在未治疗脑转移或最近活动性胃肠道出血证据患者中研究过INLYTA和在这些患者中不应使用。 （4）曾发生胃肠道穿孔和瘘管，包括死亡。对胃肠道穿孔或瘘管风险患者慎用。 （5）曾报道甲状腺低下症需要甲状腺激素替代。用NLYTA治疗开始前监视甲状腺功能，和自始至终定期。 （6）计划手术前至少24小时停止INLYTA。 （7）曾观察到可逆性后部白质脑病综合征(RPLS)。如发生RPLS体征或症状永久终止INLYTA。 （8）用INLYTA治疗开始前，和自始至终定期监视蛋白尿。对中度至严重蛋白尿，减低剂量或暂时中断用INLYTA治疗。 （9）用INLYTA治疗时曾观察到肝酶升高。用INLYTA治疗开始前和自始至终定期监视ALT，AST和胆红素。 （10）中度肝受损患者如使用INLYTA开始剂量应减低。严重肝受损患者中未曾研究过INLYTA。 （11）当给予妊娠妇女根据其作用机制INLYTA可能致胎儿危害。应忠告生育能力妇女对胎儿潜在危害和当接受INLYTA避免成为妊娠。 不良反应 最常见(≥20%)不良反应是腹泻，高血压，疲乏，食欲减低，恶心，发音障碍，手掌-足底erythrodysesthesia (手-足)综合征，体重减轻，呕吐，乏力，和便秘。 药物相互作用 （1）避免强CYP3A4/5抑制剂。如不可避免，减低INLYTA 剂量。 （2）避免强CYP3A4/5诱导剂。 INLYTA (axitinib) is a kinase inhibitor. Axitinib has the chemical name N-methyl-2-[3-((E)2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide. The molecular formula is C22H18N4OS and the molecular weight is 386.47 Daltons. The chemical structure is: Axitinib is a white to light-yellow powder with a pKa of 4.8. The solubility of axitinib in aqueous media over the range pH 1.1 to pH 7.8 is in excess of 0.2 μg/mL. The partition coefficient (noctanol/water) is 3.5. INLYTA is supplied as red, film-coated tablets containing either 1 mg or 5 mg of axitinib together with microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and Opadry® II red 32K15441 as inactive ingredients. The Opadry II red 32K15441 film coating contains lactose monohydrate, HPMC 2910/Hypromellose 15cP, titanium dioxide, triacetin (glycerol triacetate), and red iron oxide. INLYTA is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. Important Safety Information Hypertension including hypertensive crisis has been observed. Blood pressure should be well controlled prior to initiating INLYTA. Monitor for hypertension and treat as needed. For persistent hypertension, despite use of antihypertensive medications, reduce the dose. Discontinue INLYTA if hypertension is severe and persistent despite use of antihypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis. Arterial and venous thrombotic events have been observed and can be fatal. Use with caution in patients who are at increased risk or who have a history of these events. Hemorrhagic events, including fatal events, have been reported. INLYTA has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the INLYTA dose. Gastrointestinal perforation and fistula, including death, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistula. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment. Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment. Stop INLYTA at least 24 hours prior to scheduled surgery. Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed. If signs or symptoms occur, permanently discontinue treatment. Monitor for proteinuria before initiation of, and periodically throughout, treatment. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment. Liver enzyme elevation has been observed during treatment with INLYTA. Monitor ALT, AST, and bilirubin before initiation of, and periodically throughout, treatment. For patients with moderate hepatic impairment, the starting dose should be decreased. INLYTA has not been studied in patients with severe hepatic impairment. Women of childbearing potential should be advised of potential hazard to the fetus and to avoid becoming pregnant while receiving INLYTA. Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose. Grapefruit or grapefruit juice may also increase INLYTA plasma concentrations and should be avoided. Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers. The most common (≥20%) adverse events (AEs) occurring in patients receiving INLYTA (all grades, vs sorafenib) were diarrhea (55% vs 53%), hypertension (40% vs 29%), fatigue (39% vs 32%), decreased appetite (34% vs 29%), nausea (32% vs 22%), dysphonia (31% vs 14%), hand-foot syndrome (27% vs 51%), weight decreased (25% vs 21%), vomiting (24% vs 17%), asthenia (21% vs 14%), and constipation (20% vs 20%). The most common (≥10%) grade 3/4 AEs occurring in patients receiving INLYTA (vs sorafenib) were hypertension (16% vs 11%), diarrhea (11% vs 7%), and fatigue (11% vs 5%). The most common (≥20%) lab abnormalities occurring in patients receiving INLYTA (all grades, vs sorafenib) included increased creatinine (55% vs 41%), decreased bicarbonate (44% vs 43%), hypocalcemia (39% vs 59%), decreased hemoglobin (35% vs 52%), decreased lymphocytes (absolute) (33% vs 36%), increased ALP (30% vs 34%), hyperglycemia (28% vs 23%), increased lipase (27% vs 46%), increased amylase (25% vs 33%), increased ALT (22% vs 22%), and increased AST (20% vs 25%). -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: INLYTA 5MG/TAB 60TABS/BOTTLE (Controlled; can only sell to oncology centers and hospitals) 原产地英文药品名: AXITINIB 中文参考商品译名: INLYTA 5毫克/片 60片/瓶 (Controlled; can only sell to oncology centers and hospitals) 中文参考药品译名: 阿西替尼 生产厂家中文参考译名: 辉瑞 生产厂家英文名: PFIZER -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: INLYTA 1MG/TAB 180TABS/BOTTLE (Controlled; can only sell to oncology centers and hospitals) 原产地英文药品名: AXITINIB 中文参考商品译名: INLYTA 1毫克/片 180片/瓶(Controlled; can only sell to oncology centers and hospitals) 中文参考药品译名: 阿西替尼 生产厂家中文参考译名: 辉瑞 生产厂家英文名: PFIZER