诺华新型抗癌药已经通过了FDA的批准，该药用于治疗某种特定的白血病患者，即那些已经产生耐药性，或对其他药物耐受性差的Ph阳性慢性髓性白血病患者。每年在美国有4500人患这种疾病。 Tasigna每日用药两次，主要通过抑制Bcr-Abl蛋白的产生而起作用，只有哪些异常的Ph染色体细胞才能够产生这种蛋白，它正是导致白血球癌变的主要原因。 在试验中，232名患者使用该药进行六个月的治疗之后，他们的体内含有Ph染色体的细胞数量减少40%。正是基于这些试验结果，FDA对这种药物打开了大门。Tasigna已经在瑞士上市，在今年年底也将通过欧盟的批准。此外，该药的申请也已经于六月份在日本提交。 Tasigna的快速研发再次证明诺华履行了自己的承诺--不断研发创新药品，以满足患者尚未被满足的需求 日前，Tasigna®（尼洛替尼）在瑞士获得了世界范围内首个上市批准。 Tasigna是一种新型的靶向肿瘤治疗药物，它对那些产生格列卫®（伊马替尼）耐药或者不能耐受的慢性粒细胞白血病（CML）患者疗效显著。格列卫*是另外一种由诺华公司开发的用于治疗CML的优选药物。 基于一项关键的II期临床试验所产生的积极结果，瑞士卫生管理机构在加快审评后批准了Tasigna。结果显示，病人使用Tasigna后有效率高、耐受性好、安全性可管理。 每天服用两次，Tasigna可以通过靶向性地作用于Bcr-Abl蛋白，来抑制含有异常染色体的癌细胞的产生。Bcr-Abl蛋白是由含有异常的费城染色体的细胞产生的，在患有CML的患者中，这种蛋白质被认为是致癌白细胞过度增殖的一个重要因素。 在临床试验中，使用Tasigna治疗后，42%的对格列卫耐药的慢性期费城染色体阳性（Ph+）CML患者会出现异常染色体减少或者消失的情况；而在处于加速期的患者中，也有31%的患者能够获得同样的效果。 在美国、加拿大和以色列的名称为Gleevec®（伊马替尼甲磺酸盐）片剂。 “虽然在使用格列卫治疗的患者中，90%以上的人可以存活五年以上，但是我们也关注为那一小部分对格列卫耐药或不能耐受的患者提供帮助，这促使我们开发了Tasigna，”诺华公司董事长兼首席执行官魏思乐博士说。“我非常高兴，因为我们创造了一个新的记录，那就是我们为满足患者的需求而快速地推出了Tasigna??第二代选择性更强、疗效更显著的Bcr-Abl酪氨酸激酶抑制剂，它从合成到上市只用了不到五年的时间。” 今年晚些时候，美国和欧盟的卫生管理机构有望对Tasigna做出批准决定。与此同时，在日本的申报工作也将在2007年第二季度完成。7月16日，美国FDA要求对Tasigna注册的审批时间延长3个月。 2007年，诺华计划在对其他药物治疗反应不理想的CML患者以及新诊断的CML患者中开展Tasigna的III期临床试验。 在患有胃肠道间质瘤（GIST）的患者中也已经开始进行一项注册研究，此类患者在一些国家也可以使用格列卫来治疗。 最近的一系列具有里程碑意义的临床试验结果显示，使用格列卫对新诊断的慢性期Ph+ CML成年患者进行治疗后，五年后有将近90%的人存活1，但是一些患者产生了耐药或者不能耐受的情况。 2002年8月，诺华公司的一组科学家应用从格列卫中获得的重要经验研制开发了Tasigna，此时恰好是格列卫上市后一周年。Tasigna被专门设计用于更加有效、更加优先地靶向性作用于Bcr－Abl，与此同时，并没有引入可能导致其他副作用的新作用机制。Tasigna从合成到首次获得卫生管理机构的批准只用了不到五年的时间。 “Tasigna的开发速度反映了我们帮助癌症患者的激情，”诺华公司肿瘤事业部总裁兼首席执行官David Epstein说，“作为一种专门设计用于癌症治疗的药物，Tasigna再一次凸显了我们在靶向治疗领域的领导地位。” 慢性粒细胞白血病是四种最常见的白血病之一，在世界所有白血病病例中大约占15%2。它主要是由于未成熟白细胞的过度增殖而引起的，大约95%的CML患者会产生费城染色体。 基于卓越的II期临床试验结果获得批准 Tasigna被批准用于治疗对格列卫耐药或者不能耐受的慢性期或加速期的Ph+CML患者。在瑞士提交的申请是基于一项评估Tasigna安全性和有效性的II期开放性临床试验结果作出的。这项试验是在对格列卫耐药或者不能耐受的慢性期或加速期的Ph+CML患者中进行的。采用血液学缓解指标（白细胞计数恢复到正常范围）和细胞遗传学缓解指标(Ph+染色体减少或消失)来评估有效性。 经过中位时间为7.7个月的治疗后，在132名处于慢性期的患者中，有55名患者（42%）出现了明显的细胞遗传学缓解。在64名处于加速期的患者中，经过中位时间为5个月的治疗后，在20名患者（31%）中观察到了明显的细胞遗传学缓解。 在6月举行的美国临床肿瘤学会年会上，这项关键的II期临床试验的长期数据被发表。这些数据显示了更积极的结果。 Tasigna的安全性信息 在438名患者中分析了Tasigna的安全性数据。采用Tasigna治疗时，最常见的3级或4级不良事件主要为血液学毒性，包括中性粒细胞减少和血小板减少。同时还观察到胆红素、肝功能试验值、脂肪酶和血糖水平的升高，其中大多数指标的升高都是一过性的，而且随着时间的延长而逐渐缓解。这些病例都比较容易管理，而且很少会导致停药。不到1%的病例报告发生了胰腺炎。最常见的非血液学药物相关不良事件包括皮疹、搔痒、恶心、疲劳、头痛、便秘和腹泻。大多数此类不良事件都属于轻度到中度。 在伴有或可能发生QTc延长的患者中，应该慎用Tasigna，这其中包括钾或镁水平异常降低的患者，患有先天性长QT综合征的患者，服用抗心律失常药物或者其它可能导致QT间期延长的药物的患者，以及采用蓄积性高剂量蒽环类抗生素治疗的患者。如果钾或镁的水平较低，在给予Tasigna之前必须将其纠正到正常范围。 Tasigna的生物利用度随着食物的摄入而增加。Tasigna不应该随食物一起服用，而应该在餐后两小时服用。在服用药物后至少一个小时之内，不应该进食。 Tasigna Generic Name: nilotinib (nye LOE ti nib) Brand Names: Tasigna What is Tasigna? Tasigna interferes with the growth of some cancer cells. Tasigna is used to treat a type of blood cancer called Philadelphia chromosome positive chronic myeloid leukemia (CML). Tasigna is usually given to people who cannot take certain other leukemia medications, or who have tried other medications without successful treatment. Tasigna may also be used for other purposes not listed in this medication guide. --------------------------------------------------------- Important information about Tasigna You should not use Tasigna if you are allergic to nilotinib, or if you have low blood levels of potassium or magnesium, or a history of "Long QT syndrome." Do not use Tasigna if you are pregnant. It could harm the unborn baby. You should not breast-feed while you are taking Tasigna. Before using Tasigna, tell your doctor if you have heart disease or a heart rhythm disorder, liver disease, a personal history of pancreatitis, or a family history of "Long QT syndrome." There are many other drugs that can cause serious or life-threatening medical problems if you take them together with Tasigna. Tell your doctor about all medications you use. You will need regular medical tests to be sure Tasigna is not causing harmful effects. Visit your doctor regularly. Call your doctor at once if you have a serious side effect such as dizziness and fast or pounding heartbeat, pale skin, easy bruising or bleeding, fever, flu symptoms, cough with stabbing chest pain, mouth sores, feeling light-headed or short of breath, swelling, sudden headache or vision problems, upper stomach pain, dark urine, or jaundice (yellowing of the skin or eyes). --------------------------------------------------------- Before taking Tasigna You should not use Tasigna if you are allergic to nilotinib, or if you have: low blood levels of potassium or magnesium; or a history of "Long QT syndrome." If you have any of these other conditions, your doctor may need to adjust the dose of Tasigna or order special tests: heart disease or heart rhythm disorder; liver disease; a personal history of pancreatitis; or a family history of "Long QT syndrome." FDA pregnancy category D. Do not use Tasigna if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. It is not known whether nilotinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking Tasigna. Tasigna capsules may contain lactose. Talk to your doctor before using Tasigna if you have galactose intolerance, or severe problems with lactose (milk sugar). --------------------------------------------------------- How should I take Tasigna? Take Tasigna exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Tasigna is usually taken every 12 hours. Follow your doctor's instructions. Take Tasigna on an empty stomach, at least 1 hour before or 2 hours after a meal. Take this medicine with a full glass of water. Do not break or open a Tasigna capsule. Swallow the pill whole. To be sure Tasigna is helping your condition and not causing harmful effects, your blood and bone marrow will need to be tested often. Your heart function will also need to be checked using an electrocardiograph or ECG (sometimes called an EKG). This machine measures electrical activity of the heart. Visit your doctor regularly. Do not stop using Tasigna or change your dose without talking to your doctor. If you stop taking the medication too soon, your condition may get worse. Store Tasigna at room temperature away from moisture and heat. --------------------------------------------------------- What happens if I miss a dose? Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose. --------------------------------------------------------- What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. --------------------------------------------------------- What should I avoid while taking Tasigna? Do not take with food. Food can increase your blood levels of nilotinib and may increase your risk of harmful side effects. Grapefruit and grapefruit juice may interact with Tasigna and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor. --------------------------------------------------------- Tasigna side effects Get emergency medical help if you have any of these signs of an allergic reaction to Tasigna: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using Tasigna and call your doctor at once if you have a serious side effect such as: dizziness and fast or pounding heartbeat, seizure (convulsions); pale skin, weakness, feeling light-headed, rapid heart rate, trouble concentrating; easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin; fever, chills, body aches, flu symptoms, sores in your mouth and throat; feeling short of breath, even with mild exertion; swelling, rapid weight gain; sudden headache, confusion, or problems with vision; nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); severe pain in your upper stomach spreading to your back; or cough with yellow or green mucus, stabbing chest pain, wheezing, feeling short of breath. Less serious Tasigna side effects may be more likely to occur, such as: mild skin rash or itching; diarrhea, constipation, vomiting; headache; or tired feeling. This is not a complete list of Tasigna side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. --------------------------------------------------------- What other drugs will affect Tasigna? Many drugs can interact with Tasigna. Below is just a partial list. Tell your doctor if you are using: arsenic trioxide (Trisenox); conivaptan (Vaprisol); droperidol (Inapsine); imatinib (Gleevec); isoniazid (for treating tuberculosis); midazolam (Versed); pimozide (Orap); St. John's wort; a blood thinner such as warfarin (Coumadin); an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), moxifloxacin (Avelox), telithromycin (Ketek), and others; an antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend); an antidepressant such as amitriptylline (Elavil, Vanatrip), clomipramine (Anafranil), desipramine (Norpramin), or nefazodone; anti-malaria medications such as chloroquine (Arelan), halofantrine (Halfan), or mefloquine (Lariam); heart or blood pressure medication such as amiodarone (Cordarone, Pacerone), diltiazem (Cartia, Cardizem), disopyramide (Norpace), nifedipine (Nifedical, Procardia), procainamide (Pronestyl), quinidine (Quin-G), sotalol (Betapace), verapamil (Calan, Covera, Isoptin, Verelan), and others; HIV/AIDS medicine such as delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), ritonavir (Kaletra, Norvir), and others; medicine to prevent or treat nausea and vomiting, such as dolasetron (Anzemet) or ondansetron (Zofran); medicines to treat psychiatric disorders, such as clozapine (FazaClo, Clozaril), haloperidol (Haldol), and others; migraine headache medicine such as sumatriptan (Imitrex); or a narcotic such as methadone (Dolophine, Methadose). This list is not complete and there are many other drugs that can cause serious or life-threatening medical problems if you take them together with Tasigna. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. --------------------------------------------------------- Where can I get more information? Your pharmacist can provide more information about Tasigna. Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.