Pitavastatin_Calcium_DataSheet_MedChemExpress
比伐卢定简介
比伐卢定旳作用机制
比伐卢定不与血浆蛋白，红细胞结合，不与P450作用， 在血浆中游离存在，静脉注射后5min能够达峰。以浓度方 式延长血清中旳活化部分凝血酶时间（aPPT)、凝血时间 （TT)、凝血酶原时间（PT)。血清中游离旳及血栓中结合 旳凝血酶均能被克制，不受血小板释放物质旳影响。进入 人体内被蛋白酶清除，经肾脏排出，在肾功能正常状体下 半衰期为25min。
比伐卢定-----进口品未进国内，深圳信立泰产品将于今年年底上 市，单纯抗IIa因子克制剂，主推PCI手术
比伐卢定旳作用机制
活性部位
活性部位 N
C
结合部位
结合部位
凝血酶
活性部位
N
C
结合部位
直接旳、 特异旳、 可逆性克制凝血酶(Ⅱa)
Maraganore JM ,etc . Biochemistry ,1990 ,29 (30) :7095.
PCI
PPI
比伐卢定 旳利用
急性心肌梗死（AMI） HIT:血小板降低症
VBT：管内放射手术
ห้องสมุดไป่ตู้
比伐卢定旳作用机制
因凝血酶可水解本品多肽顺序中 Arg3 和 Pro4 之间旳 肽键 ,使本品失活 ，所以本品对凝血酶旳克制作用是可逆而 短暂旳。
Phe Pro Arg Pro Gly Gly Gly Gly Ans Gly
Glu Ile Glu Glu Phe Asp Gly Asn Glu Try Leu Maraganore JM ,etc . Biochemistry ,1990 ,29 (30) :7095.
比伐卢定旳理化性质
中文名：比伐卢定 英文名称：bivalirudin, AngiomaxTM（Medicines 企业） 抗凝成份:一种20肽旳水蛭素衍生片段,分子量： 2180,剂型：注射剂
间苯三酚欧洲药典翻译
间苯三酚二水合物分子式：C6H6O3·2H2O摩尔质量：162.1CAS Number：6099-90-7用途：肌肉解挛剂系统命名：1,3,5-三羟基苯二水合物含量：99.0 % ~ 101.0 %（以无水间苯三酚计算）理化性质：外观：白色或类白色粉末溶解性：难溶于水，易溶于乙醇（96 %），部分溶于二氯甲烷鉴别：A.红外光谱（2.2.24）样品制备：事先将供试品在105 °C烘箱中干燥对比：将供试品和无水间苯三酚标准品进行图谱对比B. 薄层色谱（2.2.27）供试溶液：将0.2g供试品溶解在甲醇中，并稀释至10mL参比溶液：将0.2g无水间苯三酚标准品溶解在甲醇中，并稀释至10mL薄层板：TCL F254硅胶板流动相：无水甲酸：正己烷：乙酸乙酯= 2:37.5:62.5（体积比）用量：10 µL爬板高度：超过2/3板长检测条件：在254 nm紫外光照射下检测结果：供试溶液和参比溶液的样品点在TCL板上，应大小相似、位置一致C.干燥失重（见测试）溶解：将2.5g供试品溶解在乙醇（96 %）中，并稀释至25mL外观：溶液应澄清，并不得比参比溶液BY5（方法二）颜色更深pH：将10mL溶液用去除二氧化碳的蒸馏水稀释至100mL，测得pH应在4.0 ~ 6.0之间有关物质：液相色谱：使用前现配溶液，避光保存混合溶液：流动相B：流动相A = 10:90（体积比）供试溶液：将50mg供试品溶解在混合溶液中，并稀释至10mL参比溶液（a）：取1mL供试溶液用混合溶液稀释至100mL，后取1mL此溶液用混合溶液稀释至10mL参比溶液（b）：分别取6mg的间苯二酚（杂质B），2,3',4,5',6-五羟基联苯（杂质D），邻苯三酚（杂质A）溶解于10mL的混合溶液中，加入2mL的供试溶液并用混合溶液稀释至20mL，后取1mL此溶液用混合溶液稀释至50mL参比溶液（c）：分别取4mg的邻苯三酚（杂质A），2,3',4,5',6-五羟基联苯（杂质D），杂质E，杂质I，杂质K，杂质L溶解于10mL的混合溶液中，并用混合溶液稀释至20mL参比溶液（d）：取10mg的供试品溶解于10mL的混合溶液，加入1mL的参比溶液（c）并用混合溶液稀释至20mL色谱柱：柱长：0.25m直径：4.0mm固定相：末端修饰十八烷基硅羟基耦合极性集团R（5µm）流动相：流动相A：1.36 g/L的磷酸二氢钾并用磷酸调节pH至3.0流动相B：乙腈程序洗脱流速：1.0 mL/min检测波长：265nm注射量：供试溶液，参比溶液（a），（b），（d）各20µL杂质鉴别：对比参比溶液（d）色谱图定位鉴别杂质A, D, E, I, K and L相对保留时间：以间苯三酚为参照点（保留时间大约为12min）：impurity E = about 0.7; impurity A = about 0.9; impurity D = about 1.3; impurity B = about 1.35; impurity K = about 1.5; impurity I = about 1.8; impurity L = about 2.0系统适用性：分离度：杂质A和间苯三酚大于2.5，杂质B和D大于4.0限度：校正因子：对于计算含量，各杂质的峰面积应乘以如下的校正因子：impurity A = 0.6; impurity D = 0.2; impurity E = 0.7; impurity I = 0.6; impurity K = 0.6; impurity L = 0.4且对于杂质A, D, E, I, K, L，其峰面积不应大于参比溶液（a）中主峰峰面积的1.5倍（0.15 %）非特定杂质：对于非特定杂质，其面积不应大于参比溶液（a）中主峰峰面积（0.10 %）总杂质：面积不应大于参比溶液（a）中主峰峰面积的3.0倍（0.30 %）报告限：面积不应大于参比溶液（a）中主峰峰面积的0.5倍（0.05 %）氯含量：不应大于200 ppm将2.5mL的溶液用水稀释至15mL硫酸盐：不应大于500ppm将3mL的溶液用蒸馏水稀释至15mL干燥失重：小于1.0 %将1.000g无水间苯三酚在105 °C烘箱中干燥灼烧残渣：小于0.1 %样品检测量1.0g滴定：将0.500g供试品溶解在50mL水中，用1M氢氧化钠溶液滴定，计算计量终点1mL的1M氢氧化钠相当于63.05mg的C6H6O3保存：避光保存可能存在杂质：A. benzene-1,2,3-triol (pyrogallol),B. benzene-1,3-diol (resorcinol),D. 2,3′,4,5′,6-biphenylpentol (phloroglucide),E. benzene-1,2,4-triol,I. 2,6-dichlorophenol,K. 4-chlorobenzene-1,3-diol (4-chlororesorcinol),L. 3,5-dichloroaniline,O. 4,6-dichlorobenzene-1,3-diol (4,6-dichlororesorcinol).。
卡前列素氨基丁三醇杂质汇总
用途
项目报批 纯度高于98%
项目 Carboprost Trometamol
N/A
醇杂质3
Impurity 3
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项目报批 纯度高于98%
卡前列素氨基丁三 Carboprost Trometamol
醇杂质4
76498-29-8
规格
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卡前列素氨基丁三 Carboprost Trometamol
醇杂质2(卡前列素 Impurity 2（Carboprost
氨基丁三醇EP杂质 Trometamol EP Impurity
B)
B）
35864-81-4
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卡前列素氨基丁三醇杂质列表集
中文名称
英文名称
CAS
卡前列素氨基丁三 醇杂质1（卡前列 Carboprost Trometamol
Impurity 1（Carboprost 素氨基丁三醇EP杂
质B）(反式 Trometamol EP Impurity Carboprost) A） (trans-Carboprost)
Impurity 4
N/A
10mg 25mg 50mg 100mg 更大规格请咨询
项目报批 纯度高于98%
卡前列素氨基丁三 Carboprost Trometamol
N/A
醇杂质5
Impurity 5
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项目报批 纯度高于98%
扬信医药代理各品种杂质对照品:舒更葡糖钠杂质，达托霉素杂质，依维莫司杂质，他克莫司杂质，阿奇霉素杂质，克拉维酸钾杂质， 红霉素杂质，克拉霉素杂质，林可霉素杂质，罗红霉素杂质，克林霉素杂质，恩曲他滨杂质，艾地那非杂质，瑞卢戈利杂质，艾氟康唑 杂质等；并提供COA、NMR、HPLC、MS等结构确证图谱;详情请点用户名，谢谢！ 专业<杂质对照品>解决方案，代理中检所/EP/BP/USP/LGC/TRC/DR/TLC/MC/SIGMA/BACHEM/STD等品牌。
激酶抑制剂类药物
Sutent药物基本信息〖NDA申请人〗CPPY CV〖NDA原始批准日期〗2006年07月26日〖剂型/规格〗胶囊剂/12.5mg；胶囊剂/25mg；胶囊剂/50mg；胶囊剂/37.5mg〖适应证〗50mg QD，用于治疗：Ⅰ、病情恶化后或对马来酸伊马替尼不耐受的胃肠间质瘤；Ⅱ、晚期肾细胞瘤活性成分信息〖USAN名称〗Sunitinib Malate，苹果酸舒尼替尼〖CAS号〗341031-54-7（苹果酸盐）；557795-19-4（游离碱）〖曾用代号〗SU-11248（苹果酸盐）〖作用类别〗激酶抑制剂类抗肿瘤药〖化学名〗(Z)-N-(2-(二乙基氨基)乙基)-5-((5-氟-2-氧代吲哚-3-亚基)甲基)-2,4-二甲基-1H-吡咯-3-羧酰胺苹果酸盐〖化学结构式〗专利信息年度销售情况（亿美元，信息来源：辉瑞公司年度财务报告及SEC报表）Tykerb药物基本信息〖NDA申请人〗Smithkline Beecham〖NDA原始批准日期〗2007年03月13日〖剂型/规格〗片剂/250mg；〖适应证〗1250mg QD+卡培他滨治疗肿瘤过度表达HER2且使用过包括蒽环类抗生素、紫杉烷类抗生素曲妥珠单抗在内的抗肿瘤药物治疗的晚期或转移性乳腺癌；1500 QD+来曲唑治疗HER2过度表达且需要进行激素治疗的绝经后妇女的激素受体阳性的转移性乳腺癌活性成分信息〖USAN名称〗Lapatinib ditosylate （monohydrate），拉帕替尼二（对甲基苯磺酸）盐（单水合物）〖CAS号〗388082-78-8〖曾用代号〗〖作用类别〗激酶抑制剂类抗肿瘤药；〖化学名〗N-[3-氯-4-[(3-氟苯基)甲氧基]苯基]-6-[5[[[2-(甲磺酰基)乙基]氨基]甲基]-2-呋喃基]-4-喹啉胺二（对甲基苯磺酸）盐单水合物〖理化性质〗黄色固体，25℃下于水中的溶解度为0.007mg/mL，于0.1N HCl中的溶解度为0.001mg/mL〖化学结构式〗专利信息年度销售情况（亿英磅）Tasigna药物基本信息〖NDA申请人〗诺华制药〖NDA原始批准日期〗2007.10.29〖剂型/规格〗片剂/200mg（按游离碱计）〖适应证〗300mg BID用于于慢性期治疗新近确认成年患者的费城染色体阳性慢性髓样白血病；400mg BID用于于慢性期或急性期治疗成年患者对包括伊马替尼在内的先前治疗方法耐药或不耐受的费城染色体阳性慢性髓样白血病。
760-78-1_DL-正缬氨酸_MED11074技术资料_上海_Medbio脉铂
1g
≥98%
品牌
货号
中文名称
英文名称
CAS
包装
纯度
MedBio
MED11127
Fmoc-L-丝氨酸
Fmoc-Ser-OH
73724-45-5
100g
≥98%
品牌
货号
中文名称
英文名称
CAS
包装
CAS
包装
纯度
MedBio
MED11025
N-羟基琥珀酰亚胺
HOSu
6066-82-6
100g
≥98%
品牌
货号
中文名称
英文名称
CAS
包装
纯度
MedBio
MED11040
丝氨酸苄酯盐酸盐
H-Ser-OBzl.HCl
1738-72-3
100g
≥98%
品牌
货号
中文名称
英文名称
CAS
包装
纯度
MedBio
MED11086
5g
≥98%
品牌
货号
中文名称
英文名称
CAS
包装
纯度
MedBio
MED11059
N-Fmoc-N'-Boc-L-2,3-二氨基丙酸
Fmoc-Dap(Boc)-OH
162558-25-0
1g
≥98%
纯度
MedBio
MED11049
Fmoc-N-三苯甲基-L-天冬酰胺
Fmoc-Asn(Trt)-OH
132388-59-1
100g
≥98%
品牌
货号
中文名称
Pitavastatin Calcium_CAS号147526-32-7说明书_AbMole中国
分子量880.98溶解性（25°C ）DMSO 51 mg/mL 分子式C H CaF N O Water <1 mg/mL CAS 号147526-32-7Ethanol <1 mg/mL储存条件3年 -20°C 粉末状生物活性Pitavastatin calcium (Livalo) is a novel member of the medication class of statins. Like the other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis. Most statins are metabolised in part by one or more hepatic cytochrome P450 enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). Pitavastatin appears to be a substrate of CYP2C9, and not CYP3A4(which is a common source of interactions in other statins).不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA 指南）小鼠大鼠兔豚鼠仓鼠狗重量 (kg)0.020.15 1.80.40.0810体表面积 (m )0.0070.0250.150.050.020.5K 系数36128520动物 A (mg/kg) = 动物 B (mg/kg) ×动物 B 的K 系数动物 A 的K 系数例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K 系数（3），再除以大鼠的K 系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg 。
辛伐他汀美国药典
Simvastatin(sim'' va stat' in).C25H38O5 418.57Butanoic acid, 2,2-dimethyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, [1S-[1,3,7,8(2S*,4S*),8a]].2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-2-[(1S,2S,6R,8S,8R)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one [79902-63-9].» Simvastatin contains not less than 98.0 percent and not more than 102.0 percent of C25H38O5, calculated on the dried basis. It may contain a suitable antioxidant. Packaging and storage— Preserve in well-closed containers. Store between 15 and 30, or under refrigeration.USP Reference standards 11—USP Lovastatin RSUSP Simvastatin RSIdentification—A: Infrared Absorption 197M.B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.Specific rotation 781S: between +285 and +298.Test solution: 5 mg per mL, in acetonitrile.Loss on drying 731— Dry it in vacuum at 60 for 3 hours: it loses not more than 0.5% of its weight.Residue on ignition 281: not more than 0.1%.Heavy metals, Method II 231: 0.002%.Chromatographic purity— [note—The Simvastatin solutions are stable for up to 3 days when stored at 4. Without refrigeration, they should be injected immediately after preparation. ]Mobile phase, Diluent, and Chromatographic system— Proceed as directed in the Assay.Test solution— Use the Assay preparation.Procedure— Inject about 5 µL of the Test solution into the chromatograph, record the chromatogram, identify the specified impurities listed in Table 1, and measure the areas for all the peaks. Calculate the percentage of each impurity in the portion of Simvastatin taken by the formula:100(ri / rs)in which ri is the peak area for each impurity; and rs is the sum of the areas of all the peaks. Reporting level for impurities is 0.05%.Table 1Name Relative RetentionTime Limit %Simvastatin hydroxyacid10.450.4 Epilovastatin2 and Lovastatin0.60 1.03 Methylene simvastatin40.800.4 Simvastatin 1.0n/a Acetyl simvastatin5 2.380.4 Anhydro simvastatin6 2.420.4 Simvastatin dimer7 3.800.4 Any other individual impurity—0.1 Total impurities other than lovastatin andepilovastatin— 1.01 (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-Dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid.2 (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-Hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2R)-2-methylbutanoate.3 If present, lovastatin and epilovastatin may not be completely resolved by the method. These peaks are integrated together to determine conformance.4 (1S,7S,8S,8aR)-8-[2-[(2R,4R)-4-Hydroxy-6-oxotetrahydro-2H-pyran-2-yl] ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbut-3-enoate.5 (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-(Acetyloxy)-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate.6 (1S,3R,7S,8S,8aR)-3,7-Dimethyl-8-[2-[(2R)-6-oxo-3,6-dihydro-2H-pyran-2-yl]ethyl]-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate.7 (2R,4R)-2-[[(1S,2S,6R,8S,8aR)-8-[(2,2-Dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]ethyl]-6-oxotetrahydro-2H-pyran-4-yl (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate. Assay— [note—The Simvastatin solutions are stable for up to 3 days when stored at 4. Without refrigeration, they should be injected immediately after preparation. ]Dilute phosphoric acid— Transfer 1 mL of phosphoric acid to a 1-L volumetric flask, and dilute with water to volume.Solution A— Prepare a mixture of acetonitrile and Dilute phosphoric acid (50:50).Solution B— Transfer 1 mL of phosphoric acid to a 1-L volumetric flask, and dilute with acetonitrile to volume.Mobile phase— Use variable mixtures of Solution A and Solution B, as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).Buffer solution— Prepare a solution containing 1.4 g of monobasic potassium phosphate per L, and adjust with phosphoric acid to a pH of 4.0.Diluent— Prepare a mixture of acetonitrile and Buffer solution (3:2).System suitability preparation— Dissolve accurately weighed quantities of USP Simvastatin RS and USP Lovastatin RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having known concentrations of about 1.5 mg per mL of USP Simvastatin RS and 0.015 mg per mL of USP Lovastatin RS.Standard preparation— Dissolve an accurately weighed quantity of USP Simvastatin RS in Diluent to obtain a solution having a known concentration of about 1.5 mg per mL.Assay preparation— Transfer about 75 mg of Simvastatin, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.Chromatographic system (see Chromatography 621— The liquid chromatograph is equipped with a 238-nm detector and a 4.6- × 33-mm column that contains packing L1. The flow rate is about 3.0 mL per minute. The chromatograph is programmed as follows.Time Solution A Solution BChromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.60 for lovastatin and 1.0 for simvastatin; and the resolution, R, between simvastatin and lovastatin is greater than 3. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.0%. Procedure — Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C25H38O5 in the portion of Simvastatin taken by the formula:VC(rU / rS)in which V is the volume, in mL, of the Assay preparation; C is theconcentration, in mg per mL, of USP Simvastatin RS in the Standardpreparation; and rU and rS are the responses of the simvastatin peak obtained from the Assay preparation and the Standard preparation, respectively. Auxiliary Information — Please check for your question in the FAQs before contacting USP. USP36–NF31 Page 5143Pharmacopeial Forum: Volume No. 33(5) Page 948Chromatographic Column —SIMVASTATINChromatographic columns text is not derived from, and not part of, USP 36 or NF 31.(minutes)(%) (%)Elution 0–4.51000isocratic 4.5–4.6100→950→5linear gradient 4.6–8.095→255→75linear gradient 8.0–11.52575isocratic11.5–11.625→10075→0linear gradient11.6–131000re-equilibrationTopic/Question Contact Expert CommitteeMonograph Sujatha Ramakrishna, Ph.D., MBASenior Scientific Liaison1-301-816-8349(SM22010) Monographs - SmallMolecules 2Reference Standards RS Technical Services1-301-816-8129rstech@。
匹伐他汀钙药品说明书(英文)
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use LIVALO® safely and effectively. See full prescribing information for LIVALO.LIVALO (pitavastatin) Tablet, Film Coated for Oral useInitial U.S. Approval: 2009RECENT MAJOR CHANGESDosage and AdministrationDosage in Patients with Renal Impairment (2.2) 8/2011INDICATIONS AND USAGELIVALO is a HMG-CoA reductase inhibitor indicated for:•Patients with primary hyperlipidemia or mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) (1.1)Limitations of Use (1.2):•Doses of LIVALO greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4 mg once daily dosing of LIVALO.•The effect of LIVALO on cardiovascular morbidity and mortality has not been determined.•LIVALO has not been studied in Fredrickson Type I, III, and V dyslipidemias.DOSAGE AND ADMINISTRATION•LIVALO can be taken with or without food, at any time of day (2.1) Dose Range: 1 mg to 4 mg once daily (2.1)•Primary hyperlipidemia and mixed dyslipidemia: Starting dose 2 mg. When lowering of LDL-C is insufficient, the dosage may be increased to a maximum of 4 mg per day. (2.1)•Moderate and severe renal impairment (glomerular filtration rate 30 –59 and 15 - 29 mL/min/1.73 m2, respectively) as well as end-stage renal disease on hemodialysis: Starting dose of 1 mg once daily and maximum dose of 2 mg once daily (2.2)DOSAGE FORMS AND STRENGTHS•Tablets: 1 mg, 2 mg, and 4 mg (3)CONTRAINDICATIONS•Known hypersensitivity to product components (4)•Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels (4)•Women who are pregnant or may become pregnant (4, 8.1)•Nursing mothers (4, 8.3)•Co-administration with cyclosporine (4, 7.1, 12.3)WARNINGS AND PRECAUTIONS•Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase in a dose-dependent manner, with advanced age (≥65), renal impairment, and inadequately treated hypothyroidism. Advise patientsto promptly report report unexplained and/or persistent muscle pain, tenderness, or weakness, and discontinue LIVALO (5.1)•Liver enzyme abnormalities : Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter (5.2)ADVERSE REACTIONSThe most frequent adverse reactions (rate ≥2.0% in at least one marketed dose) were myalgia, back pain, diarrhea, constipation and pain in extremity. (6)To report SUSPECTED ADVERSE REACTIONS, contact Kowa Pharmaceuticals America, Inc. at 1-877-334-3464 or FDA at 1-800-FDA-1088 or /medwatch.To report SUSPECTED ADVERSE REACTIONS, contact at or FDA at 1-800-FDA-1088 or /medwatchDRUG INTERACTIONS•Erythromycin: Combination increases pitavastatin exposure. Limit LIVALO to 1 mg once daily (2.3, 7.2)•Rifampin: Combination increases pitavastatin exposure. Limit LIVALO to 2 mg once daily (2.4, 7.3)•Concomitant lipid-lowering therapies : Use with fibrates or lipid-modifying doses (≥1 g/day) of niacin increases the risk of adverse skeletal muscle effects. Caution should be used when prescribing with LIVALO. (5.1, 7.4, 7.5)USE IN SPECIFIC POPULATIONS•Pediatric use: Safety and effectiveness have not been established. (8.4)•Renal impairment: Limitation of a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily for patientswith moderate and severe renal impairment as well as patients receiving hemodialysis (2.2, 8.6)See 17 for PATIENT COUNSELING INFORMATIONRevised: 11/2012FULL PRESCRIBING INFORMATION: CONTENTS *1 INDICATIONS AND USAGE1.1 Primary Hyperlipidemia and Mixed Dyslipidemia1.2 Limitations of Use2 DOSAGE AND ADMINISTRATION2.1 General Dosing Information2.2 Dosage in Patients with Renal Impairment2.3 Use with Erythromycin2.4 Use with Rifampin3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Skeletal Muscle Effects5.2 Liver Enzyme Abnormalities5.3 Endocrine Function6 ADVERSE REACTIONS6.1 Clinical Studies Experience6.2 Postmarketing Experience:7 DRUG INTERACTIONS7.1 Cyclosporine7.2 Erythromycin7.3 Rifampin7.4 Gemfibrozil7.5 Other Fibrates7.6 Niacin7.7 Warfarin8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal Impairment8.7 Hepatic Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility13.2 Animal Toxicology and/or Pharmacology14 CLINICAL STUDIES14.1 Primary Hyperlipidemia or Mixed Dyslipidemia16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION17.1 Dosing Time17.2 Muscle Pain17.3 Pregnancy17.4 Breastfeeding17.5 Liver Enzymes* Sections or subsections omitted from the full prescribing information are not listedFULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGEDrug therapy should be one component of multiple-risk-factor intervention in individuals who require modifications of their lipid profile. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other nonpharmacological measures has been inadequate.1.1 Primary Hyperlipidemia and Mixed DyslipidemiaLIVALO® is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia.1.2 Limitations of UseDoses of LIVALO greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4 mg once daily dosing of LIVALO.The effect of LIVALO on cardiovascular morbidity and mortality has not been determined.LIVALO has not been studied in Fredrickson Type I, III, and V dyslipidemias.2 DOSAGE AND ADMINISTRATION2.1 General Dosing InformationThe dose range for LIVALO is 1 to 4 mg orally once daily at any time of the day with or without food. The recommended starting dose is 2 mg and the maximum dose is 4 mg. The starting dose and maintenance doses of LIVALO should be individualized according to patient characteristics, such as goal of therapy and response.After initiation or upon titration of LIVALO, lipid levels should be analyzed after 4 weeks and the dosage adjusted accordingly.2.2 Dosage in Patients with Renal ImpairmentPatients with moderate and severe renal impairment (glomerular filtration rate 30 – 59 mL/min/1.73 m2 and 15 – 29 mL/min/1.73 m2 not receiving hemodialysis, respectively) as well as end-stage renal disease receiving hemodialysis should receive a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily.2.3 Use with ErythromycinIn patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded [see Drug Interactions (7.2)].2.4 Use with RifampinIn patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded [see Drug Interactions (7.3)].3 DOSAGE FORMS AND STRENGTHS1 mg: Round white film-coated tablet. Debossed “KC” on one side and “1” on the other side of the tablet.2 mg: Round white film-coated tablet. Debossed “KC” on one side and “2” on the other side of the tablet.4 mg: Round white film-coated tablet. Debossed “KC” on one side and “4” on the other side of the tablet.4 CONTRAINDICATIONSThe use of LIVALO is contraindicated in the following conditions:•Patients with a known hypersensitivity to any component of this product. Hypersensitivity reactions including rash, pruritus, and urticaria have been reported with LIVALO [see Adverse Reactions (6.1)].•Patients with active liver disease which may include unexplained persistent elevations of hepatic transaminase levels [see Warnings and Precautions (5.2), Use in Specific Populations (8.7)].•Women who are pregnant or may become pregnant. Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, LIVALO may cause fetal harm when administered to pregnant women. Additionally, there is no apparent benefit to therapy during pregnancy, and safety in pregnant women has not been established. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and the lack of known clinical benefit with continued use during pregnancy [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.2)].•Nursing mothers. Animal studies have shown that LIVALO passes into breast milk. Since HMG-CoA reductase inhibitorshave the potential to cause serious adverse reactions in nursing infants, LIVALO, like other HMG-CoA reductase inhibitors, is contraindicated in pregnant or nursing mothers [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.2)].•Co-administration with cyclosporine [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].5 WARNINGS AND PRECAUTIONS5.1 Skeletal Muscle EffectsCases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including LIVALO. These risks can occur at any dose level, but increase in a dose-dependent manner. LIVALO should be prescribed with caution in patients with predisposing factors for myopathy. These factors include advanced age (≥65 years), renal impairment, and inadequately treated hypothyroidism. The risk of myopathy may also be increased with concurrent administration of fibrates or lipid-modifying doses of niacin. LIVALO should be administered with caution in patients with impaired renal function, in elderly patients, or when used concomitantly with fibrates or lipid-modifying doses of niacin [see Drug Interactions (7.6), Use in Specific Populations (8.5, 8.6) and Clinical Pharmacology (12.3)].There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated withstatin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.LIVALO therapy should be discontinued if markedly elevated creatine kinase (CK) levels occur or myopathy is diagnosed or suspected. LIVALO therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures). All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing LIVALO.5.2 Liver Enzyme AbnormalitiesIncreases in serum transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase, or alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase) have been reported with HMG-CoA reductase inhibitors, including LIVALO. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy.In placebo-controlled Phase 2 studies, ALT >3 times the upper limit of normal was not observed in the placebo, LIVALO 1 mg, or LIVALO 2 mg groups. One out of 202 patients (0.5%) administered LIVALO 4 mg had ALT >3 times the upper limit of normal.It is recommended that liver enzyme tests be performed before the initiation of LIVALO and if signs or symptoms of liver injury occur.There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with LIVALO, promptly interrupt therapy. If an alternate etiology is not found do not restart LIVALO.As with other HMG-CoA reductase inhibitors, LIVALO should be used with caution in patients who consume substantial quantities of alcohol. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of LIVALO [see Contraindications (4)].5.3 Endocrine FunctionIncreases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including LIVALO.6 ADVERSE REACTIONSThe following serious adverse reactions are discussed in greater detail in other sections of the label:•Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see Warnings and Precautions (5.1)].•Liver Enzyme Abnormalities [see Warning and Precautions (5.2)].Of 4,798 patients enrolled in 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 patients were administered pitavastatin 1 mg to 4 mg daily. The mean continuous exposure of pitavastatin (1 mg to 4 mg) was 36.7 weeks (median 51.1 weeks). The mean age of the patients was 60.9 years (range; 18 years – 89 years) and the gender distribution was 48% males and 52% females. Approximately 93% of the patients were Caucasian, 7% were Asian/Indian, 0.2% were African American and 0.3% were Hispanic and other.6.1 Clinical Studies ExperienceBecause clinical studies on LIVALO are conducted in varying study populations and study designs, the frequency of adverse reactions observed in the clinical studies of LIVALO cannot be directly compared with that in the clinical studies of other HMG-CoA reductase inhibitors and may not reflect the frequency of adverse reactions observed in clinical practice.Adverse reactions reported in ≥ 2% of patients in controlled clinical studies and at a rate greater than or equal to placebo are shown in Table 1. These studies had treatment duration of up to 12 weeks.Table 1. Adverse Reactions* Reported by ≥2.0% of Patients Treated with LIVALO and > Placebo in Short-Term Controlled StudiesAdverse Reactions* PlaceboN= 208LIVALO1 mgN=309LIVALO2 mgN=951LIVALO4 mgN=1540Back Pain 2.9% 3.9% 1.8% 1.4% Constipation 1.9% 3.6% 1.5% 2.2% Diarrhea 1.9% 2.6% 1.5% 1.9%Myalgia 1.4% 1.9% 2.8% 3.1%Pain in extremity 1.9% 2.3% 0.6% 0.9%* Adverse reactions by MedDRA preferred term.Other adverse reactions reported from clinical studies were arthralgia, headache, influenza, and nasopharyngitis.The following laboratory abnormalities have also been reported: elevated creatine phosphokinase, transaminases, alkaline phosphatase, bilirubin, and glucose.In controlled clinical studies and their open-label extensions, 3.9% (1 mg), 3.3% (2 mg), and 3.7% (4 mg) of pitavastatin-treated patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: elevated creatine phosphokinase (0.6% on 4 mg) and myalgia (0.5% on 4 mg).Hypersensitivity reactions including rash, pruritus, and urticaria have been reported with LIVALO.6.2 Postmarketing Experience:The following adverse reactions have been identified during postapproval use of LIVALO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Adverse reactions associated with LIVALO therapy reported since market introduction, regardless of causality assessment, include the following: abdominal discomfort, abdominal pain, dyspepsia, nausea, asthenia, fatigue, malaise, hepatitis, jaundice, fatal and non-fatal hepatic failure, dizziness, hypoesthesia, insomnia, depression, interstitial lung disease, erectile dysfunction and muscle spasms. There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1)].7 DRUG INTERACTIONS7.1 CyclosporineCyclosporine significantly increased pitavastatin exposure. Co-administration of cyclosporine with LIVALO is contraindicated [see Contraindications (4), and Clinical Pharmacology (12.3)].7.2 ErythromycinErythromycin significantly increased pitavastatin exposure. In patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].7.3 RifampinRifampin significantly increased pitavastatin exposure. In patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].7.4 GemfibrozilDue to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are coadministered with gemfibrozil, concomitant administration of LIVALO with gemfibrozil should be avoided.7.5 Other FibratesBecause it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of other fibrates, LIVALO should be administered with caution when used concomitantly with other fibrates [see Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].7.6 NiacinThe risk of skeletal muscle effects may be enhanced when LIVALO is used in combination with niacin; a reduction in LIVALO dosage should be considered in this setting [see Warnings and Precautions (5.1)].7.7 WarfarinLIVALO had no significant pharmacokinetic interaction with R- and S- warfarin. LIVALO had no significant effect on prothrombin time (PT) and international normalized ratio (INR) when administered to patients receiving chronic warfarin treatment [see Clinical Pharmacology (12.3)]. However, patients receiving warfarin should have their PT and INR monitored when pitavastatin is added to their therapy.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyTeratogenic effects: Pregnancy Category XLIVALO is contraindicated in women who are or may become pregnant. Serum cholesterol and TG increase during normal pregnancy, and cholesterol products are essential for fetal development. Atherosclerosis is a chronic process and discontinuationof lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hyperlipidemia therapy [see Contraindications (4)].There are no adequate and well-controlled studies of LIVALO in pregnant women, although, there have been rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors. In a review of about 100 prospectively followed pregnancies in women exposed to other HMG-CoA reductase inhibitors, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. However, this study was only able to exclude a three-to-four-fold increased risk of congenital anomalies over background incidence. In 89% of these cases, drug treatment started before pregnancy and stopped during the first trimester when pregnancy was identified.Reproductive toxicity studies have shown that pitavastatin crosses the placenta in rats and is found in fetal tissues at ≤36% of maternal plasma concentrations following a single dose of 1 mg/kg/day during gestation.Embryo-fetal developmental studies were conducted in pregnant rats treated with 3, 10, 30 mg/kg/day pitavastatin by oral gavage during organogenesis. No adverse effects were observed at 3 mg/kg/day, systemic exposures 22 times human systemic exposure at 4 mg/day based on AUC.Embryo-fetal developmental studies were conducted in pregnant rabbits treated with 0.1, 0.3, 1 mg/kg/day pitavastatin by oral gavage during the period of fetal organogenesis. Maternal toxicity consisting of reduced body weight and abortion was observed at all doses tested (4 times human systemic exposure at 4 mg/day based on AUC).In perinatal/postnatal studies in pregnant rats given oral gavage doses of pitavastatin at 0.1, 0.3, 1, 3, 10, 30 mg/kg/day from organogenesis through weaning, maternal toxicity consisting of mortality at ≥0.3 mg/kg/day and impaired lactation at all doses contributed to the decreased survival of neonates in all dose groups (0.1 mg/kg/day represents approximately 1 time human systemic exposure at 4 mg/day dose based on AUC).LIVALO may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking LIVALO,the patient should be apprised of the potential risks to the fetus and the lack of known clinical benefit with continued use during pregnancy.8.3 Nursing MothersIt is not known whether pitavastatin is excreted in human milk, however, it has been shown that a small amount of another drug in this class passes into human milk. Rat studies have shown that pitavastatin is excreted into breast milk. Because another drug in this class passes into human milk and HMG-CoA reductase inhibitors have a potential to cause serious adverse reactions in nursing infants, women who require LIVALO treatment should be advised not to nurse their infants or to discontinue LIVALO [see Contraindications (4)].8.4 Pediatric UseSafety and effectiveness of LIVALO in pediatric patients have not been established.8.5 Geriatric UseOf the 2,800 patients randomized to LIVALO 1 mg to 4 mg in controlled clinical studies, 1,209 (43%) were 65 years and older. No significant differences in efficacy or safety were observed between elderly patients and younger patients. However, greater sensitivity of some older individuals cannot be ruled out.8.6 Renal ImpairmentPatients with moderate and severe renal impairment (glomerular filtration rate 30 – 59 mL/min/1.73 m2 and 15 – 29 mL/min/1.73m2 not receiving hemodialysis, respectively) as well as end-stage renal disease receiving hemodialysis should receive a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].8.7 Hepatic ImpairmentLIVALO is contraindicated in patients with active liver disease which may include unexplained persistent elevations of hepatic transaminase levels.10 OVERDOSAGEThere is no known specific treatment in the event of overdose of pitavastatin. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Hemodialysis is unlikely to be of benefit due to high protein binding ratio of pitavastatin.11 DESCRIPTIONLIVALO (pitavastatin) is an inhibitor of HMG-CoA reductase. It is a synthetic lipid-lowering agent for oral administration.The chemical name for pitavastatin is (+)monocalcium bis{(3R, 5S, 6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate}. The structural formula is:The empirical formula for pitavastatin is C50H46CaF2N2O8 and the molecular weight is 880.98. Pitavastatin is odorless and occursas white to pale-yellow powder. It is freely soluble in pyridine, chloroform, dilute hydrochloric acid, and tetrahydrofuran, soluble in ethylene glycol, sparingly soluble in octanol, slightly soluble in methanol, very slightly soluble in water or ethanol, and practically insoluble in acetonitrile or diethyl ether. Pitavastatin is hygroscopic and slightly unstable in light.Each film-coated tablet of LIVALO contains 1.045 mg, 2.09 mg, or 4.18 mg of pitavastatin calcium, which is equivalent to1 mg,2 mg, or 4 mg, respectively of free base and the following inactive ingredients: lactose monohydrate, low substituted hydroxypropylcellulose, hypromellose, magnesium aluminometasilicate, magnesium stearate, and film coating containing the following inactive ingredients: hypromellose, titanium dioxide, triethyl citrate, and colloidal anhydrous silica.12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionPitavastatin competitively inhibits HMG-CoA reductase, which is a rate-determining enzyme involved with biosynthesis of cholesterol, in a manner of competition with the substrate so that it inhibits cholesterol synthesis in the liver. As a result, the expression of LDL-receptors followed by the uptake of LDL from blood to liver is accelerated and then the plasma TC decreases. Further, the sustained inhibition of cholesterol synthesis in the liver decreases levels of very low density lipoproteins.12.2 PharmacodynamicsIn a randomized, double-blind, placebo-controlled, 4-way parallel, active-comparator study with moxifloxacin in 174 healthy participants, LIVALO was not associated with clinically meaningful prolongation of the QTc interval or heart rate at daily doses up to 16 mg (4 times the recommended maximum daily dose).12.3 PharmacokineticsAbsorption: Pitavastatin peak plasma concentrations are achieved about 1 hour after oral administration. Both C max and AUC0-inf increased in an approximately dose-proportional manner for single LIVALO doses from 1 to 24 mg once daily. The absolute bioavailability of pitavastatin oral solution is 51%. Administration of LIVALO with a high fat meal (50% fat content) decreases pitavastatin C max by 43% but does not significantly reduce pitavastatin AUC. The C max and AUC of pitavastatin did not differ following evening or morning drug administration. In healthy volunteers receiving 4 mg pitavastatin, the percent change from baseline for LDL-C following evening dosing was slightly greater than that following morning dosing. Pitavastatin was absorbed in the small intestine but very little in the colon.Distribution: Pitavastatin is more than 99% protein bound in human plasma, mainly to albumin and alpha 1-acid glycoprotein, and the mean volume of distribution is approximately 148 L. Association of pitavastatin and/or its metabolites with the blood cells is minimal.Metabolism: Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8. The major metabolite inhuman plasma is the lactone which is formed via an ester-type pitavastatin glucuronide conjugate by uridine 5'-diphosphate (UDP) glucuronosyltransferase (UGT1A3 and UGT2B7).Excretion: A mean of 15% of radioactivity of orally administered, single 32 mg 14C-labeled pitavastatin dose was excreted in urine, whereas a mean of 79% of the dose was excreted in feces within 7 days. The mean plasma elimination half-life is approximately 12 hours.Race: In pharmacokinetic studies pitavastatin C max and AUC were 21 and 5% lower, respectively in Black or African American healthy volunteers compared with those of Caucasian healthy volunteers. In pharmacokinetic comparison between Caucasian volunteers and Japanese volunteers, there were no significant differences in C max and AUC.Gender: In a pharmacokinetic study which compared healthy male and female volunteers, pitavastatin C max and AUC were 60 and 54% higher, respectively in females. This had no effect on the efficacy or safety of LIVALO in women in clinical studies. Geriatric: In a pharmacokinetic study which compared healthy young and elderly (≥65 years) volunteers, pitavastatin C max and AUC were 10 and 30% higher, respectively, in the elderly. This had no effect on the efficacy or safety of LIVALO in elderly subjects in clinical studies.Renal Impairment: In patients with moderate renal impairment (glomerular filtration rate of 30 – 59 mL/min/1.73 m2) and end stage renal disease receiving hemodialysis, pitavastatin AUC0-inf is 102 and 86% higher than those of healthy volunteers, respectively, while pitavastatin C max is 60 and 40% higher than those of healthy volunteers, respectively. Patients received hemodialysis immediately before pitavastatin dosing and did not undergo hemodialysis during the pharmacokinetic study. Hemodialysis patients have 33 and 36% increases in the mean unbound fraction of pitavastatin as compared to healthy volunteers and patients with moderate renal impairment, respectively.。
培非格司亭中英文介绍
王婕 913103860408NEULASTA（PEGFILGRASTIM）|培非格司亭注射液1.Introduction(简介)【产地英文商品名】:NEULASTA－6mg/0.6ml/Syringe【原产地英文药品名】:PEGFILGRASTIM【中文参考商品译名】:纽拉思塔-6毫克/0.6毫升/支【中文参考药品译名】:培非格司亭【生产厂家中文参考译名】:安进【生产厂家英文名】:Amgen, IncAmgen Announces Novel Drugs for Antitumor Chemotherapy Side Effects of FGT (TM) (pegfilgrastim), a drug developed by the US Food and Drug Administration (FDA), has been approved by the US Food and Drug Administration (FDA) Approval. Amphetamycin, the chief executive of Amgen, says that pemetrexedin will make it easier for healthcare workers to prevent chemotherapy-induced neutropenia and its serious complications.The third drug approved by Amgen in the past six months will significantly improve the prognosis of chemotherapy patients and is expected to enter the market in early April.BUSINESS WIRE 2002年2月1日美国加州THOUSAND OAKS消息，安进公司宣布抗肿瘤化疗副作用新药培非格司亭(TM) (pegfilgrastim)通过美国食品与药品管理局（FDA）的审批。
26 阿昔洛韦、异丙啶、辛那卡塞特、植物二酮、间苯三酚、卡比多巴、倍他司汀、乐卡地平
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用途
结构式
阿昔洛韦杂质31
Acyclovir Impurity 31
2190509-40-9
10mg
25mg
50mg
100mg
更大规格请咨询
项目报批
纯度高于98%
异丙啶杂质7
Picaridin Impurity 7
25mg
50mg
100mg
更大规格请咨询Βιβλιοθήκη 项目报批纯度高于98%
乐卡地平杂质37
Lercanidipine Impurity 37
624-58-8
10mg
25mg
50mg
100mg
更大规格请咨询
项目报批
纯度高于98%
有Kou各q：类2标8准5品3对1照1品7和7杂5质2
10mg
25mg
50mg
100mg
更大规格请咨询
项目报批
纯度高于98%
卡比多巴杂质18
Carbidopa Impurity 18
85933-19-3
10mg
25mg
50mg
100mg
更大规格请咨询
项目报批
纯度高于98%
倍他司汀杂质7
Betahistine Impurity 7
88796-99-0
10mg
6214-01-3
10mg
25mg
50mg
100mg
更大规格请咨询
项目报批
纯度高于98%
辛那卡塞特杂质82
Cinacalcet Impurity 82
壳聚糖及其衍生物作为药物载体研究进展
壳聚糖及其衍生物作为药物载体研究进展1邬思辉1，苏政权21广东药学院药科学院，广州 (510006)2广东药学院公共卫生学院,广州 (510006)E-mail: wsh2709@摘要：壳聚糖及其衍生物是一种资源丰富、可生物降解的天然聚合物，具有生物相容性、高电荷密度、无毒性和粘膜粘附性，广泛应用于生物医学和药物制剂领域。
本文分别从壳聚糖及其衍生物在大分子药物载体、缓控释制剂及不同部位给药系统中应用进行了综述，表明壳聚糖及其衍生物是一种优良的药物传递载体和新型药用辅料。
关键词：壳聚糖；衍生物；药物载体；缓控释制剂；给药系统1．引言壳聚糖(chitosan，CTS)也称甲壳胺，是地球上仅次于纤维素的第二大生物多糖,其化学结构是D-氨基葡萄糖通过β-1，4-糖苷键结合而成，是甲壳素(chitin)的脱乙酰衍生物。
凡能溶于1%乙酸或1%盐酸的甲壳素可称为壳聚糖[1]。
CTS具有无毒、无刺激性、无致敏性和无致突变作用，是具有良好生物相容性和生物降解性的多聚阳离子，在药剂学领域的应用极为活跃，是天然的阳离子型给药载体。
CTS作为药物载体可以控制药物释放、延长药物疗效、降低药物毒副作用，可以提高疏水性药物对细胞膜的通透性和药物稳定性及改变给药途径，还可以加强制剂的靶向给药能力。
2．大分子药物载体生物大分子药物(如多肽、蛋白类、基因、酶类药物等)的口服给药往往存在多种制约因素，如：生物利用度低，容易失去活性，难以穿过体内屏障，口服基本无效等。
壳聚糖及其衍生物具有增强穿透作用及酶抑制作用，及已被证实的生物黏附特性和生物可降解性，使其成为生物大分子药物优良运送载体，并可增加此类药物在体内的吸收。
2.1疫苗微球制备技术在口服疫苗给药过程中被广泛应用，壳聚糖微球作为口服疫苗载体具有许多优良性能，必将成为口服疫苗载体的首选对象。
Jaganathan等[2]利用乳化交联法制备载有破伤风类毒素(TT)的壳聚糖微球，粒径小于10μm，稳定剂海藻糖能够保持抗原蛋白质的活性，微球的包封率也从未加入海藻糖前的40%提高到90%。
欧洲药典7.5版
INDEX
To aid users the index includes a reference to the supplement in which the latest version of a text can be found. For example : Amikacin sulfate...............................................7.5-4579 means the monograph Amikacin sulfate can be found on page 4579 of Supplement 7.5. Note that where no reference to a supplement is made, the text can be found in the principal volume.
English index ........................................................................ 4707
Latin index ................................................................................. 4739
EUROPEAN PHARMACOPபைடு நூலகம்EIA 7.5
Index
Numerics 1. General notices ................................................................... 7.5-4453 2.1.1. Droppers...................
药用辅料中英文对照
药用辅料中英文对照1 阿拉伯胶(Acacia)2 乙酰舒泛钾(Acesulfame Potassium)3 冰醋酸(Acetic Acid,Glacial)4 乙酰枸橼酸三丁酯(AcetyltributylCitrate)5 乙酰枸橼酸三乙酯(AcetyltriethylCitrate)6 人血白蛋白(Albumin)7 乙醇(Alcohol)8 海藻酸(Alginic Acid)9 脂肪族聚酯(Aliphatic Polyesters)10 阿力糖(Alitame)11 杏仁油(Almond Oil)12 维生素E(Alpha Tocopherol)13 氨溶液(Ammonia Solution)14 维生素C(Ascorbic Acid)15 棕榈酸维生素C酯(Ascorbyl Palmitate)16 阿司帕坦(Aspartame)17 绿坡缕石(Attapulgite)18 皂土(Bentonite)19 苯扎氯铵(Benzalkonium Chloride)20 苄索氯铵(Benzethonium Chloride)21 苯甲酸(Benzoic Acid)22 苯甲醇(Benzyl Alcohol)23 苯甲酸苄酯(Benzyl Benzoate)24 溴硝丙二醇(Bronopol)25 丁羟茴醚(Butylated Hydroxyanisole)26 丁羟甲苯(Butylated Hydroxytoluene)27 羟苯丁酯(Butylparaben)28 碳酸钙(Calcium Carbonate)29 无水磷酸氢钙(Calcium Phosphate,Dibasic Anhydrous)30 磷酸氢钙二水合物(Calcium Phosphate,Dibasic Dihydrate)31 磷酸钙(Calcium Phosphate,Tribasic)32 硬脂酸钙(Calcium Stearate)33 硫酸钙(Calcium Sulfate)34 低芥酸菜籽油(Canola Oil)35 卡波姆(Carbomer)36 二氧化碳(Carbon Dioxide)37 羧甲纤维素钙(Carboxymethylcellulose Calcium)38 羧甲纤维素钠(Carboxymethylcellulose Sodium)39 角叉菜胶(Carrageenan)40 蓖麻油(Castor Oil)41 氢化蓖麻油(Castor Oil,Hydro-genated)42 微晶纤维素(Cellulose,Microcr ystalline)43 粉状纤维素(Cellulose,Powdered)44 微粉硅胶微晶纤维素(Cellulose, Silicified Microcrystalline)45 醋酸纤维素(Cellulose Acetate)46 纤维醋法酯(Cellulose Acetate Phthalate)47 角豆胶(Ceratonia)48 十八十六醇(Cetostearyl Alcohol)49 西曲溴铵(Cetrimide)50 十六醇(Cetyl Alcohol)51 壳聚糖(Chitosan)52 氯己定(Chlorhexidine)53 三氯叔丁醇(Chlorobutanol)54 氯甲酚(Chlorocresol)55 一氯二氟乙烷(Chlorodifluoroe-thane)56 氟里昂(Chlorofluorocabons)57 对氯间二甲酚(Chloroxylenol)58 胆固醇(Cholesterol)59 枸橼酸(Citric Acid Monohydrate)60 胶态二氧化硅（微粉硅胶）(Colloidal Silicon Dioxide)61 着色剂(Coloring Agents)62 玉米油(Corn Oil)63 棉籽油(Cottonseed Oil)64 甲酚(Cresol)65 交联羧甲纤维素钠(Croscarmellose Sodium)66 交联聚维酮(Crospovidone)67 环糊精(Cyclodextrins)68 环甲基硅酮(Cyclomethicone)69 苯甲地那铵(Denatonium Benzoate)70 葡萄糖结合剂(Dextrates)71 糊精(Dextrin)72 葡萄糖(Dextrose)73 邻苯二甲酸二丁酯(Dibutyl Phthalate)74 癸二酸二丁酯(Dibutyl Sebacate)75 二乙醇胺(Diethanolamine)76 邻苯二甲酸二乙酯(Diethyl Phthalate)77 二氟乙烷(Difluoroethane)78 二甲硅油(Dimethicone)79 二甲醚(Dimethyl Ether)80 邻苯二甲酸二甲酯(Dimethyl Phthalate)81 二甲亚砜(Dimethyl Sulfoxide)82 多库酯钠(Docusate Sodium)83 依地酸（乙二胺四乙酸）(Edetic Acid)84 乙酸乙酯(Ethyl Acetate)85 乙基麦芽酚(Ethyl Maltol)86 油酸乙酯(Ethyl Oleate)87 乙基香草醛(Ethyl Vanillin)88 乙基纤维素(Ethylcellulose)89 硬脂酸棕榈酸乙二醇酯(Ethylene Glycol Palmitostearate)90 羟苯乙酯(Ethylparaben)91 果糖(Fructose)92 富马酸(Fumaric Acid)93 明胶(Gelatin)94 液体葡萄糖(Glucose,Liquid)95 甘油(Glycerin)96 山萮酸甘油酯(Glyceryl Behenate)97 单油酸甘油酯(Glyceryl Monooleate)98 单硬脂酸甘油酯(Glyceryl Monostearate)99 硬脂酸棕榈酸甘油酯(Glyceryl Palmitostearate)100 四氢呋喃聚乙二醇醚(Glycofurol)101 瓜耳胶(Guar Gum)102 七氟丙烷(HFC)(Heptafluoro-propane)103 海克西定(Hexetidine)104 烷烃类（HC) (Hydrocarbons)105 盐酸(Hydrochloric Acid)106 羟乙纤维素(Hydroxyethyl Cellulose)107 羟乙甲纤维素(Hydroxyethylmethyl Cellulose)108 羟丙纤维素(Hydroxypropyl Cellulose)109 低取代羟丙纤维素(Hydroxypropyl Cellulose,Low-substituted) 110 羟丙甲纤维素(Hypromellose)111 羟丙甲纤维素酞酸酯(Hypromellose Phthalate)112 咪唑烷脲(Imidurea)113 异丙醇(Isopropyl Alcohol)114 肉豆蔻酸异丙酯(Isopropyl Myristate) 115 棕榈酸异丙酯(Isopropyl Palmitate)116 白陶土(Kaolin)117 乳酸(Lactic Acid)118 拉克替醇(Lactitol)119 乳糖(Lactose)120 羊毛脂(Lanolin)121 含水羊毛脂(Lanolin,Hydrous)122 羊毛醇(Lanolin Alcohols)123 卵磷脂(Lecithin)124 硅酸镁铝(Magnesium Aluminum Silicate) 125 碳酸镁(Magnesium Carbonate)126 氧化镁(Magnesium Oxide)127 硅酸镁(Magnesium Silicate)128 硬脂酸镁(Magnesium Stearate)129 三硅酸镁(Magnesium Trisilicate)130 苹果酸(Malic Acid)131 麦芽糖醇(Maltitol)132 麦芽糖醇溶液(Maltitol Solution)133 麦芽糖糊精(Maltodextrin)134 麦芽酚(Maltol)135 麦芽糖(Maltose)136 甘露醇(Mannitol)137 中链脂肪酸甘油三酯(Medium-chain Triglycerides) 138 葡甲胺(Meglumine)139 薄荷脑(Menthol)140 甲基纤维素(Methylcellulose)141 羟苯甲酯(Methylparaben)142 液体石蜡(Mineral Oil)143 轻质液体石蜡(Mineral Oil,Light)144 液体石蜡羊毛醇(Mineral Oil and Lanolin Alcohols) 145 单乙醇胺(Monoethanolamine)146 谷氨酸一钠(Monosodium Glutamate)147 硫代甘油(Monothioglycerol)148 氮(Nitrogen)149 一氧化二氮(Nitrous Oxide)150 油酸(Oleic Acid)151 橄榄油(Olive Oil)152 石蜡(Paraffin)153 花生油(Peanut Oil)154 凡士林(Petrolatum)155 凡士林羊毛醇(Petrolatum and Lanolin Alcohols) 156 苯酚(Phenol)157 苯氧乙醇(Phenoxyethanol)158 苯乙醇(Phenylethyl Alcohol)159 醋酸苯汞(Phenylmercuric Acetate)160 硼酸苯汞(Phenylmercuric Borate)161 硝酸苯汞(Phenylmercuric Nitrate)162 磷酸(Phosphoric Acid)163 波拉克林钾(Polacrilin Potassium)164 泊洛沙姆(Poloxamer)165 葡聚糖(Polydextrose)166 聚乙二醇(Polyethylene Glycol)167 聚氧乙烯(Polyethylene Oxide)168 聚(甲基)丙烯酸树脂(Polymethacr-ylates)169 聚氧乙烯烷基醚(Polyoxyethylene Alkyl Ethers)170 聚氧乙烯蓖麻油衍生物(Polyoxyeth-ylene Castor Oil Derivatives)171 聚山梨酯(Polyoxyethylene Sorbitan Fatty Acid Esters) 172 硬脂酸聚氧乙烯酯(Polyoxyethylene Stearates)173 聚醋酸乙烯酞酸酯(Polyvinyl Acetate Phthalate)174 聚乙烯醇(Polyvinyl Alcohol)175 苯甲酸钾(Potassium Benzoate)176 碳酸氢钾(Potassium Bicarbonate)177 氯化钾(Potassium Chloride)178 枸橼酸钾(Potassium Citrate)179 氢氧化钾(Potassium Hydroxide)180 焦亚硫酸钾(Potassium Metabisulfite)181 山梨酸钾(Potassium Sorbate)182 聚维酮(Povidone)183 丙酸(Propionic Acid)184 没食子酸丙酯(Propyl Gallate)185 碳酸丙烯酯(Propylene Carbonate)186 丙二醇(Propylene Glycol)187 海藻酸丙二醇酯(Propylene Glycol Alginate)188 羟苯丙酯(Propylparaben)189 糖精(Saccharin)190 糖精钠(Saccharin Sodium)191 芝麻油(Sesame Oil)192 虫胶(Shellac)193 二氧化硅二甲硅油(Simethicone)194 海藻酸钠(Sodium Alginate)195 抗坏血酸钠(Sodium Ascorbate)196 苯甲酸钠(Sodium Benzoate)197 碳酸氢钠(Sodium Bicarbonate)198 氯化钠(Sodium Chloride)199 枸橼酸钠二水合物(Sodium Citrate Dihydrate)200 环拉酸钠(Sodium Cyclamate)201 氢氧化钠(Sodium Hydroxide)202 月桂硫酸钠(十二烷基硫酸钠)(Sodium Lauryl Sulfate) 203 焦亚硫酸钠(偏亚硫酸钠)(Sodium Metabisulfite)204 磷酸氢二钠(Sodium Phosphate,Dibasic)205 磷酸二氢钠(Sodium Phosphate ,Monobasic)206 丙酸钠(Sodium Propionate)207 羧甲淀粉钠(Sodium Starch Glycolate)208 硬脂富马酸钠(Sodium Stearyl Fumarate)209 山梨酸(Sorbic Acid)210 山梨坦酯Sorbitan Esters(Sorbitan Fatty Acid Esters) 211 山梨醇(Sorbitol)212 大豆油(Soybean Oil)213 淀粉(Starch)214 预胶化淀粉(Starch,Pregelatinized)215 灭菌玉米淀粉(Starch,Sterilizable Maize)216 硬脂酸(Stearic Acid)217 硬脂醇(Stearyl Alcohol)218 羟糖氯(Sucralose)219 蔗糖(Sucrose)220 可压性蔗糖(Sugar,Compressible)221 蔗糖粉(Sugar,Confectioner’s)222 蔗糖球形颗粒(Sugar Spheres)223 硫酸(Sulfuric Acid)224 葵花籽油(Sunflower Oil)225 氢化植物油（硬脂）栓剂基质(Sup-pository Bases,Hard Fat) 226 滑石粉(Talc)227 酒石酸(Tartaric Acid)228 四氟乙烷(HFC)(Tetrafluoroe-thane)229 硫柳汞(Thimerosal)230 二氧化钛(Titanium Dioxide)231 西黄蓍胶(Tragacanth)232 海藻糖(Trehalose)233 三醋汀(Triacetin)234 枸橼酸三丁酯(Tributyl Citrate)235 三乙醇胺(Triethanolamine)236 枸橼酸三乙酯(Triethyl Citrate)237 香草醛(Vanillin)238 氢化植物油(Vegetable Oil,Hydrogenated)239 水(Water)240 阴离子乳化蜡(Wax,Anionic Emulsifying)241 巴西棕榈蜡(Wax,Carnauba)242 十六醇酯蜡(Wax,Cetyl Esters)243 微晶蜡(Wax,Microcrystalline)244 非离子乳化蜡(聚西托醇乳化蜡)(Wax,Nonionic Emulsifying) 245 白蜡(Wax,White)246 黄蜡(Wax,Yellow)247 黄原酸胶(Xanthan Gum)248 木糖醇(Xylitol)796249 玉米朊（玉米蛋白）(Zein)250 硬脂酸锌(Zinc Stearate)。
【药品名】比伐卢定 【英文名】Bivalirudin
【药品名】比伐卢定【英文名】Bivalirudin【别名】比伐芦定；Angiomax【剂型】注射剂：250mg。
【药理作用】本品是一种合成的抗凝药，是天然产生的水蛭素的类似物，是由20个氨基酸组成的多肽，能高亲和地与凝血酶结合而特异地抑制凝血酶活性，抑制凝血酶所催化和诱导的反应。
比伐卢定不仅能与血浆游离的凝血酶结合，也能与血块相连的凝血酶结合，此结合是可逆的，且不需要AT-Ⅲ的存在。
比伐卢定具有较强的抗凝作用，对多种动物动脉和静脉模型均有抗血栓作用。
比伐卢定可使部分凝血活酶时间(APTT)、凝血酶时间(PT)和活化凝血时间(ACT)延长。
【药动学】比伐卢定不结合于血浆蛋白(除了凝血酶)，在静推比伐卢定时，剂量与血浆浓度呈线性关系。
静推比伐卢定1mg/kg和静脉滴注每小时2.5mg/kg 4h后，比伐卢定血浆浓度达稳态。
比伐卢定是通过肾脏以蛋白水解方式中从血浆中清除，肾功能正常者的清除半衰期约为25min，中、重度的肾功能不全患者的清除半衰期延长。
25%的比伐卢定可被透析掉。
须监测APTT。
本品静脉注射后，立即出现抗凝作用，可见到PT，APTT的时间延长。
停药后1～2h，PT就可恢复正常范围。
【适应症】不稳定型心绞痛患者接受PTCA术；经皮干预冠脉的急性缺血性并发症。
【禁忌症】1.对本品过敏者、哺乳者禁用。
2.对任何出血患者禁用。
【注意事项】用药后，尤其是中、重度的肾功能不全患者应注意监测APTT值。
孕妇及哺乳期妇女用药，由于对妊娠及哺乳期妇女没有足够的临床研究，对妊娠妇女只有在必须用药时才可应用。
动物研究显示，本品可进入乳汁，所以应以用药对哺乳期妇女的重要性来决定是停止哺乳还是停药。
儿童用药，尚没有儿童用药的安全性资料。
老年患者用药，没有必要对老年人调整剂量。
药物过量，若应用比伐卢定过量，无特效药物纠正，须停用比伐卢定。
出血风险增高者慎用，中重度肾功能不全者不必减少开始的用量，但应减少最后20h的输注用量，并监测激活凝血时间(ACT)。
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Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
Pitavastatin Calcium is a competitive inhibitor of the enzyme HMGCR (HMG–CoA reductase) results in a reduction in LDL cholesterol synthesis
Target: HMG–CoA reductase
Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins, marketed in the United States under the trade name Livalo. Like other statins, it is an inhibitor of HMG–CoA reductase, the enzyme that catalyses the first step of cholesterolsynthesis. It has been available in Japan since 2003, and is being marketed under licence in South Korea and in India. It is likely that pitavastatin will be approved for use in hypercholesterolaemia (elevated levels of cholesterol in the blood) and for the prevention of cardiovascular disease outside South and Southeast Asia as well. In the US, it received FDA approval in 2009. Most statins are metabolised in part by one or more hepatic cytochrome P450 enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). Pitavastatin appears to be a substrate of CYP2C9, and not
CYP3A4 (which is a common source of interactions in other statins). As a result, pitavastatin is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines. References:
[1]. Mukhtar RY, et al. Pitavastatin. Int J Clin Pract. 2005 Feb;59(2):239–52.
[2]. Kajinami K, et al. Pitavastatin: efficacy and safety profiles of a novel synthetic HMG–CoA reductase inhibitor. Cardiovasc Drug Rev. 2003 Fall;21(3):199–215.
Product Name:
Pitavastatin (Calcium)Cat. No.:
HY-B0144CAS No.:
147526-32-7Molecular Formula:
C 25H 23FNO 4 . 1/2 Ca Molecular Weight:
440.49Target:
HMG–CoA Reductase (HMGCR); Autophagy Pathway:
Metabolic Enzyme/Protease; Autophagy Solubility:
10 mM in DMSO
Caution: Product has not been fully validated for medical applications. For research use only.
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