区域性

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区域性紧急使用授权（EUA）（氯化钠和柠檬酸钠肾替代和区域抗凝药溶液）

卫生服务提供者情况说明书

区域性

（氯化钠和柠檬酸钠肾替代和局部抗凝溶液）用于连续性肾脏替代治疗

仅用于体外

美国紧急使用授权

美国食品药品监督管理局（FDA）已发布紧急使用授权（EUA），以允许紧急使用未经批准的产品Regiocit：一种含有柠檬酸盐的替代溶液，用于体外回路的区域柠檬酸抗凝（RCA）。 Regiocit已被授权在COVID-19大流行期间接受连续性肾脏替代疗法（CRRT）治疗且适合RCA的成年患者紧急使用，作为替代溶液。 Regiocit适用于重症监护环境。 Regiocit可用于连续静脉血液滤过（CVVH）和连续静脉血液透析滤过（CVVHDF）模式。对Regiocit的使用仅限于百特有资格为这些紧急用途管理Regiocit的医疗保健提供者和/或机构。

Regiocit已被FDA授权用于紧急用途。区域性药物未经FDA批准。

仅在存在根据《美国法典》第21条USC§360bbb-3（b）（1）的第564（b）（1）条规定的情况下授权紧急使用Regiocit的声明期间，才授权Regiocit。授权将很快终止或撤销。

EUA的范围如下：

•

仅在接受CRRT治疗且适合RCA的成年患者中，将Regiocit用作替代溶液。

•

仅在重症监护环境中，由持牌医疗保健提供者管理Regiocit。

•

Regiocit仅可在百特医疗保健公司已通过资格并提供了有关Regiocit使用的适当培训的设施中使用。

产品描述

Regiocit是一种无菌替代溶液，旨在用于接受CRRT治疗且适合RCA的成年患者。区域内含有生理浓度的钠（140 mmol / L），氯化物（86 mmol / L）和低浓度的柠檬酸盐（18 mmol / L）。

使用说明

剂量和给药

肾脏替代溶液：不用于直接静脉输注。

对于因急性肾损伤（AKI）而接受CRRT的患者，建议的流出量为20至25 mL / kg / h。这通常需要更高的出水量处方。 Regiocit解决方案的处方必须考虑废水和其他治疗液的流速，患者的除液要求，其他液体输入和输出以及所需的酸碱和电解质平衡。

治疗模式，溶质制剂，流速和治疗时间应由负责管理治疗的医生根据患者的临床状况以及患者的体液，电解质，酸碱和葡萄糖平衡来选择。

根据患者的临床需要规定透析液和替代液的配方和流速。不建议使用含钙的透析液或替代液，因为这些溶液提供的钙可能抵消回路中柠檬酸盐的抗凝作用。

区域溶液的给药速率取决于目标柠檬酸盐剂量和规定的血液流速。将Regiocit溶液的预过滤器输注速率与血流速率挂钩，以达到3 mmol / L的目标血液柠檬酸盐浓度（参见表1）。应当对体外回路的抗凝流速进行滴定，以使过滤后的离子钙浓度在0.25至0.35 mmol / L的范围内。

表1：达到3 mmol / L血液柠檬酸剂量的区域溶液流速

在开始治疗之前，通过调整钙的补充量，患者的全身离子钙浓度应在正常的生理范围内（1.0至1.2 mmol / L）。由于废水的损失，在使用Regiocit期间始终需要单独输注钙。开始治疗时，以4 mmol / h的速度开始输注钙溶液（见表4）。停药后，应根据医生的处方调整或停止钙的注入。

柠檬酸盐也起缓冲剂的作用（由于转化为碳酸氢盐）；必须考虑与其他来源（例如，透析液和/或置换液）进行缓冲液投予的速率有关的区域溶液的输注速率。区域溶液必须与适当浓度的碳酸氢盐的透析溶液/置换溶液一起使用。

监测过滤后血液中的离子钙（iCa），全身性血液iCa和总血钙水平，以及其他实验室和临床参数（例如酸碱平衡和血清电解质），对于根据以下指标指导适当的区域性溶液剂量至关重要所需的抗凝水平。应在基线，开始（或调整）后1小时以及每6小时（见表2）中获取水平。迅速降低的全身离子钙水平是柠檬酸盐积累的早期指标。

必须测量总钙并评估总钙与电离钙的比例。柠檬酸盐的累积导致全身性离子钙水平下降，总钙离子比率增加（总钙离子比率> 2.5）。在柠檬酸盐代谢受损的情况下，需要逐步提高钙的输注速度，以将全身性离子钙浓度维持在预期目标范围内。当记录的总离子钙比> 2.5时，同时报告以下任意一种异常现象会增加柠檬酸盐累积的可能性：

Ø

尽管有足够的钙补偿，但全身iCa浓度仍迅速下降

Ø

pH值快速下降或碱过量下降

Ø

阴离子间隙迅速增加

为了避免代谢性碱中毒，可以使用血气分析来测量酸碱平衡和全身性离子钙。如果怀疑是代谢性碱中毒或柠檬酸盐蓄积，请降低柠檬酸盐剂量，同时允许过滤后的离子钙<0.5 mmol / L。这可以通过降低血液流速以降低总体柠檬酸盐负荷，增加透析液/置换流速（在适用时）以增加柠檬酸盐去除量或降低柠檬酸盐流量以降低柠檬酸盐剂量来实现。透析液溶液中的碳酸氢盐低于或高于22至26 mmol / L的生理范围，增加或降低透析液的流速会影响患者的酸碱状态。

应定期监测血浆钠，镁，钾，葡萄糖和磷酸盐的水平，并根据需要进行补充。

表2总结了RCA治疗期间要监​​测的最重要参数，以及调整选项。

表2：RCA治疗期间的监测和调整

表3提供了基于0.5 mmol / L柠檬酸盐剂量调整的区域溶液流速调整。

表3：基于0.5 mmol / L的柠檬酸盐剂量调整的区域溶液流速调整

表4提供了将全身离子钙水平维持在1.0 mmol / L至1.2 mmol / L之间的建议。

表4：钙输注的滑动比例

警告和注意事项

区域性溶液不含钙，并且由于流出液中与柠檬酸盐结合的钙的损失和/或在系统性柠檬酸盐蓄积的情况下，可能导致系统性离子低钙血症。钙

在使用Regiocit期间需要重新输注，并且必须监测血液中的钙浓度（电离的和总的）。

区域溶液不含镁。由于CRRT流出物的损失，使用Regiocit溶液可能会导致低镁血症。必须监测镁水平，因为可能需要注入镁。

区域溶液不含葡萄糖。服用区域性溶液可能会导致低血糖症。必须定期监测血糖水平。

区域溶液不含钾。在CRRT之前和期间必须监测血清钾浓度。

区域溶液包含柠檬酸盐，这会增加整体缓冲液的负荷。 1摩尔柠檬酸盐的代谢产生3摩尔碳酸氢盐。在治疗期间使用的CRRT液体或其他液体中所含的其他碳酸氢钠（或缓冲液源）可能会增加代谢性碱中毒的风险。如果柠檬酸盐的净施用量超过维持酸碱平衡所必需的速度，则可能发生代谢性碱中毒。如果发生代谢性碱中毒，请降低柠檬酸盐剂量，和/或增加透析液/置换流速（如果适用）或更改CRRT溶液的组成。

如果肝或骨骼肌对柠檬酸的代谢清除受损，则可能发生代谢性酸中毒。如果在使用Regiocit溶液治疗期间出现柠檬酸盐蓄积和/或代谢性酸中毒发展或恶化，则可能需要降低输注速率或停止给药。

肝功能不全的患者可能会破坏柠檬酸盐（碳酸氢盐）的代谢，导致柠檬酸盐的积累。如果将Regiocit溶液用于轻度至中度肝功能不全的患者，则对pH值，电解质，总离子钙与全身离子钙的比率进行定期监测以及全身性离子钙对于避免电解质和/或酸碱失衡很重要。

相对于标准CRRT替代液，区域溶液具有低渗性/低渗性，在脑外伤，脑水肿或颅内压增高的患者中应谨慎使用。

禁忌症

使用Regiocit的禁忌症包括：

•

严重肝功能衰竭

•

肌肉灌注不足的休克

•

对区域性任何成分的超敏反应

报告使用此产品遇到的不良事件或质量问题。

接受Regiocit的医疗机构和处方医疗提供者或其指定人员将跟踪与使用相关的所有药物错误以及所有可能归因于Regiocit的严重不良事件，并且必须使用以下一种方法向FDA报告：

•

在线填写并提交MedWatch表格（www.fda.gov/medwatch/report.htm）

•

通过传真（1-800-FDA-0178）填写并提交FDA表格3500（卫生专业人员）（可通过上面的链接找到此表格）。

如有疑问，请致电1-800-FDA-1088。提交的报告应在“描述事件”问题的开头注明“在EUA下使用Regiocit”，以进行进一步分析。

请致电1-866-888-2472与Baxter Healthcare Corporation联系，或发送电子邮件至global_pharmacovigilance_deerfield@baxter.com

美国FDA已通过一种称为“紧急使用授权”（EUA）的紧急访问机制，向Regiocit提供了在COVID-19大流行期间在ICU治疗患者的服务。卫生和公共服务部长（HHS）声明支持EUA，声明存在的情况足以证明在COVID-19大流行期间紧急使用药物和生物产品是合理的。

根据EUA提供的Regiocit没有经过与FDA批准的产品相同类型的审查。当满足某些标准（包括没有足够的，经过批准的可用替代方法）时，FDA可能会发布EUA。此外，FDA的决定基于现有的全部科学证据，表明有理由相信Regiocit可以有效地用作接受连续肾脏替代疗法（CRRT）治疗且需要局部柠檬酸盐抗凝治疗的成年患者的替代溶液。在2019年冠状病毒病（COVID-19）大流行期间，ICU环境中的体外回路（RCA）的使用以及Regiocit对于此类用途的已知和潜在益处大于Regiocit的已知和潜在风险。

本区域性EUA在COVID-19声明有效期内有效，以证明产品可以紧急使用，除非被终止或撤销（此后可能不再需要产品）。当声明被终止或撤销或产品的批准状态发生更改从而不再需要EUA时，EUA将终止。

可以在Baxter Healthcare的网站上获得此通信和产品信息：

要访问COVID-19资源，产品详细信息，产品使用信息以及全面的Prismaflex控制单元操作手册和PrisMax控制单元操作手册，请访问Baxter Healthcare Accute Therapies网站，网址为http://www.renalacute.com。

FDA的网页还包括指向患者情况说明书和制造商说明的链接，网址为https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#covidtherapeutics。

患者和父母/护理人员紧急区域使用情况说明书（氯化钠和柠檬酸钠肾替代和局部抗凝剂）

您将获得Regiocit：连续性肾脏替代疗法（CRRT）的替代解决方案，该解决方案还可以降低滤网凝结的风险。本情况说明书包含信息，可帮助您了解服用已收到或可能收到的Regiocit的风险和收益。

当前缺少美国食品药品管理局（FDA）批准的可用于提供CRRT的替代解决方案。在美国，Regiocit不是FDA批准的药物。目前，Regiocit已在欧洲和其他国家/地区获得批准。阅读此概况介绍，了解有关Regiocit的信息。如有疑问，请咨询您的医疗保健提供者。您可以选择随时接收或拒绝。

什么是COVID-19？
COVID-19是由一种称为冠状病毒的病毒引起的。以前从未见过这种类型的冠状病毒。该新病毒最早于2019年12月在人们中发现。您可以通过与另一个感染该病毒的人联系来获得COVID-19。

COVID-19的疾病范围从非常轻度（包括一些没有报道的症状）到严重（包括导致死亡的疾病）。尽管到目前为止的信息表明大多数COVID-19疾病是轻度的，但可能会发生严重的疾病，并可能导致您的其他一些疾病恶化。例如，老年人和患有严重，长期（慢性）疾病（如心脏病，肺病和糖尿病）的各个年龄段的人，因COVID-19住院的风险似乎更高。

COVID-19的症状是什么？
COVID-19的症状是发烧，咳嗽和呼吸急促，可能在暴露后2-14天出现。可能会发生严重疾病，包括呼吸问题，并可能导致您的其他医疗状况恶化。

什么是区域性？
Regiocit是CRRT的替代解决方案，CRRT是“透析”治疗的一种形式，它还降低了过滤器凝结的风险。在CRRT期间使用替代溶液来帮助纠正酸碱异常和电解质异常，去除“尿毒症”和其他毒素，并促进使用CRRT来控制液体超负荷。

我收到Regiocit之前应该告诉我的医疗保健提供者什么？

告诉您的医疗保健提供者您所有的医疗状况，包括是否：

•

有任何过敏

•

有肝病

•

正在怀孕或计划怀孕

•

正在母乳喂养或计划母乳喂养

•

正在服用任何药物（处方药，非处方药，维生素或草药产品）

谁不应该接受Regiocit？
如果您：

•

患有严重的肝衰竭

•

休克，肌肉血流减少（肌肉灌注不足）

•

对Regiocit中的任何成分过敏

区域性可能发生的重要副作用是什么？
Regiocit的可能副作用包括：

•

血液中钙含量低

•

血液中镁，钾或磷酸盐的含量低，或血液中葡萄糖含量的变化

•

血液中酸或碱过多（酸碱状态）

还有哪些其他治疗选择？
您的医疗保健提供者可能会为CRRT使用其他替代解决方案，或者使用不需要替代解决方案的“透析”类型。

如何报告Regiocit的副作用？
如果您有任何困扰您或不消失的副作用，请立即告诉您的医疗保健提供者。向www.fda.gov/medwatch上的FDA MedWatch报告副作用，或致电1-800-FDA-1088或致电1-866-888-2472或与global_pharmacovigilance_deerfield@baxter.com联系百特医疗保健公司。

我该如何学习？

•

询问您的医疗保健提供者

•

请访问www.cdc.gov/COVID19

•

联系您当地或州的公共卫生部门

•

请访问www.baxter.com

什么是紧急使用授权（EUA）？

美国FDA已通过称为EUA的紧急通道机制使Regiocit可用。卫生和公共服务部长（HHS）声明支持EUA，声明存在的情况足以证明在COVID-19大流行期间紧急使用药物和生物产品是合理的。

Regiocit没有经过与FDA批准或许可的产品相同类型的审查。当满足某些标准（包括没有足够的，经过批准的可用替代方法）时，FDA可能会发布EUA。此外，FDA的决定基于现有的全部科学证据，这些证据表明有理由相信该产品可能在COVID-19大流行期间有效治疗患者。必须满足所有这些标准，才能在COVID-19大流行期间将该产品用于患者的治疗，并且已知和潜在的益处要超过此类使用的已知和潜在的风险。

在COVID-19声明有效期内，区域性EUA有效，证明可以紧急使用这些产品，除非被终止或吊销（此后不得再使用这些产品）。

紧急使用授权区域包装说明书

Regiocit已被FDA授权用于紧急用途。
区域性药物未经FDA批准。
Regiocit仅在以下声明的有效期内被授权：
存在的情况证明有必要紧急使用
根据该法第564（b）（1）节的规定，《 21 USC§360bbb-3（b）（1），
除非授权被提前终止或撤销。

氯化钠和柠檬酸钠溶液

连续肾期间的血液滤过和柠檬酸局部抗凝治疗

替代疗法（CRRT）

氯化钠5.03 g / L，柠檬酸钠5.29 g / L

仅用于体外的解决方案。不用于直接静脉输液

ZH包装说明书..... 2

区域性

氯化钠和柠檬酸钠溶液

用于血液滤过和局部柠檬酸盐抗凝

连续性肾脏替代治疗（CRRT）期间

氯化钠5.03克/升，柠檬酸钠5.29克/升

仅用于体外的溶液，不用于直接静脉输液

适应症

指示使用区域性（氯化钠和柠檬酸钠）溶液作为
体外局部柠檬酸盐抗凝（RCA）的替代解决方案
连续性肾脏替代疗法（CRRT）治疗的患者的循环
特别是当禁忌使用肝素进行全身性抗凝治疗时，例如
出血风险增加的患者。

区域性治疗应仅在医师的监督下进行
在使用CRRT方面经验丰富。

儿科

儿科（<18岁）：加拿大卫生部无可用数据；因此，
加拿大卫生部未授权将其用于儿童。

老年医学

老年医学（> 65岁）：来自临床研究和经验的证据
提示在老年人群中的使用与年龄的差异无关。
安全性或有效性。

禁忌症

区域性溶液禁忌：

•

对这种药物或制剂中的任何成分（包括任何非药用成分或容器的成分）过敏的患者。有关完整列表，请参阅剂型，剂量，组成和包装。

•

严重肝功能衰竭

•

肌肉灌注不足的休克

剂量和给药

仅用于体外。不用于直接静脉输液。
区域性溶液用作肾脏替代溶液。该产品有一个
渗透压为244 mOsm / L，pH约为7.4。

剂量注意事项

药物剂量注意事项：

•

区域溶液不应用于直接静脉输注。该产品只能在预稀释模式下使用，并使用适当的用于CRRT的体外肾脏替代设备，并使用用于RCA的集成预血泵。

•

除了为体外回路和滤血器提供抗凝作用外，柠檬酸盐还因其代谢代谢转化为碳酸氢盐而起缓冲剂的作用。因此，要施用的区域溶液的输注速率应考虑到来自其他来源（例如透析液和/或置换液）的缓冲液施用速率。该产品必须与透析/置换溶液一起以适当的碳酸氢盐浓度使用。

•

轻度至中度肝功能不全的患者可能需要减少剂量。在这些患者中，建议更频繁地监测柠檬酸盐的积累。由于柠檬酸盐代谢受限（例如，禁忌症），不应对肝和肌肉灌注减少的患者（例如在脓毒性休克和乳酸酸中毒等情况下）或严重肝功能不全的患者使用区域性溶液。

•

始终需要单独全身性输注钙，以预防或治疗低钙血症。根据测得的血清总离子钙比和离子钙水平调整钙的输注，以将其值保持在生理范围内。停药区域后，请根据主治医师的指示调整或停止输钙。

•

根据全身血清镁水平，可能需要静脉补充镁。

推荐剂量和剂量调整

区域溶液的给药速率取决于目标柠檬酸盐剂量和规定的血流速率（BFR）。产品的处方必须考虑流出液和其他治疗液的流量，患者的除液要求，额外的液输入和输出以及所需的酸碱和电解质平衡。

只能由在CRRT给药方面有经验的重症监护或肾脏病医师开具区域性溶液处方，并确定其给药方式（剂量，输注速率和累积体积）。

将Regiocit溶液的预过滤器输注速度（基于其浓度）与血流速度挂钩，以达到血液中3到4 mmol / L的目标柠檬酸血药浓度。应该滴定体外回路抗凝的流速，以使过滤后的离子钙浓度达到0.25至0.35 mmol / L。通过调整钙的补充，应使患者的全身离子钙浓度保持在正常的生理范围内。

行政

监测过滤后血液中的离子钙（iCa），全身性血液iCa和总血钙水平以及其他实验室和临床参数，对于根据所需的抗凝水平指导适当的Regiocit溶液剂量至关重要（请参阅警告和注意事项） ）。还应定期监测血浆钠，镁，钾和磷酸盐的水平，并根据需要补充这些电解质。

可以将区域溶液加热到37°C以增强患者舒适度。在使用产品之前，应仅使用干热对其进行加热。由于可能导致患者受伤或不适，请勿在水或微波炉中加热溶液。

只要溶液和容器允许，在给药前应肉眼检查区域溶液中是否有颗粒物质和变色。除非溶液澄清并且密封完好，否则不要给药。

过量

过量时可能会发生电解质失衡和酸碱平衡异常，例如低钙血症，代谢性碱中毒等。立即停止管理（请参阅警告和注意事项）。

在柠檬酸盐代谢受损的患者（例如肝功能衰竭，循环休克等）中，使用Regiocit溶液过量可能表现为柠檬酸盐蓄积，代谢性酸中毒，全身性总高钙血症和离子性低钙血症以及总钙/离子钙比率增加（参见禁忌症和警告和注意事项）。

小心地补充钙可以逆转过量的影响。通过在治疗过程中进行密切监视，可以将风险降至最低。

剂量形式，强度，组成和包装

表1 –剂型，剂量，组成和包装

表2 –药用成分中的电解质浓度

区域溶液（氯化钠和柠檬酸钠）溶液装在5 000 mL袋中，带有鲁尔接头阀和尖钉接头。该袋由包含聚烯烃和弹性体的多层膜制成。

该产品不是用天然橡胶乳胶制成的。

警告和注意事项

有报告称，在使用Regiocit溶液治疗CRRT期间，由于操作员明显错误而导致系统故障，从而导致严重的不良事件，包括危及生命的低血钙症。在CRRT期间应密切监测血浆电解质和酸碱参数，如果发现电解质不平衡或酸碱平衡，则应采取适当的措施。必须严格遵守Regiocit和CRRT的使用说明。

警告和注意事项，内分泌和代谢，血液学，肝/胆/胰腺，监测和实验室测试以及药物相互作用中提供了警告性声明，以避免在执行CRRT程序时发生以下情况：

-高钙血症

-低钠血症

-液体滞留，脱水

- 恶心，呕吐

-肌肉痉挛

柠檬酸积累

对于包括肝硬化或急性肝衰竭在内的肝功能衰竭或休克患者，需要特别注意，因为柠檬酸盐的代谢可能会明显减少，因此患者可能会暴露于柠檬酸盐的积累中。在这种情况下，应更频繁地监测柠檬酸盐的积累。随着系统性柠檬酸盐的积累，可能会发生代谢性酸中毒和离子性低钙血症，血液中总钙与离子钙的比例会增加。如果总钙/离子钙比超过2.3，应减少或停止区域输注。然后可以不进行抗凝或通过使用其他抗凝手段继续进行CRRT。

严重肝功能不全或肌肉灌注不足的循环休克患者忌用区域性药物（见禁忌症）。

柠檬酸盐的过量输注会导致急性低钙血症和代谢性碱中毒，并伴有神经系统和心脏并发症。治疗包括停止柠檬酸盐输注和钙输注。

内分泌与代谢

低钙血症

区域性溶液不含钙，并且由于流出液中与柠檬酸盐结合的钙的损失和/或在系统性柠檬酸盐蓄积的情况下，可能导致全身性离子性低钙血症（请参阅《用法和用量》，《行政管理》）。

电解质和酸碱平衡

区域性溶液中含有柠檬酸盐，可能会影响患者的电解质和酸碱平衡。 CRRT期间应密切监测血浆电解质和酸碱参数。密切监视钠，镁，钾，磷酸盐和钙。可能需要注入电解质以补充任何损失。

高钙血症

用于维持CRRT患者钙稳态的含钙药品会增加高钙血症的风险，并可能导致抗凝作用降低。服用钙时应注意避免过度滴定，因为这可能导致高钙血症。经常监测pH值，电解质，总离子化钙比和全身性离子钙对于避免电解质和/或酸碱失衡很重要。

低镁血症

区域溶液不含镁。由于CRRT废水的流失，使用Regiocit溶液可能会导致低镁血症（请参见《剂量和管理》，《行政管理》）。

低血糖症

区域溶液不含葡萄糖。服用区域性溶液可能会导致低血糖症。血糖水平应定期监测。

低钾血症

区域溶液不含钾。在CRRT之前和期间必须监测血清钾浓度。

代谢性碱中毒

区域溶液包含柠檬酸盐，这会增加整体缓冲液的负荷。在治疗期间使用的CRRT液体或其他液体中所含的其他碳酸氢钠（或缓冲液源）可能会增加发生代谢性碱中毒的风险。如果柠檬酸盐的净施用量超过维持酸碱平衡所必需的速度，则可能发生代谢性碱中毒。

如果发生代谢性碱中毒，请降低柠檬酸盐剂量，和/或增加透析液流速或更改CRRT溶液的组成。

代谢性碱中毒患者应定期监测血钙，pH和碳酸氢盐，因为这种情况可能会加重低血钙症。

代谢性酸中毒

如果肝或骨骼肌对柠檬酸的代谢清除受损，可能会发生代谢性酸中毒（见禁忌症）。

如果在使用Regiocit进行治疗期间出现柠檬酸盐蓄积和/或代谢性酸中毒发展或恶化，则可能需要降低输注速度或停止给药。

低渗/低渗

Regiocit solution is hypo-osmolar/hypotonic relative to standard CRRT replacement fluids and should be used with caution in patients with traumatic brain injury, cerebral edema, or increased intracranial pressure.

Instructions for use of Regiocit must be strictly followed. Incorrect use of the access ports or other restrictions to fluid flow may lead to incorrect patient weight loss and may result in machine alarms being set off. Continuing treatment without resolving the originating cause may lead to patient injury or death.

Careful ongoing assessment is required of all solutions infused during Regiocit administration, whether related to CRRT dialysis fluids or to other solutions infused systemically.

Regiocit has a physiological sodium level of 140 mmol/L. However, sodium losses occurring during CRRT must be balanced as part of overall fluid and electrolyte management to avoid a drop in blood sodium level leading to systemic hyponatremia.

血液学

Hemodynamic Status and Fluid Balance

The patient's hematocrit, hemodynamic status and fluid balance should be monitored throughout the procedure.

- In case of hypervolemia, the net ultrafiltration rate prescribed for the CRRT device can be increased, and/or the rate of administration of solutions other than replacement fluid and/or dialysate can be reduced.

- In case of hypovolemia, the net ultrafiltration rate prescribed for the CRRT device can be reduced, and/or the rate of administration of solutions other than replacement fluid and/or dialysate can be increased.

Hepatic/Biliary/Pancreatic

Use in Patients with Mild to Moderate Hepatic Impairment

Systemic metabolism of citrate to bicarbonate may be impaired in patients with hepatic impairment, resulting in accumulation of citrate. If Regiocit solution is administered to patients with mild to moderate hepatic impairment, frequent monitoring of pH, electrolytes, total-to-ionized calcium ratio, and systemic ionized calcium is important to avoid electrolyte and/or acid–base imbalance (see CONTRAINDICATIONS).

Monitoring and Laboratory Tests

Plasma electrolyte and acid–base parameters should be closely monitored during CRRT. Closely monitor sodium, magnesium, potassium, phosphate, calcium, blood glucose levels, hematocrit, hemodynamic status and fluid balance, pH, bicarbonate, total-to-ionized calcium ratio, and systemic ionized calcium. Infusion of electrolytes may be needed to supplement any loss.

Special Populations

Pregnant Women

There are no adequate data from the use of Regiocit solution in pregnant women.

Physicians should carefully consider the potential risks and benefits for each specific patient before administering Regiocit solution.

Breast-feeding

There are no adequate data from the use of Regiocit solution in lactating women.

Physicians should carefully consider the potential risks and benefits for each specific patient before administering Regiocit solution.

It is unknown if the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised.

儿科

Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

老年医学

Geriatrics (> 65 years of age): Evidence from clinical studies and experience suggests that use in the geriatric population is not associated with differences in safety or effectiveness.

ADVERSE REACTIONS

Adverse Reaction Overview

The following adverse reactions represent those adverse reactions that are thought to have an association with the use of Regiocit solution or that may occur in conjunction with performing the CRRT procedure:

Adverse reactions reported with other CRRT products include:

- Hypotension

- Hypocalcemia (due to excessive and uncorrected effect of citrate in the body)

- Other electrolyte imbalances (hypomagnesemia, hypokalemia, hypophosphatemia)

- Acid–base balance disorders (including metabolic alkalosis, metabolic acidosis)

- Hypoglycemia

- Fluid imbalance

Clinical Trial Adverse Reactions

Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

In an open-label randomised study, 54 patients were administered RCA with an equimolar solution of citrate, sodium and chloride, as contained in Regiocit solution, and 49 received systemic anticoagulation with unfractionated heparin (UFH) while undergoing CRRT using continuous venovenous hemodiafiltration. Adverse events related to metabolic disorders occurred in 26% of patients in the RCA-treated group, compared to 28% of patients in the UFH-treated group. These adverse events were generally transient and reversible. Metabolic alkalosis was seen in 6% of patients treated with RCA, compared to none treated with UFH, and metabolic acidosis was reported in 6% and 2% of patients in the RCA and UFH groups, respectively. Six patients treated with RCA experienced severe hypocalcemia, compared to one patient treated with UFH.

In a second hemodiafiltration trial which evaluated 19 patients randomised to an equimolar solution of citrate, sodium and chloride, as contained in Regiocit solution, and 11 patients randomised to UFH anticoagulation, Hypocalcemia requiring intervention was reported in 3 patients treated with RCA, with 2 of these patients requiring treatment interruption of RCA.

Post-Market Adverse Reactions

To date, adverse events reported in the post-marketing setting for Regiocit appear to be consistent with those listed above in Adverse Reaction Overview.

药物相互作用

Overview

The blood concentration of filterable/dialyzable drugs may be reduced during treatment due to their removal by the extracorporeal filter. Corresponding corrective therapy should be instituted if necessary to establish the desired blood concentrations for drugs removed during treatment. Patient monitoring at an appropriate frequency is required.

When prescribing Regiocit, the physician needs to consider the use of other anticoagulants along with other buffer-containing and electrolyte solutions (including CRRT replacement fluid and dialysate).

药物相互作用

The drugs listed in this table are based on either drug interaction case studies or clinical trials, or potential interactions due to the expected magnitude and seriousness of the interaction (ie, those identified as contraindicated).

Table 3 - Established or Potential Drug-Drug Interactions

ACTION AND CLINICAL PHARMACOLOGY

作用机理

Citrate provides regional anticoagulation of blood in the continuous renal replacement therapy (CRRT) extracorporeal circuit by binding calcium and rendering calcium unavailable to the clotting cascade. Several steps of the clotting cascade are dependent on calcium and the absence of calcium prevents clotting in the circuit.

During CRRT, pre-dilution infusion of citrate into the access line of the extracorporeal circuit provides only regional extracorporeal anticoagulation (and thus avoids systemic anticoagulation of the patient) for two reasons. First, once blood from the extracorporeal circuit is returned to the patient, it mixes with the central venous blood which contains calcium. The second way in which a systemic anticoagulant effect is avoided is by infusion of calcium in the post-filter (return) bloodline of the extracorporeal circuit.

This procedure not only helps neutralize citrate's anticoagulant effect in the patient's blood, but also prevents any depletion of the patient's calcium stores which may result from the loss of calcium (bound to citrate) in the CRRT effluent fluid.

药效学

Citrate provides anticoagulation by its ability to form complexes with ionized calcium, making it unavailable to the clotting cascade. In Regiocit, sodium concentration has been set to 140 mmol/l as critically ill patients may develop severe hyponatremia. Chloride is set to the level required to balance cations as the solution is hydrogen carbonate free. Sodium and chloride are normal constituents of the human body and are considered to be pharmacologically inactive. Citrate is a normal metabolite in the human body that acts as a first intermediate substance in the Krebs cycle. Regiocit does not contain potassium or glucose.

Two studies provide information on the dose/response relationship between citrate concentration and anticoagulation. In one study, ex-vivo anticoagulation with anticoagulant citrate dextrose formula A (ACD-A) in blood collected from six healthy volunteers was studied. The study concluded that the clinically relevant effects of citrate anticoagulation rely solely on the disturbed formation of the calcium-dependent coagulation factors complexes. In this study, the anticoagulation effects of citrate were monitored either by methods that quantify clot formation (ie, activated clotting time) or by direct assessment of ionized calcium levels.

The correlation between concentrations of ionized calcium and clotting times revealed almost no anticoagulant effect when ionized calcium levels were up to or above 0.50 mmol/L, while clotting times showed a steep increase when calcium levels were decreased below 0.50 mmol/L. With respect to maximum effect, 5.65 mmol/L citrate induced clotting times of infinity in all samples.

药代动力学

Citrate is a normal metabolite in the human body and an intermediate substance in the Krebs cycle. This physiological pathway is capable of processing high amounts of citric acid as long as it occurs at low concentrations. The Krebs cycle takes place in the mitochondria, and all cells that contain these cellular organelles can metabolize citrate. Tissues rich in mitochondria such as liver, skeletal muscles, and kidney therefore have a higher capacity for citrate generation and elimination.

Absorption: Absorption of sodium and chloride is determined by the patient's clinical condition, metabolic status, and residual renal function.

Distribution: Extracellular citrate can be transported from the blood across the plasma membrane by a group of proteins ie the plasma membrane citrate transporters (PMCTs) into the cells and then metabolized in various organs and tissues.

Metabolism: Citrate is an intermediate in the central metabolic pathway called Krebs cycle as mentioned above. Citrate is rapidly metabolized mainly in the liver, but can also be metabolized by other organs/tissues.

Elimination: Any excess of circulating citrate is normally excreted via the kidneys.

Special Populations and Conditions

Hepatic Insufficiency:

When treating decompensated cirrhosis patients, one should also consider:

•

Impairment of citrate metabolism due to failure of microcirculation and oxidative metabolism (lactic acidosis and/or shock),

•

Impaired muscular utilization of citrate (cachexia, high doses of vasopressors),

•

Citrate load associated with blood products.

STORAGE, STABILITY AND DISPOSAL

Store at 4 °C to 30 °C. Do not freeze or expose to excessive heat.

SPECIAL HANDLING INSTRUCTIONS

Aseptic technique should be used throughout the handling and administration to the patient.

Remove the overwrap from the bag immediately before use.

Use only if the overwrap is not damaged, all seals are intact, and the solution is clear. Press bag firmly to test for any leakage. If leakage is discovered, discard the solution immediately since sterility can no longer be assured.

连接溶液袋时，请遵循以下说明正确使用检修口。

•

If the luer connector is used, remove the cap with a twist and pull motion. Connect the male luer lock on the pre-blood pump line to the female luer connector on the bag using a push and twist motion. Ensure that the connection is fully sealed and tighten (see Figure I). The connector is now open. Verify that the fluid is flowing freely. When the pre-blood pump line is disconnected from the luer connector, the connector will close and the flow of the solution will stop. The luer is a needle-less port.

•

If the injection connector (or spike connector) is used, remove the snap-off cap. Introduce the spike through the rubber septum (see Figure II). Verify that the fluid is flowing freely.

•

Before adding a substance or medication, verify that it is soluble and stable in Regiocit, and that the pH range of Regiocit is appropriate.

•

Additives known or determined to be incompatible should not be added.

•

必须参考要添加的药物的使用说明以及其他相关文献。

•

After addition, if there is a discoloration and/or the appearance of precipitates, insoluble complexes, or crystals, do not use.

•

引入添加剂后，将溶液充分混合。 The introduction and mixing of additives must always be performed prior to connecting the solution bag to the extracorporeal circuit.

•

The solution is for single use only.

•

丢弃所有未使用的部分。

READ THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINE PATIENT MEDICATION INFORMATION

Regiocit

Sodium chloride and sodium citrate solution

Read this carefully before you start taking Regiocit solution and each time you get a refill. This leaflet is a summary and will not tell you everything about this drug. Talk to your healthcare professional about your medical condition and treatment and ask if there is any new information about Regiocit solution.

What is Regiocit solution used for?

•

Is a solution for hemofiltration and prevents blood clotting during continuous renal replacement therapy (CRRT), which is a form or dialysis treatment. This medicine is used for critically ill patients particularly when other medicine used to prevent blood clotting is not an appropriate choice.

How does Regiocit solution work?

This medicine is to be administered into the blood circuit outside of your body when you have CRRT. This medicine is to be used in hospitals and administered by medical professionals only.

What are the ingredients in Regiocit solution?

Medicinal ingredients: sodium chloride and sodium citrate

Non-medicinal ingredients: hydrochloric acid, water

Regiocit solution comes in the following dosage forms:

Solution with 5.03 g/L of sodium chloride and 5.29 g/L of sodium citrate

Do not use Regiocit solution if:

•

You are allergic to any ingredients (See What are the ingredients in Regiocit solution ).

•

Severely impaired liver function

•

Severely decreased blood flow in the muscles

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take Regiocit solution. Talk about any health conditions or problems you may have, including if you:

• have diabetes

• have been treated for chronic kidney disease

• have a history of liver disease

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with Regiocit solution:

• Medicinal products that contain calcium, sodium bicarbonate, or any form of vitamin D.

How to take Regiocit solution:

Your healthcare professional will prescribe and administer the product.

Overdose:

What are possible side effects from using Regiocit solution?

These are not all the possible side effects you may feel when taking Regiocit solution. If you experience any side effects, contact your healthcare professional.

The following side effects have been associated with other CRRT products:

•

Low Blood Pressure (Hypotension)

•

Low blood calcium, due to excessive and uncorrected effect of citrate in the body (Hypocalcemia)

•

Having an imbalance in your body where you do not have enough magnesium, potassium or phosphate (Electrolyte imbalances, including hypomagnesemia, hypokalemia, hypophosphatemia)

•

Disorder where the pH in your body is not balanced (Acid-base disorders, including metabolic acidosis, metabolic alkalosis)

•

Low Blood Sugar (Hypoglycemia)

•

Having an imbalance in the fluids in your body (Fluid imbalance)

The possible side effects can be resulted from your CRRT procedure:

•

Having an imbalance in your body where you have too much calcium (Hypercalcemia) , or do not have enough sodium (Hyponatremia)

•

Having too much fluids (Fluid retention) or not enough fluids in your body (Dehydration)

•

恶心和呕吐

•

肌肉痉挛

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, talk to your healthcare professional.

存储：

Store at 4 °C to 30 °C. Do not freeze or expose to excessive heat.

Keep out of reach and sight of children.

If you want more information about Regiocit solution:

•

Talk to your healthcare professional

•

Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website (https://health-products.canada.ca/dpd-bdpp/index-eng.jsp); the manufacturer's website (http://baxter.ca), or by calling 1-888-719-9955.

The content of this leaflet was prepared by Baxter Corporation, Mississauga, Ontario L5N 0C2, Canada.

Last Revised: August 13, 2020

条码
0 719002 429008

Baxter and Regiocit are trademarks of Baxter International Inc. or its subsidiaries.

百特徽标

包装/标签主要显示面板

容器标签

DIN 02496755

Product Code: 955791

Regiocit

Sodium chloride and sodium citrate solution
5.03 g / L, 5.29 g / L
Solution de chlorure de sodium et de citrate de sodium
5,03 g / L, 5,29 g / L

Sterile / Stérile
Nonpyrogenic / Apyrogène
For hemofiltration and regional citrate anticoagulation during
Continuous Renal Replacement Therapy (CRRT) /
Pour hémofiltration et anticoagulation régionale au citrate pendant la thérapie de
remplacement rénal continue (TRRC).

Hydrochloric acid (pH adjuster) / Acide chlorhydrique (ajusteur de pH)
Water for Injection / Eau pour injection
Solution for Extracorporeal use only. Not for direct intravenous infusion. To be used in
pre-dilution only during CRRT.

For single use only .丢弃所有未使用的部分。 Product Monograph available upon
request. See patient medication information. This product is not made with natural rubber
latex.

Solution pour administration extracorporelle seulement. Ne pas administrer par
perfusion intraveineuse directe. Ne doit être utilisé en mode pré-dilution que pour la
thérapie de remplacement rénal continu (TRRC).

Pour usage unique seulement. Jeter toute portion non utilisée. Monographie disponible sur
demande. Voir les renseignements pour le patient sur le médicament. Ce produit n'est pas
fabriqué avec du latex de caoutchouc naturel.

18 Citrate
mmol / L mmol / L

140 Na +
mmol / L

5 000 mL

Store at 4°C to 30 °C. Do not freeze or
expose to excessive heat.

Conserver à une température comprise
entre 4 °C et 30 °C. Ne pas congeler ni
exposer à une chaleur excessive.

Questions and Concerns /
Des questions ou problèmes
Baxter Corporation
Mississauga, ON L5N 0C2
Customer Service /
Service à la clientèle
1-888-719-9955

2 x 5 000 mL

07-05-00-0207

百特徽标

纸箱标签

18 Citrate
mmol / L

140 Na +
mmol / L

DIN 02496755

Product code: 955791

Regiocit
Sodium chloride and sodium citrate solution
5.03 g / L, 5.29 g / L
Solution de chlorure de sodium et de citrate de sodium
5,03 g / L, 5,29 g / L

Sterile / Stérile

Nonpyrogenic / Apyrogène

For hemofiltration and regional citrate anticoagulation during Continuous Renal Replacement Therapy (CRRT) /
Pour hémofiltration et anticoagulation régionale au citrate pendant la thérapie de remplacement rénal continue (TRRC).

244 mOsm/L

5000毫升

Approx pH 7.4

Solution for Extracorporeal use only. Not for direct intravenous infusion. To be used in pre-dilution only during Continuous
Renal Replacement Therapy (CRRT).
Use only if overwrap and solution bag are not damaged and there is no leakage.
The introduction and mixing of additives must always be performed prior to connecting the solution bag to the extracorporeal circuit.引入添加剂后，将溶液充分混合。 Use only if solution is clear and free from visible particles.

Single use only.丢弃未使用的部分。 Product Monograph available upon request.
Dose: Read the package insert before use. This product is not made with natural rubber latex.
Store: 4°C to 30°C. Do n