FrancophonIA/ELRC3.0 huggingface dataset:
English: In patients with TSC and refractory seizures receiving Votubia dispersible tablets, a trend was observed toward lower Cmin normalised to dose (as mg/m2) in younger patients.
Slovenian: Pri bolnikih, ki so imeli tuberozno sklerozo in neodzivno epilepsijo ter so prejemali zdravilo Votubia disperzibilne tablete, so opažali trend zniževanja Cmin, normalizirane na višino odmerka (v mg/m2) pri mlajših bolnikih.
English: Concomitant treatment with potent CYP3A4 inhibitors result in dramatically increased blood concentrations of everolimus (see section 4.5).
Slovenian: Sočasno zdravljenje z močnimi zaviralci CYP3A4 povzroča izrazito zvišanje koncentracije everolimusa (glejte poglavje 4.5).
English: You should not breast-feed during treatment and for 2 weeks after the last dose of Votubia.
Slovenian: Med zdravljenjem in še 2 tedna po prejemu zadnjega odmerka zdravila Votubia ne smete dojiti.
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.
Slovenian: Pred in periodično med zdravljenjem boste opravljali preiskave krvi za preverjanje števila krvnih celic (belih in rdečih krvnih celic ter trombocitov) v telesu, da bi lahko opazili, če bi imelo zdravilo Votubia neželene učinke na te celice.
English: Active substance by interaction
Slovenian: Učinkovine glede na vrsto interakcije
English: 95% CI p-value (versus placebo)
Slovenian: 95-odstotni IZ vrednost p (v primerjavi s placebom)
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.
Slovenian: Ti rezultati se ujemajo z rezultati linearnega regresijskega modela za napoved logaritma absolutne pogostnosti napadov v obdobju vzdrževalnega zdravljenja v osnovnem delu študije, ki so pokazali, da je dvakrat višja TN-Cmin povezana s statistično značilnim 28-odstotnim zmanjšanjem (95-odstotni IZ: 12 %; 42 %) absolutne pogostnosti napadov.
English: • Scissors to open the blister
Slovenian: • škarje za odpiranje pretisnega omota
English: Pour the water from the dose cup into the small glass.
Slovenian: Iz odmerne skodelice prelijte vodo v majhen kozarec.
English: On rare occasions, fatal outcomes were observed in the oncology setting (see section 4.4).
Slovenian: V redkih primerih so opažali tudi smrten izid, in sicer v okviru onkološkega zdravljenja (glejte poglavje 4.4).
English: If, despite these measures, you think you may have become pregnant, ask your doctor for advice before taking any more Votubia.
Slovenian: Če kljub zaščiti pred nosečnostjo mislite, da ste zanosili, se posvetujte z zdravnikom preden nadaljujete z jemanjem zdravila Votubia.
English: For patients with TSC who have SEGA and are unable to swallow tablets, Votubia tablet(s) can be dispersed completely in a glass with approximately 30 ml of water by gently stirring until the tablet(s) is(are) fully disintegrated (approximately 7 minutes), immediately prior to drinking.
Slovenian: Za bolnike s TSC in SEGA, ki ne morejo pogoltniti tablet, je mogoče eno ali več tablet zdravila Votubia tik pred zaužitjem z rahlim mešanjem v celoti dispergirati v kozarcu s približno 30 ml vode, dokler se ena ali več tablet ne raztopi v celoti (kar traja približno 7 minut).
English: At baseline, 19.4% of patients had focal seizures with retained awareness (sensory previously confirmed on EEG or motor), 45.1% had focal seizures with impaired awareness (predominantly nonmotor), 69.1% had focal motor seizures (i.e. focal motor seizures with impaired awareness and/or secondary generalised seizures), and 1.6% had generalised onset seizures (previously confirmed by EEG).
Slovenian: Ob izhodišču je imelo 19,4 % bolnikov žariščne epileptične napade ob ohranjeni zavesti (senzorične, predhodno potrjene na EEG, ali motorične), 45,1 % jih je imelo žariščne napade z motnjami zavesti (večinoma ne-motorične), 69,1 % jih je imelo žariščne motorične napade (to je žariščne motorične epileptične napade z motnjami zavesti in/ali sekundarno generalizirane epileptične napade) in 1,6 % jih je imelo primarno generalizirane napade (predhodno potrjene z EEG).
English: SEGA associated with TSC
Slovenian: SEGA v povezavi s TSC
English: One patient met the pre-specified criteria for treatment success (>75% reduction in SEGA volume) and was temporarily taken off trial therapy; however, SEGA re-growth was evident at the next assessment at 4.5 months and treatment was restarted.
Slovenian: En bolnik je dosegel vnaprej določen kriterij za uspeh zdravljenja (zmanjšanje volumna SEGA za >75 %), zato so pri njem začasno prekinili uporabo študijskega zdravila, kasneje pa so mu zdravilo spet uvedli, saj je ob naslednji kontroli pri 4,5 mesecih prišlo do ponovne rasti SEGA.
English: Responders - n (%) Response rate 95% CI
Slovenian: Bolniki z odzivom - n (%) delež bolnikov z odzivom 95-odstotni IZ
English: If you are taking Votubia tablets for the treatment of TSC with SEGA and if you are unable to swallow the tablets, you can stir them into a glass of water:
Slovenian: Če jemljete tablete Votubia za zdravljenje tuberozne skleroze s subependimskim gigantoceličnim astrocitomom in tablet ne morete pogoltniti, jih lahko zmešate v kozarcu vode:
English: In healthy subjects, high fat meals reduced systemic exposure to Votubia 10 mg tablets (as measured by AUC) by 22% and the peak blood concentration Cmax by 54%.
Slovenian: Pri zdravih osebah je uživanje obrokov z visoko vsebnostjo maščob zmanjšalo sistemsko izpostavljenost zdravilu Votubia 10 mg tablete (merjeno z AUC) za 22 %, najvišjo koncentracijo v krvi Cmax pa za 54 %.
English: The safety and efficacy of Votubia in children aged 0 to 18 years with renal angiomyolipoma associated with TSC in the absence of SEGA have not been established.
Slovenian: Varnost in učinkovitost zdravila Votubia pri otrocih starih 0 do 18 let z ledvičnim angiomiolipomom v povezavi s TSC v odsotnosti SEGA nista bili dokazani.
English: In a population pharmacokinetic evaluation in cancer patients, no significant influence of age (27-85 years) on oral clearance of everolimus was detected.
Slovenian: Pri presoji populacijske farmakokinetike bolnikov z rakom niso zaznali pomembnega vpliva starosti bolnika (od 27 do 85 let) na peroralni očistek everolimusa.
English: Table 3 Effects of other active substances on everolimus
Slovenian: Preglednica 3 Vpliv drugih učinkovin na everolimus
English: The long-term follow-up of patients randomised to everolimus and patients randomised to placebo who thereafter crossed over to everolimus demonstrated durable responses.
Slovenian: Dolgoročno spremljanje bolnikov, ki so bili randomizirani na zdravljenje z everolimusom in bolnikov, ki so bili randomizirani na placebo in so kasneje prešli na zdravljenje z everolimusom, je pokazalo dolgotrajen odziv.
English: The potential for everolimus to cause infertility in male and female patients is unknown, however secondary amenorrhoea and associated luteinising hormone (LH)/follicle stimulating hormone (FSH) imbalance has been observed in female patients (see also section 5.3 for preclinical observations on the male and female reproductive systems).
Slovenian: Možnost everolimusa, da povzroči neplodnost pri bolnikih moškega in ženskega spola, ni znana, vendar pa so pri bolnicah opažali sekundarno amenorejo in hkrati prisotno neuravnoteženost razmerja luteinizirajoči hormon (LH)/folikle stimulirajoči hormon (FSH) (za predklinična opažanja, ki se nanašajo na reproduktivne sisteme pri moških in ženskah, glejte tudi poglavje 5.3).
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).
Slovenian: Izhodiščni podatki so pokazali blago do zmerno umsko manjrazvitost pri bolnikih, ki so bili stari od 6 do 18 let (s 60-70 točkami pri skupni oceni adaptivnega vedenja in komunikacije, pri oceni sposobnosti izvajanja aktivnosti vsakodnevnega življenja ter pri oceni socializacije).
English: Phase II study in patients with SEGA
Slovenian: Študija faze II pri bolnikih s SEGA
English: A total of 117 patients were randomised, 78 to Votubia and 39 to placebo.
Slovenian: Skupno so randomizirali 117 bolnikov, 78 v skupino z zdravilom Votubia in 39 v skupino s placebom.
English: For paediatric patients who do not require immediate treatment, completion of the recommended childhood series of live virus vaccinations is advised prior to the start of therapy according to local treatment guidelines.
Slovenian: Pri pediatričnih bolnikih, ki ne potrebujejo takojšnjega zdravljenja, je priporočeno pred začetkom zdravljenja zaključiti za otroke priporočeno serijo cepljenj z živimi cepivi v skladu z lokalnimi smernicami.
English: Based on in vitro results, the systemic concentrations obtained after oral daily doses of 10 mg make inhibition of PgP, CYP3A4 and CYP2D6 unlikely.
Slovenian: Glede na rezultate in vitro študij sistemska koncentracija, do katere pride po peroralnem odmerjanju 10 mg na dan, praktično ne more zavirati P-glikoproteina, CYP3A4 in CYP2D6.
English: If these side effects get severe please tell your doctor and/or pharmacist.
Slovenian: Če ti neželeni učinki postanejo zelo izraženi, obvestite zdravnika in/ali farmacevta.
English: Loss of either TSC1 or TSC2 leads to elevated rheb-GTP levels, a ras family GTPase, which interacts with the mTORC1 complex to cause its activation.
Slovenian: Izguba kateregakoli izmed TSC1 in TSC2 pomeni zvišano koncentracijo rheb-GTP, ta je GTP-aza iz družine beljakovin Ras, ki interagira s kompleksom mTORC1 in ga aktivira.
English: Grade 2 (<75, ≥50x10
Slovenian: Stopnja 2 (<75, ≥50x10
English: At the final analysis, the skin lesion response rate had increased to 68.2% (95% CI: 58.5, 76.9), with one patient reporting a confirmed complete clinical skin lesion response and no patients experiencing progressive disease as their best response.
Slovenian: V zaključni analizi se je delež bolnikov z odzivom patoloških sprememb kože povečal na 68,2 % (95 % IZ: 58,5, 76,9), pri čemer so pri enem bolniku poročali o potrjenem popolnem kliničnem odzivu patoloških sprememb kože, pri nobenem od bolnikov pa niso opažali, da bi bil njegov najboljši odziv napredovanje bolezni.
English: The evidence is based on analysis of change in SEGA volume.
Slovenian: Dokazi temeljijo na analizi spremembe volumna SEGA.
English: For dose reductions below the lowest available strength, alternate day dosing should be considered.
Slovenian: Če je treba odmerek znižati na odmerek, ki je nižji od najnižje razpoložljive jakosti zdravila je treba razmisliti o izmenjevanju različnih dnevnih odmerkov.
English: No signs of acute toxicity have been reported in these cases.
Slovenian: Pri navedenih primerih niso opisovali znakov akutnega toksičnega delovanja.
English: Table 2 Effects of other active substances on everolimus
Slovenian: Preglednica 2 Vpliv drugih učinkovin na everolimus
English: • A dose-dependent brain penetration of everolimus, which is consistent with the hypothesis of saturation of an efflux pump present in the brain capillary endothelial cells.
Slovenian: • da je prehajanje everolimusa v možgane odvisno od odmerka, kar je skladno s hipotezo o nasičenosti izlivne črpalke, ki se nahaja na endotelijskih celicah možganskih kapilar;
English: Non-infectious pneumonitis (including interstitial lung disease) was described very commonly in patients taking everolimus in the advanced renal cell carcinoma (RCC) setting (see section 4.8).
Slovenian: Neinfekcijsko pljučnico (vključno z intersticijsko boleznijo pljuč) so zelo pogosto opisovali pri bolnikih, ki so prejemali everolimus v okviru zdravljenja napredovanega karcinoma ledvičnih celic (glejte poglavje 4.8).
English: How to take this medicine
Slovenian: Kako jemati zdravilo
English: Votubia could harm a breast-fed baby.
Slovenian: Zdravilo Votubia lahko škoduje dojenemu otroku.
English: Titration
Slovenian: Titracija
English: Single doses of up to 70 mg have been given with acceptable acute tolerability in the adult population.
Slovenian: V populaciji odraslih so bolniki posamezne odmerke do 70 mg prenašali z akutnimi simptomi, ki so bili sprejemljivi.
English: It may be necessary to treat your infection before starting Votubia.
Slovenian: Verjetno bo treba okužbo pozdraviti, preden začnete jemati zdravilo Votubia.
English: Table 6 EXIST-1 - SEGA response
Slovenian: Preglednica 6 EXIST-1 - Odziv SEGA
English: Put the oral syringe into the patient's mouth.
Slovenian: Brizgo za peroralno dajanje položite bolniku v usta.
English: Push the plunger in slowly to release the full contents of the oral syringe.
Slovenian: Počasi pritiskajte bat, da iztisnete celotno vsebino brizge.
English: The adverse events considered to be associated with the use of Votubia (adverse reactions), based upon the review and medical assessment of all adverse events reported in the above studies, are described below.
Slovenian: Neželeni dogodki, za katere se po pregledu in medicinski oceni vseh poročanih neželenih dogodkov iz zgoraj navedenih študij domneva, da so povezani z uporabo zdravila Votubia (neželeni učinki), so opisani v nadaljevanju.
English: The European Medicines Agency has deferred the obligation to submit the results of studies with Votubia in one or more subsets of the paediatric population in refractory epilepsy associated with tuberous sclerosis complex (see section 4.2 for information on paediatric use).
Slovenian: Evropska agencija za zdravila je začasno odložila zahtevo za predložitev rezultatov študij z zdravilom Votubia za eno ali več podskupin pediatrične populacije pri neodzivni epilepsiji v povezavi s tuberozno sklerozo (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
English: The European Medicines Agency has waived the obligation to submit the results of studies with Votubia in all subsets of the paediatric population in angiomyolipoma (see section 4.2 for information on paediatric use).
Slovenian: Evropska agencija za zdravila je odstopila od zahteve za predložitev rezultatov študij z zdravilom Votubia za vse podskupine pediatrične populacije pri angiomiolipomu (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
English: The study consisted of three phases: an 8-week baseline observation phase; an 18-week double-blind, placebo-controlled core treatment phase (composed of titration and maintenance periods), an extension phase of ≥48 weeks in which all patients received Votubia and a post-extension phase of ≤48 weeks in which all patients received Votubia.
Slovenian: Študija je obsegala tri obdobja: 8-tedensko izhodiščno obdobje opazovanja, 18-tedenski osnovni del študije z dvojno slepim, s placebom kontroliranim zdravljenjem (ki je obsegalo titracijo in obdobje vzdrževalnega zdravljenja) ter obdobje podaljšanja najmanj 48 tednov, v katerem so vsi bolniki prejemali zdravilo Votubia.
English: Everolimus appeared to spontaneously exacerbate background diseases (chronic myocarditis in rats, coxsackie virus infection of plasma and heart in monkeys, coccidian infestation of the gastrointestinal tract in minipigs, skin lesions in mice and monkeys).
Slovenian: Zdi se, da je zdravljenje z everolimusom spontano poslabšalo osnovne bolezni (kronični miokarditis pri podganah, okužbo s coxsackie virusom v plazmi in srcu pri opicah, kokcidijsko infestacijo prebavil pri prašičkih, kožne lezije pri miših in opicah).
English: Votubia dispersible tablets are given together with other medicines for epilepsy.
Slovenian: Zdravilo Votubia se uporablja skupaj z drugimi zdravili za zdravljenje epilepsije.
English: Careful titration may be required to obtain the optimal therapeutic effect.
Slovenian: Za najboljši učinek zdravljenja je včasih potrebno skrbno titriranje odmerka.
English: It contains an active substance called everolimus which may reduce the size of kidney tumours called renal angiomyolipomas and brain tumours called subependymal giant cell astrocytomas (SEGA).
Slovenian: Vsebuje zdravilno učinkovino z imenom everolimus, ki lahko zmanjša obseg ledvičnih tumorjev, imenovanih ledvični angiomiolipomi, in možganskih tumorjev z imenom subependimski gigantocelični astrocitomi.
English: Votubia dispersible tablets are to be taken as a suspension only and must not be swallowed whole, chewed, or crushed.
Slovenian: Votubia disperzibilne tablete je treba zaužiti izključno v obliki suspenzije, ne sme se jih žvečiti, drobiti ali zaužiti celih.
English: Wipe the glass and spoon with a clean paper towel.
Slovenian: Kozarec in žličko temeljito sperite s čisto vodo in ju obrišite s čisto papirnato brisačo.
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.
Slovenian: Zdravila Votubia se ne sme uporabljati pri otrocih ali mladostnikih s tuberozno sklerozo, ki imajo angiomiolipom ledvice v odsotnosti subependimskega gigantoceličnega astrocitoma, saj pri teh bolnikih ni bilo proučevano.
English: An interaction study in healthy subjects demonstrated that co-administration of an oral dose of midazolam, a sensitive CYP3A substrate probe, with everolimus resulted in a 25% increase in midazolam Cmax and a 30% increase in midazolam AUC(0-inf).
Slovenian: Rezultati študije interakcij pri zdravih prostovoljcih so pokazali, da je sočasna uporaba everolimusa in peroralnega odmerka midazolama, ki je občutljiv predstavnik substratov CYP3A, povzročila zvišanje Cmax midazolama za 25 % in povečanje AUC(0-inf) midazolama za 30 %.
English: Of the enrolled patients, 79.5% had bilateral SEGAs, 42.7% had ≥2 target SEGA lesions, 25.6% had inferior growth, 9.4% had evidence of deep parenchymal invasion, 6.8% had radiographic evidence of hydrocephalus, and 6.8% had undergone prior SEGA-related surgery.
Slovenian: Od vključenih bolnikov jih je 79,5 % imelo SEGA obojestransko, 42,7 % jih je imelo najmanj 2 ciljni SEGA leziji, 25,6 % je bilo bolnikov s slabšo rastjo, 9,4 % jih je imelo znake globoke invazije tumorja v parenhim, 6,8 % jih je imelo rentgensko dokazan hidrocefalus in 6,8 % bolnikov je že prej prestalo kirurški poseg zaradi SEGA.
English: Votubia is also an anti-tumour medicine which can block certain cells in the body from growing.
Slovenian: Votubia je tudi protitumorsko zdravilo, ki lahko zavira rast določenih telesnih celic.
English: All medicines listed above should be avoided during your treatment with Votubia.
Slovenian: Vsem zgoraj navedenim zdravilom se morate izogibati med jemanjem zdravila Votubia.
English: The proportion of patients achieving at least 50% reductions in SEGA volume was 45.9% (45/98) and 62.1% (41/66) at weeks 96 and 192 after start of everolimus treatment.
Slovenian: Delež bolnikov, ki so dosegli vsaj 50-odstotno zmanjšanje volumna SEGA je bil 45,9 % (45/98) v 96. tednu in 62,1% (41/66) v 192. tednu od začetka zdravljenja z everolimusom.
English: Post-hoc sub-group analysis of EXIST-2 (study CRAD001M2302) carried out at time of primary analysis demonstrated that angiomyolipoma response rate is reduced below the threshold of 5 ng/ml (Table 5).
Slovenian: Naknadna analiza podatkov podskupin iz študije EXIST-2 (študije CRAD001M2302), ki so jo izvedli v času primarne analize, je pokazala, da je delež odziva angiomiolipoma manjši pri vrednostih, ki ne dosegajo praga 5 ng/ml (preglednica 5).
English: Draw up 5 ml of water by slowly pulling the plunger up.
Slovenian: V brizgo potegnite 5 ml vode tako, da počasi vlečete bat navzgor.
English: Caregivers are advised to avoid contact with suspensions of Votubia dispersible tablets.
Slovenian: Negovalcem svetujemo, da se izogibajo stiku s suspenzijo iz disperzibilnih tablet Votubia.
English: ≥18 years b n=21
Slovenian: ≥18 let n=21
English: Management of severe and/or intolerable suspected adverse reactions may require dose reduction and/or temporary interruption of Votubia therapy.
Slovenian: Prilagajanje odmerkov v primeru neželenih učinkov Obvladovanje hudih ali nesprejemljivih neželenih učinkov, za katere obstaja sum povezanosti z zdravilom, lahko zahteva znižanje odmerka in/ali začasno prekinitev zdravljenja z zdravilom Votubia.
English: Instructions for use and handling
Slovenian: Navodila za uporabo in rokovanje z zdravilom
English: In the study, partial-onset seizures were defined as all electroencephalogram (EEG)-confirmed sensory seizures or motor seizures in which a generalised onset had not been demonstrated on a past EEG.
Slovenian: V študiji so bili žariščni epileptični napadi definirani kot vsi z elektroencefalogramom (EEG) potrjeni senzorični epileptični napadi ali motorični epileptični napadi pri katerih generaliziran začetek ni bil prikazan s predhodnim EEG.
English: After administration of the prepared suspension, approximately 5 ml of water and 4 ml of air should be drawn into the same syringe, and the contents should be swirled to suspend remaining particles.
Slovenian: Po zaužitju pripravljene suspenzije je treba v isto brizgo potegniti še približno 5 ml vode in 4 ml zraka in z vrtenjem brizge premešati vsebino, da se porazdelijo še preostali delci.
English: Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, protein kinase inhibitors, ATC code: L01XE10
Slovenian: Farmakoterapevtska skupina: zdravila z delovanjem na novotvorbe (citostatiki), druga zdravila z delovanjem na novotvorbe (citostatiki), zaviralci protein-kinaze, oznaka ATC: L01XE10
English: Taking the medicine
Slovenian: Jemanje zdravila
English: At the time of the final analysis (4 years following the last patient randomisation), the median duration of exposure to everolimus was 204.1 weeks (range 2 to 278).
Slovenian: V času končne analize (4 leta po randomizaciji zadnjega bolnika) je bilo mediano trajanje izpostavljenosti everolimusu 204,1 tedna (razpon od 2 do 278).
English: Mixing the medicine
Slovenian: Mešanje zdravila
English: Key secondary endpoints in hierarchal order of testing included the absolute change in frequency of total seizure events per 24-hour EEG from baseline to week 24, time to SEGA progression, and skin lesion response rate.
Slovenian: Ključni sekundarni cilji opazovanja, navedeni v hierarhičnem zaporedju izvajanja preiskav, so vključevali absolutno spremembo pogostnosti vseh epileptičnih dogodkov v času 24-urnega snemanja EEG od izhodišča do 24. tedna, čas do napredovanja SEGA in delež bolnikov z odzivom kožnih sprememb.
English: Potent and moderate CYP3A4 inducers Rifampicin
Slovenian: Močni in zmerni induktorji CYP3A4 rifampicin
English: At the time of the final analysis, the median duration of exposure among all such patients was 204.9 weeks (range: 8.1 to 253.7).
Slovenian: Ob času končne analize je bilo mediano trajanje izpostavljenosti med vsemi takimi bolniki 204,9 tedna (razpon od 8,1 do 253,7).
English: If any tablets get stuck in the dry upper part of the oral syringe, gently tap the oral syringe until they fall down into the water.
Slovenian: Če se katera od tablet zatakne v zgornjem suhem delu brizge, nežno potrkajte po brizgi, tako da tableta pade v vodo.
English: For patients who require use of corticosteroids for treatment of non-infectious pneumonitis, prophylaxis for pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) may be considered.
Slovenian: Pri bolnikih, pri katerih je za zdravljenje neinfekcijske pljučnice potrebna uporaba kortikosteroidov, je smiselno razmisliti o profilaksi pljučnice, povzročene s Pneumocystis jiroveci (carinii) (PJP, PCP).