英文药名：IMBRUVICA Capsules(Ibrutinib)

中文药名：拉铁尼伯胶囊

生产厂家：杨森制药（日本）公司

イムブルビカカプセル140mg

治疗类别名称
抗肿瘤剂（布鲁顿的酪氨酸激酶抑制剂）
批准上市：2016年5月
商標名
IMBRUVICA Capsules
一般名
イブルチニブ（JAN）、Ibrutinib （JAN）
化学名
1-｛（3R）-3-［4-Amino-3-（4-phenoxyphenyl）-1H-pyrazolo［3,4-d］pyrimidin-1-yl］piperidin-1-yl｝prop-2-en-1-one
分子式
C25H24N6O2
分子量
440.50
化学構造式

性状
白色固体
可溶性
易溶于二甲亚砜，甲醇易微溶，微溶于乙腈，和几乎不溶于水。
熔点
149〜158℃
分配系数
3.97（的Log P，1-辛醇/ pH7的缓冲液）
操作注意事项
放在儿童不能接触的地方。
条件批准
1.建立药品风险管理计划的顶部，要正确实施。
2.由于试验病人在日本是非常有限的，上市后，直至有关一定数量的病例数据集成，通过实现对一切案件的使用，结果调查显示，这使得它能够及早发现这种药物的使用患者的背景资料，数据收集这种药物的安全性和有效性，采取必要的措施，正确使用此药。
药效药理
1. 作用机序
布鲁顿酪氨酸激酶（BTK），B细胞肿瘤，参与细胞增殖等（BCR）的B细胞受体和B细胞迁移的发展，信令涉及粘接等趋化因子受体的下游分子它是。 Iburuchinibu共价结合到在BTK的活性位点的半胱氨酸残基（CYS-481），它抑制BTK的激酶活性。
2. 抗肿瘤效果
在体外研究，Iburuchinibu是抑制慢性淋巴细胞白血病（CLL）的CLL细胞的患者的成长，也能抑制迁移和B细胞的粘附。
在体内试验中，Iburuchinibu是，鼠标CLL衍生TCL1-192细胞在腹腔移植重症联合免疫缺陷小鼠，抑制TCL1-192细胞在外周血的生长。
适应证
复发或难治性慢性淋巴细胞性白血病（包括小淋巴细胞淋巴瘤）
剂量和给药方法
成年人,每天给药一次为420mg口服。此外，根据该状态的患者用药。
包装规格
胶囊为；
140mg：14胶囊（14粒×1）

制造厂商
杨森制药有限公司
完整处方资料附件：http://www.info.pmda.go.jp/go/pack/4291043M1027_1_02/
IMBRUVICA™ (ibrutinib) Capsules
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage – Five percent (5%) of patients with MCL had Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily. The mechanism for the bleeding events is not well understood. Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapies and the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections – Fatal and non-fatal infections have occurred. At least 25% of patients with MCL had infections ≥ Grade 3, according to NCI Common Terminology Criteria for Adverse Events (CTCAE). Monitor patients for fever and infections and evaluate promptly.
Myelosuppression – Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%). Monitor complete blood counts monthly.
Rnal Toxicity – Fatal and serious cases of renal failure have occurred. Treatment-emergent increases in creatinine levels up to 1.5 times the upper limit of normal occurred in 67% of patients and from 1.5 to 3 times the upper limit of normal in 9% of patients. Periodically monitor creatinine levels. Maintain hydration.
Second Primary Malignancies – Other malignancies (5%) have occurred in patients with MCL who have been treated with IMBRUVICA, including skin cancers (4%), and other carcinomas (1%).
Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Adverse Reactions – The most commonly occurring adverse reactions (≥ 20%) in the clinical trial were thrombocytopenia*, diarrhea (51%), neutropenia*, anemia*, fatigue (41%), musculoskeletal pain (37%), peripheral edema (35%), upper respiratory tract infection (34%), nausea (31%), bruising (30%), dyspnea (27%), constipation (25%), rash (25%), abdominal pain (24%), vomiting (23%) and decreased appetite (21%).
* Treatment-emergent decreases (all grades) of platelets (57%), neutrophils (47%) and hemoglobin (41%) were based on laboratory measurements and adverse reactions.
The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were: pneumonia (7%), abdominal pain (5%), atrial fibrillation, diarrhea (5%), fatigue (5%), and skin infections (5%). Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients.  Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111).
The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.
Drug Interactions: CYP3A Inhibitors – Avoid concomitant administration with strong or moderate inhibitors of CYP3A. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.
CYP3A Inducers – Avoid co-administration with strong CYP3A inducers.
Special Populations – Hepatic Impairment – Avoid use in patients with baseline hepatic impairment.
For the full prescribing information, visit http://www.imbruvica.com/downloads/Prescribing_Information.pdf.
About IMBRUVICA
IMBRUVICA is indicated for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.This indication is based on overall response rate (ORR). An improvement in survival or disease-related symptoms has not been established.
IMBRUVICA works by blocking a specific protein called Bruton’s tyrosine kinase (BTK).BTK is a signaling molecule of the B-cell antigen receptor (BCR) pathway, which is emerging as a target in some B-cell malignancies.BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B cell trafficking, chemotaxis and adhesion.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dfd0279-ff17-4ea9-89be-9803c71bab44