多西他赛说明书
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核准日期:2006年11月修改日期:2008年1月2009年3月多西他赛注射液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:多西他赛注射液商品名称:泰索帝® TAXOTERE®英文名称:DOCETAXEL INJECTION汉语拼音:DUO XI TA SAI ZHUSHEYE【成份】化学名称: (2R,3S)-N-羧基-3-苯基异丝氨酸,N-叔丁基酯,13-酯链上5β-20-环氧-1,2α, 4,7β,10β, 13α-六羟紫杉醇-11-烯-9-酮4-乙酸2-苯甲酸酯三水合物泰索帝®:20mg –每支:20mg注射液为将相当于20mg 多西他赛(无水)的多西他赛三羟化合物,溶解于吐温80中而制成。
泰索帝®:80mg –每支:80mg注射液为将相当于80mg 多西他赛(无水)的多西他赛三羟化合物,溶解于吐温80中而制成。
每毫升泰索帝®注射液含有40 mg无水多西他赛。
泰索帝®溶剂-浓度为13% w/w 的注射用乙醇(以95%计)水溶液。
化学结构式:•3H2O分子式:C43H53NO14•3H2O分子量:本注射剂的全部辅料为:浓溶液:吐温80和氮气;溶剂:95%乙醇和注射用水。
【性状】黄至棕黄色的粘稠液体,配有溶剂。
几乎不溶于水,高脂溶性。
【适应症】多西他赛的适应症如下:乳腺癌1. 适用于局部晚期或转移性乳腺癌的治疗。
2. 泰索帝(多西他赛)联合曲妥珠单抗,用于HER2基因过度表达的转移性乳腺癌患者的治疗,此类患者先期未接受过转移性癌症的化疗。
3. 泰索帝(多西他赛)联合阿霉素及环磷酰胺用于淋巴结阳性的乳腺癌患者的术后辅助化疗。
非小细胞肺癌适用于局部晚期或转移性非小细胞肺癌的治疗,即使是在以顺铂为主的化疗失败后。
【规格】(1):20mg;(2):80mg【用法用量】多西他赛只能用于静脉滴注。
推荐剂量:一般性多西他赛的推荐剂量为每三周75mg/m2滴注一小时。
多西他赛注射液说明书[整理]多西他赛注射液说明书多西他赛注射液说明书查看详细说明书【批准文号】国药准字H20041128【中文名称】多西他赛注射液【产品英文名称】Docetaxel for Injection【生产企业】齐鲁制药有限公司【功效主治】1.适用于局部晚期或转移性乳腺癌的治疗。
2.适用于局部晚期或转移性非小细胞肺癌的治疗,即使以顺铂为主的化疗失败后。
【化学成分】本品主要成份为多西份赛化学名称名{2Ar-[2aα,4β,4aβ,6β,9α(αR*,Βs*),11α,12α,12aα,12bα]}-β-{[(1,1-二甲基乙氧基)羰基]氨基}-α-羟基苯丙酸[12b-乙酰氧苯甲酰氧-2a,3,4,4a,5,6,9,10,11,12,12a,12b-十二氢-4,6,11-三羟基-4a,8,13,13-四甲基-5-氧代-7,11-亚甲基-1H-环癸五烯并[3,4]苯并[1,2-b]氧杂丁环-9-基]酯。
分子式:C43H53NO14分子量:807.88【药理作用】药理作用:多西他赛为紫杉类药物,通过促进微管双聚体装配成微管,同时通过防止去多聚化过程而使微管稳定,阻滞细胞于G2和M期,从而抑制癌细胞的有丝分裂和增殖。
多西他赛的药理作用比紫杉醇强,在细胞内浓度比紫杉醇高3倍,并在细胞内滞留时间长,其对微管亲和力是紫杉醇的2倍;作为微管稳定剂和装配促进剂,活性比紫杉醇大2倍;作为微管解聚抑制剂,活性比紫杉醇大2倍。
在体外抗瘤活性试验中,已证实多西他赛的抗瘤活性是紫杉醇的1.3~12倍。
临床研究表明,对于蒽环类耐药乳腺癌,多西他赛较紫杉醇有更高的有效率。
多西他赛是目前为止蒽环类耐药乳腺癌的二线治疗中最有效的药物;在非小细胞肺癌单药治疗和联合化疗中,多西他赛是最有效的药物之一。
遗传毒性:在CHO-K1细胞染色体畸变试验和小鼠骨髓微核试验中,多西他赛表现出致断裂作用,但在Ames试验和CHO/HGPRT基因突变试验中未见致突变作用。
核准日期:2006年11月修改日期:2008年1月2009年3月多西他赛注射液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:多西他赛注射液商品名称:泰索帝? TAXOTERE?英文名称:DOCETAXEL INJECTION汉语拼音:DUO XI TA SAI ZHUSHEYE【成份】化学名称:(2R,3S)-N-羧基-3-苯基异丝氨酸,N-叔丁基酯,13-酯链上5β-20-环氧-1,2α, 4,7β,10β, 13α-六羟紫杉醇-11-烯-9-酮4-乙酸2-苯甲酸酯三水合物泰索帝?0.5ml:20mg –每支0.5ml:20mg注射液为将相当于20mg 多西他赛(无水)的多西他赛三羟化合物,溶解于0.5ml吐温80中而制成。
泰索帝?2.0ml:80mg –每支2.0ml:80mg注射液为将相当于80mg 多西他赛(无水)的多西他赛三羟化合物,溶解于2.0ml吐温80中而制成。
每毫升泰索帝?注射液含有40 mg无水多西他赛。
泰索帝?溶剂-浓度为13% w/w 的注射用乙醇(以95%计)水溶液。
化学结构式:?3H2O分子式:C43H53NO14?3H2O分子量:861.9本注射剂的全部辅料为:浓溶液:吐温80和氮气;溶剂:95%乙醇和注射用水。
【性状】黄至棕黄色的粘稠液体,配有溶剂。
几乎不溶于水,高脂溶性。
【适应症】多西他赛的适应症如下:乳腺癌1. 适用于局部晚期或转移性乳腺癌的治疗。
2.泰索帝(多西他赛)联合曲妥珠单抗,用于HER2基因过度表达的转移性乳腺癌患者的治疗,此类患者先期未接受过转移性癌症的化疗。
3. 泰索帝(多西他赛)联合阿霉素及环磷酰胺用于淋巴结阳性的乳腺癌患者的术后辅助化疗。
非小细胞肺癌适用于局部晚期或转移性非小细胞肺癌的治疗,即使是在以顺铂为主的化疗失败后。
【规格】(1)0.5ml:20mg;(2)2.0ml:80mg【用法用量】多西他赛只能用于静脉滴注。
推荐剂量:一般性多西他赛的推荐剂量为每三周75mg/m2滴注一小时。
告诫:中毒性牺牲,肝毒性,中性粒细胞缩小,超敏反应,体液潴留之阳早格格创做1.正在具备肝功能非常十分的患者,交受下剂量治疗的患者,以及既往使用过铂类为前提的化疗再交受多西他赛单药100mg/m2治疗的患者中,治疗相关牺牲的爆收率减少.2.对付于出现胆黑素>仄常值(ULN)上限的患者,大概者AST战/大概ALT>1.5ⅹULN合并碱性磷酸酶>2.5ⅹULN的患者,该当防止使用多西他赛.存留胆黑素降下大概转氨酶非常十分伴碱性磷酸酶降下的患者爆收4级的中性粒细胞缩小,收热性中性粒细胞缩小,熏染,宽重的血小板缩小,宽重胃炎,宽重皮肤毒性以及中毒性牺牲的危害更下.仅存留转氨酶>1.5ⅹULN的患者4级的中性粒细胞缩小爆收率更下,但是中毒性牺牲的爆收率不下.果此,正在每个周期启初赋予多西他赛之前应举止胆黑素、AST大概ALT以及碱性磷酸酶查看.3.中性粒细胞计数<1500 cells/ mm3的患者应防止赋予多西他赛.为了监测中性粒细胞缩小的爆收免得其死少至宽重程度引导熏染,应付于所有交受多西他赛治疗的患者举止一再的血细胞计数.4.正在交受了3天的天塞米紧预治疗的患者,报导了宽重过敏反应,表示为齐身性皮疹/黑斑,矮血压战/大概支气管痉挛,大概非常罕睹的致命性过敏症.一朝爆收,应坐时停药并赋予适合的救治.既往有对付多西他赛大概其余含吐温80制剂宽重过敏史的患者应防止使用.5. 正在交受了3天的天塞米紧预治疗的患者中有6.5%(6/92)报导宽重的体液潴留.表示为以下一种大概多种事变:不克不迭耐受的中周火肿,齐身性黑斑,心净压塞,需要主动引流的胸腔积液,呼吸艰易,明隐的背部伸展(果为背火).【药品称呼】通用称呼:多西他赛注射液商品称呼:艾素®英文称呼:Docetaxel Injection汉语拼音:Duoxitasai Zhusheye【成份】本品主要成份为多西他赛,其化教称呼为[2aR(2aα,4β,4aβ,6β,9α,(αR′,βS′),11α,12α,12aα,12bα)]β[[(1,1二甲基乙氧基)羰基]氨基]α羰基苯丙酸[12b乙酰氧12苯甲酰氧2a,3,4,4a,5,6,9,10, 11,12,12a,12b十二氢4,6,11三羟基4a,8,13,13四甲基5氧代7,11亚甲基1H环癸五烯并[3,4]苯并[1,2b]氧纯丁环9基]酯.分子式:C43H53NO14本品辅料为20%枸橼酸溶液战散山梨酯80.【性状】本品为浓黄色至黄色澄明的黏稀液体.【适应症】乳腺癌:1.适用于局部早期大概变化性乳腺癌的治疗;2.多西他赛共同直妥珠单抗用于HER2基果过分表黑的变化性乳腺癌患者的治疗,此类患者先期已交受过变化性乳腺癌症的化疗;3.多西他赛共同阿霉素及环磷酰胺用于淋凑趣阳性的乳腺癌患者的术后辅帮化疗.非小细胞肺癌:适用于局部早期大概变化性非小细胞肺癌的治疗,纵然是正在以顺铂为主的化疗波合后.前列腺癌:多西他赛共同强的紧大概强的紧龙用于治疗激素易治性变化性前列腺癌.【规格】【用法用量】多西他赛只可用于静脉滴注.推荐剂量:普遍性多西他赛的推荐剂量为每3周75 mg/m2,滴注1小时.为减少体液潴留,除有禁忌中,所有病人正在交受多西他赛治疗前均必须预服药物,此类药物只可包罗心服糖皮量激素类,如天塞米紧,正在多西他赛滴注1天前服用,每日16mg(比圆:每日2次,屡屡8 mg),持绝3天.惟有医死才搞建改治疗规划.多西他赛不克不迭用于中性粒细胞数目矮于1500/mm3的病人.多西他赛治疗功夫,如果病人爆收收热性中性粒细胞缩小且中性粒细胞数目持绝1周以上矮于500/mm3,出现宽重大概蓄积性皮肤反应大概中周神经症状,多西他赛的剂量应酌情递减.治疗前列腺癌时,共时赋予强的紧大概强的紧龙,推荐化疗前用药剂量及规划为:患者正在交受多西他赛治疗前12小时,3小时及1小时,心服天塞米紧8mg(睹[注意事项]).防止性使用粒细胞集降刺激果子(GCSF)以减少药物血液毒性爆收的危害.乳腺癌正在不妨脚术的淋凑趣阳性的乳腺癌辅帮化疗中,推荐剂量为:赋予阿霉素50mg/m2及环磷酰胺500mg/m2,1小时后,赋予多西他赛75mg/m2,每3周1次,举止6个周期(睹治疗中安排剂量).治疗局部早期大概变化性乳腺癌患者时,多西他赛简单用药的推荐剂量为100mg/m2.一线用药时,多西他赛75mg/m2共同阿霉素50mg/m2(睹仄安处置提议).与直妥珠单抗共同用药时,多西他赛推荐剂量为:100mg/m2,每3周1次,直妥珠单抗每周1次.正在一项关键临床钻研中,多西他赛尾次静脉给药应于直妥珠单抗第1次用药后1天.如果患者对付前次直妥珠单抗剂量耐受良佳,多西他赛以去的用药应紧随直妥珠单抗静脉输注之后给药.直妥珠单抗的用法及用量睹其产品证明书籍.非小细胞肺癌治疗非小细胞肺癌时,对付于前期已经治疗的患者治疗非小细胞肺癌推荐剂量为多西他赛75mg/m2,并坐时赋予顺铂75mg/m2静脉输注3060分钟.对付于前期铂类治疗波合的患者,多西他赛推荐剂量为简单用药75mg/m2.前列腺癌推荐剂量为多西他赛75 mg/m2,每3周一疗程,连绝心服强的紧大概强的紧龙每日2次,屡屡5mg.治疗中安排剂量:普遍性:多西他赛应用于中性粒细胞计数≥1500/mm3的患者.多西他赛治疗功夫,如果患者爆收收热性中性粒细胞缩小,且中性粒细胞数目<500/mm3持绝1周以上,出现重度大概蓄积性皮肤反应大概重度中周神经症状,多西他赛的剂量应由100mg/m2减至75mg/m2,及/大概由75mg/m2减至60mg/m2.若患者正在60mg/m2剂量时仍旧出现以上症状,应停止治疗.乳腺癌辅帮化疗正在关键的临床钻研中,交受乳腺癌辅帮化疗的患者,出现并收性中性粒细胞缩小(包罗中性粒细胞缩小爆收时间延少,收热性中性粒细胞缩小,大概熏染),正在所有以去的用药周期中,推荐防止使用GCSF(如:第4天至第11天).若患者持绝出现以上反应,应脆持使用GCSF,并将多西他赛剂量缩小至60mg/m2.然而,临床考查中中性粒细胞缩小大概较早出现.果此应权衡患者中性粒细胞缩小的伤害及目前使用的推荐剂量而使用GCSF.如果已使用GCSF,多西他赛剂量应由75减至60mg/m2,爆收3级大概4级心腔炎的患者应将剂量减至60mg/m2.共同顺铂治疗对付于起初剂量为多西他赛75mg/m2共同顺铂的患者,且前期疗程中曾出现血小板最矮值<25000/mm3,大概曾出现收热性中性粒细胞缩小,大概曾出现宽重的非血液教毒性,下一疗程的多西他赛剂量应减为65mg/m2.顺铂剂量安排,睹其产品介绍.对付于直妥珠单抗剂量安排,睹其产品证明书籍.特殊人群:肝功能有益伤的患者:根据100mg/m2多西他赛单药治疗的药代能源教数据,ALT战/大概AST超出仄常值上限1.5倍,共时碱性磷酸酶超出仄常值上限2.5倍的患者,多西他赛的推荐剂量为75mg/m2(睹【注意事项】及【药代能源教】).对付于血浑胆黑素超出仄常值上限战/大概ALT及AST超出仄常值上限3.5倍并伴随碱性磷酸酶超出仄常值上限6倍的患者,除非有庄重的使用指征,可则不该使用,也无减量使用提议.无肝功能有益伤患者交受多西他赛共同治疗的数据.临用前将多西他赛所对付应的溶剂局部吸进对付应的溶液中,沉沉振摇混同匀称,将混同后的药瓶室温搁置5分钟,而后查看溶液是可匀称澄明,根据估计病人所用药量,用注射器吸进混同液,注进5%葡萄糖注射液大概0.9%氯化钠注射液的注射瓶大概注射袋中,沉沉摇动,混同匀称,最后浓度不超出0.9mg/ml.【不良反应】从以下单药及共同用药的患者中,支集了与多西他赛很大概大概大概相关的不良反应:1312名患者交受100mg/m2,以及121名患者交受75mg/m2多西他赛单药治疗.258名患者交受75mg/m2多西他赛共同阿霉素50mg/m2治疗.406名患者交受75mg/m2多西他赛共同顺铂75mg/m2治疗. 92名患者交受多西他赛共同直妥珠单抗治疗.332名患者交受多西他赛共同强的紧大概强的紧龙治疗. 744名患者交受多西他赛与阿霉素及环磷酰胺共同治疗.主要根据NCI通用毒性尺度(3级=G3,34级=G3/4;4级=G4)及COSTART术语去形貌反应典型及宽重程度.部分表格中“重度”系沿用较早完毕的临床钻研本初资料中的形貌,是根据钻研者的主瞅判决,其定义为3级战/大概34级的不良事变.频度定义为:非经罕睹(>1/10),罕睹(>1/100,<1/10);不罕睹(>1/1000,<1/100);少睹(>1/10000,<1/1000);罕睹(<1/10000).正在每个频度组按宽重程度由下到矮的程序列出不良反应.多西他赛单药治疗最罕睹报告的不良反应为:中性粒细胞缩小[可顺转且不蓄积(睹【用法用量】及【注意事项】);缩小至最矮面的中位时间为7天,爆收重度中性粒细胞缩小(<500/mm3)的中位持绝时间为7天],贫血、脱收、恶心、呕吐、心腔炎、背泻战健壮.当多西他赛与其余化疗药物共同使用时可减少多西他赛不良事变的宽重程度.正在共同直妥珠单抗治疗中,列出≥10%的不良事变(所有级别)报告.正在直妥珠单抗共同组对付比多西他赛单药组,SAE爆收率(40%比31%)及4级AE(34%比23%)的爆收率删下.多西他赛罕睹不良反应如下:免疫系统非常十分过敏反应大多爆收正在多西他赛启初输注的最初几分钟内,常常是沉度至中度的.最常报告的症状是伴大概不伴随瘙痒的黑斑及皮疹,胸闷,背痛,呼吸艰易及药物性收热大概热颤.重度反应包罗,矮血压战/大概支气管痉挛大概齐身皮疹/黑斑,停止输注并举止对付症治疗后即可回复(睹【注意事项】).神经系统非常十分当出现重度中周神经毒性症状时,应缩小多西他赛的剂量(睹【用法用量】及【注意事项】).沉至中度感觉神经症状包罗感觉非常十分,感觉障碍大概痛痛包罗烧灼痛.疏通神经事变主要表示为无力.皮肤及皮下构制非常十分瞅察到常常是沉至中度可顺转的皮肤反应,常表示为皮疹,包罗主要睹于脚、足(包罗宽重的脚足概括征),大概爆收正在臀部,脸部及胸部的局部皮疹,常伴随搔痒.皮疹多爆收于输注多西他赛后一周内.较少睹的重度症状如:极少引导搞扰大概中断多西他赛治疗的皮疹既而脱皮的报导(睹【用法用量】及【注意事项】).重度的指甲病变,以色素重血液及淋巴系统非常十分少睹:出血事变合并G3/4血小板缩小症.神经系统非常十分数据标明多西他赛100mg/m2单药治疗后,35.3%具备神经毒反应患者是可顺转的.正在3个月之内自止回复.心净非常十分不罕睹:心衰(0.5%).胃肠讲不适不罕睹:食讲炎(1%,重度0.4%).皮肤及皮下构制非常十分非常少睹:一例脱收,正在钻研中断时已顺转.73%皮肤反应正在21天之内顺转.齐身及注射部位非常十分至治疗中断的中位乏积剂量为超出1000mg/m2,至体液潴留回复的中位时间为16.4周(范畴042周).爆收中度及重度体液潴留的起初时间,防止用药患者(中位乏计剂量:818.9 mg/m2)比已防止用药患者(中位乏积剂量:489.7mg/m2)延总之,交受多西他赛单药治疗的患者与交受多西他赛共同阿霉素治疗的患者相比,爆收的不良反应是相似的.多西他赛75mg/m2共同顺铂:临床上要害的治疗相关性不良事变隐现如下.下表中的仄安数据,去自于一项随机,启搁,3组规划对付照的临床考查.正在该临床考查中,807例不克不迭切除的IIIB大概者IV 期非小细胞肺癌患者,交受了多西他赛的共同治疗,那些患者往日不交受过化疗.采与好国的国坐癌症钻研所制订的罕睹毒性尺度,对付那些不良反应举止了形貌.除血液系统与交受多西他赛单药治疗相比,交受共同治疗的患者中,宽重不良事变(40%比31%)战4度不良事变(34%比23%)的爆收率较下.血液及淋巴系统非常十分非经罕睹:正在交受多西他赛共同直妥珠单抗治疗患者中,比多西他赛单药治疗的血液教毒性减少(用NCICTC尺度,G3/4中性粒细胞缩小,32%比22%).需要注意的是该反应大概被矮估,果为单用多西他赛100mg/m2时的最矮齐血计数的考验截止隐现,97%患者爆收中性粒细胞缩小症,其中76%为4级.收热性中性粒细胞缩小/中性粒细胞缩小性败血症的爆收率也正在多西他赛共同直妥珠单抗治疗组患者中较下(23%比17%于多西他赛单药治疗组).心净非常十分正在交受多西他赛共同直妥珠单抗组中报告有2.2%的患者爆收症状性心衰,而多西他赛单药组为0%.正在交受多西他另一相关的数据根源于54例交受多西他赛(75mg/m2,每3周一疗程)共同强的紧(5mg,心服,每日2次)治疗前列腺癌的患者(华夏备案钻研),该截止与TAX327类似,已创制新交受TAC规划治疗的744例患者中,与随访期内13.8%相比,治疗期内36.7%的患者出现了宽重不良事变.正在1%的治疗周期中,果为患者出现血液系统的毒性反应,而缩小了多西他赛的剂量.6%的患者果为出现不良事变而停止了多西他赛的治疗;非熏染性战非过敏性收热,是最为罕睹的停药本果.有2例患者正在他们交受终尾一次治疗后的30天内牺牲;其中1例患者的牺牲被认为与钻研药物多西他赛有关.收热战熏染交受TAC规划治疗的患者钻研期内36.6%患者出现了非熏染性收热,29.2%(G3/4:3.2%)的患者出现了熏染.钻研期内不出现果为败血症而引起的牺牲.胃肠讲不良事变除了上头表格中所反应的胃肠讲不良事变除中,据报导,另有7例患者出现了结肠炎/肠炎/大肠脱孔.治疗期内,其中2例患者需要停药;不果为那些事变而引导的牺牲.心血管非常十分钻研期内报告有下述治疗中出现的心血管事变:心律得常,所有等第 (6.2%),矮血压,所有等第(1.9%)战CHF(3.5%).钻研期内TAC组中有26名患者出现CHF,大部分病例正在随访期内报告.2名TAC患者由CHF引导牺牲,4名FAC患者由CHF引导牺牲.TAC组中第1年CHF 危害较下.慢性髓细胞样黑血病(AML)/骨髓非常十分删死概括征创制:正在744例交受多西他赛与阿霉素战环磷酰胺的患者中,有3例患者(0.4%)爆收了慢性髓细胞样黑血病(AML),正在736例交受氟尿嘧啶与阿霉素战环磷酰胺共同治疗的患者中,有1例患者(0.1%)爆收了慢性髓细胞样黑血病(AML).随访期内有一名TAC患者由于AML牺牲.其余持绝存留的反应TAC患者中随访功夫持绝的最罕睹不良事变为脱收(92.3%),健壮(31.7%)战关经(27.2%).正在那些随访功夫持绝的不良事变中>1%的患者大部分事变回复;然而,TAC 患者中关经(59.9%)战淋巴火肿(54.5%)任然继承.上市后体味良性及恶性肿瘤(包罗囊肿战息肉)当与其余化疗药物战/大概搁疗共同应用时,罕睹与多西他赛相关的慢性骨髓性黑血病战骨髓删死非常十分概括征.血液及淋巴系统非常十分骨髓压制及其余血液教不良反应有所报导.可睹报导弥集性血管内凝血(DIC)常伴随败血症大概多器官衰竭.免疫系统非常十分少睹有报导过敏性戚克病例,极罕睹正在已经交受了化疗前用药处理的患者中引导致命的截止.神经系统非常十分多西他赛治疗后少睹惊厥大概姑且性意识丧得病例.输注药物时偶我出现此反应.眼部非常十分罕睹报导一过性的视觉障碍(闪烁,闪光,盲面),特天正在药物静脉输注时,并伴随过敏反应.停止输注后可顺转.特天是正在共时交受其余抗癌药物的患者中,少睹报导伴大概不伴随结膜炎的堕泪,罕睹报导由于泪管阻塞引导的多泪.耳及迷路非常十分少睹报导耳毒性、听力益坏战/大概听觉丧得,包罗其余耳毒性药物制成的病例.心净非常十分少睹心肌梗塞报导.血管非常十分较少报导静脉栓塞事变.呼吸,胸腔及纵隔非常十分少睹报导慢性呼吸窘迫概括征,间量性肺炎及肺纤维化.少睹报导合并搁射性化疗患者出现搁射性肺炎.胃肠讲不适少睹胃肠讲事变如胃肠讲脱孔,缺血性肠炎,肠炎及中性粒细胞缩小性小肠结肠炎引起的脱火.少睹肠梗阻及肠绞痛报导.肝胆系统非常十分罕睹肝炎报导,偶我对付先前存留肝净徐患的患者是致命的.皮肤及皮下构制非常十分罕睹报导多西他赛伴伴的皮肤型黑斑狼疮战大疱状皮疹如多形性黑斑大概StevensJohnson概括征,中毒性表皮坏死紧懈症战硬皮病样的改变.有些病例中伴伴果素大概引导此类事变死少.正在某些情况下,其余共同果素比圆:伴伴熏染,伴伴用药战潜正在徐病大概也效率于那些非常十分的死少历程.齐身及注射部位非常十分少睹报导搁射回忆局里.体液潴留不伴随慢性少尿大概矮血压.少睹报导脱火及肺火肿爆收.肾净战泌尿系统不良反应肾功能不齐战肾衰可睹报导,爆收那些不良反应的病例大多为共时交受了其余肾净毒性药物.【禁忌】对付本活性物量大概所有一种赋形剂过敏.多西他赛不该用于基线中性粒细胞计数<1500/mm3的患者.多西他赛不允许用于妊娠妇女.由于不相关数据,多西他赛不该用于肝功能有宽重益伤的患者(睹【注意事项】及【用法用量】).当其余药物与多西他赛共同用药时,应按照其余药物的禁忌.【注意事项】多西他赛必须正在有癌症化疗药物应用体味的医死指挥下使用.由于大概爆收较宽重的过敏反应,应具备相映的慢救办法,注射功夫提议稀切监测主要功能指标.治疗乳腺癌及非小细胞癌时,除非有禁忌证,患者正在交受多西他赛治疗前需防止用药以减少体液潴留的爆收率战宽重程度及减少过敏反应的宽重程度,防止用药包罗心服皮量类固醇,如天塞米紧每天16mg (8mg BID),正在多西他赛注射一天前启初服用,持绝3天(睹【用法用量】).治疗前列腺癌时,患者正在交受多西他赛治疗前12小时,3小时战1小时,心服天塞米紧8mg(睹【用法用量】).血液教中性粒细胞缩小是多西他赛治疗最罕睹的不良反应.中性粒细胞缩小至最矮面的中位时间为7天,但是此隔断正在多次治疗的患者中可支缩.对付所有多西他赛治疗的患者应时常举止齐血细胞计数监测.当患者的中性粒细胞计数回复至≥1500/mm3以上时才搞交受多西他赛的治疗(睹【用法用量】).多西他赛治疗功夫如果爆收重度的中性粒细胞缩小(<500/mm3并持绝7天大概以上),推荐正在下一个疗程中缩小剂量大概采与适合的对付症处理(睹【用法用量】).过敏反应应稀切注意患者的过敏反应,特天是正在第1次及第2次输注时.正在多西他赛启初输注的最初几分钟内有大概爆收过敏反应,果此,应准备佳治疗矮血压及支气管痉挛的设备.已有报导,正在交受过化疗前用药的患者中,也会爆收重度过敏反应,如齐身皮疹/黑斑,重度矮血压,支气管痉挛大概罕睹的致命的过敏性反应,爆收过敏反应需坐时停止输注并举止对付症治疗.对付已爆收重度过敏反应的患者不克不迭再次应用多西他赛.皮肤反应瞅察到肢体终端(脚掌及足趾)爆收局部皮肤黑斑伴火肿既而脱皮局里.有报导果重度症状如皮疹既而脱皮引导搞扰大概中断多西他赛治疗(睹【用法用量】).体液潴留患者大概爆收重度体液潴留,应稀切注意如胸膜积液,心包积液及背火的爆收.肝功能有益伤的患者使用多西他赛单药治疗100mg/m2剂量的患者,如果血浑氨基变化酶(ALT战/大概AST)超出1.5倍仄常值上限,共时伴随碱性磷酸酶超出2.5倍仄常值上限,爆收重度不良反应的伤害性降下,如果毒性牺牲,包罗致死的脓毒症战胃肠讲出血,收热性中性粒细胞缩小症,熏染,血小板缩小症,心腔炎战乏力.果此,那些肝功能化验值(LFTs)降下的患者,其多西他赛的推荐剂量为75mg/m2,而且正在基线战每个周期前要检测肝功能(LFTs)(睹【用法用量】).当患者血浑胆黑素>仄常值上限且/大概ALT及AST>3.5倍仄常值上限伴血浑碱性磷酸酶>6倍仄常值上限,除非有庄重的使用指证,可则不该使用,也无减量使用提议.姑且尚无宽重肝功能益伤患者使用多西他赛共同用药的资料.肾功能有益伤的患者姑且尚无宽重肾功能益伤患者使用多西他赛的资料.神经系统当瞅察到重度中周神经毒性症状时,应缩小多西他赛的剂量(睹【用法用量】).心净毒性正在交受多西他赛共同直妥珠单抗治疗的患者中,特天是正在含蒽环类药物治疗(阿霉素大概表阿霉素)后,瞅察到心力衰竭爆收,大概是中度至重度的,并大概引导牺牲(睹【不良反应】).当患者准备交受多西他赛共同直妥珠单抗治疗时,应付于其前提心净情景举止评估.正在治疗功夫应继承监测心净功能(如:每3个月),有帮于确诊患者是可爆收心净机能混治.更多的确定睹直妥珠单抗证明书籍.其余正在治疗功夫及治疗中断后起码三个月内应采与躲孕步伐.乳腺癌辅帮化疗时的其余注意事项并收中性粒细胞缩小并收中性粒细胞缩小的患者(包罗中性粒细胞缩小爆收时间延少,收热性中性粒细胞缩小,大概熏染),应试虑使用GCSF及缩小剂量(睹【用法用量】).胃肠讲反应早期出现的症状包罗:伴大概不伴中性粒细胞缩小的背痛及胃肠讲敏感,收热,背泻.早期大概爆收宽重胃肠讲毒性反应,应赶快诊疗及治疗.充血性心力衰竭正在治疗及随访功夫,应付于患者充血性心衰的症状举止监测.正在交受TAC治疗的淋凑趣阳性乳腺癌患者中瞅察到治疗后第一年的CHF较下.黑血病交受多西他赛,阿霉素及环磷酰胺(TAC)的患者中,需要对付爆收早收型脊髓收育不良大概骨髓性黑血病的伤害性举止血液教随访.4个及以上淋凑趣阳性的患者正在4个及以上淋凑趣阳性患者中瞅察到的无病存正在期(DFS)战总存正在(OS)的获益已达到统计教隐著性,果此TAC正在4个及以上淋凑趣阳性患者中的正支益/危害比正在最后分解时已得到真足证据.老年一项正在尾次交受化疗的非小细胞肺癌患者中举止的钻研(TAX 326),交受多西他赛战顺铂治疗的患者中,有148例的年龄大于等于65岁,15例患者的年龄大于等于75岁;年龄较大的患者与年少患者举止比较后,创制二者正在治疗效验上不好别.交受多西他赛战顺铂治疗的老年患者与交受少秋瑞滨战顺铂的老年患者相比,前者背泻战3/4度神经毒性的爆收率有删加的趋势.正在一项333名前列腺癌患者交受多西他赛3周治疗规划的钻研中,209名患者为65岁大概以上,68名患者75岁以上.正在老年患者战年少患者中已隐现疗效好别.正在交受多西他赛3周治疗规划的患者中,与小于65岁的患者相比,65岁大概以上患者的贫血、熏染、指甲改变、厌食战体重减少的爆收率删下10%以上.仄安处置提议:细胞毒类药物应按以下指挥支配:·药物配制只可由受过训练的人员正在指定天面支配.·多西他赛为一抗癌药物,当与其余有毒化合物共时使用时,正在处理及配制药液时要格中留神.·处事台表面应覆以可拾弃的塑料覆膜纸.·脱戴防备脚套及衣服.。
多西他赛别名:多西紫杉、多西紫杉醇、泰索帝、艾素、多帕菲、多帕菲、多烯紫杉醇、紫杉特尔、Taxotere;[适应症]:用于治疗晚期乳腺癌、非小细胞肺癌。
也有报道用于治疗头颈部癌、小细胞肺癌、胃癌、卵巢癌等肿瘤。
;[药理作用]:本品为细胞周期特异性抗肿瘤药,可特异性作用于M期细胞。
本品可促进小管聚合成为稳定的微管,并抑制其解聚,以显著减少小管的数量,也可通过破坏微管的网状结构,抑制细胞有丝分裂,从而达到抗肿瘤的目的。
[注意事项]:1.肝功能不全者、严重衰弱者、严重水潴留者、严重感觉神经疾病患者慎用。
2.本品用于儿童的安全性尚未确定。
3.尚不清楚本品能否分泌人乳汁,哺乳期妇女的用药安全性尚未确定,用药前应停止哺乳。
4.配制本品时,粉针剂应先以指定溶剂溶解,再以生理盐水或5%葡萄糖注射液稀释后使用(配制后浓度不超过0.74mg/ml)。
工作台表面应覆盖可丢弃的塑料薄膜,操作者应穿戴防护衣服及手套。
若皮肤接触了药液,应立即用肥皂和水彻底清洗;如眼睛或黏膜接触了药液,立即用水彻底清洗。
配制好的药液应立即使用。
5.在使用本品的最初几分钟内,可能发生过敏反应,应具备相应的急救设施。
为预防液体潴留和过敏反应,推荐在用药前1天开始口服地塞米松(每天16mg,连用4~5天)。
6.如用药后仅发生面部潮红或局部皮肤反应,则不需要停止治疗。
如发生严重过敏反应(血压下降超过2.67kPa、支气管痉挛或全身皮疹/红斑),则需立即停止给药,并给予对症治疗。
已发生过严重不良反应者,不能再次使用本品。
7.使用本品治疗时如出现严重的周围神经病变、严重的或累积性皮肤反应,或严重的中性粒细胞减少(低于0.5×109/L,并持续7天或7天以上),建议下1个疗程减量给药。
8.当血胆红素高于正常值上限、氨基转移酶高于正常上限1.5倍、ALP高于正常上限2.5倍时,应停用本品治疗。
9.药物过量时,可能表现为中性粒细胞减少、皮肤反应和感觉异常。
核准日期:2006年11月 修改日期:2008年1月 2009年3月多西他赛注射液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:多西他赛注射液商品名称:泰索帝® TAXOTERE ® 英文名称:DOCETAXEL INJECTION 汉语拼音:DUO XI TA SAI ZHUSHEYE【成份】化学名称: (2R,3S)-N-羧基-3-苯基异丝氨酸,N-叔丁基酯,13-酯链上5β-20-环氧 -1,2α, 4,7β,10β, 13α-六羟紫杉醇-11-烯-9-酮4-乙酸2-苯甲酸酯三水合物泰索帝® 0.5ml:20mg –每支0.5ml:20mg 注射液为将相当于20mg 多西他赛(无水)的多西他赛三羟化合物,溶解于0.5ml 吐温80中而制成。
泰索帝® 2.0ml:80mg –每支2.0ml:80mg 注射液为将相当于80mg 多西他赛(无水)的多西他赛三羟化合物,溶解于2.0ml 吐温80中而制成。
每毫升泰索帝®注射液含有40 mg 无水多西他赛。
泰索帝®溶剂-浓度为13% w/w 的注射用乙醇(以95%计)水溶液。
化学结构式:•3H 2O分子式:C 43H 53NO 14•3H 2O 分子量:861.9本注射剂的全部辅料为:浓溶液:吐温80和氮气;溶剂:95%乙醇和注射用水。
【性状】黄至棕黄色的粘稠液体,配有溶剂。
几乎不溶于水,高脂溶性。
【适应症】多西他赛的适应症如下:乳腺癌1. 适用于局部晚期或转移性乳腺癌的治疗。
2.泰索帝(多西他赛)联合曲妥珠单抗,用于HER2基因过度表达的转移性乳腺癌患者的治疗,此类患者先期未接受过转移性癌症的化疗。
3. 泰索帝(多西他赛)联合阿霉素及环磷酰胺用于淋巴结阳性的乳腺癌患者的术后辅助化疗。
非小细胞肺癌适用于局部晚期或转移性非小细胞肺癌的治疗,即使是在以顺铂为主的化疗失败后。
【规格】(1)0.5ml:20mg;(2)2.0ml:80mg【用法用量】多西他赛只能用于静脉滴注。
泰索帝最新版说明书核准日期:2006年11月修改日期:2008年1月2009年3月多西他赛注射液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:多西他赛注射液商品名称:泰索帝® TAXOTERE®英文名称:DOCETAXEL INJECTION汉语拼音:DUO XI TA SAI ZHUSHEYE【成份】化学名称:(2R,3S)-N-羧基-3-苯基异丝氨酸,N-叔丁基酯,13-酯链上5β-20-环氧-1,2α, 4,7β,10β, 13α-六羟紫杉醇-11-烯-9-酮4-乙酸2-苯甲酸酯三水合物泰索帝® 0.5ml:20mg –每支0.5ml:20mg注射液为将相当于20mg 多西他赛(无水)的多西他赛三羟化合物,溶解于0.5ml吐温80中而制成。
泰索帝® 2.0ml:80mg –每支2.0ml:80mg注射液为将相当于80mg 多西他赛(无水)的多西他赛三羟化合物,溶解于2.0ml吐温80中而制成。
每毫升泰索帝®注射液含有40 mg无水多西他赛。
泰索帝®溶剂-浓度为13% w/w 的注射用乙醇(以95%计)水溶液。
化学结构式:•3H2O分子式:C43H53NO14•3H2O分子量:861.9本注射剂的全部辅料为:浓溶液:吐温80和氮气;溶剂:95%乙醇和注射用水。
【性状】黄至棕黄色的粘稠液体,配有溶剂。
几乎不溶于水,高脂溶性。
【适应症】多西他赛的适应症如下:乳腺癌1. 适用于局部晚期或转移性乳腺癌的治疗。
2.泰索帝(多西他赛)联合曲妥珠单抗,用于HER2基因过度表达的转移性乳腺癌患者的治疗,此类患者先期未接受过转移性癌症的化疗。
3. 泰索帝(多西他赛)联合阿霉素及环磷酰胺用于淋巴结阳性的乳腺癌患者的术后辅助化疗。
非小细胞肺癌适用于局部晚期或转移性非小细胞肺癌的治疗,即使是在以顺铂为主的化疗失败后。
【规格】(1)0.5ml:20mg;(2)2.0ml:80mg【用法用量】多西他赛只能用于静脉滴注。
多西他赛化疗方案引言多西他赛(Docetaxel)是一种广谱抗肿瘤药物,常用于治疗多种恶性肿瘤,如乳腺癌、前列腺癌、食管癌等。
本文将详细介绍多西他赛化疗方案的使用方法、副作用及护理措施,以帮助临床医生和护士提供更有效的化疗服务。
1. 多西他赛化疗方案的基本信息•药物名称:多西他赛(Docetaxel)•剂型:冻干粉剂•给药途径:静脉注射•治疗领域:乳腺癌、前列腺癌、食管癌、头颈部癌等2. 多西他赛化疗方案的使用方法多西他赛化疗方案通常采用静脉注射的方式进行给药。
具体使用方法如下:•异常用法:将多西他赛与生理盐水溶液配制成预设浓度的注射液。
•用法用量:每次剂量根据患者体表面积、肿瘤类型和临床反应进行调整。
•给药速度:通常以稀释后的40~60分钟静滴给药。
•给药间隔:一般为3周一次,连续1-6个周期。
3. 多西他赛化疗方案的副作用多西他赛化疗方案可能引起一系列副作用,包括但不限于:•骨髓抑制:包括白细胞减少、贫血和血小板减少等。
这些副作用可能导致患者免疫功能下降、易感染、出血等问题。
•消化系统反应:包括恶心、呕吐、腹泻和食欲减退等。
•神经系统反应:多西他赛可能引起周围神经病变,导致手脚发麻、感觉异常等。
•皮肤反应:多西他赛可能导致头发脱落、皮肤暗红等。
4. 多西他赛化疗方案的护理措施为了降低多西他赛化疗方案的副作用,以下是一些护理措施的建议:•骨髓抑制:护士应定期监测患者的血常规指标,及时调整治疗剂量和给予生长因子支持治疗。
•消化系统反应:护士可以建议患者采取分食多餐、少量多餐的饮食方式,避免食物刺激和油腻食物。
•神经系统反应:护士可以提醒患者避免使用过热的水来洗澡和洗手,并注意脚底的保暖。
•皮肤反应:护士可以提醒患者保持皮肤清洁、不使用刺激性化妆品,并及时就医处理头发脱落问题。
结论多西他赛化疗方案作为一种常用的抗肿瘤药物,对治疗多种恶性肿瘤具有重要作用。
然而,患者在接受多西他赛化疗方案时可能出现一系列副作用,这要求医护人员密切监测患者的病情,并提供科学合理的护理策略。
警告:中毒性死亡,肝毒性,中性粒细胞减少,超敏反应,体液潴留1.在具有肝功能异常的患者,接受高剂量治疗的患者,以及既往使用过铂类为基础的化疗再接受多西他赛单药100mg/m2治疗的患者中,治疗相关死亡的发生率增加。
2.对于出现胆红素>正常值(ULN)上限的患者,或者AST和/或ALT>ⅹULN合并碱性磷酸酶>ⅹULN的患者,应该避免使用多西他赛。
存在胆红素升高或转氨酶异常伴碱性磷酸酶升高的患者发生4级的中性粒细胞减少,发热性中性粒细胞减少,感染,严重的血小板减少,严重胃炎,严重皮肤毒性以及中毒性死亡的风险更高。
仅存在转氨酶>ⅹULN的患者4级的中性粒细胞减少发生率更高,但中毒性死亡的发生率不高。
因此,在每个周期开始给予多西他赛之前应进行胆红素、AST或ALT以及碱性磷酸酶检查。
3.中性粒细胞计数<1500 cells/ mm3的患者应避免给予多西他赛。
为了监测中性粒细胞减少的发生以免其发展至严重程度导致感染,应对所有接受多西他赛治疗的患者进行频繁的血细胞计数。
4.在接受了3天的地塞米松预治疗的患者,报道了严重过敏反应,表现为全身性皮疹/红斑,低血压和/或支气管痉挛,或非常罕见的致命性过敏症。
一旦发生,应立即停药并给予适当的救治。
既往有对多西他赛或其他含吐温-80制剂严重过敏史的患者应避免使用。
5. 在接受了3天的地塞米松预治疗的患者中有%(6/92)报道严重的体液潴留。
表现为以下一种或多种事件:不能耐受的外周水肿,全身性红斑,心脏压塞,需要积极引流的胸腔积液,呼吸困难,明显的腹部膨胀(因为腹水)。
【药品名称】通用名称:多西他赛注射液商品名称:艾素®英文名称:Docetaxel Injection汉语拼音:Duoxitasai Zhusheye【成份】本品主要成份为多西他赛,其化学名称为[2aR-(2aα,4β,4aβ,6β,9α,(αR′,βS′),11α,12α,12a α,12bα)]-β-[[(1,1-二甲基乙氧基)羰基]氨基]-α-羰基苯丙酸[12b-乙酰氧-12-苯甲酰氧-2a,3,4,4a,5,6,9,10, 11,12,12a,12b-十二氢-4,6,11-三羟基-4a,8,13,13-四甲基-5-氧代-7,11-亚甲基-1H-环癸五烯并[3,4]苯并[1,2-b]氧杂丁环-9-基]酯。
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use TAXOTERE safely and effectively. See full prescribing information for TAXOTERE.TAXOTERE (docetaxel) Injection Concentrate, Intravenous Infusion (IV). Initial U.S. Approval: 1996WARNINGSee full prescribing information for complete boxed warning •Treatment-related mortality increases with abnormal liver function, at higher doses, and in patients with NSCLC and prior platinum-based therapy receiving TAXOTERE at 100 mg/m2 ( 5.1)•Should not be given if bilirubin > ULN, or if SGOT and/or SGPT > 1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN. LFT elevations increase risk of severe or life-threatening complications. Obtain LFTs before each treatment cycle ( 8.6)•Should not be given if neutrophil counts are < 1500 cells/mm3. Obtain frequent blood counts to monitor for neutropenia ( 4)•Severe hypersensitivity, including very rare fatal anaphylaxis, has been reported in patients who received dexamethasone premedication. Severe reactions require immediate discontinuation of TAXOTERE and administration of appropriate therapy ( 5.3)•Contraindicated if history of severe hypersensitivity reactions to TAXOTERE or to drugs formulated with polysorbate 80 ( 4)•Severe fluid retention may occur despite dexamethasone ( 5.10)----------------------------RECENT MAJOR CHANGES-------------------------- Indications and usage ( 1), dosage and administration ( 2), warnings and precautions ( 5), adverse reactions( 6), 09/28/07----------------------------INDICATIONS AND USAGE--------------------------- Taxotere is a microtubule inhibitor used for:Breast Cancer(BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC ( 1.1)Non-Small Cell Lung Cancer(NSCLC):single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC ( 1.2) Hormone Refractory Prostate Cancer(HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer ( 1.3) Gastric Adenocarcinoma(GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction ( 1.4)Squamous Cell Carcinoma of the Head and Neck Cancer(SCCHN):with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN ( 1.5)----------------------DOSAGE AND ADMINISTRATION----------------------- Administer under supervision of qualified physicians experienced in using antineoplastic agents. Facilities to manage possible complications must be available.Administer IV over 1 hr every 3 weeks. PVC equipment is not recommended.•BC: locally advanced or metastatic: 60-100 mg/m2 single agent ( 2.1) •BC adjuvant: 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles ( 2.1) •NSCLC: after platinum therapy failure: 75 mg/m2 single agent ( 2.2)•NSCLC: chemotherapy-naive: 75 mg/m2followed by cisplatin 75 mg/m2( 2.2)•HRPC: 75 mg/m2 with 5 mg prednisone twice a day continuously ( 2.3)•GC: 75 mg/m2 followed by cisplatin 75 mg/m2 (both on day 1 only)followed by fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1-5), startingat end of cisplatin infusion ( 2.4)•SCCHN: 75 mg/m2 followed by cisplatin 75 mg/m2 IV (day 1), followedby fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1-5), starting at end ofcisplatin infusion; for 4 cycles ( 2.5)•SCCHN: 75 mg/m2 followed by cisplatin 100 mg/m2 IV (day 1), followedby fluorouracil 1000 mg/m2 per day as a 24-hr IV (days 1-4); for 3 cycles( 2.5)Premedication Regimen ( 2.6)•Oral corticosteroids such as dexamethasone 16 mg per day (e.g., 8 mgtwice a day) for 3 days starting 1 day before administration•HRPC: oral dexamethasone 8 mg, at 12, 3, and 1 hrs before treatmentDosage adjustments during treatment see full prescribing information ( 2.7)---------------------DOSAGE FORMS AND STRENGTHS----------------------•Single dose vial 80 mg/2 mL and diluent, 20 mg/0.5 mL and diluent ( 3)-------------------------------CONTRAINDICATIONS------------------------------•Hypersensitivity to Taxotere or polysorbate 80 ( 4)•Neutrophil counts of < 1500 cells/mm3 ( 4)-----------------------WARNINGS AND PRECAUTIONS------------------------•Acute myeloid leukemia ( 5.6)•Fetal harm can occur when administered to a pregnant woman. Women ofchildbearing potential should be advised not to become pregnant whentaking TAXOTERE ( 5.7)•Asthenia ( 5.12)------------------------------ADVERSE REACTIONS-------------------------------Most common adverse reactions are infections, neutropenia, anemia, febrileneutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia,dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain,nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, myalgia ( 6)Other adverse reactions, including serious adverse reactions have beenreported ( 6)To report SUSPECTED ADVERSE REACTIONS, contactsanofi-aventis U.S. LLC at 1-800-663-1610 or FDA at 1-800-FDA-1088 or/medwatch------------------------------DRUG INTERACTIONS-------------------------------•Compounds that induce, inhibit, or are metabolized by P450-3A4 ( 7)See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labelingRevised:09/28/07_______________________________________________________________________________________________________________________________________FULL PRESCRIBING INFORMATION: CONTENTS* WARNING1 INDICATIONS AND USAGE1.1 Breast Cancer1.2 Non-Small Cell Lung Cancer1.3 Prostate Cancer1.4 Gastric Adenocarcinoma1.5 Head and Neck Cancer2 DOSAGE AND ADMINISTRATION2.1 Breast Cancer2.2 Non-Small Cell Lung Cancer2.3 Prostate Cancer2.4 Gastric Adenocarcinoma2.5 Head and Neck Cancer2.6 Premedication Regimen2.7 Dose Adjustments During Treatment2.10 Stability3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Toxic Deaths5.2 Premedication Regimen5.3 Hypersensitivity Reactions5.4 Hematologic Effects5.5 Hepatic Impairment5.6 Acute Myeloid Leukemia5.7 Pregnancy5.8 General5.9 Cutaneous5.10 Fluid Retention5.11 Neurologic5.12 Asthenia6 ADVERSE REACTIONS7 DRUG INTERACTIONS8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Hepatic Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.3 Human Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 Breast Cancer14.2 Adjuvant Treatment of Breast Cancer14.3 Non-Small Cell Lung Cancer (NSCLC)14.4 Prostate Cancer14.5 Gastric Adenocarcinoma14.6 Head and Neck Cancer15 REFERENCES16 HOW SUPPLIED/STORAGE AND HANDLING16.1 How Supplied16.2 Storage16.3 Handling and Disposal17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not listed1FULL PRESCRIBING INFORMATION23WARNING4The incidence of treatment-related mortality associated with TAXOTERE therapy is increased in 5patients with abnormal liver function, in patients receiving higher doses, and in patients with 6non-small cell lung carcinoma and a history of prior treatment with platinum-based 7chemotherapy who receive TAXOTERE as a single agent at a dose of 100 mg/m2[see Warnings 8and Precautions (5.1)].9TAXOTERE should generally not be given to patients with bilirubin > upper limit of normal 10(ULN), or to patients with SGOT and/or SGPT >1.5 x ULN concomitant with alkaline 11phosphatase >2.5 x ULN. Patients with elevations of bilirubin or abnormalities of transaminase 12concurrent with alkaline phosphatase are at increased risk for the development of grade 4 13neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe 14skin toxicity, and toxic death. Patients with isolated elevations of transaminase >1.5 x ULN also 15had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic 16death. Bilirubin, SGOT or SGPT, and alkaline phosphatase values should be obtained prior to 17each cycle of TAXOTERE therapy and reviewed by the treating physician.18TAXOTERE therapy should not be given to patients with neutrophil counts of <1500 cells/mm3.19In order to monitor the occurrence of neutropenia, which may be severe and result in infection, 20frequent blood cell counts should be performed on all patients receiving TAXOTERE.21Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension 22and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who 23received the recommended 3-day dexamethasone premedication. Hypersensitivity reactions 24require immediate discontinuation of the TAXOTERE infusion and administration of appropriate 25therapy [see Warnings and Precautions (5.2)]. TAXOTERE must not be given to patients who 26have a history of severe hypersensitivity reactions to TAXOTERE or to other drugs formulated 27with polysorbate 80 [see Contraindications (4)].28Severe fluid retention occurred in 6.5% (6/92) of patients despite use of a 3-day dexamethasone 29premedication regimen. It was characterized by one or more of the following events: poorly 30tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, 31dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites) [see 32Warnings and Precautions (5.10)].33341. INDICATIONS AND USAGE121.1Breast Cancer3•TAXOTERE is indicated for the treatment of patients with locally advanced or 4metastatic breast cancer after failure of prior chemotherapy.5•TAXOTERE in combination with doxorubicin and cyclophosphamide is indicated for 6the adjuvant treatment of patients with operable node-positive breast cancer.781.2 Non-Small Cell Lung Cancer9•TAXOTERE as a single agent is indicated for the treatment of patients with locally 10advanced or metastatic non-small cell lung cancer after failure of prior platinum-11based chemotherapy.12•TAXOTERE in combination with cisplatin is indicated for the treatment of patients 13with unresectable, locally advanced or metastatic non-small cell lung cancer who 14have not previously received chemotherapy for this condition.15161.3 Prostate Cancer17•TAXOTERE in combination with prednisone is indicated for the treatment of patients 18with androgen independent (hormone refractory) metastatic prostate cancer.19201.4 Gastric Adenocarcinoma21•TAXOTERE in combination with cisplatin and fluorouracil is indicated for the 22treatment of patients with advanced gastric adenocarcinoma, including 23adenocarcinoma of the gastroesophageal junction, who have not received prior 24chemotherapy for advanced disease.25261.5 Head and Neck Cancer27•TAXOTERE in combination with cisplatin and fluorouracil is indicated for the 28induction treatment of patients with locally advanced squamous cell carcinoma of the 29head and neck (SCCHN).30312. DOSAGE AND ADMINISTRATION3233TAXOTERE (docetaxel) Injection Concentrate should be administered under the supervision of34a qualified physician experienced in the use of antineoplastic agents. Appropriate management35of complications is possible only when adequate diagnostic and treatment facilities are readily 36available.37382.1 Breast Cancer39•The recommended dose of TAXOTERE is 60-100 mg/m2 administered intravenously 40over 1 hour every 3 weeks.41•In the adjuvant treatment of operable node-positive breast cancer, the recommended 42TAXOTERE dose is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and 43cyclophosphamide 500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSF may 44be used to mitigate the risk of hematological toxicities [see Dosage Adjustments 1During Treatment (2.7)].232.2 Non-Small Cell Lung Cancer4•For treatment after failure of prior platinum-based chemotherapy, TAXOTERE was 5evaluated as monotherapy, and the recommended dose is 75 mg/m2 administered 6intravenously over 1 hour every 3 weeks. A dose of 100 mg/m2 in patients previously 7treated with chemotherapy was associated with increased hematologic toxicity, 8infection, and treatment-related mortality in randomized, controlled trials [see Boxed 9Warning, Dosage Adjustments During Treatment (2.7), Warnings and Precautions 10(5), Clinical Studies (14)].11•For chemotherapy-naïve patients, TAXOTERE was evaluated in combination with 12cisplatin. The recommended dose of TAXOTERE is 75 mg/m2 administered 13intravenously over 1 hour immediately followed by cisplatin 75 mg/m2 over 1430-60 minutes every 3 weeks [see Dosage Adjustments During Treatment (2.7)].15162.3 Prostate cancer17•For hormone-refractory metastatic prostate cancer, the recommended dose of 18TAXOTERE is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion.19Prednisone 5 mg orally twice daily is administered continuously [see Dosage 20Adjustments During Treatment (2.7)].21222.4 Gastric adenocarcinoma23•For gastric adenocarcinoma, the recommended dose of TAXOTERE is 75 mg/m2 as a 241 hour intravenous infusion, followed by cisplatin 75 mg/m2, as a 1 to 3 hour 25intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per 26day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end 27of the cisplatin infusion. Treatment is repeated every three weeks. Patients must 28receive premedication with antiemetics and appropriate hydration for cisplatin 29administration [see Dosage Adjustments During Treatment (2.7)].30312.5 Head and Neck Cancer32Patients must receive premedication with antiemetics, and appropriate hydration (prior to and 33after cisplatin administration). Prophylaxis for neutropenic infections should be administered.34All patients treated on the TAXOTERE containing arms of the TAX323 and TAX324 studies 35received prophylactic antibiotics.3637•Induction chemotherapy followed by radiotherapy (TAX323)38For the induction treatment of locally advanced inoperable SCCHN, the 39recommended dose of TAXOTERE is 75 mg/m2 as a 1 hour intravenous infusion 40followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by 41fluorouracil as a continuous intravenous infusion at 750 mg/m2 per day for five days.42This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, 43patients should receive radiotherapy. [see Dosage Adjustments During Treatment 44(2.7)].451•Induction chemotherapy followed by chemoradiotherapy (TAX324)2For the induction treatment of patients with locally advanced (unresectable, low 3surgical cure, or organ preservation) SCCHN, the recommended dose of TAXOTERE 4is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 5100 mg/m2 administered as a 30-minute to 3 hour infusion, followed by fluorouracil 61000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is 7administered every 3 weeks for 3 cycles. Following chemotherapy, patients should 8receive chemoradiotherapy [see Dosage Adjustments During Treatment (2.7)].9102.6 Premedication Regimen11•All patients should be premedicated with oral corticosteroids (see below for prostate 12cancer) such as dexamethasone 16 mg per day (e.g., 8 mg BID) for 3 days starting 131 day prior to TAXOTERE administration in order to reduce the incidence and 14severity of fluid retention as well as the severity of hypersensitivity reactions [see 15Boxed Warning, Warnings and Precautions (5)].16•For hormone-refractory metastatic prostate cancer, given the concurrent use of 17prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 1812 hours, 3 hours and 1 hour before the TAXOTERE infusion [see Warnings and 19Precautions (5)].20212.7 Dosage Adjustments During Treatment2223• BreastCancer24Patients who are dosed initially at 100 mg/m2 and who experience either febrile neutropenia, 25neutrophils <500 cells/mm3 for more than 1 week, or severe or cumulative cutaneous reactions 26during TAXOTERE therapy should have the dosage adjusted from 100 mg/m2 to 75 mg/m2. If 27the patient continues to experience these reactions, the dosage should either be decreased from 2875 mg/m2 to 55 mg/m2 or the treatment should be discontinued. Conversely, patients who are 29dosed initially at 60 mg/m2 and who do not experience febrile neutropenia, neutrophils 30<500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe 31peripheral neuropathy during TAXOTERE therapy may tolerate higher doses. Patients who 32develop ≥grade 3 peripheral neuropathy should have TAXOTERE treatment discontinued 33entirely.3435•Combination Therapy with TAXOTERE in the Adjuvant Treatment of Breast36Cancer37TAXOTERE in combination with doxorubicin and cyclophosphamide should be administered 38when the neutrophil count is ≥1,500 cells/mm3. Patients who experience febrile neutropenia 39should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction 40should remain on G-CSF and have their TAXOTERE dose reduced to 60 mg/m². Patients who 41experience Grade 3 or 4 stomatitis should have their TAXOTERE dose decreased to 60 mg/m².42Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory 43signs and/or symptoms during TAXOTERE therapy should have their dosage of TAXOTERE 44reduced from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², 1treatment should be discontinued.23•Non-Small Cell Lung Cancer4Monotherapy with TAXOTERE for NSCLC treatment after failure of prior platinum-based 5chemotherapy6Patients who are dosed initially at 75 mg/m2 and who experience either febrile neutropenia, 7neutrophils <500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, 8or other grade 3/4 non-hematological toxicities during TAXOTERE treatment should have 9treatment withheld until resolution of the toxicity and then resumed at 55 mg/m2. Patients who 10develop ≥grade 3 peripheral neuropathy should have TAXOTERE treatment discontinued 11entirely.12Combination therapy with TAXOTERE for chemotherapy-naïve NSCLC13For patients who are dosed initially at TAXOTERE 75 mg/m2 in combination with cisplatin, and 14whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, in 15patients who experience febrile neutropenia, and in patients with serious non-hematologic 16toxicities, the TAXOTERE dosage in subsequent cycles should be reduced to 65 mg/m2. In 17patients who require a further dose reduction, a dose of 50 mg/m2 is recommended. For cisplatin 18dosage adjustments, see manufacturers’ prescribing information.1920Cancer• Prostate21Combination therapy with TAXOTERE for hormone-refractory metastatic prostate 22cancer23TAXOTERE should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients 24who experience either febrile neutropenia, neutrophils <500 cells/mm3 for more than one week, 25severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms 26during TAXOTERE therapy should have the dosage of TAXOTERE reduced from 75 to 2760 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment 28should be discontinued.2930•Gastric or Head and Neck Cancer31TAXOTERE in combination with cisplatin and fluorouracil in gastric cancer or head and 32neck cancer33Patients treated with TAXOTERE in combination with cisplatin and fluorouracil must receive 34antiemetics and appropriate hydration according to current institutional guidelines. In both 35studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile 36neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days.37If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs 38despite G-CSF use, the TAXOTERE dose should be reduced from 75 to 60 mg/m2. If 39subsequent episodes of complicated neutropenia occur the TAXOTERE dose should be reduced 40from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the TAXOTERE dose should be 41reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of 42TAXOTERE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a 43level >100,000 cells/mm3. Discontinue treatment if these toxicities persist. [see Warnings and 44Precautions (5)].45Recommended dose modifications for toxicities in patients treated with TAXOTERE in1combination with cisplatin and fluorouracil are shown in Table 1.23Table 1 - Recommended Dose Modifications for Toxicities in Patients Treated with4TAXOTERE in Combination with Cisplatin and Fluorouracil5Toxicity Dosageadjustment Diarrhea grade 3 First episode: reduce fluorouracil dose by 20%.Second episode: then reduce TAXOTERE dose by 20%.Diarrhea grade 4 First episode: reduce TAXOTERE and fluorouracil doses by 20%.Second episode: discontinue treatment.Stomatitis/mucositis grade 3 First episode: reduce fluorouracil dose by 20%.Second episode: stop fluorouracil only, at all subsequent cycles. Third episode: reduce TAXOTERE dose by 20%.Stomatitis/mucositis grade 4 First episode: stop fluorouracil only, at all subsequent cycles. Second episode: reduce TAXOTERE dose by 20%.6Liver dysfunction:7In case of AST/ALT >2.5 to ≤5 x UNL and AP ≤2.5 x UNL, or AST/ALT >1.5 to ≤5 x UNL and 8AP >2.5 to ≤5 x UNL, TAXOTERE should be reduced by 20%.9In case of AST/ALT >5 x UNL and/or AP >5 x UNL TAXOTERE should be stopped.1011The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided 12below:13Cisplatin dose modifications and delays14Peripheral neuropathy: A neurological examination should be performed before entry into the 15study, and then at least every 2 cycles and at the end of treatment. In the case of neurological 16signs or symptoms, more frequent examinations should be performed and the following dose 17modifications can be made according to NCIC-CTC grade:18• Grade 2: Reduce cisplatin dose by 20%.19• Grade 3: Discontinue treatment.20Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.21Nephrotoxicity: In the event of a rise in serum creatinine ≥grade 2 (>1.5 x normal value) despite 22adequate rehydration, CrCl should be determined before each subsequent cycle and the following 23dose reductions should be considered (see Table 2).24For other cisplatin dosage adjustments, also refer to the manufacturers’ prescribing information.2526Table 2 – Dose Reductions for Evaluation of Creatinine Clearance1Creatinine clearance resultbefore next cycleCisplatin dose next cycle CrCl ≥60 mL/min Full dose of cisplatin was given. CrCl was to be repeatedbefore each treatment cycle.CrCl between 40 and 59 mL/min Dose of cisplatin was reduced by 50% at subsequent cycle. If CrCl was >60 mL/min at end of cycle, full cisplatin dose was reinstituted at the next cycle.If no recovery was observed, then cisplatin was omitted from the next treatment cycle.CrCl <40 mL/min Dose of cisplatin was omitted in that treatment cycle only.If CrCl was still <40 mL/min at the end of cycle, cisplatin was discontinued.If CrCl was >40 and <60 mL/min at end of cycle, a 50% cisplatin dose was given at the next cycle.If CrCl was >60 mL/min at end of cycle, full cisplatin dose was given at next cycle.CrCl = Creatinine clearance23Fluorouracil dose modifications and treatment delays4For diarrhea and stomatitis, see Table 1.5In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until 6recovery. The fluorouracil dosage should be reduced by 20%.7For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be 8delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade 9≤1 and then recommenced, if medically appropriate.10For other fluorouracil dosage adjustments, also refer to the manufacturers’ prescribing 11information.12132.8 Administration Precautions14TAXOTERE is a cytotoxic anticancer drug and, as with other potentially toxic compounds, 15caution should be exercised when handling and preparing TAXOTERE solutions. The use of 16gloves is recommended.Please refer to Handling and Disposal (16.3).17If TAXOTERE Injection Concentrate, initial diluted solution, or final dilution for intravenous 18infusion should come into contact with the skin, immediately and thoroughly wash with soap and 19water. If TAXOTERE Injection Concentrate, initial diluted solution, or final dilution for 20intravenous infusion should come into contact with mucosa, immediately and thoroughly wash 21with water.22Contact of the TAXOTERE concentrate with plasticized PVC equipment or devices used to 23prepare solutions for infusion is not recommended. In order to minimize patient exposure to the 24plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or 1 sets, the final TAXOTERE dilution for infusion should be stored in bottles (glass, 2 polypropylene) or plastic bags (polypropylene, polyolefin) and administered through 3 polyethylene-lined administration sets.4 TAXOTERE Injection Concentrate requires two dilutions prior to administration. Please follow5 the preparation instructions provided below. Note: Both the TAXOTERE Injection Concentrate6 and the diluent vials contain an overfill to compensate for liquid loss during preparation. This7 overfill ensures that after dilution with the entire contents of the accompanying diluent, there is8 an initial diluted solution containing 10 mg/mL docetaxel.9 The table below provides the fill range of the diluent, the approximate extractable volume of 10 diluent when the entire contents of the diluent vial are withdrawn, and the concentration of the 11 initial diluted solution for TAXOTERE 20 mg and TAXOTERE 80 mg (see Table 3). 1213 Table 3 – Initial Dilution of TAXOTERE Injection Concentrate 14Product Diluent 13% (w/w) ethanol in water for injection Fill Range (mL) Approximate extractable volume of diluent when entire contents are withdrawn (mL) Concentrationof the initial diluted solution (mg/mL docetaxel)Taxotere® 20 mg/0.5 mL1.88 –2.08 mL 1.8 mL 10 mg/mL Taxotere® 80 mg/2 mL6.96 –7.70 mL 7.1 mL 10 mg/mL15 2.9 Preparation and Administration 16 A. I nitial Diluted Solution17 1. TAXOTERE vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored 18 under refrigeration, allow the appropriate number of vials of TAXOTERE Injection 19 Concentrate and diluent (13% ethanol in water for injection) vials to stand at room 20 temperature for approximately 5 minutes.21 2. Aseptically withdraw the entire contents of the appropriate diluent vial (approximately 1.8 mL 22 for TAXOTERE 20 mg and approximately 7.1 mL for TAXOTERE 80 mg) into a syringe by 23 partially inverting the vial, and transfer it to the appropriate vial of TAXOTERE Injection 24 Concentrate. If the procedure is followed as described, an initial diluted solution of 10 mg 25 docetaxel/mL will result .26 3. Mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full 27 mixture of the concentrate and diluent. Do not shake.28 4. The initial diluted TAXOTERE solution (10 mg docetaxel/mL) should be clear; however, 29 there may be some foam on top of the solution due to the polysorbate 80. Allow the solution to 30 stand for a few minutes to allow any foam to dissipate. It is not required that all foam dissipate 31 prior to continuing the preparation process.32 The initial diluted solution may be used immediately or stored either in the refrigerator or at 33 room temperature for a maximum of 8 hours.34。