FrancophonIA/ELRC3.0 huggingface dataset:
English: Dose limiting toxicities included skin ulcerations, surface exudates, and acanthosis in the rat and chronic active inflammation and degeneration of the oesophagus associated with varying degrees of gastroenteropathy in dogs.
Danish: Dosisbegrænsende toksicitet inkluderede hudlæsioner, overfladeeksudat og akantose hos rotter samt kronisk aktiv inflammation og degeneration af øsofagus med varierende grader af gastroenteropati hos hunde.
English: In juvenile rats, cobimetinib administration resulted in similar changes as seen in the pivotal toxicity studies in adults, including reversible degenerative changes in the thymus and liver, decreased spleen and thyroid/parathyroid weights, increased phosphorus, bilirubin and red blood cell mass and decreased triglycerides.
Danish: Administration af cobimetinib har hos unge rotter resulteret i forandringer svarende til dem, der i de pivotale studier er set hos voksne rotter, inklusive reversible degenerative forandringer i thymus og lever, nedsat vægt af milt og thyroidea/parathyroidea, stigninger i fosfor, bilirubin og antal røde blodlegemer samt fald i triglycerider.
English: In case of suspected overdose, cobimetinib should be withheld and supportive care instituted.
Danish: Hvis der er mistanke om overdosering, skal behandling med cobimetinib afbrydes og understøttende behandling indledes.
English: No dose modification of Cotellic is required when taken in combination with vemurafenib.
Danish: Det er ikke nødvendigt at ændre Cotellic-dosis, når det tages samtidig med vemurafenib.
English: Secondary efficacy endpoints included overall survival (OS), objective response rate, duration of response (DoR) as assessed by INV and PFS as assessed by an independent review facility (IRF).
Danish: Sekundære effektendepunkter inkluderede samlet overlevelse, objektiv responsrate, responsvarighed vurderet af investigator samt progressionsfri overlevelse vurderet af et uafhængigt panel.
English: What Cotellic looks like and contents of the pack Cotellic film-coated tablets are white, round with “COB” debossed on one side.
Danish: Cotellic filmovertrukne tabletter er hvide og runde med “COB” præget på den ene side.
English: * Please refer to the paragraph Haemorrhage in the “Description of selected adverse reactions” section ** Please refer to the paragraph Cutaneous squamous cell carcinoma, keratoacanthoma and hyperkeratosis in the “Description of selected adverse reactions” section.
Danish: Se afsnittet Blødninger under ”Beskrivelse af udvalgte bivirkninger” **Se afsnittet Kutant pladecellekarcinom, keratoakantom og hyperkeratose under ”Beskrivelse af udvalgte bivirkninger” *** Se afsnittet Rabdomyolyse under ”Beskrivelse af udvalgte bivirkninger”
English: The median PFS for patients who had progressed on vemurafenib was 2.8 months, with median follow-up time of 8.1 months.
Danish: Medianen for progressionsfri overlevelse for patienter med progression under vemurafenib-behandling var 2,8 måneder, med median opfølgning på 8,1 måneder.
English: Cotellic treatment and vemurafenib treatment should be discontinued if liver laboratory abnormalities do not resolve to Grade ≤1 within 4 weeks or if Grade 4 liver laboratory abnormalities recur after initial improvement.
Danish: Cotellic og vemurafenib seponeres, hvis de abnorme leverværdier ikke reduceres til grad ≤ 1 inden for 4 uger, eller hvis grad 4 leverpåvirkning optræder igen efter initial forbedring.
English: Cotellic can cause eye problems (see also “Eye (vision) problems” in Section 4).
Danish: Cotellic kan forårsage problemer med øjnene (Se også ”Problemer med øjnene (synet)” i afsnit 4).
English: Significant improvement in the primary endpoint, investigator-assessed PFS, was observed in patients assigned to the Cotellic plus vemurafenib arm compared to the placebo plus vemurafenib arm (HR 0.51 (0.39; 0.68); p-value < 0.0001).
Danish: Signifikant forbedring i det primære endepunkt, progressionsfri overlevelse vurderet af investigator, blev observeret hos patienter i Cotellic-plus-vemurafenib-armen sammenlignet med placebo-plusvermurafenib-armen (hazard ratio: 0,51 (0,39; 0,68); p <0,0001).
English: When cobimetinib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.
Danish: Hvis cobimetinb administreres samtidig med moderate CYP3A-hæmmere, skal patienterne overvåges omhyggeligt med hensyn til sikkerhed.
English: < 10% absolute decrease from baseline
Danish: < 10% absolut fald fra baseline
English: Grade 4: Cotellic treatment should be interrupted.
Danish: Grad 4: Cotellic-behandling skal afbrydes.
English: Table 1 Recommended Cotellic dose modifications
Danish: Tabel 1 Anbefalede dosisændringer for Cotellic
English: Symptoms may include: · feeling dizzy · feeling light-headed · feeling short of breath · feeling tired · feeling like your heart is pounding, racing or beating unevenly · swelling in the legs.
Danish: Symptomerne kan være: · svimmelhed · ør i hovedet · stakåndethed · træthed · følelse af, at hjertet banker hårdere, hurtigere eller uregelmæssigt · hævede ben
English: Please also refer to the Package Leaflet for vemurafenib, which is used in combination with Cotellic.
Danish: Læs også indlægssedlen for vemurafenib, som du tager sammen med Cotellic.
English: Depending on the area of the bleeding, symptoms may include: · headaches, dizziness, or weakness · vomiting blood · abdominal pain · red or black coloured stools.
Danish: Afhængig af hvorhenne blødningen opstår, kan symptomer inkludere: · hovedpine, svimmelhed eller svaghed · opkastning af blod · mavesmerter · rød eller sortfarvet afføring
English: Median (months) (95 % CI)
Danish: Median (måneder) (95 % konfidensinterval)
English: Tell your doctor straight away if it feels like your heart is pounding, racing or beating unevenly, or if you experience dizziness, lightheadedness, shortness of breath, tiredness, or swelling in the legs.
Danish: Du skal straks kontakte lægen, hvis du føler, at dit hjerte slår hårdere, hurtigere eller uregelmæssigt, eller hvis du oplever svimmelhed, stakåndethed, træthed eller hævede ben.
English: Studies in animals have shown embryolethality and foetal malformations of the great vessels and skull (see section 5.3).
Danish: Dyrestudier har vist embryoletalitet og føtale misdannelser i store kar og kranie (se pkt.
English: In the preclinical models, the combination of cobimetinib and vemurafenib showed that by simultaneously targeting mutated BRAF V600 proteins and MEK proteins in melanoma cells, the combination of the two products inhibits MAPK pathway reactivation through MEK1/2, resulting in a stronger inhibition of intracellular signalling and decreased tumour cell proliferation
Danish: Det er i prækliniske modeller med kombination af cobimetinib og vemurafenib vist, at ved at angribe de muterede BRAF-V600-proteiner og MEK-proteinerne i melanomcellerne samtidigt hæmmer kombinationen af de to præparater MAPK-signalvejsreaktiveringen gennem MEK1/2.
English: The objective response rate (ORR) in the Cotellic plus vemurafenib arm was 67.6% vs 44.8% in the placebo plus vemurafenib arm.
Danish: Den objektive responsrate i Cotellic-plus-vemurafenib-armen var 67,6% versus 44,8% i placebo-plus-vemurafentib-armen.
English: In patients who were naive to BRAF inhibitor therapy, the median overall survival was 28.5 months (95% CI 23.3-34.6).
Danish: Hos patienter, der ikke tidligere havde fået BRAF-hæmmer, var den mediane samlede overlevelse 28,5 måneder (95% konfidensinterval 23,2 ; 34,6).
English: The median estimate for independent review of PFS was 11.3 months for the Cotellic plus vemurafenib arm vs. 6.0 months for the placebo plus vemurafenib arm (HR 0.60 (0.45; 0.79); p-value = 0.0003).
Danish: Det mediane estimat for progressionsfri overlevelse vurderet af en uafhængig komité var 11,3 måneder for Cotellic-plus-vemurafenib-armen versus 6,0 måneder for placebo-plus-vemurafenib-armen (hazard ratio 0,60 (0,45; 0,79); p = 0,0003).
English: The median estimate for investigator-assessed PFS was 9.9 months for the Cotellic plus vemurafenib arm vs. 6.2 months for the placebo plus vemurafenib arm.
Danish: Det mediane estimat for progressionsfri overlevelse vurderet af investigator var 9,9 måneder for Cotellic-plus-vemurafenib-armen versus 6,2 måneder for placebo-plus-vemurafenib-armen.
English: For Grade ≥3 diarrhoea that occurs despite supportive care, Cotellic and vemurafenib should be withheld until diarrhoea has improved to Grade ≤1.
Danish: Hvis grad ≥3 diarré forekommer trods understøttende behandling, skal behandling med Cotellic og vemurafenib afbrydes, indtil diarréen er forbedret til grad ≤1.
English: Pyrexia, Chills
Danish: Pyreksi, kuldegysninger
English: · Muscle problems
Danish: · Muskelproblemer
English: Results of the BRAFi naïve population from Study NO25395 were generally consistent with those from Study GO28141.
Danish: Resultaterne i studie NO25395 fra populationen, der ikke tidligere havde fået BRAF-hæmmer, var generelt i overensstemmelse med resultaterne fra studie GO28141.
English: Tell your doctor, pharmacist or nurse if you notice any of the following side effects: Very common (may affect more than 1 in 10 people) · increased skin sensitivity to sunlight · skin rash · feeling sick (nausea) · fever · chills · increased liver enzymes (shown in blood tests) · abnormal blood test results related to creatine phosphokinase, an enzyme found mainly in heart, brain and skeletal muscle · vomiting · skin rash with a flat discoloured area or raised bump like acne · high blood pressure · anaemia (a low level of red blood cells) · bleeding · abnormal thickening of the skin.
Danish: Meget almindelige (kan optræde hos flere end 1 ud af 10 patienter) · huden bliver mere følsom for sol · udslæt · kvalme · feber · kuldegysninger · forhøjede lever-enzymer (ses ved blodprøve) · unormale blodprøveresultater for kreatinkinase, som er et enzym, som hovedsageligt findes i hjertet, hjernen og skeletmuskulaturen · opkastning · udslæt med flade misfarvede pletter eller udslæt, der kan ligne bumser som akne · forhøjet blodtryk · anæmi (lavt antal røde blodlegemer) · blødning · unormal fortykkelse af huden
English: Symptoms of serous retinopathy include: · blurred vision · distorted vision · partly missing vision · any other changes to your sight.
Danish: Symptomer af serøs retinopati kan være: · sløret syn · forvrænget syn · indskrænket synsfelt · andre ændringer i synet
English: Women of childbearing potential should be advised to use two effective contraceptive methods, such as a condom or other barrier method (with spermicide, if available) during treatment with Cotellic and for at least three months following treatment discontinuation.
Danish: Fertile kvinder bør tilrådes brug af 2 sikre præventionsmetoder, såsom kondom eller andre barrieremetoder (med sæddræbende midler, hvis tilgængeligt) under behandling med Cotellic samt i mindst 3 måneder efter seponering.
English: Progression-free survival (PFS) as assessed by the investigator (INV) was the primary endpoint.
Danish: Det primære endepunkt var progressionsfri overlevelse vurderet af investigator.
English: Significant improvement in OS was observed in patients assigned to the Cotellic plus vemurafenib arm compared to the placebo plus vemurafenib arm (Figure 1).
Danish: Der var observeret signifikante forbedringer i den samlede overlevelse hos patienter i Cotellic plus vemurafenib-armen sammenlignet med placebo plus vemurafenib-armen (Figur 1).
English: The safety of Cotellic in combination with vemurafenib has also been evaluated in 129 patients with advanced BRAF V600 mutated melanoma in Study NO25395.
Danish: Sikkerheden af Cotellic i kombination med vemurafenib er også evalueret i studie NO25395 hos 129 patienter med fremskreden BRAF-V600-muteret melanom.
English: The median PFS for BRAFi-naïve patients was 13.8 months, with median follow-up time of 20.6 months.
Danish: Medianen for progressionsfri overlevelse for patienter, der ikke tidligere havde fået BRAF-hæmmer, var 13,8 måneder med en median opfølgningstid på 20,6 måneder.
English: Ejection fraction decreased, Blood bilirubin increased
Danish: Nedsat uddrivningsfraktion, forhøjet blod-bilirubin
English: Toxicity studies in rats and dogs identified generally reversible degenerative changes in the bone marrow, gastrointestinal tract, skin, thymus, adrenal gland, liver, spleen, lymph node, kidney, heart, ovary, and vagina at plasma exposures below clinical efficacious levels.
Danish: I toksicitetsstudier med rotter og hunde er der set generelt reversible, degenerative forandringer i knoglemarv, mave-tarmkanal, hud, thymus, binyrer, lever, milt, lymfeknuder, nyrer, hjerte, ovarier og vagina ved plasmaeksponering under det klinisk effektive niveau.
English: Recommended Cotellic daily dose
Danish: Anbefalet daglig dosis af Cotellic
English: Always take this medicine exactly as your doctor or pharmacist has told you.
Danish: Tag altid medicinen nøjagtig efter lægens eller apotekspersonalets anvisning.
English: Signs or symptoms of rhabdomyolysis warrant an appropriate clinical evaluation and treatment as indicated, along with Cotellic dose modification or discontinuation according to the severity of the adverse reaction (see section 4.2 and 4.4).
Danish: Symptomer på rabdomyolyse kræver en passende klinisk vurdering og behandling som angivet, sammen med Cotellic dosisjustering eller afbrydelse i henhold til sværhedsgraden af bivirkningen (se pkt.
English: What Cotellic is used for
Danish: Hvad bruges Cotellic til?
English: Grade ≤2 (tolerable) rash should be managed with supportive care.
Danish: Ved grad ≤ 2 (tolerabelt) udslæt gives understøttende behandling.
English: Major haemorrhagic events (including intracranial and gastrointestinal tract haemorrhage) were reported in the post-marketing setting.
Danish: Større blødninger (inklusiv intrakranial og gastrointestinale blødninger) blev rapporteret efter markedsføring.
English: In toxicology studies, degenerative changes were observed in reproductive tissues including increased apoptosis/necrosis of corpora lutea and seminal vesicle, epididymal and vaginal epithelial cells in rats, and epididymal epithelial cells in dogs.
Danish: I toksikologistudier er der observeret degenerative forandringer i reproduktive væv, inklusive øget apoptose/nekrose af corpus luteum og vesicula seminalis, epididymale og vaginale epitelceller hos rotter samt epididymale epitelceller hos hunde.
English: Grade ≤2 (tolerable) photosensitivity should be managed with supportive care.
Danish: Ved lysfølsomhedsreaktion grad ≤ 2 (tolerabel) bør der gives understøttende behandling.
English: For Grade 1 and 2 liver laboratory abnormalities, Cotellic and vemurafenib should be continued at the prescribed dose.
Danish: Ved abnorme leverværdier grad 1 og 2 fortsættes behandlingen med Cotellic og vemurafenib med den ordinerede dosis.
English: If serum CPK is elevated, check for signs and symptoms of rhabdomyolysis or other causes.
Danish: Hvis serum kreatinkinase er forhøjet, skal der undersøges for symptomer på rabdomyolyse eller andre årsager.
English: LVEF should be evaluated before initiation of treatment to establish baseline values, then after the first month of treatment and at least every 3 months or as clinically indicated until treatment discontinuation.
Danish: LVEF bør evalueres inden påbegyndelse af behandling med henblik på at fastlægge baseline-værdi, herefter efter 1 måneds behandling samt mindst hver 3. måned eller som klinisk indiceret, indtil behandlingen seponeres.
English: Tell your doctor straight away if you have any unusual bleeding or any of these symptoms: headaches, dizziness, feeling weak, blood in the stools or black stools and vomiting blood.
Danish: Du skal straks kontakte lægen, hvis du oplever enhver usædvanlig blødning eller nogle af disse symptomer: hovedpine, svimmelhed, følelse af svaghed, blod i afføringen eller sort afføring og opkastning af blod.
English: No evidence of phototoxicity was observed with Cotellic as a single agent.
Danish: Lysoverfølsomhed blev ikke observeret, når Cotellic er anvendt som enkeltstof.
English: Vemurafenib dosing should be reduced as clinically appropriate, please refer to its SmPC for further information.
Danish: Dosis af vemurafenib bør reduceres som klinisk hensigtsmæssigt, se produktresuméet for vemurafenib for yderligere information.
English: Cotellic in combination with vemurafenib in patients with brain metastases The safety and efficacy of the combination of Cotellic and vemurafenib have not been evaluated in patients with a BRAF V600 mutation-positive melanoma which has metastasised to the brain.
Danish: Cotellic i kombination med vemurafenib hos patienter med hjernemetastaser Sikkerhed og virkning af Cotellic i kombination med vemurafenib har ikke været undersøgt hos patienter med BRAF-V600-mutationspositivt melanom, som har hjernemetastaser.
English: The clinical relevance of these findings has not been investigated.
Danish: Den kliniske relevans af disse fund er ikke fastlagt.
English: Rare ≥ 1/10,000 to < 1/1,000
Danish: Sjælden ≥ 1/10.000 til < 1/1000
English: If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety.
Danish: Hvis samtidig administration af potente CYP3Ahæmmere ikke kan undgås, skal patienterne overvåges omhyggeligt med hensyn til sikkerhed.
English: Your doctor will discuss with you the benefits and risks of taking Cotellic, if you are breast-feeding.
Danish: Hvis du ammer, vil lægen snakke med dig om fordele og risici ved at tage Cotellic.
English: Serous retinopathya, Blurred vision
Danish: Serøs retinopatia, sløret syn
English: There are minimal data for Cotellic in patients with severe renal impairment.
Danish: Der er kun ganske få data vedrørende Cotellic til patienter med svært nedsat nyrefunktion.
English: Grade 3 and 4 CPK elevations, including asymptomatic elevations over baseline, also occurred in patients receiving Cotellic with vemurafenib in clinical trials (see section 4.8).
Danish: Grad 3 og 4 stigninger i kreatinkinase, som inkluderer asymptomatiske stigninger over baseline, forekom også hos patienter behandlet med Cotellic sammen med Vemurafenib i kliniske forsøg (se pkt.
English: The effects of Cotellic in people younger than 18 years old are not known.
Danish: Det vides ikke, hvordan Cotellic virker hos patienter, der er under 18 år gamle.
English: Asymptomatic increases in blood CPK levels were observed with a higher frequency in the Cotellic plus vemurafenib arm vs placebo plus vemurafenib arm in Study GO28141 (see section 4.2 and 4.4).
Danish: Asymptomatisk stigning i blod-kreatinkinase observeredes hyppigere i Cotellic-plus-vemurafenibarmen sammenlignet med placebo-plus-vemurafenib-armen i studie GO28141 (se pkt.
English: No dedicated fertility studies in animals have been performed with cobimetinib.
Danish: Der er ikke gennemført specifikke fertilitetsstudier med cobimetinib hos dyr.
English: The intracranial activity of cobimetinib is currently unknown (see sections 5.1 and 5.2).
Danish: Den intrakranielle virkning af cobimetinib er endnu ukendt (se pkt.
English: (or ≥ 10% absolute decrease from baseline)
Danish: (eller ≥10% absolut fald fra baseline)
English: 495 previously untreated patients with unresectable locally advanced or metastatic melanoma were randomised to receive either: · Placebo once daily on Days 1-21 of each 28-day treatment cycle and 960 mg vemurafenib twice daily on Days 1-28, or · Cotellic 60 mg once daily on Days 1-21 of each 28-day treatment cycle and 960 mg vemurafenib twice daily on Days 1-28
Danish: gange dagligt på dag 1-28, eller · Cotellic 60 mg 1 gang dagligt på dag 1-21 i hver 28 dages behandlingscyklus og 960 mg vemurafenib 2 gange dagligt på dag 1-28
English: One event of rhabdomyolysis was observed in each treatment arm of the study with concurrent increases in blood CPK.
Danish: I studiet blev observeret et tilfælde af rabdomyolyse i hver behandlingsarm med samtidig stigning i blod-kreatinkinase.
English: Liver laboratory abnormalities can occur with Cotellic and caution should be used in patients with any degree of hepatic impairment (see section 4.4).
Danish: 5.2) Abnorme laboratorieleverværdier kan forekomme med Cotellic og der skal udvises forsigtighed hos patienter med alle grader af nedsat leverfunktion (se pkt.
English: Your doctor should do tests before and during your treatment with Cotellic to check how well your heart can pump blood.
Danish: Lægen skal lave undersøgelser for at vurdere hjertets pumpeevne før og under din behandling med Cotellic.
English: If severity is improved by at least one grade within 4 weeks, Cotellic could be restarted at a dose reduced by 20 mg, if clinically indicated.
Danish: Hvis sværhedsgraden forbedres med mindst en grad inden for 4 uger, kan Cotellic-behandling genoptages ved en dosis reduceret med 20 mg, hvis det er klinisk indiceret.
English: There is no data on the effectiveness of Cotellic dose modification for haemorrhage events.
Danish: Der findes ingen data om effekten af Cotellic- dosisjustering ved blødninger.
English: Basal cell carcinoma, Cutaneous squamous cell carcinoma**, Keratoacanthoma**
Danish: Basalcellekarcinom, kutant planocellulært karcinom**, keratoakantom**
English: No dose adjustment is recommended in patients with hepatic impairment (see section 5.2).
Danish: Dosisjustering anbefales ikke til patienter med nedsat leverfunktion (se pkt.
English: No formal pharmacokinetic study has been conducted in patients with renal impairment.
Danish: Der er ikke gennemført formelle farmakokinetiske studier hos patienter med nedsat nyrefunktion.
English: Tell your doctor straight away if you get any of these symptoms: muscle aches, muscle spasms, weakness, or dark- or redcoloured urine.
Danish: Du skal straks kontakte lægen, hvis du oplever nogle af disse symptomer: muskelømhed, muskelkramper, svaghed eller mørk eller rødfarvet urin.
English: Study GO28141 is a multi-centre, randomised, double-blind, placebo-controlled, Phase III study to evaluate the safety and efficacy of Cotellic in combination with vemurafenib as compared to vemurafenib plus placebo, in previously untreated patients with BRAF V600 mutation-positive unresectable locally advanced (Stage IIIc) or metastatic melanoma (Stage IV).
Danish: Studie GO28141 er et randomiseret, dobbeltblindet, placebokontrolleret, fase III-multicenterstudie, der evaluerede sikkerheden og virkningen af Cotellic i kombination med vemurafenib sammenlignet med vemurafenib plus placebo hos tidligere ubehandlede patienter med BRAF-V600-mutationspositivt, ikke-operabelt, lokalt fremskredent (stadie IIIc) eller metastatisk (stadie IV) melanom.
English: Concurrent use of strong CYP3A inhibitors during treatment with Cotellic should be avoided.
Danish: Samtidig administration af potente CYP3A-hæmmere under behandling med Cotellic skal undgås.
English: If serous retinopathy is diagnosed, Cotellic treatment should be withheld until visual symptoms improve to Grade ≤1.
Danish: Hvis der konstateres serøs retinopati, afbrydes Cotellic-behandlingen, indtil symptomerne forbedres til grad ≤ 1.
English: Drug-drug interactions: CYP3A inhibitors
Danish: Lægemiddelinteraktioner: CYP3A-hæmmere
English: Vemurafenib dosing can be continued when Cotellic treatment is modified.
Danish: Vemurafenibdosering kan fortsættes, mens Cotellic-behandling ændres.
English: Cotellic can lower the amount of blood pumped by your heart (see also “Heart problems” in Section 4).
Danish: Cotellic kan svække hjertets pumpeevne (se også ”Hjerteproblemer” i afsnit 4).
English: P-glycoprotein inhibitors
Danish: P-glykoprotein-hæmmere
English: QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet contains cobimetinib hemifumarate equivalent to 20 mg cobimetinib.
Danish: KVALITATIV OG KVANTITATIV SAMMENSÆTNING Hver filmovertrukken tablet indeholder cobimetinibhemifumarat svarende til 20 mg cobimetinib.