英文药名：ZYTIGA（Abiraterone Acetate Tablets） 中文药名：醋酸阿比特龙片 生产厂家：杨森制药有限公司 ザイティガ錠250mg 治疗类别名称 前立腺癌治療剤（CYP17阻害剂） 批准上市日期：2014年9月 商標名 ZYTIGA tablets 一般名：アビラテロン酢酸エステル（JAN） Abiraterone Acetate（JAN） 化学名：17-（Pyridin-3-yl）androsta-5,16-dien-3β-yl acetate 分子式：C26H33NO2 分子量：391.55 化学構造式 性状 白色粉末 溶解度（20℃） 二氯甲烷>300毫克/毫升 乙酸乙酯98mg/ mL的 乙醇52mg/ mL的 水<为0.01mg/ mL的 熔点 147〜148℃ 分配系数 log P=5.12（1-辛醇/水） 药效药理 1. 作用机序 醋酸阿比特龙酯迅速水解为阿比特龙在体内，抑制17α羟化酶/C17,20裂解酶（CYP17）活性是雄激素合成酶。 在体外，阿比特龙被抑制睾酮在来自肿瘤细胞系（NCI-H295R）人类肾上腺皮质的合成。在小鼠和大鼠（反复腹腔或口服给药）醋酸阿比特龙降低血浆睾酮浓度 2.抗肿瘤作用 在移植了（LuCaP23CR和LuCaP35CR）的人类去势抗性前列腺癌患者来源的肿瘤组织片去势小鼠，阿比特龙乙酸酯的重复腹膜内给药降低了肿瘤的睾酮和二氢睾酮含量，抑制肿瘤的生长并且，在无进展生存的扩展。 适应病症 去势抵抗前列腺癌 用法与用量 与泼尼松龙的组合，成人通常是空腹口服：每日一次（每次为1000毫克）。 包装规格 片剂：250毫克 100片（10片×10） 56片（8粒×7） 制造厂商 杨森制药有限公司 结盟 阿斯利康有限公司 完整资料附件：http://www.info.pmda.go.jp/go/pack/4291033F1024_1_04/ 阿斯利康与强生达成协议 在日本联合推广前列腺癌药物Zytiga（abiraterone acetate） 2013年10月11日，阿斯利康（AstraZeneca）已与强生（JNJ）旗下杨森（Janssen）达成了一项协议，在日本联合推广Zytiga（abiraterone acetate，醋酸阿比特龙），该药是一种创新的口服药物，用于前列腺癌患者的治疗。此次合作，将为阿斯利康带来新的收入流，同时将加强其在日本的存在。 目前，在日本前列腺癌患者的主要治疗选择为药物去势（medical castration），但许多患者的前列腺癌仍可能继续恶化，因为其他组织也会产生雄激素（endrogen）。Zytiga是一种CYP17抑制剂，能够抑制调节雄激素生产的关键酶，而雄激素能够刺激前列腺癌细胞的生长。Zytiga能够降低可作用于前列腺癌细胞的雄激素水平，这是目前前列腺癌治疗的目标。 杨森于2013年7月向日本劳动卫生福利部（MHLW）提交了Zytiga的上市申请，该药分别于2011年4月和2011年9月获FDA和欧盟委员会（EU）批准，用于转移性去势前列腺癌患者的治疗。 ZYTIGA® (abiraterone acetate) Plus Prednisone for Asymptomatic or Mildly Symptomatic Chemotherapy-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer DESCRIPTION Abiraterone acetate, the active ingredient of ZYTIGA is the acetyl ester of abiraterone. Abiraterone is an inhibitor of CYP17 (17a-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate.   Abiraterone acetate is a white to off-white, non-hygroscopic, crystalline powder. Its molecular formula is C26H33NO2 and it has a molecular weight of 391.55. Abiraterone acetate is a lipophilic compound with an octanol-water partition coefficient of 5.12 (Log P) and is practically insoluble in water. The pKa of the aromatic nitrogen is 5.19. CLINICAL PHARMACOLOGY Mechanism of Action Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 -hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17a-hydroxy derivatives by 17-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. ZYTIGA decreased serum testosterone and other androgens in patients in the placebo-controlled phase 3 clinical trial. It is not necessary to monitor the effect of ZYTIGA on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients. INDICATIONS AND USAGE ZYTIGA 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. CONTRAINDICATIONS Pregnancy ZYTIGA may cause fetal harm when administered to a pregnant woman. 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, the patient should be apprised of the potential hazard to the fetus. PRECAUTIONS  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 is not established. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly. •Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated 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, interrupt, or discontinue ZYTIGA dosing as recommended. •Food Effect: ZYTIGA must be taken on an empty stomach. Exposure (area under the curve) of abiraterone increases up to 10 fold when abiraterone acetate is taken with meals.  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, and upper respiratory tract infection. DOSAGE AND ADMINISTRATION Recommended Dosage The recommended dose of ZYTIGA is 1,000 mg 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]. The tablets should be swallowed whole with water. Dose Modification Guidelines Hepatic Impairment In 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. Avoid ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C), as ZYTIGA has not been studied in this population, and no dose adjustment can be predicted. Hepatotoxicity For 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 or to 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. HOW SUPPLIED  HOW SUPPLIED/STORAGE AND HANDLING ZYTIGA (abiraterone acetate) 250 mg tablets are white to off-white, oval tablets debossed with AA250 on one side. ZYTIGA 250 mg tablets are available in high-density polyethylene bottles of 120 tablets. NDC Number 57894-150-12 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].