景德镇不锈钢保温施工队 针对KRAS G12C突变肺癌：阿达格拉西布（Adagrasib）中英说明书，适用情况、不良反应、注意事项

阿达格拉西布

Adagrasib、KRAZATI

阿达格拉西布（Adagrasib）是一种选择、不可逆的KRAS G12C抑制剂，具有较长的半衰期和良好的中枢神经系统渗透。2022年12月12日，FDA加速批准用于治疗先前接受过系统治疗的携带KRAS G12C突变的局部晚期或转移的NSCLC成年患者。

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阿达格拉西布通过与KRAS G12C突变蛋白的半胱氨酸残基形成共价键，抑制其GTP酶活，从而减少肿瘤细胞的增殖和生存信号。阿达格拉西布的抑制作用导致肿瘤细胞周期停滞和细胞凋亡，进而抑制肿瘤生长。

展开剩余92%

01适应症

KRAZATI is an inhibitor of the RAS GTPase family indicated for:

Non-small cell lung cancer (NSCLC)*

As a single agent, for the treatment of adult patients with KRAS G12C- mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy.

Colorectal cancer (CRC)*

In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

*These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of a clinical benefit in confirmatory trials.

中文翻译

KRAZATI是RAS GTPase家族的抑制剂，用于：

非小细胞肺癌（NSCLC）*

作为单一药物，用于治疗成年KRAS G12C突变的局部晚期或转移NSCLC患者，由FDA批准的测试确定，这些患者至少接受过一次全身治疗。

结直肠癌（CRC）*

与西妥昔单抗联用于治疗成年KRAS G12C突变的局部晚期或转移CRC患者，根据FDA批准的试验确定，这些患者先前接受过氟嘧啶，奥沙利铂和伊立替康为基础的化疗。

*这这些适应证是基于客观缓解率（ORR）和缓解持续时间（DOR）的加速批准。这些适应证的继续批准可能取决于确证试验中对临床获益的验证和描述。能取决于验证试验中临床益处的验证和描述。

02用法用量

Recommended dosage as a single agent for NSCLC and in combinationwith cetuximab for CRC: 600 mg orally twice daily. Swallow tablets whole with or without food.

中文翻译

单独用于NSCLC和与西妥昔单抗联用于CRC的荐剂量：口服，每日两次，每次 600mg。 随餐或空腹吞服片剂。

03特殊人群

Pregnancy: There are no available data on the use of KRAZATI in pregnant women. In animal reproduction studies, oral administration of adagrasib to pregnant rats and rabbits during the period of organogenesis did not cause adverse development effects or embryo-fetal lethality at exposures below the human exposure at the recommended dose of 600 mg twice daily.

Lactation： There are no data on the presence of adagrasib or its metabolites in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with KRAZATI and for 1 week after the last dose.

Females and Males of Reproductive Potential： Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential.

Pediatric Use： The safety and effectiveness of KRAZATI has not been established in pediatric patients.

Geriatric Use： Of 116 patients with metastatic NSCLC who received adagrasib 600 mg orally twice daily in KRYSTAL-1, 49% (57 patients) were ≥ 65 years of age and 13% (15 patients) were ≥ 75 years of age. No overall differences in safety or effectiveness were observed between older and younger patients.

Of 94 patients with metastatic CRC who received adagrasib 600 mg orally twice daily in combination with cetuximab in KRISTAL-1, 33% (31 patients) were ≥ 65 years of age and 2.1% (2 patients) were ≥ 75 years of age. No overall differences in safety or effectiveness were observed between older and younger patients.

中文翻译

妊娠：目前尚无关于 KRAZATI 在孕妇中使用的可用数据。在动物生殖研究中，对怀孕大鼠和兔在器官发生期进行口服阿达格拉西布给药，在低于荐剂量 600 毫克每日两次的人体暴露水平下，未引起不良发育应或胚胎胎儿致死。

哺乳期：尚无关于阿达格拉西布或其代谢物存在于母乳中的数据，或其对哺乳婴儿的影响，或对乳汁产生的影响。由于哺乳婴儿可能发生严重不良反应，建议女在服用 KRAZATI 期间以及后一次用药后1周内不要哺乳。

具有生殖潜力的女和男：根据动物研究的结果，KRAZATI 可能会影响具有生殖能力的雌和雄的生育能力。

儿童使用：KRAZATI 在儿童患者中的安全和有尚未确定。

老年使用：在 KRYSTAL-1 研究中，接受每日两次口服 600 毫克阿达格拉西布治疗的 116 名转移非小细胞肺癌患者中，49%（57 名患者）年龄≥65 岁，13%（15 名患者）年龄≥75 岁。在老年患者和年轻患者之间未观察到安全和有的总体差异。

在 KRISTAL-1 研究中，接受每日两次口服 600 毫克阿达格拉西布联西妥昔单抗治疗的 94 名转移结直肠癌患者中，33%（31 名患者）年龄≥65 岁，2.1%（2 名患者）年龄≥75 岁。在老年患者和年轻患者之间未观察到安全和有的总体差异。

随着嫦娥六号完成月背采样返回，中国探月工程“绕、落、回”三步走战略圆满收官。如何利用月球本身资源建设可持续的科研站，成为下一阶段的关键课题。

04不良反应

Single agent use in NCSLC: The most common adverse reactions (≥ 25%) were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, and decreased appetite. The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, hypokalemia, hyponatremia, increased lipase, decreased leukocytes, decreased neutrophils and increased alkaline phosphatase.

In combination with cetuximab in CRC: The most common adverse reactions (≥ 25%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, and cough. The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased potassium, decreased magnesium, decreased hemoglobin, increased aspartate aminotransferase, increased lipase, decreased albumin, and increased alanine aminotransferase.

中文翻译

NCSLC单药治疗：常见的不良反应（≥25%）是恶心，腹泻，呕吐，疲劳，肌肉骨骼疼痛，肝毒，肾功能不全，水肿，铝皮保温呼吸困难和食欲下降。常见的（≥2%）3或4级实验室异常是淋巴细胞减少，血红蛋白减少，丙氨酸氨基转移酶增加，天冬氨酸氨基转移酶增加，低钾血症，低钠血症，脂肪酶增加，白细胞减少，中粒细胞减少和碱磷酸酶增加。

联西妥昔单抗治疗CRC：常见的不良反应（≥25%）是皮疹，恶心，腹泻，呕吐，疲劳，肌肉骨骼疼痛，肝毒，头痛，皮肤干燥，腹痛，食欲下降，水肿，贫血和咳嗽。常见的（≥2%）3或4级实验室异常是淋巴细胞减少，钾减少，镁减少，血红蛋白减少，天冬氨酸氨基转移酶增加，脂肪酶增加，白蛋白减少和丙氨酸氨基转移酶增加。

05注意事项

Gastrointestinal Adverse Reactions: Monitor patients for diarrhea, nausea and vomiting and provide supportive care as needed. Withhold, reduce the dose or permanently discontinue based on severity.

QTc Interval Prolongation: Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Monitor ECG and electrolytes particularly potassium and magnesium, in patients at risk, and in patients taking medications known to prolong the QT interval. Correct electrolyte abnormalities. Withhold, reduce the dose, or permanently discontinue based on severity.

Hepatotoxicity: Monitor liver laboratory tests prior to the start of KRAZATI and monthly for 3 months after and as clinically indicated. Reduce the dose, withhold, or permanently discontinue based on severity.

Interstitial Lung Disease (ILD) / Pneumonitis: Monitor for new or worsening respiratory symptoms. Withhold KRAZATI for suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified.

中文翻译

胃肠道不良反应：监测患者的腹泻，恶心和呕吐，并根据需要提供支持治疗。根据严重程度扣留、减少剂量或永久停药。

QTc间期延长：避免与已知有可能延长QTc间期的其他产品同时使用KRAZATI。监测心电图和电解质，特别是钾和镁，对有风险的患者以及服用已知延长QT间期药物的患者进行监测。纠正电解质异常。根据严重程度扣留、减少剂量或永久停药。

肝毒：在KRAZATI开始之前监测肝脏实验室检查，并在临床指示后每月监测3个月。根据严重程度减少剂量，停止或永久停止。

间质肺病（ILD）/肺炎：监测新的或恶化的呼吸道症状。如果没有发现ILD/肺炎的其他潜在原因，则停止服用疑似ILD/肺炎的KRAZATI，并永久停止服用。

06禁忌

None.

中文翻译

无。

07药物保存

Store KRAZATI at room temperature between 68°F to 77°F (20°C to 25°C). KRAZATI comes in a child-resistant container. KRAZATI comes with a desiccant (drying agent) in the container to keep the medicine dry. Do not remove the desiccant from the container after opening. Do not eat or swallow the desiccant.

中文翻译

将 KRAZATI 储存在 68°F 至 77°F（20°C 至 25°C）的室温下。 KRAZATI 装在儿童防备型容器中。 KRAZATI 的容器内配有干燥剂以保持药品干燥。打开容器后不要取出干燥剂。不要食用或吞服干燥剂。

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发布于：河北省