ZYTIGATM(醋酸阿比特龙)片为口服给药 批准日期：2011年4月28日；公司：Centocor Ortho Biotech Inc. 醋酸阿比特龙(Zytiga片剂，Centocor Ortho生物技术公司)。是一种可减少睾酮生成的雄激素抑制剂，与强的松联用于已接受包含多西他赛化疗的转移性去势耐药性前列腺癌(mCRPC)患者。这是自2010年4月以来，该药获得批准的针对晚期前列腺癌的第四个适应证。 依据：一项纳入1,195例曾接受包含多西他赛化疗的男性患者的国际性研究。阿比特龙+强的松组患者的中位总生存期为14.8个月，优于强的松单药组的10.9个月。 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”。 美国初始批准– 2011；本申请为优先审评 作用机制 醋酸阿比特龙(ZYTIGA)在体内被转化为阿比特龙，一种雄激素生物合成抑制剂，抑制17 α-羟化酶/C17,20-裂解酶(CYP17)。在睾丸，肾上腺，和前列腺肿瘤组织中表达此酶和为雄激素生物合成所需。 CYP17催化两个顺序反应：1) 通过17α-羟化酶活性孕烯醇酮[pregnenolone]和孕酮[progesterone]转化为其17α-羟基衍生物和2)随后分别形成脱氢表雄(甾)酮[dehydroepiandrosterone，DHEA]和通过C17，20裂解酶活性雄烯二酮[androstenedione]。DHEA和雄烯二酮是雄激素和是睾丸酮的前体。通过阿比特龙CYP17的抑制作用也可导致通过肾上腺增加盐皮质激素生成(见警告和注意事项)。 雄激素敏感前列腺癌对治疗反应减低雄激素水平。去雄激素治疗，例如用促性腺激素释放激素激动剂[GnRH激动剂s]或睾丸切除术治疗，减低睾丸中雄激素生成但不影响肾上腺或肿瘤内雄激素生成。 在安慰剂-对照3期临床试验中ZYTIGA减低患者血清睾丸酮和其它雄激素。不需要监测ZYTIGA对血清睾丸酮水平的影响。 可观察血清前列腺特异性抗原(PSA)水平的变化但在个体患者中没有证实与临床效益相关。 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。 （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。 INDICATION AND IMPORTANT SAFETY INFORMATION  Indication for ZYTIGA® (abiraterone acetate) 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 Information for ZYTIGA® (abiraterone acetate) Contraindications ZYTIGA® 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 UNL, 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‑∞ (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 co-administration 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®. FDA批准前列腺癌药物Zytiga扩大适应证 2012年12月10日，杨森生物技术公司宣布美国食品药品管理局(FDA)已经批准了每日1次口服药物Zytiga(醋酸阿比特龙)的扩大适应证申请。此前，Zytiga仅被批准联合泼尼松用于曾接受含多烯紫杉醇化疗的转移性去势难治性前列腺癌(mCRPC)患者。基于这项新批准令，现在Zytiga联合泼尼松可更早用于mCRPC连续治疗，即在化疗之前使用。 根据说明书，Zytiga在体内转化为雄激素生物合成酶抑制剂阿比特龙，抑制17α-羟化酶/C17,20-裂解酶。该酶表达于睾丸、肾上腺和前列腺肿瘤组织，是雄激素生物合成所必需的酶。 这项新批准令是基于一项随机、双盲、安慰剂对照、国际多中心Ⅲ期临床研究的有效性和安全性结果。该研究评价了Zytiga+泼尼松与安慰剂+泼尼松用于1,088例未接受细胞毒性化疗、对雄激素剥夺治疗无应答的mCRPC男性患者。患者被随机分组，接受Zytiga(1,000mg，口服，1次/日)+泼尼松(5 mg，2次/日)或安慰剂+泼尼松(5 mg，2次/日)治疗。共同终点为无放射影像学进展生存期(rPFS)和总生存期(OS)。 遵照方案对rPFS的分析结果显示，与安慰剂+泼尼松组(对照组)相比，Zytiga+泼尼松组(Zytiga组) rPFS呈统计学显著改善。对照组中位rPFS为8.28个月，由于Zytiga组进展事件出现较慢尚未达到中位rPFS，结果具有统计学显著意义(P＜0.0001)。 此外，在另外一项预先设定的其中分析中，Zytiga组OS长于对照组，风险比(HR)为0.792：Zytiga组中位OS为35.3个月，而对照组为30.1个月[95%置信区间(CI)，0.655~0.956]，但未达到预先设定的统计学显著水平。 Zytiga最常见不良反应包括疲乏、关节肿胀或不适、水肿、潮热、腹泻、呕吐、咳嗽、高血压、呼吸困难、尿道感染和挫伤。最常见实验室异常包括贫血、血液碱性磷酸酶、天冬氨酸转氨酶和(或)丙氨酸转氨酶升高、高甘油三酯血症、高胆固醇血症、淋巴细胞减少症、高血糖症、低磷血症和低钾血症。 完整说明书[附件:/uploadfile/article/uploadfile/201104/20110429115153396.pdf] ---------------------------------------------------------------- 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 产地国家: 美国 所属类别: 抗癌药物->治疗前列腺癌药物 处方药:处方药 包装规格: 250毫克/片 120片/瓶