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&醋酸阿比特龙片 价格 疗效 适应症 用法用量醋酸阿比特龙片 价格 疗效 适应症 用法用量
单价：21200.00元/盒起订：1 盒供货总量：100 盒发货期限：自买家付款之日起 1 天内发货所在地：北京品牌：阿比特龙
&& 关键词：适应症
阿比特龙(阿比特龙片)ZYTIGA
【商品名】醋酸阿比特龙
【英文名】ZYTIGA
【适应证】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。
【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。
(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)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。
(3)剂型和规格250 mg片
【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。尚未确定在有射血分量LVEF & 50%或NYHA类别III或IV心衰患者中ZYTIGA的安全性。治疗前控制高血压和纠正低钾
血症。至少每月1次监查血压，血清钾和液体潴留症状。
(2)肾上腺皮质功能不全：监视肾上腺皮质功能不全的症状和征象。应急情况前，期间和后可能适应增加皮质激素剂量。
(3)肝毒性：肝酶增加曾导致药物中断，剂量调整和/或终止。监查肝功能和如建议调整，中断或终止ZYTIGA给药。
(4)食物影响：必须空腹服用ZYTIGA。当与食物同时服用醋酸阿比特龙[abiraterone acetate]阿比特龙的暴露(曲线下面积)增加达10倍。
【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
【规格价格】250mg*120片/瓶/21200元
【生产企业】美国Centocor Ortho Biotech Inc.(美国原装进口)
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>> 阿比特龙研究报告：年全球阿比特龙行业市场监测及消费需求深度调查研究报告
年全球阿比特龙行业市场监测及消费需求深度调查研究报告
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报告导读：本报告从国际阿比特龙发展、国内阿比特龙政策环境及发展、研发动态、进出口情况、重点生产企业、存在的问题及对策等多方面多角度阐述了阿比特龙市场的发展，并在此基础上对阿比特龙的发展前景做出了科学的预测，最后对阿比特龙投资潜力进行了分析。
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第一章 阿比特龙行业发展概述
第一节 阿比特龙行业定义
一、阿比特龙定义
二、阿比特龙应用
第二节 阿比特龙行业发展概况
一、全球阿比特龙行业发展简述
二、国内阿比特龙行业现状阐述
第三节 阿比特龙行业产品发展历程
第四节 阿比特龙行业产品发展所处的阶段
第五节 阿比特龙行业技术发展状况
第六节 阿比特龙行业分析
第二章 年阿比特龙行业环境分析
第一节中国经济发展环境分析
一、中国GDP分析
三、城镇人员从业状况
四、恩格尔系数分析
五、年中国宏观经济发展预测
第二节中国阿比特龙行业政策环境分析
一、产业政策分析
二、相关产业政策影响分析
第三节 中国阿比特龙行业技术环境分析
一、中国阿比特龙技术发展概况
二、中国阿比特龙产品工艺特点或流程
三、中国阿比特龙行业技术发展趋势
第三章 中国阿比特龙行业区域市场营销策略分析
第一节 华北地区
一、阿比特龙行业区域营销环境分析
二、阿比特龙行业区域市场发展概况
三、阿比特龙行业区域营销优劣势分析
四、阿比特龙行业区域重点企业营销现状
五、阿比特龙行业区域重点品牌营销现状
第二节 华东地区
一、阿比特龙行业区域营销环境分析
二、阿比特龙行业区域市场发展概况
三、阿比特龙行业区域营销优劣势分析
四、阿比特龙行业区域重点企业营销现状
五、阿比特龙行业区域重点品牌营销现状
第三节 华南地区
一、阿比特龙行业区域营销环境分析
二、阿比特龙行业区域市场发展概况
三、阿比特龙行业区域营销优劣势分析
四、阿比特龙行业区域重点企业营销现状
五、阿比特龙行业区域重点品牌营销现状
第四节 东北地区
一、阿比特龙行业区域营销环境分析
二、阿比特龙行业区域市场发展概况
三、阿比特龙行业区域营销优劣势分析
四、阿比特龙行业区域重点企业营销现状
五、阿比特龙行业区域重点品牌营销现状
第五节 西南地区
一、阿比特龙行业区域营销环境分析
二、阿比特龙行业区域市场发展概况
三、阿比特龙行业区域营销优劣势分析
四、阿比特龙行业区域重点企业营销现状
五、阿比特龙行业区域重点品牌营销现状
第六节 西北地区
一、阿比特龙行业区域营销环境分析
二、阿比特龙行业区域市场发展概况
三、阿比特龙行业区域营销优劣势分析
四、阿比特龙行业区域重点企业营销现状
五、阿比特龙行业区域重点品牌营销现状
第四章 中国阿比特龙上游行业发展状况与影响
第一节 A行业
一、行业发展概况
二、对阿比特龙行业发展的影响
第二节 B行业
一、行业发展概况
二、对阿比特龙行业发展的影响
第五章 中国阿比特龙下游行业发展状况与应用
第一节 A行业
一、行业发展概况
二、阿比特龙的应用情况
第二节 B行业
一、行业发展概况
二、阿比特龙的应用情况
第三节 C行业
一、行业发展概况
二、阿比特龙的应用情况
第六章 中国阿比特龙行业重点企业产品营销状况对比分析（3-5家企业）
1、企业基本介绍
2、产品结构分析
3、产品价格分析
4、销售渠道分析
5、市场营销区域分析
6、主要客户分析
7、未来营销策略发展趋势
第七章 中国阿比特龙市场竞争力评价
第一节 中国阿比特龙市场竞争力评价
一、品牌竞争力评价指标体系
二、品牌竞争力评价
第二节 中国阿比特龙市场品牌竞争力提升策略
一、中国阿比特龙品牌定位研究分析
二、中国阿比特龙企业品牌管理模式
三、中国阿比特龙企业品牌推广经验
四、中国阿比特龙企业品牌提升策略研究
第八章 年中国阿比特龙行业未来发展趋势
第一节 中国阿比特龙行业外部环境走势及影响
一、经济环境变化及影响
二、政策环境变化及影响
三、国际市场发展趋势动态
第二节 中国阿比特龙行业上下游产业变化及影响
一、上游行业未来变化及其影响
二、下游行业未来变化及其影响
第三节 中国阿比特龙行业发展趋势分析
一、产品及技术趋势
二、竞争格局趋势
第四节 中国阿比特龙市场供需前景分析
第九章 年中国阿比特龙企业发展策略建议
第一节 应对行业外部环境变化的策略建议
第二节 产品及技术策略建议
第三节 目标市场定位策略建议
第四节 市场竞争及营销策略建议
第十章 年中国阿比特龙市场品牌消费前景及发展预测
第一节 年中国阿比特龙行业发展前景展望
一、国内市场发展前景
二、阿比特龙市场空间预测
三、中国阿比特龙市场消费规模及增长
四、中国阿比特龙潜在需求
第二节 年中国阿比特龙行业发展趋势研究
第三节 年中国阿比特龙行业市场盈利空间预测
第四节 年中国阿比特龙发展战略路线研讨
第十一章 年中国阿比特龙行业投资战略指导
第一节 年中国阿比特龙投资环境分析
第二节 年中国阿比特龙投资机会剖析
二、投资商机
三、投资潜力
第三节 年中国阿比特龙投资风险预警
一、市场风险
二、竞争风险
四、进退风险
第四节 投资建议
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报告标题：阿比特龙研究报告：年全球阿比特龙行业市场监测及消费需求深度调查研究报告
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ZYTIGA(abiraterone acetate)醋酸阿比特龙片
ZYTIGA(abiraterone acetate)醋酸阿比特龙片
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ZYTIGA(醋酸阿比特龙)片为难治性前列腺癌患者口服给药批准日期：日；原研厂家（公司）：Centocor Ortho Biotech Inc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 ...关键字：
ZYTIGA(醋酸阿比特龙)片为难治性前列腺癌患者口服给药批准日期：日；原研厂家（公司）：Centocor Ortho Biotech Inc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5mg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。（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）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。剂型和规格 250mg片禁忌证 妊娠或可能成为妊娠妇女禁忌用ZYTIGA。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。尚未确定在有射血分量LVEF &50%或NYHA类别III或IV心衰患者中ZYTIGA的安全性。治疗前控制高血压和纠正低钾血症。至少每月1次监查血压，血清钾和液体潴留症状。（2）肾上腺皮质功能不全：监视肾上腺皮质功能不全的症状和征象。应急情况前，期间和后可能适应增加皮质激素剂量。（3）肝毒性：肝酶增加曾导致药物中断，剂量调整和/或终止。监查肝功能和如建议调整，中断或终止ZYTIGA给药。（4）食物影响：必须空腹服用ZYTIGA。当与食物同时服用醋酸阿比特龙[abiraterone acetate]阿比特龙的暴露(曲线下面积)增加达10倍。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。药物相互作用 ZYTIGA是一种肝药物代谢酶CYP2D6是抑制剂。因为治疗指数窄，避免ZYTIGA与CYP2D6底物共同给药。如果不能使用另外治疗，小心对待和考虑减低同时给予CYP2D6底物剂量。特殊人群中使用 在基线严重肝受损(Child-Pugh类别 C)患者中不要使用ZYTIGA。ZYTIGA& (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) who have received prior chemotherapy containing docetaxel.Important Safety InformationContraindications - ZYTIGA& (abiraterone acetate) may cause fetal harm (Pregnancy Category X) 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 hypertension, hypokalemia, and 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 because these patients were excluded from the randomized clinical trial. 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 has been reported in clinical trials 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 - Increases in liver enzymes have led to drug interruption, dose modification, and/or discontinuation. 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.Food Effect - ZYTIGA& must be taken on an empty stomach. Exposure of abiraterone increases up to 10-fold when abiraterone acetate is taken with meals. No food should be eaten 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.& Abiraterone Cmax and AUC0-infinity (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.Adverse Reactions - The most common adverse reactions (≥5%) are joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, fractures and upper respiratory tract infection.Drug Interactions - ZYTIGA& is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid coadministration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. Additionally, abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.Use in Specific Populations - The safety of ZYTIGA& in patients with baseline severe hepatic impairment has not been studied. These patients should not receive ZYTIGA&.
Zytiga 250 mg tablets 1. Name of the medicinal product&ZYTIGA 250 mg tablets2. Qualitative and quantitative compositionEach tablet contains 250 mg of abiraterone acetate.Excipients with known effect: Each tablet contains 189 mg of lactose and 6.8 mg of sodium.For the full list of excipients, see section 6.1.3. Pharmaceutical formTablet.White to off-white oval tablets, debossed with AA250 on one side.4. Clinical particulars4.1 Therapeutic indicationsZYTIGA is indicated with prednisone or prednisolone for:&#8226; the treatment of metastatic castration resistant prostate cancer in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated (see section 5.1)&#8226; the treatment of metastatic castration resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.4.2 Posology and method of administrationPosologyThe recommended dose is 1,000 mg (four 250 mg tablets) as a single daily dose that must not be taken with food (see information on the method of administration). Taking the tablets with food increases systemic exposure to abiraterone (see sections 4.5 and 5.2).ZYTIGA is to be taken with low dose prednisone or prednisolone. The recommended dose of prednisone or prednisolone is 10 mg daily.Medical castration with LHRH analogue should be continued during treatment in patients not surgically castrated.Serum transaminases should be measured prior to starting treatment, every two weeks for the first three months of treatment and monthly thereafter. Blood pressure, serum potassium and fluid retention should be monitored monthly. However, patients with a significant risk for congestive heart failure should be monitored every 2 weeks for the first three months of treatment and monthly thereafter (see section 4.4).In patients with pre-existing hypokalaemia or those that develop hypokalaemia whilst being treated with ZYTIGA, consider maintaining the patient's potassium level at ≥ 4.0 mM.For patients who develop Grade ≥ 3 toxicities including hypertension, hypokalaemia, oedema and other non-mineralocorticoid toxicities, treatment should be withheld and appropriate medical management should be instituted. Treatment with ZYTIGA should not be reinitiated until symptoms of the toxicity have resolved to Grade 1 or baseline.In the event of a missed daily dose of either ZYTIGA, prednisone or prednisolone, treatment should be resumed the following day with the usual daily dose.HepatotoxicityFor patients who develop hepatotoxicity during treatment (alanine aminotransferase [ALT] increases or aspartate aminotransferase [AST] increases above 5 times the upper limit of normal [ULN]), treatment should be withheld immediately (see section 4.4). Re-treatment following return of liver function tests to the patient's baseline may be given at a reduced dose of 500 mg (two tablets) once daily. For patients being re-treated, serum transaminases should be monitored at a minimum of every two weeks for three months and monthly thereafter. If hepatotoxicity recurs at the reduced dose of 500 mg daily, treatment should be discontinued.If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on therapy, treatment should be discontinued and patients should not be re-treated.Hepatic impairmentNo dose adjustment is necessary for patients with pre-existing mild hepatic impairment, Child-Pugh Class A.Moderate hepatic impairment (Child-Pugh Class B) has been shown to increase the systemic exposure to abiraterone by approximately four-fold following single oral doses of abiraterone acetate 1,000 mg (see section 5.2). There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). No dose adjustment can be predicted. The use of ZYTIGA should be cautiously assessed in patients with moderate hepatic impairment, in whom the benefit clearly should outweigh the possible risk (see sections 4.2 and 5.2). ZYTIGA should not be used in patients with severe hepatic impairment (see sections 4.3, 4.4 and 5.2).Renal impairmentNo dose adjustment is necessary for patients with renal impairment (see section 5.2). However, there is no clinical experience in patients with prostate cancer and severe renal impairment. Caution is advised in these patients (see section 4.4).Paediatric populationThere is no relevant use of this medicinal product in the paediatric population, as prostate cancer is not present in children and adolescents.Method of administrationZYTIGA should be taken at least two hours after eating and no food should be eaten for at least one hour after taking the tablets. These should be swallowed whole with water.4.3 Contraindications- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.- Women who are or may potentially be pregnant (see section 4.6).- Severe hepatic impairment [Child-Pugh Class C (see sections 4.2, 4.4 and 5.2)].4.4 Special warnings and precautions for use&Hypertension, hypokalaemia, fluid retention and cardiac failure due to mineralocorticoid excessZYTIGA may cause hypertension, hypokalaemia and fluid retention (see section 4.8) as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition (see section 5.1). Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in incidence and severity of these adverse reactions. Caution is required in treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalaemia (e.g., those on cardiac glycosides), or fluid retention (e.g., those with heart failure), severe or unstable angina pectoris, recent myocardial infarction or ventricular arrhythmia and those with severe renal impairment.ZYTIGA should be used with caution in patients with a history of cardiovascular disease. The phase 3 studies conducted with ZYTIGA excluded patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class (NYHA) III or IV heart failure (study 301) or Class II to IV heart failure (study 302) or cardiac ejection fraction measurement of & 50%. In study 302 patients with atrial fibrillation, or other cardiac arrhythmia requiring medical therapy were excluded. Safety in patients with left ventricular ejection fraction (LVEF) & 50% or NYHA Class III or IV heart failure (in study 301) or NYHA Class II to IV heart failure (in study 302) was not established (see sections 4.8 and 5.1).Before treating patients with a significant risk for congestive heart failure (e.g.a history of cardiac failure, uncontrolled hypertension, or cardiac events such as ischaemic heart disease), consider obtaining an assessment of cardiac function (e.g. echocardiogram). Before treatment with ZYTIGA, cardiac failure should be treated and cardiac function optimised. Hypertension, hypokalaemia and fluid retention should be corrected and controlled. During treatment, blood pressure, serum potassium, fluid retention (weight gain, peripheral oedema), and other signs and symptoms of congestive heart failure should be monitored every 2 weeks for 3 months, then monthly thereafter and abnormalities corrected. Assess cardiac function as clinically indicated, institute appropriate management and consider discontinuation of ZYTIGA treatment if there is a clinically significant decrease in cardiac function (see section4.2).Hepatotoxicity and Hepatic impairmentMarked increases in liver enzymes leading to treatment discontinuation or dose modification occurred in controlled clinical studies (see section 4.8). Serum transaminase levels should be measured prior to starting treatment, every two weeks for the first three months of treatment, and monthly thereafter. If clinical symptoms or signs suggestive of hepatotoxicity develop, serum transaminases should be measured immediately. If at any time the ALT or AST rises above 5 times the upper limit of normal, treatment should be interrupted immediately and liver function closely monitored. Re-treatment may take place only after return of liver function tests to the patient's baseline and at a reduced dose level (see section 4.2).If patients develop severe hepatotoxicity (ALT or AST 20 times the upper limit of normal) anytime while on therapy, treatment should be discontinued and patients should not be re-treated.Patients with active or symptomatic viral hepatitis were excluded
thus, there are no data to support the use of ZYTIGA in this population.There are no data on the clinical safety and efficacy of multiple doses of abiraterone acetate when administered to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). The use of ZYTIGA should be cautiously assessed in patients with moderate hepatic impairment, in whom the benefit clearly should outweigh the possible risk (see sections 4.2 and 5.2). ZYTIGA should not be used in patients with severe hepatic impairment (see sections 4.2, 4.3 and 5.2).Corticosteroid withdrawal and coverage of stress situationsCaution is advised and monitoring for adrenocortical insufficiency should occur if patients are withdrawn from prednisone or prednisolone. If ZYTIGA is continued after corticosteroids are withdrawn, patients should be monitored for symptoms of mineralocorticoid excess (see information above).In patients on prednisone or prednisolone who are subjected to unusual stress, an increased dose of corticosteroids may be indicated before, during and after the stressful situation.Bone densityDecreased bone density may occur in men with metastatic advanced prostate cancer (castration resistant prostate cancer). The use of ZYTIGA in combination with a glucocorticoid could increase this effect.Prior use of ketoconazoleLower rates of response might be expected in patients previously treated with ketoconazole for prostate cancer.HyperglycaemiaThe use of glucocorticoids could increase hyperglycaemia, therefore blood sugar should be measured frequently in patients with diabetes.Use with chemotherapyThe safety and efficacy of concomitant use of ZYTIGA with cytotoxic chemotherapy has not been established (see section 5.1).Intolerance to excipientsThis medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicinal product also contains more than 1 mmol (or 27.2 mg) sodium per dose of four tablets. To be taken into consideration by patients on a controlled sodium diet.Potential risksAnaemia and sexual dysfunction may occur in men with metastatic castration resistant prostate cancer including those undergoing treatment with ZYTIGA.Skeletal Muscle EffectsCases of myopathy have been reported in patients treated with ZYTIGA. Some patients had rhabdomyolysis with renal failure. Most cases developed within the first month of treatment and recovered after ZYTIGA withdrawal. Caution is recommended in patients concomitantly treated with drugs known to be associated with myopathy/rhabdomyolysis.Interactions with other medicinal productsStrong inducers of CYP3A4 during treatment are to be avoided unless there is no therapeutic alternative, due to risk of decreased exposure to ZYTIGA (see section 4.5).4.5 Interaction with other medicinal products and other forms of interactionAdministration with food significantly increases the absorption of abiraterone acetate. The efficacy and safety of ZYTIGA given with food have not been established. ZYTIGA must not be taken with food (see sections 4.2 and 5.2).In a study to determine the effects of abiraterone acetate (plus prednisone) on a single dose of the CYP2D6 substrate dextromethorphan, the systemic exposure (AUC) of dextromethorphan was increased approximately 2.9 fold. The AUC24 for dextrorphan, the active metabolite of dextromethorphan, increased approximately 33%.Caution is advised when ZYTIGA is administered with medicinal products activated by or metabolised by CYP2D6, particularly with medicinal products that have a narrow therapeutic index. Dose reduction of medicinal products with a narrow therapeutic index that are metabolised by CYP2D6 should be considered. Examples of medicinal products metabolised by CYP2D6 include metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecainide, codeine, oxycodone and tramadol (the latter three products requiring CYP2D6 to form their active analgesic metabolites).Based on in vitro data, ZYTIGA is an inhibitor of the hepatic drug-metabolising enzyme CYP2C8. Examples of medicinal products metabolised by CYP2C8 include paclitaxel and repaglinide. There are no clinical data on the use of ZYTIGA with drugs that are substrates of CYP2C8.In a clinical pharmacokinetic interaction study of healthy subjects pretreated with a strong CYP3A4 inducer rifampicin, 600 mg daily for 6 days followed by a single dose of abiraterone acetate 1,000 mg, the mean plasma AUC∞ of abiraterone was decreased by 55%.Strong inducers of CYP3A4 (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St John's wort [Hypericum perforatum]) during treatment are to be avoided, unless there is no therapeutic alternative.In a separate clinical pharmacokinetic interaction study of healthy subjects, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.4.6 Fertility, pregnancy and lactationWomen of childbearing potentialThere are no human data on the use of ZYTIGA in pregnancy and this medicinal product is not for use in women of childbearing potential.Contraception in males and femalesIt is not known whether abiraterone or its metabolites are present in semen. A condom is required if the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sex with a woman of childbearing potential, a condom is required along with another effective contraceptive method. Studies in animals have shown reproductive toxicity (see section 5.3).PregnancyZYTIGA is not for use in women. Abiraterone acetate is contraindicated in women who are or may potentially be pregnant (see section 4.3 and 5.3).Breast-feedingZYTIGA is not for use in women.FertilityAbiraterone affected fertility in male and female rats, but these effects were fully reversible (see section 5.3).4.7 Effects on ability to drive and use machines&ZYTIGA has no or negligible influence on the ability to drive or use machines.4.8 Undesirable effectsSummary of the safety profileThe most common adverse reactions seen are peripheral oedema, hypokalaemia, hypertension and urinary tract infection.Other important adverse reactions include, cardiac disorders, hepatotoxicity, fractures, and allergic alveolitis.ZYTIGA may cause hypertension, hypokalaemia and fluid retention as a pharmacodynamic consequence of its mechanism of action. Inclinical studies, anticipated mineralocorticoid adverse reactions were seen more commonly in patients treated with ZYTIGA than in patients treated with placebo: hypokalaemia 21% versus 11%, hypertension 16% versus 11% and fluid retention (peripheral oedema) 26% versus 20%, respectively. In patients treated with ZYTIGA, CTCAE (version 3.0) Grades 3 and 4 hypokalaemia and CTCAE (version 3.0) Grades 3 and 4 hypertension were observed in 4% and 2% of patients, respectively. Mineralocorticoid reactions generally were able to be successfully managed medically. Concomitant use of a corticosteroid reduces the incidence and severity of these adverse reactions (see section 4.4).Tabulated summary of adverse reactionsIn studies of patients with metastatic advanced prostate cancer who were using a luteinising hormone-releasing hormone (LHRH) analogue, or were previously treated with orchiectomy, ZYTIGA was administered at a dose of 1,000 mg daily in combination with low dose prednisone or prednisolone (10 mg daily).Adverse reactions observed during clinical studies and post-marketing experience are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to & 1/10); uncommon (≥ 1/1,000 to & 1/100); rare (≥1/10,000 to &1/1,000); very rare (&1/10,000).Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.Table 1: Adverse reactions identified in clinical studies and post-marketing
Infections and infestations
very common: urinary tract infection
common: sepsis
Endocrine disorders
uncommon: adrenal insufficiency
Metabolism and nutrition disorders
very common: hypokalaemia
common: hypertriglyceridaemia
Cardiac disorders
common: cardiac failure*, angina pectoris, arrhythmia, atrial fibrillation, tachycardia
Vascular disorders
very common: hypertension
Respiratory, thoracic and mediastinal disorders
rare: allergic alveolitisa
Gastrointestinal disorders
very common: diarrhoea
common: dyspepsia
Hepatobiliary disorders
common: alanine aminotransferase increased, aspartate aminotransferase increased
Skin and subcutaneous tissue disorders
common: rash
Musculoskeletal and connective tissue disorders
uncommon: myopathy, rhabdomyolysis
Renal and urinary disorders
common: haematuria
General disorders and administration site conditions
very common: oedema peripheral
Injury, poisoning and procedural complications
common: fractures** * Cardiac failure also includes congestive heart failure, left ventricular dysfunction and ejection fraction decreased ** Fractures includes all fractures with the exception of pathological fracture a Spontaneous reports from post-marketing experience The following CTCAE (version 3.0) Grade 3 adverse reactions occurred in patients treated with ZYTIGA: hypokalaemia 3%; urinary tract infection, alanine aminotransferase increased, hypertension, aspartate aminotransferase increased, fractures 2%; peripheral oedema, cardiac failure, and atrial fibrillation 1% each. CTCAE (version 3.0) Grade 3 hypertriglyceridaemia and angina pectoris occurred in & 1% of patients. CTCAE (version 3.0) Grade 4 peripheral oedema, hypokalaemia, urinary tract infection, cardiac failure and fractures occurred in & 1% of patients.Description of selected adverse reactionsCardiovascular reactionsBoth phase 3 studiesexcluded patients with uncontrolled hypertension, clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA Class III or IV heart failure (study 301) or Class II to IV heart failure (study 302) or cardiac ejection fraction measurement of & 50%. All patients enrolled (both active and placebo-treated patients) were concomitantly treated with androgen deprivation therapy, predominantly with the use of LHRH analogues, which has been associated with diabetes, myocardial infarction, cerebrovascular accident and sudden cardiac death. The incidence of cardiovascular adverse reactions in the phase 3 studies in patients taking ZYTIGA versus patients taking placebo were as follows: hypertension 14.5% vs. 10.5%, atrial fibrillation 3.4% vs. 3.4%, tachycardia 2.8% vs. 1.7%, angina pectoris 1.9% vs. 0.9%, cardiac failure 1.9% vs. 0.6%, and arrhythmia 1.1% vs. 0.4%.HepatotoxicityHepatotoxicity with elevated ALT, aspartate transaminase (AST) and total bilirubin has been reported in patients treated with ZYTIGA. Across all clinical studies, liver function test elevations (ALT or AST increases of & 5 x ULN or bilirubin increases & 1.5 x ULN) were reported in approximately 4% of patients who received ZYTIGA, typically during the first 3 months after starting treatment. In the 301 clinical study, patients whose baseline ALT or AST were elevated were more likely to experience liver function test elevations than those beginning with normal values. When elevations of either ALT or AST & 5 x ULN, or elevations in bilirubin & 3 x ULN were observed, ZYTIGA was withheld or discontinued. In two instances marked increases in liver function tests occurred (see section 4.4). These two patients with normal baseline hepatic function, experienced ALT or AST elevations 15 to 40 x ULN and bilirubin elevations 2 to 6 x ULN. Upon discontinuation of ZYTIGA, both patients had normalisation of their liver function tests and one patient was re-treated without recurrence of the elevations. In study 302, Grade 3 or 4 ALT or AST elevations were observed in 35 (6.5%) patients treated with ZYTIGA. Aminotransferase elevations resolved in all but 3 patients (2 with new multiple liver metastases and 1 with AST elevation approximately 3 weeks after the last dose of ZYTIGA). Treatment discontinuations due to ALT and AST increases were reported in 1.7% and 1.3% of patients treated with ZYTIGA and 0.2% and 0% of patients treated with placebo, respectively. No deaths were reported due to hepatotoxicity event.In clinical trials, the risk for hepatotoxicity was mitigated by exclusion of patients with baseline hepatitis or significant abnormalities of liver function tests. In the 301 trial, patients with baseline ALT and AST ≥ 2.5 x ULN in the absence of liver metastases and & 5 x ULN in the presence of liver metastases wereexcluded. In the 302 trial, patients with liver metastases were not eligible and patients with baseline ALT and AST ≥ 2.5 x ULN were excluded. Abnormal liver function tests developing in patients participating in clinical trials were vigorously managed by requiring treatment interruption and permitting re-treatment only after return of liver function tests to the patient's baseline (see section 4.2). Patients with elevations of ALT or AST & 20 x ULN were not re-treated. The safety of re-treatment in such patients is unknown. The mechanism for hepatotoxicity is not understood.Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: United KingdomYellow Card Scheme Website: Ireland Pharmacovigilance SectionIrish Medicines BoardKevin O'Malley HouseEarlsfort CentreEarlsfort TerraceIRL - Dublin 2Tel: +353 1 6764971Fax: +353 1 6762517Website: e-mail: 4.9 OverdoseHuman experience of overdose with ZYTIGA is limited.There is no specific antidote. In the event of an overdose, administration should be withheld and general supportive measures undertaken, including monitoring for arrhythmias, hypokalaemia and for signs and symptoms of fluid retention. Liver function also should be assessed.5. Pharmacological properties5.1 Pharmacodynamic properties&Pharmacotherapeutic group: endocrine therapy, other hormone antagonists and related agents, ATC code: L02BX03Mechanism of actionAbiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. Specifically, abiraterone selectively inhibits the enzyme 17α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in and is required for androgen biosynthesis in testicular, adrenal and prostatic tumour tissues. CYP17 catalyses the conversion of pregnenolone and progesterone into testosterone precursors, DHEA and androstenedione, respectively, by 17α-hydroxylation and cleavage of the C17,20 bond. CYP17 inhibition also results in increased mineralocorticoid production by the adrenals (see section 4.4).Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with LHRH analogues or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumour. Treatment with ZYTIGA decreases serum testosterone to undetectable levels (using commercial assays) when given with LHRH analogues (or orchiectomy).Pharmacodynamic effectsZYTIGA decreases serum testosterone and other androgens to levels lower than those achieved by the use of LHRH analogues alone or by orchiectomy. This results from the selective inhibition of the CYP17 enzyme required for androgen biosynthesis. Prostate specific antigen (PSA) serves as a biomarker in patients with prostate cancer. In a phase 3 clinical study of patients who failed prior chemotherapy with taxanes, 38% of patients treated with ZYTIGA, versus 10% of patients treated with placebo, had at least a 50% decline from baseline in PSA levels.Clinical efficacy and safetyEfficacy was established in two randomised placebo-controlled multicentre phase 3 clinical studies (studies 301 and 302) of patients with metastatic castration resistant prostate cancer. Study 302 enrolled docetaxel na& whereas, study 301 enrolled patients who had received prior docetaxel. Patients were using an LHRH analogue or were previously treated with orchiectomy. In the active treatment arm, ZYTIGA was administered at a dose of 1,000 mg daily in combination with low dose prednisone or prednisolone 5 mg twice daily. Control patients received placebo and low dose prednisone or prednisolone 5 mg twice daily.Changes in PSA serum concentration independently do not always predict clinical benefit. Therefore, in both studies it was recommended that patients be maintained on their study treatments until discontinuation criteria were met as specified below for each study.Study 302 (chemotherapy na&ve patients)This study enrolled chemotherapy na&ve patients who were asymptomatic or mildly symptomatic and for whom chemotherapy was not yet clinically indicated. A score of 0-1 on Brief Pain Inventory-Short Form (BPI-SF) worst pain in last 24 hours was considered asymptomatic, and a score of 2-3 was considered mildly symptomatic.In study 302, (n=1,088) the median age of enrolled patients was 71 years for patients treated with ZYTIGA plus prednisone or prednisolone and 70 years for patients treated with placebo plus prednisone or prednisolone. The number of patients treated with ZYTIGA by racial group was Caucasian 520 (95.4%), Black 15 (2.8%), Asian 4 (0.7%) and other 6 (1.1%). The ECOG performance status was 0 for 76% of patients, and 1 for 24% of patients in both arms. Fifty percent of patients had only bone metastases, an additional 31% of patients had bone and soft tissue or lymph node metastases and 19% of patients had only soft tissue or lymph node metastases. Patients with visceral metastases were excluded. Co-primary efficacy endpoints were overall survival and radiographic progression-free survival (rPFS). In addition to the co-primary endpoint measures, benefit was also assessed using time to opiate use for cancer pain, time to initiation of cytotoxic chemotherapy, time to deterioration in ECOG performance score by ≥ 1 point and time to PSA progression based on Prostate Cancer Working Group-2 (PCWG2) criteria. Study treatments were discontinued at the time of unequivocal clinical progression. Treatments could also be discontinued at the time of confirmed radiographic progression at the discretion of the investigator.Radiographic progression free survival was assessed with the use of sequential imaging studies as defined by PCWG2 criteria (for bone lesions) and modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria (for soft tissue lesions). Analysis of rPFS utilised centrally-reviewed radiographic assessment of progression.At the planned rPFS analysis there were 401 events, 150 (28%) of patients treated with ZYTIGA and 251 (46%) of patients treated with placebo had radiographic evidence of progression or had died. A significant difference in rPFS between treatment groups was observed (see Table 2 and Figure 1).Table 2: Study 302: Radiographic progression-free survival of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy
Radiographic Progression-free Survival (rPFS)
Progression or death
Median rPFS in months
Not reached
(11.66, NE)
(8.12, 8.54)
Hazard ratio**
0.425 (0.347, 0.522) NE=Not Estimated* P-value is derived from a log rank test stratified by baseline ECOG score (0 or 1)** Hazard ratio & 1 favours ZYTIGAFigure 1: Kaplan Meier curves of radiographic progression-free survival in patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy
AA=ZYTIGAHowever, subject data continued to be collected through the date of the second interim analysis of Overall survival (OS). The investigator radiographic review of rPFS performed as a follow up sensitivity analysis is presented in Table 3 and Figure 2.Six hundred and seven (607) subjects had radiographic progression or died: 271 (50%) in the abiraterone acetate group and 336 (62%) in the placebo group. Treatment with abiraterone acetate decreased the risk of radiographic progression or death by 47% compared with placebo (HR=0.530; 95% CI: 0.451; 0.623; p & 0.0001). The median rPFS was 16.5 months in the abiraterone acetate group and 8.3 months in the placebo group.Table 3: Study 302: Radiographic progression-free survival of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy (At second interim analysis of OS-Investigator Review)
Radiographic Progression-free Survival (rPFS)
Progression or death
Median rPFS in months
(13.80, 16.79)
(8.05, 9.43)
Hazard ratio**
0.530 (0.451, 0.623) * P-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1) ** Hazard ratio & 1 favours ZYTIGAFigure 2: Kaplan Meier curves of radiographic progression-free survival in patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy (At second interim analysis of OS-Investigator Review)
AA=ZYTIGAA planned analysis for overall survival was conducted after 333 deaths were observed. The study was unblinded based on the magnitude of clinical benefit observed. Twenty seven percent (147 of 546) of patients treated with ZYTIGA, compared with 34% (186 of 542) of patients treated with placebo, had died. Overall survival was longer for ZYTIGA than placebo with a 25% reduction in risk of death (HR=0.752; 95% CI: 0.606; 0.934). The p-value was 0.0097 which did not meet the pre-specified value for statistical significance (see Table 4 and Figure 3).Table 4: Study 302: Overall survival of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy
Overall Survival
Deaths (%)
Median survival (months)
Not reached
(25.95, NE)
Hazard ratio**
0.752 (0.606, 0.934) NE=Not Estimated
* P-value is derived from a log-rank test stratified by baseline ECOG score (0 or 1) ** Hazard ratio & 1 favours ZYTIGAFigure 3: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy
AA=ZYTIGAIn addition to the observed improvements in overall survival and rPFS, benefit was demonstrated for ZYTIGA vs. placebo treatment in all secondary endpoint measures as follows:Time to PSA progression based on PCWG2 criteria: The median time to PSA progression was 11.1 months for patients receiving ZYTIGA and 5.6 months for patients receiving placebo (HR=0.488; 95% CI: [0.420, 0.568], p & 0.0001). The time to PSA progression was approximately doubled with ZYTIGA treatment (HR=0.488). The proportion of subjects with a confirmed PSA response was greater in the ZYTIGA group than in the placebo group (62% versus 24%; p & 0.0001). In subjects with measurable soft tissue disease, significantly increased numbers of complete and partial tumor responses were seen with ZYTIGA treatment.Time to opiate use for cancer pain: The median time to opiate use for prostate cancer pain was not reached for patients receiving ZYTIGA and was 23.7 months for patients receiving placebo (HR=0.686; 95% CI: [0.566, 0.833], p=0.0001).Time to initiation of cytotoxic chemotherapy: The median time to initiation of cytotoxic chemotherapy was 25.2 months for patients receiving ZYTIGA and 16.8 months for patients receiving placebo (HR=0.580; 95% CI: [0.487, 0.691], p & 0.0001).Time to deterioration in ECOG performance score by ≥ 1 point: The median time to deterioration in ECOG performance score by ≥ 1 point was 12.3 months for patients receiving ZYTIGA and 10.9 months for patients receiving placebo (HR=0.821; 95% CI: [0.714, 0.943], p=0.0053).The following study endpoints demonstrated a statistically significant advantage in favour of ZYTIGA treatment:Objective response: Objective response was defined as the proportion of subjects with measurable disease achieving a complete or partial response according to RECIST criteria (baseline lymph node size was required to be ≥ 2 cm to be considered a target lesion). The proportion of subjects with measurable disease at baseline who had an objective response was 36% in the ZYTIGA group and 16% in the placebo group (p & 0.0001).Pain: Treatment with ZYTIGA significantly reduced the risk of average pain intensity progression by 18% compared with placebo (p=0.0490). The median time to progression was 26.7 months in the ZYTIGA group and 18.4 months in the placebo group.Time to degradation in the FACT-P (Total Score): Treatment with ZYTIGA decreased the risk of FACT-P (Total Score) degradation by 22% compared with placebo (p=0.0028). The median time to degradation in FACT-P (Total Score) was 12.7 months in the ZYTIGA group and 8.3 months in the placebo group.Study 301 (patients who had received prior chemotherapy)Study 301 enrolled patients who had received prior docetaxel. Patients were not required to show disease progression on docetaxel, as toxicity from this chemotherapy may have led to discontinuation.Patients were maintained on study treatments until there was PSA progression (confirmed 25% increase over the patient's baseline/nadir) together with protocol-defined radiographic progression and symptomatic or clinical progression. Patients with prior ketoconazole treatment for prostate cancer were excluded from this study. The primary efficacy endpoint was overall survival.The median age of enrolled patients was 69 years (range 39-95). The number of patients treated with ZYTIGA by racial group was Caucasian 737 (93.2%), Black 28 (3.5%), Asian 11 (1.4%) and other 14 (1.8%). Eleven percent of patients enrolled had an ECOG performance score of 2; 70% had radiographic evidence of disease progression with or without PSA 70% had received one prior cytotoxic chemotherapy and 30% received two. Liver metastasis was present in 11% of patients treated with ZYTIGA.In a planned analysis conducted after 552 deaths were observed, 42% (333 of 797) of patients treated with ZYTIGA compared with 55% (219 of 398) of patients treated with placebo, had died. A statistically significant improvement in median overall survival was seen in patients treated with ZYTIGA (see Table 5).Table 5: Overall survival of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy
Primary Survival Analysis
Deaths (%)
Median survival (months)
14.8 (14.1, 15.4)
10.9 (10.2, 12.0)
Hazard ratio (95% CI) b
0.646 (0.543, 0.768)
Updated Survival Analysis
Deaths (%)
Median survival (months)
15.8 (14.8, 17.0)
11.2 (10.4, 13.1)
Hazard ratio (95% CI) b
0.740 (0.638, 0.859)
a P-value is derived from a log-rank test stratified by ECOG performance status score (0-1 vs. 2), pain score (absent vs. present), number of prior chemotherapy regimens (1 vs. 2), and type of disease progression (PSA only vs. radiographic). b Hazard ratio is derived from a stratified proportional hazards model. Hazard ratio & 1 favours ZYTIGAAt all evaluation time points after the initial few months of treatment, a higher proportion of patients treated with ZYTIGA remained alive, compared with the proportion of patients treated with placebo (see Figure 4).Figure 4: Kaplan Meier survival curves of patients treated with either ZYTIGA or placebo in combination with prednisone or prednisolone plus LHRH analogues or prior orchiectomy
AA=ZYTIGASubgroup survival analyses showed a consistent survival benefit for treatment with ZYTIGA (see Figure 5).Figure 5: Overall survival by subgroup: hazard ratio and 95% confidence interval
AA=ZYTIGA; BPI=Brief Pain I C.I.= ECOG=Eastern Cooperative Oncology Gro HR= NE=not evaluableIn addition to the observed improvement in overall survival, all secondary study endpoints favoured ZYTIGA and were statistically significant after adjusting for multiple testing as follows:Patients receiving ZYTIGA demonstrated a significantly higher total PSA response rate (defined as a ≥ 50% reduction from baseline), compared with patients receiving placebo, 38% versus 10%, p & 0.0001.The median time to PSA progression was 10.2 months for patients treated with ZYTIGA and 6.6 months for patients treated with placebo (HR=0.580; 95% CI: [0.462; 0.728], p & 0.0001).The median radiographic progression-free survival was 5.6 months for patients treated with ZYTIGA and 3.6 months for patients who received placebo (HR=0.673; 95% CI: [0.585; 0.776], p & 0.0001).PainThe proportion of patients with pain palliation was statistically significantly higher in the ZYTIGA group than in the placebo group (44% versus 27%, p=0.0002). A responder for pain palliation was defined as a patient who experienced at least a 30% reduction from baseline in the BPI-SF worst pain intensity score over the last 24 hours without any increase in analgesic usage score observed at two consecutive evaluations four weeks apart. Only patients with a baseline pain score of ≥ 4 and at least one post-baseline pain score were analysed (N=512) for pain palliation.A lower proportion of patients treated with ZYTIGA had pain progression compared to patients taking placebo at 6 (22% versus 28%), 12 (30% versus 38%) and 18 months (35% versus 46%). Pain progression was defined as an increase from baseline of ≥ 30% in the BPI-SF worst pain intensity score over the previous 24 hours without a decrease in analgesic usage score observed at two consecutive visits, or an increase of ≥ 30% in analgesic usage score observed at two consecutive visits. The time to pain progression at the 25th percentile was 7.4 months in the ZYTIGA group, versus 4.7 months in the placebo group.Skeletal-related eventsA lower proportion of patients in the ZYTIGA group had skeletal-related events compared with the placebo group at 6 months (18% versus 28%), 12 months (30% versus 40%), and 18 months (35% versus 40%). The time to first skeletal-related event at the 25th percentile in the ZYTIGA group was twice that of the control group at 9.9 months versus 4.9 months. A skeletal-related event was defined as a pathological fracture, spinal cord compression, palliative radiation to bone, or surgery to bone.Paediatric populationThe European Medicines Agency has waived the obligation to submit the results of studies with ZYTIGA in all subsets of the paediatric population in advanced prostate cancer (see section 4.2 for information on paediatric use).5.2 Pharmacokinetic propertiesFollowing administration of abiraterone acetate, the pharmacokinetics of abiraterone and abiraterone acetate have been studied in healthy subjects, patients with metastatic advanced prostate cancer and subjects without cancer with hepatic or renal impairment. Abiraterone acetate is rapidly converted in vivo to abiraterone, an androgen biosynthesis inhibitor (see section 5.1).AbsorptionFollowing oral administration of abiraterone acetate in the fasting state, the time to reach maximum plasma abiraterone concentration is approximately 2 hours.Administration of abiraterone acetate with food, compared with administration in a fasted state, results in up to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure of abiraterone, depending on the fat content of the meal. Given the normal variation in the content and composition of meals, taking ZYTIGA with meals has the potential to result in highly variable exposures. Therefore, ZYTIGA must not be taken with food. It should be taken at least two hours after eating and no food should be eaten for at least one hour after taking ZYTIGA. The tablets should be swallowed whole with water (see section 4.2).DistributionThe plasma protein binding of 14C-abiraterone in human plasma is 99.8%. The apparent volume of distribution is approximately 5,630 l, suggesting that abiraterone extensively distributes to peripheral tissues.BiotransformationFollowing oral administration of 14C-abiraterone acetate as capsules, abiraterone acetate is hydrolysed to abiraterone, which then undergoes metabolism including sulphation, hydroxylation and oxidation primarily in the liver. The majority of circulating radioactivity (approximately 92%) is found in the form of metabolites of abiraterone. Of 15 detectable metabolites, 2 main metabolites, abiraterone sulphate and N-oxide abiraterone sulphate, each represents approximately 43% of total radioactivity.EliminationThe mean half-life of abiraterone in plasma is approximately 15 hours based on data from healthy subjects. Following oral administration of 14C-abiraterone acetate 1,000 mg, approximately 88% of the radioactive dose is recovered in faeces and approximately 5% in urine. The major compounds present in faeces are unchanged abiraterone acetate and abiraterone (approximately 55% and 22% of the administered dose, respectively).Patients with hepatic impairmentThe pharmacokinetics of abiraterone acetate was examined in subjects with pre-existing mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) and in healthy control subjects. Systemic exposure to abiraterone after a single oral 1,000 mg dose increased by approximately 11% and 260% in subjects with mild and moderate pre-existing hepatic impairment, respectively. The mean half-life of abiraterone is prolonged to approximately 18 hours in subjects with mild hepatic impairment and to approximately 19 hours in subjects with moderate hepatic impairment. No dose adjustment is necessary for patients with pre-existing mild hepatic impairment.The use of ZYTIGA should be cautiously assessed in patients with moderate hepatic impairment in whom the benefit clearly should outweigh the possible risk (see sections 4.2 and 4.4). ZYTIGA should not be used in patients with severe hepatic impairment (see sections 4.2, 4.3 and 4.4).For patients who develop hepatotoxicity during treatment, suspension of treatment and dose adjustment may be required (see sections 4.2 and 4.4).Patients with renal impairmentThe pharmacokinetics of abiraterone acetate was compared in patients with end-stage renal disease on a stable haemodialysis schedule versus matched control subjects with normal renal function. Systemic exposure to abiraterone after a single oral 1,000 mg dose did not increase in subjects with end-stage renal disease on dialysis. Administration in patients with renal impairment, including severe renal impairment, does not require dose reduction (see section 4.2). However, there is no clinical experience in patients with prostate cancer and severe renal impairment. Caution is advised in these patients.5.3 Preclinical safety dataIn all animal toxicity studies, circulating testosterone levels were significantly reduced. As a result, reduction in organ weights and morphological and/or histopathological changes in the reproductive organs, and the adrenal, pituitary and mammary glands were observed. All changes showed complete or partial reversibility. The changes in the reproductive organs and androgen-sensitive organs are consistent with the pharmacology of abiraterone. All treatment-related hormonal changes reversed or were shown to be resolving after a 4-week recovery period.In fertility studies in both male and female rats, abiraterone acetate reduced fertility, which was completely reversible in 4 to 16 weeks after abiraterone acetate was stopped.In a developmental toxicity study in the rat, abiraterone acetate affected pregnancy including reduced foetal weight and survival. Effects on the external genitalia were observed though abiraterone acetate was not teratogenic.In these fertility and developmental toxicity studies performed in the rat, all effects were related to the pharmacological activity of abiraterone.Aside from reproductive organ changes seen in all animal toxicology studies, non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity. Abiraterone acetate was not carcinogenic in a 6-month study in the transgenic (Tg.rasH2) mouse. In a 24-month carcinogenicity study in the rat, abiraterone acetate increased the incidence of interstitial cell neoplasms in the testes. This finding is considered related to the pharmacological action of abiraterone and rat specific. Abiraterone acetate was not carcinogenic in female rats.6. Pharmaceutical particulars6.1 List of excipients&Cellulose, microcrystallineCroscarmellose sodiumLactose monohydrateMagnesium stearatePovidone (K29/K32)Silica, colloidal anhydrousSodium laurilsulfate6.2 IncompatibilitiesNot applicable.6.3 Shelf life2 years6.4 Special precautions for storageStore below 30°C.6.5 Nature and contents of containerRound white HDPE bottles fitted with a polypropylene child-resistant closure containing 120 tablets. Each pack contains one bottle.6.6 Special precautions for disposal and other handlingBased on its mechanism of action, ZYTIGA may harm therefore, women who are pregnant or may be pregnant should not handle ZYTIGA without protection, e.g., gloves.Any unused medicinal product or waste material should be disposed of in accordance with local requirements.7. Marketing authorisation holder&Janssen-Cilag International NVTurnhoutseweg 30B-2340 BeerseBelgium8. Marketing authorisation number(s)EU/1/11/714/0019. Date of first authorisation/renewal of the authorisationDate of first authorisation: 5 September 201110. Date of revision of the text16/01/2014 Detailed information on this medicinal product is available on the website of the European Medicines Agency .
注意 本品有加拿大制造 土耳其上市品；瑞士制造，瑞士上市品---------------------------------------------------------------产地国家: 瑞士原产地英文商品名:ZYTIGA 250mg/tab 120tabs/bottle 原产地英文药品名:ABIRATERONE ACETATE中文参考商品译名:ZYTIGA 250毫克/片 120片/瓶 中文参考药品译名:醋酸阿比特龙生产厂家中文参考译名:Janssen Pharma 生产厂家英文名:Janssen Pharma
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