英文药名：ZEJULA(niraparib capsules)

中文药名：尼拉帕尼胶囊

生产厂家：美国泰萨罗公司
药品简介
近日，美国FDA批准Zejula（niraparib）用于复发性上皮性卵巢，输卵管或原发性腹膜癌的成年患者的维持治疗（旨在延缓癌症生长），相对于铂类化疗其肿瘤完全或部分收缩（完全或部分反应）。
FDA的药物评估和研究中心血液和肿瘤学产品办公室主任Richard Pazdur博士说：“维持治疗是对初次治疗积极响应的患者的癌症治疗方案的重要组成部分， FDA肿瘤学卓越中心主任。“Zejula为患者提供了一种新的治疗方案，可能有助于延缓这些癌症的未来发展，无论它们是否具有特定的基因突变。”
Zejula是一种多聚ADP-核糖聚合酶（PARP）抑制剂，可阻断涉及修复受损DNA的酶。通过阻断该酶，癌细胞内的DNA可能不太可能被修复，导致细胞死亡，并可能导致肿瘤生长的减慢或停止。
批准日期：2017年3月27日；公司：Tesaro，Inc.
ZEJULATM(尼拉帕尼[niraparib])胶囊，为口服使用
美国初次批准：2017
作用机制
Niraparib是一种聚(ADP-核糖)聚合酶(PARP)酶，PARP-1和PARP-2的抑制剂，它们在DNA修复中起作用。体外研究曽显示niraparib-诱导细胞毒性可能涉及PARP酶活性的抑制作用和增加PARP-DNA复合物的形成导致DNA损伤，凋亡和细胞死亡。在BRCA1/2有或无缺陷肿瘤细胞系中观察到增加niraparib-诱导的细胞毒性。在BRCA1/2有缺陷小鼠肿瘤细胞的异种移植模型和在人有同源重组有或突变或野生型BRCA1/2缺乏患者-衍生移植瘤模型Niraparib减低肿瘤生长。
适应证和用途
ZEJULA是一种聚(ADP-核糖)聚合酶(PARP)抑制剂适用为有复发性表皮卵巢，输卵管，或原发性腹膜癌患者对基于铂化疗是一个完全或部分缓解成年患者的维持治疗。
剂量和给药方法
● 推荐剂量是300 mg每天1次有或无食物服用.
● 继续治疗直至疾病进展或不可接受不良反应。
● 对不良反应，考虑中断治疗，剂量减低，或给药终止.
剂型和规格
胶囊：100mg
禁忌证
无。.
警告和注意事项
● 骨髓增生异常综合征/急性髓性白血病(MDS/AML)：暴露于ZEJULA患者发生MDS/AML，和有些病例是致敏性。监视患者对血液学毒性和终止如MDS/AML被确证
不良反应
最常见不良反应(发生率 ≥10%)是血小板减少，贫血，中性细胞减少，白细胞减少，心悸，恶心，便秘，呕吐，腹痛/腹胀，粘膜炎/胃炎，腹泻，消化不良，口干，疲劳/乏力，减低食欲，泌尿道感染，AST/ALT升高，肌痛，背痛，关节痛，头痛，眩晕，味觉障碍，失眠，焦虑，鼻咽炎，呼吸困难，咳嗽，皮疹，和低血压.
特殊人群中使用
● 哺乳：建议妇女治疗期间和接受最后给药后共1个月不要哺乳喂养。
供应/贮存和处置
可得到ZEJULA为胶囊有一个白色体部用黑墨水印有“100 mg”，和一个紫色帽用白色水印有“Niraparib”。每粒胶囊含100 mg的niraparib游离碱。
ZEJULA胶囊被包装为90-计数瓶NDC 69656-103-90
贮存在20°至25°C(68°至77°F)；外出允许15°C至30°C间(59°F至86°F)[见USP控制室温]。

Zejula (niraparib capsules)
General Information
Zejula (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor.
Zejula is specifically indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
Zejula is supplied as a capsule for oral administration. The recommended dose of Zejua as monotherapy is 300 mg (three 100 mg capsules) taken orally once daily. Zejula should be administered at approximately the same time each day. Each capsule should be swallowed whole and may be taken with or without food.
Patients should start treatment with Zejula no later than 8 weeks after their most recent platinum-containing regimen.
Zejula treatment should be continued until disease progression or unacceptable toxicity. In the case of a missed dose, the next dose should be administered at its regularly scheduled time. If a patient vomits or misses a dose of Zejula, an additional dose should not be taken.
Please see drug label for additional modifications.
Clinical Results
FDA Approval
The FDA approval of Zejula was based on NOVA, a double-blind, placebo-controlled trial in which 553 patients with platinum sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomized 2:1 to Zejula 300 mg orally daily or matched placebo within 8 weeks of the last therapy.
All patients had received at least two prior platinum-containing regimens and were in response (complete or partial) to their most recent platinum-based regimen. The major efficacy outcome measure, PFS (progression-free survival), was determined primarily by central independent assessment per RECIST.  Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS.
The median PFS for patients treated with niraparib was 21.0 months, compared to 5.5 months for control (p < 0.0001). For patients who were not germline BRCA mutation carriers but whose tumors were determined to be HRD positive, the niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS. The median PFS for patients with HRD-positive tumors who were treated with niraparib was 12.9 months, compared to 3.8 months for control (p < 0.0001).
Niraparib also showed statistical significance in the overall non-germline BRCA mutant cohort, which included patients with both HRD-positive and HRD-negative tumors. The niraparib arm successfully achieved statistical significance over the control arm for the primary endpoint of PFS. The median PFS for patients treated with niraparib was 9.3 months, compared to 3.9 months for control (p < 0.0001).
Mechanism of Action
Zejula (niraparib) is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death.
Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2.
Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2.
Zejula will be available as 100mg strength capsules in 90-count bottles.