FDA批准药品Nelarabine最新使用说明书
伊伐布雷定说明书
伊伐布雷定说明书一、药品名称通用名称：伊伐布雷定商品名称：＿____二、成份本品主要成份为伊伐布雷定。
化学名称：7,8-二甲氧基-3-（3-（1S)－1,2,3,4-四氢-1-萘基氨基丙基)－1,3,4,5-四氢-2H-3-苯并氮杂卓-2-酮三、性状本品为薄膜衣片，除去包衣后显白色。
四、适应症适用于窦性心律且心率≥75 次/分钟、伴有心脏收缩功能障碍的NYHA IIIV 级慢性心力衰竭患者，与标准治疗包括β受体阻滞剂联合用药，或者用于禁忌或不能耐受β受体阻滞剂治疗时。
五、规格＿____六、用法用量1、通常推荐起始剂量：5mg，口服，每日两次。
2、治疗期间，如果患者的静息心率持续低于 50 次/分钟，或者出现与心动过缓相关的症状，如头晕、乏力、黑矇等，应将剂量下调至25mg，每日两次。
3、如果患者的心率仍然较高，且耐受性良好，可在至少两周后将剂量上调至 75mg，每日两次。
七、不良反应1、常见不良反应心动过缓：这是最常见的不良反应之一。
光幻视：表现为看到闪光或彩色的光圈。
头晕、头痛。
2、少见不良反应低血压。
房室传导阻滞。
心悸。
3、罕见不良反应过敏反应，如皮疹、瘙痒、呼吸困难等。
如果出现不良反应，应及时告知医生，并根据情况调整治疗方案。
八、禁忌1、对伊伐布雷定过敏者禁用。
2、严重低血压（＜90/50mmHg）禁用。
3、急性心肌梗死禁用。
4、重度肝功能损害禁用。
5、窦房传导阻滞、病态窦房结综合征禁用。
6、不稳定或急性心力衰竭禁用。
九、注意事项1、心率监测在开始治疗前，应进行静息心率的测量。
治疗期间，应定期监测心率，尤其是在调整剂量期间。
2、与其他药物的相互作用与强效 CYP3A4 抑制剂（如酮康唑、伊曲康唑、克拉霉素等）合用时，应减少伊伐布雷定的剂量。
与CYP3A4 诱导剂（如利福平、苯妥英钠、卡马西平等）合用时，可能会降低伊伐布雷定的疗效。
3、特殊人群老年人：无需调整剂量，但应密切监测不良反应。
儿童：尚未确定儿童使用本品的安全性和有效性。
FDA批准新药信息
可能进展为鳞状细胞癌。
BYDUREON(艾塞那肽),普通注射剂的英文商品名为BYETTA,2012年FDA批准该药品注射液每周1次缓释剂型的上市,用于治疗2型糖尿病。
研究表明,治疗24周,艾塞那肽缓释剂型可较基线降低糖化血红蛋白1.6%,而每日2次的剂型降低0.9%。
该药最常见的不良反应是恶心、低血糖、呕吐、腹泻、紧张不安感、眩晕、头痛、消化不良、便秘和无力。
INLYTA(阿西替尼)辉瑞公司产品,用于治疗对其它药物没有应答的晚期肾癌(肾细胞癌)。
INLYTA是一种小分子酪氨酸激酶抑制剂,对多个靶点有效,包括VEGF受体1,2和3。
最常见不良反应包括腹泻,高血压,疲劳,食欲下降,恶心。
FDA表示,高血压患者在接受阿西替尼治疗之前应当控制好血压。
ERIVEDGE由基因泰克公司生产,用于治疗基底细胞癌(basal cell carcinoma,BCC),适用于无法开刀或使用化疗的癌症晚期患者,及癌细胞已经扩散到其他身体器官的病人。
患者每日服用一次。
ERIVEDGE药瓶上的标签警告,此药若用于孕妇将可能导致婴儿死亡,它最常见的副作用包括肌肉痉挛,脱发,消瘦,腹泻,疲劳,改变或丧失味觉,食欲下降,便秘,呕吐。
KALYDECO用于治疗囊肿性纤维化(CF)。
每12小时服用1片。
中度和重度肝功能不全患者剂量相应减少。
与中度或强CYP3A的抑制剂的药物合用时,减少剂量。
雷诺嗪 药典标准
雷诺嗪药典标准
雷诺嗪（Ranolazine）是一种心血管选择性抗缺血药，其药典标准主要参考美国药典（USP）或者中国药典（Ch.P）中关于雷诺嗪的规定。
以下是雷诺嗪的药典标准概述。
1.品名：雷诺嗪
2.化学名称：5-[2-[[4-[(2-氰基乙基)氨基]苯基]-1,3-二氧杂-2-丙醇]-2-甲基-1,3-二氧杂-2-丙醇
3.分子式：C24H31N3O4
4.分子量：433.51
5.CAS号：95635-55-5
6.外观：白色或类白色结晶性粉末
7.熔点：178-182℃
8.用途：抗心绞痛药
9.制剂：片剂、缓释片剂
10.规格：500mg、1000mg（美国）；375mg、500mg、750mg（英国）
需要注意的是，雷诺嗪的药典标准可能会随着不同国家和地区的药典版本而有所差异。
在实际应用中，应遵循医生开具的处方以及药品说明书上的用法用量。
如有疑问，请咨询专业医生。
美国华法林药品说明书
美国华法林药品说明书美国华法林药品说明书1.介绍美国华法林是一种抗凝血药物，通常用于预防和治疗血栓症的形成。
本药品说明书将详细介绍美国华法林的用途、剂量、副作用等相关信息。
2.适应症美国华法林适用于以下情况：- 静脉血栓形成- 肺栓塞- 心房纤颤- 心瓣膜病- 人工心脏瓣膜植入术后3.用法和用量- 患者在使用美国华法林之前应首先接受凝血指标检测，以确定个体化的起始剂量。
- 剂量的选择应考虑到患者的疾病状态、年龄、体重、性别和其他相关因素。
- 初始剂量通常在2-5mg之间，每日一次口服。
- 根据凝血指标的变化，可能需要逐渐调整剂量，以维持合适的抗凝状态。
4.注意事项- 在使用美国华法林期间，患者需要密切监测凝血指标，例如国际标准化比值（INR）。
- 注意合理饮食，避免大量摄入富含维生素K的食物，因为维生素K可以影响美国华法林的疗效。
- 避免与其他药物相互作用，尤其是其他抗凝药物、抗生素和非处方药。
5.不良反应- 常见的不良反应包括出血、血肿、头晕、疲劳、恶心等。
- 去甲肾上腺素和维生素K可以用作美国华法林的拮抗剂。
6.孕妇和儿童用药- 孕妇和哺乳期妇女应在医生的指导下使用美国华法林。
- 儿童使用美国华法林的安全性和有效性尚未确立。
附件：本文档附带的文件包括：- 美国华法林使用指南- 鉴定不良反应报告表法律名词及注释：1.抗凝血药物：用于阻止血液凝块形成的药物。
2.凝血指标：用于评估机体凝血功能的指标。
3.国际标准化比值（INR）：用于标准化凝血指标的国际标准方法。
4.作为拮抗剂：指用于对抗另一药物或化学物质效果的药物或化学物质。
枸橼酸阿尔维林胶囊Alverine Citrate Capsules-详细说明书及重点
枸橼酸阿尔维林胶囊Alverine Citrate Capsules汉语拼音：JuYuanSuanAErWeiLin JiaoNang【成份】本品主要成份为枸橼酸阿尔维林化学名：N-乙基-3,3‘-二苯二丙胺枸橼酸盐分子式：C20H27N.C6H8O7 分子量：473.57【性状】本品为绿色软胶囊，内容物为白色粘稠半固体。
【适应症】➢适用于肠易激综合症、肠痉挛、腹痛、憩室炎引起的疼痛、胆道痉挛。
➢痛经、子宫颈乱。
➢泌尿道结石或感染引发的痉挛性疼痛、下泌尿道感染引起的尿频、膀胱痉挛及其他痉挛性疼痛。
【用法用量】每次1粒，每日2-3次，饭前服；疗程，一个月。
【药理毒理】➢阿尔维林为人工合成的罂粟碱衍生物，直接作用于平滑肌，是一种选择性平滑肌松弛剂，其作用机制为影响离子通道的电位敏感度与磷酸．肌醇代谢途径。
➢本品选择性地作用于胃肠遭、子宫、生殖泌尿道器官的平滑肌，在正常剂量下对气管和血管平滑肌几无影响。
➢对平滑肌的解痉作用约为罂粟碱的2.5～3倍。
抑制组织胺的反应为阿托品的5倍，但抑制乙酰胆碱反应仅为阿托品的万分之一。
故对青光眼及前列腺肥大的患者无禁忌。
本品无成瘾性。
【药代动力学】本品口服吸收后在体内迅速被代谢，其代谢物有4种，其中对平滑肌产生抑制作用的主要为第一种代谢产物，其作用强度为本品原形的数倍。
口服本品6O～120mg，0.5～lh血药浓度达峰值，峰值浓度为9.7±0.8mg/m1．血浆半衰期为0.8±lh。
主要随尿以结合形态排出。
【不良反应】过量服用可能出现中枢神经系统兴奋的症状和低血压。
【注意事项】妊娠时的前3个月禁用。
【禁忌】1、对本品过敏、麻痹性肠梗塞者禁用。
2、前列腺肿瘤患者不宜使用。
3、孕妇或哺乳期妇女慎用。
4、三环类抗抑郁药、普鲁卡因或衍生物、抗组胺药等可加强其作用。
氟康唑、咪康唑、全身性胆碱能药可降低其作用。
儿童难治复发急性淋巴细胞白血病的新治疗策略
doi:10.3969/j.issn.1000-3606.2018.08.018儿童难治复发急性淋巴细胞白血病的新治疗策略赵 旸综述 陆爱东 张乐萍审校北京大学人民医院儿科（北京 100044）摘要： 儿童急性淋巴细胞白血病虽已取得显著疗效，但一旦出现复发或难治，其长期存活机会极少，预后不良。
随着人们对儿童复发难治急性淋巴细胞白血病的分子生物学机制的深入认识，靶向治疗、免疫治疗等新的疗法被用于临床，且已取得较好的临床效果。
文章就儿童难治复发急性淋巴细胞白血病的新疗法进行综述。
关键词： 急性淋巴细胞白血病； 靶向治疗； 免疫治疗； 儿童New therapy of childhood refractory/relapsed acute lymphoblastic leukemia Reviewer: ZHAO Yang, Reviser: LU Aidong, ZHANG Aiping (Department of Pediatrics, Peking University People’s Hospital, Bejing 100044,China) Abstract: Nowdays, the curability of childhood acute lymphoblastic leukemia(ALL) has improved dramatically. However, the subgroup of children with refractory/relapsed ALL still presents a dismal prognosis. New trials such as targeted therapy and immunotherapy are used in practice based on a better genomic characterization, and good clinical effect has been achieved. In this article, we review the current new treatments of childhood refractory/relapsed ALL.Key words: lymphoblastic leukemia; targeted therapy; immunotherapy; child急性淋巴细胞白血病是儿童时期最常见的恶性肿瘤。
Clofarabine 克罗拉滨 产品手册说明书
Clofarabine ；克罗拉滨；氯法拉滨产品编号：MB1061质量标准：>99%,BR包装规格：5MG ；25MG ；100MG产品形式：白色至类白色粉末基本信息简介：克罗拉滨 Clofarabine(Clolar; Clofarex)能抑制核苷酸还原酶，IC50为65 nM ，还能抑制DNA 聚合酶活性。
别名：(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol, 2-chloro-2′-arabino-fluoro-2′-deoxyadenosine ；Clolar ； Clofarex物理性状及指标：外观：……………………白色至类白色粉末熔点：……………………202-205 °C(lit.)溶解性：…………………DMSO 60 mg/mL (197.57 mM)；Water Insoluble ；Ethanol Insoluble 纯度：………………………>99%,BR储存条件：2-8℃，避光防潮密闭干燥生物活性及研究进展Clofarabine 是一种第二代嘌呤核苷类似物，目前已被合成，以克服其局限性，并结合了氟达滨和cladribine 的最佳品质。
氯法拉滨通过抑制核苷酸还原酶和DNA 聚合酶的作用，从而耗尽细胞内用于DNA 复制的脱氧核苷三磷酸酯的数量。
与前体相比，氯法拉滨对脱氨基和磷解有更强的抵抗力，因此具有更好的稳定性和对脱氧胞苷激酶(deoxycytidine kinase, dCyd)的更高的亲和力，后者是核苷酸磷酸化的限速步骤。
自1993年第一阶段开始，研究了clofarabine 在血液学和固体恶性肿瘤患者中的应用，clofarabine 在成人急性白血病(包括急性髓细胞白血病(AML))中显示了单剂抗肿瘤活性。
在治疗成人急性髓性白血病和骨髓增生异常综合症中具有科研价值。
那素达(马来酸非尼拉敏盐酸萘甲唑啉滴眼液)
那素达(马来酸非尼拉敏盐酸萘甲唑啉滴眼液)【药品名称】商品名称：那素达通用名称：马来酸非尼拉敏盐酸萘甲唑啉滴眼液英文名称：Pheniramine Maleate Naphazoline Hydrochloride Eye Drops【成份】盐酸萘甲唑啉naphazoline HCl 0.025 %, 马来酸非尼拉敏pheniramine maleate 0.3 % 【适应症】主要用于缓解因尘埃、感冒、过敏、揉眼、配戴角膜接触镜、游泳以及眼睛疲劳等引起的眼睛充血、瘙痒、灼热感以及其他刺激症状。
【用法用量】滴眼，一次1～2滴，每3～4小时1次。
可根据症状缓解情况而减少滴眼次数。
【不良反应】1.偶见瞳孔散大，眼压增高症状。
2.长期使用可能产生全身反应，如高血压、心律失常及高血糖等，但罕见，且停药可恢复【禁忌】1.对本品各成份过敏者禁用。
2.闭角型青光眼禁用。
【注意事项】1.婴儿和儿童应在医师的指导及成人监护下使用。
2.连用3～4日，症状未缓解者应咨询医师或药师。
3.患有严重心血管疾病的老年患者、孕妇和哺乳期妇女以及未控制好的高血压、糖尿病患者慎用。
4.在使用过程中，如发现眼红、疼痛等情况，应停药就医。
5.配带隐形眼镜者滴药前摘下，滴入后15分钟再带上。
6.使用后应将瓶盖拧紧以免污染药液。
7.本品启盖1个月后应弃之，当本品性状发生改变时禁用。
8.请将此药品放在儿童不能接触的地方。
【药物相互作用】1.单胺氧化酶抑制剂或拟交感神经药物与本品和用可加强前者的药效。
2.如正在使用其他药品，使用本品前请咨询医师或药师。
【药理作用】本品所含马来酸非尼拉敏为抗组胺药，可减轻过敏症状；盐酸萘甲唑啉为血管α1受体激动剂，可收缩眼部血管而缓解眼部炎症所致的充血。
【贮藏】室温下保存。
【批准文号】H20050185。
那格列奈片说明书
那格列奈片说明书那格列奈片(联邦)可以单独用于经饮食与运动不能有效控制高血糖的2型糖尿病病人。
下面是店铺整理的那格列奈片说明书，欢迎阅读。
那格列奈片商品介绍通用名：那格列奈片生产厂家: 珠海联邦制药股份有限公司中山分公司批准文号：国药准字H20041649药品规格：30mg*24片药品价格：￥44元那格列奈片说明书【通用名称】那格列奈片【商品名称】那格列奈片(联邦)【英文名称】NateglinideTablets【拼音全码】NaGeLieNaiPian【主要成份】那格列奈片主要成份为那格列奈。
化学名：N-(反式-4-异丙基环已基-1-甲酰基)-D-苯丙氨酸分子式：C19H27NO3分子量：317.42【性状】那格列奈片为白色片。
【适应症/功能主治】那格列奈片可以单独用于经饮食与运动不能有效控制高血糖的2型糖尿病病人。
也可用于使用二甲双胍不能有效控制高血糖的2型糖尿病病人，采用与二甲双胍联合应用，但不能替代二甲双胍。
【规格型号】30mg*24s【用法用量】口服。
通常成年人每次60～120mg(2～4片)，一日三次，餐前1～15分钟以内服用。
建议从小剂量开始，并根据定期的HbAlc或餐后1～2小时血糖检测结果调整剂量。
【不良反应】1、低血糖：与其他抗糖尿病药物一样，服用那格列奈后，可观察到低血糖的症状，这些症状包括出汗、发抖、头晕、食欲不振、心悸、恶心疲劳和无力。
这些症状一般较轻且较易处理，如需要可进食碳水化合物。
临床研究报告显示出现低血糖症状，且证实血糖降低(血糖<3.3mmol/L的患者的比例为7.69%;2、肝功能：极少患者出现肝酶增高，其程度较轻且为一过性，很少导致停药;3、过敏：极少有皮疹、瘙痒和荨麻疹等过敏反应的报道;4、其他反应：包括胃肠道反应(腹痛、消化不良、腹泻)、头痛、轻微水肿以及乳酸、丙酮酸、尿酸、血清钾升高等。
【禁忌】那格列奈在下列患者中禁用：1、对药物的活性成分或任何赋形剂过敏;2、Ⅱ型糖尿病(胰岛素依赖性糖尿病);3、糖尿病酮症酸中毒。
萘林那敏溴铵喷雾剂使用说明书
萘林那敏溴铵喷雾剂使用说明书
请仔细阅读说明书并在医师指导下使用
萘林那敏溴铵喷雾剂使用说明书
【药品名称】
通用名称：萘林那敏溴铵喷雾剂
汉语拼音：Nailinnaminxiu’an Penwuji
【成份】盐酸萘甲唑林、马来酸氯苯那敏、苯扎溴铵溶液、丙二胺。
【性状】本品为无色至微黄色的澄清液体，强烈振摇，则发生多量泡沫。
【适应症】
用于缓解感冒症状。
【用法用量】喷雾吸入。
成人：每次喷1~2下，儿童：每次喷1下，或遵医嘱。
打开瓶盖，拇指置瓶底，食指与中指置瓶喷头肩处，将瓶口对准鼻孔，用力挤压，使药液成雾状喷入鼻腔，每个鼻孔各喷一次。
首次用药后，间隔10分钟左右，待清除鼻腔分泌物后再喷一次，以后每日3次。
【注意事项】使用时严禁瓶口向下挤压而成水滴或水柱状灌入鼻孔，以免用量过大导致面色苍白，血压升高、头痛、昏睡等症状。
【贮藏】遮光，密闭保存。
【有效期】暂定18个月
说明书字数：438。
奈若普利说明书
奈若普利说明书
口服：一日1次，一般常用剂量为10～40mg，开始剂量为
10mg，早餐后服用，根据血压反应调整用量，最高剂量为80mg。
本品为第三代血管紧张素转换酶抑制剂，可抑制血管紧张素转换酶的活性，使血管紧张素Ⅱ和醛固酮的浓度降低，升高血浆肾素活性，导致外周血管扩张和血管阻力下降，从而产生降压效应。
口服后降压作用约在2小时内产生，最大降压作用约在口服后4～6小时出现，与血药浓度峰值时间一致。
降压作用持续24小时，停药后不会产生血压反跳，服药后心率无明显变化。
药代动力学：本品为依那普利拉的赖氨酸衍生物，口服时吸收不受食物影响，约6～8小时达血药浓度峰值。
生物利用度约为25%～50%。
本品不易与血浆蛋白结合，口服10mg后，平均分布容积为1.24L。
本药不再进一步代谢，吸收的药物以原形从尿排出。
本品呈多相清除，大部分的药物在快速相清除。
有效半衰期约为12.6小时，终末半衰期约为30个小时。
每日服用一次，3天后达血药浓度达稳态，肾功能减退时药物有蓄积。
肾清除率平均为每分钟
106ml，主要通过肾脏排泄。
注射用阿拉瑞林说明书
注射用阿拉瑞林注射用阿拉瑞林使用说明书•【药品名称】通用名称：注射用阿拉瑞林英文名称：Alarelin for Injection•【成份】阿拉瑞林•【性状】本品为白色冻干疏松块状物或粉末。
•【适应症】用于治疗子宫内膜异位症。
•【规格】0.15mg•【用法用量】【用法与用量】皮下或肌内注射，月经来潮的第1～2天开始治疗，150μg/次，每天一次，或遵医嘱。
制剂在临用前用2ml灭菌生理盐水溶解。
对子宫内膜异位症3～6月为一个疗程。
•【不良反应】可出现因低雌激素状态引起的症状，如潮热、盗汗、阴道干燥或情绪改变，个别患者出现皮疹，停药后即可消失。
•【禁忌】孕妇、哺乳期妇女及原因不明阴道出血者禁用；对GnRH或类似物过敏者禁用。
•【注意事项】除因子宫内膜异位症引起的不孕症患者可采用突然停药外，其余患者均需采用逐步撤药的方法；用药期间如出现淋漓出血，可咨询医生调整剂量至200μg疗程一般不超过6个月，以防发生骨质丢失。
•【孕妇及哺乳期妇女用药】【孕妇及哺乳用药】•【药理毒理】本品为人工合成的促性腺激素释放激素（GnRH）的九肽类似物，用药初期可刺激垂体释放促黄体生成素（LH）和促卵泡素（FSH），引起卵巢源性甾体激素短暂升高；重复用药可抑制垂体释放LH和FSH，使血中的雌二醇水平下降，达到药物去卵巢的作用，这种抑制作用可用于治疗子宫内膜异位症等激素依赖性疾病。
•【药代动力学】动物实验表明：本品在大鼠肌肉注射后吸收迅速，20min左右血药浓度达到峰值，血药浓度下降符合二房室模型，肌注给药时t1/2α约为0.2h,t1/2β约为1.8h。
静脉给药时t1/2α为0.08h,t1/2β约为1.2h。
其生物利用度可达80%左右。
与血浆蛋白结合率为27%～35%，组织分布中以肾脏最高，其次是肝脏、性腺和垂体，药物可从胆汁分泌，24h内在体内完全代谢分解，并全部从尿和粪中排出，其中80%由尿中排出。
•【贮藏】遮光、密闭保存【注意】药物说明书里面有三种标识，一般要注意一下：1.第一种就是禁用，就是绝对禁止使用。
Arranon(nelarabine)2016版使用说明书(中文)
FDA已批准其Arranon（nelarabine）注射剂用于至少接受过两种化学疗法之后病情复发或对药物无应答的T细胞急性成淋巴细胞性白血病（T-ALL）和T细胞淋巴瘤（T-LBL）患者。
临床试验结果：Arranon治疗后复发或治疗抵抗患者的多中心II期临床试验(28例成人患者，39例儿童患者)的数据显示，21%的成人和23%的儿童可获得完全缓解或未达到血液学完全复原的完全缓解。
缓解的时间通常足够进行干细胞移植程序，Arranon 治疗的总体中位生存时间为成年人21周、儿童13周。
Arranon（nelarabine）注射剂部分重点处方资料：【药品名称】英文药名：Arranon（nelarabine）中文药名：（阿仑恩）奈拉滨注射液【适应症】用于治疗至少两种治疗方案无效或治疗后复发的T细胞急性淋巴细胞性白血病(T-ALL)和T细胞淋巴母细胞性淋巴瘤(T-LBL)。
【剂型规格】静脉注射剂，250mg/50ml。
【用法用量】成人剂量：1500mg，静脉输注2小时，21天为一疗程，在第1、3、5天给药，无需稀释。
儿童剂量：650mg，静脉输注1小时，21天为一疗程，连续输注5天，无需稀释。
成人儿童的推荐治疗期未明确，临床试验中，除非患者病情加重，不能耐受毒性，即将进行骨髓移植或不再进行治疗。
【不良反应】最常见（≥20％）的不良反应为：成人：贫血，血小板减少，白细胞减少，恶心，腹泻，呕吐，便秘，疲劳，发热，咳嗽，呼吸困难；儿童：贫血，中性粒细胞减少，血小板减少，白细胞减少症。
神经系统最常见（> 10％）的不良反应为：成人：嗜睡，头晕，周围神经系统疾病，感觉减退，头痛，感觉异常；儿童：头痛，周边神经系统疾病。
【在特殊人群中使用】肾功能不全：密切监测毒性中度或重度肾功能不全患者。
肝功能不全：密切监测毒性严重肝损伤患者。
【购买须知】美国是医药分开的国家，药房全部实行严格的销售管理。
对处方药的销售，必须凭美国医生（电子或纸质）处方购买。
阿格列汀FDA说明书(英文)
CENTER FOR DRUG EVALUATION ANDRESEARCHAPPLICATION NUMBER:022271Orig1s000LABELINGHIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use NESINA safely and effectively. See full prescribing information for NESINA.NESINA (alogliptin) tabletsInitial U.S. Approval: 2013----------------------------INDICATIONS AND USAGE---------------------------- NESINA is a dipeptidyl peptidase-4 (DPP-4) inh bitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1.1, 14)Limitation of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1.2)------------------------DOSAGE AND ADMINISTRATION----------------------- ∙The recommended dose in patients with normal renal function or mild renal impairment is 25 mg once daily. (2.1)∙Can be taken with or without food. (2.1)∙Adjust dose if moderate or severe renal impairment or end-stage renal disease (ESRD). (2.2)Degree of Renal Impairment CreatinineClearance(mL/min) RecommendedDosingModerate ≥30 to <60 12.5 mg once dailySevere/ESRD <30 6.25 mg once daily----------------------DOSAGE FORMS AND STRENGTHS--------------------- Tablets: 25 mg, 12.5 mg and 6.25 mg (3)-----------------------------CONTRAINDICATIONS--------------------------- History of a serious hypersensitivity reaction to alogliptin-containing products, such as anaphylaxis, angioedema or severe cutaneous adverse reactions. (4) -----------------------WARNINGS AND PRECAUTIONS-------------------∙Acute pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptlydiscontinue NESINA. (5.1)∙Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with NESINA such as anaphylaxis, angioedema and severe cutaneous adverse reactions. In such cases, promptly discontinue NESINA, assessfor other potential causes, institute appropriate monitoring andtreatment, and initiate alternative treatment for diabetes. (5.2)∙Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury isdetected, promptly interrupt NESINA and assess patient forprobable cause, then treat cause if possible, to resolution orstabilization. Do not restart NESINA if liver injury is confirmedand no alternative etiology can be found. (5.3)∙Hypoglycemia: When an insulin secretagogue (e.g. sulfonylurea) or insulin is used in combination with NESINA, a lower dose of the insulin secretagogue or insulin may be required to minimize therisk of hypoglycemia. (5.4)∙Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with NESINA or any other antidiabetic drug. (5.5)----------------------------ADVERSE REACTIONS---------------------------- Common adverse reactions (reported in ≥4% of patients treated with NESINA 25 mg and more frequently than in patients who received placebo) are: nasopharyngitis, headache, and upper respiratory tract infection. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at1-800-FDA-1088 or /medwatch.See 17 for PATIENT COUNSELING INFORMATION and Medication GuideRevised: 01/2013FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONSANDUSAGE1.1 Monotherapy and Combination Therapy1.2 Limitation of Use2 DOSAGEANDADMINISTRATION2.1 RecommendedDosing2.2 Patients with Renal Impairment3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGSANDPRECAUTIONS5.1 Pancreatitis5.2 HypersensitivityReactions5.3 HepaticEffects5.4 Use with Medications Known to Cause Hypoglycemia5.5 MacrovascularOutcomes6 ADVERSEREACTIONS6.1 Clinical Studies Experience6.2 PostmarketingExperience7 DRUGINTERACTIONS8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 NursingMothers8.4 PediatricUse8.5 GeriatricUse8.6 HepaticImpairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 Patients with Inadequate Glycemic Control on Diet andExercise14.2 Combination Therapy16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION17.1 Instructions* Sections or subsections omitted from the full prescribing information are not listedFULL PRESCRIBING INFORMATION121 INDICATIONS AND USAGE31.1 Monotherapy and Combination TherapyNESINA is indicated as an adjunct to diet and exercise to improve glycemic control in45adults with type 2 diabetes mellitus in multiple clinical settings[see Clinical Studies6(14)].71.2 Limitation of Use8NESINA should not be used in patients with type 1 diabetes mellitus or for the treatment 9of diabetic ketoacidosis, as it would not be effective in these settings.2 DOSAGE AND ADMINISTRATION10112.1 Recommended Dosing12The recommended dose of NESINA is 25 mg once daily.13NESINA may be taken with or without food.142.2 Patients with Renal Impairment15No dose adjustment of NESINA is necessary for patients with mild renal impairment16(creatinine clearance [CrCl] ≥60 mL/min).17The dose of NESINA is 12.5 mg once daily for patients with moderate renal impairment 18(CrCl ≥30 to <60 mL/min).19The dose of NESINA is 6.25 mg once daily for patients with severe renal impairment20(CrCl ≥15 to <30 mL/min) or with end-stage renal disease (ESRD) (CrCl <15 mL/min or 21requiring hemodialysis). NESINA may be administered without regard to the timing of 22dialysis. NESINA has not been studied in patients undergoing peritoneal dialysis [see 23Clinical Pharmacology (12.3)].24Because there is a need for dose adjustment based upon renal function, assessment of 25renal function is recommended prior to initiation of NESINA therapy and periodically26thereafter.273 DOSAGE FORMS AND STRENGTHS28∙25 mg tablets are light red, oval, biconvex, film-coated, with “TAK ALG-25” printed 29on one side.30∙12.5 mg tablets are yellow, oval, biconvex, film-coated, with “TAK ALG-12.5”31printed on one side.32∙ 6.25 mg tablets are light pink, oval, biconvex, film-coated, with “TAK ALG-6.25”33printed on one side.344 CONTRAINDICATIONS35History of a serious hypersensitivity reaction to alogliptin-containing products, such as 36anaphylaxis, angioedema or severe cutaneous adverse reactions.375 WARNINGS AND PRECAUTIONS385.1 Pancreatitis39There have been postmarketing reports of acute pancreatitis in patients taking NESINA.40After initiation of NESINA, patients should be observed carefully for signs and41symptoms of pancreatitis. If pancreatitis is suspected, NESINA should promptly be42discontinued and appropriate management should be initiated. It is unknown whether 43patients with a history of pancreatitis are at increased risk for the development of44pancreatitis while using NESINA.455.2 HypersensitivityReactions46There have been postmarketing reports of serious hypersensitivity reactions in patients 47treated with NESINA. These reactions include anaphylaxis, angioedema, and severe 48cutaneous adverse reactions including Stevens-Johnson syndrome. If a serious49hypersensitivity reaction is suspected, discontinue NESINA, assess for other potential 50causes for the event, and institute alternative treatment for diabetes [see Adverse51Reactions (6.2)]. Use caution in a patient with a history of angioedema with another52DPP-4 inhibitor because it is unknown whether such patients will be predisposed to53angioedema with NESINA.545.3 HepaticEffects55There have been postmarketing reports of fatal and non-fatal hepatic failure in patients 56taking NESINA, although some of the reports contain insufficient information necessary 57to establish the probable cause [see Adverse Reactions (6.2)]. In randomized controlled 58studies, serum alanine aminotransferase (ALT) elevations greater than three times the 59upper limit of normal (ULN) were observed: 1.3% in alogliptin-treated patients and 1.5% 60in all comparator-treated patients.61Patients with type 2 diabetes may have fatty liver disease which may cause liver test62abnormalities, and they may also have other forms of liver disease, many of which can 63be treated or managed. Therefore, obtaining a liver test panel and assessing the patient 64before initiating NESINA therapy is recommended. In patients with abnormal liver tests, 65NESINA should be initiated with caution.Measure liver tests promptly in patients who report symptoms that may indicate liver6667injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or68jaundice. In this clinical context, if the patient is found to have clinically significant liver 69enzyme elevations and if abnormal liver tests persist or worsen, NESINA should be70interrupted and investigation done to establish the probable cause. NESINA should not 71be restarted in these patients without another explanation for the liver testabnormalities.72735.4 Use with Medications Known to Cause Hypoglycemia74Insulin and insulin secretagogues, such as sulfonylureas, are known to causehypoglycemia. Therefore, a lower dose of insulin or insulin secretagogue may be7576required to minimize the risk of hypoglycemia when used in combination with NESINA.775.5 Macrovascular OutcomesThere have been no clinical studies establishing conclusive evidence of macrovascular7879risk reduction with NESINA or any other antidiabetic drug.6 ADVERSE80REACTIONS816.1 Clinical Studies ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction8283rates observed in the clinical trials of a drug cannot be directly compared to rates in the 84clinical trials of another drug and may not reflect the rates observed in clinical practice.85Approximately 8500 patients with type 2 diabetes have been treated with NESINA in 14 86randomized, double-blind, controlled clinical trials with approximately 2900 subjects87randomized to placebo and approximately 2200 to an active comparator. The mean88exposure to NESINA was 40 weeks with more than 2400 subjects treated for more than 89one year. Among these patients, 63% had a history of hypertension, 51% had a history 90of dyslipidemia, 25% had a history of myocardial infarction, 8% had a history of unstable 91angina, and 7% had a history of congestive heart failure. The mean duration of diabetes was 7 years, the mean body mass index (BMI) was 31 kg/m2 (51% of patients had a9293BMI ≥30 kg/m2), and the mean age was 57 years (24% of patients ≥65 years of age).94Two placebo-controlled monotherapy trials of 12 and 26 weeks of duration were95conducted in patients treated with NESINA 12.5 mg daily, NESINA 25 mg daily and96placebo. Four placebo-controlled add-on combination therapy trials of 26 weeks97duration were also conducted: with metformin, with a sulfonylurea, with athiazolidinedione, and with insulin.9899Five placebo-controlled trials of 16 weeks up through two years in duration wereconducted in combination with metformin, in combination with pioglitazone and with100101pioglitazone added to a background of metformin therapy.102Three active-controlled trials of 52 weeks in duration were conducted in patients treated 103with pioglitazone and metformin, in combination with metformin and as monotherapy 104compared to glipizide.105In a pooled analysis of these 14 controlled clinical trials, the overall incidence of adverse 106events was 66% in patients treated with NESINA 25 mg compared to 62% with placebo 107and 70% with active comparator. Overall discontinuation of therapy due to adverse108events was 4.7% with NESINA 25 mg compared to 4.5% with placebo or 6.2% with109active comparator.110Adverse reactions reported in ≥4% of patients treated with NESINA 25 mg and more 111frequently than in patients who received placebo are summarized in Table 1.112113Table 1. Adverse Reactions Reported in ≥4% Patients Treated with NESINA 25 mg and More Frequently Than in Patients Given Placebo in Pooled StudiesNumber of Patients (%)NESINA 25 mg Placebo ActiveComparatorN =5902 N=2926 N=2257Nasopharyngitis 257 (4.4) 89 (3.0) 113 (5.0)Headache 247 (4.2) 72 (2.5) 121 (5.4)Upper respiratory tract infection 247 (4.2) 61 (2.1) 113 (5.0)Pancreatitis114In the clinical trial program, pancreatitis was reported in 11 of 5902 (0.2%) patients 115receiving NESINA 25 mg daily compared to 5 of 5183 (˂0.1%) patients receiving all 116comparators.117Hypersensitivity Reactions118In a pooled analysis, the overall incidence of hypersensitivity reactions was 0.6% 119with NESINA 25 mg compared to 0.8% with all comparators. A single event of serum 120sickness was reported in a patient treated with NESINA 25 mg.121Hypoglycemia122Hypoglycemic events were documented based upon a blood glucose value and/or 123clinical signs and symptoms of hypoglycemia.124In the monotherapy study, the incidence of hypoglycemia was 1.5% in patients125treated with NESINA compared to 1.6% with placebo. The use of NESINA as add-on 126therapy to glyburide or insulin did not increase the incidence of hypoglycemia127compared to placebo. In a monotherapy study comparing NESINA to a sulfonylurea 128in elderly patients, the incidence of hypoglycemia was 5.4% with NESINA compared 129to 26% with glipizide (Table 2).130Page 6 of 30131 Table 2. Incidence and Rate of Hypoglycemia* in Placebo and Active-ControlledStudies when NESINA was Used as Add-on Therapy to Glyburide, Insulin,Metformin, Pioglitazone, or Compared to Glipizide Add-on to Glyburide(26 Weeks) NESINA 25 mg + Glyburide Placebo + GlyburideN =198 N=99 Overall (%) 19 (9.6)11 (11.1)Severe (%)†0 1 (1)Add-on to Insulin (+/- Metformin)(26 Weeks)NESINA 25 mg + Insulin (+/- Metformin) Placebo+ Insulin (+/- Metformin)N =129 N =129Overall (%) 35 (27)31 (24)Severe (%)†1 (0.8)2 (1.6)Add-on to Metformin(26 Weeks)NESINA 25 mg + MetforminPlacebo + MetforminN =207 N =104 Overall (%) 0 3 (2.9) Severe (%)†0 0Add-on to Pioglitazone (± Metformin or Sulfonylurea) (26 Weeks) NESINA 25 mg + PioglitazonePlacebo + PioglitazoneN =199 N =97Overall (%) 14 (7.0)5 (5.2)Severe (%)† 0 1 (1)Compared to Glipizide (52 Weeks)NESINA 25 mgGlipizideN =222 N =219 Overall (%) 12 (5.4)57 (26)Severe (%)† 0 3 (1.4)Add on to Metformin (26 Weeks) NESINA 25 mgMetformin 500 mgtwice dailyN =112 N =109Overall (%) 2 (1.8) 2 (1.8) Severe (%)†00Add on to Metformin Compared to Glipizide (52 Weeks)NESINA 25 mg+ MetforminGlipizide+ MetforminN =877N=869Overall (%) 12 (1.4) 207 (23.8)Severe (%)†0 4(0.5)*Adverse reactions of hypoglycemia were based on all reports of symptomatic andasymptomatic hypoglycemia; a concurrent glucose measurement was not required; intent-to-treat population.†Severe events of hypoglycemia were defined as those events requiring medical assistance orexhibiting depressed level or loss of consciousness or seizure.Vital Signs132No clinically meaningful changes in vital signs or in electrocardiograms were observed 133in patients treated with NESINA.134Laboratory Tests135No clinically meaningful changes in hematology, serum chemistry, or urinalysis were 136observed in patients treated with NESINA.1376.2 Postmarketing Experience138The following adverse reactions have been identified during the postmarketing use of 139NESINA outside the United States. Because these reactions are reported voluntarily 140from a population of uncertain size, it is not always possible to reliably estimate their 141frequency or establish a causal relationship to drug exposure.142Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and143severe cutaneous adverse reactions including Stevens-Johnson syndrome; hepatic 144enzyme elevations; fulminant hepatic failure; and acute pancreatitis.1457 DRUG INTERACTIONS146NESINA is primarily renally excreted. Cytochrome (CYP) P450-related metabolism is 147negligible. No significant drug-drug interactions were observed with the CYP-substrates 148or inhibitors tested, or with renally excreted drugs [see Clinical Pharmacology (12.3)]. 1498 USE IN SPECIFIC POPULATIONS1508.1 Pregnancy151Pregnancy Category B152No adequate or well-controlled studies in pregnant women have been conducted with 153NESINA. Based on animal data, NESINA is not predicted to increase the risk of154developmental abnormalities. Because animal reproduction studies are not always155156predictive of human risk and exposure, NESINA, like other antidiabetic medications, 157should be used during pregnancy only if clearly needed.158Alogliptin administered to pregnant rabbits and rats during the period of organogenesis 159was not teratogenic at doses of up to 200 and 500 mg/kg, or 149-times and 180-times, 160respectively, the clinical dose based on plasma drug exposure (AUC).161Doses of alogliptin up to 250 mg/kg (approximately 95-times clinical exposure based on 162AUC) given to pregnant rats from gestation day 6 to lactation day 20 did not harm the 163developing embryo or adversely affect growth and development of offspring.164Placental transfer of alogliptin into the fetus was observed following oral dosing to165pregnant rats.8.3 Nursing Mothers166167Alogliptin is secreted in the milk of lactating rats in a 2:1 ratio to plasma. It is not known 168whether alogliptin is excreted in human milk. Because many drugs are excreted inhuman milk, caution should be exercised when NESINA is administered to a nursing 169170woman.1718.4 Pediatric Use172Safety and effectiveness of NESINA in pediatric patients have not been established. 1738.5 Geriatric Use174Of the total number of patients (N=8507) in clinical safety and efficacy studies treated 175with NESINA, 2064 (24.3%) patients were 65 years and older and 341 (4%) patients 176were 75 years and older. No overall differences in safety or effectiveness were177observed between patients 65 years and over and younger patients. While this clinical 178experience has not identified differences in responses between the elderly and younger 179patients, greater sensitivity of some older individuals cannot be ruled out.1808.6 Hepatic Impairment181No dose adjustments are required in patients with mild to moderate hepatic impairment 182(Child-Pugh Grade A and B) based on insignificant change in systemic exposures (e.g., 183AUC) compared to subjects with normal hepatic function in a pharmacokinetic study. 184NESINA has not been studied in patients with severe hepatic impairment (Child-Pugh 185Grade C). Use caution when administering NESINA to patients with liver disease [see 186Warnings and Precautions (5.3)].18710 OVERDOSAGE188The highest doses of NESINA administered in clinical trials were single doses of 800 189mg to healthy subjects and doses of 400 mg once daily for 14 days to patients with type 1902 diabetes (equivalent to 32 times and 16 times the maximum recommended clinical 191dose of 25 mg, respectively). No serious adverse events were observed at these doses. 192In the event of an overdose, it is reasonable to institute the necessary clinical monitoring 193and supportive therapy as dictated by the patient's clinical status. Per clinical judgment, it may be reasonable to initiate removal of unabsorbed material from the gastrointestinal 194195tract.Alogliptin is minimally dialyzable; over a 3-hour hemodialysis session, approximately 7% 196 of the drug was removed. Therefore, hemodialysis is unlikely to be beneficial in an 197 overdose situation. It is not known if NESINA is dialyzable by peritoneal dialysis. 198 11 DESCRIPTION199 NESINA tablets contain the active ingredient alogliptin, which is a selective, orally-200 bioavailable inhibitor of the enzymatic activity of dipeptidyl peptidase-4 (DPP-4). 201 Chemically, alogliptin is prepared as a benzoate salt, which is identified as 2-({6-[(3R )-3-202 aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H )-203 yl}methyl)benzonitrile monobenzoate. It has a molecular formula of C 18H 21N 5O 2•C 7H 6O 2 204 and a molecular weight of 461.51 daltons. The structural formula is:205NN(Z)CNOO2HO 2CH 3C •206 Alogliptin benzoate is a white to off-white, crystalline powder containing one asymmetric 207 carbon in the aminopiperidine moiety. It is soluble in dimethylsulfoxide, sparingly soluble 208 in water and methanol, slightly soluble in ethanol, and very slightly soluble in octanol 209 and isopropyl acetate.210 Each NESINA tablet contains 34 mg, 17 mg, or 8.5 mg alogliptin benzoate which is 211 equivalent to 25 mg, 12.5 mg, or 6.25 mg, respectively, of alogliptin and the following 212 inactive ingredients: mannitol, microcrystalline cellulose, hydroxypropyl cellulose,213 croscarmellose sodium, and magnesium stearate. In addition, the film-coating contains 214 the following inactive ingredients: hypromellose, titanium dioxide, ferric oxide (red or 215 yellow), and polyethylene glycol, and is marked with printing ink (Gray F1). 216 12 CLINICAL PHARMACOLOGY217 12.1 Mechanism of Action218 Increased concentrations of the incretin hormones such as glucagon-like peptide-1 219 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the 220 bloodstream from the small intestine in response to meals. These hormones cause 221 insulin release from the pancreatic beta cells in a glucose-dependent manner but are 222 inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion 223 from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 224 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is 225 preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin 226 hormones, thereby increasing their bloodstream concentrations and reducing fasting 227 and postprandial glucose concentrations in a glucose-dependent manner in patients228with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not 229230DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures. 23112.2 Pharmacodynamics232Single-dose administration of NESINA to healthy subjects resulted in a peak inhibition of233DPP-4 within 2 to 3 hours after dosing. The peak inhibition of DPP-4 exceeded 93%234across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24hours for doses greater than or equal to 25 mg. Peak and total exposure over 24 hours 235236to active GLP-1 were 3- to 4-fold greater with NESINA (at doses of 25 to 200 mg) than237placebo. In a 16-week, double-blind, placebo-controlled study, NESINA 25 mgdemonstrated decreases in postprandial glucagon while increasing postprandial active 238239GLP-1 levels compared to placebo over an 8-hour period following a standardized240meal. It is unclear how these findings relate to changes in overall glycemic control in241patients with type 2 diabetes mellitus. In this study, NESINA 25 mg demonstrated242decreases in 2-hour postprandial glucose compared to placebo (-30 mg/dL versus 17243mg/dL, respectively).244Multiple-dose administration of alogliptin to patients with type 2 diabetes also resulted in245a peak inhibition of DPP-4 within 1 to 2 hours and exceeded 93% across all doses (25246mg, 100 mg, and 400 mg) after a single dose and after 14 days of once-daily dosing. At247these doses of NESINA, inhibition of DPP-4 remained above 81% at 24 hours after 14days of dosing.248249Cardiac Electrophysiology250In a randomized, placebo-controlled, 4-arm, parallel-group study, 257 subjects were251administered either alogliptin 50 mg, alogliptin 400 mg, moxifloxacin 400 mg, or placebo252once-daily for a total of 7 days. No increase in QTc was observed with either dose of253alogliptin. At the 400 mg dose, peak alogliptin plasma concentrations were 19-fold254higher than the peak concentrations following the maximum recommended clinical dose255of 25 mg.25612.3 Pharmacokinetics257The pharmacokinetics of NESINA has been studied in healthy subjects and in patients258with type 2 diabetes. After administration of single, oral doses up to 800 mg in healthysubjects, the peak plasma alogliptin concentration (median T max) occurred 1 to 2 hours 259260after dosing. At the maximum recommended clinical dose of 25 mg, NESINA waseliminated with a mean terminal half-life (T1/2) of approximately 21 hours.261After multiple-dose administration up to 400 mg for 14 days in patients with type 2262263diabetes, accumulation of alogliptin was minimal with an increase in total (i.e., AUC) and264peak (i.e., C max) alogliptin exposures of 34% and 9%, respectively. Total and peak265exposure to alogliptin increased proportionally across single doses and multiple doses266of alogliptin ranging from 25 mg to 400 mg. The inter-subject coefficient of variation for267alogliptin AUC was 17%. The pharmacokinetics of NESINA was also shown to besimilar in healthy subjects and in patients with type 2 diabetes.268269Absorption270The absolute bioavailability of NESINA is approximately 100%. Administration ofNESINA with a high-fat meal results in no significant change in total and peak exposure 271272to alogliptin. NESINA may therefore be administered with or without food.Distribution273274Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the 275volume of distribution during the terminal phase was 417 L, indicating that the drug is 276well distributed into tissues.277Alogliptin is 20% bound to plasma proteins.278MetabolismAlogliptin does not undergo extensive metabolism and 60% to 71% of the dose is279280excreted as unchanged drug in the urine.281Two minor metabolites were detected following administration of an oral dose of282[14C] alogliptin, N-demethylated, M-I (<1% of the parent compound), and N-acetylated 283alogliptin, M-II (<6% of the parent compound). M-I is an active metabolite and is an 284inhibitor of DPP-4 similar to the parent molecule; M-II does not display any inhibitory 285activity towards DPP-4 or other DPP-related enzymes. In vitro data indicate that286CYP2D6 and CYP3A4 contribute to the limited metabolism of alogliptin.287Alogliptin exists predominantly as the (R)-enantiomer (>99%) and undergoes little or no 288chiral conversion in vivo to the (S)-enantiomer. The (S)-enantiomer is not detectable at 289the 25 mg dose.290ExcretionThe primary route of elimination of [14C] alogliptin-derived radioactivity occurs via renal 291excretion (76%) with 13% recovered in the feces, achieving a total recovery of 89% of 292293the administered radioactive dose. The renal clearance of alogliptin (9.6 L/hr) indicates some active renal tubular secretion and systemic clearance was 14.0 L/hr.294295Specific Populations296Renal ImpairmentA single-dose, open-label study was conducted to evaluate the pharmacokinetics of 297298alogliptin 50 mg in patients with chronic renal impairment compared with healthy299subjects.300In patients with mild renal impairment (creatinine clearance (CrCl) ≥60 to <90 mL/min), 301an approximate 1.2-fold increase in plasma AUC of alogliptin was observed. Because 302increases of this magnitude are not considered clinically relevant, dose adjustment for 303patients with mild renal impairment is not recommended.304In patients with moderate renal impairment (CrCl ≥30 to <60 mL/min), an approximate 3052-fold increase in plasma AUC of alogliptin was observed. To maintain similar systemic 306exposures of NESINA to those with normal renal function, the recommended dose is 30712.5 mg once daily in patients with moderate renal impairment.308In patients with severe renal impairment (CrCl ≥15 to <30 mL/min) and end-stage renal 309disease (CrCl <15 mL/min or requiring dialysis), an approximate 3- and 4-fold increase 310in plasma AUC of alogliptin were observed, respectively. Dialysis removed311approximately 7% of the drug during a 3-hour dialysis session. NESINA may beadministered without regard to the timing of the dialysis. To maintain similar systemic 312313exposures of NESINA to those with normal renal function, the recommended dose is。
抗血栓药使用说明书正确使用抗血栓药品的方法和注意事项
抗血栓药使用说明书正确使用抗血栓药品的方法和注意事项说明书：抗血栓药使用指南1. 产品介绍抗血栓药是一类用于防治血栓形成的药物，主要用于预防心脑血管疾病的发生。
本说明书将详细介绍正确使用抗血栓药品的方法和注意事项。
2. 使用方法2.1 剂量和频率根据医生的指导，按照处方中规定的剂量和频率服用抗血栓药品。
剂量和频率可能因个体差异而有所不同，确保严格按照医嘱执行。
2.2 服药时间抗血栓药通常在饭后或者餐中服用，可以有效减少胃肠道不适的发生。
遵守饮食和药物之间的时间间隔，确保药物充分吸收。
2.3 药物形式根据医生建议，选择适合的药物形式。
抗血栓药通常有片剂、胶囊剂或注射剂等形式，确保正确实施药物给药方式。
2.4 忌烟酒在使用抗血栓药过程中，应避免饮酒或吸烟。
烟酒会增加药物的代谢速度，从而降低药效，甚至对身体健康产生不利影响。
3. 注意事项3.1 不良反应抗血栓药在使用过程中可能出现一些不良反应，如咳嗽、胃部不适、皮肤发红等。
如出现不适症状，应及时告知医生，遵从其指导。
3.2 药物相互作用在服用抗血栓药时，需避免与其他药物同时使用，以免发生药物相互作用。
如果正在使用其他药物，请告知医生，以便根据具体情况调整用药方案。
3.3 孕妇和哺乳期妇女孕妇和哺乳期妇女在使用抗血栓药品前应咨询医生。
医生会根据个人情况权衡利弊，评估是否适合使用抗血栓药品。
3.4 特殊人群对于年龄较大、肝肾功能不全的患者，需特别注意抗血栓药的使用。
在使用之前，请咨询医生，并遵循医嘱进行合理用药。
4. 储存条件请将抗血栓药存放在阴凉干燥处，避免阳光直射和高温潮湿环境。
保持药品包装完好，避免与其他药品混放，以免产生不必要的风险。
5. 使用期限抗血栓药品在购买后，应按照包装上的使用期限合理使用。
过期的药品可能失去药效或产生其他不良反应，应及时更新。
6. 禁忌症在一些特定情况下，个别人群存在禁忌症，如出血性疾病等。
在使用抗血栓药品前，请详细阅读产品说明书，了解禁忌症内容，并遵循相关警示。
怡可安（Canagliflozin Tablets）说明书
核准日期：2017年09月29日修改日期：2019年06月27日2019年09月25日2020年03月16日2020年04月20日2020年06月24日2021年07月22日卡格列净片说明书请仔细阅读说明书并在医师指导下使用。
【药品名称】通用名称：卡格列净片商品名称：怡可安®英文名称：Canagliflozin Tablets汉语拼音：Kageliejing Pian【成份】主要成份：卡格列净化学名称：（1S）-1,5-脱水-1-C-（3-{[5-（4-氟苯基）噻吩-2-基]甲基}-4-甲基苯基）-D-葡萄糖醇化学结构式：分子式：C24H25FO5S 1/2 H2O分子量：453.53【性状】本品为黄色胶囊形薄膜衣片（100mg规格）或白色至类白色胶囊形薄膜衣片（300mg 规格），除去包衣后应显白色。
【适应症】本品与二甲双胍联用：当单独使用二甲双胍血糖控制不佳时，可与二甲双胍联合使用，配合饮食和运动改善成人2型糖尿病患者的血糖控制。
本品与二甲双胍和磺脲类药物联用：当联用二甲双胍和磺脲类药物血糖控制不佳时，可与二甲双胍和磺脲类药物联合使用，配合饮食和运动改善成人2型糖尿病患者的血糖控制。
本品不建议用于1型糖尿病患者或糖尿病酮症酸中毒（患者）的治疗。
【规格】（1）100mg；（2）300mg（以卡格列净无水物（C24H25FO5S）计）【用法用量】1. 开始本品治疗前在开始本品治疗前，应评估肾功能，并在治疗开始后定期进行评估。
（参见【注意事项】）对于既往未接受过本品治疗的血容量不足患者，开始本品治疗前建议纠正这种情况。
（参见【注意事项】、【老年用药】）2. 推荐剂量本品的推荐起始剂量为100mg每天一次，当天第一餐前服用。
对于耐受本品 100mg每天一次的剂量、肾小球滤过率估计值（eGFR）≥60mL/min/1.73m2且需要额外血糖控制的患者，剂量可增加至300mg每天一次（参见【注意事项】、【药理毒理】）。
安乃近 Novalgin、Analgin说明书.
品名：
安乃近Metamizole Sodium（罗瓦而精Novalgin、诺瓦经、Analgin）剂型与规格：
片剂：0.25g、0.5g；注射剂：0.25g/lml、0.5g/2ml；滴鼻剂：10％～20％溶液。
用法与用量：
口服，每次0.5g，每日3次；儿童每次8～10mg/kg，每日3次。
肌注(深部)，每次0.25～0.5g；儿童，每次5～10mg/kg。
滴鼻，儿童退热常以10～20%溶液滴鼻，5岁以下每次每侧鼻孔1～2滴，必要时重复用1次。
5岁以上适当加量。
药理与用途：
氨基比林与亚硫酸钠的合成物，具有较显著的解热作用与较强的镇痛作用。
临床适用于退热，亦用于头痛，急性关节炎，风湿性神经痛，牙痛，肌肉痛。
不良反应：
可发生虚脱，过敏性皮肤反应，过敏性休克，重者引起死亡；长期应用可引起粒细胞减少、血小板减少性紫癜，再生障碍性贫血，并可危及生命。
注意事项：注射部位多有红肿、疼痛，数天后消退；肌注不要过量，以免引起不良反应；服用期间应定期查血象；不宜用于穴位注射，尤其在关节部位，不得与其他药物混合注射；对吡唑酮类药物有过敏史者禁用。
安乃近滴剂使用说明
安乃近滴剂
【用法用量】口服小儿按体重一次10～20mg/kg，一日2～3次。
【注意事项】1.本品与阿司匹林有交叉过敏反应。
2.不宜长期应用。
3.本品一般不作首选用药，仅在急性高热、病情急重，又无其他有效解热药可用的情况下用于紧急退热。
4.本品用药超过1周时应定期检查血象，一旦发生粒细胞减少，应立即停药。
5.体弱者慎用。
【不良反应】本品对胃肠道的刺激虽较小，但可引起以下各种：1.血液方面，可引起粒细胞缺乏症，发生率约1.1%，急性起病，重者有致命危险，亦可引起自身免疫性溶血性贫血、血小板减少性紫癜、再生障碍性贫血等；2.皮肤方面，可引起荨麻疹、渗出性红斑等过敏性表现，严重者可发生剥脱性皮炎、表皮松解症等；3.个别病例可发生过敏性休克，甚至导致死亡。
【禁忌】对本品或氨基比林有过敏史者禁用。
【适应症】用于小儿高热解热。
【药物相互作用】如与其他药物同时使用可能会发生，详情请咨询医师或药师。
【药理毒理】本品为氨基比林和亚硫酸钠相结合的化合物，易溶于水，解热、镇痛作用较氨基比林快而强。
【包装】1ml:0.2g/支
【医保】非
【国家/地区】国产
【药代动力学】未进行该项实验且无可靠参考文献。
【成份】本品主要成分及其化学名称为：本品主要成分为安乃近，其化学名为[（1,5-二甲基-2-苯基-3-2，3-二氢-1H-吡唑-4-基）甲氨基]甲烷磺酸钠盐—水合物。
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奈拉滨（Nelarabine）是用于治疗至少两种治疗方案无效或治疗后复发的T细胞急性淋巴细胞性白血病(T-ALL)和T细胞淋巴母细胞性淋巴瘤(T-LBL)。
中文名称:奈拉滨
中文别名:奈拉滨及其中间体(研发);奈拉滨及其中间体;奈拉宾;9beta-D-阿拉伯呋喃糖-6-甲氧基-9H-嘌呤-2-胺;9-beta-D-阿拉伯呋喃糖-6-甲氧基-9H-嘌呤-2-胺
英文名称:Nelzarabine
英文别名:NELARABINE; Nelzarabine [USAN];
9-beta-D-Arabinofuranosyl-6-methoxy-9H-purin-2-amine;
9-(D-arabinofuranosyl)-6-methoxy-9H-purin-2-amine
CAS:121032-29-9
分子式:C11H15N5O5
分子量:297.2673
原研企业：GSK
适应症：用于治疗至少对两种以上化疗方案无应答或复发的急性T一细胞淋巴母细胞性白血病(T—ALL)T一细胞淋巴母细胞性淋巴瘤(T—LBL)患者。
用法用量：
成年人：采用静脉滴注给药，推荐剂量为1500mg·m-2·d-1，5天隔日给药，2l天为一周期。
儿童：采用静脉滴注给药，推荐剂量为650mg·m-2·d-1，连续5天，21
天为一周期。
作用机制
奈拉滨在腺苷脱氨酶作用下，去甲基转化成ara—G，在脱氧鸟苷激酶和脱氧苷激酶作用下单磷酸化，接着转化为活性5-三磷酸盐ara-GTP。
Ara-GTP在白血病胚细胞中蓄积到一定程度后嵌合入DNA中，从而抑制DNA的合成，最终导致细胞死亡。
此外，BeesleyAH等人研究发现，T细胞对奈拉滨的敏感度是B细胞的8倍。
E1ineJ等人研究表明，ara—GTP在T细胞内比在B细胞内的累积速度更快，累积量更多，ara—GTP对T细胞有更强的选择性细胞毒作用。
药代
BergSL等人对T-ALL和T-LBL患者奈拉滨药代动力学研究表明，药物及其活性代谢物ara—G 能迅速分布到血浆中。
奈拉滨及其活性代谢物ara—G半衰期分为l5分钟和3小时。
成人和儿童体内，奈拉滨表观分布容积分别为(197±216)L/m。
和(213±358)L/m。
，ara—G表观分布容积分别为(50+24)L/m。
以及(33--+9.3)L/m。
注射1500mg/m2奈拉滨两小时后成年患者体内的奈拉滨和ara—G的平均血浆浓度值分别为(5.0-+3.0)ug/mL和(31.4-+5.6)ug/mL。
静脉滴注奈拉滨104~2900mm。
后，成人和儿童表观平均清除值分别为(197-+189)L·h-1·m-2和(259±409)L·h-1·m-2，儿童较成年人高30%。
成人和儿童体内ara—G平均清除值大致与奈拉宾相等，分别为(197±189)L·h-1·m-2和（259±409)L·h-1·m-2
奈拉滨的主要代谢途径是，在腺苷脱氨酶的作用下，脱甲基生成ara-G，进一步水解形成鸟嘌呤，最后脱甲基生成尿酸。
部分奈拉滨直接水鸟嘌吟’然后胛基生成尿酸。
奈拉滨和ara—G在肾脏部分消除，分别以原药形式从尿中排泄(6.6-+4.7)%和(27±l5)%。
规定给药剂量下(650mg·m-2·d-1)，28位成年患者注射给药24小时后测得奈拉滨和araG的肾清除率平均值为(24±23)L/h和(6.2±5.0)L/h。
临床试验
FDA发布一份奈拉滨临床研究报告，将参与试验的患者分为儿童组和成年组。
采用静脉滴注给药，儿童组剂量为650 mg·m-2·d-1连续5天。
成人组为在第一，三和五天1500 mg·m-2·d-1。
治疗周期为2l天。
评价指标为血液或骨髓完全恢复应答(CR)和血液或骨髓不完全恢复应答(CR*)。
结果显示，儿童组39名患者，其中对奈拉滨有完全应答（CR）的人数为5，占总数的13%，完全应答和部分恢复应答(CR+CR*)人数为9，占总数的23%。
成年组28名患者，其中完全应答(CR)有5位，占总数的18%，完全应答和部分恢复应答(CR+CR*)人数为6，占总数的21%。
Kurtzberg J等人对奈拉滨最大耐受剂量研究表明，以2l天为一周期，每天静脉滴注1小时，连续5天给药，儿童和成人最大的耐受量分别为60mg/kg和40mg/kg。
没有发现骨髓抑制和其他器官的毒副作用。
DeAngelo DJ等人的临床研究报告，奈拉滨为隔日给药一次，每次1.5 g·m·d，22天为一周期。
患者平均年龄为34岁(从16~66岁)，32位为男性，占总数的82%。
结果，31%患者病情完全缓解，45%患者完全应答主要毒性是3～4级的嗜中性白血球霎37%和26%。
仅有一例4级神经不良反应，主要症状为抑郁。
临床治疗表明奈拉滨有良好耐受性和抗肿瘤活性。
如何购买此药
好医友美国药房提供专科药物、处方药物、非处方药物、处方药物、药物配置、药物注射以及各类非住院患者的药物分发、咨询、配送等各项服务。
如今国内患者可以依托科技，实现远程的病历交互，由美国医生根据患者病情开具电子处方，以正规渠道在美国药房购买到处方药。