natgillin/translations-raw huggingface dataset:
Mediantid til første dosisreduktion var 38 dage og til første dosisafbrydelse 28 dage.
The median time to first dose reduction was 38 days, and to first dose interruption was 28 days.
Hvis en patient skal skifte fra cabozantinib-kapsler til cabozantinibtabletter, skal patienten fortsætte med en CABOMETYX-dosis, der ikke overstiger 60 mg eller den aktuelle COMETRIQ-dosis (alt efter, hvad der er lavest).
If a patient must switch from cabozantinib capsules to cabozantinib tablets, the patient should continue at a CABOMETYX dose not to exceed 60 mg or the current COMETRIQ dose (whichever is lower).
Der er begrænsede data fra patienter med moderat nedsat leverfunktion (n=15) i henhold til NCI-ODWG (National Cancer Institute - Organ Dysfunction Working Group)kriterierne.
There is limited data in patients with moderate hepatic impairment (n=15) as per NCI-ODWG (National Cancer Institute - Organ Dysfunction working Group) criteria.
Virkning af andre lægemidler på cabozantinib
Effect of other medicinal products on cabozantinib
Diarré førte til dosisændringer, -afbrydelser og -seponeringer hos henholdsvis 84/467 (18 %), 69/467 (15 %) og 5/467 (1 %) af forsøgspersonerne.
Diarrhoea led to dose modifications, interruptions and discontinuations in 84/467 (18%), 69/467 (15%) and 5/467 (1%) of subjects, respectively.
Udvis forsigtighed, når du kører motorkøretøjer eller betjener maskiner.
Use caution when driving or using machines.
Forekomsten af systemisk ikke-strålebehandling og lokal leverrettet systemisk anticancerbehandling uden for protokollen (NPACT) var 26 % i cabozantinib-armen og 33 % i placebo-armen.
The incidence of systemic non-radiation and local liver-directed systemic non-protocol anticancer therapy (NPACT) was 26% in the cabozantinib arm and 33% in the placebo arm.
Disse kan være tegn på perforation af mave-tarm-kanalen (et hul i din mave eller tarm), hvilket kan være livstruende.
These may be signs of a gastrointestinal perforation, a hole that develops in your stomach or intestine that could be life-threatening.
Stabil sygdom Progredierende sygdom
Stable disease Progressive Disease
HR (95% CI) ; stratificeret b,c
HR (95% CI); stratified b,c
Kvinder, der tager CABOMETYX, bør ikke amme under behandlingen og i mindst 4 måneder efter, at behandlingen er afsluttet, da cabozantinib og/eller dets metabolitter kan udskilles i mælken og være skadeligt for barnet.
Women taking CABOMETYX should not breast-feed during treatment and for at least 4 months after treatment has finished, as cabozantinib and/or its metabolites may be excreted in breast milk and be harmful to your child.
Tabel 6: Effektresultater ved HCC (ITT population, CELESTIAL) CABOMETYX (N=470)
Table 6: Efficacy results in HCC (ITT population, CELESTIAL) CABOMETYX (N=470)
Bivirkninger af grad 1 og grad 2, som er tålelige og nemme at håndtere
Grade 1 and Grade 2 adverse reactions which are tolerable and easily managed
De fleste patienter (87 %) havde en Eastern Cooperative Oncology Group (ECOG) performance status på 0 eller 1; 13 % havde en ECOG performance status på 2.
Most patients (87%) had ECOG performance status of 0 or 1; 13% had an ECOG performance status of 2.
Progressionsfri overlevelse (PFS) blev vurderet radiologisk af en blindet uafhængig komité, og den primære analyse blev udført blandt de første 375 randomiserede patienter.
Progression-free survival (PFS) was assessed by a blinded independent radiology review committee, and the primary analysis was conducted among the first 375 subjects randomized.
Objektive responsrater er opsummeret i Tabel 4.
Objective response rate findings are summarized in Table 4.
Cabozantinib påvirker i mindre grad evnen til at føre motorkøretøj og betjene maskiner.
Cabozantinib has minor influence on the ability to drive and use machines.
Du skal tage CABOMETYX en gang dagligt.
CABOMETYX should be taken once a day.
Undersøgelsen var ikke designet med henblik på OS-analyse og data er ikke fuldt udviklet.
The study was not powered for the OS analysis and the data are immature.
Patienterne kunne have fået andre tidligere behandlinger, herunder cytokiner, og antistoffer rettet mod VEGF- eller PD-1- (programmeret celledød-1) receptoren eller dens ligander.
Patients could have received other prior therapies, including cytokines, and antibodies targeting VEGF, the programmed death 1 (PD-1) receptor, or its ligands.
Baseret på ikke-kliniske sikkerhedsfund kan mandlig og kvindelig fertilitet blive kompromitteret af behandling med cabozantinib (se pkt.
Based on non-clinical safety findings, male and female fertility may be compromised by treatment with cabozantinib (see section 5.3).
Undgå at blive gravid under behandlingen med CABOMETYX.
Avoid becoming pregnant while being treated with CABOMETYX.
Tilstedeværelse af makroskopisk vaskulær invasion og/eller ekstrahepatisk tumorspredning: 78 %, alfafetoprotein (AFP)-niveauer ≥400 µg/l: 41 %.
Presence of macroscopic vascular invasion and/ or extra-hepatic tumour spread:78%, Alfa-fetoprotein (AFP) levels ≥400 μg/L: 41%.
Fortæl det til lægen, hvis du eller din partner bliver gravid eller planlægger at blive gravid, mens du tager CABOMETYX.
Tell your doctor if you or your partner become pregnant or plan to become pregnant while you are being treated with CABOMETYX.
Patienter med behandlede hjernemetastaser blev inkluderet.
Patients with treated brain metastases were allowed.
Fortæl det til din læge, hvis noget af ovenstående gælder for dig.
Tell your doctor if any of these affect you.
71 % havde fået kun én tidligere VEGFR TKI; 41 % af patienterne havde fået sunitinib som deres eneste tidligere VEGFR TKI.
Seventy-one percent (71%) received only one prior VEGFR TKI; 41% of patients received sunitinib as their only prior VEGFR TKI.
En specifik justering af cabozantinibdosis er ikke nødvendig til ældre mennesker (≥65 år).
No specific dose adjustment for the use of cabozantinib in older people (≥ 65 years) is recommended.
PFS og ORR-fund er opsummeret i tabel 6.
PFS and ORR findings are summarized in Table 6.
• Lavt niveau af en type hvide blodlegemer (lymfocytter)
• Low level of a type of white blood cell (lymphocytes)
Plasmakoncentration-tid-kurver viser endnu en absorptionstop cirka 24 timer efter administration, hvilket antyder, at cabozantinib kan gennemgå enterohepatisk recirkulation.
Plasma-concentration time profiles show a second absorption peak approximately 24 hours after administration, which suggests that cabozantinib may undergo enterohepatic recirculation.
Der blev observeret en negativ effekt af Cabometyx i forhold til placebo på EQ-5D-brugsindeksresultatet i løbet af de første ugers behandling.
A negative effect of Cabometyx versus placebo on the EQ-5D utility index score was observed during the first weeks of treatment.
Fund i uterus/ovarier og nedsat hæmatopoiese syntes at være forbigående, mens virkninger på knogleparametre og leverpigmentering var vedvarende.
Findings in uterus/ovaries and decreased haematopoiesis appeared to be transient, while effects on bone parameters and liver pigmentation were sustained.
Juvenile rotter (sammenlignelige med en < 2 årig pædiatrisk population) udviste lignende behandlingsrelaterede fund, men syntes at være mere sensitive for cabozantinib-relateret toksicitet ved sammenlignelige dosisniveauer.
Juvenile rats (correlating to a <2- year paediatric population) showed similar treatment-related findings but appeared to be more sensitive to cabozantinib-related toxicity at comparable dose levels.
Cabozantinib har ikke udvist mutagent eller klastogent potentiale i et standardbatteri af genotoksicitetsassays.
Cabozantinib has shown no mutagenic or clastogenic potential in a standard battery of genotoxicity assays.
Der blev observeret en mindre end 10 % forskel i AUC mellem cabozantinibtablet- (CABOMETYX) og kapsel- (COMETRIQ) formuleringerne.
A less than 10% difference in the AUC was observed between cabozantinib tablet (CABOMETYX) and capsule (COMETRIQ) formulations.
Det anbefales at monitorere de biokemiske parametre under cabozantinib-behandling og anvende passende erstatningsterapi i overensstemmelse med klinisk standardpraksis, hvis det er nødvendigt.
It is recommended to monitor biochemical parameters during cabozantinib treatment and to institute appropriate replacement therapy according to standard clinical practice if required.
Den gennemsnitlige estimerede clearance (CL/F) ved steady state var 2,48 l/time.
Mean clearance (CL/F) at steady-state was estimated to be 2.48 L/hr .
Patientfordelingen ifølge IMDC risikogrupperne var 81 % middel risiko (1-2 risikofaktorer) og 19 % høj risiko (≥ 3 risikofaktorer).
Patient distribution by IMDC risk groups was 81% intermediate (1-2 risk factors) and 19% poor (≥3 risk factors).
• Alvorlig eller ukontrollerbar blødning med symptomer såsom opkastning af blod, sort afføring, blod i urinen, hovedpine, ophostning af blod.
• Severe or uncontrollable bleeding with symptoms such as: vomiting blood, black stolls, bloody urine, headache, coughing up blood.
For middel sygdomsrisiko, blev en eller to af de følgende faktorer mødt, mens der for høj risiko blev mødt tre eller flere faktorer: tid fra diagnose af RCC til systemisk behandling < 1 år, Hgb < LLN, korrigeret calcium > ULN, KPS < 80 %, neutrofiltælling > ULN og trombocyttal > ULN.
For intermediate risk disease, one or two of the following risk factors were met, while for poor risk, three or more factors were met: time from diagnosis of RCC to systemic treatment < 1 year, Hgb < LLN, Corrected calcium > ULN, KPS < 80%, Neutrophil count > ULN and Platelet count > ULN.
Patienterne skal informeres om ikke at spise noget i mindst 2 timer før og 1 time efter at have taget CABOMETYX.
Patients should be instructed to not eat anything for at least 2 hours before through 1 hour after taking CABOMETYX.
Håndtering af formodede lægemiddelbivirkninger kan nødvendiggøre midlertidig behandlingsafbrydelse og/eller dosisreduktion af CABOMETYX (se Tabel 1).
Management of suspected adverse drug reactions may require temporary treatment interruption and/or dose reduction of CABOMETYX therapy (see Table 1).
Det anbefales derfor at udvise forsigtighed, når der føres motorkøretøj eller betjenes maskiner.
Therefore, caution should be recommended when driving or operating machines.
Disse kan være tegn på en tilstand, der kaldes reversibelt posteriort leukoencefalopatisyndrom (RPLS).
These may be signs of a condition called reversible posterior leukoencephalopathy syndrome (RPLS).
Hvis du har taget flere CABOMETYX, end du har fået besked på, så kontakt en læge eller tag på hospitalet med det samme.
If you have taken more CABOMETYX than you have been instructed to, talk to a doctor or go to the hospital with the tablets and this leaflet straight away.
Vedvarende eller tilbagevendende diarré under behandlingen kan være en risikofaktor for udvikling af en analfistel.
Persistent or recurring diarrhoea while on treatment may be a risk factor for the development of anal fistula.
Tilfælde af hepatisk encefalopati hos HCC-patienter kan tilskrives udviklingen af elektrolytforstyrrelser.
Cases of hepatic encephalopathy in HCC patients can be attributed to the development of electrolyte disturbances.
Det bør overvejes i stedet at vælge et lægemiddel med intet eller minimalt potentiale til at inducere eller hæmme CYP3A4.
Selection of an alternative concomitant medicinal product with no or minimal potential to induce or inhibit CYP3A4 should be considered.
Du skal også anvende en barrieremetode (f.eks. kondom eller pessar), mens du tager CABOMETYX og i mindst 4 måneder efter, at behandlingen er afsluttet.
You should also use a barrier contraceptive (e.g. condom or diaphragm) whilst taking CABOMETYX and for at least 4 months after treatment has finished.
• Mundtørhed og smerter i munden
• Dry mouth and pain in the mouth
Da der kun foreligger begrænsede data for patienter med moderat nedsat leverfunktion (Child Pugh B), kan der ikke gives en doseringsanbefaling.
Since only limited data are available for patients with moderate hepatic impairment (Child Pugh B), no dosing recommendation can be provided.
Lokalregionale transarterielle emboliseringsprocedurer eller infusion af kemoterapi: 44 % Strålebehandling før cabozantinib-behandling: 37 % Median varighed af sorafenib-behandling: 5,32 måneder
Loco-regional transarterial embolisation or chemoinfusion procedures: 44% Radiotherapy prior to cabozantinib treatment: 37% Median duration of sorafenib treatment: 5.32 months
Tilfældene var af grad 4 og 5.
Events were Grade 4 and 5.
Der kunne ikke påvises bioækvivalens mellem cabozantinibkapslen og tabletformuleringerne efter en enkelt dosis på 140 mg hos raske frivillige.
Bioequivalence could not be demonstrated between the cabozantinib capsule and tablet formulations following a single 140 mg dose in healthy subjects.
Et neutraliserende antistof mod CYP2C9 viste en minimal indvirkning på dannelsen af cabozantinibmetabolitter (dvs. en <20 % reduktion).
A neutralizing antibody to CYP2C9 showed a minimal effect on cabozantinib metabolite formation (ie, a <20% reduction).
Den mediane behandlingsvarighed var 7,6 måneder (0,3-20,5) for patienter, der fik CABOMETYX, og 4,4 måneder (0,21-18,9) for patienter, der fik everolimus.
The median duration of treatment was 7.6 months (range 0.3 - 20.5) for patients receiving CABOMETYX and 4.4 months (range 0.21 - 18.9) for patients receiving everolimus.
CELESTIAL-studiet ekskluderede patienter med samtidig antikoagulationsbehandling eller trombocythæmmende midler.
The CELESTIAL study excluded patients with concomitant anticoagulation treatment or antiplatelet agents.
På grund af den potentielle skade for spædbarnet, bør mødre stoppe med at amme under behandling med cabozantinib og i mindst 4 måneder efter afsluttet behandling.
Because of the potential harm to the infant, mothers should discontinue breast-feeding during treatment with cabozantinib, and for at least 4 months after completing therapy.
En højere relativ andel af patienter med moderat nedsat leverfunktion (Child-Pugh B) udviklede hepatisk encefalopati med cabozantinib-behandling.
A higher relative proportion of patients with moderate hepatic impairment (Child-Pugh B) developed hepatic encephalopathy with cabozantinib treatment.
Der blev ikke rapporteret tilfælde af RPLS i METEOR-, CABOSUN- eller CELESTIAL-studierne, men RPLS er i sjældne tilfælde blevet rapporteret i andre kliniske studier (hos 2/4872 forsøgspersoner; 0,04 %).
No case of RPLS was reported in the METEOR or CABOSUN or CELESTIAL studies, but RPLS has been reported rarely in other clinical studies (in 2/4872 subjects; 0.04%).
54 % af patienterne havde 3 eller flere organer med metastatisk sygdom, herunder lunger (63 %), lymfekirtler (62 %), lever (29 %) og knogler (22 %).
Fifty-four percent (54%) of patients had 3 or more organs with metastatic disease, including lung (63%), lymph nodes (62%), liver (29%), and bone (22%).
Hvis PPES er alvorligt, bør det overvejes at afbryde behandlingen med cabozantinib.
When PPES is severe, interruption of treatment with cabozantinib should be considered.
Blodtrykket skal være velkontrolleret før påbegyndelse af cabozantinib.
Blood pressure should be well-controlled prior to initiating cabozantinib.
Hvis du har glemt at tage CABOMETYX
If you forget to take CABOMETYX
Der blev observeret en 19 % stigning i Cmax i tabletformuleringen (CABOMETYX) sammenlignet med kapselformuleringen (COMETRIQ).
A 19% increase in the Cmax of the tablet formulation (CABOMETYX) compared to the capsule formulation (COMETRIQ) was observed.
Farmakoterapeutisk klassifikation: antineoplastisk middel, proteinkinase-hæmmer, ATC-kode: L01XE26.
Pharmacotherapeutic group: antineoplastic agent, protein kinase inhibitor, ATC code: L01XE26.
Det primære effekt-endpoint var samlet overlevelse (OS).
The primary efficacy endpoint was overall survival (OS).
CABOMETYX er et lægemiddelmod kræft, der indeholder det aktive stof cabozantinib.
CABOMETYX is a cancer medicine that contains the active substance cabozantinib.
40 Boulevard de Champaret 38300 Bourgoin Jallieu, Frankrig
40 Boulevard de Champaret 38300 Bourgoin Jallieu, France
Hos HCC-patienter med nedsat leverfunktion kan disse ikke-hepatiske virkninger være risikofaktorer for udviklingen af hepatisk encefalopati.
In HCC patients with compromised livers, these non-hepatic effects may be precipitating factors for the development of hepatic encephalopathy.
Demografiske og sygdomskarakteristika ved baseline var ens for CABOMETYX- og placebo-armene og er vist nedenfor for alle 707 randomiserede patienter:
The baseline demographic and disease characteristics were similar between the CABOMETYX and placebo arms and are shown below for all 707 randomised patients:
Beslutningen om at genoptage behandlingen med cabozantinib efter operation skal baseres på klinisk bedømmelse af tilstrækkelig sårheling.
The decision to resume cabozantinib therapy after surgery should be based on clinical judgment of adequate wound healing.
Da orale kontraceptiva muligvis ikke kan betragtes som ”effektive kontraceptionsmetoder”, bør der samtidig anvendes en anden metode, fx en barrieremetode (se pkt.
Because oral contraceptives might possibly not be considered as “effective methods of contraception”, they should be used together with another method, such as a barrier method (see section 4.5).
Der blev ikke rapporteret tilfælde af hepatisk encefalopati i RCC-studierne (METEOR og CABOSUN).
No cases of hepatic encephalopathy were reported in the RCC studies (METEOR and CABOSUN).
PVC/PCTFE-blister med aluminiumsfoliebagside indeholdende 7 filmovertrukne tabletter.
PVC/PCTFE blister with push-through aluminum foil backing containing 7 film-coated tablets.
Hvis bivirkningerne ikke forsvinder, seponeres CABOMETYX permanent.
If adverse reaction does not resolve, permanently discontinue CABOMETYX.
Baseret på den populationsfarmakokinetiske (PK) model blev fordelingsvoluminet af det centrale rum (Vc/F) estimeret til at være 212 l. Proteinbindingen var ikke ændret hos forsøgspersoner med let til moderat nedsat nyre- eller leverfunktion.
Based on the populationpharmacokinetic (PK) model, the volume of distribution of the central compartment (Vc/F) was estimated to be 212 L. Protein binding was not altered in subjects with mild or moderately impaired renal or hepatic function.
Hvis der er 12 timer eller mere til din næste dosis, så tag den glemte dosis lige så snart, du kommer i tanker om det.
If there are still 12 hours or more before your next dose is due, then take the missed dose as soon as you remember.
CABOMETYX er indiceret som monoterapi til behandling af hepatocellulært karcinom (HCC) hos voksne, der tidligere er blevet behandlet med sorafenib.
CABOMETYX is indicated as monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib.
Objektiv responsrate n (%)3
Objective Response Rate n (%)3
• Forhøjet eller nedsat blodsukkerniveau
• Increased or decreased blood glucose level
Det anbefales at udføre leverfunktionstests (ALAT, ASAT og bilirubin) inden initiering af behandling med cabozantinib samt at monitorere tæt under behandlingen.
It is recommended to perform liver function tests (ALT, AST and bilirubin) before initiation of cabozantinib treatment and to monitor closely during treatment.
Dette kan betyde, at din læge er nødt til at ændre den dosis, du skal have.
This could mean that your doctor needs to change the dose(s) that you take.
CABOMETYX indeholder lactose (en sukkerart).
CABOMETYX contains lactose (a type of sugar).
Diarré, kvalme/opkastning, nedsat appetit og stomatitis/orale smerter var nogle af de hyppigst rapporterede GI-bivirkninger (se pkt.
Diarrhoea, nausea/vomiting, decreased appetite, and stomatitis/oral pain were some of the most commonly reported GI adverse reactions (see section 4.8).
Prædisponerende risikofaktorer for svær blødning i den fremskredne HCCpopulation kan omfatte tumorinvasion af store blodkar og tilstedeværelsen af underliggende levercirrhose, der resulterer i øsofageale varicer, portal hypertension og trombocytopeni.
Predisposing risk factors for severe haemorrhage in the advanced HCC population may include tumour invasion of major blood vessels and the presence of underlying liver cirrhosis resulting in oesophageal varices, portal hypertension, and thrombocytopenia.
• Hævelse i dine ben og arme
• Swelling in your legs and arms
Samlet overlevelse Median OS i måneder (95% CI)
Overall Survival Median OS in months (95% CI)
Abnormiteter i leverfunktionstests (stigninger i alaninaminotransferase [ALAT], aspartataminotransferase [ASAT] og bilirubin) er blevet observeret hyppigt hos patienter behandlet med cabozantinib.
Hepatic effects Abnormalities of liver function tests (increases in alanine aminotransferase [ALT], aspartate aminotransferase [AST] and bilirubin) have been frequently observed in patients treated with cabozantinib.
Alle hændelser var grad 3 eller 4.
All events were Grade 3 or 4.
I studiet af behandlingsnaivt RCC (CABOSUN) blev der ikke rapporteret tilfælde af fistler.
In the treatment-naïve RCC study (CABOSUN), no cases of fistulas were reported.
Randomisering blev stratificeret ved sygdomsætiologi (HBV [med eller uden HCV], HCV [uden HBV] eller andet), geografisk region (Asien, andre regioner) og ved forekomst af ekstrahepatisk sygdomsspredning og/eller makrovaskulære invasioner (Ja/Nej).
Randomization was stratified by aetiology of disease (HBV [with or without HCV], HCV [without HBV], or other), geographic region (Asia, other regions) and by presence of extrahepatic spread of disease and/or macrovascular invasions (Yes, No).
Efter oral administration af cabozantinib opnås cabozantinib-peak-plasmakoncentrationer 3 til 4 timer efter dosering.
Following oral administration of cabozantinib, peak cabozantinib plasma concentrations are reached at 3 to 4 hours post-dose.
Eller:
NN:
CABOMETYX er til oral anvendelse.
Method of administration CABOMETYX is for oral use.
Hændelserne var grad 2 eller 3.
Events were Grade 2 or 3.
Forlængelse af QT-intervallet
Prolongation of QT interval
CABOMETYX (cabozantinib)-tabletter og COMETRIQ (cabozantinib)-kapsler er ikke bioækvivalente og må ikke udskiftes indbyrdes (se pkt.
CABOMETYX (cabozantinib) tablets and COMETRIQ (cabozantinib) capsules are not bioequivalent and should not be used interchangeably (see section 5.2).
Akut medicinsk behandling, herunder støttende behandling med antiemetika, midler mod diarré eller antacida, bør indledes for at forhindre dehydrering, elektrolytubalancer og vægttab.
Prompt medical management, including supportive care with antiemetics, antidiarrhoeals, or antacids, should be instituted to prevent dehydration, electrolyte imbalances and weight loss.
Hvad CABOMETYX er
What CABOMETYX is
Ingen cabozantinibbehandlede patienter i dette studie havde en bekræftet QTcF >500 ms og heller ingen af de cabozantinibbehandlede patienter i RCC- eller HCC-studier (ved en dosis på 60 mg).
No cabozantinib-treated subjects in this study had a confirmed QTcF >500 ms, nor did any cabozantinib-treated subjects in the RCC or HCC studies (at a dose of 60 mg).
Cabozantinib skal anvendes med forsigtighed til patienter med forlænget QT-interval i anamnesen, patienter, som tager antiarytmika, og patienter med allerede eksisterende hjertesygdom, bradykardi eller elektrolytforstyrrelser.
Cabozantinib should be used with caution in patients with a history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances.
Kaplan-Meier-estimater af antal forsøgspersoner uden hændelser i % efter 3 måneder % (95 % CI)
Kaplan-Meier landmark estimates of percent of subjects event-free at 3 months % (95% CI)
Hvis der er mindre end 12 timer til din næste dosis, så lad være at tage den dosis, som du har glemt.
If your next dose is due in less than 12 hours, then do not take the dose that you have missed.
Hvis bivirkningerne reduceres til grad ≤1, genstartes behandlingen ved en reduceret dosis.
If adverse reaction resolves to Grade ≤1, re-initiate at a reduced dose.