Romidepsin（Istodax）属注射类药物，用于治疗皮肤T淋巴细胞瘤（CTCL）。CTCL为一种生长缓慢并且能够影响T淋巴细胞的肿瘤。大多数病例以皮肤干燥、红疹和瘙痒为首发症状，并且症状会逐渐加重。皮肤形成肿瘤后可发生溃疡，进而引发感染。在某些情况下CTCL可播散至血液、淋巴结及内脏器官。美国每年约有1500例新发病例。

皮肤局限性CTCL患者可采用局部药物治疗或光疗，如果肿瘤进展则可使用化疗。Romidepsin能够干扰细胞增殖的关键进程。当CTCL患者出现病情恶化或化疗后复发时，可考虑将Romidepsin用于治疗。两项共涉及167例患者的临床试验对Romidepsin进行了评价，研究中均有约35%的患者出现肿瘤缓解，其中一项研究的平均缓解时间为15个月，另一项为11个月，研究中有6%的患者出现完全缓解。
Romidepsin常见的副作用包括恶心、疲劳、感染、呕吐、食欲减退、红细胞降低、血小板减少和白细胞降低。Romidepsin还可能导致心电图（ECG）发生变化。使用该药物时应定期监测电解质，具有心律不齐风险者应定期监测ECG。Romidepsin可能对胎儿具有不良影响，因此女性在使用期间应避免受孕。

生产商：Gloucester Pharmaceutical

ISTODAX®（romidepsin）仅用于静脉滴注

最初美国批准：2009年
 
适应症
ISTODAX是一种组蛋白去乙酰化酶（HDAC）抑制剂表示为：

治疗皮肤T细胞淋巴瘤患者中，已收到至少有一个事先全身治疗（CTCL的）。
治疗外周T细胞淋巴瘤患者已收到至少有一个事先疗法（1）型（PTCL）。
这些迹象是基于响应速度。尚未得到证实，如在改善整体存活率的临床受益。
剂量和用法
14 mg/m2的静脉注射（IV）超过4小时内的第1天，8，28天为一周期的15。重复周期，每28天提供病人继续受益于和容忍的药物。
可能需要停药或中断或无剂量减少至10 mg/m2的管理药品不良反应。
剂型和优势
ISTODAX注射10毫克，提供了一个稀释液小瓶含2毫升溶液（交割量）。
禁忌
没有。
注意事项：
与ISTODAX治疗已与血小板减少，白细胞减少症（中性粒细胞和淋巴细胞），贫血，因此，监测与ISTODAX治疗期间这些血液学参数，修改剂量，必要时。
严重，有时甚至是致命的感染与ISTODAX治疗后，已在治疗过程中和在30天内报告。
已经观察到心电图（ECG）的变化。考虑先天性长QT综合征，显着的心血管疾病的历史，和患者服用药用产品，导致显着的QT间期延长患者的心血管疾病的监测防范。确保ISTODAX给药前的正常范围内的钾和镁。
已与ISTODAX治疗期间肿瘤溶解综合征。晚期疾病和/或高肿瘤负担的患者应密切监测，并采取适当的预防措施。
ISTODAX可能引起胎儿危害孕妇管理。建议妇女对胎儿的潜在危险，并同时接收Istodax，以避免怀孕。
 
不良反应
最常见的不良反应为中性粒细胞，淋巴细胞，血小板减少症，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
仔细监测凝血酶原时间（PT）和国际标准化比值患者同时给予ISTODAX和香豆的衍生物。
强CYP3A4抑制剂可能会增加了的ISTODAX浓度和应避免。
强效CYP3A4诱导剂可能降低的ISTODAX浓度，并应避免。

更新日期：03/2012

ISTODAX® (romidepsin) for injection is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

This indication is based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.

Important Safety Information
WARNINGS AND PRECAUTIONS:
Treatment with ISTODAX has been associated with thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, monitor these hematological parameters during treatment with ISTODAX and modify the dose as necessary
Serious and sometimes fatal infections have been reported during treatment and within 30 days after treatment with ISTODAX and the risk of life threatening infections may be higher in patients with a history of extensive or intensive chemotherapy
Electrocardiographic (ECG) changes have been observed with ISTODAX
In patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as monitoring electrolytes and ECGs at baseline and periodically during treatment
Ensure that potassium and magnesium are within the normal range before administration of ISTODAX
Tumor lysis syndrome has been reported during treatment with ISTODAX. Patients with advanced stage disease and/or high tumor burden should be closely monitored and appropriate precautions taken, and treatment should be instituted as appropriate
ISTODAX may cause fetal harm when administered to a pregnant woman. Advise women to avoid pregnancy while receiving ISTODAX. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus (Pregnancy Category D)
ADVERSE REACTIONS:
Cutaneous T-Cell Lymphoma
The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 1 (N=102) were infections (11%) and asthenia/fatigue (8%), and in Study 2 (N=83) were lymphopenia (37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).

Infections were the most common type of serious adverse event reported in both Study 1 (N=102) and Study 2 (N=83) with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection.

The most common adverse reactions regardless of causality in Study 1 (N=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%) and in Study 2 (N=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), lymphopenia (57%), infections (54%), anorexia (54%), vomiting (52%), hypocalcemia (52%), hyperglycemia (51%), hypoalbuminemia (48%), leukopenia (46%), dysgeusia (40%), and constipation (39%).

DRUG INTERACTIONS:
ISTODAX is metabolized by CYP3A4. Avoid concomitant use with strong CYP3A4 inhibitors and potent CYP3A4 inducers if possible
Caution should also be exercised with concomitant use of moderate CYP3A4 inhibitors and P-glycoprotein (P-gp, ABCB1) inhibitors
Physicians should carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin sodium derivatives
USE IN SPECIFIC POPULATIONS:
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution.

Celgene公司注射剂Istodax新适应证获批

美国食品药品管理局（FDA）近日批准了Celgene公司的注射用药物Istodax (romidepsin)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。
Istodax，即组蛋白去乙酰化酶（HDAC）抑制剂，是抗癌药物类中的一种。
该药新适应证的获批是以两项研究的结果为支撑的，其中一项研究是对外周T细胞淋巴瘤患者体内的Istodax进行检测的Ⅱ期临床试验，这些患者在之前接受的至少一次的系统治疗中并未被治愈。
另外一项研究是对在以往治疗中未愈的外周T细胞淋巴瘤患者体内的Istodax进行的单臂临床试验。
Istodax也可用于治疗曾接受过多次系统治疗的T细胞淋巴瘤患者。