适应症和用途

高血压

氯沙坦钾和氢氯噻嗪片可用于治疗高血压，降低血压。降低血压可以降低致命和非致命性心血管（CV）事件（主要是中风和心肌梗塞）的风险。在包括氯沙坦和氢氯噻嗪在内的各种药理学类别的抗高血压药物的对照试验中已经看到了这些益处。

高血压的控制应成为全面心血管风险管理的一部分，包括适当地控制血脂，控制糖尿病，抗血栓治疗，戒烟，运动和限制钠摄入量。许多患者需要多种药物才能达到血压目标。有关目标和管理的具体建议，请参见已发布的指南，例如国家高血压教育计划的全国预防，检测，评估和治疗高血压联合委员会（JNC）的指南。

随机对照试验显示，来自各种药理学类别且作用机制不同的多种降压药可降低心血管疾病的发病率和死亡率，可以得出结论，这是降低血压，而不是降低其某些药理特性。药物，这是造成这些好处的主要原因。最大和最一致的心血管结局获益是降低中风风险，但也经常观察到心肌梗塞和心血管死亡率的降低。

收缩压或舒张压升高会增加心血管疾病的风险，而在较高的血压下，每mmHg的绝对危险度增加更大，因此，即使是轻度降低严重的高血压也可以带来实质性的益处。在绝对风险不同的人群中，降低血压带来的相对风险降低是相似的，因此，相对于高血压独立处于较高风险中的患者（例如糖尿病或高脂血症患者），绝对收益更大。受益于更积极的治疗以降低血压目标。

在黑人患者中，某些降压药对血压的影响较小（作为单一疗法），许多降压药具有其他批准的适应症和作用（例如，对心绞痛，心力衰竭或糖尿病肾病）。这些考虑因素可以指导治疗的选择。

这种固定剂量的联合用药并未用于高血压的初始治疗，除非高血压严重到足以立即控制血压的价值超过了在这些患者中开始联合用药的风险[见临床研究（14）和剂量与用法（2.1）]。

氯沙坦钾和氢氯噻嗪片可以与其他降压药一起服用。

高血压左室肥厚患者

氯沙坦钾和氢氯噻嗪片可降低高血压和左心室肥厚患者的中风风险，但有证据表明，这种益处不适用于黑人患者。 [请参阅在特定人群中使用（8.6），临床药理学（12.3）和剂量和给药方法（2.5）。]

剂量和给药

高血压

氯沙坦钾和氢氯噻嗪片的通常起始剂量为每天一次50 / 12.5（氯沙坦50 mg /氢氯噻嗪12.5 mg）。治疗3周后，可根据需要控制血压，每天增加一次剂量，最大剂量为每天100/25（氯沙坦100 mg /氢氯噻嗪25 mg） [见临床研究（14.2）]。

每天一次使用氯沙坦50 mg氯沙坦钾和氢氯噻嗪片50 / 12.5的单药治疗不能充分控制血压的患者。如果经过约3周的治疗后血压仍无法控制，则可将剂量增加至每天两次洛沙坦钾和氢氯噻嗪片50 / 12.5或每天一次洛沙坦钾和氢氯噻嗪片100/25。

每天一次使用洛沙坦钾和氢氯噻嗪片100 / 12.5（氯沙坦100 mg /氢氯噻嗪12.5 mg）的氯沙坦100 mg单药治疗不能充分控制血压的患者。如果经过约3周的治疗后血压仍无法控制，则将剂量增加至每天两次洛沙坦钾和氢氯噻嗪片50 / 12.5，或一次洛沙坦钾和氢氯噻嗪片100/25。

每天一次用洛沙坦钾盐和氢氯噻嗪片50 / 12.5每天一次用氢氯噻嗪25 mg来控制血压不足或被控制但经历低钾血症的患者，每天一次，减少氢氯噻嗪的剂量而不降低总体预期的降压药响应。评估对氯沙坦钾和氢氯噻嗪片50 / 12.5的临床反应，如果在治疗约3周后血压仍无法控制，则将剂量增加至两片洛沙坦钾和氢氯噻嗪片50 / 12.5，每天一次或一片洛沙坦钾氢氯噻嗪片100/25每天一次。

高血压左室肥厚患者

对于50 mg氯沙坦钾无法充分控制血压的患者，请开始使用Losartan钾和氢氯噻嗪片50 / 12.5进行治疗。如果需要进一步降低血压，请增加Losartan钾和氢氯噻嗪片100 / 12.5的剂量，然后增加Losartan钾和氢氯噻嗪片100/25的剂量。为了进一步降低血压，请添加其他抗高血压药[请参阅临床研究（14）] 。

剂量形式和强度

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USP 50 / 12.5的洛沙坦钾盐和氢氯噻嗪片是黄色的胶囊状薄膜衣片，在一侧凹有“ HH”，在另一侧凹有“ 211”。

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美国药典100 / 12.5的洛沙坦钾盐和氢氯噻嗪片剂为白色至类白色的胶囊状薄膜衣片，一侧凹陷有“ HH”，另一侧凹陷了“ 213”。

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美国药典100/25的洛沙坦钾盐和氢氯噻嗪片是黄色的胶囊状薄膜衣片，一侧凹陷有“ HH”，另一侧凹陷了“ 212”。

禁忌症

氯沙坦钾和氢氯噻嗪片禁忌：

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对本产品的任何成分过敏的患者。

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无尿患者

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与阿利吉仑共同治疗糖尿病患者

警告和注意事项

胎儿毒性

给孕妇服用氯沙坦钾和氢氯噻嗪片会造成胎儿伤害。在妊娠的中期和晚期使用药物作用于肾素-血管紧张素系统会降低胎儿的肾功能，并增加胎儿和新生儿的发病率和死亡率。羊水过少可能与胎儿肺发育不全和骨骼变形有关。潜在的新生儿不良反应包括颅骨发育不全，无尿，低血压，肾衰竭和死亡。如果检测到怀孕，应尽快停用氯沙坦钾和氢氯噻嗪片。

噻嗪类药物穿过胎盘屏障并出现在脐带血中。不良反应包括胎儿或新生儿黄疸，血小板减少症[见在特定人群中使用（8.1）]。

容量不足或缺盐患者的低血压

在具有激活的肾素-血管紧张素系统的患者中，例如体量或盐分贫乏的患者（例如，正在接受大剂量利尿剂治疗的患者），在开始使用氯沙坦钾和氢氯噻嗪片治疗后，可能会出现症状性低血压。在服用氯沙坦钾和氢氯噻嗪片之前，要纠正体积或盐分的消耗。对于血管内容量减少的患者，请勿使用氯沙坦钾和氢氯噻嗪片作为初始治疗。

肾功能受损

抑制肾素-血管紧张素系统的药物和利尿剂可引起包括急性肾功能衰竭在内的肾功能变化。肾功能可能部分取决于肾素-血管紧张素系统活性的患者（例如，患有肾动脉狭窄，慢性肾脏疾病，严重充血性心力衰竭或体质衰竭的患者）可能特别容易患上氯沙坦钾和氢氯噻嗪片。定期监测这些患者的肾功能。对于在氯沙坦钾和氢氯噻嗪片上肾功能出现临床上显着下降的患者，请考虑停药或中止治疗[见药物相互作用（7.3）和特定人群的使用（8.8）] 。

过敏症

对氢氯噻嗪的超敏反应可能发生在有或没有过敏或支气管哮喘病史的患者中，但在有此类病史的患者中更可能发生。

电解质和代谢作用

在各种剂量的氯沙坦钾和氢氯噻嗪的双盲临床试验中，发生低钾血症（血清钾<3.5 mEq / L）的高血压患者的发生率为6.7％，而安慰剂为3.5％。高钾血症（血清钾> 5.7 mEq / L）的发生率为0.4％，而安慰剂为0％。

氯沙坦钾和氢氯噻嗪片含有氢氯噻嗪，可引起低血钾，低钠血症和低镁血症。低镁血症可导致低钾血症，尽管钾补充不足，低钾血症仍可能难以治疗。氯沙坦钾和氢氯噻嗪片也含有氯沙坦，可能引起高钾血症。定期监测血清电解质[参见药物相互作用（7.1）] 。

并用可能增加血钾的其他药物可能导致高钾血症[见药物相互作用（7.1）] 。

氢氯噻嗪可能会改变葡萄糖耐量，并升高血清胆固醇和甘油三酸酯的水平。

接受噻嗪类药物治疗的患者可能会发生高尿酸血症或坦白痛风。由于氯沙坦降低了尿酸，氯沙坦与氢氯噻嗪联用可减轻利尿剂引起的高尿酸血症。

氢氯噻嗪可减少尿钙排泄并可能引起血清钙升高。监测钙水平。

急性近视和继发性闭角型青光眼

氢氯噻嗪（一种磺酰胺）可引起特发性反应，导致急性短暂性近视和急性闭角型青光眼。症状包括视力下降或眼痛的急性发作，通常在药物启动后数小时至数周内发生。未经治疗的急性闭角型青光眼可导致永久性视力丧失。主要治疗方法是尽快终止氢氯噻嗪。如果眼内压保持不受控制，可能需要考虑及时的医学或外科治疗。发生急性闭角型青光眼的危险因素可能包括磺酰胺或青霉素过敏史。

系统性红斑狼疮

据报道，噻嗪类利尿剂可导致全身性红斑狼疮恶化或活化。

不良反应

临床试验经验

由于临床试验是在广泛不同的条件下进行的，因此无法将在某种药物的临床试验中观察到的不良反应率直接与另一种药物在临床试验中观察到的不良反应率进行比较，并且可能无法反映实际中观察到的不良反应率。

氯沙坦-氢氯噻嗪钾已在858例原发性高血压患者和3889例高血压和左心室肥厚患者中进行了安全性评估。大多数不良反应本质上都是轻度和短暂的，不需要停止治疗。在对照的临床试验中，分别用联合用药和安慰剂治疗的患者中，仅需要2.8％和2.3％的患者因临床不良事件而终止治疗。

在这些双盲对照临床试验中，使用氯沙坦-氢氯噻嗪治疗的受试者中发生不良反应的发生率超过2％，且发生率高于安慰剂，其不良反应为：腰痛（2.1％vs. 0.6％），头晕（5.7％vs 2.9％） ）和上呼吸道感染（6.1％对4.6％）。

在氯沙坦钾和氢氯噻嗪片和/或单个成分的临床试验中，还报告了以下其他不良反应：

血液和淋巴系统疾病：贫血，再生障碍性贫血，溶血性贫血，白细胞减少症，粒细胞缺乏症。

代谢和营养失调：厌食症，高血糖症，高尿酸血症，电解质失衡，包括低钠血症和低钾血症。

精神疾病：失眠，不安。

神经系统疾病：消化不良，头痛，偏头痛，感觉异常。

眼部疾病：黄褐斑，短暂性视力模糊。

心脏疾病：心Pal，心动过速。

血管疾病：剂量相关的体位作用，坏死性血管炎（血管炎，皮肤血管炎）。

呼吸，胸和纵隔疾病：鼻充血。

胃肠道疾病：消化不良，腹痛，胃刺激，痉挛，恶心，呕吐，胰腺炎，唾液腺炎。

肝胆疾病：黄疸（肝内胆汁淤积性黄疸）。

皮肤和皮下组织疾病：皮疹，瘙痒，紫癜，毒性表皮坏死溶解，荨麻疹，光敏性，皮肤性红斑狼疮。

肌肉骨骼和结缔组织疾病：肌肉痉挛，肌肉痉挛。

肾和泌尿系统疾病：糖尿，肾功能不全，间质性肾炎，肾功能衰竭。

生殖系统和乳房疾病：勃起功能障碍/阳im。

一般疾病和给药部位情况：胸痛，全身乏力，无力。

检查：肝功能异常。

咳嗽

持续性干咳与使用ACE抑制剂有关，在实践中可能是停止使用ACE抑制剂的原因。进行了两项前瞻性，平行组，双盲，随机，对照试验，以评估氯沙坦对接受ACE抑制剂治疗后出现咳嗽的高血压患者咳嗽发生率的影响。接受赖诺普利攻击后出现典型ACE抑制剂咳嗽且在安慰剂上消失的患者被随机分配至氯沙坦50 mg，赖诺普利20 mg或安慰剂（一项研究，n = 97）或25 mg氢氯噻嗪（n = 135） 。双盲治疗期长达8周。咳嗽的发生率示于下表1。

这些研究表明，在所有与ACE抑制剂治疗相关的咳嗽的人群中，与氯沙坦治疗相关的咳嗽发生率与氢氯噻嗪或安慰剂治疗相关。

据报道，在上市后的工作中使用氯沙坦可引起咳嗽，包括积极的再次挑战。

上市后经验

在批准洛沙坦钾和氢氯噻嗪片的批准后使用过程中，发现了以下不良反应。由于这些反应是从不确定大小的人群中自愿报告的，因此并非总是能够可靠地估计其频率或建立与药物暴露的因果关系。

消化系统：氯沙坦治疗的患者很少有肝炎的报道。

血液学：血小板减少症。

过敏反应：氯沙坦治疗的患者很少有血管性水肿，包括喉和声门肿胀，引起气道阻塞和/或面部，嘴唇，咽和/或舌头肿胀；这些患者中有一些以前曾与其他药物（包括ACE抑制剂）发生血管性水肿。氯沙坦已报道血管炎，包括Henoch-Schönlein紫癜。有过敏反应的报道。

肌肉骨骼：横纹肌溶解。

皮肤：红皮病。

药物相互作用

增加血清钾的药剂

氯沙坦与其他升高血清钾水平的药物合用可能导致高钾血症。监测此类患者的血钾。

锂

据报道，伴随使用血管紧张素II受体拮抗剂或噻嗪类利尿剂，血清锂浓度和锂毒性增加。监测接受氯沙坦钾和氢氯噻嗪片及锂的患者的锂水平。

非甾体类抗炎药，包括选择性环氧合酶-2抑制剂

氯沙坦钾

对于年老，体量减少（包括利尿剂治疗）或肾功能不全的患者，将NSAIDs（包括选择性COX-2抑制剂）与血管紧张素II受体拮抗剂（包括氯沙坦）并用可能会导致肾功能恶化包括可能的急性肾衰竭。这些影响通常是可逆的。定期监测接受氯沙坦和NSAID治疗的患者的肾功能。

包括氯沙坦的血管紧张素II受体拮抗剂的抗高血压作用可能会被包括选择性COX-2抑制剂在内的NSAID减弱。

氢氯噻嗪

施用包括选择性COX-2抑制剂的非甾体类抗炎药可以降低of，保钾和噻嗪类利尿剂的利尿，利钠和降压作用。因此，当同时使用氯沙坦钾盐和氢氯噻嗪片以及包括选择性COX-2抑制剂的非甾体类抗炎药时，应密切观察以确定利尿剂是否达到理想的效果。

在接受利尿剂治疗的患者中，将NSAIDs与血管紧张素受体阻滞剂（包括氯沙坦）并用可能会导致肾功能恶化，包括可能的急性肾衰竭。这些影响通常是可逆的。定期监测接受氢氯噻嗪，氯沙坦和NSAID治疗的患者的肾功能。

肾素-血管紧张素系统（RAS）的双重阻断

与单一疗法相比，用血管紧张素受体阻滞剂，ACEI抑制剂或阿利吉仑双重阻断RAS与低血压，晕厥，高钾血症和肾功能变化（包括急性肾衰竭）的风险增加有关。

糖尿病退伍军人事务性肾脏病（VA NEPHRON-D）试验招募了1448名2型糖尿病，尿白蛋白与肌酐比率升高，肾小球滤过率估计值降低（肾小球滤过率30至89.9 mL / min）的患者，将他们随机分配至接受氯沙坦治疗的赖诺普利或安慰剂，随访时间中位数为2.2年。与单药治疗相比，接受氯沙坦和赖诺普利联合治疗的患者并未获得GFR下降，终末期肾脏疾病或死亡的综合终点，但是与单药治疗相比，高钾血症和急性肾损伤的发生率增加组。

使用氯沙坦钾和氢氯噻嗪片以及其他影响RAS的药物密切监测患者的血压，肾功能和电解质。

糖尿病患者请勿将阿利吉仑与氯沙坦钾和氢氯噻嗪片同时使用。肾功能不全（GFR <60 mL / min）的患者应避免将阿利吉仑与氯沙坦钾和氢氯噻嗪片一起使用。

氢氯噻嗪与其他药物的使用

当同时给药时，以下药物可能与噻嗪类利尿剂相互作用[参见临床药理学（12.3）]：

抗糖尿病药（口服药物和胰岛素）-可能需要调整抗糖尿病药的剂量。

胆甾醇胺和colestipol树脂-在阴离子交换树脂的存在下，氢氯噻嗪的吸收受到损害。单剂量的胆甾胺或胆甾醇树脂可与氢氯噻嗪结合，并降低其从胃肠道的吸收率，分别高达85％和43％。错开氢氯噻嗪和树脂的剂量，使氢氯噻嗪至少在树脂给药前4小时或给药后4至6小时给药。

在特定人群中的使用

怀孕

风险摘要

给孕妇服用氯沙坦钾和氢氯噻嗪片会造成胎儿伤害。妊娠中期和晚期使用作用于肾素-血管紧张素系统的药物会降低胎儿的肾功能，并增加胎儿和新生儿的发病率和死亡率。多数在妊娠前三个月检查过抗高血压药后检查胎儿异常的流行病学研究并未将影响肾素-血管紧张素系统的药物与其他抗高血压药区分开。当检测到怀孕时，应尽快停用氯沙坦钾和氢氯噻嗪片（请参阅临床注意事项）。

对于指定人群，估计的主要先天缺陷和流产的背景风险尚不清楚。所有怀孕都有出生缺陷，流产或其他不良后果的背景风险。在美国普通人群中，临床公认的怀孕中主要先天缺陷和流产的估计背景风险分别为2％至4％和15％至20％。

临床注意事项

与疾病相关的母体和/或胚胎/胎儿风险妊娠高血压会增加孕妇患先兆子痫，妊娠糖尿病，早产和分娩并发症的风险（例如，需要剖腹产，产后出血）。高血压会增加胎儿受到宫内生长受限和宫内死亡的风险。患有高血压的孕妇应予以认真监测和相应管理。

胎儿/新生儿不良反应

洛沙坦：

在妊娠中期和中期使用对肾素-血管紧张素系统起作用的药物可导致以下情况：羊水过少，胎儿肾功能下降导致无尿和肾衰竭，胎儿肺发育不全，骨骼变形，包括颅骨发育不全，低血压和死亡。在特殊情况下，除了针对特定患者的影响肾素-血管紧张素系统的药物治疗之外，没有其他适当的替代方法，请告知母亲该胎儿的潜在危险。进行连续超声检查以评估羊膜内环境。如果发现羊水过少，请停止服用氯沙坦钾和氢氯噻嗪片，除非它被认为可以挽救母亲的生命。根据孕周，可能需要进行胎儿检查。但是，患者和医生应该意识到，羊水过少可能要等到胎儿遭受不可逆转的伤害之后才会出现。密切观察有子宫内接触洛沙坦钾和氢氯噻嗪片的婴儿的低血压，少尿和高钾血症的历史。对于有宫内接触氯沙坦钾和氢氯噻嗪片史的新生儿，如果发生少尿或低血压，则可支持血压和肾脏灌注。可能需要进行交换输血或透析，以逆转低血压和替代肾功能。

氢氯噻嗪：

噻嗪类药物可以穿过胎盘，并且在脐静脉中达到的浓度接近母体血浆中的浓度。像其他利尿剂一样，氢氯噻嗪会引起胎盘灌注不足。它在羊水中积聚，据报道其浓度高达脐静脉血浆中的19倍。怀孕期间使用噻嗪类药物会导致胎儿或新生儿黄疸或血小板减少症。由于它们不会改变先兆子痫的病程，因此不应将这些药物用于治疗孕妇的高血压。应避免在怀孕期间将氢氯噻嗪用于其他适应症。

数据

动物资料

没有证据表明在最大氯沙坦钾剂量为10 mg / kg /天与2.5 mg / kg /天的氢氯噻嗪联合治疗的大鼠或兔子中有致畸作用。在这些剂量下，氯沙坦，其活性代谢产物和氢氯噻嗪在兔子中的各自暴露量（AUCs）约为在人类中100 mg氯沙坦与25 mg氢氯噻嗪组合所达到的暴露量的5倍，1.5倍和1.0倍。从氯沙坦以50 mg / kg /天的剂量与12.5 mg / kg /天的氢氯噻嗪联合给药于大鼠所获得的数据推算出氯沙坦，其活性代谢物和氢氯噻嗪的AUC值约为6、2和2 100倍氯沙坦与25毫克氢氯噻嗪联用的人获得的抗癌药的功效是人类的两倍。雌性大鼠在妊娠前和整个妊娠期间均接受10 mg / kg /天的氯沙坦联合2.5 mg / kg /天的氢氯噻嗪治疗时，观察到了对大鼠的胎儿毒性，其肋骨略有增加。正如在单独使用氯沙坦的研究中所观察到的那样，当妊娠大鼠在妊娠后期和/或哺乳期用50 mg / kg / day氯沙坦联合治疗时，会产生不利的胎儿和新生儿影响，包括体重减轻，肾脏毒性和死亡率降低。 12.5 mg / kg /天的氢氯噻嗪。在大鼠中使用这些剂量时，氯沙坦，其活性代谢产物和氢氯噻嗪的各自AUC分别比使用100 mg氯沙坦和25 mg氢氯噻嗪的人获得的AUC高约35、10和10倍。当在怀孕小鼠和大鼠各自的主要器官发生期间分别以最高3000和1000 mg / kg / day的剂量给怀孕的小鼠和大鼠施用氢氯噻嗪而不使用氯沙坦时，没有证据表明对胎儿有害。

哺乳期

风险摘要

尚不知道氯沙坦是否会在人乳中排泄，但已证明老鼠乳中存在大量的氯沙坦及其活性代谢产物。噻嗪类药物出现在人乳中。由于可能会对哺乳婴儿产生不利影响，因此应考虑该药物对母亲的重要性，决定是否停止护理或停止使用该药物。

儿科用

尚未确定氯沙坦钾和氢氯噻嗪片在儿科患者中的安全性和有效性。

有宫内接触氯沙坦钾和氢氯噻嗪片的新生儿：如果发生少尿或低血压，请直接注意支持血压和肾脏灌注。作为逆转低血压和/或替代功能紊乱的肾功能的手段，可能需要进行换血或透析。

老人用

在一项针对降低左室肥厚的高血压患者的心血管死亡，中风和心肌梗死合并风险的对照临床研究中，有2857例患者（62％）为65岁及以上，而808例患者（18％）为75岁以上。为了控制这项研究中的血压，将患者服用研究药物的总时间中的氯沙坦和氢氯噻嗪合用了74％。在这些患者和年轻患者之间未观察到总体疗效差异。与非老年人相比，氯沙坦-氢氯噻嗪和对照组的老年人不良事件发生频率更高[见临床药理学（12.3）] 。

种族

在Losartan降低高血压终点干预措施（LIFE）的研究中，与接受氯沙坦治疗的黑人患者（均接受氢氯噻嗪治疗）相比，接受阿替洛尔治疗的高血压和左心室肥厚的黑人患者发生卒中的风险更低，这是主要的复合终点在大多数患者中）。在黑人患者亚组（n = 533，占LIFE研究患者的6％）中，有263例接受阿替洛尔治疗的患者有29个主要终点（11％，每千患者年26个），有270个患者有46个主要终点（17 ％，每1000病人-年42片氯沙坦。不能根据种族以外的种族差异或治疗组之间的任何不平衡来解释这一发现。此外，黑人和非黑人患者在两个治疗组中的血压降低均一致。鉴于在大型试验中难以解释子集差异，因此无法确定观察到的差异是否是偶然的结果。但是，LIFE研究没有提供证据表明氯沙坦在降低左室肥大的高血压患者中降低心血管事件风险的益处适用于黑人患者[参见临床药理学（12.3）] 。

肝功能不全

对于肝功能不全的患者，不建议开始使用氯沙坦钾和氢氯噻嗪片，因为没有合适的洛沙坦起始剂量25毫克。

肾功能不全

据报道易感人群的肾功能发生了变化[参见剂量和用法（2.1），警告和注意事项（5.4）和临床药理学（12.3）]。尚无氯沙坦钾和氢氯噻嗪片在严重肾功能不全（肌酐清除率<30 mL / min）患者中的安全性和有效性。

过量

氯沙坦钾

分别口服1000 mg / kg和2000 mg / kg的小鼠和大鼠，观察到显着的致死性，以mg / m 2为基础，为最大推荐人剂量的约44倍和170倍。

关于人类用药过量的数据有限。药物过量的最可能的表现是低血压和心动过速。心动过缓可能由副交感神经（迷走神经）刺激引起。如果出现症状性低血压，应采取支持治疗。

氯沙坦或其活性代谢物均不能通过血液透析去除。

氢氯噻嗪

在小鼠和大鼠中，氢氯噻嗪的口服LD 50均大于10 g / kg。观察到的最常见的体征和症状是由电解质消耗（低钾血症，低氯血症，低钠血症）和过度利尿导致的脱水引起的。如果还进行了洋地黄的治疗，则低钾血症可能会加剧心律不齐。尚未确定通过血液透析去除氢氯噻嗪的程度。

描述

氯沙坦钾和氢氯噻嗪片（50 / 12.5 mg），氯沙坦钾和氢氯噻嗪片（100 / 12.5 mg）和氯沙坦钾和氢氯噻嗪片（100/25 mg）结合了作用于AT 1受体亚型的血管紧张素II受体阻滞剂和利尿剂氢氯噻嗪。 。

氯沙坦钾是一种非肽分子，化学上称为2-丁基-4-氯-1- [对- （邻-1 H-四唑-5-基苯基）苄基]咪唑-5-甲醇单钾盐。其经验公式为C 22 H 22 ClKN 6 O，其结构公式为：

氯沙坦钾是白色至类白色的自由流动的结晶性粉末，分子量为461.01。它可自由溶于水，可溶于醇，并微溶于常见的有机溶剂，如乙腈和甲乙酮。

咪唑环上的5-羟甲基被氧化会产生氯沙坦的活性代谢产物。

氢氯噻嗪是6-氯-3,4-二氢-2 H -1,2,4-苯并噻二嗪-7-磺酰胺1,1-二氧化物。它的经验公式为C 7 H 8 ClN 3 O 4 S 2 ，其结构式为：

氢氯噻嗪是一种白色或几乎白色的结晶性粉末，分子量为297.74，微溶于水，但易溶于氢氧化钠溶液。

USP的氯沙坦钾和氢氯噻嗪片可通过氯沙坦和氢氯噻嗪的三种片剂组合口服给药。氯沙坦钾和氢氯噻嗪片50 / 12.5 mg含有50 mg氯沙坦钾和12.5 mg氢氯噻嗪。氯沙坦钾和氢氯噻嗪片100 / 12.5 mg包含100 mg氯沙坦钾和12.5 mg氢氯噻嗪。氯沙坦钾和氢氯噻嗪片100/25 mg含有100 mg氯沙坦钾和25 mg氢氯噻嗪。非活性成分是微晶纤维素，一水合乳糖，预糊化淀粉，硬脂酸镁，胶体二氧化硅，羟丙基纤维素，羟丙甲纤维素和二氧化钛。氯沙坦钾和氢氯噻嗪片50 / 12.5 mg和100/25 mg还包含D＆C黄色10号铝色淀和FD＆C蓝色1号/亮蓝FCF铝色淀。

氯沙坦钾和氢氯噻嗪片50 / 12.5 mg含4.24 mg（0.108 mEq）钾，氯沙坦钾和氢氯噻嗪片100 / 12.5 mg含8.48 mg（0.216 mEq）钾，氯沙坦钾和氢氯噻嗪片100/25 mg含8.48毫克（0.216 mEq）的钾。

临床药理学

作用机理

氯沙坦钾

Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)], is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor found in many tissues (eg, vascular smooth muscle, adrenal gland). There is also an AT 2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Neither losartan nor its principal active metabolite exhibits any partial agonist activity at the AT 1 receptor, and both have much greater affinity (about 1000-fold) for the AT 1 receptor than for the AT 2 receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT 1 receptor. The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT 1 receptor.

Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.噻嗪类药物降压作用的机制尚不清楚。

药效学

Losartan Potassium

Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25-40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a doubling to tripling in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients. Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration. In spite of the effect of losartan on aldosterone secretion, very little effect on serum potassium was observed.

The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3-6 weeks. In long-term follow-up studies (without placebo control) the effect of losartan appeared to be maintained for up to a year. There is no apparent rebound effect after abrupt withdrawal of losartan. There was essentially no change in average heart rate in losartan-treated patients in controlled trials.

Hydrochlorothiazide

After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours.

药物相互作用

Hydrochlorothiazide

Alcohol, barbiturates, or narcotics — potentiation of orthostatic hypotension may occur.

Other antihypertensive drugs — additive effect or potentiation.

Skeletal muscle relaxants, nondepolarizing (eg, tubocurarine) — possible increased responsiveness to the muscle relaxant.

Corticosteroids, ACTH, or glycyrrhizin (found in liquorice) — intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (eg, norepinephrine) — possible decreased response to pressor amines but not sufficient to preclude their use.

药代动力学

Losartan Potassium

Absorption : Following oral administration, losartan is well absorbed and undergoes substantial first-pass metabolism. The systemic bioavailability of losartan is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3-4 hours, respectively. While maximum plasma concentrations of losartan and its active metabolite are approximately equal, the AUC (area under the curve) of the metabolite is about 4 times as great as that of losartan. A meal slows absorption of losartan and decreases its C max but has only minor effects on losartan AUC or on the AUC of the metabolite (~10% decrease). The pharmacokinetics of losartan and its active metabolite are linear with oral losartan doses up to 200 mg and do not change over time.

Distribution: The volume of distribution of losartan and the active metabolite is about 34 liters and 12 liters, respectively. Both losartan and its active metabolite are highly bound to plasma proteins, primarily albumin, with plasma free fractions of 1.3% and 0.2%, respectively. Plasma protein binding is constant over the concentration range achieved with recommended doses. Studies in rats indicate that losartan crosses the blood-brain barrier poorly, if at all.

Metabolism: Losartan is an orally active agent that undergoes substantial first-pass metabolism by cytochrome P450 enzymes. It is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonism that follows losartan treatment. About 14% of an orally-administered dose of losartan is converted to the active metabolite. In addition to the active carboxylic acid metabolite, several inactive metabolites are formed. In vitro studies indicate that cytochrome P450 2C9 and 3A4 are involved in the biotransformation of losartan to its metabolites.

Elimination: Total plasma clearance of losartan and the active metabolite is about 600 mL/min and 50 mL/min, respectively, with renal clearance of about 75 mL/min and 25 mL/min, respectively. The terminal half-life of losartan is about 2 hours and of the metabolite is about 6-9 hours. After single doses of losartan administered orally, about 4% of the dose is excreted unchanged in the urine and about 6% is excreted in urine as active metabolite. Biliary excretion contributes to the elimination of losartan and its metabolites. Following oral 14 C-labeled losartan, about 35% of radioactivity is recovered in the urine and about 60% in the feces. Following an intravenous dose of 14 C-labeled losartan, about 45% of radioactivity is recovered in the urine and 50% in the feces. Neither losartan nor its metabolite accumulate in plasma upon repeated once-daily dosing.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.

特定人群

Geriatric and Gender

Losartan pharmacokinetics have been investigated in the elderly (65-75 years) and in both genders. Plasma concentrations of losartan and its active metabolite are similar in elderly and young hypertensives. Plasma concentrations of losartan were about twice as high in female hypertensives as male hypertensives, but concentrations of the active metabolite were similar in males and females.

种族

Pharmacokinetic differences due to race have not been studied [see also Use in Specific Populations (8.6)].

肝功能不全

Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of losartan and its active metabolite were, respectively, 5 times and about 1.7 times those in young male volunteers. Compared to normal subjects, the total plasma clearance of losartan in patients with hepatic insufficiency was about 50% lower, and the oral bioavailability was about doubled. The lower starting dose of losartan recommended for use in patients with hepatic impairment cannot be given using Losartan Potassium and Hydrochlorothiazide tablets. Its use in such patients as a means of losartan titration is, therefore, not recommended [see Warnings and Precautions (5.3) and Use in Specific Populations (8.7)] .

肾功能不全

Losartan

Following oral administration, plasma concentrations and AUCs of losartan and its active metabolite are increased by 50-90% in patients with mild (creatinine clearance of 50 to 74 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal insufficiency. In this study, renal clearance was reduced by 55-85% for both losartan and its active metabolite in patients with mild or moderate renal insufficiency. Neither losartan nor its active metabolite can be removed by hemodialysis.

Hydrochlorothiazide

Following oral administration, the AUC for hydrochlorothiazide is increased by 70 and 700% for patients with mild and moderate renal insufficiency, respectively. In this study, renal clearance of hydrochlorothiazide decreased by 45 and 85% in patients with mild and moderate renal impairment, respectively.

Use the usual regimens of therapy with Losartan Potassium and Hydrochlorothiazide tablets as long as the patient's creatinine clearance is greater than 30 mL/min. Safety and effectiveness of Losartan Potassium and Hydrochlorothiazide tablets in patients with severe renal impairment (creatinine clearance less than 30 mL/min) have not been established [see Use in Specific Populations (8.8)].

药物相互作用

Losartan Potassium

No clinically significant drug interactions have been found in studies of losartan potassium with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. However, rifampin has been shown to decrease the AUC of losartan and its active metabolite by 30% and 40%, respectively. Fluconazole, an inhibitor of cytochrome P450 2C9, decreased the AUC of the active metabolite by approximately 40%, but increased the AUC of losartan by approximately 70% following multiple doses. Conversion of losartan to its active metabolite after intravenous administration is not affected by ketoconazole, an inhibitor of P450 3A4.The AUC of active metabolite following oral losartan was not affected by erythromycin, an inhibitor of P450 3A4, but the AUC of losartan was increased by 30%.

The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan to active metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite is mediated primarily by P450 2C9 and not P450 3A4.

非临床毒理学

致癌，诱变，生育力受损

Losartan Potassium-Hydrochlorothiazide

No carcinogenicity studies have been conducted with the losartan potassium-hydrochlorothiazide combination.

Losartan potassium-hydrochlorothiazide when tested at a weight ratio of 4:1, was negative in the Ames microbial mutagenesis assay and the V-79 Chinese hamster lung cell mutagenesis assay. In addition, there was no evidence of direct genotoxicity in the in vitro alkaline elution assay in rat hepatocytes and in vitro chromosomal aberration assay in Chinese hamster ovary cells at noncytotoxic concentrations.

Losartan potassium, coadministered with hydrochlorothiazide, had no effect on the fertility or mating behavior of male rats at dosages up to 135 mg/kg/day of losartan and 33.75 mg/kg/day of hydrochlorothiazide. These dosages have been shown to provide respective systemic exposures (AUCs) for losartan, its active metabolite and hydrochlorothiazide that are approximately 60, 60 and 30 times greater than those achieved in humans with 100 mg of losartan potassium in combination with 25 mg of hydrochlorothiazide. In female rats, however, the coadministration of doses as low as 10 mg/kg/day of losartan and 2.5 mg/kg/day of hydrochlorothiazide was associated with slight but statistically significant decreases in fecundity and fertility indices. AUC values for losartan, its active metabolite and hydrochlorothiazide, extrapolated from data obtained with losartan administered to rats at a dose of 50 mg/kg/day in combination with 12.5 mg/kg/day of hydrochlorothiazide, were approximately 6, 2, and 2 times greater than those achieved in humans with 100 mg of losartan in combination with 25 mg of hydrochlorothiazide.

Losartan Potassium

Losartan potassium was not carcinogenic when administered at maximally tolerated dosages to rats and mice for 105 and 92 weeks, respectively. Female rats given the highest dose (270 mg/kg/day) had a slightly higher incidence of pancreatic acinar adenoma. The maximally tolerated dosages (270 mg/kg/day in rats, 200 mg/kg/day in mice) provided systemic exposures for losartan and its pharmacologically active metabolite that were approximately 160 and 90 times (rats) and 30 and 15 times (mice) the exposure of a 50 kg human given 100 mg per day.

Losartan potassium was negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays and in the in vitro alkaline elution and in vitro and in vivo chromosomal aberration assays. In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution, and in vitro chromosomal aberration assays.

Fertility and reproductive performance were not affected in studies with male rats given oral doses of losartan potassium up to approximately 150 mg/kg/day. The administration of toxic dosage levels in females (300/200 mg/kg/day) was associated with a significant (p<0.05) decrease in the number of corpora lutea/female, implants/female, and live fetuses/female at C-section. At 100 mg/kg/day only a decrease in the number of corpora lutea/female was observed. The relationship of these findings to drug-treatment is uncertain since there was no effect at these dosage levels on implants/pregnant female, percent post-implantation loss, or live animals/litter at parturition. In nonpregnant rats dosed at 135 mg/kg/day for 7 days, systemic exposure (AUCs) for losartan and its active metabolite were approximately 66 and 26 times the exposure achieved in man at the maximum recommended human daily dosage (100 mg).

Hydrochlorothiazide

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day).但是，NTP发现雄性小鼠肝癌的模棱两可的证据。

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation.

临床研究

Losartan Monotherapy

Reduction in the Risk of Stroke: The LIFE study was a multinational, double-blind study comparing losartan and atenolol in 9193 hypertensive patients with ECG-documented left ventricular hypertrophy. Patients with myocardial infarction or stroke within six months prior to randomization were excluded. Patients were randomized to receive once daily losartan 50 mg or atenolol 50 mg. If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan or atenolol was then increased to 100 mg once daily. If necessary, other antihypertensive treatments (eg, increase in dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic therapy, calcium channel blockers, alpha-blockers, or centrally acting agents, but not ACE inhibitors, angiotensin II antagonists, or beta-blockers) were added to the treatment regimen to reach the goal blood pressure.

In efforts to control blood pressure, the patients in both arms of the LIFE study were coadministered hydrochlorothiazide the majority of time they were on study drug (73.9% and 72.4% of days in the losartan and atenolol arms, respectively).

Of the randomized patients, 4963 (54%) were female and 533 (6%) were Black. The mean age was 67 with 5704 (62%) age ≥65. At baseline, 1195 (13%) had diabetes, 1326 (14%) had isolated systolic hypertension, 1469 (16%) had coronary heart disease, and 728 (8%) had cerebrovascular disease. Baseline mean blood pressure was 174/98 mmHg in both treatment groups. The mean length of follow-up was 4.8 years. At the end of study or at the last visit before a primary endpoint, 77% of the group treated with losartan and 73% of the group treated with atenolol were still taking study medication. Of the patients still taking study medication, the mean doses of losartan and atenolol were both about 80 mg/day, and 15% were taking atenolol or losartan as monotherapy, while 77% were also receiving hydrochlorothiazide (at a mean dose of 20 mg/day in each group). Blood pressure reduction measured at trough was similar for both treatment groups but blood pressure was not measured at any other time of the day. At the end of study or at the last visit before a primary endpoint, the mean blood pressures were 144.1/81.3 mmHg for the group treated with losartan and 145.4/80.9 mmHg for the group treated with atenolol [the difference in SBP of 1.3 mmHg was significant (p<0.001), while the difference of 0.4 mmHg in DBP was not significant (p=0.098)].

The primary endpoint was the first occurrence of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Patients with nonfatal events remained in the trial, so that there was also an examination of the first event of each type even if it was not the first event (eg, a stroke following an initial myocardial infarction would be counted in the analysis of stroke). Treatment with losartan resulted in a 13% reduction (p=0.021) in risk of the primary endpoint compared to the atenolol group; this difference was primarily the result of an effect on fatal and nonfatal stroke. Treatment with losartan reduced the risk of stroke by 25% relative to atenolol (p=0.001).

Losartan Potassium-Hydrochlorothiazide

The 3 controlled studies of losartan and hydrochlorothiazide included over 1300 patients assessing the antihypertensive efficacy of various doses of losartan (25, 50 and 100 mg) and concomitant hydrochlorothiazide (6.25, 12.5 and 25 mg). A factorial study compared the combination of losartan/hydrochlorothiazide 50/12.5 mg with its components and placebo. The combination of losartan/hydrochlorothiazide 50/12.5 mg resulted in an approximately additive placebo-adjusted systolic/diastolic response (15.5/9.0 mmHg for the combination compared to 8.5/5.0 mmHg for losartan alone and 7.0/3.0 mmHg for hydrochlorothiazide alone). Another study investigated the dose-response relationship of various doses of hydrochlorothiazide (6.25, 12.5 and 25 mg) or placebo on a background of losartan (50 mg) in patients not adequately controlled (Sitting Diastolic Blood Pressure [SiDBP] 93-120 mmHg) on losartan (50 mg) alone. The third study investigated the dose-response relationship of various doses of losartan (25, 50 and 100 mg) or placebo on a background of hydrochlorothiazide (25 mg) in patients not adequately controlled (SiDBP 93-120 mmHg) on hydrochlorothiazide (25 mg) alone. These studies showed an added antihypertensive response at trough (24 hours post-dosing) of hydrochlorothiazide 12.5 or 25 mg added to losartan 50 mg of 5.5/3.5 and 10.0/6.0 mmHg, respectively. Similarly, there was an added antihypertensive response at trough when losartan 50 or 100 mg was added to hydrochlorothiazide 25 mg of 9.0/5.5 and 12.5/6.5 mmHg, respectively. There was no significant effect on heart rate.

There was no difference in response for men and women or in patients over or under 65 years of age.

Black patients had a larger response to hydrochlorothiazide than non-Black patients and a smaller response to losartan. The overall response to the combination was similar for Black and non-Black patients.

Severe Hypertension (SiDBP ≥110 mmHg)

The safety and efficacy of Losartan Potassium and Hydrochlorothiazide tablets as initial therapy for severe hypertension (defined as a mean SiDBP ≥110 mmHg confirmed on 2 separate occasions off all antihypertensive therapy) was studied in a 6-week double-blind, randomized, multicenter study. Patients were randomized to either losartan and hydrochlorothiazide (50/12.5 mg, once daily) or to losartan (50 mg, once daily) and followed for blood pressure response. Patients were titrated at 2-week intervals if their SiDBP did not reach goal (<90 mmHg). Patients on combination therapy were titrated from losartan 50 mg/hydrochlorothiazide 12.5 mg to losartan 50 mg/hydrochlorothiazide 12.5 mg (sham titration to maintain the blind) to losartan 100 mg/hydrochlorothiazide 25 mg. Patients on monotherapy were titrated from losartan 50 mg to losartan 100 mg to losartan 150 mg, as needed. The primary endpoint was a comparison at 4 weeks of patients who achieved goal diastolic blood pressure (trough SiDBP <90 mmHg).

The study enrolled 585 patients, including 264 (45%) females, 124 (21%) blacks, and 21 (4%) ≥65 years of age. The mean blood pressure at baseline for the total population was 171/113 mmHg

综上所述

较常报道的副作用包括：头晕。有关不良影响的完整列表，请参见下文。

对于消费者

适用于氢氯噻嗪/氯沙坦：口服片剂

需要立即就医的副作用

氢氯噻嗪/氯沙坦及其所需的作用可能会引起某些不良作用。尽管并非所有这些副作用都可能发生，但如果确实发生了，则可能需要医疗护理。

服用氢氯噻嗪/氯沙坦时，如果有下列任何副作用，请立即咨询医生：

罕见

• 黑色柏油凳
• 尿液或大便中有血
• 咳嗽或声音嘶哑，伴有发冷或发烧，下背部或侧面疼痛或排尿疼痛或困难
• 晕倒
• 查明皮肤上的红色斑点
• 跳动的心跳
• 严重的胃痛，恶心和呕吐
• 皮疹
• 脚或小腿肿胀
• 异常出血或瘀伤

发病率未知

• 牙龈出血
• 起泡，脱皮，皮肤松弛
• 模糊的视野
• 胸痛
• 发冷
• 昏迷
• 混乱
• 咳嗽
• 深色尿液
• 尿频减少
• 尿量减少
• 腹泻
• 吞咽困难
• 头晕
• 口干
• 快速，不规则，剧烈震动或心跳或脉搏加快
• 发热
• 全身疲倦和虚弱
• 荨麻疹，皮肤瘙痒，皮疹
• 增加皮肤对阳光的敏感性
• 口渴
• 易怒
• 关节或肌肉疼痛
• 皮肤上的大块，扁平，蓝色或紫色的斑块
• 面部，眼睑，嘴唇，舌头，喉咙，手，腿，脚或性器官上的大型蜂巢状肿胀
• 浅色凳子
• 食欲不振
• 下背部或侧面疼痛
• 肌肉痉挛或疼痛
• 肌肉痉挛
• 肌肉僵硬
• 肌肉抽搐
• 恶心或呕吐
• 手，脚或嘴唇麻木或刺痛
• 膝盖和脚踝疼痛
• 眼睑或眼睛，面部，嘴唇或舌头周围浮肿或肿胀
• 在皮肤，臀部，腿部或脚踝上出现红色肿胀
• 眼睛发红
• 皮肤病变为红色，中心常为紫色
• 皮肤发红或其他变色
• 躁动
• 癫痫发作
• 严重晒伤
• 咽喉痛
• 口腔或嘴唇上的疮，溃疡或白斑
• 脸，脚踝或手肿胀
• 胸闷
• 呼吸困难
• 右上腹或胃痛
• 异常疲倦或虚弱
• 心律微弱或不规则
• 体重增加
• 眼睛和皮肤发黄

不需要立即就医的副作用

可能会发生氢氯噻嗪/氯沙坦的某些副作用，通常不需要医疗。随着身体对药物的适应，这些副作用可能会在治疗期间消失。另外，您的医疗保健专业人员可能会告诉您一些预防或减少这些副作用的方法。

请咨询您的医疗保健专业人员，是否持续存在以下不良反应或令人讨厌，或者是否对这些副作用有任何疑问：

比较普遍;普遍上

• 身体酸痛或疼痛
• 头痛
• 失去声音
• 打喷嚏
• 咽喉痛
• 鼻塞或流鼻涕

罕见

• 干咳

发病率未知

• 胃酸或酸
• ching
• 口味变化或丧失
• 排便困难（凳子）
• 普遍感到不适或生病
• 胃灼热
• 无法勃起或勃起
• 消化不良
• 性能力，欲望，动力或表现丧失
• 睡眠困难
• 减肥

对于医疗保健专业人员

适用于氢氯噻嗪/氯沙坦：口服片剂

一般

最常见的不良反应是头晕。 ^[参考]

神经系统

常见（1％至10％）：头晕，头痛

洛沙坦：

未报告频率：晕厥，脑血管意外，共济失调，感觉异常，记忆障碍，偏头痛，感觉异常，周围神经病变，嗜睡，眩晕，震颤，味觉变态，耳鸣^[参考]

呼吸道

常见（1％至10％）：咳嗽，鼻窦炎，上呼吸道感染，支气管炎，咽炎

氢氯噻嗪：

未报告频率：呼吸窘迫，肺炎，肺水肿

洛沙坦：

未报告频率：呼吸困难，鼻epi，鼻充血，咽部不适，呼吸道充血，鼻炎，鼻窦疾病

上市后报告：干咳^[参考]

胃肠道

常见（1％至10％）：腹痛，腹泻，恶心

氢氯噻嗪：

未报告频率：胰腺炎，涎腺炎，痉挛，胃刺激

洛沙坦：

未报告频率：便秘，牙齿疼痛，口干，消化不良，肠胃气胀，胃炎，呕吐^[参考]

心血管的

常见（1％至10％）：心Pal，原发性高血压

罕见（0.1％至1％）：低血压

氢氯噻嗪：

未报告频率：血管炎

洛沙坦：

未报告频率：心绞痛，心律不齐，心房纤颤，窦性心动过缓，心动过速，室性心动过速，室颤，低血压，心肌梗死，二度房室传导阻滞，潮红

上市后报告：血管炎^[参考]

其他

常见（1％至10％）：水肿/肿胀，乏力/疲劳

氢氯噻嗪：

未报告频率：虚弱，发烧

洛沙坦：

未报告频率：胸痛，面部浮肿，发烧，体位正常，不适。 ^[参考]

皮肤科

普通（1％至10％）：皮疹

氢氯噻嗪：

未报告频率：紫癜，光敏性，荨麻疹，皮肤血管炎，多形性红斑，史蒂文斯-约翰逊综合征，剥脱性皮炎，中毒性表皮坏死

洛沙坦：

普通（1％至10％）：皮疹

未报告频率：血管性水肿，手掌表皮剥落，脱发，皮炎，皮肤干燥，瘀斑，红斑，光敏性，瘙痒，出汗，荨麻疹

上市后报告：红皮病^[参考]

肌肉骨骼

常见（1％至10％）：背痛

氢氯噻嗪：

未报告频率：肌肉痉挛

洛沙坦：

未报告的频率：手臂疼痛，关节痛，关节炎，纤维肌痛，髋关节痛，关节肿胀，膝盖痛，腿痛，肌肉抽筋，肌肉无力，肌肉骨骼疼痛，肌痛，肩痛，僵硬

上市后报告：横纹肌溶解症^[参考]

肾的

罕见（0.1％至1％）：血清肌酐增加超过5 mg / dL，BUN增加

氢氯噻嗪：

未报告频率：肾功能衰竭，肾功能不全，间质性肾炎

洛沙坦：

常见（1％至10％）：血清肌酐升高大于5 mg / dL ^[参考]

肝的

未报告频率：肝酶升高，血清胆红素升高

上市后报告：肝炎

氢氯噻嗪：

未报告频率：肝内胆汁淤积性黄疸

洛沙坦：

上市后报告：肝炎^[参考]

血液学

未报告频率：血红蛋白减少，血细胞比容减少

氢氯噻嗪：

未报告频率：再生障碍性贫血，粒细胞缺乏症，白细胞减少症，溶血性贫血，血小板减少症

洛沙坦：

未报告频率：溶血，贫血^[参考]

新陈代谢

上市后报告：高钾血症

氢氯噻嗪：

未报告频率：高血糖，高尿酸血症

洛沙坦：

未报告频率：厌食，痛风

上市后报告：高钾血症，低钠血症^[参考]

眼科

氢氯噻嗪：

频率未报告：暂时性视力模糊，黄腐病

洛沙坦：

未报告频率：视力模糊，眼睛灼热/刺痛，结膜炎，视力下降^[参考]

精神科

氢氯噻嗪：

未报告频率：躁动

洛沙坦：

未报告频率：焦虑，焦虑症，意识错乱，梦境异常，抑郁，失眠，性欲下降，神经质，恐慌症，睡眠障碍^[参考]

泌尿生殖

氢氯噻嗪：

未报告频率：糖尿

洛沙坦：

未报告频率：阳Imp，夜尿，尿频，尿路感染^[参考]

免疫学的

洛沙坦：

上市后报告：过敏反应^[参考]

某些副作用可能没有报道。您可以将其报告给FDA。

成年人通常的高血压剂量

高血压：
氢氯噻嗪12.5至25 mg-洛沙坦50至100 mg每天口服一次

最大剂量：氢氯噻嗪25毫克-洛沙坦100毫克，每天一次

评论：
-氢氯噻嗪或氯沙坦单药治疗不能充分控制血压的患者，每天一次应改为口服氢氯噻嗪12.5 mg-氯沙坦50 mg。
-如果约3周后血压仍无法控制，可能会增加剂量。

用途：治疗高血压。除非高血压严重到足以迅速控制血压的益处超过了开始联合治疗的风险，否则不建议将该药物用于初始治疗。

严重高血压：
初始治疗：每天口服一次氢氯噻嗪12.5 mg-洛沙坦50 mg；如果2至4周后血压仍无法控制，则可以开始最大剂量。

最大剂量：氢氯噻嗪25毫克-洛沙坦100毫克，每天一次

左室肥厚性高血压：
初始疗法：氯沙坦单一疗法；如果血压保持不受控制，可以开始使用这种药物。

附加疗法：每天口服一次氢氯噻嗪12.5 mg-洛沙坦50 mg；如果血压无法控制，则每天口服一次口服氢氯噻嗪12.5 mg-氯沙坦100 mg，然后如果需要，每天口服一次氢氯噻嗪25 mg-氯沙坦100 mg。

使用：减少高血压和左心室肥大患者中风的风险，但有证据表明，这种益处不适用于黑人患者。

肾脏剂量调整

轻至中度肾功能不全（CrCl 30 mL / min或更高）：不建议调整
严重肾功能不全（CrCl低于30 mL / min）：不推荐

肝剂量调整

不建议作为初始疗法

预防措施

美国盒装警告：
-毒性：如果检测到怀孕，请尽快停药。直接作用于肾素血管紧张素系统（RAS）的药物可能导致发育中的胎儿受伤甚至死亡。

未确定18岁以下患者的安全性和疗效。

有关其他预防措施，请参阅“警告”部分。

透析

数据不可用

其他的建议

监控：
-有血管性水肿病史（面部，嘴唇，喉咙和/或舌头肿胀）的患者应予以密切监测。
-定期监测血清电解质和肾功能。

患者建议：
-应告知育龄女性在怀孕期间接触该药物的后果；请这些患者尽快报告妊娠。
-鼓励患者报告在治疗开始期间可能出现的任何头昏眼花的情况，并停止服用该药物，直到晕厥发生时咨询医生。
-脱水可能导致血压过度降低；如果患者出汗过多，呕吐或腹泻，请告知患者与他们的医疗保健提供者联系。