FrancophonIA/ELRC3.0 huggingface dataset:
English: There are no clinical data in subjects with moderate to severe hepatic impairment and the potential need for dose adjustment cannot be determined (see section 5.2).
Danish: Der foreligger ingen kliniske data fra patienter med moderat til svært nedsat leverfunktion, og det kan derfor ikke afgøres, om dosisjustering eventuelt er nødvendig (se pkt.
English: • Immunosuppressants (e.g. cyclosporin, tacrolimus, sirolimus)
Danish: • Immunsupprimerende midler (fx ciclosporin, tacrolimus, sirolimus)
English: Co-administration of repeat dosing of trametinib 2 mg once daily and dabrafenib 150 mg twice daily resulted in no clinically meaningful changes in trametinib or dabrafenib Cmax and AUC with increases of 16 and 23%, respectively, in dabrafenib Cmax and AUC.
Danish: Samtidig administration af gentagne doser trametinib 2 mg en gang daglig og dabrafenib 150 mg 2 gange dagligt medførte ikke klinisk relevante ændringer i Cmax og AUC for trametinib eller dabrafenib, med stigninger på henholdsvis 16 % og 23 % i dabrafenib-Cmax og -AUC.
English: Cardiovascular effects, including coronary arterial degeneration/necrosis and/or haemorrhage, cardiac atrioventricular valve hypertrophy/haemorrhage and atrial fibrovascular proliferation were seen in dogs (≥2 times clinical exposure based on AUC).
Danish: Hos hunde blev der set kardiovaskulære effekter, herunder koronararteriedegeneration/-nekrose og/eller blødning fra koronararterierne, hypertrofi af/blødning fra de atrioventrikulære hjerteklapper og fibrovaskulær proliferation i atrium (ved ≥ 2 gange den kliniske eksponering hos mennesker baseret på AUC).
English: • Take Tafinlar in combination with trametinib exactly as your doctor, nurse or pharmacist tells you.
Danish: • Tag Tafinlar i kombination med trametinib nøjagtigt efter lægens, sundhedspersonalets eller apotekspersonalets anvisning.
English: Trametinib is not recommended if you have ever had a blockage of the vein draining the eye (retinal vein occlusion).
Danish: Trametinib anbefales ikke, hvis du har eller har haft en blokering af den vene, der fører blodet væk fra øjet (retinal veneokklusion).
English: Hazard ratio (95% CI) p-value
Danish: Hazard ratio (95% CI) p-værdi
English: The efficacy and safety of dabrafenib in combination with trametinib were studied in a Phase III, multicentre, randomised, double-blind, placebo-controlled study in patients with Stage III (Stage IIIA [lymph node metastasis >1 mm], IIIB, or IIIC) cutaneous melanoma with a BRAF V600 E/K mutation, following complete resection.
Danish: Effekten og sikkerheden af dabrafenib i kombination med trametinib blev undersøgt i et randomiseret, dobbeltblindet, placebo-kontrolleret, fase III multicenter-studie hos patienter med stadie III (stadie IIIA [metastaser i lymfeknuderne > 1 mm], IIIB eller IIIC) kutant melanom med en BRAF V600 E/K-mutation efter komplet resektion.
English: There are no clinical data in subjects with severe renal impairment and the potential need for dose adjustment cannot be determined (see section 5.2).
Danish: Der foreligger ingen kliniske data fra patienter med svært nedsat nyrefunktion, og det kan derfor ikke afgøres, om dosisjustering eventuelt er nødvendig (se pkt.
English: Cohort D N=17
Danish: Kohorte D N=17
English: • some antibiotics, such as clarithromycin, doxycyline and telithromycin
Danish: • visse antibiotika, fx clarithromycin, doxycyklin og telithromycin
English: The safety profile from MEK116513 is generally similar to that of MEK115306 with the following exceptions: 1) The following adverse reactions have a higher frequency category as compared to MEK115306: muscle spasm (very common); renal failure and lymphoedema (common); acute renal failure (uncommon); 2) The following adverse reactions have occurred in MEK116513 but not in MEK115306: cardiac failure, left ventricular dysfunction, interstitial lung disease (uncommon).
Danish: Forhøjet kreatinkinase i blodet a Sikkerhedsprofilen fra MEK116513 svarer generelt til den for MEK115306 med følgende undtagelser: 1) Følgende bivirkninger har en højere frekvenskategori sammenlignet med MEK115306: Muskelspasmer (meget almindelig), nyresvigt og lymfødem (almindelig), akut nyresvigt (ikke almindelig).
English: Tell your doctor as soon as possible if you have severe abdominal pain.
Danish: Fortæl det straks til lægen, hvis du får kraftige mavesmerter.
English: Fever has been reported in clinical trials with dabrafenib as monotherapy and in combination with trametinib; the incidence and severity of pyrexia are increased with the combination therapy (see section 4.4).
Danish: Der er rapporteret pyreksi i kliniske studier med dabrafenib som monoterapi og i kombination med trametinib; forekomsten og graden af pyreksi øges ved kombinationsbehandling (se pkt.
English: Dabrafenib dose Used as monotherapy or in combination with trametinib
Danish: Dabrafenib-dosis Anvendt som monoterapi eller i kombination med trametinib
English: OS analysis (data cut-off: 12-Jan-2015)
Danish: OS analyse (skæringsdato for dataindsamling: 12-jan-2015)
English: • HIV antivirals (e.g. amprenavir, atazanavir, darunavir, delavirdine, efavirenz, fosamprenavir,
Danish: • Antivirale midler mod hiv (fx amprenavir, atazanavir, darunavir, delvirdin, efavirenz,
English: RPED and RVO may occur with dabrafenib in combination with trametinib.
Danish: RPED og RVO kan opstå ved behandling med dabrafenib i kombination med trametinib.
English: Duration of intracranial response, median, months (95% CI)
Danish: Varighed af intrakranialt respons, median, måneder (95 % CI)
English: Dabrafenib should be used with caution in patients with moderate or severe hepatic impairment when administered as monotherapy or in combination with trametinib.
Danish: Dabrafenib bør anvendes med forsigtighed hos patienter med moderat eller svært nedsat leverfunktion, når det administreres som monoterapi eller i kombination med trametinib.
English: • some medicines to treat HIV, such as ritonavir, amprenavir, indinavir, darunavir, delavirdine,
Danish: • visse lægemidler til behandling af hiv, fx ritonavir, amprenavir, indinavir, darunavir,
English: The safety and efficacy of the combination of dabrafenib and trametinib have been evaluated in a multi-cohort, open-label, Phase II study in patients with BRAF V600 mutant melanoma with brain metastases.
Danish: Sikkerheden og effekten af kombinationen dabrafenib og trametinib er blevet evalueret i et åbent, multikohorte fase II-studie hos patienter med BRAF V600-mutationspositivt melanom med hjernemetastaser.
English: • Anticancer agents (e.g. cabazitaxel)
Danish: • Lægemidler mod cancer (fx cabazitaxel)
English: Hepatic metabolism and biliary secretion are the primary routes of elimination of dabrafenib and its metabolites and patients with moderate to severe hepatic impairment may have increased exposure.
Danish: Dabrafenib og dets metabolitter elimineres primært via hepatisk metabolisering og biliær udskillelse, og patienter med moderat til svært nedsat leverfunktion kan være udsat for højere eksponering.
English: Figure 1 Kaplan-Meier overall survival curves for Study MEK115306 (ITT population)
Danish: Figur 1 Kaplan-Meier-kurver over samlet overlevelse i studiet MEK115306 (ITT-population)
English: OS analysis data cut-off: 13-Mar-2015)
Danish: OS analyse (skæringsdato for dataindsamling: 13-mar-2015)
English: Cases of pneumonitis or ILD have been reported in clinical trials with dabrafenib in combination with trametinib.
Danish: Tilfælde med pneumonitis eller ILD er rapporteret i kliniske studier med dabrafenib i kombination med trametinib.
English: The safety of dabrafenib monotherapy is based on the integrated safety population from five clinical trials, BRF113683 (BREAK-3), BRF113929 (BREAK-MB), BRF113710 (BREAK-2), BRF113220, and BRF112680, which included 578 patients with BRAF V600 mutant unresectable or metastatic melanoma treated with dabrafenib 150 mg twice daily.
Danish: Sikkerheden af dabrafenib-monoterapi er baseret på den integrerede sikkerhedspopulation fra fem kliniske forsøg, BRF113683 (BREAK-3), BRF113929 (BREAK-MB), BRF113710 (BREAK-2), BRF113220 og BRF112680, som omfattede 578 patienter med BRAF V600-muteret, inoperabelt eller metastatisk melanom, der fik dabrafenib 150 mg to gange dagligt.
English: Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.
Danish: Undgå samtidig administration af dabrafenib og kraftige induktorer af CYP2C8 eller CYP3A4 (fx rifampicin, phenytoin, carbamazepin, phenobarbital eller perikon (Hypericum perforatum)).
English: Colitis and gastrointestinal perforation, including fatal outcome, have been reported in patients taking dabrafenib in combination with trametinib (see section 4.8).
Danish: Colitis og gastrointestinal perforation, inklusive med fatalt udfald, har været rapporteret hos patienter, der tog dabrafenib i kombination med trametinib (se pkt.
English: • new wart
Danish: • en ny vorte
English: Patients with brain metastases (results from the Phase II study (BREAK-MB) BREAK-MB was a multicentre, open-label, two-cohort, Phase II study designed to evaluate the intracranial response of dabrafenib in subjects with histologically confirmed (Stage IV) BRAF-mutation positive (V600E or V600K) melanoma metastatic to the brain.
Danish: Patienter med hjernemetastaser (resultater fra fase II-studiet (BREAK-MB)) BREAK-MB var et ublindet fase II multicenterstudie med to kohorter, som var designet til vurdering af den intrakranielle respons på dabrafenib hos patienter med histologisk bekræftet BRAF-mutationspositivt (V600E eller V600K) melanom (stadium IV), som var metastaseret til hjernen.
English: The efficacy and safety of dabrafenib in combination with trametinib in patients with BRAF mutant-positive melanoma that has metastasised to the brain was studied in a non-randomised, open-label, multicentre, Phase II study (COMBI-MB study).
Danish: Patienter med hjernemetastaser Effekten og sikkerheden af dabrafenib i kombination med trametinib hos patienter med BRAF mutationspositivt melanom med hjernemetastaser blev undersøgt i et ikke-randomiseret, åbent, multicenter fase II-studie (COMBI-MB-studiet).
English: Patients should be closely monitored when re-starting dabrafenib after an episode of pancreatitis (see section 4.4).
Danish: Patienterne skal monitores tæt, når behandlingen med dabrafenib genoptages efter en episode med pancreatitis (se pkt.
English: Skin reactions (rash) can happen while taking Tafinlar in combination with trametinib.
Danish: Hudreaktioner (udslæt) kan opstå, når Tafinlar tages i kombination med trametinib.
English: Cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with dabrafenib/trametinib combination therapy.
Danish: Under dabrafenib/trametinib kombinationsbehandling er der blevet rapporteret tilfælde af svære kutane bivirkninger (SCARs), herunder Stevens-Johnsons syndrom og lægemiddelreaktion med eosinofili og systemiske symptomer (DRESS), der kan være livstruende eller dødelige.
English: Take the doses of Tafinlar and trametinib exactly as your doctor, nurse or pharmacist tells you.
Danish: Tag doserne af Tafinlar og trametinib nøjagtigt efter lægens, sundhedspersonalets eller apotekspersonalets anvisning.
English: Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Danish: Inden for hver hyppighedsgruppe er bivirkningerne opstillet efter, hvor alvorlige de er, med den alvorligste bivirkning anført først.
English: Dabrafenib related material is excreted primarily in faeces, with 71% of an oral dose recovered in faeces; 23% of the dose was recovered in urine in the form of metabolites only.
Danish: Dabrafenibrelaterede metabolitter udskilles primært i fæces, hvor 71 % af en oral dosis genfindes i fæces.
English: When dabrafenib is given in combination with trametinib, the SmPC of trametinib must be consulted prior to intiation of combination treatment.
Danish: Når dabrafenib gives i kombination med trametinib, skal produktresuméet for trametinib kontrolleres, inden behandlingen påbegyndes.
English: b This study was designed to support or reject the null hypothesis of OIRR ≤10% (based on historical results) in favour of the alternative hypothesis of OIRR ≥ 30% in BRAF V600E mutation positive subjects.
Danish: b Dette studie var designet til at underbygge eller forkaste nul-hypotesen om OIRR ≤ 10 %
English: The efficacy and safety of dabrafenib have not been established in patients with wild-type BRAF melanoma or wild-type BRAF NSCLC therefore dabrafenib should not be used in patients with wild-type BRAF melanoma or wild-type BRAF NSCLC (see sections 4.2 and 5.1).
Danish: Dabrafenibs sikkerhed og virkning er ikke klarlagt hos patienter med vildtype BRAF-melanom eller vildtype BRAF-NSCLC, og derfor bør dabrafenib ikke anvendes til patienter med vildtype BRAF-melanom eller vildtype BRAF-NSCLC (se pkt.
English: Co-administration of repeat doses of dabrafenib 150 mg twice daily and the pH-elevating agent rabeprazole 40 mg once daily resulted in a 3% increase in AUC and a 12% decrease in dabrafenib Cmax.
Danish: Samtidig administration af gentagne doser af dabrafenib 150 mg to gange daglig og det pH-forhøjende stof rabeprazol 40 mg én gang daglig medførte 3 % stigning i AUC og 12 % fald af dabrafenib Cmax.
English: (actinic keratosis), chapping or cracking of the skin
Danish: (aktinisk keratose), sprukken eller revnet hud
English: Upon discontinuation of dabrafenib offset of induction is gradual, concentrations of sensitive CYP3A4, CYP2B6, CYP2C8, CYP2C9 and CYP2C19, UDP glucuronosyl transferase (UGT) and transporter substrates (e.g. Pgp or MRP-2) may increase and patients should be monitored for toxicity and dose of these agents may need to be adjusted.
Danish: Efter seponering af dabrafenib aftager induktionen gradvist, og koncentrationerne af følsomt CYP3A4, CYP2B6, CYP2C8, CYP2C9 og CYP2C19 samt UDP-glukuronosyltransferase (UGT) og transportørsubstrater (fx Pgp eller MRP-2) kan stige.
English: Patients taking Tafinlar may commonly (may affect up to 1 in 10 people) develop a different type of skin cancer called cutaneous squamous cell carcinoma (cuSCC).
Danish: Patienter, der tager Tafinlar, kan udvikle en anden form for hudkræft, som kaldes kutant planocellulært karcinom (cuSCC).
English: Cohort A N=74
Danish: Kohorte A N = 74
English: • some medicines that reduce cholesterol levels, such as atorvastatin and simvastatin
Danish: • visse kolesterolsænkende lægemidler, fx atorvastatin og simvastatin
English: Study MEK116513 was a 2-arm, randomised, open-label, Phase III study comparing dabrafenib and trametinib combination therapy with vemurafenib monotherapy in BRAF V600 mutation-positive unresectable or metastatic melanoma.
Danish: Studiet MEK116513 var et 2-armet, randomiseret, åbent fase III-studie, der sammenlignede kombinationsbehandling med dabrafenib og trametinib med vemurafenib-monoterapi ved BRAF V600-mutationspositivt inoperabelt eller metastatisk melanom.
English: Patients with serious non-infectious febrile events responded well to dose interruption and/or dose reduction and supportive care (see sections 4.2 and 4.4).
Danish: Patienter, der oplevede alvorlige tilfælde af ikke-infektiøs feber, responderede godt på pausering af behandlingen og/eller dosisreduktion og understøttende behandling (se pkt.
English: Elevations in blood pressure have been reported in association with dabrafenib in combination with trametinib, in patients with or without pre-existing hypertension (see section 4.8).
Danish: Der er rapporteret forhøjelse af blodtrykket i forbindelse med dabrafenib i kombination med trametinib hos patienter med eller uden allerede eksisterende hypertension (se pkt.
English: Rash has been observed in about 24% of patients in clinical trials when dabrafenib is used in combination with trametinib (see section 4.8).
Danish: Der er observeret udslæt hos ca. 24 % af patienterne i kliniske forsøg, når dabrafenib anvendes i kombination med trametinib (se pkt.
English: In 1% of patients in clinical trials with dabrafenib monotherapy, serious non-infectious febrile events were identified defined as fever accompanied by severe rigors, dehydration, hypotension and/or acute renal insufficiency of pre-renal origin in subjects with normal baseline renal function (see section 4.8).
Danish: Hos 1 % af patienterne i kliniske studier med dabrafenib som monoterapi blev der identificeret alvorlige tilfælde af ikke-infektiøs feber, defineret som feber ledsaget af svære kulderystelser, dehydrering, hypotension og/eller akut nyreinsufficiens af prærenal oprindelse hos patienter med normal nyrefunktion ved baseline (se pkt.
English: RAS-mutation-positive non-cutaneous malignancies The benefits and risks should 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: Primary analysis (data cut-off: 26-Aug-2013)
Danish: Primær analyse (skæringsdato for dataindsamling: 26-aug
English: If patients develop symptoms of pulmonary embolism or deep vein thrombosis such as shortness of breath, chest pain, or arm or leg swelling, they should immediately seek medical care.
Danish: Patienterne skal oplyses om straks at søge læge, hvis de udvikler symptomer på lungeemboli eller dyb venetrombrose såsom åndenød, brystsmerter eller hævede arme eller ben.
English: Administration of gemfibrozil (a CYP2C8 inhibitor) 600 mg twice daily, with dabrafenib 75 mg twice daily, resulted in a 47% increase in dabrafenib AUC but did not alter dabrafenib Cmax relative to administration of dabrafenib 75 mg twice daily alone.
Danish: Administration af gemfibrozil (en CYP2C8-hæmmer) 600 mg to gange daglig og dabrafenib 75 mg to gange daglig resulterede i en stigning på 47 % i dabrafenib-AUC, men ændrede ikke dabrafenib-Cmax i forhold til administration af dabrafenib 75 mg to gange daglig alene.
English: Hypotension Lymphoedema
Danish: Hypotension Lymfødem
English: • Antiepileptic (e.g. carbamazepine, phenytoin, primidone, valproic acid)
Danish: • Antiepileptika (fx carbamazepin, phenytoin, primidon, valproat)
English: Administration of rifampin (a CYP3A4/CYP2C8 inducer) 600 mg once daily with dabrafenib 150 mg twice daily resulted in a decrease in repeat dose dabrafenib Cmax (27%) and AUC (34%).
Danish: Administration af rifampicin (en CYP3A4/CYP2C8-induktor) 600 mg én gang daglig sammen med dabrafenib 150 mg to gange daglig resulterede i et fald af Cmax (27 %) og AUC (34 %) for dabrafenib ved gentagne doser.
English: Arthralgia was reported very commonly in the integrated safety population of dabrafenib monotherapy (25%) and dabrafenib in combination with trametinib (25%) although these were mainly Grade 1 and 2 in severity with Grade 3 occurring uncommonly (<1%) and no Grade 4 occurrences being reported.
Danish: Artralgi blev rapporteret med frekvensen ”meget almindelig” i den integrerede sikkerhedspopulation med dabrafenib som monoterapi (25 %) og dabrafenib i kombination med trametinib (25 %) og var hovedsageligt af sværhedsgrad 1 og 2.
English: • Skin tags
Danish: • stilkevorter (skin tags)
English: Granulomatous nephritis has been reported (see section 4.8).
Danish: Der er set tilfælde af granulomatøs nefritis (se pkt.
English: Non-cutaneous malignancies
Danish: Ikke-kutan malignitet
English: Heart disorder
Danish: Hjerteproblemer
English: • some medicines used for pain relief, such as fentanyl and methadone
Danish: • visse smertestillende lægemidler, fx fentanyl og methadon
English: Administration of ketoconazole (a CYP3A4 inhibitor) 400 mg once daily, with dabrafenib 75 mg twice daily, resulted in a 71% increase in dabrafenib AUC and a 33% increase in dabrafenib Cmax relative to administration of dabrafenib 75 mg twice daily alone.
Danish: Administration af ketoconazol (en CYP3A4-hæmmer) 400 mg en gang daglig sammen med dabrafenib 75 mg to gange daglig resulterede i en stigning på 71 % i dabrafenib-AUC og en stigning på 33 % i dabrafenib-Cmax i forhold til dabrafenib 75 mg to gange daglig administreret alene.
English: Overall survival, median, months (95% CI) Median, months
Danish: Median samlet overlevelse, måneder (95 % CI) Median, måneder
English: No dose adjustment is required for patients with mild or moderate renal impairment.
Danish: Dosisjustering er ikke nødvendig hos patienter med let til moderat nedsat nyrefunktion.
English: Cohort A N=76
Danish: Kohorte A N=76
English: Based on updated data with an additional 10 months of follow-up compared to the primary analysis (minimum follow-up of 40 months), the RFS benefit was maintained with an estimated HR of 0.49 [95% CI: (0.40, 0.59)] (Figure 4).
Danish: RFS-fordelen blev bibeholdt med en estimeret HR på 0,49 [95 % CI: (0,40; 0,59)], baseret på opdaterede data med yderligere 10 måneders opfølgning, sammenlignet med den primære analyse (minimum 40 måneders opfølgning) (figur 4).
English: Hypophosphataemia Hyperglycaemia
Danish: Hypofosfatæmi Hyperglykæmi
English: No dose modification of dabrafenib is required when taken in combination with trametinib for confirmed cases of RVO or RPED.
Danish: Justering af dabrafenib-dosis er ikke nødvendig, når det tages i kombination med trametinib ved bekræftede tilfælde af RVO eller RPED.
English: The most common adverse reactions (incidence 20%) for dabrafenib in combination with trametinib were: pyrexia, fatigue, nausea, chills, headache, diarrhoea, vomiting, arthralgia and rash.
Danish: De hyppigste bivirkninger (incidens ≥ 20 %) ved drabrafenib i kombination med trametinib var pyreksi, træthed, kvalme, kulderystelser, hovedpine, diarré, opkastning, artralgi og udslæt.
English: 1.5 mg once daily
Danish: 1,5 mg en gang daglig
English: Overall confirmed response n (%) (95% CI)
Danish: Samlet, bekræftet respons n (%) (95 % CI)
English: MEK115306 was a Phase III, randomised, double-blinded study comparing the combination of dabrafenib and trametinib to dabrafenib and placebo in first-line therapy for subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.
Danish: MEK115306 var et randomiseret, dobbeltblindet fase III-studie, hvor kombinationen dabrafenib og trametinib blev sammenlignet med dabrafenib og placebo som førstelinjebehandling hos forsøgsdeltagere med inoperabelt (stadie IIIC) eller metastatisk (stadie IV) BRAF V600E-/K-mutationspositivt kutant melanom.
English: • Thickening of the outer layers of the skin
Danish: • fortykkelse af hudens yderste lag
English: Cutaneous squamous cell carcinoma b
Danish: Kutant planocellulært karcinom b
English: Dabrafenib should be used with caution in patients with severe renal impairment when administered as monotherapy or in combination with trametinib.
Danish: Dabrafenib bør anvendes med forsigtighed hos patienter med svært nedsat nyrefunktion, når det administreres som monoterapi eller i kombination med trametinib.
English: Erythema, generalised erythema i Muscle spasms, musculoskeletal stiffness
Danish: Muskelspasmer, muskuloskeletal stivhed
English: Patients should be made aware of the potential for fatigue and eye problems to affect these activities.
Danish: Patienterne bør gøres opmærksom på, at de mulige bivirkninger med træthed og øjenproblemer kan påvirke evnen til at føre motorkøretøj og betjene maskiner.
English: Sixty percent of patients were male and 99.6% were Caucasian; the median age was 52 years with 21% of patients being ≥65 years, 98.4% had ECOG status of 0 or 1, and 97% of patients had metastatic disease.
Danish: 98,4 % havde en ECOG-status på 0 eller 1, og 97 % af patienterne havde metastatisk sygdom.