natgillin/translations-raw huggingface dataset:
The initial period was followed by an open label maintenance period of three months, during which both groups received leflunomide 20 mg daily. 
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.
Elimination of A771726 is slow and characterised by an apparent clearance of about 31 ml/hr. 
Eliminacija A771726 je spora i karakterizirana je prividnim klirensom od oko 31 ml/sat.
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. 
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.
Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide. 
Rijetki slučajevi teškog oštećenja jetre, uključujući slučajeve sa smrtnim ishodom, zabilježeni su tijekom liječenja leflunomidom.
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. 
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.
Most patients improved after discontinuation of leflunomide. 
Stanje se popravilo u većine bolesnika nakon prekida terapije leflunomidom.
It is recommended that monitoring of liver enzymes be maintained after discontinuation of leflunomide treatment, until liver enzyme levels have normalised. 
Preporučuje se kontrola jetrenih enzima nakon prekida liječenja sve dok se njihova razina ne normalizira.
The Physician Leaflet should contain the following key messages: 
• Uputu za liječnika Uputa za liječnika treba sadržavati sljedeće ključne poruke:
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. 
Stoga, pri pojavi tih toksičnosti ili potrebe za brzim uklanjanjem A771726 iz organizma zbog bilo kojeg drugog razloga treba obaviti postupak ispiranja ("washout").
Leflunomide is metabolised to one primary (A771726) and many minor metabolites including TFMA (4-trifluoromethylaniline). 
Leflunomid se metabolizira u jedan glavni (A771726) i više manjih metabolita, uključujući TFMA (4-trifluorometilanilin).
In vitro plasma protein binding interaction studies with warfarin at clinically relevant concentrations, however, showed no interaction. 
Međutim, u in vitro ispitivanjima interakcija s varfarinom kod vezanja za proteine plazme nisu zabilježene interakcije pri klinički relevantnim koncentracijama.
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. 
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).
Your doctor may perform tests to see if you have tuberculosis. 
Vaš liječnik može provesti testove kako bi ustanovio imate li tuberkulozu. - ako ste muškarac i želite postati otac.
The usual starting dose of Leflunomide Zentiva is one 100 mg tablet once daily for the first three days. 
Uobičajena početna doza lijeka Leflunomide Zentiva je jedna tableta od 100 mg jedanput na dan tijekom prva 3 dana.
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. 
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.
Patients were 3-17 years of age with active polyarticular course JRA regardless of onset type and naive to methotrexate or leflunomide. 
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.
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. 
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.
The principal faecal component was A771726. 
Glavna komponenta u stolici bio je A771726.
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. 
U ispitivanjima višekratnih doza u bolesnika s reumatoidnim artritisom farmakokinetički parametri A771726 bili su linearni u rasponu doza od 5 do 25 mg.
Packs of 30, 50 and 100 tablets are available. 
Dostupna su pakiranja od 30, 50 i 100 tableta.
Effect of other medicinal products on leflunomide: 
Učinak drugih lijekova na leflunomid:
In the event that severe, uncontrolled infections occur, it may be necessary to interrupt leflunomide treatment and administer a washout procedure as described below. 
U slučaju pojave teških nekontroliranih infekcija može biti potrebno prekinuti primjenu leflunomida i započeti postupak ispiranja, kako je opisano u nastavku teksta.
Leflunomide is effective in animal models of arthritis and of other autoimmune diseases and transplantation, mainly if administered during the sensitisation phase. 
Leflunomid je učinkovit na životinjskim modelima artritisa i ostalih autoimunih bolesti te transplantacije, uglavnom ako se primjenjuje u fazi senzibilizacije.
Symptoms of rheumatoid arthritis include inflammation of joints, swelling, difficulty moving and pain. 
Simptomi reumatoidnog artritisa uključuju upalu i oticanje zglobova, otežano kretanje i bolove.
Binding of A771726 appeared slightly reduced and more variable in plasma from patients with rheumatoid arthritis or chronic renal insufficiency. 
Vezanje A771726 blago je smanjeno i varijabilnije u plazmi bolesnika s reumatoidnim artritisom ili kroničnom insuficijencijom bubrega.
Effect on warfarin (CYP2C9 substrate) 
Učinak na varfarin (CYP2C9 supstrat)
Thereafter, the A771726 plasma concentration must be determined again after an interval of at least 14 days. 
Nakon toga koncentracija A771726 u plazmi mora se ponovo utvrditi nakon intervala od najmanje 14 dana.
Haematological reactions 
Hematološke reakcije
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. 
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.
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. 
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.
Adverse events consistent with the safety profile for leflunomide were: abdominal pain, nausea, diarrhoea, elevated liver enzymes, anaemia, leucopenia, pruritus and rash. 
Nuspojave u skladu sa sigurnosnim profilom leflunomida bile su: bol u abdomenu, mučnina, proljev, povišene vrijednosti jetrenih enzima, anemija, leukopenija, pruritus i osip.
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product Characteristics, section 4.2). 
Lijek se izdaje na ograničeni recept (vidjeti Dodatak I: Sažetak opisa svojstava lijeka, dio 4.2).
Leflunomide Zentiva tablets are for oral use. 
Leflunomide Zentiva tablete namijenjene su za peroralnu primjenu.
Rare: 
Rijetko:
Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/. 
Detaljnije informacije o ovom lijeku dostupne su na internetskoj stranici Europske agencije za lijekove http://www.ema.europa.eu/.
The following pharmacokinetic and pharmacodynamic interaction studies were conducted with A771726 (principal active metabolite of leflunomide). 
Sljedeća farmakokinetička i farmakodinamička ispitivanja interakcija provedena su za A771726 (glavni aktivni metabolit leflunomida).
Therefore, the plausibility of observed decreased ionised calcium levels needs to be questioned in patients under treatment with leflunomide or teriflunomide. 
Stoga, potrebno je preispitati vjerodostojnost opaženih smanjenih razina ioniziranog kalcija u bolesnika koji se liječe leflunomidom ili teriflunomidom.
Symptoms of active psoriatic arthritis include inflammation of joints, swelling, difficulty moving, pain and patches of red, scaly skin (skin lesions). 
Simptomi aktivnog psorijatičnog artritisa uključuju upalu i oticanje zglobova, otežano kretanje, bol i područja crvene, ljuskaste kože (kožne lezije).
In the case of side effects such as dizziness the patient's ability to concentrate and to react properly may be impaired. 
U slučaju pojave nuspojava, poput omaglice, može biti oslabljena bolesnikova sposobnost koncentracije i reagiranja.
However, a 25% decrease in peak international normalised ratio (INR) was observed when A771726 was co-administered with warfarin as compared with warfarin alone. 
Ipak, primjećeno je 25%-tno smanjenje vršne vrijednosti internacionalnog normaliziranog omjera (INR) kod istodobne primjene A771726 s varfarinom, u usporedbi s monoterapijom varfarinom.
In responders, this response was maintained during 48 weeks (see section 4.2). 
U bolesnika u kojih je zabilježen odgovor na liječenje on se održao kroz 48 tjedana (vidjeti dio 4.2).
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/. 
Detaljnije informacije o ovom lijeku dostupne su na internetskoj stranici Europske agencije za lijekove http://www.ema.europa.eu/
Imprint on one side: ZBN. 
Utisnuta oznaka na jednoj strani: ZBN.
There is no dose adjustment recommended in patients with mild renal insufficiency. 
Nema preporuka za prilagodbu doze u bolesnika s blagom bubrežnom insuficijencijom.
Metabolism and nutrition disorders Common: 
Poremećaji metabolizma i prehrane Često:
elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin) 
povišene vrijednosti jetrenih enzima (transaminaze [posebno ALT], rjeđe gama-GT, alkalne fosfataze, bilirubina)
severe anaphylactic/anaphylactoid reactions, vasculitis, including cutaneous necrotizing vasculitis 
Vrlo rijetko: teške anafilaktične/anafilaktoidne reakcije, vaskulitis, uključujući kožni nekrotizirajući vaskulitis
Leflunomide was administered as a single oral 100 mg dose to 3 haemodialysis patients and 3 patients on continuous peritoneal dialysis (CAPD). 
Jednu oralnu dozu od 100 mg leflunomida primila su 3 hemodijalizirana bolesnika i 3 bolesnika na kontinuiranoj peritonealnoj dijalizi (CAPD).
• The identified risk of synergistic hepato- or haematotoxicity associated with combination therapy with another Disease-Modifying Antirheumatic Drug (e.g. methotrexate). 
• Prepoznat rizik od sinergije između hepatotoksičnosti ili hematotoksičnosti i kombinirane terapije s nekim drugim antireumatikom koji modificira tijek bolesti (primjerice metotreksatom).
These processes may be affected by hepatic dysfunction. 
Jetrena disfunkcija može utjecati na te procese.
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. 
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.
The pharmacokinetics of A771726 in CAPD subjects appeared to be similar to healthy volunteers. 
Farmakokinetika A771726 u bolesnika na kontinuiranoj peritonealnoj dijalizi bila je slična onoj u zdravih dobrovoljaca.
Effect on repaglinide (CYP2C8 substrate) 
Učinak na repaglinid (CYP2C8 supstrat)
Leflunomide Zentiva is contraindicated in patients with severe hypoproteinaemia or impairment of liver function (see section 4.3). 
Leflunomide Zentiva je kontraindiciran u bolesnika s teškom hipoproteinemijom ili oštećenom jetrenom funkcijom (vidjeti dio 4.3).
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). 
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).
• For psoriatic arthritis: 20 mg Leflunomide Zentiva once daily. 
• Za psorijatični artritis: 20 mg lijeka Leflunomide Zentiva jedanput na dan.
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. 
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.
A more rapid elimination of A771726 was observed in haemodialysis subjects which was not due to extraction of medicinal product in the dialysate. 
Znatno brža eliminacija A771726 zapažena je u hemodijaliziranih bolesnika, što nije bilo povezano s ekstrakcijom lijeka u dijalizat.
cutaneous lupus erythematosus, pustular psoriasis or worsening psoriasis, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 
kožni eritemski lupus, pustularna psorijaza ili pogoršanje psorijaze, reakcija na lijek s eozinofilijom i sistemskim simptomima (engl.
At a dose level of 20 mg/day, average plasma concentration of A771726 at steady state is approximately 35 µg/ml. 
Pri dozi od 20 mg/dan prosječna koncentracija A771726 u plazmi u stanju dinamičke ravnoteže iznosila je oko 35 μg/ml.
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. 
U manjem ispitivanju (n=30) istodobne primjene leflunomida (10 do 20 mg na dan) i metotreksata (10 do 25 mg na tjedan) opaženo je povišenje jetrenih enzima od 2 do 3 puta u 5 od 30 bolesnika.
Cases of peripheral neuropathy have been reported in patients receiving leflunomide. 
Slučajevi periferne neuropatije zabilježeni su u bolesnika koji su uzimali leflunomid.
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. 
Čim se pojave reakcije na koži i/ili sluznici koje izazivaju sumnju na teške nuspojave, uzimanje lijeka Leflunomide Zentiva ili bilo kojeg dodatnog lijeka treba prekinuti i odmah započeti postupak ispiranja leflunomida.
In human plasma, A771726 is extensively bound to protein (albumin). 
U ljudskoj se plazmi A771726 značajno veže za proteine plazme (albumin).
A pharmacokinetic interaction with oral contraceptives was observed with A771726 (see below). 
Farmakokinetička interakcija s oralnim kontraceptivima primjećena je za A771726 (vidjeti ispod).
Colitis, including microscopic colitis has been reported in patients treated with leflunomide. 
Kolitis, uključujući mikroskopski kolitis, prijavljen je u bolesnika liječenih leflunomidom.
DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes. 
DRESS se u početku javlja u vidu simptoma nalik na gripu i osipa na licu, a zatim kao prošireni osip s visokom temperaturom, povišenom razinom jetrenih enzima vidljivom na krvnim pretragama i porastom broja određenog tipa bijelih krvnih stanica (eozinofilija) te povećanim limfnim čvorovima.
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. 
Nakon istodobne primjene pojedinačne doze leflunomida u osoba koje su primale višestruke doze rifampicina (nespecifičnog induktora citokroma P450), vršne koncentracije A771726 porasle su za 40%, dok se vrijednost AUC nije značajno promijenila.
In other studies, unchanged leflunomide levels in plasma have rarely been detected, however, at ng/ml plasma levels. 
U ostalim ispitivanjima rijetko je zabilježena koncentracija nepromijenjenog leflunomida u plazmi (izmjerena u ng/ml).
Blood and lymphatic system disorders Common: 
Poremećaji krvi i limfnog sustava Često:
The recommended maintenance dose is leflunomide 10 mg to 20 mg once daily depending on the severity (activity) of the disease. 
Preporučena doza održavanja je 10 do 20 mg leflunomida jedanput na dan, ovisno o težini (aktivnosti) bolesti.
Do not take Leflunomide Zentiva when you are breast-feeding, as leflunomide passes into the breast milk. 
Nemojte uzimati lijek Leflunomide Zentiva dok dojite jer se leflunomid izlučuje u majčino mlijeko.
Recent, concomitant or consecutive use of potentially myelotoxic agents may be associated with a higher risk of haematological effects. 
Nedavno, istodobno ili naknadno uzimanje potencijalno mijelotoksičnih lijekova može povećati rizik od takvih hematoloških učinaka.
hypouricemia Psychiatric disorders Uncommon: anxiety Nervous system disorders Common: 
Psihijatrijski poremećaji Manje često: anksioznost Poremećaji živčanog sustava Često:
If ALT (SGPT) elevations of more than 2-fold the upper limit of normal persist or if ALT elevations of more than 3-fold the upper limit of normal are present, leflunomide must be discontinued and wash-out procedures initiated. 
Ako dvostruko veća koncentracija ALT (SGPT) u odnosu na gornju granicu normale potraje ili ako se ALT poveća više od 3 puta u odnosu na gornju granicu normale, liječenje leflunomidom valja prekinuti i započeti postupak ispiranja („washout“).
In case of severe haematological reactions, including pancytopenia, Leflunomide Zentiva and any concomitant myelosuppressive treatment must be discontinued and a leflunomide washout procedure initiated. 
U slučaju teških hematoloških reakcija, uključujući pancitopeniju, treba prekinuti liječenje lijekom Leflunomide Zentiva i bilo kojim istodobno primijenjenim mijelosupresivnim lijekom te početi postupak ispiranja leflunomida.
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). 
Zabilježeno je da peroralna primjena suspenzije aktivnog ugljika ili kolestiramina u ljudi ubrzava i značajno povećava brzinu eliminacije A771726 i smanjuje njegovu koncentraciju u plazmi (vidjeti dio 4.9).
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. 
Ispitivanja interakcija s cimetidinom (nespecifični inhibitor citokroma P450) i rifampicinom (nespecifični induktor citokroma P450) pokazuju da in vivo CYP enzimi u metabolizmu leflunomida sudjeluju tek u manjoj mjeri.
Leflunomide can be administered with food, since the extent of absorption is comparable in the fed and fasting state. 
Leflunomid se može uzimati s hranom jer se opseg apsorpcije uz hranu može usporediti s onim kad se lijek uzima natašte.
Studies with both hemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicate that A771726, the primary metabolite of leflunomide, is not dialysable. 
Ispitivanja s hemodijalizom i kroničnom ambulantnom peritonealnom dijalizom upućuju da se A771726, primarni metabolit leflunomida, ne može dijalizirati.
Therefore, when co-administered with substrates of OAT3, such as cefaclor, benzylpenicillin, ciprofloxacin, indomethacin, ketoprofen, furosemide, cimetidine, methotrexate, zidovudine, caution is recommended. 
Stoga, preporučuje se oprez kod istodobne primjene leflunomida sa supstratima OAT3, kao što su cefaklor, benzilpenicilin, ciprofloksacin, indometacin, ketoprofen, furosemid, cimetidin, metotreksat, zidovudin.
Concomitant administration of hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) is not advisable. 
Ne preporučuje se istodobna primjena hepatotoksičnih ili hematotoksičnih DMARD-a (npr. metotreksata).
It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. 
Također može uzrokovati neke ozbiljne alergijske reakcije (uključujući reakciju na lijek s eozinofilijom i sistemskim simptomima, engl.
Serious undesirable effects might occur (e.g. hepatotoxicity, haematotoxicity or allergic reactions, see below), even if the treatment with leflunomide has been stopped. 
Ozbiljne nuspojave (npr. hepatotoksičnost, hematotoksičnost ili alergijske reakcije; vidjeti u nastavku teksta) mogu se javiti čak i nakon prestanka liječenja leflunomidom.
After a 2-year waiting period, the A771726 plasma concentration is measured for the first time. 
Nakon dvogodišnjeg čekanja koncentracija A771726 mjeri se prvi put.
Consistent with extensive protein binding A771726 has a low apparent volume of distribution (approximately 11 litres). 
Zbog ekstenzivnog vezanja za bjelančevine A771726 ima mali prividni volumen distribucije (oko 11 litara).
Animal pharmacology 
Farmakologija u životinja
severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal 
Vrlo rijetko: teško oštećenje jetre poput zatajenja jetre i akutne hepatičke nekroze koja može imati smrtni ishod
Leflunomide Zentiva may be taken with or without food. 
Leflunomide Zentiva s hranom, pićem i alkoholom Leflunomide Zentiva se može uzimati s hranom ili bez nje.