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<CourseDefinition>
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    <Version>3.0</Version>
    <Date>20120717</Date>
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  <Details>
    <RegimId>NRB-7921</RegimId>
    <Name>Larotrektinib</Name>
    <ShortName/>
    <MajorVersion>1</MajorVersion>
    <MinorVersion>4</MinorVersion>
    <DefinitionStatus>COMPLETED</DefinitionStatus>
    <PatientMaxSurface/>
    <CourseICDZCode>NONE</CourseICDZCode>
    <CourseAUC>0.00</CourseAUC>
    <MaxAge/>
    <CycleLength/>
    <ValidForAllDiagnoses/>
    <IsStudyDefinition>NO</IsStudyDefinition>
    <PhysicianComment>Villkor för start av regimen: NTRK-genfusionspositiv status för solida tumörer ska fastställas.\nKontroll av blod-, lever och elektrolytstatus inkl. kreatinin. Vid förhöjda värden av ALAT och/eller ASAT följs dessa med en till två veckors mellanrum.\nLarotrektinib är en interaktionsbenägen substans som kan påverkas av och påverka effekten av andra läkemedel, se FASS eller nedan. En genomgång av läkemedel som kan ges samtidigt bör därför göras innan behandlingsstart.\n\nAnvisningar för ordination: Efter en månads behandling och därefter regelbundet: Kontroll av blod-, lever och elektrolytstatus inkl. kreatinin. \n\n\nDosreduktion rekommendation: Dosreduktioner kan göras i tre steg: till 75 mg x 2; till 50 mg x 2 och lägsta dos 100 mg x 1. Dosjustering pga biverkningar, se tabell 1 i produktresumén.\n\nEmetogenicitet:Låg.\n\nBehandlingsöversikt: Kontinuerlig behandling. \nSolida tumörer med NTRK-genfusionspositiv status..\n\nDiagnoskod: C34.\n\nBiverkningar för substanser i regimen\nlarotrektinib\nHematologisk toxicitet(Anemi och neutropeni vanligt, oftast grad 1- 2, men kan nå grad 3 - 4.\nGastrointestinal påverkan(Illamående och kräkningar vanligt. Förstoppning vanligt.\nLevertoxicitet(Förhöjda transaminaser vanligt, oftast grad 1-2. Kontroll av leverprover före och under behandlingen. Eventuellt behov av uppehåll eller utsättning av behandlingen, se FASS.\nCNS påverkan(Yrsel mycket vanligt, oftast grad 1- 2. Parestesi vanligt, oftast grad 1- 2.\nGångstörningar förekommer. \nNeurologiska biverkningar oftast debut inom första tre månader av behandlingen.\nÖvrigt(Trötthet mycket vanligt. Myalgi och muskelsvaget förekommer.\nInteraktionsbenägen substans(Samtidig administrering av larotrektinib och starka CYP3A4, P-gp- och BCRP-hämmare kan öka plasmakoncentration av larotrektinib. (Exempel på starka CYP3A4, P-gp- och BCRP-hämmare: atazanavir, klaritromycin, indinavir, itrakonazol, ketokonazol, nefazodon, nelfinavir, ritonavir, sakvinavir, telitromycin, troleandomycin, vorikonazol eller grapefrukt.)\nSamtidig administrering av larotrektinib och starka eller måttliga CYP3A- och P-gp-inducerare kan minska plasmakoncentrationen av larotrektinib och ska undvikas. (Exempel på starka eller måttliga CYP3A- och P-gp-inducerare: karbamazepin, fenobarbital, fenytoin, rifabutin, rifampin eller johannesört.)\nSamtidig administrering av larotrektinib och CYP3A-substrat med ett snävt terapeutisk intervall ska ske med försiktighet och dosminskning av CYP3A-substrat kan behövas. (Exempel på CYP3A-substrat med ett snävt terapeutisk intervall: alfentanil, ciklosporin, dihydroerotamin, ergotamin, fentanyl, pimozid, kinidin, sirolimus eller takrolimus.)\nSamtidig administrering av larotrektinib och CYP2B6-substrat kan minska CYP2B6-substratets koncentration. (Exempel på CYP2B6-substrat: bupropion, efavirenz.)\nSamtidig administrering av larotrektinib och OATP1B1-substrat (t.ex. valsartan, statiner) skulle kunna (men ännu ej bevisat) öka OATP1B1-substratets  koncentration. (Exempel på OATP1B1-substrat: valsartan, statiner.)\nSamtidig administrering av larotrektinib och PXR-reglerade enzymer (t ex CYP2C-familjen och UGT) skulle kunna (men ännu ej bevisat) minska koncentrationer av substrat till PXR-reglerade enzymer. (Exempel på substrat till PXR-reglerade enzymer: repaglinid, warfarin, tolbutamid eller omeprazol.)\n</PhysicianComment>
    <NurseComment>Villkor och kontroller för administration: Grapefrukt och johannesört ska ej intas under behandlingen.\nVid missad dos eller vid kräkningar tas inte någon extra dos, utan nästa dos tas vid nästa planerade tidpunkt.\n\nInformation från basfakta för substanser i regimen\nlarotrektinib\nDosering i förhållande till måltid: Tas med eller utan mat vid ungefär samma tidpunkt varje dag\n\nÖvrig information: Kapslarna finns i styrkorna 25 och 100 mg.\n\n</NurseComment>
    <PharmacistComment/>
    <PatientComment/>
    <ExternalDocumentation/>
    <ExternalPhysicianDoc>https://kunskapsbanken.cancercentrum.se/redirect/regim/7921</ExternalPhysicianDoc>
    <ExternalNurseDoc>https://kunskapsbanken.cancercentrum.se/redirect/regim/7921</ExternalNurseDoc>
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  </Details>
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    <OriginOfExport>Regimbiblioteket</OriginOfExport>
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    <CommittedBy/>
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    <CreatedDate>20260430</CreatedDate>
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    <Substance Name="larotrektinib">
      <Observandum Name="Hematologisk toxicitet" Tillagg="Anemi och neutropeni vanligt, oftast grad 1- 2, men kan nå grad 3 - 4."/>
      <Observandum Name="Gastrointestinal påverkan" Tillagg="Illamående och kräkningar vanligt. Förstoppning vanligt."/>
      <Observandum Name="Levertoxicitet" Tillagg="Förhöjda transaminaser vanligt, oftast grad 1-2. Kontroll av leverprover före och under behandlingen. Eventuellt behov av uppehåll eller utsättning av behandlingen, se FASS."/>
      <Observandum Name="CNS påverkan" Tillagg="Yrsel mycket vanligt, oftast grad 1- 2. Parestesi vanligt, oftast grad 1- 2.\nGångstörningar förekommer. \nNeurologiska biverkningar oftast debut inom första tre månader av behandlingen."/>
      <Observandum Name="Övrigt" Tillagg="Trötthet mycket vanligt. Myalgi och muskelsvaget förekommer."/>
      <Observandum Name="Interaktionsbenägen substans" Tillagg="Samtidig administrering av larotrektinib och starka CYP3A4, P-gp- och BCRP-hämmare kan öka plasmakoncentration av larotrektinib. (Exempel på starka CYP3A4, P-gp- och BCRP-hämmare: atazanavir, klaritromycin, indinavir, itrakonazol, ketokonazol, nefazodon, nelfinavir, ritonavir, sakvinavir, telitromycin, troleandomycin, vorikonazol eller grapefrukt.)\nSamtidig administrering av larotrektinib och starka eller måttliga CYP3A- och P-gp-inducerare kan minska plasmakoncentrationen av larotrektinib och ska undvikas. (Exempel på starka eller måttliga CYP3A- och P-gp-inducerare: karbamazepin, fenobarbital, fenytoin, rifabutin, rifampin eller johannesört.)\nSamtidig administrering av larotrektinib och CYP3A-substrat med ett snävt terapeutisk intervall ska ske med försiktighet och dosminskning av CYP3A-substrat kan behövas. (Exempel på CYP3A-substrat med ett snävt terapeutisk intervall: alfentanil, ciklosporin, dihydroerotamin, ergotamin, fentanyl, pimozid, kinidin, sirolimus eller takrolimus.)\nSamtidig administrering av larotrektinib och CYP2B6-substrat kan minska CYP2B6-substratets koncentration. (Exempel på CYP2B6-substrat: bupropion, efavirenz.)\nSamtidig administrering av larotrektinib och OATP1B1-substrat (t.ex. valsartan, statiner) skulle kunna (men ännu ej bevisat) öka OATP1B1-substratets  koncentration. (Exempel på OATP1B1-substrat: valsartan, statiner.)\nSamtidig administrering av larotrektinib och PXR-reglerade enzymer (t ex CYP2C-familjen och UGT) skulle kunna (men ännu ej bevisat) minska koncentrationer av substrat till PXR-reglerade enzymer. (Exempel på substrat till PXR-reglerade enzymer: repaglinid, warfarin, tolbutamid eller omeprazol.)"/>
    </Substance>
  </Sideeffects>
  <Diagnoses>
    <Diagnose Text="Lungcancer"/>
  </Diagnoses>
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