natgillin/translations-raw huggingface dataset:
Steady state-koncentrationen af sunitinib og dets aktive hovedmetabolit nås inden for 10-14 dage.
Steady-state concentrations of sunitinib and its primary active metabolite are achieved within 10 to 14 days.
Tilsvarende var legemsoverfladeareal en signifikant kovariat for den tilsyneladende clearance af den aktive metabolit (jo mindre legemsoverfladeareal, jo lavere tilsyneladende clearance).
Similarly, body surface area was a significant covariate on the apparent clearance of the active metabolite (the lower the body surface area, the lower the apparent clearance).
Størstedelen af disse bivirkninger observeret i kliniske studier, kunne dog ikke relateres til behandlingen i de kliniske studier (se pkt.
Nevertheless, most of these adverse events observed in clinical studies were not considered related to study treatment (see section 4.4).
Hos patienter uden kardielle risikofaktorer bør en vurdering af uddrivningsfraktionen ved baseline overvejes.
In patients without cardiac risk factors, a baseline evaluation of ejection fraction should be considered.
• Hjerteanfald på grund af afbrudt eller nedsat blodtilførsel til hjertet.
• Heart attack caused by an interrupted or decreased blood supply to the heart.
Lægen beslutter, hvornår du kan starte med Sutent-behandlingen igen.
Your doctor will decide when to start Sutent again.
Beslutning om genoptagelse af sunitinib-behandlingen efter et større kirurgisk indgreb bør tages på grundlag af klinisk bedømmelse af restitution efter indgrebet.
Therefore, the decision to resume sunitinib therapy following a major surgical intervention should be based upon clinical judgment of recovery from surgery.
Der blev observeret dosisbegrænsende kardiotoksicitet i den første del af studiet, hvorfor det blev ændret, så patienter med tidligere eksponering for potentielt kardiotoksiske behandlinger (herunder antracykliner) eller stråling af hjertet blev ekskluderet.
Dose-limiting cardiotoxicity was observed in the first part of the study which was therefore amended to exclude patients with previous exposure to potentially cardiotoxic therapies (including anthracyclines) or cardiac radiation.
Det virkede ikke som om, at sunitinibs benefit/risk-forhold blev negativt påvirket af en yngre alder og mindre legemsstørrelse, og det var primært afhængigt af plasma-eksponeringen.
Sunitinib benefit/risk did not appear to be negatively affected by younger age or lower body size, and was mainly driven by its plasma exposure.
Inden indledning af behandling med sunitinib, bør denne risiko overvejes nøje for patienter med risikofaktorer såsom hypertension eller tidligere aneurisme.
Before initiating sunitinib, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
Pivotal-studiet af NET i pancreas blev afsluttet før tid efter anbefaling fra en uafhængig lægemiddel-monitorerings-komité, og den primære parameter var baseret på investigatorvurdering, begge faktorer kan have haft indflydelse på skønnet over behandlingseffekten.
The pivotal study in pancreatic NET was terminated prematurely at the recommendation of an independent drug monitoring committee and the primary endpoint was based upon investigator assessment, both of which may have affected the estimates of the treatment effect.
Bivirkningerne er inden for hver hyppighed anført efter faldende alvorlighed.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Ved dosisintervallet 25-100 mg øges både arealet under plasmakoncentrationstidskurven (AUC) og Cmax proportionalt med dosis.
In the dosing ranges of 25 to 100 mg, the area under the plasma concentration-time curve (AUC) and Cmax increase proportionally with dose.
Andre endepunkter omfattede ORR, OS og sikkerhed.
Other endpoints included ORR, OS, and safety.
I en kohorte på 66 patienter med ø-celle tumorer var responsraten - det primære endepunkt - 17%.
In a pancreatic islet cell tumour cohort of 66 patients, the primary endpoint of response rate was 17%.
Sutent bør derfor ikke anvendes ved graviditet eller hos kvinder, der ikke anvender sikker antikonception, medmindre den potentielle fordel for kvinden opvejer den potentielle risiko for fostret.
Sutent should not be used during pregnancy or in women not using effective contraception, unless the potential benefit justifies the potential risk to the foetus.
Administration af sunitinib bør afbrydes og/eller dosis bør reduceres hos patienter unden kliniske tegn på CHF, men med en uddrivningsfraktion på <50%->20% under baseline.
The administration of sunitinib should be interrupted and/or the dose reduced in patients without clinical evidence of CHF but with an ejection fraction < 50% and > 20% below baseline.
Dosis af sunitinib blev reduceret, eller administration af sunitinib blev midlertidtigt indstillet hos ca. 2,7% af patienterne, som fik hypertension.
The dose of sunitinib was reduced or its administration temporarily suspended in approximately 2.7% of the patients who experienced hypertension.
Analyser af populationsfarmakokinetik tyder på, at sunitinibs tilsyneladende clearance (CL/F) ikke er påvirket af kreatininclearence (CrCl) inden for det vurderede område (42-347 ml/min).
Population PK analyses indicated that sunitinib apparent clearance (CL/F) was not affected by creatinine clearance (CLcr) within the range evaluated (42-347 ml/min).
Svær hypertension (>200 mmHg systolisk eller 110 mmHg diastolisk) sås hos 4,7% af patienterne med solide tumorer.
Severe hypertension (> 200 mmHg systolic or 110 mmHg diastolic) was reported in 4.7% of patients with solid tumours.
Hvis skjoldbruskkirtlen ikke producerer nok hormon, kan du blive behandlet med skjoldbruskkirtelhormon-erstatning.
If your thyroid gland is not producing enough thyroid hormone, you may be treated with thyroid hormone replacement.
Baseret på modelleringsanalyser virkede det ikke som om, at yngre alder og mindre legemsstørrelse påvirkede sikkerheds- og virkningsresponse på plasma-eksponeringen for sunitinib negativt.
Based on the modelling analyses, the younger age and lower body size did not appear to affect negatively the safety and efficacy responses to sunitinib plasma exposures.
Placebo cross-over gruppe
Placebo cross-over group treatment b
Sutent kan give hjerteproblemer.
Sutent can cause heart problems.
• Hævelse af væv på grund af væske under huden og omkring øjnene, dybtliggende allergisk udslæt.
• Swelling caused by fluid under the skin and around the eye, deep allergic rash.
Ændring i hårfarve Tør hud
Hair colour changes Dry skin
Ændringer i sunitinibs farmakokinetiske parametre havde ingen klinisk signifikans og viste ingen interaktioner, men i betragtning af det relativt lave antal forsøgspersoner (dvs. N=7+4) og den moderat til store forskel i de farmakokinetiske parametre patienterne imellem, bør der dog udvises forsigtighed ved fortolkning af fundene vedrørende farmakokinetisk interaktion fra dette studie.
Changes in sunitinib PK parameters were of no clinical significance and did not indicate any drug-drug interactions; however, considering the relatively low number of subjects (i.e. N=7+4) and the moderate-large interpatient variability in the pharmacokinetic parameters, caution needs to be taken when interpreting the PK drug-drug interaction findings from this study.
Moxifloxacin (400 mg), der blev brugt som positiv kontrol, viste en maksimal middelændring af QTcF-intervallet på 5,6 msek fra baseline.
Moxifloxacin (400 mg) used as a positive control showed a 5.6 msec maximum mean QTcF interval change from baseline.
28 x 1 hård kapsel
28 x 1 hard capsules
Lunge- eller vejrtrækningsproblemer.
Lung or breathing problems.
Alligevel var seponeringsraten på grund af bivirkninger 20% for sunitinib og 23% for IFN-α.
However, the discontinuation rates due to adverse events were 20% for sunitinib and 23% for IFN-α.
Patienter, som havde haft lungeemboli indenfor de seneste 12 måneder, blev ekskluderet fra de kliniske studier med sunitinib.
Patients who presented with pulmonary embolism within the previous 12 months were excluded from sunitinib clinical studies.
Data fra non-kliniske studier (in vivo og in vitro) med doser, der var højere end de anbefalede humane doser, tyder på, at sunitinib potentielt kan hæmme hjertets repolarisering (f.eks forlængelse af QTintervallet).
Data from non clinical (in vitro and in vivo) studies, at doses higher than the recommended human dose, indicated that sunitinib has the potential to inhibit the cardiac action potential repolarisation process (e.g., prolongation of QT interval).
Sunitinib metaboliseres hovedsageligt af CYP3A4, CYP-isoformen, som producerer dets aktive hovedmetabolit, desethylsunitinib, og som derefter metaboliseres yderligere af det samme isoenzym.
Sunitinib is metabolised primarily by CYP3A4, the CYP isoform which produces its primary active metabolite, desethyl sunitinib, which is then further metabolised by the same isoenzyme.
Denne analyse var baseret på data indsamlet fra voksne med GIST eller solide tumorer samt fra pædiatriske patienter med solide tumorer.
This analysis was based on data collected from adults with GIST or solid tumours and from paediatric patients with solid tumours.
Hvis du er gravid eller ammer, har mistanke om, at du er gravid, eller planlægger at blive gravid, skal du spørge din læge til råds, før du tager Sutent.
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Det primære effektendepunkt var den objektive responsrate (ORR) baseret på Response Evaluation Criteria in Solid Tumours (RECIST = respons evaluering af kriterier for solide tumorer).
The primary efficacy endpoint was ORR, based on Response Evaluation Criteria in Solid Tumours (RECIST).
Resultater fra spørgeskema (EORTC QLQ-C30) om livskvalitet fra den europæiske kræftforskningsorganisation, European Organisation for Research and Treatment of Cancer, viser, at den samlede totale helbredsrelaterede livskvalitet og de 5 funktionsevner (fysik, karakter, kognitiv, følelsesmæssig og social) blev opretholdt hos patienter i behandling med sunitinib i sammenligning med placebo med begrænsede symptomatiske bivirkninger.
Results from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) showed that the overall global health-related quality of life and the 5 functioning domains (physical, role, cognitive, emotional, and social) were maintained for patients on sunitinib treatment as compared to placebo with limited adverse symptomatic effects.
De kalkulerede in vitro Ki-værdier for alle undersøgte cytokrom-isoformer (CYP) (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5 og CYP4A9/11) tyder på, at det er usandsynligt, at sunitinib og dets aktive hovedmetabolit inducerer metaboliseringen af lægemidler, der metaboliseres af disse enzymer i klinisk relevant grad.
The calculated in vitro Ki values for all cytochrome P450 (CYP) isoforms tested (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, and CYP4A9/11) indicated that sunitinib and its primary active metabolite are unlikely to induce metabolism, to any clinically relevant extent, of other actives substances that may be metabolised by these enzymes.
Alle fund opstod ved klinisk relevante sunitinib-plasmaeksponeringsniveauer.
All findings occurred at clinically relevant sunitinib plasma exposure levels.
Patienter bør informeres om, at depigmentering af hår eller hud kan forekomme under behandling med sunitinib.
Patients should be advised that depigmentation of the hair or skin may occur during treatment with sunitinib.
• Unormal nedbrydning af muskelvæv, som kan give nyreproblemer (rhabdomyolyse).
• Abnormal muscle breakdown which can lead to kidney problems (rhabdomyolysis).
• Influenzalignende symptomer.
• Influenza-like syndrome.
2-sidet ustratificeret logrank test b
a 2-sided unstratified log-rank test b
Hovedmetabolitten udviser samme styrke sammenlignet med sunitinib i biokemiske analyser og celleanalyser.
The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.
Disse patienter bør følges nøje og behandles efter gældende praksis, og profylaktisk hydrering bør overvejes.
These patients should be monitored closely and treated as clinically indicated, and prophylactic hydration should be considered.
High-density polyethylen (HDPE) beholder med et polypropylenlåg, indeholdende 30 hårde kapsler.
High-density polyethylene (HDPE) bottle with a polypropylene closure containing 30 hard capsules.
Da aktive stoffer almindeligvis udskilles i modermælk, og da der er risiko for alvorlige bivirkninger hos det ammede barn, bør Sutent ikke anvendes i ammeperioden.
Because active substances are commonly excreted in human milk and because of the potential for serious adverse reactions in breast-feeding infants, women should not breast-feed while taking Sutent.
• Komplikationer i forbindelse med alvorlig infektion (infektion i blodbanen) der kan resultere i vævsskade, organsvigt og dødsfald.
• Complication of severe infection (infection is present in the bloodstream) that can lead to tissue damage, organ failure, and death.
Der er begrænset klinisk erfaring med, hvornår behandling skal genoptages efter større kirurgiske indgreb.
There is limited clinical experience regarding the timing of reinitiation of therapy following major surgical intervention.
Sutent er ikke godkendt til behandling af patienter med lungecancer.
Sutent is not approved for use in patients with lung cancer.
Stigningerne i lipaseaktiviteten var forbigående og var sædvanligvis ikke ledsaget af symptomer på pankreatitis hos forsøgspersoner med forskellige solide tumorer (se pkt.
Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours (see section
Patienter skulle have dokumenteret progression, baseret på RECIST inden for de sidste 12 måneder, og blev randomiseret (1:1) til at få enten 37,5 mg sunitinib 1 gang dagligt uden planlagte pauser (n = 86) eller placebo (n = 85).
Patients were required to have documented progression, based on RECIST, within the prior 12 months and were randomised (1:1) to receive either 37.5 mg sunitinib once daily without a scheduled rest period (N = 86) or placebo (N = 85).
Ingen patienter oplevede en effekt på QTc-intervallet større end grad 2 (CTCAE-version 3,0) (se pkt.
No subjects experienced an effect on the QTc interval greater than Grade 2 (CTCAE version 3.0) (see section 4.4).
Desuden havde 49% af sunitinib-patienterne tumorer uden funktion versus 52% af placebo-patienterne, og 92% af patienterne i begge behandlingsarme havde levermetastaser.
Additionally, 49% of sunitinib patients had nonfunctioning tumours versus 52% of placebo patients and 92% of patients in both arms had liver metastases.
Oralt ubehag Eruktation
Oral discomfort Eructation
Ved tilstedeværelse af kliniske manifestationer på CHF anbefales seponering af sunitinib.
In the presence of clinical manifestations of CHF, discontinuation of sunitinib is recommended.
Sunitinibs sikkerhedsprofil er blevet undersøgt i et fase 1-dosiseskaleringsstudie, et ublindet fase 2studie, et fase 1/2-enkeltarmsstudie og i publikationerne, som beskrevet herunder.
The safety profile of sunitinib has been derived from a Phase 1 dose-escalation study, a Phase 2 open-label study, a Phase 1/2 single-arm study and from publications as described below.
Nedbrydning af svulst, som fører til hul i tarmene.
Tumour destruction leading to hole in the intestine.
Lægen vil fastsætte den dosis du har brug for samt, hvornår du skal stoppe behandlingen med Sutent.
Your doctor will determine the appropriate dose you need to take, as well as if and when you need to stop treatment with Sutent.
Sunitinib bør anvendes med forsigtighed hos patienter med kendt forlængelse af QT-intervallet i anamnesen, patienter der tager antiarytmika eller lægemidler der kan forlænge QT-intervallet, eller patienter med relevant præeksisterende hjertesygdom, bradykardi eller elektrolytforstyrrelser.
Sunitinib should be used with caution in patients with a known history of QT interval prolongation, patients who are taking antiarrhythmics or medicinal products that can prolong QT interval, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances.
Hypertension er rapporteret i forbindelse med sunitinib, herunder alvorlig hypertension (>200 mmHg diastolisk systolisk eller > 100 mmHg).
Hypertension has been reported in association with sunitinib, including severe hypertension (> 200 mmHg systolic or 110 mmHg diastolic).
Farmakokinetikken af sunitinib blev vurderet hos 135 raske forsøgspersoner og 266 patienter med solide tumorer.
The PK of sunitinib were evaluated in 135 healthy volunteers and 266 patients with solid tumours.
Samlet overlevelse [5-årsopfølgning] [median, måneder (95% CI)]
Overall survival [5 years follow-up] [median, months (95% CI)]
Risikoen for kardielle bivirkninger forekom at være højere hos pædiatriske patienter med tidligere eksponering for stråling af hjertet eller antracyklin, sammenlignet med pædiatriske patienter uden tidligere eksponering.
The risk of cardiac adverse drug reactions appeared to be higher in paediatric patients with previous exposure to cardiac irradiation or anthracycline compared to those paediatric patients without previous exposure.
Udslættet kan udvikle sig til udbredt blæredannelse eller afskalning af huden og kan være livstruende.
The rash may progress to widespread blistering or peeling of the skin and may be life-threatening.
CYP3A4-hæmmere/induktorer
CYP3A4 inhibitors/inducers
Blandt de testede kovariater, der var relaterede til alder og legemsstørrelse, var alder en signifikant kovariat for den tilsyneladende clearance af sunitinib (jo yngre den pædiatriske patient var, jo lavere tilsyneladende clearance).
Among age and bodysize related covariates tested, age was a significant covariate on apparent clearance of sunitinib (the younger the age of the paediatric patient, the lower the apparent clearance).
Behandlingen kan genoptages, når hypertensionen er under passende kontrol (se pkt.
Treatment may be resumed once hypertension is appropriately controlled (see section 4.8).
Dette kan være symptomer på hjerteproblemer som hjertesvigt eller hjertemuskelproblemer (kardiomyopati).
These may be symptoms of heart problems that may include heart failure and heart muscle problems (cardiomyopathy).
Selvom der sås en effekt på QTcF-intervallet 24 timer efter indtagelse af dosis på dag 3 (dvs. ved den forventede terapeutiske plasmakoncentration efter den anbefalede startdosis på 50 mg) ved brug af ”within-day” baseline-korrektionsmetoden, er den kliniske betydning af dette fund uklart.
Although an effect on QTcF interval was observed on Day 3 at 24 hours postdose (i.e., at therapeutic plasma concentration expected after the recommended starting dose of 50 mg) with the within-day baseline correction method, the clinical significance of this finding is unclear.
De hyppigste hændelser omfattede cerebrovaskulær hændelse, transitorisk cerebral iskæmi og cerebralt infarkt.
The most frequent events included cerebrovascular accident, transient ischaemic attack, and cerebral infarction.
Sunitinib hæmmer gentagne RTK'er, som indgår i tumorvækst, neoangiogenese og metastaserende progression af cancer.
Sunitinib inhibits multiple RTKs that are implicated in tumour growth, neoangiogenesis, and metastatic progression of cancer.
Der blev udført trinvise kovariatmodelleringsanalyser for at evaluere indvirkningen af alder og legemsstørrelse (total legemsvægt eller legemsoverfladeareal) samt andre kovariater på vigtige farmakokinetiske parametre for sunitinib og den aktive metabolit.
Stepwise covariate modelling analyses were performed to evaluate the effect of age and body size (total body weight or body surface area) as well as other covariates on important PK parameters for sunitinib and its active metabolite.
Patienter med eksisterende hypotyreose eller hypertyreose bør behandles efter gældende klinisk praksis, før behandling med sunitinib initieres.
Patients with pre-existing hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of sunitinib treatment.
Det primære mål var at sammenligne PFS hos patienter, som fik sunitinib, versus patienter, som fik placebo.
The primary objective was to compare PFS in patients receiving sunitinib versus patients receiving placebo.
Sunitinib og dets primære metabolit metaboliseres hovedsageligt i leveren.
Sunitinib and its primary metabolite are mainly metabolised by the liver.
Sutent findes i plastikbeholder med 30 kapsler og i en perforeret enkeltdosis-blisterpakning med 28 x 1 kapsel.
It is available in plastic bottles of 30 capsules and in perforated unit dose blisters containing 28 x 1 capsules.
Fuldstændig blodtælling bør udføres i begyndelsen af hver behandlingscyklus hos patienter, der behandles med sunitinib (se pkt.
Complete blood counts should be performed at the beginning of each treatment cycle for patients receiving treatment with sunitinib (see section 4.8).
I alt fik 225 patienter sunitinib i studiets åben-label fase, inklusive de 99 patienter der blev behandlet med placebo i starten.
A total of 255 patients received sunitinib in the open-label treatment phase of the study, including 99 patients who were initially treated with placebo.
I denne analyse indeholder placebo-armen de patienter, som var randomiseret til placebo, men senere fik åben-label sunitinib-behandling.
In this analysis, the placebo arm included those patients randomised to placebo who subsequently received open-label sunitinib treatment.
Gennemsigtigt poly(chlortrifluorethylen) PVC endosisblister med aluminiumsfolie belagt med varmeforseglet lak, der indeholder 28 x 1 hårde kapsler.
Poly(chlorotrifluoroethylene)/PVC transparent perforated unit dose blister with aluminium foil coated with heat seal lacquer containing 28 x 1 hard capsules.
I alt 59 ud af 85 patienter (69,4%) fra placebo-gruppen fik ublindet sunitinibbehandling efter sygdomsprogression eller afblinding ved studieafslutning.
A total of 59 out of 85 patients (69.4%) from the placebo arm crossed over to open-label sunitinib following disease progression or unblinding at study closure.
Den mediane samlede overlevelse (OS) var 5,1 måneder i gruppen med gliom af høj grad og 12,3 måneder i ependymom-gruppen.
Median overall OS was 5.1 months in the HGG group and 12.3 months in the ependymoma group.
Udfør leverfunktionstest (alanin-aminotransferase [ALAT], aspartat-aminotransferase [ASAT], bilirubinniveau) før behandlingen påbegyndes, under hver behandlingscyklus, og hvis det er klinisk indiceret.
Monitor liver function tests (alanine transaminase [ALT], aspartate transaminase [AST], bilirubin levels) before initiation of treatment, during each cycle of treatment, and as clinically indicated.
Bivirkninger indberettet hos patienter med GIST, mRCC og hos pNET-patienter i et samlet datasæt på 7.115 patienter er anført nedenfor efter organklasse, hyppighed og sværhedsgrad (NCI-CTCAE).
Adverse reactions that were reported in GIST, MRCC, and pNET patients in a pooled dataset of 7,115 patients are listed below, by system organ class, frequency and grade of severity (NCI-CTCAE).
Farmakoterapeutisk klassifikation: Antineoplastiske stoffer, proteinkinase-hæmmere, ATC-kode: L01XE04
Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors; ATC code: L01XE04
Baseline og regelmæssige vurderinger af LVEF bør overvejes, mens patienterne behandles med sunitinib.
Baseline and periodic evaluations of LVEF should also be considered while the patient is receiving sunitinib.
Sunitinib og dets hovedmetabolit er de vigtigste forbindelser identificeret i plasma, urin og fæces med henholdsvis 91,5%, 86,4% og 73,8% af radioaktivitet i poolede prøver.
Sunitinib and its primary active metabolite were the major compounds identified in plasma, urine, and faeces, representing 91.5%, 86.4%, and 73.8% of radioactivity in pooled samples, respectively.
Dysgeusi, ageusi og smagsforstyrrelser
Dysgeusia, ageusia, and taste disturbance.