部份中文达沙替尼处方资料（仅供参考） 中文名：达沙替尼片 商品名：Sprycel(Dasatinib Tablets) 通用名：Dasatinib 生产厂家：百时美施贵宝 藥理類別 L01XE06 dasatinib 用藥分級:D級： 在對照的人體研究試驗中顯示該藥物對胚胎有不良影響，若此藥能帶來之效益遠超過其它藥物的使用，因此即使在其危險性的存在下，仍可接受此藥物用於懷孕婦女上。 藥理類別:抗癌藥物 結構式 N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide monohydrate UpToDate UpToDate 連結  藥理作用  Dasatinib 是多種 tyrosine kinases 的抑制劑，包括BCR-ABL (Breakpoint Cluster Region-Abelson)，可抑制白血病細胞過度表現的生長與繁殖，同時也抑制 SRC kinases相關的其它訊號路徑，因此可使白血球的數量穩定或降低。  適應症  治療患有慢性、加速或急性期慢性骨髓性白血病，對先前含imatinib的治療有抗藥性或無耐受性的成人。亦適用於患有費城染色體陽性急性淋巴性白血病，且對先前含 imatinib的治療有抗藥性或無耐受性的成人。  用法用量  Sprycel(dasatinib)的建議劑量為一天140mg，分早晚兩次服用口服(一次70mg每日二次[BID])，隨餐或空腹服用不拘。  藥動力學  Absorption T max is between 0.5 and 6 h. Distribution Vd is 2,505 L, suggesting extensive distribution in extravascular space. Protein binding 96%; active metabolite 93%. Metabolism Extensively metabolized by CYP3A4 to an active metabolite, which is equipotent to dasatinib. Also metabolized by flavin-containing monooxygenase-3 and uridine diphosphate-glucuronosyltransferase enzymes. Elimination Terminal half-life is 3 to 5 h. Excretion is primarily fecal (85%) and 4% in urine. Special Populations Renal Function Impairment There are no studies in patients with impaired renal function; however, only 4% of the drug and its metabolites are excreted by the kidney. 副作用  最常見的不良事件包括體液滯留事件如肋膜積水，胃腸道事件包括腹瀉、噁心、腹痛及嘔吐，以及出血事件。  交互作用  Antacids Based on nonclinical data, if antacid therapy cannot be avoided, administer the antacid at least 2 h before or after dasatinib. CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort) May reduce dasatinib plasma levels, decreasing the therapeutic effect. When possible, use alternative therapy. CYP3A4 inhibitors (eg, atazanavir, clarithromycin, erythromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) May elevate dasatinib plasma concentrations, increasing the risk of adverse reactions. CYP3A4 substrates (eg, alfentanil, astemizole, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, quinidine, simvastatin, sirolimus, tacrolimus, terfenadine) Plasma levels may be altered by dasatinib; therefore, use with caution. H2 antagonists (eg, famotidine), proton pump inhibitors (eg, omeprazole) May reduce dasatinib plasma levels, decreasing the therapeutic effect. Concommitant use is not recommended. 禁忌  目前未知。  給付規定  Dasatinib (如Sprycel)：(98/1/1、102/4/1、104/12/1) 限用於 1.第一線使用(102/4/1、104/12/1)： 治療新診斷的費城染色體陽性之慢性期慢性骨髓性白血病的成人。 2.第二線使用(104/12/1)： (1)治療患有慢性、加速或急性期慢性骨髓性白血病，對先前經imatinib 400mg(含)以上治療後有抗藥性或無耐受性的成人。 (2)治療患有費城染色體陽性急性淋巴性白血病，且對先前經imatinib 400mg(含)以上治療後有抗藥性或無耐受性的成人。 (3)需檢送病歷及對imatinib耐受性不良或無效的證明(104/12/1)。 注意事項  1.未知SPRYCEL是否會分泌到人類乳汁。服用SPRYCEL的婦女不應授乳。 2.SPRYCEL用於18歲以下患者的安全性與療效尚未確立。 3.須整粒吞服，不可切割及磨粉。  保存方式  藥品應置於攝氏 15 ~ 25 度乾燥處所；如發生變質或過期，不可再食用。 国内外上市情况 2006年6月，达沙替尼被FDA加速批准用于治疗抵抗或不能耐受的CP-CML。经过对一系列早期临床研究的24个月随访，达沙替尼的安全性和疗效得到证实，2009年5月它被正式批准。美国FDA于2011年批准达沙替尼 dasatinib（商品名Sprycel）用于费城染色体阳性慢性期慢性粒细胞白血病（PH+ CP-CML）一线治疗，这是达沙替尼的新适应症，此前它的获准适应症为：对先前治疗（包括伊马替尼，imatinib）抵抗或不能耐受的成人的慢性加速期，粒细胞或淋巴急变期慢性粒细胞白血病；对先前治疗抵抗或不能耐受的成人费城染色体阳性急性淋巴细胞白血病。6月29日，FDA批准了百时美施贵宝的Sprycel(dasatinib)用于成年患者，治疗两种新的适应症：对伊马替尼等一线药物化疗不敏感的各期慢性粒细胞白血病(CML)，以及对其他疗法无效或不能耐受的Ph染色体阳性的急性淋巴细胞白血病(ALL)。 SPRYCEL(Dasatinib) IMPORTANT SAFETY INFORMATION FOR SPRYCEL® (DASATINIB) Myelosuppression: Treatment with SPRYCEL is associated with severe (NCI CTCAE Grade 3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier and more frequently in patients with advanced phase CML or Ph+ ALL than in patients with chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities. •In patients with chronic phase CML, perform complete blood counts (CBCs) every 2 weeks for 12 weeks, then every 3 months thereafter, or as clinically indicated •In patients with advanced phase CML or Ph+ ALL, perform CBCs weekly for the first 2 months and then monthly thereafter, or as clinically indicated •Myelosuppression is generally reversible and usually managed by withholding SPRYCEL temporarily and/or dose reduction -In clinical studies, myelosuppression may have also been managed by discontinuation of study therapy -Hematopoietic growth factor has been used in patients with resistant myelosuppression Bleeding-Related Events: SPRYCEL can cause serious and fatal bleeding. In all CML or Ph+ ALL clinical studies, Grade ≥3 central nervous system (CNS) hemorrhages, including fatalities, occurred in <1% of patients receiving SPRYCEL. The incidence of Grade 3/4 hemorrhage, occurred in 5.8% of adult patients and generally required treatment interruptions and transfusions. The incidence of Grade 5 hemorrhage occurred in 0.4% of adult patients. The most frequent site of hemorrhage was gastrointestinal. •Most bleeding events in clinical studies were associated with severe thrombocytopenia •In addition to causing thrombocytopenia in human subjects, dasatinib caused platelet dysfunction in vitro •Concomitant medications that inhibit platelet function or anticoagulants may increase the risk of hemorrhage Fluid Retention: SPRYCEL may cause fluid retention. After 5 years of follow-up in the adult randomized newly diagnosed chronic phase CML study (n=258), Grade 3/4 fluid retention was reported in 5% of patients, including 3% of patients with Grade 3/4 pleural effusion. In adult patients with newly diagnosed or imatinib resistant or intolerant chronic phase CML, grade 3/4 fluid retention occurred in 6% of patients treated with SPRYCEL at the recommended dose (n=548). In adult patients with advanced phase CML or Ph+ ALL treated with SPRYCEL at the recommended dose (n=304), grade 3/4 fluid retention was reported in 8% of patients, including grade 3/4 pleural effusion reported in 7% of patients. In pediatric patients with chronic phase CML cases of Grade 1 or 2 fluid retention were reported in 10.3% of patients. •Patients who develop symptoms of pleural effusion or other fluid retention, such as new or worsened dyspnea on exertion or at rest, pleuritic chest pain, or dry cough should be evaluated promptly with a chest x-ray or additional diagnostic imaging as appropriate •Fluid retention events were typically managed by supportive care measures that may include diuretics or short courses of steroids •Severe pleural effusion may require thoracentesis and oxygen therapy •Consider dose reduction or treatment interruption Cardiovascular Events: SPRYCEL can cause cardiac dysfunction. After 5 years of follow-up in the randomized newly diagnosed chronic phase CML trial in adults (n=258), the following cardiac adverse reactions occurred: •Cardiac ischemic events (3.9% dasatinib vs 1.6% imatinib), cardiac related fluid retention (8.5% dasatinib vs 3.9% imatinib), and conduction system abnormalities, most commonly arrhythmia and palpitations (7.0% dasatinib vs 5.0% imatinib). Two cases (0.8%) of peripheral arterial occlusive disease occurred with imatinib and 2 (0.8%) transient ischemic attacks occurred with dasatinib Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately. Pulmonary Arterial Hypertension (PAH): SPRYCEL may increase the risk of developing PAH in adult and pediatric patients, which may occur any time after initiation, including after more than 1 year of treatment. Manifestations include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible on discontinuation of SPRYCEL. •Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should be permanently discontinued QT Prolongation: SPRYCEL may increase the risk of prolongation of QTc in patients including those with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking antiarrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy •Correct hypokalemia or hypomagnesemia prior to and during SPRYCEL administration Severe Dermatologic Reactions: Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported in patients treated with SPRYCEL. •Discontinue permanently in patients who experience a severe mucocutaneous reaction during treatment if no other etiology can be identified Tumor Lysis Syndrome (TLS): TLS has been reported in patients with resistance to prior imatinib therapy, primarily in advanced phase disease. •Due to potential for TLS, maintain adequate hydration, correct uric acid levels prior to initiating therapy with SPRYCEL, and monitor electrolyte levels •Patients with advanced stage disease and/or high tumor burden may be at increased risk and should be monitored more frequently Embryo-Fetal Toxicity: Based on limited human data, SPRYCEL can cause fetal harm when administered to a pregnant woman. Hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to SPRYCEL. Transplacental transfer of dasatinib has been measured in fetal plasma and amniotic fluid at concentrations comparable to those in maternal plasma. •Advise females of reproductive potential to avoid pregnancy, which may include the use of effective contraception, during treatment with SPRYCEL and for 30 days after the final dose Effects on Growth and Development in Pediatric Patients: In pediatric trials of SPRYCEL in chronic phase CML after at least 2 years of treatment, adverse reactions associated with bone growth and development were reported in 5 (5.2%) patients, one of which was severe in intensity (Growth Retardation Grade 3). These 5 cases included cases of epiphyses delayed fusion, osteopenia, growth retardation, and gynecomastia. Of these 5 cases, 1 case of osteopenia and 1 case of gynecomastia resolved during treatment. Lactation: No data are available regarding the presence of dasatinib in human milk, the effects of the drug on the breastfed child or the effects of the drug on milk production. However, dasatinib is present in the milk of lactating rats. •Because of the potential for serious adverse reactions in nursing children from SPRYCEL, breastfeeding is not recommended during treatment with SPRYCEL and for 2 weeks after the final dose Drug Interactions: Effect of Other Drugs on Dasatinib •Strong CYP3A4 inhibitors: The coadministration with strong CYP3A inhibitors may increase dasatinib concentrations. Increased dasatinib concentrations may increase the risk of toxicity. Avoid concomitant use of strong CYP3A4 inhibitors. If concomitant administration of a strong CYP3A4 inhibitor cannot be avoided, consider a SPRYCEL dose reduction -Grapefruit juice may increase plasma concentrations of SPRYCEL and should be avoided •Strong CYP3A4 inducers: The coadministration of SPRYCEL with strong CYP3A inducers may decrease dasatinib concentrations. Decreased dasatinib concentrations may reduce efficacy. Consider alternative drugs with less enzyme induction potential. If concomitant administration of a strong CYP3A4 inducer cannot be avoided, consider a SPRYCEL dose increase -St. John’s wort may decrease plasma concentrations of SPRYCEL and should be avoided •Gastric Acid Reducing Agents: The coadministration of SPRYCEL with a gastric acid reducing agent may decrease the concentrations of dasatinib. Decreased dasatinib concentrations may reduce efficacy. Do not administer H2 antagonists or proton pump inhibitors with SPRYCEL. Consider the use of antacids in place of H2 antagonists or proton pump inhibitors. Administer the antacid at least 2 hours prior to or 2 hours after the dose of SPRYCEL. Avoid simultaneous administration of SPRYCEL with antacids. Adverse Reactions: The safety data reflects exposure to SPRYCEL at all doses tested in clinical studies (n=2809) including 324 adult patients with newly diagnosed chronic phase CML, 2388 adult patients with imatinib resistant or intolerant chronic or advanced phase CML or Ph+ ALL, and 97 pediatric patients with chronic phase CML. The median duration of therapy in a total of 2712 SPRYCEL-treated adult patients was 19.2  months (range 0–93.2 months). Median duration of therapy in: •1618 adult patients with chronic phase CML was 29 months (range 0–92.9 months) -Median duration for 324 adult patients in the newly diagnosed chronic phase CML trial was approximately 60 months •1094 adult patients with advanced phase CML or Ph+ ALL was 6.2 months (range 0–93.2 months) In two non-randomized trials in 97 pediatric patients with chronic phase CML (51 patients newly diagnosed and 46 patients resistant or intolerant to previous treatment with imatinib), the median duration of therapy was 51.1 months (range 1.9 to 99.6 months). In the newly diagnosed adult chronic phase CML trial, after a minimum of 60 months of follow-up, the cumulative discontinuation rate for 258 patients was 39%. In the overall population of 2712 adult SPRYCEL-treated patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation. Among the 1618 adult SPRYCEL-treated patients with chronic phase CML, drug-related adverse reactions leading to discontinuation were reported in 329 (20.3%) patients. •In the adult newly diagnosed chronic phase CML trial, drug was discontinued for adverse reactions in 16% of SPRYCEL-treated patients with a minimum of 60 months of follow-up Among the 1094 SPRYCEL-treated patients with advanced phase CML or Ph+ ALL, drug-related adverse reactions leading to discontinuation were reported in 191 (17.5%) patients. Among the 97 pediatric subjects, drug-related adverse reactions leading to discontinuation were reported in 1 patient (1%). Patients ≥65 years are more likely to experience the commonly reported adverse reactions of fatigue, pleural effusion, diarrhea, dyspnea, cough, lower gastrointestinal hemorrhage, and appetite disturbance, and more likely to experience the less frequently reported adverse reactions of abdominal distention, dizziness, pericardial effusion, congestive heart failure, hypertension, pulmonary edema and weight decrease, and should be monitored closely. •In adult newly diagnosed chronic phase CML patients: -Drug-related serious adverse reactions (SARs) were reported for 16.7% of patients. Serious adverse reactions reported in ≥5% of patients included pleural effusion (5%) -Grade 3/4 laboratory abnormalities included neutropenia (29%), thrombocytopenia (22%), anemia (13%), hypophosphatemia (7%), hypocalcemia (4%), elevated bilirubin (1%), and elevated creatinine (1%) •In adult patients resistant or intolerant to prior imatinib therapy: -Drug-related SARs were reported for 26.1% of SPRYCEL-treated patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥5% of patients included pleural effusion (10%) -Grade 3/4 hematologic laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily with a minimum follow up of 60 months included neutropenia (36%), thrombocytopenia (24%), and anemia (13%). Other grade 3/4 laboratory abnormalities included: hypophosphatemia (10%), and hypokalemia (2%) -Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative grade 3/4 cytopenias were similar at 2 and 5 years including: neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia (13% vs 13%) •Grade 3/4 elevations of transaminases or bilirubin and Grade 3/4 hypocalcemia, hypokalemia, and hypophosphatemia were reported in patients with all phases of CML -Elevations in transaminases or bilirubin were usually managed with dose reduction or interruption -Patients developing Grade 3/4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation •In pediatric subjects with Ph+ CML in chronic phase -Drug-related SARs were reported for 14.4% of pediatric patients -In the pediatric studies, the rates of laboratory abnormalities were consistent with the known profile for laboratory parameters in adults Most common adverse reactions (≥15%) in patients included myelosuppression, fluid retention events, diarrhea, headache, skin rash, hemorrhage, dyspnea, fatigue, nausea, and musculoskeletal pain. ------------------------------------------------------- 注：以下产品不同规格和不同价格，采购者以咨询为准 ------------------------------------------------------- 产地国家: 美国 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 ------------------------------------------------------ 产地国家: 美国 原产地英文商品名: SPRYCEL-70mg/Tablet,60Tablets 原产地英文药品名: DASATINIB 中文参考商品译名: 扑瑞赛-70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 -------------------------------------------------------- 产地国家: 美国 原产地英文商品名: SPRYCEL-20mg/Tablet,60Tablets 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 -------------------------------------------------------- 产地国家: 美国 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 -------------------------------------------------------- 产地国家: 美国 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 -------------------------------------------------------- 产地国家: 美国 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