FrancophonIA/ELRC3.0 huggingface dataset:
English: In a study in which leflunomide was given concomitantly with a triphasic oral contraceptive pill containing 30 µg ethinyloestradiol to healthy female volunteers, there was no reduction in contraceptive activity of the pill, and A771726 pharmacokinetics were within predicted ranges.
Danish: I et forsøg, hvor leflunomid blev givet samtidig med en trifasisk oral kontraceptionstablet indeholdende 30 µg ethinyløstradiol til raske frivillige kvinder, reduceredes præparatets kontraceptive effekt ikke, og farmakokinetikken af A771726 lå indenfor de forventede værdier.
English: Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Danish: Inden for hver enkelt frekvensgruppe er bivirkningerne opstillet i rækkefølge efter hvor alvorlige de er.
English: Leflunomide is metabolised to one primary (A771726) and many minor metabolites including TFMA (4-trifluoromethylaniline).
Danish: Leflunomid metaboliseres til 1 primær (A771726) og mange mindre væsentlige metabolitter herunder TFMA (4-trifluoromethylanilin).
English: The principal urinary metabolites were glucuronide products derived from leflunomide (mainly in 0 to 24 hour samples) and an oxanilic acid derivative of A771726.
Danish: De væsentligste metabolitter i urinen var glukoronidprodukter afledt af leflunomid (især opsamlet i tiden 0-24 timer) og et oxanilderivat af A771726.
English: If both plasma concentrations are below 0.02 mg/L, and after a waiting period of at least 3 months, the risk of foetal toxicity is very low.
Danish: Hvis begge plasmakoncentrationsmålinger er under 0,02 mg/l og efter en pause på mindst 3 måneder er risikoen for føtal toksicitet meget lille.
English: This may be reduced to a few weeks by taking certain medicines which speed up removal of Leflunomide Zentiva from your body.
Danish: Denne periode kan forkortes til få uger, hvis du tager visse lægemidler, som øger udskillelsen af Leflunomid Zentiva.
English: The long half-life of leflunomide should be considered when contemplating administration of a live attenuated vaccine after stopping Leflunomide Zentiva.
Danish: Den lange halveringstid af leflunomid skal tages i betragtning, når vaccination med levende svækket vaccine til patienter, som er stoppet med Leflunomid Zentiva, overvejes.
English: Repeated doses of A771726 had no effect on the pharmacokinetics of S-warfarin, indicating that A771726 is not an inhibitor or an inducer of CYP2C9.
Danish: Gentagne doser af A771726 havde ingen effekt på farmakokinetikken af S-warfarin, hvilket indikerer, at A771726 ikke hæmmer eller inducerer CYP2C9.
English: Following concomitant administration of a single dose of leflunomide to subjects receiving multiple doses of rifampicin (non-specific cytochrome P450 inducer) A771726 peak levels were increased by approximately 40%, whereas the AUC was not significantly changed.
Danish: Efter samtidig indgift af enkeltdoser af leflunomid til personer, som fik multiple doser af rifampicin (non-specifik cytochrom P450 inducer) steg peakværdierne af A771726 med ca. 40%, mens AUC ikke ændredes signifikant.
English: A771726 was still detectable in urine and faeces 36 days after a single administration.
Danish: A771726 kunne stadig genfindes i urin og fæces 36 dage efter indgift af enkeltdosis.
English: Management
Danish: Administration
English: Co-administration of teriflunomide with leflunomide is not recommended, as leflunomide is the parent compound of teriflunomide.
Danish: Samtidig anvendelse af teriflunomid og leflunomid anbefales ikke, da leflunomid er stamforbindelsen af teriflunomid.
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, sygeplejerske eller apoteket.
English: Blood and lymphatic system disorders Common:
Danish: Blod og lymfesystem Almindelig:
English: Colestyramine given orally at a dose of 8 g three times a day for 24 hours to three healthy volunteers decreased plasma levels of A771726 by approximately 40% in 24 hours and by 49% to 65% in 48 hours.
Danish: Colestyramin givet oralt i doser på 8 g 3 gange daglig i 1 døgn til 3 raske frivillige forsøgspersoner reducerede plasmakoncentrationen af A771726 med ca. 40% i løbet af 24 timer og 49-65% i løbet af 48 timer.
English: Women of childbearing potential must not take Leflunomide Zentiva without using reliable contraceptive measures.
Danish: Kvinder i den fødedygtige alder må ikke tage Leflunomid Zentiva, medmindre de anvender sikker prævention.
English: Consistent with extensive protein binding A771726 has a low apparent volume of distribution (approximately 11 litres).
Danish: I overensstemmelse med den udtalte proteinbinding har A771726 et lille fordelingsvolumen (ca. 11 liter).
English: Leflunomide Zentiva is contraindicated in patients with severe hypoproteinaemia or impairment of liver function (see section 4.3).
Danish: Leflunomid Zentiva er kontraindiceret til patienter med svær hypoproteinæmi eller nedsat leverfunktion (se pkt.
English: A pharmacokinetic interaction with oral contraceptives was observed with A771726 (see below).
Danish: En farmakokinetisk interaktion med orale antikonceptiva med A771726 blev observeret (se nedenfor).
English: Similarly, recent treatment with hepatotoxic or haematotoxic medicinal products (e.g. methotrexate) may result in increased side effects; therefore, the initiation of leflunomide treatment has to carefully be considered regarding these benefit/risk aspects and closer monitoring is recommended in the initial phase after switching.
Danish: På lignende måde kan nylig behandling med hepatotoksiske eller hæmatotoksiske lægemidler (f.eks. methotrexat) give flere bivirkninger, hvorfor iværksættelse af leflunomidbehandling skal nøje overvejes med hensyn til disse risiko/benefit aspekter og mere omhyggelig kontrol i den første periode efter præparatskiftet anbefales.
English: In human plasma, A771726 is extensively bound to protein (albumin).
Danish: I humant plasma er A771726 i udtalt grad proteinbundet (albumin).
English: In a small prospective study in women (n=64) who became inadvertently pregnant while taking leflunomide for no more than three weeks after conception and followed by a drug elimination procedure, no significant differences (p=0.13) were observed in the overall rate of major structural defects (5.4%) compared to either of the comparison groups (4.2% in the disease matched group [n=108] and 4.2% in healthy pregnant women [n=78]).
Danish: I en lille, prospektiv undersøgelse hos kvinder (n=64), som uforvarende blev gravide, mens de tog leflunomid (højst 3 uger efter undfangelse efterfulgt af en udvaskningsprocedure), blev ingen signifikante forskelle (p=0,13) observeret i den totale hyppighed af større misdannelser (5,4%) sammenlignet med de to sammenligningsgrupper (4,2% i sygdomsgruppen [n=108]) og 4,2% i gruppen med raske kvinder [n=78]).
English: Immune system disorders Common:
Danish: Immunsystemet: Almindelig:
English: • active rheumatoid arthritis as a "disease-modifying antirheumatic drug" (DMARD),
Danish: • aktiv reumatoid artrit som et sygdomsmodificerende antireumatisk middel ("Disease-Modifying
English: • Patients with impairment of liver function.
Danish: • Patienter med nedsat leverfunktion,
English: For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration should also be undertaken with caution.
Danish: For andre substrater af BCRP (f.eks. methotrexat, topotecan, sulfasalazin, daunorubicin, doxorubicin) og OATP-familien, især HMG-CoA reduktasehæmmere (f.eks. simvastatin, atorvastatin, pravastatin, methotrexat, nateglinid, repaglinid, rifampicin), bør samtidig administration også ske med forsigtighed.
English: In vitro inhibition studies in human liver microsomes suggest that cytochrome P450 (CYP) 1A2, 2C19 and 3A4 are involved in leflunomide metabolism.
Danish: In vitro hæmningsforsøg i humane levermikrosomer tyder på, at cytochrom P450 (CYP) 1A2, 2C19 og 3A4 er involverede i leflunomids metabolisering.
English: Studies with both hemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicate that A771726, the primary metabolite of leflunomide, is not dialysable.
Danish: Forsøg med både hæmodialyse og CAPD (Chronic ambulatory peritoneal dialysis) tyder på at A771726, den primære metabolit af leflunomid ikke kan dialyseres.
English: There were no adverse events reported in the majority of case reports of overdose.
Danish: I hovedparten af rapporterne om overdosering blev der ikke rapporteret bivirkninger.
English: In female mice an increased incidence, dose-dependent, of bronchiolo-alveolar adenomas and carcinomas of the lung was noted.
Danish: Hos hunmus sås en dosisafhængig øget forekomst af bronkiole-alveolære adenomer og lungecarcinomer.
English: Increased side effects may occur in case of recent or concomitant use of hepatotoxic or haematotoxic medicinal products or when leflunomide treatment is followed by such medicinal products without a washout period (see also guidance concerning combination with other treatments, section 4.4).
Danish: Et øget antal bivirkninger kan ses i tilfælde af nylig eller samtidig anvendelse af hepatotoksiske eller hæmatotoksiske lægemidler, eller såfremt leflunomidbehandlingen efterfølges af behandling med sådanne lægemidler uden forudgående udvaskningsperiode (se også vejledning vedrørende kombination med anden behandling, pkt.
English: If you are already taking a nonsteroidal anti-inflammatory drug (NSAID) and/or corticosteroids, you may continue to take them after starting Leflunomide Zentiva.
Danish: Hvis du allerede tager non-steroid antiinflammatorisk medicin (NSAID) og/eller kortikosteroider, kan du fortsætte med at tage dem, efter du er begyndt at tage Leflunomid Zentiva.
English: The following pharmacokinetic and pharmacodynamic interaction studies were conducted with A771726 (principal active metabolite of leflunomide).
Danish: Følgende farmakokinetiske og farmakodynamiske interaktionsforsøg blev udført med A771726 (primære aktive metabolit af leflunomid).
English: Effect on repaglinide (CYP2C8 substrate)
Danish: Effekt på repaglinid (CYP2C8 substrat)
English: Therefore, when co-administered with substrates of OAT3, such as cefaclor, benzylpenicillin, ciprofloxacin, indomethacin, ketoprofen, furosemide, cimetidine, methotrexate, zidovudine, caution is recommended.
Danish: Forsigtighed anbefales derfor ved samtidig administration med substrater af OAT3 såsom cefaclor, benzylpenicillin, ciprofloxacin, indomethacin, ketoprofen, furosemid, cimetidin, methotrexat og zidovudin.
English: Keep the bottle tightly closed.
Danish: Hold tabletbeholderen tæt tillukket.
English: Administration of activated charcoal (powder made into a suspension) orally or via nasogastric tube (50 g every 6 hours for 24 hours) has been shown to reduce plasma concentrations of the active metabolite A771726 by 37% in 24 hours and by 48% in 48 hours.
Danish: Indgift af aktivt kul (suspension ud fra pulver) oralt eller via sonde (50 g hver 6. time i 24 timer) har vist sig at reducere plasmakoncentrationen af den aktive metabolit, A771726, med 37% i løbet af 24 timer og med 48% i løbet af 48 timer.
English: Breast-feeding women must, therefore, not receive leflunomide.
Danish: Ammende kvinder må derfor ikke behandles med leflunomid.
English: severe anaphylactic/anaphylactoid reactions, vasculitis, including cutaneous necrotizing vasculitis
Danish: Meget sjælden: svære anafylaktiske/anafylaktoide reaktioner, vasculitis inklusive kutan nekrotiserende vasculitis.
English: In patients on leflunomide treatment presenting unexplained chronic diarrhoea appropriate diagnostic procedures should be performed.
Danish: Ved kronisk diarré af ukendt årsag i forbindelse med leflunomidbehandling skal patienten udredes med passende diagnostiske procedurer.
English: • colestyramine 8 g is administered 3 times daily for a period of 11 days,
Danish: • colestyramin 8 g 3 gange dagligt i 11 dage,
English: • Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.
Danish: • Patienter med svær hypoproteinæmi, f.eks. ved nefrotisk syndrom,
English: There is no dose adjustment recommended in patients with mild renal insufficiency.
Danish: Dosisjustering anbefales ikke til patienter med let nyreinsufficiens.
English: Recent or concurrent treatment with hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) may result in an increased risk of serious adverse reactions; therefore, the initiation of leflunomide treatment has to be carefully considered regarding these benefit/risk aspects.
Danish: Nylig eller samtidig behandling med hepatotoksiske eller hæmatotoksiske DMARD'er (f.eks. methotrexat) kan være forbundet med en øget risiko for alvorlige bivirkninger, hvorfor iværksættelse af leflunomidbehandling nøje må overvejes med hensyn til disse risiko/benefit aspekter.
English: 3 film-coated tablets
Danish: 3 filmovertrukne tabletter
English: The extent of leflunomide absorption is not affected if it is taken with food.
Danish: Absorptionen af leflunomid påvirkes ikke af samtidig fødeindtagelse.
English: Leflunomide was embryotoxic and teratogenic in rats and rabbits at doses in the human therapeutic range and exerted adverse effects on male reproductive organs in repeated dose toxicity studies.
Danish: Leflunomid er embryotoksisk og teratogent hos rotter og kaniner ved doser i det terapeutiske dosisinterval til mennesker og i toksicitetsforsøg med gentagen dosering er set bivirkninger på de mandlige forplantningsorganer.
English: It contains the active substance leflunomide.
Danish: Det indeholder det aktive stof leflunomid.
English: The main effects were anaemia, leucopenia, decreased platelet counts and panmyelopathy and reflect the basic mode of action of the compound (inhibition of DNA synthesis).
Danish: De primære virkninger er anæmi, leukopeni, fald i trombocyttal og panmyelopati, hvilket afspejler stoffets primære virkningsmekanisme (hæmning af DNA-syntesen).
English: Leflunomide is rapidly converted to the active metabolite, A771726, by first-pass metabolism (ring opening) in gut wall and liver.
Danish: Leflunomid omdannes hurtigt til den aktive metabolit, A771726, via ”first pass”-metabolisme (ringåbning) i tarmvæggen og leveren.
English: Tablet core:
Danish: Tabletbeholder:
English: The recommended maintenance dose is leflunomide 10 mg to 20 mg once daily depending on the severity (activity) of the disease.
Danish: Den anbefalede vedligeholdelsesdosis er 10-20 mg leflunomid en gang daglig afhængigt af sygdommens sværhedsgrad (aktivitet).
English: In case of ulcerative stomatitis, leflunomide administration should be discontinued.
Danish: I tilfælde af ulcerøs stomatit bør behandling med leflunomid seponeres.
English: Adverse events consistent with the safety profile for leflunomide were: abdominal pain, nausea, diarrhoea, elevated liver enzymes, anaemia, leucopenia, pruritus and rash.
Danish: Bivirkninger som var i overensstemmelse med sikkerhedsprofilen for leflunomid var: mavesmerter, kvalme, diarre, forhøjede leverenzymer, anæmi, leukopeni, kløe og udslæt.
English: All of these also resolved, 2 with continuation of both medicinal products and 3 after discontinuation of leflunomide.
Danish: Alle disse normaliseredes også, 2 efter fortsat behandling med begge lægemidler og 3 efter seponering af leflunomid.
English: Reliable contraception during treatment with leflunomide should also be guaranteed.
Danish: Der skal anvendes sikker kontraception under behandling med leflunomid.
English: METHOD AND ROUTE(S) OF ADMINISTRATION
Danish: ANVENDELSESMÅDE OG ADMINISTRATIONSVEJ (E)
English: Skin and subcutaneous tissue disorders Common:
Danish: Hud og subkutane væv Almindelig:
English: It is recommended that patients receiving leflunomide are not treated with colestyramine or activated powdered charcoal because this leads to a rapid and significant decrease in plasma A771726 (the active metabolite of leflunomide; see also section 5) concentration.
Danish: Det anbefales, at patienter i leflunomidbehandling ikke behandles med colestyramin eller aktivt kul, da det fremkalder et hurtig og markant fald i plasmakoncentrationen af A771726 (leflunomids aktive metabolit, se også pkt.
English: Men wishing to father a child should contact their doctor who may advise them to stop taking Leflunomide Zentiva and take certain medicines to remove Leflunomide Zentiva rapidly and sufficiently from their body.
Danish: Mænd der ønsker at få børn, skal kontakte lægen, der kan tilråde at stoppe med at tage Leflunomid Zentiva og ordinere bestemte typer medicin, der kan udrense Leflunomid Zentiva fra kroppen hurtigt og tilstrækkeligt.
English: Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomide Zentiva, as you need to ensure that all traces of Leflunomide Zentiva have left your body before trying to become pregnant.
Danish: Hvis du planlægger at blive gravid efter du er stoppet i behandling med Leflunomid Zentiva, skal du fortælle det til din læge forinden, da du skal kunne sikre dig, at alle spor af Leflunomid Zentiva i kroppen er væk før du forsøger at blive gravid.
English: Alternatively, 50 g of activated powdered charcoal is administered 4 times daily.
Danish: Alternativt administreres 50 g aktivt kul 4 gange dagligt.
English: Interaction studies with cimetidine (non-specific cytochrome P450 inhibitor) and rifampicin (non-specific cytochrome P450 inducer), indicate that in vivo CYP enzymes are involved in the metabolism of leflunomide only to a small extent.
Danish: Interaktionsforsøg med cimetidin (nonspecifik cytochrom P450 hæmmer) og rifampicin (non-specifik cytochrom P450 inducer) tyder på, at CYP enzymer in vivo kun er ansvarlig for en lille del af metaboliseringen af leflunomid.
English: colitis including microscopic colitis such as lymphocytic colitis, collagenous colitis, diarrhoea, nausea, vomiting, oral mucosal disorders (e.g., aphthous stomatitis, mouth ulceration), abdominal pain
Danish: colitis, herunder mikroskopisk colitis, såsom lymfocytær colitis, kollagenøs colitis, diarré, kvalme, opkastning, påvirkning af mundslimhinden (f.eks. aftøs stomatit, mundsår), abdominalsmerter
English: In a small (n=30) study with co-administration of leflunomide (10 to 20 mg per day) with methotrexate (10 to 25 mg per week) a 2- to 3-fold elevation in liver enzymes was seen on 5 of 30 patients.
Danish: I et mindre forsøg (n=30), hvor leflunomid (10-20 mg daglig) blev givet samtidig med methotrexat (10-25 mg ugentlig), sås en 2-3 gange forhøjelse af leverenzymer hos 5 ud af 30 patienter.
English: A pharmacodynamics interaction with warfarin was observed with A771726 in a clinical pharmacology study (see below).
Danish: En farmakodynamisk interaktion med warfarin blev observeret med A771726 i et klinisk farmakologisk forsøg (se nedenfor).
English: Washout procedure
Danish: Udvaskningsprocedure
English: anorexia, weight loss (usually insignificant), asthenia
Danish: anoreksi, vægttab (sædvanligvis ubetydeligt), asteni
English: Interstitial lung disease, as well as rare cases of pulmonary hypertension have been reported during treatment with leflunomide (see section 4.8).
Danish: Interstitiel lungesygdom samt sjældne tilfælde af pulmonal hypertension er rapporteret under behandling med leflunomid (se pkt.
English: Thereafter, the A771726 plasma concentration must be determined again after an interval of at least 14 days.
Danish: Plasmakoncentrationen af A771726 måles derefter igen efter en periode på mindst 14 dage.
English: There are no specific data on the risk of male-mediated foetal toxicity.
Danish: Der er ingen specifikke oplysninger om risikoen for føtal toksicitet overført fra mandlig partner.
English: The use of leflunomide with antimalarials used in rheumatic diseases (e.g. chloroquine and hydroxychloroquine), intramuscular or oral gold, D-penicillamine, azathioprine and other immunosuppressive agents including Tumour Necrosis Factor alpha-Inhibitors has not been adequately studied up to now in randomised trials (with the exception of methotrexate, see section 4.5).
Danish: Samtidig anvendelse af leflunomid og antimalariamidler, som benyttes ved reumatiske sygdomme (f.eks. chloroquin og hydroxychloroquin), intramuskulært eller oralt guld, Penicillamin, azathioprin og andre immunsuppressive lægemidler, inklusive tumor nekrosis faktor alfa-hæmmere er på nuværende tidspunkt ikke tilstrækkeligt undersøgt i randomiserede forsøg (dog undtaget methotrexat, se pkt.
English: As soon as skin and/or mucosal reactions are observed which raise the suspicion of such severe reactions, Leflunomide Zentiva and any other possibly associated treatment must be discontinued, and a leflunomide washout procedure initiated immediately.
Danish: Så snart der ses hud- og/eller slimhindereaktioner, som giver mistanke om sådanne alvorlige reaktioner, skal Leflunomid Zentiva og alle øvrige behandlinger, som kan give sådanne reaktioner, seponeres, og leflunomid udvaskningsprocedure skal straks påbegyndes.
English: • Breast-feeding women (see section 4.6).
Danish: • Ammende kvinder (se pkt.
English: hepatitis, jaundice/cholestasis
Danish: hepatitis, gulsot, kolestase.
English: Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide.
Danish: Sjældne tilfælde af svær leverskade, heraf nogle letalt forløbende, har været rapporteret i forbindelse med behandling med leflunomid.
English: In such cases re-exposure to leflunomide is contraindicated (see section 4.3).
Danish: I sådanne situationer er fornyet behandling med leflunomid kontraindiceret (se pkt.
English: The information provided in the Physician Leaflet should provide information on dose reduction, discontinuation and wash out procedures.
Danish: Folderen skal oplyse om dosisreduktion, seponering samt udvaskningsprocedure.
English: - an increase in the numbers of blood cells called eosinophiles (eosinophilia); mild decrease in the number of white blood cells (leucopenia); decrease in the number of all blood cells
Danish: - stigning i antallet af såkaldte eosinofile blodceller, et svagt fald i antallet af hvide blodlegemer
English: Tell your doctor immediately and stop taking Leflunomide Zentiva: - if you experience weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic reaction, - if you develop a skin rash or ulcers in your mouth, as these may indicate severe, sometimes life-threatening reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section
Danish: Fortæl omgående lægen, og stop med at tage Leflunomid Zentiva: - hvis du oplever svaghed, føler dig ør i hovedet eller svimmel, eller har åndedrætsbesvær, da disse symptomer kan være tegn på en alvorlig allergisk reaktion - hvis du får udslæt, eller mundsår, da disse kan være tegn på alvorlige, nogle gange livstruende reaktioner (f.eks. Stevens-Johnsons syndrom, toksisk epidermisk nekrolyse, erythema multiforme, lægemiddelreaktion med eosinofili og systemiske symptomer [DRESS]), se punkt
English: An in vivo interaction study with leflunomide and cimetidine (non-specific weak cytochrome P450 (CYP) inhibitor) has demonstrated a lack of a significant impact on A771726 exposure.
Danish: Et in vivo interaktionsforsøg med leflunomid og cimetidin (non-specifik svag cytochrom P450 (CYP) hæmmer) viste ikke signifikant indvirkning på A771726 eksponering.
English: It has been shown in man that administration of an oral suspension of activated powdered charcoal or colestyramine leads to a rapid and significant increase in A771726 elimination rate and decline in plasma concentrations (see section 4.9).
Danish: Indgift af en oral suspension af aktivt kul eller colestyramin til mennesker fører til en hurtig og markant øgning i eliminationen af A771726 og fald i plasmakoncentrationen (se pkt.
English: General disorders and administration site conditions Common:
Danish: Almene symptomer og reaktioner på administrationsstedet Almindelig: