近日，美国食品和药物管理局（FDA）已批准表观遗传学药物Tazverik（tazemetostat）上市，用于以下2种不同的滤泡性淋巴瘤（FL）适应症：（1）其肿瘤经FDA批准的检测方法证实为EZH2突变阳性、先前接受过至少2种系统疗法的复发或难治性（R/R）FL成人患者；（2）没有令人满意的替代治疗选择的R/R FL成人患者。上述适应症通过加速审批程序和优先审查程序获得批准。
Tazverik（tazemetostat）是获美国FDA批准的第一个也是唯一一个EZH2抑制剂，也是该机构批准专门针对ES患者的第一个也是唯一一个疗法。 
批准日期：2020年01月24日 公司：Epizyme, Inc
TAZVERIK（tazemetostat）片剂，口服
美国初次批准：2020年
作用机理
Tazemetostat是甲基转移酶EZH2和一些EZH2功能获得性突变的抑制剂，包括Y646X和A687V。Tazemetostat还以392nM的一半最大抑制浓度（IC50）抑制EZH1，约为抑制EZH2的IC50的36倍。
EZH2最有特色的功能是作为多梳阻遏复合物2（PRC2）的催化亚基，催化组蛋白H3的赖氨酸27的单，二和三甲基化。组蛋白H3的三甲基化导致转录抑制。SWItch/蔗糖不可发酵（SWI/ SNF）复合物可以拮抗PRC2在调节某些基因表达中的功能。具有某些SWI/SNF复杂成员（例如整合酶相互作用子1[INI1/SNF5/SMARCB1/BAF47]，SMARCA4和SMARCA2）缺失或功能障碍的临床前体外和体内模型可导致异常的EZH2活性或表达，从而导致异常 对EZH2的致癌依赖性。
适应症和用途
TAZVERIK是一种甲基转移酶抑制剂，适用于治疗16岁及以上患有转移性或局部晚期上皮样肉瘤的成人和儿童患者，不适合完全切除。该指示根据总体响应率和响应时间在加速批准下获得批准。继续批准该适应症可能要取决于验证试验中对临床益处的验证和描述。
剂量和给药
推荐剂量：800mg每天口服两次，含或不含食物。
剂量形式和强度
片：200毫克
禁忌症
没有。
警告和注意事项
继发性恶性肿瘤：TAZVERIK增加了发生继发性恶性肿瘤的风险，包括T细胞淋巴母细胞淋巴瘤，骨髓增生异常综合症和急性髓细胞性白血病。
胚胎-胎儿毒性：可引起胎儿伤害。建议可能对胎儿有潜在危险的患者，并使用有效的非激素避孕方法。
不良反应
最常见的不良反应（≥20％）为疼痛，疲劳，恶心，食欲下降，呕吐和便秘。
要报告可疑的不良反应，请致电1-866-4EPZMED联系Epizyme或致电1-800-FDA-1088或访问www.fda.gov/medwatch与FDA联系。
药物相互作用
强和中度细胞色素P450（CYP）3A抑制剂：避免将强和中度CYP3A抑制剂与TAZVERIK并用。如果无法避免中度CYP3A抑制剂的共同给药，减低TAZVERIK的剂量。
强和中度CYP3A诱导剂：避免与TAZVERIK共同给药。
在特定人群中的使用
哺乳期：建议不要母乳喂养。
包装供应/存储和处理方式
TAZVERIK 200mg薄膜衣片为红色，圆形，双凸形状，在一侧凹陷有“ EZM 200”，在另一侧凹陷。 TAZVERIK可用于：
装有干燥剂的240片瓶； NDC 72607-100-00
请勿在30°C（86°F）以上的温度下存放。
完整说明资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7db07b5f-4e22-467c-9c0a-f830b08dbb1d
TAZVERIK (tazemetostat) tablets, for oral use
Initial U.S. Approval: 2020
TAZVERIK™ (tazemetostat) is indicated for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Important Safety Information
Warnings and Precautions
Secondary Malignancies
The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 668 adults who received TAZVERIK 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 0.6% of patients. One pediatric patient developed T‑cell lymphoblastic lymphoma (T‑LBL).
Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug‑associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose‑dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC0‑45h]) at the 800 mg twice daily dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose. Because of the potential risk for serious adverse reactions from TAZVERIK in the breastfed child, advise women not to breastfeed during treatment with TAZVERIK and for one week after the final dose.
Adverse Reactions
In 62 clinical study patients with epithelioid sarcoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurring in ≥3% were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress. The most common (≥20%) adverse reactions were pain (52%), fatigue (47%), nausea (36%), decreased appetite (26%), vomiting (24%) and constipation (21%).
Drug Interactions
Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. If coadministration of moderate CYP3A inhibitors cannot be avoided, reduce TAZVERIK dose.
Avoid coadministration of moderate and strong CYP3A inducers with TAZVERIK, which may decrease the efficacy of TAZVERIK.
Coadministration of TAZVERIK with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates.