美国FDA批准Istodax（romidepsin）注射液新药：用于治疗至少有1年治疗史的外周T细胞淋巴瘤（PTCL）患者。 注射用药物Istodax，即组蛋白去乙酰化酶（HDAC）抑制剂，是抗癌药物类中的一种表现遗传注射疗法。该注射用药物获得批准用于治疗曾接受过至少一次治疗的外周T细胞淋巴瘤患者。 处方修改批准日期：2016年7月 公司：Clegene ISTODAX®（罗米地辛 romidepsin）注射，用于静脉内使用 最初美国批准：2009年 目前的主要变化 用法与用量 7/2016 作用机理 罗米地辛是组蛋白脱乙酰酶（HDAC）抑制剂。HDAC催化除去乙酰基从乙酰化赖氨酸残基的组蛋白，在基因表达的调节所得。HDAC所以脱乙酰非组蛋白，转录因子：如。在体外，罗米地辛导致乙酰化组蛋白的积累，和诱导细胞周期停滞和细胞凋亡在纳摩尔范围的IC 50值某些癌细胞系。romidepsin在非临床和临床研究中观察到的抗肿瘤作用机制处理不当已充分的特点。 适应症和用法 ISTODAX是一种组蛋白去乙酰化酶（HDAC）抑制剂指示为： 在患者皮肤T细胞淋巴瘤（CTCL）治疗谁收到至少一个全身治疗。 谁收到至少一个前治疗的患者外周血T细胞淋巴瘤（PTCL）的处理。 这些指示是基于响应率。临床好处：比如在总生存期的改善尚未实例阐述。 用法用量 14毫克/m2静脉注射（IV）在4小时内对天1，8，和28天周期的15。重复周期所提供的病人每28天没有继续受益和耐受药物。 中止或中断治疗（有或无剂量降低至10毫克/米2）来管理药物毒性。 剂型和规格 ISTODAX注射，10毫克。 禁忌症 无。 警告和注意事项 骨髓抑制： ISTODAX可能引起血小板减少，白细胞减少（中性粒细胞和淋巴细胞），和贫血;监测与ISTODAX治疗期间血细胞计数;中断和/或修改的剂量为是必要的。 感染：致命和严重感染。DNA病毒（埃巴和乙肝）激活。考虑病人的监测和预防事先乙型肝炎的证据 心电图图形（ECG）的变化：考虑患者的心血管监测与先天性长QT综合征，显著心血管疾病史，患者服用药品确实导致显著QT间期延长。确保没有钾和镁是ISTODAX给药前的正常范围内。 肿瘤溶解综合征：患者晚期疾病和/或高肿瘤负荷有更大的风险和shoulderstand进行密切监测，并采取适当的预防措施。 胚胎胚胎毒性：ISTODAX可能引起胎儿危害当给予孕妇。提醒潜在危险的女性胎儿和避免怀孕，而接受ISTODAX。 不良反应 最常见的不良反应为中性粒细胞减少，淋巴细胞减少，血小板减少，感染，恶心，乏力，呕吐，厌食，贫血，心电图T波改变。 药物相互作用 仔细地监测患者的凝血酶原时间（PT）和国际标准化比值（INR）同时给予ISTODAX和华法林或香豆素衍生物。 监测当共同给予的romidepsin具有较强的CYP3A4抑制剂与增加曝光罗米地辛的毒性。 避免与利福平和CYP3A4强诱导剂使用。 包装规格/储存与处理 SuppliedISTODAX IS如何SUPPLIED作为试剂盒包含在10毫克单一剂量小瓶含11毫克的romidepsin和22毫克的增量剂，聚维酮，USP的无菌，冻干粉末。此外，每个套件包括单剂量无菌稀释剂小瓶含80％丙二醇，USP，和20％的无水乙醇，USP2.4毫升（2.2毫升交付体积）。 NDC59572-984-01：ISTODAX®KIT包含的romidepsin1瓶及每箱的romidepsin1瓶稀释剂。 StorageISTODAX（罗米地辛）注射是作为一个工具包包含2瓶在一个纸箱。 15°之间的纸板箱必须存储在20°至25℃，允许至30℃游览（见USP控制室温。） 为妥善处理和处置的抗癌药物的程序应予以考虑。关于这一问题的指导方针已经公布[见参考文献。 完整处方资料附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03b39d40-90fe-11df-9de6-0002a5d5c51b Istodax (romidepsin) General Information Istodax (romidepsin) is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. Istodax is specifically indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. Istodax is supplied as solution for intravenous administration. The recommended dose of romidepsin is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8 and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the therapy. ISTODAX® (romidepsin) for injection is a prescription medicine used for: Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated. It is not known if ISTODAX is safe and effective in children under 18 years of age.  Important Safety Information BEFORE RECEIVING ISTODAX: Tell your doctor if you: have any heart problems, including an irregular or fast heartbeat, or a condition called QT prolongation have kidney problems have liver problems, including a past history of hepatitis B have problems with the amount of potassium or magnesium in your blood have nausea, vomiting, or diarrhea have any other medical conditions are pregnant or plan to become pregnant. ISTODAX may harm your unborn baby. Talk to your doctor about the best way to prevent pregnancy while receiving ISTODAX. Tell your doctor right away if you become pregnant while receiving ISTODAX are breastfeeding or plan to breastfeed. It is not known if ISTODAX passes into your breast milk. You and your doctor should decide if you will receive ISTODAX or breastfeed. Talk to your doctor about the best way to feed your baby while you are being treated with ISTODAX DRUG INTERACTIONS: Tell your doctor about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements and any recent changes in medications Some medicines may affect how ISTODAX works, or ISTODAX may affect how other medicines work. Especially tell your doctor if you take or use: Warfarin sodium (Coumadin®, Jantoven®) or any other blood thinner medicine. Ask your doctor if you are not sure if you are taking a blood thinner. Your doctor may want to test your blood more often A medicine to treat abnormal heartbeats St. John’s Wort (Hypericum perforatum) Dexamethasone (a steroid) Medicine for: tuberculosis (TB), seizures (epilepsy), bacterial infections (antibiotics), fungal infections (antifungals), HIV (AIDS), or depression Ask your doctor if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine SIDE EFFECTS: ISTODAX may cause serious side effects, including: Low blood cell counts: Your doctor will regularly do blood tests to check your blood counts Low platelets: can cause unusual bleeding, or bruising under the skin. Talk to your doctor right away if this happens Low red blood cells: may make you feel tired and you may get tired easily. You may look pale, and feel short of breath. Tell your doctor if you have these symptoms Low white blood cells: can cause you to get infections, which may be serious Serious infections: People receiving ISTODAX can develop serious infections that can sometimes lead to death. These infections can happen during treatment and within 30 days after treatment with ISTODAX. Your risk of infection may be higher if you have had chemotherapy in the past Tell your doctor right away if you have any of these symptoms of infection: fever, cough, shortness of breath with or without chest pain, burning with urination, flu-like symptoms, muscle aches, or worsening skin problems Changes in your heartbeat: Your doctor may check your heart by doing an ECG (electrocardiogram) and blood tests to check your potassium and magnesium levels before you start ISTODAX treatment. Tell your doctor if you feel an abnormal heartbeat, feel dizzy or faint, have chest pain or shortness of breath Tumor Lysis Syndrome (TLS): TLS is a problem of the rapid breakdown of cancer cells that can happen during your treatment with ISTODAX. You should drink plenty of fluids in the 3 days after you receive treatment with ISTODAX. Your doctor may do blood tests to check for TLS and may give you medicine to prevent or treat TLS Common side effects of ISTODAX include: nausea, vomiting, diarrhea, and loss of appetite tiredness Your doctor will check your blood cell counts and other blood tests regularly during your treatment with ISTODAX to check for side effects of ISTODAX. Your doctor may decide to do other tests to check your health as needed Your doctor may stop your treatment, change when you get your treatment, or change the dose of your treatment if you have certain side effects while receiving ISTODAX Tell your doctor if you have any side effect that bothers you or does not go away. These are not all the possible side effects of ISTODAX FDA扩展批准注射用药物Istodax的新适应症 6月16日，Clegene公司宣布，FDA批准了Istodax注射液(romidepsin)的一个新适应症：用于治疗至少有1年治疗史的外周T细胞淋巴瘤(PTCL)患者。 Istodax是一种表观遗传治疗，属于组蛋白去乙酰化酶抑制剂类抗癌药。该药还适用于治疗至少有1年全身性治疗史的皮肤T细胞淋巴瘤患者。 是否适合使用Istodax治疗，应根据应答率判断。目前该药的临床收益尚未得到证实，比如总生存状况的改善。 FDA批准这个新适应证是基于2项研究的结果。第一项研究是有关Istodax的Ⅱ期多中心、国际性、开放性、单组研究，其受试者为对既往至少1年的全身性治疗无应答的PTCL患者；第2项研究是有关Istodax的单组临床试验，受试者为对既往治疗无应答的PTCL患者。 对PTCL患者进行的Istodax研究显示，最常见且最严重的不良反应包括感染、血小板减少、中性粒细胞减少、贫血、无力或倦怠、白细胞减少、发热、恶心以及呕吐等。 由于Istodax经CYP3A4系统代谢，故应尽可能避免联用强CYP3A4抑制剂和强CYP3A4诱导剂。另外，联用中等强度的CYP3A4抑制剂和P-糖蛋白抑制剂时应谨慎。对于同时接受Istodax和华法林钠衍生物治疗的患者，建议进行密切监测。