ST LOUIS (MD Consult) - On June 17, 2010, Novartis and the US Food and Drug Administration (FDA) announced that the approved indications for Tasigna (nilotinib) have been expanded. The new approval allows for use of the drug in the treatment of newly diagnosed Philadelphia chromosome positive chronic phase chronic myeloid leukemia (Ph+ CP-CML).

The FDA originally approved Tasigna in October 2007 for the treatment of Ph+ CP-CML in adult patients whose disease had progressed or who could not tolerate other therapies, including Gleevec (imatinib). Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CP-CML. It is also active against a broad spectrum of Bcr-Abl mutations associated with resistance to Gleevac.

The effectiveness of Tasigna for this expanded indication is derived from confirmed hematologic and unconfirmed cytogenetic response rates. Study data are provided in the June 17, 2010, issue of The New England Journal of Medicine (abstract). No controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival, currently exist.

The most frequent grade 3 or 4 adverse events associated with Tasigna use were primarily hematologic in nature and included neutropenia and thrombocytopenia. Elevations seen in bilirubin levels, liver function tests, lipase enzymes, and blood glucose were mostly transient and resolved over time. The most frequent nonhematologic drug-related adverse events were rash, pruritus, nausea, fatigue, headache, constipation, and diarrhea. Most of these adverse events were mild to moderate in severity.

Tasigna should be used with caution in patients with uncontrolled or significant cardiac disease as well as in patients who have previously experienced or may experience QTc prolongation. This would include patients with abnormally low potassium or magnesium levels, patients with congenital long-QT syndrome, and patients receiving antiarrhythmic medicines or other drugs that may lead to QT prolongation. Low levels of potassium or magnesium must be corrected before Tasigna administration. Close monitoring for an effect on the QTc interval is advisable, and baseline echocardiography is recommended before initiating therapy with Tasigna and as clinically indicated.

Tasigna should not be taken with food, and patients should wait at least 2 hours after a meal before taking Tasigna. In addition, no food should be consumed for at least 1 hour after dosing.

圣路易斯(MD Consult)——2010年6月17日，诺华公司与美国食品药品管理局(FDA)宣布，Tasigna (尼罗替尼)已获准扩大治疗指征。新批准令允许该药用于治疗新诊断的费城染色体阳性的慢性期慢性髓系白血病(Ph+ CP-CML)。

FDA最初于2007年10月批准Tasigna用于治疗病情已进展或无法耐受其他治疗(其中包括伊马替尼)的成人Ph+ CP-CML患者。Tasigna是Bcr-Abl蛋白的强效选择性抑制剂，而Bcr-Abl蛋白是导致Ph+ CP-CML患者癌细胞生成的罪魁祸首。该药也是与格列卫耐药相关的Bcr-Abl突变的广谱抑制剂。

Tasigna对这项扩大的治疗指征有效，此结果来自经证实的血液学和未经证实的细胞遗传学反应率。研究数据已发表于6月17日出版的《新英格兰医学杂志》(摘要)。目前尚无对照试验证实该药有改善疾病相关症状或提高生存率等临床收益。

最常见的与应用Tasigna相关的3或4级不良事件主要是血液学改变，其中包括中性粒细胞减少。所观察到的胆红素水平、肝功能试验、脂肪酶、血糖升高大多为暂时性的，随着时间的推移可恢复。最常见的非血液学药物相关的不良事件为皮疹、瘙痒、恶心、疲乏、头痛、便秘及腹泻，其中大多数不良事件为轻至中度。

Tasigna应慎用于心脏病未得到控制或很严重的患者以及既往曾出现或可能出现QTc延长的患者。可能包括异常低钾或低镁的患者、先天性长QT综合征患者以及接受抗心律失常药或其他可能导致QT延长药物的患者。在应用Tasigna之前必须纠正低钾或低镁。最好密切监测其对QTc间期的影响，推荐在Tasigna初始治疗前做基线超声心动图检查。

Tasigna不得在进餐时服用，应于进餐后至少2 h以后服用。另外，用药后至少1 h内不得进食任何食物。