英文药名: Zytiga(Abiraterone Acetate Tablets) 中文药名: 醋酸阿比特龙片 生产厂家: Janssen Pharmaceutical Inc 药品介绍 Zytiga(阿比特龙 abiraterone)片 供口服给药治疗去势或无效的转移性前列腺癌，与强的松(类固醇)联合用于治疗晚期(转移)去势抵抗前列腺癌患者。 美国首次批准：2011 目前的主要变化 剂量和给药方法。 （2.2）05/2014 适应症和用法 ZYTIGA是组合表示与强的松用于治疗转移性去势抗性前列腺癌的治疗CYP17抑制剂。 用法用量 推荐剂量：ZYTIGA 1000毫克（4 250毫克片剂）口服，每日一次联合强的松5毫克口服，每日两次。 ZYTIGA必须采取空着肚子。否应该进食为至少两小时ZYTIGA的剂量被取前和至少一小时取ZYTIGA的剂量后。片剂应整粒吞服水。不要碾碎或咀嚼片剂。 对于患者的基线中度肝受损（Child-Pugh分级B级），每天一次降低ZYTIGA开始剂量为250毫克。 对于谁在治疗过程中培养肝患者，持有ZYTIGA直至痊愈。再处理可在降低的剂量开始。如出现严重的肝毒性ZYTIGA应停药。 剂型和规格 片剂250毫克 禁忌 ZYTIGA是禁忌的妇女谁是或可能怀孕。 警告和注意事项 盐皮质激素过多：用ZYTIGA慎用于心血管疾病患者的病史。 ZYTIGA患者在研究2 IV心脏衰竭的安全性与左室射血分数<50％或NYHA III或IV级心脏衰竭在研究1或左室射血分数<50％或心功能II级是不成立的。治疗前控制高血压，低血钾正确。监测血压体液潴留，血钾症状至少每月一次。 肾上腺皮质功能不全：监视的症状和肾上腺皮质功能减退的迹象。皮质类固醇的增加的剂量可被指示之前，期间和之后压力的情况。 肝毒性：使肝酶导致药物中断，调整剂量和/或停药。监测肝功能，并修改，中断，或终止ZYTIGA给药的建议。 不良反应 最常见的不良反应（≥10％）是疲劳，关节肿胀或不适，水肿，潮红，腹泻，呕吐，咳嗽，高血压，呼吸困难，尿路感染及挫伤。 最常见的实验室异常（> 20％）是贫血，碱性磷酸酶升高，高甘油三酯血症，淋巴细胞减少，高胆固醇血症，高血糖，AST升高，低磷血症，ALT升高和低钾血症。 要报告疑似不良反应，请联系扬森Biotech公司在1-800-526-7736（1-800-JANSSEN）或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。 药物相互作用 CYP3A4诱导剂：避免在ZYTIGA治疗强CYP3A4诱导剂。如果强大的CYP3A4诱导必须共同给药，可增加ZYTIGA给药频率。 CYP2D6底物：避免ZYTIGA的共施用与CYP2D6基片具有窄的治疗指数。如果无法用一种替代治疗，谨慎操作，并考虑减少剂量伴随CYP2D6基板。 特殊人群中使用 不要在患者的基线严重肝受损（Child-Pugh类别C）使用ZYTIGA。 患者咨询信息和FDA批准的患者标签见17。 修订：5/2015 Important Safety Information for ZYTIGA® (abiraterone acetate) Contraindications – ZYTIGA® (abiraterone acetate) is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant. Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess – Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly. Adrenocortical Insufficiency (AI) – AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations. Hepatotoxicity – Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient's baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function. Adverse Reactions – The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion. The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia. Drug Interactions – Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone. ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA®. Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA®. Use in Specific Populations – Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e338e89-3cf2-48eb-b6e2-a06c608c6513 ——美国FDA扩展Zytiga的使用治疗晚期前列腺癌 2012年12月10日美国食品药品监督管理局(FDA)扩展批准使用Zytiga(醋酸阿比特龙[abiraterone acetate])晚期(转移)去势-耐药前列腺癌男性在接受化疗前治疗。 2011年4月FDA初次批准Zytiga为用多西紫杉醇[docetaxel], 一种化疗药物后前列腺癌进展患者中使用。 Zytiga是药丸减低男性性激素睾丸酮的生成。 在前列腺癌中, 睾丸酮刺激前列腺肿瘤生长。药物Drugs或手术被用于减低睾丸酮生成或阻断睾丸酮的作用。有些男性有去势-耐药前列腺癌, 意味着前列腺癌细胞基线生成即使有低水平睾丸酮。 FDA的药物评价和研究中心肿瘤药物室主任Richard Pazdur, M.D.说：“今天的批准证实进一步评价某个药物在疾病早期情况下的获益和提供患者和卫生保健提供者在治疗过程早期使用Zytiga的选择”。 FDA是在监管局优先审评程序下审评Zytiga的这个新适应证。 这个程序对治疗中提供重要进展当当前无适当治疗的药物提供提前6个月审评。 在1,088例有晚期，去势-耐药前列腺癌既往未曾接受过化疗男性的一项临床研究中确定Zytiga为其扩展使用的安全性和有效性。参加者接受或 Zytiga或安慰剂(糖丸)与泼尼松[prednisone]联用。 研究被设计成通过影像研究评估测量患者死亡前活存时间长度(总生存)和影像学评估肿瘤生长(放射影像无进展生存。或rPFS)无进一步肿瘤生长时间长度。 接受Zytiga患者有中位总生存35.3个月与之比较接受安慰剂患者30.1个月。研究结果还显示Zytiga 改善rPFS。在分析时安慰剂组中位rPFS为 8.3个月和用Zytiga治疗患者还未达到。 接受Zytiga患者报道的最常见副作用包括疲乏，关节肿胀或不适，液体潴留引起肿胀，热潮红，腹泻， 呕吐，咳嗽，高血压，气短，尿道感染，和瘀斑。 最常见实验室异常包括红细胞计数低；高水平碱性磷酸酶，可能是其它严重医学问题的征象；血中高水平脂肪酸，糖，和肝酶；和血中低水平淋巴细胞，磷和钾。