2014年7月23日，美国食品药品管理局（FDA）批准口服激酶抑制剂idelalisib用于治疗复发性慢性淋巴细胞白血病、滤泡性淋巴瘤和小淋巴细胞性淋巴瘤，但同时有治疗相关性致死性严重毒性的加框警告。 批准日期: 7月23, 2014；公司: Gilead Sciences,公司 ZYDELIG® (idelalisib) 片为不同类型血癌的患者口服使用 美国初次批准：2014 商品名称：Zydelig 通用名称：idelalisib 审批分类：突破性药物+加速批准+孤儿药 作用机制 Idelalisib是一种在正常和恶性B-细胞内表达的PI3Kδ激酶的抑制剂。Idelalisib诱导凋亡和抑制来自恶性B-细胞细胞株和原代肿瘤细胞增殖。Idelalisib抑制几条细胞信号通路，包括B-细胞受体(BCR)信号和CXCR4和CXCR5信号，这参与B-细胞交易和归巢[trafficking和homing]至淋巴结和骨髓。淋巴瘤细胞用idelalisib治疗导致趋化和黏附的抑制，和减低细胞活力。 适应证和用途 Zydelig是一种激酶抑制剂适用为以下患者的治疗： ⑴复发慢性淋巴细胞性白血病(CLL)，与利妥昔单抗联用，在由于其他共患病将考虑对单独利妥昔单抗 适当治疗患者。 ⑵复发滤泡B-细胞非霍奇金淋巴瘤(FL)接受至少2次既往全身治疗患者。 ⑶复发性小淋巴细胞淋巴瘤(SLL)曾至少接受2次既往全身治疗患者。 被授权加速批准对FL和SLL根据总体反应率。未确定改善患者生存或疾病相关症状。继续批准这些适应证，取决于在验证试验中证实临床获益。 剂量和给药方法 推荐起始剂量：150mg口服，每天2次。 剂型和规格 片：150mg，100mg。 禁忌证 严重过敏性反应包括过敏反应和毒性表皮细胞坏死病史。 警告和注意事项 ⑴严重皮肤反应：对患者严重皮肤反应的发展监视和终止Zydelig。 ⑵过敏反应：患者对过敏反应监视和终止Zydelig。 ⑶中性粒细胞减少：监视血细胞计数。 ⑷胚胎-胎儿毒性：可能致胎儿危害。忠告妇女对胎儿潜在风险和服用Zydelig时避免妊娠。 不良反应 最常见不良反应(发生率≥20%)是腹泻，发热，疲劳，恶心，咳嗽，肺炎，腹痛，畏寒，和皮疹。 最常见实验室异常(发生率≥30%)是中性粒细胞减少，高三酸甘油血症，高血糖，ALT升高，和AST升高。 报告怀疑不良反应，联系Gilead Sciences公司电话1-800-GILEAD-5或FDA电话1-800-FDA-1088或www.fda.gov/medwatch 药物相互作用 CYP3A诱导剂：避免强CYP3A诱导剂与Zydelig共同给药。 CYP3A底物：避免CYP3A底物与Zydelig共同给药。 特殊人群中使用 哺乳母亲：终止药物或哺乳。 ZYDELIG 100MG TAB 60/EA    IDELALISIB     61958-1701-01            ZYDELIG 150MG TAB 60/EA    IDELALISIB     61958-1702-01   Important Safety Information WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, AND INTESTINAL PERFORATION Fatal and/or serious hepatotoxicity occurred in 14% of ZYDELIG-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue ZYDELIG as recommended Fatal and/or serious and severe diarrhea or colitis occurred in 14% of ZYDELIG-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue ZYDELIG as recommended Fatal and serious pneumonitis can occur. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue ZYDELIG as recommended Fatal and serious intestinal perforation can occur in ZYDELIG-treated patients. Discontinue ZYDELIG for intestinal perforation Contraindications History of serious allergic reactions, including anaphylaxis and toxic epidermal necrolysis (TEN) Warnings and Precautions Hepatotoxicity: Findings were generally observed within the first 12 weeks of treatment and reversed with dose interruption. Upon rechallenge at a lower dose, ALT/AST elevations recurred in 26% of patients. In all patients, monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, and every 1 to 3 months thereafter. If ALT/AST is >3x upper limit of normal (ULN), monitor for liver toxicity weekly. If ALT/AST is >5x ULN, withhold ZYDELIG and monitor ALT/AST and total bilirubin weekly until resolved. Discontinue ZYDELIG for recurrent hepatotoxicity. Avoid concurrent use with other hepatotoxic drugs Severe diarrhea or colitis: Grade 3+ diarrhea can occur at any time and responds poorly to antimotility agents. Avoid concurrent use with other drugs that cause diarrhea Pneumonitis: Evaluate for pneumonitis in patients presenting with pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on radiologic exam, or oxygen saturation decline by ≥5% Intestinal perforation: Advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting Severe cutaneous reactions: One case of TEN occurred in a study of ZYDELIG in combination with rituximab and bendamustine. Other severe or life-threatening (grade ≥3) cutaneous reactions have been reported. Monitor patients for the development of severe cutaneous reactions and discontinue ZYDELIG if a reaction occurs Anaphylaxis: Serious allergic reactions including anaphylaxis have been reported. Discontinue ZYDELIG permanently and institute appropriate supportive measures if a reaction occurs Neutropenia: Treatment-emergent grade 3-4 neutropenia occurred in 31% of ZYDELIG-treated patients in clinical trials. In all patients, monitor blood counts ≥every 2 weeks for the first 3 months. In patients with neutrophil counts <1.0 Gi/L, monitor weekly. Embryo-fetal toxicity: ZYDELIG may cause fetal harm. Women who are or become pregnant while taking ZYDELIG should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking ZYDELIG and to use effective contraception during and at least 1 month after treatment with ZYDELIG Adverse Reactions Most common adverse reactions (incidence ≥20%; all grades) in clinical studies, when used alone or in combination with rituximab, were diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash Most frequent serious adverse reactions (SAR) in clinical studies in combination with rituximab were pneumonia (17%), pyrexia (9%), sepsis (8%), febrile neutropenia (5%), and diarrhea (5%); SAR were reported in 49% of patients and 10% of patients discontinued due to adverse reactions. Most frequent SAR in clinical studies when used alone were pneumonia (15%), diarrhea (11%), and pyrexia (9%); SAR were reported in 50% of patients and 53% of patients discontinued or interrupted therapy due to adverse reactions Most common lab abnormalities (incidence ≥30%; all grades) in clinical studies were neutropenia, hypertriglyceridemia, hyperglycemia, and ALT/AST elevations Drug Interactions CYP3A inducers: Avoid coadministration with strong CYP3A inducers CYP3A inhibitors: When coadministered with strong CYP3A inhibitors, monitor closely for ZYDELIG toxicity CYP3A substrates: Avoid coadministration with CYP3A substrates Dosage and Administration Adult starting dose: One 150 mg tablet twice daily, swallowed whole with or without food. Continue treatment until disease progression or unacceptable toxicity. The safe dosing regimen for patients who require treatment longer than several months is unknown Dose modification: Consult the ZYDELIG full Prescribing Information for dose modification and monitoring recommendations for the following specific toxicities: pneumonitis, ALT/AST elevations, bilirubin elevations, diarrhea, neutropenia, and thrombocytopenia. For other severe or life-threatening toxicities, withhold ZYDELIG until toxicity is resolved and reduce the dose to 100 mg, twice daily, upon resuming treatment. If severe or life-threatening toxicities recur upon rechallenge, ZYDELIG should be permanently discontinued INDICATIONS Zydelig is indicated for the treatment of Relapsed chronic lymphocytic leukemia (CLL) in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies The FL and SLL indications were granted accelerated approval based on overall response rate; improvement in patient survival or disease related symptoms has not been established You are encouraged to report negative side effects of Zydelig to Gilead at 1-800-445-3235 and/or the FDA at www.fda.gov/medwatch or call 1-800-FDA-1088. FDA批准吉利德重磅药物Zydelig用于3种血癌 2014年7月24日,吉利德（Gilead）抗癌药Zydelig（idelalisib）获FDA批准，用于3种B细胞血癌的治疗，分别为：（1）批准Zydelig联合罗氏（Roche）抗癌药美罗华（Rituxan，通用名：rituximab，利妥昔单抗），用于适合Rituxan单药疗法的复发性慢性淋巴细胞白血病（CLL）患者的治疗；（2）批准Zydelig作为单药疗法，用于既往接受过至少2种系统治疗方案的复发性滤泡B细胞非霍奇金淋巴瘤（FL）患者和小细胞淋巴瘤（SLL）患者的治疗。FDA加速批准Zydelig用于FL和SLL适应症，是基于总缓解率（ORR）数据。 EvaluatePharma分析师预计，到2020年，Zydelig的年销售额将突破12亿美元。而Bernstein分析师Geoff Porges则预计，到2017年，Zydelig的年销售额将突破15亿美元，使其当之无愧的成为吉利德后期管线中的一枚重磅明星药物。 Zydelig获批用于CLL，主要是基于一项关键III期研究（Study 116）的数据，该项研究在既往已接受治疗但对标准化疗不耐受的慢性淋巴细胞白血病（CLL）患者中开展。一项既定中期分析数据表明，与安慰剂+美罗华（Rituxan）治疗组相比，Zydelig+Rituxan治疗组在研究的主要终点—疾病无进展生存期（PFS）具有统计学意义的显著改善（PFS：10.7个月 vs 5.5个月，p＜0.0001）。 此前，FDA已授予Zydelig治疗复发性CLL的突破性疗法认定。 Zydelig加速批准用于FL和SLL，基于一项关键II期研究（Study 101-09）的数据，该项研究在既往经美罗华（Rituxan）和含烷化剂化疗方案治疗的难治性惰性非霍奇金淋巴瘤（iNHL，注：FL和SLL是2种类型的iNHL）患者中开展，评价了Zydelig的疗效和安全性。研究结果表明，Zydelig单药疗法取得了57%的总缓解率（ORR），其中，6%的患者实现了完全缓解，50%的患者实现部分缓解，1%的患者取得轻微缓解。研究中，平均缓解持续时间达12.5个月，距离缓解的平均时长为1.9个月，平均无进展生存期为11.0个月，平均总生存期为20.3个月，90%的患者经历了淋巴结的缩小。 Zydelig（idelalisib）是一种首创的高度选择性、口服有效的磷酸肌醇3-激酶delta（PI3K-delta）抑制剂。PI3K-delta信号对于B淋巴细胞的活化、增殖、生存、迁移（trafficking）至关重要，该信号在多种B细胞恶性肿瘤中过度活动。目前，吉利德正开发idelalisib作为单一制剂，以及与一些已获批的疗法和实验性疗法配伍，调查用于不同类型血癌的治疗。 ----------------------------------------------------- 产地国家: 美国 原产地英文商品名: Zydelig TABLET 150mg/tab 60tabs/bottle 原产地英文药品名: idelalisib 中文参考商品译名: Zydelig片 150毫克/片 60片/瓶 中文参考药品译名: idelalisib 生产厂家中文参考译名: 美国吉利德科学 生产厂家英文名: Gilead Sciences ----------------------------------------------------- 产地国家: 美国 原产地英文商品名: Zydelig TABLET 100mg/tab 60tabs/bottle 原产地英文药品名: idelalisib 中文参考商品译名: Zydelig片 100毫克/片 60片/瓶 中文参考药品译名: idelalisib 生产厂家中文参考译名: 美国吉利德科学 生产厂家英文名: Gilead Sciences