natgillin/translations-raw huggingface dataset:
Oralt administreret dimethylfumarat undergår en hurtig præsystemisk hydrolyse ved hjælp af esteraser og omdannes til dets primære metabolit, monomethylfumarat, som også er aktivt.
Orally administered dimethyl fumarate undergoes rapid presystemic hydrolysis by esterases and is converted to its primary metabolite, monomethyl fumarate, which is also active.
Skulle der være klinisk mistanke om PML, skal MR-skanning foretages med det samme til diagnostisk formål.
In case of clinical suspicion of PML, MRI should be performed immediately for diagnostic purposes.
Tecfidera kan påvirke antallet af hvide blodlegemer, dine nyrer og din lever.
Tecfidera may affect your white blood cell counts, your kidneys and liver.
I gennemsnit faldt lymfocyttallene cirka 30% under baselineværdien.
On average, lymphocyte counts decreased by approximately 30% of baseline value.
Patienter med alvorlige infektioner bør ikke starte behandling med Tecfidera, før infektionen/infektionerne er overstået.
Patients with serious infections should not start treatment with Tecfidera until the infection(s) is resolved.
Gennem hele behandlingsperioden (120 uger) var den årlige attakrate 0,2, hvilket udgør en 84,5% relativ reduktion i attakker (n=20; 95% CI [66,8, 92,8], p < 0,0001) sammenlignet med året inden behandlingsstart.
Over the full treatment period (120-week), ARR was 0.2 representing an 84.5% relative reduction in relapses (n=20; 95% CI [66.8, 92.8], p<0.0001), when compared to the year prior to treatment initiation.
Andre cirkulerende metabolitter inkluderede fumarsyre, citronsyre og monomethylfumarat.
Other circulating metabolites included fumaric acid, citric acid and monomethyl fumarate.
Den øgede hyppighed af forhøjede leveraminotransferaser hos patienter behandlet med Tecfidera i forhold til placebo sås primært i de første 6 måneder af behandlingen.
The increased incidence of elevations of hepatic transaminases in patients treated with Tecfidera relative to placebo was primarily seen during the first 6 months of treatment.
Kapslen eller dens indhold må ikke knuses, deles, opløses, suttes eller tygges, da mikrotabletternes syreresistente overtræk forebygger gastrointestinal irritation.
The capsule or its contents should not be crushed, divided, dissolved, sucked or chewed as the enteric-coating of the microtablets prevents irritant effects on the gut.
Downstream-metaboliseringen af fumarsyre sker gennem tricarboxylsyrecyklussen med CO2-udskillelse som den primære eliminationsvej.
The downstream metabolism of fumaric acid occurs through the tricarboxylic acid cycle, with exhalation of CO2 serving as a primary route of elimination.
I sjældne tilfælde kan der forekomme hypofosfatæmisk osteomalaci med ikke-lokaliserede knoglesmerter, forhøjet alkalisk fosfatase i serum og stress-frakturer.
In rare cases hypophosphataemic osteomalacia with nonlocalised bone pain, elevated alkaline phosphatase in serum and stress fractures may occur.
Rødme beskrives sædvanligvis som rødme eller hedestigning, men kan inkludere andre gener (f.eks. varme, rødlige pletter, kløe og brændende fornemmelse).
Flushing is usually described as flushing or hot flush, but can include other events (e.g. warmth, redness, itching, and burning sensation).
På baggrund af de videnskabelige konklusioner for dimethylfumarat (multipel sklerose) er CHMP af den opfattelse, at benefit/risk-forholdet for det lægemiddel/de lægemidler, der indeholder dimethylfumarat (multipel sklerose), forbliver uændret under forudsætning af, at de foreslåede ændringer indføres i produktinformationen.
On the basis of the scientific conclusions for dimethyl fumarate (multiple sclerosis) the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing dimethyl fumarate (multiple sclerosis) is unchanged subject to the proposed changes to the product information.
Symptomerne kan inkludere ny eller forværret svaghed i den ene side af kroppen, klodsethed, synsændringer, ændret tankevirksomhed eller hukommelse, forvirring eller personlighedsforandringer, der varer mere end nogle dage.
Symptoms may include new or worsening weakness on one side of the body; clumsiness; changes in vision, thinking, or memory; or confusion or personality changes lasting for more than several days.
Relevansen af disse fund for risikoen hos mennesker kendes ikke.
The relevance of these findings to human risk is unknown.
Fire procent (4%) af patienterne behandlet med Tecfidera afbrød behandlingen pga. gastrointestinale hændelser.
Four per cent (4%) of patients treated with Tecfidera discontinued due to gastrointestinal events.
Studie 2 inkluderede glatirameracetat som undersøgelsesblindet (dvs. at den studieansvarlige læge/investigatoren, der vurderede responsen på studiebehandlingen, var blindet) referencekomparator.
Study 2 contained a rater-blinded (i.e. study physician/ investigator assessing the response to study treatment was blinded) reference comparator of glatiramer acetate.
Disse tilfælde kan forekomme når som helstunder behandlingen.
These events may occur at any time during treatment.
Patienter med progressiv multipel sklerose deltog ikke i disse studier.
Subjects with progressive forms of MS were not included in these studies.
Det vides ikke, om det aktive stof i Tecfidera udskilles i modermælk.
It is not known whether the active substance of Tecfidera passes into breast milk.
Herpes zoster-infektioner
Herpes zoster infections
Baseret på kliniske, farmakologiske studier er dosisjustering ikke nødvendig (se pkt.
Based on clinical pharmacology studies, no dose adjustments are needed (see section 5.2).
Dimethylfumarat demonstrerede terapeutisk aktivitet i flere modeller med inflammatoriske eller neuroinflammatoriske skader.
Dimethyl fumarate demonstrated therapeutic activity in multiple models of inflammatory and neuroinflammatory injury.
Dette resulterede i en minimal eksponeringsakkumulation, som gav en stigning i den mediane Cmax på 12% sammenlignet med dosering to gange dagligt (1,72 mg/l for dosering to gange dagligt sammenlignet med 1,93 mg/l for dosering tre gange dagligt) uden sikkerhedsimplikationer.
This resulted in a minimal accumulation of exposure yielding an increase in the median Cmax of 12% compared to the twice daily dosing (1.72 mg/l for twice daily compared to 1.93 mg/l for three times daily) with no safety implications.
Patienterne fik 120 mg Tecfidera to gange dagligt i 7 dage efterfulgt af 240 mg to gange dagligt i 24 uger.
Subjects received Tecfidera 120 mg twice a day for 7 days followed by 240 mg twice a day for 24 weeks.
Vurdering af nyrefunktion (f.eks. kreatinin, blodureanitrogen og urinundersøgelse) anbefales inden behandlingsstart, 3 og 6 måneder efter behandlingsstart og derefter hver 6. til 12. måned samt på klinisk indikation.
Assessment of renal function (e.g. creatinine, blood urea nitrogen and urinalysis) is recommended prior to treatment initiation, after 3 and 6 months of treatment, every 6 to 12 months thereafter and as clinically indicated.
Hos mennesker metaboliseres dimethylfumarat i vidt omfang, og under 0,1% af dosis udskilles som umetaboliseret dimethylfumarat i urinen.
In humans, dimethyl fumarate is extensively metabolised with less than 0.1% of the dose excreted as unchanged dimethyl fumarate in urine.
Der blev ikke observereret misdannelser ved nogen dosis af dimethylfumarat hos rotter eller kaniner.
No malformations were observed at any dose of dimethyl fumarate in rats or rabbits.
Det er vist, at dimethylfumarat opregulerer Nrf2afhængige antioxidantgener hos patienter (f.eks. NAD(P)H-dehydrogenase, quinon 1; [NQO1]).
Dimethyl fumarate has been shown to up regulate Nrf2-dependent antioxidant genes in patients (e.g. NAD(P)H dehydrogenase, quinone 1; [NQO1]).
Kapselindhold (syreresistente mikrotabletter)
Capsule contents (enteric-coated microtablets)
Data fra prækliniske studier tyder ikke på, at dimethylfumarat er forbundet med en øget risiko for nedsat fertilitet (se pkt.
Data from preclinical studies do not suggest that dimethyl fumarate would be associated with an increased risk of reduced fertility (see section 5.3).
Der blev ikke observeret nogen negative kliniske konsekvenser i de kliniske forsøg.
No untoward clinical consequences were observed in clinical trials.
Der er ikke udført interaktionsstudier med orale præventionsmidler med andre progestogener, men det forventes ikke, at Tecfidera påvirker deres virkning.
No interaction studies have been performed with oral contraceptives containing other progestogens, however an effect of Tecfidera on their exposure is not expected.
Dimethylfumarats farmakokinetiske profil ved en dosis på 240 mg to gange dagligt blev evalueret i et lille, åbent, ikke kontrolleret studie med patienter i alderen 13 til 17 år med RRMS (n=21).
The pharmacokinetic profile of 240 mg dimethyl fumarate twice a day was evaluated in a small, openlabel, uncontrolled study in patients with RRMS aged 13 to 17 years (n=21).
Et kort behandlingsforløb med 75 mg acetylsalicylsyre uden entero-overtræk kan gavne patienter, der er påvirket af intolerabel rødme (se pkt.
A short course of treatment with 75 mg non-enteric coated acetylsalicylic acid may be beneficial in patients affected by intolerable flushing (see section 4.5).
Forekomsten af bivirkninger herunder udtrykkes i henhold til følgende kategorier: - Meget almindelig (≥ 1/10) - Almindelig (≥ 1/100 til < 1/10) - Ikke almindelig (≥ 1/1.000 til < 1/100) - Sjælden (≥ 1/10.000 til < 1/1.000) - Meget sjælden (< 1/10.000) - Ikke kendt (hyppighed kan ikke estimeres ud fra forhåndenværende data)
- Very common (≥1/10) - Common (≥1/100 to <1/10) - Uncommon (≥1/1, 000 to <1/100) - Rare (≥1/10, 000 to <1/1,000)
Kapslen må ikke deles, knuses, opløses, suttes eller tygges, idet dette kan øge hyppigheden af nogle af bivirkningerne.
Do not divide, crush, dissolve, suck or chew the capsule as this may increase some side effects.
Der er rapporteret tilfælde af overdosering med Tecfidera.
Cases of overdose with Tecfidera have been reported.
Forhøjede aminotransferaser ≥ 3 gange ULN med samtidige forhøjelser i totalt bilirubin > 2 gange ULN blev ikke observeret i placebokontrollerede studier.
Elevations in transaminases ≥3 times ULN with concomitant elevations in total bilirubin >2 times ULN, were not observed in placebo-controlled studies.
Tecfidera bør ikke anvendes under amning.
Tecfidera should not be used during breast-feeding.
Farmakokinetiske data er bestemt hos patienter med multipel sklerose og hos raske frivillige.
Pharmacokinetic data were obtained in subjects with multiple sclerosis and healthy volunteers.
Typiske symptomer forbundet med PML er forskellige, udvikles i løbet af dage eller uger og omfatter progressiv svaghed i den ene side af kroppen eller klodsethed af lemmer, synsforstyrrelser og ændret tankegang, hukommelse og orientering, hvilket fører til forvirring og personlighedsændringer.
Typical symptoms associated with PML are diverse, progress 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.
Dette kan medføre irritation i maven, især hos personer der allerede har tilbøjelighed til dette.
This could cause inflammation of the stomach (gastritis), especially in people already prone to gastritis.
MINDSTEKRAV TIL MÆRKNING PÅ BLISTER ELLER STRIP VARMEFORSEGLET BLISTERKORT
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS HEAT SEALED BLISTER CARD
Tecfidera er medicin, der indeholder det aktive stof dimethylfumarat.
Tecfidera is a medicine that contains the active substance dimethyl fumarate.
Lægemiddelinduceret leverskade, herunder forhøjede leverenzymer (≥ 3 øvre normalgrænse, upper limit of normal (ULN)) og forhøjede niveauer af totalt bilirubin (≥ 2 ULN), kan forekomme som følge af behandling med dimethylfumarat.
Drug-induced liver injury, including liver enzyme increase (≥ 3 upper limit of normal (ULN)) and elevation of total bilirubin levels (≥ 2 ULN) can result from treatment with dimethyl fumarate.
Dimethylfumarat er ikke blevet undersøgt hos patienter med eksisterende lave lymfocyttal, og der skal udvises forsigtighed ved behandling af disse patienter.
Dimethyl fumarate has not been studied in patients with pre-existing low lymphocyte counts and caution should be exercised when treating these patients.
I kliniske studier oplevede 3 ud af i alt 2.560 patienter behandlet med dimethylfumarat alvorlig rødme, der formodentlig var overfølsomheds- eller anafylaktoide reaktioner.
In clinical trials, 3 patients out of a total of 2,560 patients treated with dimethyl fumarate experienced serious flushing symptoms that were probable hypersensitivity or anaphylactoid reactions.
En tidlig diagnosticering af Fanconis syndrom og seponering af dimethylfumarat-behandlingen er vigtig for at forhindre opståen af nyreinsufficiens og osteomalaci, da syndromet normalt er reversibelt.
Early diagnosis of Fanconi syndrome and discontinuation of dimethyl fumarate treatment are important to prevent the onset of renal impairment and osteomalacia, as the syndrome is usually reversible.
Kaliumhydroxid Sort jernoxid (E172)
Potassium hydroxide Black iron oxide (E172)
Hvis rødmen ledsages af et rødt udslæt eller nældefeber, og du samtidig får et eller flere af følgende symptomer:
However, should flushing be accompanied by a red rash or hives and you get any of these symptoms:
I testis blev der observeret degeneration af det seminiferøse epitel hos rotter og hunde.
In the testes, degeneration of the seminiferous epithelium was seen in rats and dogs.
I kliniske studier med psoriasis-patienter påvirkede dimethylfumarat lymfocytfenotyper via en nedregulering af proinflammatoriske cytokinprofiler (TH1, TH17) og viste tendens til antiinflammatorisk produktion (TH2).
In clinical studies with psoriasis patients, dimethyl fumarate affected lymphocyte phenotypes through a down-regulation of pro-inflammatory cytokine profiles (TH1, TH17), and biased towards anti-inflammatory production (TH2).
In vitro-studier af CYP-induktion viste ikke interaktion mellem Tecfidera og p-piller.
In vitro CYP induction studies did not demonstrate an interaction between Tecfidera and oral contraceptives.
Der blev ikke identificeret potentielle risici for interaktion med andre lægemidler i in vitrostudier af CYP-hæmning og -induktion, et p-glykoprotein-studie eller studier af dimethylfumarats og monomethylfumarats proteinbinding (en primær metabolit af dimethylfumarat).
Potential drug interaction risks were not identified from in vitro CYP-inhibition and induction studies, a p-glycoprotein study, or studies of the protein binding of dimethyl fumarate and monomethyl fumarate (a primary metabolite of dimethyl fumarate).
Det er vist, at dimethylfumarat passerer placentamembranen ind i føtalt blod hos rotter og kaniner med ratio af føtal:maternel plasmakoncentration på henholdsvist 0,48-0,64 og 0,1.
Dimethyl fumarate has been shown to cross the placental membrane into fetal blood in rats and rabbits, with ratios of fetal to maternal plasma concentrations of 0.48 to 0.64 and 0.1 respectively.
Hos rotter var hyppigheden af renalt tubulært karcinom øget ved 100 mg/kg/dag, en omtrent 2 gange højere eksponering end ved den anbefalede humane dosis.
In rats, the incidence of renal tubular carcinoma was increased at 100 mg/kg/day, approximately 2 times higher exposure than the recommended human dose.
Indtagelse af mere end en lille mængde (mere end 50 ml) stærk alkohol (mere end 30 volumen%; f.eks. spiritus) skal undgås den første time efter indtagelse af Tecfidera, da alkohol kan interagere med denne medicin.
Consumption of more than a small quantity (more than 50 ml) of strong alcoholic drinks (more than 30% alcohol by volume, e.g. spirits) should be avoided within an hour of taking Tecfidera, as alcohol can interact with this medicine.
Efter 7 dage øges dosis til den anbefalede vedligeholdelsesdosis på 240 mg to gange dagligt (se pkt.
After 7 days, the dose should be increased to the recommended maintenance dose of 240 mg twice a day (see section 4.4).
Patienter med multipel sklerose fik to doser på 240 mg med 4 timers mellemrum som en del af et tre gange dagligt dosisregime.
In subjects with multiple sclerosis, two 240 mg doses were administered 4 hours apart as part of a three times a day dosing regimen.
Alvorlige gastrointestinale hændelser, herunder gastroenteritis og gastritis, blev set hos 1% af patienterne behandlet med Tecfidera (se pkt.
The incidence of serious gastrointestinal events, including gastroenteritis and gastritis, was seen in 1% of patients treated with Tecfidera (see section 4.2).
Efter administration af 240 mg to gange dagligt sammen med mad var den mediane peak-værdi (Cmax) 1,72 mg/l, og det totale areal under kurven (AUC) for eksponering var 8,02 timer∙mg/l hos patienter med multipel sklerose.
Following 240 mg twice a day administered with food, the median peak (Cmax) was 1.72 mg/l and overall area under the curve (AUC) exposure was 8.02 h.mg/l in subjects with multiple sclerosis.
I studie 1 havde patienterne følgende mediane baseline-værdier: Alder 39 år, sygdomsvarighed 7,0 år, EDSS-score 2,0.
In Study 1, patients had the following median baseline characteristics: age 39 years, disease duration 7.0 years, EDSS score 2.0.
I studie 2 havde patienterne følgende mediane baseline-værdier: Alder 37 år, sygdomsvarighed 6,0 år, EDSS-score 2,5.
In Study 2, patients had the following median baseline characteristics: age 37 years, disease duration 6.0 years, EDSS score 2.5.
Der blev set forhøjede alaninaminotransferase og aspartataminotransferase ≥ 3 gange ULN hos henholdsvis 5% og 2% af patienterne behandlet med placebo og hos 6% og 2% af patienterne behandlet med Tecfidera.
Elevations of alanine aminotransferase and aspartate aminotransferase ≥3 times ULN, respectively, were seen in 5% and 2% of patients treated with placebo and 6% and 2% of patients treated with Tecfidera.
5.1) skal det imidlertid overvejes at seponere behandlingen med Tecfidera, hvis patienten udvikler en alvorlig infection, og fordele og risici skal revurderes, før behandlingen genoptages.
However, due to Tecfidera immunomodulatory properties (see section 5.1), if a patient develops a serious infection, suspending treatment with Tecfidera should be considered and the benefits and risks should be reassessed prior to re-initiation of therapy.
Magnetisk resonansskanning (MR-skanning)
Magnetic Resonance imaging (MRI)
De hyppigste bivirkninger (≥ 10%) hos patienter behandlet med dimethylfumarat var rødme og gastrointestinale gener (dvs. diaré, kvalme, abdominalsmerter, smerter i den øverste del af abdomen).
The most common adverse reactions (incidence ≥10%) for patients treated with dimethyl fumarate were flushing and gastrointestinal events (i.e. diarrhoea, nausea, abdominal pain, abdominal pain upper).
Sammenlignet med placebo observeredes der hos patienter behandlet med Tecfidera en klinisk relevant og statistisk signifikant reduktion i det primære endepunkt i studie 1 - antal patienter med attakker efter 2 år - og i det primære endepunkt i studie 2 - årlig attakrate efter 2 år.
Compared to placebo, subjects treated with Tecfidera had a clinically meaningful and statistically significant reduction on: the primary endpoint in Study 1, proportion of subjects relapsed at 2 years; and the primary endpoint in Study 2, annualised relapse rate at 2 years.
Baseret på data fra placebokontrollerede studier havde størstedelen af de patienter, der oplevede en stigning, leveraminotransferaser, som lå under 3 gange den øvre normalgrænse (ULN).
Based on data from placebo-controlled studies, the majority of patients with elevations had hepatic transaminases that were <3 times the upper limit of normal (ULN).
En vurdering af niveauerne af serum-aminotransferaser (f.eks.alaninaminotransferase (ALAT), aspartataminotransferase (ASAT)) og totalt bilirubin anbefales før behandlingsstart og under behandlingen, efter klinisk indikation.
Assessment of serum aminotransferases (e.g. alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and total bilirubin levels are recommended prior to treatment initiation and during treatment as clinically indicated.
Der sås små numeriske forskelle i responset over for tetanustoksoid og pheumokok serotype 3-polysaccharid i ikke-pegyleret interferons favør.
Small numerical differences in the response to tetanus toxoid and pneumococcal serotype 3 polysaccharide were noted in favour of non-pegylated interferon.
Prækliniske studier indikerer, at dimethylfumarats farmakodynamiske respons formentlig primært sker via aktivering af transkriptionsfaktorens Nuclear Factor (erythroid-derived 2)Related Factor 2 (Nrf2) transkriptionsproces.
Preclinical studies indicate that dimethyl fumarate pharmacodynamic responses appear to be primarily mediated through activation of the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcriptional pathway.
Forhøjet alaninaminotransferase Almindelig Lægemiddelinduceret leverskade1
Aspartate aminotransferase increased Common Alanine aminotransferase increased Common Drug-induced liver injury1
Inden behandling med Tecfidera bør der foretages en aktuel komplet blodtælling, der inkluderer lymfocytter.
Prior to initiating treatment with Tecfidera, a current complete blood count, including lymphocytes, must be performed.
kan dette dog være tegn på en svær overfølsomhedsreaktion (anafylaksi)
then this may represent a severe allergic reaction (anaphylaxis)
Fundene blev observeret hos rotter ved omtrent den anbefalede dosis og hos hunde ved 3 gange den anbefalede dosis (baseret på AUC).
The findings were observed at approximately the recommended dose in rats and 3 times the recommended dose in dogs (AUC basis).
Tilfælde med anafylaksi/anafylaktoide reaktioner er blevet rapporteret efter administration af Tecfidera hos patienter efter markedsføringen.
Cases of anaphylaxis/anaphylactoid reaction have been reported following Tecfidera administration in the post-marketing setting.
Da nyrerne er en sekundær eliminationsvej for dimethylfumarat og står for under 16% af den administrerede dosis, blev der ikke foretaget nogen evaluering af farmakokinetikken hos individer med nyreinsufficiens.
Since the renal pathway is a secondary route of elimination for dimethyl fumarate accounting for less than 16% of the dose administered, evaluation of pharmacokinetics in individuals with renal impairment was not conducted.
Hyppigheden af gastrointestinale gener (f.eks. diaré [14% versus 10%], kvalme [12% versus 9%], øvre abdominalsmerter [10% versus 6%], abdominalsmerter [9% versus 4%], opkastning [8% versus 5%] og dyspepsi [5% versus 3%]) var højere hos de patienter, der fik Tecfidera, sammenlignet med placebo.
The incidence of gastrointestinal events (e.g. diarrhoea [14% versus 10%], nausea [12% versus 9%], upper abdominal pain [10% versus 6%], abdominal pain [9% versus 4%], vomiting [8% versus 5%] and dyspepsia [5% versus 3%]) was increased in patients treated with Tecfidera compared to placebo, respectively.
Relevansen af disse fund kendes ikke hos mennesker.
The relevance of these findings to humans is not known.
vanddrivende medicin (diuretika), visse typer smertestillende midler (såsom ibuprofen og andre lignende lægemidler mod gigt og medicin, som købes uden recept) og medicin, der indeholder lithium - vaccination med visse typer vacciner (levende, svækkede vacciner) under behandling med Tecfidera kan forårsage, at du får en infektion, og skal derfor undgås.
- medicines that affect the kidneys including some antibiotics (used to treat infections), “water tablets” (diuretics), certain types of painkillers (such as ibuprofen and other similar antiinflammatories and medicines purchased without a doctor's prescription) and medicines that contain lithium - Taking Tecfidera with certain types of vaccines (live vaccines) may cause you to get an infection and should, therefore, be avoided.
- hævelse af ansigt, læber, mund eller tunge (angioødem) - hivende vejrtrækning, vejrtrækningsbesvær eller kortåndethed (dypnø, hypoksi) - svimmelhed eller bevidstløshed (hypotension)
- swelling of the face, lips, mouth or tongue (angioedema) - wheezing, difficulty breathing or shortness of breath (dyspnoea, hypoxia) - dizziness or loss of consciousness (hypotension)