FrancophonIA/ELRC3.0 huggingface dataset:
English: In patients treated with Combo 450 (n = 274), 194 patients (70.8 %) were < 65 years old, 65 patients (23.7 %) were 65 -74 years old and 15 patients (5.5 %) were aged > 75.
Danish: Blandt de patienter, der blev behandlet med Combo 450 (n=274), var 194 patienter (70,8 %) <65 år, 65 patienter (23,7 %) var 65-74 år, og 15 patienter (5,5 %) var >75 år.
English: If you forget to take Mektovi
Danish: Hvis du har glemt at tage Mektovi
English: Yellow to dark yellow, unscored biconvex, ovaloid film-coated tablets approximately 12 mm in length and 5 mm in width, with the “A” logo debossed on one side of the tablet and “15” on the other side.
Danish: Gule til mørkegule, bikonvekse, ovale, filmovertrukne tabletter uden delekærv, der måler cirka 12 mm i længden og 5 mm i bredden, og som er præget med et ”A”-logo på den ene side og med ”15” på den anden side.
English: How to take Mektovi How much to take
Danish: Sådan skal du tage Mektovi Så meget skal du tage
English: If treatment-related toxicities occur when binimetinib is used in combination with encorafenib, then both treatments should be simultaneously dose reduced, interrupted or discontinued.
Danish: Hvis der opstår behandlingsrelateret toksicitet under kombinationsbehandling med binimetinib og encorafenib, bør doseringen af begge behandlinger reduceres, pauseres eller seponeres samtidigt.
English: • Grade 2 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x - ≤ 5x upper limit of normal (ULN)
Danish: • Grad 2 aspartataminotransferase (ASAT) eller alaninaminotransferase (ALAT) > 3x - ≤ 5x øvre normalgrænse (ULN))
English: No effects were noted at 14-times the human therapeutic exposure .
Danish: Der blev ikke set nogen virkninger ved eksponeringer, der var 14 gange højere end den terapeutiske eksponering hos mennesker.
English: Binimetinib is 97.2 % bound to human plasma proteins in vitro.
Danish: Binimetinibs bindingsgrad til humane plasmaproteiner er 97,2 %.
English: However, if the missed dose is more than 6 hours late, skip that dose and take your next dose at the usual time.
Danish: Hvis det er mere end 6 timer siden, du skulle have taget dosen, skal du dog springe den glemte dosis over og tage den næste dosis på det sædvanlige tidspunkt.
English: A similar proportion of patients in each treatment arm received subsequent treatment with checkpoint inhibitors, mainly pembrolizumab, nivolumab and ipilimumab (34.4 % Combo 450 arm, 36.1 % encorafenib arm, 39.8 % vemurafenib arm).
Danish: En ensartet andel af patienterne i hver behandlingsarm fik efterfølgende behandling med checkpointhæmmere, primært pembrolizumab, nivolumab og ipilimumab (34,4 % i Combo 450-armen, 36,1 % i encorafenib-armen, 39,8 % i vemurafenib-armen).
English: Hypertensive adverse reactions required additional therapy in 8.0 % (22/274) of patients.
Danish: Hypertensive bivirkninger krævede yderligere behandling hos 8,0 % (22/274) af patienterne.
English: Dermatologic evaluations should be performed prior to initiation of therapy with binimetinib in combination with encorafenib, every 2 months while on therapy and for up to 6 months following discontinuation of the combination.
Danish: Der bør gennemføres dermatologiske vurderinger inden opstart af behandling med binimetinib i kombination med encorafenib, hver 2. måned under behandlingen og i op til 6 måneder efter seponering af kombinationen.
English: Repeated oral administration of binimetinib in rats for up to 6 months was associated with soft tissue mineralisation, gastric mucosal lesions and reversible minimal to mild clinical pathology changes at 7 to 12.5 times human therapeutic exposures.
Danish: Gentagen oral administration af binimetinib i op til 6 måneder hos rotter var forbundet med mineralisering af bløddele, gastriske slimhindelæsioner og reversible minimale til milde kliniske patologiske forandringer ved eksponeringer, der var 7-12,5 gange højere end eksponeringen hos mennesker.
English: In case of vomiting after administration of binimetinib, the patient should not re-take the dose and should take the next scheduled dose.
Danish: I tilfælde af opkastning efter administration af binimetinib skal patienten ikke tage en ekstra dosis men blot tage næste dosis som planlagt.
English: Effect of binimetinib on CYP substrates Binimetinib is a weak reversible inhibitor of CYP1A2 and CYP2C9.
Danish: Binimetinibs indvirkning på CYP-substrater Binimetinib er en svag reversibel hæmmer af CYP1A2 og CYP2C9.
English: LVD defined as symptomatic or asymptomatic decreases in ejection fraction can occur when binimetinib is administered.
Danish: LVD, defineret som symptomatisk eller asymptomatisk fald i ejektionsfraktionen, kan forekomme ved administration af binimetinib.
English: • blurred vision, loss of vision, or other vision changes (such as coloured dots in your vision)
Danish: • sløret syn, synstab eller andre synsforstyrrelser (såsom farvede prikker i synsfeltet)
English: Binimetinib pharmacokinetics have been shown to be approximately dose-linear.
Danish: Binimetinibs farmakokinetik har vist sig at være stort set dosislineær.
English: • Symptomatic retinal pigment epithelial detachments (RPED) (Grade 2 or 3)
Danish: • Symptomatisk løsning af retinalt pigmentepitel (RPED) (grad 2 eller 3)
English: The most common adverse events reported with a higher incidence in patients aged ≥ 65 years compared to patients aged < 65 years included diarrhoea, pruritus, GGT and blood phosphatase alkaline elevation.
Danish: De mest almindelige uønskede hændelser, som er rapporteret med en højere hyppighed hos patienter ≥65 år sammenlignet med patienter <65 år, omfattede diarré, kløe, GGT og forhøjet alkalisk fosfatase i blodet.
English: New onset elevated blood pressure or worsening of pre-existing hypertension were reported in 11.7 % (32/274) of patients treated with the Combo 450.
Danish: Der blev rapporteret om indtræden af forhøjet blodtryk eller forværring af eksisterende hypertension hos 11,7 % (32/274) af de patienter, der blev behandlet med Combo 450 mg.
English: An increased litter incidence of foetal ventricular septal defects and pulmonary trunk alterations was noted at the highest doses.
Danish: Der blev set en øget forekomst af føtale ventrikulære septumdefekter og lungearterieforandringer i kuldene med de højeste doser.
English: - The active substance is binimetinib.
Danish: - Aktivt stof: binimetinib.
English: • Grade 3 or grade 4 (CK > 5x ULN) with muscle symptoms or renal impairment
Danish: • Grad 3 eller grad 4 (CK > 5x ULN) med muskelsymptomer eller nedsat nyrefunktion
English: In a gastric irritation study in rats, an increased incidence of superficial mucosal lesions and of hemorrhagic ulcers were observed.
Danish: I et studie af gastrisk irritation hos rotter blev der set en øget forekomst af overfladiske slimhindelæsioner og blødende mavesår.
English: Standard genotixicity studies with binimetinib were negative.
Danish: Standardstudier af binimetinibs genotoksicitet var negative.
English: Binimetinib is a weak inhibitor of OAT3, and caution should be taken when it is used with sensitive substrates (such as pravastatin or ciprofloxacin).
Danish: Binimetinib er en svag hæmmer af OAT3, og der skal udvises forsigtighed, når det bruges sammen med følsomme substrater (såsom pravastin eller ciprofloxacin).
English: No patients discontinued treatment due to anaemia, 1.5 % (4/274) required dose interruption or dose modification.
Danish: Ingen patienter fik seponeret behandlingen på grund af anæmi; hos 1,5 % (4/274) var det nødvendigt at pausere behandlingen eller ændre dosis.
English: Fertility studies were not conducted with binimetinib.
Danish: Der er ikke udført fertilitetsstudier med binimetinib.
English: In this patient, rhabdomyolysis was observed with concomitant symptomatic Grade 4 CK elevation.
Danish: Hos denne patient optrådte rabdomyolyse samtidig med symptomatisk CK-stigning af grad 4.
English: The highest dose of binimetinib evaluated as single agent in clinical studies was 80 mg administered orally twice daily and was associated with ocular (chorioretinopathy) and skin toxicities (dermatitis acneiform).
Danish: Den højeste monoterapi-dosis af binimetinib, der blev vurderet i de kliniske studier, var 80 mg administreret oralt to gange dagligt; denne dosis var forbundet med okulær toksicitet (korioretinopati) og hudtoksicitet (akneiform dermatitis).
English: No effects were observed at 3times the human therapeutic exposure.
Danish: Der blev ikke set nogen virkninger ved eksponeringer, der var 3 gange højere end den terapeutiske eksponering hos mennesker.
English: Binimetinib in combination with encorafenib should not be used in patients with wild type BRAF malignant melanoma.
Danish: Binimetinib i kombination med encorafenib bør ikke anvendes hos patienter med malignt melanom med vildtype-BRAF.
English: Binimetinib should be withheld until improved to Grade 0 or 1.
Danish: Binimetinib skal pauseres indtil bedring til grad 0 eller 1.
English: • headaches, dizziness or weakness
Danish: • hovedpine, svimmelhed eller svaghed
English: If binimetinib is temporarily interrupted, encorafenib should be reduced to 300 mg once daily during the time of binimetinib dose interruption (see Tables 1 and 2) as encorafenib is not well-tolerated at the dose of 450 mg as a single agent.
Danish: Hvis binimetinib pauseres, skal encorafenib reduceres til 300 mg én gang dagligt i perioden med pausering af binimetinib (se tabel 1 og 2), da encorafenib ikke er veltolereret i dosen 450 mg som monoterapi.
English: Talk to your doctor immediately if you get muscle pain, cramps, stiffness, spasm, dark urine.
Danish: Kontakt omgående lægen, hvis du får smerter i musklerne, kramper, stivhed, spasmer, mørkfarvet urin.
English: • Grade 4 (CK > 10x ULN) asymptomatic
Danish: • Grad 4 (CK 10x ULN), asymptomatisk
English: In cell free system, binimetinib inhibits MEK1 and MEK2 with the half maximal inhibitory concentration (IC50)'s in the 12-46 nM. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation.
Danish: I et cellefrit system hæmmer binimetinib MEK1 og MEK2 med koncentrationer, der giver 50 % hæmning (IC50), på 12-46 nM. MEK-proteiner er opstrømsregulatorer af den ekstracellulære signal-regulerede kinase (ERK)-signalvej, der fremmer cellulær proliferation.
English: Other medicines and Mektovi
Danish: Brug af anden medicin sammen med Mektovi
English: In rats, lower gestational body weight gain and fetal body weights and a decreased number of ossified fetal sternebrae were noted.
Danish: Hos rotter blev der set lavere gestationel vægtøgning og føtal kropsvægt og nedsat antal ossificerede sternebrae hos fostrene.
English: An interim OS analysis of study CMEK162B2301 Part 1, (cut-off date 07 November 2017) demonstrated a statistically significant improvement in OS for Combo 450 compared with vemurafenib (see Table 5 and Figure 2).
Danish: En foreløbig OS-analyse af Studie CMEK162B2301 Del 1, (skæringsdato 7. november 2017) viste en statistisk significant forbedring i OS for Combo 450 sammenlignet med vemurafenib (se tabel 5 og figur 2).
English: Each film-coated tablet contains 15 mg binimetinib.
Danish: Hver filmovertrukken tablet indeholder 15 mg binimetinib.
English: Visual disturbances have been reported in patients treated with binimetinib during clinical studies.
Danish: Der er rapporteret om synsforstyrrelser hos patienter, der fik behandling med binimetinib i kliniske studier.
English: Pyrexia*
Danish: Pyreksi*
English: Hypertension events were reported as Grade 3 in 5.5 % (15/274) of patients, including hypertensive crisis (0.4 % (1/274)).
Danish: Hypertensionshændelserne blev indberettet som grad 3 hos 5,5 % (15/274) af patienterne, inklusive hypertensiv krise (0,4 % (1/274).
English: Most events were Grade 1-2, with Grade 3 reported in 0.4 % (1/274) of patients and no event led to discontinuation.
Danish: De fleste hændelser var af grad 1-2, mens grad 3 blev rapporteret hos 0,4 % (1/274) af patienterne, og ingen hændelser førte til seponering.
English: While encorafenib is a relatively potent reversible inhibitor of UGT1A1, no differences in binimetinib exposure have been observed clinically when binimetinib is co-administered with encorafenib (see section 5.2).
Danish: Selvom encorafenib er en relativt potent reversibel UGT1A1-hæmmer, er der ikke set nogen forskel i eksponeringen for binimetinib ved klinisk samtidig administration af binimetinib og encorafenib (se pkt.
English: Tell your doctor immediately if you detect any skin changes during and after the treatment including: new wart, skin sore or reddish bump that bleeds or does not heal, or a change in size or colour of a mole.
Danish: Kontakt omgående lægen, hvis du opdager eventuelle hudforandringer under eller efter behandlingen, herunder: nye vorter, sår i huden eller en rødlig bule, der bløder eller ikke heler, eller ændringer i et modermærkes størrelse eller farve.
English: • Liver problems: Mektovi can cause abnormal blood tests related to your liver (raised levels of liver enzymes).
Danish: • Leverproblemer: Mektovi kan give uregelmæssige blodprøveresultater med hensyn til, hvordan din lever virker (forhøjede niveauer af leverenzymer).
English: Other skin cancers: When Mektovi is taken with encorafenib, the patient may develop different types of skin cancer such as cutaneous squamous cell carcinoma.
Danish: Andre former for hudkræft: Når Mektovi tages sammen med encorafenib, kan patienten udvikle forskellige former for hudkræft, såsom kutant planocellulært karcinom.
English: Talk to your doctor immediately if you have any symptoms of heart problems such as feeling dizzy, tired, lightheaded, if you have shortness of breath, if you feel like your heart is pounding, racing, beating irregularly or if you have swelling in the legs.
Danish: Tal straks med lægen, hvis du har symptomer på hjerteproblemer, som f.eks. at du føler dig svimmel, træt, omtumlet, hvis du har åndenød, hvis du føler, at dit hjerte hamrer, slår hurtigt eller uregelmæssigt, eller hvis du får hævede ben.
English: • Eye problems: Mektovi can cause serious eye problems.
Danish: • Øjenproblemer: Mektovi kan forårsage alvorlige øjenproblemer.
English: Binimetinib is not recommended during pregnancy and in women of childbearing potential not using contraception.
Danish: Binimetinib bør ikke anvendes under graviditeten og til kvinder i den fertile alder, som ikke anvender sikker kontraception.
English: At the recommended dose (n = 274) in patients with unresectable or metastatic melanoma, the most common adverse reactions (> 25 %) occurring in patients treated with binimetinib administered with encorafenib were fatigue, nausea, diarrhoea, vomiting, retinal detachment, abdominal pain, arthralgia, blood CK increased and myalgia.
Danish: Ved brug af den anbefalede dosis (n = 274) hos patienter med inoperabelt eller metastatisk melanom var de mest almindelige bivirkninger (> 25 %) hos patienter, der fik binimetinib i kombination med encorafenib, træthed, kvalme, diarré, opkastning, retinal løsning, mavesmerter, artralgi, øget CK i blodet og myalgi.
English: Binimetinib is metabolised by UGTs and CYP1A2 and is a substrate for Pgp.
Danish: Binimetinib metaboliseres af UGT'er og CYP1A2 og er et substrat for P-gp.
English: Ocular toxicities including RPED and RVO can occur when binimetinib is administered.
Danish: Okulær toksicitet, herunder RPED og RVO, kan forekomme i forbindelse med administration af binimetinib.
English: In Study CMEK162B2301-Part 2, in the Combo 300 arm, the incidences of liver laboratory abnormalities are listed below:
Danish: I studiet CMEK162B2301-del 2, i Combo 300-armen, var forekomsten af abnorme levertal som anført nedenfor:
English: • Grade 3 (CK > 5 - 10x upper limit of normal (ULN)) asymptomatic
Danish: • Grad 3 (CK > 5 - 10x øvre normalgrænse (ULN)), asymptomatisk
English: A two-fold increase in total binimetinib exposure (AUC) was observed in patients with moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment (see section 4.2).
Danish: Der blev set en tofoldig stigning i den totale eksponering for binimetinib (AUC) hos patienter med moderat nedsat (Child Pugh-klasse B) og svært nedsat (Child Pugh-klasse C) leverfunktion (se pkt.
English: Treatment with binimetinib should be withheld in patients with suspected pneumonitis or ILD, including patients presenting new or progressive pulmonary symptoms or findings such as cough, dyspnoea, hypoxia, reticular opacities or pulmonary infiltrates (see Table 1 in section 4.2).
Danish: Behandlingen med binimetinib bør pauseres hos patienter med formodet pneumonitis eller ILD, herunder patienter med nye eller progressive lungesymptomer eller fund såsom hoste, dyspnø, hypoksi, retikulære uklarheder eller lungeinfiltrater
English: *composite terms which included more than one preferred term a includes keratoacanthoma, squamous cell carcinoma, lip squamous cell carcinoma and squamous cell carcinoma of skin b includes angioedema, drug hypersensitivity, hypersensitivity, hypersensitivity vasculitis and urticaria c includes facial nerve disorder, facial paralysis, facial paresis d includes left ventricular dysfunction, ejection fraction decreased, cardiac failure and ejection fraction abnormal e includes haemorrhage at various sites including cerebral haemorrhage f includes pulmonary embolism, deep vein thrombosis, embolism, thrombophlebitis, thrombophlebitis superficial and thrombosis g includes colitis, colitis ulcerative, enterocolitis and proctitis h includes myalgia, muscular weakness, muscle spasm, muscle injury, myopathy, myositis i includes fluid retention, peripheral oedema, localised oedema
Danish: *sammensatte termer, som omfattede mere end én foretrukken term a Omfatter keratoakantom, planocellulært karcinom, planocellulært karcinom i læben og planocellulært karcinom i huden b Omfatter angioødem, lægemiddeloverfølsomhed, overfølsomhed, overfølsomhedsvaskulitis og nældefeber c Omfatter facialisnerveforstyrrelser, facialisparalyse, facialisparese d Omfatter dysfunktion af venstre ventrikel, nedsat ejektionsfraktion, hjertesvigt og abnorm ejektionsfraktion e Omfatter blødning på forskellige steder, herunder cerebral blødning f Omfatter lungeemboli, dyb venetrombose, emboli, tromboflebitis, overfladisk tromboflebitis og trombose g Omfatter colitis, ulcerøs colitis, enterocolitis og proctitis h Omfatter myalgi, muskelsvaghed, muskelsammentrækninger, muskelskader, myopati, myositis i Omfatter væskeretention, perifert ødem, lokalt ødem
English: Few patients requiring dose interruptions or dose reductions (0.7 % or 2/274).
Danish: Hos nogle få patienter var det nødvendigt at pausere behandlingen eller reducere dosis (0,7 % eller 2/274).
English: • Grade 3 or Grade 4
Danish: • Grad 3 eller grad 4
English: Following a single oral dose of 45 mg [14C] binimetinib in healthy subjects, the primary biotransformation pathways of binimetinib observed in humans include glucuronidation, Ndealkylation, amide hydrolysis, and loss of ethane-diol from the side chain.
Danish: Efter en enkelt oral dosis af 45 mg [14C]-binimetinib hos raske forsøgsdeltagere var de primære biotransformationsveje for binimetinib hos mennesker glukuronidering, N-dealkylering, amidhydrolyse og tab af ethandiol fra sidekæden.
English: Talk to your doctor immediately if you get chest pain, sudden shortness of breath, trouble breathing, pain in your legs with or without swelling, swelling in your arms and legs, or a cool, pale arm or leg.
Danish: Kontakt omgående lægen, hvis du får smerter i brystet, pludselig åndenød, vejrtrækningsproblemer, smerter i benene med eller uden hævelse, hævede arme og ben eller en kølig, bleg arm eller ditto ben.
English: As Mektovi is to be used in combination with encorafenib, read the encorafenib leaflet carefully as well as this leaflet.
Danish: Eftersom Mektovi skal anvendes i kombination med encorafenib, bør du også læse indlægssedlen for encorafenib grundigt.
English: There are no data from the use of binimetinb in pregnant women.
Danish: Der er ingen eller utilstrækkelige data fra anvendelse af binimetinib til gravide kvinder.
English: The mean (CV %) Cmax,ss was 654 ng/mL (34.7 %) and mean AUCss was 2.35 ug.h/mL (28.0 %) in combination with encorafenib as estimated by population PK modelling.
Danish: Den gennemsnitlige (CV %) Cmax var 654 ng/ml (34,7 %), og gennemsnitligt AUC var 2,35 ug.t/ml (28,8 %) i kombination med encorafenib som estimeret ved PKmodellering af populationen.
English: Study CMEK162B2301, Part 2
Danish: Studie CMEK162B2301, Del 2:
English: High blood pressure: Mektovi can increase blood pressure.
Danish: Højt blodtryk: Mektovi kan øge blodtrykket.
English: In repeat-dose toxicity studies, no concern in terms of fertility was raised from pathological examination of reproductive organs in rats and monkeys.
Danish: I studier vedrørende toksicitet efter gentagen dosering hos rotter og aber gav patologiske undersøgelser af reproduktionsorganerne ikke anledning til bekymring, hvad angik fertiliteten.
English: The median relative dose intensity (RDI) for Combo 450 was 99.6 % for binimetinib and 100 % for encorafenib the median RDI was 86.2 % for Enco 300 and 94.5 % for vemurafenib.
Danish: Medianværdien af den relative dosisintensitet (RDI) for Combo 450 var 99,6 % for binimetinib og 100 % for encorafenib; medianRDI var 86,2 % for Enco 300 og 94,5 % for vemurafenib.
English: The recommended dose of Mektovi is 45 mg (3 tablets of 15 mg) twice daily, taken about 12 hours apart (corresponding to a daily dose of 90 mg).
Danish: Den anbefalede dosis af Mektovi er 45 mg (3 tabletter à 15 mg) to gange dagligt med cirka 12 timers mellemrum (svarende til en daglig dosis på 90 mg).
English: Preliminary Part 2 data at a cut-off date of 9 November 2016 demonstrated the contribution of binimetinib with an improved median PFS estimate of 12.9 months (95 % CI: 10.1, 14.0) for Combo 300 compared to 9.2 months (95 % CI: 7.4, 11.0) for Enco 300 (Parts 1 and 2) per independent central review (BIRC).
Danish: Præliminære data for Del 2, ved skæringsdatoen 9. november 2016, viste binimetinibs bidrag med en forbedret estimat for median PFS på 12,9 måneder (95 % CI: 10,1, 14,0) for Combo 300 sammenlignet med 9,2 måneder (95 % CI: 7,4, 11,0) for Enco 300 (del 1 og 2) ifølge uafhængig central vurdering (BIRC).
English: Venous thromboembolism (VTE)
Danish: Venøs tromboembolisme (VTE)
English: Table 3: Adverse reactions occurring in patients receiving binimetinib in combination with encorafenib at the recommended dose (n = 274) System Organ Class
Danish: Tabel 3: Bivirkninger hos patienter, der fik binimetinib i kombination med encorafenib i den anbefalede dosis (n = 274)
English: carbamazepine
Danish: carbamazepin
English: Dermatitis acneiform*
Danish: Akneiform dermatitis*
English: Cerebral haemorrhage occurred in 1.5 % (4/274) of patients with fatal outcome in 3 patients.
Danish: Cerebral blødning forekom hos 1,5 % (4/274) af patienterne med dødelig udgang hos 3 patienter.
English: Most events were mild, with Grade 3 or 4 events reported in 0.7 % (2/274) of patients.
Danish: De fleste hændelser var milde; hændelser af grad 3 eller 4 blev indberettet hos 0,7 % (2/274) af patienterne.
English: The pharmacokinetics of binimetinib were studied in healthy subjects and patients with solid tumours and advanced and unresectable or metastatic cutaneous melanoma.
Danish: Binimetinibs farmakokinetik er blevet undersøgt hos raske forsøgsdeltagere og hos patienter med solide tumorer og fremskredent og inoperabelt eller metastatisk kutant melanom.
English: Talk to your doctor, pharmacist or nurse before taking Mektovi about all of your medical conditions, particularly if you have any of the following:
Danish: Inden du begynder at tage Mektovi, skal du tale med lægen, apotekspersonalet eller sundhedspersonalet om alle dine helbredsproblemer, især om du har: