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。 欧盟核准VIDAZA® 正式上市，用于治疗高危骨髓增生异常综合征(MDS)和急性髓系细胞白血病(AML) • 首个并且是唯一证实能显著延长中度-2和高危MDS和AML患者生存期的表观遗传类抗癌药 • 首个获得核准的抗癌药，对世界卫生组织(WHO)分类的MDS各种亚型均有效，包括伴20-30%原始细胞和多系病态的急性髓系细胞白血病(AML) • 首个获得核准的、且国际预后评分系统(IPSS)危险划分为中度-2和高危的患者免输血率超过40%的MDS治疗药物 Celgene International Sàrl (Nasdaq:CELG)今天宣布，该公司的抗癌药VIDAZA (阿扎胞苷)已获得欧盟上市正式许可，用于患有下列疾病而又不符合接受造血干细胞移植条件的患者: • IPSS评分为中度-2和高危MDS者，或 • 慢性粒单核细胞白血病(CMML)伴10-29%原始细胞，无骨髓增生障碍者，或 • WHO分类示AML，伴20-30%原始细胞和多系病态 Celgene欧洲分公司总裁Philippe Van Holle说：“欧盟核准VIDAZA是对该药在危重血液肿瘤中显著生存收益的认可。本公司现将就医保和分销事务与欧盟各成员国的药政管理部门开始逐一交涉。” 该核准是基于评估VIDAZA治疗MDS和RAEB-T患者(根据WHO分类系统定义，属于AML类别)的临床研究中的有效性和安全性数据。这些关键的有效性和安全性数据主要来自于VIDAZA生存试验(AZA-001)，该试验是高危MDS 和WHO分类的AML患者中进行的有史以来样本最大的国际III期随机对照研究，结果显示，中位生存期比传统治疗方案延长9.4个月（24.4 vs 15个月），具有临床意义。 AZA-001生存试验的主要研究者、巴黎大学的Pierre Fenaux, M.D., Ph.D.说：“由于VIDAZA彰显了前所未有的生存收益，该药亟待进入医保，这方面患者的迫切需求显得尤为重要了。以往这类患者的治疗手段极为短缺，我深感欣慰的是他们如今可以得到这样一种管用的药物。” 除了总生存延长以外，AZA-001研究还显示，接受VIDAZA®治疗的患者中45%无需进行红细胞输血。患者的耐受性也属良好。研究者旨在提供治疗直至疾病进展，共完成中位9个周期。 AZA-001生存研究中，接受VIDAZA的患者最常见的主要不良事件是血小板减少(69.7%)、中性粒细胞减少(65.7%)和贫血(51.4%)。 VIDAZA已在欧盟列入治疗MDS和AML的罕用药。 关于VIDAZA 2008年8月，VIDAZA成为首个并且是唯一获得FDA核准的、在中度-2和高危MDS和AML中总生存延长显著优于传统治疗方案的药物。VIDAZA属于一个名为低甲基化剂的新型药物类别，并且是该类别中的第一种药物，FDA核准该药用于治疗MDS法美英(FAB)分类的所有5种亚型，低危和高危患者均包括在内。这些亚型包括：难治性贫血(RA)或环状铁粒幼细胞性难治性贫血(RARS) (若伴有中性粒细胞减少或血小板减少，或需输血)；原始细胞过多难治性贫血(RAEB)，转化中原始细胞过多难治性贫血(RAEB-T)和慢性粒单核细胞白血病(CMML)。较新近的WHO分类系统将RAEB-T患者划分至AML类别中。VIDAZA已在若干市场列入罕用药，包括欧盟、美国和日本。 关于表观遗传学 据信，VIDAZA的抗肿瘤效应涉及多重机制，包括对骨髓中异常造血细胞的细胞毒性以及DNA的低甲基化。VIDAZA的细胞毒性效应可能来源于多重机制，包括抑制DNA、RNA和蛋白质合成、整合入RNA和DNA，以及激活DNA损伤通路。相对而言，非增生细胞对VIDAZA不敏感。VIDAZA整合入DNA导致DNA甲基转移酶灭活，使DNA低甲基化。正常细胞周期调节、分化和死亡通路中异常甲基化的基因发生DNA低甲基化，可导致基因重新表达和对癌细胞的癌症抑制功能恢复。VIDAZA中DNA低甲基化相对于细胞毒性或其他活性的临床转归重要性尚未确立。 关于骨髓增生异常综合征 MDS是一组血液学肿瘤，全球约有300,000例患者。MDS发生时，骨髓中的血细胞无法成熟，即处于“原始”阶段，无法发育为成熟细胞，从而无法发挥其必要的功能。骨髓中最终布满原始细胞，抑制正常细胞发育。高危MDS患者中位生存期约6-12个月。MDS患者通常需要输血，才能控制贫血和疲乏症状，由于频繁输血，可出现为致命的铁超载和/或毒性，因此，迫切需要对因而非简单对症的创新治疗方式。 关于急性髓系细胞白血病 急性髓系细胞白血病(AML)是骨髓细胞的一种癌症，常由MDS进展转化而来。AML是骨髓中异常细胞的增生，干扰所有正常血细胞的生成(即多系病态)。AML的传统治疗是高强度化疗，但绝大多数患者(老年患者)耐受不良。这些患者中多数最终未能获得治疗，同时由于他们不符合根治疗法的条件，其生存期短至数周至数月。 VIDAZA-azacitidine injection, powder, lyophilized, for suspension Pharmion Corporation What is Azacitidine injection? AZACITIDINE (Vidaza™) is a chemotherapy agent used to treat myelodysplastic syndromes and may be used to treat some types of leukemia. Azacitidine interferes with the growth of rapidly dividing cells, like cancer cells, and eventually causes these cells to die. Generic azacitidine injections are not available. What should I tell my health care provider before I take this medicine? They need to know if you have any of these conditions: • dental disease • infection (especially viral infections such as chickenpox or herpes) • kidney disease • liver disease • an unusual reaction to Azacitidine, other medicines, foods, dyes, or preservatives • pregnant or trying to get pregnant • breast-feeding How should this medicine be used? Azacitidine is given as an injection under the skin by a trained health care profesiional. It has also been given by an infusion into a vein. Azacitidine is usually administered in a hospital or clinic setting. Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed. What drug(s) may interact with Azacitidine? • vaccines Talk to your prescriber or health care professional before taking any of these medicines: • aspirin • acetaminophen • ibuprofen • naproxen • ketoprofen Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines. What should I watch for while taking Azacitidine? Visit your prescriber or health care professional for checks on your progress. You will need to have regular blood checks. The side effects can continue after you finish your treatment; report side effects promptly. Azacitidine may make you feel generally unwell. This is not uncommon because azacitidine affects good cells as well as cancer cells. Report any side effects as above, but continue your course of medicine even though you feel ill, unless your prescriber or health care professional tells you to stop. Azacitidine may decrease your body's ability to fight infections. Call your prescriber or health care professional if you have a fever, chills, sore throat or other symptoms of a cold or flu. Do not treat these symptoms yourself. Try to avoid being around people who are sick. Azacitidine may increase your risk to bruise or bleed. Call your prescriber or health care professional if you notice any unusual bleeding. Be careful not to cut, bruise or injure yourself because you may get an infection and bleed more than usual. Avoid taking aspirin, acetaminophen (Tylenol®), ibuprofen (Advil®), naproxen (Aleve®), or ketoprofen (Orudis® KT) products as they may mask a fever, unless instructed to by your prescriber or health care professional. Be careful brushing and flossing your teeth or using a toothpick while receiving azacitidine because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving azacitidine. There is a possibility that azacitidine could cause harm to an unborn child; this applies to both men and women. If you are pregnant or you or your partner are considering getting pregnant, talk to your health care provider about the risks of azacitidine therapy. Women or men whose partner may have children should use appropriate birth control methods during azacitidine therapy. Discuss possible methods of birth control with your health care provider. If you are going to have surgery or dental work, tell your prescriber or health care professional that you are using azacitidine. What side effects may I notice from receiving Azacitidine? The side effects you may experience with azacitidine therapy depend upon the dose, other types of chemotherapy or radiation therapy given, and the disease being treated. Not all of these effects occur in all patients. Discuss any concerns or questions with your prescriber or health care professional. Side effects that you should report to your prescriber or health care professional as soon as possible: • low blood counts - azacitidine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding. • signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine • signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine • signs of decreased red blood cells - unusual weakness or tiredness, fainting spells, lightheadedness • reactions at the injection site including redness, pain, itching, or bruising Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome): • constipation • diarrhea • fatigue • headache • loss of appetite • nausea, vomiting • skin rash, itching • stomach pain • water retention Where can I keep my medicine? This does not apply. You will only receive this medicine in a hospital or clinic setting and will not need to store it at home.