恩度基本知識(shí)說(shuō)明書(shū)電子版

1、商品名稱：恩商品名稱：恩binantHumanin漢語(yǔ)拼音：ChongzuRenXueguanneipiyizhisu 本品為無(wú)色澄明液體pH5.50.5有 例27者生 改傳 消化系統(tǒng)反應(yīng)：偶見(jiàn)腹瀉，肝功能異常，主要包括無(wú)癥狀性轉(zhuǎn)氨酶升高，黃疸，主要為輕度及中度，罕 例【】 有嚴(yán)重心臟病或病史者，包括：的充血性心力衰竭病史、高危性不能控制的心率失常、需藥物【】 有嚴(yán)重心臟病或病史者，包括：的充血性心力衰竭病史、高危性不能控制的心率失常、需藥物 本30210 mg/m2（4.8105 33.6105 U/m2）或連續(xù) 28 天本品臨床研究中，單次靜脈滴注給藥量達(dá)脈滴注 mg/m2（1.21054

2、.8105 U/m2）時(shí)出現(xiàn)反應(yīng)見(jiàn)【不良反應(yīng)】項(xiàng)下描述的情況，尚無(wú)單藥治療：本品的A 期臨床試驗(yàn)（單藥）采用單藥、隨機(jī)、開(kāi)放、對(duì)照、多中心的研究方法，主要評(píng)價(jià)本7.5mg/m2（1.2105 U/m2）和15mg/m2（2.4105 U/m2）的量效關(guān)系和安全性的差異，從其中 60 例患者完成了療效評(píng)估，結(jié)果見(jiàn)表 1。7.5 15 P有 效 率（） 注：有效率（CRPR總例數(shù)100）、臨床受益率（CRPRMRSD總例數(shù)試驗(yàn)結(jié)果表明，7.5mg/m2（1.2105 U/m2）劑量組和15mg/m2（2.4105 U/m2）劑量組在療效和安全性7.5mg/m2作為臨床常規(guī)使用劑量評(píng)價(jià)療效，試驗(yàn)組對(duì)

3、照組322164 例，初治復(fù)治347139 例。結(jié)果見(jiàn)表 2。NPNPNP有效率P（）P膜 肺 6 長(zhǎng)期毒性：大鼠的長(zhǎng)期毒性試驗(yàn)顯示，連續(xù)腹腔注射3、6、12mg/kg/day（4.8104、9.6104 、 (167.9mg/m2)，30mg（4.8105 U）/kg/day503.7mg/m2)三個(gè)劑量組共9月，各組獼猴體征、外觀行為、 U）/kg/day (503.7 mg/m2)的劑量范圍內(nèi)連續(xù)靜9 個(gè)月，未見(jiàn)明顯毒性反應(yīng)，為安全劑量。mg（4.8105 U）60 mg（9.6105 U）/m2，120min120mg（19.2105U）210mg（33.6105 U）/m2（1、21

4、1.75 mg/m2 19.2105U/m2）劑量范圍于正腫瘤患在給藥 P 值P 值1生存P 值例受試患者中，治療組 20 例，對(duì)照組 11 例，結(jié)果治療組 2 例出現(xiàn)顯示抗本品IgA 陽(yáng)性，產(chǎn)生時(shí)間分別32天、241His-tagIgA性，對(duì)2顯示IgG性，滴度均110，其余患者治療。試行標(biāo)準(zhǔn)國(guó)藥準(zhǔn)字生物工(YantaiMedgenn：，6383080免：ApprovedonSeptember12,RevisedJune19,PreparationguideforusebinantHumaninReadtheentirecontentspriortothepreparationofEndos

5、taranduseunderdoctors【Drug names】 GenericName:binantHumaninTradeApprovedonSeptember12,RevisedJune19,PreparationguideforusebinantHumaninReadtheentirecontentspriortothepreparationofEndostaranduseunderdoctors【Drug names】 GenericName:binantHumaninTradeName: EnglishbinantHumanin【NamePinyin):ChongzuRenXue

6、guanneipiyizhisuZhusheye MainbinantHuman e,Aceticacid,Excipients：SoddiumColorlesstransparentliquid.pHENDOSTARor hemotherapyregimenisusedtotreatStageIII/IVNSCLCpatientseitherThisindicationisbasedonacompletedmulti-cent 15mg/3ml/vial (2.4105 U/【DoseandadministrationhaseIIIclinicaltrial (seeAddravenousl

7、yatuniformspeedforAtcombinedadministrationhemotherapyregimen,ENDOSTARisadministeredat7.5mg/m2 (1.2105U/m2)onceadayduringDay114oftreatmentcycle,andthencontinuesthetreatment cycle only after the rest for k (generally 24 treatment cycles). The n mendedtoproperlyextenditsadministrationtimeinclinicalappl

8、icationwith of patients. heDuringPhaseIIIIclinicaltrial,ENDOSTARisadministeredin470advancedNSCLCpatients.The frequentadversereactions(1-10%)mainlyoccurredonheart,andrareadversereactions(0.1-1%)mainly occurred in digestive system and skin/annexa allergy.1.Heart:Attheearlystageofadministration,tientsh

9、avemildfatigue,chestand ostcases, thesesymptoms may improveenough so asnottoinfluence administrationcontinuationafterthesymptomatictreatment.Buttheycanpersisttodiscontinuethe administration in very few cases. A minority of cases had to stop the drug for the continuing above-mentionedsymptoms.30patie

10、nts(6.38%)haveDegreeI/IIormild/moderatecardiologicadverseto thepatientslife.6.4ofthesecaseshavemoreevidentbutreversiblesymptoms,whichnotinfluencetheadministrationcontinuationleviatewithoutanysymptomaticOnly2.1ofthecases stopthetreatmentduetoadversehepatientswithcoronaryheartdiseaseand,ENDOSTARcauses

11、thefollowingfrequentcardiologicfor the patient withcardiologicadversereactions during clinicalapplication.Thepatientpreviousseriousheart diseases mustuseENDOSTARcarefullyunder the guidanceof 2. Digestive System: Rare diarrhea and liver dysfunction (mainly symptom-free transaminase elevationandjaundi

12、ce).Alltheseadversereactionsaremainlymild/moderatebutrarelyserious.Most arereversibleandmildcasesdonotrequirefor the patient withcardiologicadversereactions during clinicalapplication.Thepatientpreviousseriousheart diseases mustuseENDOSTARcarefullyunder the guidanceof 2. Digestive System: Rare diarr

13、hea and liver dysfunction (mainly symptom-free transaminase elevationandjaundice).Alltheseadversereactionsaremainlymild/moderatebutrarelyserious.Most arereversibleandmildcasesdonotrequiresymptomatictreatment;Moderateorseriouscasesmayalleviatedthroughtheslowingofspeedorthroughthepropersymptomatictrea

14、tmentdrugwithdrawal;andonlyfewcasesrequiresymptomatictreatmentbutgenerallyhavenoinfluenceon administration continuation.3. Skin/Annexa:Theallergymainlyincludesreversiblesystemicpanieditching vableafterdrug withdrawal) and mostlymild/moderatefever and Nodeathrelatedtoadversereactionswasobserved ENDOS

15、TAR-treated patients.Use hepatientwithheart/renal2.Use carefullyforthepatientwith existing or previous seriousheart diseases,congestiveheartfailure,high-riskuncontrollablearrhythmia,ctorisrequiring ECG monitoring performedforthepatientswith cardiologicadverse3.Thisproductiscolorlesstransparentliquid

16、,andmustnotbeusedincaseofabnormalities (such as turbidity and sediment), broken packaging vial and expired.【PregnancyandionThus,useonly undertheclose 【PediatricuseofNopreviousclinicaltrialonitsadministrationinpediatricpatients.Usedonlyifis yneededandonlyunder the guidanceof 【GeriatricuseUseonlyunder

17、thecloseobservationofphysi heart disease.【Noprevioussystematicresearchonits donot mix with otherdrugsor eractionwithotherdrugs.Duringtheclinicalapplication, sibly influencing its pH value.hisclinicaltrial,theabove-mentionedadversereactionsoccurafterthedripof30210mg/m2 (4.810533.6105U/m2)orafterthe r

18、avenous drip of 【Clinicalstudiesof Medical ,leda research teamto ly conducta multi-centerclinicalSingle-drug Administration: clinicaltrial(single-drugadministration)adoptsrandomlycontrolled,open-labeledandmulti-centerethod.ItmainlyassessestheofENDOSTAR,comparesthedose-efficacyrelationandsafetydiffer

19、enceof7.5mg/m2 (1.2105U/m2)and 15mg/m2 (2.4105U/m2),andthusdeterminestheoptimumeffectivedoseforclinicalapplication.subjectsareretreated tumorpatientspathologicallyand/orcytologically diagnosedyg cancer (NSCLC). The subjects are dividedo7.5mg/m2 and15mg/m2 dosegroupat ravenous drip for 312h once a da

20、y continuously for 28d respectively. After the completion ofadministration,theefficacy isassessedaccordingtothe EfficacyEvaluationCriteriononSolid(WHO). Atotalof8 hospitalshistrial toobserve68NSCLCpatients,amongTable1Efficacyafter Single-drug7.5 15 Value Number ofResponserate33Clinicalbenefitrateto

21、progress(TTP,Asshownbytestresults,7.5mg/m2 (1.2105U/m2)dosegroupand15mg/m2 (2.4105U/m2)dosearesignificantlydifferentinefficacyandsafety.Thus,7.5mg/m2 is Combinationtreatment:A7.5 15 Value Number ofResponserate33Clinicalbenefitrateto progress(TTP,Asshownbytestresults,7.5mg/m2 (1.2105U/m2)dosegroupand

22、15mg/m2 (2.4105U/m2)dosearesignificantlydifferentinefficacyandsafety.Thus,7.5mg/m2 is Combinationtreatment:Arandomlycontrolled,open-labeledandmulti-mendedasroutinehaseIIItrialismadeonthecombinedadministrationofENDOSTARandNPregimenin493advancedNSCLCpatients. Administrationregimenoftestgroup:25mg/m2 N

23、VBatDay1andDay5;30mg/m2 DDPatDay2,Day3,and Day 4; and 7.5mg/m2 (1.2105U/m2) ENDOSTARcontinuouslyduring Day 114.Administrationregimenof controlgroup:25mg/m2 NVBatDay1andDay5;30mg/m2 DDPatDay2,Day3,andDay4;andnormalclinical benefit rate （CRPRMRSDtotal cases100）, TTP, median survive time, one-year surv

24、ivalrate,qualityoflife(QOL)andsafety.Thereare486caseswithevaluableefficacy,i.e. testgroup:controlgroup=322:164(cases),anduntreated:pretreated=347:139(cases).(Table2)Table2 EfficacyofChemotherapy+ 【Pharmacologyandtoxicology1.PharmacologicalRh-angiogenesisendothelialcells, inhibitstheformationof tumor

25、newblood , obstructsnutritionsupplyof tumorcells,andthusinhibits theproliferation ormetastasisof Asshownbyinvitrotestresults,ENDOSTARinhibitsthemetastasisofHHECandtheformationof Tube,significantlyinhibitstheangiogenesisofchickenembryoallantoicmembrane.Thus,ENDOSTAR suppressesangiogenesis invitro toa

26、certainextent.In addition,itinhibits thegrowthofgadenocarcinoma cellsSPC-A4to acertainTotalNumberof Cases(untreated, n=347)Second-LineTreatment (pretreated,n= NP +NP+ NP +NP+ NP +NP+ value benefitrate (%) value P value Pvalue Pvalue As shownbyinvivotestresults,ENDOSTARhasextensive effectsofinhibitin

27、gthemousem Bel7402 livercancer,Helacervicalcarcinoma,SMMC-77212.Toxicologicalravenousinjectionof1.5,3and6mg/kg(2.4104 -GeneralPharmacology:Afterand9.6104U/kg)(low,mediumandhighdosegroup),suchparametersasbloodpre re,respiration, As shownbyinvivotestresults,ENDOSTARhasextensive effectsofinhibitingthem

28、ousem Bel7402 livercancer,Helacervicalcarcinoma,SMMC-77212.Toxicologicalravenousinjectionof1.5,3and6mg/kg(2.4104 -GeneralPharmacology:Afterand9.6104U/kg)(low,mediumandhighdosegroup),suchparametersasbloodpre re,respiration, activity frequency of mouse is not influenced.rritonealinjectionof0.5ml/guine

29、a-pig (0.036mg/ml)everyotherday for3timesandthenthe1ml/guinea-pig(0.036mg/ml)14dand21dafteradministration;dnoevidentirritantreactions(suchasvasodila changes (suchasvascularwall thickening) invenousionandredswelling)ormorphological ion test.6ofn450.5mg（225.2510 U）/kgafterAcuteToxicity:Mousehadaritone

30、aladministrationofritonealinjection of 3,6,and12mg/kg/day(4.8104, 9.6104, of r19.2104U/kg/day)for45drespectively,allthesethreedosegroupsarenotsignificantlyg,brain,stomach,estine, uterusandAsshownbylong-termtoxicitytestonbeagledog,afterthe2,10and25mg/kg/day(3.2104,16.0104,and40.0104U/kg/day)forksresp

31、ectively,dogdoesveevidenttoxicreactionsansordelayedtoxicreactions,butonlytheadversereactionofelevatedreticuloerythrocytewhichisreversibleafterthedrugAsshownbylong-termtoxicitytestonrhesus,aftertheravenousinjectionof(4.8104U)/kg/day (50.4mg/m2), 10mg(1.6105U)/kg/day (167.9mg/m2), and 30mg (4.8105U)/k

32、g/day (503.7mg/m2)continuouslyfor9monthsrespectively,eachdosegrouphadnoevidentabnormalchangeinvitalsigns,appearancebehavior,andactivities;itsexaminationresultsfluctuatedrangeofnormal valueforweight,ake,andhematological/bloodexamination(i.e.noevidentimpairmentofliverandrenalfunction;i fat,andglucosem

33、etabolism;anditisnotsignificantlydifferentindbasicallynormalprotein, ancoefficientandhaddose-relatedabnormalchangeaccordingtothehistopathologicalresults.Inbrief,noevidentravenousinjectionofn30mg(4.8105U)/kg/day,reactionsoccurafterthechdose rangeis safeforAftertheravenousdripof30mg(4.8105U)/m2 and60m

34、g(9.6105U)/m2 within30minaspeedof1and2mg/m2/minrespectively)andof120mg(19.2105U)/m2 and210mg(33.6105U)/m2 120min(ataspeedof1and1.75mg/m2/minrespectively)inhealthteer,ENDOSTARhasaclearancehalf-life2humanbody, ENDOSTARfollowsy the linearpharmacokineticshe doserange 30120mg/m2(4.810519.2105U/m2).Thelin

35、earatdifferenttotaldose,drip concentration level.speedand time,which can influenceAUCumorpatient,ENDOSTARshowser-individualdifferenceindrugconcentration-timeaftertheravenousdripwithin2hcontinuouslyfor28d.Theminimumconcentrationtendsincreasecontinuouslywiththeincrease in administrationtimes,andbothtotaldoseanddrip can influence both the peak and trough concentrations.After ravenousadministrationof in normalmouse, the drug concentrationishighestninplasma,anduscle,fat,andbrain.AfterravenousthesystemicdistributionofENDOSTARissimilartinnormalmouse