近日，美国FDA批准Onivyde（irinotecan liposome injection，MM-398）为胰腺癌一种新的上市药物，联合氟尿嘧啶和亚叶酸治疗吉西他滨化疗效果不佳的晚期(转移)胰腺癌患者。
FDA药品评价与研究中心血液与抗肿瘤产品办公室主任Richard Pazdur博士指出：“FDA许多新药审评专家也是临床医生，每当我们能够加速批准可用于尚未得到治疗满足需求患者的新药时，感觉特别有益。Onivyde通过优先审评获批，患者可早日得到这一药物治疗，有助于延长生存时间。”
批准日期：2015年10月28日  公司：梅里马克制药
ONIVYDE™（伊立替康脂质体 irinotecan liposome）注射液，供静脉使用
美国首次批准：1996
警告：
严重中性粒细胞和严重腹泻查看全部处方信息进行完整的黑框警告
致命的中性粒细胞减少败血症的发生率为0.8％，接受ONIVYDE，严重或危及生命的中性粒细胞减少发热或败血症发生在3％和严重或危及生命的中性粒细胞减少发生在接收ONIVYDE与氟尿嘧啶和亚叶酸结合患者的20％。ONIVYDE的绝对中性粒细胞计数低于1500个/mm3或中性粒细胞减少发热。治疗期间定期监测血细胞数。
严重的腹泻发生在接收ONIVYDE与氟尿嘧啶和亚叶酸结合患者的13％。不要给予ONIVYDE给患者肠梗阻。扣压ONIVYDE为2-4级严重腹泻。辖洛哌丁胺任何程度的后期腹泻辖阿托品，如果没有禁忌，任何严重程度的早期腹泻。
作用机制
伊立替康脂质体注射液是一种拓扑异构酶1抑制剂包封在脂质双层囊泡或脂质体中。拓扑异构酶1通过诱导单链断裂减轻在DNA中的扭转变形。伊立替康及其活性代谢物的SN-38结合可逆的拓扑异构酶1-DNA复合体，并防止再结扎的单链断裂，导致曝光时间依赖双链DNA损伤和细胞死亡。在小鼠中携带人肿瘤异种移植物，伊立替康脂质体施用伊立替康盐酸等效剂量5倍低于伊立替康盐酸达到类似SN-38的肿瘤内照射。
适应症和用法
ONIVYDE是拓扑异构酶抑制剂所指出的，在结合氟尿嘧啶和甲酰四氢叶酸，用于治疗患有以下吉西他滨为基础的治疗疾病进展后胰腺的转移性腺癌的治疗：
使用:ONIVYDE限制没有指示为用于治疗患有胰腺转移性腺癌的治疗单一试剂.
用法用量
不要代替ONIVYDE含有盐酸伊立替康等药物。
ONIVYDE的推荐剂量是70毫克/米2静脉输注在90分钟内每两个星期。
ONIVYDE的纯合子患者UGT1A1推荐起始剂量*28是50毫克/米2每两个星期。
没有推荐剂量ONIVYDE的患者的血清胆红素以上的正常上限。
Premedicate与前30分钟ONIVYDE皮质类固醇和抗催吐剂。
剂型和规格
注射剂：43毫克/10毫升单剂量小瓶
禁忌
严重过敏反应到ONIVYDE或伊立替康HCl中。
警告和注意事项
间质性肺病（ILD）：致命ILD中已经发生接收伊立替康盐酸请停止ONIVYDE患者如果ILD诊断.
严重的过敏反应：永久停止ONIVYDE严重过敏反应.
胚胎 - 胎儿毒性：可引起胎儿危害提醒女性的潜在风险生殖潜力的一个胎儿，并使用有效的避孕
不良反应
ONIVYDE:腹泻，疲劳/乏力，呕吐，恶心，最常见的不良反应（≥20％），食欲下降，口腔炎和发热最常见的实验室异常（≥10％3或4级）分别为淋巴细胞和中性粒细胞减少。
要报告疑似不良反应，请联系梅里马克制药公司在1-844-441-6225或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
强CYP3A4诱导剂:避免使用强CYP3A4诱导剂如可能替代非酶诱导治疗至少2周前ONIVYDE的开始.
强CYP3A4抑制剂：避免使用强CYP3A4或UGT1A1的抑制剂，如果可能的话，在开始治疗前至少1周停止强CYP3A4抑制剂.
特殊人群中使用
哺乳期：不要母乳喂养.
包装规格/储存与处理
供应
ONIVYDE可在含有43毫克伊立替康的游离碱以4.3毫克/ mL的浓度单剂量小瓶
NDC：69171-398-01
存储和处理
商店ONIVYDE在2℃至8ºC（36°F至46°F）。不要冷冻。避光。
ONIVYDE是细胞毒性药。按照适用的特殊处理和处置程序.

Onivyde(MM-398/irinotecan liposome injection) is an intravenous injection indicated for the treatment of metastatic pancreatic cancer.
Onivyde(irinotecan liposome injection) is a topoisomerase inhibitor.
Onivyde is specifically indicated in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.
Onivyde is supplied as an injection for intravenous infusion. Administer Onivyde prior to leucovorin and fluorouracil. The recommended dose of Onivyde is 70mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. Increase the dose of Onivyde to 70 mg/m2 as tolerated in subsequent cycles.
Please see drug label for dosing in specific populations and for dose modifications.
Clinical Results
FDA Approval
The FDA approval of Onivyde was based on a three-arm, randomized, open-label trial in 417 patients with metastatic pancreatic adenocarcinoma with documented disease progression, after gemcitabine or gemcitabine-based therapy. Subjects were were randomized to receive Onivyde plus fluorouracil/leucovorin (Onivyde/5-FU/LV), Onivyde, or fluorouracil/leucovorin (5-FU/LV). Randomization was stratified by ethnicity (White vs. East Asian vs. other), KPS (70-80 vs. 90-100), and baseline albumin level (≥ 4 g/dL vs. 3.0-3.9 g/dL). Patients randomized to Onivyde/5-FU/LV received Onivyde 70 mg/m2 as an intravenous infusion over 90 minutes, followed by leucovorin 400 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks. The Onivyde dose of 70 mg/m2 is based on irinotecan free base (equivalent to 80 mg/m2 of irinotecan as the hydrochloride trihydrate). Patients randomized to Onivyde as a single agent received Onivyde 100 mg/m2 as an intravenous infusion over 90 minutes every 3 weeks. Patients randomized to 5-FU/LV received leucovorin 200 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2000 mg/m2 intravenously over 24 hours, administered on Days 1, 8, 15 and 22 of a 6-week cycle. Patients homozygous for the UGT1A1*28 allele initiated Onivyde at a reduced dose (50 mg/m2 Onivyde if given with 5-FU/LV or 70 mg/m2 Onivyde as a single agent). The major efficacy outcome measure was overall survival (OS) with two pair-wise comparisons: Onivyde versus 5-FU/LV and Onivyde/5-FU/LV versus 5-FU/LV. The study showed a statistically significant improvement in overall survival for the Onivyde/5-FU/LV arm over the 5-FU/LV arm. There was no improvement in overall survival for the Onivyde arm over the 5-FU/LV arm.
Mechanism of Action
Onivyde (irinotecan liposome injection) is a topoisomerase inhibitor encapsulated in a lipid bilayer vesicle or liposome. Topoisomerase 1 relieves torsional strain in DNA by inducing single-strand breaks. Irinotecan and its active metabolite SN-38 bind reversibly to the topoisomerase 1-DNA complex and prevent re-ligation of the single-strand breaks, leading to exposure time-dependent double-strand DNA damage and cell death. In mice bearing human tumor xenografts, irinotecan liposome administered at irinotecan HCl-equivalent doses 5-fold lower than irinotecan HCl achieved similar intratumoral exposure of SN-38.
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52ef5879-4cb5-443a-a355-5de14c497f22