FrancophonIA/ELRC3.0 huggingface dataset:
English: In patients with rheumatoid arthritis, no pharmacokinetic interaction between the leflunomide (10 to 20 mg per day) and methotrexate (10 to 25 mg per week) was demonstrated.
Croatian: U bolesnika s reumatoidnim artritisom nisu zabilježene farmakokinetičke interakcije između leflunomida (10 do 20 mg na dan) i metotreksata (10 do 25 mg na tjedan).
English: Effect on caffeine (CYP1A2 substrate)
Croatian: Učinak na kofein (CYP1A2 supstrat)
English: Swallow the tablet whole and with plenty of water.
Croatian: Tabletu treba progutati cijelu s većom količinom vode.
English: The measurement of ionised calcium levels might show falsely decreased values under treatment with leflunomide and/or teriflunomide (the active metabolite of leflunomide) depending on the type of ionised calcium analyser used (e.g. blood gas analyser).
Croatian: Interferencija pri utvrđivanju razina ioniziranog kalcija Mjerenje razina ioniziranog kalcija može pokazati lažno smanjene vrijednosti kod liječenja leflunomidom i/ili teriflunomidom (aktivnim metabolitom leflunomida) ovisno o vrsti korištenog analizatora ioniziranog kalcija (npr. analizator plina u krvi).
English: Similar studies showed that ibuprofen and diclofenac did not displace A771726, whereas the unbound fraction of A771726 is increased 2- to 3-fold in the presence of tolbutamide.
Croatian: Slična ispitivanja pokazala su da ibuprofen i diklofenak ne istiskuju A771726, dok je nevezana frakcija A771726 povećana 2 do 3 puta u prisutnosti tolbutamida.
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.
Croatian: Ponovljene doze A771726 nisu imale učinak na farmakokinetiku S-varfarina, što ukazuje da A771726 nije niti inhibitor ni induktor CYP2C9.
English: Co-administration of teriflunomide with leflunomide is not recommended, as leflunomide is the parent compound of teriflunomide.
Croatian: Istodobna primjena teriflunomida s leflunomidom se ne preporučuje, s obzirom da je leflunomid ishodišni spoj teriflunomida.
English: Alanine aminotransferase (ALT) or serum glutamopyruvate transferase (SGPT) and a complete blood cell count, including a differential white blood cell count and a platelet count, must be checked simultaneously and with the same frequency:
Croatian: Alanin aminotransferazu (ALT) ili serumsku glutamopiruvat transferazu (SGPT) i kompletnu krvnu sliku, uključujući diferencijalnu bijelu krvnu sliku i broj trombocita, mora se provjeravati istodobno i u jednakim intervalima:
English: In a carcinogenicity study in mice an increased incidence of malignant lymphoma occurred in males of the highest dose group, considered to be due to the immunosuppressive activity of leflunomide.
Croatian: U ispitivanjima karcinogenosti u miševa zabilježena je povećana incidencija malignog limfoma u mužjaka koji su primali najviše doze, što se pripisuje imunosupresivnom djelovanju leflunomida.
English: Leflunomide Zentiva is contraindicated in pregnancy(see section 4.3).
Croatian: Leflunomide Zentiva je kontraindiciran u trudnoći (vidjeti dio 4.3).
English: A771726 was still detectable in urine and faeces 36 days after a single administration.
Croatian: A771726 se još mogao otkriti u mokraći i stolici 36 dana nakon primjene jedne doze.
English: It is possible that rapidly lowering the blood level of the active metabolite, by instituting the drug elimination procedure described below, at the first delay of menses may decrease the risk to the foetus from leflunomide.
Croatian: Naime, brzo smanjenje koncentracije aktivnog metabolita leflunomida u krvi uvođenjem u nastavku opisanog postupka eliminacije lijeka pri prvom kašnjenju menstruacije može smanjiti rizik za fetus.
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.
Croatian: Glavni metaboliti u mokraći bili su glukuronidi proizašli iz leflunomida (uglavnom u uzorcima od 0 do 24 sata) i derivati oksanilne kiseline A771726.
English: Leflunomide was studied in a single multicenter, randomized, double-blind, active-controlled trial in 94 patients (47 per arm) with polyarticular course juvenile rheumatoid arthritis.
Croatian: Leflunomid je ispitivan u jednom multicentričnom, randomiziranom, dvostruko slijepom, aktivno kontroliranom kliničkom ispitivanju na 94 bolesnika (47 po skupini) s poliartikularnim oblikom juvenilnog reumatoidnog artritisa.
English: This is thought to be achieved by a gastrointestinal dialysis mechanism and/or by interrupting enterohepatic recycling.
Croatian: Smatra se da se taj učinak postiže gastrointestinalnom dijalizom i/ili prekidom enterohepatičke recirkulacije.
English: In these studies, the clinical effect was closely related to the plasma concentration of A771726 and to the daily dose of leflunomide.
Croatian: U tim ispitivanjima klinički učinak bio je usko povezan s koncentracijom A771726 u plazmi i dnevnom dozom leflunomida.
English: If you have to be vaccinated, ask your doctor for advice.
Croatian: Ako se trebate cijepiti, posavjetujte se sa svojim liječnikom.
English: The Marketing Authorisation Holder (MAH) shall ensure that, prior to launch, all physicians who are expected to prescribe/use Leflunomide Zentiva are provided with a physician educational pack containing the following:
Croatian: Nositelj odobrenja za stavljanje lijeka u promet dužan je, prije stavljanja lijeka u promet, osigurati da svi liječnici koji bi mogli propisivati/upotrebljavati lijek Leflunomide Zentiva dobiju edukacijski komplet za liječnike koji sadrži sljedeće:
English: If you are pregnant or become pregnant while taking Leflunomide Zentiva, the risk of having a baby with serious birth defects is increased.
Croatian: Ako ste trudni ili zatrudnite dok uzimate lijek Leflunomide Zentiva, rizik od pojave ozbiljnih prirođenih mana u Vašeg djeteta je povećan.
English: In patients with pre-existing anaemia, leucopenia, and/or thrombocytopenia as well as in patients with impaired bone marrow function or those at risk of bone marrow suppression, the risk of haematological disorders is increased.
Croatian: U bolesnika s postojećom anemijom, leukopenijom i/ili trombocitopenijom, kao i u bolesnika s oštećenom funkcijom koštane srži ili rizikom od supresije koštane srži, povećan je rizik od pojave hematoloških poremećaja.
English: The ACR (American College of Rheumatology) response rates in study YU203 were 27.7% for placebo, 31.9% for 5 mg, 50.5% for 10 mg and 54.5% for 25 mg/day.
Croatian: American College of Rheumatology, ACR) u ispitivanju YU203 iznosile su 27,7% za placebo, 31,9% za 5 mg/dan, 50,5% za 10 mg/dan i 54,5% za 25 mg/dan.
English: Due to a potential for additive hepatotoxic effects, it is recommended that alcohol consumption be avoided during treatment with leflunomide.
Croatian: Zbog mogućnosti dodatnog hepatotoksičnog učinka tijekom liječenja leflunomidom preporučuje se izbjegavati uzimanje alkohola.
English: If a waiting period of up to approximately 2 years under reliable contraception is considered unpractical, prophylactic institution of a washout procedure may be advisable.
Croatian: Ako nije moguće čekati 2 godine uz odgovarajuću kontracepciju, preporučuje se profilaktički započeti postupak ispiranja.
English: Therefore, when warfarin is co-administered, close INR follow-up and monitoring is recommended.
Croatian: Stoga, kod istodobne primjene varfarina, preporučuje se pomno praćenje i nadzor INR-a.
English: Imprint on one side: ZBO.
Croatian: Utisnuta oznaka na jednoj strani: ZBO.
English: pancytopenia (probably by antiproliferative mechanism), leucopenia (leucocytes <2 G/L), eosinophilia
Croatian: pancitopenija (vjerojatno povezana s antiproliferativnim mehanizmom djelovanja), leukopenija (leukociti < 2 g/l), eozinofilija Vrlo rijetko: agranulocitoza
English: The initial period was followed by an open label maintenance period of three months, during which both groups received leflunomide 20 mg daily.
Croatian: Nakon početnog razdoblja uslijedilo je otvoreno ispitivanje doze održavanja u trajanju od tri mjeseca, tijekom kojeg su obje skupine dobivale luflonamid u dozi od 20 mg na dan.
English: Elimination of A771726 is slow and characterised by an apparent clearance of about 31 ml/hr.
Croatian: Eliminacija A771726 je spora i karakterizirana je prividnim klirensom od oko 31 ml/sat.
English: Moreover, switching from leflunomide to another DMARD without following the washout procedure (see section 4.4) may also increase the risk of serious adverse reactions even for a long time after the switching.
Croatian: Osim toga, prijelaz s leflunomida na neki drugi DMARD bez provedbe postupka ispiranja ("washout") leflunomida (vidjeti dio 4.4) također može povećati rizik od ozbiljnih nuspojava, čak i dulje vrijeme nakon promjene lijeka.
English: Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide.
Croatian: Rijetki slučajevi teškog oštećenja jetre, uključujući slučajeve sa smrtnim ishodom, zabilježeni su tijekom liječenja leflunomidom.
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.
Croatian: Za ostale supstrate BCRP (npr. metotreksat, topotekan, sulfasalazin, daunorubicin, doksorubicin) i OATP porodice, osobito inhibitore HMG-CoA reduktaze (npr. simvastatin, atorvastatin, pravastatin, metotreksat, nateglinid, repaglinid, rifampicin), istodobna primjena se također mora provoditi uz oprez.
English: Most patients improved after discontinuation of leflunomide.
Croatian: Stanje se popravilo u većine bolesnika nakon prekida terapije leflunomidom.
English: It is recommended that monitoring of liver enzymes be maintained after discontinuation of leflunomide treatment, until liver enzyme levels have normalised.
Croatian: Preporučuje se kontrola jetrenih enzima nakon prekida liječenja sve dok se njihova razina ne normalizira.
English: The Physician Leaflet should contain the following key messages:
Croatian: • Uputu za liječnika Uputa za liječnika treba sadržavati sljedeće ključne poruke:
English: Therefore, when such toxicities occur or if for any other reason A771726 needs to be cleared rapidly from the body, the washout procedure has to be followed.
Croatian: Stoga, pri pojavi tih toksičnosti ili potrebe za brzim uklanjanjem A771726 iz organizma zbog bilo kojeg drugog razloga treba obaviti postupak ispiranja ("washout").
English: Leflunomide is metabolised to one primary (A771726) and many minor metabolites including TFMA (4-trifluoromethylaniline).
Croatian: Leflunomid se metabolizira u jedan glavni (A771726) i više manjih metabolita, uključujući TFMA (4-trifluorometilanilin).
English: In vitro plasma protein binding interaction studies with warfarin at clinically relevant concentrations, however, showed no interaction.
Croatian: Međutim, u in vitro ispitivanjima interakcija s varfarinom kod vezanja za proteine plazme nisu zabilježene interakcije pri klinički relevantnim koncentracijama.
English: The pharmacokinetics of A771726 following oral administration of leflunomide have been investigated in 73 paediatric patients with polyarticular course Juvenile Rheumatoid Arthritis (JRA) who ranged in age from 3 to 17 years.
Croatian: Farmakokinetika A771726 nakon peroralne primjene leflunomida ispitivana je u 73 pedijatrijska bolesnika u dobi od 3 do 17 godina s poliartikuliranim oblikom juvenilnog reumatoidnog artritisa (JRA).
English: Your doctor may perform tests to see if you have tuberculosis.
Croatian: Vaš liječnik može provesti testove kako bi ustanovio imate li tuberkulozu. - ako ste muškarac i želite postati otac.
English: The usual starting dose of Leflunomide Zentiva is one 100 mg tablet once daily for the first three days.
Croatian: Uobičajena početna doza lijeka Leflunomide Zentiva je jedna tableta od 100 mg jedanput na dan tijekom prva 3 dana.
English: Therefore, monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.
Croatian: Stoga, preporučuje se praćenje bolesnika koji istodobno uzimaju lijekove koji se metaboliziraju uz CYP2C8, kao što su repaglinid, paklitaksel, pioglitazon ili roziglitazon, zbog moguće povećane izloženosti lijeku.
English: Patients were 3-17 years of age with active polyarticular course JRA regardless of onset type and naive to methotrexate or leflunomide.
Croatian: Bolesnici su bili u dobi između 3 i 17 godina, imali su aktivni poliartikularni oblik juvenilnog reumatoidnog artritisa, bez obzira na tip nastupa bolesti, i do tada nisu primali metotreksat ili leflunomid.
English: The metabolic biotransformation of leflunomide to A771726 and subsequent metabolism of A771726 is not controlled by a single enzyme and has been shown to occur in microsomal and cytosolic cellular fractions.
Croatian: Metaboličku biotransformaciju leflunomida u A771726 i naknadni metabolizam A771726 ne kontrolira samo jedan enzim, a pokazalo se da se odvija u mikrosomalnim i citosolnim staničnim dijelovima.
English: The principal faecal component was A771726.
Croatian: Glavna komponenta u stolici bio je A771726.
English: In multiple dose studies in patients with rheumatoid arthritis, the pharmacokinetic parameters of A771726 were linear over the dose range of 5 to 25 mg.
Croatian: U ispitivanjima višekratnih doza u bolesnika s reumatoidnim artritisom farmakokinetički parametri A771726 bili su linearni u rasponu doza od 5 do 25 mg.
English: Packs of 30, 50 and 100 tablets are available.
Croatian: Dostupna su pakiranja od 30, 50 i 100 tableta.
English: Effect of other medicinal products on leflunomide:
Croatian: Učinak drugih lijekova na leflunomid:
English: In the event that severe, uncontrolled infections occur, it may be necessary to interrupt leflunomide treatment and administer a washout procedure as described below.
Croatian: U slučaju pojave teških nekontroliranih infekcija može biti potrebno prekinuti primjenu leflunomida i započeti postupak ispiranja, kako je opisano u nastavku teksta.
English: Leflunomide is effective in animal models of arthritis and of other autoimmune diseases and transplantation, mainly if administered during the sensitisation phase.
Croatian: Leflunomid je učinkovit na životinjskim modelima artritisa i ostalih autoimunih bolesti te transplantacije, uglavnom ako se primjenjuje u fazi senzibilizacije.
English: Symptoms of rheumatoid arthritis include inflammation of joints, swelling, difficulty moving and pain.
Croatian: Simptomi reumatoidnog artritisa uključuju upalu i oticanje zglobova, otežano kretanje i bolove.
English: Binding of A771726 appeared slightly reduced and more variable in plasma from patients with rheumatoid arthritis or chronic renal insufficiency.
Croatian: Vezanje A771726 blago je smanjeno i varijabilnije u plazmi bolesnika s reumatoidnim artritisom ili kroničnom insuficijencijom bubrega.
English: Effect on warfarin (CYP2C9 substrate)
Croatian: Učinak na varfarin (CYP2C9 supstrat)
English: Thereafter, the A771726 plasma concentration must be determined again after an interval of at least 14 days.
Croatian: Nakon toga koncentracija A771726 u plazmi mora se ponovo utvrditi nakon intervala od najmanje 14 dana.
English: Haematological reactions
Croatian: Hematološke reakcije
English: Due to the very long half-life of A771726 (approximately 2 weeks), a loading dose of 100 mg for 3 days was used in clinical studies to facilitate the rapid attainment of steady-state levels of A771726.
Croatian: Zbog veoma dugog poluvijeka A771726 (približno 2 tjedna) u kliničkim je ispitivanjima primjenjivana udarna doza od 100 mg tijekom 3 dana kako bi se ubrzalo postizanje koncentracija A771726 u stanju dinamičke ravnoteže.
English: However, also following either of the washout procedures, verification by 2 separate tests at an interval of at least 14 days and a waiting period of one-and-a-half months between the first occurrence of a plasma concentration below 0.02 mg/L and fertilisation is required.
Croatian: Međutim, nakon primjene bilo kojeg od navedenih postupaka ispiranja, potrebno je provjeriti koncentraciju u plazmi na osnovi 2 testa provedena u razmaku od najmanje 14 dana i uz razdoblje čekanja od najmanje mjesec i pol između prvog nalaza koncentracije u plazmi niže od 0,02 mg/l i začeća.
English: Adverse events consistent with the safety profile for leflunomide were: abdominal pain, nausea, diarrhoea, elevated liver enzymes, anaemia, leucopenia, pruritus and rash.
Croatian: Nuspojave u skladu sa sigurnosnim profilom leflunomida bile su: bol u abdomenu, mučnina, proljev, povišene vrijednosti jetrenih enzima, anemija, leukopenija, pruritus i osip.
English: Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product Characteristics, section 4.2).
Croatian: Lijek se izdaje na ograničeni recept (vidjeti Dodatak I: Sažetak opisa svojstava lijeka, dio 4.2).
English: Leflunomide Zentiva tablets are for oral use.
Croatian: Leflunomide Zentiva tablete namijenjene su za peroralnu primjenu.
English: Rare:
Croatian: Rijetko:
English: Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/.
Croatian: Detaljnije informacije o ovom lijeku dostupne su na internetskoj stranici Europske agencije za lijekove http://www.ema.europa.eu/.
English: The following pharmacokinetic and pharmacodynamic interaction studies were conducted with A771726 (principal active metabolite of leflunomide).
Croatian: Sljedeća farmakokinetička i farmakodinamička ispitivanja interakcija provedena su za A771726 (glavni aktivni metabolit leflunomida).
English: Therefore, the plausibility of observed decreased ionised calcium levels needs to be questioned in patients under treatment with leflunomide or teriflunomide.
Croatian: Stoga, potrebno je preispitati vjerodostojnost opaženih smanjenih razina ioniziranog kalcija u bolesnika koji se liječe leflunomidom ili teriflunomidom.
English: Symptoms of active psoriatic arthritis include inflammation of joints, swelling, difficulty moving, pain and patches of red, scaly skin (skin lesions).
Croatian: Simptomi aktivnog psorijatičnog artritisa uključuju upalu i oticanje zglobova, otežano kretanje, bol i područja crvene, ljuskaste kože (kožne lezije).
English: In the case of side effects such as dizziness the patient's ability to concentrate and to react properly may be impaired.
Croatian: U slučaju pojave nuspojava, poput omaglice, može biti oslabljena bolesnikova sposobnost koncentracije i reagiranja.
English: However, a 25% decrease in peak international normalised ratio (INR) was observed when A771726 was co-administered with warfarin as compared with warfarin alone.
Croatian: Ipak, primjećeno je 25%-tno smanjenje vršne vrijednosti internacionalnog normaliziranog omjera (INR) kod istodobne primjene A771726 s varfarinom, u usporedbi s monoterapijom varfarinom.
English: In responders, this response was maintained during 48 weeks (see section 4.2).
Croatian: U bolesnika u kojih je zabilježen odgovor na liječenje on se održao kroz 48 tjedana (vidjeti dio 4.2).
English: Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/.
Croatian: Detaljnije informacije o ovom lijeku dostupne su na internetskoj stranici Europske agencije za lijekove http://www.ema.europa.eu/
English: Imprint on one side: ZBN.
Croatian: Utisnuta oznaka na jednoj strani: ZBN.
English: There is no dose adjustment recommended in patients with mild renal insufficiency.
Croatian: Nema preporuka za prilagodbu doze u bolesnika s blagom bubrežnom insuficijencijom.
English: Metabolism and nutrition disorders Common:
Croatian: Poremećaji metabolizma i prehrane Često:
English: elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin)
Croatian: povišene vrijednosti jetrenih enzima (transaminaze [posebno ALT], rjeđe gama-GT, alkalne fosfataze, bilirubina)
English: severe anaphylactic/anaphylactoid reactions, vasculitis, including cutaneous necrotizing vasculitis
Croatian: Vrlo rijetko: teške anafilaktične/anafilaktoidne reakcije, vaskulitis, uključujući kožni nekrotizirajući vaskulitis
English: Leflunomide was administered as a single oral 100 mg dose to 3 haemodialysis patients and 3 patients on continuous peritoneal dialysis (CAPD).
Croatian: Jednu oralnu dozu od 100 mg leflunomida primila su 3 hemodijalizirana bolesnika i 3 bolesnika na kontinuiranoj peritonealnoj dijalizi (CAPD).
English: • The identified risk of synergistic hepato- or haematotoxicity associated with combination therapy with another Disease-Modifying Antirheumatic Drug (e.g. methotrexate).
Croatian: • Prepoznat rizik od sinergije između hepatotoksičnosti ili hematotoksičnosti i kombinirane terapije s nekim drugim antireumatikom koji modificira tijek bolesti (primjerice metotreksatom).
English: These processes may be affected by hepatic dysfunction.
Croatian: Jetrena disfunkcija može utjecati na te procese.
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.
Croatian: Preporučuje se da se bolesnici koji uzimaju leflunomid ne liječe kolestiraminom ili aktivnim ugljenom u prahu jer oni uzrokuju brzo i značajno smanjenje koncentracije A771726 (aktivnog metabolita leflunomida; vidjeti dio 5.) u plazmi.
English: The pharmacokinetics of A771726 in CAPD subjects appeared to be similar to healthy volunteers.
Croatian: Farmakokinetika A771726 u bolesnika na kontinuiranoj peritonealnoj dijalizi bila je slična onoj u zdravih dobrovoljaca.
English: Effect on repaglinide (CYP2C8 substrate)
Croatian: Učinak na repaglinid (CYP2C8 supstrat)
English: Leflunomide Zentiva is contraindicated in patients with severe hypoproteinaemia or impairment of liver function (see section 4.3).
Croatian: Leflunomide Zentiva je kontraindiciran u bolesnika s teškom hipoproteinemijom ili oštećenom jetrenom funkcijom (vidjeti dio 4.3).
English: As leflunomide has a long persistence in the body, a switching to another DMARD (e.g. methotrexate) without performing the washout procedure (see below) may raise the possibility of additive risks even for a long time after the switching (i.e. kinetic interaction, organ toxicity).
Croatian: Kako se leflunomid dugo zadržava u tijelu, prijelaz na neki drugi DMARD (npr. metotreksat) bez provođenja postupka ispiranja („washout“) (vidjeti nastavak teksta) može povećati mogućnost pojave dodatnih rizika, čak i dugo nakon promjene lijeka (npr. kinetička interakcija, organska toksičnost).
English: • For psoriatic arthritis: 20 mg Leflunomide Zentiva once daily.
Croatian: • Za psorijatični artritis: 20 mg lijeka Leflunomide Zentiva jedanput na dan.
English: Repeated oral administration of leflunomide to mice for up to 3 months, to rats and dogs for up to 6 months and to monkeys for up to 1 month's duration revealed that the major target organs for toxicity were bone marrow, blood, gastrointestinal tract, skin, spleen, thymus and lymph nodes.
Croatian: Ponavljana oralna primjena leflunomida na miševima do tri mjeseca, štakorima i psima do 6 mjeseci te majmunima do jednog mjeseca pokazala je da je toksičnost najočitija na koštanoj srži, krvi, gastrointestinalnom sustavu, koži, slezeni, timusu i limfnim čvorovima.
English: A more rapid elimination of A771726 was observed in haemodialysis subjects which was not due to extraction of medicinal product in the dialysate.
Croatian: Znatno brža eliminacija A771726 zapažena je u hemodijaliziranih bolesnika, što nije bilo povezano s ekstrakcijom lijeka u dijalizat.