米泊美生钠注射液-KYNAMRO-(mipomersen-sodium)-FDA药品说明书翻译

FULLPRESCRIBINGINFORMATIONWARNING:RISKOFHEPATOTOXICITY警告：肝毒性风险KYNAMROcancauseelevationsintransaminases.IntheKYNAMROclinicaltrialinpatientswithHoFH,4(12%)ofthe34patientstreatedwithKYNAMROcomparedwith0%ofthe17patientstreatedwithplacebohadatleastoneelevationinalanineaminotransferase(ALT)≥3xupperlimitofnormal(ULN).Therewerenoconcomitantclinicallymeaningfulelevationsoftotalbilirubin,internationalnormalizedratio(INR)orpartialthromboplastintime(PTT)[seeWarningsandPrecautions(5.1)].本药可导致氨基转移酶升高。在本药的临床试验中，34名接受本药治疗纯合子型家族性高胆固醇血症(HoFH)的患者，有4名(12%)患者至少出现1次丙氨酸氨基转移酶(ALT)≥3倍正常值上限(ULN)，而17名接受安慰剂的患者无（0%）人出现。未同时出现有临床意义的总胆红素、国际标准化比值(INR)或部分凝血活酶时间(PPT)升高。KYNAMROalsoincreaseshepaticfat,withorwithoutconcomitantincreasesintransaminases.Inthetrialsinpatientswithheterozygousfamilialhypercholesterolemia(HeFH)andhyperlipidemia,themedianabsoluteincreaseinhepaticfatwas10%after26weeksoftreatment,from0%atbaseline,measuredbymagneticresonanceimaging(MRI).Hepaticsteatosisisariskfactorforadvancedliverdisease;includingsteatohepatitisandcirrhosis[seeWarningsandPrecautions(5.1)].本药还可增加肝脏脂肪，伴或不伴氨基转移酶升高。在本药治疗杂合子型家族性高胆固醇血症(HeFH)和高脂血症的临床试验中，接受本药治疗26周后，由核磁共振成像(MRI)测定，肝脏脂肪平均绝对值由基线的0%增加至10%。肝脏脂肪变性是肝病晚期(包括脂肪肝和肝硬化)的风险因素之一。MeasureALT,AST,alkalinephosphatase,andtotalbilirubinbeforeinitiatingtreatmentandthenALT,ASTregularlyasrecommended.Duringtreatment,withholdthedoseofKYNAMROiftheALTorASTare≥3xULN.DiscontinueKYNAMROforclinicallysignificantlivertoxicity[seeDosageandAdministration(2.3)andWarningsandPrecautions(5.1)].开始治疗前应检测ALT、AST、碱性磷酸酶和总胆红素，之后建议定期检测ALT和AST。治疗期间，如ALT或AST≥3倍ULN，应暂停用药。如出现临床显著的肝毒性，应停药。Becauseoftheriskofhepatotoxicity,KYNAMROisavailableonlythrougharestrictedprogramunderaRiskEvaluationandMitigationStrategy(REMS)calledtheKYNAMROREMS[seeWarningsandPrecautions(5.2)].由于肝毒性风险，本药只能通过被称为KYNAMROREMS计划的风险评估和减低计划(REMS)限制的计划获取。1INDICATIONSANDUSAGE适应症和用途KYNAMROTMisindicatedasanadjuncttolipid-loweringmedicationsanddiettoreducelowdensitylipoprotein-cholesterol(LDL-C),apolipoproteinB(apoB),totalcholesterol(TC),andnon-highdensitylipoprotein-cholesterol(non-HDL-C)inpatientswithhomozygousfamilialhypercholesterolemia(HoFH).本药作为降脂药物和饮食疗法的辅助治疗，用于纯合子型家族性高胆固醇血症(HoFH)患者，以降低低密度脂蛋白胆固醇(LDL-C)、载脂蛋白B(apoB)、总胆固醇(TC)和非高密度脂蛋白胆固醇(non-HDL-C)。LimitationsofUse使用限制ThesafetyandeffectivenessofKYNAMROhavenotbeenestablishedinpatientswithhypercholesterolemiawhodonothaveHoFH.尚未建立非HoFH高胆固醇血症患者使用本药的安全性和有效性。TheeffectofKYNAMROoncardiovascularmorbidityandmortalityhasnotbeendetermined.尚不确定本药对心血管病发病率和死亡率的影响。ThesafetyandeffectivenessofKYNAMROasanadjuncttoLDLapheresishavenotbeenestablished;therefore,theuseofKYNAMROasanadjuncttoLDLapheresisisnotrecommended.尚未建立采用LDL血浆置换分离法时合用本药的安全性和有效性，故不推荐采用LDL血浆置换分离法时合用本药。2DOSAGEANDADMINISTRATION用法用量2.1GeneralDosingInformation一般给药信息BeforebeginningtreatmentwithKYNAMRO,measuretransaminases(ALT,AST),alkalinephosphatase,andtotalbilirubin[seeWarningsandPrecautions(5.1)].开始治疗前应检测ALT、AST、碱性磷酸酶和总胆红素。TherecommendeddoseofKYNAMROis200milligrams(mg)onceweeklyasasubcutaneousinjection.本药的推荐剂量为一次200mg，一周1次，皮下注射。KYNAMROisintendedforsubcutaneoususeonly.Donotadministerintramuscularlyorintravenously.本药仅用于皮下注射，禁止肌内或静脉注射。Theinjectionshouldbegivenonthesamedayeveryweek,butifadoseismissed,theinjectionshouldbegivenatleast3daysfromthenextweeklydose注射应于每周同一日进行，但如错过用药时间，应于下一剂量至少3日前注射。AfterinitiationofKYNAMROtherapylipidlevelsshouldbemonitoredatleastevery3monthsforthefirstyear.MaximalreductionofLDL-CmaybeseenwithKYNAMROtherapyafterapproximately6months(basedonthetimetosteadystateseeninclinicalstudies).Healthcareprovidersshouldassessthepatient’sLDL-Clevelafter6monthstodetermineiftheLDL-CreductionachievedwithKYNAMROissufficientlyrobusttowarrantthepotentialriskoflivertoxicity.开始治疗后第1年，应至少每3个月检测血脂水平。用药6个月后LDL-C可降至最低水平(基于临床试验稳定状态时间)，故用药6个月后应评估患者LDL-C水平，确定LDL-C降低是否足够确定肝毒性的潜在风险。2.2Administration给药方法Eachvialorpre-filledsyringeofKYNAMROprovides200mgofmipomersensodiuminadeliverablevolumeof1milliliter(mL)ofsolutionandisintendedforsingle-useonly.每小瓶或预填充注射器中含200mg(即1ml溶液)米泊美生钠，仅供一次性使用。TheKYNAMROvialorpre-filledsyringeshouldberemovedfrom2-8°C(36-46°F)refrigeratedstorageandallowedtoreachroomtemperatureforatleast30minutespriortoadministration.用药前，应将本药小瓶或填充注射器从2-8℃冷藏环境中取出，并于用药前30分钟置于室温。Parenteraldrugproductsshouldbeinspectedvisuallypriortoadministration.Ifthesolutioniscloudyorcontainsvisibleparticulatematter,thecontentsmustnotbeinjectedandtheproductshouldbereturnedtothepharmacy.用药前应目测检查，如溶液浑浊或含颗粒物，不得注射，并将产品退回药房。Thefirstinjectionadministeredbythepatientorcaregivershouldbeperformedundertheguidanceandsupervisionofanappropriatelyqualifiedhealthcareprofessional.患者或护理人员的初次注射应在专业人士的指导和监督下进行。KYNAMROshouldbeinjectedintotheabdomen,thighregion,orouterareaoftheupperarm.KYNAMROshouldnotbeinjectedinareasofactiveskindiseaseorinjurysuchassunburns,skinrashes,inflammation,skininfections,activeareasofpsoriasis,etc.Areasoftattooedskinandscarringshouldalsobeavoided.本药可于腹部、大腿、上臂外侧注射。不得于活动性皮肤病或损伤处注射，如晒伤、皮疹、炎症、皮肤感染、银屑病活动区域，也应避免在纹身或结疤部位注射。2.3AdjustmentsforPatientsDevelopingTransaminaseElevations氨基转移酶升高患者剂量调整Table1summarizesrecom