FrancophonIA/ELRC3.0 huggingface dataset:
English: Urinary excretion of the unchanged active substance within 48 h was about 0.05 % of the dose (31.5 % gCV) after oral and about 1.4 % of dose (24.2 % gCV) after intravenous administration; the renal clearance was 20 mL/min (32.6 % gCV).
Danish: Urinudskillelsen af det uomdannede aktive stof inden for 48 timer var ca. 0,05 % af dosis (31,5 % gCV) efter oral administration og ca. 1,4 % af dosis (24,2 % gCV) efter intravenøs administration; den renale clearance var 20 ml/min (32,6 % gCV).
English: In rats, small amounts of radiolabelled nintedanib and/or its metabolites were excreted into the milk (≤ 0.5 % of the administered dose).
Danish: Hos rotter blev små mængder radioaktivt mærket nintedanib og/eller dets metabolitter udskilt i mælken (≤ 0,5 % af den administrerede dosis).
English: Nintedanib is a triple angiokinase inhibitor blocking vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR α and ß) and fibroblast growth factor receptors (FGFR 1-3) kinase activity.
Danish: Nintedanib er en trippel angiokinasehæmmer, som blokerer kinaseaktiviteten i vaskulær endotelial vækstfaktor receptorer (VEGFR 1-3), trombocytderiveret vækstfaktor receptorer (PDGFR α og ß) og fibroblast vækstfaktor receptorer (FGFR 1-3).
English: The values should be monitored as clinically indicated or periodically during treatment, i.e. in the combination phase with docetaxel at the beginning of each treatment cycle and monthly in case Vargatef is continued as monotherapy after discontinuation of docetaxel.
Danish: Værdierne skal også kontrolleres som klinisk indiceret eller regelmæssigt under behandlingen, dvs. i kombinationsfasen med docetaxel i starten af hver behandlingscyklus og hver måned, hvis Vargatef fortsættes som monoterapi efter seponering af docetaxel.
English: Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signalling which is crucial for the proliferation and survival of endothelial as well as perivascular cells (pericytes and vascular smooth muscle cells).
Danish: Nintedanib binder sig kompetitivt til disse receptorers adenosintrifosfat (ATP)-bindende lommer og blokerer den intracellulære signalvej, som er afgørende for proliferation og overlevelse af både endotelceller og perivaskulære celler (pericytter og glatte muskelceller i blodkar).
English: The proportion of adenocarcinoma patients with stage < IIIB/IV at diagnosis was small and balanced across treatment arms (placebo: 54 patients (16.1 %); nintedanib: 50 patients, (15.5 %)).
Danish: Andelen af adenokarcinom patienter med sygdomsstadium < IIIB/IV på diagnosetidspunktet, var lille og næsten den samme i begge behandlingsgrupper (placebo: 54 patienter (16,1 %); nintedanib: 50 patienter (15,5 %)).
English: Painful, numb and/or tingling feeling in fingers and toes (peripheral neuropathy) Feeling sick (nausea)
Danish: Smerter, følelsesløshed og/eller en prikkende/snurrende fornemmelse i fingre og tæer (perifer neuropati)
English: Vargatef has minor influence on the ability to drive and use machines.
Danish: Vargatef påvirker i mindre grad evnen til at føre motorkøretøj og betjene maskiner.
English: Women who can become pregnant must use an effective combination of birth control methods, including barrier methods as a second form of contraception, while they are taking Vargatef and for at least 3 months after stopping treatment.
Danish: Kvinder som kan blive gravide skal bruge en sikker kombination af præventionsmetoder, herunder barrieremetoden som ekstra sikkerhed, så længe de får Vargatef og i mindst 3 måneder efter endt behandling.
English: Not all pack-sizes of Vargatef 100 mg soft capsules may be marketed.
Danish: Ikke alle pakningsstørrelser af Vargatef 100 mg bløde kapsler er nødvendigvis markedsført.
English: In repeat dose toxicology studies in rats, adverse effects (e.g. thickening of epiphyseal plates, lesions of the incisors) were mostly related to the mechanism of action (i.e. VEGFR-2 inhibition) of nintedanib.
Danish: I toksikologiske studier med gentagne doser til rotter var bivirkninger (f.eks. fortykkelse af epifyseskiver, læsioner på fortænder) for det meste relaterede til nintedanibs virkningsmekanisme (dvs. VEGFR-2-hæmning).
English: Preclinical studies showed that small amounts of nintedanib and its metabolites (≤ 0.5 % of the administered dose) were secreted into milk of lactating rats.
Danish: Prækliniske studier påviste, at små mængder nintedanib og dets metabolitter (≤ 0,5 % af den administrerede dosis) blev udskilt i mælken hos diegivende rotter.
English: Based on population pharmacokinetic (PK) analyses, no a priori dose adjustments of Vargatef are necessary (see section 5.2).
Danish: Farmakokinetiske (PK) populationsanalyser har påvist, at a priori dosisjusteringer af Vargatef ikke er nødvendige (se pkt.
English: Vargatef should be discontinued in patients with life-threatening venous thromboembolic reactions.
Danish: Vargatef skal seponeres hos patienter med livstruende venøse tromboemboliske reaktioner.
English: Recommended dose adjustments for Vargatef (nintedanib) in case of AST and/or ALT and bilirubin elevations
Danish: Anbefalede dosisjusteringer af Vargatef (nintedanib) i tilfælde af forhøjet ASAT og/eller ALAT og bilirubin
English: An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)
Danish: En udvidelse og svækkelse af en blodårevæg eller en rift i en blodårevæg (aneurismer og arterielle dissektioner)
English: Less than 1 % of a single dose of nintedanib is excreted via the kidney (see section 5.2).
Danish: Mindre end 1 % af en enkeltdosis nintedanib udskilles via nyrerne (se pkt.
English: Five point eight percent (5.8 %) of the patients had stable brain metastasis at trial entry and 3.8 % had prior bevacizumab treatment.
Danish: 5,8 % af patienterne havde stabile hjernemetastaser ved indgang i forsøget, og 3,8 % havde fået forudgående behandling med bevacizumab.
English: Limited safety data available from 9 patients with moderate hepatic impairment (Child Pugh B) are insufficient to characterize this population.
Danish: Der findes begrænsede sikkerhedsdata fra 9 patienter med moderat nedsat leverfunktion (Child Pugh B), hvilket er utilstrækkeligt til at karakterisere denne population.
English: LIST OF EXCIPIENTS Contains soya.
Danish: LISTE OVER HJÆLPESTOFFER Indeholder soja.
English: After food intake, nintedanib exposure increased by approximately 20 % compared to administration under fasted conditions (CI: 95.3 - 152.5 %) and absorption was delayed (median tmax fasted: 2.00 hours; fed: 3.98 h).
Danish: Efter fødeindtagelse steg eksponeringen for nintedanib med ca. 20 % sammenlignet med administration under faste (CI: 95,3-152,5 %), og absorptionen blev forsinket (median tmax fastende: 2,00 timer; kort efter et måltid: 3,98 timer).
English: Therefore, it is not recommended to treat these patients with Vargatef.
Danish: Derfor anbefales behandling med Vargatef ikke til disse patienter.
English: Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE31
Danish: Farmakoterapeutisk klassifikation: Antineoplastiske stoffer, proteinkinasehæmmere, ATC-kode: L01XE31.
English: The potential for interactions of nintedanib with hormonal contraceptives was not explored.
Danish: Potentialet for interaktioner mellem Vargatef og hormonale kontraceptiva er ikke undersøgt.
English: Only a minor extent of the biotransformation of nintedanib consisted of CYP pathways with CYP 3A4 being the predominant enzyme involved.
Danish: Biotransformationen af nintedanib omfattede kun i mindre grad CYP-reaktionsveje med CYP 3A4 som det dominerende af de involverede enzymer.
English: Vargatef is indicated in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after first-line chemotherapy.
Danish: Vargatef er indiceret i kombination med docetaxel til behandling af voksne patienter med lokalt fremskreden, metastatisk eller lokalt recidiverende ikke-småcellet lungekræft (NSCLC) med adenokarcinom tumorhistologi efter førstelinje kemoterapi.
English: The safety data provided in the sections below are based on the global, double-blind randomised pivotal phase 3 trial 1199.13 (LUME-Lung 1) comparing treatment with nintedanib plus docetaxel against placebo plus docetaxel in patients with locally advanced, or metastatic, or recurrent NSCLC after first-line chemotherapy and based on data observed during the post-marketing period.
Danish: De sikkerhedsdata, der beskrives i afsnittene nedenfor, er baseret på det globale, dobbeltblindede, randomiserede fase 3-hovedstudie 1199.13 (LUME-Lung 1), der sammenlignede behandling med nintedanib plus docetaxel over for placebo plus docetaxel hos patienter med lokalt fremskreden eller metastatisk eller recidiverende NSCLC efter førstelinje kemoterapi, og baseret på data observeret i perioden efter markedsføring.
English: Therapy with Vargatef should be permanently discontinued in patients who develop gastrointestinal perforation.
Danish: Behandling med Vargatef skal seponeres permanent hos patienter, der udvikler gastrointestinal perforation.
English: Frequent monitoring of complete blood counts should be performed at the beginning of each treatment cycle and around the nadir for patients receiving treatment with nintedanib in combination with docetaxel, and as clinically indicated after the administration of the last combination cycle.
Danish: Der skal hyppigt tages et fuldstændigt blodbillede i starten af hver behandlingscyklus og omkring nadir for patienter, der får behandling med nintedanib i kombination med docetaxel, og som klinisk indiceret efter administration af den sidste kombinationscyklus.
English: In the pivotal trial 1199.13, 85 patients (12.9 % of the patients with adenocarcinoma histology) were ≥ 70 years of age (median age: 72 years, range: 70 - 80 years) (see section 5.1).
Danish: I hovedforsøget 1199.13 var 85 patienter (12,9 % af patienterne med adenokarcinom histologi) ≥ 70 år gamle (medianalder: 72 år, variationsbredde: 70-80 år (se pkt.
English: Nausea and vomiting, mostly of mild to moderate severity, were frequently reported gastrointestinal adverse reactions (see section 4.8).
Danish: Kvalme og opkastning, for det meste af mild til moderat sværhedsgrad, var hyppigt indberettede gastrointestinale bivirkninger (se pkt.
English: Women of childbearing potential being treated with Vargatef should be advised to avoid becoming pregnant while receiving this treatment and to use adequate contraception during and at least 3 months after the last dose of Vargatef.
Danish: Fertile kvinder i behandling med Vargatef skal rådes til at undgå at blive gravide, mens de får denne behandling, og til at anvende sikker prævention under behandlingen med Vargatef og i mindst 3 måneder efter den sidste dosis.
English: Diarrhoea, Vomiting, Nausea, Abdominal pain
Danish: Diarré, opkastning, kvalme, mavesmerter
English: Do not use this medicine after the expiry date which is stated on the carton, wrapper and blisters.
Danish: Brug ikke lægemidlet efter den udløbsdato, der står på kartonen, indpakningen og blisterne.
English: The efficacy and safety of Vargatef was investigated in 1314 adult patients with locally advanced, metastatic or recurrent NSCLC after one prior line of chemotherapy.
Danish: Vargatefs virkning og sikkerhed blev undersøgt hos 1314 voksne patienter med lokalt fremskreden, metastatisk eller recidiverende NSCLC efter én tidligere kemoterapi linje.
English: Most patients recovered from diarrhoea following treatment interruption, anti-diarrhoeal therapy and nintedanib dose reduction.
Danish: Hos de fleste patienter bedredes diarréen efter afbrydelse af behandlingen, behandling mod diarré og reduktion af dosis af nintedanib.
English: In case of bleeding, dose adjustment, interruption or discontinuation should be considered based on clinical judgement (see section 4.2).
Danish: I tilfælde af blødning bør dosisjustering, afbrydelse eller seponering overvejes, baseret på klinisk vurdering (se pkt.
English: Teratogenic effects on the aortic arches in combination with the heart and the urogenital system were noted at an exposure 4 times higher than at the MRHD and on the embryofoetal development of the axial skeleton at an exposure 3 times higher than at the MRHD.
Danish: Der sås teratogene virkninger på aortabuerne samt hjertet og urogenitalsystemet ved en eksponering, der var 4 gange større end eksponeringen ved MRHD, og på den embryoføtale udvikling af det aksiale skelet ved en eksponering, der var 3 gange større end eksponeringen ved MRHD.
English: As expected via its mechanism of action perforation might occur in patients treated with nintedanib.
Danish: Som forventet ud fra nintedanibs virkningsmekanisme kan perforation forekomme hos patienter i behandling med nintedanib.
English: Blood counts should be monitored during therapy, in particular during the combination treatment with docetaxel.
Danish: Blodbilledet skal kontrolleres under behandlingen, især under kombinationsbehandling med docetaxel.
English: Neutropenia and sepsis
Danish: Neutropeni og sepsis
English: In clinical trials the frequency was not increased in patients treated with nintedanib plus docetaxel as compared to placebo plus docetaxel.
Danish: I kliniske studier var hyppigheden ikke øget hos patienter, der blev behandlet med nintedanib plus docetaxel sammenlignet med placebo plus docetaxel.
English: Do not take Vargatef - if you are allergic to nintedanib, to peanut or soya, or to any of the other ingredients of this medicine (listed in section 6).
Danish: Tag ikke Vargatef - hvis du er allergisk over for nintedanib, jordnødder eller soja eller over for et af de øvrige indholdsstoffer i Vargatef (angivet i afsnit 6).
English: In a drug-drug interaction study with the potent P-gp inducer rifampicin, exposure to nintedanib decreased to 50.3 % based on AUC and to 60.3 % based on Cmax upon co-administration with rifampicin compared to administration of nintedanib alone.
Danish: I et lægemiddel-lægemiddel interaktionsstudie med den potente P-gp-induktor rifampicin faldt eksponeringen for nintedanib til 50,3 % baseret på AUC og til 60,3 % baseret på Cmax ved samtidig administration af rifampicin sammenlignet med administration af nintedanib alene.
English: The major route of elimination of drug related radioactivity after oral administration of [14C] nintedanib was via faecal/biliary excretion (93.4 % of dose, 2.61 % gCV).
Danish: Den vigtigste eliminationsvej for lægemiddelrelateret radioaktivitet efter oral administration af [14C] nintedanib var udskillelse med fæces/galden (93,4 % af dosis; 2,61 % gCV).
English: However, no thorough QT-trial of nintedanib administered in combination with docetaxel was conducted.
Danish: Der er dog ikke udført grundige QT-studier med nintedanib i kombination med docetaxel.
English: Jaundice (hyperbilirubinaemia)
Danish: Gulsot (hyperbilirubinæmi)
English: If necessary, your doctor may further reduce your daily dose to 200 mg per day (two capsules of 100 mg).
Danish: Hvis det er nødvendigt, kan din læge nedsætte din daglige dosis yderligere til 200 mg om dagen (to kapsler a 100 mg).
English: A higher frequency of neutropenia of CTCAE grade ≥ 3 was observed in patients treated with Vargatef in combination with docetaxel as compared to treatment with docetaxel alone.
Danish: Neutropeni af CTCAE grad ≥ 3 blev observeret hyppigere hos patienter, der blev behandlet med Vargatef i kombination med docetaxel, sammenlignet med behandling med docetaxel alene.
English: Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) measurements showed an anti-angiogenic effect of nintedanib in humans.
Danish: DCE-MRI-målinger (dynamisk MR-scanning med kontrast) påviste en anti-angiogen virkning af nintedanib hos mennesker.
English: Your doctor may reduce your recommended dose to 300 mg per day (two capsules of 150 mg).
Danish: Din læge kan nedsætte din anbefalede dosis til 300 mg om dagen (to kapsler a 150 mg).
English: If you forget to take Vargatef
Danish: Hvis du har glemt at tage Vargatef
English: Vargatef capsules contain the active substance nintedanib.
Danish: Vargatef kapsler indeholder det aktive stof nintedanib.
English: Table 3 summarizes the frequencies of adverse drug reactions that were reported in the pivotal trial LUME-Lung 1 for patients with NSCLC of adenocarcinoma tumour histology (n = 320) or from the post-marketing period.
Danish: Tabel 3 opsummerer hyppighederne af de bivirkninger, der blev indberettet i hovedforsøget LUMELung 1 for patienter med NSCLC med adenokarcinom tumorhistologi (n=320) eller i perioden efter markedsføring.
English: QT/QTc measurements were recorded and analysed from a dedicated trial comparing nintedanib monotherapy against sunitinib monotherapy in patients with renal cell carcinoma.
Danish: QT/QTc-målinger blev registreret og analyseret i et målrettet forsøg, der sammenlignede nintedanibmonoterapi og sunitinib-monoterapi hos patienter med nyrecellekarcinom.
English: As several other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administering nintedanib in patients who may develop QTc prolongation.
Danish: Da man ved, at flere andre tyrosinkinasehæmmere har indvirkning på QT-intervallet, skal der udvises forsigtighed, når Vargatef bliver givet til patienter, som måske kan få QTc-forlængelse.
English: Venous thromboembolism Hypertension
Danish: Venøs tromboembolisme hypertension
English: In a post-hoc analysis in adenocarcinoma patients having progressed and entered the trial ≥ 9 months since start of their first-line therapy the difference did not reach statistical significance (HR for OS: 0.89, 95 % CI 0.66 - 1.19).
Danish: I en post hoc-analyse blandt de adenokarcinom patienter, der havde oplevet progression, og som var indgået i forsøget ≥ 9 måneder efter initiering af deres førstelinjebehandling, var forskellen ikke statistisk signifikant (HR for OS: 0,89; 95 % CI: 0,66-1,19).
English: BIBF 1202 is subsequently glucuronidated by UGT enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide.
Danish: BIBF 1202 glucuronideres efterfølgende af UGTenzymer, nærmere bestemt UGT 1A1, UGT 1A7, UGT 1A8 og UGT 1A10, til BIBF 1202-glucuronid.
English: Elevation of AST and/or ALT values to > 5 x ULN
Danish: ASAT og/eller ALAT forhøjet til > 5 x ULN
English: However, an increased frequency of arterial thromboembolic events was observed in patients with idiopathic pulmonary fibrosis (IPF) when treated with nintedanib monotherapy.
Danish: Der sås dog en øget hyppighed af arterielle tromboemboliske hændelser hos patienter med idiopatisk lungefibrose (IPF), når de blev behandlet med nintedanib som monoterapi.
English: You should discuss the most appropriate methods of contraception for you with your doctor.
Danish: Tal med lægen om, hvilke præventionsmetoder der er mest velegnede for dig.
English: In such cases, patients should be monitored closely for tolerability of nintedanib.
Danish: I sådanne tilfælde skal patienterne kontrolleres tæt med hensyn til tolerabiliteten af Vargatef.
English: Cases of drug-induced liver injury have been observed with nintedanib treatment, including severe liver injury with fatal outcome.
Danish: Der er observeret tilfælde af lægemiddelinduceret leverskade underbehandling med nintedanib, herunder svær leverskade med dødelig udgang.
English: Vomiting ≥ grade 2
Danish: Opkastning ≥ grad 2
English: If you stop taking Vargatef
Danish: Hvis du holder op med at tage Vargatef
English: Peripheral neuropathy is also known to occur with docetaxel treatment.
Danish: Der kan også forekomme perifer neuropati ved behandling med docetaxel.
English: Vargatef may have minor influence on your ability to drive and use machines.
Danish: Vargatef påvirker i mindre grad din evne til at føre motorkøretøj eller betjene maskiner.
English: If you cannot tolerate the recommended dose of 300 mg per day because of side effects (see section 4), your doctor may reduce your recommended daily dose of Vargatef to 200 mg per day (two capsules of 100 mg).
Danish: Hvis du ikke kan tåle den anbefalede dosis på 300 mg om dagen på grund af bivirkninger (se afsnit 4), kan din læge nedsætte din anbefalede daglige dosis Vargatef til 200 mg om dagen (to kapsler a 100 mg).
English: Diarrhoea was the most frequently reported gastro-intestinal adverse reaction and appeared in close temporal relationship with the administration of docetaxel (see section 4.8).
Danish: Diarré var den hyppigst indberettede gastrointestinale bivirkning, og den forekom i en tæt tidsmæssig sammenhæng med administration af docetaxel (se pkt.
English: Very common side effects (may affect more than 1 in 10 people) Diarrhoea - please see above
Danish: Meget almindelige bivirkninger (kan forekomme hos flere end 1 ud af 10 personer) Diarré - se ovenfor
English: Fluid loss (dehydration)
Danish: Væsketab (dehydrering)
English: Drug-drug interactions between nintedanib and CYP substrates, CYP inhibitors, or CYP inducers are not expected, since nintedanib, BIBF 1202, and BIBF 1202 glucuronide did not inhibit or induce CYP enzymes in preclinical studies nor was nintedanib metabolized by CYP enzymes to a relevant extent.
Danish: Lægemiddel-lægemiddel interaktioner mellem nintedanib og CYP-substrater, CYP-hæmmere eller CYP-induktorer forventes ikke, da nintedanib, BIBF 1202 og BIBF 1202-glucuronid hverken hæmmede eller inducerede CYP-enzymer i prækliniske studier, ligesom nintedanib ikke metaboliseres af CYP-enzymer i relevant omfang.
English: Neutropenia, febrile neutropenia and sepsis
Danish: Neutropeni, febril neutropeni og sepsis
English: Therefore, women should not breast-feed during treatment with Vargatef.
Danish: Derfor må kvinder ikke amme, mens de er i behandling med Vargatef.
English: It is important that the patient's blood counts are monitored during therapy, in particular during the combination treatment with docetaxel (see section 4.4).
Danish: Det er vigtigt, at patientens blodbillede kontrolleres under behandlingen, især under kombinationsbehandling med docetaxel (se pkt.
English: In volunteers with moderate hepatic impairment (Child Pugh B), exposure was 7.6-fold higher based on Cmax (90 % CI 4.4 - 13.2) and 8.7fold higher (90 % CI 5.7 - 13.1) based on AUC, respectively, compared to healthy volunteers.
Danish: Hos frivillige med moderat nedsat leverfunktion (Child Pugh B) var eksponeringen henholdsvis 7,6 gange højere baseret på Cmax (90 %-CI 4,4-13,2) og 8,7 gange højere (90 %-CI 5,7-13,1) baseret på AUC end hos raske frivillige.
English: In trial 1199.13 (LUME-Lung 1), there was a higher frequency of SAEs in patients treated with nintedanib plus docetaxel with a body weight of less than 50 kg compared to patients with a weight ≥ 50 kg; however the number of patients with a body weight of less than 50 kg was small.
Danish: I forsøg 1199.13 (LUME-Lung 1) var hyppigheden af alvorlige hændelser (SAEs) hos de patienter, der blev behandlet med nintedanib plus docetaxel, større hos patienter der vejede under 50 kg end hos patienter der vejede ≥ 50 kg.
English: In the overall population, 16.0 % of the patients had disease stage < IIIB/IV, 22.4 %, had disease stage IIIB and 61.6 % had disease stage IV. 9.2 % of the patients entered the trial with locally recurrent disease stage as had been evaluated at baseline.
Danish: I den samlede population havde 16,0 % af patienterne sygdomsstadium < IIIB/IV, 22,4 % havde sygdomsstadium IIIB, og 61,6 % havde sygdomsstadium IV. Ni komma to procent (9,2 %) af patienterne indgik i forsøget med sygdomsstadiet “lokalt recidiverende”, vurderet ved baseline.
English: In rats, embryofoetal lethality and teratogenic effects were observed at exposure levels below human exposure, at the maximum recommended human dose (MRHD) of 200 mg b.i.d.
Danish: Hos rotter blev der observeret embryoføtal letalitet og teratogene virkninger ved en eksponering, der var lavere end den humane eksponering ved den højeste anbefalede dosis til mennesker (MRHD) på 200 mg to gange daglig.