natgillin/translations-raw huggingface dataset:
Tabletterne må derfor ikke knuses, deles, opløses eller tygges.
Therefore, the tablets should not be crushed, divided, dissolved or chewed.
Biotransformationen af dimethylfumarat involverer ikke cytokrom P450-systemet isoenzymer.
The biotransformation of dimethyl fumarate does not involve cytochrome P450 isoenzymes.
Meget almindelig Meget almindelig Almindelig Almindelig Meget sjælden Meget sjælden
Very common Very common Common Common Very rare Very rare
E-08740 Sant Andreu de la Barca, Barcelona Spanien
E-08740 Sant Andreu de la Barca, Barcelona Spain
Der bør udvises forsigtighed ved ordination af lægemidler med et snævert terapeutisk indeks, som kræver absorption i tarmkanalen.
Caution should be exercised when prescribing medicinal products with a narrow therapeutic index that require absorption in the intestinal tract.
593, Sant Andreu de la Barca, Barcelona, 08740, Spanien
593, Sant Andreu de la Barca, Barcelona, 08740, Spain
Patienter bør gøres opmærksomme på, at de sandsynligvis vil opleve rødmen i de første få uger af behandlingen med Skilarence (se pkt.
Patients should be made aware that they are likely to experience flushing in the first few weeks of taking Skilarence (see section 4.8).
Risikofaktorer kan omfatte tidligere immunosuppressiv behandling og tilstedeværelse af visse samtidige lidelser (såsom visse autoimmune lidelser eller maligne hæmatologiske tilstande).
Risk factors can include previous immunosuppressive treatment and the existence of certain concomitant disorders (such as some autoimmune disorders or malignant haematological conditions).
Typiske symptomer forbundet med PML er meget forskellige, de forværres over nogle dage til uger, og omfatter tiltagende svaghed i den ene side af kroppen eller bevægeforstyrrelser, synsforstyrrelser og ændringer i tænkemåde, hukommelse og orientering, der fører til forvirring og personlighedsændringer.
Typical symptoms associated with PML are diverse, become worse over days to weeks and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision and changes in thinking, memory and orientation leading to confusion and personality changes.
I det placebokontrollerede kliniske fase III-studie sås der under behandlingen ingen påvirkning af nyrefunktionen på tværs af behandlingsgrupper.
During the Phase III placebo-controlled clinical trial, renal function was not seen to deteriorate during therapy across treatment groups.
Brug af Skilarence sammen med alkohol
Skilarence with alcohol
Nyren blev identificeret som et vigtigt målorgan for toksicitet i non-kliniske forsøg.
The kidney was identified as a major target organ of toxicity in non-clinical studies.
Det er vigtigt at foretage en tidlig diagnose af Fanconis syndrom og seponere Skilarence-behandlingen for at forhindre opståen af nedsat nyrefunktion og osteomalaci, da syndromet normalt er reversibelt.
Early diagnosis of Fanconi syndrome and discontinuation of Skilarence treatment are important to prevent the onset of renal impairment and osteomalacia, as the syndrome is usually reversible.
Specielt i det kliniske studie var der et mindre fald i middellymfocyttallet, startende mellem uge 3 og 5, og det nåede et maksimum i uge 12, hvor cirka en tredjedel af patienterne havde lymfocytværdier under 1,0x10
In particular, in the clinical study there was a slight decrease in mean lymphocyte counts starting between weeks 3 and 5 and reaching a maximum in week 12 where approximately one third of patients had lymphocyte values below 1.0x10
Nogle af disse bivirkninger, såsom rødfarvning af ansigt eller krop (rødmen), diarré, maveproblemer og kvalme, forbedres normalt, når du fortsætter behandlingen.
Some of these side effects, such as reddening of the face or body (flushing), diarrhoea, stomach problems and nausea usually improve as you continue treatment.
Se instruktionerne i indlægssedlen for det præventionsmiddel, du tager.
See the instructions in the patient leaflet of the contraceptive you are taking.
De fleste patienter berettede, at psoriasis havde en ”meget stor” eller ”ekstremt stor” effekt på deres liv baseret på DLQI indeks (valideret mål af livskvaliteten i psoriasis) med en gennemsnitlig DLQI-score på 11,5.
The majority of patients reported a “very large” or “extremely large” effect of psoriasis on their life based on the Dermatology Life Quality Index (DLQI), with a mean DLQI score of 11.5.
Det skal fremhæves, at Fanconis syndrom kan forekomme uden forhøjede kreatininniveauer eller lav glomerulær filtrationshastighed.
Importantly, Fanconi syndrome can occur without elevated creatinine levels or low glomerular filtration rate.
704 patienter blev randomiseret til at modtage Skilarence, en aktiv komparator (Funaderm, et kombinationsprodukt med samme indhold af dimethylfumarat plus 3 monoethylfumaratsalte) og placebo i forholdet 2:2:1.
704 patients were randomised to receive Skilarence, an active comparator (Fumaderm, a combination product with the same content of dimethyl fumarate plus 3 monoethyl fumarate salts) and placebo in a ratio of 2:2:1.
Når patienter skiftes over fra sådanne behandlinger til Skilarence, bør halveringstiden og virkningsmekanismen for den anden behandling overvejes for at undgå additiv indvirkning på immunsystemet.
When switching patients from such therapies to Skilarence, the half-life and mode of action of the other therapy should be considered in order to avoid additive effects on the immune system.
Fanconis syndrom er en sjælden, men alvorlig nyrelidelse, som kan forekomme med Skilarence.
Fanconi syndrome is a rare but serious kidney disorder which may occur with Skilarence.
Dimethylfumarat viser ikke nogen bindingsaffinitet over for serumproteiner, hvilket yderligere kan bidrage til dets hurtige eliminering i kredsløbet.
Dimethyl fumarate does not show any binding affinity to serum proteins which may further contribute to its rapid elimination from the circulation.
Hvis du opdager, du lader mere vand, er mere tørstig og drikker mere end normalt, dine muskler virker svagere, du brækker en knogle eller bare har ømhed og smerter, skal du hurtigst muligt tale med din læge, så det kan undersøges nærmere.
If you notice you are passing more urine, are more thirsty and drinking more than normal, your muscles seem weaker, you break a bone, or just have aches and pains, talk to your doctor as soon as possible so that this can be investigated further.
Hvis der er uklare symptomer, bør det overvejes, om det kan være Fanconis syndrom, og passende undersøgelser bør iværksættes.
In case of unclear symptoms Fanconi syndrome should be considered and appropriate examinations should be performed.
PGA=Physician's Global Assessment (Lægens overordnede vurdering); a Superioritet af Skilarence vs. Placebo med en forskel på 22,2 % for PASI 75 og 20,0 % for PGA-score klar eller næsten klar, overlegen Fumaderm vs placebo med en forskel på 25,0 % for PASI 75 og 24,4 % for PGA-scoren klar eller næsten klar; b Non-inferioritet af Skilarence vs Fumaderm med en forskel på -2,8 % for PASI 75 og -4,4 % for PGA-scoren klar eller næsten klar.
Placebo with a difference of 22.2% for PASI 75 and 20.0% for PGA score clear or almost clear, superiority of Fumaderm vs Placebo with a difference of 25.0% for PASI 75 and 24.4% for PGA score clear or almost clear; b Non-inferiority of Skilarence vs. Fumaderm with a difference of -2.8% for PASI 75 and -4.4% for PGA score clear or almost clear.
Tlf.: +34 93 291 30 00
Tel. +34 93 291 30 00
De mest alvorlige bivirkninger, der kan opstå med Skilarence, er allergiske reaktioner eller overfølsomhedsreaktioner; nyresvigt eller en nyresygdom kaldet Fanconis syndrom; eller en alvorlig hjerneinfektion kaldet progressiv multifokal leukoencefalopati (PML).
The most serious side effects that may occur with Skilarence are allergic or hypersensitivity reactions; kidney failure or a kidney disease called Fanconi syndrome; or a severe brain infection called progressive multifocal leukoencephalopathy (PML).
Sjældne bivirkninger (kan påvirke op til 1 ud af 1.000 personer): - allergisk hudreaktion
Rare side effects (may affect up to 1 in 1,000 people): - allergic skin reaction
Skilarence er ikke undersøgt hos patienter som har en eksisterende gastrointestinal sygdom.
Skilarence has not been studied in patients with pre-existing gastrointestinal disease.
I det kliniske studie oplevede i alt 20,8 % af patienterne, som fik Skilarence, rødmen, som var mild i de fleste tilfælde (se pkt.
In the clinical study a total of 20.8% of patients receiving Skilarence experienced flushing, which was mild in the majority of cases (see section 4.4).
Tosidet 99,24 % CI
Two-sided 99.24% CI
De mest almindelige bivirkninger, som er observeret med Skilarence i det kliniske fase III-studie (1102) hos psoriasispatienter, var gastrointestinale hændelser (62,7 %), rødmen (20,8 %) og lymfopeni (10,0 %).
The most common adverse reactions observed with Skilarence in the Phase III clinical study (1102) in psoriasis patients were gastrointestinal events (62.7%), flushing (20.8%) and lymphopenia (10.0%).
Tag ikke Skilarence - hvis du er allergisk over for dimethylfumarat eller et af de øvrige indholdsstoffer i dette lægemiddel (angivet i punkt 6) - hvis du har alvorlige problemer med din mave eller tarme - hvis du har alvorlige lever- eller nyreproblemer - hvis du er gravid eller ammer
Do not take Skilarence - if you are allergic to dimethyl fumarate or any of the other ingredients of this medicine (listed in section 6) - if you have severe problems with your stomach or intestines - if you have severe liver or kidney problems - if you are pregnant or breast-feeding
Mere end 90 % af disse diarréhændelser var af mild til moderat sværhedsgrad (se pkt.
More than 90% of these diarrhoea events were of mild to moderate severity (see section 4.4).
Indehaver af markedsføringstilladelsen Almirall, S.A.
Marketing Authorisation Holder Almirall, S.A.
Allerede eksisterende gastrointestinal sygdom
Pre-existing gastrointestinal disease
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultater af studier med Skilarence i alle undergrupper af den pædiatriske population med denne indikation (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with Skilarence in all subsets of the paediatric population in this indication (see section 4.2 for information on paediatric use).
Offentliggjorte kliniske erfaringer med dimethylfumarat-holdige produkter viser, at individuelle episoder af rødmen begynder kort tid efter at tabletterne er taget, og forsvinder inden for få timer.
Published clinical experience with dimethyl fumarate-containing products shows that individual episodes of flushing usually begin shortly after taking the tablets and resolve within a few hours.
I sjældne tilfælde kan der forekomme hypophosphatæmisk osteomalaci med ikke-lokaliserede knoglesmerter, forhøjet alkalisk fosfatase i serum samt stressfrakturer.
In rare cases hypophosphataemic osteomalacia with non-localised bone pain, elevated alkaline phosphatase in serum and stress fractures may occur.
I uge 16 havde patienter behandlet med Skilarence en lavere gennemsnitlig DLQI sammenlignet med placebo (5,4 vs. 8,8).
At week 16, patients treated with Skilarence had a lower mean DLQI compared to placebo (5.4 vs 8.8).
Vurderet ud fra dimethylfumarats farmakologiske egenskaber forventes der ikke at være behov for at foretage dosisjustering hos ældre.
Based on the pharmacology of dimethyl fumarate, a need for dose adjustment in the elderly is not expected.
Dimethylfumarat er påvist at krydse placentamembranen ind i det føtale blod i rotter.
Dimethyl fumarate has been shown to cross the placental membrane into foetal blood in rats.
Der er ingen beviser for, at Skilarence interagerer med cytochrom P450 og de mest almindelige effluxog optagelsestransportører, så der forventes ikke interaktioner med lægemidler, der metaboliseres eller transporteres af disse systemer (se pkt.
There is no evidence for Skilarence interaction with cytochrome P450 and the most common efflux and uptake transporters, thus no interactions are expected with medicinal products metabolised or transported by these systems (see section 5.2).
Under behandlingen skal der udføres en komplet blodtælling (med differentialtælling og trombocyttælling) hver 3. måned.
During treatment a complete blood count with differential should be performed every 3 months.
Fumaderm = Aktiv komparator, et kombinationsprodukt med samme indhold af dimethylfumarat plus 3 monoethylhydrogenfumaratsalte; n=number of patients with available data (antal patienter med tilgængelige data); N=number of patients in population (antal patienter i population); PASI=Psoriasis Area Severity Index;
Fumaderm = Active comparator, a combination product with the same content of dimethyl fumarate plus 3 monoethyl hydrogen fumarate salts; n=number of patients with available data; N=number of patients in population; PASI=Psoriasis Area Severity Index; PGA=Physician's Global Assessment; a Superiority of Skilarence vs.
Efter oral administration af en enkelt tablet Skilarence på 120 mg til raske forsøgspersoner opnåede monomethylfumarat plasma-peakkoncentrationer på omkring 1325 ng/ml og 1311 ng/ml i hhv. fastende eller mæt tilstand.
After oral administration of a single Skilarence 120 mg tablet in healthy subjects, monomethyl fumarate reached plasma peak concentrations of around 1325 ng/mL and 1311 ng/mL under fasted or fed conditions, respectively.
De anti-inflammatoriske og immunmodulerende virkninger af dimethylfumarat og dets metabolit monomethylfumarat er ikke fuldstændigt belyst, men menes hovedsagelig at skyldes interaktionen med den intracellulære reducerede glutathion i celler, der direkte indgår i patogenesen af psoriasis.
The anti-inflammatory and immunomodulating effects of dimethyl fumarate and its metabolite monomethyl fumarate are not fully elucidated but are thought to be mainly due to the interaction with the intracellular reduced glutathione of cells directly involved in the pathogenesis of psoriasis.
Hovedaktiviteten af dimethylfumarat og monomethylfumarat anses for at være immunmodulerende, hvilket resulterer i et skift i T-hjælpercellerne (Th) fra en Th1- og Th17-profil til en Th2-fænotype.
The main activity of dimethyl fumarate and monomethyl fumarate is considered to be immunomodulatory, resulting in a shift in T helper cells (Th) from the Th1 and Th17 profile to a Th2 phenotype.
Hvis du får alvorlig eller længerevarende diarré med Skilarence, vil anden medicin muligvis ikke virke så godt, som den burde.
If you get severe or prolonged diarrhoea with Skilarence, other medicines may not work as well as they should.
Yderligere studier har vist, at dimethylfumarat (og i mindre udstrækning monomethylfumarat) reagerer delvist med reduceret glutathion og danner en glutathion-addukt.
Further studies have shown that dimethyl fumarate (and to a lesser extent monomethyl fumarate) reacts partially with reduced glutathione forming a glutathioneadduct.
Skilarence-tabletter bruges til at behandle moderat til svær plaque psoriasis hos voksne.
Skilarence tablets are used to treat moderate to severe plaque psoriasis in adults.
Før påbegyndelse af behandling med Skilarence skal der foreligge en aktuel komplet blodtælling (herunder differentialtælling og trombocyttal).
Prior to initiating treatment with Skilarence, a current complete blood count (including differential blood count and platelet count) should be available.
(1,1 %) af de patienter, der startede med Skilarence.
3/279 (1.1%) of the patients started on Skilarence.
Hvad er Skilarence
What Skilarence is
Patienter påbegyndte behandling med tabletter indeholdende 30 mg/dag dimethylfumarat eller placebo med optitrering til maksimalt 720 mg/dag i begge aktive behandlingsarme som beskrevet i pkt.
Patients began treatment with tablets containing 30 mg/day dimethyl fumarate or placebo, titrating up to a maximum of 720 mg/day in both active treatment arms as described in section 4.2.
Efter at der er opnået klinisk relevant forbedring af hudlæsioner, bør det overvejes gradvist at reducere den daglige dosis Skilarence til den vedligeholdelsesdosis, som er nødvendig for den enkelte patient.
After clinically relevant improvement of the skin lesions has been achieved, consideration should be given to gradual reduction of the daily dose of Skilarence to the maintenance dose required by the individual.
Der er ikke foretaget undersøgelser af indflydelsen på evnen til at føre motorkøretøjer og betjene maskiner.
No studies on the ability to drive and use machines have been conducted.
• Vejledningen for sundhedspersonale skal indeholde følgende hovedelementer: o Relevant information om PML (f.eks. alvorlighed, sværhedsgrad, hyppighed, tid til start, reversibilitet af uønsket hændelse hvis relevant) o Oplysninger om population med højere risiko for PML o Oplysninger om, hvordan risikoen for PML minimeres gennem passende overvågning og behandling, herunder laboratorieovervågning af lymfocyt- og leukocyttælling før og under behandlingen samt kriterier for behandlingsophør o Vigtigste budskaber, som skal formidles under rådgivning af patienter
• The guide for healthcare professionals shall contain the following key elements: o Relevant information on PML (e.g. seriousness, severity, frequency, time to onset, reversibility of the AE as applicable) o Details of the population at higher risk for PML o Details on how to minimise the risk of PML through appropriate monitoring and management, including laboratory monitoring of lymphocyte and leukocyte prior to and during treatment, and criteria for treatment discontinuation o Key messages to convey in counselling of patients
Din dosis vil blive øget, hver uge, som vist i nedenstående tabel (skift til 120 mg Skilarence-tabletter fra uge 4 og frem).
Your dose will be increased every week as shown in the table below (switching to 120 mg Skilarence tablets from week 4 onwards).
Allergiske reaktioner eller overfølsomhedsreaktioner Allergiske reaktioner eller overfølsomhedsreaktioner er sjældne, men kan være meget alvorlige.
Allergic or hypersensitivity reactions are rare but may be very serious.
Slug Skilarence tabletterne hele med væske.
Swallow Skilarence tablets whole with liquid.
Hvis du har en alvorlig infektion, enten før behandlingen med Skilarence eller under behandlingen, vil din læge muligvis råde dig til ikke at tage Skilarence, før infektionen er opklaret.
If you have a serious infection, either before starting treatment with Skilarence or during treatment, your doctor may advise you not to take Skilarence until the infection has resolved.
Dosisændringer kan også være nødvendige, hvis der ses afvigelser i laboratorieværdier (se pkt.
Dosage modifications may also be necessary if abnormalities in laboratory parameters are observed (see section 4.4).
Opportunistiske infektioner/progressiv multifokal leukoencefalopati (PML) Tilfælde af opportunistiske infektioner, især af progressiv multifokal leukoencefalopati (PML) er blevet indberettet med andre dimethylfumarat-holdige produkter (se pkt.
Opportunistic infections/progressive multifocal leukoencephalopathy (PML) Cases of opportunistic infections, particularly of progressive multifocal leukoencephalopathy (PML) have been reported with other dimethyl fumarate-containing products (see section 4.8).
Aften af dimethylfumarat
Evening of dimethyl fumarate
Skilarence kan i mindre grad påvirke evnen til at føre motorkøretøj og betjene maskiner.
Skilarence may have a minor influence on the ability to drive and use machines.
Methacrylsyre - ethylacrylat copolymer (1:1) Talcum
Methacrylic acid-ethyl acrylate copolymer (1:1) Talc
På trods af den store variation mellem forsøgspersoner var den eksponering, som måltes som AUC og Cmax generelt proportional med dosis efter administration af en enkelt dosis på 4 x 30 mg dimethylfumarat-tabletter (samlet dosis på 120 mg) og 2 x 120 mg dimethylfumarat-tabletter (samlet dosis på 240 mg).
Despite the high inter-subject variability, the exposure measured as AUC and Cmax was generally dose-proportional after single dose administration of 4 x 30 mg dimethyl fumarate tablets (total dose of 120 mg) and 2 x 120 mg dimethyl fumarate tablets (total dose of 240 mg).
Den inflammatoriske cytokinproduktion reduceres med induktion af proapoptotiske aktivitet, hæmning af keratinocytproliferation, reduceret ekspression af adhæsionsmolekyler og formindsket inflammatorisk infiltrat i plaque psoriasis.
The inflammatory cytokine production is reduced with induction of proapoptotic events, inhibition of keratinocyte proliferation, reduced expression of adhesion molecules, and diminished inflammatory infiltrate within psoriatic plaques.
Tidligere og samtidig behandling med immunosuppressive eller immunmodulerende behandlinger Der findes begrænsede data om effekten og sikkerheden af Skilarence hos patienter, som tidligere er blevet behandlet med andre immunosuppressive eller immunmodulerende behandlinger.
Prior and concomitant treatment with immunosuppressive or immunomodulating therapies Limited data are available on the efficacy and safety of Skilarence in patients who have been previously treated with other immunosuppressive or immunomodulating therapies.
Der er ikke udført karcinogenicitetsforsøg med Skilarence.
No carcinogenicity studies have been performed for Skilarence.
Følgende er en liste over bivirkninger oplevet af patienter, der blev behandlet med Skilarence under det kliniske studie og med Fumaderm, et relateret lægemiddel, som indeholder dimethylfumarat samt andre fumarsyreestere.
The following is a list of adverse reactions experienced by patients treated with Skilarence during the clinical study and with Fumaderm, a related medicinal product containing dimethyl fumarate along with other fumaric acid esters.
Under den behandlingsfri opfølgning observeredes der lymfocytniveauer på <0,7x 10
During the treatment free follow up, lymphocyte levels of <0.7x 10
*Yderligere bivirkninger indberettet med Fumaderm, et relateret lægemiddel, som indeholder dimethylfumarat sammen med andre fumarsyreestere.
*Additional adverse reactions reported with Fumaderm, a related medicinal product containing dimethyl fumarate along with other fumaric acid esters.
Disse addukter blev påvist i dyreundersøgelser i tarmslimhinder hos rotter og i mindre grad i portåren.
These adducts were detected in animal studies in the intestinal mucosa of rats and to a smaller extent in portal vein blood.
Hæmatologiske forandringer
Haematological changes
Amning Det er ukendt, om dimethylfumarat/metabolitter udskilles i human mælk.
It is unknown whether dimethyl fumarate or its metabolites are excreted in human milk.
Skilarence er indiceret til behandling af moderat til svær plaque psoriasis hos voksne med behov for systemisk lægemiddelbehandling.
Skilarence is indicated for the treatment of moderate to severe plaque psoriasis in adults in need of systemic medicinal therapy.
For patienter med eksisterende klinisk relevante infektioner skal lægen afgøre, om behandlingen med Skilarence skal vente til infektionen er overstået.
For patients with pre-existing infections of clinical relevance, the physician should decide if treatment with Skilarence should only be initiated once the infection has resolved.
Ukonjugeret monomethylfumarat kan derimod påvises i plasma.
By contrast, unconjugated monomethyl fumarate is detectable in plasma.
Formålet med uddannelsesprogrammet er at informere sundhedspersonale om risikoen for alvorlige infektioner, primært opportunistiske infektioner, såsom progressiv multifokal leukoencefalopati (PML), og give vejledning om overvågning af lymfocyt- og leukocyttællingsabnormiteter.
The objectives of the educational programme are to inform health care professionals about the risk of serious infections, mainly opportunistic infections such as progressive multifocal leukoencephalopathy (PML), and to provide guidance on the monitoring of lymphocyte and leukocyte count abnormalities.
Skilarence 30 mg fås i pakninger indeholdende 42, 70 og 210 enterotabletter.
Skilarence 30 mg is available in packs containing 42, 70 and 210 gastro-resistant tablets.