近日，美国FDA批准新型抗癌药组合剂量Inqovi（cedazuridine/decitabine[地西他滨和西屈嘧啶]，口服C-DEC，ASTX727），用于治疗骨髓增生异常综合症（MDS）和慢性骨髓单核细胞白血病（CMML）成人患者的治疗。
Inqovi（cedazuridine 100mg/地西他滨 35mg，口服片剂）是由固定剂量的cedazuridine（一种胞苷脱氨酶抑制剂）和地西他滨（一种已获批的抗癌DNA去甲基化剂）组成的一种新的口服组合疗法。其中，cedazuridine组分能够抑制肠道和肝脏中的胞苷脱氨酶，避免降解地西他滨，从而使Inqovi能够实现口服给药地西他滨，达到与地西他滨静脉输注同等的暴露当量。
用药推荐的剂量；Inqovi空腹服用，每日一次、每次一片，连续5天（每个周期的第1-5天），每28天为一个周期。
批准日期：2020年07月08日 公司：Taiho Oncology, Inc.
INQOVI（地西他滨和西屈嘧啶[decitabine and cedazuridine]）片剂，口服
美国初次批准：2020年
作用机理
地西他滨是一种核苷代谢抑制剂，据信在磷酸化并直接掺入DNA和抑制DNA甲基转移酶后发挥其作用，从而引起DNA的甲基化不足以及细胞分化和/或凋亡。地西他滨在体外抑制DNA甲基化，这是
在不会严重抑制DNA合成的浓度下实现的。地西他滨诱导的次甲基化可能会使癌细胞的正常功能恢复，而这些基因对于控制细胞分化和增殖至关重要。在快速分裂的细胞中，地西他滨的细胞毒性也可能
这归因于DNA甲基转移酶和并入地西他滨之间的共价加合物的形成。非增殖细胞对地西他滨相对不敏感。
胞苷脱氨酶（CDA）是一种催化胞苷降解的酶，包括胞苷类似物地西他滨。胃肠道和肝脏中高水平的CDA会降低地西他滨并限制其口服生物利用度。Cedazuridine是CDA抑制剂。西地苏定与地西他滨一起给药会增加地西他滨的全身暴露。
适应症和用途
INQOVI是地西他滨（一种核苷代谢抑制剂）和西地西丁（一种胞苷脱氨酶抑制剂）的组合，适用于治疗患有以下疾病的法裔美英亚型（包括难治性贫血）的成年骨髓增生异常综合症（MDS）患者：伴有成环铁母细胞的难治性贫血，具有过量母细胞的难治性贫血和慢性粒细胞单核细胞白血病（CMML），中级1，中级2和高风险国际预后评分系统组。
剂量和给药
•INQOVI的推荐剂量是在每个28天周期的第1至5天每天口服1片（35毫克地西他滨和100毫克西屈嘧啶）。
•空腹服用INQOVI。
剂量形式和强度
片剂：35mg地西他滨和100mg cezuridine。
禁忌症
没有。
警告和注意事项
•骨髓抑制：可能发生致命和严重的骨髓抑制和感染性并发症。在开始INQOVI之前，每个周期之前，以及如临床指示，监测反应和毒性，获取完整的血细胞计数。延迟下一个周期，并按照建议的相同剂量或减少剂量恢复。
•胚胎-胎儿毒性：可引起胎儿伤害。建议具有潜在胎儿生殖风险的患者，并使用有效的避孕方法。
不良反应
最常见的不良反应（发生率≥20％）是疲劳，便秘，出血，肌痛，粘膜炎，关节痛，恶心，呼吸困难，腹泻，皮疹，头晕，发热性中性粒细胞减少，水肿，头痛，咳嗽，食欲下降，上呼吸道感染，肺炎和转氨酶升高。最常见的3级或4级实验室异常（≥50％）是白细胞减少，血小板计数减少，中性粒细胞计数减少和血红蛋白减少。
要报告可疑的不良反应，请致电1-844-878-2446与TaihoOncology，Inc.或致电1-800-FDA-1088与FDA联系，或访问www.fda.gov/medwatch。
药物相互作用
胞苷脱氨酶代谢的药物：避免与INQOVI并用。
在特定人群中的使用
•哺乳期：建议不要母乳喂养。
•不育：会损害生育能力。
包装供应/存储和处理方式
供应方式
INQOVI片剂为双凸，椭圆形，薄膜包衣，红色，并在一侧凹陷有“ H35”。
片剂包装在水泡中，并按以下方式提供：
•NDC：64842-0727-9；5片装在一张儿童安全纸箱中的一张吸塑卡中，在20°C至25°C（68°F至77°F）的温度下存储和处理; 允许的温度偏移范围是15°C至30°C（59°F至86°F）[请参阅USP控制的室温]。
用原包装分配药物。
INQOVI是一种危险药物。 请遵循适用的特殊处理和处置程序。

完整说明资料附件：
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212576s000lbl.pdf
U.S. Food and Drug Administration (FDA) and Health Canada have approved INQOVI(decitabine and cedazuridine) tablets. The three companies are all part of the Otsuka group of companies.
INQOVI is the first and only orally administered hypomethylating agent for the treatment for adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia(CMML),two blood malignancies.
INDICATIONS
INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes(MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate, intermediate, and high-risk International Prognostic Scoring System groups.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%.
Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.
Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.
Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6months (females) or 3 months (males) after last dose.
ADVERSE REACTIONS
Serious adverse reactions in > 5% of patients included febrile neutropenia(30%), pneumonia (14%), and sepsis(13%).Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure(1%), and one case each of cerebral hemorrhage and sudden death.
The most common adverse reactions(≥20%) were fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities(≥50%)were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased.
USE IN SPECIFIC POPULATIONS
Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for at least 2 weeks after the last dose.
Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance[CLcr]of 30 to 89 mL/min based on Cockcroft-Gault).Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions.INQOVI has not been studied in patients with severe renal impairment(CLcr 15 to 29mL/min)or end-stage renal disease (ESRD: CLcr<15 mL/min).