natgillin/translations-raw huggingface dataset:
Nintedanibs velfunderede virkning på reduktionen af den årlige grad af forværring i FVC blev bekræftet i alle præ-specificerede sensitivitetsanalyser.
The robustness of the effect of nintedanib in reducing the annual rate of decline in FVC was confirmed in all pre-specified sensitivity analyses.
Vaskulær endotelial vækstfaktor-receptorhæmning (VEGFR-hæmning) kan være forbundet med en øget risiko for blødning.
Vascular endothelial growth factor receptor (VEGFR) inhibition might be associated with an increased risk of bleeding.
Antal analyserede patienter
Number of analysed patients
Din behandling med Ofev bliver derfor som regel afbrudt, hvis du skal opereres.
Therefore your treatment with Ofev will usually be stopped for a while if you are having a surgery.
Opbevares i original pakning for at beskytte mod fugt.
Store in the original package in order to protect from moisture.
Der er rapporteret om tilfælde af gastrointestinal perforation, blandt hvilke nogle havde dødelig udgang, i perioden efter markedsføringen.
Cases of gastrointestinal perforations, some of which were fatal, have been reported in the post-marketing period.
En præspecificeret sensitivitetsanalyse af tiden til første 'bekræftede' eller 'formodede' vurderede akutte IPF-eksacerbation blev udført på de samlede data.
A pre-specified sensitivity analysis of the time to first 'confirmed' or 'suspected' adjudicated acute IPF exacerbation was performed on the pooled data.
Derfor bør hepatisk aminotransferase- og bilirubin-niveauer måles før behandlingsinitiering og i løbet af den første måneds behandling med Ofev.
Therefore, hepatic transaminase and bilirubin levels should be investigated before treatment initiation and during the first month of treatment with Ofev.
Dalværdier for nintedanibkoncentrationen forblev stabile i mere end et år.
Nintedanib trough concentrations remained stable for more than one year.
To patienter i onkologiprogrammet fik en overdosis på højst 600 mg to gange dagligt i op til otte dage.
Two patients in the oncology programme had an overdose of maximum 600 mg twice daily up to eight days.
Der er ingen information om anvendelse af Ofev til gravide kvinder, men prækliniske dyrestudier har vist reproduktionstoksicitet af dette aktive stof (se pkt.
There is no information on the use of Ofev in pregnant women, but pre-clinical studies in animals have shown reproductive toxicity of this active substance (see section 5.3).
SÆRLIGE OPBEVARINGSBETINGELSER Må ikke opbevares over 25 °C.
SPECIAL STORAGE CONDITIONS Do not store above 25°C.
Diarré kan medføre dehydrering: tab af væske og vigtige salte (elektrolytter, som f.eks. natrium eller kalium) fra din krop.
Diarrhoea may lead to dehydration: a loss of fluid and important salts (electrolytes, such as sodium or potassium) from your body.
Arvævet reducerer lungernes evne til at transportere ilt fra lungerne til blodet, og det bliver vanskeligt at trække vejret dybt.
As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream and it becomes difficult to breathe deeply.
Alle uønskede hændelser ved akut IPF-eksacerbation, der blev indberettet af investigatoren, blev vurderet af en blindet evalueringskomité.
All adverse events of acute IPF exacerbation reported by the investigator were adjudicated by a blinded adjudication committee.
DATO FOR FØRSTE MARKEDSFØRINGSTILLADELSE/FORNYELSE AF TILLADELSEN Dato for første markedsføringstilladelse: 15. januar 2015 Dato for seneste fornyelse: 23. september 2019
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 15 January 2015
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 ischemia.
ENTYDIG IDENTIFIKATOR - 2D-STREGKODE Der er anført en 2D-stregkode, som indeholder en entydig identifikator.
UNIQUE IDENTIFIER - 2D BARCODE 2D barcode carrying the unique identifier included.
Patienter med kendt risiko for blødning, herunder patienter med hereditær disposition for blødning eller patienter, der får en fuld dosis antikoagulerende behandling, var ikke inkluderet i INPULSISstudierne.
Patients at known risk for bleeding including patients with inherited predisposition to bleeding or patients receiving a full dose of anticoagulative treatment were not included in the INPULSIS studies.
Der blev kun observeret potentiale for svag hæmning af OCT-1, BCRP og P-gp in vitro, hvilket anses for at have ringe 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.
Figur 1:
Figure 1:
Behandling med Ofev bør initieres af læger, der har erfaring med diagnosticering og behandling af IPF.
Treatment with Ofev should be initiated by physicians experienced in the diagnosis and treatment of IPF.
Begge patienter kom sig efter disse bivirkninger.
Both patients recovered from these adverse reactions.
Børn og unge Børn og unge under 18 år må ikke tage Ofev.
Children and adolescents Ofev should not be taken by children and adolescents under 18 years of age.
• Periodiske, opdaterede sikkerhedsindberetninger (PSUR'er)
• Periodic safety update reports
NAVN PÅ INDEHAVEREN AF MARKEDSFØRINGSTILLADELSEN Boehringer Ingelheim (logo)
NAME OF THE MARKETING AUTHORISATION HOLDER Boehringer Ingelheim (logo)
Behandling med Ofev anbefales derfor ikke til sådanne patienter (se pkt.
Therefore treatment with Ofev is not recommended in such patients (see section 4.2).
Dette sikrer, at der hele tiden er en konstant mængde nintedanib i blodbanen.
This ensures that a steady amount of nintedanib is maintained in your blood stream.
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%).
Benefit-risk-forholdet for samtidig behandling med pirfenidon er ikke klarlagt.
The benefit-risk balance of concomitant treatment with pirfenidone has not been established.
AUCτ,ss faldt med 16 % hos en 45-årig patient og blev øget med 13 % hos en 76-årig patient i forhold til en patient med en gennemsnitsalder på 62 år.
AUCτ,ss decreased by 16% for a 45-year old patient and increased by 13% for a 76-year old patient relative to a patient with the median age of 62 years.
Der blev observeret en omvendt korrelation mellem legemsvægt og nintedanib-eksponering.
An inverse correlation between body weight and exposure to nintedanib was observed.
I betragtning af det begrænsede antal patienter detekterede dette studie kun de hyppigste bivirkninger, og viste en stigning i mavetarm-bivirkninger og en tendens til flere lever-bivirkninger.
In view of the limited number of patients, this study detected only the most frequent adverse events and showed an increase in gastrointestinal adverse events and a trend toward increased hepatic adverse events.
Kontakt lægen, hvis du får bivirkninger.
Talk to your doctor if you get any side effects.
Patienterne skal rådes til at udvise forsigtighed, når de fører motorkøretøj eller betjener maskiner under behandling med Ofev.
Patients should be advised to be cautious when driving or using machines during treatment with Ofev.
Responderpatienter er dem, der ikke har noget absolut fald større end 5 % eller større end 10 % i FVC % forventet, afhængigt af tærskelværdien og med FVC-evaluering efter 52 uger.
Responder patients are those with no absolute decline greater than 5% or greater than 10% in FVC % predicted, depending on the threshold and with an FVC evaluation at 52 weeks.
Det primære endepunkt var procentdelen af patienter med mave-tarm-bivirkninger fra baseline til uge 12.
The primary endpoint was the percentage of patients with gastrointestinal adverse events from baseline to week 12.
Leverenzymforhøjelse var reversibel og ikke forbundet med klinisk manifest leversygdom.
Elevations of liver enzymes were reversible and not associated with clinically manifest liver disease.
Inden indledning af behandling med Ofev bør denne risiko overvejes nøje for patienter med risikofaktorer såsom hypertension eller tidligere aneurisme.
Before initiating Ofev, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
Akkumuleringen efter gentagne administrationer var 1,04 gange for Cmax og 1,38 gange for AUCτ.
Accumulation upon multiple administrations was 1.04-fold for Cmax and 1.38-fold for AUCτ.
Hvis symptomerne varer ved på trods af behørig, støttende behandling (herunder antiemetisk behandling), kan dosisreduktion eller behandlingsafbrydelse være nødvendig.
If symptoms persist despite appropriate supportive care (including anti-emetic therapy), dose reduction or treatment interruption may be required.
Nintedanib er en lav-molekylær tyrosinkinasehæmmer, herunder påvirkes trombocytderiverede vækstfaktor-receptorer (PDGFR) α og β, fibroblast vækstfaktor-receptorer (FGFR) 1-3 og VEGFR 1-3.
Nintedanib is a small molecule tyrosine kinase inhibitor including the receptors platelet-derived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, and VEGFR 1-3.
Inden for de enkelte hyppighedskategorier er bivirkningerne opstillet efter faldende alvorlighed.
Within each frequency grouping adverse reactions are presented in order of decreasing seriousness.
Der var ingen evidens for forhøjede leverenzymer hos rotter, hunde eller cynomolgusaber.
There was no evidence of liver enzyme increases in rats, dogs, and Cynomolgus monkeys.
Patienter med FVC < 50 % af forventet ved baseline eller carbonmonooxid diffusionskapacitet (DLCO, korrigeret for hæmoglobin) < 30 % af forventet ved baseline, blev ekskluderet fra studierne.
Patients with FVC baseline < 50% predicted or carbon monoxide diffusing capacity (DLCO, corrected for haemoglobin) < 30% predicted at baseline were excluded from the trials.
På grund af den høje interindividuelle variabilitet i eksponeringen anses disse virkninger ikke for klinisk relevante (se pkt.
Based on the high inter-individual variability of exposure observed moderate effects are considered not clinically relevant (see section 4.4).
Baseret på en PopPK-model blev der observeret en stigning i nintedanib-eksponeringen på omkring 20-25 % hos patienter i alderen ≥ 75 år sammenlignet med patienter under 65 år.
Based on a PopPK model, an increase in nintedanib exposure of approximately 20 - 25% was observed in patients ≥ 75 years compared with patients under 65 years.
Patienter med kendt allergi over for jordnøddeprotein har en øget risiko for svære reaktioner på sojapræparater.
Patients with known allergy to peanut protein carry an enhanced risk for severe reactions to soya preparations.
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%.
Nintedanib fordeles fortrinsvis i plasma med et blod/plasma-forhold på 0,869.
Nintedanib is preferentially distributed in plasma with a blood to plasma ratio of 0.869.
Da nintedanibs virkning på kontraceptivas metabolisme og virkning ikke er undersøgt, skal en barrieremetode anvendes som en ekstra præventionsmetode for at undgå graviditet.
Since the effect of nintedanib on the metabolism and efficacy of hormonal contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.
De observerede bivirkninger var forenelige med den kendte sikkerhedsprofil for nintedanib, dvs. forhøjede leverenzymer og gastrointestinale symptomer.
Observed adverse reactions were consistent with the known safety profile of nintedanib, i.e. increased liver enzymes and gastrointestinal symptoms.
Vægttab Nedsat appetit
Weight decreased, Decreased appetite
Gastrointestinal perforation
Gastrointestinal perforations
Endvidere blev der observeret lignende effekt på andre endepunkter vedrørende lungefunktionen, f.eks. ændring fra baseline i FVC i uge 52 og FVC-responderanalyser, der yderligere understøttede nintedanibs forsinkende effekt på sygdomsprogression.
In addition, similar effects were observed on other lung function endpoints e.g. change from baseline in FVC at week 52 and FVC responder analyses providing further substantiation of the effects of nintedanib on slowing disease progression.
Diarré og opkastning ledsaget af nedsat fødeindtagelse og vægttab blev observeret i toksicitetsstudier hos ikke-gnavere.
Diarrhoea and vomiting accompanied by reduced food consumption and loss of body weight were observed in toxicity studies in non-rodents.
Valg af et andet lægemiddel med intet eller kun svagt P-gp-induktionspotentiale skal overvejes.
Selection of an alternate concomitant medicinal product with no or minimal Pgp induction potential should be considered.
Et studie af fertiliteten hos hanner og tidlig embryonal udvikling indtil implantation hos rotter viste ingen virkninger på reproduktionsorganer eller fertilitet hos hanner.
A study of male fertility and early embryonic development up to implantation in rats did not reveal effects on the male reproductive tract and male fertility.
Endvidere hæmmer nintedanib Flt-3 (Fms-lignende tyrosinproteinkinase), Lck (lymfocytspecifik tyrosinproteinkinease), Lyn (tyrosinproteinkinase lyn) og Src (proto-onkogen tyrosinproteinkinase src) -kinaser.
In addition nintedanib inhibits Flt-3 (Fms-like tyrosine-protein kinase), Lck (lymphocyte-specific tyrosine-protein kinase), Lyn (tyrosine-protein kinase lyn) and Src (proto-oncogene tyrosine-protein kinase src) kinases.
I så fald vil din læge ordinere Ofev 100 mg bløde kapsler til din behandling.
In this case your doctor will prescribe Ofev 100 mg capsules for your treatment.
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.
Hos mere end totredjedel af de patienter, der fik diarré, var første forekomst allerede i de første tre måneder af behandlingen.
More than two thirds of patients experiencing diarrhoea reported its first onset already during the first three months of treatment.
Det er vist, at nintedanib hverken er et substrat for eller en hæmmer af OATP-1B1, OATP1B3, 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.
Kapslerne skal synkes hele sammen med vand og må ikke tygges eller knuses.
The capsules should be taken with food, swallowed whole with water, and should not be chewed or crushed.
De væsentligste sekundære endepunkter var ændring fra baseline i den samlede score i Saint Georges spørgeskema (Saint George's Respiratory Questionnaire, SGRQ) ved 52 uger og tid til første akutte IPF-eksacerbation.
The key secondary endpoints were change from baseline in Saint George's Respiratory Questionnaire (SGRQ) total score at 52 weeks and time to first acute IPF exacerbation.
Hazard ratio
Odds ratio
Estimat baseret på en tilfældig koefficientregressionsmodel.
Estimated based on a random coefficient regression model.
Der skal udvises forsigtighed ved behandling af patienter med øget kardiovaskulær risiko, herunder kendt koronararteriesygdom.
Caution should be used when treating patients at higher cardiovascular risk including known coronary artery disease.
Nintedanib binder kompetitivt til disse receptorers ATP-bindende lommer og blokerer den intracellulære signalvej.
Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signalling.
p-værdi
p-value
I prækliniske sygdomsmodeller af lungefibrose udviser nintedanib potent antifibrotisk og antiinflammatorisk aktivitet.
In preclinical disease models of lung fibrosis nintedanib exerts potent anti-fibrotic and anti-inflammatory activity.
Det er ikke nødvendigt at justere startdosis til patienter med let til moderat nedsat nyrefunktion.
Adjustment of the starting dose in patients with mild to moderate renal impairment is not required.
Nintedanibs farmakokinetik kan anses for at være lineær med hensyn til tid (dvs. data for en enkeltdosis kan ekstrapoleres til data for gentagne doser).
The pharmacokinetics (PK) of nintedanib can be considered linear with respect to time (i.e. singledose data can be extrapolated to multiple-dose data).
For nintedanibs potentiale for interaktion med denne transportør, se pkt.
For the interaction potential of nintedanib with this transporter, see section 4.5.
Det samme gælder for nintedanibs rolle som substrat for OCT-1.
The same applies for nintedanib being a substrate of OCT-1.
Antal i risiko Patienter med hændelser, N (%) Sammenlignet med placebo p-værdi Hazard ratio 95 % CI
Number at risk Patients with events, N (%) Comparison vs placebo p-value Hazard ratio 95% CI
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med Ofev i alle undergrupper af den pædiatriske population ved IPF (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with Ofev in all subsets of the paediatric population in IPF (see section 4.2 for information on paediatric use).
Sandsynligheden for lægemiddel-lægemiddel interaktioner med nintedanib på grundlag af 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.
Alvorlige blødningshændelser forekom med lav og samme hyppighed i de 2 behandlingsgrupper (placebo: 1,4 %; Ofev: 1,3 %).
Serious bleeding events occurred with low and similar frequencies in the 2 treatment groups (placebo: 1.4%; Ofev: 1.3%).
Den gennemsnitlige eksponering for nintedanib var 33-50 % højere hos kinesiske, taiwanesiske og indiske patienter, og 16 % højere 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).
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.
Nintedanib elimineres primært ved udskillelse via galde/fæces (> 90 %).
Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%).
Administration sammen med andre lægemidler Potentialet for interaktioner mellem nintedanib og hormonale kontraceptiva er ikke undersøgt.
Co-administration with other medicinal products The potential for interactions of nintedanib with hormonal contraceptives was not explored.
Generelt er virkningen af nintedanib på livskvalitet, målt ved den samlede SGRQ-score, beskeden og indikerer mindre forværring sammenlignet med placebo.
Overall, the effect of nintedanib on health-related quality of life as measured by the SGRQ total score is modest, indicating less worsening compared to placebo.
Efter intravenøs infusion blev der observeret et højt fordelingsvolumen (Vss: 1.050 l; 45,0 % gCV).
After intravenous infusion, a high volume of distribution (Vss: 1,050 L, 45.0% gCV) was observed.
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.
Der er rapporteret om ikke-alvorlige og alvorlige blødninger, hvoraf nogle havde dødelig udgang i perioden efter markedsføringen (både hos patienter, der blev behandlet med koagulationshæmmende lægemidler eller andre lægemidler, der kan forårsage blødning og hos patienter, der ikke blev behandlet med sådanne lægemidler).
Non-serious and serious bleeding events, some of which were fatal, have been reported in the postmarketing period (including patients with or without anticoagulant therapy or other medicinal products that could cause bleeding).
Mave-tarm-bivirkninger var hyppige og på niveau med med den fastlagte sikkerhedsprofil for hver komponent.
Gastrointestinal adverse events were frequent and in line with the established safety profile of each component.
Pædiatrisk population Ofevs sikkerhed og virkning hos børn i alderen 0-18 år er ikke klarlagt.
The safety and efficacy of Ofev in children aged 0-18 years have not been established.
Farmakokinetiske populationsanalyser i særlige populationer Nintedanibs farmakokinetiske egenskaber var de samme hos raske frivillige personer, patienter med IPF og patienter med kræft.
Population pharmocokinetic analysis in special populations The PK properties of nintedanib were similar in healthy volunteers, patients with IPF, and cancer patients.
Lægemiddel-lægemiddel-interaktioner mellem nintedanib og CYP-substrater, CYP-hæmmere eller CYP-induktorer forventes derfor ikke.
Drug-drug interactions between nintedanib and CYP substrates, CYP inhibitors, or CYP inducers are therefore not expected.
Ikke kendt (kan ikke estimeres ud fra forhåndenværende data) - Nyresvigt - En udvidelse og svækkelse af en blodårevæg eller en rift i en blodårevæg (aneurismer og arterielle dissektioner)
Not known (cannot be estimated from the available data) - Renal failure - An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)
De hyppigst indberettede bivirkninger forbundet med nintedanib omfattede diarré, kvalme og opkastning, abdominalsmerter, nedsat appetit, vægttab og forhøjede leverenzymer.
The most frequently reported adverse reactions associated with the use of nintedanib included diarrhoea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
Der skal udvises særlig forsigtighed ved behandling af patienter, der tidligere har undergået abdominalkirurgi, hvis anamnese omfatter ulcus pepticum, diverticulosis coli eller som samtidigt modtager kortikosteroider eller NSAIDs.
Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs.
Da der er ligheder i sikkerhedsprofilerne for begge lægemidler, kan additive bivirkninger, herunder mave-tarm- og lever-bivirkninger forventes.
Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected.
.percentilen) og faldt med 19 % hos en patient på 100 kg (95 % percentilen) i forhold til en patient med en medianvægt på 71,5 kg.
th percentile) and decreased by 19% for a 100 kg patient th percentile) relative to a patient with the median weight of 71.5 kg.
Blod- og lymfesystem
Blood and lymphatic system disorders
Hos de fleste patienter havde bivirkningen let til moderat intensitet og opstod inden for de første 3 behandlingsmåneder.
In most patients the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment.
Du må ikke amme under behandlingen med Ofev, da der kan være en risiko for det ammede barn.
Do not breast-feed during the treatment with Ofev since there may be a risk for harm to the breastfeeding child.
Nintedanib var heller ikke et substrat for BCRP.
Nintedanib was also not a substrate of BCRP.
De skal informeres om at anvende sikker prævention under behandlingen med Ofev og i mindst 3 måneder efter den sidste dosis.
They should be advised to use adequate contraception during and at least 3 months after the last dose of Ofev.
Hvis patienten ikke tåler 100 mg to gange dagligt, bør Ofev seponeres.
If a patient does not tolerate 100 mg twice daily, treatment with Ofev should be discontinued.
Patienterne blev randomiseret i forholdet 3:2 til behandling med Ofev 150 mg eller placebo to gange dagligt i 52 uger.
Patients were randomized in a 3:2 ratio to treatment with Ofev 150 mg or placebo twice daily for 52 weeks.