FrancophonIA/ELRC3.0 huggingface dataset:
English: PHARMACEUTICAL FORM AND CONTENTS 63 film-coated tablets
Danish: LÆGEMIDDELFORM OG INDHOLD (PAKNINGSSTØRRELSE) 63 filmovertrukne tabletter
English: Hazard ratio (95% CI) b
Danish: Hazard ratio (95% konfidensinterval)b
English: In vitro studies show that cobimetinib is not a substrate of the liver uptake transporters OATP1B1, OATP1B3 and OCT1, however, it weakly inhibits these transporters.
Danish: In vitro-studier viser, at cobimetinib ikke er substrat for de hepatiske transportproteiner OATP1B1, OATP1B3 og OCT1, men at det i let grad hæmmer disse transportproteiner.
English: Effects of cobimetinib on other medicinal products
Danish: Cobimetinibs virkning på andre lægemidler
English: Table 4 Liver function and other laboratory tests observed in the Phase III Study GO28141
Danish: Tabel 4 Leverfunktionsværdier samt andre blodprøveværdier observeret i fase III-studiet GO28141
English: Given that cobimetinib concentrations are likely to be significantly reduced when co-administered with moderate to strong CYP3A inducers, patient's efficacy may be compromised.
Danish: Da koncentrationen af cobimetinib sandsynligvis vil være betydeligt reduceret ved samtidig administration af potente CYP3A-inducerer, kan patientens effekt være kompromitteret.
English: The most common adverse reactions (>20%) observed with a higher frequency in the placebo plus vemurafenib arm were arthralgia, alopecia, and hyperkeratosis.
Danish: De hyppigste bivirkninger (>20%), som blev observeret ned højere frekvens i placebo-plusvemurafenib-armen, var artralgi, alopeci og hyperkeratose.
English: Table 2 Recommended dose modifications for Cotellic in patients with left ventricular ejection fraction (LVEF) decrease from baseline
Danish: Tabel 2 Vejledning i dosisændring for Cotellic hos patienter med fald i venstre ventrikels uddrivningsfraktion (LVEF) i forhold til baseline
English: The median duration of response was 14.3 months.
Danish: Den mediane responsvarighed var 14,3 måneder.
English: If you are sick (vomit) after taking Cotellic, do not take an extra dose of Cotellic on that day.
Danish: Hvis du kaster op, efter du har taget Cotellic, skal du ikke tage en ny dosis Cotellic samme dag.
English: · The other ingredients are: · lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate in the tablet core; and · polyvinyl alcohol, titanium dioxide, macrogol and talc in the film-coating.
Danish: · Øvrige indholdsstoffer: · lactosemonohydrat, mikrokrystallinsk cellulose, croscarmellosenatrium og magnesiumstearat i tabletkernen og · polyvinylalkohol, titandioxid, macrogol og talcum i filmovertrækket.
English: · Diarrhoea
Danish: · Diarré
English: Key baseline characteristics included: 58% of patients were male, median age was 55 years (range 23 to 88 years), 60% had metastatic melanoma stage M1c and the proportion of patients with elevated LDH was 46.3% in the cobimetinib plus vemurafenib arm and 43.0% in the placebo plus vemurafenib arm.
Danish: Primære baseline-karakteristika: 58% af patienterne var mænd, medianalderen var 55 år (23-88 år), 60% havde metastatisk melanom stadie M1c, og andelen af patienter med forhøjet LDH var 46,3% i Cobimetinib-plus-vemurafenib-armen og 43,0% i placebo-plus-vemurafenib-armen.
English: When administered to pregnant rats, cobimetinib caused embryolethality and foetal malformations of the great vessels and skull at systemic exposures similar to human exposure at recommended dose.
Danish: Ved administration til drægtige rotter har cobimetinib forårsaget embryoletalitet og føtale misdannelser af de store kar og kraniet ved systemiske eksponeringer svarende til den humane eksponering ved anbefalede doser.
English: The final OS analysis for Study GO28141 was conducted with a data-cut off date of 28 August 2015.
Danish: Den endelige analyse for den samlede overlevelse for studie GO28141 var udført med data cut off dato 28. august 2015.
English: Taking the medicine · Swallow the tablets whole with water.
Danish: Sådan tages medicinen: · Synk tabletten hel med vand.
English: This study treated 129 patients with Cotellic and vemurafenib: 63 were BRAF inhibitor (BRAFi) therapy naïve and 66 patients had previously progressed on prior vemurafenib therapy.
Danish: I dette studie blev 129 patienter behandlet med Cotellic og vemurafenib: 63 havde ikke tidligere fået BRAF-hæmmerbehandling, og 66 patienter havde tidligere oplevet progression under behandling med vemurafenib.
English: Some of these eye problems may be a result of “serous retinopathy” (a build-up of fluid under the retina in the eye).
Danish: Nogle af disse øjenproblemer kan skyldes ophobning af væske under nethinden i øjet (serøs retinopati).
English: Asymptomatic
Danish: Asymptomatisk
English: Co-administration of cobimetinib with a strong CYP3A inducer was not assessed in a clinical study, however, a reduction in cobimetinib exposure is likely.
Danish: Samtidig administration af cobimetinib og en potent CYP3A-inducer er ikke undersøgt i kliniske studier, men det er sandsynligt, at eksponeringen af cobimetinib vil falde.
English: The safety profile of Study NO25395 was consistent with that observed in Study GO28141.
Danish: Sikkerhedsprofilen i studie NO25395 svarede til den, der sås i studie GO28141.
English: The dose of vemurafenib may be reduced as clinically appropriate.
Danish: Dosis af vemurafenib kan reduceres, hvis dette er klinisk hensigtsmæssigt.
English: · It is not known if Cotellic passes into breast milk.
Danish: · Det vides ikke, om Cotellic udskilles i mælken hos mennesker.
English: A decision should be made whether to discontinue breast-feeding or discontinue Cotellic therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Danish: Det skal besluttes, om amning eller behandling med Cotellic skal ophøre, idet der tages højde for fordelene ved amning for barnet i forhold til de terapeutiske fordele for moderen.
English: If you get side effects your doctor may decide to lower your dose, stop treatment temporarily or permanently.
Danish: Hvis du får bivirkninger, kan lægen beslutte at nedsætte dosis eller afbryde behandlingen midlertidigt eller permanent.
English: The proportion of patients experiencing adverse events (AE) was similar in the patients aged <65 years and those aged ³65 years.
Danish: Antallet af patienter, som oplevede bivirkninger, var sammenligneligt mellem patienter < 65 år og patienter ≥ 65 år.
English: Blood creatine phosphokinase increase
Danish: Forhøjet blod-kreatinfosfokinase
English: The efficacy of Cotellic was evaluated in Phase Ib Study, NO25395, which was designed to assess the safety, tolerability, pharmacokinetics and efficacy of Cotellic when added to vemurafenib for the treatment of patients with BRAFV600 mutation-positive (as detected by the cobas® 4800 BRAF V600
Danish: Cotellics virkning blev evalueret i fase Ib-studiet, NO25395, som var designet til at vurdere sikkerheden, tolerabiliteten, farmakokinetikken og virkningen af Cotellic som tillæg til vemurafenib til behandling af patienter med BRAF-V600-mutationspositiv (verificeret ved cobas® 4800 BRAF-V600
English: Therefore, cobimetinib blocks the cell proliferation induced by the MAPK pathway through inhibition of the MEK1/2 signalling node.
Danish: Cobimetinib blokerer dermed celleproliferationen, der induceres af MAPK-signalvejen ved at hæmme MEK1/2-signalknuden.
English: No clinical DDI studies have been conducted to assess the clinical relevance of this finding.
Danish: Det er ikke udført kliniske interaktionsstudier for at vurdere den kliniske betydning af dette fund.
English: This can be a sign of muscle damage (rhabdomyolysis) (see also “Muscle problems” in Section 4).
Danish: Dette kan være et tegn på muskelbeskadigelse (rabdomyolyse) (se også ”Muskelproblemer” i afsnit 4).
English: Cotellic dosing can be continued without modification.
Danish: Cotellic dosering kan fortsættes uden ændringer.
English: General dose modifications
Danish: Generelle dosisændringer
English: Effects of other medicinal products on cobimetinib
Danish: Andre lægemidlers virkning på cobimetinib
English: Cotellic should be used with caution in patients with severe renal impairment.
Danish: Cotellic skal anvendes med forsigtighed til patienter med svært nedsat nyrefunktion.
English: Patients with severe hepatic impairment may have increased plasma concentrations of unbound cobimetinib compared to patients with normal hepatic function (see section 5.2).
Danish: Patienter med svært nedsat leverfunktion kan have forhøjet plasmakoncentration af frit cobimetinib sammenlignet med patienter med normal leverfunktion (se pkt.
English: In animals, no fertility studies have been performed, but adverse effects were seen on reproductive organs (see section 5.3).
Danish: Der er ikke gennemført fertilitetsstudier hos dyr, men der er set negative virkninger i forhold til hunners kønsorganer (se pkt.
English: Photosensitivity
Danish: Lysoverfølsomhed
English: The sequencing of treatments following progression on a BRAF inhibitor therapy has not been established.
Danish: Rækkefølgen af behandlinger efter progredigering under BRAF-inhibitor-behandling er ikke etableret.
English: Table 3 Adverse drug reactions in patients treated with Cotellic in combination with vemurafenib in Study GO28141^
Danish: Tabel 3 Bivirkninger hos patienter behandlet med Cotellic i kombination med vemurafenib i studiet GO28141
English: Increased GGT
Danish: Forhøjet GGT
English: Carcinogenicity studies have not been conducted with cobimetinib.
Danish: Der er ikke gennemført karcinogenicitetsstudier med cobimetinib.
English: In vitro, cobimetinib produced moderate hERG ion channel inhibition (IC50= 0.5 µM [266 ng/mL]), which is approximately 18 fold higher than peak plasma concentrations (Cmax) at the 60 mg to be marketed dose (unbound Cmax=14 ng/mL [0.03 µM]).
Danish: In vitro forårsagede cobimetinib en moderat hæmning af hERG-ionkanalen ved koncentrationer (IC50꞊ 0,5 µM [266 ng/ml]), som er ca. 18 gange højere end de maksimale plasmakoncentrationer (Cmax) ved den anbefalede 60 mg dosis (ubundet Cmax꞊14 ng/ml [0,03 µM]).
English: Median time to initial onset of serous retinopathy events was 1 month (range 0-9 months).
Danish: Mediantiden til debut af serøs retinopati var 1 måned (0-9 måneder).
English: Blood CPK increased, ALT increased, AST increased, GammaGlutamyltransferase (GGT) increased, Blood ALP increased
Danish: Forhøjet blodkreatinkinase, forhøjet ALAT, forhøjet ASAT, forhøjet gammaglutamyltransferase (GGT), forhøjet blodALP
English: nefadozone for depression amiodarone for an uneven heartbeat diltiazem, verapamil for high blood pressure imatinib for cancer carbamazepine, phenytoin for fits (seizures)
Danish: nefadozon for depression amiodaron for uregelmæssig hjerterytme diltiazem, verapamil for højt blodtryk imatinib for kræft carbamazepin, phenytoin for kramper perikon naturmedicin for depression.
English: Eye (vision) problems (very common: may affect more than 1 in 10 people) Cotellic can cause eye problems.
Danish: Øjenproblemer (syn) (meget almindelige: kan optræde hos flere end 1 ud af 10 patienter) Cotellic kan give øjenproblemer.
English: Purpose of the medicine itraconazole, clarithromycin, erythromycin, telithromycin, voriconazole, rifampicin, posaconazole, fluconazole, miconazole for some fungal and bacterial infections ritonavir, cobicistat, lopinavir, delavirdine, amprenavir, fosamprenavir for HIV infection telaprevir for hepatitis C
Danish: Medicinens formål itraconazol, clarithromycin, erythromycin, telithromycin, voriconazol, rifampicin, posaconazol, fluconazol, miconazol for bestemte svampe- og bakterieinfektioner ritonavir, cobicistat, lopinavir, delavirdin, amprenavir, fosamprenavir for HIV-infektion telaprevir for hepatitis C
English: If concomitant use with a strong or moderate CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety and dose modifications applied if clinically indicated (see Table 1 in section 4.2).
Danish: Hvis samtidig administration af potente eller moderate CYP3A-hæmmere ikke kan undgås, skal patienterne kontrolleres omhyggeligt for bivirkninger, og dosis skal ændres, hvis dette er klinisk indiceret (se tabel 1 i pkt.
English: Patients should be assessed at each visit for symptoms of new or worsening visual disturbances.
Danish: Patienten skal vurderes for nye eller forværrede synsforstyrrelser ved hvert besøg.
English: · Heart problems
Danish: · Hjerteproblemer
English: The median time to first occurrence of Grade 3 or 4 CPK elevations was 16 days (range: 11 days to 10 months); the median time to complete resolution was 16 days (range: 2 days to 15 months).
Danish: Mediantiden, der går ind til første forekomst af grad 3 eller 4 stigninger i kreatinkinase var 16 dage (spænder fra: 11 dage til 10 måneder); mediantiden, der går før bivirkningen er helt væk var 16 dage (spænder fra: 2 dage til 15 måneder).
English: Cobimetinib is a substrate of P-glycoprotein (P-gp).
Danish: Cobimetinib er substrat for P-glykoprotein (P-gp).
English: · Start your next Cotellic 21 day treatment period after the 7 day break.
Danish: · Start næste behandlingsperiode (21 dage) med Cotellic efter 7 dages pausen.
English: If you get any side effects, talk to your doctor, pharmacist or nurse.
Danish: Hvis du oplever bivirkninger, bør du tale med din læge, sygeplejersken eller apoteket.
English: 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.
Danish: 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.
English: This is because Cotellic can affect the way some other medicines work.
Danish: Det er vigtigt, fordi Cotellic kan påvirke virkningen af anden medicin, og anden medicin kan påvirke virkningen af Cotellic.
English: Table 1 below gives general Cotellic dose modification guidance.
Danish: Tabel 1 nedenfor giver generel vejledning i dosisændringer for Cotellic.
English: Interrupt treatment until Grade ≤ 1, restart treatment at 20 mg once daily (1 tablet)
Danish: Afbryd behandling indtil grad ≤ 1, og genoptag behandling med 20 mg én gang dagligt (1 tablet)
English: Left ventricular dysfunction
Danish: Nedsat funktion af venstre ventrikel
English: If you are not sure, talk to your doctor, pharmacist or nurse before taking Cotellic.
Danish: Hvis du ikke er sikker, skal du kontakte lægen, apotekspersonalet eller sundhedspersonalet, inden du tager Cotellic.
English: Maintain Cotellic at a dose of 60 mg once daily (3 tablets)
Danish: Fortsæt med Cotellic i en dosis på 60 mg én gang dagligt (3 tabletter)
English: Cobimetinib is the predominant moiety in plasma.
Danish: Cobimetinib er den dominerende substans i plasma.
English: The dose of Cotellic and/or vemurafenib may be either temporarily interrupted and/or reduced as clinically indicated.
Danish: Behandling med Cotellic og/eller vemurafenib kan enten afbrydes midlertidigt, og/eller dosis kan reduceres, hvis dette er klinisk indiceret.
English: · Eye problems
Danish: · Øjenproblemer
English: There are no data in humans for cobimetinib.
Danish: Der foreligger ingen humandata vedrørende cobimetinib.
English: The pharmacokinetics of cobimetinib are not altered when administered in the fed state (high-fat meal) compared with the fasted state in healthy subjects.
Danish: Hos raske frivillige ændres cobimetinibs farmakokinetik ikke, når det administreres sammen med mad (måltid med højt fedtindhold) sammenlignet med fastende tilstand.
English: Grade 2 (intolerable) or Grade ≥3 acneiform rash: General dose modification recommendations in Table 1 for Cotellic should be followed.
Danish: Ved grad 2 (intolerabelt) eller grad ≥ 3 akneiformt udslæt: Anbefalinger for generelle dosisændringer angivet i tabel 1 for Cotellic skal følges.
English: Ask your pharmacist how to throw away medicines you no longer use.
Danish: · Spørg på apoteket, hvordan du skal bortskaffe medicinrester.
English: A human mass balance study was conducted in healthy subjects, and showed that cobimetinib was extensively metabolised and eliminated in faeces.
Danish: Der er gennemført et massebalance-studie med raske frivillige, der har vist, at cobimetinib i stort omfang metaboliseres og elimineres via fæces.
English: Dose modification of Cotellic is independent of vemurafenib dose modification.
Danish: Dosisændringer af Cotellic er uafhængige af dosisændringer af vemurafenib.
English: 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.
Danish: 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.
English: Missed doses
Danish: Manglende dosering
English: The recommended dose is 3 tablets (a total of 60 mg) once a day.
Danish: Den anbefalede dosis er 3 tabletter (i alt 60 mg) 1 gang dagligt.
English: What Cotellic is Cotellic is an anti-cancer medicine that contains the active substance cobimetinib.
Danish: Cotellic er et lægemiddel mod kræft og indeholder det aktive stof cobimetinib.
English: Your doctor will do blood tests to check these amounts and monitor how well your liver is working.
Danish: Lægen vil tage blodprøver for at undersøge disse stigninger for at holde øje med din leverfunktion.
English: 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.
Danish: 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.
English: Grade 3: Cotellic should be continued at the prescribed dose.
Danish: Grad 3: Behandling med Cotellic fortsættes med den ordinerede dosis.
English: Grade 2 (intolerable) or Grade ≥3 non-acneiform or maculopapular rash: Cotellic dosing can be continued without modification if clinically indicated.
Danish: Ved grad 2 (intolerabelt) eller grad ≥ 3 non-akneiformt eller makulopapuløst udslæt: Cotellicbehandlingen kan fortsættes uden dosisændring, hvis dette er klinisk indiceret.
English: The recommended dose of Cotellic is 60 mg (3 tablets of 20 mg) once daily.
Danish: Anbefalet dosis af Cotellic er 60 mg (3 tabletter på 20 mg) én gang dagligt.
English: Moderate CYP3A inhibitors include, but are not limited to, amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, imatinib.
Danish: Moderate CYP3A-hæmmere inkluderer, men er ikke begrænset til, amiodaron, erythromycin, fluconazol, miconazol, diltiazem, verapamil, delavirdin, amprenavir, fosamprenavir, imatinib.
English: 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.
Danish: 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.
English: Cobimetinib is metabolized by CYP3A and cobimetinib AUC increased approximately 7 fold in the presence of a strong CYP3A inhibitor (itraconazole) in healthy subjects.
Danish: Cobimetinib metaboliseres via CYP3A, og hos raske frivillige øgedes cobimetinibs AUC ca. 7 gange ved tilstedeværelse af en potent CYP3A-hæmmer (itraconazol).
English: Patients ≥65 years were more likely to experience serious adverse events (SAEs) and experience AEs leading to discontinuation of cobimetinib than those <65 years.
Danish: Patienter ≥ 65 år oplevede oftere alvorlige bivirkninger og bivirkninger, som førte til seponering af cobimetinib, sammenlignet med patienter < 65 år.
English: CYP3A inducers
Danish: CYP3A-inducerer
English: Asymptomatic and < 10% absolute decrease from baseline
Danish: Asymptomatisk og < 10% absolut fald fra baseline
English: 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.
Danish: 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.
English: Interrupt treatment until Grade ≤ 1, restart treatment at 40 mg once daily (2 tablets)
Danish: Afbryd behandling indtil grad ≤ 1, og genoptag behandling med 40 mg én gang dagligt (2 tabletter)
English: · Keep this leaflet.
Danish: · Gem indlægssedlen.
English: Therefore other treatment options should be considered before treatment with the combination in this prior BRAF inhibitor treated population.
Danish: Derfor skal andre behandlingsmuligheder overvejes, inden kombinationsbehandlingen igangsættes hos en patient, som har progredigeret under tidligere behandling med en BRAF-inhibitor.
English: Most events resolved with no change in Cotellic dose.
Danish: De fleste bivirkninger blev afviklet uden ændring i Cotellic-dosis.
English: Increased blood bilirubin Other laboratory abnormalities Increased blood CPK
Danish: Forhøjet blod-bilirubin Andre abnorme laboratorieværdier Forhøjet blodkreatinkinase
English: Cobimetinib is a substrate of P-gp in vitro.
Danish: Cobimetinib er substrat for P-gp in-vitro.
English: 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.
Danish: Du skal straks kontakte lægen, hvis du får følgende symptomer: sløret syn, forvrænget syn, indskrænket synsfelt eller andre ændringer i dit syn under behandlingen.
English: 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.
Danish: 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.
English: What Cotellic contains · The active substance is cobimetinib.
Danish: Cotellic indeholder: · Aktivt indholdsstof: cobimetinib.
English: 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.
Danish: 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).
English: Treatment can be restarted with no change in Cotellic dose.
Danish: Behandlingen kan genoptages uden ændring i Cotellic-dosis.
English: Grade 4 events or cerebral haemorrhage: Cotellic treatment should be interrupted.
Danish: Grad 4 bivirkninger eller hjerneblødning: Cotellic-behandling skal afbrydes.