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2019年10月临床医学DOI :10.19347/ki.2096-1413.201930013基金项目：国家自然科学基金项目（No.71603199）；陕西省自然科学基础研究计划项目（No.2018JM7083）。
作者简介：蒋玲（1978-），女，汉族，江苏徐州人，高级工程师，硕士。
研究方向：药剂学。
*通讯作者：毕学苑，E -mail:vickeymu@.西洛他唑由日本大冢制药公司开发，1999年获得FDA 注册批准。
西洛他唑不仅可抑制血小板聚集，防止血栓形成和血管闭塞[1]，还可降低皮层下梗死患者血浆炎症因子水平[2]。
因此，控制西洛他唑的质量对临床用药意义重大。
本研究就《美国药典》（USP40）收载的西洛他唑质量标准，与《中国药典》2015版二部对比，旨在更好地控制西洛他唑的质量，现报道如下。
1方法比较1.1定义按干燥品计算，含西洛他唑应为98.0%~102.0%。
与《中国药典》2015版二部相同。
1.2包装与储存密闭容器中室温储存。
USP40规定了储存温度，《中国药典》2015版二部中规定为密封保存，未要求储存温度。
1.3鉴别1.3.1红外光谱法。
供试品与对照品红外光谱一致。
与《中国药典》2015版二部相同。
红外光谱法特征性强、测定快速、试样用量少、操作简便、分析灵敏度高。
两国药典均采用此法，均可准确对西洛他唑鉴别。
1.3.2液相色谱法。
供试品溶液和对照品溶液主峰的保留时间一致。
与《中国药典》2015版二部相同。
液相色谱法广泛应用于药物的鉴别，由于保留时间与组分的结构和性质有关，是定性的参数，保留时间一致，表示药物和对照品一致。
两国药典均采用此法，均可准确对西洛他唑鉴别。
1.4干燥失重USP40中规定为110℃下干燥3h ，减失重量不得超过0.3%。
《中国药典》2015版二部中规定为105℃干燥至恒重，减失重量不得超过0.5%。
干燥失重的测定准确与否影响着化学结构的判断和含量测定的结果[3]，因此，限度越严格，对于含量测定的影响越小。
碘海醇注射液说明书之答禄夫天创作【药品名称】通用名：碘海醇注射液曾用名：商品名：英文名：Iohexol Injection汉语拼音：Diɑnhɑichun Zhusheye本品主要成分及其化学名称为：N, N'-双(2,3-二羟基丙基)-5-[N-(2,3-二羟基丙基)乙酰胺基]-2,4,6-三碘-1,3-苯二甲酰胺.结构式：分子式：C19H26I3N3O9【性状】本品为无色至淡黄色的澄明液体.本品是一种含有三个碘原子的非离子水溶性造影剂, 碘含量为46.4％.它以经过消毒的水溶液为剂型, 随时可用, 并有分歧的碘浓度, 分别为每毫升浓度含有140、180、240、300或350mg碘.【药理毒理】药理学本品为X光及CT检查经常使用的造影剂, 可供血管内、椎管内和体腔内使用.植物试验结果标明本品对犬肝脏、腹主动脉、CT 扫描影像有增强效应.毒理学犬肾动脉造影时有卵白尿发生的现象.【药代动力学】通过静脉注射到体内的碘海醇, 于24小时内几乎全部药物以原形经尿液排出.注射后一小时, 尿液中浓度最高.无代谢物发生.健康志愿者接受静脉内注射碘海醇后, 其血流动力学参数、临床化学参数及凝结参数与接受注射前的数值分歧甚微, 其改变无临床意义.年夜鼠、兔及犬静脉注射时主要从尿中排出, 小部份（年夜鼠5％, 犬1％）从粪中排出, 尚未发现任何器官吸收的现象, 也未在植物中检测就任何代谢产物.本品卵白结合率少于2％或几乎不与卵白结合.【适应症】1．血管内应用临床应用本品于成人及儿童的尿路造影和心血管造影, 以及成人的年夜脑血管造影, 外周及各种动脉造影、静脉造影、数字减影和CT增强扫描.2．蛛网膜下应用适用于成人及儿童的脊髓造影, 以及应用于蛛网膜下注射后进行脑池CT扫描检查.3．体腔内应用适用于各种体腔检查, 包括口服.如关节造影；内窥镜逆行胰胆管造影（ERCP）；疝囊造影；尿路造影；子宫输卵管造影；涎管造影以及各种使用口服水溶造影剂进行的胃肠道检查等.【用法用量】1．血管内应用剂量参考表应用项目浓度用量注释尿道造影成人300mgI/ml或350mgI/ml 40～80ml40～80ml在年夜剂量的尿路造影时可用较高浓度的造影剂儿童＞7kg ＜7kg240mgI/ml或300mgI/ml240mgI/ml或300mgI/ml4ml/kg3ml/kg3ml/kg2ml/kg（最高40ml）动脉造影主动脉与血管造影选择性年夜脑动脉造影主动脉造影四肢动脉造影其他动脉造影静脉造影（四肢）300mgI/ml300mgI/ml350mgI/ml300mgI/ml或350mgI/ml300mgI/ml240mgI/ml每次注射30～40ml每次注射5～10ml每次注射40～60ml取决于检查的项目20～100ml（四肢）心血管造影成人左心室主动脉根注射选择性冠状动脉造影儿童或300mgI/ml350mgI/ml350mgI/ml300mgI/ml或350mgI/ml每次注射30～60ml每次注射4～8ml取决于年龄、体重和病种（最高8ml/kg）数字减影动脉内注射静脉内注射140mgI/ml或240mgI/ml或300mgI/ml300mgI/ml每次注射1～15ml每次注射1～15ml每次注射1～15ml每次注射20～60ml每次注射20～60ml取决于造影部位.或350mgI/mlCT增强扫描140mgI/ml或240mgI/ml或300mgI/ml或350mgI/ml 100～400ml100～250ml100～200ml100～150ml总碘量通常为30～60g；低浓度造影剂适宜静脉滴注, 高浓度造影剂适宜静脉快速注入, 儿童用量酌减2．蛛网膜下应用剂量与浓度视检查的类别、采纳的技术及蛛网膜下腔的年夜小而定.一般注射方法是腰椎穿刺术, 在腰椎第3/4节间穿刺（腰部及胸部脊髓造影）, 或在颈椎第1/2节间作侧颈穿刺（颈部脊髓造影）.若采纳腰椎穿刺术作颈脊髓造影, 把病人倾倒时要非常小心, 以免年夜量的高浓度造影剂进入脑内.为减少造影剂与脑脊液混合, 可采纳1至2分钟的注射速度注入, 造影剂用量见下表.造影剂剂量参考表应用项目浓度用量腰及胸脊髓造影（腰椎穿刺）颈脊髓造影（腰椎穿刺）180mgI/ml或240mgI/ml240mgI/ml或300mgI/ml10～15ml8～12ml10～12ml7～10ml颈脊髓造影（颈正面穿刺）CT脑室造影（腰椎穿刺）240mgI/ml或300mgI/ml180mgI/ml或240mgI/ml6～10ml6～8ml5～15ml4～12ml儿科脊髓造影＜2岁2～6岁＞6岁180毫克碘/毫升180毫克碘/毫升180毫克碘/毫升2～6毫升4～8毫升6～12毫升总含碘量不应超越3g, 以减低发生不良反应的可能性. 3．体腔内应用造影剂剂量参考表应用项目浓度用量关节造影240mgI/ml或300mgI/ml或350mgI/ml 5～20ml 5～15ml 5～10ml内窥镜进行胰管/胆管及胰管联合造影240mgI/ml 20～50ml 疝囊造影240mgI/ml 50ml子宫输卵管造影240mgI/ml或300mgI/ml 15～50ml 15～25ml涎管造影240mgI/ml或300mgI/ml 0.5～2ml 0.5～2ml胃肠道检查－（口服）180mgI/ml或350mgI/ml 10～200ml 10～200ml【不良反应】1．少数病人可能会发生一些轻微的反应, 例如：长久的温感、微痛、脸红、恶心/呕吐、轻微胸口作痛、皮肤瘙痒及风疹等.2．头痛、恶心及呕吐都是脊髓造影中最罕见的不良反应.继续数天的剧烈头痛, 可能间断发生.迄今发现的其他轻微不良反应有长久的头晕、背痛、颈痛或四肢痛楚以及各种感觉异常现象.也曾发生脑电图记录显示不明确的长久变动（慢波）.用水溶性造影剂作脊髓造影后曾发现无菌性脑膜炎.使用本品作脊髓造影也曾报道过类似情况, 但十分轻微且继续时间长久.3．有的病人在造影后数小时至数日内呈现迟发性不良反应的报道也有.4．严重不良反应甚少呈现, 但休克、惊厥、昏迷、重度喉头水肿或支气管痉挛、肾功能衰竭、死亡等也有报道.据日本片山教授等收集的30万病例统计, 非离子造影剂（包括碘海醇）轻度不良反应发生率约为3.08％, 中度不良反应发生率约为0.04％, 重度不良反应发生率约为0.004％.【禁忌】1．有明显的甲状腺病症患者.2．对碘海醇注射液有严重反应既往史者.3．有癫痫病史的人, 不宜在蛛网膜下腔使用碘海醇.4．有严重的局部感染或全身感染, 而可能形成菌血症的患者, 禁忌腰椎穿刺术.5．鉴于怀孕期间应尽量防止接触放射线, 故需权衡X线检查的利弊关系.除非医生认为需要, 否则孕妇应禁用.6．由于剂量限制, 对造影时失败者, 也不宜即时进行重复造影.【注意事项】1．含碘造影剂可能会引起过敏性反应或其他过敏现象.虽然碘海醇引起剧烈反应的风险甚微, 但仍应事先制定紧急救治法式, 以便发生严重的反应时能马上进行治疗.有过敏症或气喘病史, 或是曾对含碘造影剂有不良反应的病人, 使用此造影剂时需要特别小心.必需造影时, 可考虑在造影前使用皮质类固醇及抗组胺剂.2．一旦发现有年夜量造影剂流入病人脑内的迹象, 可考虑使用巴比妥酸盐进行抗惊厥治疗.（1）术前护理及术前用药：倘若病人需要镇静剂, 可使用苯甲二氮卓.病人若感觉到强烈的痛楚, 可服用止痛药.需确保病人在进行检查前有充分的水分.（2）术后护理及术后用药：病人接受脊髓造影后, 须仰卧病床, 头部坚持高抬至少6小时, 并在24小时内不得自行移动.若怀疑病人的癫痫发病阈有所降低, 需密切监护.倘若癫痫发作, 须马上给予抗癫痫治疗, 例如把10mg苯甲二氮卓缓慢的注射入静脉.要防止复发, 可在停止发病20～30分钟后, 在肌肉内注射200mg苯巴比妥.鼓励病人进食流质食品和可以接受的固体食物.若发生继续性恶心或呕吐现象, 应立即考虑进行静脉输液, 以更换体液.需要时, 可给予止吐剂.（3）后备术后护理：在脊髓造影后, 病人挺身危坐在轮椅上, 可能会减少发生不良反应.这种挺身危坐姿势, 可能有助于延迟造影剂向上身散播, 并加强腰部蛛网膜的吸收能力.要告诫病人切记在术后24小时内不成弯身下俯.同时要指导病人, 应尽量防止移出发体, 以减少脑脊液泄漏.3．体外试验标明非离子型造影剂对止血（即血凝固机理）的抑制作用比浓度相似的离子型造影剂为低.因此, 血管造影应按标准步伐进行.血管造影导管应经常冲刷并防止血液和造影剂在注射器及导管中长时间接触.4．对高危病人如患有严重肝脏或肾脏机能不全, 甲状腺病及骨髓白血病的病人, 使用时应特别小心, 给予特别监护, 且应防止脱水.需要时术后进行透析治疗.5．碘造影剂可加重重症肌无力的症状.嗜铬细胞瘤患者进行静脉注射时, 应预防性地给予α－受体阻断剂, 以防止呈现高血压危象.血清内肌酸酐浓度超越500μmol/L的糖尿病患者, 应防止用此造影剂（除非检查为病人带来的益处明显超越冒险成分）.6．确保病人在接受造影剂前后有良好的水电解质平衡.7．所有含碘质造影剂均可能妨碍甲状腺功能的检查.甲状腺组织的碘结合能力可能会受造影剂影响而降低, 而且需要数日甚至两星期才华完全恢复.8．孕妇及哺乳期妇女应尽量防止使用.虽然植物实验并未显示碘海醇会损害生育能力或招致畸形婴儿, 但怀孕期间应尽量减少使用, 直至在病人中进行严格控制的研究有明确的结论为止.此造影剂被排入母乳的水平, 虽然估计是相当轻微, 但实际情况尚未确定.9．造影剂也不应与其它药物混合, 应使用专用的注射针和针筒.10．每瓶碘海醇只应供一名病人使用, 剩余的部份应弃失落.11．造影前2小时应禁食.12．本品如有变色、沉淀则不能使用.【孕妇及哺乳期妇女用药】请拜会禁忌症和注意事项.【儿童用药】【老年患者用药】【药物相互作用】1．使用造影剂可能会招致长久性肾功能不全, 这可使服用降糖药（二甲双胍）的糖尿病人发生乳酸性中毒.作为预防, 在使用造影剂前48小时应停服双胍类降糖药, 只有在肾功能稳定后再恢复用药.2．两周内用白介素－2治疗的病人其延迟反应的危险性会增加（感冒样症状和皮肤反应）.3．所有含碘质造影剂均可能妨碍甲状腺功能的检查.甲状腺组织的碘结合能力可能会受造影剂影响而降低, 而且需要数日甚至两星期才华完全恢复.4．血清和尿中高浓度的造影剂会影响胆红素、卵白或无机物（如铁、铜、钙和磷）的实验室测定结果.在使用造影剂确当天不应做这些检查.【药物过量】【规格】（1）10ml：3g（2）20ml：6g（3）20ml：7g（4）50ml：15g（8）100ml：30g（9）100ml：35g（10）200ml：70g【贮藏】遮光, 密闭保管.【包装】【有效期】【批准文号】【生产企业】企业名称：地址：邮政编码：德律风号码：传真号码：网址：。
美国专利到期的药物精选一、精神、神经系统药类1、郁复伸中文通用名:文拉法辛;别名:维拉法辛。
英文通用名:venlafaxine ;英文商品名:Effexor。
药品简介:文拉法辛是中枢神经系统药物,用于治疗精神失常、躁狂抑郁症和抑郁症。
由惠氏公司开发并于1994 年4 月首次在美国上市,此后相继在加拿大、丹麦、英国、意大利、澳大利亚等国上市。
文拉法辛具有临床疗效好、安全性高和治疗成本较低等特点,其2002 年全球销售约为21 亿美元,位列药品销售400 强的第21 位。
美国专利名称:2-苯基-2-(1-羟基环炔基或1-羟基环烷基-2-烯基) 乙胺衍生物(专利号:US4535186)专利权人:American Home Prod注:该专利到期日:2007 年12 月13 日(该专利申请日:1983 年10 月26 日;原来到期日:2002 年12 月13日;后被批准延长5 年) 。
该专利因获得美国儿科药市场独占,到期日延至2008 年6 月13 日。
同族专利: US4535186[1985208213 ]2、罗匹尼罗英文通用名:Ropinirole ;英文商品名:ReQuip 。
药品简介:罗匹尼罗于1997 年首次被批准用于帕金森病,是一种类似多巴胺的多巴胺激动剂,与第一代多巴胺激动剂不同的是其没有麦角林结构。
因为多巴胺激动剂较少引起运动不良反应,2001 年7 月,新的帕金森病治疗指南建议用多巴胺激动剂如葛兰素- 史克公司的罗匹尼罗(ropinirole ,ReQuip ○R ) 代替左旋多巴作为疾病早期的初始一线治疗用药。
2005 年美国食品药品管理局(FDA) 批准罗匹尼罗用于治疗中度到重度的多动腿综合征(RLS) 。
美国专利名称:42氨烷基22 (3H)2吲哚酮类化合物(专利号:US4452808 )专利权人: Smithkline Beckman Corp该专利到期日:2007 年12 月7 日(该专利申请日:1982 年12 月7 日;原来到期日:2002 年12 月7 日;后被批准延长5 年) 。
碘海醇注射液说明书之邯郸勺丸创作【药品名称】通用名：碘海醇注射液曾用名：商品名：英文名：Iohexol Injection汉语拼音：Diɑnhɑichun Zhusheye本品主要成份及其化学名称为：N，N'-双(2,3-二羟基丙基)-5-[N-(2,3-二羟基丙基)乙酰胺基]-2,4,6-三碘-1,3-苯二甲酰胺。
结构式：分子式：C19H26I3N3O9【性状】本品为无色至淡黄色的澄明液体。
本品是一种含有三个碘原子的非离子水溶性造影剂，碘含量为46.4％。
它以经过消毒的水溶液为剂型，随时可用，并有分歧的碘浓度，分别为每毫升浓度含有140、180、240、300或350mg碘。
【药理毒理】药理学本品为X光及CT检查经常使用的造影剂，可供血管内、椎管内和体腔内使用。
动物试验结果标明本品对犬肝脏、腹主动脉、CT扫描影像有增强效应。
毒理学犬肾动脉造影时有蛋白尿发生的现象。
【药代动力学】通过静脉注射到体内的碘海醇，于24小时内几乎全部药物以原形经尿液排出。
注射后一小时，尿液中浓度最高。
无代谢物发生。
健康志愿者接受静脉内注射碘海醇后，其血流动力学参数、临床化学参数及凝结参数与接受注射前的数值不同甚微，其改变无临床意义。
大鼠、兔及犬静脉注射时主要从尿中排出，小部分（大鼠5％，犬1％）从粪中排出，尚未发现任何器官吸收的现象，也未在动物中检测到任何代谢产品。
本品蛋白结合率少于2％或几乎不与蛋白结合。
【适应症】1．血管内应用临床应用本品于成人及儿童的尿路造影和心血管造影，以及成人的大脑血管造影，外周及各种动脉造影、静脉造影、数字减影和CT增强扫描。
2．蛛网膜下应用适用于成人及儿童的脊髓造影，以及应用于蛛网膜下注射后进行脑池CT扫描检查。
3．体腔内应用适用于各种体腔检查，包含口服。
如关节造影；内窥镜逆行胰胆管造影（ERCP）；疝囊造影；尿路造影；子宫输卵管造影；涎管造影以及各种使用口服水溶造影剂进行的胃肠道检查等。
碘海醇注射液说明书【药品名称】通用名：碘海醇注射液曾用名：商品名：英文名：Iohexol? Injection汉语拼音：Diɑnhɑichun Zhusheye本品主要成份及其化学名称为：N，N'-双(2,3-二羟基丙基)-5-[N-(2,3-二羟基丙基)乙酰胺基]-2,4,6-三碘-1,3-苯二甲酰胺。
结构式：分子式：C19H26I3N3O9分子量：【性状】本品为无色至淡黄色的澄明液体。
本品是一种含有三个碘原子的非离子水溶性造影剂，碘含量为％。
它以经过消毒的水溶液为剂型，随时可用，并有不同的碘浓度，分别为每毫升浓度含有140、180、240、300或350mg碘。
【药理毒理】药理学本品为X光及CT检查常用的造影剂，可供血管内、椎管内和体腔内使用。
动物试验结果表明本品对犬肝脏、腹主动脉、CT扫描影像有增强效应。
毒理学犬肾动脉造影时有蛋白尿发生的现象。
【药代动力学】通过静脉注射到体内的碘海醇，于24小时内几乎全部药物以原形经尿液排出。
注射后一小时，尿液中浓度最高。
无代谢物产生。
健康志愿者接受静脉内注射碘海醇后，其血流动力学参数、临床化学参数及凝结参数与接受注射前的数值差别甚微，其改变无临床意义。
大鼠、兔及犬静脉注射时主要从尿中排出，小部分（大鼠5％，犬1％）从粪中排出，尚未发现任何器官吸收的现象，也未在动物中检测到任何代谢产物。
本品蛋白结合率少于2％或几乎不与蛋白结合。
【适应症】1．血管内应用?? 临床应用本品于成人及儿童的尿路造影和心血管造影，以及成人的大脑血管造影，外周及各种动脉造影、静脉造影、数字减影和CT增强扫描。
2．蛛网膜下应用适用于成人及儿童的脊髓造影，以及应用于蛛网膜下注射后进行脑池CT扫描检查。
3．体腔内应用? 适用于各种体腔检查，包括口服。
如关节造影；内窥镜逆行胰胆管造影（ERCP）；疝囊造影；尿路造影；子宫输卵管造影；涎管造影以及各种使用口服水溶造影剂进行的胃肠道检查等。
碘酊Dian DingIodine Tincture本品含碘（I）应为9.0%～11.0%（g/ml），含碘化钾（KI）应为1.80%～2.20%（g/ml）。
【处方】碘 100g碘化钾 20g水 20ml乙醇适量__________________________制成 1000ml【制法】取碘化钾，加水20ml溶解后，加碘及乙醇，搅拌使溶解，再加乙醇使成1000ml，搅匀，即得。
【性状】本品为深红棕色的澄清液体；有碘与乙醇的特臭。
【鉴别】（1）取本品1滴，滴入淀粉指示液1ml与水10ml的混合液，即显深蓝色。
（2）取本品5ml，置水浴上蒸干，缓缓炽灼，使游离碘完全挥发，残渣加水溶解后，显钾盐与碘化物的鉴别反应（中国药典2010年版二部附录Ⅲ）。
【含量测定】碘精密量取本品5ml，置25ml量瓶中，用70%乙醇稀释至刻度，摇匀，精密量取5ml，置碘瓶中，加醋酸1滴，用硫代硫酸钠滴定液（0.1mol/L）滴定至溶液显淡黄色，加淀粉指示液1ml，继续滴定至蓝色消失。
每1ml硫代硫酸钠滴定液（0.1mol/L）相当于12.69mg 的I。
碘化钾取上述滴定后的溶液，加醋酸2ml与曙红钠指示液0.1ml，用硝酸银滴定液（0.1mol/L）滴定，至沉淀由黄色转为玫瑰红色，将消耗的硝酸银滴定液（0.1mol/L）的容积（ml）减去上述消耗的硫代硫酸钠滴定液（0.1mol/L）的容积（ml）。
每1ml硝酸银滴定液（0.1mol/L）相当于16.60mg的KI。
【类别】消毒防腐药。
【规格】10%【贮藏】密封，在凉暗处保存。
外碘酊说明书请仔细阅读说明书并在医生指导下使用【制剂名称】通用名：碘酊英文名：Iodine Tincture汉语拼音：Dian Ding【成分】碘，辅料为碘化钾、乙醇。
【性状】本品为深红棕色的澄清液体；有碘与乙醇的特臭。
【适应症】用于甲癣真菌病。
【规格】10%【用法用量】外用。
取适量，涂擦患处，一日1次。
药品名称普罗碘铵拼⾳名 Puluodian’an英⽂名 PROLONIUM IODIDE来源(分⼦式)与标准本品为⼆碘化（2-羟基-1，3-亚丙基）双（三甲铵）。
按⼲燥品计算，含C9H24I2N 2O不得少于99.0％。
性状 本品为⽩⾊或类⽩⾊粉末；⽆臭；暴露空⽓中渐变黄⾊。
本品在⽔中极易溶解，在⼄醇或氯仿中⼏乎不溶。
检查 酸度 本品1.0 ％⽔溶液的pH值应为5.5 ～7.5 （附录Ⅵ H）。
溶液的颜⾊ 本品2.0 ％的⽔溶液与黄⾊6 号标准⽐⾊液（附录Ⅸ A第⼀法）⽐较，不得更深。
游离碘取本品0.50g,置试管中，加⽔10ml，淀粉指⽰液2ml,振摇，不得显蓝⾊。
氯化物 取本品0.10g,加⽔5ml 、浓氨溶液5ml 与硝酸银试液10ml，摇匀，滤过，沉淀以⽔10ml洗涤，滤液与洗液合并，取半量，加硝酸(1→4)10ml，⽤⽔稀释⾄50ml，依法检查（附录Ⅷ A）,与标准氯化钠溶液4.0ml制成的对照液⽐较，不得更浓(0.04％)。
⼲燥失重 取本品，在105 ℃⼲燥⾄恒重，减失重量不得过0.5 ％（附录Ⅷ L）。
重⾦属 取本品1.0g，加⽔适量溶解后，加醋酸盐缓冲液(pH3.5)2ml与⽔适量使成 25ml，依法检查（附录Ⅷ H第⼀法），含重⾦属不得过百万分之⼗。
鉴别 (1) 取本品约20mg，加⽔1ml、氯仿1ml与1％重铬酸钾的稀硫酸溶液1滴，振摇，氯仿层应显玫瑰红⾊；再加淀粉指⽰液2滴，⽔层显蓝⾊。
(2) 取本品约0.1g，置⼩烧杯中，加⼊10％氢氧化钠溶液2ml ，加热即有鱼腥臭，烧杯上覆盖⼀表⾯⽫，内悬垂碱性碘化汞钾试液1 滴，即缓缓出现淡棕黄⾊沉淀。
(3) 本品的红外光吸收图谱应与对照的图谱（光谱集512 图）⼀致。
含量测定 取本品约0.4g，精密称定，加⽔20ml溶解，加铬酸钾指⽰液1.0ml, ⽤硝酸银滴定液(0.1mol/L)滴定⾄显桔红⾊沉淀。
每1ml 的硝酸银滴定液(0.1mol/L)相当于21.51mg 的C9H24I2N2O。
碘海醇打针液解释书【药品名称】通用名：碘海醇打针液曾用名：商品名：英文名：Iohexol Injection汉语拼音：Diɑnhɑichun Zhusheye本品重要成份及其化学名称为：N,N'-双(2,3-二羟基丙基)-5-[N-(2,3-二羟基丙基)乙酰胺基]-2,4,6-三碘-1,3-苯二甲酰胺.构造式：分子式：C19H26I3N3O9【性状】本品为无色至淡黄色的澄明液体.本品是一种含有三个碘原子的非离子水溶性造影剂,碘含量为46.4％.它以经由消毒的水溶液为剂型,随时可用,并有不合的碘浓度,分离为每毫升浓度含有140.180.240.300或350mg碘.【药理毒理】药理学本品为X光及CT检讨经常运用的造影剂,可供血管内.椎管内和体腔内运用.动物实验成果标明本品对犬肝脏.腹自动脉.CT扫描影像有加强效应.毒理学犬肾动脉造影时有蛋白尿产生的现象.【药代动力学】经由过程静脉打针到体内的碘海醇,于24小时内几乎全体药物以本相经尿液排出.打针后一小时,尿液中浓度最高.无代谢物产生.健康自愿者接收静脉内打针碘海醇后,其血流淌力学参数.临床化学参数及凝聚参数与接收打针前的数值不同甚微,其转变无临床意义.大鼠.兔及犬静脉打针时重要从尿中排出,小部分（大鼠5％,犬1％）从粪中排出,尚未发明任何器官接收的现象,也未在动物中检测到任何代谢产品.本品蛋白结合率少于2％或几乎不与蛋白结合.【顺应症】1．血管内运用临床运用本品于成人及儿童的尿路造影和血汗管造影,以及成人的大脑血管造影,外周及各类动脉造影.静脉造影.数字减影和CT加强扫描.2．蛛网膜下运用实用于成人及儿童的脊髓造影,以及运用于蛛网膜下打针落后行脑池CT扫描检讨.3．体腔内运用实用于各类体腔检讨,包含口服.如关节造影;内窥镜逆行胰胆管造影（ERCP）;疝囊造影;尿路造影;子宫输卵管造影;涎管造影以及各类运用口服水溶造影剂进行的胃肠道检讨等.【用法用量】1．血管内运用剂量参考表运用项目浓度用量注释尿道造影成人儿童＞7kg ＜7kg300mgI/ml或350mgI/ml240mgI/ml或300mgI/ml240mgI/ml或300mgI/ml40～80ml40～80ml4ml/kg3ml/kg3ml/kg2ml/kg（最高40ml）在大剂量的尿路造影时可用较高浓度的造影剂动脉造影自动脉与血管造影选择性大脑动脉造影自动脉造影四肢动脉造影其他动脉造影静脉造影（四肢）300mgI/ml300mgI/ml350mgI/ml300mgI/ml或350mgI/ml300mgI/ml240mgI/ml每次打针30～40ml每次打针5～10ml每次打针40～60ml取决于检讨的项目20～100ml（四肢）血汗管造影成人左心室自动脉根打针选择性冠状动脉造影儿童或300mgI/ml350mgI/ml350mgI/ml300mgI/ml或350mgI/ml每次打针30～60ml每次打针4～8ml取决于年纪.体重和病种（最高8ml/kg）数字减影动脉内打针静脉内打针140mgI/ml或240mgI/ml或300mgI/ml300mgI/ml或350mgI/ml每次打针1～15ml每次打针1～15ml每次打针1～15ml每次打针20～60ml每次打针20～60ml取决于造影部位.CT加强扫描140mgI/ml或240mgI/ml或300mgI/ml或350mgI/ml 100～400ml100～250ml100～200ml100～150ml总碘量平日为30～60g;低浓度造影剂合适静脉滴注,高浓度造影剂合适静脉快速注入,儿童用量酌减2．蛛网膜下运用剂量与浓度视检讨的类别.采取的技巧及蛛网膜下腔的大小而定.一般打针办法是腰椎穿刺术,在腰椎第3/4节间穿刺（腰部及胸部脊髓造影）,或在颈椎第1/2节间作侧颈穿刺（颈部脊髓造影）.若采取腰椎穿刺术作颈脊髓造影,把病人倾倒时要平常当心,以免大量的高浓度造影剂进入脑内.为削减造影剂与脑脊液混杂,可采取1至2分钟的打针速度注入,造影剂用量见下表.造影剂剂量参考表运用项目浓度用量腰及胸脊髓造影（腰椎穿刺）颈脊髓造影（腰椎穿刺）颈脊髓造影（颈正面穿刺）CT脑室造影（腰椎穿刺）180mgI/ml或240mgI/ml240mgI/ml或300mgI/ml240mgI/ml或300mgI/ml180mgI/ml或240mgI/ml10～15ml8～12ml10～12ml7～10ml6～10ml6～8ml5～15ml4～12ml儿科脊髓造影＜2岁180毫克碘/毫升2～6毫升总含碘量不该超出3g,以减低产生不良反响的可能性. 3．体腔内运用造影剂剂量参考表运用项目浓度用量关节造影240mgI/ml或300mgI/ml或350mgI/ml 5～20ml 5～15ml 5～10ml内窥镜进行胰管/胆管及胰管结合造影240mgI/ml 20～50ml 疝囊造影240mgI/ml 50ml子宫输卵管造影240mgI/ml或300mgI/ml 15～50ml 15～25ml涎管造影240mgI/ml或300mgI/ml 0.5～2ml 0.5～2ml胃肠道检讨－（口服）180mgI/ml或350mgI/ml 10～200ml 10～200ml【不良反响】1．少数病人可能会产生一些稍微的反响,例如：短暂的温感.微痛.脸红.恶心/吐逆.稍微胸口作痛.皮肤瘙痒及风疹等.2．头痛.恶心及吐逆都是脊髓造影中最罕有的不良反响.中断数天的激烈头痛,可能间断产生.迄今发明的其他稍微不良反响有短暂的头晕.背痛.颈痛或四肢苦楚以及各类感到平常现象.也曾产生脑电图记载显示不明白的短暂变更（慢波）.用水溶性造影剂作脊髓造影后曾发明无菌性脑膜炎.运用本品作脊髓造影也曾报导过类似情形,但十分稍微且中断时光短暂.3．有的病人在造影后数小时至数日内消失迟发性不良反响的报导也有.4．轻微不良反响甚少消失,但休克.惊厥.晕厥.重度喉头水肿或支气管痉挛.肾功效衰竭.逝世亡等也有报导.据日本片山传授等收集的30万病例统计,非离子造影剂（包含碘海醇）轻度不良反响产生率约为3.08％,中度不良反响产生率约为0.04％,重度不良反响产生率约为0.004％.【禁忌】1．有显著的甲状腺病症患者.2．对碘海醇打针液有轻微反响既往史者.3．有癫痫病史的人,不宜在蛛网膜下腔运用碘海醇.4．有轻微的局部沾染或全身沾染,而可能形成菌血症的患者,禁忌腰椎穿刺术.5．鉴于怀孕时代应尽量防止接触放射线,故需衡量X线检讨的利弊关系.除非大夫以为须要,不然妊妇应禁用.6．因为剂量限制,对造影时掉败者,也不宜即时进行反复造影.【留意事项】1．含碘造影剂可能会引起过敏性反响或其他过敏现象.固然碘海醇引起激烈反响的风险甚微,但仍应事先制订紧迫救治程序,以便产生轻微的反响时能立时进行治疗.有过敏症或气喘病史,或是曾对含碘造影剂有不良反响的病人,运用此造影剂时须要特殊当心.必须造影时,可斟酌在造影前运用皮质类固醇及抗组胺剂.2．一旦发明有大量造影剂流入病人脑内的迹象,可斟酌运用巴比妥酸盐进行抗惊厥治疗.（1）术前护理及术前用药：倘使病人须要沉着剂,可运用苯甲二氮卓.病人若感到到强烈的苦楚,可服用止痛药.需确保病人在进行检讨前有充足的水分.（2）术后护理及术后用药：病人接收脊髓造影后,须仰卧病床,头部保持高抬至少6小时,并在24小时内不得自行移动.若疑惑病人的癫痫发病阈有所下降,需亲密监护.倘使癫痫发生发火,须立时赐与抗癫痫治疗,例如把10mg苯甲二氮卓迟缓的打针入静脉.要防止复发,可在停滞发病20～30分钟后,在肌肉内打针200mg苯巴比妥.勉励病人进食流质食物和可以接收的固体食物.若产生中断性恶心或吐逆现象,应立刻斟酌进行静脉输液,以改换体液.须要时,可赐与止吐剂.（3）后备术后护理：在脊髓造影后,病人挺身危坐在轮椅上,可能会削减产生不良反响.这种挺身危坐姿态,可能有助于延迟造影剂向上身散布,并加强腰部蛛网膜的接收才能.要申饬病人切记在术后24小时内不成弯身下俯.同时要指点病人,应尽量防止移出发体,以削减脑脊液泄露.3．体外实验标明非离子型造影剂对止血（即血凝固机理）的克制造用比浓度类似的离子型造影剂为低.是以,血管造影应按尺度步调进行.血管造影导管应经常冲洗并防止血液和造影剂在打针器及导管中长时光接触.4．对高危病人如患有轻微肝脏或肾脏机能不全,甲状腺病及骨髓白血病的病人,运用时应特殊当心,赐与特殊监护,且应防止脱水.须要时术落后行透析治疗.5．碘造影剂可加重重症肌无力的症状.嗜铬细胞瘤患者进行静脉打针时,应预防性地赐与α－受体阻断剂,以防止消失高血压危象.血清内肌酸酐浓度超出500μmol/L的糖尿病患者,应防止用此造影剂（除非检讨为病人带来的益处显著超出冒险成分）.6．确保病人在接收造影剂前后有优越的水电解质均衡.7．所有含碘质造影剂均可能妨害甲状腺功效的检讨.甲状腺组织的碘结合才能可能会受造影剂影响而下降,并且须要数日甚至两礼拜才干完整恢复.8．妊妇及哺乳期妇女应尽量防止运用.固然动物实验并未显示碘海醇会伤害生育才能或导致畸形婴儿,但怀孕时代应尽量削减运用,直至在病人中进行严厉掌握的研讨有明白的结论为止.此造影剂被排入母乳的程度,固然估量是相当稍微,但现实情形尚未肯定.9．造影剂也不该与其它药物混杂,应运用专用的打针针和针筒.10．每瓶碘海醇只应供一名病人运用,残剩的部分应弃掉落.11．造影前2小时应禁食.12．本品若有变色.沉淀则不克不及运用.【妊妇及哺乳期妇女用药】请拜见禁忌症和留意事项.【儿童用药】【老年患者用药】【药物互相感化】1．运用造影剂可能会导致短暂性肾功效不全,这可使服用降糖药（二甲双胍）的糖尿病人产生乳酸性中毒.作为预防,在运用造影剂前48小时应停服双胍类降糖药,只有在肾功效稳固后再恢复用药.2．两周内用白介素－2治疗的病人其延迟反响的安全性会增长（伤风样症状和皮肤反响）.3．所有含碘质造影剂均可能妨害甲状腺功效的检讨.甲状腺组织的碘结合才能可能会受造影剂影响而下降,并且须要数日甚至两礼拜才干完整恢复.4．血清和尿中高浓度的造影剂会影响胆红素.蛋白或无机物（如铁.铜.钙和磷）的实验室测定成果.在运用造影剂的当天不该做这些检讨.【药物过量】【规格】（1）10ml：3g（2）20ml：6g （3）20ml：7g （4）50ml：15g （8）100ml：30g （9）100ml：35g （10）200ml：70g 【贮藏】遮光,密闭保管.【包装】【有用期】【同意文号】【临盆企业】企业名称：地址：邮政编码：德律风号码：传真号码：网址：。
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use AVYCAZ safely and effectively. See full prescribing information for AVYCAZ.AVYCAZ (ceftazidime-avibactam) for injection, for intravenous use Initial U.S. Approval: 2015----------------------------INDICATIONS AND USAGE--------------------------AVYCAZ (ceftazidime-avibactam) is a combination of a cephalosporin and a beta-lactamase inhibitor indicated for the treatment of patients 18 years or older with the following infections caused by designated susceptible microorganisms:• Complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole (1.1)• Complicated Urinary Tract Infections (cUTI), including Pyelonephritis(1.2)As only limited clinical safety and efficacy data for AVYCAZ are currently available, reserve AVYCAZ for use in patients who have limited or no alternative treatment options. [see Clinical Studies (14)].To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.----------------------DOSAGE AND ADMINISTRATION----------------------Estimated Creatinine Clearance (mL/min)a Recommended Dosage Regimen for AVYCAZ Infuse each dose intravenously over 2 hoursgreater than 50 2.5 grams (2 grams/0.5 grams) every 8 hours31 to 50 1.25 grams (1 grams/0.25 grams) every 8 hours 16 to 30 0.94 grams (0.75 grams/0.19 grams every 12 hours 6 to 15b 0.94 grams (0.75 grams/0.19 grams) every 24 hours Less than or equal 5b 0.94 grams (0.75 grams/0.19 grams) every 48 hoursa As calculated using the Cockcroft-Gault formula.b Both ceftazidime and avibactam are hemodialyzable; thus, administer AVYCAZ after hemodialysis on hemodialysis days.Recommended duration of treatment: (2.1)cIAI: 5 to 14 dayscUTI including pyelonephritis: 7 to 14 days • See Full Prescribing Information for instructions for constituting supplied dry powder and subsequent required dilution. (2.3)• See Full Prescribing Information for drug compatibilities. (2.4)---------------------DOSAGE FORMS AND STRENGTHS---------------------AVYCAZ (ceftazidime-avibactam) for Injection in single-use vials containing 2 grams ceftazidime and 0.5 grams avibactam. (3)-------------------------------CONTRAINDICATIONS-----------------------------Known serious hypersensitivity to ceftazidime, avibactam or other members of the cephalosporin class. (4)-----------------------WARNINGS AND PRECAUTIONS-----------------------• Decreased efficacy in patients with baseline CrCL of 30 to 50 mL/ min.Monitor CrCL at least daily in patients with changing renal function and adjust the dose of AVYCAZ accordingly. (5.1)• Hypersensitivity reactions: Includes anaphylaxis and serious skin reactions.Cross-hypersensitivity may occur in patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue AVYCAZ. (5.2)• Clostridium difficile-associated diarrhea: Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including AVYCAZ. Evaluate if diarrhea occurs. (5.3)• Central Nervous System Reactions: Seizures and other neurologic events may occur, especially in patients with renal impairment. Adjust dose in patients with renal impairment. (5.4)------------------------------ADVERSE REACTIONS------------------------------Most common adverse reactions (incidence of > 10% in either indication) are vomiting, nausea, constipation, and anxiety. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Forest Laboratories, LLC, at 1-800-678-1605 or FDA at 1-800-FDA-1088or /medwatch.See 17 for PATIENT COUNSELING INFORMATIONRevised: 02/2015______________________________________________________________________________________________________________________________________FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE1.1 Complicated Intra-Abdominal Infections (cIAI)1.2 Complicated Urinary Tract Infections (cUTI), includingPyelonephritis1.3 Usage2 DOSAGE AND ADMINISTRATION2.1 Recommended Dosage2.2 Dosage Adjustments in Patients with Renal Impairment2.3 Preparation of the AVYCAZ Solution for Administration2.4 Drug Compatibility2.5 Storage of Constituted Solutions3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Decreased Clinical Response in Patients with Baseline CreatinineClearance of 30 to 50 mL/min5.2 Hypersensitivity Reactions5.3 Clostridium difficile-associated Diarrhea5.4 Central Nervous System Reactions5.5 Development of Drug-Resistant Bacteria6 ADVERSE REACTIONS6.1 Clinical Trial Experience7 DRUG INTERACTIONS7.1 Probenecid7.2 Drug/Laboratory Test Interactions8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics12.4 Microbiology13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES15 REFERENCES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not listed_______________________________________________________________________________________________________________________________________FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGE1.1 Complicated Intra-Abdominal Infections (cIAI)AVYCAZ (ceftazidime-avibactam), in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca, and Pseudomonas aeruginosa in patients 18 years or older.As only limited clinical safety and efficacy data for AVYCAZ are currently available, reserve AVYCAZ for use in patients who have limited or no alternative treatment options. [see Clinical Studies (14)].1.2 Complicated Urinary Tract Infections (cUTI), including PyelonephritisAVYCAZ (ceftazidime-avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Proteus spp., and Pseudomonas aeruginosa in patients 18 years or older.As only limited clinical safety and efficacy data for AVYCAZ are currently available, reserve AVYCAZ for use in patients who have limited or no alternative treatment options .[see Clinical Studies (14)].1.3 UsageTo reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used to treat only indicated infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy [see Dosage and Administration (2.1)].2 DOSAGE AND ADMINISTRATION2.1 Recommended DosageThe recommended dosage of AVYCAZ is 2.5 grams (2 grams ceftazidime and 0.5 grams avibactam) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older. For treatment of cIAI, metronidazole should be given concurrently. The guidelines for dosage of AVYCAZ in patients with normal renal function are listed in Table 1.Table 1. Dosage of AVYCAZ by IndicationInfection Dosage Frequency Infusion Time(hours)Recommended Duration of TotalAntimicrobial TreatmentComplicated Intra-abdominal Infections [used in combination with metronidazole]2.5 grams(2 grams/0.5 grams)Every 8 hours 2 5 to14 daysComplicated Urinary Tract Infections including Pyelonephritis2.5 grams(2 grams/0.5 grams)Every 8 hours 2 7 to 14 days2.2 Dosage Adjustments in Patients with Renal ImpairmentThe recommended AVYCAZ dosage in patients with varying degrees of renal function is presented in Table 2. For patients with changing renal function, monitor creatinine clearance (CrCL) at least daily and adjust the dosage of AVYCAZ accordingly [see Warnings and Precautions (5.1), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].Table 2. Recommended AVYCAZ Dosage in Patients with Renal Impairment with cUTI or cIAIEstimated CreatinineRecommended Dosage Regimen for AVYCAZClearance (mL/minute)aGreater than 50 2.5 grams (2 grams/0.5 grams) intravenously (over 2 hours) every 8 hours31 to 50 1.25 grams (1 grams/0.25 grams) intravenously (over 2 hours) every 8 hours16 to 30 0.94 grams (0.75 grams/0.19 grams) intravenously (over 2 hours) every 12 hours6 to 15b 0.94 grams (0.75 grams/0.19 grams) intravenously (over 2 hours) every 24 hoursLess than or equal to 5b 0.94 grams (0.75 grams/0.19 grams) intravenously (over 2 hours) every 48 hoursa As calculated using the Cockcroft-Gault formula.b Both ceftazidime and avibactam are hemodialyzable; thus, administer AVYCAZ after hemodialysis on hemodialysis days.2.3 Preparation of the AVYCAZ Solution for AdministrationAVYCAZ is supplied as a dry powder, which must be constituted and subsequently diluted, using aseptic technique prior to intravenous infusion.a) Constitute the powder in the AVYCAZ vial with 10 mL of one of the following solutions:• sterile water for injection, USP• 0.9% of sodium chloride injection, USP (normal saline)• 5% of dextrose injection, USP• all combinations of dextrose injection and sodium chloride injection, USP, containing up to 2.5% dextrose, USP, and 0.45% sodium chloride, USP, or• lactated Ringer’s injection, USP.b) Mix gently. The constituted AVYCAZ solution will have an approximate ceftazidime concentration of0.167 grams/mL and an approximate avibactam concentration of 0.042 grams/mL.c) With the same diluent used for constitution of the powder (except sterile water for injection), dilute theconstituted AVYCAZ solution further to achieve a total volume between 50 mL (40 and 10 mg/mL of ceftazidime and avibactam, respectively) to 250 mL (8 and 2 mg/mL of ceftazidime and avibactam,respectively) before infusion.d) Mix gently and ensure that the contents are dissolved completely. Visually inspect the diluted AVYCAZsolution (for administration) for particular matter and discoloration prior to administration (the color of the AVYCAZ infusion solution for administration ranges from clear to light yellow).e) Use the diluted AVYCAZ solution in the infusion bags within 12 hours when stored at roomtemperature. The diluted AVYCAZ solution in the infusion bags may be stored under refrigeration at 2 to 8°C (36 to 46°F) up to 24 hours following dilution and use within 12 hours of subsequent storage at room temperature.2.4 Drug CompatibilityThe AVYCAZ solution for administration at concentrations between 0.008 g/mL ceftazidime + 0.002 g/mL avibactam and 0.04 g/mL ceftazidime + 0.01 g/mL avibactam is compatible with the more commonly used intravenous infusion fluids in infusion bags (including Baxter® Mini-Bag Plus™) such as: • 0.9% sodium chloride injection, USP• 5% dextrose injection, USP• all combinations of dextrose injection and sodium chloride injection, USP, containing up to 2.5% dextrose, USP, and 0.45% sodium chloride, USP• lactated ringer's injection, USP, and• in Baxter® Mini-Bag Plus™ containing 0.9% sodium chloride injection or 5% dextrose injection. Compatibility of AVYCAZ solution for administration with other drugs has not been established.2.5 Storage of Constituted Solutions• Constituted solutions of AVYCAZ in the infusion bags should be used within 12 hours when stored at room temperature.• Constituted solutions of AVYCAZ in the infusion bags may be refrigerated for up to 24 hours following constitution; and then should be used within 12 hours of subsequent storage at room temperature.3 DOSAGE FORMS AND STRENGTHSAVYCAZ (ceftazidime-avibactam) for injection is supplied as a white to yellow sterile powder in a single use, sterile, clear glass vial containing 2 grams of ceftazidime (equivalent 2.635 grams of ceftazidime pentahydrate/sodium carbonate powder) and 0.5 grams of avibactam (equivalent to 0.551 grams of avibactam sodium).4 CONTRAINDICATIONSAVYCAZ is contraindicated in patients with known serious hypersensitivity to AVYCAZ,avibactam-containing products, ceftazidime, or other members of the cephalosporin class [see Warnings and Precautions (5.2)].5 WARNINGS AND PRECAUTIONS5.1 Decreased Clinical Response in Patients with Baseline Creatinine Clearance of 30 to 50mL/minIn a Phase 3 cIAI trial, clinical cure rates were lower in a subgroup of patients with baseline CrCL of 30 to 50 mL/min compared to those with CrCL greater than 50 mL/min (Table 3). The reduction in clinical cure rates was more marked in patients treated with AVYCAZ plus metronidazole compared to meropenem-treated patients. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCL 30 to 50 mL/min. Monitor CrCL at least daily in patients with changing renal function and adjust the dosage of AVYCAZ accordingly [see Dosage and Administration (2.2), and Adverse Reactions (6.1)].Table 3. Clinical Cure Rate at Test of Cure, by Baseline Renal Function – mMITT Population1AVYCAZ + Metronidazole% (n/N) Meropenem % (n/N)Normal function / mild impairment(CrCL greater than 50 mL/min)85% (322/379) 86% (321/373)Moderate impairment45% (14/31) 74% (26/35)(CrCL 30 to 50 mL/min)1Microbiological modified intent-to-treat (mMITT) population included patients who had at least one bacterial pathogen at baseline and received at least one dose of study drug.5.2 Hypersensitivity ReactionsSerious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with AVYCAZ is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Exercise caution if this product is to be given to a penicillin or other beta-lactam-allergic patient because cross sensitivity among beta-lactam antibacterial drugs has been established. Discontinue the drug if an allergic reaction to AVYCAZ occurs.5.3 Clostridium difficile-associated DiarrheaClostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including AVYCAZ, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial drugs alters the normal flora of the colon and may permit overgrowth of C. difficile.C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial drugs.If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued. Manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C. difficile, and institute surgical evaluation as clinically indicated.5.4 Central Nervous System ReactionsSeizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dosing based on creatinine clearance [see Dosage and Administration (2.2)].5.5 Development of Drug-Resistant BacteriaPrescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Indications and Usage (1.3)].6 ADVERSE REACTIONSThe following are discussed in greater detail in the Warnings and Precautions section:• Decreased Clinical Response in Patients with Baseline CrCL of 30 to 50 mL/min [see Warnings and Precautions (5.1)]• Hypersensitivity Reactions [see Warnings and Precautions (5.2)]• Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3)]• Central Nervous System Reactions [see Warnings and Precautions (5.4)]• Development of Drug-Resistant Bacteria [see Warnings and Precautions (5.5)]6.1 Clinical Trial ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.AVYCAZ was evaluated in two active-controlled Phase 2 clinical trials, one each in cIAI and cUTI, including pyelonephritis. The Phase 2 trials included a total of 169 adult patients treated with AVYCAZ and 169 patients treated with comparators.Complicated Intra-Abdominal InfectionsThe Phase 2 cIAI trial included 101 adult patients treated with AVYCAZ (2 grams ceftazidime and 0.5 grams avibactam) administered intravenously over 30 minutes every 8 hours plus 500 mg metronidazole administered intravenously over 60 minutes every 8 hours and 102 patients treated with meropenem. The median age of patients treated with AVYCAZ was 41 years (range 18 to 79 years). Patients were predominantly male (69.3%) and Caucasian (55.4%). Patients with an estimated baseline CrCL 50 mL/min or less were excluded.Serious adverse reactions occurred in 9/101 (8.9%) of patients receiving AVYCAZ (with metronidazole) and 11/102 (10.8%) of patients receiving meropenem. The most common adverse reactions leading to discontinuation in patients receiving AVYCAZ were skin and subcutaneous tissue disorders (3%).Adverse reactions occurring in 10% or more of patients receiving AVYCAZ were vomiting and nausea. Increased MortalityIn a Phase 3 cIAI trial, death occurred in 2.5% (13/529) of patients who received AVYCAZ/ metronidazole and in 1.5% (8/529) of patients who received meropenem. Among a subgroup of patients with baseline CrCL 30 to 50 mL/min, death occurred in 25.8% (8/31) of patients who received AVYCAZ/metronidazole and in 8.6% (3/35) of patients who received meropenem. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCL 30 to 50 mL/min [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)]. In patients with normal renal function or mild renal impairment (baseline CrCL greater than 50 mL/min), death occurred in 1.0% (5/498) of patients who received AVYCAZ/metronidazole and in 1.0% (5/494) of patients who received meropenem. The causes of death varied and contributing factors included progression of underlying infection, baseline pathogens isolated that were unlikely to respond to the study drug, and delayed surgical intervention.Complicated Urinary Tract Infections, Including PyelonephritisThe Phase 2 cUTI trial included 68 adult patients treated with AVYCAZ (0.5 grams ceftazidime + 0.125 grams avibactam) administered intravenously over 30 minutes every 8 hours and 67 patients treated with imipenemcilastatin (0.5 grams intravenously every 6 hours). The dose of AVYCAZ in this trial was lower than the recommended dose [see Dosage and Administration (2.2)]. Median age of patients treated with AVYCAZ was 47.5 years (range 18 to 85 years). Patients were predominantly female (75%) and Caucasian (58.8%). Patients with CrCL less than 70 mL/min were excluded.Serious adverse reactions occurred in 6/68 (8.8%) of patients receiving AVYCAZ and 2/67 (3.0%) of patients receiving imipenem-cilastatin. Two patients prematurely discontinued treatment with AVYCAZ: one due to an accidental overdose and one due to atrial fibrillation.Adverse reactions occurring in 10% or more of patients receiving AVYCAZ were constipation and anxiety. Table 4 lists adverse reactions occurring in 5% or more of patients receiving AVYCAZ in the Phase 2 cIAI trial or the Phase 2 cUTI trial.Table 4. Incidence of Selected Adverse Drug Reactions Occurring in 5% or more of Patients Receiving AVYCAZ in the Phase 2 cIAI Trial or the Phase 2 cUTI TrialPhase 2 cIAI Trial Phase 2 cUTI TrialAVYCAZ plus Metronidazole a (N = 101) Meropenem b(N = 102)AVYCAZ c(N = 68)Imipenem-Cilastatin d(N = 67)Gastrointestinal disordersVomiting 14% 5% 0% 0%Nausea 10% 6% 2% 5%Constipation 4% 1% 10% 3%Abdominal pain 8% 3% 7% 5%Upper abdominal pain 1% 0% 7% 2%InvestigationsIncreased blood alkaline phosphatase 9% 7% 3% 2%Increased alanine aminotransferase 8% 13% 3% 6%Nervous system disordersDizziness 0% 2% 6% 0%Psychiatric disordersAnxiety 5% 1% 10% 8%a 2.5 grams (2 grams/0.5 grams) intravenously over 30 minutes every 8 hours (with metronidazole 500 mg intravenously every 8 hours)b 1 gram intravenously over 30 minutes every 8 hoursc 0.625 grams (0.5 grams/0.125 grams) intravenously over 30 minutes every 8 hoursd 0.5 grams intravenously over 30 minutes every 6 hoursOther Adverse Reactions of AVYCAZ and CeftazidimeThe following selected adverse reactions were reported in AVYCAZ-treated subjects at a rate of less than 5% in the Phase 2 trials and are not described elsewhere in the labeling.Blood and lymphatic disorders -Eosinophilia, ThrombocytopeniaInvestigations -Increased gamma-glutamyltransferase, Prolonged prothrombin timeMetabolism and nutrition disorders -HypokalemiaRenal and urinary disorders -Acute renal failure, Renal impairmentSkin and subcutaneous tissue disorders -RashAdditionally, adverse reactions reported with ceftazidime alone that were not reported in AVYCAZ clinical trials are listed below:Blood and lymphatic disorders -Agranulocytosis, Hemolytic anemia, Leukopenia, Lymphocytosis,Neutropenia, ThrombocytosisGeneral disorders and administration site conditions -Infusion site inflammation, Injection site hematoma, Injection site phlebitis, Injection site thrombosisHepatobiliary disorders – JaundiceInfections and infestations -CandidiasisInvestigations -Increased blood lactate dehydrogenaseNervous system disorders -Dysgeusia, ParesthesiaRenal and urinary disorders -Tubulointerstitial nephritisReproductive and breast disorders -Vaginal inflammationSkin and subcutaneous tissue disorders -Angioedema, Erythema multiforme, Pruritis, Stevens-Johnson syndrome, Toxic epidermal necrolysis, UrticariaLaboratory ChangesSeroconversion from a negative to a positive direct Coombs’ test result occurred in 6/82 (7.3%) of patients receiving AVYCAZ plus metronidazole and 2/84 (2.4%) of patients receiving meropenem in the cIAI trial. Seroconversion from a negative to a positive direct Coombs’ test result occurred in 1/52 (1.9%) of patients receiving AVYCAZ and 5/60 (8.3%) of patients receiving imipenem cilastatin in the cUTI trial. No adverse reactions representing hemolytic anemia were reported in any treatment group.7 DRUG INTERACTIONS7.1 ProbenecidIn vitro, avibactam is a substrate of OAT1 and OAT3 transporters which might contribute to the active uptake from the blood compartment, and thereby its excretion. As a potent OAT inhibitor, probenecid inhibits OAT uptake of avibactam by 56% to 70% in vitro and, therefore, has the potential to decrease the elimination of avibactam when co-administered. Because a clinical interaction study of AVYCAZ or avibactam alone with probenecid has not been conducted, co-administration of AVYCAZ with probenecid is not recommended [see Clinical Pharmacology (12.3)].7.2 Drug/Laboratory Test InteractionsThe administration of ceftazidime may result in a false-positive reaction for glucose in the urine with certain methods. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category BAnimal reproductive toxicity studies have been conducted with ceftazidime and with avibactam. However, there are no adequate and well-controlled studies of AVYCAZ, ceftazidime, or avibactam in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed.CeftazidimeReproduction studies have been performed in mice and rats at doses up to 40 times the human dose and showed no evidence of harm to the fetus due to ceftazidime.AvibactamAvibactam was not teratogenic in rats or rabbits. In the rat, intravenous studies showed no embryofetal toxicity at doses of 1000 mg/kg/day, approximately 9 times the human dose based on exposure (AUC). In a rat pre-and postnatal study at up to 825 mg/kg/day intravenously (11 times the human exposure based on AUC), there were no effects on pup growth and viability. A dose-related increase in the incidence of renal pelvic and ureter dilatation was observed in female weanling pups that was not associated with pathological changes to renal parenchyma or renal function, with renal pelvic dilatation persisting after female weanling pups became adults. Reproductive studies performed during early pregnancy in rabbits showed no effects on embryofetal development at doses of 100 mg/kg, twice the human exposure (AUC). At higher doses, increased post-implantation loss, lower mean fetal weights, delayed ossification of several bones and other anomalies were observed.8.3 Nursing MothersCeftazidime is excreted in human milk in low concentrations. It is not known whether avibactam is excreted into human milk, although avibactam was shown to be excreted in the milk of rats in a dose dependent manner. Exercise caution if AVYCAZ is to be administered to a nursing woman.8.4 Pediatric UseSafety and effectiveness in patients less than 18 years of age have not been established.8.5 Geriatric UseOf the 169 patients treated with AVYCAZ in the Phase 2 cIAI and cUTI trials, 18 (10.7%) were 65 years of age and older. Because of limited data, differences in outcomes or specific risks with AVYCAZ cannot be ruled out for patients 65 years of age and older.Ceftazidime and avibactam are excreted primarily by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment. Because elderly patients are more likely to have renal impairment, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Healthy elderly subjects had 17% greater exposure relative to healthy young subjects when administered the same single dose of avibactam, which may have been related to decreased renal function in the elderly subjects. Dosage adjustment for elderly patients should be based on renal function [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].8.6 Renal ImpairmentDosage adjustment is required in patients with moderately or severely impaired renal function (CrCL50 mL/min or less). For patients with changing renal function, CrCL should be monitored at least daily and dosage of AVYCAZ adjusted accordingly. Both ceftazidime and avibactam are hemodialyzable; thus, AVYCAZ should be administered after hemodialysis on hemodialysis days [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].10 OVERDOSAGEIn the event of overdose, discontinue AVYCAZ and institute general supportive treatment.Ceftazidime and avibactam can be removed by hemodialysis. In subjects with ESRD administered 1 gram ceftazidime, the mean total recovery in dialysate following a 4-hour hemodialysis session was 55% of the administered dose. In subjects with ESRD administered 100 mg avibactam, the mean total recovery in dialysate following a 4 hour hemodialysis session started 1 hour after dosing was approximately 55% of the dose.No clinical information is available on the use of hemodialysis to treat AVYCAZ overdosage [see Clinical Pharmacology (12.3)].11 DESCRIPTIONAVYCAZ is an antibacterial combination product consisting of the semisynthetic cephalosporin ceftazidime pentahydrate and the beta-lactamase inhibitor avibactam sodium for intravenous administration.CeftazidimeCeftazidime is a semisynthetic, beta-lactam antibacterial drug. It is the pentahydrate of (6R,7R,Z)-7-(2-(2aminothiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetamido)-8-oxo-3-(pyridinium-1-ylmethyl)-5-thia-1。
碘海醇注射液说明书【药品名称】通用名：碘海醇注射液曾用名：商品名：英文名：Iohexol Injection汉语拼音：Diɑnhɑichun Zhusheye本品主要成份与其化学名称为：N，N'-双(2,3-二羟基丙基)-5-[N-(2,3-二羟基丙基)乙酰胺基]-2,4,6-三碘-1,3-苯二甲酰胺。
结构式：分子式：C19H26I3N3O9分子量：821.14【性状】本品为无色至淡黄色的澄明液体。
本品是一种含有三个碘原子的非离子水溶性造影剂，碘含量为46.4％。
它以经过消毒的水溶液为剂型，随时可用，并有不同的碘浓度，分别为每毫升浓度含有140、180、240、300或350mg碘。
【药理毒理】药理学本品为X光与CT检查常用的造影剂，可供血管、椎管和体腔使用。
动物试验结果说明本品对犬肝脏、腹主动脉、CT扫描影像有增强效应。
毒理学犬肾动脉造影时有蛋白尿发生的现象。
【药代动力学】通过静脉注射到体的碘海醇，于24小时几乎全部药物以原形经尿液排出。
注射后一小时，尿液中浓度最高。
无代物产生。
安康志愿者承受静脉注射碘海醇后，其血流动力学参数、临床化学参数与凝结参数与承受注射前的数值差异甚微，其改变无临床意义。
大鼠、兔与犬静脉注射时主要从尿中排出，小局部〔大鼠5％，犬1％〕从粪中排出，尚未发现任何器官吸收的现象，也未在动物中检测到任何代产物。
本品蛋白结合率少于2％或几乎不与蛋白结合。
【适应症】1．血管应用临床应用本品于成人与儿童的尿路造影和心血管造影，以与成人的大脑血管造影，外周与各种动脉造影、静脉造影、数字减影和CT增强扫描。
2．蛛网膜下应用适用于成人与儿童的脊髓造影，以与应用于蛛网膜下注射后进展脑池CT扫描检查。
3．体腔应用适用于各种体腔检查，包括口服。
如关节造影；窥镜逆行胰胆管造影〔ERCP〕；疝囊造影；尿路造影；子宫输卵管造影；涎管造影以与各种使用口服水溶造影剂进展的胃肠道检查等。
【用法用量】1．血管应用剂量参考表应用项目浓度用量注释尿道造影成人儿童＞7kg ＜7kg300mgI/ml或350mgI/ml240mgI/ml或300mgI/ml240mgI/ml或300mgI/ml40～80ml40～80ml4ml/kg3ml/kg3ml/kg2ml/kg〔最高40ml〕在大剂量的尿路造影时可用较高浓度的造影剂动脉造影主动脉与血管造影选择性大脑动脉造300mgI/ml 每次注射30～40ml影主动脉造影四肢动脉造影其他动脉造影静脉造影〔四肢〕300mgI/ml350mgI/ml300mgI/ml或350mgI/ml300mgI/ml240mgI/ml每次注射5～10ml每次注射40～60ml取决于检查的项目20～100ml〔四肢〕心血管造影成人左心室主动脉根注射选择性冠状动脉造影儿童或300mgI/ml350mgI/ml350mgI/ml300mgI/ml或350mgI/ml每次注射30～60ml每次注射4～8ml取决于年龄、体重和病种〔最高8ml/kg〕数字减影动脉注射静脉注射140mgI/ml或240mgI/ml或300mgI/ml300mgI/ml或350mgI/ml每次注射1～15ml每次注射1～15ml每次注射1～15ml每次注射20～60ml每次注射20～60ml取决于造影部位。
