Generic Name and Formulations:
Ceritinib 150mg; hard gel caps.

Company:
Novartis Pharmaceuticals Corp

Indications for ZYKADIA:
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.

Adult:
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.

Pharmacological Class:
Tyrosine kinase inhibitor.

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 (Cat. D). Females of reproductive potential should use effective contraception during treatment and for at least 2 weeks after completion. Nursing mothers: not recommended.

Interactions:
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 Reactions:
Diarrhea, nausea, vomiting, abdominal pain, constipation, elevated transaminases, fatigue, decreased appetite; bradycardia, hepatotoxicity, ILD/pneumonitis, QTc prolongation, hyperglycemia.

How Supplied:
Caps—70

 Zykadia (Ceritinib) Approved for metastatic Lung Cancer FDA批准诺华色瑞替尼用于晚期肺癌治疗 

Novartis’ Ceritinib (Trade Name: Zykadia, previously known as LDK378, Chinese Name:色瑞替尼), an oral selective inhibitor of anaplastic lymphoma kinase (ALK),  was approved four months ahead of schedule on April 29, 2014 by the U.S. Food And Drug Administration (FDA) to treat patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who were previously treated with Pfizer’s Xalkori (Crizotinib), the only other approved ALK tyrosine kinase inhibitor.

Lung cancer is the leading cause of cancer-related death among men and women worldwide. The most common type of lung cancer is non-small cell lung cancer (NSCLC), accounting for 85-90% of all cases. Only 2-7 percent of patients with NSCLC are ALK-positive. Since its launch in 2011, crizotinib has become a standard of care in this small patient population, with data showing that it doubles progression-free survival when compared with chemotherapy.However, some patients become resistant to crizotinib, and until now, there has been no other targeted therapy to offer these patients. Ceritinib now fills that role. Analysts predict Zykadia (Ceritinib) will have annual sales of $423 million by 2018 lagging the $830 million expected for Xalkori.

The accelerated approval for the second-generation ALK inhibitor Ceritinib was supported by results from an analysis of 163 patients treated with single-agent ceritinib at 750 mg daily following progression on crizotinib. In these select patients, the ORR was 54.6% with a 7.4-month median duration of response. FDA also granted ceritinib a Breakthrough Therapy designation, Priority Review, and orphan product designation.

Trade Name：Zykadia
Generic Name：ceritinib
Synonym：LDK378
Chemical Name:5-Chloro-N2-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N4-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine
CAS number：1032900-25-6
Mechanism of Action:Anaplastic lymphoma kinase inhibitor
Clinical Trail Data:among 163-treated patients, Zykadia achieved an overall response rate (ORR) of 54.6% and a median duration of response (DOR) of 7.4 months
Dosage and Administration:750 mg orally once daily
Date of Approval: April 29, 2014
Indication：ALK positive non-small cell lung cancer (ALK+ NSCLC)
Company:Novartis Pharmaceuticals Corporation

诺华色瑞替尼(Zykadia)用于晚期肺癌治疗获FDA批准

2014年4月29日，美国FDA批准Zykadia (色瑞替尼, ceritinib， LDK378)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。所有受试者均以Zykadia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。

商品名：Zykadia
通用名：色瑞替尼 (ceritinib)
曾用名：LDK378
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。
临床试验：一项开放标签试验入组了163例crizotinib耐药或不耐受的患者，总应答率为54.6%（完全应答1.2%+部分应答53.4%），持续应答时间为7.4个月
审批分类：突破性药物+优先审评+加速批准+孤儿药
药企：诺华