英文药名: Vidaza (Azacitidine Injection)

中文药名: 维达扎(阿扎胞苷注射液)

药品介绍

阿扎胞苷(Azacitidine)
英文名称：Azacitidine
英文别名：5-Azacytidine、Ladakamycin
其他名：5aza-C，拉达卡霉素(Ladakamycin),5-氮杂胞苷、5-氮杂胞嘧啶核苷、氮胞苷、氮杂胞苷。

作用机制：
嘧啶类抗代谢药，干扰核苷酸的合成，以假嘧啶形式掺入DNA和RNA中，并与之结合。

适应症：
急性非淋巴细胞性白血病。用于乳腺癌、肠癌、黑色素瘤等有一定疗效。

常用剂量：
100mg／m2，静脉推注，每8小时一次，连用5天，200mg／(m2·d)静脉持续滴注，连用5天。

注意事项：
由于药物的稳定性差，因此应该在用药前配药，配药后立即使用，配药后8小时未用则应丢弃。静脉滴注应该用新鲜林格液配制，每8小时配制一次。

毒性反应：
(1)骨髓抑制和其他血液学反应：所有的病人都会出现严重的骨髓抑制和其他血液学反应，表现为白细胞于第12~14天降至最低，偶见抑制持续超过几周。
(2)恶心呕吐和其他胃肠道反应：常见。静脉持续滴注可减轻恶心呕吐和其他胃肠道反应反应。
(3)皮肤粘膜反应：粘膜炎及皮肤红疹偶见
(4)其他反应：
1)腹泻：常见。
2)神经系统反应：肌肉疼痛、虚弱、嗜睡及昏迷，少见。
3)肝毒性：罕见，但可能严重。
4)暂时性发热：偶见。

The Vidaza (azacitidine) injections are the most appropriate solution for the patients who cannot take a stem cells transplant and suffer from myelodysplastic syndroms, chronic myelomonocytic leukemia and acute myeloid leukemia.

Dosage and administration
The Vidaza (azacitidine) treatment must be started and monitored by a specialist doctor in chemotherapy. Before starting the treatment, the patients are supposed to stick to a less important treatment to prevent nausea and vomiting.

The initial dose is of 75mg per square meter of corporal surface. It is calculated according to the patient's height and weight. The medication is administered through injections in the arms, thighs or abdomen ever day for a week. The first week is then followed by three weeks of rest. This period of four weeks represents a cycle.

The treatment consists of at least seven cycles and then the patient can take as much time as needed to recover. Before each cycle, the specialist doctor will have to investigate the liver, kidneys and blood. If the amount of sanguine elements is too low or if the patient manifests renal affections, the next cycle must be delayed. The dose also needs to be decreased.

The patients with severe hepatic affections must be highly monitored for secondary effects. However, those suffering from hepatic cancer are not allowed to go through a Vidaza (azacitidine) treatment.

Therapeutic action
The active substance in this drug is the azacitidine, a cytidine analogous incorporated in the generic material of the DNA and RNA. It acts by harming the process a cell has to go through in order to activate and deactivate the genes. Such actions correct the problems with the young cells provoking the myelodysplastic disorders and can kill the cancerous cells.

The studies are very encouraging from this positive point of view. There are however the major side effects coming with this treatment, which cannot be ignored at all.

Contraindications
Vidaza (azacitidine) must not be administered to the individuals that may be allergic to azacitidine or other ingredients. Aside from the severe hepatic cancer patients, the nursing women must also avoid going through this treatment.

Secondary effects
The most frequent secondary effects associated with Vidaza (azacitidine) are the sanguine reactions, including thrombocytopenia (small amount of sanguine elements), neutropenia (small amount of neutrophils) and leukopenia (small amount of white particles). Unfortunately, these side effects affect over 60 percent of the patients.

Other less aggressive secondary affects affect the stomach and can cause nausea and vomiting. Other than that, the injection spot may also manifest unwanted reactions.

FDA批准Vidaza(阿扎胞苷)用于治疗骨髓增生异常综合症
FDA于04年5月19日宣布批准Vidaza(商品名：维达扎；通用名：azacitidine<阿扎胞苷>)注射液为治疗骨髓增生异常综合症(Myelodysplastic Syndrome, MDS)的第一个有效药物。

FDA代理专员Lester M. Crawford博士说：“通过恢复骨髓细胞的正常生长和分化，该新药将向有此种罕见的并且在一些病例中恶化为白血病的那些患者提供一个非常需要的治疗手段。FDA将继续给予这类具有显著疗效的产品的批准以最高的优先权。”

MDS是由骨髓细胞功能异常、正常血细胞生成减少而引起的一系列疾病的总称。MDS可由治疗其它疾病的药物或放射治疗所致，也可由未知病因引起。MDS的某些类型会恶化为急性髓细胞样白血病(AML)。AML是白细胞增生过度活跃的一种癌症。

FAB（法国-美国-英国）协作组织将MDS分为5型，分别是：顽固性贫血（RA）、环形铁粒幼红细胞性难治性贫血（RARS）、原始细胞过多性难治性贫血（RAEB）、转化型原始细胞过多性难治性贫血（RAEB-T）和慢性粒单核细胞白血病（CMMoL）。

Vidaza属于罕见病治疗药。罕见病治疗药用于治疗患者人数在美国少于20万的罕见疾病或症状。《罕见病药物法》规定：获得所指定罕见病药物上市批准的首个申报者将享有该药物在美国市场上7年期的独占上市权。

据估计，美国每年有7000－12,000的MDS新病例被确诊。这种疾病在各年龄段都可能发生，但是60岁以上人群发病率最高。典型症状包括虚弱、疲劳、感染、易淤伤、出血和发热。MDS患者可能需要接受红血球和血小板的输入，以及针对感染的抗生素治疗。

Indication

VIDAZA is indicated for treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL).

IMPORTANT SAFETY INFORMATION

• VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors.
• In Studies 1 and 2, the most commonly occurring adverse reactions by SC route were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (36.4%), injection site erythema (35.0%), constipation (33.6%), neutropenia (32.3%), and ecchymosis (30.5%). Other adverse reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%), myalgia (15.9%), injection site reaction (13.6%), and malaise (10.9%). In Study 3, the most common adverse reactions by IV route also included petechiae (45.8%), weakness (35.4%), rigors (35.4%), and hypokalemia (31.3%).
• In Study 4, the most commonly occurring adverse reactions were thrombocytopenia (69.7%), neutropenia (65.7%), anemia (51.4%), constipation (50.3%), nausea (48.0%), injection site erythema (42.9%), and pyrexia (30.3%). The most commonly occurring Grade 3/4 adverse reactions were neutropenia (61.1%), thrombocytopenia (58.3%), leukopenia (14.9%), anemia (13.7%) and febrile neutropenia (12.6%).
• Because treatment with VIDAZA is associated with anemia, neutropenia and thrombocytopenia, complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle.
• Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease. In addition, azacitidine and its metabolites are substantially excreted by the kidneys and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
• VIDAZA may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be apprised of the potential hazard to the fetus. Men should be advised not to father a child while receiving VIDAZA.
• Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.