natgillin/translations-raw huggingface dataset:
Nintedanibs terminale halveringstid var mellem 10 og 15 timer (gCV % ca. 50 %).
The terminal half-life of nintedanib was between 10 and 15 h (gCV % approximately 50 %).
Hvis en dosis nintedanib springes over, skal administrationen genoptages på det næste planlagte tidspunkt og i den anbefalede dosis.
If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose.
AUCτ,ss steg med 25 % hos en patient på 50 kg (5 %
AUCτ,ss increased by 25 % for a 50 kg patient (5
Sandsynligheden for lægemiddel-lægemiddel interaktioner med nintedanib baseret på CYP-metabolisme anses derfor for at være lav.
The likelihood of drug-drug interactions with nintedanib based on CYP metabolism is therefore considered to be low.
Der blev kun observeret et svagt hæmningspotentiale over for OCT-1, BCRP og P-gp in vitro, hvilket anses for at have en lille klinisk relevans.
Only a weak inhibitory potential on OCT-1, BCRP, and P-gp was observed in vitro which is considered to be of low clinical relevance.
Terapeutisk antikoagulation
Therapeutic anticoagulation
Dalværdier for koncentrationen af nintedanib forblev stabile i mere end et år.
Nintedanib trough concentrations remained stable for more than one year.
Hos de fleste patienter var de forhøjede levertal reversible.
In the majority of patients, elevations of liver parameters were reversible.
Behandling med Vargatef skal initieres og superviseres af en læge med erfaring i anvendelse af kræftbehandlinger.
Treatment with Vargatef should be initiated and supervised by a physician experienced in the use of anticancer therapies.
Det anbefales at tage kapslen sammen med mad, dvs. under eller umiddelbart før eller efter et måltid.
It is recommended to take the capsule with food, i.e. during or immediately before or after a meal.
Inden for de enkelte hyppighedskategorier er bivirkningerne opstillet efter faldende alvorlighed.
Within each frequency grouping adverse reactions are presented in order of decreased seriousness.
Din behandling med Vargatef bliver derfor som regel afbrudt, hvis du skal opereres.
Therefore treatment with Vargatef will usually be interrupted if you are having surgery.
Det skal bemærkes, at de på forhånd planlagte analyser i henhold til histologi kun påviste en statistisk signifikant forskel i OS mellem behandlingsgrupperne i adenokarcinom-populationen (Tabel 4).
Of note, pre-planned analyses according to histology showed statistically significant difference in OS between treatment arms in the adenocarcinoma population only (Table 4).
I prækliniske eksperimenter in vivo udviste BIBF 1202 ingen virkning på trods af dets aktivitet ved stoffets målreceptorer.
In preclinical in vivo experiments, BIBF 1202 did not show efficacy despite its activity at target receptors of the substance.
Det anbefales at justere dosis med 100 mg per dag (dvs. en reduktion på 50 mg per dosering), på grundlag af sikkerheden og tolerabiliteten hos den enkelte patient, som beskrevet i Tabel 1 og Tabel 2.
Dose adjustments in 100 mg steps per day (i.e. a 50 mg reduction per dosing) based on individual safety and tolerability are recommended as described in Table 1 and Table 2.
Der blev ikke fundet nogen korrelation mellem DCE-MRI-respons og efterfølgende kliniske betydende reduktion af mållæsionsstørrelse, men DCE-MRI-respons var forbundet med sygdomsstabilisering.
No correlation of the DCE-MRI response and subsequent clinically significant reduction in target lesion size was found, but DCE-MRI response was associated with disease stabilization.
Det anbefales at tage kapslerne sammen med mad, dvs. under eller umiddelbart før eller efter et måltid.
It is recommended to take the capsules with food, i.e. during or immediately before or after a meal.
Diarré (meget almindelig, kan forekomme hos flere end 1 ud af 10 personer) Diarré kan medføre tab af væske og vigtige salte (elektrolytter, som f.eks. natrium eller kalium) i din krop.
Diarrhoea (very common, may affect more than 1 in 10 people) Diarrhoea may lead to a loss of fluid and important salts (electrolytes, such as sodium or potassium) in your body.
Progressionsfri overlevelse (PFS)* - primær analyse Patienter, n
Progression free survival (PFS)* - primary analysis Patients, n
Det primære endepunkt var progressionsfri overlevelse (PFS) bedømt af en uafhængig bedømmelseskomité (IRC) og baseret på intent-to-treat (ITT)-populationen og i forhold til histologisk diagnose.
The primary endpoint was progression-free survival (PFS) as assessed by an independent review committee (IRC) based on the intent-to-treat (ITT) population and tested by histology.
Den højeste enkeltdosis nintedanib, der blev givet i fase I-studier, var 450 mg én gang daglig.
The highest single dose of nintedanib administered in phase I studies was 450 mg once daily.
De fleste af de fatale blødningshændelser var tumorrelaterede.
The majority of fatal bleeding events were tumour-associated.
“Lokalt recidiverende” blev defineret som lokalt recidiv af tumor uden metastaser ved indgang i forsøget.
`Locally recurrent´ was defined as local re-occurrence of the tumour without metastases at trial entry.
Transaminase-, ALKP- og bilirubin-niveauer bør undersøges før initiering af kombinationsbehandling med Vargatef plus docetaxel.
Transaminase, ALKP and bilirubin levels should be investigated before initiation of the combination treatment with Vargatef plus docetaxel.
Når lægemidlet tages på den måde, så er man sikker på, at der hele tiden er en konstant mængde nintedanib i kroppen.
Taking the medicine this way ensures that a steady amount of nintedanib is maintained in the body.
Der blev observeret en omvendt korrelation mellem legemsvægt og eksponering for nintedanib.
An inverse correlation between body weight and exposure to nintedanib was observed.
Der er ingen information om anvendelse af Vargatef til gravide kvinder, men prækliniske dyrestudier har påvist reproduktionstoksicitet af dette aktive stof (se pkt.
There is no information on the use of Vargatef in pregnant women, but preclinical studies in animals have shown reproductive toxicity of this active substance (see section 5.3).
Pædiatrisk population Vargatefs sikkerhed og virkning hos børn i alderen 0-18 år er ikke klarlagt.
The safety and efficacy of Vargatef in children aged 0-18 years have not been established.
In vitro proteinbindingen af nintedanib i humant plasma var høj, med en bundet fraktion på 97,8 %.
The in vitro protein binding of nintedanib in human plasma was high, with a bound fraction of 97.8 %.
Da nintedanibs virkning på kontraceptivas metabolisme og virkning ikke er undersøgt, skal der anvendes barrieremetoder som en ekstra præventionsmetode for at undgå graviditet.
Since the effect of nintedanib on the metabolism and efficacy of contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.
Ansøgeren vil implementere indsamlingen af materiale med henblik på undersøgelse af biomarkørdata i studieprotokollen for alle nye onkologiske studier, der er planlagt for Vargatef i fremtiden, når det er klinisk relevant.
The applicant will implement collection of material for biomarker investigation and analyses of biomarker data into the study protocol of all new oncology studies planned for nintedanib in the future, wherever clinically appropriate.
Samtidig administration af nintedanib og docetaxel (75 mg/m²) ændrede ingen af lægemidlernes farmakokinetik i relevant omfang.
Co-administration of nintedanib with docetaxel (75 mg/m²) did not alter the pharmacokinetics of either medicinal product to a relevant extent.
Det vides ikke, om dette lægemiddel udskilles i modermælk og kan skade det ammede barn.
It is not known if the medicine passes into breast milk and could cause harm to a breast-fed child.
For at undersøge relevante biomarkører/tumormarkører (herunder VEGF), så det bliver muligt at identificere og udvælge en mere målrettet patientpopulation, der med stor sandsynlighed vil profitere af behandling med Vargatef, vil ansøgeren gennemføre og indsende resultaterne af et biomarkør-forskningsprogram, der omfatter:
In order to investigate suitable bio-/tumour markers (including VEGF) to allow identification and selection of a more targeted population of patients most likely to benefit from the treatment of nintedanib, the Applicant will conduct and submit results from a Biomarkers research programme including: 1.
Gastrointestinale perforationer
Gastrointestinal perforations
Afbrydelse af behandlingen skal overvejes hos patienter, der udvikler tegn eller symptomer på akut myokardieiskæmi.
Treatment interruption should be considered in patients who develop signs or symptoms of acute myocardial ischaemia.
Dette lægemiddel bruges i kombination med en anden kræftmedicin (docetaxel) til behandling af en type kræft i lungerne, der kaldes ikke-småcellet lungekræft (NSCLC).
This medicine is used in combination with another cancer medicine (docetaxel) to treat a cancer of the lung called non-small cell lung cancer (NSCLC).
Aluminium/aluminiumsblistere, der indeholder 10 kapsler hver.
Aluminium/aluminium blisters containing 10 capsules each.
Diarré ≥ grad 2 i flere end 7 dage i træk trods behandling mod diarré ELLER
Diarrhoea ≥ grade 2 for more than 7 consecutive days despite anti-diarrhoeal treatment OR
Behandling med nintedanib medførte ikke en signifikant ændring i tiden til forværring af de forud specificerede symptomer hoste, dyspnø og smerter, men medførte en signifikant forværring i symptomskalaen for diarré.
Treatment with nintedanib did not significantly change the time to deterioration of the pre-specified symptoms cough, dyspnoea and pain, but resulted in a significant deterioration in the diarrhoea symptom scale.
Den absolutte biotilgængelighed af en dosis på 100 mg var 4,69 % (90 % CI: 3,615-6,078) hos raske frivillige.
The absolute bioavailability of a 100 mg dose was 4.69 % (90 % CI: 3.615 - 6.078) in healthy volunteers.
Let forhøjede leverenzymer, der ikke skyldtes alvorlige bivirkninger som f.eks. diarré, blev kun observeret hos rhesusaber.
Mild liver enzyme increases, which were not due to serious adverse effects such as diarrhoea, were only observed in Rhesus monkeys.
Den populationsmæssige gennemsnitlige eksponering for nintedanib var 33-50 % større hos kinesiske, taiwanesiske og indiske patienter, og 16 % større hos japanske patienter, mens den var 16-22 % lavere hos koreanere, sammenlignet med kaukasiere (korrigeret for legemsvægt).
The population mean exposure to nintedanib was 33 - 50 % higher in Chinese, Taiwanese, and Indian patients and 16 % higher in Japanese patients while it was 16 - 22 % lower in Koreans compared to Caucasians (body weight corrected).
Patienter med nylig pulmonal blødning (> 2,5 ml rødt blod) samt patienter med centralt lokaliserede tumorer med radiologisk evidens for lokal invasion af større blodkar eller radiologisk evidens for kavernøse eller nekrotiske tumorer blev ekskluderet fra de kliniske studier.
Patients with recent pulmonary bleeding (> 2.5 ml of red blood) as well as patients with centrally located tumours with radiographic evidence of local invasion of major blood vessels or radiographic evidence of cavitary or necrotic tumours have been excluded from clinical trials.
Data vedrørende bio- / tumormarkører fra samtlige kliniske studier i det kliniske program for Vargatef.
Data on bio-/tumour markers from all clinical studies in the clinical program for nintedanib.
For dosering, administration og dosisjustering af docetaxel henvises til den tilsvarende produktinformation for docetaxel.
For posology, methods of administration, and dose modifications of docetaxel, please refer to the corresponding product information for docetaxel.
Patienterne skal rådes til at udvise forsigtighed, når de fører motorkøretøj eller betjener maskiner under behandling med Vargatef.
Patients should be advised to be cautious when driving or using machines during treatment with Vargatef.
Der findes ingen specifik antidot eller behandling efter overdosering med nintedanib.
There is no specific antidote or treatment for nintedanib overdose.
Efter intravenøs infusion blev der observeret et højt fordelingsvolumen (Vss: 1050 l; 45,0 % gCV).
After intravenous infusion, a high volume of distribution (Vss: 1050 L, 45.0 % gCV) was observed.
Desuden hæmmes Fms-lignende tyrosin-proteinkinase (Flt)-3, lymfocytspecifik tyrosin-proteinkinase (Lck) og proto-onkogen tyrosin-proteinkinase Src (Src).
In addition Fms-like tyrosine-protein kinase (Flt)-3, lymphocyte-specific tyrosine-protein kinase (Lck) and proto-oncogene tyrosine-protein kinase Src (Src) are inhibited.
Perifer neuropati blev indberettet hos 16,5 % af patienterne i placebogruppen og hos 19,1 % af patienterne i nintedanibgruppen.
Peripheral neuropathy was reported in 16.5 % of patients in the placebo arm and in 19.1 % of patients in the nintedanib arm.
Denne population omfattede de adenokarcinom patienter, der ved baseline var blevet identificeret som havende udvist progression, og som var indgået i forsøget mindre end 9 måneder efter initiering af deres førstelinjebehandling.
This population included those adenocarcinoma patients identified at baseline as having progressed and entered the trial less than 9 months since start of their first-line therapy.
Der skal udvises særlig forsigtighed ved behandling af patienter med tidligere abdominalkirurgi eller nylig perforation af et hulorgan i anamnesen.
Particular caution should be exercised when treating patients with previous abdominal surgery or a recent history of a hollow organ perforation.
Patienter med nyligt myokardieinfarkt eller slagtilfælde i anamnesen blev ekskluderet fra dette forsøg.
Patients with a recent history of myocardial infarction or stroke were excluded from this trial.
Inden indledning af behandling med Vargatef bør denne risiko overvejes nøje for patienter med risikofaktorer såsom hypertension eller tidligere aneurisme.
Before initiating Vargatef, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
VEGFR-hæmning kan være forbundet med en øget risiko for blødning.
VEGFR inhibition might be associated with an increased risk of bleeding.
Hyperbilirubinæmi, forhøjet gammaglutamyltransferase (GGT)
Hyperbilirubinaemia, Gammaglutamyltransferase (GGT) increased
Der er ingen information om udskillelse af nintedanib og dets metabolitter i modermælk hos mennesker.
There is no information on the excretion of nintedanib and its metabolites in human milk.
Der blev foretaget en forudspecificeret evaluering i den population af adenokarcinom patienter, der ansås for at være indgået i forsøget med en særlig dårlig behandlingsprognose, nemlig de patienter, der havde udvist progression under eller kort efter førstelinjebehandling før indgang i forsøget.
A pre-specified evaluation was performed in the population of adenocarcinoma patients considered to have entered the trial with a particularly poor treatment prognosis, namely, patients who progressed during or shortly after first-line therapy prior to trial entry.
Nintedanibs farmakokinetik kan anses for at være lineær mht. tid (dvs. data for en enkeltdosis kan ekstrapoleres til data for gentagne doser).
The pharmacokinetics of nintedanib can be considered linear with respect to time (i.e. single-dose data can be extrapolated to multiple-dose data).
AUCτ,ss faldt med 16 % hos en 45-årig patient
AUCτ,ss decreased by 16 % for a 45-year old patient (5
Forhøjelse af leverenzymer (ALAT, ASAT, ALKP, gammaglutamyltransferase (GGT)) og bilirubin var i de fleste tilfælde reversible ved dosisreduktion eller dosisafbrydelse.
Elevation of liver enzymes (ALT, AST, ALKP, gammaglutamyltransferase (GGT)) and bilirubin were reversible upon dose reduction or interruption in the majority of cases.
Dette resultat blev bekræftet i den opfølgende PFS-analyse (HR 0,85; 95 % CI: 0,75-0,96; p = 0,0070), der omfattede alle registrerede hændelser på tidspunktet for den endelige OS-analyse.
This result was confirmed in the follow-up PFS analysis (HR 0.85, 95 % CI: 0.75 - 0.96; p = 0.0070) which included all events collected at the time of the final OS analysis.
Der foreligger ingen data fra mennesker eller dyr om nintedanibs mulige virkninger på den kvindelige fertilitet.
There are no human or animal data on potential effects of nintedanib on female fertility available.
De indsamlede blodprøver fra LUME-Lung 1- og LUME-Lung 2 studierne bliver analyseret for genetisk variation i kimcellelinjen med hensyn til angiogene faktorer, herunder VEGF eller dennes downstream receptorer.
Collected blood samples from the LUME-Lung 1 and LUME-Lung 2 studies will be assessed for germline genetic variability in angiogenic factors, including VEGF or its downstream receptors.
Nintedanib elimineres primært ved udskillelse via galden/fæces (> 90 %).
Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90 %).
Den var ikke klart dosisafhængig, men respons blev for det meste set ved doser ≥ 200 mg. Logistisk regression påviste en statistisk signifikant sammenhæng mellem antiangiogen virkning og eksponering for nintedanib.
It was not clearly dose dependent, but most responses were seen at doses of ≥ 200 mg. Logistic regression revealed a statistically significant association of the anti-angiogenic effect to nintedanib exposure.
Logistisk regression viste en statistisk signifikant sammenhæng mellem eksponering for nintedanib og DCE-MRI-respons.
Logistic regression revealed a statistically significant association between nintedanib exposure and DCE-MRI response.
Den renale udskillelses bidrag til den totale clearance var lavt (0,649 % af dosis; 26,3 % gCV).
The contribution of renal excretion to the total clearance was low (0.649 % of dose, 26.3 % gCV).
Patienter bør overvåges under behandlingen med nintedanib, med særlig opmærksomhed på patienter med risikofaktorer for nedsat nyrefunktion/-svigt.
Patients should be monitored during nintedanib therapy, with particular attention to those patients exhibiting risk factors for renal impairment/failure.
Ophør af behandlingen med Vargatef bør overvejes.
Termination of the treatment with Vargatef should be considered.
Der blev ikke observeret en øget hyppighed af cerebral blødning hos patienter med tilstrækkeligt forbehandlede hjernemetastaser, som var stabile i ≥ 4 uger før initiering af behandling med Vargatef.
No increased frequency of cerebral bleeding in patients with adequately pre-treated brain metastases which were stable for ≥ 4 weeks before start of treatment with Vargatef was observed.
Behandling med Vargatef bør derfor kun initieres eller - i tilfælde af perioperativ afbrydelse - genoptages på grundlag af en klinisk vurdering af om sårhelingen er tilfredsstillende.
Treatment with Vargatef should therefore only be initiated or - in case of perioperative interruption - resumed based on clinical judgement of adequate wound healing.
Nedsættelse af dosis
Dose reduction
Virkning i fase 3-hovedstudiet LUME-Lung 1
Efficacy in the pivotal phase 3 trial LUME-Lung 1
Hyppigheden af sepsis (1,3 %) og febril neutropeni (7,5 %) var større under behandling med nintedanib sammenlignet med placebogruppen.
The rates of sepsis (1.3 %) and febrile neutropenia (7.5 %) were increased under treatment with nintedanib as compared to the placebo arm.
De fleste af bivirkningerne forekom i en tæt tidsmæssig sammenhæng med administration af docetaxel.
The majority of adverse reactions appeared in close temporal relationship with the administration of docetaxel.
Kapslerne skal synkes hele sammen med vand og må ikke tygges eller knuses.
Swallow the capsules whole with water and do not chew or crush them.
Diarré forekom hos 43,4 % (≥ grad 3: 6,3 %) af adenokarcinom patienterne i nintedanib gruppen.
Diarrhoea occurred in 43.4 % (≥ grade 3: 6.3 %) of adenocarcinoma patients in the nintedanib arm.
Patienterne skal kontrolleres tæt for tromboemboliske hændelser.
Patients should be closely monitored for thromboembolic events.
Farmakokinetisk populationsanalyse i særlige populationer Nintedanibs farmakokinetiske egenskaber var de samme hos raske frivillige, kræftpatienter og patienter fra målgruppen.
Population pharmocokinetic analysis in special populations The pharmacokinetic properties of nintedanib were similar in healthy volunteers, cancer patients, and patients of the target population.
Tæt kontrol af patienter med flere af disse risikofaktorer anbefales dog (se pkt.
However, close monitoring is recommended in patients with several of these risk factors (see section 4.4).
Udvis forsigtighed ved behandling af patienter med en øget kardiovaskulær risiko, herunder kendt koronararteriesygdom.
Use caution when treating patients with a higher cardiovascular risk including known coronary artery disease.
Ikke kendt (hyppigheden kan ikke beregnes ud fra tilgængelige data) Betændelse i tyktarmen
Not known (cannot be estimated from the available data) Inflammation of the large bowel
Stratificeret log-rank-test, p-værdi** Progressionsfri overlevelse (PFS)*** - opfølgende analyse Patienter, n
Stratified Log-Rank Test p-value** Progression free survival (PFS)*** - follow-up analysis Patients, n
Brug ikke lægemidlet efter den udløbsdato, der står på kartonen og blisterne.
Do not use this medicine after the expiry date which is stated on the carton and blisters.
Den anbefalede dosis nintedanib er 200 mg to gange daglig givet med ca. 12 timers mellemrum på dag 2 til 21 i en standard 21-dages behandlingscyklus med docetaxel.
The recommended dose of nintedanib is 200 mg twice daily administered approximately 12 hours apart, on days 2 to 21 of a standard 21 day docetaxel treatment cycle.
Frugtbarhed Dette lægemiddels virkning på frugtbarheden hos mennesker er ikke undersøgt.
Fertility The effect of this medicine on human fertility has not been investigated.
Nintedanib har vist sig hverken at være et substrat for, eller en hæmmer af, OATP-1B1, OATP-1B3, OATP-2B1, OCT-2 eller MRP-2 in vitro.
Nintedanib was shown to be not a substrate or inhibitor of OATP-1B1, OATP-1B3, OATP-2B1, OCT-2, or MRP-2 in vitro.
De observerede hændelser var forenelige med den kendte sikkerhedsprofil for nintedanib, dvs. forhøjede leverenzymer og gastrointestinale symptomer.
Observed adverse events were consistent with the known safety profile of nintedanib, i.e. increased liver enzymes and gastrointestinal symptoms.
Nintedanib blokerer aktiviteten af en gruppe proteiner, der har betydning for udviklingen af nye blodkar, som kræftcellerne skal bruge til at få næring og ilt.
Nintedanib blocks the activity of a group of proteins which are involved in the development of new blood vessels that cancer cells need to supply them with food and oxygen.
Hvis en eller flere bivirkninger varer ved, dvs. hvis patienten ikke tåler 100 mg to gange daglig, skal behandlingen med Vargatef seponeres permanent.
In case of further persistence of the adverse reaction(s), i.e. if a patient does not tolerate 100 mg twice daily, treatment with Vargatef should be permanently discontinued.
Patienter med aktive hjernemetastaser blev ekskluderet fra de kliniske studier, og behandling med Vargatef anbefales ikke.
Patients with active brain metastasis were excluded from clinical trials and are not recommended for treatment with Vargatef.
Analysen af samlet overlevelse i den samlede population påviste ikke statistisk signifikans (HR 0,94; 95 % CI: 0,83-1,05).
Overall survival analysis in the overall population did not reach statistical significance (HR 0.94; 95 % CI: 0.83 - 1.05).
Hos patienter i kronisk lavdosisbehandling med lavmolekylære hepariner eller acetylsalicylsyre blev der ikke observeret øget blødningshyppighed.
In patients on chronic low dose therapy with low molecular weight heparins or acetylsalicylic acid, no increased frequency of bleeding was observed.
Vargatef må ikke tages samme dag, som der bliver givet kemoterapimidlet docetaxel (= dag 1).
Vargatef must not be taken on the same day of docetaxel chemotherapy administration (= day 1).
Disse patienters HR for PFS og OS var henholdsvis 1,24 (95 % CI: 0,68; 2,28) og 1,09 (95 % CI: 0,70; 1,70).
The HR for these patients for PFS and OS was 1.24 (95 % CI: 0.68, 2.28) and 1.09 (95 % CI: 0.70, 1.70), respectively.