FrancophonIA/ELRC3.0 huggingface dataset:
English: The incidence of Grade ≥2 stomatitis at 8 weeks was 2.4% (n=2/85 evaluable patients) which was lower than historically reported.
Croatian: Incidencija stomatitisa stupnja ≥2 u 8. tjednu bila je 2,4% (n=2/85 ocjenjivih bolesnika), što je bilo manje nego kod povijesnih podataka.
English: The p-values for superiority versus placebo were 0.003 (LT) and <0.001 (HT).
Croatian: P-vrijednosti za superiornost u odnosu na placebo bile su 0,003 (DN) i <0,001 (GN).
English: The effect of everolimus on infantile/epileptic spasms or on seizures associated with Lennox-Gastaut syndrome has not been studied and is not established for generalised-onset seizures and subjects without cortical tubers.
Croatian: Učinak everolimusa na infantilne/epileptičke spazme ili napadaje povezane s Lennox-Gastaut sindromom nije ispitivan i nije ustanovljen za generalizirane napadaje i ispitinike bez kortikalnih tubera.
English: • severe itching of the skin, with a red rash or raised bumps
Croatian: • jak svrbež kože, s crvenim osipom ili ispupčenim kvržicama
English: These will check the amount of blood cells (white blood cells, red blood cells and platelets) in your body to see if Votubia is having an unwanted effect on these cells.
Croatian: Time se provjerava količina krvnih stanica (bijelih krvnih stanica, crvenih krvnih stanica i krvnih pločica) u Vašem organizmu i tako utvrđuje ima li Votubia kakvog neželjenog učinka na spomenute stanice.
English: This will look like a cloudy liquid (known as an oral suspension).
Croatian: Lijek će izgledati kao zamućena tekućina (koja se naziva oralna suspenzija).
English: Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients listed in section 6.1.
Croatian: Preosjetljivost na djelatnu tvar, druge derivate rapamicina ili neku od pomoćnih tvari navedenih u dijelu 6.1.
English: If you feel unusually tired (fatigue is a common side effect), take special care when driving or using machines.
Croatian: Osjećate li se neobično umorno (umor je česta nuspojava liječenja), posebno oprezno upravljajte motornim vozilima, odnosno rukujte strojevima.
English: Healthcare professionals and patients should be vigilant for signs and symptoms of bleeding throughout the treatment period, especially if risk factors for haemorrhage are combined.
Croatian: Zdravstveni djelatnici i bolesnici moraju budno pratiti pojavu znakova i simptoma krvarenja tijekom razdoblja liječenja, osobito ako postoje združeni čimbenici rizika za krvarenje.
English: In the pivotal phase III study in patients with TSC and refractory seizures, 299 of the 366 patients studied were below the age of 18 years.
Croatian: U ključnom ispitivanju faze III u bolesnika s KTS-om i refraktorrnim napadajima, 299 od 366 ispitivanih bolesnika bilo je mlađe od 18 godina.
English: In summary, everolimus is highly active in this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 inhibition.
Croatian: Sažeto, everolimus je visoko aktivan u ovom neuronskom modelu KTS-a, pri čemu se korist izgleda može pripisati učincima inhibicije mTORC1.
English: The baseline data indicated mild to moderate mental retardation in patients 6-18 years of age (scores of 60-70 on the Adaptive Behavior Composite and Communication, Daily Living Skills, and Socialization Domain Scores).
Croatian: Početni podaci ukazivali su na blagu do umjerenu mentalnu retardaciju u bolesnika u dobi od 6-18 godina (rezultati od 60-70 za Adaptivni kompozit ponašanja u domenama Komunikacije, Vještina svakodnevnog života i Socijalizacije).
English: Patients who develop radiological changes suggestive of non-infectious pneumonitis and have few or no symptoms may continue Votubia therapy without dose adjustments.
Croatian: Bolesnici u kojih se razviju radiološke promjene koje govore u prilog neinfektivnog pneumonitisa, a koji imaju malo simptoma, ili uopće nemaju simptoma, mogu nastaviti liječenje Votubiom bez prilagodbe doze.
English: Similarly, at the same timepoints, ≥50% reductions in volume were observed in 44.2%, 63.3%, and 68.9% of the treated patients, respectively.
Croatian: Slično, u istim vremenskim točkama, smanjenja u volumenu ≥50% uočena su u 44,2%, 63,3%, odnosno 68,9% liječenih bolesnika.
English: The everolimus trough concentration should be assessed at least 1 week later (see sections 4.2 and 4.4).
Croatian: Najniža koncentracija everolimusa treba se odrediti najmanje 1 tjedan kasnije (vidjeti dijelove 4.2 i 4.4).
English: However, a clinically relevant effect on the exposure of systemically administered CYP3A4 substrates is not expected (see section 4.4).
Croatian: Međutim ne očekuje se klinički značajna promjena izloženosti sistemski primijenjenih CYP3A4 supstrata (vidjeti dio 4.4).
English: Among patients treated with everolimus during the study, no cases of angiomyolipoma-related nephrectomy and only one case of renal embolisation were reported.
Croatian: Među bolesnicima liječenim everolimusom tijekom ispitivanja, nije bilo prijavljenih slučajeva nefrektomije povezane s angiomiolipomom te je prijavljen samo jedan slučaj embolizacije bubrega.
English: Administration of everolimus for up to 2 years did not indicate any oncogenic potential in mice and rats up to the highest doses, corresponding respectively to 4.3 and 0.2 times the estimated clinical exposure.
Croatian: Primjena everolimusa u trajanju do 2 godine, nije pokazala onkogeni potencijal u miševa odnosno štakora čak ni u najvišim dozama koje odgovaraju dozi 4,3 odnosno 0,2 puta višoj od procijenjene kliničke izloženosti.
English: Add about 25 ml of water to the 30 ml dose cup.
Croatian: Dodajte otprilike 25 ml vode u čašu za doziranje od 30 ml.
English: Table 5 EXIST-2 - Angiomyolipoma response rates by time-averaged Cmin category, at primary analysis
Croatian: Tablica 5 EXIST-2 - Stope odgovora angiomiolipoma prema vremenski uprosječenoj kategoriji Cmin, u primarnoj analizi
English: Votubia dispersible tablets are to be taken as a suspension only and must not be swallowed whole, chewed, or crushed.
Croatian: Votubia tablete za oralnu suspenziju moraju se uzimati samo kao suspenzija i ne smiju se gutati cijele, žvakati ili drobiti.
English: The contents should be gently stirred with a spoon and then administered immediately.
Croatian: Sadržaj treba nježno žlicom promiješati i zatim odmah ispiti.
English: The suspension can be prepared either in an oral syringe or in a small glass.
Croatian: Suspenzija se može pripremiti ili u štrcaljki za usta ili u maloj čaši.
English: Carefully remove the oral syringe from the patient's mouth.
Croatian: Pažljivo izvadite štrcaljku iz usta bolesnika.
English: Do not use this medicine after the expiry date which is stated on the carton and blister foil.
Croatian: Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na kutiji i foliji blistera.
English: If you receive Votubia for the treatment of TSC with angiomyolipoma of the kidney, the usual dose is 10 mg, to be taken once daily.
Croatian: Ako uzimate Votubiu za liječenje KTS-a s angiomiolipomom bubrega, uobičajena doza je 10 mg koja se uzima jedanput dnevno.
English: The efficacy results for the primary endpoint are summarised in Table 5.
Croatian: Rezultati djelotvornosti za mjeru primarnog ishoda sažeto su prikazani u tablici 5.
English: Agents whose plasma concentration may be altered by everolimus
Croatian: Lijekovi čiju koncentraciju u plazmi everolimus može promijeniti
English: Symptoms of heart failure such as breathlessness, difficulty breathing when lying down, swelling of the feet or legs
Croatian: Simptomi zatajenja srca kao što su nedostatak zraka, otežano disanje u ležećem položaju, oticanje stopala ili nogu
English: Fluconazole
Croatian: Flukonazol
English: Use scissors to open the blister along the dotted line.
Croatian: Upotrijebite škare kako biste otvorili blister uzduž iscrtane linije.
English: Votubia may increase blood sugar levels and worsen diabetes mellitus.
Croatian: Votubia može povisiti razinu šećera u krvi i pogoršati šećernu bolest.
English: Votubia could harm a breast-fed baby.
Croatian: Votubia može naštetiti dojenčetu.
English: The overall type, frequency and severity of adverse reactions observed in children and adolescents have been generally consistent with those observed in adults, with the exception of infections which were reported at a higher frequency and severity in children below the age of 6 years.
Croatian: Ukupno su vrsta, učestalost i težina nuspojava primijećenih u djece i adolescenata u načelu bile u skladu s onima primijećenim u odraslih bolesnika, uz iznimku infekcija koje su bile zabilježene uz veću učestalost i težinu kod djece mlađe od 6 godina.
English: Concomitant antiepileptic therapy may affect the metabolism of everolimus and may contribute to this variance (see section 4.5).
Croatian: Istodobno liječenje antiepilepticima može utjecati na metabolizam everolimusa i pridonijeti ovoj varijabilnosti (vidjeti dio 4.5).
English: In the oncology safety pooling, 37% of the patients treated with everolimus were ≥65 years of age.
Croatian: U objedinjenim onkološkim sigurnosnim podacima, 37% bolesnika liječenih everolimusom bilo je u dobi od 65 godina ili starije.
English: Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, protein kinase inhibitors, ATC code: L01XE10
Croatian: Farmakoterapijska skupina: Antineoplastici, ostali antineoplasci, inhibitori protein kinaze, ATK oznaka: L01XE10
English: Getting ready
Croatian: Priprema
English: After the dispersion has been swallowed, any residue must be re-dispersed in the same volume of water and swallowed (see section 5.2).
Croatian: Nakon što je bolesnik popio otopinu, sve ostatke treba iznova otopiti u jednakom volumenu vode i popiti (vidjeti dio 5.2).
English: Results showed that Votubia was superior to placebo for the primary endpoint of best overall SEGA response (p<0.0001).
Croatian: Rezultati su pokazali da je Votubia superiorna u odnosu na placebo kada je riječ o mjeri primarnog ishoda najboljeg ukupnog odgovora SEGA-e (p<0,0001).
English: St John's Wort (Hypericum perforatum)
Croatian: Gospina trava (Hypericum perforatum)
English: If you are taking other medicines at the same time as Votubia, your doctor may need to change the dose of Votubia or the other medicines.
Croatian: Uzimate li istodobno s Votubiom i druge lijekove, Vaš liječnik će dozu Votubie ili tih drugih lijekova možda morati promijeniti.
English: However, oral doses of everolimus in female rats at ≥ 0.1 mg/kg (approximately 4% of the AUC0-24h in patients receiving the 10 mg daily dose) resulted in increases in pre-implantation loss.
Croatian: Međutim, peroralne doze everolimusa u ženki štakora pri dozi od ≥0,1 mg/kg (otprilike 4% AUC0-24h u bolesnika koji primaju dnevnu dozu od 10 mg) rezultirale su povećanjem u gubitku ploda prije implantacije.
English: Everolimus had no impact on pre-dose concentrations of antiepileptics that are substrates of CYP3A4 (clonazepam, diazepam, felbamate and zonisamide).
Croatian: Everolimus nije imao utjecaja na koncentracije antiepileptika koji su supstrati CYP3A4 (klonazepam, diazepam, felbamat i zonisamid) prije doziranja.
English: If a diagnosis of invasive systemic fungal infection is made, Votubia treatment should be promptly and permanently discontinued and the patient treated with appropriate antifungal therapy.
Croatian: Ako je postavljena dijagnoza invazivne sistemske gljivične infekcije, liječenje Votubiom potrebno je odmah i trajno prekinuti i u bolesnika provesti odgovarajuće antifungalno liječenje.
English: Grapefruit juice or other food affecting CYP3A4/PgP
Croatian: Sok od grejpa ili druga hrana koja utječe na CYP3A4/PgP
English: In the everolimus treated population (N=111) of the study, including patients who crossed over from the placebo group, tumour response, starting as early as after 12 weeks on everolimus, was sustained at later time points.
Croatian: U populaciji koja je u ispitivanju bila liječena everolimusom (N=111), što uključuje i bolesnike koji su prešli iz placebo skupine, odgovor tumora, koji je počeo već nakon 12 tjedana, na everolimusu, održao se u kasnijim vremenskim točkama.
English: At the end of the core phase, overall quality of life in patients aged 2 to <11 years (as measured by the mean change from baseline in overall Quality Of Life score [total score] in the Childhood Epilepsy Questionnaire [QOLCE]) was maintained in each Votubia treatment arm as well as in the placebo arm.
Croatian: Na kraju osnovne faze, ukupna kvaliteta života bolesnika u dobi od 2 do <11 godina (mjereno srednjom promjenom od početne vrijednosti u ukupnom rezultatu na Upitniku o kvaliteti života s dječjom epilepsijom [QOLCE]) održala se u svakoj od terapijskih skupina s Votubiom, kao i u placebo skupini.
English: Preclinical studies in models of mTOR dysregulation in the brain demonstrated that treatment with an mTOR inhibitor such as everolimus could prolong survival, suppress seizures, prevent the development of new-onset seizures and prevent premature death.
Croatian: Pretklinička ispitivanja na modelima disreguliranog mTOR-a u mozgu pokazala su da liječenje mTOR inhibitorom kao što je everolimus može produžiti preživljenje, potisnuti napadaje, spriječiti razvoj novih napadaja i spriječiti prijevremenu smrt.
English: Blockage or obstruction of a blood vessel (vein) in the leg (deep vein thrombosis).
Croatian: Blokada ili začepljenje krvnih žila (vena) u nozi (duboka tromboza vena).
English: Antiepileptics (e.g. carbamazepine, phenobarbital, phenytoin)
Croatian: Antiepileptici (npr. karbamazepin, fenobarbital, fenitoin)
English: After administration of the prepared suspension, 25 ml of water should be added and be stirred with the same spoon to re-suspend any remaining particles.
Croatian: Nakon primjene pripremljene suspenzije potrebno je dodati 25 ml vode i promiješati istom žlicom kako bi se suspendirale sve preostale čestice.
English: If you miss a dose, take your next dose as scheduled.
Croatian: Propustite li uzeti dozu lijeka, sljedeću dozu uzmite prema uobičajenom rasporedu.
English: Progressions were observed in 3.8% of patients in the everolimus arm compared with 20.5% in the placebo arm.
Croatian: Progresije su bile uočene u 3,8% bolesnika u skupini koja je primala everolimus u usporedbi s 20,5% u placebo skupini.
English: Fertility Votubia may affect male and female fertility.
Croatian: Votubia može utjecati na plodnost muškaraca i žena.
English: There was no indication of kidney toxicity in monkeys or minipigs.
Croatian: Nije bilo znakova bubrežne toksičnosti u majmuna ili patuljastih svinja.
English: This is to measure the amount of Votubia in your blood and find the best daily dose for you.
Croatian: Time će se mjeriti količina Votubie u krvi i određivati dnevna doza lijeka koja Vam najbolje odgovara.
English: ≥6 years
Croatian: ≥6 godina
English: Following the administration of a single dose of radiolabelled everolimus in conjunction with ciclosporin, 80% of the radioactivity was recovered from the faeces, while 5% was excreted in the urine.
Croatian: Nakon primjene jednokratne doze radioaktivno obilježenog everolimusa i ciklosporina, 80% radioaktivnosti izmjereno je u stolici, a 5% je bilo izlučeno u mokraći.
English: The analysis was stratified by use of enzyme-inducing antiepileptics at randomisation (yes/no).
Croatian: Analiza je bila stratificirana prema primjeni antiepileptika koji induciraju enzime pri randomizaciji (da/ne).
English: The two treatment arms were generally well balanced with respect to demographic and baseline disease characteristics and history of prior anti-SEGA therapies.
Croatian: Dvije terapijske skupine bile su općenito dobro uravnotežene s obzirom na demografske značajke i početne značajke bolesti te prijašnje terapije za liječenje SEGA-e.
English: mTOR is a key serine-threonine kinase, the activity of which is known to be upregulated in a number of human cancers.
Croatian: mTOR je serin-treonin kinaza od ključne važnosti, čija je aktivnost povećana u raznih karcinoma u ljudi.
English: Everolimus can reduce levels of vascular endothelial growth factor (VEGF).
Croatian: Everolimus može sniziti razine vaskularnog endotelnog čimbenika rasta (VEGF).
English: Gently stir the contents of the glass until the tablet(s) break apart (approximately 7 minutes) and then drink the contents immediately.
Croatian: Sadržaj čaše lagano miješajte sve dok se tableta(e) ne otopi(e) (otprilike 7 minuta) te sadržaj čaše potom odmah popijte.
English: • If you need to take a higher dose or need to use more than 5 dispersible tablets, split the dose and repeat the steps using the same oral syringe or small glass.
Croatian: • Ako trebate uzeti veću dozu ili trebate koristiti više od 5 tableta za oralnu suspenziju, podijelite dozu i ponovite korake koristeći istu štrcaljku za usta ili čašu.
English: Missing
Croatian: Nedostaje
English: This outcome was consistent with the results of a linear regression model predicting the log of absolute seizure frequency during the maintenance period of the core phase, which indicated that for a 2-fold increase in TN-Cmin there was a statistically significant 28% reduction (95% CI: 12%, 42%) in absolute seizure frequency.
Croatian: Taj je ishod bio u skladu s rezultatima linearnog regresijskog modela koji predviđaju log apsolutne učestalosti napadaja tijekom razdoblja održavanja u osnovnoj fazi i koji su ukazali na to da je za dvostruko povećanje VN-Cmin postojalo statistički značajno smanjenje od 28% (95% CI: 12%, 42%) u apsolutnoj učestalosti napadaja.
English: In addition, all 8 patients on the Votubia arm who had radiographic evidence of hydrocephalus at baseline had a decrease in ventricular volume.
Croatian: Nadalje, kod svih 8 bolesnika u skupini koja je primala Votubiu koji su imali radiološki dokaz prisutnosti hidrocefalusa pri određivanju početnih vrijednosti došlo je do smanjenja u volumenu moždanih klijetki.
English: Ciclosporin oral
Croatian: Oralni ciklosporin
English: Percentage reduction from baseline, n (%)
Croatian: Postotak smanjenja od početne vrijednosti, n (%)
English: Everolimus has immunosuppressive properties and may predispose patients to bacterial, fungal, viral or protozoal infections, including infections with opportunistic pathogens (see section 4.8).
Croatian: Everolimus ima imunosupresivna svojstva i može povećati sklonost bolesnika prema bakterijskim, gljivičnim, virusnim ili protozoalnim infekcijama, uključujući infekcije uzrokovane oportunističkim uzročnicima (vidjeti dio 4.8).
English: Key secondary endpoints included time to angiomyolipoma progression and skin lesion response rate.
Croatian: Ključni sekundarni ishodi uključivali su vrijeme do progresije angiomiolipoma i stopu odgovora kožnih lezija.
English: In patients with SEGA, everolimus Cmin was approximately dose-proportional within the dose range from 1.35 mg/m to 14.4 mg/m
Croatian: U bolesnika oboljelih od SEGA-e, Cmin everolimusa bio je otprilike proporcionalan dozi unutar raspona doze od 1,35 mg/m do 14,4 mg/m
English: Take the carton and this leaflet, so that the doctor knows what has been taken.
Croatian: Sa sobom ponesite originalno pakiranje i ovu Uputu o lijeku, kako bi liječnik znao što je uzeto.
English: Range 0.49
Croatian: Raspon 0,49
English: The stability of the ready to use suspension has been demonstrated for 60 minutes.
Croatian: Suspenzija spremna za uporabu stabilna je 60 minuta.
English: If a higher dose or number of tablets is required, an additional glass must be prepared.
Croatian: Ako je potrebna veća doza ili broj tableta, pripremiti za to dodatnu čašu.
English: Headache, dizziness, signs of high blood pressure (hypertension)
Croatian: Glavobolja, omaglica, znakovi visokog krvnog tlaka (hipertenzije)
English: For patients not receiving concomitant strong inducers at the start of everolimus treatment, the co-administration may require an increased Votubia dose.
Croatian: Za bolesnike koji ne primaju istodobno snažne induktore na početku liječenja everolimusom, istodobna primjena mogla bi zahtijevati povećanu dozu Votubie.
English: Votubia is not to be used in children or adolescents with TSC who have angiomyolipoma of the kidney in the absence of SEGA, as it has not been studied in such patients.
Croatian: Votubia se ne smije koristiti u djece ili adolescenata s KTS-om koji imaju angiomiolipom bubrega bez SEGA-e, budući da nije bila ispitivana u tih bolesnika.
English: higher starting dose of 7 mg/m is recommended for patients 1 to less than 3 years of age based on pharmacokinetic simulations (see section 5.2).
Croatian: Viša početna doza od 7 mg/m preporučena je za bolesnike u dobi od 1 godine do mlađe od 3 godine na temelju farmakokinetičkih simulacija (vidjeti dio 5.2).
English: The majority of patients (67%) failed 5 or more antiepileptics prior to the study and 41.0% and 47.8% of patients were taking 2 and ≥3 antiepileptics during the study.
Croatian: U većine bolesnika (67%) je terapija s 5 ili više antiepileptika bila neuspješna prije ispitivanja, a 41,0% odnosno 47,8% bolesnika uzimalo je 2 odnosno ≥3 antiepileptika tijekom ispitivanja.
English: Final analysis Votubia Placebo p-value Votubia N=78
Croatian: Završna analiza Votubia Placebo p-vrijednost Votubia n=79
English: Serious side effects of Votubia include:
Croatian: Ozbiljne nuspojave Votubie uključuju:
English: In the first study, the average AUC of everolimus in 8 subjects with moderate hepatic impairment (Child-Pugh B) was twice that found in 8 subjects with normal hepatic function.
Croatian: U prvom ispitivanju, prosječni AUC everolimusa u 8 ispitanika s umjerenim oštećenjem funkcije jetre (Child-Pugh B) bio je dvostruko veći od AUC-a uočenoga u 8 ispitanika s normalnom funkcijom jetre.
English: Prepare the oral suspension by mixing the dispersible tablets with water either in an oral syringe or in a small glass.
Croatian: Pripremite oralnu suspenziju miješanjem tableta za oralnu suspenziju s vodom ili u štrcaljki za usta ili u maloj čaši.
English: Change in SEGA volume during the core 6-month treatment phase, as assessed via an independent central radiology review, was the primary efficacy endpoint.
Croatian: Promjena volumena SEGA-e postignuta tijekom prvih 6 mjeseci liječenja, prema neovisnom centralnom radiološkom očitanju, je bio primarni ishod djelotvornosti.
English: Disturbed taste (dysgeusia)
Croatian: Promijenjen osjet okusa (disgeuzija)
English: (see sections 4.2 and 5.2).
Croatian: C) (vidjeti dijelove 4.2 i 5.2).
English: Long-term follow-up to a median duration of 67.8 months (range: 4.7 to 83.2) demonstrated sustained efficacy.
Croatian: Dugoročno praćenje do medijana trajanja od 67,8 mjeseci (raspon: 4,7 do 83,2) pokazalo je održanu djelotvornost.
English: When possible optimal glycaemic control should be achieved before starting a patient on Votubia.
Croatian: Kada je moguće, treba postići optimalnu kontrolu glukoze u krvi prije nego bolesnik počne uzimati Votubiu.
English: Other symptoms may include fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), and pain in the upper right abdomen.
Croatian: Ostali simptomi mogu biti umor, gubitak apetita, mučnina, žutica (žutilo kože) i bol u gornjem desnom dijelu trbuha.
English: No patient developed new lesions, worsening hydrocephalus or increased intracranial pressure, and none required surgical resection or other therapy for SEGA.
Croatian: Ni u jednog bolesnika nisu se razvile nove lezije niti je došlo do pogoršanja postojećeg hidrocefalusa ili porasta intrakranijalnoga tlaka, te nije bilo nužno učiniti kiruršku resekciju niti uvesti drugu terapiju SEGA-e.
English: In vitro, everolimus is a competitive inhibitor of CYP3A4 and a mixed inhibitor of CYP2D6.
Croatian: In vitro, everolimus je kompetitivni inhibitor CYP3A4 i miješani inhibitor CYP2D6.
English: There are no adequate data from the use of everolimus in pregnant women.
Croatian: Nema odgovarajućih podataka o primjeni everolimusa u trudnica.
English: Open the blister just before taking the Votubia tablets.
Croatian: Blister otvorite neposredno prije uzimanja Votubia tableta.