课题atezolizumab完整的处方信息英文版0518.docx
- 文档编号:23237311
- 上传时间:2023-05-15
- 格式:DOCX
- 页数:7
- 大小:17.92KB
课题atezolizumab完整的处方信息英文版0518.docx
《课题atezolizumab完整的处方信息英文版0518.docx》由会员分享,可在线阅读,更多相关《课题atezolizumab完整的处方信息英文版0518.docx(7页珍藏版)》请在冰豆网上搜索。
课题atezolizumab完整的处方信息英文版0518
atezolizumab完整的处方信息(英文版)20160518
Newonsetdiabeteswithketo;Otherimmune-relatedadver;syndrome/myastheniagravi;Meningitis/Encephalitis;Monitorpatientsforclinic;60mg/dayorequivalent)onc;MotorandSensoryNeuropath;Monito
NewonsetdiabeteswithketoacidosishasoccurredinpatientsreceivingTECENTRIQ.Diabetesmellituswithoutanalternativeetiologyoccurredinone(0.2%)patientwithurothelialcarcinoma.Initiatetreatmentwithinsulinfortype1diabetesmellitus.For≥Grade3hyperglycemia(fastingglucose>250–500mg/dL),withholdTECENTRIQ.ResumetreatmentwithTECENTRIQwhenmetaboliccontrolisachievedoninsulinreplacementtherapy[seeDosageandAdministration(2.2)andAdverseReactions(6.1)].5.5OtherImmune-RelatedAdverseReactions
Otherimmune-relatedadversereactionsincludingmeningoencephalitis,myasthenic
syndrome/myastheniagravis,Guillain-Barré,ocularinflammatorytoxicity,andpancreatitis,includingincreasesinserumamylaseandlipaselevels,haveoccurredin≤1.0%ofpatientstreatedwithTECENTRIQ.
Meningitis/Encephalitis
Monitorpatientsforclinicalsignsandsymptomsofmeningitisorencephalitis.PermanentlydiscontinueTECENTRIQforanygradeofmeningitisorencephalitis.TreatwithIVsteroids(1–2mg/kg/daymethylprednisoloneorequivalent)andconverttooralsteroids(prednisone
60mg/dayorequivalent)oncethepatienthasimproved.Whensymptomsimproveto≤Grade1,tapersteroidsover≥1month[seeDosageandAdministration(2.2)andAdverseReactions(6.1)].
MotorandSensoryNeuropathy
Monitorpatientsforsymptomsofmotorandsensoryneuropathy.PermanentlydiscontinueTECENTRIQforanygradeofmyasthenicsyndrome/myastheniagravisorGuillain-Barrésyndrome.Institutemedicalinterventionasappropriate.Considerinitiationofsystemic
corticosteroids at adoseof1–2mg/kg/dayprednisone[seeDosageandAdministration(2.2)andAdverseReactions(6.1)].
Pancreatitis
Symptomaticpancreatitiswithoutanalternativeetiologyoccurredin0.1%(2/1978)ofpatientsacrossclinicaltrials.Monitorpatientsforsignsandsymptomsofacutepancreatitis.WithholdTECENTRIQfor≥Grade3serumamylaseorlipaselevels(>2.0ULN),orGrade2or3pancreatitis.Treatwith1?
2mg/kgIVmethylprednisoloneorequivalentperday.Once
symptomsimprove,followwith1?
2mg/kgoforalprednisoneorequivalentperday.ResumetreatmentwithTECENTRIQifserumamylaseandlipaselevelsimproveto≤Grade1within12weeks,symptomsofpancreatitishaveresolved,andcorticosteroidshavebeenreducedto≤10mgoralprednisoneorequivalentperday.PermanentlydiscontinueTECENTRIQforGrade4oranygradeofrecurrentpancreatitis[seeDosageandAdministration(2.2)andAdverseReactions(6.1)].
5.6Infection
Severeinfections,includingsepsis,herpesencephalitis,andmycobacterialinfectionleadingtoretroperitonealhemorrhageoccurredinpatientsreceivingTECENTRIQ.Acrossclinicaltrials,infectionsoccurredin38.4%(759/1978)ofpatients.In523patientswithurothelialcarcinomawhoreceivedTECENTRIQ,infectionoccurredin197(37.7%)patients.Grade3or4infectionoccurredin60(11.5%)patients,whilethreepatientsdiedduetoinfections.Urinarytract
infectionswerethemostcommoncauseofGrade3orhigherinfection,occurringin37(7.1%)patients.
Inarandomizedtrialinpatientswithnon-smallcelllungcancer,infectionsweremorecommoninpatientstreatedwithTECENTRIQ(42%)comparedwiththosetreatedwithdocetaxel(33%).Grade3or4infectionsoccurredin9.2%ofpatientstreatedwithTECENTRIQcomparedwith
2.2%inpatientstreatedwithdocetaxel.Onepatient(0.7%)treatedwithTECENTRIQdiedduetoinfection,comparedtotwopatients(1.5%)treatedwithdocetaxel.PneumoniawasthemostcommoncauseofGrade3orhigherinfection,occurringin6.3%ofpatientstreatedwithTECENTRIQ.
Monitorpatientsforsignsandsymptomsofinfectionandtreatwithantibioticsforsuspectedorconfirmedbacterialinfections.WithholdTECENTRIQfor≥Grade3infection[seeDosageandAdministration(2.2)andAdverseReactions(6.1)].
5.7Infusion-RelatedReactions
SevereinfusionreactionshaveoccurredinpatientsinclinicaltrialsofTECENTRIQ.Infusion-relatedreactionsoccurredin1.3%(25/1978)ofpatientsacrossclinicaltrialsandin1.7%(9/523)ofpatientswithurothelialcarcinoma.Interruptorslowtherateofinfusioninpatientswithmildormoderateinfusionreactions.PermanentlydiscontinueTECENTRIQinpatientswithGrade3or4infusionreactions[seeDosageandAdministration(2.2)andAdverseReactions(6.1)].
5.8Embryo-FetalToxicity
Basedonitsmechanismofaction,TECENTRIQcancausefetalharmwhenadministeredtoapregnantwoman.AnimalstudieshavedemonstratedthatinhibitionofthePD-L1/PD-1pathwaycanleadtoincreasedriskofimmune-relatedrejectionofthedevelopingfetusresultinginfetaldeath.Ifthisdrugisusedduringpregnancy,orifthepatientbecomespregnantwhiletakingthisdrug,advisethepatientofthepotentialrisktoafetus.AdvisefemalesofreproductivepotentialtouseeffectivecontraceptionduringtreatmentwithTECENTRIQandfor at least5monthsafterthelastdose[seeUseinSpecificPopulations(8.1,8.3)].
6ADVERSEREACTIONS
Thefollowingadversereactionsarediscussedingreaterdetailinothersectionsofthelabel:
?
Immune-RelatedPneumonitis[seeWarningsandPrecautions(5.1)]
?
Immune-RelatedHepatitis[seeWarningsandPrecautions(5.2)]
?
Immune-RelatedColitis[seeWarningsandPrecautions(5.3)]
?
Immune-RelatedEndocrinopathies[seeWarningsandPrecautions(5.4)]
?
OtherImmune-RelatedAdverseReactions[seeWarningsandPrecautions(5.5)]
?
Infection[seeWarningsandPrecautions(5.6)]
?
Infusion-RelatedReactions[seeWarningsandPrecautions(5.7)]
6.1ClinicalTrialsExperience
Becauseclinicaltrialsareconductedunderwidelyvaryingconditions,adversereactionratesobservedintheclinicaltrialsofadrugcannotbedirectlycomparedtoratesintheclinicaltrialsofanotherdrugandmaynotreflecttheratesobservedinpractice.
ThedatadescribedinTable1reflectsexposuretoTECENTRIQinCohort2ofStudy1.Thiscohortenrolled310patientsinasinglearmtrialwithlocallyadvancedormetastaticurothelialcarcinomawhohaddiseaseprogressionduringorfollowing at leastoneplatinum-containingchemotherapyregimenorwhohaddiseaseprogressionwithin12monthsoftreatmentwithaplatinum-containingneoadjuvantoradjuvantchemotherapyregimen[seeClinicalStudies(14.1)].Patientsreceived1200mgofTECENTRIQintravenouslyevery3weeksuntilunacceptabletoxicityoreitherradiographicorclinicalprogression.Themediandurationofexposurewas12.3weeks(range:
0.1,46weeks).
Themostcommonadversereactions(≥20%)werefatigue(52%),decreasedappetite(26%),nausea(25%),urinarytractinfection(22%),pyrexia(21%),andconstipation(21%).Themost
commonGrade3–4adversereactions(≥2%)wereurinarytractinfection,anemia,fatigue,
dehydration,intestinalobstruction,urinaryobstruction,hematuria,dyspnea,acutekidneyinjury,abdominalpain,venousthromboembolism,sepsis,andpneumonia.
Threepatients(0.9%)whoweretreatedwithTECENTRIQexperiencedeithersepsis,
pneumonitis,orintestinalobstructionwhichledtodeath.TECENTRIQwasdiscontinuedforadversereactionsin3.2%(10/310)ofthe310patients.Sepsisledtodiscontinuationin0.6%(2/310)ofpatients.AdversereactionsleadingtointerruptionofTECENTRIQoccurredin27%ofpatients;themostcommon(>1%)wereliverenzymeincrease,urinarytractinfection,diarrhea,fatigue,confusionalstate,urinaryobstruction,pyrexia,dyspnea,venous
thromboembolism,andpneumonitis.Seriousadversereactionsoccurredin45%ofpatients.Themostfrequentseriousadversereactions(>2%)wereurinarytractinfection,hematuria,acutekidneyinjury,intestinalobstruction,pyrexia,venousthromboembolism,urinaryobstruction,pneumonia,dyspnea,abdominalpain,sepsis,andconfusionalstate.
Table1summarizestheadversereactionsthatoccurredin≥10%ofpatientswhileTable2summarizesGrade3–4selectedlaboratoryabnormalitiesthatoccurredin≥1%ofpatientstreatedwithTECENTRIQinCohort2ofStudy1.
Table1:
AllGradeAdverseReactionsin≥10%ofPatientswithUrothelialCarcinomain
Study1
AdverseReaction
AllAdverseReactions
GastrointestinalDisorders
Nausea
Constipation
Diarrhea
Abdominalpain
Vomiting
GeneralDisordersandAdministration
Fatigue
Pyrexia
Peripheraledema
InfectionsandInfestations
Urinarytractinfection
MetabolismandNutritionDisorders
Decreasedappetite
MusculoskeletalandConnectiveTissueDisorders
Back/Neckpain
Arthralgia
Renalandurinarydisorders
Hematuria
Respiratory,Thoracic,andMediastinalDisorders
Dyspnea
Cough
SkinandSubcutaneousTissueDisorders
Rash
Pruritus15130.30.3161440.3143151421261229522118611AllGrades(%)962521181717TECENTRIQN=310Grades3–4(%)5020.3141
Table2:
Grade3–4LaboratoryAbnormalitiesinPatientswithUrothelialCarcinomainStudy1in>1%ofPatientsLaboratoryTest
LymphopeniaHyponatremiaAnemia
Hyperglycemia
IncreasedAlkalinephosphatase
IncreasedCreatinine
IncreasedALT
IncreasedAST
HypoalbuminemiaGrades3–4(%)10108543221
6.2Immunogenicity
Aswithalltherapeuticproteins,thereisapotentialforimmunogenicity.Among275patientsinStudy1,114patients(41.5%)testedpositivefortreatment-emergent(treatment-inducedor
treatment-enhanced)anti-therapeuticantibodies(ATA) at oneormorepost-dosetimepoints.InStudy1,thepresenceofATAsdidnotappeartohaveaclinicallysignificantimpactonpharmacokinetics
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 课题 atezolizumab 完整 处方 信息 英文 0518