natgillin/translations-raw huggingface dataset:
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. 
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).
Det indeholder et aktivt stof, der hedder everolimus, som kan mindske størrelsen af nyresvulster, kaldet renale angiomyolipomer, og hjernesvulster, kaldet subependymale kæmpecelle-astrocytomer (SEGA). 
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).
I så fald må en daglig dosis på 2,5 mg ikke overskrides (se pkt. 
In this case, a dose of 2.5 mg daily must not be exceeded (see sections 4.4
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. 
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.
- SEGA forbundet med TSC hos voksne og børn, hvor operation ikke er hensigtsmæssig. 
SEGA associated with TSC in adults and children for whom surgery is not appropriate.
I alt 117 patienter blev randomiseret, 78 til Votubia og 39 til placebo. 
A total of 117 patients were randomised, 78 to Votubia and 39 to placebo.
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. 
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.
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. 
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.
Aktivt stof: everolimus. 
The active substance is everolimus.
I EXIST-3 (studie CRAD001M2304) øgede everolimus præ-doseringskoncentrationen af de antiepileptiske farmaka carbamazepin og clobazam og clobazams metabolit N-desmethylclobazam med omkring 10 %. 
In EXIST-3 (Study CRAD001M2304), everolimus increased pre-dose concentrations of the antiepileptics carbamazepine, clobazam, and the clobazam metabolite N-desmethylclobazam by about 10%.
Imens spidsen af den orale sprøjte peger opad, hvivles vandet rundt for at samle det af lægemidlet, der evt. er tilbage i sprøjten. 
With the tip of the oral syringe pointing upwards, swirl the water around to collect any medicine that is left inside.
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. 
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.
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. 
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.
Put den orale sprøjte ind i patientens mund. 
Put the oral syringe into the patient's mouth.
Steady state-farmakokinetik 
Steady-state pharmacokinetics
Profylaktisk behandling af PJP/PCP bør overvejes, når det er nødvendigt med samtidig behandling med kortikosteroider eller andre immunosupressive lægemidler. 
Prophylaxis for PJP/PCP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required.
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. 
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.
Radiologisk bevis for seriel SEGA-vækst var et af inklusionskriterierne. 
Radiological evidence of serial SEGA growth was required for entry.
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. 
If you are following a specific diet to reduce the frequency of your seizures, please inform your doctor before taking Votubia.
Der var ingen tegn på nyretoksicitet hos aber og minigrise. 
There was no indication of kidney toxicity in monkeys or minipigs.
Farmakoterapeutisk klassifikation: Antineoplastiske midler, andre antineoplastiske midler, proteinkinasehæmmere, ATC-kode: L01XE10 
Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, protein kinase inhibitors, ATC code: L01XE10
Telithromycin, clarithromycin Nefazodon 
Telithromycin, clarithromycin
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. 
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.
≤5 nanogram/ml >5 nanogram/ml Forskel Forskel er “≤5 nanogram/ml” minus “>5 nanogram/ml” 
≤5 ng/ml >5 ng/ml Difference Difference is “≤5 ng/ml” minus “>5 ng/ml”
Everolimus har immunsuppressive egenskaber og kan prædisponere patienter for infektioner forårsaget af bakterier, svampe, vira eller protozoer, inklusive infektioner med opportunistiske patogener (se pkt. 
Everolimus has immunosuppressive properties and may predispose patients to bacterial, fungal, viral or protozoal infections, including infections with opportunistic pathogens (see section 4.8).
Tabel 7 EXIST-1 - SEGA respons 
Table 7 EXIST-1 - SEGA response
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. 
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.
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). 
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).
Everolimus kan derfor påvirke biotilgængeligheden af samtidigt administrerede orale CYP3A4-substrater. 
Hence everolimus may affect the bioavailability of orally co-administered CYP3A4 substrates.
Tabel 3 Bivirkninger rapporteret i TSC-studier 
Table 3 Adverse reactions reported in TSC studies
Votubia dispergible tabletter anvendes til at behandle SEGA forbundet med TSC hos voksne og børn, hvor operation ikke er hensigtsmæssig. 
Votubia dispersible tablets are used to treat SEGA associated with TSC in adults and children for whom surgery is not appropriate.
Ved tuberøs sklerose-komplekssyndrom fører inaktiverende mutationer i et af generne TSC1 og TSC2 til dannelse af hamartomer alle steder i kroppen. 
In tuberous sclerosis complex syndrome, inactivating mutations in the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body.
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. 
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.
Samtidig administration med hæmmere og induktorer af CYP3A4 og/eller Multidrug efflux pump P-glykoprotein (PgP) skal undgås. 
Co-administration with inhibitors and inducers of CYP3A4 and/or the multidrug efflux pump P-glycoprotein (PgP) should be avoided.
Opportunistiske infektioner som pneumocystis jirovecii (carinii) pneumoni (PJP, PCP) bør udelukkes i differentialdiagnosticeringen af non-infektiøs pneumonitis (se afsnittet om ”Infektioner” nedenfor). 
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).
Instruktioner for anvendelse og håndtering 
Instructions for use and handling
Vurdér everolimus-dal-niveauet 2 uger efter start af den ekstra induktor. 
Assess the everolimus trough level 2 weeks after initiating the additional inducer.
Næseblod (epistaxis) 
Nose bleeds (epistaxis)
Læg dem ned i sprøjtens cylinder med det samme. 
Place them into the barrel of the oral syringe straight away.
Respondenter - n (%) Responsrate 95 % CI 
Responders - n (%) Response rate 95% CI
I kliniske studier er everolimus forbundet med tilfælde af hæmoragi. 
In clinical studies, everolimus has been associated with haemorrhage events.
Fjern luften 
Removing air
Tabel 4 Bivirkninger rapporteret i TSC-studier 
Table 4 Adverse reactions reported in TSC studies
For børn med SEGA, er det vigtigt at tale med lægen om børnevaccinationsprogrammet, inden behandling med Votubia. 
For children with SEGA, it is important to have a discussion with the doctor about the childhood vaccination program before treatment with Votubia.
<6 år n=33 
<6 years n=33
Der er ikke rapporteret nogen alvorlige tilfælde af renal hæmoragi i forbindelse med TSC. 
No serious cases of renal haemorrhage were reported in the TSC setting.
Perikon (Hypericum perforatum) 
St John's Wort (Hypericum perforatum)
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). 
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).
Menstruationsforstyrrelser, såsom længere intervaller mellem menstruationerne Forhøjet niveau af kvindeligt forplantningshormon (follikelstimulerende hormon) 
Menstruation disorders such as delayed periods Higher level of female reproductive hormone (blood follicle stimulating hormone increased)
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. 
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.
Blodglucose 
Blood glucose
Højt niveau af lipider (fedtstoffer) i blodet (hyperkolesterolæmi) Nedsat appetit 
High level of lipids (fats) in the blood (hypercholesterolaemia) Decreased appetite
Tabel 6 EXIST-1 - SEGA respons 
Table 6 EXIST-1 - SEGA response
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. 
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.
Patienten skal med det samme drikke hele suspensionen fra glasset. 
The patient must immediately drink all of the oral suspension from the glass.
Sæt den fyldte sprøjte i et rent og tomt glas, så spidsen peger opad. 
Put the filled oral syringe in the clean, empty glass with the tip pointing up.
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). 
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).
Derfor bør omsorgspersoner undgå kontakt med suspensionen. 
Therefore caregivers are advised to avoid contact with the suspension.
Seponer Votubia. 
Discontinue Votubia.
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). 
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.
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. 
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.
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. 
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.
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). 
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).
Kom ca. 25 ml vand i 30 ml doseringskoppen. 
Add about 25 ml of water to the 30 ml dose cup.
Menstruationsforstyrrelser, såsom kraftig menstruation (menorragi) eller vaginal blødning Søvnløshed 
Menstruation disorders such as heavy periods (menorrhagia) or vaginal bleeding Trouble sleeping (insomnia)
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. 
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.
På tidspunktet for den endelige analyse (4 år efter sidste patientrandomisering) var den mediane eksponeringsvarighed for everolimus 204,1 uger (interval 2 til 278). 
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).
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. 
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.
Fortæl det straks til din læge, hvis du oplever nogen af disse alvorlige bivirkninger, da det kan have livstruende konsekvenser. 
If you experience any of these side effects, tell your doctor immediately as this might have lifethreatening consequences.
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. 
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.
Hvis du får Votubia til behandling af TSC med angiomyolipom i nyrerne, er den normale, daglige dosis 10 mg. 
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.
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. 
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.
Antimykotiske lægemidler må ikke anvendes, medmindre der er konstateret en svampeinfektion (se pkt. 
Antifungal agents should not be used unless fungal infection has been diagnosed (see section 4.5).
I et fertilitetsstudie med hanrotter påvirkedes testikelmorfologien ved 0,5 mg/kg og derover, og sædcellemotilitet, antal sædceller og plasmatestosteronniveau faldt ved 5 mg/kg, hvilket er inden for det terapeutiske eksponeringsområde og medførte et fald i fertilitet hos hanrotterne. 
In a male fertility study in rats, testicular morphology was affected at 0.5 mg/kg and above, and sperm motility, sperm head count, and plasma testosterone levels were diminished at 5 mg/kg, which is within the range of therapeutic exposure and which caused a reduction in male fertility.
Fase III-studie med SEGA-patienter 
Phase III study in SEGA patients
Votubia må ikke bruges til børn og unge med TSC, som har angiomyolipom i nyrerne, men ikke SEGA, da det ikke er blevet undersøgt hos denne patientgruppe. 
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.
Vurdér everolimus-dal-niveauet 2 uger efter seponering af en af flere potente CYP3A4-induktorer. 
Assess the everolimus trough level 2 weeks after discontinuation of one of multiple strong CYP3A4 inducers.
Baselineanfaldsfrekvensen var en væsentlig faktor for anfaldsresponset (oddsratio 0,978 [95 % CI: 0,959; 
Baseline seizure frequency was a significant factor in the seizure response (with an odds ratio of 0.978 [95% CI: 0.959, 0.998]).
Votubia er også en medicin mod kræft, som kan forhindre visse celler i kroppen i at vokse. 
Votubia is also an anti-tumour medicine which can block certain cells in the body from growing.
phenytoin, carbamazepin eller phenobarbital og andre lægemidler mod epilepsi, som bruges til at standse krampeanfald. 
phenytoin, carbamazepine or phenobarbital and other anti-epileptics used to stop seizures or fits.
Dispergibel tablet. 
Dispersible tablet.
De første symptomer kan omfatte feber, hududslæt, ledsmerter og betændelse. 
The first symptoms may include fever, skin rash, joint pain and inflammation.
Dal-everolimus-koncentrationen bør måles 2 til 4 uger senere, eftersom der bør tages højde for den naturlige nedbrydningstid for de inducerede enzymer (se pkt. 
The everolimus trough concentrations should be assessed 2 to 4 weeks later since the natural degradation time of the induced enzymes has to be taken into account (see sections 4.2 and 4.4).
• 2 rene glas • Ca. 30 ml vand 
• 2 clean glasses • Approximately 30 ml of water
Respons var defineret som: ≥50 % reduktion i summen af SEGA-volumen i forhold til baseline, plus ingen utvetydig forværring af ikke-mål-SEGA-læsioner, plus fravær af ny SEGA ≥1 cm for den længste diameter, plus ingen ny eller forværret hydrocephalus Primær analyse for dobbeltblindet periode Endelig analyse inkluderer patienter, som skiftede over fra placebogruppen; median eksponeringsvarighed for everolimus på 204,9 uger 
Response was defined as: ≥50% reduction in the sum of SEGA volume relative to baseline, plus no unequivocal worsening of non-target SEGA lesions, plus absence of new SEGA ≥1 cm in longest diameter, plus no new or worsening hydrocephalus Primary analysis for double blind period Final analysis includes patients who crossed over from the placebo group; median duration of exposure to everolimus of 204.9 weeks
Forhøjet blodfollikel-stimulerende hormon a 
Uncommon Blood follicle stimulating hormone increased a
Genoptag behandlingen med Votubia ved samme dosis. 
Re-initiate Votubia at same dose.
Vedvarende reduktion var tydelig ved uge 24; 41,9 % (31/74) af patienterne havde ≥50 % reduktion, og 78,4 % (58/74) af patienterne havde ≥30 % reduktion i SEGA-volumen. 
Sustained reductions were evident at week 24, 41.9% (31/74) of patients had ≥50% reductions and 78.4% (58/74) of patients had ≥30% reductions in SEGA volume.
Grad 2 (≥1x10 
Grade 2 (≥1x10
Hvis der kræves en højere dosis eller antal af tabletter, skal der klargøres en ekstra sprøjte. 
If a higher dose or number of tablets is required, an additional syringe must be prepared.
Tag den orale 10 ml sprøjte og træk stemplet ud, så det adskilles helt fra sprøjtens cylinder. 
Take the 10 ml oral syringe and pull out the plunger, removing it completely from the barrel of the syringe.
Votubia er indiceret som supplerende behandling hos patienter i alderen 2 år og ældre med refraktære partielle anfald, med eller uden sekundær generalisering, i forbindelse med tuberøst sklerosekompleks. 
Votubia is indicated as adjunctive treatment of patients aged 2 years and older whose refractory partial-onset seizures, with or without secondary generalisation, are associated with tuberous sclerosis complex (TSC).