natgillin/translations-raw huggingface dataset:
Myokardieinfarkt
Myocardial infarction
I toksikologistudier med gentagne doser til rotter var virkningerne (f.eks. fortykkelse af epifyseskiver, læsioner på fortænder) for det meste relaterede til nintedanibs virkningsmekanisme (dvs. VEGFR-2-hæmning).
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.
Hvis de målte aminotransferaseniveauer (ASAT eller ALAT) er > 3 x ULN, anbefales dosisreduktion eller afbrydelse af behandlingen med Ofev, og patienten skal monitorers nøje.
If transaminase (AST or ALT) elevations > 3x ULN are measured, dose reduction or interruption of the therapy with Ofev is recommended and the patient should be monitored closely.
60 x 1 bløde kapsler
60 x 1 soft capsules
Den estimerede forskel mellem behandlingsgrupperne var 0,131 l/år (95 % CI 0,027-0,235).
The estimated difference between the treatment groups was 0.131 L/year (95% CI 0.027, 0.235).
Dette indikerer, at risikoen for at få en første akut IPF-eksacerbation statistisk var signifikant lavere i nintedanib-gruppen end i placebogruppen på et hvilket som helst tidspunkt.
This indicates that the risk of having a first acute adjudicated IPF exacerbation was statistically significantly lower in the nintedanib group than in the placebo group at any time point.
Bidraget fra renal udskillelse 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).
Forhøjelse af leverenzymer (ALAT, ASAT, basisk fosfatase i blodet (ALKP), gammaglutamyltransferase (GGT)) og bilirubin var i de fleste tilfælde reversible ved dosisreduktion eller dosisafbrydelse.
Elevations of liver enzymes (ALT, AST, blood alkaline phosphatase (ALKP), gamma-glutamyltransferase (GGT)) and bilirubin were reversible upon dose reduction or interruption in the majority of cases.
Den dominerende metaboliske reaktion for nintedanib er hydrolytisk spaltning ved hjælp af esteraser, som resulterer i den frie syredel BIBF 1202.
The prevalent metabolic reaction for nintedanib is hydrolytic cleavage by esterases resulting in the free acid moiety BIBF 1202.
Hvis en patient bliver gravid under behandling med Ofev, skal hun gøres opmærksom på den mulige risiko for fosteret.
If the patient becomes pregnant while receiving Ofev, she should be apprised of the potential hazard to the foetus.
Andre årsager til de forhøjede leverenzymer bør undersøges.
Alternative causes of the liver enzyme elevations should be investigated.
Den estimerede middelændring fra baseline i den samlede SGRQ-score i uge 52 var 5,46 for placebo, hvilket indikerer en forværring af livskvalitet, og -0,66 for nintedanib, hvilket indikerer en stabil livskvalitet.
The estimated mean change from baseline in SGRQ total score at 52 weeks was 5.46 for placebo, indicating worsening of the health-related quality of life and -0.66 for nintedanib, indicating stable health-related quality of life.
Hos de fleste patienter med kvalme og opkastning havde bivirkningen let til moderat intensitet.
In most patients with nausea and vomiting, the event was of mild to moderate intensity.
I de 2-årige karcinogenicitetsstudier hos mus og rotter var der ingen evidens for et karcinogent potentiale af nintedanib.
From the 2-year carcinogenicity studies in mice and rats, there was no evidence for a carcinogenic potential of nintedanib.
Baseret på resultaterne fra en populationsfarmakokinetisk (PopPK) analyse hos patienter med IPF og småcellet lungekræft (NSCLC) (N=1.191) og beskrivende undersøgelser, blev eksponeringen for nintedanib ikke påvirket af køn (korrigeret for legemsvægt), let og moderat nedsat nyrefunktion (estimeret ved kreatininclearance), alkoholforbrug eller P-gpgenotype.
Based on results of a Population PK (PopPK) analysis in patients with IPF and non small cell lung cancer (NSCLC) (N=1,191) and descriptive investigations, exposure to nintedanib was not influenced by sex (body weight corrected), mild and moderate renal impairment (estimated by creatinine clearance), alcohol consumption, or P-gp genotype.
De maksimale plasmakoncentrationer af nintedanib blev nået ca. 2-4 timer efter oral administration af en blød gelatinekapsel kort efter et måltid (variationsbredde 0,5-8 timer).
Nintedanib reached maximum plasma concentrations approximately 2 - 4 h after oral administration as soft gelatine capsule under fed conditions (range 0.5 - 8 h).
Ofev bør seponeres permanent hos patienter, der udvikler gastrointestinal perforation.
Therapy with Ofev should be permanently discontinued in patients who develop gastrointestinal perforation.
Nintedanibs kliniske virkning er blevet undersøgt hos patienter med IPF i to randomiserede, dobbeltblindede, placebokontrollerede fase III-studier med identisk design (INPULSIS-1 (1199.32) og INPULSIS-2 (1199.34)).
The clinical efficacy of nintedanib has been studied in patients with IPF in two phase III, randomised, double-blind, placebo-controlled studies with identical design (INPULSIS-1 (1199.32) and INPULSIS-2 (1199.34)).
Den mulige virkning af VEGFR-hæmning vha. nintedanib og nintedanibs antiangiogene aktivitet på IPF-patogeneseer på nuværende tidspunkt ikke fuldt klarlagt.
The potential impact of VEGFR inhibition by nintedanib and the antiangiogenic activity of nintedanib on IPF pathology are currently not fully elucidated.
Samtidig behandling med pirfenidon
Concomitant treatment with pirfenidone
Fertile kvinder skal rådes til at undgå at blive gravide, mens de er i behandling med Ofev.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Ofev.
1 (SE) af forværring i 52 uger Sammenlignet med placebo Forskel 95 % CI
1 (SE) of decline over 52 weeks Comparison vs placebo Difference 95% CI
LÆGEMIDDELFORM OG INDHOLD (PAKNINGSSTØRRELSE) 30 x 1 bløde kapsler
PHARMACEUTICAL FORM AND CONTENTS 30 x 1 soft capsules
Kapselskal:
Capsule fill:
I INPULSIS-2 havde patienterne, der fik placebo, en større stigning i den samlede SGRQ-score fra baseline sammenlignet med patienter, der fik nintedanib 150 mg to gange dagligt.
In INPULSIS-2, patients receiving placebo had a larger increase from baseline SGRQ total score as compared to patients receiving nintedanib 150 mg twice daily.
Hos patienter med let nedsat leverfunktion (Child Pugh A) er den anbefalede dosis af Ofev 100 mg to gange dagligt med ca. 12 timers mellemrum.
In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Ofev is 100 mg twice daily approximately 12 hours apart.
Eftersom nogle tyrosinkinasehæmmere vides at have effekt på QT, skal der udvises forsigtighed, når nintedanib administreres til patienter i risikogruppe for at udvikle QT-forlængelse.
As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when nintedanib is administered in patients who may develop QTc prolongation.
- hvis du har eller har haft et aneurisme (udvidelse og svækkelse af en blodårevæg) eller en rift i en blodårevæg.
- if you have high blood pressure - if you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall
Nintedanib hæmmer proliferation, migration og transformation af fibroblast til myofibroblast af humane lungefibroplaster fra patienter med IPF.
Nintedanib inhibits proliferation, migration and fibroblast to myofibroblast transformation of human lung fibroblasts from patients with IPF.
Tabel 1 opsummerer hyppigheden for bivirkninger, der blev indberettet i nintedanib-grupperne (638 patienter) i de to placebokontrollerede kliniske fase III-studier af 52 ugers varighed eller efter markedsføring.
Table 1 summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the nintedanib group (638 patients) pooled from the two placebo-controlled Phase III clinical trials of 52 weeks duration or from the post-marketing period.
Tag ikke Ofev - hvis du er allergisk over for nintedanib, jordnødder, soja eller et af de øvrige indholdsstoffer i
Do not take Ofev - if you are allergic to nintedanib, peanut or soya, or any of the other ingredients of this medicine
Vedrørende håndtering af udvalgte bivirkninger henvises også til pkt.
For the management of selected adverse reactions please also refer to section 4.4.
En dosis på 100 mg to gange dagligt anbefales udelukkende til patienter, der ikke tolererer en dosis på 150 mg to gange dagligt.
The 100 mg twice daily dose is only recommended to be used in patients who do not tolerate the 150 mg twice daily dose.
Administration sammen med pirfenidon
Co-administration with pirfenidone
Kvindelige patienter skal informeres om at underrette deres læge eller apotekspersonalet, hvis de bliver gravide under behandling med Ofev.
Female patients should be advised to notify their doctor or pharmacist if they become pregnant during therapy with Ofev.
C]nintedanib var udskillelse med fæces/galde (93,4 % af dosis; 2,61 % gCV).
C] nintedanib was via faecal/biliary excretion (93.4% of dose, 2.61% gCV).
Hos rotter blev små mængder radioaktivt mærket nintedanib og/eller dets metabolitter udskilt i mælken (≤ 0,5 % af den administrerede dosis).
In rats, small amounts of radiolabelled nintedanib and/or its metabolites were excreted into the milk (≤ 0.5% of the administered dose).
Eksponeringen for nintedanib steg lineært med patienternes alder, hvilket også kan medføre en øget risiko for udviklingen af forhøjede leverenzymer (se pkt.
Nintedanib exposure increased linearly with patient age, which may also result in a higher risk of developing liver enzyme elevations (see section 5.2).
Se Figur 1 for udvikling i ændringen over tid fra baseline i de 2 behandlingsgrupper, baseret på den samlede analyse af studierne INPULSIS-1 og INPULSIS-2.
See Figure 1 for the evolution of change from baseline over time in both treatment groups, based on the pooled analysis of studies INPULSIS-1 and INPULSIS-2.
Den totale plasmaclearance efter intravenøs infusion var høj (CL: 1.390 ml/min; 28,8 % gCV).
Total plasma clearance after intravenous infusion was high (CL: 1,390 mL/min, 28.8% gCV).
Blødningshændelser set i perioden efter markedsføringen omfatter, men er ikke begrænset til, mave-tarm-kanalen, åndedrætsorganerne og centralnervesystemet, og hyppigst mave-tarm-kanalen.
Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal.
For yderligere information om særlige populationer, anbefalede foranstaltninger og dosisjustering i tilfælde af diarré og forhøjede leverenzymer henvises til henholdsvis pkt.
For further information about special populations, recommended measures and dosing adjustments in case of diarrhoea and hepatic enzyme increased, refer additionally to sections 4.4 and 4.2, respectively.
Prækliniske studier viste, at små mængder nintedanib og dets metabolitter (≤ 0,5 % af den administrerede dosis) blev udskilt i mælken hos diegivende rotter.
Pre-clinical studies showed that small amounts of nintedanib and its metabolites (≤ 0.5% of the administered dose) were secreted into milk of lactating rats.
Hvis du har glemt at tage Ofev
If you forget to take Ofev
I INPULSIS-studierne var hyppigheden af patienter med perforation meget lav i begge behandlingsgrupper; 0 % placebo, 0,03 % Ofev (involverede to patienter).
In the INPULSIS trials, the frequency of patients with perforation was very low in both treatment groups: 0% placebo, 0.3% Ofev (involving two patients).
I et specifikt studie med patienter med nyrecellecancer blev QT/QTc-målinger registreret og viste, at hverken orale enkeltdoser på 200 mg nintedanib eller gentagne orale doser på 200 mg nintedanib givet to gange dagligt i 15 dage forlængede QTcF-intervallet.
In a dedicated study in renal cell cancer patients, QT/QTc measurements were recorded and showed that a single oral dose of 200 mg nintedanib as well as multiple oral doses of 200 mg nintedanib administered twice daily for 15 days did not prolong the QTcF interval.
På grund af nintedanibs virkningsmekanisme kan patienter have en øget risiko for gastrointestinal perforation.
Due to the mechanism of action of nintedanib patients might have an increased risk of gastrointestinal perforation.
Hvis eventuelle leverenzymforhøjelser forbindes med kliniske tegn eller symptomer på leverskade, f.eks. gulsot, skal Ofev seponeres permanent.
If any liver test elevations are associated with clinical signs or symptoms of liver injury, e.g. jaundice, treatment with Ofev should be permanently discontinued.
Hovedparten af leverhændelserne opstår i løbet af de første 3 måneders behandling.
The majority of hepatic events occur within the first three months of treatment.
Diarré førte til permanent seponering hos 4,4 % af patienterne; hos resten blev bivirkningen behandlet med obstipantia, dosisreduktion eller behandlingsafbrydelse (se pkt.
Diarrhoea led to permanent treatment discontinuation in 4.4% of patients; otherwise the events were managed by antidiarrhoeal therapy, dose reduction or treatment interruption (see section 4.4).
Følgende lægemidler kan øge blodets indhold af nintedanib og kan derfor øge risikoen for bivirkninger (se afsnit 4): - et lægemiddel, der bruges til behandling af svampeinfektioner (ketoconazol) - et lægemiddel, der bruges til behandling af bakterieinfektioner (erythromycin) - et lægemiddel, der indvirker på dit immunsystem (ciclosporin).
The following medicines are examples that may increase the levels of nintedanib in your blood, and hence may increase the risk for side effects (see section 4): - a medicine used to treat fungal infections (ketoconazole) - a medicine used to treat bacterial infections (erythromycin) - a medicine that affects your immune system (cyclosporine)
I begge INPULSIS-studier var andelen af FVC-respondere, defineret som patienter med en absolut forværring i FVC % af forventet ikke højere end 5 % (en tærskelværdi indikativ for den øgede risiko for mortalitet ved IPF), signifikant højere i nintedanib-gruppen sammenlignet med placebo.
In both INPULSIS trials, the proportion of FVC responders, defined as patients with an absolute decline in FVC % predicted no greater than 5% (a threshold indicative of the increasing risk of mortality in IPF), was significantly higher in the nintedanib group as compared to placebo.
Nintedanibs sikkerhed, virkning og farmakokinetik er ikke undersøgt hos patienter med svært nedsat nyrefunktion (kreatininclearance < 30 ml/min).
The safety, efficacy, and pharmacokinetics of nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).
Diarré resulterede i dosisreduktion hos 10,7 % af patienterne og seponering af nintedanib hos 4,4 % af patienterne i kliniske studier.
Diarrhoea led to dose reduction in 10.7% of the patients and to discontinuation of nintedanib in 4.4% of the patients in clinical trials.
Baseret på disse resultater er der ikke evidens for en relevant farmakokinetisk lægemiddelinteraktion mellem nintedanib og pirfenidon, når de administreres i kombination (se pkt.
Based on these results, there is no evidence of a relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone when administered in combination (see section 5.2).
BIBF 1202 glukuronideres efterfølgende til BIBF 1202-glukuronid af uridin 5'-diphosphat-glucuronosyltransferase-enzymer (UGT-enzymer), nærmere bestemt UGT 1A1, UGT 1A7, UGT 1A8 og UGT 1A10.
BIBF 1202 is subsequently glucuronidated by uridine 5'-diphosphoglucuronosyltransferase enzymes (UGT) enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide.
Der er observeret tilfælde af lægemiddelinduceret leverskade under behandling med nintedanib, herunder svær leverskade med dødelig udgang.
Cases of drug-induced liver injury have been observed with nintedanib treatment, including severe liver injury with fatal outcome.
Hvis du holder op med at tage Ofev
If you stop taking Ofev
Den anbefalede dosis er 150 mg nintedanib to gange dagligt med ca. 12 timers mellemrum.
The recommended dose is 150 mg nintedanib twice daily administered approximately 12 hours apart.
Dosisproportionalitet blev vist ved forøgelse af eksponeringen for nintedanib (dosisområde 50-450 mg én gang dagligt og 150-300 mg to gange dagligt).
Dose proportionality was shown by increase of nintedanib exposure (dose range 50 - 450 mg once daily and 150 - 300 mg twice daily).
Ofev indeholder: - Aktivt stof: nintedanib.
What Ofev contains - The active substance is nintedanib.
Ofev indeholder det aktive stof nintedanib og bruges til behandling af idiopatisk lungefibrose (IPF) hos voksne.
Ofev contains the active substance nintedanib and it is used for the treatment of idiopathic pulmonary fibrosis (IPF) in adults.
Mindre end 1 % af en enkeltdosis nintedanib udskilles via nyrerne (se pkt.
Less than 1% of a single dose of nintedanib is excreted via the kidney (see section 5.2).
I et målrettet farmakokinetisk studie blev samtidig behandling med nintedanib og pirfenidon undersøgt hos patienter med IPF.
In a dedicated pharmacokinetic study, concomitant treatment of nintedanib with pirfenidone was investigated in patients with IPF.
Tag altid lægemidlet nøjagtigt efter lægens eller apotekspersonalets anvisning.
Always take this medicine exactly as your doctor or pharmacist has told you.
Diarré, kvalme og opkastning var de hyppigst rapporterede bivirkninger hos hhv. 20 (37,7 %) versus 16 (31,4 %), hos 22 (41,5 %) versus 6 (11,8 %) og hos 15 (28,3 %) versus 6 (11,8 %) patienter, der blev behandlet med pirfenidon som tillægsbehandling til nintedanib versus nintedanib alene.
Diarrhoea, nausea and vomiting were the most frequent adverse events reported in 20 (37.7%) versus 16 (31.4%), in 22 (41.5%) versus 6 (11.8%) and in 15 (28.3%) versus 6 (11.8%) patients, treated with pirfenidone added to nintedanib versus nintedanib alone, respectively.
Ofev 150 mg to gange dagligt
Ofev 150 mg twice daily
Hvis du ikke kan tåle den anbefalede dosis på to Ofev 100 mg kapsler om dagen (se bivirkninger i afsnit 4), kan din læge bede dig om at holde op med at tage dette lægemiddel.
If you do not tolerate the recommended dose of two Ofev 100 mg capsules per day (see possible side effects in section 4) your doctor may advise you to stop taking this medicine.
Biotransformationen af nintedanib omfatter kun i mindre grad CYP-metaboliseringsveje med CYP 3A4 som det dominerende af de involverede enzymer.
Only a minor extent of the biotransformation of nintedanib consisted of CYP pathways, with CYP 3A4 being the predominant enzyme involved.
Ofev påvirker i mindre grad evnen til at føre motorkøretøj og betjene maskiner.
Ofev has minor influence on the ability to drive and use machines.
Mens uønskede hændelser, der afspejlede iskæmisk hjertesygdom, var jævnt fordelt mellem nintedanib- og placebogrupperne, oplevede en højere procentdel af patienterne i nintedanib-gruppen myokardieinfarkt (1,6 %) sammenlignet med placebogruppen (0,5 %).
While adverse events reflecting ischaemic heart disease were balanced between the nintedanib and placebo groups, a higher percentage of patients experienced myocardial infarctions in the nintedanib group (1.6%) compared to the placebo group (0.5%).
Den årlige grad af forværring i FVC (i ml) blev signifikant reduceret hos patienter, der fik nintedanib, sammenlignet med patienter, der fik placebo.
The annual rate of decline of FVC (in mL) was significantly reduced in patients receiving nintedanib compared to patients receiving placebo.
Tid indtil progression (≥ 10 % absolut fald i FVC % forventet eller død) I begge INPULSIS-studier var risikoen for progression statistisk signifikant reduceret hos patienter, der blev behandlet med nintedanib, i forhold til placebogruppen.
Time to progression (≥ 10% absolute decline of FVC % predicted or death) In both INPULSIS trials, the risk of progression was statistically significantly reduced for patients treated with nintedanib compared with placebo.
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 administration sammen med rifampicin sammenlignet med administration af nintedanib alene.
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.
Håndtering af bivirkninger kan kræve behandlingsafbrydelse, dosisreduktion eller seponering af Ofev (se pkt.
Management of side effects may require interruption, dose reduction, or discontinuation of therapy with Ofev (see section 4.2).
Tag din næste dosis Ofev på 100 mg efter planen på det næste fastlagte tidspunkt og i den dosis, som lægen eller apotekspersonalet har anbefalet.
You should take your next 100mg dose of Ofev as planned at the next scheduled time recommended by your doctor or pharmacist.
Placebo Ofev 150 mg to gange dagligt
Placebo Ofev 150 mg twice daily
Ofev kan have en mindre virkning på evnen til at føre motorkøretøj og betjene maskiner.
Ofev may have minor influence on your ability to drive and use machines.
Aneurismer og arterielle dissektioner
Aneurysms and artery dissections
Der blev set virkninger på den præ- og postnatale udvikling i et studie af præ- og postnatal udvikling hos rotter ved en eksponering, der var lavere end eksponeringen ved MRHD.
In a pre- and postnatal development study in rats, effects on pre- and post-natal development were seen at an exposure below the MRHD.
Trombocytopeni
Thrombocytopenia
Patienter med nyligt myokardieinfarkt eller apopleksi i anamnesen blev ekskluderet fra INPULSISstudierne.
Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials.
Ved de første tegn på diarré skal der iværksættes behandling i form af tilstrækkelig hydrering og lægemidler mod diarré, f.eks. loperamid, og afbrydelse af behandlingen kan være nødvendig.
Patients should be treated at first signs with adequate hydration and anti-diarrhoeal medicinal products, e.g. loperamide, and may require treatment interruption.
Nintedanib hæmmer aktiveringen af FGFR- og PDGFR-signaleringskaskader, som er en væsentlig del af proliferation, migration og differentering af lungefibroblaster/myofribroblaster, som er de kendetegnende celler i patagenese for IPF.
Nintedanib inhibits the activation of FGFR and PDGFR signalling cascades which are critically involved in proliferation, migration and differentiation of lung fibroblasts/myofibroblasts, the hallmark cells in the pathology of IPF.
Potente P-gp-induktorer (f.eks. rifampicin, carbamazepin, phenytoin og perikon) kan reducere eksponeringen for nintedanib.
Potent P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, and St. John's Wort) may decrease exposure to nintedanib.
Eksponeringen for nintedanib steg med ca. 20 % efter fødeindtagelse 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).
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 h; fed: 3.98 h).
Dette kan være symptomer på alvorlige leverproblemer; - hvis du får stærke mavesmerter, feber, kulderystelser, kvalme, opkastning eller hårdhed/oppustning af maven, da det kan være et tegn på et hul i tarmvæggen (gastrointestinal perforation).
This could be symptoms of serious liver problems; - if you have severe pain in your stomach, fever, chills, sickness, vomiting, or abdominal rigidity or bloating, as these could be symptoms of a hole in the wall of your gut (‘gastrointestinal perforation').
Du skal tale med din læge om, hvilke præventionsmetoder der er de bedste for dig.
You should discuss the most appropriate methods of contraception for you with your doctor.
Eksponeringen øgedes hos patienter med nedsat leverfunktion (Child Pugh A, Child Pugh B; se pkt.
Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B; see section 5.2).