SmartRx Gaba套件

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加巴喷丁胶囊USP

加巴喷丁胶囊USP

SmartRx Gaba试剂盒的适应症和用法

• 加巴喷丁胶囊适用于：
• 成人疱疹后神经痛
• 在3岁及以上癫痫的成人和儿童患者中，辅助治疗可用于部分发作和不伴继发性泛发

加巴喷丁胶囊（USP）用于：

• 成人带状疱疹后遗神经痛的治疗
• 在3岁及以上癫痫的成人和儿童患者中，辅助治疗可用于部分发作和不伴继发性泛发

SmartRx Gaba Kit剂量和管理

• 带状疱疹后神经痛
• 剂量可根据需要调整至1800 mg /天
• 第1天：单次300毫克剂量
• 第2天：600毫克/天（即每天两次300毫克）
• 第3天：900毫克/天（即每天3次300毫克）
• 癫痫伴部分发作
• 12岁及以上的患者：起始剂量为300毫克，每天3次；每天最多可滴定600毫克，三次
• 3至11岁的患者：起始剂量范围为10至15 mg / kg /天，分三剂； 3至4岁患者的推荐剂量为40 mg / kg /天，分三剂服用； 5至11岁患者的推荐剂量为25至35 mg / kg /天，分三剂服用。在约3天的时间内通过向上滴定达到推荐剂量
• 肾功能减退的患者应调整剂量

带状疱疹后神经痛的剂量

对于患有疱疹后神经痛加巴喷丁胶囊的成人，USP可以在第1天以单次300 mg剂量，在第2天以600 mg /天（每天两次300 mg）和在第3天以900 mg /天的剂量开始服用（ 300毫克，每天3次）。随后可以根据需要将剂量调整为1800毫克/天（600毫克，一天3次）以减轻疼痛。在临床研究中，在1800 mg /天至3600 mg /天的剂量范围内证明了疗效，并且在整个剂量范围内具有可比的作用。但是，在这些临床研究中，未证明使用大于1800 mg /天的剂量具有额外的益处。

癫痫发作部分发作的剂量

12岁以上的患者

起始剂量为每天三次300毫克。加巴喷丁胶囊的建议维持剂量USP为300毫克至600毫克，每天3次。长期临床研究中耐受高达2400 mg / day的剂量。 3600毫克/天的剂量也已在较短时间内施用于少数患者，并且耐受性良好。每天3次使用300 mg或400 mg胶囊管理加巴喷丁胶囊（USP）。两次给药之间的最长时间不应超过12小时。

儿科患者年龄3至11岁

起始剂量范围为10毫克/千克/天至15毫克/千克/天，分为三个剂量，建议的维持剂量通过约3天的向上滴定达到。加巴喷丁胶囊（USP）在3至4岁患者中的推荐维持剂量为40 mg / kg /天，分为三个剂量。加巴喷丁胶囊USP在5至11岁患者中的建议维持剂量为25毫克/千克/天至35毫克/千克/天，分三剂服用。 USP加巴喷丁胶囊可以口服溶液，胶囊或片剂形式使用，也可以组合使用这些制剂。在长期的临床研究中，耐受高达50 mg / kg / day的剂量。两次给药之间的最大时间间隔不应超过12小时。

肾功能不全患者的剂量调整

建议对12岁及12岁以上肾功能不全或接受血液透析的患者进行剂量调整（有关每种适应症的有效剂量，请参见上述剂量建议）：

TID =一天三次； BID =每天两次； QD =单日剂量

a对于肌酐清除率<15 mL / min的患者，应按肌酐清除率的比例减少每日剂量（例如，肌酐清除率7.5 mL / min的患者应接受肌酐清除率15 mL的患者的一半的日剂量/ min接收）。

b接受血液透析的患者应根据表上部指示的肌酐清除率估算值接受维持剂量，并按表下部指示的每4小时进行血液透析补充剂量。

肌酐清除率（CLCr）在门诊患者中很难测量。对于肾功能稳定的患者，可使用Cockcroft和Gault方程合理地估算肌酐清除率。

尚未研究加巴喷丁胶囊在小于12岁肾功能受损的患者中使用USP的情况。

老年人用量

由于老年患者更有可能肾功能下降，因此应谨慎选择剂量，并应根据这些患者的肌酐清除率值调整剂量。

行政资讯

口服或不加食物可口服加巴喷丁胶囊（USP）。

加巴喷丁胶囊，USP应当用水完全吞咽。

如果加巴喷丁胶囊的USP剂量减少，停药或用替代药物替代，则应在至少1周内逐步进行（开处方者可以酌情决定更长的疗程）。

剂型和优势

胶囊：100 mg，300 mg和400 mg

胶囊：

100 mg：白色，不透明的硬明胶胶囊，在瓶盖和阀体上均印有“ IP 101”。

300毫克：浅黄色，不透明的硬明胶胶囊，在帽子和身体上均印有“ IP 102”。

400毫克：浅焦糖-浅焦糖，不透明的硬明胶胶囊，在瓶盖和瓶体上均印有“ IP 103”。

禁忌症

• 已知对加巴喷丁或其成分过敏

已证明对药物或其成分过敏的患者禁用加巴喷丁胶囊（USP）。

警告和注意事项

• 嗜酸性粒细胞增多和全身症状的药物反应（多器官超敏反应）：如果无法确定其他病因，则停用加巴喷丁
• 过敏反应和血管性水肿：停用加巴喷丁并立即评估患者
• 驾驶障碍：警告患者不要驾驶，除非他们有足够的加巴喷丁经验，以评估它是否会削弱他们的驾驶能力
• 嗜睡/镇静和头晕：加巴喷丁可能损害患者操作复杂器械的能力
• 如果突然停用加巴喷丁，癫痫发作患者的癫痫发作频率可能会增加
• 自杀行为和观念：监视自杀思想和行为
• 3至12岁儿童的神经精神病学不良反应：监测此类事件

嗜酸性粒细胞增多和全身症状（DRESS）/多器官超敏反应的药物反应

加巴喷丁已发生与嗜酸性粒细胞增多和全身症状（DRESS）的药物反应，也称为多器官超敏反应。其中一些反应是致命的或威胁生命的。 DRESS通常（尽管不是唯一）表现为发烧，皮疹和/或淋巴结病，并伴有其他器官系统受累，例如肝炎，肾炎，血液学异常，心肌炎或有时类似于急性病毒感染的肌炎。嗜酸性粒细胞增多症经常存在。该疾病的表达是可变的，可能涉及此处未提及的其他器官系统。

重要的是要注意，即使皮疹不明显，也可能出现过敏的早期表现，如发烧或淋巴结肿大。如果出现此类征兆或症状，应立即对患者进行评估。如果无法确定迹象或症状的替代病因，则应停用加巴喷丁。

过敏反应和血管性水肿

加巴喷丁在首次给药后或治疗期间的任何时间都可能引起过敏反应和血管性水肿。报告病例的体征和症状包括呼吸困难，嘴唇，喉咙和舌头肿胀以及需要紧急治疗的低血压。如果患者出现过敏反应或血管性水肿的体征或症状，应指导患者停用加巴喷丁并立即就医。

对驾驶和操作重型机械的影响

服用加巴喷丁的患者在获得足够的经验以评估加巴喷丁是否会损害其驾驶能力之前，不应开车。使用加巴喷丁的前药（加巴喷丁enacarbil片剂，延长释放）进行的驾驶性能研究表明，加巴喷丁可能会导致严重的驾驶障碍。处方者和患者应意识到，患者评估自己的驾驶能力的能力以及评估由加巴喷丁引起的嗜睡程度的能力可能是不完善的。加巴喷丁开始治疗后驾驶障碍的持续时间未知。损害是否与加巴喷丁的嗜睡或其他作用有关尚不清楚。

此外，由于加巴喷丁会引起嗜睡和头晕，因此建议患者在获得足够的加巴喷丁经验以评估加巴喷丁是否削弱其执行此类任务的能力之前，不要操作复杂的器械。

嗜睡/镇静和头晕

在接受12天以上加巴喷丁每日1800毫克剂量的12岁以上患者的对照癫痫试验中，与安慰剂相比，加巴喷丁患者的嗜睡，头昏和共济失调发生率更高：即，药物治疗组和安慰剂治疗组分别为19％安慰剂用于失眠的患者占9％，药物占17％，晕眩占安慰剂的7％，共济失调，药物占13％，安慰剂占6％。在这些试验中，嗜睡，共济失调和疲劳是导致12岁以上患者停用加巴喷丁的常见不良反应，其中分别有1.2％，0.8％和0.6％的患者停用加巴喷丁。

在疱疹后神经痛患者的对照试验中，据报道，接受加巴喷丁的患者每天嗜睡和头晕的发生率高于安慰剂，最高剂量为3600 mg：即加巴喷丁治疗的患者为21％，而最高为5％安慰剂治疗的患者有嗜睡感，加巴喷丁治疗的患者有28％晕眩，安慰剂治疗的患者有8％头晕。头晕和嗜睡是导致加巴喷丁停用的最常见不良反应。

当加巴喷丁与其他具有镇静作用的药物一起使用时，由于潜在的协同作用，应仔细观察患者的中枢神经系统（CNS）抑郁征兆，例如嗜睡和镇静作用。此外，需要同时使用吗啡治疗的患者可能会加巴喷丁浓度升高，可能需要调整剂量。

退出突然发作，癫痫持续状态

抗癫痫药不应突然停药，因为可能会增加癫痫发作的频率。

在大于12岁的患者中进行的安慰剂对照癫痫研究中，接受加巴喷丁治疗的患者癫痫持续状态的发生率为0.6％（543为3），而接受安慰剂的患者为0.5％（378 of 2）。在所有癫痫研究（对照和非对照）中，使用加巴喷丁治疗的2074位年龄大于12岁的患者中，有31位（1.5％）患有癫痫持续状态。其中，有14例患者在治疗前或使用其他药物时没有癫痫持续状态病史。由于没有足够的历史数据，因此无法说加巴喷丁治疗与癫痫持续状态的发生率相比，是否比未加巴喷丁治疗的相似人群更高或更低。

自杀行为和观念

包括加巴喷丁在内的抗癫痫药物（AED）会增加服用这些药物用于任何适应症的患者发生自杀念头或行为的风险。应监测接受任何AED治疗的任何适应症患者的抑郁症，自杀念头或行为和/或情绪或行为的任何异常变化的出现或恶化。

对11种不同AED的199例安慰剂对照临床试验（单一和辅助治疗）的汇总分析表明，随机分配到其中一种AED的患者发生自杀的风险约为两倍（调整后相对风险1.8，95％CI：1.2，2.7）。与随机接受安慰剂的患者相比。在这些中位治疗时间为12周的试验中，在27,863例接受AED治疗的患者中，自杀行为或意念的估计发生率为0.43％，相比之下，在1,029例接受安慰剂治疗的患者中，自杀行为或意念的发生率为0.24％，增加了约一倍。每530名接受治疗的患者有自杀念头或行为。在试验中，接受药物治疗的患者中有四种自杀，而在接受安慰剂治疗的患者中没有自杀，但是数量太少，无法得出有关药物对自杀影响的任何结论。

最早在开始使用AED进行药物治疗后一周，就观察到AED产生自杀念头或行为的风险增加，并且在评估的治疗期间一直存在。由于分析中包括的大多数试验都没有超过24周，因此无法评估24周后有自杀念头或行为的风险。

在所分析的数据中，自杀想法或行为的风险在药物之间通常是一致的。发现具有不同作用机制且适应症范围广泛的AED会增加患病风险，这表明该风险适用于用于任何适应症的所有AED。在所分析的临床试验中，该风险在年龄（5至100岁）之间没有显着变化。表2通过指示显示了所有评估的AED的绝对和相对风险。

在癫痫症的临床试验中，自杀想法或行为的相对风险高于在精神病或其他疾病的临床试验中，但对于癫痫症和精神病指征，绝对风险差异相似。

任何考虑加巴喷丁或其他AED处方的人都必须在自杀念头或行为的风险与未治疗疾病的风险之间取得平衡。开具AED的癫痫病和许多其他疾病本身与发病率和死亡率以及自杀念头和行为的风险增加有关。如果在治疗过程中出现自杀念头和行为，则处方者需要考虑在任何给定患者中这些症状的出现是否与所治疗的疾病有关。

应告知患者，其护理人员和家属，AED增加自杀思想和行为的风险，并应告知需要警惕抑郁症的迹象和症状的出现或恶化，情绪或行为的任何异常变化，或自杀念头，行为或关于自我伤害的念头的出现。关注的行为应立即报告给医疗保健提供者。

神经精神病学不良反应（3至12岁的小儿患者）

加巴喷丁在3至12岁的小儿癫痫患者中的使用与中枢神经系统发生的不良反应有关。其中最重要的几类可分为以下几类：1）情绪不稳（主要是行为问题），2）敌对行为，包括攻击性行为，3）思维障碍，包括注意力不集中和学校成绩的变化，以及4）运动过度（主要是躁动和多动）。在加巴喷丁治疗的患者中，大多数反应的强度为轻度至中度。

在针对3至12岁儿童的临床癫痫对照试验中，这些不良反应的发生率是：情绪不稳6％（加巴喷丁治疗的患者）对1.3％（安慰剂治疗的患者）；敌意为5.2％和1.3％;运动亢进4.7％对2.9％;和思想障碍1.7％对0％。其中一种反应是敌意的报道，被认为是严重的。加巴喷丁治疗中断的患者中有1.3％的患者报告有情绪不稳和运动亢进，而0.9％的加巴喷丁治疗的患者中有敌意和思想障碍。一名接受安慰剂治疗的患者（0.4％）由于情绪不稳而退出。

致瘤潜力

在一项口服致癌性研究中，加巴喷丁增加了大鼠胰腺腺泡细胞肿瘤的发生率。这一发现的临床意义尚不清楚。加巴喷丁上市前的发展过程中的临床经验没有提供直接的方法来评估其在人体内诱发肿瘤的潜力。

在癫痫辅助疗法的临床研究中，> 12岁的患者中有2085个患者-年的接触年，据报道有10位患者出现新肿瘤（2例乳腺癌，3例脑，2例肺，1例肾上腺，1例非霍奇金淋巴瘤，1例）。加巴喷丁停用后或停用后两年内，有11例患者（9例大脑，1例乳腺，1例前列腺癌）和原发性子宫内膜癌恶化。如果不了解在未接受加巴喷丁治疗的类似人群中的背景发病率和复发情况，就不可能知道该人群中的发病率是否受到治疗的影响。

癫痫患者猝死原因不明

在加巴喷丁的上市前发展过程中，记录了使用加巴喷丁治疗的2203例癫痫患者（接触2103病人-年）队列中的8例突然和无法解释的死亡。

其中一些可能代表与癫痫发作有关的死亡，其中未观察到癫痫发作，例如在晚上。这表示每患者年0.0038例死亡。尽管该比率超出了按年龄和性别匹配的健康人群的预期比率，但仍在未接受加巴喷丁的癫痫患者突然无法解释的死亡发生率的估计范围之内（从癫痫总人口的0.0005到癫痫患者的0.003）。与加巴喷丁计划相似的临床试验人群，难治性癫痫患者的临床试验人群为0.005）。因此，这些数字是否令人放心还是需要进一步关注，取决于向加巴喷丁队列报告的人群的可比性以及所提供估计数的准确性。

药物相互作用

吗啡可增加加巴喷丁的浓度；可能需要调整剂量

其他抗癫痫药

加巴喷丁没有明显的代谢，也不会干扰通常共同使用的抗癫痫药的代谢。

阿片类药物

氢可酮

加巴喷丁与氢可酮合用可降低氢可酮的暴露量。在服用氢可酮的患者开始或停用加巴喷丁时，应考虑改变氢可酮暴露的可能性和影响。

吗啡

加巴喷丁与吗啡合用时，应观察患者中枢神经系统（CNS）抑郁的征兆，例如嗜睡，镇静和呼吸抑制。

药物/实验室测试的相互作用

由于在将加巴喷丁添加到其他抗癫痫药中后，尿液蛋白的Ames N-MultistixSG®试纸测试报告了错误的阳性读数，因此建议使用更具体的磺基水杨酸沉淀程序来确定尿蛋白的存在。

过量

在单次口服剂量高达8000 mg / kg的小鼠和大鼠中，未鉴定出加巴喷丁的致死剂量。动物的急性毒性迹象包括共济失调，呼吸困难，上睑下垂，镇静，机能减退或兴奋。

据报道急性加巴喷丁口服过量达49克。在这些情况下，观察到双眼，言语不清，嗜睡，嗜睡和腹泻。所有患者均在支持治疗下康复。据报道，接受加巴喷丁治疗的慢性肾功能衰竭患者可通过透析解决昏迷。

加巴喷丁可以通过血液透析去除。尽管在一些报道的用药过量病例中并未进行血液透析，但可能由患者的临床状况或严重肾功能不全的患者表明。

如果发生过度暴露，请致电1-800-222-1222与您的毒物控制中心联系。

SmartRx Gaba套件说明

加巴喷丁胶囊USP中的活性成分是加巴喷丁USP，化学名称为1-（氨基甲基）环己烷乙酸。加巴喷丁的分子式为C9H17NO2，分子量为171.24。加巴喷丁的结构式为：

USP加巴喷丁是白色至类白色结晶固体，pKa1为3.7，pKa2为10.7。它可自由溶于水以及碱性和酸性水溶液。 pH 7.4时分配系数（正辛醇/0.05M磷酸盐缓冲液）的对数为–1.25。

每个加巴喷丁USP胶囊均包含100 mg，300 mg或400 mg加巴喷丁和以下非活性成分：硬脂酸镁，预糊化淀粉（玉米），淀粉（玉米）和滑石粉。 100 mg胶囊壳包含明胶，十二烷基硫酸钠和二氧化钛。 300毫克胶囊的外壳包含明胶，十二烷基硫酸钠，二氧化钛和氧化铁黄。 400毫克胶囊壳包含明胶，十二烷基硫酸钠，二氧化钛，FD＆C黄色6号和FD＆C蓝色1号。

SmartRx Gaba试剂盒-临床药理学

作用机理

加巴喷丁产生镇痛和抗癫痫作用的确切机制尚不清楚。

加巴喷丁在结构上与神经递质γ-氨基丁酸（GABA）有关，但对GABA结合，摄取或降解没有影响。体外研究表明，加巴喷丁与电压激活钙通道的α2δ亚基具有高亲和力。然而，这种结合与加巴喷丁的治疗作用之间的关系尚不清楚。

药代动力学

加巴喷丁给药后的所有药理作用归因于母体化合物的活性。加巴喷丁在人体内没有明显代谢。

口服生物利用度

加巴喷丁的生物利用度与剂量不成比例。即，随着剂量增加，生物利用度降低。加巴喷丁在900、1200、2400、3600和4800毫克/天的剂量下分3次服用，其生物利​​用度分别约为60％，47％，34％，33％和27％。食物对加巴喷丁的吸收速率和吸收程度影响很小（AUC和C max增加14％）。

分配

少于3％的加巴喷丁循环结合血浆蛋白。加巴喷丁150 mg静脉内给药后的表观分布体积为58±6 L（平均±SD）。在癫痫患者中，脑脊髓液中加巴喷丁的稳态给药前剂量（C min）约为相应血浆浓度的20％。

消除

加巴喷丁作为未改变的药物通过肾脏排泄从体循环中消除。加巴喷丁在人体内没有明显代谢。

加巴喷丁消除半衰期为5到7小时，并且不受剂量或多次给药后的影响。加巴喷丁消除速率常数，血浆清除率和肾脏清除率与肌酐清除率成正比。在老年患者和肾功能受损的患者中，加巴喷丁的血浆清除率降低。加巴喷丁可以通过血液透析从血浆中去除。

特定人群

年龄

在20至80岁的受试者中研究了年龄的影响。加巴喷丁的表观口腔清除率（CL / F）随着年龄的增加而降低，从30岁以下的人约225 mL / min降至70岁以上的人约125 mL / min。肾脏清除率（CLr）和根据体表面积调整的CLr也随着年龄的增长而下降；然而，加巴喷丁的肾脏清除率随年龄的下降在很大程度上可以归因于肾功能的下降。

性别

尽管尚未进行正式的研究来比较加巴喷丁在男性和女性中的药代动力学，但看来男性和女性的药代动力学参数相似，并且没有明显的性别差异。

种族

尚未研究由于种族引起的药代动力学差异。由于加巴喷丁主要通过肾脏排泄，并且肌酐清除率没有重要的种族差异，因此无法预期种族引起的药代动力学差异。

小儿科

在约10 mg / kg的剂量下，在1个月至12岁之间的48位儿科受试者中确定了加巴喷丁的药代动力学。整个年龄段的血浆血浆峰值相似，并且在给药后2至3小时内出现。一般而言，在1个月至<5岁之间的儿科受试者的暴露量（AUC）比在5岁以上的人群中低约30％。因此，在幼儿中，按体重归一化的口腔清除率较高。加巴喷丁的表观口腔清除率与肌酐清除率成正比。加巴喷丁消除半衰期平均为4.7小时，在所研究的各个年龄段中相似。

在1个月至13岁之间的253名儿科患者中进行了群体药代动力学分析。患者每天接受3次，剂量为10至65 mg / kg /天。表观口腔清除率（CL / F）与肌酐清除率成正比，这种关系在单剂量和稳态后相似。按体重归一化后，在5岁以下的儿童中观察到的口腔清除率值高于5岁以上的儿童。 <1岁以下婴儿的清除率差异很大。在5岁及以上的小儿患者中观察到的标准化CL / F值与单剂后在成人中观察到的值一致。在各个年龄段，按体重归一化后的口腔分布体积是恒定的。

这些药代动力学数据表明，患有3岁和4岁癫痫病的小儿患者的有效日剂量应为40 mg / kg /天，以达到与5岁及以上接受加巴喷丁30 mg /岁的患者的平均血浆浓度相似的平均血浆浓度。公斤/天。

成人肾功能不全患者

肾功能不全（平均肌酐清除率范围为13至114 mL / min）的受试者（N = 60）被给予单次400 mg口服加巴喷丁的剂量。加巴喷丁的平均半衰期约为6.5小时（肌酐清除率> 60 mL / min的患者）至52小时（肌酐清除率<30 mL / min），加巴喷丁的肾清除率约为90 mL / min（> 60 mL / min）。组）至约10 mL / min（<30 mL / min）。平均血浆清除率（CL / F）从约190 mL / min降低至20 mL / min。尚未对有肾功能不全的小儿患者进行研究。

血液透析

在一项针对无尿成年受试者（N = 11）的研究中，加巴喷丁在非透析日的表观消除半衰期约为132小时。在透析过程中，加巴喷丁的表观半衰期缩短至3.8小时。因此，血液透析对无尿对象的加巴喷丁消除具有显著作用。

肝病

由于加巴喷丁不代谢，因此未对肝功能不全患者进行任何研究。

药物相互作用

• 体外研究

进行了体外研究，以研究加巴喷丁使用同工型选择性标记底物和人肝微粒体制剂抑制主要细胞色素P450酶（CYP1A2，CYP2A6，CYP2C9，CYP2C19，CYP2D6，CYP2E1和CYP3A4）的潜力，这些酶介导药物和异种生物的代谢。 。仅在最高测试浓度（171 mcg / mL； 1 mM）下，观察到亚型CYP2A6的轻度抑制（14％至30％）。在高达171 mcg / mL的加巴喷丁浓度下（3600毫克/天的C max的15倍左右），未观察到任何其他受试异构体的抑制作用。

• 体内研究

本节中描述的药物相互作用数据来自健康成年人和癫痫成年患者的研究。

苯妥英

在单次（400毫克）和多次剂量（400毫克，一天三次）研究中，使用苯妥英单药治疗至少2个月的癫痫患者（N = 8）中加巴喷丁对稳态低谷血浆无影响苯妥英钠和苯妥英钠的浓度对加巴喷丁的药代动力学没有影响。

卡马西平

稳态加谷血浆卡马西平和卡马西平10、11的环氧浓度不受加巴喷丁（400毫克，每天3次； N = 12）的同时给药的影响。同样地，卡马西平的给药未改变加巴喷丁的药代动力学。

丙戊酸

加巴喷丁联合给药前后和给药期间的稳态谷血清丙戊酸平均浓度（每天400 mg，3次； N = 17）无差异，加巴喷丁的药代动力学参数也不受丙戊酸影响。

苯巴比妥

无论是单独给药还是一起给药，苯巴比妥或加巴喷丁的稳态药代动力学参数估计值（一天三次，每次300 mg； N = 12）相同。

萘普生

萘普生钠胶囊（250 mg）与加巴喷丁（125 mg）的共同给药（N = 18）似乎会使加巴喷丁的吸收量增加12％至15％。加巴喷丁对萘普生的药代动力学参数没有影响。这些剂量低于两种药物的治疗剂量。两种药物在推荐剂量范围内的相互作用程度尚不清楚。

氢可酮

与单独施用氢可酮相比，加巴喷丁（125至500 mg； N = 48）共同给药可降低氢可酮（10 mg； N = 50）的Cmax和AUC值，且呈剂量依赖性。施用125 mg加巴喷丁后Cmax和AUC值分别降低3％至4％，而施用500 mg加巴喷丁后Cmax和AUC值分别降低21％至22％。这种相互作用的机制尚不清楚。氢可酮使加巴喷丁的AUC值增加14％。其他剂量下的相互作用强度尚不清楚。

吗啡

一篇文献文章报道说，在600 mg加巴喷丁胶囊之前2小时服用60 mg控释吗啡胶囊（N = 12），与不加吗啡的加巴喷丁相比，平均加巴喷丁AUC增加了44％。吗啡给药2小时后，加巴喷丁的给药不会影响吗啡的药代动力学参数值。其他剂量下的相互作用强度尚不清楚。

西咪替丁

在QID为300 mg的西咪替丁存在下（N = 12），加巴喷丁的平均表观口服清除率降低了14％，肌酐清除率降低了10％。因此，西咪替丁似乎改变了加巴喷丁和肌酐的肾脏排泄，肌酐是肾功能的内源性标志物。西咪替丁对加巴喷丁排泄的这种小幅减少预计不会具有临床意义。未评估加巴喷丁对西咪替丁的作用。

口服避孕药

根据AUC和半衰期，服用含2.5 mg乙酸炔诺酮和50 mcg乙炔雌二醇的片剂给药后，炔诺酮和炔雌醇的多剂量药代动力学相似，加巴喷丁（400 mg，3次，每次3 mg）天； N = 13）。当与加巴喷丁共同使用时，炔诺酮的C max升高13％。预期这种相互作用不具有临床重要性。

抗酸剂（Maalox®）（氢氧化铝，氢氧化镁）

含有镁和氢氧化铝的抗酸剂（Maalox®）使加巴喷丁（N = 16）的平均生物利用度降低了约20％。当在Maalox后2小时施用加巴喷丁时，生物利用度降低约10％。

丙磺舒

丙磺舒是肾小管分泌的阻滞剂。加巴喷丁在没有丙磺舒和有丙磺舒的情况下的药代动力学参数是相当的。这表明加巴喷丁没有被丙磺舒所阻断的途径经历肾小管分泌。

非临床毒理学

致癌，诱变，生育力受损

在两年的致癌性研究中，将加巴喷丁口服给予小鼠和大鼠。在剂量高达2000 mg / kg / day的小鼠中未观察到药物相关的致癌性。在MRHD为3600 mg / day的情况下，小鼠的血浆加巴喷丁暴露（AUC）约为人类的2倍。在大鼠中，在接受最高剂量（2000 mg / kg）的雄性大鼠中发现胰腺腺泡细胞腺瘤和癌的发生率增加，但在250或1000 mg / kg / day的剂量中则没有。在MRHD下，大鼠血浆加巴喷丁暴露量（AUC）为1000 mg / kg时，约为人的5倍。

旨在研究加巴喷丁诱导的大鼠胰腺癌发生机理的研究表明，加巴喷丁在体外刺激大鼠胰腺腺泡细胞中的DNA合成，因此可能通过增强促有丝分裂活性而充当肿瘤启动子。尚不知道加巴喷丁是否具有增加其他细胞类型或其他物种（包括人类）中细胞增殖的能力。

加巴喷丁在三个体外和四个体内试验中均未显示出诱变或遗传毒性潜力。中国仓鼠肺细胞的Ames试验和体外HGPRT正向突变试验均为阴性。在体外中国仓鼠肺细胞分析中，它没有产生明显的染色体畸变；在中国仓鼠骨髓的体内染色体畸变试验和体内微核试验中均为阴性。在体内小鼠微核试验中为阴性；而且它不会诱导加巴喷丁大鼠肝细胞中非计划的DNA合成。

在剂量高达2000 mg / kg的大鼠中未观察到对生育力或生殖的不利影响。 At 2000 mg/kg, the plasma gabapentin exposure (AUC) in rats is approximately 8 times that in humans at the MRHD.

临床研究

Postherapetic Neuralgia

Gabapentin was evaluated for the management of postherpetic neuralgia (PHN) in two randomized, double-blind, placebo-controlled, multicenter studies. The intent-to-treat (ITT) population consisted of a total of 563 patients with pain for more than 3 months after healing of the herpes zoster skin rash (Table 6).

Each study included a 7-or 8-week double-blind phase (3 or 4 weeks of titration and 4 weeks of fixed dose). Patients initiated treatment with titration to a maximum of 900 mg/day gabapentin over 3 days. Dosages were then to be titrated in 600 to 1200 mg/day increments at 3-to 7-day intervals to the target dose over 3 to 4 weeks. Patients recorded their pain in a daily diary using an 11-point numeric pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). A mean pain score during baseline of at least 4 was required for randomization. Analyses were conducted using the ITT population (all randomized patients who received at least one dose of study medication).

Both studies demonstrated efficacy compared to placebo at all doses tested.

The reduction in weekly mean pain scores was seen by Week 1 in both studies, and were maintained to the end of treatment. Comparable treatment effects were observed in all active treatment arms.Pharmacokinetic/pharmacodynamic modeling provided confirmatory evidence of efficacy across all doses.

Epilepsy for Partial Onset Seizures (Adjunctive Therapy)

The effectiveness of gabapentin as adjunctive therapy (added to other antiepileptic drugs) was established in multicenter placebo-controlled, double-blind, parallel-group clinical trials in adult and pediatric patients (3 years and older) with refractory partial seizures.

Evidence of effectiveness was obtained in three trials conducted in 705 patients (age 12 years and above) and one trial conducted in 247 pediatric patients (3 to 12 years of age). The patients enrolled had a history of at least 4 partial seizures per month in spite of receiving one or more antiepileptic drugs at therapeutic levels and were observed on their established antiepileptic drug regimen during a 12-week baseline period (6 weeks in the study of pediatric patients). In patients continuing to have at least 2 (or 4 in some studies) seizures per month, gabapentin or placebo was then added on to the existing therapy during a 12-week treatment period. Effectiveness was assessed primarily on the basis of the percent of patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the “responder rate”) and a derived measure called response ratio, a measure of change defined as (T -B)/(T + B), in which B is the patient's baseline seizure frequency and T is the patient's seizure frequency during treatment. Response ratio is distributed within the range -1 to +1. A zero value indicates no change while complete elimination of seizures would give a value of -1; increased seizure rates would give positive values. A response ratio of -0.33 corresponds to a 50% reduction in seizure frequency. The results given below are for all partial seizures in the intent-to-treat (all patients who received any doses of treatment) population in each study, unless otherwise indicated.

One study compared gabapentin 1200 mg/day, in three divided doses with placebo. Responder rate was 23% (14/61) in the gabapentin group and 9% (6/66) in the placebo group; the difference between groups was statistically significant. Response ratio was also better in the gabapentin group (-0.199) than in the placebo group (-0.044), a difference that also achieved statistical significance.

A second study compared primarily gabapentin 1200 mg/day, in three divided doses (N=101), with placebo (N=98). Additional smaller gabapentin dosage groups (600 mg/day, N=53; 1800 mg/day, N=54) were also studied for information regarding dose response. Responder rate was higher in the gabapentin 1200 mg/day group (16%) than in the placebo group (8%), but the difference was not statistically significant. The responder rate at 600 mg (17%) was also not significantly higher than in the placebo, but the responder rate in the 1800 mg group (26%) was statistically significantly superior to the placebo rate. Response ratio was better in the gabapentin 1200 mg/day group (-0.103) than in the placebo group (-0.022); but this difference was also not statistically significant (p = 0.224). A better response was seen in the gabapentin 600 mg/day group (-0.105) and 1800 mg/day group (-0.222) than in the 1200 mg/day group, with the 1800 mg/day group achieving statistical significance compared to the placebo group.

A third study compared gabapentin 900 mg/day, in three divided doses (N=111), and placebo (N=109). An additional gabapentin 1200 mg/day dosage group (N=52) provided dose-response data. A statistically significant difference in responder rate was seen in the gabapentin 900 mg/day group (22%) compared to that in the placebo group (10%). Response ratio was also statistically significantly superior in the gabapentin 900 mg/day group (-0.119) compared to that in the placebo group (-0.027), as was response ratio in 1200 mg/day gabapentin (-0.184) compared to placebo.

Analyses were also performed in each study to examine the effect of gabapentin on preventing secondarily generalized tonic-clonic seizures. Patients who experienced a secondarily generalized tonic-clonic seizure in either the baseline or in the treatment period in all three placebo-controlled studies were included in these analyses. There were several response ratio comparisons that showed a statistically significant advantage for gabapentin compared to placebo and favorable trends for almost all comparisons.

Analysis of responder rate using combined data from all three studies and all doses (N=162, gabapentin; N=89, placebo) also showed a significant advantage for gabapentin over placebo in reducing the frequency of secondarily generalized tonic-clonic seizures.

In two of the three controlled studies, more than one dose of gabapentin was used. Within each study, the results did not show a consistently increased response to dose. However, looking across studies, a trend toward increasing efficacy with increasing dose is evident.

Figure 4. Responder Rate in Patients Receiving Gabapentin Expressed as a Difference from Placebo by Dose and Study: Adjunctive Therapy Studies in Patients ≥12 Years of Age with Partial Seizures

In the figure, treatment effect magnitude, measured on the Y axis in terms of the difference in the proportion of gabapentin and placebo-assigned patients attaining a 50% or greater reduction in seizure frequency from baseline, is plotted against the daily dose of gabapentin administered (X axis).

Although no formal analysis by gender has been performed, estimates of response (Response Ratio) derived from clinical trials (398 men, 307 women) indicate no important gender differences exist. There was no consistent pattern indicating that age had any effect on the response to gabapentin. There were insufficient numbers of patients of races other than Caucasian to permit a comparison of efficacy among racial groups.

A fourth study in pediatric patients age 3 to 12 years compared 25 to 35 mg/kg/day gabapentin (N=118) with placebo (N=127). For all partial seizures in the intent-to-treat population, the response ratio was statistically significantly better for the gabapentin group (-0.146) than for the placebo group (-0.079). For the same population, the responder rate for gabapentin (21%) was not significantly different from placebo (18%).

A study in pediatric patients age 1 month to 3 years compared 40 mg/kg/day gabapentin (N=38) with placebo (N=38) in patients who were receiving at least one marketed antiepileptic drug and had at least one partial seizure during the screening period (within 2 weeks prior to baseline). Patients had up to 48 hours of baseline and up to 72 hours of double-blind video EEG monitoring to record and count the occurrence of seizures. There were no statistically significant differences between treatments in either the response ratio or responder rate.

供应/存储和处理方式

Gabapentin capsules, USP are supplied as follows:

100 mg capsules:

White-White, opaque hard gelatin capsules printed with “IP 101” on both cap and body. They are available as follows:

Bottles of 30: NDC 65162-101-03
Bottles of 100: NDC 65162-101-10
Bottles of 500: NDC 65162-101-50
Bottles of 1000: NDC 65162-101-11

300 mg capsules:

Buff-Buff, opaque hard gelatin capsules printed with “IP 102” on both cap and body. They are available as follows:

Bottles of 30: NDC 65162-102-03
Bottles of 100: NDC 65162-102-10
Bottles of 500: NDC 65162-102-50
Bottles of 1000: NDC 65162-102-11

400 mg capsules:

Light caramel-Light caramel, opaque hard gelatin capsules printed with “IP 103” on both cap and body. They are available as follows:

Bottles of 30: NDC 65162-103-03
Bottles of 100: NDC 65162-103-10
Bottles of 500: NDC 65162-103-50
Bottles of 1000: NDC 65162-103-11

Store gabapentin capsules at 20° to 25°C (68° to 77°F);允许在15°至30°C（59°至86°F）的范围内进行偏移[请参阅USP控制的室温]。 Dispense in tight (USP), child-resistant containers.

用药指南

Gabapentin (GA-be-PEN-tin) Capsules

Read the Medication Guide before you start taking gabapentin capsules and each time you get a refill.可能有新的信息。此信息不能代替您与医疗保健提供者谈论您的医疗状况或治疗方法。

What is the most important information I should know about gabapentin capsules? Do not stop taking gabapentin capsuleswithout first talking to your healthcare provider.

Stopping gabapentin capsules suddenly can cause serious problems.

Gabapentin capsules can cause serious side effects including:

1. Suicidal Thoughts. Like other antiepileptic drugs, gabapentin capsules may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

• 关于自杀或死亡的想法
• 企图自杀
• 新的或更严重的抑郁症
• 新的或更严重的焦虑
• feeling agitated or restless
• 惊恐发作
• 睡眠困难（失眠）
• 烦躁不安
• 表现出攻击性，生气或暴力
• 采取危险的冲动
• 活动和交谈的极端增加（躁狂）
• 行为或情绪上的其他异常变化

How can I watch for early symptoms of suicidal thoughts and actions?

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop taking gabapentin capsules without first talking to a healthcare provider.

• Stopping gabapentin capsules suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).
• Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

2. Changes in behavior and thinking - Using gabapentin capsules in children 3 to 12 years of age can cause emotional changes, aggressive behavior, problems with concentration, restlessness, changes in school performance, and hyperactivity.

3. Gabapentin capsules may cause serious or life-threatening allergic reactions or other parts of your body such as your liver or blood cells. This may cause you to be hospitalized or to stop gabapentin capsules. You may or may not have rash with an allergic reaction caused by gabapentin capsules. Call a healthcare provider right away if you have any of the following symptoms:

• 皮疹
• 麻疹
• 呼吸困难
• 发热
• swollen glands that do not go away
• swelling of your face, lips, throat, or tong
• yellowing of your skin or of the whites of the eyes
• unusual bruising or bleeding
• severe fatigue or weakness
• unexpected muscle pain
• frequent infections

These symptoms may be the first signs of a serious reaction. A healthcare provider should examine you to decide if you should continue taking gabapentin capsules.

What are gabapentin capsules?

Gabapentin capsules are a prescription medicine used to treat:

• Pain from damaged nerves (postherpetic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection) in adults.
• Partial seizures when taken together with other medicines in adults and children 3 years of age and older with seizures.

Who should not take gabapentin capsules?

Do not take gabapentin capsules if you are allergic to gabapentin or any of the other ingredients in gabapentin capsules. See the end of this Medication Guide for a complete list of ingredients in gabapentin capsules.

What should I tell my healthcare provider before taking gabapentin capsules?

Before taking gabapentin capsules, tell your healthcare provider if you:

• have or have had kidney problems or are on hemodialysis
• have or have had depression, mood problems, or suicidal thoughts or behavior
• 患有糖尿病
• 正在怀孕或打算怀孕。 It is not known if gabapentin capsules can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking gabapentin capsules. You and your healthcare provider will decide if you should take gabapentin capsules while you are pregnant.
  • If you become pregnant while taking gabapentin capsules, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. You can enroll in this registry by calling 1-888-233-2334.
• 正在母乳喂养或计划母乳喂养。 Gabapentin can pass into breast milk. You and your healthcare provider should decide how you will feed your baby while you take gabapentin capsules.

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

  Taking gabapentin capsules with certain other medicines can cause side effects or affect how well they work.在未与您的医疗服务提供者交谈的情况下，请勿启动或停止其他药物。

  知道你吃的药。 Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

  How should I take gabapentin capsules?

• Take gabapentin capsules exactly as prescribed. Your healthcare provider will tell you how much gabapentin capsules to take.
• Do not change your dose of gabapentin capsules without talking to your healthcare provider.

• Take gabapentin capsules with water.

• Gabapentin capsules can be taken with or without food. If you take an antacid containing aluminum and magnesium, such as Maalox ®, Mylanta ®, Gelusil ®, Gaviscon ®, or Di-Gel ®, you should wait at least 2 hours before taking your next dose of gabapentin capsules.

If you take too much gabapentin capsules, call your healthcare provider or your local Poison Control Center right away at 1-800-222-1222.

What should I avoid while taking gabapentin capsules?

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking gabapentin capsules without first talking with your healthcare provider. Taking gabapentin capsules with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not drive, operate heavy machinery, or do other dangerous activities until you know how gabapentin capsules affects you. Gabapentin capsules can slow your thinking and motor skills.

What are the possible side effects of gabapentin capsules?

Gabapentin capsules may cause serious side effects including:

• See “What is the most important information I should know about gabapentin capsules?”
• problems driving while using gabapentin capsules. See “What I should avoid while taking gabapentin capsules?”
• sleepiness and dizziness, which could increase the occurrence of accidental injury, including falls
• The most common side effects of gabapentin capsules include:

• lack of coordination
• viral infection
• feeling drowsy
• 恶心和呕吐
• 说话困难
• 震颤
• swelling, usually of legs and feet
• 感觉累了
• 发热
• jerky movements
• difficulty with coordination
• 双重视野
• unusual eye movement

告诉您的医疗保健提供者，如果您有任何困扰您或不会消失的副作用。

These are not all the possible side effects of gabapentin capsules.有关更多信息，请咨询您的医疗保健提供者或药剂师。

打电话给您的医生，征求有关副作用的医疗建议。您可以通过1-800-FDA-1088向FDA报告副作用。

How should I store gabapentin capsules?

• Store Gabapentin Capsules between 68°F to 77°F (20°C to 25°C).

Keep gabapentin capsules and all medicines out of the reach of children.

General information about the safe and effective use of gabapentin capsules

除《药物指南》中列出的药物外，有时还会开出其他药物。 Do not use gabapentin capsules for a condition for which it was not prescribed. Do not give gabapentin capsules to other people, even if they have the same symptoms that you have.可能会伤害他们。

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

For more information go to http://www.amneal.com or call 1-877-835-5472.

What are the ingredients in gabapentin capsules?

Active ingredient: gabapentin, USP

Inactive ingredients in the capsules: magnesium stearate, pregelatinized starch (corn), starch (corn) and talc.

The 100-mg capsule shell contains: gelatin, sodium lauryl sulfate, and titanium dioxide.

The 300-mg capsule shell contains: gelatin, sodium lauryl sulfate, titanium dioxide, and iron oxide yellow.

The 400-mg capsule shell contains: gelatin, sodium lauryl sulfate, titanium dioxide, FD&C Yellow No. 6, and FD&C Blue No. 1.

本药物指南已获得美国食品和药物管理局的批准。

该产品的标签可能已更新。 For current full prescribing information, please visit www.amneal.com

*Trademarks are the property of their respective owners.

分配者：

Amneal Pharmaceuticals

布里奇沃特，NJ 08807

Rev. 10-2015-04

MAALOX® (aluminum hydroxide, magnesium hydroxide)

The mean bioavailability of gabapentin was reduced by about 20% with concomitant use of an antacid (Maalox®) containing magnesium and aluminum hydroxides. It is recommended that gabapentin be taken at least 2 hours following Maalox administration.

不良反应

Most common adverse reactions (incidence ≥8% and at least twice that for placebo) were:

• Postherpetic neuralgia: dizziness, somnolence, and peripheral edema
• Epilepsy in patients >12 years of age: somnolence, dizziness, ataxia, fatigue, and nystagmus
• Epilepsy in patients 3 to 12 years of age: viral infection, fever, nausea and/or vomiting, somnolence, and hostility

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or www.amneal.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
• Anaphylaxis and Angioedema
• Somnolence/Sedation and Dizziness
• Withdrawal Precipitated Seizure, Status Epilepticus
• Suicidal Behavior and Ideation
• Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age)
• Sudden and Unexplained Death in Patients with Epilepsy

Clinical Trials Experience

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。

Postherpetic Neuralgia

The most common adverse reactions associated with the use of gabapentin in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema.

In the 2 controlled trials in postherpetic neuralgia, 16% of the 336 patients who received gabapentin and 9% of the 227 patients who received placebo discontinued treatment because of an adverse reaction. The adverse reactions that most frequently led to withdrawal in gabapentin-treated patients were dizziness, somnolence, and nausea.

Table 3 lists adverse reactions that occurred in at least 1% of gabapentin-treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the gabapentin group than in the placebo group.

Other reactions in more than 1% of patients but equally or more frequent in the placebo group included pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome.

There were no clinically important differences between men and women in the types and incidence of adverse reactions. Because there were few patients whose race was reported as other than white, there are insufficient data to support a statement regarding the distribution of adverse reactions by race.

Epilepsy with Partial Onset Seizures (Adjunctive Therapy)

The most common adverse reactions with gabapentin in combination with other antiepileptic drugs in patients >12 years of age, not seen at an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus.

The most common adverse reactions with gabapentin in combination with other antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostilit .

Approximately 7% of the 2074 patients >12 years of age and approximately 7% of the 449 pediatric patients 3 to 12 years of age who received gabapentin in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with withdrawal in patients >12 years of age were somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and/or vomiting (0.6%), and dizziness (0.6%). The adverse reactions most commonly associated with withdrawal in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%).

a Plus background antiepileptic drug therapy

b Amblyopia was often described as blurred vision.

Among the adverse reactions occurring at an incidence of at least 10% in gabapentin-treated patients, somnolence a