natgillin/translations-raw huggingface dataset:
Patienter med ECOG-performancestatus ≥2 eller med signifikant komorbiditet kan have større risiko for et dårligt klinisk resultat og bør overvåges nøje for tidlig klinisk forværring. 
Patients with ECOG performance status ≥ 2 or having significant co-morbidities may be at greater risk for a poor clinical outcome and should be carefully monitored for early clinical deterioration.
De farmakokinetisie egenskaber, der er beskrevet nedenfor, er i vidt omfang udledt fra en populationsfarmakokinetisk analyse med data fra 1.507 patienter med forskellige typer fremskredne maligniteter. 
The pharmacokinetic properties described below have to a large extent been derived from a population pharmacokinetic analysis with data from 1,507 patients with various types of advanced malignancies.
• ændring af stemmen, f.eks. udvikling af hæshed 
• change of the voice, e.g. developing a hoarse voice
Der er meget begrænsede data for patienter med svært nedsat nyrefunktion; derfor skal disse patienter behandles med forsigtighed. 
There are very limited data in patients with severe renal impairment; therefore, these patients should be treated with caution.
Irinotecan-dosis bør reduceres med 15-20 %. 
Irinotecan dose should be reduced by 15-20 %.
Observerede virkninger omfattede nedsat kropsvægt hos moderdyret, et øget antal fosterresorptioner og en øget forekomst af eksterne, viscerale og skeletale fostermisdannelser. 
Observed effects included decreases in maternal body weights, an increased number of foetal resorptions, and an increased incidence of external, visceral, and skeletal foetal malformations.
Vaskulær endotelial vækstfaktor A og B (VEGF-A, VEGF-B) og placental vækstfaktor (PlGF) er medlemmer af VEGF-familien af angiogene faktorer, der kan virke som potente mitogene, kemotaktiske og vaskulære permeabilitetsfaktorer for endoteliale celler. 
Vascular endothelial growth factor A and B (VEGF-A, VEGF-B), and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as potent mitogenic, chemotactic, and vascular permeability factors for endothelial cells.
Farmakoterapeutisk klassifikation: Antineoplastiske stoffer, andre antineoplastiske stoffer ATC-kode: L01XX44 
Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, ATC code: L01XX44
Der skal udvises forsigtighed, når ZALTRAP og intravenøse bisfosfonater administreres samtidigt eller sekventielt. 
Caution should be exercised when Zaltrap and intravenous bisphosphonates are administered concurrently or sequentially.
Aflibercept, også kaldet VEGF TRAP i den videnskabelige litteratur, er et rekombinant fusionsprotein bestående af de VEGF-bindende dele fra de ekstracellulære områder af humane VEGF-receptorer 1 og 2 bundet til Fc-delen af det humane IgG1. 
Aflibercept, also known as VEGF TRAP in the scientific literature, is a recombinant fusion protein consisting of VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2 fused to the Fc portion of the human IgG1.
• polyethylen-belagt PVC 
• polyethylene lined PVC
Et begrænset antal patienter med moderat/svært nedsat nyrefunktion ved baseline (N=49) blev behandlet med ZALTRAP. 
A limited number of patients having moderate/severe renal impairment at baseline (N = 49) were treated with ZALTRAP.
Tal omgående med lægen, hvis du bemærker nogen af ovenstående virkninger. 
Talk to your doctor straight away, if you notice any of the side effects above.
Hætteglasset må ikke punkteres påny efter den første punktur. 
Do not re-enter the vial after the initial puncture.
• ZALTRAP er et hætteglas til engangsbrug. 
• ZALTRAP is a single-use vial.
Nøje overvågning anbefales for hurtigt at kunne opdage og behandle tegn og symptomer på diarré og dehydrering samt for at minimere den potentielle risiko (se pkt. 
Careful monitoring is recommended in order to rapidly detect and treat signs and symptoms of diarrhoea and dehydration and to minimize potential risk (see section 4.8).
De hyppigst observerede bivirkninger ved disse doser svarede til det, der blev observeret ved den terapeutiske dosis. 
The most commonly observed adverse reactions at these doses were similar to those observed at the therapeutic dose.
• du har blødningsproblemer, eller hvis du opdager en blødning efter en behandling (se punkt 4), eller hvis du føler dig ekstremt træt, svag, svimmel eller har ændringer i farven på din afføring. 
• you have any bleeding problems or if you notice any bleeding after treatment (see section 4) or if you feel extreme tiredness, weakness, dizziness, or have changes in the colour of your stool.
Patienter med grad 3 DVT bør behandles med antikoagulantia efter klinisk indikation, og aflibercept-behandlingen bør fortsættes. 
Patients with Grade 3 DVT should be treated with anticoagulation as clinically indicated, and aflibercept therapy should be continued.
• en stigning i protein i urinen, en stigning i kolesterol i blodet og hævelse pga. overskydende væske (ødem) (også kaldet ‘nefrotisk syndrom') 
• an increase in protein in the urine, an increase in cholesterol in the blood, and swelling from excess fluid (oedema) (also called ‘nephrotic syndrome')
• fald i antallet af hvide blodlegemer (leukopeni) 
• drop in the number of white blood cells (leucopenia)
Aflibercept bindes til humant VEGF-A (ligevægtsdissociationskonstant KD på 0,5 pM for VEGF-A165 og 0,36 pM for VEGF-A121), til humant PlGF (KD på 39 pM for PlGF-2), og til humant VEGF-B (KD på 1,92 pM) og danner et stabilt, inert kompleks, der ikke har nogen detekterbar biologisk aktivitet. 
Aflibercept binds to human VEGF-A (equilibrium dissociation constant KD of 0.5 pM for VEGF-A165 and 0.36 pM for VEGF-A121), to human PlGF (KD of 39 pM for PlGF-2), and to human VEGF-B (KD of 1.92 pM) to form a stable, inert complex which has no detectable biological activity.
VEGF-A virker via to receptortyrosinkinaser, VEGFR-1 og VEGFR-2, som er til stede på overfladen af endotelceller. 
VEGF-A acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells.
Stratificeret Log-Rank test p-værdi Samlet respons-rate (CR+PR) (95 % CI) (%) 
Stratified log-rank test p-value Overall Response Rate (CR+PR) (95 % CI) (%)
Symptomerne kan omfatte svimmelhed, især når du rejser dig fra siddende stilling. 
Signs may include dizziness especially when going from sitting to standing.
Administration af aflibercept til mus, der var bærere af xenotransplantat- eller allotransplantattumorer, hæmmede væksten af forskellige cancertyper. 
Administration of aflibercept to mice bearing xenotransplant or allotransplant tumours inhibited the growth of various cancer types.
Ved doser på over 2 mg/kg, var clearance af frit aflibercept cirka 1,0 L/dag med en halveringstid på 6 dage. 
At doses greater than 2 mg/kg, free aflibercept clearance was approximately 1.0L/day with a terminal half-life of 6 days.
Ved det anbefalede dosis-regime på 4 mg/kg hver anden uge var koncentrationen af frit aflibercept nær steady-state-niveauer i den anden cyklus af behandlingen med essentielt ingen akkumulering (akkumulationsratio på 1,2 ved steady-state sammenlignet med den første administration). 
At the recommended dose regimen of 4 mg/kg every two weeks, concentration of free aflibercept were near steady-state levels by the second cycle of treatment with essentially no accumulation (accumulation ratio of 1.2 at steady-state compared to the first administration).
Diarré (1) Stomatitis 
Diarrhoea (1) Stomatitis
Lægen vil jævnligt udtage blodprøver for at kontrollere dit antal hvide blodlegemer under hele din behandling. 
Your doctor will do blood tests regularly to check your white blood cell counts throughout your treatment.
En tandlægeundersøgelse og passende forebyggende tandbehandling skal overvejes før behandlingen med ZALTRAP opstartes. 
A dental examination and appropriate preventive dentistry should be considered prior to starting the treatment with Zaltrap.
Opbevares i den originale emballage for at beskytte produktet mod lys. 
Store in the original package in order to protect from light.
• du har problemer med din mund eller dine tænder, så som dårlig tandhygiejne, sygdom i gummerne eller har en planlagt tandudtrækning, særligt hvis du tidligere er blevet behandlet med et bisfosfonat (anvendes til at forebygge knoglesygdomme). 
• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction and especially if you have previously been treated with a bisphosphonate (used to treat or prevent bone disorders).
Febril neutropeni eller neutropenisk sepsis 
Febrile neutropenia or neutropenic sepsis
• du har fået trukket en tand ud eller foretaget andre typer operationer i de seneste 4 uger, eller du skal have foretaget en operation eller et indgreb foretaget af en tandlæge eller læge, eller hvis du har et operationssår, som endnu ikke er læget. 
• you have had a tooth removed or any form of surgery in the last 4 weeks, or you are going to have an operation or a dental or medical procedure, or you have a wound after surgery that has not healed.
Hvis hypertensionen ikke kan kontrolleres i tilstrækkelig grad, bør behandling med aflibercept ikke initieres. 
If hypertension cannot be adequately controlled, treatment with aflibercept should not be initiated.
Patienter med tromboemboli af grad 3 eller derunder skal monitoreres omhyggeligt. 
Patients with thromboembolic events of Grade 3 or lower need to be closely monitored.
Der er ingen tilgængelige data for patienter med svært nedsat leverfunktin (total bilirubin >3 x ULN og evt. ASAT). 
There are no data available for patients with severe hepatic impairment (total bilirubin > 3 x ULN and any AST).
Dyretoksikologi og farmakologi 
Animal toxicology and pharmacology
Resultater efter forudgående bevacizumab eksponering er opsummeret i tabel 3. 
Results by prior bevacizumab exposure are summarised in Table 3.
ZALTRAP skal administreres udelukkende som intravenøs infusion over 1 time. 
ZALTRAP is to be administered only as an intravenous infusion over 1 hour.
Ved recidiv efter dosisreduktion af irinotecan og 5-FU kan reduktion af ZALTRAP-dosis til 2 mg/kg overvejes. 
If recurrence after irinotecan and 5-FU dose reductions, reduction of ZALTRAP dose to 2 mg/kg could be considered.
Denne populationsfarmakokinetiske analyse afslørede ingen klinisk betydningsfulde forskelle i clearance eller systemisk eksponering (AUC) for frit aflibercept hos patienter med moderat og let nedsat nyrefunktion ved 4 mg/kg dosis ZALTRAP sammenlignet med den samlede undersøgte population. 
This population pharmacokinetic analysis revealed no clinically meaningful differences in clearance or systemic exposure (AUC) of free aflibercept in patients with moderate and mild renal impairment at the 4 mg/kg dose of ZALTRAP as compared to the overall population studied.
ZALTRAP bør kun anvendes under graviditet, hvis den potentielle fordel opvejer den potentielle risiko. 
ZALTRAP should be used only if the potential benefit justifies the potential risk during pregnancy.
ZALTRAP i kombination med irinotecan/5-fluoruracil/folinsyre (FOLFIRI) kemoterapi er indiceret til voksne med metastaserende kolorektalcancer (mCRC), som er resistent overfor eller er progredieret efter et oxaliplatinholdigt regime. 
ZALTRAP in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) chemotherapy is indicated in adults with metastatic colorectal cancer (MCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen.
Der kan ikke udledes nogen konklusion for patienter med svært nedsat nyrefunktion på grund af yderst begrænsede tilgængelige data. 
No conclusion can be drawn for patients with severe renal impairment due to very limited data available.
Hos patienter med ≥2+ for protein på en urinstick eller UPCR >1 eller en protein/kreatinin ratio (PCR) >100 mg/mmol bør en døgnurinopsamling udføres. 
Patients with a dipstick of ≥ 2+ for protein or a UPCR > 1 or a protein/creatinine ratio (PCR)> 100 mg/mmol should undergo a 24-hour urine collection.
Må kun anvendes efter fortynding. 
Use only after dilution.
Ved at blokere væksten af blodkar medvirker ZALTRAP til at stoppe eller forsinke tumorens vækst. 
By blocking the growth of blood vessels, ZALTRAP helps to stop or slow down the growth of the tumour.
Hvis den ikke anvendes med det samme er brugeren ansvarlig for holdbarheden og for de forhold, som den opbevares under, hvilket normalt ikke vil være mere end 24 timer ved 2 °C til 8 °C, medmindre fortynding har fundet sted under kontrollerede og validerede aseptiske forhold. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C unless dilution has taken place in controlled and validated aseptic conditions.
I tilfælde af recidiv trods passende antikoagulationsbehandling bør aflibercept seponeres. 
In the event of recurrence, despite appropriate anticoagulation, aflibercept treatment should be discontinued.
Det kan være nødvendigt at bruge mere end et hætteglas til klargøring af infusionsopløsningen. 
More than one vial could be needed for the preparation of the infusion solution.
Der skal udvises forsigtighed ved håndtering af ZALTRAP, idet der tages hensyn til brugen af indkapslingsanordninger, personligt beskyttelsesudstyr (f.eks. handsker) og klargøringsprocedurer. 
Caution should be exercised when handling ZALTRAP, taking into account the use of containment devices, personal protective equipment (e.g. gloves), and preparation procedures.
Svær diarré 
Severe diarrhoea
ZALTRAP bør midlertidigt seponeres i mindst 4 uger forud for elektiv kirurgi (se pkt. 
ZALTRAP should be temporarily suspended for at least 4 weeks prior to elective surgery (see section
Populationsfarmakokinetisk analyse og sammenligning mellem studier viste ingen farmakokinetisk lægemiddelinteraktion mellem aflibercept og FOLFIRI-regimet. 
Population pharmacokinetics analysis and inter study comparisons did not reveal any pharmacokinetic drug-drug interaction between aflibercept and the FOLFIRI regimen.
Din læge kan give dig medicin, der kan stoppe eller behandle diarré og kvalme (opkastning). 
Your doctor may give you medicines to stop or treat diarrhoea and being sick (vomiting).
Proteinuri (1),(3) 
Proteinuria (1),(3)
• Inspicer hætteglasset med ZALTRAP visuelt før brug. 
• Inspect the ZALTRAP vial visually prior to use.
ZALTRAP bør seponeres midlertidigt, indtil hypertensionen er under kontrol. 
ZALTRAP should be temporarily suspended until hypertension is controlled.
ZALTRAP indeholder det aktive stof aflibercept, et protein der virker ved at blokere væksten af nye blodkar i tumoren. 
ZALTRAP contains the active substance aflibercept, a protein that works by blocking the growth of new blood vessels within the tumour.
Aflibercept har vist sig at være embryotoksisk og teratogent ved intravenøs administration i drægtige kaniner hver 3. dag under organogenesen (drægtighedsdag 6 til 18) i doser på cirka 1 til 15 gange den humane dosis på 4 mg/kg hver 2. uge. 
Aflibercept has been shown to be embryotoxic and teratogenic when administered intravenously to pregnant rabbits every 3 days during the organogenesis period (gestation days 6 to18) at doses approximately 1 to 15 times the human dose of 4 mg/kg every 2 weeks.
Hvis svær diarré vedvarer efter de 2 dosisreduktioner, skal FOLFIRI seponeres. 
If severe diarrhoea persists with both dose reductions, FOLFIRI should be discontinued.
Eksplorative biomarkøranalyser blev gennemført i VELOUR-studiet, herunder RAS-analyser af mutationsstatus hos 482 af 1.226 patienter (n=240 aflibercept; 242 placebo). 
Exploratory biomarker analyses were undertaken in the VELOUR trial including analyses of RAS mutational status in 482 of 1,226 patients (n = 240 aflibercept; 242 placebo).
ZALTRAPS virkning og sikkerhed blev evalueret i et randomiseret, dobbelt-blindet, placebokontrolleret studie hos patienter med metastaserende kolorektalcancer, som tidligere var blevet behandlet med en oxaliplatin-baseret behandling med eller uden forudgående bevacizumab. 
The efficacy and safety of ZALTRAP were evaluated in a randomised, double-blind, placebo-controlled study in patients with metastatic colorectal cancer who had previously been treated with an oxaliplatin-based treatment with or without prior bevacizumab.
Forekomsten af diarré, svimmelhed, asteni, vægttab og dehydrering var øget med ≥5 % hos ældre sammenlignet med yngre patienter. 
The incidence of diarrhoea, dizziness, asthenia, weight decrease, and dehydration was increased by ≥5% in elderly compared to younger patients.
Oplysninger om opbevarings- og anvendelsestid for ZALTRAP, efter at det er fortyndet og klar til brug, er beskrevet i ‘Praktiske oplysninger for sundhedspersonale vedrørende klargøring og håndtering af ZALTRAP 25 mg/ml koncentrat til infusionsvæske, opløsning' i slutningen af denne indlægsseddel. 
Information about storage and the time to use ZALTRAP, after it has been diluted and is ready to use, is described in the ‘Practical information for healthcare professionals on preparation and handling of ZALTRAP 25 mg / ml concentrate for solution for infusion' at the end of this leaflet.
Advarsler og forsigtighedsregler Kontakt lægen, apoteket eller sundhedspersonalet, før du bruger ZALTRAP og under behandlingen, hvis: 
Warnings and precautions Talk to your doctor, pharmacist or nurse before you are given ZALTRAP and during your treatment if:
Stratificeret på ECOG performance status (0 versus 1 versus 2) og tidligere bevacizumab (ja versus nej). 
Stratified on ECOG performance status (0 versus 1 versus 2) and prior bevacizumab (yes versus no).
VTE omfatter dyb venetrombose og lungeemboli. 
VTE include deep venous thrombosis and pulmonary embolism.
Ældre bør monitoreres nøje for udvikling af diarré og potentiel dehydrering (se pkt. 
Elderly people should be closely monitored for the development of diarrhoea and potential dehydration (see section 4.4).
Post hoc analyser for patienter med eller uden forudgående behandling med bevacizumab, eksklusive patienter, som progredierede under eller indenfor 6 måneder efter adjuverende behandling, er opsummeret i tabel 4. 
Post-hoc analyses excluding patients who progressed during or within 6 months of adjuvant therapy for patients with or without prior bevacizumab treatment are summarised in Table 4.
Koncentrationen af den endelige ZALTRAP-opløsning til intravenøs infusion skal holdes inden for området 0,6 mg/ml til 8 mg/ml for aflibercept. 
The concentration of the final ZALTRAP solution for intravenous infusion should be kept within the range of 0.6 mg / ml to 8 mg / ml of aflibercept.
• betændelse inde i munden 
• inflammation inside the mouth
19,8 (16,4 til 23,2) 
19.8 (16.4 to 23.2)
I overensstemmelse med målmedieret lægemiddeldisposition udviser frit aflibercept en hurtigere (ikke-lineær) clearance ved doser under 2 mg/kg, sandsynligvis på grund af højaffinitetsbinding af aflibercept til endogent VEGF. 
Consistent with target-mediated drug disposition, free aflibercept exhibits a faster (non-linear) clearance at doses below 2 mg/kg, likely due to the high affinity binding of aflibercept to endogenous VEGF.
EU/1/12/814/001 1 hætteglas (100 mg/4 ml) EU/1/12/814/002 3 hætteglas (100 mg/4 ml) EU/1/12/814/003 1 hætteglas (200 mg/8 ml) 
EU/1/12/814/001 1 vial (100 mg/4 ml) EU/1/12/814/002 3 vials (100 mg/4 ml) EU/1/12/814/003 1 vial (200 mg/8 ml)
Hvis du oplever nogen af disse symptomer, skal du tale med din læge med det samme, da din læge muligvis vil behandle dine symptomer og stoppe din behandling med ZALTRAP. 
If you experience any of these symptoms, talk to your doctor immediatley since your doctor may want to treat your symptoms and stop your treatment with ZALTRAP.
Tabel 3 - OS og PFS ved forudgående bevacizumab eksponering a 
Table 3 - OS and PFS by prior bevacizumab exposure a
Der skal udvises forsigtighed ved genbehandling af patienter med tidligere overfølsomhedsreaktioner da der er observeret recidiverende overfølsomhedsreaktioner hos visse patienter trods profylakse, inklusive kortikosteroider. 
Caution should be used when retreating patients with prior hypersensitivity reactions as recurrent hypersensitivity reactions have been observed in some patients despite prophylaxis, including corticosteroids.
Aflibercept virker som en opløselig lokke-receptor, der bindes til VEGF-A, med højere affinitet end dets naturlige receptorer, samt de relaterede ligander PlGF og VEGF-B. Ved at fungere som en ligandfælde hindrer aflibercept binding af endogene ligander til deres sammenhørende receptorer og blokerer derved receptormedieret signalering. 
Aflibercept acts as a soluble decoy receptor that binds to VEGF-A, with higher affinity than its native receptors, as well as the related ligands PlGF and VEGF-B. By acting as a ligand trap, aflibercept prevents binding of endogenous ligands to their cognate receptors and thereby blocks receptor mediated signaling.
En numerisk lavere behandlingseffekt på OS for ZALTRAP/FOLFIRI-regimet blev rapporteret for patienter med forudgående eksponering for bevacizumab sammenlignet med patienter uden forudgående eksponering for bevacizumab, uden tegn på heterogenitet i behandlingseffekt (ikke-signifikant interaktionstest). 
A numerically lower treatment effect on OS with the ZALTRAP/FOLFIRI regimen was reported for patients with prior bevacizumab as compared to patients without prior bevacizumab exposure, with no evidence of heterogeneity in treatment effect (non significant interaction test).
Samlede effektresultater for ZALTRAP/FOLFIRI-regimet versus placebo/FOLFIRI-regimet er opsummeret i Figur 1 og Tabel 2. 
Overall efficacy results for the ZALTRAP/FOLFIRI regimen versus the placebo/FOLFIRI regimen are summarised in Figure 1 and Table 2.
du har forhøjet blodtryk. 
• you have high blood pressure.
Behandling med antidiarrépræparater og rehydrering kan benyttes efter behov. 
Treatment with anti-diarrhoeal medicinal products and rehydration can be used as needed.
3,9 (3,02 til 4,30) 
3.9 (3.02 to 4.30)
Fortyndede opløsninger af ZALTRAP bør administreres ved hjælp af infusionssæt indeholdende et 0,2 mikrometer polyethersulfonfilter. 
Diluted solutions of ZALTRAP should be administered using infusion sets containing a 0.2 micron polyethersulfone filter.
Desuden kan den observerede forekomst af antistofpositivitet i en analyse være påvirket af flere faktorer, inklusive prøvehåndtering, tidspunktet for prøveudtagningen, samtidig medicinering og bagvedliggende sygdomme. 
Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medicinal products, and underlying disease.
Yderligere forhøjelser af aflibercept-dosis resulterede i dosis-relaterede forhøjelser i koncentrationen af cirkulerende frit aflibercept, men kun små yderligere forhøjelser i koncentrationen af VEGF-bundet aflibercept. 
Further increases in the aflibercept dose resulted in dose-related increases in circulating free aflibercept concentrations but only small further increases in the VEGF-bound aflibercept concentration.
Ældre ≥65 år havde en øget risiko for diarré, svimmelhed, asteni, vægttab og dehydrering. 
Elderly patients ≥65 years had an increased risk of diarrhoea, dizziness, asthenia, weight loss and dehydration.
Din læge kan blive nødt til at behandle dig med anden medicin og/eller give dig væske intravenøst. 
Your doctor may need to treat you with other medicines and/or fluids given intravenously.
Det skal besluttes, om amning skal ophøre eller behandling med ZALTRAP seponeres/undlades, idet der tages højde for fordelene ved amning for barnet i forhold til de terapeutiske fordele for moderen. 
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ZALTRAP therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Proteiner med høj molekylvægt udskilles ikke via nyrerne, derfor forventes udskillelse via nyrerne af aflibercept at være minimal. 
High molecular weight proteins are not cleared by the renal route, therefore renal elimination of aflibercept is expected to be minimal.