慢性髓细胞白血病（细粒）是我国三大白血病之一，约占白血病患者的13%，是造血干细胞的骨髓增殖性疾病，分慢期、加速期、和急性期，急性期直接面临死亡威胁。酪氨酸激酶抑制剂是目前国际权威专家首推的治疗药物、治疗慢性髓细胞白血病患者最有效方案。
椐全球肿瘤权威专家多年临床介绍；慢粒早期症状不典型，病因不明，是一种无法预防，往往在体验或其他疾病检查时发现白细胞数异常增高或脾肿大，进一步检查发现该病。
第一代治疗药物经常出现耐受药和不良反应而不能继续使用。新一代酪氨酸激酶抑制剂（施达赛）“达沙替尼”抑制慢粒致病细胞的能力比传统药物高达325倍，多靶发挥作用，可用于成人费城染色体阳性(ph+)慢性髓细胞白血病的全部过程。研究显著，“达沙替尼”治疗5年的患者总生存率高达78%，服药不受时间和食物限制性，能改善患者的依从性，易于自我管理，对提高慢粒治疗效果至关重要，也是白血病（细粒）疾病克星。
部份SPRYCEL®（达沙替尼片)中文说明介绍
最初美国批准：2006年
最近的重大变化
警告和注意事项，
肺动脉高压
适应症
SPRYCEL是一种激酶抑制剂治疗表明
新诊断的成人费城染色体阳性（Ph +）慢性髓性白血病慢性期（CML）。审判正在进行，将需要进一步的数据，以确定长期的结果。
成人慢性，加速或髓系或淋巴爆炸相的pH值+与之前的治疗包括伊马替尼耐药或不能耐受的慢性粒细胞白血病。
费城染色体阳性急性淋巴细胞白血病，与之前的治疗耐药或不能耐受（的Ph + ALL）的成年人。
剂量和用法
CML慢性期：100毫克，每天一次。
骨髓或淋巴急变期慢性粒细胞白血病加速期CML的Ph + ALL：140毫克每日一次。
口服，带或不带一顿饭。片不应该被压碎或切断。
剂型和优势
片剂：20毫克，50毫克，70毫克，80毫克，100毫克和140毫克。
禁忌
没有。
注意事项：
骨髓抑制：可能会出现严重的血小板减少症，中性粒细胞减少，贫血和需要剂量中断或减少。定期监测全血细胞计数。
出血的相关活动（主要是与严重的血小板减少关联）：中枢神经系统和胃肠道出血，包括死亡，时有发生。严重出血可能需要中断治疗和输血。用在需要的药物，抑制血小板功能或抗凝剂的患者慎用SPRYCEL。
液体潴留：SPRYCEL体液潴留，有时很严重，包括腹水，水肿，胸腔和心包积液。管理与适当的支持治疗措施。
QT间期延长：使用或可能发展的QT间隔的延长患者慎用SPRYCEL。
充血性心力衰竭，左室功能不全和心肌梗死：监测病人的症状和体征，心功能不全一致和适当的治疗。
肺动脉高压（PAH）：SPRYCEL可能会增加可逆的多环芳香烃，这可能是对停产的危险。评估潜在的心肺疾病的症状和体征，前发起Sprycel和治疗期间的患者。
使用在怀孕时可能出现的管理到孕妇胎儿造成伤害。妇女应被告知对胎儿的潜在危险和避免怀孕。
不良反应
最常见的不良反应，在新诊断的慢性期CML患者（≥10％），包括骨髓抑制，液体潴留，腹泻，头痛，肌肉疼痛，皮疹。前伊马替尼治疗耐药或不能耐受的患者最常见的不良反应（≥20％）包括骨髓抑制，液体滞留事件，腹泻，头痛，呼吸困难，皮疹，疲劳，恶心，和出血。
报告疑似不良反应，联系施贵宝公司在1-800-721-5072或FDA在1-800-FDA-1088或www.fda.gov / medwatch
药物相互作用
CYP3A4抑制剂可能增加达沙替尼的药物浓度，并应避免。如果不能避免合用，密切监测，并考虑减少SPRYCEL剂量。
CYP3A4诱导剂：可能会降低达沙替尼的药物浓度。如果合用无法避免，考虑增加SPRYCEL剂量。
抗酸剂：可能会降低达沙替尼的药物浓度。避免同时服用。如果需要，管理SPRYCEL剂量前至少2小时或2小时后的抗酸剂。
H2受体拮抗剂/质子泵抑制剂可能降低达沙替尼的药物浓度。考虑抗酸剂，H2受体拮抗剂或质子泵抑制剂的地方。
在特殊人群中使用
肝功能不全：肝功能不全患者慎用SPRYCEL。
规格：70mg*60片/50MG*60片/25MG/片*60片
更新日期：10/2011
INDICATIONS
 |
Chronic, accelerated, or myeloid or lymphoid blast phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior therapy including imatinib
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy
IMPORTANT SAFETY INFORMATION
Myelosuppression:
Treatment with SPRYCEL® (dasatinib) can cause severe (NCI CTC Grade 3/4) thrombocytopenia, neutropenia, and anemia, occurring more frequently in advanced phase CML or Ph+ ALL than in chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities
Perform complete blood counts (CBCs) weekly for the first 2 months and then monthly thereafter, or as clinically indicated
Myelosuppression was generally reversible and usually managed by dose interruption, dose reduction, or discontinuation
Hematopoietic growth factor has been used in patients with resistant myelosuppression
Bleeding Related Events:
Sprycel caused platelet dysfunction in vitro and thrombocytopenia in humans
In all clinical trials, severe central nervous system (CNS) hemorrhage, including fatalities, occurred in 1% of patients. Severe gastrointestinal (GI) hemorrhage, including fatalities, occurred in 4% of patients receiving SPRYCEL, which generally required treatment interruptions and transfusions. Other cases of severe hemorrhage occurred in 2% of patients
Most bleeding events were associated with severe thrombocytopenia
Exercise caution in patients required to take medications that inhibit platelet function or anticoagulants
Fluid Retention:
Sprycel is associated with fluid retention
In clinical trials, fluid retention was severe in up to 10% of patients. Ascites (<1%), generalized edema (<1%), and severe pulmonary edema (1%) were also reported
Patients who develop symptoms suggestive of pleural effusion such as dyspnea or dry cough should be evaluated by chest X-ray
Severe pleural effusion may require thoracentesis and oxygen therapy
Fluid retention was typically managed by supportive care measures that included diuretics or short courses of steroids
QT Prolongation:
In vitro data suggest that Sprycel has the potential to prolong cardiac ventricular repolarization (QT interval)
In 865 patients with leukemia treated with SPRYCEL in five phase 2 single-arm studies, the maximum mean changes in QTcF (90% upper bound CI) from baseline ranged from 7.0 ms to 13.4 ms
In clinical trials of CML patients treated with SPRYCEL (N=2440), 15 patients (<1%) had QTc prolongation as an adverse reaction. Twenty-two patients (1%) experienced a QTcF >500 ms
Administer Sprycel with caution to patients who have or may develop prolongation of QTc, including patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome and patients taking anti-arrhythmic drugs, other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy
Correct hypokalemia or hypomagnesemia prior to Sprycel administration
Congestive Heart Failure, Left Ventricular Dysfunction, and Myocardial Infarction:
Cardiac adverse reactions were reported in 5.8% of 258 patients taking Sprycel, including 1.6% of patients with cardiomyopathy, heart failure congestive, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction. Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately.
Pregnancy:
Sprycel may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Sprycel in pregnant women. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant when taking Sprycel.
Nursing Mothers:
It is unknown whether Sprycel is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Sprycel.
Drug Interactions:
Sprycel is a CYP3A4 substrate and a weak time-dependent inhibitor of CYP3A4.
Drugs that may increase Sprycel plasma concentrations are:
CYP3A4 inhibitors: Concomitant use of Sprycel and drugs that inhibit CYP3A4 should be avoided. If administration of a potent CYP3A4 inhibitor cannot be avoided, close monitoring for toxicity and a Sprycel dose reduction or temporary discontinuation should be considered
Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). If Sprycel must be administered with a strong CYP3A4 inhibitor, a dose decrease should be considered
Grapefruit juice may also increase plasma concentrations of Sprycel and should be avoided
Drugs that may decrease Sprycel plasma concentrations are:
CYP3A4 inducers: If Sprycel must be administered with a CYP3A4 inducer, a dose increase in Sprycel should be considered.
Strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital), should be avoided. Alternative agents with less enzyme induction potential should be considered. If the dose of Sprycel is increased, the patient should be monitored carefully for toxicity
St John’s Wort may decrease Sprycel plasma concentrations unpredictably and should be avoided
Antacids. Antacids may decrease Sprycel drug levels. Simultaneous administration of SPRYCEL and antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of Sprycel
H2 antagonists/proton pump inhibitors, such as famotidine and omeprazole. Long-term suppression of gastric acid secretion by use of H2 antagonists or proton pump inhibitors is likely to reduce Sprycel exposure. Therefore, concomitant use of H2 antagonists or proton pump inhibitors with Sprycel is not recommended
Drugs that may have their plasma concentration altered by Sprycel are:
CYP3A4 substrates such as simvastatin. CYP3A4 substrates with a narrow therapeutic index should be administered with caution in patients receiving Sprycel
Adverse Reactions:
The safety data reflect exposure to Sprycel in 2182 patients with imatinib resistant or intolerant CML or Ph+ ALL in clinical studies (minimum of 2 years follow-up).
The majority of Sprycel-treated patients experienced adverse reactions at some time. Patients aged 65 years and older are more likely to experience toxicity. In patients resistant or intolerant to prior imatinib therapy, Sprycel was discontinued for adverse reactions in 15% of patients in chronic phase, 16% in accelerated phase, 15% in myeloid blast phase, 8% in lymphoid blast phase CML, and 8% in Ph+ ALL.
In patients resistant or intolerant to prior imatinib therapy:
The most frequently reported serious adverse reactions included pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and CNS hemorrhage (1%)
The most frequently reported adverse reactions (reported in ≥20% of patients) included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage
Grade 3/4 laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily included neutropenia (36%), thrombocytopenia (23%), anemia (13%), hypophosphatemia (10%), and hypokalemia (2%)
Grade 3/4 elevations of transaminase or bilirubin and Grade 3/4 hypocalcemia, hypokalemia and hypophosphatemia were reported in patients with all phases of CML, but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML
Elevations in transaminase 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
製品名 スプリセル®錠20mg スプリセル®錠50mg
一般名 ダサチニブ水和物
規制区分 劇薬 処方せん医薬品注)
(注意―医師等の処方せんにより使用すること)
貯法 室温保存
使用期限 3年
承認番号
スプリセル錠20mg
スプリセル錠50mg
製造販売元 ブリストル・マイヤーズ株式会社
効能・効果 1. 慢性骨髄性白血病
2. 再発又は難治性のフィラデルフィア染色体陽性急性リンパ性白血病
用法・用量
1. 慢性骨髄性白血病
(1)慢性期
通常、成人にはダサチニブとして1日1回100mgを経口投与する。
なお、患者の状態により適宜増減するが、1日1回140mgまで増量できる。
(2)移行期又は急性期
通常、成人にはダサチニブとして1回70mgを1日2回経口投与する。
なお、患者の状態により適宜増減するが、1回90mgを1日2回まで増量できる。
2. 再発又は難治性のフィラデルフィア染色体陽性急性リンパ性白血病
通常、成人にはダサチニブとして1回70mgを1日2回経口投与する。なお、患者の状態により適宜増減するが、1回90mgを1日2回まで増量できる。
日本上市图示
包装
スプリセル錠20mg：30錠（PTP）
スプリセル錠50mg：30錠（PTP）
