FrancophonIA/ELRC3.0 huggingface dataset:
English: In rats decreased foetal weights and increased post-implantation loss were seen at exposures below or slightly above the clinical exposures based on AUC.
Danish: Hos rotter sås lavere fødselsvægt og større tab efter implantation ved eksponeringer lavere eller lidt højere end de kliniske eksponeringer baseret på AUC.
English: Grade (CTC-AE)* Recommended trametinib dose modifications Used as monotherapy or in combination with dabrafenib
Danish: Grad (CTC-AE)* Anbefalede justeringer af trametinib-dosis Anvendt som monoterapi eller i kombination med dabrafenib
English: The efficacy and safety of the recommended dose of trametinib (2 mg once daily) in combination with dabrafenib (150 mg twice daily) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation was studied in two Phase III studies and one supportive Phase I/II study.
Danish: Effekten og sikkerheden af den anbefalede dosis af trametinib (2 mg en gang daglig) i kombination med dabrafenib (150 mg to gange dagligt) til behandling af voksne patienter med inoperabelt eller metastatisk melanom med en BRAF V600-mutation blev undersøgt i to fase III-studier og et understøttende fase I/II-studie.
English: Chemotherapy included patients on dacarbazine (DTIC) 1000 mg/m2 every 3 weeks or paclitaxel 175 mg/m every 3 weeks.
Danish: Kemoterapi omfattede patienter i behandling med en dosis dacarbazin (DTIC) på 1.000 mg/m hver 3. uge eller en dosis paclitaxel på 175 mg/m2 hver 3. uge.
English: • Inflammation of hair follicles in the skin
Danish: • betændelse i hårsækkene i huden
English: The risk of haemorrhage may be increased with concomitant use of antiplatelet or anticoagulant therapy.
Danish: Risikoen for blødning kan være øget ved samtidig brug af trombocytfunktionshæmmende eller antikoagulerende behandling.
English: Please refer to sections 4.4 and 4.8 of the dabrafenib SmPC.
Danish: 4.4 og 4.8 i produktresuméet for dabrafenib.
English: • Inflammation of the fatty layer under the skin (panniculitis)
Danish: • inflammation i fedtlaget under huden (panniculitis)
English: Combination with dabrafenib
Danish: Kombination med dabrafenib
English: Tell your doctor or nurse as soon as possible if you get any skin rash, or if you have a rash that gets worse.
Danish: Fortæl det hurtigst muligt til lægen eller sundhedspersonalet, hvis du får nogen form for hududslæt, eller hvis du har et udslæt, der bliver værre.
English: problems” earlier in section 4)
Danish: “Hjerteproblemer” tidligere i punkt 4)
English: Rash has been observed in about 60% of patients when given as monotherapy and in about 24% of patients in trametinib and dabrafenib combination studies in the integrated safety population.
Danish: Der er observeret udslæt hos ca. 60 % af patienterne, når trametinib gives som monoterapi, og hos ca. 24 % af patienterne i den integrerede sikkerhedspopulation i kombinationsstudierne med trametinib og dabrafenib.
English: The efficacy and safety of trametinib in patients with BRAF unresectable or metastatic mutant melanoma (V600E and V600K) were evaluated in a randomised open-label Phase III study (MEK114267 [METRIC]).
Danish: Effekten og sikkerheden af trametinib hos patienter med BRAF-mutationspositivt inoperabelt eller metastatisk melanom (V600E og V600K) blev vurderet i et randomiseret, ublindet fase III-studie (MEK114267 [METRIC]).
English: The usual dose of Mekinist either used alone or in combination with dabrafenib is one 2 mg tablet once a day.
Danish: Den sædvanlige dosis af Mekinist, enten alene eller i kombination med dabrafenib, er én tablet på 2 mg en gang daglig.
English: In patients with BRAF and NRAS mutation positive melanoma, administration of trametinib resulted in dose-dependent changes in tumour biomarkers including inhibition of phosphorylated ERK, inhibition of Ki67 (a marker of cell proliferation), and increases in p27 (a marker of apoptosis).
Danish: Hos patienter med BRAF- og NRAS-mutationspositivt melanom resulterede administration af trametinib i dosisafhængige ændringer i niveauerne af tumorbiomarkører, herunder hæmning af niveauet af fosforyleret ERK, hæmning af niveauet af Ki67 (en markør for celledeling) og øgning af niveauet af p27 (en markør for apoptose).
English: Animal studies have shown reproductive toxicity (see section 5.3).
Danish: Der er i dyrestudier påvist reproduktionstoksicitet (se pkt.
English: The incidence and severity of pyrexia are increased with the combination therapy (see dabrafenib SmPC section 4.4).
Danish: Forekomsten og sværhedsgraden af pyreksi øges ved kombinationsterapi (se produktresuméet for dabrafenib pkt.
English: If trametinib is being used in combination with dabrafenib then therapy with dabrafenib may be continued at the same dose.
Danish: Hvis trametinib anvendes i kombination med dabrafenib, kan behandling med dabrafenib fortsættes ved samme dosis.
English: Data cut-off: 8
Danish: Data cut-off: 8. august 2016
English: In clinical trials, central testing for BRAF V600 mutation using a BRAF mutation assay was conducted on the most recent tumour sample available.
Danish: I kliniske studier blev der udført en central test for BRAF V600-mutation ved brug af en BRAF-mutationsanalyse på den nyeste tumorprøve.
English: In clinical trials with the combination of trametinib and dabrafenib 11 patients reported trametinib overdose (4 mg); no SAEs were reported.
Danish: I kliniske studier med en kombination af trametinib og dabrafenib rapporterede 11 patienter trametinib-overdosering (4 mg).
English: Dose adjustment for dabrafenib below 50 mg twice daily is not recommended when used in combination with trametinib.
Danish: Justering af dabrafenib-dosis til en dosis lavere end 50 mg to gange dagligt anbefales ikke, når det anvendes i kombination med trametinib.
English: Mekinist is not recommended if you have ever had blockage of the vein draining the eye (retinal vein occlusion).
Danish: Mekinist anbefales ikke, hvis du har haft blokade af den vene, som leder væske fra øjet (retinal veneokklusion).
English: Trametinib should be used with caution in patients with impaired left ventricular function.
Danish: Trametinib bør anvendes med forsigtighed hos patienter med nedsat funktion af venstre ventrikel.
English: Dose adjustment for trametinib below 1 mg once daily is not recommended, whether used as monotherapy or in combination with dabrafenib.
Danish: Justering af trametinib-dosis til en dosis lavere end 1 mg en gang dagligt anbefales ikke, hvad enten det anvendes som monoterapi eller i kombination med dabrafenib.
English: The safety of trametinib monotherapy has been evaluated in the integrated safety population of 329 patients with BRAF V600 mutant unresectable or metastatic melanoma treated with trametinib 2 mg once daily in studies MEK114267, MEK113583, and MEK111054.
Danish: Sikkerheden ved trametinib-monoterapi er blevet undersøgt hos den integrerede sikkerhedspopulation på 329 patienter med BRAF V600-muteret, inoperabelt eller metastatisk melanom, der blev behandlet med 2 mg trametinib en gang daglig i studierne MEK114267, MEK113583 og MEK111054.
English: The trametinib 2 mg once daily and dabrafenib 150 mg twice daily combination demonstrated limited clinical activity in patients who had progressed on a BRAF inhibitor (see section 4.4).
Danish: Kombinationen med 2 mg trametinib en gang daglig og 150 mg dabrafenib to gange dagligt viste begrænset klinisk aktivitet hos patienter, der var progredieret på en BRAF-hæmmer (se pkt.
English: Left ventricular dysfunction Ejection fraction decreased Bradycardia
Danish: Venstre ventrikel dysfunktion Reduceret ejektionsfraktion Bradykardi
English: Of the patients with confirmed disease progression in the chemotherapy arm, a total of 51 (47%) crossed over to receive trametinib.
Danish: I alt 51 (47 %) af patienterne med bekræftet sygdomsprogression i kemoterapi-armen skiftede over til behandling med trametinib.
English: Liver monitoring may be continued thereafter as clinically indicated (see section 4.4).
Danish: Monitorering af leverfunktionen kan herefter fortsættes som klinisk indiceret (se pkt.
English: In a single-arm Phase II study, designed to evaluate the objective response rate, safety, and pharmacokinetics following dosing of trametinib at 2 mg once daily in patients with BRAF V600E, V600K, or V600D mutation-positive metastatic melanoma (MEK113583), two separate cohorts were enrolled: Cohort A: patients with prior treatment with a BRAF inhibitor either with or without other prior therapy, Cohort B: patients with at least 1 prior chemotherapy or immunotherapy, without prior treatment with a BRAF inhibitor.
Danish: Patienter, der tidligere har været behandlet med BRAF-hæmmer I et fase II-studie med én arm, hvor formålet var at vurdere objektiv responsrate, sikkerheden og farmakokinetikken efter dosering af 2 mg trametinib en gang daglig hos patienter med BRAF V600E-, V600K- eller V600D-mutationspositivt metastatisk melanom (MEK113583), blev to særskilte kohorter inkluderet: Kohorte A: patienter, der tidligere var blevet behandlet med en BRAF-hæmmer og enten med eller uden tidligere anden behandling, og kohorte B: patienter med mindst én tidligere kemoterapi eller immunoterapi og uden tidligere behandling med en BRAF-hæmmer.
English: Mekinist is not recommended if you have ever had a blockage of the vein draining the eye (retinal vein occlusion).
Danish: Mekinist anbefales ikke, hvis du har eller har haft en blokering af den vene, der fører blodet væk fra øjet (retinal veneokklusion).
English: Please refer to dabrafenib SmPC for information on method of administration when given in combination with trametinib.
Danish: Se produktresuméet for dabrafenib for yderligere oplysninger om administration, når det gives i kombination med trametinib.
English: In juvenile rats, increased heart weight with no histopathology was observed at 0.35 mg/kg/day (approximately twice the adult human clinical exposure based on AUC).
Danish: Hos unge rotter blev der observeret øget hjertevægt uden histopatologi ved en dosis på 0,35 mg/kg/dag (ca. to gange den kliniske eksponering hos voksne mennesker baseret på AUC).
English: Trametinib monotherapy has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy (see section 5.1).
Danish: Trametinib-monoterapi har ikke påvist klinisk aktivitet hos patienter, som har haft sygdomsprogression under en tidligere behandling med en BRAF-hæmmer (se pkt.
English: In patients who are diagnosed with RVO, treatment with trametinib, whether given as monotherapy or in combination with dabrafenib, should be permanently discontinued.
Danish: Hvis patienter diagnosticeres med RVO, skal behandling med trametinib, hvad enten det gives som monoterapi eller i kombination med dabrafenib, seponeres permanent.
English: In mice, lower heart rate, heart weight and left ventricular function were observed without cardiac histopathology after 3 weeks at ≥0.25 mg/kg/day trametinib (approximately 3 times human clinical exposure based on AUC) for up to 3 weeks.
Danish: Hos mus blev der observeret nedsat hjertefrekvens, hjertevægt og funktion af venstre ventrikel uden kardiel histopatologi efter 3 uger ved en dosis trametinib på ≥ 0,25 mg/kg/dag (ca. 3 gange den kliniske eksponering hos mennesker baseret på AUC) i op til 3 uger.
English: The most common adverse reactions (incidence ≥20%) for trametinib were rash, diarrhoea, fatigue, oedema peripheral, nausea, and dermatitis acneiform.
Danish: De hyppigste bivirkninger (incidens ≥ 20 %) ved trametinib var udslæt, diarré, træthed, perifert ødem, kvalme og akneiform dermatitis.
English: Trametinib in combination with dabrafenib in patients with melanoma who have progressed on a BRAF inhibitor
Danish: Trametinib i kombination med dabrafenib hos patienter med melanom, som har progredieret på en BRAF-hæmmmer
English: Female patients of reproductive potential must be advised to use effective methods of contraception during treatment with trametinib and for 16 weeks after stopping treatment.
Danish: Kvinder i den fertile alder skal informeres om at anvende sikre kontraceptionsmetoder under behandlingen med trametinib og i 16 uger efter seponering af trametinib.
English: Improvements for the primary endpoint of PFS were sustained over a 5 year timeframe in the combination arm compared to dabrafenib monotherapy.
Danish: Forbedringer i det primære endepunkt PFS blev opretholdt i en tidsramme på 5 år i kombinationsarmen, sammenlignet med dabrafenib monoterapi.
English: Table 13 Investigator-assessed RFS results for Study BRF115532 (COMBI-AD)
Danish: Tabel 13 Investigator-vurderede RFS-resultater for studie BRF115532 (COMBI-AD)
English: Improvements for the secondary endpoint of PFS were sustained over a 5 year timeframe in the combination arm compared to vemurafenib monotherapy.
Danish: Forbedringer i det sekundære endepunkt PFS blev opretholdt i en tidsramme på 5 år i kombinationsarmen, sammenlignet med vemurafenib monoterapi.
English: Ask your doctor, nurse or pharmacist for advice.
Danish: Spørg lægen, sundhedspersonalet eller apotekspersonalet til råds.
English: The majority of these cases were Grade 1 or 2 and did not require any dose interruptions or dose reductions (see sections 4.2 and 4.4).
Danish: Størstedelen af disse tilfælde var af grad 1 eller 2 og krævede ingen behandlingspauser eller dosisreduktion (se pkt.
English: Dermatitis acneiform Dry skin
Danish: Akneiform dermatitis Tør hud
English: Mekinist 2 mg film-coated tablets EU/1/14/931/005
Danish: Mekinist 2 mg filmovertrukne tabletter EU/1/14/931/005
English: *Please refer to the dabrafenib SmPC, Posology and method of administration, for dosing instructions for treatment with dabrafenib monotherapy.
Danish: *Se produktresuméet for dabrafenib, Dosering og administration, vedrørende doseringsvejledning til dabrafenib-monoterapi.
English: Trametinib suppressed levels of phosphorylated ERK in BRAF mutant melanoma tumour cell lines and melanoma xenograft models.
Danish: Trametinib hæmmede niveauet af fosforyleret ERK i BRAF-muterede melanomtumorcellelinjer og melanomxenograftmodeller.
English: Refer to the dabrafenib SmPC for further information.
Danish: Se produktresuméet for dabrafenib for yderligere oplysninger.
English: Patients ≥65 years were more likely to experience SARs and 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 alvorlige bivirkninger og bivirkninger, der førte til permanent seponering af lægemiddel, dosisreduktion eller midlertidig behandlingsafbrydelse, end patienter < 65 år.
English: Additionally, in juvenile rats given trametinib, decreased ovarian weights, slight delays in hallmarks of female sexual maturation (vaginal opening and increased incidence of prominent terminal end buds within the mammary gland) and slight hypertrophy of the surface epithelium of the uterus were observed.
Danish: Der blev desuden observeret nedsat ovarievægt, en mindre forsinkelse af kendetegnene for hunners seksuelle modning (vaginal åbning og øget forekomst af fremtrædende terminale endeknopper i mælkekirtlen) og let hypertrofi af overfladeepitelet på uterus hos unge rotter, der fik trametinib.
English: If possible, show them the Mekinist pack and this leaflet.
Danish: Vis Mekinist-pakningen og denne indlægsseddel, hvis det er muligt.
English: Mekinist, or the combination with dabrafenib, can cause problems with your liver which may develop into serious conditions such as hepatitis and liver failure, which may be fatal.
Danish: Mekinist alene eller i kombination med dabrafenib kan forårsage leverproblemer, som kan udvikle sig til alvorlige tilstande, såsom leverbetændelse og leversvigt, som kan være dødeligt.
English: Of these patients, 211 were treated with trametinib for BRAF V600 mutant melanoma in the randomised open-label Phase III study MEK114267 (METRIC) (see section 5.1).
Danish: Af disse patienter blev 211 behandlet med trametinib på grund af BRAF V600-mutationspositivt melanom i det randomiserede, åbne fase III-studie MEK114267 (METRIC) (se pkt.
English: When trametinib is given in combination with dabrafenib, the SmPC of dabrafenib must be consulted prior to initiation of treatment.
Danish: Når trametinib gives i kombination med dabrafenib, skal produktresuméet for dabrafenib kontrolleres, inden behandlingen påbegyndes.
English: Retinal vein occlusion (RVO) and retinal pigment epithelial detachment (RPED) If patients report new visual disturbances such as diminished central vision, blurred vision, or loss of vision at any time while on trametinib therapy, a prompt ophthalmological assessment is recommended.
Danish: Retinal veneokklusion (RVO) og løsning af retinalt pigmentepitel (RPED) Hvis patienter rapporterer nye synsforstyrrelser som fx nedsat centralsyn, tågesyn eller synstab på noget tidspunkt under behandlingen med trametinib, anbefales der en omgående oftalmologisk undersøgelse.
English: In clinical trials, the median time to first occurrence of left ventricular dysfunction, cardiac failure and LVEF decrease was between 2 to 5 months.
Danish: I kliniske studier var mediantiden til første forekomst af venstre ventrikel dysfunktion, hjertesvigt eller reduktion af LVEF mellem 2 og 5 måneder.
English: The safety of trametinib in combination with dabrafenib has been evaluated in the integrated safety population of 1,076 patients with BRAF V600 mutant unresectable or metastatic melanoma, Stage III BRAF V600 mutant melanoma following complete resection (adjuvant treatment) and advanced NSCLC treated with trametinib 2 mg once daily and dabrafenib 150 mg twice daily.
Danish: Sikkerheden af trametinib i kombination med dabrafenib er blevet evalueret i den integrerede sikkerhedspopulation på 1.076 patienter med BRAF V600-muteret, inoperabelt eller metastatisk melanom, stadie III BRAF V600-muteret melanom efter komplet resektion (adjuverende behandling) og fremskreden NSCLC, der blev behandlet med 2 mg trametinib en gang dagligt og dabrafenib 150 mg to gange dagligt.
English: • Skin rash with pus-filled blisters (see also “Changes in your skin” earlier in section 4)
Danish: • hududslæt med pusfyldte blærer (se også “Forandringer i huden” tidligere i punkt 4)
English: Rash has been observed in about 60% of patients in trametinib monotherapy studies and in about 24% of patients when trametinib is used in combination with dabrafenib (see section 4.8).
Danish: Der er observeret udslæt hos ca. 60 % af patienterne i studier med trametinib-monoterapi og hos ca. 24 % af patienterne når trametinib anvendes i kombination med dabrafenib (se pkt.
English: Trametinib must be permanently discontinued in patients diagnosed with treatment-related ILD or pneumonitis.
Danish: Trametinib skal seponeres permanent hos patienter, der diagnosticeres med behandlingsrelateret ILD eller pneumonitis.
English: Malignant melanoma, metastatic malignant melanoma, and superficial spreading melanoma Stage III e Includes drug hypersensitivity f
Danish: Papillom, hudpapillom d Malignt melanom, metastatisk malignt melanom og melanom med overfladisk spredning stadie III
English: Cut-off dates
Danish: UDLØBSDATO
English: NA = Not applicable
Danish: NA = ikke relevant
English: Hypertension Haemorrhage b
Danish: Hypertension Blødning b
English: CYP3A4 oxidation is considered a minor pathway of metabolism.
Danish: Trametinib synes kun i mindre grad at blive metaboliseret ved oxidation via CYP3A4.
English: What Mekinist contains
Danish: Mekinist indeholder:
English: Mekinist 0.5 mg film-coated tablets EU/1/14/931/001
Danish: Mekinist 0,5 mg filmovertrukne tabletter EU/1/14/931/001
English: Overall confirmed response n (%) (95% CI)
Danish: Samlet bekræftet respons n (%) (95 % CI)
English: Do not stop unless your doctor advises you to.
Danish: Hold ikke op med at tage Mekinist, medmindre lægen foreskriver det.
English: • A hole (perforation) in the stomach or intestines
Danish: • et hul i maven eller tarmene
English: • Infection of the skin (cellulitis)
Danish: • hudinfektion (cellulitis)
English: • dark-coloured urine
Danish: • mørk urin
English: Pyrexia has been reported in clinical trials with trametinib as monotherapy and in combination with dabrafenib; however, the incidence and severity of pyrexia are increased with the combination therapy.
Danish: Der er rapporteret pyreksi i kliniske studier med trametinib som monoterapi og i kombination med dabrafenib, og forekomsten og graden af pyreksi øges med kombinationsbehandlingen.
English: Pyrexia When trametinib is used in combination with dabrafenib and the patient's temperature is ≥38.5
Danish: 4.2) vedrørende justering af dabrafenib-dosis, når trametinib anvendes i kombination med dabrafenib, og patientens temperatur er ≥ 38,5
English: There are limited data in patients taking the combination of trametinib with dabrafenib who have progressed on a prior BRAF inhibitor.
Danish: Der foreligger begrænsede data om patienter, som tager kombinationen af trametinib og dabrafenib, og som havde progredieret på en tidligere behandling med BRAF-hæmmer.
English: Tell your doctor or nurse as soon as possible if you get any of these symptoms for the first time or if they get worse.
Danish: Fortæl det hurtigst muligt til lægen eller sundhedspersonalet, hvis du får nogen af disse symptomer for første gang, eller hvis de bliver værre.
English: Serious skin reactions have been reported in people taking Mekinist in combination with dabrafenib.
Danish: Der er rapporteret tilfælde af alvorlige hudreaktioner hos personer, der tog Mekinist i kombination med dabrafenib.
English: The 5-year overall survival rate was 46% (95% CI: 38.8, 52.0) in the combination arm versus 28% (95% CI: 22.5, 34.6) in the vemurafenib monotherapy arm for patients who had a normal lactate dehydrogenase level at baseline, and 16% (95% CI: 9.3, 23.3) in the combination arm versus 10% (95% CI: 5.1, 17.4) in the vemurafenib monotherapy arm for patients with an elevated lactate dehydrogenase level at baseline.
Danish: 5 års samlet overlevelsesrate var 46% (95% CI: 38,8; 52,0) i kombinationsarmen versus 28% (95% CI: 22,5; 34,6) i vemurafenib monoterapiarmen, for patienter der havde normal laktatdehydrogenaseniveau ved baseline, og 16% (95% CI: 9,3; 23,3) i kombinationsarmen versus 10% (95% CI: 5,1; 17,4) i vemurafenib monoterapiarmen, for patienter med forhøjet laktatdehydrogenaseniveau ved baseline.
English: The recommended dose of dabrafenib, when used in combination with Mekinist, is 150 mg twice daily.
Danish: Den anbefalede dosis af dabrafenib, når det anvendes i kombination med Mekinist, er 150 mg to gange dagligt.
English: RAS-mutation-positive non-cutaneous malignancies The benefits and risks must be considered before continuing treatment with dabrafenib in patients with a non-cutaneous malignancy that has a RAS mutation.
Danish: Fordele og ricisi skal evalueres inden behandling med dabrafenib fortsættes hos patienter med en ikke-kutan malignitet, som har en RAS-mutation.
English: Yellow, modified oval, biconvex, film-coated tablets, approximately 4.8 x 8.9 mm, with “GS” debossed on one face and “TFC” on the opposing face.
Danish: Gule, bikonvekse, filmovertrukne tabletter med modificeret oval form, ca. 4,8 x 8,9 mm, påtrykt “GS” på den ene side og “TFC” på den anden side.
English: The combination of trametinib with dabrafenib has shown anti-tumour activity in BRAF V600 mutation positive melanoma cell lines in vitro and delays the emergence of resistance in vivo in BRAF V600 mutation positive melanoma xenografts.
Danish: Kombinationen af trametinib og dabrafenib har vist anti-tumoraktivitet i BRAF V600-mutationspositive melanomcellelinjer in vitro og forsinker udvikling af resistens in vivo i xenografter med BRAF V600-mutationspositive melanomer.
English: Folliculitis Paronychia Cellulitis Rash pustular
Danish: Folliculitis Paronykie Cellulitis Pustuløst udslæt
English: Figure 2 Kaplan-Meier curves Updated OS analysis for Study MEK116513
Danish: Figur 2 Kaplan-Meier-kurver for opdateret analyse af samlet overlevelse i studiet MEK116513