natgillin/translations-raw huggingface dataset:
<ansøgeren kan i sin ansøgning påvise, at lægemidlet, selv om det er similært med {det godkendte lægemiddel til sjældne sygdomme}, er sikrere, mere effektivt eller på anden vis klinisk overlegent (som defineret i artikel 3 i Kommissionens forordning (EC) nr. 847/2000) ved den samme terapeutiske indikation> <og> 
<the applicant could establish in the application that the medicinal product, although similar to <authorised orphan medicinal product>, is safer, more effective or otherwise clinically superior (as defined in Article 3 of Commission Regulation (EC) No. 847/2000) for the same therapeutic indication>.
[Art 74(a)- legal status switch]<Endvidere gennemgik CHMP de oplysninger, som indehaveren af markedsføringstilladelsen havde indsendt, jf. artikel 74, litra a, i direktiv 2001/83/EC, og er af den opfattelse, at de indsendte oplysninger er væsentlige og understøtter en klassificering af {lægemidlets navn} som et ikke-receptpligtigt lægemiddel. 
[Art 74(a)- legal status switch]<Furthermore, the CHMP reviewed the data submitted by the Marketing Authorisation Holder, taking into account the provisions of Article 74(a) of Directive 2001/83/EC, and considers that the data submitted in support of the classification of {specify medicinal product name} as ‘medicinal product not subject to medical prescription' were significant as further explained in the European Public Assessment Report.>
Følgende konvention er anvendt til klassifikation af hyppighed: 
The following convention has been used for the classification of frequency:
· Risikostyringsplan (RMP) 
· Risk Management Plan (RMP)
Patienterne skal overvåges tæt. 
Patients should be closely monitored.
^ Data cut-off dato 19. september 2014 
^ Data cut-off date of 19 September 2014
I gennemsnit kunne 94% af dosis genfindes inden for 17 dage. 
On average, 94% of the dose was recovered within 17 days.
De kan tages sammen med eller uden mad. 
They can be taken with or without food.
Effektresultaterne opsummeres i tabel 5. 
Efficacy results are summarized in Table 5.
Omfanget af interaktionen kan potentielt være lavere hos patienter. 
The magnitude of interaction could potentially be lower in patients.
Alle grader Grad 3-4 Alle grader Grad 3-4 
All Grades Grades 3-4 All Grades Grades 3-4
(20,3; IE) 
(20.3, NE)
MARKEDSFØRINGSTILLADELSESNUMMER (-NUMRE) EU/1/15/1048/001 
MARKETING AUTHORISATION NUMBER(S) EU/1/15/1048/001
Fortsæt med nuværende dosis 
Continue at current dose
Cotellic tages i en 28 dages cyklus. 
Cotellic is taken on a 28 day cycle.
Fortæl straks lægen, hvis du får diarré. 
Tell your doctor straight away if you get diarrhoea.
Gennemsigtige PVC/PVDC-blistere indeholdende 21 tabletter. 
Transparent PVC/PVDC blisters containing 21 tablets.
· Tag tabletterne hver dag i 21 dage (kaldes en behandlingsperiode). 
· Take the tablets every day for 21 days (called a “treatment period”).
· Brug ikke lægemidlet efter den udløbsdato, der står på blisterpakningen og kartonen efter EXP. 
· Do not take this medicine after the expiry date which is stated on the blister and the carton after EXP.
Grad (CTC-AE)* 
Grade (CTC-AE)*
Træthed blev observeret med samme frekvenser i de 2 arme. 
Fatigue was observed at similar frequencies in both arms.
Hvis der undlades doser på grund af toksicitet, bør disse doser ikke erstattes. 
If doses are omitted for toxicity, these doses should not be replaced.
Din læge vil tage blodprøver for at monitorere dette. 
Your doctor will do blood tests to monitor for this.
Når dosis én gang er reduceret, bør den ikke senere øges igen. 
Once the dose has been reduced, it should not be increased at a later time.
Hver pakning indeholder 63 tabletter. 
Each pack contains 63 tablets.
Der forekom dødsfald hos unge dyr i doser (3 mg/kg), som ikke medførte dødsfald hos voksne dyr. 
Mortality occurred in juvenile animals at a dose (3 mg/kg) which did not lead to mortalities in adult animals.
Transporten over blodhjernebarrieren er ikke kendt. 
The transport across the blood brain barrier is unknown.
Symptomatisk uanset LVEF Permanent seponering 
Symptomatic regardless of LVEF Permanent discontinuation
Der er ingen data fra anvendelse af Cotellic til gravide kvinder. 
There are no data from the use of Cotellic in pregnant women.
· Cotellic kan tages sammen med eller uden mad. 
· Cotellic can be taken with or without food.
· Det kan kun bruges af patienter, hvis kræftsygdom har en ændring (mutation) i et protein, der kaldes BRAF. 
· It can only be used in patients whose cancer has a change (mutation) in a protein called “BRAF”.
Der er ikke observeret oxidative metabolitter på mere end 10% af den totale cirkulerende radioaktivitet eller humanspecifikke metabolitter i plasma. 
No oxidative metabolites greater than 10% of total circulating radioactivity or human specific metabolites were observed in plasma.
Størstedelen af bivirkningerne var af grad 1 eller 2 og ikke alvorlige. 
The majority of events were Grade 1 or 2 and non-serious.
Ingen dosisreduktion. 
No dose reduction.
Ændringer i indberettede laboratoriedata 
Changes in reported laboratory data
N/A= Ikke relevant 
N/A = Not Applicable
Spørg lægen, hvilken prævention der er bedst for dig. 
Ask your doctor about the best contraception for you.
Afbryd behandlingen i 4 uger 
Interrupt treatment for 4 weeks
Patienter med ECOG-performancestatus 2 eller højere blev ekskluderet fra studiet. 
Patients with ECOG performance status 2 or higher were excluded from the study.
· Hvis du bliver gravid, mens du er i behandling med Cotellic eller inden for 3 måneder efter din sidste dosis, skal du straks kontakte lægen. 
· If you become pregnant during treatment with Cotellic or in the 3 months after your last dose, tell your doctor straight away.
Da mad ikke ændrer cobimetinibs farmakokinetik, kan det administreres sammen med eller uden mad. 
Since food does not alter the pharmacokinetics of cobimetinib, it can be administered with or without food.
· Du må ikke tage en dobbeltdosis som erstatning for den glemte dosis. 
· Do not take a double dose to make up for a missed dose.
Behandlingen med Cotellic bør fortsætte, indtil patienten ikke længere har gavn af behandlingen, eller der udvikles uacceptabel toksicitet (se tabel 1 nedenfor). 
Treatment with Cotellic should continue until the patient no longer derives benefit or until the development of unacceptable toxicity (see Table 1 below).
Det kan derfor tage op til 2 uger efter seponering, før cobimetinib er fuldstændigt fjernet fra den systemiske cirkulation. 
Therefore, it may take up to 2 weeks following treatment cessation for cobimetinib to be completely removed from systemic circulation.
Hvis du har taget flere Cotellic, end du skulle, skal du straks kontakte en læge. 
If you take more Cotellic than you should, talk to a doctor straight away.
Derudover: 
Additionally, for:
Afbryd behandlingen i 2 uger 
Interrupt treatment for 2 weeks
Grad 1 eller grad 2 (tolerabel) 
Grade 1 or Grade 2 (tolerable)
Filmovertræk Polyvinylalkohol Titandioxid (E171) Macrogol 3350 
Film coating Polyvinyl alcohol Titanium dioxide (E171) Macrogol 3350
Malta (see United Kingdom) 
Malta (see Ireland)
· Dette lægemiddel kræver ikke særlige opbevaringsforhold. 
· This medicine does not require any special storage conditions.
Den absorberede fraktion var ~88%, hvilket tyder på høj absorption og første-passage-metabolisme. 
The fraction absorbed was ~88% indicating high absorption and first pass metabolism.
Samlet overlevelse g 
Overall Survival (OS)g
Diarré (meget almindelig: kan optræde hos flere end 1 ud af 10 patienter) Fortæl straks lægen, hvis du får diarré, og følg lægens anvisning om, hvordan diarréen kan forhindres eller behandles. 
Diarrhoea (very common: may affect more than 1 in 10 people) Tell your doctor straight away if you get diarrhoea and follow your doctor's instructions for what to do to help prevent or treat diarrhoea.
Før du begynder behandling, vil lægen undersøge, om du har denne mutation. 
Before starting treatment, your doctor will test for this mutation.
Den gennemsnitlige akkumuleringsratio ved steady-state er ca. 2,4 gange. 
The mean accumulation ratio at steady state was approximately 2.4-fold.
Tabletterne synkes hele med vand. 
The tablets should be swallowed whole with water.
Undgå at køre motorkøretøj eller anvende maskiner, hvis du har problemer med synet eller andre problemer, som kan påvirke din evne, f.eks. hvis du er svimmel eller træt. 
Avoid driving or using machines if you have problems with your vision or other problems that might affect your ability e.g. if you feel dizzy or tired.
Cotellic kan forårsage forhøjede niveauer af kreatinkinase, som er et enzym, der hovedsageligt findes i musker, hjerte og hjerne. 
Cotellic can cause increased levels of creatine phosphokinase, an enzyme that is found mainly in the muscle, heart, and brain.
Patienterne skal rådes til ikke at føre motorkøretøj eller betjene maskiner, hvis de oplever synsforstyrrelser eller andre bivirkninger, som kan påvirke denne evne. 
Patients should be advised not to drive or use machines if they experience visual disturbances or any other adverse effects that may affect their ability.
Der er ikke observeret selektiv binding til humane røde blodlegemer (blod-til-plasma-ratio 0,93). 
No preferential binding to human red blood cells was observed (blood to plasma ratio 0.93).
Leverfunktionstest Forhøjet ALP 
Liver function test Increased ALP
· Det bruges sammen med et andet lægemiddel mod kræft, der hedder vemurafenib. 
· It is used in combination with another anti-cancer medicine called vemurafenib.
g Data cut-off dato for den endelig analyse for samlet overlevelse var 28. august 2015 og median opfølgning var 18,5 måneder-. 
g The data cut-off date for the final OS analysis is 28 August 2015 and median follow-up was 18.5 months.
Hvis du er gravid eller ammer, har mistanke om, at du er gravid, eller planlægger at blive gravid, skal du spørge lægen eller apotekspersonalet til råds, før du tager dette lægemiddel. 
If you are pregnant or breast-feeding, think you might be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
· Efter de 21 dage skal du ikke tage Cotellic i 7 dage. 
· After the 21 days, do not take any Cotellic tablets for 7 days.
Generel helbredsstatus/helbredsrelateret livskvalitet indberettet af patienten blev målt ved hjælp af EORTC-skemaet Core 30 [Quality of Life Questionnaire (QLQ-) C30]. 
Global health status / health-related quality of life by patient-report were measured using the EORTC Quality of Life Questionnaire - Core 30 (QLQ-C30).
Cobimetinib er 94,8% bundet til humane plasmaproteiner in vitro. 
Cobimetinib is 94.8% bound to human plasma proteins in vitro.
I tilfælde af opkastning efter administration af Cotellic bør patienten ikke tage en yderligere dosis samme dag, men fortsætte behandlingen næste dag som foreskrevet. 
In case of vomiting after administration of Cotellic, the patient should not take an additional dose on that day and treatment should be continued as prescribed the following day.
Uomdannet lægemiddel i fæces og urin udgjorde henholdsvis 6,6% og 1,6% af den administrerede dosis, hvilket tyder på, at cobimetinib primært metaboliseres med minimal renal elimination. 
Unchanged medicinal product in faeces and urine accounted for 6.6% and 1.6% of the administered dose, respectively, indicating that cobimetinib is primarily metabolised with minimal renal elimination.
Alle patienter, som genstarter Cotellic-behandling med dosisreduktion, skal have foretaget LVEFmåling efter ca. 2 uger, 4 uger, 10 uger og 16 uger og herefter som klinisk indiceret. 
All patients restarting treatment with a dose reduction of Cotellic should have LVEF measurements taken after approximately 2 weeks, 4 weeks, 10 weeks and 16 weeks, and then as clinically indicated.
1. forekomst: 40 mg 2. forekomst: 20 mg 3. forekomst: permanent seponering 
1st occurrence: 40 mg nd occurrence: 20 mg rd occurrence: permanent discontinuation
Cotellic må ikke anvendes under graviditet, medmindre det er strengt nødvendigt og kun efter omhyggelig vurdering af moderens behov i forhold til risikoen for fostret. 
Cotellic should not be used during pregnancy unless clearly necessary and after a careful consideration of the needs of the mother and the risk to the foetus.
Den gennemsnitlige eliminationshalveringstid efter oral dosering af cobimetinib var 43,6 timer (23,1 til 69,6 timer). 
The mean elimination half-life following oral dosing of cobimetinib was 43.6 hours (range: 23.1 to 69.6 hours).
En opdateret RMP skal fremsendes: · på anmodning fra Det Europæiske Lægemiddelagentur · når risikostyringssystemet ændres, særlig som følge af, at der er modtaget nye oplysninger, der kan medføre en væsentlig ændring i risk/benefit-forholdet, eller som følge af, at en vigtig milepæl (lægemiddelovervågning eller risikominimering) er nået. 
· At the request of the European Medicines Agency; · Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
Fordelingsvolumenet er 1.050 l hos raske frivillige, der fik en intravenøs dosis på 2 mg. 
The volume of distribution was 1050 L in healthy subjects given an intravenous dose of 2 mg.
0,70 (95% konfidensinterval: 0,55; 0,90) (p-værdi = 0,0050e) 
0.70 (95% CI: 0.55, 0.90) (p-value = 0.0050
Behandlingen skal tages i 21 på hinanden følgende dage efterfulgt af 7 dages pause 
Treatment should be taken for 21 consecutive days followed by a 7-day break
Cotellics sikkerhed og virkning til ikke-kaukasiske patienter er ikke klarlagt. 
The safety and efficacy of Cotellic in non-Caucasian patients have not been established.
Den mediane responsvarighed var 6,8 måneder. 
The median duration of response was 6.8 months.
· Periodiske, opdaterede sikkerhedsindberetninger (PSUR'er) 
· Periodic safety update reports
Standardmæssige genotoksicitetsstudier med cobimetinib var negative. 
Standard genotoxicity studies with cobimetinib were negative.
mutationstest), ikke-operabelt eller metastatisk melanom. 
Mutation Test), unresectable or metastatic melanoma.
Hos kræftpatienter var det tilsyneladende fordelingsvolumen 806 l, baseret på en farmakokinetisk populationsanalyse. 
The apparent volume of distribution was 806 L in cancer patients based on population pharmacokinetic analysis.
Lactosemonohydrat Mikrokrystallinsk cellulose (E460) Croscarmellosenatrium (E468) Magnesiumstearat (E470b) 
Lactose monohydrate Microcrystalline cellulose (E460) Croscarmellose sodium (E468) Magnesium stearate (E470b)
Baseline-alder og baselinekropsvægt er identificeret som statistisk signifikante covariater for henholdsvis cobimetinib-clearance og fordelingsvolumen. 
Baseline age and baseline body weight were identified as statistically significant covariates on cobimetinib clearance and volume of distribution respectively.
Farmakoterapeutisk klassifikation: Antineoplastiske midler, ATC-kode:L01XE38. 
Pharmacotherapeutic group: Antineoplastic agents, ATC code: L01XE38
Hvis en dosis bliver glemt, kan den tages i op til 12 timer inden næste planlagte dosis for at opretholde et doseringsregime på én gang dagligt. 
If a dose is missed, it can be taken up to 12 hours prior to the next dose to maintain the once-daily regimen.
Median opfølgning var 14,2 måneder. 
The median follow up was 14.2 months.
Denne mutation kan være skyld i melanomet. 
This change may have led to the development of melanoma.
· Det frarådes at tage Cotellic under graviditet - selvom Cotellic ikke er undersøgt hos gravide kvinder, kan det muligvis skade det ufødte barn og forårsage misdannelser. 
· Cotellic is not recommended during pregnancy - although the effects of Cotellic have not been studied in pregnant women, it may cause permanent harm or birth defects to an unborn baby.
Blandt de patienter, der havde oplevet progression under behandling med vemurafenib (n=66), var den objektive responsrate 15%. 
Among patients who had progressed on vemurafenib (n=66), the objective response rate was 15%.
Cotellic bruges til at behandle voksne patienter med en bestemt form for hudkræft, melanom, som har spredt sig til andre dele af kroppen eller ikke kan fjernes ved en operation. 
Cotellic is used to treat adult patients with a type of skin cancer called melanoma, that has spread to other parts of the body or cannot be removed by surgery.
Bedste overordnede respons Komplet respons Partielt respons Stabil sygdom 
Best Overall Response (BOR) Complete Response Partial Response
Dosisjustering er ikke nødvendig til patienter ≥ 65 år. 
No dose adjustment is required in patients aged ≥65 years old.
Der findes én pakningsstørrelse: 63 tabletter (3 blistere med 21 tabletter). 
One pack size is available: 63 tablets (3 blisters of 21 tablets).
Svær diarré kan forårsage væsketab (dehydrering). 
Severe diarrhoea can cause loss of body fluid (dehydration).
Det kan øge mængden af Cotellic i blodet. 
This is because it could increase the amount of Cotellic in your blood.
· Lægen har ordineret dette lægemiddel dig personligt. 
· This medicine has been prescribed for you only.
Score fra alle funktionsområder og de fleste symptomer (appetitmangel, obstipation, kvalme og opkastning, dyspnø, smerter, træthed) viste at den gennemsnitlige ændring fra baseline var sammenlignelig i de to behandlingsarme og viste ingen klinisk betydningsfuld ændring ( alle score havde ≤10 points ændring i forhold til baseline). 
Scores for all functioning domains and most symptoms (appetite loss, constipation, nausea and vomiting, dyspnoea, pain, fatigue) showed that the mean change from baseline was similar between the two treatment arms and did not demonstrate a clinically meaningful change (all scores were ≤ 10 point change from baseline).
Følg lægens anvisning om, hvordan diarréen kan forhindres eller behandles. 
Follow your doctor's instructions for what to do to help prevent or treat diarrhoea.
I studie GO28141 var 89 patienter (18,1%) i alderen 65-74 år, 38 patienter (7,7%) i alderen 75-84 år og 5 patienter (1,0%) 85 år og ældre. 
In Study GO28141, there were 89 patients (18.1%) aged 65-74, 38 patients (7.7%) aged 75-84 and 5 patients (1.0%) aged 85 years and older.
Når Cotellic tages sammen med vemurafenib (som virker på det muterede BRAF-protein), vil det yderligere nedsætte eller stoppe væksten af kræftcellerne. 
When Cotellic is used in combination with vemurafenib (which targets the changed “BRAF” protein), it further slows down or stops the growth of your cancer.
Cobimetinib er en potentiel inducer af CYP1A2 in vitro og kan derfor nedsætte eksponeringen af substrater for dette enzym, f.eks. theophyllin. 
In vitro, cobimetinib is a potential inducer of CYP1A2 and may therefore reduce the exposure of substrates of this enzyme e.g., theophylline.
Tag medicinpakningen og denne indlægsseddel med. 
Take the medicine package and this leaflet with you.
Kontakt lægen, inden du tager Cotellic, hvis du får: Medicin eller aktivt indholdsstof 
Talk to your doctor before taking Cotellic if you are taking: Medicine or active substance
Cotellic indeholder lactose 
Cotellic contain lactose
Figur 1 Kaplan-Meier kurver over den endelige samlede overlevelse - intent-to-treat- population (cut-off dato: 28. august 2015) 
Figure 1 Kaplan-Meier curves of final overall survival - Intent to treat population (cut-off date: 28 August 2015)
Blandt de 63 patienter, der ikke tidligere havde fået BRAF-hæmmer, havde 20 patienter tidligere fået systemisk behandling for fremskredent melanom, størstedelen (80%) immunterapi. 
Among the 63 BRAFi naïve patients, 20 patients had received prior systemic therapy for advanced melanoma with the majority (80%) being immunotherapy.
Oxidering via CYP3A og glukuronidering via UGT2B7 synes at være de primære metaboliseringsveje for cobimetinib. 
Oxidation by CYP3A and glucuronidation by UGT2B7 appear to be the major pathways of cobimetinib metabolism.
Den kardiovaskulære sikkerhed af cobimetinib i kombination med vemurafenib er ikke evalueret in vivo. 
Cardiovascular safety of cobimetinib in combination with vemurafenib has not been evaluated in vivo.
Samtidig brug af moderate og potente CYP3A-inducerer (fx carbamazepin, rifampicin, phenytoin og perikon) bør derfor undgås. 
Therefore, concomitant use of moderate and strong CYP3A inducers (e.g. carbamazepine, rifampicin, phenytoin, and St. John's Wort) should be avoided.
Cotellic kan påvirke din evne til at køre motorkøretøj eller anvende maskiner. 
Cotellic can affect your ability to drive or use machines.
Bivirkningsfrekvenserne er baseret på sikkerhedsanalyser hos patienter behandlet med cobimetinib plus vemurafenib med median opfølgning på 11, 2 måneder (data cut-off dato 19. september 2014). 
ADR frequencies are based upon the safety analysis of patients treated with cobimetinib plus vemurafenib with a median follow up of 11.2 months (data cut-off date of 19 September 2014).
De bivirkninger, der er indberettet hos melanompatienter, angives nedenfor i overensstemmelse med MedDRA's organklassesystem og efter hyppighed og sværhedsgrad. 
ADRs which were reported in melanoma patients are listed below by MedDRA body system organ class, frequency and grade of severity.
Grad 2 (intolerabel) eller grad 3 /4 1. 
Grade 2 (intolerable) or Grade 3/4 1st Appearance
Efter en oral dosis på 60 mg til kræftpatienter har cobimetinib en moderat absorptionshastighed med en median Tmax på 2,4 timer. 
Following oral dosing of 60 mg in cancer patients, cobimetinib showed a moderate rate of absorption with a median Tmax of 2.4 hours.
Der er ingen erfaring med overdosering fra kliniske studier med mennesker. 
There is no experience with overdose in human clinical trials.
Tabel 3 angiver bivirkninger, der vurderes at være forbundet med brug af Cotellic. 
Table 3 lists adverse reactions considered associated with the use of Cotellic.
Den absolutte biotilgængelighed af cobimetinib er 45,9% (90% konfidensinterval: 39,7%; 53,1%) hos raske frivillige. 
The absolute bioavailability of cobimetinib was 45.9% (90% CI: 39.7%, 53.1%) in healthy subjects.
De fleste af disse bivirkninger, der blev observeret i kliniske forsøg, forsvandt eller forbedredes til asymptomatisk grad 1 efter behandlingsafbrydelse eller dosisreduktion. 
Most events observed in clinical trials were resolved, or improved to asymptomatic Grade 1, following dose interruption or reduction.
Diarré skal håndteres med midler mod diarré og understøttende behandling. 
Diarrhoea should be managed with anti-diarrhoeal agents and supportive care.
Samtidig administration af P-gp-hæmmere som ciclosporin og verapamil kan potentielt øge plasmakoncentrationen af cobimetinib. 
Concomitant administration of P-gp inhibitors such as ciclosporin and verapamil may have the potential to increase plasma concentrations of cobimetinib.
De patienter, der ikke tidligere havde fået BRAF-hæmmer (n꞊63), opnåede en objektiv responsrate på 87%, inklusive komplet respons hos 16% af patienterne. 
The BRAFi-naïve patients (n=63) attained an 87% objective response rate, including a complete response in 16% of patients.
Sensitivitetsanalyser har dog ikke vist, at disse covariater har klinisk signifikant betydning for eksponeringen ved steady-state. 
However, sensitivity analysis suggests neither of these covariates had clinically significant impact on steady state exposure.
Hver dosis består af 3 tabletter på 20 mg (60 mg) og skal tages én gang dagligt i 21 på hinanden følgende dage (dag 1-21 behandlingsperiode), efterfulgt af 7 dages pause (dag 22-28 behandlingspause). 
Each dose consists of three 20 mg tablets (60 mg) and should be taken once daily for 21 consecutive days (Days 1 to 21-treatment period); followed by a 7-day break (Days 22 to 28-treatment break).
I et toksicitetsstudie med gentagne doser hos unge rotter var den systemiske eksponering af cobimetinib 2-11 gange højere på postnatal dag 10 end på postnatal dag 38, hvor eksponeringen svarede til den hos voksne rotter. 
In a repeat dose toxicity study in juvenile rats, cobimetinib systemic exposures were 2 to11 fold higher on post natal day 10 than on post natal day 38 when exposures were similar to those in adult rats.