FrancophonIA/ELRC3.0 huggingface dataset:
English: In repeat-dose studies the effects seen after trametinib exposure are found mainly in the skin, gastrointestinal tract, haematological system, bone and liver.
Danish: I studier med gentagne doser ses effekterne efter eksponering for trametinib primært i huden, mave-tarm-kanalen, det hæmatologiske system, knoglerne og leveren.
English: • yellowing of your skin or the whites of your eyes (jaundice)
Danish: • gulfarvning af huden eller det hvide i øjnene (gulsot)
English: In patients receiving trametinib in combination with dabrafenib, pyrexia may be accompanied by severe rigors, dehydration, and hypotension which in some cases can lead to acute renal insufficiency.
Danish: Hos patienter, som får trametinib i kombination med dabrafenib, kan pyreksi være ledsaget af svære kulderystelser, dehydrering og hypotension, som i nogle tilfælde kan medføre akut nyresvigt.
English: Left ventricular ejection fraction (LVEF) reduction/Left ventricular dysfunction Trametinib should be interrupted in patients who have an asymptomatic, absolute decrease of >10% in LVEF compared to baseline and the ejection fraction is below the institution's lower limit of normal (LLN) (see section 4.4).
Danish: Reduktion af venstre ventrikels ejektionsfraktion (LVEF)/venstre ventrikel dysfunktion Behandlingen med trametinib bør afbrydes hos patienter, der har et asymptomatisk absolut fald på > 10 % i LVEF sammenlignet med baseline, og ejektionsfraktionen ligger under den nedre normalgrænse (se pkt.
English: If possible, show them the Mekinist and dabrafenib pack with each leaflet.
Danish: Vis dem om muligt Mekinist- og dabrafenib-pakningerne med hver sin indlægsseddel.
English: Subjects were stratified by lactate dehydrogenase (LDH) level (> the upper limit of normal (ULN) versus ULN) and BRAF mutation (V600E versus V600K).
Danish: Forsøgsdeltagerne blev stratificeret efter laktatdehydrogenase (LDH)-niveau (> den øvre normalgrænse (ULN) versus  ULN) og BRAF-mutation (V600E versus V600K).
English: Use with dabrafenib may render hormonal contraceptives less effective and therefore an alternative method of contraception, such as a barrier method, should be used when trametinib is used in combination with dabrafenib.
Danish: Anvendelse sammen med dabrafenib kan nedsætte effekten af hormonelle præventionsmidler, hvorfor der skal benyttes en alternativ præventionsmetode såsom en barrieremetode, når trametinib anvendes i kombination med dabrafenib.
English: Most subjects had LDH ≤ULN (67%), ECOG performance status of 0 (70%), and visceral disease (78%) at baseline.
Danish: De fleste forsøgsdeltagere havde LDH ≤ ULN (67 %), ECOG-performancestatus 0 (70 %) og visceral sygdom (78 %) ved baseline.
English: In studies MEK115306 and MEK116513 <1% (2/209) and 1 % (4/350), respectively, of patients treated with trametinib in combination with dabrafenib developed pneumonitis or ILD (see section 4.8).
Danish: I MEK115306 og MEK116513 udviklede henholdsvis < 1 % (2/209) og 1 % (4/350) af de patienter, der fik trametinib i kombination med dabrafenib, pneumonitis eller ILD (se pkt.
English: Lung or breathing problems
Danish: Lunge- eller vejrtrækningsproblemer
English: LVEF should be evaluated in all patients prior to initiation of treatment with trametinib, one month after initiation of therapy, and then at approximately 3-monthly intervals while on treatment (see section 4.2 regarding dose modification).
Danish: LVEF skal måles hos alle patienter før opstart af behandling med trametinib, én måned efter opstart af behandlingen og herefter med ca. 3 måneders mellemrum i behandlingsperioden (se pkt.
English: When trametinib and dabrafenib are taken in combination, the once-daily dose of trametinib should be taken at the same time each day with either the morning dose or the evening dose of dabrafenib.
Danish: Når trametinib og dabrafenib tages i kombination, skal den daglige dosis af trametinib tages på samme tid hver dag sammen med enten morgendosis eller aftendosis af dabrafenib.
English: • have eye problems including blockage of the vein draining the eye (retinal vein occlusion) or swelling in the eye which may be caused by fluid blockage (chorioretinopathy).
Danish: • har øjenproblemer, herunder blokering af den vene, der leder væske fra øjet (retinal veneokklusion) eller hævelse i øjet, som kan være forårsaget af væskeophobning (korioretinopati).
English: Usually, these skin changes remain local and can be removed with surgery and treatment with Mekinist and dabrafenib can be continued without interruption.
Danish: Normalt forbliver disse hudændringer på et begrænset område og kan fjernes ved operation, og behandlingen med Mekinist og dabrafenib kan fortsættes uden afbrydelse.
English: Tell your doctor or nurse if you have any new or worsening symptoms, including:
Danish: Fortæl det til lægen eller sundhedspersonalet, hvis du får nye eller forværrede symptomer, herunder:
English: Progressive disease or death, n (%) Median PFS (months) (95% CI)
Danish: Progressiv sygdom eller død, n (%) Median PFS (måneder) (95 % CI)
English: If treatment-related toxicities occur when trametinib is used in combination with dabrafenib, then both treatments should be simultaneously dose reduced, interrupted or discontinued.
Danish: Hvis der opstår behandlingsrelateret toksicitet, når trametinib anvendes i kombination med dabrafenib, skal dosis i begge behandlinger samtidigt reduceres, pauseres eller seponeres.
English: Not known (cannot be estimated from the available data) Categories have been assigned based on absolute frequencies in the clinical trial data.
Danish: Kategorierne er blevet tildelt på basis af absolutte hyppigheder i henhold til data fra de kliniske studier.
English: Patients should take trametinib as monotherapy or in combination with dabrafenib at least one hour prior to or two hours after a meal due to the effect of food on trametinib absorption (see section 4.2 and 5.2).
Danish: Patienterne skal tage trametinib (som monoterapi eller i kombination med dabrafenib) mindst 1 time før eller mindst 2 timer efter et måltid på grund af fødens indvirkning på absorptionen af trametinib (se pkt.
English: Patients treated with trametinib or combination with dabrafenib may develop ILD or pneumonitis.
Danish: Patienter, som behandles med trametinib alene eller i kombination med dabrafenib, kan udvikle ILD eller pneumonitis.
English: Of these patients, 559 were treated with the combination for BRAF V600 mutant melanoma in two randomised Phase III studies, MEK115306 (COMBI-d) and MEK116513 (COMBI-v), 435 were treated with the combination in the adjuvant treatment of Stage III BRAF V600 mutant melanoma after complete resection in a randomised Phase III study BRF115532 (COMBI-AD) and 82 were treated with the combination for BRAF V600 mutant NSCLC in a multi-cohort, non-randomised Phase II study BRF113928 (see section 5.1).
Danish: 559 af disse patienter blev behandlet med kombinationen for BRAF V600-muteret melanom i to randomiserede fase III-studier, MEK115306 (COMBI-d) og MEK116513 (COMBI-v), 435 blev behandlet med kombinationen i den adjuverende behandling af stadie III BRAF V600-muteret melanom efter komplet resektion i et randomiseret fase III-studie BRF115532 (COMBI-AD) og 82 blev behandlet med kombinationen for BRAF V600-muteret NSCLC i et ikke-randomiseret fase II-studie med flere kohorter BRF113928 (se pkt.
English: Trametinib should be permanently discontinued in patients with Grade 3 or 4 left ventricular cardiac dysfunction or clinically significant LVEF reduction which does not recover within 4 weeks (see section 4.4).
Danish: Trametinib skal seponeres permanent hos patienter med venstre ventrikel dysfunktion grad 3 eller 4, eller klinisk signifikant reduktion af LVEF, der ikke normaliseres inden for 4 uger (se pkt.
English: The primary endpoint of the study was to evaluate the efficacy of trametinib compared to chemotherapy with respect to PFS in patients with advanced/metastatic BRAF V600E/K mutation-positive melanoma without a prior history of brain metastases (N=273) which is considered the primary efficacy population.
Danish: Studiets primære formål var at vurdere effekten af trametinib sammenlignet med kemoterapi med hensyn til PFS hos patienter med fremskredent/metastatisk BRAF V600E/K-mutationspositivt melanom uden hjernemetastaser i anamnesen (N = 273), som anses for at være den primære effekt-population.
English: For the primary endpoint of investigator-assessed ORR, the ORR in the first-line population was 61.1% (95% CI, 43.5%, 76.9%) and in the previously-treated population was 66.7% (95% CI, 52.9%, 78.6%).
Danish: Det primære endepunkt, investigatorvurderet ORR, var for førstelinjepopulationen 61,1 % (95 % CI, 43,5 %; 76,9 %) og 66,7 % (95 % CI, 52,9 %; 78,6 %) for den behandlingserfarne population.
English: The pharmacokinetics of trametinib were characterised in 223 patients enrolled in clinical trials with trametinib who had mild renal impairment and 35 patients with moderate renal impairment using a population pharmacokinetic analysis.
Danish: Farmakokinetikken af trametinib blev karakteriseret hos 223 patienter med let nedsat nyrefunktion og 35 patienter med moderat nedsat nyrefunktion, der var inkluderet i kliniske studier med trametinib, ved at udføre en farmakokinetisk populationsanalyse.
English: Changes in your skin Serious skin reactions have been reported in people taking Mekinist in combination with dabrafenib (frequency not known).
Danish: Forandringer i huden Der er rapporteret tilfælde af alvorlige hudreaktioner hos personer, der tog Mekinist i kombination med dabrafenib (hyppigheden er ukendt).
English: Call your doctor or nurse right away if you develop high blood pressure, your blood pressure worsens, or you have severe headache, light-headedness, or dizziness.
Danish: Kontakt straks lægen eller sundhedspersonalet, hvis du får forhøjet blodtryk, hvis dit høje blodtryk forværres eller hvis du har alvorlig hovedpine, føler dig svimmel eller ør.
English: These melanomas are usually removed by surgery and treatment with Mekinist and dabrafenib can be continued without interruption.
Danish: Disse melanomer fjernes normalt ved operation, og behandlingen med Mekinist og dabrafenib kan fortsættes uden afbrydelse.
English: In an embryo-foetal developmental toxicity study with rabbits, decreased foetal body weight, increased abortions, increased incidence of incomplete ossification and skeletal malformations were seen at sub-clinical exposures based on AUC).
Danish: I et studie med kaniner vedrørende embryoføtal udviklingstoksicitet sås lavere fødselsvægt, et øget antal aborter, øget incidens af ufuldstændig ossifikation samt misdannelser af skelettet ved subkliniske eksponeringer baseret på AUC.
English: • Eyesight problems (see also “Eye (vision) problems” earlier in section 4)
Danish: • synsproblemer (se også “Øjenproblemer (synsproblemer)” tidligere i punkt 4)
English: • Decreased red blood cells (anaemia), abnormal test related to creatine phosphokinase, an enzyme found mainly in heart, brain, and skeletal muscle
Danish: • nedsat antal røde blodlegemer (anæmi), unormalt niveau af kreatinkinase, som er et enzym, der primært findes i hjertet, hjernen og skeletmusklerne
English: You may also get additional side effects due to taking dabrafenib at the same time as Mekinist in the list below.
Danish: Du kan også få yderligere bivirkninger, fordi du tager dabrafenib samtidig med Mekinist, se nedenfor.
English: Patients ≥65 years were more likely to experience ARs leading to permanent discontinuation of medicinal product, dose reduction and dose interruption than those <65 years.
Danish: Patienter ≥ 65 år oplevede i højere grad bivirkninger, der førte til permanent seponering af lægemiddel, dosisreduktion eller pauséring af behandling, end patienter < 65 år.
English: • Unusual hair loss or thinning
Danish: • usædvanligt hårtab eller udtynding af håret
English: • If you do become pregnant while you are taking Mekinist, tell your doctor immediately.
Danish: • Fortæl det straks til lægen, hvis du bliver gravid, mens du tager Mekinist.
English: Effects of other drugs on trametinib: In vivo and in vitro data suggest that the pharmacokinetics of trametinib are unlikely to be affected by other medicinal products.
Danish: Andre lægemidlers effekt på trametinib: In vivo- og in vitro-data tyder på, at det ikke er sandsynligt, at trametinibs farmakokinetik påvirkes af andre lægemidler.
English: It is recommended that patients receiving treatment with trametinib monotherapy or in combination with dabrafenib have liver function monitored every four weeks for 6 months after treatment initiation with trametinib.
Danish: Det anbefales, at patienter, der behandles med trametinib-monoterapi eller i kombination med dabrafenib, får målt leverfunktionen hver 4. uge i 6 måneder efter opstart af behandling med trametinib.
English: • If you take too much Mekinist or dabrafenib, immediately contact your doctor, nurse or pharmacist.
Danish: • Hvis du har taget for meget Mekinist eller dabrafenib, skal du straks kontakte lægen, sundhedspersonalet eller apotekspersonalet.
English: 7 film-coated tablets 30 film-coated tablets
Danish: 7 filmovertrukne tabletter 30 filmovertrukne tabletter
English: Tell your doctor or nurse if you have any new or worsening symptoms of lung or breathing problems, including:
Danish: Fortæl det til lægen eller sundhedspersonalet hvis du oplever nye eller forværringer af symptomer på lunge- eller vejrtrækningsproblemer, herunder:
English: If the missed dose is more than12 hours late, skip that dose and take your next dose at the usual time.
Danish: Hvis den glemte dosis skulle være taget for mere end 12 timer siden, skal du springe den dosis over og tage din næste dosis på det sædvanlige tidspunkt.
English: Disorders associated with visual disturbances, including RPED and RVO, have been observed with trametinib.
Danish: Tilstande forbundet med synsforstyrrelser, herunder RPED og RVO, er set under behandling med trametinib.
English: Your doctor may arrange to check your lung function before you start taking your medicine.
Danish: Lægen vil eventuelt sørge for, at du får kontrolleret din lungefunktion, inden du begynder at tage din medicin.
English: Carcinogenicity studies with trametinib have not been conducted.
Danish: Der er ikke udført studier, hvor karcinogeniciteten af trametinib er blevet undersøgt.
English: Dabrafenib dose* Only when used in combination with trametinib
Danish: Dabrafenib-dosis* Kun ved anvendelse i kombination med trametinib
English: The response was durable with median DoR in the previously-treated population reaching 9.8 months (95% CI, 6.9, 16.0) by investigator assessment.
Danish: Der blev opnået et varigt respons med median investigatorvurderet DoR i den behandlingserfarne population på 9,8 måneder (95 % CI, 6,9; 16,0).
English: Trametinib is an in vitro substrate of BSEP and the efflux transporter P-gp.
Danish: Trametinib er et in vitro-substrat for BSEP og effluxtransportøren P-gp.
English: Deep vein thrombosis (DVT)/Pulmonary embolism (PE)
Danish: Dyb venetrombrose (DVT)/lungeemboli
English: Contact your doctor immediately if you get a severe skin rash with any of the following symptoms: blisters on your skin, blisters or sores in your mouth, peeling of your skin, fever, redness or swelling of your face, or soles of your feet.
Danish: Kontakt straks lægen, hvis du får et alvorligt hududslæt med nogen af følgende symptomer: blærer på huden, blærer eller sår i munden, afskalning af huden, feber, rødme eller hævelse af dit ansigt eller dine fodsåler.
English: The other side effects that you may see when you take Mekinist alone are as follows:
Danish: Andre bivirkninger, som du kan få, når du tager Mekinist alene:
English: As trametinib is metabolised predominantly via deacetylation mediated by hydrolytic enzymes (e.g. carboxyl-esterases), its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions (see section 5.2).
Danish: Da trametinib primært metaboliseres via deacetylering medieret af hydrolytiske enzymer (fx carboxylesteraser), er det ikke sandsynligt, at trametinibs farmakokinetik påvirkes af andre stoffer gennem metaboliske interaktioner (se pkt.
English: If you stop taking Mekinist Take Mekinist for as long as your doctor recommends.
Danish: Tag Mekinist, så længe som lægen foreskriver.
English: 7.5d a - Progression-free survival (investigator assessed) b - Overall Response Rate = Complete Response + Partial Response c - Duration of response d - At the time of the reporting the majority (59% of dabrafenib+trametinib and 42% of vemurafenib) of investigator-assessed responses were still ongoing
Danish: investigators vurdering) b - Samlet responsrate = samlet respons + partiel respons c - Responsvarighed d - På rapporteringstidspunktet var størstedelen af responserne (investigatorvurderede) stadig bestående (59 % af dabrafenib+trametinib og 42% af vemurafenib) NR = Ikke nået
English: NR=not reached
Danish: NR = Ikke nået
English: If a dose of dabrafenib is missed, when trametinib is given in combination with dabrafenib, the dose of dabrafenib should only be taken if it is more than 6 hours until the next scheduled dose.
Danish: Hvis en dosis af dabrafenib glemmes, når det gives i kombination med trametinib, må dabrafenib-dosen kun tages, hvis der er mere end 6 timer til den næste planlagte dosis.
English: NE2 (8.3, NE) NE (6.9, NE)
Danish: (8,3; NE) NE (6,9; NE)
English: In these patients a 13% (95% CI: 5.0, 27.0) confirmed response rate was observed with a median PFS of 3.6 months (95% CI: 2, 4).
Danish: Hos disse patienter blev der observeret en bekræftet responsrate på 13 % (95 % CI: 5,0; 27,0) med en median PFS på 3,6 måneder (95 % CI: 2; 4).
English: In rats, hepatocellular necrosis and transaminase elevations were seen after 8 weeks at ≥0.062 mg/kg/day (approximately 0.8 times human clinical exposure based on AUC).
Danish: Hos rotter blev der set hepatocellulær nekrose og forhøjede transaminaseniveauer efter 8 uger på ≥ 0,062 mg/kg/dag (ca. 0,8 gange den kliniske eksponering hos mennesker baseret på AUC).
English: Trametinib should not be administered to breast-feeding mothers.
Danish: Trametinib må ikke administreres til ammende mødre.
English: Trametinib accumulates with repeat daily dosing with a mean accumulation ratio of 6.0 at 2 mg once daily dose.
Danish: Ved gentagen daglig dosering akkumuleres trametinib med et gennemsnitligt akkumuleringsforhold på 6,0 ved en dosis på 2 mg en gang daglig.
English: Trametinib is an in vitro substrate of the efflux transporter P-gp.
Danish: Trametinib er et in vitro-substrat for effluxtransportøren P-gp.
English: In the integrated safety population of trametinib in combination with dabrafenib (n=1,076) 265 patients (25%) were ≥65 years of age; 62 patients (6%) were ≥75 years of age.
Danish: I den integrerede sikkerhedspopulation med trametinib i kombination med dabrafenib (n = 1076) var 265 patienter (25 %) ≥ 65 år, og 62 patienter (6 %) var ≥ 75 år.
English: Do not throw away medicines in wastewater or household waste.
Danish: Af hensyn til miljøet må du ikke smide medicinrester i afløbet, toilettet eller skraldespanden.
English: Chemotherapy (n=108)
Danish: Kemoterapi (n = 108)
English: Improvements were also observed for ORR and a longer DoR was observed in the combination arm compared to vemurafenib monotherapy (Table 9).
Danish: Forbedringer blev også set i ORR og der blev observeret en længere DoR i kombinationsarmen, sammenlignet med vemurafenib monoterapi (tabel 9).
English: Cough Dyspnoea
Danish: Hoste Dyspnø
English: Mekinist can cause inflammation of the lung (pneumonitis or interstitial lung disease).
Danish: Mekinist kan give betændelse i lungerne (pneumonitis eller interstitiel lungesygdom).
English: Following administration of 2 mg once daily, steady-state geometric mean Cmax, AUC(0-) and predose concentration were 22.2 ng/ml, 370 ng*hr/ml and 12.1 ng/ml, respectively with a low peak:trough ratio (1.8).
Danish: Efter administration af 2 mg en gang dagligt var den geometriske middelværdi ved steady state af Cmax, AUC(0-) og koncentration før dosering henholdsvis 22,2 ng/ml, 370 ng·time/ml og 12,1 ng/ml med et lille forhold mellem maks.
English: • Trametinib in combination with dabrafenib
Danish: • Trametinib i kombination med dabrafenib
English: In rats and dogs given trametinib at or below clinical exposures, bone marrow necrosis, lymphoid atrophy in thymus and GALT and lymphoid necrosis in lymph nodes, spleen and thymus were observed, which have the potential to impair immune function.
Danish: Hos rotter og hunde, som fik trametinib ved eller under de kliniske eksponeringer, blev der observeret knoglemarvsnekrose, lymfoid atrofi af thymus og GALT (gut-associated lymphoid tissue) og lymfoid nekrose i lymfeknuder, milt og thymus, hvilket måske kan nedsætte immunforsvaret.
English: High-density polyethylene (HDPE) bottle with child-resistant polypropylene closure.
Danish: Højdensitetspolyethylen (HDPE)-beholder med børnesikret polypropylenlåg.
English: In a Phase III trial, 2.4% (5/211) of patients treated with trametinib monotherapy developed ILD or pneumonitis; all five patients required hospitalisation.
Danish: I et fase III-studie udviklede 2,4 % (5/211) af de patienter, der fik trametinib-monoterapi, ILD eller pneumonitis.
English: • widespread rash, fever, and enlarged lymph nodes (DRESS-syndrome or drug hypersensitivity syndrome).
Danish: • udbredt udslæt, feber og forstørrede lymfeknuder (DRESS-syndrom eller lægemiddel overfølsomhedssyndrom).
English: • Skin rash, acne-like rash, redness of the face, dry or itching skin (see also “Changes in your skin” earlier in section 4)
Danish: • hududslæt, aknelignende udslæt, rødme i ansigtet, tør eller kløende hud (se også “Forandringer i huden” tidligere i punkt 4)
English: Trametinib may result in transient inhibition of BCRP substrates (e.g. pitavastatin) in the gut, which may be minimised with staggered dosing (2 hours apart) of these agents and trametinib.
Danish: Trametinib kan resultere i forbigående hæmning af BCRP-substrater (fx pitavastatin) i tarmen, hvilket kan minimeres ved at forskyde doseringen af disse stoffer (med 2 timers interval) og doseringen af trametinib.
English: Effects of trametinib on drug-metabolising enzymes and transporters: In vitro and in vivo data suggest that trametinib is unlikely to affect the pharmacokinetics of other medicinal products.
Danish: Trametinibs effekt på lægemiddelmetaboliserende enzymer og transportører: In vitro- og in vivo-data tyder på, at det er usandsynligt, at trametinib påvirker andre lægemidlers farmakokinetik.
English: Trametinib was found to be an in vitro inhibitor of CYP2C8, CYP2C9 and CYP2C19, an inducer of CYP3A4 and an inhibitor of the transporters OAT1, OAT3, OCT2, MATE1, OATP1B1, OATP1B3, P-gp and BCRP.
Danish: Det viste sig, at trametinib er en hæmmer af CYP2C8, CYP2C9 og CYP2C19, en induktor af CYP3A4 og en hæmmer af transportørerne OAT1, OAT3, OCT2, MATE1, OATP1B1, OATP1B3, P-gp og BCRP in vitro.
English: Although trametinib exposure is unlikely to be affected by inhibition of BSEP, increased levels of trametinib upon strong inhibition of hepatic P-gp cannot be excluded (see section 4.5).
Danish: Selvom tramatinib-eksponering sandsynligvis ikke påvirkes af hæmning af BSEP, kan forhøjede trametinib-niveauer ikke udelukkes ved stærk hæmning af P-gp (se pkt.
English: Trametinib is absorbed orally with median time to achieve peak concentrations of 1.5 hours post-dose.
Danish: Trametinib absorberes oralt, og den maksimale plasmakoncentration nås med en mediantid på 1,5 timer efter dosering.
English: Therefore other treatment options should be considered before treatment with the combination in this prior BRAF inhibitor treated population.
Danish: Andre behandlingsmuligheder skal derfor overvejes, inden patienter, der tidligere har været behandlet med en BRAF-hæmmer, behandles med kombinationen.
English: The efficacy and safety of trametinib have not been evaluated in patients whose melanoma tested negative for the BRAF V600 mutation.
Danish: Trametinibs virkning og sikkerhed er ikke undersøgt hos patienter med melanom, der er testet negativt for BRAF V600-mutationen.