艾伏尼布

Ivosidenib、Tibsovo

艾伏尼布（Ivosidenib）是全球首个且当今国内独一获批的异柠檬酸脱氢酶1（IDH1）扼制剂，用于调治佩戴IDH1突变的复发性或难治性急性髓系白血病（R/R AML）成东谈主患者。

每年的新发病例中约有6～10%的AML患者佩戴IDH1突变，而当IDH1突变时，就会产生无数的D-2-HG，使得其浓度升高，从而导致细胞增殖、分化相配等惬心。而艾伏尼布的作用机制则是灵验扼制IDH1的活性，从而减少D-2-HG的产生，达到调治白血病的遵循。

01适当症

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:

Newly Diagnosed Acute Myeloid Leukemia (AML)

In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

Relapsed or refractory AML

For the treatment of adult patients with relapsed or refractory AML.

Relapsed or refractory Myelodysplastic Syndromes (MDS)

For the treatment of adult patients with relapsed or refractory myelodysplastic syndromes.

Locally Advanced or Metastatic Cholangiocarcinoma

For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated.

汉文翻译

TIBSOVO是一种异柠檬酸脱氢酶-1（IDH1）扼制剂，适用于易感IDH1突变的患者，通过FDA批准的测试检测到：

新会诊的急性髓细胞白血病（AML）

结合阿扎胞苷或行为单一疗法调治75岁或以上的成年东谈主新会诊的AML，或患有摈斥使用强化同样化疗的团结症的患者。

复发或难治性AML

用于调治复发或难治性AML的成年患者。

复发或难治性骨髓增生相配概述征（MDS）

用于调治复发或难治性骨髓增生相配概述征的成年患者。

局部晚期或飘零性胆管癌

用于调治先前收受过调治的局部晚期或飘零性胆管癌的成年患者。

02用法用量

500 mg orally once daily with or without food until disease progression or unacceptable toxicity. Avoid a high-fat meal.

汉文翻译

500 mg口服，逐日1次，随食或空心服用，直至疾病发挥或出现不行收受的毒性。幸免高脂肪食品。

03畸形东谈主群

Pregnancy: Based on animal embryo-fetal toxicity studies, TIBSOVO may cause fetal harm when administered to a pregnant woman. There are no available data on TIBSOVO use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal embryo-fetal toxicity studies, oral administration of ivosidenib to pregnant rats and rabbits during organogenesis was associated with embryo-fetal mortality and alterations to growth starting at 2 times the steady state clinical exposure based on the AUC at the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus.

Lactation： There are no data on the presence of ivosidenib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for 1 month after the last dose.

Pediatric Use： The safety and effectiveness of TIBSOVO in pediatric patients have not been established.

Geriatric Use： No overall differences in effectiveness or safety were observed between patients who were 65 years and older compared to younger patients.

Hepatic Impairment： No modification of the starting dose is recommended for patients with mild or moderate (Child-Pugh A or B) hepatic impairment. The pharmacokinetics and safety of ivosidenib in patients with severe hepatic impairment (Child-Pugh C) are unknown. For patients with pre-existing severe hepatic impairment, consider the risks and potential benefits before initiating treatment with TIBSOVO.

Renal Impairment： No modification of the starting dose is recommended for patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73m2 , MDRD). The pharmacokinetics and safety of ivosidenib in patients with severe renal impairment (eGFR < 30 mL/min/1.73m 2 , MDRD) or renal impairment requiring dialysis are unknown. For patients with pre-existing severe renal impairment or who are requiring dialysis, consider the risks and potential benefits before initiating treatment with TIBSOVO.

汉文翻译

妊娠：证据动物胚胎-胎儿毒性不息，TIBSOVO给妊妇服用时可能会变成胎儿伤害。没关系于妊妇使用TIBSOVO的可用数据来示知与药物相干的紧要出身颓势和流产风险。在动物胚胎-胎儿毒性不息中，在器官发生流程中向孕珠大鼠和兔子口服艾伏尼布与胚胎-胎儿升天率和助长改变相干，从推选东谈主类剂量下基于AUC的稳态临床清楚的2倍运转。若是在孕珠技术使用这种药物，约略若是患者在服用这种药物时孕珠，讲演知患者对胎儿的潜在风险。

哺乳期：没关系于母乳中是否存在伊沃替尼或其代谢物、对母乳喂养儿童的影响或对产奶量的影响的数据。由于好多药物是从母乳中排出的，而且母乳喂养的儿童可能会出现不良反映，因此淡薄女性在使用TIBSOVO调治技术以及终末一次给药后1个月内不要母乳喂养。

儿童使用：TIBSOVO在儿科患者中的安全性和灵验性尚未详情。

老年使用：与年青患者比拟，65岁及以上患者的灵验性或安全性莫得总体各别。

肝功能不全：关于轻度或中度（Child-Pugh A或B）肝挫伤的患者，不淡薄修改肇始剂量。严重肝功能不全（Child-Pugh C）患者的艾伏尼布药代能源学和安全性尚不明晰。关于先前存在严重肝功能损害的患者，在运转使用TIBSOVO调治之前，请磋议其风险和潜在益处。

肾功能不全：关于轻度或中度肾功能损害（eGFR≥30 mL/min/1.73m2，MDRD）的患者，不淡薄修改肇始剂量。严重肾功能不全（eGFR<30 mL/min/1.73m 2，MDRD）或需要透析的肾功能不全患者的艾伏尼布药代能源学和安全性尚不明晰。关于先前存在严重肾功能不全或需要透析的患者，在运转使用TIBSOVO调治之前，请磋议其风险和潜在益处。

04不良反映

The most common adverse reactions including laboratory abnormalities (≥ 25%) in patients with AML are leukocytes decreased, diarrhea, hemoglobin decreased, platelets decreased, glucose increased, fatigue, alkaline phosphatase increased, edema, potassium decreased, nausea, vomiting, phosphate decreased, decreased appetite, sodium decreased, leukocytosis, magnesium decreased, aspartate aminotransferase increased, arthralgia, dyspnea, uric acid increased, abdominal pain, creatinine increased, mucositis, rash, electrocardiogram QT prolonged, differentiation syndrome, calcium decreased, neutrophils decreased, and myalgia.

The most common adverse reactions including laboratory abnormalities (≥ 25%) in patients with relapsed or refractory MDS are creatinine increased, hemoglobin decrease, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash.

The most common adverse reactions (≥ 15%) in patients with cholangiocarcinoma are fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.

The most common laboratory abnormalities (≥ 10%) in patients with cholangiocarcinoma are hemoglobin decreased, aspartate aminotransferase increased, and bilirubin increased.

汉文翻译

AML患者最常见的不良反映包括推行室相配（≥25%），包括白细胞减少，泻肚，血红卵白减少，血小板减少，血糖增多，疲惫，碱性磷酸酶增多，水肿，钾减少，恶心，吐逆，磷酸盐减少，食欲下落，钠减少，白细胞增多，镁减少，天冬氨酸氨基飘零酶增多，要津痛，呼吸穷苦，尿酸增多，腹痛，肌酐增多，粘膜炎，皮疹，心电图QT延伸，分化概述征，钙减少，中性粒细胞减少，肌痛。

复发或难治性MDS患者最常见的不良反映包括推行室相配（≥25%）是肌酐升高，血红卵白镌汰，要津痛，白卵白镌汰，天冬氨酸转氨酶升高，疲惫，泻肚，咳嗽，钠减少，粘膜炎，食欲下落，肌痛，磷酸盐减少，瘙痒和皮疹。

胆管癌患者最常见的不良反映（≥15%）是疲惫，恶心，腹痛，泻肚，咳嗽，食欲下落，腹水，吐逆，贫血和皮疹。

胆管癌患者最常见的推行室相配（≥10%）是血红卵白镌汰，天冬氨酸转氨酶升高和胆红素升高。

05缜密事项

QTc Interval Prolongation: Monitor electrocardiograms and electrolytes. If QTc interval prolongation occurs, dose reduce or withhold, then resume dose or permanently discontinue TIBSOVO.

Guillain-Barré Syndrome: Monitor patients for signs and symptoms of new motor and/or sensory findings. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

汉文翻译

QTc间期延伸：监测心电图和电解质。若是QTc间期延伸，剂量减少或住手，然后复原剂量或永久住手TIBSOVO。

吉兰-巴雷概述征：监测患者新的理会和/或嗅觉发现的体征和症状。被会诊患有吉兰-巴雷概述征的患者永久停用TIBSOVO。

06禁忌

None.

汉文翻译

无。

07药物保存

汉文翻译

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