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 详细处方信息以本药内容附件（202371022262626.pdf）文件为准
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部分中文 处方资料（仅供参考）

部份中文阿扎胞苷处方资料（仅供参考）

商品名：Onureg Filmtabl

英文名：azacitidine

中文名：阿扎胞苷薄膜片

生产商：百时美施贵宝

药品简介：

抗癌新药Onureg是欧洲第一个也是唯一一个可用于治疗处于首次缓解的广泛AML亚型患者，每日一次口服一线维持疗法。

2021年06月18日，欧盟委员会（EC）已批准Onureg（azacitidine，阿扎胞苷薄膜片），作为一种一线口服维持疗法，用于治疗在诱导治疗（有或无巩固治疗）后获得完全缓解（CR）或血小板计数未完全恢复的完全缓解（CRi）、并且不适合或选择不进行造血干细胞移植（ASCT）的急性髓性白血病（AML）成人患者。AML是成人中最常见的急性白血病之一。

作用机制：

阿扎胞苷是一种DNA甲基转移酶抑制剂和表观遗传学修饰物。掺入阿扎胞苷在细胞摄取和酶生物转化为核苷酸后转化为DNA和RNA三磷酸盐。将阿扎胞苷掺入AML细胞的DNA，修饰表观遗传途径通过抑制DNA甲基转移酶和减少DNA甲基化。这导致基因表达的改变，包括调节肿瘤抑制的基因的再表达，免疫途径、细胞周期和细胞分化。将阿扎胞苷掺入AML细胞，抑制RNA甲基转移酶，降低RNA甲基化，降低RNA稳定性，以及蛋白质合成减少。

适应症：

Onureg适用于成人急性髓细胞白血病（AML）患者的维持治疗达到完全缓解（CR）或完全缓解但血细胞计数恢复不完全的患者（CRi）在诱导治疗后，无论是否进行巩固治疗，并且不是候选人包括那些选择不进行造血干细胞移植的人。

用法与用量：

Onureg治疗应在有经验的医生的监督下开始并监测

在化疗药物产品的使用中。

患者在每次服用第一剂Onureg前30分钟接受止吐药治疗2个治疗周期。如果没有恶心，两个周期后可以省略止吐预防和呕吐。

剂量：

推荐剂量为300 mg阿扎胞苷，每日口服一次。每个重复循环由一个14天的治疗期之后是14天的无治疗期（28天的治疗周期）。

应继续Onureg治疗，直到在外周血中观察到不超过15%的成纤维细胞或骨髓，或直至出现不可接受的毒性（参见疾病的剂量表修改指南复发）。Onureg不应与注射用阿扎胞苷互换使用，因为暴露、剂量和治疗计划。建议医疗保健专业人员验证药品名称、剂量和给药途径。                          

Preclinical safety data

In a 14-day oral toxicity study in dogs, mortality occurred at doses of 8 and 16 mg/m2 /day. The maximum tolerated dose (MTD) was 4 mg/m2 /day. At 1 or all doses, pancytopenia correlated with bone marrow hypoplasia, lymphoid depletion, gland/lumen dilation and single cell necrosis in mucosal crypts of small and large intestines and/or centrilobular hepatocellular vacuolation were observed. At the MTD, these findings were partially or completely resolved after 3 weeks. Following parenteral azacitidine administrations at comparable dose ranges, mortality and similar target organ toxicities were observed in rodents, dogs and monkeys. Non-clinical data from repeat-dose toxicity studies with azacitidine revealed no special hazard for humans.

Azacitidine induces both gene mutations and chromosomal aberrations in bacterial and mammalian cell systems in vitro. The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumours of the haematopoietic system in female mice, when administered intraperitoneally 3 times per week for 52 weeks. An increased incidence of tumours in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with azacitidine administered intraperitoneally for 50 weeks. A tumorigenicity study in rats revealed an increased incidence of testicular tumours.

Early embryotoxicity studies in mice revealed a 44% rate of intrauterine embryonal death (increased resorption) after a intraperitoneal injection of azacitidine during organogenesis. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before closure of the hard palate. In rats, azacitidine caused no adverse reactions when given pre-implantation, but it was clearly embryotoxic when given during organogenesis. Foetal abnormalities during organogenesis in rats included: Central nervous system (CNS) anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly) and others (microphthalmia, micrognathia, gastroschisis, oedema, and rib abnormalities).

Administration of azacitidine to male mice prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development. Treatment of male rats resulted in decreased weight of the testes and epididymides, decreased sperm counts, decreased pregnancy rates, an increase in abnormal embryos and increased loss of embryos in mated females (see section 4.6).

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 详细处方信息以本药内容附件（202371022262626.pdf）文件为准
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