温馨提醒：本说明书仅供参考，最新的说明书详见药品附带的说明书。

完整的处方信息

1 适应症和用法

ONUREG适用于在强化诱导化疗后达到首次完全缓解（CR）或血细胞计数不完全恢复（CRi）的完全缓解且无法完成强化治疗的成人急性髓系白血病患者的持续治疗。

2 剂量和给药方法

2.1 重要管理信息

不要用 ONUREG 代替静脉注射或皮下注射阿扎胞苷。ONUREG的适应症和给药方案不同于静脉内或皮下阿扎胞苷 [见警告和注意事项(5.1) ]。

2.2 推荐用量

ONUREG 的推荐剂量是在每个 28 天周期的第 1 天至第 14 天，每天一次口服 300 毫克，有或没有食物。继续 ONUREG 直至疾病进展或出现不可接受的毒性。

在前 2 个周期的每剂 ONUREG 前 30 分钟给予止吐剂。如果没有恶心和呕吐，可以在 2 个周期后省略止吐预防。

如果在一个周期的第 1 天绝对中性粒细胞计数 (ANC) 低于 0.5 Gi/L，不要给予 ONUREG。延迟循环开始，直到 ANC 为 0.5 Gi/L 或更高。

对患者进行以下指导：

• 整片吞服。不要切割、压碎或咀嚼药片。
• 每天大约在同一时间服用一剂。
• 如果漏服一剂 ONUREG，或未在通常时间服用，请在同一天尽快服用该剂量，并在第二天恢复正常计划。不要在同一天服用 2 剂。
• 如果呕吐了一剂，请不要在同一天服用另一剂。第二天恢复正常的日程安排。

ONUREG 是一种危险药物。遵循适用的特殊处理和处置程序。1

2.3 不良反应的监测和剂量调整

在前 2 个周期中每隔一周监测一次全血细胞计数，此后在每个周期开始之前。在骨髓抑制的任何剂量减少后，每隔一周增加监测 2 个周期。

表1中提供了针对不良反应的推荐剂量修改。

3 剂型和规格

片剂：

• 200 mg，粉红色，椭圆形，薄膜包衣片，一侧刻有“200”，另一侧刻有“ONU”。
• 300 mg，棕色，椭圆形，薄膜包衣片，一侧刻有“300”，另一侧刻有“ONU”。

4 禁忌症

ONUREG 禁用于已知对阿扎胞苷或其成分有严重超敏反应的患者[见不良反应 (6.2)，描述 (11) ]。

5 警告和注意事项

5.1 用其他阿扎胞苷产品替代的风险

由于药代动力学参数的显着差异[见临床药理学(12.3)]，ONUREG的推荐剂量和时间表不同于静脉内或皮下阿扎胞苷产品的那些。以推荐剂量的 ONUREG静脉或皮下注射阿扎胞苷治疗患者可能会导致致命的不良反应。以静脉或皮下阿扎胞苷推荐剂量使用 ONUREG 治疗患者可能无效。

不要用 ONUREG 代替静脉内或皮下阿扎胞苷 [见剂量和给药方法(2.1) ]。

5.2 骨髓抑制

接受 ONUREG 治疗的患者中，分别有 49% 和 22% 的患者出现新的或恶化的 3 级或 4 级中性粒细胞减少症和血小板减少症。12% 发生发热性中性粒细胞减少症。由于中性粒细胞减少症和血小板减少症，分别有 7% 和 2% 的患者需要减少剂量。由于中性粒细胞减少症或血小板减少症，不到 1% 的患者停止 ONUREG。

监测全血细胞计数并按照推荐修改剂量[见剂量和给药方法 (2.2 , 2.3) ]。如果发生骨髓抑制，提供标准的支持性护理，包括造血生长因子。

5.3 骨髓增生异常综合征患者早期死亡率增加

在 AZA-MDS-003 (NCT01566695) 中，216 名因骨髓增生异常综合征而患有红细胞输血依赖性贫血和血小板减少症的患者被随机分配至 ONUREG 或安慰剂组。177 名患者在 28 天周期的 21 天中每天接受 5 个周期的 ONUREG 300 mg。由于与安慰剂相比，接受 ONUREG 的患者早期致命和/或严重不良反应的发生率更高，因此提前终止了招募。最常见的致命不良反应是败血症。ONUREG 治疗骨髓增生异常综合征的安全性和有效性尚未确定。除对照试验外，不推荐使用 ONUREG 治疗骨髓增生异常综合征患者。

5.4 胚胎-胎儿毒性

根据动物的作用机制和发现，ONUREG 给孕妇服用时可能会造成胎儿伤害。阿扎胞苷通过单次腹膜内剂量施用给怀孕的大鼠小于推荐人体每日剂量口服的阿扎胞苷一毫克/米上2基础造成胎儿死亡和畸形。

告知孕妇对胎儿的潜在风险。建议有生育潜力的女性在 ONUREG 治疗期间和最后一次给药后至少 6 个月内使用有效的避孕措施。忠告有生殖潜能女性伴侣的男性在用 ONUREG 治疗期间和最后一次给药后至少 3 个月内使用有效的避孕措施[见特殊人群中的使用 (8.1,8.3) ]。

6 不良反应

以下临床上显着的不良反应在说明书的其他地方描述：

• 骨髓抑制[见警告和注意事项(5.2) ]

6.1 临床试验经验

因为临床试验是在广泛不同的条件下进行的，在一种药物的临床试验中观察到的不良反应率不能直接与另一种药物临床试验中的发生率进行比较，并且可能无法反映实践中观察到的发生率。

急性髓性白血病

ONUREG 的安全性在 QUAZAR 中进行了评估[见临床研究 (14) ]。患者在每个 28 天周期的第 1 天至第 14 天每天口服一次 ONUREG 300 mg（N=236）或安慰剂（N=233）。在接受 ONUREG 的患者中，71% 的患者暴露时间为 6 个月或更长时间，49% 的患者暴露时间超过一年。ONUREG 暴露的中位持续时间为 11.6 个月（范围：0.5 至 74.3 个月），中位周期数为 12（范围：1 至 82 个周期）。

15% 接受 ONUREG 的患者发生严重不良反应。≥ 2% 接受 ONUREG 的患者的严重不良反应是肺炎 (8%) 和发热性中性粒细胞减少症 (7%)。一名接受 ONUREG 的患者发生了一个致命的不良反应（败血症）。

8% 的患者因不良反应而永久停用 ONUREG。导致超过 1% 患者永久停用 ONUREG 的不良反应包括恶心 (2.1%)、腹泻 (1.7%) 和呕吐 (1.3%)。35% 的患者因不良反应而中断 ONUREG。在> 5% 的患者中需要中断 ONUREG 的不良反应包括中性粒细胞减少症 (20%)、血小板减少症 (8%) 和恶心 (6%)。

14% 的患者因不良反应而减少 ONUREG 的剂量。需要减少 1% 以上患者剂量的不良反应包括中性粒细胞减少症 (6%)、腹泻 (3.4%)、血小板减少症 (1.7%) 和恶心 (1.7%)。

最常见（≥ 10%）的不良反应是恶心、呕吐、腹泻、疲劳/乏力、便秘、肺炎、腹痛、关节痛、食欲下降、发热性中性粒细胞减少、头晕和四肢疼痛。

表 2 总结了 QUAZAR 中的不良反应。

不符合列入表2 标准的临床相关不良反应是接受 ONUREG 的患者体重下降 (4%)。

接受 ONUREG 治疗的患者中有 74%、65% 和 25% 的患者出现中性粒细胞减少、血小板减少和任何级别的贫血。表 3 总结了 QUAZAR 中选定的 3 级或 4 级血液实验室异常。

6.2 售后体验

在批准后使用静脉或皮下阿扎胞苷期间已确定以下不良反应。由于这些反应是从数量不确定的人群中自愿报告的，因此并不总是能够可靠地估计它们的频率或建立与药物暴露的因果关系。

• 超敏反应
• 间质性肺病
• 肿瘤溶解综合征
• Sweet 综合征（急性发热性中性粒细胞皮肤病）
• 坏死性筋膜炎（包括死亡病例）
• 分化综合症

8 在特定人群中的使用

8.1 怀孕

风险总结

根据其作用机制[见临床药理学(12.1) ]和在动物中的发现，当给予孕妇ONUREG可致胎儿危害。没有关于孕妇使用 ONUREG 来评估药物相关风险的可用数据。以mg/m 2 为基础，当剂量低于推荐的人口服阿扎胞苷每日剂量时，阿扎胞苷具有致畸性并导致动物胚胎-胎儿致死（见数据）。告知孕妇对胎儿的潜在风险。

指示人群主要出生缺陷和流产的估计背景未知。所有怀孕都有出生缺陷、流产或其他不良后果的背景风险。在美国一般人群中，临床认可的妊娠中主要出生缺陷和流产的估计背景风险分别为 2% 至 4% 和 15% 至 20%。

数据

动物数据

尚未对口服阿扎胞苷进行生殖或发育毒性研究。

小鼠早期胚胎毒性研究显示，单次腹膜内注射 6 mg/m 2 阿扎胞苷（剂量低于推荐的人口服阿扎胞苷每日剂量，以 mg/m 2 为基础）后，宫内胚胎死亡（吸收增加）的频率为 44% ) 在妊娠第 10 天。在妊娠第 15 天或之前给予阿扎胞苷的小鼠中检测到大脑发育异常，剂量约为 3 至 12 mg/m 2（剂量低于推荐的人类每日剂量，以 mg/m 2基础）。

在大鼠中，当在妊娠第 4 至 8 天（植入后）以 6 mg/m 2的剂量（以 mg/m 2 为基础，低于推荐的人类每日剂量）进行腹腔注射时，阿扎胞苷明显具有胚胎毒性，尽管植入前阶段（妊娠第 1 至 3 天）的治疗对胚胎没有不利影响。在妊娠第 9、10、11 或 12 天给予阿扎胞苷单次腹膜内剂量 3 至 12 mg/m 2（剂量低于推荐的人体每日剂量，以 mg/m 2 为基础）后，阿扎胞苷导致大鼠多胎畸形. 在本研究中，阿扎胞苷以 3 至 12 mg/m 2给药时导致胎儿死亡在妊娠第 9 天和第 10 天；在妊娠第 9 天以最高剂量将每窝活体动物的平均数量减少到对照组的 9%。 胎儿异常包括：CNS 异常（无脑畸形/脑膨出）、肢体异常（小畸形、畸形足、并指、寡指）和其他（小颌畸形） 、腹裂、水肿和肋骨异常）。

8.2 泌乳

风险总结

没有关于人乳中阿扎胞苷的存在或对母乳喂养的儿童或产奶量的影响的数据。由于母乳喂养的孩子可能出现严重的不良反应，建议妇女在 ONUREG 治疗期间和最后一次给药后 1 周内不要母乳喂养。

8.3 具有生殖潜力的女性和男性

当对孕妇给药时 ONUREG 可导致胚胎-胎儿伤害[见在特殊人群中使用(8.1)]。

怀孕测试

建议在开始 ONUREG 之前对具有生殖潜力的女性进行妊娠测试。

避孕

女性

建议有生育潜力的女性在 ONUREG 治疗期间和最后一次给药后至少 6 个月内使用有效的避孕措施。

男性

建议有生殖潜能女性伴侣的男性在 ONUREG 治疗期间和最后一次给药后至少 3 个月内使用有效的避孕措施。

不孕症

根据动物数据，ONUREG 可能损害男性或女性的生育能力[见非临床毒理学(13.1)]。

8.4 儿科使用

ONUREG 在儿科患者中的安全性和有效性尚未确定。

8.5 老年人使用

在 QUAZAR 接受 ONUREG 的 238 名患者中，72% 的年龄为 65 岁或以上，而 12% 的年龄为 75 岁或以上。在这些患者和年轻患者之间未观察到 ONUREG 的安全性或有效性的总体差异。

8.6 肾损害

更频繁地监测有严重肾受损患者(肌酐清除率 [CLcr] 15 至 29 mL/min，通过 Cockcroft-Gault 公式计算) 对不良反应和修改 ONUREG 剂量对不良反应[见剂量和给药方法 (2.3)]。

对于轻度至重度肾功能不全(CLcr 15 至 89 mL/min) 的患者，建议不调整 ONUREG 的剂量[见临床药理学 (12.3)]。

8.7 肝损伤

ONUREG 尚未在预先存在严重肝功能损害（总胆红素 > 3 × ULN）的患者中进行研究。

对于中度肝功能不全（总胆红素 > 1.5 至 3 × ULN）患者，ONUREG 的推荐剂量尚未确定。

对于轻度肝受损患者（总胆红素 ≤ ULN 和 AST > ULN，或总胆红素 1 至 1.5 × ULN 和任何 AST），建议不调整 ONUREG 的剂量[见临床药理学(12.3) ]。

11 说明

阿扎胞苷是一种核苷代谢抑制剂，分子式为C 8 H 12 N 4 O 5，分子量为244 g/mol。化学名称为：4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one，化学结构为：

阿扎胞苷为白色至灰白色固体。发现阿扎胞苷在 1.0 至 7.0 的 pH 范围内可溶于水性介质。

ONUREG（阿扎胞苷）以薄膜包衣片形式提供，含 200 毫克或 300 毫克阿扎胞苷口服。每个片芯含有以下非活性成分：交联羧甲基纤维素钠、硬脂酸镁、甘露醇和硅化微晶纤维素。200 和 300 毫克片剂包衣含有羟丙甲纤维素、乳糖一水合物、聚乙二醇、二氧化钛和三醋精。此外，200mg 片剂包衣含有氧化铁红，300mg 片剂包衣含有氧化铁黑、氧化铁红和氧化铁黄。

12 临床药理学

12.1 作用机制

阿扎胞苷是胞苷的嘧啶核苷类似物，可抑制 DNA/RNA 甲基转移酶。在细胞摄取和酶促生物转化为核苷酸三磷酸后，阿扎胞苷掺入 DNA 和 RNA。

在体外将阿扎胞苷掺入癌细胞的 DNA 中，包括急性髓性白血病细胞，抑制 DNA 甲基转移酶，降低 DNA 甲基化和改变基因表达，包括调节肿瘤抑制和细胞分化的基因的重新表达。将阿扎胞苷掺入癌细胞（包括白血病细胞）的 RNA 中，可抑制 RNA 甲基转移酶，降低 RNA 甲基化，降低 RNA 稳定性并减少蛋白质合成。

抗白血病活性的阿扎胞苷是通过减少细胞存活力的和诱导凋亡在体外AML细胞系证实。在体内白血病肿瘤模型中，阿扎胞苷降低了肿瘤负荷并增加了存活率。

12.2 药效学

在28 天周期的 14 天接受 ONUREG 的 AML 患者中，随着阿扎胞苷血浆暴露的增加，观察到整体 DNA 甲基化的降低更大。

12.3 药代动力学

阿扎胞苷的全身暴露量在 120 mg 至 600 mg 每天一次 ONUREG（推荐剂量的 0.4 至 2 倍）的剂量范围内大致与剂量成正比。以下ONUREG，平均的单300毫克的剂量（变异系数[CV％]）C最大的阿扎胞苷是145毫微克/毫升（64％）和平均AUC阿扎胞苷是242纳克H /毫升（65％）。ONUREG 300 mg 每天一次后未观察到蓄积。

吸收

相对于皮下给药，平均口服生物利用度约为 11%。阿扎胞苷血浆浓度达到峰值的中位时间为 1 小时。

食物的作用

高脂肪、高热量膳食（约 800 至 1000 卡路里，50% 脂肪）不影响 AUC 0-INF并将 C max降低 21%。

分配

阿扎胞苷的平均 (CV%) 表观分布容积 (V z / F)为 881 L (67%)。阿扎胞苷的体外血清蛋白结合率约为 6% 至 12%。血液与血浆的比率约为 0.3。

消除

平均 (CV%) 终末半衰期约为 0.5 小时 (27%)，表观清除率 (CL/F) 为 1240 L/小时 (64%)。

代谢

阿扎胞苷经历由胞苷脱氨酶介导的自发水解和脱氨作用。

排泄

每天一次口服给予 ONUREG 300 mg 后，< 2% 的剂量在尿液中恢复原状。

特定人群

年龄（46 岁至 93 岁）、性别、体重（39.3 公斤至 129 公斤）、轻度肝功能损害（总胆红素 ≤ ULN 且 AST > ULN，或总胆红素 1 至 1.5 × ULN 和任何 AST），以及轻度至中度肾功能不全（CLcr 30 至 89 mL/min）对口服阿扎胞苷的药代动力学没有临床意义的影响。种族/民族、中度至重度肝功能损害（总胆红素 > 1.5 × ULN 和任何 AST）和严重肾功能损害（CLcr 15 至 29 mL/min）对口服阿扎胞苷药代动力学的影响尚不清楚。

单次或多次皮下每日给药后，严重肾功能损害使阿扎胞苷暴露量增加约 70% 或 41%。

药物相互作用研究

胃酸还原剂对阿扎胞苷的影响：

奥美拉唑（一种质子泵抑制剂）与 ONUREG 的共同给药使阿扎胞苷AUC 0-INF增加了 19% 并且对 C max没有影响。

体外研究

细胞色素 P450 (CYP) 酶： 阿扎胞苷在临床相关浓度下不抑制 CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4 或 CYP2E1。阿扎胞苷不是 CYP1A2、CYP2C19 或 CYP3A 的诱导剂。

转运蛋白系统：阿扎胞苷不是 P-糖蛋白 (P-gp) 的底物。阿扎胞苷不抑制P-gp的，乳腺癌耐药蛋白（BCRP），有机阴离子转运体（OAT）OAT1和OAT3，有机阴离子转运多肽（OATP）OATP1B1和OATP1B3，或有机阳离子转运蛋白（OCT）OCT2在临床相关浓度。

13 非临床毒理学

13.1 致癌作用、诱变作用、生育力受损

在小鼠和大鼠中评估了阿扎胞苷的潜在致癌性。阿扎胞苷2.2毫克/千克诱导雌性小鼠造血系统的肿瘤（6.6毫克/米2，的约4％推荐的口服的人每日剂量阿扎胞苷上的毫克/米2周的基础上）腹膜内每周3次施用52周。在小鼠腹腔注射阿扎胞苷2 mg/kg（6 mg/m 2，约为人体推荐的每日口服阿扎胞苷剂量的 3% ）时观察到淋巴网状系统、肺、乳腺和皮肤肿瘤的发生率增加。毫克/米2基础）每周一次，持续 50 周。大鼠的致瘤性研究以 15 或 60 mg/m 2每周两次给药（大约为人推荐的每日口服阿扎胞苷剂量的 8% 至 32%，以 mg/m 2 为基础）显示与对照组相比睾丸肿瘤的发病率增加.

在体外细菌系统鼠伤寒沙门氏菌菌株 TA100 和几种 trpE8 菌株、大肠杆菌菌株 WP14 Pro、WP3103P、WP3104P 和 CC103 中测试了阿扎胞苷的致突变性和致裂性潜能；在小鼠淋巴瘤细胞和人淋巴母细胞的体外正向基因突变试验中；以及在小鼠 L5178Y 淋巴瘤细胞和叙利亚仓鼠胚胎细胞中的体外微核试验。阿扎胞苷在细菌和哺乳动物细胞系统中具有致突变性。通过在 L5178Y 小鼠细胞和叙利亚仓鼠胚胎细胞中诱导微核显示了阿扎胞苷的致畸作用。

施用阿扎胞苷通过腹膜内注射到雄性小鼠在9.9毫克/米2（以小于所推荐的人的每日剂量以mg / m时，剂量2周的基础上）每日与未处理的雌性小鼠交配前3天导致生育率和损失降低在随后的胚胎和出生后发育过程中的后代。以 15 至 30 mg/m 2的剂量（剂量低于推荐的人体每日剂量，以 mg/m 2 为基础）每周治疗雄性大鼠 3 次，持续 11 或 16 周，导致睾丸和附睾重量减轻，精子数量减少伴随着妊娠率降低，以及交配雌性胚胎丢失增加。在一项相关研究中，雄性大鼠以 24 mg/m2 治疗 16 周在妊娠第 2 天检查时，2导致已交配雌性的异常胚胎增加。

14 临床研究

ONUREG 的疗效在 QUAZAR (NCT01757535) 中进行了评估，这是一项多中心、随机、双盲、安慰剂对照研究。符合条件的患者年龄在 55 岁或以上，患有 AML，并且在通过强化诱导化疗实现首次完全缓解（CR）或血细胞计数不完全恢复（CRi）的完全缓解后 4 个月内。患者可能接受了巩固治疗（见表 4）。如果患者在筛选时是造血干细胞移植的候选者，则被排除在外。

在有或没有巩固治疗的情况下完成诱导的总共 472 名患者按 1:1 随机分配接受 ONUREG 300 mg（n=238）或安慰剂（n=234）在每个 28 天周期的第 1 天至第 14 天口服。根据诱导治疗时的年龄（55 至 64 岁与 ≥ 65 岁）、诱导治疗时的细胞遗传学风险类别（中等风险与低风险）、MDS/CMML 既往史（是与否）对随机化进行分层，并在诱导治疗后接受巩固治疗（是与否）。基线人口统计学和疾病特征见表 4。

ONUREG 的疗效建立在总生存期 (OS) 的基础上。该试验表明，与安慰剂相比，随机分配至 ONUREG 的患者的 OS 具有统计学上的显着改善。亚组分析显示 CR 或 CRi 患者的 OS 获益一致。功效结果总结在表 5 和图 1 中。

15 参考

1.“职业安全与健康管理局有害药物”。职业安全与健康管理局。http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 如何供应/储存和处理

如何供应

ONUREG 片剂可作为：

• 200 mg：粉红色，椭圆形，薄膜包衣片，一侧刻有“200”，另一侧刻有“ONU”。
• 300 mg：棕色、椭圆形、薄膜包衣片，一侧刻有“300”，另一侧刻有“ONU”。

表 6 列出了封装配置和强度。

贮存

• 将瓶子储存在 20°C 至 25°C（68°F 至 77°F）；允许在 15°C 至 30°C（59°F 至 86°F）之间进行远足 [参见 USP 控制室温]。
  保持瓶子紧闭。
  在原瓶中储存和分配（带有两个干燥剂罐）。
• 将水泡储存在 20°C 至 25°C（68°F 至 77°F）；允许在 15°C 至 30°C（59°F 至 86°F）之间进行远足 [参见 USP 控制室温]。
  存放在原铝铝泡罩中。

处理和处置

ONUREG 是一种危险药物。遵循适用的特殊处理和处置程序。1

如果粉末接触到皮肤，请立即用肥皂和水彻底清洗。如果粉末接触到粘膜，请立即用水冲洗该区域。

17 患者咨询信息

建议患者阅读 FDA 批准的患者标签（患者信息）。

骨髓抑制

忠告患者用 ONUREG 骨髓抑制的风险和需要在治疗前和治疗期间监测全血细胞计数[见警告和注意事项 (5.2) ]。

胃肠道毒性

忠告患者用 ONUREG 胃肠道毒性风险和治疗期间可能需要使用止吐或止泻药物[见不良反应 (6.1) ]。

胚胎-胎儿毒性

告知孕妇对胎儿的潜在风险。建议有生育潜力的女性将已知或疑似怀孕告知其医疗保健提供者[见警告和注意事项 (5.4)，在特殊人群中使用 (8.1) ]。

忠告有生育潜力的女性在用 ONUREG 治疗期间和最后一次给药后至少 6 个月使用有效避孕[见特殊人群中的使用(8.3) ]。

忠告有生殖潜能女性伴侣的男性在用 ONUREG 治疗期间和最后一次给药后至少 3 个月使用有效避孕[见特殊人群中使用(8.3) ]。

哺乳期

建议妇女在用 ONUREG 治疗期间和最后一次给药后 1 周内不要母乳喂养[见特殊人群中的使用 (8.2) ]。

行政

建议患者每天大约在同一时间服用 ONUREG 有或没有食物，以及如何弥补错过或呕吐的剂量。建议患者整片吞服。忠告患者不要切割、压碎或咀嚼片剂[见剂量和给药方法(2.2) ]。

储存说明

建议患者将 ONUREG 保存在原始容器（瓶子或水泡）中。如果分配瓶子，建议患者保持容器密闭，里面有两个干燥剂罐，不要吃干燥剂罐[参见如何供应/储存和处理 (16) ]。

制造商：新基公司
Bristol-Myers Squibb 的全资子公司
86 Morris Avenue
Summit, NJ 07901

ONUREG ®是新基公司的注册商标。

© 2020 新基公司。

版权所有。

ONUPI.003

主要显示面板 - 200 毫克瓶子标签

NDC 59572-730-14

ONUREG™
（阿扎胞苷）片

200毫克

整片吞服。
不要切割、压碎或咀嚼药片。

Rx 仅
14 片

注意：有害物质

主显示面板 - 200 毫克吸塑卡

NDC 59572-730-07 仅限
Rx

ONUREG™
（阿扎胞苷）片

200毫克

每片含有200毫克阿扎胞苷。

一张
包含 7 片的吸塑卡
注意：危险品

新基

NDC 59572-730-07 仅限
Rx

ONUREG™
（阿扎胞苷）片

200毫克

每片含有200毫克阿扎胞苷。

一张
包含 7 片的吸塑卡
注意：危险品

新基

主要显示面板 - 300 毫克瓶子标签

NDC 59572-740-14

ONUREG™
（阿扎胞苷）片

300毫克

整片吞服。
不要切割、压碎或咀嚼药片。

Rx 仅
14 片

注意：有害物质

主显示面板 - 300 毫克吸塑卡

NDC 59572-740-07 仅限
Rx

ONUREG™
（阿扎胞苷）片

300毫克

每片含 300 毫克阿扎胞苷。

一张
包含 7 片的吸塑卡
注意：危险品

新基

主要显示面板 - 300 毫克泡罩包装

NDC 59572-740-07 仅限
Rx

ONUREG™
（阿扎胞苷）片

300毫克

每片含 300 毫克阿扎胞苷。
整片吞服。不要切割、压碎或咀嚼药片。

一张
包含 7 片的吸塑卡
注意：危险品

新基

抬起这里
打开

主要显示面板 - 300 毫克泡罩包装纸箱

NDC 59572-740-07 仅限
Rx

ONUREG™
（阿扎胞苷）片

300毫克

每片含 300 毫克阿扎胞苷。

整片吞服。不要切割、压碎或咀嚼药片。

一张
包含 7 片的吸塑卡

新基

注意：有害物质

【备注】以上内容仅供参考，不作为用药依据，详情请参照药品附带说明书。

本说明书来源于：美国FDA

https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/0e95e33f-8aba-4f19-b332-2416580d358b/spl-doc?hl=Azacitidine

温馨提醒：

①建议您用 谷歌浏览器  在电脑上或手机  打开以上链接，就可以自动翻译成简体中文，而且翻译的还比较准确。

②本说明书仅供参考，最新的说明书详见药品附带的说明书

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

ONUREG is indicated for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Information

Do not substitute ONUREG for intravenous or subcutaneous azacitidine. The indications and dosing regimen for ONUREG differ from that of intravenous or subcutaneous azacitidine [see Warnings and Precautions (5.1)].

2.2 Recommended Dosage

The recommended dosage of ONUREG is 300 mg orally once daily with or without food on Days 1 through 14 of each 28-day cycle. Continue ONUREG until disease progression or unacceptable toxicity.

Administer an antiemetic 30 minutes prior to each dose of ONUREG for the first 2 cycles. Antiemetic prophylaxis may be omitted after 2 cycles if there has been no nausea and vomiting.

If the absolute neutrophil count (ANC) is less than 0.5 Gi/L on Day 1 of a cycle, do not administer ONUREG. Delay the start of the cycle until the ANC is 0.5 Gi/L or more.

Instruct patients on the following:

• Swallow tablets whole. Do not cut, crush, or chew the tablets.
• Take a dose about the same time each day.
• If a dose of ONUREG is missed, or not taken at the usual time, take the dose as soon as possible on the same day, and resume the normal schedule the following day. Do not take 2 doses on the same day.
• If a dose is vomited, do not take another dose on the same day. Resume the normal schedule the following day.

ONUREG is a hazardous drug. Follow applicable special handling and disposal procedures.1

2.3 Monitoring and Dosage Modifications for Adverse Reactions

Monitor complete blood count every other week for the first 2 cycles and prior to the start of each cycle thereafter. Increase monitoring to every other week for the 2 cycles after any dose reduction for myelosuppression.

The recommended dosage modifications for adverse reactions are provided in Table 1.

3 DOSAGE FORMS AND STRENGTHS

Tablets:

• 200 mg, pink, oval, film-coated tablet with debossed "200" on one side and "ONU" on the other side.
• 300 mg, brown, oval, film-coated tablet with debossed "300" on one side and "ONU" on the other side.

4 CONTRAINDICATIONS

ONUREG is contraindicated in patients with known severe hypersensitivity to azacitidine or its components [see Adverse Reactions (6.2), Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Risks of Substitution with Other Azacitidine Products

Due to substantial differences in the pharmacokinetic parameters [see Clinical Pharmacology (12.3)], the recommended dose and schedule for ONUREG are different from those for the intravenous or subcutaneous azacitidine products. Treatment of patients using intravenous or subcutaneous azacitidine at the recommended dosage of ONUREG may result in a fatal adverse reaction. Treatment of patients using ONUREG at the doses recommended for intravenous or subcutaneous azacitidine may not be effective.

Do not substitute ONUREG for intravenous or subcutaneous azacitidine [see Dosage and Administration (2.1)].

5.2 Myelosuppression

New or worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received ONUREG, respectively. Febrile neutropenia occurred in 12%. A dose reduction was required for 7% and 2% of patients due to neutropenia and thrombocytopenia, respectively. Less than 1% of patients discontinued ONUREG due to either neutropenia or thrombocytopenia.

Monitor complete blood counts and modify the dosage as recommended [see Dosage and Administration (2.2, 2.3)]. Provide standard supportive care, including hematopoietic growth factors, if myelosuppression occurs.

5.3 Increased Early Mortality in Patients with Myelodysplastic Syndromes

In AZA-MDS-003 (NCT01566695), 216 patients with red blood cell transfusion-dependent anemia and thrombocytopenia due to myelodysplastic syndromes were randomized to ONUREG or placebo. One-hundred and seven patients received a median of 5 cycles of ONUREG 300 mg daily for 21 days of a 28-day cycle. Enrollment was discontinued early due to a higher incidence of early fatal and/or serious adverse reactions in patients who received ONUREG compared with placebo. The most frequent fatal adverse reaction was sepsis. The safety and effectiveness of ONUREG for treatment of myelodysplastic syndromes have not been established. Treatment of patients with myelodysplastic syndromes with ONUREG is not recommended outside of controlled trials.

5.4 Embryo-Fetal Toxicity

Based on the mechanism of action and findings in animals, ONUREG can cause fetal harm when administered to a pregnant woman. Azacitidine administered to pregnant rats via a single intraperitoneal dose less than the recommended human daily dose of oral azacitidine on a mg/m2 basis caused fetal death and anomalies.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Myelosuppression [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Acute Myeloid Leukemia

The safety of ONUREG was evaluated in QUAZAR [see Clinical Studies (14)]. Patients received ONUREG 300 mg (N=236) or placebo (N=233) orally once daily on Days 1 through 14 of each 28-day cycle. Among patients who received ONUREG, 71% were exposed for 6 months or longer, and 49% were exposed for greater than one year. The median duration of exposure to ONUREG was 11.6 months (range: 0.5 to 74.3 months) and the median number of cycles was 12 (range: 1 to 82 cycles).

Serious adverse reactions occurred in 15% of patients who received ONUREG. Serious adverse reactions in ≥ 2% of patients who received ONUREG were pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received ONUREG.

Permanent discontinuation of ONUREG due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ONUREG in > 1% of patients included nausea (2.1%), diarrhea (1.7%), and vomiting (1.3%). Interruptions of ONUREG due to an adverse reaction occurred in 35% of patients. Adverse reactions which required an interruption of ONUREG in > 5% of patients included neutropenia (20%), thrombocytopenia (8%), and nausea (6%).

Dose reductions of ONUREG due to an adverse reaction occurred in 14% of patients. Adverse reactions which required a dose reduction in > 1% of patients included neutropenia (6%), diarrhea (3.4%), thrombocytopenia (1.7%), and nausea (1.7%).

The most common (≥ 10%) adverse reactions were nausea, vomiting, diarrhea, fatigue/asthenia, constipation, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, and pain in extremity.

Table 2 summarizes the adverse reactions in QUAZAR.

Clinically relevant adverse reactions that did not meet criteria for inclusion in Table 2 were weight decreased (4%) in patients who received ONUREG.

Neutropenia, thrombocytopenia, and anemia of any grade occurred in 74%, 65%, and 25% of patients who received ONUREG. Table 3 summarizes select Grades 3 or 4 hematological laboratory abnormalities in QUAZAR.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of intravenous or subcutaneous azacitidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hypersensitivity reaction
• Interstitial lung disease
• Tumor lysis syndrome
• Sweet's syndrome (acute febrile neutrophilic dermatosis)
• Necrotizing fasciitis (including fatal cases)
• Differentiation syndrome

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Based on its mechanism of action [see Clinical Pharmacology (12.1)] and findings in animals, ONUREG can cause fetal harm when administered to a pregnant woman. There are no available data on ONUREG use in pregnant women to evaluate for a drug-associated risk. Azacitidine was teratogenic and caused embryo-fetal lethality in animals at doses less than the recommended human daily dose of oral azacitidine on a mg/m2 basis (see Data). Advise pregnant women of the potential risk to the fetus.

The estimated background of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

No reproductive or developmental toxicity studies have been conducted with oral azacitidine.

Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single intraperitoneal injection of 6 mg/m2 azacitidine (at doses less than the recommended human daily dose of oral azacitidine on a mg/m2 basis) on gestation Day 10. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation Day 15 at doses of approximately 3 to 12 mg/m2 (at doses less than the recommended human daily dose on a mg/m2 basis).

In rats, azacitidine was clearly embryotoxic when given an intraperitoneal injection on gestation Days 4 to 8 (postimplantation) at a dose of 6 mg/m2 (at doses less than the recommended human daily dose on a mg/m2 basis), although treatment in the preimplantation period (on gestation Days 1 to 3) had no adverse effect on the embryos. Azacitidine caused multiple fetal abnormalities in rats after a single intraperitoneal dose of 3 to 12 mg/m2 (at doses less than the recommended human daily dose on a mg/m2 basis) given on gestation Days 9, 10, 11, or 12. In this study, azacitidine caused fetal death when administered at 3 to 12 mg/m2 on gestation Days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation Day 9. Fetal anomalies included: CNS anomalies (exencephaly/encephalocele), limb anomalies (micromelia, club foot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities).

8.2 Lactation

Risk Summary

There are no data regarding the presence of azacitidine in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with ONUREG and for 1 week after the last dose.

8.3 Females and Males of Reproductive Potential

ONUREG can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)].

Pregnancy Testing

Pregnancy testing is recommended for females of reproductive potential before starting ONUREG.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose.

Males

Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose.

Infertility

Based on animal data, ONUREG may impair male or female fertility [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

The safety and effectiveness of ONUREG in pediatric patients have not been established.

8.5 Geriatric Use

Of the 238 patients in QUAZAR who received ONUREG, 72% were 65 years of age or older, while 12% were 75 years of age or older. No overall differences in safety or effectiveness of ONUREG were observed between these patients and younger patients.

8.6 Renal Impairment

Monitor patients with severe renal impairment (creatinine clearance [CLcr] 15 to 29 mL/min calculated by Cockcroft-Gault formula) more frequently for adverse reactions and modify the ONUREG dosage for adverse reactions [see Dosage and Administration (2.3)].

No dose adjustment of ONUREG is recommended for patients with mild to severe renal impairment (CLcr 15 to 89 mL/min) [see Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

ONUREG has not been studied in patients with pre-existing severe hepatic impairment (total bilirubin > 3 × ULN).

A recommended dosage of ONUREG has not been established for patients with moderate hepatic impairment (total bilirubin > 1.5 to 3 × ULN).

No dose adjustment of ONUREG is recommended for patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 × ULN and any AST) [see Clinical Pharmacology (12.3)].

11 DESCRIPTION

Azacitidine is a nucleoside metabolic inhibitor with a molecular formula of C8H12N4O5 and a molecular weight of 244 g/mol. The chemical name is: 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one and the chemical structural is:

Azacitidine is a white to off-white solid. Azacitidine was found to be soluble in aqueous media across a pH range from 1.0 to 7.0.

ONUREG (azacitidine) is supplied as film-coated tablets containing 200 mg or 300 mg of azacitidine for oral use. Each core tablet contains the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, and silicified microcrystalline cellulose. The 200 and 300 mg tablet coating contains hypromellose, lactose monohydrate, polyethylene glycol, titanium dioxide, and triacetin. In addition, the 200 mg tablet coating contains iron oxide red and the 300 mg tablet coating contains black iron oxide, iron oxide red, and iron oxide yellow.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Azacitidine is a pyrimidine nucleoside analog of cytidine that inhibits DNA/RNA methyltransferases. Azacitidine is incorporated into DNA and RNA following cellular uptake and enzymatic biotransformation to nucleotide triphosphates.

Incorporation of azacitidine into the DNA of cancer cells in vitro, including acute myeloid leukemia cells, inhibited DNA methyltransferases, reduced DNA methylation and altered gene expression, including re-expression of genes regulating tumor suppression and cell differentiation. Incorporation of azacitidine into the RNA of cancer cells, including leukemic cells, inhibited RNA methyltransferases, reduced RNA methylation, decreased RNA stability and decreased protein synthesis.

Antileukemic activity of azacitidine was demonstrated by reduction of cell viability and induction of apoptosis in AML cell lines in vitro. Azacitidine decreased tumor burden and increased survival in leukemic tumor models in vivo.

12.2 Pharmacodynamics

Greater reduction in global DNA methylation was observed with higher azacitidine plasma exposure in patients with AML administered ONUREG for 14 days of a 28-day cycle.

12.3 Pharmacokinetics

The systemic exposure of azacitidine is approximately dose proportional over the dose range of 120 mg to 600 mg once daily of ONUREG (0.4 to 2 times the recommended dosage). Following a single 300 mg dose of ONUREG, the mean (coefficient of variation [CV%]) Cmax of azacitidine was 145 ng/mL (64%) and the mean AUC of azacitidine was 242 ng h/mL (65%). No accumulation was observed following ONUREG 300 mg once daily.

Absorption

The mean oral bioavailability is approximately 11% relative to subcutaneous administration. The median time to peak plasma concentration of azacitidine is 1 hour.

Effect of Food

A high-fat, high-calorie meal (approximately 800 to 1000 calories, 50% fat) did not affect AUC0-INF and decreased Cmax by 21%.

Distribution

The mean (CV%) apparent volume of distribution (Vz/F) of azacitidine is 881 L (67%). The in vitro serum protein binding of azacitidine is approximately 6% to 12%. The blood-to-plasma ratio is approximately 0.3.

Elimination

The mean (CV%) terminal half-life is approximately 0.5 hours (27%) and the apparent clearance (CL/F) is 1240 L/hour (64%).

Metabolism

Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase.

Excretion

Following the administration of ONUREG 300 mg orally once daily, < 2% of the dose was recovered unchanged in the urine.

Specific Populations

Age (46 years to 93 years), sex, body weight (39.3 kg to 129 kg), mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 × ULN and any AST), and mild to moderate renal impairment (CLcr 30 to 89 mL/min) have no clinically meaningful effect on the pharmacokinetics of oral azacitidine. The effects of race/ethnicity, moderate to severe hepatic impairment (total bilirubin > 1.5 × ULN and any AST), and severe renal impairment (CLcr 15 to 29 mL/min) on the pharmacokinetics of oral azacitidine is unknown.

Severe renal impairment increased azacitidine exposure by approximately 70% after a single or 41% after multiple subcutaneous daily administration.

Drug Interaction Studies

Effect of Gastric Acid Reducing Agents on Azacitidine:

Coadministration of omeprazole (a proton pump inhibitor) with ONUREG increased azacitidine AUC0-INF by 19% and had no effect on Cmax.

In Vitro Studies

Cytochrome P450 (CYP) Enzymes: Azacitidine does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, or CYP2E1 at clinically relevant concentrations. Azacitidine is not an inducer of CYP1A2, CYP2C19, or CYP3A.

Transporter Systems: Azacitidine is not a substrate of P-glycoprotein (P-gp). Azacitidine does not inhibit P-gp, breast cancer resistance protein (BCRP), organic anion transporters (OAT) OAT1 and OAT3, organic anion transporting polypeptides (OATP) OATP1B1 and OATP1B3, or organic cation transporter (OCT) OCT2 at clinically relevant concentrations.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumors of the hematopoietic system in female mice at 2.2 mg/kg (6.6 mg/m2, approximately 4% of the recommended human daily dose of oral azacitidine on a mg/m2 basis) administered intraperitoneal 3 times per week for 52 weeks. An increased incidence of tumors in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with intraperitoneal azacitidine at 2 mg/kg (6 mg/m2, approximately 3% of the recommended human daily dose of oral azacitidine on a mg/m2 basis) once a week for 50 weeks. A tumorigenicity study in rats dosed twice weekly at 15 or 60 mg/m2 (approximately 8% to 32% of the recommended human daily dose of oral azacitidine on a mg/m2 basis) revealed an increased incidence of testicular tumors compared with controls.

The mutagenic and clastogenic potential of azacitidine was tested in in vitro bacterial systems Salmonella typhimurium strains TA100 and several strains of trpE8, Escherichia coli strains WP14 Pro, WP3103P, WP3104P, and CC103; in an in vitro forward gene mutation assay in mouse lymphoma cells and human lymphoblast cells; and in an in vitro micronucleus assay in mouse L5178Y lymphoma cells and Syrian hamster embryo cells. Azacitidine was mutagenic in bacterial and mammalian cell systems. The clastogenic effect of azacitidine was shown by the induction of micronuclei in L5178Y mouse cells and Syrian hamster embryo cells.

Administration of azacitidine by intraperitoneal injection to male mice at 9.9 mg/m2 (at doses less than the recommended human daily dose on a mg/m2 basis) daily for 3 days prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development. Treatment of male rats 3 times per week for 11 or 16 weeks at doses of 15 to 30 mg/m2 (at doses less than the recommended human daily dose on a mg/m2 basis) resulted in decreased weight of the testes and epididymides, decreased sperm counts accompanied by decreased pregnancy rates, and increased loss of embryos in mated females. In a related study, male rats treated for 16 weeks at 24 mg/m2 resulted in an increase in abnormal embryos in mated females when examined on Day 2 of gestation.

14 CLINICAL STUDIES

The efficacy of ONUREG was evaluated in QUAZAR (NCT01757535), a multicenter, randomized, double-blind, placebo-controlled study. Eligible patients were ages 55 years or older, had AML, and were within 4 months of achieving first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with intensive induction chemotherapy. Patients may have received consolidation (see Table 4). Patients were excluded if they were candidates for hematopoietic stem cell transplantation at the time of screening.

A total of 472 patients who completed induction with or without consolidation therapy were randomized 1:1 to receive ONUREG 300 mg (n=238) or placebo (n=234) orally on Days 1 through 14 of each 28-day cycle. Randomization was stratified by age at time of induction therapy (55 to 64 vs. ≥ 65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs. poor risk), prior history of MDS/CMML (yes vs. no), and received consolidation therapy following induction therapy (yes vs. no). Baseline demographic and disease characteristics are shown in Table 4.

The efficacy of ONUREG was established on the basis of overall survival (OS). The trial demonstrated a statistically significant improvement in OS for patients randomized to ONUREG compared to placebo. A subgroup analysis showed consistency in the OS benefit for patients in either CR or CRi. The efficacy results are summarized in Table 5 and Figure 1.

15 REFERENCES

1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

ONUREG tablets are available as:

• 200 mg: pink, oval, film-coated tablets with debossed "200" on one side and "ONU" on the other side.
• 300 mg: brown, oval, film-coated tablets with debossed "300" on one side and "ONU" on the other side.

Table 6 lists the package configurations and strengths.

Storage

• Store bottles at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
  Keep bottle tightly closed.
  Store and dispense in the original bottle (with two desiccant canisters).
• Store blisters at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
  Store in the original aluminum-aluminum blisters.

Handling and Disposal

ONUREG is a hazardous drug. Follow applicable special handling and disposal procedures.1

If powder comes in contact with skin, immediately and thoroughly wash with soap and water. If powder comes in contact with mucous membranes, immediately flush the area with water.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Myelosuppression

Advise patients of the risk of myelosuppression with ONUREG and of the need to monitor complete blood counts before and during treatment [see Warnings and Precautions (5.2)].

Gastrointestinal Toxicity

Advise patients of the risk of gastrointestinal toxicity with ONUREG and of the potential need to use anti-emetic or anti-diarrheal medications during treatment [see Adverse Reactions (6.1)].

Embryo-Fetal Toxicity

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)].

Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose [see Use in Specific Populations (8.3)].

Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose [see Use in Specific Populations (8.3)].

Lactation

Advise women not to breastfeed during treatment with ONUREG and for 1 week after the last dose [see Use in Specific Populations (8.2)].

Administration

Advise patients to take ONUREG with or without food at about the same time each day and how to make up a missed or vomited dose. Advise patients to swallow tablets whole. Advise patients not to cut, crush, or chew the tablets [see Dosage and Administration (2.2)].

Storage Instructions

Advise patients to keep ONUREG in the original container (bottles or blisters). If bottles are dispensed, advise patients to keep the container tightly closed with both desiccant canisters inside and to not eat the desiccant canisters [see How Supplied/Storage and Handling (16)].

Manufactured by:
Celgene Corporation
A Wholly Owned Subsidiary of Bristol-Myers Squibb
86 Morris Avenue
Summit, NJ 07901

ONUREG® is a registered trademark of Celgene Corporation.

© 2020 Celgene Corporation.

All Rights Reserved.

ONUPI.003

PRINCIPAL DISPLAY PANEL - 200 mg Bottle Label

NDC 59572-730-14

ONUREG™
(azacitidine) tablets

200 mg

Swallow tablets whole.
Do not cut, crush, or chew the tablets.

Rx only
14 Tablets

CAUTION: Hazardous Agent

PRINCIPAL DISPLAY PANEL - 200 mg Blister Card

NDC 59572-730-07
Rx only

ONUREG™
(azacitidine) tablets

200 mg

Each tablet contains 200 mg of azacitidine.

One Blister Card
Containing 7 Tablets
CAUTION: Hazardous Agent

Celgene

PRINCIPAL DISPLAY PANEL - 200 mg Blister Pack

NDC 59572-730-07
Rx only

ONUREG™
(azacitidine) tablets

200 mg

Each tablet contains 200 mg of azacitidine.
Swallow tablets whole. Do not cut, crush, or chew the tablets.

One Blister Card
Containing 7 Tablets
CAUTION: Hazardous Agent

Celgene

LIFT HERE
TO OPEN

PRINCIPAL DISPLAY PANEL - 200 mg Blister Pack Carton

NDC 59572-730-07
Rx only

ONUREG™
(azacitidine) tablets

200 mg

Each tablet contains 200 mg of azacitidine.

Swallow tablets whole. Do not cut, crush, or chew the tablets.

One Blister Card
Containing 7 Tablets

Celgene

CAUTION: Hazardous Agent

PRINCIPAL DISPLAY PANEL - 300 mg Bottle Label

NDC 59572-740-14

ONUREG™
(azacitidine) tablets

300 mg

Swallow tablets whole.
Do not cut, crush, or chew the tablets.

Rx only
14 Tablets

CAUTION: Hazardous Agent

PRINCIPAL DISPLAY PANEL - 300 mg Blister Card

NDC 59572-740-07
Rx only

ONUREG™
(azacitidine) tablets

300 mg

Each tablet contains 300 mg of azacitidine.

One Blister Card
Containing 7 Tablets
CAUTION: Hazardous Agent

Celgene

PRINCIPAL DISPLAY PANEL - 300 mg Blister Pack

NDC 59572-740-07
Rx only

ONUREG™
(azacitidine) tablets

300 mg

Each tablet contains 300 mg of azacitidine.
Swallow tablets whole. Do not cut, crush, or chew the tablets.

One Blister Card
Containing 7 Tablets
CAUTION: Hazardous Agent

Celgene

LIFT HERE
TO OPEN

PRINCIPAL DISPLAY PANEL - 300 mg Blister Pack Carton

NDC 59572-740-07
Rx only

ONUREG™
(azacitidine) tablets

300 mg

Each tablet contains 300 mg of azacitidine.

Swallow tablets whole. Do not cut, crush, or chew the tablets.

One Blister Card
Containing 7 Tablets

Celgene

CAUTION: Hazardous Agent

【备注】以上内容仅供参考，不作为用药依据，详情请参照药品附带说明书。