部分中文SPRYCEL处方资料（仅供参考） SPRYCEL的适应症 Dasatinib被FDA批准用于治疗对之前治疗耐药或无法耐受的成人慢性期、加速期、髓系或淋巴系慢性髓性白血病。Dasatinib的有效性是以血液学和遗传学反应为基础，目前还没有对照试验来显示dasatinib的临床益处，例如疾病相关症状的改善或生存时间的延长。Dasatinib也被批准用来治疗对之前治疗耐药或不能耐受的Ph+急性淋巴母细胞白血病人。 商品名：Sprycel 开发与上市厂商 本品由美国百时美施贵宝公司开发，于2006 年2月首次在美国上市。 适应证 本品适用于对包括甲磺酸伊马替尼在内的治疗方案耐药或不能耐受的慢性髓细胞样白血病（CML）所有病期（慢性期、加速期、淋巴细胞急变期和髓细胞急变期）的成人患者。另外本品可用于对以往治疗药物耐药或不能耐受的费城染色体阳性急性淋巴细胞性白血病（Ph+ALL）成年患者。 药理作用 本品为多酪氨酸激酶抑制剂，可抑制BCR- ABL、SRC家族（SRC、LCK、YES、FYN）、c-KIT, EPHA2和尸DGFRβ等激酶。在体外，本品对多种不同的伊马替尼敏感或耐药的白血病细胞株有活性，可抑制 BCR-ABL过表达的CML和ALL细胞株的生长。 本品的最大血药浓度(Cmax)出现在口服后0.5～6小时。在一日15～240mg范围内，AUC及体内消除参数与剂量存在线性相关，总体平均终末半衰期（t1/2)为3～5 小时。本品的表观分布容积为2505L，显示本品组织分布广泛。体外试验中，本品及其活性代谢物血浆蛋白结合率约为96%和93%,在100～500ng/mL浓度范围内基本恒定。本品在人体内被广泛代谢，主要代谢酶为细胞色素P450(CYP)3A4。 临床评价 4项单组多中心临床研究考察了本品对伊马替尼耐药或不耐受的CML或Ph+ALL患者的疗效和安全性。该研究纳入慢性期CML患者186例，急变期CML 患者107例，淋巴细胞急变期/Ph+ALL患者78例及髓细胞急变期患者74例。大部分患者有很长的病史并经过大量药物治疗（包括伊马替尼、细胞毒化疗药物、干扰素和干细胞移植等）。经过本品治疗的所有患者均获得了血液学和细胞遗传学反应。慢性期CML患者的显著细胞遗传学缓解率(MCyR)为45%，完全缓解率为 33%；急变期CML患者的显著血液学缓解率(MaHR)为 59%；髓细胞急变期、淋巴细胞急变期及Ph+ALL患者的MaHR率分别为32%、31％和42%。 不良反应 本品最常见不良反应包括体液潴留（胸腔积液）、胃肠道反应（包括腹泻、恶心、腹痛和呕吐）及出血事件。最常见严重不良反应包括发热（9%）、胸腔积液（8%）、发热性中性粒细胞减少症（7%）、胃肠道出血（6 %）、肺炎（6%）、血小板减少症（5%）、呼吸困难 (4％）、贫血（3％）、心力衰竭（3%）和腹泻（2%）等。 注意事项 本品可导致严重的血小板减少症、中性粒细胞减少和贫血。骨髓抑制在晚期CML或Ph+ALL患者中发生率较慢性期CML患者高。此外，本品在体外还可导致血小板功能不良，在接受本品治疗的患者中约有 1％发生严重中枢神经系统出血，甚至死亡。 用法与用量 本品推荐剂量一日140mg，分早晚2次口服，空腹或进餐后服用均可。片剂不可碾碎或切开，需整片吞下。 制剂 本品为白色或类白色、双凸椭圆型薄膜包衣片，有20、50和70mg，3种规格。 Sprycel Generic Name: dasatinib (da SAT in ib) Brand Names: Sprycel -------------------------------------------- What is Sprycel? Sprycel (dasatinib) is a cancer medication that slows the growth and spread of cancer cells in the body. Sprycel is used to treat chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) when other cancer treatments have not been effective. Sprycel may also be used for purposes not listed in this medication guide. -------------------------------------------- Important information about Sprycel Do not use Sprycel if you are pregnant. It could harm the unborn baby. Use birth control to prevent pregnancy while you are receiving Sprycel, whether you are a man or a woman. Sprycel use by either parent may cause birth defects. Before taking Sprycel, tell your doctor if you have liver disease, low levels of potassium or magnesium in your blood, heart disease or a heart rhythm disorder, or if you have a personal or family history of "Long QT syndrome." Do not crush, chew, or break a Sprycel tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time. There are many other drugs that can interact with Sprycel. 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. Sprycel can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Visit your doctor regularly. Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection. -------------------------------------------- Before taking Sprycel You should not use Sprycel if: you have not first received a medication called imatinib (Gleevec); or if you are pregnant or planning to become pregnant during treatment with Sprycel. To make sure you can safely take Sprycel, tell your doctor if you have any of these other conditions: liver disease; low levels of potassium or magnesium in your blood; heart disease or a heart rhythm disorder; or a personal or family history of "Long QT syndrome." FDA pregnancy category D. Do not use Sprycel if you are pregnant. It could harm the unborn baby. Tell your doctor if you become pregnant during treatment. Use birth control to prevent pregnancy while you are receiving Sprycel, whether you are a man or a woman. Sprycel use by either parent may cause birth defects. A man taking Sprycel should use a condom during any sexual activity. It is not known whether dasatinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking Sprycel. This medication may affect fertility (your ability to have children), whether you are a man or a woman. Sprycel tablets contain lactose. Talk to your doctor before using this medication if you are lactose-intolerant. -------------------------------------------- How should I take Sprycel? Take Sprycel 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. This medicine is usually taken once in the morning and once in the evening. Follow your doctor's instructions. You may take the medication with or without food. Your doctor may occasionally change your dose to make sure you get the best results. Take Sprycel tablets with a full glass of water. Do not crush, chew, or break a Sprycel tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time. Do not use a pill that has been accidentally broken. Dasatinib from a crushed or broken Sprycel tablet can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If this occurs, wash your skin with soap and water or rinse your eyes with water. Ask your doctor or pharmacist how to safely handle and dispose of a broken tablet. Sprycel can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Visit your doctor regularly. Store Sprycel 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 Sprycel? Avoid taking an antacid within 2 hours before or 2 hours after you take Sprycel. Use only the type of antacid your doctor recommends. Some antacids can make it harder for your body to absorb Sprycel. Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection. Grapefruit and grapefruit juice may interact with Sprycel 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. -------------------------------------------- Sprycel side effects Get emergency medical help if you have any of these signs of an allergic reaction to Sprycel: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as: pale skin, feeling light-headed or short of breath, 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; black, bloody, or tarry stools; coughing up blood or vomit that looks like coffee grounds; orswelling in your hands, ankles, or feet. Less serious Sprycel side effects may include: headache; tired feeling; nausea, diarrhea; or mild skin rash; This is not a complete list of 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 Sprycel? Tell your doctor about all other medicines you use, especially: alfentanil (Alfenta), fentanyl (Actiq, Duragesic); bosentan (Tracleer); conivaptan (Vaprisol); cyclosporine (Gengraf, Neoral, Sandimmune); dexamethasone (Decadron, Hexadrol); ergotamine (Ergomar, Cafergot, Migergot); imatinib (Gleevec); isoniazid (for treating tuberculosis); pimozide (Orap); rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), or rifapentine (Priftin); St. John's wort; an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), or telithromycin (Ketek); an antidepressant such as nefazodone; antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend); phenobarbital (Solfoton) and other barbiturates; a blood thinner such as warfarin (Coumadin); heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others; HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), saquinavir (Invirase), or ritonavir (Kaletra, Norvir); medicines to treat narcolepsy, such as armodafanil (Nuvigil) or modafanil (Progivil); medication used to prevent blood clots, such as bivalirudin (Angiomax), clopidogrel (Plavix), dalteparin (Fragmin), dipyridamole (Persantine, Aggrenox), enoxaparin (Lovenox), fondaparinux (Arixtra), lepirudin (Refludan), ticlopidine (Ticlid); medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Prograf); seizure medication such as carbamazepine (Carbatrol, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenytoin (Dilantin), or primidone (Mysoline); or stomach acid reducers such as cimetidine (Tagamet), esomeprazole (Nexium), famotidine (Pepcid), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec, Zegerid), pantoprazole (Protonix), rabeprazole (Aciphex), or ranitidine (Zantac). This list is not complete and there are many other drugs that can interact with Sprycel. 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 Sprycel. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. 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 Sprycel现已完全获准治疗慢性骨髓性白血病 2009年5月26日，百时美施贵宝公司宣布，美国食品药品管理局(FDA)已完全批准Sprycel(达沙替尼)用于治疗对甲磺酸伊马替尼(Imatinib mesylate/Gleevec)等先前的疗法耐药或不能耐受的慢性骨髓性白血病(CML)所有病期(慢性期、加速期、髓细胞急变期和淋巴系细胞急变期)的成人患者。Sprycel是一种口服酪氨酸激酶抑制剂，FDA先前已批准该药为治疗CML的罕见药品，并完全批准其用于治疗对以前的疗法耐药或不能耐受、费城染色体阳性(Ph+)的急性淋巴细胞性白血病(ALL)成人患者。 FDA完全批准Sprycel用于治疗CML，这在某种程度上是依据一项III期随机、开放标记、剂量优化研究的结果，该研究共纳入670例已证实对Gleevec耐药或不能耐受的慢性期CML患者；其主要终点为Gleevec耐药患者的主要细胞遗传学缓解(McyR)(完全缓解加部分缓解，Ph+中期细胞比例为0~35%)。研究资料包括开始Sprycel治疗(剂量为100 mg，1日1次)后最少2年的随访。现将这167例接受Sprycel治疗(剂量为100 mg，1日1次)的患者的研究结果总结如下： 采用Kaplan-Meier法估计的2年无进展生存率为80%(95% CI，73%~87%)； 采用Kaplan-Meier法估计的2年总体生存率为91%(95% CI，86%-96%)； 63%的患者实现McyR(95% CI，56%-71%；治疗期中位数为22个月)； 采用Kaplan-Meier法估计，获得McyR且疗效持续18个月的患者占93%(95% CI，88%-98%)。 Sprycel新近获准的说明书中有一个新的建议初始剂量。目前在对Gleevec等其他疗法耐药或不能耐受的加速期、髓细胞急变期和淋巴系细胞急变期CML患者，或者在已显示对其他疗法耐药或不耐受的Ph+ ALL患者，建议初始剂量为140 mg，1日1次。 Sprycel说明书中的安全性资料来自7项临床试验、逾2,100例CML或Ph+ ALL患者的研究结果。Sprycel报告最多的严重不良反应为胸腔积液(11%)、胃肠道出血(4%)、发热性中性白细胞减少(4%)、呼吸困难(3%)、肺炎(3%)、发热(3%)、腹泻(3%)、感染(2%)、充血性心力衰竭/心功能不全(2%)、心包积液(1%)，以及中枢神经系统出血(1%)。报告最多的不良反应(在患者中占至少20%)为骨髓抑制、液体潴留事件、腹泻、头痛、呼吸困难、皮疹、乏力、恶心以及出血。 --------------------------------------------------------------- 注：以下产品不同规格和不同价格，购买时请以电话咨询为准！ --------------------------------------------------------------- 原产地英文商品名: SPRYCEL 100mg/Tablet 30Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛 100毫克/片 30片/瓶 中文参考药品译名: 达沙替尼 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: Bristol Myers Squibb --------------------------------------------------------------- 原产地英文商品名: SPRYCEL 140mg/Tablet 30Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛 140毫克/片 30片/瓶 中文参考药品译名: 达沙替尼 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: Bristol Myers Squibb --------------------------------------------------------------- 原产地英文商品名: SPRYCEL 20mg/Tablet 60Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛 20毫克/片 60片/瓶 中文参考药品译名: 达沙替尼 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: Bristol Myers Squibb   --------------------------------------------------------------- 原产地英文商品名: SPRYCEL 50mg/Tablet 60Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛 50毫克/片 60片/瓶 中文参考药品译名: 达沙替尼 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: Bristol Myers Squibb --------------------------------------------------------------- 原产地英文商品名: SPRYCEL 80mg/Tablet 30Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛 80毫克/片 30片/瓶 中文参考药品译名: 达沙替尼 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: Bristol Myers Squibb --------------------------------------------------------------- 原产地英文商品名: SPRYCEL 80mg/Tablet 30Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛 80毫克/片 30片/瓶 中文参考药品译名: 达沙替尼 生产厂家中文参考译名: 百时美施贵宝 生产厂家英文名: Bristol Myers Squibb --------------------------------------------------------------- 原产地英文商品名: DASATINIB(Sprycel Equivalent)70mg/Tablet 60Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 达沙替尼(扑瑞赛仿制药) 70毫克/片 60片/瓶 中文参考药品译名: 达沙替尼 --------------------------------------------------------------- 原产地英文商品名: DASATINIB(Sprycel Equivalent)50mg/Tablet 60Tablets/bottle 原产地英文药品名: DASATINIB 中文参考商品译名: 达沙替尼(扑瑞赛仿制药) 50毫克/片 60片/瓶 中文参考药品译名: 达沙替尼