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醋酸阿比特龙片Abiraterone-详细说明书与重点

醋酸阿比特龙片Abiraterone 【成份】主要成份：醋酸阿比特龙，化学名称：17-(3-吡啶基)-雄甾-5,16-二烯-3β–乙酸酯，化学结构式：【性状】本品为白色或类白色片。

【适应症】本品与泼尼松或泼尼松龙合用，治疗转移性去势抵抗性前列腺癌（mCRPC）新诊断的高危转移性内分泌治疗敏感性前列腺癌（mHSPC），包括未接受过内分泌治疗或接受内分泌治疗最长不超过3个月。

【规格】250mg【用法用量】推荐剂量：本品推荐剂量为1000mg（4x250mg片）口服每日一次。

本品与泼尼松或泼尼松龙5mg口服每日2次联用，治疗转移性去势抵抗性前列腺癌（mCRPC）患者。

本品与泼尼松或泼尼松龙5mg口服每日1次联用，治疗新诊断的高危转移性内分泌治疗敏感性前列腺癌（mHSPC）。

接受本品治疗的患者还应同时接受促性腺激素释放激素类似物（GnRHa）或应进行过双侧睾丸切除术。

本品须在餐前至少1小时和餐后至少2小时空腹服用（见【药代动力学】）。

本品应当伴水整片吞服。

请勿掰碎或咀嚼服用。

用药期间毒性监测：在开始使用本品治疗之前，应当检测血清转氨酶；并在接受治疗的前3个月每两周检测一次，此后每个月检测一次。

对血压、血清钾和体液潴留应当每月监测一次。

但对于存在充血性心力衰竭重大风险的患者，应在接受治疗的前3个月每两周监测一次，此后每月监测一次。

对于接受本品治疗前或治疗期间出现低钾血症的患者，应注意维持患者的血钾水平不低于4.0mM。

如果患者发生3级及3级以上毒性事件，包括高血压、低钾血症、水肿或其他非盐皮质激素毒性事件，则应停止治疗，并进行适当的医学处理。

直到毒性症状缓解至1级或基线水平，方可重新开始使用本品治疗。

如果患者出现漏服本品、泼尼松或泼尼松龙，应以常规剂量于次日重新开始治疗。

肝功能损害和肝毒性情况下的剂量调整原则肝功能损害：基线轻度肝功能损害的患者不需要调整剂量。

对于基线中度肝功能损害（Child-PughB级）的患者，本品的推荐剂量应降低至250mg,每天一次。

阿比特龙简介

阿比特龙简介摘要：Abiraterone（阿比特龙）是一种口服前列腺癌治疗新药，由英国皇家马斯登医院（世界著名的癌症研究治疗中心）的研究人员发明，2011年4月28日美国食品药品管理局（FDA）作为抗癌新药批准上市——Zytiga（醋酸阿比特龙）。

阿比特龙是一种选择性雄激素生物合成抑制剂，通过抑制甾（类）17α-羟化酶/C17-20裂解酶（P450c17）来阻止睾酮生成。

能令80%前列腺癌病人的癌细胞缩小，免去他们接受化疗和电疗之苦，它可以抑制身体任何部位雄激素产生，降低前列腺特异性抗原（PSA）水平，同时适用于过去有过化疗者的肿瘤患者。

临床实验结果显示，本品能明显延长晚期前列腺癌患者包括采用一种或两种含有多烯紫衫醇化疗药但病情仍恶化的患者生命，使死亡风险降低35%，且药物的副作用很小，安全性良好。

因此其抗肿瘤活性值得期待，包括其在晚期前列腺癌中的应用前景可观。

1 背景前列腺癌是老年男性生殖系统常见的恶性肿瘤之一，发病率随着年龄增长而增长，位于男性癌症死亡的第二位。

随着人口老龄化、食品安全问题、空气污染等问题的愈发严重，前列腺癌（PC）的发病几率显著上升。

2012年我国肿瘤登记地区前列腺癌发病率为9.92/10万，是男性恶性肿瘤发病的第六位，且于55岁后发病几率显著上升，70-80岁达到高峰[1]。

对晚期前列腺癌来说，最终进展为去势抵抗性前列腺癌。

临床上常用的治疗方法有生物免疫治疗、放化疗和内分泌治疗。

一般的放疗方法为前列腺区或转移病变部位的减症放疗，对癌细胞有较直接的杀灭作用，但放疗的副作用明显，即不可避免地会对正常细胞有损伤；化疗也是晚期前列腺癌的辅助治疗方法，敏感的化疗药物为环磷酰胺（CTX）等，但都显示副作用比较大，不同患者的疗效也不尽相同，所以研发新药以及找到有效且副作用较小的治疗方法是重中之重。

英国皇家马斯登医院的研究人员发明的阿比特龙是一种口服前列腺癌治疗新药，阿比特龙是一类选择性雄激素生物合成抑制剂，通过抑制甾（类）17α-羟化酶/C17-20裂解酶来阻止睾酮生成。

泽珂醋酸阿比特龙片印度版中文说明书、服用方法、不良反应及注意事项

泽珂醋酸阿比特龙片印度版中文说明书、服用方法、不良反应及注意事项【原厂版性状】椭圆形，白色至灰色片，一侧有AA250凹痕。

【印度版阿比特龙图片】【阿比特龙适应症和医疗用途】醋酸阿比特龙由美国强生研发的一种口服的CYP17抑制剂，在2011年4月28日阿比特龙获得美国FDA的批准，安百健abn536薇了解到临床上主要适用于与泼尼松联用为治疗既往接受含化疗转移去势难治性前列腺癌患者。

于2015年5月22日阿比特龙片在我国获准注册，正式批准阿比特龙上市，商品名为泽珂。

【阿比特龙服用剂量和方法】阿比特龙的剂量是每天口服1000mg，当天仅需服用一次；泼尼松的剂量是每天5mg，当天服用2次。

安百健abn536薇提醒服用需印度版阿比特龙要空腹，在前两小时无食物消耗，然后服用阿比特龙（泽珂）后，再保持一小时无食物消耗，即可保证空腹。

醋酸阿比特龙片应整片吞服，不可磨碎，咬碎。

若是患者有中度肝功能受损，需减量为250mg每天一次，若严重肝功能受损，应终止泽珂印度版。

【阿比特龙服用前注意事项】①有心血管疾病史患者慎用阿比特龙。

②对患者肾上腺皮质功能不全的症状和征象进行监控。

应急情况前、期间和期后可适当增加皮质激素剂量。

③临床研究中肝酶增加曾导致药物剂量调整、中断或终止治疗。

对患者的肝功能进行监控，如有需要则对药物进行剂量调整或中断、终止给药。

④必须空腹服用。

【不良反应】最常见不良反应(≥5%）是关节肿胀或不适，低钾血症，水肿，肌肉不适，热潮红，腹泻，泌尿道感染，咳嗽，高血压，心律失常，尿频，夜尿，消化不良和上呼吸道感染。

【禁忌证】妊娠或可能成为妊娠妇女禁忌用ZYTIGA。

下文为MYRBETRIQ的完整处方资料.pdf

Myrbetriq(mirabegron)缓释片使用说明书2012年第一版批准日期: 2012年6月28日；公司：Astellas Pharma美国药物评价和研究中心药物评价III室主任Victoria Kusiak，M.D说“估计美国有3千3百万患膀胱过度活动症(OAB)，是一种不舒适的，破坏和潜在严重的，”“今天的批准为有这种失能情况患者提供一种新治疗选择“。

处方资料：/drugsatfda_docs/label/2012/202611s000lb l.pdf处方资料重点这些重点不包括安全和有效使用MYRBETRIQTM所需所有资料。

请参阅下文为MYRBETRIQ的完整处方资料MYRBETRIQTM (mirabegron)，为口服使用美国初次批准：2012适应证和用途Myrbetriq是一种β-3肾上腺能激动剂适用于有急迫性尿失禁，急迫，和尿频症状膀胱过度活动症(OAB)的治疗( 1)剂量和给药方法（1）推荐起始剂量是25 mg每天1次，有或无食物。

(2.1)（2）25 mg是在8周内有效。

根据个体疗效和耐受性，可增加剂量至50mg每天1次。

(2.1，14)（3）与水完整吞咽，不要咀嚼，分开或压碎。

(2.1)（4）患者有严重肾受损或有中度肝受损患者，最大剂量为25mg每天1次。

(2.2，8.6，8.7，12.3)（5）有终末肾病(ESRD)或患者有严重肝受损患者。

不建议使用。

(2.2，8.6，8.7，12.3)剂量和规格缓释片：25 mg和50 mg (3)禁忌证无(4)警告和注意事项（1）血压增加：Myrbetriq可增加血压。

建议定期测定血压，特别在高血压患者。

在严重未控制高血压患者中建议不使用Myrbetriq。

(5.1).（2）有膀胱出口阻塞尿潴留患者和对膀胱过度活动症用抗胆碱药物患者：因为尿潴留风险在这些患者中谨慎给药。

(5.2).（3）用被CYP2D6代谢药物的患者：Myrbetriq是一种CYP2D6中度抑制剂。

晚期前列腺癌治疗药醋酸阿比特龙综述

晚期前列腺癌治疗药醋酸阿比特龙综述[摘要]2011年4月28日，美国fda 批准醋酸阿比特龙联合泼尼松（类固醇）治疗晚期转移性前列腺癌患者。

前列腺癌患者分泌的男性荷尔蒙睾丸素会刺激前列腺肿瘤生长。

因此，前列腺癌患者需要通过药物或手术来减少或阻止睾丸素的影响。

但是，即使在睾丸素的水平很低的情况下，前列腺肿瘤依旧能够生长。

细胞色素酶p4507a1在睾丸素的合成中起到了重要作用[1]。

醋酸阿比特龙是一种靶向细胞色素酶p4507a1（cyp17a1）的药物，通过抑制酶的活性从而降低激素的水平，以减少癌细胞的生长。

[关键字]醋酸阿比特龙；综述；前列腺癌一、简介图1 阿比特龙fig.1 abiraterone化学名：（3β）-17-（3-吡啶基）-雄甾-5，16-二烯-3-醇醋酸酯英文名：（3β）17-（3-pyridinyl）androsta-5，16-dien-3-yl 商品名：zytiga 通用名：abiraterone熔点为500.2°c at 760 mmhg ，密度为1.14g/cm3 ，闪电为256.3°c蒸汽压为7.99e-11mmhg at 25°c临床应用为其醋酸盐，醋酸阿比特龙是一种白色至淡白色，不吸潮，结晶粉。

二、合成路线图2 阿比特龙的合成路线fig.2 the synthesis of abiraterone此合成路线经过了酮与肼的亲核加成反应，消除反应，取代反应，酯化反应生成了阿比特龙。

三、作用机制阿比特龙的作用机制是抑制17α-羟化酶/c17，20-裂解酶（cyp17a1），这是一种表达在睾丸，肾上腺，和前列腺肿瘤组织的酶。

cyp17的两个催化连续反应：（一）转换孕烯醇酮和孕酮的17 -α-羟基衍生物的17α-羟化酶活性，和（二）后形成的脱氢表雄酮（dhea）和雄烯二酮，尤其是其c17，20裂解酶的活动[2]脱氢表雄酮、雄烯二酮是雄激素和前体睾酮。

阿比特龙联合地塞米松的用法-概念解析以及定义

阿比特龙联合地塞米松的用法-概述说明以及解释1.引言1.1 概述概述：阿比特龙与地塞米松是常用于治疗某些疾病的药物。

阿比特龙是一种糖皮质激素类药物，具有抗炎、免疫调节等作用，常用于治疗类风湿性关节炎、强直性脊柱炎等自身免疫性疾病。

而地塞米松则属于一种肾上腺皮质激素类药物，可用于治疗变态反应、哮喘等疾病。

随着药物研究的不断进步，阿比特龙联合地塞米松的治疗方案逐渐得到关注。

这种联合用药的方式往往能够在一定程度上增强药物的疗效，并减少某些副作用的发生。

本文将对阿比特龙联合地塞米松的用法进行详细讨论。

在正文部分，我们将先介绍阿比特龙和地塞米松的基本信息，包括药物的特点、作用机制和常见的适应症。

接着，我们将重点探讨阿比特龙联合地塞米松的用法。

这涉及到联合用药的时机、剂量及疗程等方面的内容。

同时，我们也将总结阿比特龙联合地塞米松的优势，以及对患者的影响。

最后，我们将展望未来该研究领域的发展方向。

通过本文的撰写，我们的目的在于为临床医生和研究人员提供一个全面了解阿比特龙联合地塞米松的用法的平台，以促进其在临床实践中的应用。

同时，希望能够对相关领域的研究人员提供一些启示，鼓励他们在未来深入探索这个领域，以进一步完善阿比特龙联合地塞米松的治疗方案，提高患者的治疗效果。

文章结构部分的内容可以如下编写：1.2 文章结构：本篇长文将分为以下几个部分进行论述：2. 正文：本部分将重点介绍阿比特龙和地塞米松这两种药物的基本情况以及它们分别在临床上的应用。

同时，将详细探讨阿比特龙联合地塞米松的使用方法，并分析其在治疗特定疾病或症状方面的优势。

3. 结论：在本章节中，将对阿比特龙联合地塞米松的优势进行总结，概括地列举其在治疗中的优势，从多个角度对这种联合用药的疗效进行评价，并对患者的治疗结果和病情变化进行探讨。

4. 展望未来的研究方向：本部分将对阿比特龙联合地塞米松的现有研究进行总结，并提出对未来的研究方向和发展趋势的展望。

对这种联合用药的潜在应用领域以及可能存在的问题进行分析和探讨，为进一步的研究提供方向和思路。

醋酸阿比特龙机理

醋酸阿比特龙机理
醋酸阿比特龙是一种药物，其作用机理主要是通过抑制肾上腺皮质类固醇合成过程中的关键酶，从而抑制肾上腺皮质类固醇的合成和释放。

具体来说，醋酸阿比特龙能够抑制11β-羟化酶和17α-羟化酶这两种酶的活性，从而减少肾上腺皮质类固醇的合成和释放。

肾上腺皮质类固醇是一种激素，它在人体内发挥着重要的作用，例如调节免疫系统、代谢、心血管系统和行为反应等。

当肾上腺皮质类固醇的合成和释放过多时，会导致一系列疾病的发生，例如Cushing 综合征、免疫系统失调、糖尿病等。

醋酸阿比特龙在临床上主要用于治疗一些与肾上腺皮质类固醇相关的疾病，例如Cushing综合征、肾上腺皮质癌等。

通过抑制肾上腺皮质类固醇的合成和释放，醋酸阿比特龙能够有效地控制病情，减轻患者的症状，提高患者的生活质量。

值得注意的是，醋酸阿比特龙的使用需要在医生的指导下进行，因为不正确的使用可能会导致一些不良反应的发生。

同时，对于某些患者来说，醋酸阿比特龙可能不是最佳的治疗选择，因此在治疗前需要进行全面的评估和诊断。

阿帕他胺片与阿比特龙的区别

阿帕他胺片与阿比特龙的区别
阿帕他胺片与阿比特龙片主要在药物适应证、用法及毒性方面存在一定区别，但均属于抗癌药物，用于治疗前列腺癌。

这两种药物在应用前，应同时接受雄激素剥夺治疗，即促性腺激素释放激素类似物治疗，或接受双侧睾丸切除术。

1、适应证：阿帕他胺片更适用于治疗有高危转移风险的、非转移性去势抵抗性前列腺癌的成年患者，而阿比特龙片一般与泼尼松、泼尼松龙等糖皮质激素联用，多用于治疗伴有转移性去势抵抗性前列腺癌，以及新诊断的高危转移性内分泌治疗敏感性前列腺癌，包括未接受过内分泌治疗，或接受内分泌治疗最长不超过3个月的患者；
2、用法：阿帕他胺片一般需要口服，整片吞下，可以单独服用或与食物同服，而阿比特龙片需空腹服用，且要与糖皮质激素联合应用；
3、毒性：服用阿帕他胺片后可能会发生中毒性表皮坏死松解症、多形性红斑等严重皮肤疾病，同时还可能会出现腹泻、恶心、高血压、甲状腺功能减退的情况。

若出现此类不良的毒性反应，应需要暂停服药，并在医生指导下进行相应的处理。

阿比特龙片具有一定的毒性，可能会导致血压、血钾升高，关节出现肿胀或不适感等不良反应。

在服药期间应定期检测相关指标，治疗前应检测血清转氨酶，并在接受治疗的前3个月每2周检测1次，此后每个月检测1次，同时对血压、血清钾和体液潴留应每月检测1次。

阿比特龙和泼尼松的正确用法

阿比特龙和泼尼松的正确用法
阿比特龙（Abilify）和泼尼松（Prednisone）是两种不同的药物，具有不同的治疗用途和使用方式。

阿比特龙是一种抗精神病药物，用于治疗精神疾病，例如精神分裂症和双相情感障碍。

它也可以用于辅助治疗抑郁症、自闭症和焦虑症。

使用阿比特龙时，应遵循医生的处方剂量和使用说明。

一般来说，阿比特龙片剂每天一次口服，可以餐前或餐后服用。

如果有任何不适或不良反应，应及时告知医生。

泼尼松是一种皮质类固醇药物，具有抗炎和免疫抑制作用。

它被用于治疗各种炎症性和自身免疫性疾病，包括风湿性关节炎、过敏反应、哮喘和疱疹性眼炎等。

使用泼尼松时，也需要按照医生的处方剂量和使用说明进行。

一般来说，泼尼松片剂可以每天一次口服，同时根据病情需要逐渐减少剂量。

使用泼尼松时，应遵循安全用药原则，避免突然停药或过量使用。

总之，正确使用阿比特龙和泼尼松是根据医生的建议和处方进行的。

在使用过程中应遵循医生的指导，按照剂量和使用频率进行用药，同时告知医生有关任何不适或不良反应。

前列腺癌用阿比特龙时，要不要服用强的松？...

前列腺癌用阿比特龙时，要不要服用强的松？...
前列腺癌用阿比特龙时，要不要服用强的松？
前列腺癌是一种依赖雄激素的疾病。

阿比特龙，因其抑制雄激素而用于治疗前列腺癌。

在多个早期的临床试验中，观察到会发生盐皮质毒性，表现为高血压、低血钾、水肿等。

从作用机制来讲，是抑制雄激素同时，也抑制了糖皮质激素的合成，负反馈性导致ACTH分泌增多，出现盐皮质激素分泌多，出现盐皮质毒性。

后续的试验中加入强的松来减弱这种负反馈调节，间接减弱盐皮质毒性。

也就出现了阿比特龙的用法，需要联合强的松。

简单来说，早期新发的加用强的松5mg/d，去势抵抗的加用强的松10mg/d。

也有人质疑这种普遍联合的用法，是否可以考虑不联合强的松，只给予降压补钾等对症治疗也可以。

随后做了小样本的临床试验，得出结果表示，阿比特龙联合强的松有益，但是部分患者，如容易出现糖皮质激素相关毒性，或基线有高血压、低血钾的患者，属于盐皮质毒性的高危人群，要注意强的松的联合使用。

阿比特龙的临床应用及疗效

阿比特龙的临床应用及疗效阿比特龙是一种针对骨质疏松症的药物，主要是通过抑制破骨细胞的活性，从而减少骨质丢失，促进骨密度的增加。

阿比特龙在骨质疏松症的治疗中是一种非常有效的药物，下面我们将从以下四个方面详细介绍阿比特龙的临床应用及疗效。

一、骨质疏松症治疗阿比特龙是一种常用的骨质疏松症治疗药物，在骨质疏松症的治疗中效果显著，可以明显增加骨密度，减少骨折风险，同时还可以有效的改善骨质疏松症患者的骨质结构和骨质强度。

二、乳腺癌治疗除了骨质疏松症的治疗外，阿比特龙还可以用于乳腺癌患者的辅助治疗。

在乳腺癌手术后放化疗的过程中，患者经常会发生骨质丢失的现象，同时由于激素治疗会降低雌激素的含量，导致骨质丢失的速度加快。

在这种情况下，阿比特龙可以有效的抑制破骨细胞的活性，防止骨质丢失的发生。

三、男性低睾酮骨质疏松症治疗男性低睾酮骨质疏松症是男性中相对较少出现的一种骨质疏松症类型，往往由于睾丸功能下降导致睾酮含量减少。

在这种情况下，阿比特龙可以通过抑制破骨细胞的活性，可有效的预防骨密度的降低，提高骨质强度，避免骨折的发生。

四、慢性肾病骨病治疗慢性肾病患者往往会因为肾功能的下降而导致骨质丢失的问题。

在这种情况下，阿比特龙可以通过抑制破骨细胞的活性，减少骨质丢失的速度，并通过促进骨形态和骨质组织的重建来改善慢性肾病骨病患者的骨密度和骨骼健康状况。

总的来说，阿比特龙是一种非常有效的骨质疏松症治疗药物，对骨质疏松症的治疗有着明显的效果。

同时，阿比特龙还可以用于乳腺癌患者的辅助治疗、男性低睾酮骨质疏松症的治疗以及慢性肾病骨病患者的治疗。

但是，在使用阿比特龙时，我们需要注意药物的副作用，如头痛、头晕、恶心、呕吐等，不能随意用药，必须根据医生的指导进行使用才能达到更好的治疗效果。

醋酸阿比特龙原料药安全操作及保养规程

醋酸阿比特龙原料药安全操作及保养规程背景介绍醋酸阿比特龙是一种重要的原料药，用于治疗高血压、心绞痛等心脏疾病。

但是，它也存在一定的危险性，需要严格的操作和保养。

本文将介绍醋酸阿比特龙的安全操作及保养规程。

安全操作规程1. 个人防护在操作醋酸阿比特龙时，必须使用适当的个人防护装备。

包括：•戴上手套。

应选用乙烯基乙烯醇共聚物手套或聚乙烯手套等，避免接触醋酸阿比特龙。

•戴上防护眼镜或面罩。

避免醋酸阿比特龙进入眼睛和口腔等部位。

•穿戴适宜的工作服。

应选用防护性能好、耐酸碱液的工作服，避免醋酸阿比特龙喷溅到身体上。

2. 储存条件醋酸阿比特龙应存放在凉爽、干燥、通风良好的地方，避免受潮、受热、受阳光直射和与活性酸碱物质接触。

且应在储存区域内设置防火、防盗等安全设施，确保储存安全。

3. 操作步骤在操作醋酸阿比特龙前，应事先了解相关的化学性质和安全信息，严格按照以下步骤进行：1.先准备好必要的操作工具、器材等。

2.穿戴适宜的个人防护装备。

3.取出所需的醋酸阿比特龙，称量、预处理等。

4.在化学实验室或药厂内操作，注意周围人员的安全。

5.遵循操作规程，进行溶解、加热、混合等操作。

6.操作完成后，应妥善处理废弃物。

4. 废弃物处理醋酸阿比特龙废弃物的处理应遵循相关法律法规和企业规定，切勿随意倾倒、泼洒或放置。

要避免对环境造成污染和危害，应采取以下措施：1.醋酸阿比特龙残留的容器、管道等应进行彻底清洗和处理。

可以使用异丙醇和水进行混合清洗，然后分别处理废水和异丙醇溶液。

2.遗漏在操作台或地面上的醋酸阿比特龙应及时清理，并进行安全处置。

3.废弃固体应经过包装、贴标和封存等措施后，交由专业的废弃物处理单位进行销毁或处置。

保养规程1.醋酸阿比特龙容器的保养应定期进行。

定期清洗容器内部，避免容器内积存杂质和污垢，影响药品质量。

2.在将醋酸阿比特龙存放时，需将盖子密封好，防止潮气进入或氧化。

3.双层包装的醋酸阿比特龙药品应保持外层包装的完整，避免外界物质的污染。

100-阿比特龙-FDA2015年05月版说明书

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use ZYTIGA safely and effectively. See full prescribing information for ZYTIGA.ZYTIGA® (abiraterone acetate) TabletsFor Oral AdministrationInitial U.S. Approval: 2011----------------------------RECENT MAJOR CHANGES-------------------------Dosage and Administration. (2.2) 05/2014 ----------------------------INDICATIONS AND USAGE---------------------------ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. (1)-----------------------DOSAGE AND ADMINISTRATION----------------------Recommended dose: ZYTIGA 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. The tablets should be swallowed whole with water. Do not crush or chew tablets. (2.1)• For patients with baseline moderate hepatic impairment (Child-Pugh ClassB), reduce the ZYTIGA starting dose to 250 mg once daily. (2.2)• For patients who develop hepatotoxicity during treatment, hold ZYTIGA until recovery. Retreatment may be initiated at a reduced dose. ZYTIGA should be discontinued if patients develop severe hepatotoxicity. (2.2)-------------------DOSAGE FORMS AND STRENGTHS---------------------Tablet 250 mg (3)-------------------------------CONTRAINDICATIONS------------------------------• ZYTIGA is contraindicated in women who are or may become pregnant.(4.1, 8.1)---------------------------WARNINGS AND PRECAUTIONS-----------------• Mineralocorticoid excess: Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with LVEF < 50% or NYHA Class III or IV heart failure in Study 1 or LVEF < 50% or NYHA Class II to IV heart failure in Study 2 was not established.Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly. (5.1)FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION2.1 Recommended Dosage2.2 Dose Modification Guidelines in HepaticImpairment and Hepatotoxicity2.3 Dose Modification Guidelines for Strong CYP3A4Inducers3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS4.1 Pregnancy5 WARNINGS AND PRECAUTIONS5.1 Hypertension, Hypokalemia and Fluid RetentionDue to Mineralocorticoid Excess5.2 Adrenocortical Insufficiency5.3 Hepatotoxicity6 ADVERSE REACTIONS6.1 Clinical Trial Experience6.2 Post Marketing Experience7 DRUG INTERACTIONS7.1 Drugs that Inhibit or Induce CYP3A4 Enzymes7.2 Effects of Abiraterone on Drug MetabolizingEnzymes • Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations. (5.2)• Hepatotoxicity: Increases in liver enzymes have led to drug interruption, dose modification and/or discontinuation. Monitor liver function andmodify, interrupt, or discontinue ZYTIGA dosing as recommended. (5.3) ------------------------------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. (6)To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA1088 or /medwatch.---------------------------------DRUG INTERACTIONS---------------------------• CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency. (2.3, 7.1)• CYP2D6 Substrates: Avoid co-administration of ZYTIGA with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of theconcomitant CYP2D6 substrate. (7.2)-----------------------USE IN SPECIFIC POPULATIONS----------------------• Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). (8.6)See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.Revised: 5/2015 8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Patients with Hepatic Impairment8.7 Patients with Renal Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.3 Pharmacokinetics12.6 QT Prolongation13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, and Impairment ofFertility13.2 Animal Toxicology and/or Pharmacology14 CLINICAL STUDIES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not listed.FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGEZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.2 DOSAGE AND ADMINISTRATION2.1 Recommended DosageThe recommended dose of ZYTIGA is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken [see Clinical Pharmacology (12.3)]. The tablets should be swallowed whole with water. Do not crush or chew tablets.2.2 Dose Modification Guidelines in Hepatic Impairment and HepatotoxicityHepatic ImpairmentIn patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. A once daily dose of 250 mg in patients with moderate hepatic impairment is predicted to result in an area under the concentration curve (AUC) similar to the AUC seen in patients with normal hepatic function receiving 1,000 mg once daily. However, there are no clinical data at the dose of 250 mg once daily in patients with moderate hepatic impairment and caution is advised. In patients with moderate hepatic impairment monitor ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. If elevations in ALT and/or AST greater than 5X upper limit of normal (ULN) or total bilirubin greater than 3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA and do not re-treat patients with ZYTIGA [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh ClassC).HepatotoxicityFor patients who develop hepatotoxicity during treatment with ZYTIGA (ALT and/or AST greater than 5X ULN or total bilirubin greater than 3X ULN), interrupt treatment with ZYTIGA [see Warnings and Precautions (5.3)]. Treatment may be restarted at a reduced dose of 750 mg once daily following return of liver function tests to the patient’s baseline orto AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN. For patients who resume treatment, monitor serum transaminases and bilirubin at a minimum of every two weeks for three months and monthly thereafter.If hepatotoxicity recurs at the dose of 750 mg once daily, re-treatment may be restarted at a reduced dose of 500 mg once daily following return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN.If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with ZYTIGA. The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.2.3 Dose Modification Guidelines for Strong CYP3A4 InducersAvoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during ZYTIGA treatment. Although there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers, because of the potential for an interaction, if a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].3 DOSAGE FORMS AND STRENGTHSZYTIGA (abiraterone acetate) 250 mg tablets are white to off-white, oval-shaped tablets debossed with AA250 on one side.4 CONTRAINDICATIONS4.1 PregnancyZYTIGA can cause fetal harm when administered to a pregnant woman. ZYTIGA is not indicated for use in women. ZYTIGA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations (8.1)].5 WARNINGS AND PRECAUTIONS5.1 Hypertension, Hypokalemia and Fluid Retention Due to MineralocorticoidExcessZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1)]. In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with ZYTIGA [see Adverse Reactions (6)].Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Use caution when treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, e.g., those with heart failure, recent myocardial infarction or ventricular arrhythmia. Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with left ventricular ejection fraction <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) was not established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14)]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with ZYTIGA.5.2 Adrenocortical InsufficiencyAdrenal insufficiency occurred in the two randomized clinical studies in 0.5% of patients taking ZYTIGA and in 0.2% of patients taking placebo. Adrenocortical insufficiency was reported in patients receiving ZYTIGA in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress.Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency.Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions (5.1)].5.3 HepatotoxicityIn the two randomized clinical trials, grade 3 or 4 ALT or AST increases (at least 5X ULN) were reported in 4% of patients who received ZYTIGA, typically during the first 3 monthsafter starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to liver enzyme increases occurred in 1% of patients taking ZYTIGA.No deaths clearly related to ZYTIGA were reported due to hepatotoxicity events.Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two 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 ULN, or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function.Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [see Dosage and Administration (2.2)].The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.6 ADVERSE REACTIONSThe following are discussed in more detail in other sections of the labeling:• Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess [see Warnings and Precautions (5.1)].• Adrenocortical Insufficiency [see Warnings and Precautions (5.2)].• Hepatotoxicity [see Warnings and Precautions (5.3)].6.1 Clinical Trial ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Two randomized placebo-controlled, multicenter clinical trials enrolled patients who had metastatic castration-resistant prostate cancer who were using a gonadotropin-releasing hormone (GnRH) agonist or were previously treated with orchiectomy. In both Study 1 and Study 2 ZYTIGA was administered at a dose of 1,000 mg daily in combination withprednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to control patients.The most common adverse drug reactions (≥10%) reported in the two randomized clinical trials that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.The most common laboratory abnormalities (>20%) reported in the two randomized clinical trials that occurred more commonly(≥2%)in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.Study 1: Metastatic CRPC Following ChemotherapyStudy 1 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy.Patients were not eligible if AST and/or ALT≥2.5 XULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN.Table 1 shows adverse reactions on the ZYTIGA arm in Study 1 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA was 8 months.Table 1: Adverse Reactions due to ZYTIGA in Study 1ZYTIGA with Prednisone Placebo with Prednisone(N=791) (N=394)System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Musculoskeletal and connective tissuedisordersJoint swelling/discomfort2 29.5 4.2 23.4 4.1Muscle discomfort3 26.2 3.0 23.1 2.3 General disordersEdema4 26.7 1.9 18.3 0.8 Vascular disordersHot flush 19.0 0.3 16.8 0.3Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disordersDiarrhea 17.6 0.6 13.5 1.3Dyspepsia 6.1 0 3.3 0 Infections and infestationsUrinary tract infection 11.5 2.1 7.1 0.5Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinaldisordersCough 10.6 0 7.6 0Renal and urinary disordersUrinary frequency 7.2 0.3 5.1 0.3Nocturia 6.2 0 4.1 0 Injury, poisoning and proceduralcomplicationsFractures5 5.9 1.4 2.3 0 Cardiac disordersArrhythmia6 7.2 1.1 4.6 1.0Chest pain or chest discomfort7 3.8 0.5 2.8 0Cardiac failure8 2.3 1.9 1.0 0.31 Adverse events graded according to CTCAE version 3.02 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness4 Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema5 Includes all fractures with the exception of pathological fracture6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia7 Includes terms Angina pectoris, Chest pain, and Angina unstable. Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively).8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreasedTable 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm.Table 2: Laboratory Abnormalities of Interest in Study 1Abiraterone (N=791) Placebo (N=394) Laboratory Abnormality All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Hypertriglyceridemia 62.5 0.4 53.0 0High AST 30.6 2.1 36.3 1.5 Hypokalemia 28.3 5.3 19.8 1.0 Hypophosphatemia 23.8 7.2 15.7 5.8High ALT 11.1 1.4 10.4 0.8High Total Bilirubin 6.6 0.1 4.6 0Study 2: Metastatic CRPC Prior to ChemotherapyStudy 2 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT≥2.5X ULN and patients were excluded if they had liver metastases.Table 3 shows adverse reactions on the ZYTIGA arm in Study 2 that occurred with a≥2% absolute increase in frequency compared to placebo. The median duration of treatment with ZYTIGA was 13.8 months.Table 3: Adverse Reactions in≥5%of Patients on the Z YTIGA Arm in Study 2Placebo with PrednisoneZYTIGA with Prednisone (N=542) (N=540) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % General disordersFatigueEdema2PyrexiaMusculoskeletal and connective tissue disordersJoint swelling/discomfort3Groin painGastrointestinal disordersConstipationDiarrheaDyspepsiaVascular disordersHot flushHypertensionRespiratory, thoracic and mediastinal disordersCoughDyspneaPsychiatric disordersInsomniaInjury, poisoning and procedural complicationsContusionFallsInfections and infestationsUpper respiratory tractinfectionNasopharyngitisRenal and urinary disordersHematuriaSkin and subcutaneous tissue disorders Rash 39.1 2.2 34.3 1.7 25.1 0.4 20.7 1.1 8.7 0.6 5.9 0.2 30.3 2.0 25.2 2.0 6.6 0.4 4.1 0.723.1 0.4 19.1 0.6 21.6 0.9 17.8 0.9 11.1 0.0 5.0 0.222.3 0.2 18.1 0.0 21.6 3.9 13.1 3.0 17.3 0.0 13.5 0.2 11.8 2.4 9.6 0.9 13.5 0.2 11.3 0.013.3 0.0 9.1 0.0 5.9 0.0 3.3 0.0 12.7 0.0 8.0 0.0 10.7 0.0 8.1 0.0 10.3 1.3 5.6 0.6 8.1 0.0 3.7 0.01 Adverse events graded according to CTCAE version 3.02 Includes terms Edema peripheral, Pitting edema, and Generalized edema3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffnessTable 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebo in Study 2. Grade 3-4 lymphopenia (9%), hyperglycemia (7%) and high alanine aminotransferase (6%) occurred ata greater than 5% rate in the ZYTIGA arm.Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of Study 2Abiraterone (N=542) Placebo (N=540)Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Laboratory Abnormality %% %%HematologyLymphopenia 38.2 8.7 31.7 7.4 ChemistryHyperglycemia1 56.6 6.5 50.9 5.2High ALT 41.9 6.1 29.1 0.7High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.71 Based on non-fasting blood drawsCardiovascular Adverse Reactions:In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%).Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group.In Study 1 and 2, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and one patient with sudden death in the ZYTIGA arms and no deaths in the placebo arms. There were 7 (0.5%) deaths due to cardiorespiratory arrest in the ZYTIGA arms and 3 (0.3%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 2 deaths in the ZYTIGA arms. 6.2 Post Marketing ExperienceThe following additional adverse reactions have been identified during post approval use of ZYTIGA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Respiratory, Thoracic and Mediastinal Disorders: non-infectious pneumonitis.Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis.7 DRUG INTERACTIONS7.1 Drugs that Inhibit or Induce CYP3A4 EnzymesBased on in vitro data, ZYTIGA is a substrate of CYP3A4.In a dedicated 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 [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].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 [see Clinical Pharmacology (12.3)].7.2 Effects of Abiraterone on Drug Metabolizing EnzymesZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8.In a CYP2D6 drug-drug interaction trial, the C max and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8-and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3)].In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA [see Clinical Pharmacology (12.3)].8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category X [see Contraindications (4.1)].ZYTIGA can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with ZYTIGA in pregnant women and ZYTIGA is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. ZYTIGA is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancyloss. Advise females of reproductive potential to avoid becoming pregnant during treatment with ZYTIGA.In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03,0.1 and 0.3 times, respectively, the AUC in patients.8.3 Nursing MothersZYTIGA is not indicated for use in women. It is not known if abiraterone acetate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZYTIGA, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.8.4 Pediatric UseSafety and effectiveness of ZYTIGA in pediatric patients have not been established.8.5 Geriatric UseOf the total number of patients receiving ZYTIGA in Phase 3 trials, 73% of patients were65 years and over and 30% were 75 years and over. No overall differences in safety oreffectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.8.6 Patients with Hepatic ImpairmentThe pharmacokinetics of abiraterone were examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) ofabiraterone after a single oral 1,000 mg dose of ZYTIGA increased by approximately1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment,respectively compared to subjects with normal hepatic function.。

阿比特龙片使用说明书

Zytiga(阿比特龙[abiraterone])片使用说明书2011年4月第一版- [使用说明书]版权声明：转载时请以超链接形式标明文章原始出处和作者信息及本声明Zytiga(阿比特龙[abiraterone])片为口服给药的ZYTIGATM(醋酸阿比特龙)片批准日期：2011年4月28日；公司：Centocor Ortho Biotech Inc.译自：本申请是在FDA 的优先审评计划下进行评审，此计划对可能在治疗中提供重要进展，或提供不存在适当治疗一种治疗提供加快6个月审评。

Zytiga的批准早于常规目标日期2011年6月20日。

FDA药物审评和研究中心中的肿瘤药品室主任Richard Pazdur, M.D.说“Zytiga延长有晚期前列腺癌已接受既往治疗和很少治疗选择男性的生命”。

处方资料的重点这些重点不包括安全和有效使用ZYTIGA的所有资料。

请参阅下文ZYTIGA的完整处方资料。

美国初始批准– 2011；本申请为优先审评适应证和用途ZYTIGA是一种CYP17抑制剂适用于与泼尼松联用为治疗既往接受含多烯紫杉醇[docetaxel]化疗转移去势难治性前列腺癌患者。

剂量和给药方法推荐剂量：ZYTIGA 1,000 mg口服给予每天1次与泼尼松联用5 mg口服给予每天2次。

必须空腹服用ZYTIGA。

在服用ZYTIGA 剂量前至少2小时和服用ZYTIGA剂量后至少1小时不应消耗食物。

(2.1)（1）对基线中度肝受损(Child-Pugh类别B)患者，减低ZYTIGA开始剂量至250 mg每天1次。

(2.2)（2）对治疗期间发生肝毒性患者，不用ZYTIGA直至恢复。

可在减低剂量再次治疗。

如患者发生严重肝毒性应终止ZYTIGA。

(2.2)剂型和规格: 250 mg片(3)禁忌证妊娠或可能成为妊娠妇女禁忌用ZYTIGA。

(4.1)警告和注意事项（1）盐皮质激素过量：有心血管疾病史患者谨慎使用ZYTIGA。

口服给药ZYTIGA(醋酸阿比特龙)片

口服給藥ZYTIGA(醋酸阿比特龍)片適應證和用途阿比特龍 ZYTIGA是壹種CYP17抑制劑適用于與潑尼松聯用爲治療既往接受含多烯紫杉醇[docetaxel]化療轉移去勢難治性前列腺癌患者。

劑量和給藥方法推薦劑量：阿比特龍ZYTIGA 1,000 mg口服給予每天1次與潑尼松聯用5 mg口服給予每天2次。

必須空腹服用阿比特龍ZYTIGA。

在服用ZYTIGA 劑量前至少2小時和服用阿比特龍ZYTIGA劑量後至少1小時不應消耗食物。

（1）對基線中度肝受損(Child-Pugh類別B)患者，減低ZYTIGA開始劑量至250 mg每天1次。

（2）對治療期間發生肝毒性患者，不用ZYTIGA直至恢複。

可在減低劑量再次治療。

如患者發生嚴重肝毒性應終止阿比特龍ZYTIGA。

劑型和規格:250 mg片禁忌證:妊娠或可能成爲妊娠婦女禁忌用阿比特龍ZYTIGA。

警告和注意事項:（1）鹽皮質激素過量：有心血管疾病史患者謹慎使用ZYTIGA。

尚未確定在有射血分量LVEF < 50%或NYHA類別III或IV心衰患者中ZYTIGA的安全性。

治療前控制高血壓和糾正低鉀血症。

至少每月1次監查血壓，血清鉀和液體潴留症狀。

（2）腎上腺皮質功能不全：監視腎上腺皮質功能不全的症狀和征象。

應急情況前，期間和後可能適應增加皮質激素劑量。

（3）肝毒性：肝酶增加曾導致藥物中斷，劑量調整和/或終止。

監查肝功能和如建議調整，中斷或終止ZYTIGA給藥。

（4）食物影響：必須空腹服用阿比特龍ZYTIGA。

當與食物同時服用醋酸阿比特龍[abiraterone acetate]阿比特龍的暴露(曲線下面積)增加達10倍。

不良反應最常見不良反應(≥ 5%)是關節腫脹或不適，低鉀血症，水腫，肌肉不適，熱潮紅，腹瀉，泌尿道感染，咳嗽，高血壓，心律失常，尿頻，夜尿，消化不良，和上呼吸道感染。

藥物相互作用ZYTIGA是壹種肝藥物代謝酶CYP2D6是抑制劑。

因爲治療指數窄，避免ZYTIGA與CYP2D6底物共同給藥。

阿比特龙和恩杂鲁胺

阿比特龙和恩杂鲁胺
阿比特龙是治疗前列腺癌的一线靶向药物，但是由于长期服药的缘故很有可能导致耐药，耐药的话对前列腺癌晚期患者来说是很痛苦的一件事，因为他们将不确定自己的生命会在什么时候结束。

那么，阿比特龙耐药后有什么二代药物呢？
恩杂鲁胺是一种有效的雄激素受体拮抗剂，据临床试验所得数据分析，恩杂鲁胺较之阿比特龙在无进展生存期方面高出3.5个月。

那阿比特龙耐药后可以使用恩杂鲁胺治疗吗?
答案虽是肯定的，但恩杂鲁胺作为阿比特龙耐药后的二线治疗疗效并不理想。

据恩杂鲁胺作为二线用药的临床实验结果显示，137位患者中，仅有52位患者的PSA浓度下降超过30%，中位生存期也只有8.3个月。

故而将恩杂鲁胺用于前列腺癌一线治疗更为适宜。

所以患者子啊服用阿比特龙的时候一定要正确服用阿比特龙，劲量然噶比特龙的耐药时间推后，这样的话就有可能在医学家研究出更好的药物之后得到证明的延续。

【JCO】“食物效应”助前列腺癌患者省钱“一臂之力”！——阿比特龙低剂量方案非劣于常规方案

【JCO】“食物效应”助前列腺癌患者省钱“一臂之力”！——阿比特龙低剂量方案非劣于常规方案醋酸阿比特龙（AA）是去势抵抗性前列腺癌患者的标准治疗药物。

但AA像其它一些口服药物一样，有着较强的“食物效应”。

服用高脂或低脂餐时，血液中的药物浓度可分别升高17倍或5倍左右。

目前AA的给药说明要求空腹，每日1000mg。

那么能否利用AA的“食物效应”，在用餐时服用AA，在既不显著降低疗效的同时能够减轻患者的经济负担呢？小编带您一探究竟。

01背景醋酸阿比特龙是一种强效、选择性、不可逆的CYP17（性腺外雄激素合成的关键酶）抑制剂。

2012年美国FDA批准AA作为转移去势抵抗性前列腺癌（mCRPC）患者的标准标准治疗药物。

本次AA获批的主要依据是一项随机、III期临床试验的结果。

在该试验中，接受AA 治疗（空腹口服，每天1次，1000 mg AA联合泼尼松5 mg口服，每天2次）的mCRPC患者，相对于安慰剂加泼尼松治疗的患者，可以提高患者的总生存率OS、无进展生存率PFS以及提高患者的生活质量。

后续的研究表明AA联合ADT方案能够进一步提高mCRPC或者的生存状况。

基于此，AA成为目前CRPC患者最为广泛和主要应用的一线治疗药物。

根据药厂的数据，AA问世的前5年中，在美国就累计开出超过10万份处方。

但还有一些其它的临床研究发现，与空腹给药相比，服药的同时再摄入一些食物，会增加AA暴露的血药浓度。

根据药物说明上的提示：低脂饮食会促使血药浓度增加5-7倍，而高脂饮食则可以增加10-17倍。

但由于在上述AA获批的关键性临床试验中采用的是空腹使用AA，导致目前获批的治疗方案就是空腹口服，每天250mg×4片。

那么能否借助饮食的作用来降低AA每天的口服剂量，继而减轻CRPC治疗相关的经济负担呢？基于这个目的，芝加哥大学的研究人员开展了本次临床研究。

01方法：纳入确诊为CRPC的患者；ECOG评分2分或2分以下；肝肾功能正常；血压、电解质状况良好。