FrancophonIA/ELRC3.0 huggingface dataset:
English: Neratinib is an irreversible pan-erythroblastic leukaemia viral oncogene homolog (ERBB) tyrosine kinase inhibitor (TKI) that blocks mitogenic growth factor signal transduction through covalent, high affinity binding to the ATP binding site of 3 epidermal growth factor receptors (EGFRs): EGFR (encoded by ERBB1), HER2 (encoded by ERBB2), and HER4 (encoded by ERBB4) or their active heterodimers with HER3 (encoded by ERBB3).
Danish: Neratinib er en irreversibel pan-erythroblastisk, leukæmi virus onkogen homolog (ERBB)tyrosinkinasehæmmer, der blokerer mitogen vækstfaktorsignal transduktion ved kovalent høj-affin binding til ATP-bindingsstedet på 3 epidermale vækstfaktorreceptorer (EGFR'er): EGFR (kodet fra ERBB1 genet), HER2 (kodet fra ERBB2 genet) og HER4 (kodet fra ERBB4 genet) eller af deres aktive heterodimere med HER3 (kodet fra ERBB3 genet).
English: Neratinib metabolites M3, M6, M7 and M11 are negative in the standard battery of in vitro genotoxicity studies.
Danish: Neratinib-metabolitterne M3, M6, M7 og M11 er negative i standardbatteri af genotoksiske in vitrostudier.
English: Neratinib at 10 µM appeared to inhibit the BCRP efflux transporter.
Danish: Neratinib ved 10 mikroM syntes at hæmme BCRP-efflukstransportøren.
English: • diltiazem, verapamil (calcium-channel blockers)
Danish: • diltiazem, verapamil (calciumantagonister)
English: It appeared that the inhibitory effect of neratinib was primarily on P-gp activity in the gastrointestinal tract as a result of pre-systemic inhibition.
Danish: Det fremgik, at neratinibs hæmmende virkning primært gjaldt P-gp-aktiviteten i mave-tarm-kanalen som følge af præsystemisk hæmning.
English: Neratinib was not a potent inhibitor of human BSEP efflux transporter activity in vitro, with a reported IC50 value of > 10µM.
Danish: Neratinib var ikke en potent hæmmer af human BSEP-efflukstransportør-aktivitet in vitro og havde en rapporteret IC50-værdi på > 10 mikroM.
English: • Key messages on how to prevent and minimise GI toxicity through appropriate monitoring (with reference to treatment journal) and management: o prophylactic treatment with antidiarrhoeal medicinal product o dietary changes o when to alert HCP and the importance of it for further treatment adjustment
Danish: • Vigtige oplysninger om, hvordan man forebygger og minimerer gastrointestinal toksicitet gennem relevant overvågning (med henvisning til behandlingsjournalen) og behandling: o forebyggende behandling med et middel mod diarré o kostændringer o hvornår man skal kontakte en sundhedsperson og betydningen af dette for justering af den videre behandling
English: Patients with a significant chronic gastrointestinal disorder Patients with a significant chronic gastrointestinal disorder with diarrhoea as a major symptom were not included in the pivotal study, and should be carefully monitored.
Danish: Patienter med betydelig kronisk sygdom i mave-tarm-kanalen Patienter med betydelig kronisk sygdom i mave-tarm-kanalen og diarré som et alvorligt symptom indgik ikke i det pivotale studie, og de bør overvåges nøje.
English: Grade 3 diarrhoea was reported in 37.5% of Nerlynx patients.
Danish: Grad 3-diarré blev rapporteret hos 37,5 % af Nerlynxpatienterne.
English: If you forget to take Nerlynx
Danish: Hvis du har glemt at tage Nerlynx
English: Nerlynx has not been studied in patients with less than lower limit of normal left ventricular ejection fraction (LVEF) or with significant cardiac history.
Danish: Nerlynx er ikke undersøgt hos patienter med en venstre ventrikel uddrivningsfraktion (LVEF), der ligger under nedre normalgrænse, eller hos patienter med tidligere betydelig hjertesygdom.
English: Abdominal distension, dry mouth and dyspepsia
Danish: Abdominal distension, mundtørhed og dyspepsi
English: Pregnancy Neratinib may cause foetal harm when administered to pregnant women (see Section 4.6).
Danish: Graviditet Neratinib kan forårsage fosterskader, hvis det gives til gravide kvinder (se pkt.
English: Nerlynx has not been studied in patients with severe renal impairment including patients on dialysis.
Danish: Nerlynx er ikke undersøgt hos patienter med svært nedsat nyrefunktion, herunder patienter i dialyse.
English: Following the administration of a single radiolabelled dose of 200 mg neratinib oral solution, 97.1% and 1.1% of the administered dose was recovered in the faeces and urine, respectively.
Danish: Efter administration af en enkelt radioaktivt mærket dosis på 200 mg neratinib som oral opløsning blev 97,1 % og 1,1 % af den administrerede dosis genfundet i hhv. fæces og urin.
English: Nerlynx is indicated for the extended adjuvant treatment of adult patients with early-stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago.
Danish: Nerlynx er indiceret til forlænget adjuverende behandling af voksne patienter med tidlige stadier af hormonreceptor-positiv brystkræft med overudtryk af HER2, som har afsluttet en adjuverende trastuzumab-baseret behandling for mindre end et år siden..
English: The film-coated tablets are red oval shaped and debossed with ‘W104' on one side and plain on the other side.
Danish: De filmovertrukne tabletter er røde, ovale og præget med "W104" på den ene side og ingenting på den anden side.
English: o The Summary of Product Characteristics o Guide for healthcare professionals o Patient educational material The Guide for healthcare professionals shall contain the following key elements: o Name of the product, active substance and approved indication of the product o Relevant information on the safety concern “Gastrointestinal toxicity (diarrhoea)” (e.g. seriousness, severity, frequency, time to onset, duration, reversibility of the AE as applicable) o Details of the population at higher risk for the safety concern o Key message to convey in patients counselling on how to prevent and minimise Gastrointestinal toxicity through appropriate monitoring and management: o prophylactic treatment with antidiarrhoeal medicinal product o dietary changes o dose modification (with guideline to adjust doses)/ discontinuation of treatment o The importance of handing over the educational material to the patients/carers at the end of counselling o Remarks on the importance of reporting ADRs
Danish: o Produktresuméet o Vejledning til sundhedspersoner o Informationsmateriale til patienter Vejledningen til sundhedspersoner skal indeholde følgende hovedelementer: o Produktnavn, aktivt stof og godkendt indikation for produktet o Relevante oplysninger om sikkerhedsproblemet "gastrointestinal toksicitet (diarré)" (f.eks. alvorlighed, sværhedsgrad, hyppighed, tid til debut, varighed, bivirkningens reversibilitet hvis relevant) o Oplysninger om den population, der har særligt høj risiko for at få diarré o Hovedbudskab om at instruere patienterne i, hvordan de skal forebygge og minimere gastrointestinal toksicitet gennem relevant overvågning og behandling: o forebyggende behandling med et middel mod diarré o kostændringer o dosisjustering (med vejledning i dosisjustering)/behandlingsophør o Betydningen af at overdrage informationsmaterialet til patienterne/omsorgspersonerne efter rådgivningen o Understregning af betydningen af at indberette bivirkninger.
English: Estimated 2 year event free rates1 (%)
Danish: Estimeret frekvens for hændelsesfri 2 årsperiode1 (%)
English: Patients who experience ≥ Grade 3 diarrhoea requiring IV fluid treatment or any signs or symptoms of hepatotoxicity, such as worsening of fatigue, nausea, vomiting, jaundice, right upper quadrant pain or tenderness, fever, rash, or eosinophilia, should be evaluated for changes in liver function tests.
Danish: Patienter, der oplever diarré af grad 3 eller derover, og som kræver intravenøs væskebehandling, eller som har tegn eller symptomer på levertoksicitet som f.eks. forværring af udmattelse, kvalme, opkastning, gulsot, smerter eller ømhed i den øvre højre kvadrant, feber, udslæt eller eosinofili, bør undersøges for ændringer i leverfunktionstest.
English: • Grade 2 diarrhoea lasting 5 days or longer‡
Danish: • Grad 2-diarré, der varer i 5 dage eller længere‡
English: Guidelines for adjusting doses of Nerlynx in the setting of diarrhoea are shown in Table 3.
Danish: Retningslinjer for justering af Nerlynx-dosen i tilfælde af diarré er vist i tabel 3.
English: Pharmacokinetic studies in patients with renal impairment or undergoing dialysis have not been carried out.
Danish: Der er ikke udført farmakokinetiske studier hos patienter med nedsat nyrefunktion eller i dialyse.
English: This results in sustained inhibition of these growth promoting pathways with HER2-amplified or over-expressed, or HER2-mutant breast cancers.
Danish: Dette medfører vedvarende hæmning af disse vækstfaktor afhængige signalveje ved HER2-positiv eller HER2-muteret brystkræft.
English: Very common Fatigue
Danish: Meget almindelig Udmattelse
English: • rifampicin (antimycobacterial)
Danish: • rifampicin (antimykobakterielt middel).
English: A decision must be made whether to discontinue breast-feeding or to discontinue Nerlynx, taking into account the importance of Nerlynx to the mother and the benefit of breast-feeding to the child.
Danish: Det skal besluttes, om amning skal ophøre eller behandling med Nerlynx seponeres, idet der tages højde for fordelene ved amning for barnet i forhold til de treapeutiske forele for for moderen.
English: Patients with renal impairment are at a higher risk of complications of dehydration if they develop diarrhoea, and these patients should be carefully monitored (see Section 4.2).
Danish: Patienter med nedsat nyrefunktion har en højere risiko for komplikationer som følge af dehydrering, hvis de får diarré, og disse patienter bør overvåges nøje (se pkt.
English: Patients who are treated concomitantly with therapeutic agents whose metabolism involves P-gp substrates in the gastrointestinal tract should be monitored carefully.
Danish: Patienter, der samtidigt behandles med terapeutiske stoffer, hvis metabolisering involverer P-gp-substrater i mave-tarm-kanalen, bør overvåges nøje.
English: Secondary endpoints of the study included disease-free survival (DFS) including ductal carcinoma in situ (DFS-DCIS), time to distant recurrence (TTDR), distant disease-free survival (DDFS), cumulative incidence of central nervous system recurrence and overall survival (OS).
Danish: Sekundære endepunkter i studiet omfattede sygdomsfri overlevelse (DFS), herunder duktalt carcinom in situ (DFS-DCIS), tid til metastaserecidiv (TTDR), metastasefri overlevelse (DDFS), kumulativ forekomst af centralnervesystem-recidiv og samlet overlevelse (OS).
English: 52.3 years (59.9% was ≥50 years old, 12.3% was ≥65 years old); 81.0% were Caucasian, 2.6% black or African American, 13.6% Asian and 2.9% other.
Danish: Den mediane alder i intention-to-treat (ITT)-populationen var 52,3 år (59,9 % var 50 år eller derover, 12,3 % var 65 år eller derover); 81,0 % var kaukasere, 2,6% var sorte eller afro-amerikanere, 13,6 % var asiater, og 2,9 % havde anden etnisk baggrund.
English: Neratinib bound predominantly to HSA and human alpha-1 acid glycoprotein (AAG).
Danish: Neratinib bandt fortrinsvis til HSA og humant alfa-1-syreglykoprotein (AAG).
English: In the clinical trial setting, adverse reactions associated with overdose were most commonly diarrhoea, with or without nausea, vomiting and dehydration.
Danish: I de kliniske studier var de bivirkninger, der blev forbundet med overdosering, i de fleste tilfælde diarré, med eller uden kvalme, opkastning og dehydrering.
English: Following concomitant administration with repeated doses of 600 mg rifampicin, a strong CYP3A4/Pgp inducer, neratinib exposures were significantly decreased with mean values that were 24% and 13% of reference values (neratinib administered alone) for Cmax and AUC, respectively.
Danish: Efter samtidig administration af gentagne 600 mg-doser rifampicin, der er en stærk CYP3A4/P-gpinducer, faldt eksponeringen for neratinib signifikant med gennemsnitlige værdier, der var 24 % og 13 % af referenceværdierne (neratinib administreret alene) for hhv. Cmax og AUC.
English: Co-administration with the following medical products that are strong inducers of the CYP3A4/P-gp isoform of cytochrome P450:
Danish: Samtidig administration af følgende lægemidler, der er stærke inducere af CYP3A4/P-gp-isoformen af cytokrom P450:
English: Carton 2D barcode carrying the unique identifier included.
Danish: Der er anført en 2D-stregkode, som indeholder en entydig identifikator.
English: Do not use this medicine after the expiry date which is stated on the bottle and carton after EXP.
Danish: Brug ikke lægemidlet efter den udløbsdato, der står på pakningen efter EXP. Udløbsdatoen er den sidste dag i den nævnte måned.
English: Your doctor will tell you if you need to keep taking anti-diarrhoea medicine after the first two months to control your diarrhoea.
Danish: Lægen vil fortælle dig, om du fortsat skal tage et lægemiddel mod diarré efter de første to måneder.
English: If grade 3 toxicity does not recover within 3 weeks, discontinue Nerlynx permanently.
Danish: Hvis en toksicitet af grad 3 ikke bedres inden for 3 uger, skal Nerlynx seponeres permanent.
English: Both rash and nail disorders led to treatment discontinuation in 0.6% of Nerlynx-treated patients.
Danish: Både udslæt og neglelidelser medførte seponering af behandlingen hos 0,6 % af de Nerlynxbehandlede patienter.
English: Concomitant use of strong CYP3A4/P-gp inhibitors (e.g. atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, ketoconazole, itraconazole, clarithromycin, telithromycin, and voriconazole) should be avoided.
Danish: Samtidig brug af stærke CYP3A4/P-gp-hæmmere (f.eks. atazanavir, indinavir, nefazodon, nelfinavir, ritonavir, saquinavir, ketoconazol, itraconazol, clarithromycin, telithromycin og voriconazol) bør undgås.
English: Neratinib may inhibit breast cancer resistance protein (BCRP) moderately as suggested by in vitro studies.
Danish: Neratinib kan hæmme brystkræftresistent protein (BCRP) i moderat grad i henhold til in vitro-studier.
English: - antacid medicines - the dose of these medicines and Nerlynx should be separated by at least 3 hours.
Danish: - syreneutraliserende lægemidler - indtagelse af disse lægemidler og Nerlynx bør foregå med mindst 3 timers mellemrum.
English: Contents of the pack and other information What Nerlynx contains
Danish: Pakningsstørrelser og yderligere oplysninger Nerlynx indeholder:
English: Figure 2:
Danish: Figur 2:
English: The neratinib metabolites M3, M6, M7 and M11 were shown to have similar potencies to neratinib in either in vitro enzyme (binding assays) or cell based assays against cells expressing ERBB1, ERBB2 (HER2) and ERBB4.
Danish: Det er påvist, at neratinib-metabolitterne M3, M6, M7 og M11 i både in vitro-enzymanalyser (bindingsanalyser) og cellebaserede analyser har samme potens som neratinib mod celler, der udtrykker ERBB1, ERBB2 (HER2) og ERBB4.
English: A single 240 mg dose of neratinib combined with lansoprazole decreased AUC by up to 70%.
Danish: En enkeltdosis på 240 mg neratinib i kombination med lansoprazol reducerede AUC med op til 70 %.
English: The MedDRA frequency convention and system organ class database has been utilised for the classification of frequency: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (cannot be estimated from the available data)
Danish: Ikke almindelig (≥ 1/1.000 til < 1/100) Sjælden (≥ 1/10.000 til < 1/1.000) Meget sjælden (< 1/10.000)
English: Proton pump inhibitors, H2-receptor antagonists and antacids The solubility of neratinib is pH-dependent.
Danish: Protonpumpehæmmere, H2-receptor antagonister og antacider Opløseligheden af neratinib er pH-afhængig.
English: Nerlynx 40 mg film-coated tablets
Danish: Nerlynx 40 mg filmovertrukne tabletter
English: Breast cancer resistance protein inhibitors
Danish: Hæmmere af brystkræftresistent protein
English: Neratinib binds to the HER2 receptor, reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and potently inhibits tumour cell proliferation in vitro.
Danish: Neratinib binder til HER2-receptoren, reducerer EGFR- og HER2-autophosphorylering samt MAPK- og AKT (downstream) signalering, og hæmmer i kraftig grad tumorcellevækst in vitro.
English: How much Nerlynx to take
Danish: Så meget Nerlynx skal du tage
English: In vitro studies demonstrated that neratinib is a substrate for P-glycoprotein (P-gp).
Danish: In vitro-studier har påvist, at neratinib er et substrat for Pglykoprotein (P-gp).
English: The recommended dose of Nerlynx is 240 mg (six 40 mg tablets) taken orally once daily, continuously for one year.
Danish: Den anbefalede dosis Nerlynx er 240 mg (seks 40 mg tabletter), der tages én gang dagligt i et år.
English: Diarrhoea, vomiting, nausea, abdominal pain, abdominal pain upper, and stomatitis1
Danish: Diarré, opkastning, kvalme, mavesmerter, smerter i den øvre del af maven og stomatitis1
English: Hepatotoxicity has been reported in patients treated with Nerlynx.
Danish: Der er rapporteret om levertoksicitet hos patienter, der behandles med Nerlynx.
English: Uncommon: may affect up to 1 in 100 people - kidney failure - changes in liver blood test results (i.e., blood bilirubin increased)
Danish: Ikke almindelige bivirkninger: kan forekomme hos op til 1 ud af 100 patienter - Nyresvigt - ændringer i leverværdierne (f.eks. forhøjet bilirubin i blodet)
English: Co-administration of a single oral dose of 240 mg of neratinib in the presence of ketoconazole (400 mg once daily for 5 days), a strong CYP3A4/P-gp inhibitor, increased neratinib systemic exposure.
Danish: Samtidig administration af en enkeltdosis oralt neratinib (240 mg) og ketoconazol (400 mg én gang dagligt i fem dage), en stærk CYP3A4/P-gp-hæmmer, øgede den systemiske neratinibeksponering.
English: There were 0.2% of Nerlynx treated patients who experienced Grade 3 nail disorder.
Danish: 0,2 % af de Nerlynx-behandlede patienter oplevede neglelidelser af grad 3.
English: In subjects with severe pre-existing hepatic impairment (Child-Pugh Class C) without cancer, the clearance of neratinib was decreased by 36% and exposure to neratinib increased by about 3-fold as compared to healthy volunteers.
Danish: Hos patienter med svært nedsat leverfunktion (ChildPugh C) uden kræft faldt neratinib-clearance med 36 %, og eksponeringen for neratinib steg ca. 3 gange sammenholdt med hos raske forsøgspersoner.
English: Nerlynx can cause diarrhoea early during treatment unless anti-diarrhoeal medicines are taken to prevent or reduce diarrhoea.
Danish: Nerlynx kan medføre diarré tidligt i behandlingen, medmindre du samtidigt tager et lægemiddel mod diarré for at forebygge eller mindske dette.
English: ULN=Upper Limit Normal; ALT= Alanine Aminotransferase * Per CTCAE v4.0
Danish: ALAT = alaninaminotransferase * I henhold til CTCAE v4.0
English: • If diarrhoea resolves to Grade 0-1 in one week or less, then resume Nerlynx treatment at the same dose.
Danish: • Hvis diarréen bedres til grad 0-1 i løbet af en uge eller derunder, bør Nerlynx genoptages i samme dosis.
English: Diarrhoea usually happens early in treatment with Nerlynx and may be severe, causing you to get dehydrated.
Danish: Diarréen opstår typisk tidligt i behandlingen med Nerlynx og kan være så kraftig, at du dehydrerer.
English: • For patients that are unable to tolerate 120 mg daily
Danish: • ikke kan tåle 120 mg dagligt.
English: If you become pregnant while taking this medicine, the doctor will assess the potential benefit to you and the risk to the foetus, of continuing this medicine.
Danish: Hvis du bliver gravid under behandlingen, vil lægen vurdere den mulige fordel for dig og risikoen for fostret ved at fortsætte behandlingen.
English: Nerlynx contains the active substance ‘neratinib'.
Danish: Nerlynx indeholder det aktive stof neratinib.
English: Each film-coated tablet contains neratinib maleate, equivalent to 40 mg neratinib.
Danish: Hver filmovertrukket tablet indeholder neratinibmaleat svarende til 40 mg neratinib.
English: Women who can become pregnant must use an effective method of contraception, including a barrier method: - while taking Nerlynx and - for one month after treatment has finished.
Danish: Kvinder, der kan blive gravide, skal bruge en sikker præventionsmetode, herunder en barrieremetode: - mens de tager Nerlynx og - i en måned efter behandlingens afslutning.
English: Tell your doctor or pharmacist if you notice any of the following side effects:
Danish: Fortæl det til lægen eller apotekspersonalet, hvis du oplever en eller flere af nedenstående bivirkninger:
English: The serious adverse reactions most frequently reported in the ≥65 years-old group were vomiting (2.3%), diarrhoea (1.7%), dehydration (1.2%), and renal failure (1.2%).
Danish: De hyppigst indberettede alvorlige bivirkninger i gruppen af patienter på 65 år eller derover var opkastning (2,3 %), diarré (1,7 %), dehydrering (1,2 %) og nyresvigt (1,2 %).
English: - The active substance is neratinib.
Danish: - Aktivt stof: neratinib.
English: Severity of diarrhoea*
Danish: Sværhedsgrad af diarré*
English: Neratinib produced inhibitory activity in OCT1 uptake transporter, with an IC50 of 2.9 µM.
Danish: Neratinib medførte hæmmende aktivitet over for OCT1-uptake-transportøren med en IC50 på 2,9 mikroM.
English: Concomitant treatment with inhibitors of CYP3A4 and P-gp Concomitant treatment with strong CYP3A4 and P-gp inhibitors should be avoided due to risk of increased exposure to neratinib (see Section 4.2 and Section 4.5).
Danish: Samtidig behandling med CYP3A4- og P-gp-hæmmere Samtidig behandling med stærke CYP3A4- og P-gp-hæmmere bør undgås på grund af risikoen for øget eksponering for neratinib (se pkt.
English: • Stop Nerlynx until recovery to ≤ Grade 1
Danish: • Stop Nerlynx-behandlingen indtil bedring til ≤
English: 3 Includes nail disorder, paronychia, onychoclasis, and nail discolouration.
Danish: 3 Omfatter neglelidelser som paronychion, onykoklase og misfarvning af neglene.
English: • If grade 3 diarrhoea persists longer than 3weeks, discontinue Nerlynx permanently.
Danish: • Hvis grad 3-diarréen varer ved i mere end 3 uger, bør Nerlynx seponeres permanent.
English: Section 6), - if you have a severe liver problem, - if you are taking fluconazole (a medicine for fungal infections), - if you are taking rifampicin (a medicine for tuberculosis (TB)), - if you are taking erythromycin (antibiotic for infections), - if you are taking carbamazepine, phenobarbital, or phenytoin (medicines for seizures), - if you are taking diltiazem or verapamil (medicines for high blood pressure and chest pain), - if you are taking St. John's wort (herbal product for depression).
Danish: (angivet i punkt 6), - hvis du har en alvorlig leversygdom, - hvis du tager fluconazol (et lægemiddel mod svampeinfektioner), - hvis du tager rifamcipin (et lægemiddel mod tuberkulose), - hvis du tager erythromycin (antibiotikum mod infektioner), - hvis du tager carbamazepin, phenobarbital eller phenytoin (lægemidler mod krampeanfald), - hvis du tager diltiazem eller verapamil (lægemidler mod forhøjet blodtryk og brystsmerter), - hvis du tager prikbladet perikon (naturlægemiddel mod nedtrykthed, modløshed og tristhed).