FrancophonIA/ELRC3.0 huggingface dataset:
English: Overactivation of mTOR results in neuronal dysplasia, aberrant axonogenesis and dendrite formation, increased excitatory synaptic currents, reduced myelination, and disruption of the cortical laminar structure causing abnormalities in neuronal development and function.
Danish: Overaktivering af mTOR resulterer i neuronal dysplasi, atypisk axonogenese og dannelse af dendritceller, øgede excitatoriske synaptiske strømme, reduceret myelinering og forstyrrelse af den kortikale laminære struktur, hvilket forårsager abnormiteter i den neuronale udvikling og funktion.
English: Population pharmacokinetic model simulations showed that a starting dose of 7 mg/m would be necessary to attain Cmin within the 5 to 15 ng/ml range in patients younger than 3 years of age.
Danish: Simuleringer fra en farmakokinetisk populationsanalysemodel viste, at en startdosis på 7 mg/m var nødvendig for at opnå Cmin inden for intervallet 5 til 15 nanogram/ml hos patienter under 3 år.
English: Instructions for caregivers preparing the suspension using an oral syringe:
Danish: Instruktioner til omsorgspersoner om klargøring af suspensionen ved brug af en oral sprøjte:
English: Votubia 3-7 ng/ml Votubia 9-15 ng/ml Placebo
Danish: Votubia 3-7 nanogram/ml Votubia 9-15 nanogram/ml Placebo
English: If you are taking an anti-seizure medicine, a change in the dose of the anti-seizure medicine (increase or decrease) may make a change in the Votubia dose necessary.
Danish: Hvis du tager medicin mod krampeanfald, kan ændring af din dosis af den pågældende medicin (forøgelse eller nedsættelse) gøre det nødvendigt at ændre din Votubia-dosis.
English: Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Danish: Inden for hver enkelt frekvensgruppe skal bivirkningerne opstilles efter, hvor alvorlige de er.
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).
Danish: Et interaktionsstudie med raske forsøgspersoner viste, at samtidig administration af en oral dosis midazolam, et sensitivt CYP3A-testsubstrat, og everolimus resulterede i en stigning på 25 % i Cmax og på 30 % i AUC(0-inf) for midazolam.
English: Table 7 Change in primary SEGA volume over time
Danish: Tabel 7 Forandring i primær SEGA-volumen over tid
English: Do not take a double dose to make up for the forgotten tablets.
Danish: Du må ikke tage en dobbeltdosis som erstatning for de glemte tabletter.
English: Everolimus trough concentrations should be assessed at least 1 week after the addition of a moderate CYP3A4 or PgP inhibitor.
Danish: Everolimus dal-koncentrationen bør vurderes mindst 1 uge efter tilføjelse af en moderat CYP3A4- eller PgP-hæmmer.
English: Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG (Bacillus Calmette-Guérin), yellow fever, varicella, and TY21a typhoid vaccines.
Danish: Eksempler på levende vaccine er: intranasal influenza, mæslinger, fåresyge, røde hunde, oral polio, BCG (Bacillus Calmette-Guérin), gul feber, varicella og TY21a-tyfusvacciner.
English: Gently stir the contents of the glass until the tablet(s) break apart (approximately 7 minutes) and then drink the contents immediately.
Danish: Rør forsigtigt i glassets indhold, indtil tabletten/tabletterne går i stykker (ca. 7 minutter), og drik så indholdet straks.
English: Some of these infections have been severe (e.g. leading to sepsis [including septic shock], respiratory or hepatic failure) and occasionally fatal in adult and paediatric patients (see section 4.8).
Danish: Nogle af disse infektioner har været alvorlige (har fx ført til sepsis [inklusive septisk shock], respirations- eller leversvigt), og i nogle tilfælde været letale hos voksne og pædiatriske patienter (se pkt.
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).
Danish: Det indeholder et aktivt stof, der hedder everolimus, som kan mindske størrelsen af nyresvulster, kaldet renale angiomyolipomer, og hjernesvulster, kaldet subependymale kæmpecelle-astrocytomer (SEGA).
English: In this case, a dose of 2.5 mg daily must not be exceeded (see sections 4.4
Danish: I så fald må en daglig dosis på 2,5 mg ikke overskrides (se pkt.
English: Votubia is indicated for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumour size or presence of aneurysm, or presence of multiple or bilateral tumours) but who do not require immediate surgery.
Danish: Votubia er indiceret til behandling af voksne patienter med renal angiomyolipom i tilknytning til tuberøst sklerosekompleks (TSC) med risiko for komplikationer (baseret på faktorer som f.eks. tumorstørrelse eller tilstedeværelse af aneurisme eller af multiple eller bilaterale tumorer), men hvor umiddelbart indgreb ikke er påkrævet.
English: SEGA associated with TSC in adults and children for whom surgery is not appropriate.
Danish: - SEGA forbundet med TSC hos voksne og børn, hvor operation ikke er hensigtsmæssig.
English: A total of 117 patients were randomised, 78 to Votubia and 39 to placebo.
Danish: I alt 117 patienter blev randomiseret, 78 til Votubia og 39 til placebo.
English: If you are being treated for TSC with angiomyolipoma of the kidney, Votubia will only be prescribed for you by a doctor with experience in treating patients with TSC.
Danish: Hvis du behandles for TSC med angiomyolipom i nyrerne, ordineres Votubia kun til dig af en læge med erfaring i behandling af patienter med TSC.
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.
Danish: Orale doser af everolimus på ≥0,1 mg/kg (ca. 4 % af AUC0-24h hos patienter, der fik en dosis på 10 mg daglig) til hunrotter, resulterede dog i en stigning i præ-implantationstab.
English: The active substance is everolimus.
Danish: Aktivt stof: everolimus.
English: In EXIST-3 (Study CRAD001M2304), everolimus increased pre-dose concentrations of the antiepileptics carbamazepine, clobazam, and the clobazam metabolite N-desmethylclobazam by about 10%.
Danish: I EXIST-3 (studie CRAD001M2304) øgede everolimus præ-doseringskoncentrationen af de antiepileptiske farmaka carbamazepin og clobazam og clobazams metabolit N-desmethylclobazam med omkring 10 %.
English: With the tip of the oral syringe pointing upwards, swirl the water around to collect any medicine that is left inside.
Danish: Imens spidsen af den orale sprøjte peger opad, hvivles vandet rundt for at samle det af lægemidlet, der evt. er tilbage i sprøjten.
English: The stability of the ready to use suspension has been demonstrated for 30 minutes when using an oral syringe or 60 minutes when using a small glass.
Danish: For en klargjort suspension er der påvist en stabilitet på 30 minuter, når der anvendes en oral sprøjte, eller 60 minutter, når der anvendes et lille glas.
English: In an exploratory analysis of patients with TSC with angiomyolipoma who also had SEGA, the SEGA response rate (proportion of patients with ≥50% reduction from baseline in target lesion volumes in the absence of progression) was 10.3% in the everolimus arm in the primary analysis (versus no responses reported in the 13 patients randomised to placebo with a SEGA lesion at baseline) and increased to 48.0% in the final analysis.
Danish: I en eksplorativ analyse af patienter med TSC og angiomyolipom, som også havde SEGA, var SEGAresponsraten (andelen af patienter med ≥50 % reduktion af mållæsionsvolumen fra baseline i fravær af progression) 10,3 % i everolimus-armen i den primære analyse (versus intet rapporteret respons hos de 13 patienter med SEGA-læsion ved baseline, der blev randomiseret til placebo) og steg til 48,0 % i den endelige analyse.
English: Put the oral syringe into the patient's mouth.
Danish: Put den orale sprøjte ind i patientens mund.
English: Steady-state pharmacokinetics
Danish: Steady state-farmakokinetik
English: Prophylaxis for PJP/PCP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required.
Danish: Profylaktisk behandling af PJP/PCP bør overvejes, når det er nødvendigt med samtidig behandling med kortikosteroider eller andre immunosupressive lægemidler.
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.
Danish: I studiepopulationen, som fik everolimus, inklusive patienter, som skiftede over fra placebogruppen (N=111), startede tumorresponset så tidligt som efter 12 uger på everolimus og var opretholdt på senere tidspunkter.
English: Radiological evidence of serial SEGA growth was required for entry.
Danish: Radiologisk bevis for seriel SEGA-vækst var et af inklusionskriterierne.
English: If you are following a specific diet to reduce the frequency of your seizures, please inform your doctor before taking Votubia.
Danish: Hvis du følger en særlig diæt for at nedsætte antallet af epileptiske anfald, skal du fortælle det til din læge, før du begynder at tage Votubia.
English: There was no indication of kidney toxicity in monkeys or minipigs.
Danish: Der var ingen tegn på nyretoksicitet hos aber og minigrise.
English: Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, protein kinase inhibitors, ATC code: L01XE10
Danish: Farmakoterapeutisk klassifikation: Antineoplastiske midler, andre antineoplastiske midler, proteinkinasehæmmere, ATC-kode: L01XE10
English: Telithromycin, clarithromycin
Danish: Telithromycin, clarithromycin Nefazodon
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.
Danish: I det ene studie var gennemsnitlig AUC for everolimus hos 8 personer med moderat nedsat leverfunktion (Child-Pugh B) to gange større end AUC hos 8 personer med normal leverfunktion.
English: ≤5 ng/ml >5 ng/ml Difference Difference is “≤5 ng/ml” minus “>5 ng/ml”
Danish: ≤5 nanogram/ml >5 nanogram/ml Forskel Forskel er “≤5 nanogram/ml” minus “>5 nanogram/ml”
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).
Danish: Everolimus har immunsuppressive egenskaber og kan prædisponere patienter for infektioner forårsaget af bakterier, svampe, vira eller protozoer, inklusive infektioner med opportunistiske patogener (se pkt.
English: Table 7 EXIST-1 - SEGA response
Danish: Tabel 7 EXIST-1 - SEGA respons
English: In juvenile rat toxicity studies, systemic toxicity included decreased body weight gain, food consumption, and delayed attainment of some developmental landmarks, with full or partial recovery after cessation of dosing.
Danish: I toksicitetsstudier med unge rotter omfattede den systemiske toksicitet nedsat legemsvægtstigning og fødeindtag samt forsinket opnåelse af visse udviklingsmæssige milepæle, med fuld eller delvis bedring efter afbrydelse af doseringen.
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).
Danish: En post-hoc-undergruppe-analyse af EXIST-2 (studie CRAD001M2302), udført på tidspunktet for den primære analyse, viste, at angiomyolipom-responsraten er reduceret ved en tærskelværdi på under 5 nanogram/ml (Tabel 5).
English: Hence everolimus may affect the bioavailability of orally co-administered CYP3A4 substrates.
Danish: Everolimus kan derfor påvirke biotilgængeligheden af samtidigt administrerede orale CYP3A4-substrater.
English: Table 3 Adverse reactions reported in TSC studies
Danish: Tabel 3 Bivirkninger rapporteret i TSC-studier
English: Votubia dispersible tablets are used to treat SEGA associated with TSC in adults and children for whom surgery is not appropriate.
Danish: Votubia dispergible tabletter anvendes til at behandle SEGA forbundet med TSC hos voksne og børn, hvor operation ikke er hensigtsmæssig.
English: In tuberous sclerosis complex syndrome, inactivating mutations in the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body.
Danish: Ved tuberøs sklerose-komplekssyndrom fører inaktiverende mutationer i et af generne TSC1 og TSC2 til dannelse af hamartomer alle steder i kroppen.
English: Once a stable dose is attained, trough concentrations should be monitored every 3 to 6 months in patients with changing body surface area, or every 6 to 12 months in patients with stable body surface area, for the duration of treatment.
Danish: Når en stabil dosis er opnået, skal dal-koncentrationen monitoreres hver 3. til 6. måned hos patienter med vekslende overfladeareal eller hver 6. til 12. måned hos patienter med stabilt overfladeareal, så længe behandlingen står på.
English: Co-administration with inhibitors and inducers of CYP3A4 and/or the multidrug efflux pump P-glycoprotein (PgP) should be avoided.
Danish: Samtidig administration med hæmmere og induktorer af CYP3A4 og/eller Multidrug efflux pump P-glykoprotein (PgP) skal undgås.
English: Opportunistic infections such as pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) should be ruled out in the differential diagnosis of non-infectious pneumonitis (see section “Infections” below).
Danish: Opportunistiske infektioner som pneumocystis jirovecii (carinii) pneumoni (PJP, PCP) bør udelukkes i differentialdiagnosticeringen af non-infektiøs pneumonitis (se afsnittet om ”Infektioner” nedenfor).
English: Instructions for use and handling
Danish: Instruktioner for anvendelse og håndtering
English: Assess the everolimus trough level 2 weeks after initiating the additional inducer.
Danish: Vurdér everolimus-dal-niveauet 2 uger efter start af den ekstra induktor.
English: Nose bleeds (epistaxis)
Danish: Næseblod (epistaxis)
English: Place them into the barrel of the oral syringe straight away.
Danish: Læg dem ned i sprøjtens cylinder med det samme.
English: Responders - n (%) Response rate 95% CI
Danish: Respondenter - n (%) Responsrate 95 % CI
English: In clinical studies, everolimus has been associated with haemorrhage events.
Danish: I kliniske studier er everolimus forbundet med tilfælde af hæmoragi.
English: Dexamethasone
Danish: Dexamethason
English: Removing air
Danish: Fjern luften
English: Table 4 Adverse reactions reported in TSC studies
Danish: Tabel 4 Bivirkninger rapporteret i TSC-studier
English: For children with SEGA, it is important to have a discussion with the doctor about the childhood vaccination program before treatment with Votubia.
Danish: For børn med SEGA, er det vigtigt at tale med lægen om børnevaccinationsprogrammet, inden behandling med Votubia.
English: <6 years n=33
Danish: <6 år n=33
English: No serious cases of renal haemorrhage were reported in the TSC setting.
Danish: Der er ikke rapporteret nogen alvorlige tilfælde af renal hæmoragi i forbindelse med TSC.
English: St John's Wort (Hypericum perforatum)
Danish: Perikon (Hypericum perforatum)
English: In clinical studies and post-marketing spontaneous reports, everolimus has been associated with cases of pneumocystis jirovecii (carinii) pneumonia (PJP, PCP), some with fatal outcome (see section 4.4).
Danish: I kliniske studier og spontane rapporter modtaget efter markedsføring er everolimus blevet associeret med tilfælde af pneumocystis jirovecii (carinii) pneumoni (PJP, PCP), hvoraf nogle var med fatal udgang (se pkt 4.4).
English: Menstruation disorders such as delayed periods Higher level of female reproductive hormone (blood follicle stimulating hormone increased)
Danish: Menstruationsforstyrrelser, såsom længere intervaller mellem menstruationerne Forhøjet niveau af kvindeligt forplantningshormon (follikelstimulerende hormon)
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.
Danish: Efter administration af den klargjorte suspension, trækkes ca. 5 ml vand og 4 ml luft ind i den samme sprøjte og indholdet skvulpes rundt for at opslæmme de resterende partikler.
English: Blood glucose
Danish: Blodglucose
English: High level of lipids (fats) in the blood (hypercholesterolaemia) Decreased appetite
Danish: Højt niveau af lipider (fedtstoffer) i blodet (hyperkolesterolæmi) Nedsat appetit
English: Table 6 EXIST-1 - SEGA response
Danish: Tabel 6 EXIST-1 - SEGA respons
English: Everolimus is a potent inhibitor of the growth and proliferation of tumour cells, endothelial cells, fibroblasts and blood-vessel-associated smooth muscle cells and has been shown to reduce glycolysis in solid tumours in vitro and in vivo.
Danish: Everolimus er en potent hæmmer af vækst og proliferation af tumorceller, endotelceller, fibroblaster og vaskulære glatte muskelceller og har vist at reducere glykolysen i solide tumorer in vitro og in vivo.
English: The patient must immediately drink all of the oral suspension from the glass.
Danish: Patienten skal med det samme drikke hele suspensionen fra glasset.
English: Put the filled oral syringe in the clean, empty glass with the tip pointing up.
Danish: Sæt den fyldte sprøjte i et rent og tomt glas, så spidsen peger opad.
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).
Danish: Everolimus syntes spontant at forværre baggrundssygdomme (kronisk myokarditis hos rotter, Coxsackie virusinfektion i plasma og hjerte hos aber, coccidial infestation i mave-tarmkanalen hos minigrise, hudlæsioner hos mus og aber).
English: Therefore caregivers are advised to avoid contact with the suspension.
Danish: Derfor bør omsorgspersoner undgå kontakt med suspensionen.
English: Discontinue Votubia.
Danish: Seponer Votubia.
English: In the second study of 34 subjects with different impaired hepatic function compared to normal subjects, there was a 1.6-fold, 3.3-fold and 3.6-fold increase in exposure (i.e. AUC0-inf) for subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, respectively.
Danish: I det andet studie med 34 personer med forskellige grader af nedsat leverfunktion, der blev sammenlignet med personer med normal leverfunktion var der 1,6 gange, 3,3 gange og 3,6 gange øget eksponering (dvs. AUC0-uendelig) for personer med henholdsvis let (Child-Pugh A), moderat (Child-Pugh B) og svært nedsat leverfunktion (Child-Pugh C).
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.
Danish: Votubias sikkerhed og virkning hos børn i alderen 0 til 18 år med renal angiomyolipom i tilknytning til TSC under fravær af SEGA, er ikke klarlagt.
English: Women of childbearing potential must use a highly effective method of contraception (e.g. oral, injected, or implanted non-oestrogen-containing hormonal method of birth control, progesterone-based contraceptives, hysterectomy, tubal ligation, complete abstinence, barrier methods, intrauterine device [IUD], and/or female/male sterilisation) while receiving everolimus, and for up to 8 weeks after ending treatment.
Danish: Kvinder i den fertile alder skal anvende yderst sikker kontraception (fx orale, injicerede eller implanterede ikke-østrogen-indeholdende hormonale præventionsmetoder, progesteron-baserede kontraceptiva, hysterektomi, aflukning af æggeledere, fuldstændig afholdenhed, barriereprævention, intrauterint udstyr [IUD] og/eller kvindelig/mandlig sterilisation) under behandlingen med everolimus og i op til 8 uger efter endt behandling.
English: The robustness and consistency of the primary analysis were supported by the: change in primary SEGA volume as per local investigator assessment (p<0.001), with 75.0% and 39.3% of patients experiencing reductions of ≥30% and ≥50%, respectively change in total SEGA volume as per independent central review (p<0.001) or local investigator assessment (p<0.001).
Danish: Den primære analyses styrke og konsistens blev understøttet af: ændringen i primært SEGA-volumen ifølge den lokale investigators vurdering (p<0,001), hvor 75,0 % og 39,3 % af patienterne oplevede reduktioner på henholdsvis ≥30 % og ≥50 % ændringen i samlet SEGA-volumen ifølge uafhængig central gennemgang (p<0,001) eller den stedlige investigators vurdering (p<0,001).
English: Add about 25 ml of water to the 30 ml dose cup.
Danish: Kom ca. 25 ml vand i 30 ml doseringskoppen.
English: Menstruation disorders such as heavy periods (menorrhagia) or vaginal bleeding Trouble sleeping (insomnia)
Danish: Menstruationsforstyrrelser, såsom kraftig menstruation (menorragi) eller vaginal blødning Søvnløshed
English: Median age was 31 years (range: 18 to 61 years; 46.6% were <30 years at enrolment), 33.9% were male, and 89.0% were Caucasian.
Danish: Medianalderen var 31 år (fra 18 til 61 år; 46,6 % var <30 år ved inklusion), 33,9 % var mænd, og 89,0 % var kaukasere.
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).
Danish: På tidspunktet for den endelige analyse (4 år efter sidste patientrandomisering) var den mediane eksponeringsvarighed for everolimus 204,1 uger (interval 2 til 278).
English: In a population pharmacokinetic analysis of 170 patients with advanced solid tumours, no significant influence of creatinine clearance (25-178 ml/min) was detected on CL/F of everolimus.
Danish: I en farmakokinetisk populationsanalyse af 170 patienter med fremskredne massive tumorer sås der ingen signifikant effekt af kreatininclearance (25-178 ml/min) på everolimus CL/F.
English: If you experience any of these side effects, tell your doctor immediately as this might have lifethreatening consequences.
Danish: Fortæl det straks til din læge, hvis du oplever nogen af disse alvorlige bivirkninger, da det kan have livstruende konsekvenser.
English: Response was defined as: ≥50% reduction in the sum of angiomyolipoma volume relative to baseline, plus absence of new angiomyolipoma ≥1.0 cm in longest diameter, plus no increase in renal volume >20% from nadir, plus absence of grade ≥2 angiomyolipoma-related bleeding.
Danish: Respons var defineret som: ≥50 % reduktion i summen af angiomyolipom-volumen i forhold til baseline plus fravær af nyt angiomyolipom ≥1,0 cm for den længste diameter plus ingen stigning i renal volumen >20 % fra nadir plus fravær af grad ≥2 angiomyolipom-relateret blødning.
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.
Danish: Hvis du får Votubia til behandling af TSC med angiomyolipom i nyrerne, er den normale, daglige dosis 10 mg.
English: During the double-blind period, reduction of SEGA volume was evident within the initial 12 weeks of Votubia treatment: 29.7% (22/74) of patients had ≥50% reductions in volume and 73.0% (54/74) had ≥30% reductions in volume.
Danish: I løbet af den dobbeltblindede periode var reduktionen af SEGA-volumen tydelig inden for de første 12 ugers behandling med Votubia: 29,7 % (22/74) af patienterne havde ≥50 % reduktion af volumen, og 73,0 % (54/74) havde ≥30 % reduktion af volumen.
English: Antifungal agents should not be used unless fungal infection has been diagnosed (see section 4.5).
Danish: Antimykotiske lægemidler må ikke anvendes, medmindre der er konstateret en svampeinfektion (se pkt.