部份中文色瑞替尼处方资料（仅供参考）
商品名：Zykadia
通用名：ceritinib
中文名：色瑞替尼
审批分类：
突破性药物+优先审评+加速批准+孤儿药
适应症：
ALK阳性转移性非小细胞肺癌。
剂型规格：
本品为胶囊剂，推荐剂量为750mg/天。
作用机理：
ceritinib是ALK抑制剂，对表达EML4-ALK、NPM-ALK融合蛋白的细胞有抑制作用，能够克服crizotinib耐药性。
药企：Novartis
ZYKADIA Rx
Pharmacological Class:
Tyrosine kinase inhibitor.

Active Ingredient(s):
Ceritinib 150mg; hard gel caps.

Company
Novartis Pharmaceuticals Corp

Indication(s):
Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. Not established for improvement in survival or disease-related symptoms.

Pharmacology:
Ceritinib inhibits autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays.

Clinical Trials:
The efficacy of Zykadia was established in a multicenter, single-arm, open-label clinical trial (Study 1) involving 163 patients with metastatic ALK-positive NSCLC who progressed while receiving or were intolerant to crizotinib. All patients received Zykadia 750mg once daily. The major efficacy outcome measure was objective response rate (ORR) according to RECIST v1.0 as evaluated by both investigators and a Blinded Independent Central Review Committee (BIRC). Duration of response (DOR) was an additional outcome measure.

Results showed that the overall response rate in patients with ALK-positive NSCLC who received prior crizotinib was 54.6% (95% CI: 47, 62) and 43.6% (95% CI: 36, 52) in the investigator (N=163) and BIRC assessment (N=163), respectively. Also, in the investigator assessment, 1.2% achieved a complete response while 53.4% achieved a partial response with a median DOR of 7.4 months (95% CI: 5.4, 10.1). In the BIRC assessment, 2.5% achieved a complete response while 41.1% achieved a partial response with a median DOR of 7.1 months (95% CI: 5.6, NE).

Legal Classification:
Rx

Adults:
Take on an empty stomach (at least 2 hours before or after a meal). 750mg once daily until disease progression or unacceptable toxicity. Discontinue if 300mg once daily not tolerated. Moderate-to-severe hepatic impairment: not established. Dose modifications: see full labeling.

Children:
Not established.

Warnings/Precautions:
Monitor for severe or persistent GI toxicity; if occurs, withhold until improved; resume at reduced dose. Monitor ALT/AST and total bilirubin once monthly, and more frequently if elevated transaminases develop; withhold then reduce dose, or permanently discontinue as clinically indicated. Congenital long QT syndrome; avoid. CHF, bradyarrhythmias, electrolyte abnormalities; monitor ECG, electrolytes periodically. Permanently discontinue if QTc prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or serious arrhythmia develop. Monitor HR and BP regularly; serum glucose and pulmonary symptoms as clinically indicated. Permanently discontinue if treatment-related interstitial lung disease (ILD)/pneumonitis, uncontrolled hyperglycemia, or life-threatening bradycardia occur. Pregnancy (Category D). Females of reproductive potential should use effective contraception during treatment and for at least 2 weeks after completion. Nursing mothers: not recommended.

Interaction(s)
Avoid concomitant strong CYP3A4 inhibitors (eg, ritonavir, macrolides, ketoconazole, nefazodone), grapefruit juice; if unavoidable, reduce ceritinib dose by 1/3. Avoid concomitant strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) or CYP2C9 substrates (eg, phenytoin, warfarin) with narrow therapeutic indices; if unavoidable, reduce doses of these drugs. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine CCBs, clonidine, digoxin).

Adverse Reaction(s)
Diarrhea, nausea, vomiting, abdominal pain, constipation, elevated transaminases, fatigue, decreased appetite; bradycardia, hepatotoxicity, ILD/pneumonitis, QTc prolongation, hyperglycemia.

How Supplied:
Caps—70

LAST UPDATED:
7/7/2014

http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm395299.htm
晚期肺癌新药Zykadia获FDA批准在美上市
4月29日美国FDA批准Zykadia (ceritinib)用于治疗晚期转移性非小细胞肺癌(NSCLC)。Zykadia是一种间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂，它可以阻断促癌蛋白。这款药物适用于之前接受过克唑替尼(Crizotinib)治疗的转移性ALK阳性NSCLC患者，克唑替尼是仅有的另一款ALK酪氨酸激酶抑制剂。
肺癌是因癌死亡的主要因素。根据美国国家癌症研究所提供的信息，今年美国预计有22.421万人将被确诊为肺癌，有15.92万人将死于这种疾病。大约85%的肺癌是NSCLC，这使其成为最常见的肺癌类型。然而，只有2-7%的NSCLC患者其ALK呈阳性。
Zykadia是第四款以突破性治疗药物资格获得FDA批准的药物。它比这款药物的处方药用户付费目标日期2014年8月24日相比，提前4个月获得批准，后者是FDA计划完成药物申请审评的预期日期。
FDA授予Zykadia突破性治疗药物资格，优先审评及孤儿药资格，因为这款药物的申请者通过初步临床试验证据证明这款药物可能会提供一种相对现有治疗药物的实质性改善;这款药物在其申请提交时，在一种严重疾病治疗的安全性或有效性方面可能有显著改善，并且这款药物旨在治疗一种罕见疾病。
Zykadia的安全性及有效性基于一项由163名转移性ALK阳性NSCLC受试者参与的临床试验。所有受试者均接受了zykadia的治疗。结果显示，大约50%的受试者其肿瘤缩小，这种效果平均持续了大约7个月。
Zykadia的常见副作用包括消化道症状，如腹泻、恶心、呕吐和腹痛。肝酶增加、胰酶及葡萄糖水平增加等实验室异常也有被观察到。Zykadia由诺华上市销售。