制造商：
Celgene公司公司
药理分类：
抗肿瘤（组蛋白去乙酰酶抑制剂）
活性成分（补）：
Romidepsin 10mg/vial;为四输液密码重组和稀释后，包含聚维酮。
指示（补）：
皮肤T细胞淋巴瘤谁得到至少有一个事先全身治疗的患者（CTCL的）。
药理：
组蛋白脱乙酰酶催化来自非组蛋白和赖氨酸残基乙酰乙酰基去除组蛋白，从而影响基因的表达。这种酶抑制剂，如romidepsin，干扰组蛋白和转录介导的蛋白质的活动。在体外，romidepsin已被证明导致组蛋白的乙酰化积累，促使某些肿瘤细胞株细胞周期阻滞和凋亡，但其确切作用机制CTCL的治疗尚未阐明。
临床试验：
两个多中心，单臂临床研究，来评估治疗皮肤T细胞淋巴癌的romidepsin疗效。患者治疗药物的研究在建议的剂量，直到病情在调查和当地的监管权进展。目标疾病的反应进行了评估使用复合终点，其中包括参与评估，皮肤，淋巴结及内脏的参与，以及不正常循环T细胞。每个研究的主要终点是总的目标疾病的反应效率（ORR），作为与患者比例界定确认完全缓解或部分缓解。
1包括96个研究与证实后，至少有1前全身治疗失败CTCL患者。在本研究Orr曾34％（完全缓解6％+部分缓解28％）。中位缓解时间为15个月。
研究2中包含的71 CTCL的谁的至少接受2之前，初步诊断病人皮肤直接疗法或至少一个全身治疗。在这项研究中，氧还原为35％（完全缓解6％+部分缓解30％）。中位缓解时间为11个月。
中位时间为第一个反应是这两项研究的2个月。中位数的时间完成了6个月的反应研究中的1和第4研究中的2个月。
法律分类：
接收
成人：
≥18yrs：由四输注给了4小时。 14mg/m2的天1，8和1 28 15天周期，重复周期每28天;继续作为容忍和有益的。 5月中断，减少剂量10mg/m2，或停止基于毒性（见文献）。
儿童：
“18yrs：不推荐。
预防措施（补）：
纠正电解质失衡（特别是钾，镁+ +）开始之前。监测心电图和先天性长QT综合征的电解质，重要的心血管疾病。中度至重度肝损害。终末期肾病。央行监测的差距。妊娠（Cat.D，可能会对胎儿造成伤害）。哺乳母亲：不推荐。
互动（补）：
可能会干扰荷尔蒙（雌激素）的避孕药具。注意与其他药物可能导致QT间期延长（监视器）。监视器葡萄牙/法林起始子。通过药物抑制P -糖蛋白和CYP3A4 Potentiated，避免随之而来的强烈的CYP3A4抑制剂（如氮唑类抗真菌，蛋白酶抑制剂，克拉霉素，奈法唑酮）。注意中度CYP3A4抑制剂。 CYP3A4的诱导剂强拮抗（如卡马西平，苯妥英，苯巴比妥，利福平;避免。Concomittant贯叶连翘：不推荐。
不良反应（补）：
胃肠不适，疲劳，感染，厌食，贫血，血小板减少，心电图T波变化，中性粒细胞，淋巴细胞。
如何提供：
洁1（单用小瓶+稀释剂和用品）
ISTODAX
Generic Name for ISTODAX
Romidepsin 10mg/vial; pwd for IV infusion after reconstitution and dilution; contains povidone.
Legal Classification:
Rx
Pharmacological Class for ISTODAX
Histone deacetylase inhibitor.
Manufacturer of ISTODAX
Celgene Corp
Indications for ISTODAX
Cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy.
Adult dose for ISTODAX
≥18yrs: Give by IV infusion over 4hrs. 14mg/m2 on days 1, 8, and 15 of a 28-day cycle; repeat cycle every 28 days; continue as tolerated and as beneficial. May interrupt, reduce dose to 10mg/m2, or discontinue based on toxicities (see literature).
Children's dosing for ISTODAX
<18yrs: not recommended.
Warnings/Precautions for ISTODAX
Correct electrolyte imbalances (esp. K+, Mg++) before starting. Monitor ECG and electrolytes in congenital long QT syndrome, significant cardiovascular disease. Moderate to severe hepatic impairment. End-stage renal disease. Monitor CBC with differential. Pregnancy (Cat.D; may cause fetal harm). Nursing mothers: not recommended.
Interactions for ISTODAX
May interfere with hormonal (estrogen) contraceptives. Caution with other drugs that can cause QT prolongation (monitor). Monitor PT/INR with warfarin. Potentiated by drugs that inhibit P-glycoprotein and CYP3A4 ; avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, clarithromycin, nefazodone). Caution with moderate CYP3A4 inhibitors. Antagonized by strong CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin; avoid). Concomittant St. John’s Wort: not recommended.
Adverse Reactions for ISTODAX
GI upset, fatigue, infections, anorexia, anemia, thrombocytopenia, ECG T-wave changes, neutropenia, lymphopenia.
How is ISTODAX supplied?
Kit—1 (single-use vial + diluent and supplies)
Related Disease:
Lymphoma, cutaneous T-cell
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ISTODAX was evaluated in 2 multicenter, single-arm, international clinical studies in patients with cutaneous T-cell lymphoma (CTCL).
Patients were treated with ISTODAX at a starting dose of 14 mg/m2 infused over 4 hours on days 1, 8, and 15 every 28 days
In both studies, patients could be treated until disease progression at the discretion of the investigator and local regulators
Objective disease response rate (ORR) was evaluated according to a composite endpoint that included assessments of skin involvement, lymph node involvement, abnormal circulating T-cells (Sézary cells), and visceral involvement (Study 2 only)
The primary efficacy endpoint for both studies was overall ORR based on the investigator assessments, and defined as the proportion of patients with confirmed complete response (CR) or partial response (PR)
CR was defined as no evidence of disease
PR was defined as ≥50% improvement in disease
Secondary endpoints in both studies included duration of response and time to response
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
Please see full Prescribing Information, including, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.