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Omontys(peginesatide)注射剂使用说明书2010年第一版
批准日期：2012年3月27日；公司： Affymax, Inc.和Takeda Pharmaceutical Company Limited
FDA的药物评价和研究中心血液学和肿瘤学办公室主任Richard Pazdur, M.D.说：“Omontys 代表自2001年后为这种情况被FDA-批准和上市的第一个新红细胞生成-刺激药物 ，” “这个新药提供患者和卫生保健提供者the 接受红细胞生成-刺激药物治疗的便利一个月仅一次替代更频繁注射。”
处方资料：http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202799s000lbl.pdf

处方资料重点
这些重点不包括安全和有效使用OMONTYS®所需所有资料。请参阅下文为OMONTYS的完整处方资料
OMONTYS® (peginesatide)注射液，为静脉或皮下使用
美国初始批准：2012年
适应证和用途
OMONTYS是一种红细胞生成-刺激药物(ESA)适用于在成年由于慢性肾病(CKD)用透析患者中治疗贫血(1.1)。
使用的限制
对于以下情况不适用OMONTYS和不推荐使用：
（1）有慢性肾病 不在透析患者 (1.2).
（2）为癌症接受治疗患者和其贫血不是由于慢性肾病 (1.2).
（3）需要立即纠正贫血患者作为对RBC输注替代物(1.2).
（4）OMONTYS未曾显示改善症状，身体功能或健康-相关生活质量。(1.2).

剂量和给药方法
（1）初始治疗：0.04 mg/kg体重每月给药1次 (2.3).
（2）从另一种红细胞生成-刺激药物转换：在转换时剂量每周1次根据每周重组人类促红细胞生成素[epoetin]或阿法达贝泊汀[darbepoetin alfa]总剂量(2.4)。

剂型和规格
禁忌证
（1）未控制高血压 (4).

警告和注意事项
（1）增加死亡率，心肌梗死，卒中，和血栓栓塞：使用各种红细胞生成-刺激药物至目标血红蛋白水平大于11 g/dL增加的风险严重不良心血管反应和未曾显示提供梁歪效益(5.1)。在有共存心血管疾病和卒中患者中使用应谨慎 (5.1).
（2）高血压：开始前和用OMONTYS治疗期间控制高血压 (5.3).

不良反应
最常见不良事件(≥ 10%)是呼吸困难，腹泻，恶心，咳嗽，和动静脉瘘部位并发症(6)。

为报告怀疑不良反应，联系Affymax, Inc.公司电话1-855-466-6689或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.

特殊人群中使用
（1）哺乳母亲：当OMONTYS给予哺乳妇女应谨慎对待(8.3)。
（2）儿童使用：尚未确定在儿童患者中OMONTYS 的 安全性和疗效(8.4)。

完整处方资料

1 适应证和用途
1.1 贫血 由于慢性肾病
OMONTYS® 是适用于成年正在透析患者中由于慢性肾病(CKD)贫血的治疗。
1.2 使用的限制
OMONTYS不适用和不建议使用：
（1）不进行透析慢性肾病患者因为在此人群安全性担忧[见警告和注意事项(5.1)]。
（2）接受癌症治疗和不是由于慢性肾病贫血患者，因为在某些情况中曾显示各种红细胞生成-刺激药物危害和尚未评价OMONTYS在这个情况中获益-风险因子[见警告和注意事项(5.2)]。
（3）作为需要立即纠正贫血输注RBC的替代。
（4）未曾显示OMONTYS改善症状，身体功能或健康相关生活质量。
2 剂量和给药方法
2.1 铁贮备和营养因子
评价 the铁status在所有患者治疗前和期间评价铁状态和维持铁充足。纠正或排除贫血的其它原因(如，维生素缺乏，代谢性或慢性炎症情况，出血，等) 开始OMONTYS前[见警告和注意事项(5.6)]。
2.2  慢性肾病患者
个体化给药和使用最低剂量的OMONTYS足以减少对RBC输注需求[见警告和注意事项(5.1)]。在对照试验中，当给予各种红细胞生成刺激药物(ESAs)达到目标血红蛋白水平大于11 g/dL，患者经受死亡，严重不良心血管反应，和卒中更大风险。未曾鉴定血红蛋白目标水平，红细胞生成-刺激药物剂量，或给药战略不增加这些风险的试验。医生和患者应权衡减少输血可能的获益和死亡和其它严重心血管不良事件风险的增加[见框警告和临床研究 (14)]。
2.3 初始治疗和开始剂量
当血红蛋白水平小于10 g/dL时开始OMONTYS治疗。.
对当前没有用一种红细胞生成-刺激药物治疗患者中对治疗贫血建议的开始剂量是0.04 mg/kg体重单次静脉或皮下注射每月1次给药。
2.4 正在透析慢性肾病患者从重组人类促红细胞生成素[epoetin]α或阿法达贝泊汀转换至OMONTYS
OMONTYS是每月给药1次，或皮下或静脉。
在既往患者接受重组人类促红细胞生成素[epoetin]α或阿法达贝泊汀，在重组人类促红细胞生成素[epoetin]α或阿法达贝泊汀每周剂量基础上估算在替代时对患者OMONTYS的每月开始剂量(见表1)。保持给药途径(静脉或皮下注射).
（1）对既往接受重组人类促红细胞生成素[epoetin]α患者，OMONTYS的首次剂量应在末次重组人类促红细胞生成素[epoetin]α剂量给药在一周后给予。
（2）对既往接受阿法达贝泊汀患者，OMONTYS的首次剂量应在下一次计划阿法达贝泊汀剂量时替代之。
2.5 一般指导原则包括剂量调整
监视血红蛋白水平至少每2周直至稳定，然后监视至少每月。当调整治疗时，考虑血红蛋白上升率, 下降率, 红细胞生成-刺激药物反应性和血红蛋白变异性。一个单次血红蛋白偏移可能无需剂量变化。
（1）不要增加剂量比每四周1次更频。
（2）如血红蛋白迅速上升(如，给药前2周超过1 g/dL或四周内多于2 g/dL)，当需要减低迅速反应，减低OMONTYS剂量25%或更多。
（3）如血红蛋白水平接近或超过11 g/dL，减低或中断OMONTYS的给药。一个剂量已保留后和一旦血红蛋白开始减低，可在剂量约低于以前给予剂量约25%重新开始OMONTYS。
（4）对反应不适当的患者如四周治疗血红蛋白没有增加多于1 g/dL ，增加剂量25%。
（5）对当历时12-周剂量递增期反应不适患者，进一步增加OMONTYS剂量不像改善反应和可能增加风险。使用最低剂量将维持血红蛋白水平足以减少RBC输注需求。评价贫血的其它原因。如反应性不改善终止OMONTYS [见警告和注意事项(5.4)]。
（6）如果丢失1次OMONTYS给药，尽可能马上给予丢失剂量和按处方再开始OMONTYS以每月给药1次频度。当治疗透析慢性肾病患者有癌症，医生应参照警告和注意事项(5.1和5.2)。
自身给药OMONTYS患者参考用药指导[见患者咨询资料 (17)]。
2.6 准备和给予OMONTYS
OMONTYS被包装为单次使用小瓶，单次使用预装注射器，和多次使用小瓶。OMONTYS包装在单次使用小瓶和单次使用预装注射器不含防腐剂。OMONTYS或皮下或静脉给药。
（1）使用单次使用小瓶或单次使用预装注射器仅1次。遗弃单次使用小瓶内未使用OMONTYS部分。
（2）贮存多次使用小瓶内未使用部分OMONTYS在36 °F至46 °F(2 °C至8 °C)。首次使用后28天遗弃。
（3）避光保护OMONTYS。用前贮存OMONTYS小瓶或预装注射器在其纸盒。
（4）不要使用如密封纸盒明显削弱被破损或丢失。
（5）不要稀释OMONTYS和不要与其它药物溶液结合给药。
（6）给药前应肉眼观察OMONTYS有无颗粒物质和变色。不要使用表现颗粒物质或除了无色至浅黄色外任何OMONTYS小瓶或预装注射器。
3 剂型和规格
4 禁忌证
在未控制高血压患者中禁忌使用OMONTYS。[见警告和注意事项(5.3)].
5 警告和注意事项
5.1 增加死亡率, 心肌梗死, 卒中,和血栓栓塞
（1）在其它各种红细胞生成-刺激药物对照临床试验，在慢性肾病患者中比较较高目标血红蛋白(13 - 14 g/dL)与较低目标(9 - 11.3 g/dL)(见表2)，观察到在较高目标组中死亡，心肌梗死，卒中，充血性心衰，血液透析血管通路处的血栓形成，和其它血栓栓塞事件的风险增加。
（2）用各种红细胞生成-刺激药物至目标血红蛋白水平大于11 g/dL，严重不良心血管反应风险的增加和未曾显示提供另外获益。有共存心血管疾病和卒中患者中慎用[见剂量和给药方法(2.2)]。有慢性肾病和对红细胞生成-刺激药物治疗血红蛋白反应不充分患者可能比其它患者心血管反应和死亡率风险甚至更大。血红蛋白上升率大于1 g/dL历时2周 可能对这些风险有贡献。
（3）在各种红细胞生成-刺激药物对照临床试验中，有癌症患者, 观察到对死亡和严重不良心血管反应风险增加。这些不良反应包括心肌梗死和卒中。
（4）在对照临床试验，各种红细胞生成-刺激药物中在患者进行冠状动脉旁路移植术(CABG)和深部静脉血栓形成(DVT)观察到在患者进行整形术死亡的风险增加。
表2中显示设计和3项大型试验比较较高和较低目标血红蛋白的总体结果(正常血细胞比容研究(NHS)，在肾功能不全(CHOIR)纠正血红蛋白结局和用Aranesp® 治疗试验对减低心血管事件(TREAT))。
慢性肾病不在用透析患者
OMONTYS不适用和不建议在不正在透析的慢性肾病患者中治疗贫血。
在两项983例由于慢性肾病不在透析贫血患者随机化，阳性-对照，开放，多中心试验中，接受OMONTYS经受一个组合的心血管安全性终点较高百分率患者(22%)与之比较接受阿法达贝泊汀为17%。该试验有一个预先指定，前瞻性分析由死亡，心肌梗死，卒中，或充血性心衰的严重不良事件, 不稳定性心绞痛或心律失常组成一个组合安全性终点 (危害比 1.32, 95% CI: 0.97, 1.81)。
5.2 癌症患者接受各种红细胞生成-刺激药物增加死亡率和/或增加肿瘤进展或复发的风险
OMONTYS不适用和不建议为在癌症患者接受治疗减少RBC输血和患者贫血不是由于慢性肾病，因为在某些情况中曾显示各种红细胞生成-刺激药物危害和尚未在这个情况中评价过OMONTYS的获益-风险因子。
尚未确定由于用化疗癌症患者贫血中使用OMONTYS的安全性和疗效。在由于癌症治疗贫血患者从各种红细胞生成-刺激药物临床试验的结果显示减低局部控制，无进展生存和/或减低总体生存。在各种红细胞生成-刺激药物临床试验观察到这个发现用其他给予患者：乳癌接受化疗, 晚期头和颈部癌接受放疗, l淋巴样恶性病，宫颈癌，非小细胞肺癌，和与各种恶性病是不接受化疗或放疗。
5.3 高血压
在未控制高血压患者中禁忌OMONTYS 。
开始用OMONTYS前和治疗期间适当地控制高血压。如血压变得难以控制减低或不给OMONTYS 忠告患者依从抗高血压治疗和限制饮食的重要性[见患者咨询资料(17)]。
5.4 缺乏或丧失对OMONTYS的反应
对缺乏或丧失对OMONTYS血红蛋白反应，开始寻找所致因素(如，铁缺乏，感染，炎症，出血)。如排除典型引起缺乏或上市血红蛋白反应，评价患者是否存在对peginesatide的抗体。在缺乏对peginesatide抗体，按照对OMONTYS治疗血红蛋白反应不充分患者处理的给药建议[见剂量和给药方法(2.2)]。
联系Affymax, Inc.公司(电话1-855-466-6689)进行结合和中和抗体分析。
5.5 透析处理
开始OMONTYS后患者可能需要调整他们的透析处方。患者接受OMONTYS可能需要增加抗凝作用用肝素预防血液透析期间体外循环的凝固。
5.6 实验室监视
OMONTYS治疗前和期间评价铁传递蛋白饱和度和血清铁蛋白。当血清铁蛋白小于100 μg/L或当血清铁传递蛋白饱和度小于20%时给予补充铁治疗[见剂量和给药方法(2.1)]。慢性肾病患者的大多数红细胞生成-刺激药物疗程期间将需要补充铁。治疗开始后和每次剂量调整后，每2周监视血红蛋白直至血红蛋白稳定和足以RBC输注需求最小化。其后，应至少每月监视血红蛋白提供血红蛋白水平保持稳定。
6 不良反应
在说明书其它章节中更详细讨论观察到的下严重不良反应：
（1）死亡率，心肌梗死，卒中，和血栓栓塞的增加[见警告和注意事项(5.1)]
（2）高血压 [见警告和注意事项(5.3)]
6.1 临床试验经验
因为临床试验是在广泛不同情况下进行的，OMONTYS的临床试验观察到不良反应率不能与另一种药临床试验发生率直接比较而且可能不反映实践中观察到的发生率。
有慢性肾病患者
根据来自1066例用Omontys治疗透析患者两项阳性对照研究和542例用重组人类促红细胞生成素[epoetin]治疗包括938理暴露至少OMONTYS 6个月和825例暴露大于1年的合并数据确定不良反应。ulation for OMONTYS人群是20至93岁，58.5%男性，和高加索，黑人(包括非洲美国人)，和亚裔患者的百分率分别是57.9%，37.4%，和3.1%。中位体重校正的OMONTYS剂量是0.07 mg/kg和113 U/week/kg的重组人类促红细胞生成素[epoetin]。
表3 总结了在用Omontys治疗透析患者中最频发的不良反应(≥ 10%)。
 参加OMONTYS临床研究患者中曾发生癫痫发作。在开始用OMONTYS后头几个月期间，应密切监视血压和前兆性神经学症状的存在。
忠告患者对新发生癫痫发作，前兆性症状，或在癫痫发作频繁变化联系他们的保健医生。
用OMONTYS治疗患者中曾报道过敏反应。终止OMONTYS和给予适当治疗如发生严重过敏反应，或输注-相关反应。
6.2 免疫原性
2357例受试患者中29例(1.2%)有可检测水平的peginesatide-特异性结合抗体。与静脉给药(0.7%)比较，皮下给药患者中peginesatide-特异性结合抗体发生率较高(1.9%)。were detected在体外用一种基于-细胞功能试验在21例这些患者中检出Peginesatide中和抗体(0.9%)。所有抗体-阳性患者约半数中，存在抗体伴随血红蛋白水平下降，需要增加OMONTYS剂量以维持血红蛋白水平，和/或为慢性肾病贫血输血。在临床试验期间接受OMONTYS患者未发生纯红细胞再生障碍(PRCA)病例。
7 药物相互作用
未进行正式药物/药物相互作用研究。如在在大鼠，猴和人血清体外蛋白结合研究中显示Peginesatide不结合至血清白蛋白或脂蛋白。在体外用人肝细胞或微粒体进行研究曾显示peginesatide无诱导或抑制各种CYP450酶的潜能。
8 特殊人群中使用
8.1 妊娠
妊娠类别C
在妊娠妇女中无适当和对照良好研究。当给予妊娠动物在剂量和/或暴露导致红细胞增多症时Peginesatide是致畸胎剂和致死胚胎胎畜。妊娠期间只有如潜在获益合理地大于对胎儿潜在风险时才应使用OMONTYS。
在器官形成期通过静脉注射给予大鼠和兔peginesatide伴随胚胎胎畜毒性和畸形。在大鼠中给药是每第三天给药总共5剂和在兔中每第5天总共3剂(0.01至50 mg/kg/剂)。在大鼠和兔中，不良胚胎胎畜效应包括胎畜体重减轻, 增加再吸收，胚胎胎畜致死，腭裂(仅大鼠)，胸骨异常，胸骨和跖骨未骨化，和有些骨骨化减少。在大鼠中在peginesatide剂量≥ 1 mg/kg胚胎胎畜毒性明显而在剂量 ≥ 10 mg/kg畸形(腭裂和胸骨裂，和血管变异)大多数明显。剂量1 mg/kg导致暴露(AUC)与人中正在透析患者中剂量0.35 mg/kg静脉给药后暴露有可比性。在大鼠中分开的一项胚胎胎畜发育研究，在一个较低剂量0.25 mg/kg见到胎畜体重减轻和骨化减少。在兔中剂量≥ 0.5 mg/kg/剂peginesatide观察到胎畜体重减轻和骨化延长。兔中一项分开胚胎胎畜发育研究，在较低剂量观察到不良发现和包括在0.25 mg/kg融合胸骨发生率增加。在兔中效应是在剂量比患者0.35 mg/kg剂量较低时观察到(5% - 50%)。
8.3 哺乳母亲
不知道peginesatide是否排泄至人乳汁。因为许多药物被排泄至人乳汁，当OMONTYS被给予哺乳妇女时应谨慎对待。
8.4 儿童使用
尚未确定OMONTYS在儿童患者中的安全性和疗效。
8.5 老年人使用
在OMONTYS的3期临床研究透析患者总数之中，32.5%是年龄65岁和以上，而13%是年龄75岁和以上。这些受试者和较年轻受试者间未观察到安全性和有效性的总体差别。
10 药物过量
OMONTYS的药物过量可能升高血红蛋白水平超过想要水平，当临床指示时应该终止或减低OMONTYS剂量和/或用放血处理[见药效动力学(12.2)]。用各种红细胞生成-刺激药物过量后曾观察到严重高血压病例[见警告和注意事项(5.3)]。
11 一般描述
Peginesatide是一种红细胞生成-刺激药物，是一种合成的，聚乙二醇化二聚肽由两个相同的，21-氨基酸链共价结合至一个从亚氨基二乙酸和β-丙氨酸衍生的连接物。Peginesatide以醋酸盐制成。二聚肽(MW约4,900 道尔顿)被共价地连接至一个单一的赖氨酸-分支的双-(甲氧基聚(乙二醇)) (PEG)链(MW约40,000道尔顿)。图1中提供其结构；peginesatide的氨基酸序列与红细胞生成素没有同源性。经验式是C2031H3950N62O958S6 (游离碱)。总分子量是约45,000 道尔顿。
图1.醋酸peginesatide的结构 。

OMONTYS(peginesatide)注射剂是被制剂化成为无菌，无色至浅黄色无防腐剂溶液和一种无菌，无色至浅黄色可保存溶液为静脉或皮下给药。
供应多种强度规格的在小瓶和预装注射器中个单次使用，无防腐剂可注射OMONTYS溶液。每个0.5 mL小瓶或预装注射器含peginesatide，23.5 mg山梨醇，1.5 mg磷酸二氢钠(二水)，0.06 mg磷酸氢二钠，0.02 mg 聚山梨醇20，和注射用水，USP。加入氢氧化钠调节pH。pH值为6.0 ± 0.3。
供应在两种在小瓶中充填体积的多次使用，可保存可注射的OMONTYS溶液：1 mL和2 mL。每mL含10 mg peginesatide，47 mg山梨醇，5 mg苯酚，1.5 mg L-甲硫氨酸，0.6 mg冰醋酸，和注射用水，USP。加入氢氧化钠调节pH。pH值是5.4 ± 0.5。
12 临床药理学
12.1 作用机制
Peginesatide与人红细胞生成素受体结合和激活人人红细胞生成素受体并在体外在人红细胞前体细胞中刺激红细胞生成。.
12.2 药效动力学
Peginesatide增加网织红细胞计数，接着增加血红蛋白。患者中血红蛋白增加的速率变化不一和依赖于给予peginesatide的剂量。
对心脏复极的影响
在一项随机化，双盲，双模拟，三阶段交叉彻底QT研究在56例健康受试者中评价OMONTYS(0.1 mg/kg 静脉ly)对QTc间期的影响。静脉给予剂量0.1 mg/kg与安慰剂比较不延缓心脏复极。在3期试验中剂量0.1 mg/kg 是适当代表中位剂量(0.07 mg/kg)，但是不足以代表在意向患者中较高于0.1 mg/kg。.
12.3 药代动力学
单次静脉和皮下注射在剂量范围从0.03至0.1 mg/kg至透析患者后，血浆峰浓度(Cmax)和血浆浓度时间曲线下面积(AUC)随剂量增加。皮下给药后，达峰时间约48小时。皮下给予peginesatide后的生物利用度约为46%。
在人类中未进行物料平衡研究。临床前放射性标记peginesatide研究表明peginesatide是不被代谢而静脉或皮下给药后尿排泄是主要消除途径。
在健康受试者中静脉给药后平均半衰期是25.0 ± 7.6 小时和皮下给药为53.0 ± 17.7小时。在透析患者中静脉给药后平均半衰期是47.9 ± 16.5 小时。在透析患者中静脉给药后平均全身清除率是0.5 ± 0.2 mL/hr•kg和平均分布容积是34.9 ± 13.8 mL/kg。每四周静脉或皮下给药后未观察到积蓄。根据群体药代动力学分析慢性肾病正在透析患者中Peginesatide的药代动力学不受年龄、性别或种族改变。
13 非临床毒理学
13.1 癌发生，突变发生，生育能力受损
在大鼠中一项2-年研究在剂量至0.25 mg/kg静脉注射给予每3周Peginesatide不是致癌剂。这个剂量在正在透析患者中在剂量0.35 mg/kg人暴露(AUC)的约14%。在一项26-周研究在rasH2 转基因小鼠当静脉注射给予剂量0.1，0.25，或0.5 mg/kg/dose 每3周，Peginesatide不是致癌剂。
在体外Ames试验，在体外哺乳动物染色体畸变试验，和体内小鼠红细胞微核试验，Peginesatide不是致突变剂或致染色体断裂畸变剂。
当peginesatide被静脉每周间隔给予雄性和雌性大鼠在交配前和交配时，和处理大鼠交配，在≥ 0.1 mg/kg (在患者剂量0.35 mg/kg的约5%)生育能力减低和在剂量 ≥ 1.0 mg/kg的peginesatide最为明显。在雄性中不良作用包括精囊和前列腺重量减低。雌性中在≥ 0.1 mg/kg出现活胎减少是由于植入前和后丢失。对动情周期周期和黄体数无药物相关作用。
14 临床研究
在两项随机化，阳性-对照，开放，多中心临床研究，在研究纳入时正在用另一种红细胞生成-刺激药物(重组人类促红细胞生成素[epoetin]α或重组人类促红细胞生成素[epoetin]β)的患者中评价OMONTYS维持血红蛋白浓度，在用透析慢性肾病患者中证实OMONTYS的疗效和安全性。对每项研究主要疗效终点是血红蛋白从基线至评价阶段(第29至36周)变化，用一种非劣效性与重组人类促红细胞生成素[epoetin]比较。在研究1中，患者接受重组人类促红细胞生成素[epoetin]通过静脉途径给药和随机化后继续使用这个途径至或OMONTYS或重组人类促红细胞生成素[epoetin]任何一种治疗。对OMONTYS平均患者暴露年[PEY]每患者是1.14年和对重组人类促红细胞生成素[epoetin]平均PEY每患者是1.25年。在研究2中，对重组人类促红细胞生成素[epoetin]既往所用给药途径(静脉或皮下)。对OMONTYS平均PEY每患者为1.17年和对重组人类促红细胞生成素[epoetin]平均PEY每患者是1.16年。OMONTYS的中位剂量是0.07 mg/kg每月给药1次和重组人类促红细胞生成素[epoetin]中位给药剂量为113 单位/kg 每周给药(在1至3剂)。
患者被随机化2比1)接受OMONTYS每月1次，或继续用其当前红细胞生成-刺激药物治疗1至3次每周。OMONTYS起始剂量是根据在筛选阶段末周期间患者的总体每周红细胞生成-刺激药物剂量，如表4中所示，用OMONTYS治疗每月1次和用重组人类促红细胞生成素[epoetin]治疗每周1-3次维持血红蛋白浓度在研究预先指定的血红蛋白范围(10至12 g/dL)以内。在两项研究中，在各个治疗组中接受输血患者比例相似。
研究1和2 有一个预先指定，前瞻性，合并分析的组合心血管安全性终点由死亡，心肌梗死，卒中，或充血性心脏衰竭严重不良事件，不稳定性心绞痛或心律不齐组成。在接受OMONTYS患者中，22.8% 经受这些事件之一，与之比较接受重组人类促红细胞生成素[epoetin]为24.4% (危害比0.95，95% CI 0.77, 1.17)。

16 如何供应/贮存和处置
16.1 如何供应
可得到在单次使用小瓶单次使用预装注射器，和多次使用小瓶的OMONTYS。对各种强度规格的小瓶盖帽和预装注射器的芯用独特衍生指定。单次使用预装注射器与27号，½ 英寸针供应。
为减低应用后意外针扎的风险，每个单次使用预装注射器装配有安全设备在剂量已给予时激活和盖住针。
可以得到以下包装大小的OMONTYS：
16.2 稳定性和贮存
建议的贮存温度是冰箱在2 °C至8 °C (36 °F至46 °F)。避光保护。用前保存在 纸盒内。
单次使用小瓶，单次使用预装注射器或多次使用小瓶的贮存历时建议的温度(2 °C至8 °C)，当需要时，只允许温度至25 °C(77 °F)和不超过30 天。
在第一次使用时， 多次使用小瓶应贮存在2 °C 至8 °C，和然后28天后遗弃。.
17 患者咨询资料
见FDA-批准的患者使用说明书(用药指南).
治疗前。告知患者OMONTYS的风险和获益.
告知患者：
（1）阅读用药指南和复习和开始用OMONTYS前和在常规间隔当接受OMONTYS时，与他们的卫生保健提供者讨论任何问题或担忧。
（2）死亡率, 严重心血管反应，血栓栓塞反应，卒中，和肿瘤进展的风险增加[见警告和注意事项(5.1, 5.2)]。
（3）进行常规血压监视，坚持处方抗高血压方案和遵循建议的饮食限制。
（4）对新发生神经学症状或在癫痫发作频繁变化联系他们的卫生保健提供者。
（5）对血红蛋白需要常规实验室测试.
在一名卫生保健提供者直接监督下给予OMONTYS或，在患者曾受训练在家给予OMONTYS情况中，提供指导关于适当使用OMONTYS，包括指导以下：
（1）仔细复习用药指南和为使用指导
（2）避免再次使用各种针，注射器，或单次使用小瓶或单次使用预装注射器未使用的OMONTYS部分和适当遗弃这些。
（3）为了遗弃使用过的注射器和针头经常保持可以得到防针刺遗弃容器。

 

 

Omontys

Generic Name: peginesatide
Dosage Form: injection solution

Medically reviewed on December 1, 2017

 

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE

Chronic Kidney Disease:

· In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.

· No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks [see Warnings and Precautions (5.1)].

· Use the lowest Omontys dose sufficient to reduce the need for red blood cell (RBC) transfusions [see Warnings and Precautions (5.1)].

 

 

 

 

Indications and Usage for OmontysAnemia Due to Chronic Kidney Disease

Omontys® is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis.

Limitations of Use

Omontys is not indicated and is not recommended for use:

· In patients with CKD not on dialysis because of safety concerns in this population [see Warnings and Precautions (5.1)].

· In patients receiving treatment for cancer and whose anemia is not due to CKD, because ESAs have shown harm in some settings and the benefit-risk factors for Omontys in this setting have not been evaluated [see Warnings and Precautions (5.2)].

· As a substitute for RBC transfusions in patients who require immediate correction of anemia.

· Omontys has not been shown to improve symptoms, physical functioning or health-related quality of life.

 

 

 

Omontys Dosage and AdministrationEvaluation of Iron Stores and Nutritional Factors

Evaluate the iron status in all patients before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating Omontys [see Warnings and Precautions (5.7)].

 

 

 

Patients with Chronic Kidney Disease

Individualize dosing and use the lowest dose of Omontys sufficient to reduce the need for RBC transfusions [see Warnings and Precautions (5.1)]. In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events [see Boxed Warning and Clinical Studies (14)].

Initiation of Treatment and Starting Dose

Initiate Omontys treatment when the hemoglobin level is less than 10 g/dL.

The recommended starting dose for the treatment of anemia in patients who are not currently treated with an ESA is 0.04 mg/kg body weight administered as a single intravenous or subcutaneous injection once monthly.

Conversion from Epoetin Alfa or Darbepoetin Alfa to Omontys in Patients with CKD on Dialysis

Omontys is administered once monthly, either subcutaneously or intravenously.

In patients previously receiving epoetin alfa or darbepoetin alfa, estimate the starting monthly dose of Omontys for patients on the basis of the weekly dose of epoetin alfa or darbepoetin alfa at the time of substitution (see Table 1). Maintain the route of administration (intravenous or subcutaneous injection).

· For patients previously receiving epoetin alfa, the first dose of Omontys should be administered one week after the last epoetin alfa dose was administered.

· For patients previously receiving darbepoetin alfa, the first dose of Omontys should be administered at the next scheduled dose in place of darbepoetin alfa.

Table 1 Estimated Omontys Starting Doses for Patients Based on Previous Weekly ESA Dose
Previous Total Weekly Epoetin Alfa Dose (U/week)	Previous Weekly Darbepoetin Alfa Dose (mcg/week)	Omontys Dose Once Monthly (mg/month)
Less than 2,500	Less than 12	2
2,500 to less than 4,300	12 to less than 18	3
4,300 to less than 6,500	18 to less than 25	4
6,500 to less than 8,900	25 to less than 35	5
8,900 to less than 13,000	35 to less than 45	6
13,000 to less than 19,000	45 to less than 60	8
19,000 to less than 33,000	60 to less than 95	10
33,000 to less than 68,000	95 to less than 175	15
greater than or equal to 68,000	greater than or equal to 175	20

General Guidance including Dose Adjustments

Monitor hemoglobin levels at least every 2 weeks until stable, then monitor at least monthly. When adjusting therapy, consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.

· Do not increase the dose more frequently than once every 4 weeks.

· If the hemoglobin rises rapidly (e.g., more than 1 g/dL in the 2 weeks prior to the dose or more than 2 g/dL in 4 weeks), reduce the dose of Omontys by 25% or more as needed to reduce rapid responses.

· If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Omontys. After a dose has been withheld and once the hemoglobin begins to decrease, Omontys may be restarted at a dose approximately 25% below the previously administered dose.

· For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.

· For patients who do not respond adequately over a 12-week escalation period, increasing the Omontys dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Omontys if responsiveness does not improve [see Warnings and Precautions (5.5)].

· If a dose of Omontys is missed, administer the missed dose as soon as possible and restart Omontys at the prescribed once monthly dosing frequency.

When treating dialysis patients who have chronic kidney disease and cancer, physicians should refer to Warnings and Precautions (5.1 and 5.2).

Refer patients who self-administer Omontys to the Instructions for Use [see Patient Counseling Information (17)].

Preparation and Administration of Omontys

Omontys is packaged as single use vials, single use pre-filled syringes, and multiple use vials. Omontys packaged in single use vials and single use pre-filled syringes contains no preservatives. Omontys is administered either subcutaneously or intravenously.

· Use the single use vial or single use pre-filled syringe only one time. Discard unused portion of Omontys in single use vials.

· Store unused portions of Omontys in multiple use vials at 36 °F to 46 °F (2 °C to 8 °C). Discard 28 days after first use.

· Protect Omontys from light. Store Omontys vials or pre-filled syringes in their cartons until time of use.

· Do not use if tamper-evident seal on carton is broken or missing.

· Do not dilute Omontys and do not administer in conjunction with other drug solutions.

· Omontys should be inspected visually for particulate matter and coloration prior to administration. Do not use any vials or pre-filled syringes of Omontys exhibiting particulate matter or a coloration other than colorless to slightly yellow.

Dosage Forms and Strengths

Dosage Form	Strengths
Single use vials (preservative-free)	2 mg/0.5 mL, 3 mg/0.5 mL, 4 mg/0.5 mL, 5 mg/0.5 mL, and 6 mg/0.5 mL
Single use pre-filled syringes (preservative-free)	1 mg/0.5 mL, 2 mg/0.5 mL, 3 mg/0.5 mL, 4 mg/0.5 mL, 5 mg/0.5 mL, and 6 mg/0.5 mL
Multiple use vials (with preservative)	10 mg/mL and 20 mg/2 mL

Contraindications

Omontys is contraindicated in patients with:

· Uncontrolled hypertension [see Warnings and Precautions (5.3)].

· Serious allergic reactions to Omontys which may include anaphylaxis [see Warnings and Precautions (5.4)].

Warnings and PrecautionsIncreased Mortality, Myocardial Infarction, Stroke, and Thromboembolism

· In controlled clinical trials of other ESAs in patients with CKD comparing higher hemoglobin targets (13 - 14 g/dL) to lower targets (9 - 11.3 g/dL) (see Table 2), increased risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events was observed in the higher target groups.

· Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke [see Dosage and Administration (2.2)]. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.

· In controlled clinical trials of ESAs in patients with cancer, increased risk for death and serious adverse cardiovascular reactions was observed. These adverse reactions included myocardial infarction and stroke.

· In controlled clinical trials, ESAs increased risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and deep venous thrombosis (DVT) was observed in patients undergoing orthopedic procedures.

The design and overall results of 3 large trials comparing higher and lower hemoglobin targets are shown in Table 2 (Normal Hematocrit Study (NHS), Correction of Hemoglobin Outcomes in Renal Insufficiency (CHOIR) and Trial to Reduce Cardiovascular Events with Aranesp® Therapy (TREAT)).

Table 2 Adverse Cardiovascular Outcomes in Randomized Controlled Trials Comparing Higher and Lower Hemoglobin Targets in Patients with CKD
	NHS (N = 1265)	CHOIR (N = 1432)	TREAT (N = 4038)
Time Period of Trial	1993 to 1996	2003 to 2006	2004 to 2009
Population	Patients with CKD on hemodialysis with coexisting CHF or CAD, hematocrit 30 ± 3% on epoetin alfa	Patients with CKD not on dialysis with hemoglobin < 11 g/dL not previously administered epoetin alfa	Patients with CKD not on dialysis with type II diabetes, hemoglobin ≤ 11 g/dL
Hemoglobin Target; Higher vs. Lower (g/dL)	14.0 vs. 10.0	13.5 vs. 11.3	13.0 vs. ≥ 9.0
Median (Q1, Q3) Achieved Hemoglobin level (g/dL)	12.6 (11.6, 13.3) vs. 10.3 (10.0, 10.7)	13.0 (12.2, 13.4) vs. 11.4 (11.1, 11.6)	12.5 (12.0, 12.8) vs. 10.6 (9.9, 11.3)
Primary Endpoint	All-cause mortality or non-fatal MI	All-cause mortality, MI, hospitalization for CHF, or stroke	All-cause mortality, MI, myocardial ischemia, heart failure, and stroke
Hazard Ratio or Relative Risk (95% CI)	1.28 (1.06 - 1.56)	1.34 (1.03 - 1.74)	1.05 (0.94 - 1.17)
Adverse Outcome for Higher Target Group	All-cause mortality	All-cause mortality	Stroke
Hazard Ratio or Relative Risk (95% CI)	1.27 (1.04 - 1.54)	1.48 (0.97 - 2.27)	1.92 (1.38 - 2.68)

Patients with Chronic Kidney Disease Not on Dialysis

Omontys is not indicated and is not recommended for the treatment of anemia in patients with CKD who are not on dialysis.

A higher percentage of patients (22%) who received Omontys experienced a composite cardiovascular safety endpoint event compared to 17% who received darbepoetin alfa in two randomized, active-controlled, open-label, multi-center trials of 983 patients with anemia due to CKD who were not on dialysis. The trials had a pre-specified, prospective analysis of a composite safety endpoint consisting of death, myocardial infarction, stroke, or serious adverse events of congestive heart failure, unstable angina or arrhythmia (hazard ratio 1.32, 95% CI: 0.97, 1.81).

Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence in Patients with Cancer receiving ESAs

Omontys is not indicated and is not recommended for reduction of RBC transfusions in patients receiving treatment for cancer and whose anemia is not due to CKD because ESAs have shown harm in some settings and the benefit-risk factors for Omontys in this setting have not been evaluated.

The safety and efficacy of Omontys have not been established for use in patients with anemia due to cancer chemotherapy. Results from clinical trials of ESAs in patients with anemia due to cancer therapy showed decreased locoregional control, progression-free survival and/or decreased overall survival. The findings were observed in clinical trials of other ESAs administered to patients with: breast cancer receiving chemotherapy, advanced head and neck cancer receiving radiation therapy, lymphoid malignancy, cervical cancer, non-small cell lung cancer, and with various malignancies who were not receiving chemotherapy or radiotherapy.

Hypertension

Omontys is contraindicated in patients with uncontrolled hypertension.

Appropriately control hypertension prior to initiation of and during treatment with Omontys. Reduce or withhold Omontys if blood pressure becomes difficult to control. Advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions [see Patient Counseling Information (17)].

Serious Allergic Reactions

Serious allergic reactions, including anaphylactic reactions, hypotension, bronchospasm, angioedema and generalized pruritus, may occur in patients treated with Omontys. Immediately and permanently discontinue Omontys and administer appropriate therapy if a serious allergic reaction occurs.

Lack or Loss of Response to Omontys

For lack or loss of hemoglobin response to Omontys, initiate a search for causative factors (e.g., iron deficiency, infection, inflammation, bleeding). If typical causes of lack or loss of hemoglobin response are excluded, evaluate the patient for the presence of antibodies to peginesatide. In the absence of antibodies to peginesatide, follow dosing recommendations for management of patients with an insufficient hemoglobin response to Omontys therapy [see Dosage and Administration (2.2)].

Contact Affymax, Inc. (1-855-466-6689) to perform assays for binding and neutralizing antibodies.

Dialysis Management

Patients may require adjustments in their dialysis prescriptions after initiation of Omontys. Patients receiving Omontys may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.

Laboratory Monitoring

Evaluate transferrin saturation and serum ferritin prior to and during Omontys treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20% [see Dosage and Administration (2.1)]. The majority of patients with CKD will require supplemental iron during the course of ESA therapy. Following initiation of therapy and after each dose adjustment, monitor hemoglobin every 2 weeks until the hemoglobin is stable and sufficient to minimize the need for RBC transfusion. Thereafter, hemoglobin should be monitored at least monthly provided hemoglobin levels remain stable.

Adverse Reactions

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

· Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism [see Warnings and Precautions (5.1)].

· Hypertension [see Warnings and Precautions (5.3)].

· Serious allergic reactions [see Warnings and Precautions (5.4)]

Clinical Trials Experience

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

Patients with Chronic Kidney Disease

Adverse reactions were determined based on pooled data from two active controlled studies of 1066 dialysis patients treated with Omontys and 542 treated with epoetin, including 938 exposed for at least 6 months and 825 exposed for greater than one year to Omontys. The population for Omontys was 20 to 93 years of age, 58.5% male, and the percentages of Caucasian, Black (including African Americans), and Asian patients were 57.9%, 37.4%, and 3.1%, respectively. The median weight adjusted dose of Omontys was 0.07 mg/kg and 113 U/week/kg of epoetin.

Table 3 summarizes the most frequent adverse reactions (≥ 10%) in dialysis patients treated with Omontys

Table 3 Adverse Reactions Occurring in ≥ 10% of Dialysis Patients treated with Omontys
Adverse Reactions	Dialysis Patients Treated with Omontys (N = 1066)	Dialysis Patients Treated with Epoetin (N = 542)
Gastrointestinal Disorders
Diarrhea	18.4%	15.9%
Nausea	17.4%	19.6%
Vomiting	15.3%	13.3%
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea	18.4%	19.4%
Cough	15.9%	16.6%
Injury, Poisoning and Procedural Complications
Arteriovenous Fistula Site Complication	16.1%	16.6%
Procedural Hypotension	10.9%	12.5%
Nervous System Disorders
Headache	15.4%	15.9%
Musculoskeletal and Connective Tissue Disorders
Muscle Spasms	15.3%	17.2%
Pain in Extremity	10.9%	12.7%
Back Pain	10.9%	11.3%
Arthralgia	10.7%	9.8%
Vascular Disorders
Hypotension	14.2%	14.6%
Hypertension	13.2%	11.4%
General Disorders and Administration Site Conditions
Pyrexia	12.2%	14.0%
Metabolism and Nutrition Disorders
Hyperkalemia	11.4%	11.8%
Infections and Infestations
Upper Respiratory Tract          Infection	11.0%	12.4%

Seizures have occurred in patients participating in Omontys clinical studies. During the first several months following initiation of Omontys, blood pressure and the presence of premonitory neurologic symptoms should be monitored closely.

Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms, or change in seizure frequency.

Allergic and infusion-related reactions have been reported in patients treated with Omontys.

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious allergic reactions have been reported during postmarketing use of Omontys [see Warnings and Precautions (5.4)].

Immunogenicity

Of the 2357 patients tested during clinical trials, 29 (1.2%) had detectable levels of peginesatide-specific binding antibodies. There was a higher incidence of peginesatide-specific binding antibodies in patients dosed subcutaneously (1.9%) as compared to those dosed intravenously (0.7%). Peginesatide neutralizing antibodies were detected in vitro using a cell-based functional assay in 21 of these patients (0.9%). In approximately half of all antibody-positive patients, the presence of antibodies was associated with declining hemoglobin levels, the requirement for increased doses of Omontys to maintain hemoglobin levels, and/or transfusion for anemia of CKD. No cases of pure red cell aplasia (PRCA) developed in patients receiving Omontys during clinical trials.

Drug Interactions

No formal drug/drug interaction studies have been performed. Peginesatide does not bind to serum albumin or lipoproteins as demonstrated in in vitro protein binding studies in rat, monkey and human sera. In vitro studies conducted with human hepatocytes or microsomes have shown no potential for peginesatide to induce or inhibit CYP450 enzymes.

USE IN SPECIFIC POPULATIONSPregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Peginesatide was teratogenic and caused embryofetal lethality when administered to pregnant animals at doses and/or exposures that resulted in polycythemia. Omontys should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Administration of peginesatide by intravenous injection to rats and rabbits during organogenesis was associated with embryofetal toxicity and malformations. Dosing was every third day in rats for a total of 5 doses and every fifth day in rabbits for a total of 3 doses (0.01 to 50 mg/kg/dose). In rats and rabbits, adverse embryofetal effects included reduced fetal weight, increased resorption, embryofetal lethality, cleft palate (rats only), sternum anomalies, unossification of sternebrae and metatarsals, and reduced ossification of some bones. Embryofetal toxicity was evident in rats at peginesatide doses of ≥ 1 mg/kg and the malformations (cleft palate and sternoschisis, and variations in blood vessels) were mostly evident at doses of ≥ 10 mg/kg. The dose of 1 mg/kg results in exposures (AUC) comparable to those in humans after intravenous administration at a dose of 0.35 mg/kg in patients on dialysis. In a separate embryofetal developmental study in rats, reduced fetal weight and reduced ossification were seen at a lower dose of 0.25 mg/kg. Reduced fetal weight and delayed ossification in rabbits were observed at ≥ 0.5 mg/kg/dose of peginesatide. In a separate embryofetal developmental study in rabbits, adverse findings were observed at lower doses and included increased incidence of fused sternebrae at 0.25 mg/kg. The effects in rabbits were observed at doses lower (5% - 50%) than the dose of 0.35 mg/kg in patients.

Nursing Mothers

It is not known whether peginesatide is excreted in human milk. Because many drugs are excreted into human milk, caution should be exercised when Omontys is administered to a nursing woman.

Pediatric Use

The safety and efficacy of Omontys in pediatric patients have not been established.

Geriatric Use

Of the total number of dialysis patients in Phase 3 clinical studies of Omontys, 32.5% were age 65 and over, while 13% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Overdosage

Omontys overdosage can elevate hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of Omontys dosage and/or with phlebotomy, as clinically indicated [see Pharmacodynamics (12.2)]. Cases of severe hypertension have been observed following overdose with ESAs [see Warnings and Precautions (5.3)].

Omontys Description

Peginesatide is an ESA that is a synthetic, pegylated dimeric peptide comprised of two identical, 21-amino acid chains covalently bonded to a linker derived from iminodiacetic acid and β-alanine. Peginesatide is manufactured as an acetate salt. The dimeric peptide (approximate MW 4,900 daltons) is covalently linked to a single lysine-branched bis-(methoxypoly(ethylene glycol)) (PEG) chain (approximate MW 40,000 daltons). The structure is provided in Figure 1; peginesatide has no amino acid sequence homology to erythropoietin. The empirical formula is C2031H3950N62O958S6 (free base). The total molecular weight is approximately 45,000 daltons.

Figure 1: Structure of peginesatide acetate

Omontys (peginesatide) Injection is formulated as a sterile, colorless to slightly yellow preservative-free solution and a sterile, colorless to slightly yellow preserved solution for intravenous or subcutaneous administration.

Single use, preservative-free injectable solutions of Omontys in vials and pre-filled syringes are supplied in multiple strengths. Each 0.5 mL vial or pre-filled syringe contains peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH. The pH is 6.0 ± 0.3.

Multiple use, preserved injectable solutions of Omontys in vials are supplied in two fill volumes: 1 mL and 2 mL. Each mL contains 10 mg peginesatide, 47 mg sorbitol, 5 mg phenol, 1.5 mg L-methionine, 0.6 mg glacial acetic acid, and water for injection, USP. Sodium hydroxide added to adjust pH. The pH is 5.4 ± 0.5.

Omontys - Clinical PharmacologyMechanism of Action

Peginesatide binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in vitro.

Pharmacodynamics

Peginesatide increases the reticulocyte count, followed by increases in hemoglobin. The rate of hemoglobin increase varies among patients and is dependent upon the dose of peginesatide administered.

Effect on Cardiac Repolarization

The effect of Omontys (0.1 mg/kg intravenously) on QTc interval was evaluated in a randomized, double-blind, double-dummy, three-period crossover thorough QT study in 65 healthy subjects. A dose of 0.1 mg/kg administered intravenously did not delay cardiac repolarization compared to placebo. The dose of 0.1 mg/kg is adequate to represent the median dose (0.07 mg/kg) in the phase 3 trials, however is not sufficient to represent doses higher than 0.1 mg/kg in the intended patients.

Pharmacokinetics

Following single intravenous and subcutaneous injections at doses ranging from 0.03 to 0.1 mg/kg to dialysis patients, maximal plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increase with dose. Following subcutaneous administration, the maximum concentrations of peginesatide are reached in approximately 48 hours. The bioavailability of peginesatide following subcutaneous administration is approximately 46%.

No mass balance study has been conducted in humans. Preclinical radiolabeled peginesatide study indicated that peginesatide is not metabolized and that urinary excretion was the predominant route of elimination following either intravenous or subcutaneous dosing.

The mean half-life is 25.0 ± 7.6 hours following intravenous administration and 53.0 ± 17.7 hours following subcutaneous administration in healthy subjects. The mean half-life in dialysis patients is 47.9 ± 16.5 hours following intravenous administration. Mean systemic clearance is 0.5 ± 0.2 mL/hr•kg and mean volume of distribution is 34.9 ± 13.8 mL/kg following intravenous administration in dialysis patients. No accumulation is observed following administration every 4 weeks following intravenous or subcutaneous administration. The pharmacokinetics of peginesatide in patients with CKD on dialysis are not altered by age, gender or race based on population pharmacokinetic analyses.

Nonclinical ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility

Peginesatide was not carcinogenic in a 2-year study in rats at doses up to 0.25 mg/kg administered every 3 weeks by intravenous injection. This dose is approximately 14% the human exposure (AUC) at a dose of 0.35 mg/kg in patients on dialysis. Peginesatide was not carcinogenic in a 26-week study in rasH2 transgenic mice when administered by intravenous injection at doses of 0.1, 0.25, or 0.5 mg/kg/dose every 3 weeks.

Peginesatide was not mutagenic or clastogenic in the in vitro Ames assay, in vitro mammalian chromosome aberration assay, and an in vivo mouse erythrocyte micronucleus assay.

When peginesatide was administered intravenously to male and female rats at weekly intervals prior to and during mating, and treated rats mated, fertility was reduced at ≥ 0.1 mg/kg (approximately 5% of the dose of 0.35 mg/kg in patients) and was most evident at doses ≥ 1.0 mg/kg of peginesatide. Adverse effects in males included reduced weight of seminal vesicles and prostate. Decreased viable fetuses at ≥ 0.1 mg/kg in females appeared to be due to pre- and post-implantation losses. There was no apparent drug-related effect on estrous cycles or number of corpora lutea.

Clinical Studies

The efficacy and safety of Omontys in patients with CKD on dialysis were demonstrated in two randomized, active-controlled, open-label, multi-center clinical studies that evaluated Omontys in the maintenance of hemoglobin concentrations in patients who were being treated with another ESA (epoetin alfa or epoetin beta) at the time of study entry. The primary efficacy endpoint for each study was the change in hemoglobin from Baseline to the Evaluation Period (Weeks 29 to 36) using a non-inferiority comparison with epoetin. In Study 1, patients received epoetin via the intravenous route of administration and continued to use this route after randomization to either Omontys or epoetin. The average patient exposure year [PEY] per patient was 1.14 years for Omontys and the average PEY per patient was 1.25 years for epoetin. In Study 2, the route of administration previously used for epoetin (intravenous or subcutaneous) was used. The average PEY per patient was 1.17 years for Omontys and the average PEY per patient was 1.16 years for epoetin. The median dose of Omontys was 0.07 mg/kg administered once monthly and the median dose of epoetin was 113 units/kg administered weekly (in 1 to 3 doses).

Patients were randomized (2 to 1) to receive Omontys once monthly, or to continue on their current ESA treatment 1 to 3 times per week. The Omontys starting dose was based on the patient's total weekly ESA dose during the last week of the screening period. As shown in Table 4, treatment with Omontys once monthly and treatment with epoetin 1-3 times per week maintained hemoglobin concentrations within the study pre-specified hemoglobin range (10 to 12 g/dL). In both studies, the proportion of patients receiving transfusions was similar in each treatment group.

Table 4: Clinical Studies in Dialysis Patients
Group (N)	Mean baseline Hemoglobin	Change from Baseline to Weeks 29-36	Between group difference, Least Squares Mean g/dL (95% CI)
Study 1
Omontys (524)	11.3 g/dL	-0.24 g/dL	-0.15 g/dL (-0.30, -0.01)
Epoetin (269)	11.3 g/dL	-0.09 g/dL
Study 2
Omontys (542)	11.2 g/dL	-0.07 g/dL	0.10 g/dL (-0.05, 0.26)
Epoetin (273)	11.2 g/dL	-0.17 g/dL

Studies 1 and 2 had a pre-specified, prospective, pooled analysis of a composite cardiovascular safety endpoint consisting of death, myocardial infarction, stroke, or serious adverse events of congestive heart failure, unstable angina or arrhythmia. In patients receiving Omontys, 22.8% experienced one of these events compared to 24.4% receiving epoetin (hazard ratio 0.95, 95% CI 0.77, 1.17).

How Supplied/Storage and HandlingHow Supplied

Omontys is available in single use vials, single use pre-filled syringes, and multiple use vials. The vial caps and plungers of the pre-filled syringes are designated with unique colors for each dosage strength. The single use pre-filled syringes are supplied with a 27 gauge, ½ inch needle. To reduce the risk of accidental needle sticks after application, each single use pre-filled syringe is equipped with a safety device that activates and covers the needle once the dose has been given.

Omontys is available in the following pack sizes:

Single use vials	Single use pre-filled syringes with a 27 gauge, ½ inch needle with an UltraSafe Passive® Needle Guard	Multiple use vials
1 Vial/Carton	1 Syringe/Carton	1 Vial/Carton
2 mg/0.5 mL (NDC 64764-602-05)	1 mg/0.5 mL (NDC 64764-601-99)	10 mg/mL (NDC 64764-610-10)
3 mg/0.5 mL (NDC 64764-603-05)	2 mg/0.5 mL (NDC 64764-602-99)	20 mg/2 mL (NDC 64764-620-20)
4 mg/0.5 mL (NDC 64764-604-05)	3 mg/0.5 mL (NDC 64764-603-99)
5 mg/0.5 mL (NDC 64764-605-05)	4 mg/0.5 mL (NDC 64764-604-99)
6 mg/0.5 mL (NDC 64764-606-05)	5 mg/0.5 mL (NDC 64764-605-99)
	6 mg/0.5 mL (NDC 64764-606-99)

Stability and Storage

The recommended storage temperature is refrigerated at 2 °C to 8°C (36°F to 46°F). Protect from light. Retain in carton until time of use.

Storage of single use vials, single use pre-filled syringes or multiple use vials over the recommended temperature (2°C to 8°C), when necessary, is permissible only for temperatures up to 25°C (77°F) and for no more than 30 days.

After first use, the multiple use vials should be stored at 2 °C to 8 °C, and then discarded after 28 days.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide).

Prior to treatment, inform patients of the risks and benefits of Omontys.

Inform patients:

· To read the Medication Guide and to review and discuss any questions or concerns with their healthcare provider before starting Omontys and at regular intervals while receiving Omontys.

· Of the increased risks of mortality, serious cardiovascular reactions, thromboembolic reactions, stroke, and tumor progression [see Warnings and Precautions (5.1, 5.2)].

· To undergo regular blood pressure monitoring, adhere to prescribed anti-hypertensive regimen and follow recommended dietary restrictions.

· To seek medical care immediately if they experience any symptoms of an allergic reaction with use of Omontys [see Warnings and Precautions (5.4)].

· To contact their healthcare provider for new-onset neurologic symptoms or change in seizure frequency.

· Of the need to have regular laboratory tests for hemoglobin.

Administer Omontys under the direct supervision of a healthcare provider or, in situations where a patient has been trained to administer Omontys at home, provide instruction on the proper use of Omontys, including instructions to:

· Carefully review the Medication Guide and the Instructions for Use

· Avoid the reuse of needles, syringes, or unused portions of the Omontys single use vials or single use pre-filled syringes and properly dispose of these items

· Always keep a puncture-proof disposal container available for the disposal of used syringes and needles.

Marketed by:

Affymax, Inc.
Palo Alto, CA 94304

Distributed and Marketed by:

Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. registered in the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.

All other trademarks are the property of their respective owners.

PEG096 R3

 

 

 

 

 

Instructions for Use

Omontys® (O-mon-tis)

(peginesatide)

Injection

Single use vials

Multiple use vials

Use these instructions if you or your caregiver has been trained to give Omontys injections at home. Do not give yourself the injection unless you have received training from your healthcare provider. If you are not sure about giving the injection or if you have questions, ask your healthcare provider for help.

Before reading these Instructions for Use, read the Medication Guide that comes with Omontys for the most important information you need to know.

When you receive your Omontys vial and syringes, make sure that:

· The name Omontys appears on the carton and vial label.

· The tamper evident seal on the carton is not damaged. Do not use if the tamper evident seal on carton is broken or missing.

· Omontys is used before the expiration date on the vial label. Do not use Omontys on or after the expiration date on the label.

· The dose strength of the Omontys vial (number of mg (milligrams) per mL (milliliter) on the vial label) is the same as your healthcare provider prescribed.

· You understand what the dose strength of Omontys means. Omontys vials come in different dose strengths. For example, the dose strength may be described as 10 mg/mL on the vial label. This means that there is 10 mg of medicine in each 1 mL of liquid. Your healthcare provider may also refer to a mL as a “cc”. One mL is the same as one “cc”.

· The Omontys liquid in the vial is clear and colorless to slightly yellow. Do not use Omontys if the liquid in the vial looks discolored or cloudy, or if the liquid has lumps, flakes or particles.

· The Omontys vial has a colored cap on the top of the vial of Omontys. Do not use the vial of Omontys if the colored cap has been removed or is missing.

· Use only the type of disposable syringe and needle that your healthcare provider has prescribed.

· Keep Omontys away from light. Store Omontys vials in their cartons in the refrigerator between 36 °F to 46 °F (2 °C to 8 °C) until time of use.

· Single-use vials of Omontys should be used only one time. Dispose of the vial after one use even if there is medicine left in the vial.

· After removing a dose from the multiple use vial, store the vial in the refrigerator (but not in the freezer) in its carton to protect from light. Do not store the vial for more than 28 days.

· Store unused portion of Omontys in the multiple use vials in the refrigerator between 36 °F to 46 °F (2 °C to 8 °C).

· Throw away the multiple use vial as directed by your healthcare provider if it has been more than 28 days since you first put a needle into the multiple use vial.

How should I prepare for an injection of Omontys?

Your healthcare provider should show you how to give the correct dose of Omontys:

· Always keep an extra syringe and needle on hand.

· Follow your healthcare provider’s instructions on how to measure your dose of Omontys.

· Only use disposable syringes and needles that your healthcare provider prescribed. If you do not use the correct syringe, you could inject too much or too little Omontys.

· Be sure you know which line on the syringe matches the dose of Omontys that your healthcare provider prescribed. Use a syringe and needle only one time and then dispose of them as instructed by your healthcare provider.

What do I need to know about the different types of Omontys vials?

Omontys comes in two different types of vials.

· Single use vials

· Multiple use vials

Important: Follow these instructions exactly to help avoid infections.

1. Prepare a clean, flat work surface.

2. Gather the supplies you will need for an injection (see Figure A). You will need:

o Omontys vial and the correct disposable syringe and needle

o Alcohol wipes and cotton ball or gauze

o Puncture-proof disposable container for safely disposing of the needle and syringe after injection

3. Take a carton of Omontys from the refrigerator.

4. Take the vial of Omontys out of its carton and place it on your flat work surface.

5. Check the date on the Omontys vial to be sure that the medicine has not expired.

6. Do not use a single use vial of Omontys more than one time.

7. Wash your hands well with soap and warm water before preparing the dose (see Figure B).

Preparing the dose of Omontys

1. Remove the protective flip-off colored cap from the vial. Leave the rubber stopper on the vial (see Figure C).

2. Clean the rubber stopper with one alcohol wipe and put the vial on your flat work surface (see Figure D).

3. Check the package containing the disposable syringe. If the syringe package is not damaged, open it and take out the syringe. If the package is damaged or has already been opened, do not use that syringe. Dispose of the syringe in the puncture-proof disposable container and get a new one.

4. Pull off the needle cover carefully (see Figure E). Always use the syringe and needle that has been recommended by your healthcare provider.

5. Pull back on the plunger to the line on the syringe that matches the dose instructions of Omontys that your healthcare provider has given you (see Figure F).

6. Keep the vial on your flat work surface and insert the needle straight through the center of the rubber stopper of the Omontys vial (see Figure G).

7. Push down on the plunger of the syringe to inject the air from the syringe into the vial. The air injected into the vial will allow Omontys to be easily withdrawn into the syringe (see Figure H).

8. Keep the needle inside the vial. Turn the vial upside down. Keep the vial upside down and make sure that the tip of the needle remains below the surface of the Omontys liquid. Slowly pull back on the plunger to fill the syringe with Omontys liquid to the number (mL or cc) on the syringe that matches the dose your healthcare provider has given you (see Figure I).

9. Keep the needle in the vial. Check for air bubbles in the syringe. Small air bubbles are harmless, but too large an air bubble will not let you draw up the right amount of Omontys.

. To remove air bubbles, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe.

i. Slowly push on the plunger to push the air bubbles out of the syringe and back into the vial (see Figure J).

ii. If you have pushed any liquid back into the vial, pull the plunger back slowly to the line on the syringe that matches your dose while making sure the tip of the needle is below the surface the liquid. Check again for air bubbles. If there are still air bubbles, remove them by repeating Step 8 (see Figure K).

1. Check again to make sure you have the right dose. Put the vial on its side with the needle still in it. This will keep the needle from touching anything before you use it (see Figure L).

Selecting and preparing the injection site:

Omontys can be injected into your body using two different ways (routes) as described below. Follow your healthcare provider’s instructions about how you should inject Omontys.

Subcutaneous Route:

Omontys can be injected under your skin. This is called a subcutaneous injection. When giving subcutaneous injections, follow your healthcare provider’s instructions about changing the site for each injection.

1. Choose one injection site from those shown in Figure M. The four sites where you can inject Omontys include:

o The outer area of the upper arms

o The front of the middle thighs

o The abdomen (except for the two inch area around the navel)

o The upper outer area of the buttocks

Do not inject Omontys into an area on your body that is tender, red, bruised, hard, or that has scars or stretch marks.

2.

Clean the injection site with an alcohol wipe. Do not touch this area again before giving the injection (see Figure N).

3.

Check that the correct amount of Omontys is in the syringe.

4.

Remove the prepared syringe and needle from the vial of Omontys and hold it in the hand that you will use to inject the medicine. Use the other hand to pinch a fold of skin at the cleaned injection site. Do not touch the cleaned area of skin (see Figure O).

5.

Hold the syringe like you would hold a pencil. Insert the needle in a quick “dart like” motion. Insert the needle either at a slight angle (45 degree angle) or straight up and down (90 degree angle) into the skin. Inject the prescribed dose by pushing the plunger all the way down as directed by your healthcare provider, nurse or pharmacist (see Figure P).

6.

Pull the needle out of your skin. Do not recap the needle. Place a cotton ball or gauze over the injection site and press gently for several seconds. Do not rub (see Figure Q).

7.

Dispose of the used syringe and needle as described below. Do not reuse the syringes and needles.

Intravenous Route:

· Omontys can be injected in your vein through a special access port on the dialysis tubing while dialysis is underway. This type of Omontys injection is called an intravenous injection. This route is usually for hemodialysis patients.

· If you have a hemodialysis vascular access, make sure it is working by checking it as your healthcare provider has shown you. Be sure to let your healthcare provider know right away if you are having any problems, or if you have any questions.

Peritoneal Dialysis Patients: If you are a peritoneal dialysis patient, administer Omontys only by subcutaneous route under your skin (See Subcutaneous Route section above)

1. Clean the venous port of the hemodialysis tubing with an alcohol wipe (see Figure R).

2. Insert the needle of the syringe into the cleaned venous port and push the plunger all the way down to inject all the Omontys (see Figure S).

3. Remove the syringe from the venous port. Do not recap the needle. Dispose of the syringe and needle as described below.

How should I dispose of vials, syringes and needles?

Do not reuse the single-use vials, syringes, or needles. Follow the required state and local laws for disposal of needles and syringes. Ask your healthcare provider or pharmacist about correct disposal of used vials, syringes and needles.

Use the information below as a general guideline:

· Do not put the needle cover back on the needle.

· Place all used needle and syringes in the puncture-proof disposable container with a lid.

· Dispose of the full puncture-proof disposable container as instructed by your healthcare provider or pharmacist.

· Do not dispose of the vial, needle, syringe, or disposable container in the household trash or recycle.

· Do not use glass or clear plastic containers to dispose of the needle and syringe.

· Keep the puncture-proof disposable container out of the reach of children. Do not recycle.

· When the puncture-proof disposable container is full, tape around the cap or lid to make sure the cap or lid does not come off. Throw away the puncture-proof disposable container as instructed by your healthcare provider.

Keep Omontys and all medicines out of reach of children.

These Instructions for Use have been approved by the U.S. Food and Drug Administration.

Marketed by:

Affymax, Inc.

Palo Alto, CA 94304

Distributed and Marketed by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

PEG098 R1 March 2012

 

 

 

 

 

Instructions for Use

Omontys® (O-mon-tis)

(peginesatide)

Injection

Single Use Pre-filled Syringe

Use these instructions if you or your caregiver has been trained to give Omontys injections at home. Do not give yourself the injection unless you have received training from your healthcare provider. If you are not sure about giving the injection or if you have questions, ask your healthcare provider for help.

Before reading these Instructions for Use, read the Medication Guide that comes with Omontys for the most important information you need to know.

When you receive your Omontys pre-filled syringe, make sure that:

· The name Omontys appears on the carton and pre-filled syringe label.

· The tamper evident seal on the carton is not damaged. Do not use if the tamper evident seal on carton is broken or missing.

· Omontys is used before the expiration date on the pre-filled syringe label. Do not use Omontys on or after the expiration date on the label.

· The amount of Omontys on the pre-filled syringe label matches the amount prescribed (the number of mg (milligrams) per mL (milliliter)) by your healthcare provider.

· The Omontys liquid in the pre-filled syringe is clear and colorless to slightly yellow. Do not use Omontys if the liquid in the syringe looks discolored or cloudy, or if the liquid has lumps, flakes or particles.

· Store Omontys in the refrigerator between 36 °F to 46 °F (2 °C to 8 °C).

· Keep Omontys away from light. Store Omontys pre-filled syringes in their cartons until time of use.

How should I prepare for an injection of Omontys?

· Your healthcare provider should show you how to give the correct dose of Omontys.

· Use the pre-filled syringe only one time and dispose of it as instructed by your healthcare provider.

Important: Follow these instructions exactly to help avoid infections.

1. Prepare a clean, flat work surface.

2. Gather the supplies you will need for an injection (see Figure A). You will need:

o Omontys pre-filled syringe

o Alcohol wipes and cotton ball or gauze

o Puncture-proof disposable container for safely disposing of the pre-filled syringe after injection

3. Take a carton of Omontys from the refrigerator.

4. Take the pre-filled syringe of Omontys out of its carton and place it on your flat work surface. Do not remove from wrapper at this point.

5. Use a pre-filled syringe only one time.

6. Wash your hands well with soap and warm water before preparing the dose (see Figure B).

Preparing the dose of Omontys

1. Open the wrapper and remove the pre-filled syringe from the tray.

o Check to see that the needle cover is on and the needle guard is covering only the barrel of the syringe (see Figure C).

o If the needle guard is covering the needle, then it has already been activated (see Figure D). Do not use that syringe. Dispose of the syringe in the puncture-proof disposable container. Use a new pre-filled syringe.

2. Hold the syringe with the needle pointing up to prevent the Omontys from leaking out of the needle. Pull the needle cover straight off (see Figure E).

3. Check the syringe for air bubbles. If there are air bubbles, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. Slowly push the plunger up to force the air bubbles out of the syringe (see Figure F).

4. When you put the syringe down on your flat work surface, be careful not to let the needle touch anything (see Figure G).

Selecting and preparing the injection site

Omontys can be injected into your body using two different ways (routes) as described below. Follow your healthcare provider’s instructions about how you should inject Omontys.

Subcutaneous Route:

Omontys can be injected under your skin. This is called a subcutaneous injection. When giving subcutaneous injections, follow your healthcare provider’s instructions about changing the site for each injection.

1. Choose one injection site from those shown in Figure H. The four sites where you can inject Omontys include:

o The outer area of the upper arms

o The front of the middle thighs

o The abdomen (except for the two-inch area around the navel)

o The upper outer area of the buttocks

Do not inject Omontys into an area on your body that is tender, red, bruised, hard, or that has scars or stretch marks.

2.

Clean the injection site with an alcohol wipe. Do not touch this area again before giving the injection (see Figure I).

3.

Hold the pre-filled syringe in the hand that you will use to inject Omontys. Use the other hand to pinch a fold of skin at the cleaned injection site. Do not touch the cleaned area of skin (see Figure J).

4.

Hold the pre-filled syringe like you would hold a pencil between the thumb and fore finger with the syringe resting on the middle finger (see Figure K).

5.

Insert the needle in a quick “dart like” motion. Insert the needle either at a slight angle (45 degree angle) or straight up and down (90 degree angle) into the skin. Inject the prescribed dose subcutaneously as directed by your healthcare provider, nurse or pharmacist (see Figure L). The plunger must be fully depressed during injection in order for the needle guard (a safety mechanism to prevent accidental needle sticks) to activate.

6.

Take the needle out of the skin without releasing the plunger. Let go of the plunger after removing the needle from the skin to allow the syringe to move up until the entire needle is guarded and locks into place (see Figure M).

7.

Place a cotton ball or gauze over the injection site and press gently for several seconds. Do not rub (see Figure N).

8.

Dispose of the used pre-filled syringe as described below. Use the pre-filled syringe one time only.

Intravenous Route:

· Omontys can be injected in your vein through a special access port on the dialysis tubing while dialysis is underway. This type of Omontys injection is called an intravenous injection. This route is usually for hemodialysis patients.

· If you have a hemodialysis vascular access, make sure it is working by checking it as your healthcare provider has shown you. Be sure to let your healthcare provider know right away if you are having any problems, or if you have any questions.

Peritoneal Dialysis Patients: If you are a peritoneal dialysis patient, administer Omontys only by subcutaneous route under your skin (See subcutaneous route section above)

1. Clean the venous port of the hemodialysis tubing with a new alcohol wipe (see Figure O).

2. Insert the needle of the pre-filled syringe into the cleaned venous port and push the plunger all the way down to inject all the medicine (see Figure P). The plunger must be fully depressed during injection in order for the needle guard (a safety mechanism to prevent accidental needle sticks) to activate.

3. Remove the syringe from the venous port without releasing the plunger. Then, let go of the plunger to allow the syringe to move up until the entire needle is guarded and locks into place.

4. Dispose of the used pre-filled syringe as described below. Use the pre-filled syringe one time only.

How should I dispose of pre-filled syringes?

Do not reuse the single use pre-filled syringe. Follow the required state and local laws for disposal of needles and syringes. Ask your healthcare provider or pharmacist about correct disposal of used pre-filled syringes.

Use the information below as a general guideline:

· Do not put the needle cover back on the needle.

· Place all used pre-filled syringes in the puncture-proof disposable container with a lid.

· Dispose of the full puncture-proof disposable container as instructed by your healthcare provider or pharmacist.

· Do not dispose of the pre-filled syringe or disposable container in the household trash or recycle.

· Do not use glass or clear plastic containers to dispose of pre-filled syringes.

· Keep the puncture-proof disposable container out of the reach of children. Do not recycle.

· When the puncture-proof disposable container is full, tape around the cap or lid to make sure the cap or lid does not come off. Throw away the puncture-proof disposable container as instructed by your healthcare provider.

Keep Omontys and all medicines out of reach of children.

These Instructions for Use have been approved by the U.S. Food and Drug Administration.

Marketed by:

Affymax, Inc.

Palo Alto, CA 94304

Distributed and Marketed by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

PEG099 R1 March 2012

 

 

 

 

 

MEDICATION GUIDE

Omontys® (O-mon-tis)

(peginesatide)

Injection

Read this Medication Guide:

· before you start Omontys.

· if you are told by your healthcare provider that there is new information about Omontys.

· if you are told by your healthcare provider that you may inject Omontys at home, read this Medication Guide each time you receive a new supply of medicine.

This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment. Talk with your healthcare provider regularly about the use of Omontys and ask if there is new information about Omontys.

What is the most important information I should know about Omontys?

Using Omontys or other erythropoiesis-stimulating agents (ESAs) can lead to serious side effects including death.

· If you decide to take Omontys, your healthcare provider should prescribe the smallest dose of Omontys that is needed to reduce your chance of needing red blood cell transfusions.

· You may get serious heart problems such as heart attack, stroke, heart failure, and may die sooner if you are treated with Omontys to reach a normal or near-normal hemoglobin level.

· You may get blood clots while receiving Omontys. If you are receiving Omontys and you are going to have surgery, talk to your healthcare provider about whether or not you need to take a blood thinner to lessen the chance of blood clots during or following surgery. Clots can form in blood vessels (veins), especially in your leg (deep venous thrombosis or DVT). Pieces of a blood clot may travel to the lungs and block the blood circulation in the lungs (pulmonary embolus).

Call your healthcare provider or get medical help right away if you have any of these symptoms of blood clots:

· Chest pain

· Trouble breathing or shortness of breath

· Pain in the legs, with or without swelling

· A cool or pale arm or leg

· Sudden confusion, trouble speaking, or understanding others’ speech

· Sudden numbness or weakness of the face, arm, or leg, especially on one side of your body

· Sudden trouble seeing

· Sudden trouble walking, dizziness, loss of balance or coordination

· Loss of consciousness (fainting)

· Hemodialysis vascular access stops working.

See “What are the possible side effects of Omontys?” below.

What is Omontys?

Omontys is a prescription medicine that works like the human protein erythropoietin. Omontys is given to treat anemia (low red blood cells) in adults with chronic kidney disease (CKD) who are on dialysis.

Omontys stimulates your bone marrow to make more red blood cells. Having more red blood cells raises your hemoglobin level. If your hemoglobin level stays too high or if your hemoglobin goes up too quickly, this may lead to serious health problems which may result in death. These serious health problems may happen even if you take Omontys and do not have an increase in your hemoglobin level.

Omontys should not be used for the treatment of anemia:

· if you have chronic kidney disease (CKD) and are not on dialysis,

· if you are receiving treatment for cancer and your anemia is not caused by CKD,

· in place of emergency treatment for anemia (red blood cell transfusions).

Omontys has not been proven to improve the quality of life, fatigue, or well-being.

It is not known if Omontys is safe and effective in children.

Who should not use Omontys?

Do not use Omontys if you:

· have high blood pressure that is not controlled (uncontrolled hypertension).

· have had a serious allergic reaction to Omontys.

What should I tell my healthcare provider before using Omontys?

Before using Omontys tell your healthcare provider if you:

· have heart disease

· have or develop cancer

· have high blood pressure

· have any history of stroke, blood clot or seizure (convulsion)

· have blood disorders (such as sickle cell anemia or clotting disorders)

· have any other medical conditions

· are pregnant or plan to become pregnant. It is not known if Omontys will harm your unborn baby.

· are breastfeeding or plan to breastfeed. It is not known if Omontys passes into your breast milk.

Tell your healthcare provider about all of the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of your medicines with you and show it to your healthcare provider when you get a new medicine.

How should I use Omontys?

· Continue to follow your healthcare provider’s instructions for diet, dialysis, and medicines, including medicines for high blood pressure, while using Omontys.

· Have your blood pressure checked as instructed by your healthcare provider.

· Your healthcare provider should do blood tests to check your hemoglobin and iron levels before and during your treatment with Omontys.

· Omontys is given one time a month into the vein, through your hemodialysis vascular access (intravenous), or under your skin (subcutaneous).

· Omontys should be given by your healthcare provider. In some cases, your healthcare provider may allow you or your caregiver to give the injections at home.

· If you or your caregiver has been trained to give the injections at home, it is important that you:

o Carefully follow the instructions that your healthcare provider gives you. Be sure that you read, understand, and follow the “Instructions for Use” that come with Omontys.

o Use Omontys exactly as your healthcare provider tells you to. Do not change the dose of Omontys unless told to do so by your healthcare provider.

o Your healthcare provider will show you or your caregiver how much Omontys to use, how to inject it, how often it should be injected and how to safely dispose of the used containers, needles and syringes.

o If you miss a dose of Omontys, call your healthcare provider right away for instructions on what to do.

o If you inject more than the prescribed amount of Omontys, call your healthcare provider right away for instructions on what to do.

What are the possible side effects of Omontys?

Omontys may cause serious side effects, including:

· See “What is the most important information I should know about Omontys?”

· High blood pressure. High blood pressure is a common side effect of Omontys in people with chronic kidney disease. Your blood pressure may go up or be difficult to control with blood pressure medicine while taking Omontys. This can happen even if you have never had high blood pressure before. Your healthcare provider should check your blood pressure often. If your blood pressure does increase, your healthcare provider may prescribe new or more blood pressure medicine.

· Serious allergic reactions. Serious allergic reactions can cause dizziness or fainting because of a drop in blood pressure, trouble breathing, tightness in the chest, swelling around your mouth, tongue or face, or itching all over your body. If you have a serious allergic reaction, stop using Omontys and call your healthcare provider or get emergency medical help right away.

· Antibodies to Omontys. Your body may make antibodies to Omontys. These antibodies can block or lessen your body’s ability to make red blood cells and cause you to have severe anemia. Call your healthcare provider if you have unusual tiredness, lack of energy, dizziness, or fainting. You may need to stop taking Omontys.

The most common side effects of Omontys include:

· shortness of breath

· diarrhea

· nausea

· vomiting

· cough

· problems with your hemodialysis access

· headache

· muscle spasms

· joint, back, leg, or arm pain

· low blood pressure (hypotension)

· fever

· increase in blood potassium level

· upper respiratory infection

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Omontys. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Omontys?

· Keep Omontys in the original package.

· Protect Omontys from light.

· Store Omontys in the refrigerator between 36 °F to 46 °F (2 °C to 8 °C).

· If a refrigerator is not available, Omontys vials and pre-filled syringes can be stored at 77 °F or less (25 °C or less) for up to 30 days.

· Throw away multiple use vials of Omontys no later than 28 days from the first day that you put a needle into the vial.

· Omontys single use vials and pre-filled syringes should be used only one time. Dispose of the single use vial and the pre-filled syringe after use even if there is medicine left in the container.

Keep Omontys and all medicines out of the reach of children.

General Information about the safe and effective use of Omontys

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Omontys for a condition for which it was not prescribed. Do not give Omontys to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Omontys. If you would like more information about Omontys, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Omontys that is written for healthcare professionals.

For more information go to www.Omontys.com or call 1-855-466-6689.

What are the ingredients in Omontys?

Active ingredient: peginesatide

Inactive ingredients:

· Single Use Vials and Single Use Pre-filled Syringes: sorbitol, sodium phosphate monobasic (dihydrate), sodium phosphate dibasic, polysorbate 20, and sodium hydroxide in Water for Injection.

· Multiple Use Vials: sorbitol, phenol, L-methionine, glacial acetic acid, and sodium hydroxide in Water for Injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Marketed by:

Affymax, Inc.

Palo Alto, CA 94304

Distributed and Marketed by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Revised: December 2012

PEG097 R3

 

 

 

 

 

2 mg/0.5 mL Single Use Vial Label

NDC 64764-602-05

Omontys®

(peginesatide) Injection

2 mg/0.5 mL Single Use Vial Only Discard Unused Portion

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L058-01

Lot

Exp

3 mg/0.5 mL Single Use Vial Label

NDC 64764-603-05

Omontys®

(peginesatide) Injection

3 mg/0.5 mL Single Use Vial Only Discard Unused Portion

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L059-01

Lot

Exp

4 mg/0.5 mL Single Use Vial Label

NDC 64764-604-05

Omontys®

(peginesatide) Injection

4 mg/0.5 mL Single Use Vial Only Discard Unused Portion

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L060-01

Lot

Exp

    

5 mg/0.5 mL Single Use Vial Label

NDC 64764-605-05

Omontys®

(peginesatide) Injection

5 mg/0.5 mL Single Use Vial Only Discard Unused Portion

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L061-01

Lot

Exp

6 mg/0.5 mL Single Use Vial Label

NDC 64764-606-05

Omontys®

(peginesatide) Injection

6 mg/0.5 mL Single Use Vial Only Discard Unused Portion

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L062-01

Lot

Exp

2 mg/0.5 mL Single Use Vial Carton Label

NDC 64764-602-05 Rx only

Omontys®

(peginesatide) Injection

Single Use Vial Only

Discard Unused Portion

2 mg/0.5 mL

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Preservative free.

Each 0.5 mL contains 2 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

3 mg/0.5 mL Single Use Vial Carton Label

NDC 64764-603-05 Rx only

Omontys®

(peginesatide) Injection

Single Use Vial Only

Discard Unused Portion

3 mg/0.5 mL

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Preservative free.

Each 0.5 mL contains 3 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

4 mg/0.5 mL Single Use Vial Carton Label

NDC 64764-604-05 Rx only

Omontys®

(peginesatide) Injection

Single Use Vial Only

Discard Unused Portion

4 mg/0.5 mL

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Preservative free.

Each 0.5 mL contains 4 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

5 mg/0.5 mL Single Use Vial Carton Label

NDC 64764-605-05 Rx only

Omontys®

(peginesatide) Injection

Single Use Vial Only

Discard Unused Portion

5 mg/0.5 mL

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Preservative free.

Each 0.5 mL contains 5 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

6 mg/0.5 mL Single Use Vial Carton Label

NDC 64764-606-05 Rx only

Omontys®

(peginesatide) Injection

Single Use Vial Only

Discard Unused Portion

6 mg/0.5 mL

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Preservative free.

Each 0.5 mL contains 6 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

10 mg/ mL Multiple Use Vial Label

NDC 64764-610-10

Omontys®

(peginesatide) Injection

10 mg/mL Multiple Use Vial

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L063-01

Lot

Exp

20 mg/ 2 mL Multiple Use Vial Label

NDC 64764-620-20

Omontys®

(peginesatide) Injection

20 mg/ 2 mL (10 mg/mL) Multiple Use Vial

For Intravenous or Subcutaneous Use Only

Dist. by: Takeda Pharmaceuticals America, Inc.,

Deerfield, IL 60015

L064-01

Lot

Exp

10 mg/mL Multiple Use Vial Carton Label

NDC 64764-610-10 Rx only

Omontys®

(peginesatide) Injection

Multiple Use Vial

10 mg/ mL

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Each mL contains 10 mg peginesatide, 47 mg sorbitol, 5 mg phenol, 1.5 mg L-methionine, 0.6 mg glacial acetic acid, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

20 mg/2 mL Multiple Use Vial Carton Label

NDC 64764-620-20 Rx only

Omontys®

(peginesatide) Injection

Multiple Use Vial

20 mg/ 2 mL

(10 mg/mL)

For Intravenous or

Subcutaneous Use Only

ATTENTION: Dispense enclosed

Medication Guide to each patient.

Sterile.

Each mL contains 10 mg peginesatide, 47 mg sorbitol, 5 mg phenol, 1.5 mg L-methionine, 0.6 mg glacial acetic acid, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

1 mg/0.5 mL Single Use Pre-Filled Syringe Label

NDC 64764-601-99

Omontys®

(peginesatide) Injection

1 mg/0.5 mL

Single Use Pre-Filled Syringe. Discard After One Use.

Dist. by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

L121-01

Lot

Exp

2 mg/0.5 mL Single Use Pre-Filled Syringe Label

NDC 64764-602-99

Omontys®

(peginesatide) Injection

2 mg/0.5 mL

Single Use Pre-Filled Syringe. Discard After One Use.

Dist. by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

L065-01

Lot

Exp

3 mg/0.5 mL Single Use Pre-Filled Syringe Label

NDC 64764-603-99

Omontys®

(peginesatide) Injection

3 mg/0.5 mL

Single Use Pre-Filled Syringe. Discard After One Use.

Dist. by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

L066-01

Lot

Exp

4 mg/0.5 mL Single Use Pre-Filled Syringe Label

NDC 64764-604-99

Omontys®

(peginesatide) Injection

4 mg/0.5 mL

Single Use Pre-Filled Syringe. Discard After One Use.

Dist. by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

L067-01

Lot

Exp

5 mg/0.5 mL Single Use Pre-Filled Syringe Label

NDC 64764-605-99

Omontys®

(peginesatide) Injection

5 mg/0.5 mL

Single Use Pre-Filled Syringe. Discard After One Use.

Dist. by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

L068-01

Lot

Exp

6 mg/0.5 mL Single Use Pre-Filled Syringe Label

NDC 64764-606-99

Omontys®

(peginesatide) Injection

6 mg/0.5 mL

Single Use Pre-Filled Syringe. Discard After One Use.

Dist. by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015

L069-01

Lot

Exp

1 mg/0.5 mL Single Use Pre-Filled Syringe Thermoform Tray Label

Sterile. Preservative free.

Store refrigerated at 2° to 8°C (36° to 46°F).

Protect from light.

KEEP IN CARTON UNTIL TIME OF USE.

Dist. by: Takeda Pharmaceuticals

America, Inc., Deerfield, IL 60015

NDC 64764-601-99 Rx only

Omontys®

(peginesatide) Injection

1 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

X007-01

Lot

Exp

2 mg/0.5 mL Single Use Pre-Filled Syringe Thermoform Tray Label

Sterile. Preservative free.

Store refrigerated at 2° to 8°C (36° to 46°F).

Protect from light.

KEEP IN CARTON UNTIL TIME OF USE.

Dist. by: Takeda Pharmaceuticals

America, Inc., Deerfield, IL 60015

NDC 64764-602-99 Rx only

Omontys®

(peginesatide) Injection

2 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

X002-01

Lot

Exp

3 mg/0.5 mL Single Use Pre-Filled Syringe Thermoform Tray Label

Sterile. Preservative free.

Store refrigerated at 2° to 8°C (36° to 46°F).

Protect from light.

KEEP IN CARTON UNTIL TIME OF USE.

Dist. by: Takeda Pharmaceuticals

America, Inc., Deerfield, IL 60015

NDC 64764-603-99 Rx only

Omontys®

(peginesatide) Injection

3 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

X003-01

Lot

Exp

4 mg/0.5 mL Single Use Pre-Filled Syringe Thermoform Tray Label

Sterile. Preservative free.

Store refrigerated at 2° to 8°C (36° to 46°F).

Protect from light.

KEEP IN CARTON UNTIL TIME OF USE.

Dist. by: Takeda Pharmaceuticals

America, Inc., Deerfield, IL 60015

NDC 64764-604-99 Rx only

Omontys®

(peginesatide) Injection

4 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

X004-01

Lot

Exp

5 mg/0.5 mL Single Use Pre-Filled Syringe Thermoform Tray Label

Sterile. Preservative free.

Store refrigerated at 2° to 8°C (36° to 46°F).

Protect from light.

KEEP IN CARTON UNTIL TIME OF USE.

Dist. by: Takeda Pharmaceuticals

America, Inc., Deerfield, IL 60015

NDC 64764-605-99 Rx only

Omontys®

(peginesatide) Injection

5 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

X005-01

Lot

Exp

6 mg/0.5 mL Single Use Pre-Filled Syringe Thermoform Tray Label

Sterile. Preservative free.

Store refrigerated at 2° to 8°C (36° to 46°F).

Protect from light.

KEEP IN CARTON UNTIL TIME OF USE.

Dist. by: Takeda Pharmaceuticals

America, Inc., Deerfield, IL 60015

NDC 64764-606-99 Rx only

Omontys®

(peginesatide) Injection

6 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

X006-01

Lot

Exp

1 mg/0.5 mL Single Use Pre-Filled Syringe Carton Label

Sterile.

Preservative free.

Each 0.5 mL contains 1 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

NDC 64764-601-99 Rx only

Omontys®

(peginesatide) Injection

1 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

C121-01

2 mg/0.5 mL Single Use Pre-Filled Syringe Carton Label

Sterile.

Preservative free.

Each 0.5 mL contains 2 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

NDC 64764-602-99 Rx only

Omontys®

(peginesatide) Injection

2 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

C064-01

3 mg/0.5 mL Single Use Pre-Filled Syringe Carton Label

Sterile.

Preservative free.

Each 0.5 mL contains 3 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

NDC 64764-603-99 Rx only

Omontys®

(peginesatide) Injection

3 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

C065-01

    

4 mg/0.5 mL Single Use Pre-Filled Syringe Carton Label

Sterile.

Preservative free.

Each 0.5 mL contains 4 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

NDC 64764-604-99 Rx only

Omontys®

(peginesatide) Injection

4 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

C066-01

5 mg/0.5 mL Single Use Pre-Filled Syringe Carton Label

Sterile.

Preservative free.

Each 0.5 mL contains 5 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

NDC 64764-605-99 Rx only

Omontys®

(peginesatide) Injection

5 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

C067-01

6 mg/0.5 mL Single Use Pre-Filled Syringe Carton Label

Sterile.

Preservative free.

Each 0.5 mL contains 6 mg peginesatide, 23.5 mg sorbitol, 1.5 mg sodium phosphate monobasic (dihydrate), 0.06 mg sodium phosphate dibasic, 0.02 mg polysorbate 20, and water for injection, USP. Sodium hydroxide added to adjust pH.

Usual Dosage: See package insert.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light. KEEP IN CARTON UNTIL TIME OF USE.

NDC 64764-606-99 Rx only

Omontys®

(peginesatide) Injection

6 mg/0.5 mL

Single Use Pre-Filled Syringe

Discard After One Use

For Intravenous or Subcutaneous Use Only

ATTENTION: Dispense enclosed Medication Guide to each patient.

Mktd. by:

Affymax, Inc.

Palo Alto, CA 94304

Dist. and Mktd. by:

Takeda Pharmaceuticals America, Inc.

Deerfield, IL 60015

Omontys is a trademark of Affymax, Inc. and used under license by Takeda Pharmaceuticals America, Inc.

Lot

Exp

Product of

C068-01

1 mg/0.5 mL Single Use Pre-Filled Syringe Safety Device Barcode Label

2 mg/0.5 mL Single Use Pre-Filled Syringe Safety Device Barcode Label

3 mg/0.5 mL Single Use Pre-Filled Syringe Safety Device Barcode Label

4 mg/0.5 mL Single Use Pre-Filled Syringe Safety Device Barcode Label

5 mg/0.5 mL Single Use Pre-Filled Syringe Safety Device Barcode Label

6 mg/0.5 mL Single Use Pre-Filled Syringe Safety Device Barcode Label

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-601 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 1 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE   POLYSORBATE 20   SODIUM HYDROXIDE   WATER   SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Packaging # Item Code Package Description   1 NDC:64764-601-99 1 TRAY in 1 CARTON   1   1 SYRINGE, GLASS in 1 TRAY   1   0.5 mL in 1 SYRINGE, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-602 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 2 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE   POLYSORBATE 20   SODIUM HYDROXIDE   WATER   SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Packaging # Item Code Package Description   1 NDC:64764-602-99 1 TRAY in 1 CARTON   1   1 SYRINGE, GLASS in 1 TRAY   1   0.5 mL in 1 SYRINGE, GLASS   2 NDC:64764-602-05 1 VIAL, GLASS in 1 CARTON   2   0.5 mL in 1 VIAL, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-603 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 3 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE   POLYSORBATE 20   SODIUM HYDROXIDE   WATER   SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Packaging # Item Code Package Description   1 NDC:64764-603-99 1 TRAY in 1 CARTON   1   1 SYRINGE, GLASS in 1 TRAY   1   0.5 mL in 1 SYRINGE, GLASS   2 NDC:64764-603-05 1 VIAL, GLASS in 1 CARTON   2   0.5 mL in 1 VIAL, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-604 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 4 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE   POLYSORBATE 20   SODIUM HYDROXIDE   WATER   SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Packaging # Item Code Package Description   1 NDC:64764-604-99 1 TRAY in 1 CARTON   1   1 SYRINGE, GLASS in 1 TRAY   1   0.5 mL in 1 SYRINGE, GLASS   2 NDC:64764-604-05 1 VIAL, GLASS in 1 CARTON   2   0.5 mL in 1 VIAL, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-605 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 5 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE   POLYSORBATE 20   SODIUM HYDROXIDE   WATER   SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Packaging # Item Code Package Description   1 NDC:64764-605-99 1 TRAY in 1 CARTON   1   1 SYRINGE, GLASS in 1 TRAY   1   0.5 mL in 1 SYRINGE, GLASS   2 NDC:64764-605-05 1 VIAL, GLASS in 1 CARTON   2   0.5 mL in 1 VIAL, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-606 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 6 mg  in 0.5 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE   POLYSORBATE 20   SODIUM HYDROXIDE   WATER   SODIUM PHOSPHATE, DIBASIC, ANHYDROUS

Packaging # Item Code Package Description   1 NDC:64764-606-99 1 TRAY in 1 CARTON   1   1 SYRINGE, GLASS in 1 TRAY   1   0.5 mL in 1 SYRINGE, GLASS   2 NDC:64764-606-05 1 VIAL, GLASS in 1 CARTON   2   0.5 mL in 1 VIAL, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-610 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 10 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   METHIONINE   ACETIC ACID   PHENOL   SODIUM HYDROXIDE   WATER

Packaging # Item Code Package Description   1 NDC:64764-610-10 1 VIAL, MULTI-DOSE in 1 CARTON   1   1 mL in 1 VIAL, MULTI-DOSE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Omontys peginesatide injection solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-620 Route of Administration PARENTERAL, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PEGINESATIDE (PEGINESATIDE) PEGINESATIDE 20 mg  in 2 mL

Inactive Ingredients Ingredient Name Strength SORBITOL   METHIONINE   ACETIC ACID   PHENOL   SODIUM HYDROXIDE   WATER

Packaging # Item Code Package Description   1 NDC:64764-620-20 1 VIAL, MULTI-DOSE in 1 CARTON   1   2 mL in 1 VIAL, MULTI-DOSE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA202799 04/23/2012

Labeler - Takeda Pharmaceuticals America, Inc. (830134016)

Registrant - Affymax, Inc. (128062176)

Establishment
Name		Address		ID/FEI		Operations
Baxter Pharmaceutical Solutions, LLC				604719430		MANUFACTURE(64764-601, 64764-602, 64764-603, 64764-604, 64764-605, 64764-606, 64764-610, 64764-620)
Establishment
Name	Address		ID/FEI		Operations
Takeda Pharmaceutical Company Ltd.			695132431		MANUFACTURE(64764-601, 64764-602, 64764-603, 64764-604, 64764-605, 64764-606, 64764-610, 64764-620)

Establishment
Name	Address	ID/FEI	Operations
Packaging Coordinators, LLC		078525133	LABEL(64764-601, 64764-602, 64764-603, 64764-604, 64764-605, 64764-606, 64764-610, 64764-620)

 

Takeda Pharmaceuticals America, Inc.