抗癌新药Xtandi（Enzalutamide 恩杂鲁胺）胶囊是一种雄激素受体抑制剂，由日本安斯泰来制药研发，于2012年获FDA批准上市，适用于治疗有转移去势耐受前列腺癌既往曾接受多西他奇[docetaxel]患者，恩杂鲁胺和强生杨森旗下阿比特龙，目前已成为国际治疗前列腺癌的主流用药。 批准日期：2012年9月4日 公司：安斯泰来制药 XTANDI（恩杂鲁胺 enzalutamide）胶囊，用于口服 美国最初批准：2012年 最近的重大变化 禁忌症:10/2016 警告和注意事项：07/2017 作用机制 Enzalutamide是一种雄激素受体抑制剂，可作用于雄激素受体信号通路的不同步骤。 Enzalutamide已被证明具有竞争性抑制雄激素与雄激素受体的结合，并抑制雄激素受体核转位和与DNA的相互作用。主要代谢产物N-去甲基恩杂鲁胺表现出与恩杂鲁胺相似的体外活性。 恩杂鲁胺在体外降低前列腺癌细胞的增殖和诱导细胞死亡，并且在小鼠前列腺癌异种移植模型中降低肿瘤体积。 适应症和用法 XTANDI是一种雄激素受体抑制剂，适用于治疗转移性去势抵抗性前列腺癌患者。 剂量和给药 XTANDI 160mg（4个40mg胶囊）每日口服一次。燕子胶囊整个。XTANDI可以带或不带食物。 剂量形式和强度 胶囊40毫克 禁忌症 怀孕 警告和注意事项 •接受XTANDI的患者中有0.5％发生癫痫发作。在有诱发因素的患者中，2.2％的患者报告癫痫发作。在治疗期间发生癫痫发作的患者中永久停用XTANDI。 •后部可逆性脑病综合征（PRES）：停用XTANDI。 不良反应 最常见的不良反应（≥10％）是虚弱/疲劳，背痛，食欲减退，便秘，关节痛，腹泻，热潮红，上呼吸道感染，外周性水肿，呼吸困难，肌肉骨骼疼痛，体重减轻，头痛，高血压，和头晕/眩晕。 要报告疑似不良反应，请致电1-800-727-7003联系Astellas Pharma US，Inc。或致电1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH联系FDA。 药物相互作用 •避免使用强效CYP2C8抑制剂，因为它们可以增加血浆对XTANDI的暴露。如果需要共同给药，减少XTANDI的剂量。 •避免使用强CYP3A4诱导剂，因为它们可以减少血浆暴露于XTANDI。如果需要共同给药，增加XTANDI的剂量。 •避免使用具有较窄治疗指数的CYP3A4，CYP2C9和CYP2C19底物，因为XTANDI可能会降低这些药物的血浆暴露。如果XTANDI与华法林（CYP2C9底物）共同给药，则进行额外的INR监测。 用于特定人群 •具有生殖潜力的女性和男性：向具有生殖潜力的女性伴侣的男性提供建议，以使用有效的避孕方法。 包装提供/存储和处理 •XTANDI（enzalutamide）40毫克胶囊以白色至米白色椭圆形软明胶胶囊供应，用ENZ印成黑色墨水。 XTANDI胶囊有以下包装尺寸： •120粒胶囊（NDC 0469-0125-99） 推荐储存：将XTANDI胶囊在20°C至25°C（68°F至77°F）的温度下存放在干燥的地方，并保持容器密闭。 允许的偏差为15°C至30°C（59°F至86°F）。 完整说明附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b129fdc9-1d8e-425c-a5a9-8a2ed36dfbdf Xtandi(enzalutamide) capsules Indication XTANDI (enzalutamide) is indicated for the treatment of patients with castration-resistant prostate cancer (CRPC). Important Safety Information Warnings and Precautions Seizure occurred in 0.4% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. Patients in the study had one or more of the following pre-disposing factors: use of medications that may lower the seizure threshold; history of traumatic brain or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment. Posterior Reversible Encephalopathy Syndrome (PRES)   In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES. Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions. Ischemic Heart Disease  In the placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.7% vs 1.2%). Grade 3-4 ischemic events occurred in 1.2% of patients on XTANDI versus 0.5% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease. Falls and Fractures  In the placebo-controlled clinical studies, falls occurred in 10% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 8% of patients treated with XTANDI and in 3% of patients treated with placebo. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. Embryo-Fetal Toxicity  Safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI. XTANDI should not be handled by females who are or may become pregnant. Adverse Reactions The most common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in the XTANDI patients from the randomized placebo-controlled trials were asthenia/fatigue, decreased appetite, hot flush, arthralgia, dizziness/vertigo, hypertension, headache and weight decreased. In the bicalutamide-controlled study, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss. In the placebo-controlled study of metastatic CRPC (mCRPC) patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve mCRPC patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher adverse reactions were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an adverse event as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients. In the bicalutamide-controlled study of chemotherapy-naïve mCRPC patients, Grade 3-4 adverse reactions were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients. Lab Abnormalities:  In the two placebo-controlled trials in patients with mCRPC, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). In the placebo-controlled trial in patients with nmCRPC, Grade 1-4 neutropenia occurred in 8% of patients receiving XTANDI (0.5% Grade 3-4) and in 5% of patients receiving placebo (0.2% Grade 3-4). Hypertension:  In the two placebo-controlled trials in patients with mCRPC, hypertension was reported in 11% of XTANDI patients and 4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm. In the placebo-controlled trial in patients with nmCRPC, hypertension was reported in 12% of patients receiving XTANDI and 5% of patients receiving placebo. Drug Interactions Effect of Other Drugs on XTANDI   Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI. Effect of XTANDI on Other Drugs   Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.