英文药名：Bosulif tablets（Bosutinib Hydrate） 中文药名：博舒替尼水合物 生产厂家：辉瑞日本公司 ボシュリフ錠100mg 治疗类别名称 抗肿瘤药 酪氨酸激酶抑制剂 商標名 Bosulif tablets 一般名 ボスチニブ水和物（Bosutinib Hydrate） 化学名 4-［（2,4-Dichloro-5-methoxyphenyl）amino］-6-methoxy-7-［3-（4-methylpiperazin-1-yl）propyloxy］quinoline-3-carbonitrile monohydrate 分子式 C26H29Cl2N5O3・H2O 分子量 548.46 構造式 性状 本产品为白色至黄褐色粉末。 它是易溶于二甲基亚砜，难溶于乙醇（99.5），乙腈，略溶于甲醇，和几乎不溶于水。 分配系数（logD） 3.1（pH7.4,1-辛醇/水） 药效药量 1. 抗肿瘤作用 波舒替尼，在体外，抑制BCR-ABL融合基因阳性的人慢性骨髓性白血病的细胞系（KU812，K562，梅格-01，喇嘛84和KCL22）的生长。此外，与K562细胞系的裸鼠皮下植入，通过波舒替尼给药所观察到的肿瘤生长抑制效果和存活时间的延长。 2. 作用机理 通过抑制Abl的和的Src酪氨酸激酶活性波舒替尼被认为抑制肿瘤的BCR-ABL融合基因阳性的生长。 适应病症 慢性粒细胞白血病耐药或不能耐受之前治疗的药物 用法与用量 成人；每日口服一次，每次500毫克。所述剂量可根据病人的情况进行调整，但可提高到600毫克，每天一次。 包装规格 片 100毫克*50片（PTP） 生产和销售（进口） 辉瑞公司日本 日本上市和资料附件：http://www.info.pmda.go.jp/go/pack/4291036F1028_1_05/ Bosulif (Bosutinib Monohydrate) INDICATIONS AND USAGE BOSULIF is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. DOSAGE AND ADMINISTRATION Recommended Dosing The recommended dose and schedule of BOSULIF is 500 mg orally once daily with food. Continue treatment with BOSULIF until disease progression or patient intolerance. If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day. Dose Escalation Consider dose escalation to 600 mg once daily with food in patients who do not reach complete hematological response (CHR) by week 8 or a complete cytogenetic response (CCyR) by week 12, who did not have Grade 3 or higher adverse reactions, and who are currently taking 500 mg daily. Dose Adjustments for Non-Hematologic Adverse Reactions Elevated liver transaminases: If elevations in liver transaminases greater than 5 — institutional upper limit of normal (ULN) occur, withhold BOSULIF until recovery to less than or equal to 2.5 — ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue BOSULIF. If transaminase elevations greater than or equal to 3 — ULN occur concurrently with bilirubin elevations greater than 2 — ULN and alkaline phosphatase less than 2 — ULN (Hy's law case definition), discontinue BOSULIF [see Warnings and Precautions]. Diarrhea: For NCI CTCAE Grade 3—4 diarrhea (increase of greater than or equal to 7 stools/day over baseline/pretreatment), withhold BOSULIF until recovery to Grade less than or equal to 1. BOSULIF may be resumed at 400 mg once daily [see Warnings and Precautions]. For other clinically significant, moderate or severe non-hematological toxicity, withhold BOSULIF until the toxicity has resolved, then consider resuming BOSULIF at 400 mg once daily. If clinically appropriate, consider re-escalating the dose of BOSULIF to 500 mg once daily. Dose Adjustments for Myelosuppression Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 1). Concomitant Use With CYP3A Inhibitors Avoid the concomitant use of strong or moderate CYP3A and/or P-gp inhibitors with BOSULIF as an increase in bosutinib plasma concentration is expected (strong CYP3A inhibitors include ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, boceprevir, telaprevir, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and conivaptan. Moderate CYP3A inhibitors include fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, grapefruit products and ciprofloxacin) [see Drug Interactions]. Concomitant Use With CYP3A Inducers Avoid the concomitant use of strong or moderate CYP3A inducers with BOSULIF as a large reduction in exposure is expected (strong CYP3A inducers include rifampin, phenytoin, carbamazepine, St. John's Wort, rifabutin and phenobarbital. Moderate CYP3A inducers include bosentan, nafcillin, efavirenz, modafinil and etravirine) [see Drug Interactions]. Hepatic Impairment In patients with pre-existing mild, moderate, and severe hepatic impairment, the recommended dose of BOSULIF is 200 mg daily. A daily dose of 200 mg in patients with 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 500 mg daily. However, there are no clinical data for efficacy at the dose of 200 mg once daily in patients with hepatic impairment and CML [see Use in Special Populations]. DOSAGE FORMS AND STRENGTHS 100 mg tablets: yellow, oval, biconvex, film-coated tablets debossed with "Pfizer" on one side and "100" on the other. 500 mg tablets: red, oval, biconvex, film-coated tablets debossed with "Pfizer" on one side and "500" on the other. HOW SUPPLIED/STORAGE AND HANDLING How Supplied BOSULIF (bosutinib) tablets are supplied for oral administration in two strengths: a 100 mg yellow, oval, biconvex, film-coated tablet debossed with "Pfizer" on one side and "100" on the other; and a 500 mg red, oval, biconvex, film-coated tablet debossed with "Pfizer" on one side and "500" on the other. BOSULIF (bosutinib) tablets are available in the following packaging configurations (Table 8): Storage 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]. Handling and Disposal Procedures for proper disposal of anticancer drugs should be considered. Any unused product or waste material should be disposed of in accordance with local requirements, or drug take back programs.