natgillin/translations-raw huggingface dataset:
Hvis du oplever bivirkninger, bør du tale med din læge, sygeplejersken eller apoteket.
If you get any side effects, talk to your doctor, pharmacist or nurse.
De hyppigste bivirkninger (>20%) i studie GO28141, som blev observeret med højere frekvens i Cotellic-plus-vemurafenib-armen, var diarré, udslæt, kvalme, feber, lysfølsomhedsreaktioner, forhøjet alaninaminotransferase, forhøjet aspartaminotransferase, forhøjet blod-kreatinkinase og opkastning.
In Study GO28141, the most common adverse reactions (>20%) observed with a higher frequency in the Cotellic plus vemurafenib arm were diarrhoea, rash, nausea, pyrexia, photosensitivity reaction, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood creatine phosphokinase, and vomiting.
Det er vigtigt, fordi Cotellic kan påvirke virkningen af anden medicin, og anden medicin kan påvirke virkningen af Cotellic.
This is because Cotellic can affect the way some other medicines work.
Tabel 1 nedenfor giver generel vejledning i dosisændringer for Cotellic.
Table 1 below gives general Cotellic dose modification guidance.
Afbryd behandling indtil grad ≤ 1, og genoptag behandling med 20 mg én gang dagligt (1 tablet)
Interrupt treatment until Grade ≤ 1, restart treatment at 20 mg once daily (1 tablet)
Nedsat funktion af venstre ventrikel
Left ventricular dysfunction
Hvis du ikke er sikker, skal du kontakte lægen, apotekspersonalet eller sundhedspersonalet, inden du tager Cotellic.
If you are not sure, talk to your doctor, pharmacist or nurse before taking Cotellic.
Fortsæt med Cotellic i en dosis på 60 mg én gang dagligt (3 tabletter)
Maintain Cotellic at a dose of 60 mg once daily (3 tablets)
Cobimetinib er den dominerende substans i plasma.
Cobimetinib is the predominant moiety in plasma.
Behandling med Cotellic og/eller vemurafenib kan enten afbrydes midlertidigt, og/eller dosis kan reduceres, hvis dette er klinisk indiceret.
The dose of Cotellic and/or vemurafenib may be either temporarily interrupted and/or reduced as clinically indicated.
· Øjenproblemer
· Eye problems
Der foreligger ingen humandata vedrørende cobimetinib.
There are no data in humans for cobimetinib.
Hos raske frivillige ændres cobimetinibs farmakokinetik ikke, når det administreres sammen med mad (måltid med højt fedtindhold) sammenlignet med fastende tilstand.
The pharmacokinetics of cobimetinib are not altered when administered in the fed state (high-fat meal) compared with the fasted state in healthy subjects.
Ved grad 2 (intolerabelt) eller grad ≥ 3 akneiformt udslæt: Anbefalinger for generelle dosisændringer angivet i tabel 1 for Cotellic skal følges.
Grade 2 (intolerable) or Grade ≥3 acneiform rash: General dose modification recommendations in Table 1 for Cotellic should be followed.
· Spørg på apoteket, hvordan du skal bortskaffe medicinrester.
Ask your pharmacist how to throw away medicines you no longer use.
Der er gennemført et massebalance-studie med raske frivillige, der har vist, at cobimetinib i stort omfang metaboliseres og elimineres via fæces.
A human mass balance study was conducted in healthy subjects, and showed that cobimetinib was extensively metabolised and eliminated in faeces.
Dosisændringer af Cotellic er uafhængige af dosisændringer af vemurafenib.
Dose modification of Cotellic is independent of vemurafenib dose modification.
Cobimetinib er en reversibel, selektiv, allosterisk, oral hæmmer, der blokerer mitogen-aktiveret proteinkinase- (MAPK) signalvejen ved angreb mod mitogen-aktiveret ekstracellulær signalreguleret kinase (MEK)1 og MEK2.
Cobimetinib is a reversible, selective, allosteric, oral inhibitor that blocks the mitogen-activated protein kinase (MAPK) pathway by targeting the mitogen-activated extracellular signal-regulated kinase (MEK) 1 and MEK 2 which results in inhibition of phosphorylation of the extracellular signalregulated kinase (ERK) 1 and ERK 2.
Manglende dosering
Missed doses
Den anbefalede dosis er 3 tabletter (i alt 60 mg) 1 gang dagligt.
The recommended dose is 3 tablets (a total of 60 mg) once a day.
Cotellic er et lægemiddel mod kræft og indeholder det aktive stof cobimetinib.
What Cotellic is Cotellic is an anti-cancer medicine that contains the active substance cobimetinib.
Lægen vil tage blodprøver for at undersøge disse stigninger for at holde øje med din leverfunktion.
Your doctor will do blood tests to check these amounts and monitor how well your liver is working.
Der er ingen tegn på klinisk signifikant interaktion mellem cobimetinib og vemurafenib hos patienter med ikke-operabelt eller metastatisk melanom og derfor ingen anbefalinger om dosisjustering.
There is no evidence of any clinically significant drug-drug interaction between cobimetinib and vemurafenib in unresectable or metastatic melanoma patients and therefore no dose adjustments is recommended.
Grad 3: Behandling med Cotellic fortsættes med den ordinerede dosis.
Grade 3: Cotellic should be continued at the prescribed dose.
Ved grad 2 (intolerabelt) eller grad ≥ 3 non-akneiformt eller makulopapuløst udslæt: Cotellicbehandlingen kan fortsættes uden dosisændring, hvis dette er klinisk indiceret.
Grade 2 (intolerable) or Grade ≥3 non-acneiform or maculopapular rash: Cotellic dosing can be continued without modification if clinically indicated.
Anbefalet dosis af Cotellic er 60 mg (3 tabletter på 20 mg) én gang dagligt.
The recommended dose of Cotellic is 60 mg (3 tablets of 20 mg) once daily.
Moderate CYP3A-hæmmere inkluderer, men er ikke begrænset til, amiodaron, erythromycin, fluconazol, miconazol, diltiazem, verapamil, delavirdin, amprenavir, fosamprenavir, imatinib.
Moderate CYP3A inhibitors include, but are not limited to, amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, imatinib.
Kvinder, der kan få børn, bør bruge 2 forskellige former for sikker prævention, såsom kondom eller andre barrieremetoder (med sæddræbende middel, hvis tilgængeligt), under behandlingen og i mindst 3 måneder efter, behandlingen er afsluttet.
Women of childbearing potential should use two effective methods of contraception, such as a condom or other barrier method (with spermicide, if available) during treatment and for at least 3 months after treatment has finished.
Cobimetinib metaboliseres via CYP3A, og hos raske frivillige øgedes cobimetinibs AUC ca. 7 gange ved tilstedeværelse af en potent CYP3A-hæmmer (itraconazol).
Cobimetinib is metabolized by CYP3A and cobimetinib AUC increased approximately 7 fold in the presence of a strong CYP3A inhibitor (itraconazole) in healthy subjects.
Patienter ≥ 65 år oplevede oftere alvorlige bivirkninger og bivirkninger, som førte til seponering af cobimetinib, sammenlignet med patienter < 65 år.
Patients ≥65 years were more likely to experience serious adverse events (SAEs) and experience AEs leading to discontinuation of cobimetinib than those <65 years.
CYP3A-inducerer
CYP3A inducers
Asymptomatisk og < 10% absolut fald fra baseline
Asymptomatic and < 10% absolute decrease from baseline
Hvis du har glemt at tage Cotellic · Hvis der er mere end 12 timer til næste dosis, skal du tage den glemte dosis, så snart du kommer i tanker om det. · Hvis der er mindre end 12 timer til næste dosis, skal du springe den glemte dosis over og tage næste dosis på det planlagte tidspunkt.
If you forget to take Cotellic · If it is more than 12 hours before your next dose, take the missed dose as soon as you remember.
Afbryd behandling indtil grad ≤ 1, og genoptag behandling med 40 mg én gang dagligt (2 tabletter)
Interrupt treatment until Grade ≤ 1, restart treatment at 40 mg once daily (2 tablets)
· Gem indlægssedlen.
· Keep this leaflet.
Derfor skal andre behandlingsmuligheder overvejes, inden kombinationsbehandlingen igangsættes hos en patient, som har progredigeret under tidligere behandling med en BRAF-inhibitor.
Therefore other treatment options should be considered before treatment with the combination in this prior BRAF inhibitor treated population.
De fleste bivirkninger blev afviklet uden ændring i Cotellic-dosis.
Most events resolved with no change in Cotellic dose.
Forhøjet blod-bilirubin Andre abnorme laboratorieværdier Forhøjet blodkreatinkinase
Increased blood bilirubin Other laboratory abnormalities Increased blood CPK
Cobimetinib er substrat for P-gp in-vitro.
Cobimetinib is a substrate of P-gp in vitro.
Du skal straks kontakte lægen, hvis du får følgende symptomer: sløret syn, forvrænget syn, indskrænket synsfelt eller andre ændringer i dit syn under behandlingen.
Tell your doctor straight away if you get the following symptoms: blurred vision, distorted vision, partly missing vision, or any other changes to your sight during treatment.
Det er lægen, der på baggrund af en vurdering af den enkelte patients sikkerhed og tolerabilitet beslutter, om dosis skal reduceres for én eller begge behandlinger.
The decision on whether to reduce the dose for either or both treatments should be based on the prescriber's assessment of individual patient safety or tolerability.
Cotellic indeholder: · Aktivt indholdsstof: cobimetinib.
What Cotellic contains · The active substance is cobimetinib.
Systemisk total cobimetinibeksponering efter en enkeltdosis var sammenlignelig hos forsøgspersoner med let og moderat nedsat leverfunktion og raske forsøgspersoner, men forsøgspersoner med svært nedsat leverfunktion havde en lavere total cobimetinib eksponering (AUC0-∞ geometrisk gennemsnit ratio er 0,69 sammenlignet med raske forsøgspersoner).
Systemic total cobimetinib exposures after a single dose were similar in subjects with mild or moderate hepatic impairment compared to healthy subjects, while subjects with severe hepatic impairment had lower total cobimetinib exposures (AUC0-∞ geometric mean ratio of 0.69 compared to healthy subjects) which is not considered to be clinically significant.
Behandlingen kan genoptages uden ændring i Cotellic-dosis.
Treatment can be restarted with no change in Cotellic dose.
Grad 4 bivirkninger eller hjerneblødning: Cotellic-behandling skal afbrydes.
Grade 4 events or cerebral haemorrhage: Cotellic treatment should be interrupted.
Dosisbegrænsende toksicitet inkluderede hudlæsioner, overfladeeksudat og akantose hos rotter samt kronisk aktiv inflammation og degeneration af øsofagus med varierende grader af gastroenteropati hos hunde.
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.
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.
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.
Hvis der er mistanke om overdosering, skal behandling med cobimetinib afbrydes og understøttende behandling indledes.
In case of suspected overdose, cobimetinib should be withheld and supportive care instituted.
Det er ikke nødvendigt at ændre Cotellic-dosis, når det tages samtidig med vemurafenib.
No dose modification of Cotellic is required when taken in combination with vemurafenib.
Sekundære effektendepunkter inkluderede samlet overlevelse, objektiv responsrate, responsvarighed vurderet af investigator samt progressionsfri overlevelse vurderet af et uafhængigt panel.
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).
Cotellic filmovertrukne tabletter er hvide og runde med “COB” præget på den ene side.
What Cotellic looks like and contents of the pack Cotellic film-coated tablets are white, round with “COB” debossed on one side.
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”
* 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.
Medianen for progressionsfri overlevelse for patienter med progression under vemurafenib-behandling var 2,8 måneder, med median opfølgning på 8,1 måneder.
The median PFS for patients who had progressed on vemurafenib was 2.8 months, with median follow-up time of 8.1 months.
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.
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.
Cotellic kan forårsage problemer med øjnene (Se også ”Problemer med øjnene (synet)” i afsnit 4).
Cotellic can cause eye problems (see also “Eye (vision) problems” in Section 4).
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).
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).
Hvis cobimetinb administreres samtidig med moderate CYP3A-hæmmere, skal patienterne overvåges omhyggeligt med hensyn til sikkerhed.
When cobimetinib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.
< 10% absolut fald fra baseline
< 10% absolute decrease from baseline
Grad 4: Cotellic-behandling skal afbrydes.
Grade 4: Cotellic treatment should be interrupted.
Tabel 1 Anbefalede dosisændringer for Cotellic
Table 1 Recommended Cotellic dose modifications
Symptomerne kan være: · svimmelhed · ør i hovedet · stakåndethed · træthed · følelse af, at hjertet banker hårdere, hurtigere eller uregelmæssigt · hævede ben
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.
Læs også indlægssedlen for vemurafenib, som du tager sammen med Cotellic.
Please also refer to the Package Leaflet for vemurafenib, which is used in combination with Cotellic.
Afhængig af hvorhenne blødningen opstår, kan symptomer inkludere: · hovedpine, svimmelhed eller svaghed · opkastning af blod · mavesmerter · rød eller sortfarvet afføring
Depending on the area of the bleeding, symptoms may include: · headaches, dizziness, or weakness · vomiting blood · abdominal pain · red or black coloured stools.
Median (måneder) (95 % konfidensinterval)
Median (months) (95 % CI)
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.
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.
Dyrestudier har vist embryoletalitet og føtale misdannelser i store kar og kranie (se pkt.
Studies in animals have shown embryolethality and foetal malformations of the great vessels and skull (see section 5.3).
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.
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
Den objektive responsrate i Cotellic-plus-vemurafenib-armen var 67,6% versus 44,8% i placebo-plus-vemurafentib-armen.
The objective response rate (ORR) in the Cotellic plus vemurafenib arm was 67.6% vs 44.8% in the placebo plus vemurafenib arm.
Hos patienter, der ikke tidligere havde fået BRAF-hæmmer, var den mediane samlede overlevelse 28,5 måneder (95% konfidensinterval 23,2 ; 34,6).
In patients who were naive to BRAF inhibitor therapy, the median overall survival was 28.5 months (95% CI 23.3-34.6).
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).
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).
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.
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.
Hvis grad ≥3 diarré forekommer trods understøttende behandling, skal behandling med Cotellic og vemurafenib afbrydes, indtil diarréen er forbedret til grad ≤1.
For Grade ≥3 diarrhoea that occurs despite supportive care, Cotellic and vemurafenib should be withheld until diarrhoea has improved to Grade ≤1.
Pyreksi, kuldegysninger
Pyrexia, Chills
· Muskelproblemer
· Muscle problems
Resultaterne i studie NO25395 fra populationen, der ikke tidligere havde fået BRAF-hæmmer, var generelt i overensstemmelse med resultaterne fra studie GO28141.
Results of the BRAFi naïve population from Study NO25395 were generally consistent with those from Study GO28141.
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
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.
Symptomer af serøs retinopati kan være: · sløret syn · forvrænget syn · indskrænket synsfelt · andre ændringer i synet
Symptoms of serous retinopathy include: · blurred vision · distorted vision · partly missing vision · any other changes to your sight.
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.
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.
Det primære endepunkt var progressionsfri overlevelse vurderet af investigator.
Progression-free survival (PFS) as assessed by the investigator (INV) was the primary endpoint.
Der var observeret signifikante forbedringer i den samlede overlevelse hos patienter i Cotellic plus vemurafenib-armen sammenlignet med placebo plus vemurafenib-armen (Figur 1).
Significant improvement in OS was observed in patients assigned to the Cotellic plus vemurafenib arm compared to the placebo plus vemurafenib arm (Figure 1).
Sikkerheden af Cotellic i kombination med vemurafenib er også evalueret i studie NO25395 hos 129 patienter med fremskreden BRAF-V600-muteret melanom.
The safety of Cotellic in combination with vemurafenib has also been evaluated in 129 patients with advanced BRAF V600 mutated melanoma in Study NO25395.
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.
The median PFS for BRAFi-naïve patients was 13.8 months, with median follow-up time of 20.6 months.
Nedsat uddrivningsfraktion, forhøjet blod-bilirubin
Ejection fraction decreased, Blood bilirubin increased
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.
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.
Anbefalet daglig dosis af Cotellic
Recommended Cotellic daily dose
Tag altid medicinen nøjagtig efter lægens eller apotekspersonalets anvisning.
Always take this medicine exactly as your doctor or pharmacist has told you.
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.
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).
Hvad bruges Cotellic til?
What Cotellic is used for
Ved grad ≤ 2 (tolerabelt) udslæt gives understøttende behandling.
Grade ≤2 (tolerable) rash should be managed with supportive care.
Større blødninger (inklusiv intrakranial og gastrointestinale blødninger) blev rapporteret efter markedsføring.
Major haemorrhagic events (including intracranial and gastrointestinal tract haemorrhage) were reported in the post-marketing setting.
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.
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.
Ved lysfølsomhedsreaktion grad ≤ 2 (tolerabel) bør der gives understøttende behandling.
Grade ≤2 (tolerable) photosensitivity should be managed with supportive care.
Ved abnorme leverværdier grad 1 og 2 fortsættes behandlingen med Cotellic og vemurafenib med den ordinerede dosis.
For Grade 1 and 2 liver laboratory abnormalities, Cotellic and vemurafenib should be continued at the prescribed dose.