Abra ane 白蛋白紫杉醇 FDA说明书

HIGHLIGHTSOFPRESCRIBINGINFORMATIONThesehighlightsdonotincludealltheinformationneededtouseABRAXANEsafelyandeffectively.SeefullprescribinginformationforABRAXANE.ABRAXANE®forInjectableSuspension(paclitaxelprotein-boundparticlesforinjectablesuspension)(albumin-bound)InitialU.S.Approval:2005WARNING:NEUTROPENIASeefullprescribinginformationforcompleteboxedwarning.•DonotadministerABRAXANEtherapytopatientswithbaselineneutrophilcountsoflessthan1,500cells/mm3.(4)•Itisrecommendedthatfrequentperipheralbloodcellcountsbeperformedtomonitortheoccurrenceofbonemarrowsuppression.(4,5.1,6.1,6.2,6.3)DONOTSUBSTITUTEFORORWITHOTHERPACLITAXELFORMULATIONS.--------------------------RECENTMAJORCHANGES-------------------------­•IndicationsandUsage(1.3) 09/2013•DosageandAdministration(2.3,2.5) 09/2013• WarningsandPrecautions,HematologicEffects(5.1),NervousSystem(5.2),Sepsis(5.3),Pneumonitis(5.4)09/2013--------------------------INDICATIONSANDUSAGE---------------------------­ABRAXANEisamicrotubuleinhibitorindicatedforthetreatmentof:• Metastaticbreastcancer,afterfailureofcombinationchemotherapyformetastaticdiseaseorrelapsewithin6monthsofadjuvantchemotherapy.Priortherapyshouldhaveincludedananthracyclineunlessclinicallycontraindicated.(1.1)• Locallyadvancedormetastaticnon-smallcelllungcancer(NSCLC),asfirst-linetreatmentincombinationwithcarboplatin,inpatientswhoarenotcandidatesforcurativesurgeryorradiationtherapy.(1.2)• Metastaticadenocarcinomaofthepancreasasfirst-linetreatment,incombinationwithgemcitabine.(1.3)-----------------------DOSAGEANDADMINISTRATION---------------------­• MetastaticBreastCancer:RecommendeddosageofABRAXANEis260mg/m2intravenouslyover30minutesevery3weeks.(2.1)• Non-SmallCellLungCancer:RecommendeddosageofABRAXANEis100mg/m2intravenouslyover30minutesonDays1,8,and15ofeach21-daycycle;administercarboplatinonDay1ofeach21-daycycleimmediatelyafterABRAXANE.(2.2)• AdenocarcinomaofthePancreas:RecommendeddosageofABRAXANEis125mg/m2intravenouslyover30-40minutesonDays1,8and15ofeach28-daycycle;administergemcitabineonDays1,8and15ofeach28-daycycleimmediatelyafterABRAXANE.(2.3)• Noadjustmentisnecessaryforpatientswithmildhepaticimpairment.WithholdABRAXANEifAST>10xULNorbilirubin>5xULN.Reducestartingdoseinpatientswithmoderatetoseverehepaticimpairment.(2.4)• DoseReductions:Dosereductionsordiscontinuationmaybeneededbasedonseverehematologic,neurologic,cutaneous,orgastrointestinaltoxicities.(2.5)• Usecautionwhenhandlingcytotoxicdrugs.Closelymonitortheinfusionsiteforextravasationandinfiltration.Nopremedicationisrequiredpriortoadministration.(2.6)---------------------DOSAGEFORMSANDSTRENGTHS-------------------­• Forinjectablesuspension:lyophilizedpowdercontaining100mgofpaclitaxelinsingle-usevialforreconstitution.(3)------------------------------CONTRAINDICATIONS----------------------------­•Neutrophilcountsof<1,500cells/mm3.(4)•SeverehypersensitivityreactiontoABRAXANE.(4)-----------------------WARNINGSANDPRECAUTIONS---------------------­• ABRAXANEcausesmyelosuppression.MonitorCBCandwithholdand/orreducethedoseasneeded.(5.1)• Sensoryneuropathyoccursfrequentlyandmayrequiredosereductionortreatmentinterruption.(5.2)• SepsisoccurredinpatientswithorwithoutneutropeniawhoreceivedABRAXANEincombinationwithgemcitabine;interruptABRAXANEandgemcitabineuntilsepsisresolves,andifneutropenic,untilneutrophilsareatleast1500cells/mm3,thenresumetreatmentatreduceddoselevels.(5.3)• PneumonitisoccurredwiththeuseofABRAXANEincombinationwithgemcitabine;permanentlydiscontinuetreatmentwithABRAXANEandgemcitabine.(5.4)• Severehypersensitivityreactionswithfataloutcomehavebeenreported.Donotre-challengewiththisdrug.(5.5)• Exposureandtoxicityofpaclitaxelcanbeincreasedinpatientswithhepaticimpairment;thereforeadministerwithcaution.(5.6)• ABRAXANEcontainsalbuminderivedfromhumanblood,whichhasatheoreticalriskofviraltransmission.(5.7)• Fetalharmmayoccurwhenadministeredtoapregnantwoman.AdvisewomenofchildbearingpotentialtoavoidbecomingpregnantwhilereceivingABRAXANE.(5.8)•AdvisemennottofatherachildwhileonABRAXANE.(5.9)------------------------------ADVERSEREACTIONS----------------------------­• Themostcommonadversereactions(≥20%)inmetastaticbreastcancerarealopecia,neutropenia,sensoryneuropathy,abnormalECG,fatigue/asthenia,myalgia/arthralgia,ASTelevation,alkalinephosphataseelevation,anemia,nausea,infections,anddiarrhea.(6.1)• Themostcommonadversereactions(≥20%)inNSCLCareanemia,neutropenia,thrombocytopenia,alopecia,peripheralneuropathy,nausea,andfatigue.(6.2)• Themostcommon(≥20%)adversereactionsofABRAXANEinadenocarcinomaofthepancreasareneutropenia,fatigue,peripheralneuropathy,nausea,alopecia,peripheraledema,diarrhea,pyrexia,vomiting,decreasedappetite,rash,anddehydration.(6.3)ToreportSUSPECTEDADVERSEREACTIONS,contactCelgeneCorporationat1-888-423-5436orFDAat1-800-FDA-1088orwww.fda.gov/medwatch.------------------------------DRUGINTERACTIONS-----------------------------­• UsecautionwhenconcomitantlyadministeringABRAXANEwithinhibitorsorinducersofeitherCYP2C8orCYP3A4.(7)See17forPATIENTCOUNSELINGINFORMATIONandFDA-approvedpatientlabeling.Revised:October2013ReferenceID:33990141FULLPRESCRIBINGINFORMATION:CONTENTS*WARNING:NEUTROPENIA1INDICATIONSANDUSAGE1.1 MetastaticBreastCancer1.2 Non-SmallCellLungCancer1.3 AdenocarcinomaofthePancreas2DOSAGEANDADMINISTRATION2.1 MetastaticBreastCancer2.2 Non-SmallCellLungCancer2.3 AdenocarcinomaofthePancreas2.4 DosageinPatientswithHepaticImpairment2.5 DoseReduction/DiscontinuationRecommendations2.6 PreparationandAdministrationPrecautions2.7 PreparationforIntravenousAdministration2.8 Stability3DOSAGEFORMSANDSTRENGTHS4CONTRAINDICATIONS5WARNINGSANDPRECAUTIONS5.1 HematologicEffects5.2 NervousSystem5.3 Sepsis5.4 Pneumonitis5.5 Hypersensitivity5.6 HepaticImpairment5.7 Albumin(Human)5.8 UseinPregnancy5.9 UseinMen6ADVERSEREACTIONS6.1 ClinicalTrialsExperienceinMetastaticBreastCancer6.2 ClinicalTrialsExperienceinNon-SmallCellLungCancer6.3 ClinicalTrialsExperienceinAdenocarcinomaofthePancreas6.4 Post-MarketingExperiencewithABRAXANEandotherPaclitaxelFormulations6.5 AccidentalExposure7DRUGINTERACTIONS8USEINSPECIFICPOPULATIONS8.1 Pregnancy8.3 NursingMothers8.4 PediatricUse8.5 GeriatricUse8.6 PatientswithHepaticImpairment8.7 PatientswithRenalImpairment10OVERDOSAGE11DESCRIPTION12CLINICALPHARMACOLOGY12.1 MechanismofAction12.3 Pharmacokinetics13NONCLINICALTOXICOLOGY13.1Carcinogenesis,Mutagenesis,ImpairmentofFertility14CLINICALSTUDIES14.1 MetastaticBreastCancer14.2 Non-SmallCellLungCancer14.3 AdenocarcinomaofthePancreas15REFERENCES16HOWSUPPLIED/STORAGEANDHANDLING16.1 HowSupplied16.2 Storage16.3 HandlingandDisposal17PATIENTCOUNSELINGINFORMATION*SectionsorsubsectionsomittedfromtheFullPrescribingInformationarenotlisted.ReferenceID:33990142FULLPRESCRIBINGINFORMATIONABRAXANE®forInjectableSuspension(paclitaxelprotein-boundparticlesforinjectablesuspension)(albumin-bound)WARNING:NEUTROPENIA• DonotadministerABRAXANEtherapytopatientswhohavebaselineneutrophilcountsoflessthan1,500cells/mm3.Inordertomonitortheoccurrenceofbonemarrowsuppression,primarilyneutropenia,whichmaybesevereandresultininfection,itisrecommendedthatfrequentperipheralbloodcellcountsbeperformedonallpatientsreceivingABRAXANE[seeContraindications(4),WarningsandPrecautions(5.1)andAdverseReactions(6.1,6.2,6.3)].• Note:Analbuminformofpaclitaxelmaysubstantiallyaffectadrug’sfunctionalpropertiesrelativetothoseofdruginsolution.DONOTSUBSTITUTEFORORWITHOTHERPACLITAXELFORMULATIONS.1INDICATIONSANDUSAGE1.1MetastaticBreastCancerABRAXANEisindicatedforthetreatmentofbreastcancerafterfailureofcombinationchemotherapyformetastaticdiseaseorrelapsewithin6monthsofadjuvantchemotherapy.Priortherapyshouldhaveincludedananthracyclineunlessclinicallycontraindicated.1.2Non-SmallCellLungCancerABRAXANEisindicatedforthefirst-linetreatmentoflocallyadvancedormetastaticnon-smallcelllungcancer,incombinationwithcarboplatin,inpatientswhoarenotcandidatesforcurativesurgeryorradiationtherapy.1.3AdenocarcinomaofthePancreasABRAXANEisindicatedforthefirst-linetreatmentofpatientswithmetastaticadenocarcinomaofthepancreas,incombinationwithgemcitabine.2DOSAGEANDADMINISTRATION2.1MetastaticBreastCancerAfterfailureofcombinationchemotherapyformetastaticbreastcancerorrelapsewithin6monthsofadjuvantchemotherapy,therecommendedregimenforABRAXANEis260mg/m2administeredintravenouslyover30minutesevery3weeks.2.2Non-SmallCellLungCancerTherecommendeddoseofABRAXANEis100mg/m2administeredasanintravenousinfusionover30minutesonDays1,8,and15ofeach21-daycycle.AdministercarboplatinonDay1ofeach21daycycleimmediatelyafterABRAXANE[seeClinicalStudies(14.2)].2.3AdenocarcinomaofthePancreasTherecommendeddoseofABRAXANEis125mg/m2administeredasanintravenousinfusionover30-40minutesonDays1,8and15ofeach28-daycycle.AdministergemcitabineimmediatelyafterABRAXANEonDays1,8and15ofeach28-daycycle[seeClinicalStudies(14.3)].2.4DosageinPatientswithHepaticImpairmentNodoseadjustmentisnecessaryforpatientswithmildhepaticimpairment.PatientswithmoderateandseverehepaticimpairmenttreatedwithABRAXANEmaybeatincreasedriskoftoxicitiesknowntopaclitaxel.WithholdABRAXANEifAST>10xULNorbilirubin>5xULN.RecommendationsfordosageadjustmentforthefirstcourseoftherapyareshowninTable1.Formetastaticbreastcancer,thedoseofABRAXANEcanbeincreasedfrom130mg/m2upto200mg/m2inpatientswithseverehepaticimpairmentinsubsequentcyclesbasedonindividualtolerance.Fornon-smallcelllungcancer,reducethedoseofABRAXANEto50mg/m2inpatientswithseverehepaticimpairment.Insubsequentcycles,thedoseofABRAXANEmaybeincreasedto75mg/m2astolerated.Monitorpatientsclosely[seeWarningsandPrecautions(5.6),UseinSpecificPopulations(8.6)andClinicalPharmacology(12.3)].ReferenceID:33990143Table1:RecommendationsforStartingDoseinPatientswithHepaticImpairmentSGOT(AST)LevelsBilirubinLevelsABRAXANEDoseaMBCNSCLCcPancreaticcAdenocarcinomaMild<10xULNAND>ULNto≤1.25xULN260mg/m2100mg/m2125mg/m2Moderate<10xULNAND1.26to2xULN200mg/m275mg/m2notrecommendedSevere<10xULNAND2.01to5xULN130mg/m2b50mg/m2notrecommended>10xULNOR>5xULNnotrecommendednotrecommendednotrecommendedMBC=MetastaticBreastCancer;NSCLC=Non-SmallCellLungCancer.aDosagerecommendationsareforthefirstcourseoftherapy.Theneedforfurtherdoseadjustmentsinsubsequentcoursesshouldbebasedonindividualtolerance.bAdoseincreaseto200mg/m2insubsequentcoursesshouldbeconsideredbasedonindividualtolerance.cPatientswithbilirubinlevelsabovetheupperlimitofnormalwereexcludedfromclinicaltrialsforpancreaticorlungcancer.2.5DoseReduction/DiscontinuationRecommendationsMetastaticBreastCancerPatientswhoexperiencesevereneutropenia(neutrophil<500cells/mm3foraweekorlonger)orseveresensoryneuropathyduringABRAXANEtherapyshouldhavedosagereducedto220mg/m2forsubsequentcoursesofABRAXANE.Forrecurrenceofsevereneutropeniaorseveresensoryneuropathy,additionaldosereductionshouldbemadeto180mg/m2.ForGrade3sensoryneuropathyholdtreatmentuntilresolutiontoGrade1or2,followedbyadosereductionforallsubsequentcoursesofABRAXANE[seeContraindications(4),WarningsandPrecautions(5.1,5.2)andAdverseReactions(6.1)].Non-SmallCellLungCancer•DonotadministerABRAXANEonDay1ofacycleuntilabsoluteneutrophilcount(ANC)isatleast1500cells/mm3andplateletcountisatleast100,000cells/mm3[seeContraindications(4),WarningsandPrecautions(5.1)andAdverseReactions(6.2)].• Inpatientswhodevelopsevereneutropeniaorthrombocytopeniawithholdtreatmentuntilcountsrecovertoanabsoluteneutrophilcountofatleast1500cells/mm3andplateletcountofatleast100,000cells/mm3onDay1ortoanabsoluteneutrophilcountofatleast500cells/mm3andplateletcountofatleast50,000cells/mm3onDays8or15ofthecycle.Uponresumptionofdosing,permanentlyreduceABRAXANEandcarboplatindosesasoutlinedinTable2.• WithholdABRAXANEforGrade3-4peripheralneuropathy.ResumeABRAXANEandcarboplatinatreduceddoses(seeTable2)whenperipheralneuropathyimprovestoGrade1orcompletelyresolves[seeWarningsandPrecautions(5.2)andAdverseReactions(6.2)].Table2:PermanentDoseReductionsforHematologicandNeurologicAdverseDrugReactionsinNSCLCAdverseDrugReactionOccurrenceWeeklyABRAXANEDose(mg/m2)Every3-WeekCarboplatinDose(AUCmg•min/mL)NeutropenicFever(ANClessthan500/mm3withfever>38°C)ORDelayofnextcyclebymorethan7daysforANClessthan1500/mm3ORANClessthan500/mm3formorethan7daysFirst754.5Second503ThirdDiscontinueTreatmentPlateletcountlessthan50,000/mm3First754.5SecondDiscontinueTreatmentFirst754.5SeveresensoryNeuropathy–Grade3or4Second503ThirdDiscontinueTreatmentReferenceID:33990144AdenocarcinomaofthePancreasDoselevelreductionsforpatientswithadenocarcinomaofthepancreas,asreferencedinTables4and5,areprovidedinTable3.Table3:DoseLevelReductionsforPatientswithAdenocarcinomaofthePancreasDoseLevelABRAXANE(mg/m2)Gemcitabine(mg/m2)Fulldose12510001stdosereduction1008002nddosereduction75600IfadditionaldosereductionrequiredDiscontinueDiscontinueRecommendeddosemodificationsforneutropeniaandthrombocytopeniaforpatientswithadenocarcinomaofthepancreasareprovidedinTable4.Table4:DoseRecommendationandModificationsforNeutropeniaand/orThrombocytopeniaattheStartofaCycleorwithinaCycleforPatientswithAdenocarcinomaofthePancreasCycleDayANC(cells/mm3)Plateletcount(cells/mm3)ABRAXANE/GemcitabineDay1<1500OR<100,000DelaydosesuntilrecoveryDay8500to<1000OR50,000to<75,000Reduce1doselevel<500OR<50,000WithholddosesDay15:IFDay8doseswerereducedorgivenwithoutmodification:500to<1000OR50,000to<75,000Reduce1doselevelfromDay8<500OR<50,000WithholddosesDay15:IFDay8doseswerewithheld:≥1000OR≥75,000Reduce1doselevelfromDay1500to<1000OR50,000to<75,000Reduce2doselevelsfromDay1<500OR<50,000WithholddosesAbbreviations:ANC=AbsoluteNeutrophilCountRecommendeddosemodificationsforotheradversedrugreactionsinpatientswithadenocarcinomaofthepancreasareprovidedinTable5.Table5:DoseModificationsforOtherAdverseDrugReactionsinPatientswithAdenocarcinomaofthePancreasAdverseDrugReactionABRAXANEGemcitabineFebrileNeutropenia:Grade3or4WithholduntilfeverresolvesandANC≥1500;resumeatnextlowerdoselevelPeripheralNeuropathy:Grade3or4Withholduntilimprovesto≤Grade1;resumeatnextlowerdoselevelNodosereductionCutaneousToxicity:Grade2or3Reducetonextlowerdoselevel;discontinuetreatmentiftoxicitypersistsGastrointestinalToxicity:Grade3mucositisordiarrheaWithholduntilimprovesto≤Grade1;resumeatnextlowerdoselevel2.6PreparationandAdministrationPrecautionsABRAXANEisacytotoxicdrugand,aswithotherpotentiallytoxicpaclitaxelcompounds,cautionshouldbeexercisedinhandlingABRAXANE.Theuseofglovesisrecommended.IfABRAXANE(lyophilizedcakeorreconstitutedsuspension)contactstheskin,washtheskinimmediatelyandthoroughlywithsoapandwater.Followingtopicalexposuretopaclitaxel,eventsmayincludetingling,burningandredness.IfABRAXANEcontactsmucousmembranes,themembranesshouldbeflushedthoroughlywithwater.ReferenceID:33990145Giventhepossibilityofextravasation,itisadvisabletocloselymonitortheinfusionsiteforpossibleinfiltrationduringdrugadministration.LimitingtheinfusionofABRAXANEto30minutes,asdirected,reducesthelikelihoodofinfusion-relatedreactions[seeAdverseReactions(6.4)].PremedicationtopreventhypersensitivityreactionsisgenerallynotneededpriortotheadministrationofABRAXANE.PremedicationmaybeneededinpatientswhohavehadpriorhypersensitivityreactionstoABRAXANE.PatientswhoexperienceaseverehypersensitivityreactiontoABRAXANEshouldnotbere-challengedwiththisdrug[seeWarningsandPrecautions(5.5)].2.7PreparationforIntravenousAdministrationABRAXANEissuppliedasasterilelyophilizedpowderforreconstitutionbeforeuse.AVOIDERRORS,READENTIREPREPARATIONINSTRUCTIONSPRIORTORECONSTITUTION.1. Aseptically,reconstituteeachvialbyinjecting20mLof0.9%SodiumChlorideInjection,USP.2. Slowlyinjectthe20mLof0.9%SodiumChlorideInjection,USP,overaminimumof1minute,usingthesterilesyringetodirectthesolutionflowontotheINSIDEWALLOFTHEVIAL.3. DONOTINJECTthe0.9%SodiumChlorideInjection,USP,directlyontothelyophilizedcakeasthiswillresultinfoaming.4. Oncetheinjectioniscomplete,allowthevialtositforaminimumof5minutestoensureproperwettingofthelyophilizedcake/powder.5. Gentlyswirland/orinvertthevialslowlyforatleast2minutesuntilcompletedissolutionofanycake/powderoccurs.Avoidgenerationoffoam.6. Iffoamingorclumpingoccurs,standsolutionforatleast15minutesuntilfoamsubsides.EachmLofthereconstitutedformulationwillcontain5mg/mLpaclitaxel.Calculatetheexacttotaldosingvolumeof5mg/mLsuspensionrequiredforthepatient:Dosingvolume(mL)=Totaldose(mg)/5(mg/mL).Thereconstitutedsuspensionshouldbemilkyandhomogenouswithoutvisibleparticulates.Ifparticulatesorsettlingarevisible,thevialshouldbegentlyinvertedagaintoensurecompleteresuspensionpriortouse.Discardthereconstitutedsuspensionifprecipitatesareobserved.Discardanyunusedportion.InjecttheappropriateamountofreconstitutedABRAXANEintoanempty,sterileintravenousbag[plasticizedpolyvinylchloride(PVC)containers,PVCornon-PVCtypeintravenousbag].TheuseofspecializedDEHP-freesolutioncontainersoradministrationsetsisnotnecessarytoprepareoradministerABRAXANEinfusions.Theuseofanin-linefilterisnotrecommended.Parenteraldrugproductsshouldbeinspectedvisuallyforparticulatematteranddiscolorationpriortoadministrationwheneversolutionandcontainerpermit.2.8StabilityUnopenedvialsofABRAXANEarestableuntilthedateindicatedonthepackagewhenstoredbetween20ºCto25ºC(68ºFto77ºF)intheoriginalpackage.Neitherfreezingnorrefrigerationadverselyaffectsthestabilityoftheproduct.StabilityofReconstitutedSuspensionintheVialReconstitutedABRAXANEinthevialshouldbeusedimmediately,butmayberefrigeratedat2ºCto8ºC(36ºFto46ºF)foramaximumof8hoursifnecessary.Ifnotusedimmediately,eachvialofreconstitutedsuspensionshouldbereplacedintheoriginalcartontoprotectitfrombrightlight.Discardanyunusedportion.StabilityofReconstitutedSuspensionintheInfusionBagThesuspensionforinfusionwhenpreparedasrecommendedinaninfusionbagshouldbeusedimmediatelybutmaybestoredatambienttemperature(approximately25ºC)andlightingconditionsforupto4hours.Discardanyunusedportion.3DOSAGEFORMSANDSTRENGTHSForinjectablesuspension:lyophilizedpowdercontaining100mgofpaclitaxelinsingle-usevialforreconstitution.4CONTRAINDICATIONS•ABRAXANEshouldnotbeusedinpatientswhohavebaselineneutrophilcountsof<1,500cells/mm3.•PatientswhoexperienceaseverehypersensitivityreactiontoABRAXANEshouldnotberechallengedwiththedrug.ReferenceID:339901465WARNINGSANDPRECAUTIONS5.1HematologicEffectsBonemarrowsuppression(primarilyneutropenia)isdose-dependentandadose-limitingtoxicityofABRAXANE.Inclinicalstudies,Grade3-4neutropeniaoccurredin34%ofpatientswithmetastaticbreastcancer(MBC),47%ofpatientswithnon-smallcelllungcancer(NSCLC),and38%ofpatientswithpancreaticcancer.Monitorformyelotoxicitybyperformingcompletebloodcellcountsfrequently,includingpriortodosingonDay1(forMBC)andDays1,8,and15(forNSCLCandforpancreaticcancer).DonotadministerABRAXANEtopatientswithbaselineabsoluteneutrophilcounts(ANC)oflessthan1,500cells/mm3.Inthecaseofsevereneutropenia(<500cells/mm3forsevendaysormore)duringacourseofABRAXANEtherapy,reducethedoseofABRAXANEinsubsequentcoursesinpatientswitheitherMBCorNSCLC.InpatientswithMBC,resumetreatmentwithevery-3-weekcyclesofABRAXANEafterANCrecoverstoalevel>1,500cells/mm3andplateletsrecovertoalevel>100,000cells/mm3.InpatientswithNSCLC,resumetreatmentifrecommended(seeDosageandAdministration,Table2)atpermanentlyreduceddosesforbothweeklyABRAXANEandevery-3-weekcarboplatinafterANCrecoverstoatleast1500cells/mm3andplateletcountofatleast100,000cells/mm3onDay1ortoanANCofatleast500cells/mm3andplateletcountofatleast50,000cells/mm3onDays8or15ofthecycle[seeDosageandAdministration(2.5)].Inpatientswithadenocarcinomaofthepancreas,withholdABRAXANEandgemcitabineiftheANCislessthan500cells/mm3orplateletsarelessthan50,000cells/mm3anddelayinitiationofthenextcycleiftheANCislessthan1500cells/mm3orplateletcountislessthan100,000cells/mm3onDay1ofthecycle.Resumetreatmentwithappropriatedosereductionifrecommended[seeDosageandAdministration(2.5)].5.2NervousSystemSensoryneuropath