Omeclamox-Pak

Omeclamox-Pak的适应症和用法

患有活动性十二指肠溃疡或有十二指肠溃疡病史的患者根除幽门螺杆菌

Omeclamox-Pak（奥美拉唑缓释胶囊，克拉霉素片和阿莫西林胶囊一起服用）适用于治疗幽门螺杆菌感染和十二指肠溃疡病（活跃或已有一年历史）的患者，以根除成人幽门螺杆菌。已证明根除幽门螺杆菌可降低十二指肠溃疡复发的风险[参见临床研究（ 14.1 ） ]。

用法

为了减少耐药菌的产生并保持Omeclamox-Pak和其他抗菌药物的有效性，Omeclamox-Pak仅应用于治疗或预防已证实或强烈怀疑由易感细菌引起的感染。当可获得文化和药敏性信息时，在选择或修改抗菌疗法时应考虑它们。在缺乏此类数据的情况下，局部流行病学和易感性模式可能有助于经验性治疗的选择。

Omeclamox-Pak剂量和给药

推荐的成人口服剂量和方案是奥美拉唑缓释胶囊20毫克加克拉霉素500毫克加阿莫西林1000毫克，每餐每天两次，每天10天，早晨和晚上在饭前服用。告知患者不要压碎或咀嚼奥美拉唑，克拉霉素和阿莫西林，应将其整个吞下。

在开始治疗时出现溃疡的患者中，建议每天额外服用18天的奥美拉唑20 mg，以治愈溃疡和缓解症状。

剂型和优势

Omeclamox-Pak以纸箱形式提供，其中包含十张独立的日常管理卡。每张卡包含：

• 奥美拉唑缓释胶囊，美国药典，20毫克

两个不透明的硬质明胶熏衣草和灰色胶囊，胶囊上分别用黑色墨水印有“ R 158”和“ OMEPRAZOLE 20 mg”，其中包含灰白色至浅黄色椭圆球形颗粒。

• 克拉霉素片，美国药典，500毫克

两片白色，双凸面，斜边，胶囊状包衣片，一侧刻有“ 54 312”，另一侧刻有纯色。

• 阿莫西林胶囊（USP），500毫克

四个不透明的硬明胶黄色胶囊，标记为“ GG849”。

禁忌症

过敏症

Omeclamox-Pak在以下患者中禁用：

• 对奥美拉唑或苯并咪唑，任何大环内酯类抗菌药物或任何青霉素过敏的已知病史。对奥美拉唑的超敏反应可能包括过敏反应，过敏性休克，血管性水肿，支气管痉挛，间质性肾炎和荨麻疹。对克拉霉素的超敏反应可能包括过敏反应，史蒂文斯-约翰逊综合征和中毒性表皮坏死。对阿莫西林的超敏反应可能包括血清病，如反应，红斑丘疹，多形红斑，史蒂文斯-约翰逊综合症，剥脱性皮炎，中毒性表皮坏死，急性全身性皮炎性脓疱病，超敏性血管炎和荨麻疹[参见不良反应（ 6.3 ） 。
• 据报道，接受青霉素治疗的患者出现严重的，偶发性的致命过敏反应。尽管在肠胃外治疗后过敏反应更为频繁，但口服青霉素的患者已经发生过敏反应。这些反应更容易发生在具有青霉素过敏史和/或对多种变应原过敏史的个体中。在开始用阿莫西林治疗之前，应仔细询问先前对青霉素，头孢菌素或其他过敏原的超敏反应。

严重的药物相互作用（心脏毒性，麦角症）

Omeclamox-Pak是服用麦角胺或二氢麦角胺和匹莫齐的患者的禁忌症。据报道，使用克拉霉素和/或红霉素和匹莫齐特可导致心律失常，甚至致命。心律失常已经包括QT间期延长，室性心动过速，心室纤颤，和尖端扭转型，并且最可能是由于由克拉霉素和/或红霉素[见药物相互作用（抑制这些药物的代谢的7.2 ， 7.3 ）]。

警告和注意事项

胚胎-胎儿毒性

克拉霉素是Omeclamox-Pak的成分，已证明对猴子，大鼠，小鼠和兔子的妊娠结局和/或胚胎胎儿发育有不利影响，其剂量所产生的血浆浓度是人体在室温下所达到的血清浓度的2至17倍。推荐的最大人类剂量。

根据动物研究的结果，不建议将Omeclamox-Pak用于孕妇，除非在临床环境中没有合适的替代疗法。如果在怀孕期间使用Omeclamox-Pak，或者在患者服用该药物期间发生怀孕，则应告知患者对胎儿的潜在危害[参见在特定人群中使用（ 8.1 ） ]。

秋水仙碱与克拉霉素的毒性

上市后有秋水仙碱毒性的报告，一些致命，并与克拉霉素和秋水仙碱同时使用，尤其是在老年人中，其中一些发生在肾功能不全的患者中。监测患者秋水仙碱毒性的临床症状[参见药物相互作用（ 7.1 ） ]。

重症肌无力

据报道，在接受克拉霉素治疗的患者中，重症肌无力症状加重和肌无力综合征的新症状发作。监视患者的症状。

艰难梭状芽胞杆菌相关性腹泻

据报道，使用克拉霉素和阿莫西林可引起艰难梭菌相关性腹泻（CDAD），严重程度从轻度腹泻到致命性结肠炎[见不良反应（ 6.3 ） ]。用抗菌剂处理会改变结肠的正常菌群，导致艰难梭菌的过度生长。

艰难梭菌产生毒素A和B，这有助于CDAD的发展。产生高毒素的艰难梭菌菌株会增加发病率和死亡率，因为这些感染对于抗菌治疗可能是难治的，可能需要行结肠切除术。所有在使用抗生素后出现腹泻的患者中都必须考虑CDAD。有必要仔细的病史，因为据报道CDAD在服用抗菌药物后两个月内发生。

如果怀疑或证实了CDAD，则可能需要停止不针对艰难梭菌的抗生素持续使用。应根据临床情况进行适当的液体和电解质管理，蛋白质补充，艰难梭菌的抗生素治疗以及手术评估。

伴随胃恶性肿瘤

对奥美拉唑治疗的症状反应并不排除存在胃恶性肿瘤。

急性间质性肾炎

在服用包括奥美拉唑在内的PPI患者中已观察到急性间质性肾炎（AIN）。急性间质性肾炎可在PPI治疗期间的任何时间发生，通常归因于特发性超敏反应。如果AIN发作，请停用奥美拉唑[参见禁忌症（ 4.1 ） ]。

皮肤性和系统性狼疮

据报道，服用奥美拉唑等PPI的患者皮肤红斑狼疮（CLE）和系统性红斑狼疮（SLE）。这些事件既发生在新的发作中，也加剧了现有的自身免疫性疾病。大多数由PPI引起的红斑狼疮病例为CLE。

在接受PPI治疗的患者中，最常见的CLE形式是亚急性CLE（SCLE），发生在连续药物治疗后数周至数年内，从婴儿到老年人。通常，观察到组织学结果而没有器官参与。

在接受PPI的患者中，系统性红斑狼疮（SLE）的报道少于CLE。与PPI相关的SLE通常比非药物诱发的SLE轻。 SLE的发作通常在开始治疗后的几天到几年内发生，主要发生在从年轻人到老年人的患者中。大多数患者出现皮疹；但是，也有关节痛和血细胞减少症的报道。

避免PPI的给药时间超过医学指示的时间。如果在接受Omeclamox-Pak的患者中发现与CLE或SLE一致的体征或症状，请停药，并将患者转至适当的专家进行评估。大多数患者仅在4至12周内停止PPI即可改善症状。血清学检测（例如ANA）可能是阳性的，而血清学检测结果升高可能需要比临床表现更长的时间才能解决。

细菌感染的发展

在使用Omeclamox-Pak进行治疗期间，由于克拉霉素和阿莫西林成分的存在，应谨记真菌或细菌病原体重复感染的可能性。如果发生超级感染，应终止Omeclamox-Pak并采取适当的治疗措施。

单核细胞增多症和氨苄西林

接受氨苄西林的单核细胞增多症患者中有很大一部分会出现红斑皮疹。因此，不建议单核细胞增多症患者使用氨苄西林类抗生素。

耐药菌的发展

在没有被证实的或强烈怀疑的细菌感染或预防性指征的情况下开具奥美拉莫-朴（克拉霉素或阿莫西林成分）的处方不太可能为患者带来益处，并增加了产生耐药细菌的风险。

不良反应

标签上其他地方描述了以下严重不良反应：

• 超敏反应[参见禁忌症（ 4.1 ） ]
• 重症肌无力[见警告和注意事项（ 5.3 ） ]
• 难辨梭状芽孢杆菌相关性腹泻[请参阅警告和注意事项（ 5.4 ） ]

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。

在使用奥美拉唑，克拉霉素和阿莫西林三联疗法的临床试验中，未观察到三联疗法特有的不良反应。观察到的不良反应仅限于先前使用奥美拉唑，克拉霉素或阿莫西林报道的不良反应。在临床试验中，与奥美拉唑，克拉霉素和阿莫西林（n = 274）联合治疗的最常见不良反应为腹泻（14％），味觉变态（10％）和头痛（7％）。这些事件的发生频率均比单独服用抗微生物剂的患者报告的发生频率更高。

Omeclamox-Pak各个成分的标签不良反应

以下安全性数据反映了全球临床试验中针对各种适应症使用的奥美拉唑缓释胶囊和克拉霉素暴露的情况，这些适应症的剂量和疗程可能与它们作为Omeclamox-Pak成分的使用方式不同。有关这些反应的完整信息，请参阅奥美拉唑缓释胶囊和克拉霉素的完整处方信息。

奥美拉唑：

在临床试验中报道的3096例奥美拉唑缓释胶囊治疗患者中最常见的不良反应（即，发生率≥2％）包括头痛（6.9％），腹痛（5.2％），恶心（4.0） ％），腹泻（3.7％），呕吐（3.2％）和肠胃气胀（2.7％）。

发生率≥1％的其他不良反应包括反酸（1.9％），上呼吸道感染（1.9％），便秘（1.5％），头晕（1.5％），皮疹（1.5％），乏力（1.3） ％），背部疼痛（1.1％）和咳嗽（1.1％）。

65岁以上患者的临床试验安全性与65岁以下患者相似。

克拉霉素：

成人中最常报告的事件是腹泻（3％），恶心（3％），异味（3％），消化不良（2％），腹痛/不适（2％）和头痛（2％）。这些事件大多数被描述为轻度或中度。在所报告的不良事件中，只有1％被描述为严重。由于药物相关的副作用，只有不到3％的没有分枝杆菌感染的成人患者中止治疗。

Omeclamox-Pak各个成分的上市后经验

由于这些反应是从不确定大小的人群中自愿报告的，因此始终无法可靠地估计其实际发生频率或建立与药物暴露的因果关系。

奥美拉唑：

整体身体：过敏反应，包括过敏反应，过敏性休克，血管性水肿，支气管痉挛，间质性肾炎，荨麻疹（另见下文皮肤）；发热;疼痛;疲劳;不适。

心血管疾病：胸痛或心绞痛，心动过速，心动过缓，心，血压升高，周围水肿。

内分泌：男性乳房发育。

胃肠道：胰腺炎（部分致命），厌食，结肠易怒，粪便变色，食道念珠菌病，舌头黏膜萎缩，口腔炎，腹部肿胀，口干。在用奥美拉唑治疗期间，很少注意到胃底腺息肉。这些息肉是良性的，并且在停止治疗时似乎是可逆的。长期接受奥美拉唑治疗的Zollinger-Ellison综合征患者中已报告胃十二指肠类癌。该发现被认为是潜在病症的表现，已知与这种肿瘤有关。

肝：肝病，包括肝衰竭（一些致命），肝坏死（一些致命），肝性脑病，肝细胞疾病，胆汁淤积性疾病，混合性肝炎，黄疸和肝功能检查升高[ALT，AST，GGT，碱性磷酸酶和胆红素]。

代谢/营养：低血糖，低钠血症，体重增加。

肌肉骨骼：肌肉无力，肌痛，肌肉痉挛，关节痛，腿痛。

神经系统/精神病学：精神病学和睡眠障碍，包括抑郁，躁动，攻击性，幻觉，意识错乱，失眠，神经质，冷漠，嗜睡，焦虑和梦境异常；震颤，感觉异常；眩晕。

呼吸道：鼻出血，咽痛。

皮肤：严重的全身性皮肤反应，包括毒性表皮坏死溶解（有些致命），史蒂文斯-约翰逊综合症和多形性红斑；光敏性荨麻疹;皮疹;皮肤发炎;瘙痒瘀点紫癜脱发皮肤干燥;多汗症。

特殊感觉：耳鸣，口味变态。

眼：视神经萎缩，前部缺血性视神经病变，视神经炎，干眼症候群，眼刺激，视力模糊，复视。

泌尿生殖系统：间质性肾炎，血尿，蛋白尿，血清肌酐升高，镜下脓尿，尿路感染，糖尿，尿频，睾丸疼痛。

血液学：粒细胞缺乏症（某些致命），溶血性贫血，全血细胞减少，中性粒细胞减少，贫血，血小板减少，白细胞减少症，白细胞增多。

克拉霉素：

过敏反应：发生了过敏反应，从荨麻疹和轻度皮肤喷发到罕见的过敏反应，史蒂文斯-约翰逊综合症和中毒性表皮坏死症。

胃肠道：舌炎，口腔炎，口腔念珠菌病，厌食，呕吐，胰腺炎，舌头变色。

血液学：血小板减少症，白细胞减少症，中性粒细胞减少症。

其他：有报道称克拉霉素治疗的患者牙齿变色。牙齿变色通常可以通过专业的牙齿清洁来逆转。

神经系统/精神病学：有单独的听力损失报告，通常是可逆的，主要发生在老年妇女中。也有关于气味感改变的报道，通常伴随着味觉变态或味觉丧失。

在上市后的监测过程中，已经报告了中枢神经系统的短暂事件，包括焦虑，行为改变，精神错乱，抽搐，人格解体，迷失方向，幻觉，失眠，躁狂行为，噩梦，精神病，耳鸣，震颤，头晕和眩晕。事件通常通过停药而解决。

肝：克拉霉素很少报道肝功能异常，包括肝酶增加，以及肝细胞和/或胆汁淤积性肝炎，伴或不伴黄疸。这种肝功能障碍可能很严重，通常是可逆的。在极少数情况下，已经报道了具有致命后果的肝衰竭，并且通常与严重的基础疾病和/或伴随用药有关。

代谢：很少有低血糖的报道，其中一些发生在服用口服降糖药或胰岛素的患者中。

心脏：与其他大环内酯类药物一样，克拉霉素与QT延长和室性心律不齐有关，包括室性心动过速和尖锐湿疣。

肾：有报告称克拉霉素同时存在间质性肾炎。

阿莫西林：

胃肠道：恶心，呕吐，腹泻，厌食，胃炎，黑舌，舌炎，口腔炎和出血性/艰难梭菌相关性结肠炎。 [请参阅警告和注意事项（ 5.4 ） ]。

过敏反应：已有反应如血清病，红斑性红斑丘疹，多形性红斑，史蒂文斯-约翰逊综合症，剥脱性皮炎，中毒性表皮坏死，急性全身性化脓性脓疱病，超敏性血管炎和荨麻疹。以前对青霉素过敏的人和有过敏，哮喘，花粉症或荨麻疹病史的人更容易发生反应。

肝：已注意到AST（SGOT）和/或ALT（SGPT）适度升高，但这一发现的意义尚不清楚。肝功能障碍包括胆汁淤积性黄疸，肝胆汁淤积和急性细胞溶解性肝炎。

肾：晶体尿症也有报道[见药物过量（ 10 ） ]。

血液和淋巴系统：青霉素治疗期间已报告了贫血，包括溶血性贫血，血小板减少，血小板减少性紫癜，嗜酸性粒细胞增多，白细胞减少和粒细胞缺乏症。这些反应通常在停止治疗时是可逆的，并且被认为是超敏现象。

神经系统/精神病学：很少报道可逆的活动过度，躁动，焦虑，失眠，意识模糊，无菌性脑膜炎，行为改变和/或头晕。

杂项：牙齿变色（棕色，黄色或灰色染色）的报道很少。大多数报道发生在儿科患者中。在大多数情况下，通过刷牙或牙齿清洁可减少或消除变色。

实验室值的变化：可能具有临床意义的实验室值的变化如下：肝– SGPT（ALT）升高小于1％，SGOT（AST）降低1％，GGT降低1％，碱性磷酸酶降低1％ ，LDH小于1％，总胆红素小于1％；血液学–白细胞减少少于1％，凝血酶原时间增加1％；肾脏– BUN升高4％，血清肌酐升高不到1％。 GGT，碱性磷酸酶和凝血酶原时间数据仅来自成人研究。

药物相互作用

奥美拉唑的作用

奥美拉唑是体内CYP2C19的底物和抑制剂，体内CYP3A4的底物和体外CYP2C19的抑制剂。因此，奥美拉唑可能会影响被这些CYP酶代谢的药物的代谢和血浆浓度。尽管在健康受试者中没有与茶碱或普萘洛尔发生相互作用的报道，但已有报道与通过CYP酶系统代谢的其他药物（例如环孢素，双硫仑，苯并二氮杂）发生相互作用。仔细监测服用这些药物的患者，以确定与奥美拉唑同时服用时是否需要调整这些药物的剂量。

克拉霉素的作用

克拉霉素是CYP3A酶的底物和抑制剂。克拉霉素与经CYP3A代谢的药物共同给药可能与药物浓度升高有关，该浓度可能会增加伴随药物的治疗和不良反应。有报道称基于CYP3A的红霉素和/或克拉霉素与环孢菌素，他克莫司，阿芬太尼，利福布汀，甲基强的松龙，西洛他唑和溴隐亭相互作用。此外，有报告称红霉素或克拉霉素与不被CYP3A代谢的药物发生相互作用，包括：己糖巴比妥，苯妥英和丙戊酸盐。

秋水仙碱

秋水仙碱和Omeclamox-Pak并用可能会增加血浆秋水仙碱的浓度。秋水仙碱是CYP3A和外向转运蛋白P-糖蛋白（Pgp）的底物。 Omeclamox-Pak的克拉霉素成分可抑制CYP3A和Pgp。当克拉霉素和秋水仙碱并用时，克拉霉素对Pgp和/或CYP3A的抑制作用可能导致血浆中秋水仙碱的暴露增加。监测患者秋水仙碱毒性的临床症状[参见警告和注意事项（ 5.2 ） ]。

麦角胺/二氢麦角胺

当与Omeclamox-Pak并用时，麦角胺/二氢麦角胺的血浆浓度可能会增加。上市后的报告表明，克拉霉素与麦角胺或二氢麦角胺的并用与以血管痉挛和四肢及其他组织（包括中枢神经系统）缺血为特征的急性麦角毒性有关。禁忌同时使用克拉霉素和麦角胺或二氢麦角胺[见禁忌症（ 4.2 ） ]。

吡im嗪

由于与Omeclamox-Pak的clarithromycin成分发生相互作用，因此将pimozide和Omeclamox-Pak并用可能会增加pimozide的血浆浓度。上市后的报告表明，克拉霉素与匹莫齐合用与心律不齐有关（QT延长，室性心动过速，室性纤颤和尖端扭转型室速）。据报道，将克拉霉素加入正在进行的匹莫齐治疗中有两例突然死亡。 Pimozide被CYP3A4部分代谢。当克拉霉素和匹莫齐一起给药时，克拉霉素对CYP3A4的抑制作用可能导致血浆中匹莫齐的暴露增加。 Omeclamox-Pak是接受匹莫齐特治疗的患者的禁忌症[见禁忌症（ 4.2 ） ]。

抗心律失常药

抗心律失常药物和Omeclamox-Pak并用可能会增强抗心律失常作用，因为它与Omeclamox-Pak的克拉霉素成分相互作用。上市后的报告中指出，同时使用克拉霉素和奎尼丁或二吡甲酰胺会引起尖端扭转型室速。上市后监测中还报告了同时接受克拉霉素和地高辛患者的地高辛血清浓度升高。一些患者显示出与地高辛毒性相一致的临床体征，包括潜在的致命性心律失常。 Omeclamox-Pak与抗心律不齐药物合用时，监测心电图以了解QTc延长。还应监测血清抗心律失常药的浓度，包括地高辛。

抗凝剂

由于与奥美拉唑-帕克的奥美拉唑和克拉霉素成分相互作用，抗凝剂和奥美拉昔-帕克同时给药可能改变华法林和其他口服抗凝剂的抗凝作用。监测同时接受Omeclamox-Pak和口服抗凝剂的患者的凝血酶原时间和INR。

有报道称接受质子泵抑制剂（包括奥美拉唑和华法林）的患者，INR和凝血酶原时间增加。 INR和凝血酶原时间的增加可能导致异常出血甚至死亡。

上市后的自发报告表明，克拉霉素和口服抗凝剂同时给药可能会增强口服抗凝剂的作用。

抗逆转录病毒药物

同时使用抗逆转录病毒药物和Omeclamox-Pak可能会由于与Omeclamox-Pak的奥美拉唑或克拉霉素成分相互作用而改变抗逆转录病毒作用。据报道奥美拉唑与一些抗逆转录病毒药物如阿扎那韦，奈非那韦和沙奎那韦相互作用。

不建议将阿扎那韦或奈非那韦与奥美拉唑同时使用，除非将阿扎那韦或奈非那韦与奥美拉莫昔-帕克一起服用的益处大于风险。 Atazanavir或nelfinavir与质子泵抑制剂的共同给药有望大大降低atazanavir或nelfinavir的血浆浓度，从而降低这两种药物的治疗效果[参见临床药理学（ 12.3 ） ]。

沙奎那韦与奥美拉唑的共同给药可能会增加沙奎那韦的血清浓度。当与Omeclamox-Pak并用时，应考虑降低沙奎那韦的剂量[参见临床药理学（ 12.3 ） ]。

西洛他唑

由于与Omeclamox-Pak的奥美拉唑成分发生相互作用，Omeclamox-Pak和西洛他唑的同时给药可能增加西洛他唑的全身暴露。因此，与Omeclamox-Pak并用时，应考虑将西洛他唑的剂量降低50％[参见临床药理学（ 12.3 ） ]。

他克莫司

由于与Omeclamox-Pak的奥美拉唑成分相互作用，Omeclamox-Pak和他克莫司的同时给药可能会增加他克莫司的血清浓度。与Omeclamox-Pak并用时，建议经常监测他克莫司的全血谷浓度。

茶碱

由于与Omeclamox-Pak的克拉霉素成分相互作用，正在接受茶碱的患者使用Omeclamox-Pak可能与血清茶碱浓度升高有关。对于接受大剂量茶碱或基线浓度在治疗上限范围内的患者，应考虑监测血清茶碱浓度[见临床药理学（ 12.3 ） ]。

卡马西平

由于与Omeclamox-Pak的克拉霉素成分相互作用，卡马西平和Omeclamox-Pak的同时给药可能会改变卡马西平的作用。已显示单剂量克拉霉素和卡马西平的同时给药会导致卡​​马西平的血浆浓度升高。当与Omeclamox-Pak并用时，应考虑对卡马西平进行血药浓度监测。

西地那非

西地那非与Omeclamox-Pak并用时，其全身暴露量可能会增加，因为它与Omeclamox-Pak的克拉霉素成分相互作用。考虑减少西地那非的剂量（请参阅西地那非的完整处方信息）。

HMG-CoA还原酶抑制剂（他汀类）

HMG-CoA还原酶抑制剂（他汀类药物）和Omeclamox-Pak同时使用可能会由于与Omeclamox-Pak的克拉霉素成分相互作用而改变HMG-CoA的作用。与其他大环内酯类药物一样，克拉霉素被认为会增加他汀类药物（例如洛伐他汀和辛伐他汀）的浓度。伴随服用这些药物的患者中很少有横纹肌溶解的报道。

三唑并二氮杂卓（例如三唑仑和阿普唑仑）和相关的苯二氮杂（例如咪达唑仑）

当与Omeclamox-Pak并用时，由于与克拉霉素成分的相互作用，可能会改变三唑并苯并二氮杂卓/相关苯并二氮杂卓的作用。上市后有药物相互作用和中枢神经系统作用（例如嗜睡和神志不清）与克拉霉素和三唑仑同时使用的报道。

丙磺舒

丙磺舒减少阿莫西林的肾小管分泌。同时使用Omeclamox-Pak和丙磺舒可能会导致Omeclamox-Pak的阿莫西林成分的血药浓度升高和延长。

胃液pH值会影响生物利用度的药物

由于其对胃酸分泌的影响，奥美拉唑可以减少药物的吸收，而胃的pH值是决定其生物利用度的重要因素。与降低胃内酸度的其他药物一样，酮康唑，阿扎那韦，铁盐，厄洛替尼和霉酚酸酯等药物的吸收会降低，而奥美拉唑治疗期间地高辛等药物的吸收会增加。

在健康受试者中与奥美拉唑（每天20 mg）和地高辛同时治疗可将地高辛的生物利用度提高10％（两名受试者为30％）。地高辛与奥美拉唑的共同给药有望增加地高辛的全身暴露。因此，当与奥美拉唑同时服用地高辛时，可能需要对患者进行监测。

据报道，在健康受试者和接受霉酚酸酯的移植患者中，奥美拉唑的共同给药可减少暴露于活性成分霉酚酸（MPA）的暴露，这可能是由于在胃pH升高时MPA溶解度降低所致。在接受质子泵抑制剂（PPI）和霉酚酸酯的移植患者中，尚未确定减少MPA暴露与器官排斥的临床相关性。在接受霉酚酸酯的移植患者中谨慎使用奥美拉唑[参见临床药理学（ 12.3 ） ]。

药物实验室测试的相互作用

当使用基于本尼迪克特的铜还原反应的葡萄糖测试来检测尿液中葡萄糖的含量时，高尿液中氨苄青霉素的浓度可能导致假阳性反应，该测试确定了尿液中葡萄糖等还原性物质的量。由于这种作用在阿莫西林中也可能发生，因此建议使用基于酶促葡萄糖氧化酶反应的葡萄糖测试。

向孕妇服用氨苄西林后，已注意到总结合雌二醇，雌三醇-葡糖醛酸苷，结合雌酮和雌二醇的血浆浓度短暂降低。阿莫西林也可能发生这种作用。

在特定人群中的使用

怀孕

风险摘要

根据奥美拉唑和克拉霉素（奥美拉莫-朴的成分）在动物研究中的发现，怀孕期间使用奥美拉莫-朴可能会对胎儿造成伤害。不建议将Omeclamox-Pak用于孕妇，除非在临床情况下没有合适的替代疗法。如果在怀孕期间使用Omeclamox-Pak或在服用Omeclamox-Pak期间怀孕，则应告知患者对胎儿的潜在危害[见警告和注意事项（ 5.1 ） ]。孕妇中没有奥美拉唑，克拉霉素或阿莫西林（单独使用或一起使用）的充分且控制良好的研究。克拉霉素在临床相关剂量下对四种动物表现出不利的发育作用。奥美拉唑增加了兔子的胚胎胎儿损失，但动物研究和多项人体研究并未显示出重大畸形的风险增加。没有证据表明阿莫西林对小鼠和大鼠的胎儿有伤害。

奥美拉唑

没有针对孕妇的奥美拉唑的充分且对照良好的研究。现有的流行病学数据未能证明使用早孕奥美拉唑会增加重大先天畸形或其他不良妊娠结局的风险。在大鼠和兔子中进行的生殖研究显示，奥美拉唑剂量约为人口服40毫克剂量的3.4至34倍，其剂量依赖性胚胎致死性。

在动物生殖研究中未观察到胎儿畸形，在器官形成过程中在大鼠和兔子中口服口服埃索美拉唑（奥美拉唑的对映体）镁分别为人口服40毫克埃索美拉唑或40毫克奥美拉唑约68倍和42倍。 。在大多数妊娠和哺乳期给药的大鼠后代中，观察到骨形态变化，剂量等于或大于奥美拉唑临床剂量的约34倍。当仅将孕妇给药仅限于妊娠时，在任何年龄对后代的骨骨形态都没有影响[见数据]。

克拉霉素

少数已发表的关于在怀孕期间使用克拉霉素的人体研究的有限数据不足以告知与药物相关的重大先天缺陷，流产或不良母婴后果的风险。在动物繁殖研究中，根据体表面积比较，在器官发生期间向怀孕的小鼠，大鼠，兔子和猴子口服克拉霉素可导致大鼠（心血管异常）和小鼠（c裂）畸形。通常认为小鼠，大鼠和猴子的胎儿效应（例如，胎儿存活率降低，体重增加，体重增加）和兔子的着床损失是继母体毒性之后产生的（见动物数据）。

阿莫西林

数十年来使用阿莫西林的流行病学研究报告和药物警戒病例报告提供的可用数据尚未确定主要的先天缺陷，流产或不良的母体或胎儿结局与药物相关的风险（参见数据）。在动物生殖研究中，未对妊娠小鼠和大鼠服用阿莫西林的剂量高达建议人类剂量的3倍和6倍时，未观察到不利的发育影响（请参见数据）。

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％。

数据

动物资料

奥美拉唑

用奥美拉唑在大鼠中进行的生殖研究最高口服剂量为138 mg / kg /天（基于体表面积比较约为口服人类剂量40 mg的34倍），在兔子中最高剂量为69.1 mg / kg /天（在器官发生过程中，口服人类口服剂量40毫克的约34倍剂量）没有发现奥美拉唑具有致畸性的任何证据。在兔子中，在器官发生期间服用奥美拉唑的剂量范围为6.9至69.1 mg / kg /天（约为口服人类剂量40 mg的3.4至34倍），导致胚胎致死率，胎儿吸收和妊娠中断的剂量相关增加。在大鼠中，观察到剂量相关的胚胎/胎儿毒性和产后发育毒性，这是在父母给以13.8至138.0 mg / kg /天的奥美拉唑治疗的父母的后代中观察到的（是口服人类剂量40 mg的约3.4至34倍）在哺乳期交配。

克拉霉素

在口服，静脉注射克拉霉素的小鼠，大鼠，兔子和猴子中进行了动物繁殖研究。在怀孕的小鼠中，克拉霉素在器官发生过程中（妊娠第6至15天）以15、60、250、500或1000 mg / kg / day的口服剂量给药。 Reduced body weight observed in dams at 1000 mg/kg/day (3 times the maximum recommended human dose [MRHD]) resulted in reduced survival and body weight of the fetuses. At ≥ 500 mg/kg/day, increases in the incidence of post-implantation loss and cleft palate in the fetuses were observed. No adverse developmental effects were observed in mice at ≤ 250 mg/kg/day (≤ 1 times MRHD comparison).

In pregnant Sprague Dawley rats, clarithromycin administered during organogenesis (GD 6 to 15) at oral doses of 15, 50, or 150 mg/kg/day resulted in reduced body weight and food consumption in dams at 150 mg/kg/day. Reductions in body weight and food consumption was observed in dams at 150 mg/kg/day. Increased resorptions and reduced body weight of the fetuses at this dose were considered secondary to maternal toxicity. Additionally, at 150 mg/kg/day (1 times MRHD), a low incidence of cardiovascular anomalies (complete situs inversus, undivided truncus, IV septal defect) was observed in the fetuses. Clarithromycin did not cause adverse developmental effects in rats at 50 mg/kg/day (0.3 times MRHD comparison). Intravenous dosing of clarithromycin during organogenesis in rats (GD 6 to 15) at 15, 50, or 160 mg/kg/day was associated with maternal toxicity (reduced body weight, body-weight gain, and food consumption) at 160 mg/kg/day but no evidence of adverse developmental effects at any dose (≤ 1 times MRHD comparison).

In pregnant Wistar rat, clarithromycin was administered during organogenesis (GD 7 to 17) at oral doses of 10, 40, or 160 mg/kg/day. Reduced body weight and food consumption were observed in dams at 160 mg/kg/day but there was no evidence of adverse developmental effects at any dose (≤ 1 times MRHD comparison).

In pregnant rabbits, clarithromycin administered during organogenesis (GD 6 to 18) at oral doses of 10, 35, or 125 mg/kg/day resulted in reduced maternal food consumption and decreased body weight at the highest dose, with no evidence of any adverse developmental effects at any dose (≤ 2 times MRHD comparison). Intravenously administered clarithromycin to pregnant rabbits during organogenesis (GD 6 to 18) in rabbits at 20, 40, 80, or 160 mg/kg/day (≥ 0.3 times MRHD comparison) resulted in maternal toxicity and implantation losses at all doses.

In pregnant monkeys, clarithromycin administered (GD 20 to 50) at oral doses of 35 or 70 mg/kg/day resulted in dose-dependent emesis, poor appetite, fecal changes, and reduced body weight in dams at all doses (≥ 0.5 times MRHD comparison). Growth retardation in 1 fetus at 70 mg/kg/day was considered secondary to maternal toxicity. There was no evidence of primary drug related adverse developmental effects at any dose tested.

In a reproductive toxicology study in rats administered oral clarithromycin late in gestation through lactation (GD 17 to post-natal day 21) at doses of 10, 40, or 160 mg/kg/day (≤ 1 times MRHD comparison), reductions in maternal body weight and food consumption were observed at 160 mg/kg/day. Reduced body-weight gain observed in offspring at 160 mg/kg/day was considered secondary to maternal toxicity. No adverse developmental effects were observed with clarithromycin at any dose tested.

Amoxicillin

Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (3 and 6 times the 3 g human dose based on a body surface area comparison and have revealed no evidence of harm to the fetus due to amoxicillin.

人数据

Omeprazole

Four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H2-receptor antagonists or other controls.

A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population.

A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester.

A retrospective cohort study reported on 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H2-blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively.

A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups.

Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia.

Amoxicillin

While available studies cannot definitively establish the absence of risk, published epidemiological data and post-marketing case reports have not reported a consistent association with amoxicillin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when amoxicillin was used during pregnancy. Available studies have methodologic limitations, including small sample size, retrospective data collection, under-capture of non-live births, exposure misclassification and inconsistent comparator groups.

哺乳期

风险摘要

Based on limited human data, clarithromycin and its active metabolite 14-OH clarithromycin are present in human milk at less than 2% of the maternal weight-adjusted dose (see Data ) . In a separate observational study, reported adverse effects on breast-fed children (rash, diarrhea, loss of appetite, somnolence) were comparable to amoxicillin (see Data ) . No data are available to assess the effects of clarithromycin or 14-OH clarithromycin on milk production.

Limited data from a single case report suggest omeprazole may be present in human milk. There are no clinical data on the effects of omeprazole on the breastfed infant or on milk production.

Data from a published clinical lactation study indicate that amoxicillin is present in human milk. Published adverse effects with amoxicillin exposure in the breast-fed infant include diarrhea. There are no data on the effects of amoxicillin on milk production.

The development and health benefits of breastfeeding should be considered along with the mother's clinical need for omeprazole or clarithromycin or amoxicillin and any potential adverse effects on the breast-fed child from clarithromycin or from the underlying maternal condition.

数据

Clarithromycin

Serum and milk samples were obtained after 3 days of treatment, at steady state, from one published study of 12 lactating women who were taking clarithromycin 250 mg orally twice daily. Based on the limited data from this study, and assuming milk consumption of 150 mL/kg/day, an exclusively human milk fed infant would receive an estimated average of 136 mcg/kg/day of clarithromycin and its active metabolite, with this maternal dosage regimen. This is less than 2% of the maternal weight-adjusted dose (7.8 mg/kg/day, based on the average maternal weight of 64 kg), and less than 1% of the pediatric dose (15 mg/kg/day) for children greater than 6 months of age.

A prospective observational study of 55 breastfed infants of mothers taking a macrolide antibacterial (6 were exposed to clarithromycin) were compared to 36 breastfed infants of mothers taking amoxicillin. Adverse reactions were comparable in both groups. Adverse reactions occurred in 12.7% of infants exposed to macrolides and included rash, diarrhea, loss of appetite, and somnolence.

Amoxicillin

Penicillins are excreted in human milk. Data from a published clinical lactation study indicates that amoxicillin produces low levels in human milk. Published adverse effects with amoxicillin exposure in the breastfed infant include diarrhea and rash.

生殖潜力的男性和女性

不孕症

Clarithromycin

Administration of clarithromycin resulted in testicular atrophy in rats, dogs and monkeys [ See Nonclinical Toxicology ( 13.1 ) ].

儿科用

The safety and effectiveness of Omeclamox-Pak for pediatric patients with H. pylori have not been established.

老人用

Omeprazole

Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the US and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly [ See Clinical Pharmacology ( 12.3 ) ].

Clarithromycin

In a steady-state study in which healthy elderly subjects (age 65 to 81 years old) were given 500 mg every 12 hours, the maximum serum concentrations and area under the curves of clarithromycin and 14-OH clarithromycin were increased compared to those achieved in healthy young adults. These changes in pharmacokinetics parallel known age-related decreases in renal function. In clinical trials, elderly patients did not have an increased incidence of adverse events when compared to younger patients.

Amoxicillin

An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. Of the 1811 subjects treated with amoxicillin, 85% were < 60 years old, 15% were ≥ 61 years old and 7% were ≥ 71 years old. This analysis and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

已知该药物基本上被肾脏排泄，并且在肾功能受损的患者中对该药物产生毒性反应的风险可能更大。由于老年患者更容易出现肾功能下降，因此应谨慎选择剂量，这对监测肾功能可能有用。

肾功能不全

In the presence of severe renal impairment with or without coexisting hepatic impairment, prolonged dosing intervals for the clarithromycin component may be appropriate.

肝功能不全

It is recommended to avoid the use of Omeclamox-Pak in patients with hepatic impairment [ See Clinical Pharmacology ( 12.3 ) ].

Asian Patients

It is recommended to avoid the use of Omeclamox-Pak in Asian patients unless it is deemed that the benefits outweigh the risks [ See Clinical Pharmacology ( 12.3 ) ].

过量

In case of an overdose, patients should contact a physician, poison control center, or emergency room. There is neither a pharmacologic basis nor data suggesting an increased toxicity of the combination compared to individual components.

As with the management of any overdose, the possibility of multiple drug ingestion should be considered. For current information on treatment of any drug overdose, contact your local Poison Control Center at 1-800-222-1222.

Omeprazole :

Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience [ See Adverse Reactions ( 6.3 ) ]. Symptoms were transient, and no serious clinical outcome has been reported when omeprazole was taken alone. No specific antidote for omeprazole overdosage is known. Omeprazole is extensively protein bound and is, therefore, not readily dialyzable.如果剂量过量，应对症治疗和支持治疗。

Single oral doses of omeprazole at 1350, 1339, and 1200 mg/kg were lethal to mice, rats, and dogs, respectively. Animals given these doses showed sedation, ptosis, tremors, convulsions, and decreased activity, body temperature, and respiratory rate and increased depth of respiration.

Clarithromycin :

Overdosage of clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea.

Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.

Amoxicillin :

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying 1 .

在过量服用阿莫西林后，已有少数患者报告了间质性肾炎，导致少尿性肾功能衰竭。在成人和小儿患者中过量服用阿莫西林后，也曾报道过结晶尿症，在某些情况下会导致肾衰竭。如果过量，应保持足够的液体摄入和利尿，以减少阿莫西林结晶的风险。停止给药后，肾功能损害似乎是可逆的。 High blood concentrations may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin can be removed from circulation by hemodialysis.

Omeclamox-Pak Description

Omeclamox-Pak consists of a pack of ten individual daily administration cards, each card containing two omeprazole delayed-release 20 mg capsules, USP, two clarithromycin 500 mg tablets, USP, and four amoxicillin 500 mg capsules, USP, for oral administration.

Omeprazole Delayed-Release Capsules, USP

The active ingredient in omeprazole delayed-release capsules is a substituted benzimidazole, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl- 2-pyridinyl) methyl] sulfinyl]1H-benzimidazole, a proton pump inhibitor that inhibits gastric acid secretion. Its empirical formula is C17H19N3O3S, with a molecular weight of 345.42.结构式为：

Omeprazole is a white to off-white crystalline powder that melts with decomposition at about 155°C. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol, and very slightly soluble in water. The stability of omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.

Each omeprazole delayed-release capsule contains 20 mg of omeprazole in the form of enteric-coated granules with the following inactive ingredients: crospovidone, hypromellose, lactose, magnesium stearate, mannitol, meglumine, methacrylic acid copolymer, poloxamer, povidone and triethyl acetate. The capsule shells contain: D&C Red #28, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, yellow iron oxide, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Imprinting ink contains: D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, n-butyl alcohol, pharmaceutical glaze, propylene glycol, SDA-3A alcohol and synthetic black iron oxide.

Clarithromycin Tablets, USP

Clarithromycin is a semi-synthetic macrolide antimicrobial. Chemically, it is 6- 0 -methylerythromycin. The molecular formula is C 38 H 69 NO 13 , and the molecular weight is 747.96. Clarithromycin has the following structural formula:

Clarithromycin is a white to off-white crystalline powder. It is soluble in acetone, slightly soluble in methanol, ethanol, and acetonitrile, and practically insoluble in water. Each tablet for oral administration contains 500 mg of clarithromycin and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, Opadry II (White), povidone, stearic acid, and talc. Opadry II (White) contains hypromellose, polyethylene glycol, polydextrose, titanium dioxide and triacetin.

Amoxicillin Capsules, USP :

Amoxicillin, a semisynthetic penicillin class antibacterial, is an analogue of ampicillin, with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Chemically it is (2S, 5R, 6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido]- 3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0] heptane-2-carboxylic acid trihydrate. Its empirical formula is C16H19N3O5S •3H2O with a molecular weight of 419.45. Amoxicillin has the following structural formula:

Amoxicillin capsules contain amoxicillin trihydrate equivalent to 500 mg of amoxicillin. Amoxicillin capsules USP also contain magnesium stearate and sodium lauryl sulfate. The capsule shell contains D&C Red No. 33, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, gelatin, sodium lauryl sulfate and titanium dioxide. Each 500 mg capsule contains up to 0.0052 mEq (0.119 mg) of sodium.

Omeclamox-Pak - Clinical Pharmacology

作用机理

Omeprazole is an antisecretory drug whereas clarithromycin and amoxicillin are antibacterial drugs [ See Clinical Pharmacology ( 12.4 ) ].

药代动力学

Pharmacokinetics when all three of the Omeclamox-Pak components were coadministered has not been studied. Studies have shown the low risk of clinically significant interactions of omeprazole and amoxicillin or omeprazole and clarithromycin when administered together. There is no information about the gastric mucosal concentrations of omeprazole, clarithromycin and amoxicillin after administration of these drugs concomitantly. The systemic pharmacokinetic information presented below is based on studies in which each product was administered alone, or in combination of two components.

Omeprazole Delayed-Release Capsules, USP

Absorption and Distribution

Omeprazole delayed-release capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid- labile), so that absorption of omeprazole begins only after the granules leave the stomach. Absorption is rapid, with peak plasma concentrations of omeprazole occurring within 0.5 to 3.5 hours. Peak plasma concentrations of omeprazole and AUC are approximately proportional to doses up to 40 mg, but because of a saturable first-pass effect, a greater than linear response in peak plasma concentration and AUC occurs with doses greater than 40 mg. Absolute bioavailability (compared with intravenous administration) is about 30-40% at doses of 20-40 mg, due in large part to presystemic metabolism. In healthy subjects the plasma half-life is 0.5 to 1 hour, and the total body clearance is 500-600 mL/min.

The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole delayed-release capsules.

Omeprazole delayed-release capsules 40 mg was bioequivalent when administered with and without applesauce. However, omeprazole delayed-release capsules 20 mg was not bioequivalent when administered with and without applesauce. When administered with applesauce, a mean 25% reduction in Cmax was observed without a significant change in AUC for omeprazole delayed-release capsules 20 mg. The clinical relevance of this finding is unknown. Protein binding is approximately 95%.

代谢与排泄

Among those females aged 18 to 44 years of age, 22.4% were diagnosed with skin infections and 7.6% had pneumonia.

老年患者

The elimination rate of omeprazole was somewhat decreased in the elderly, and bioavailability was increased. Omeprazole was 76% bioavailable when a single 40 mg