natgillin/translations-raw huggingface dataset:
Ved baseline havde 55 % af patienterne i siltuximabarmen og 65 % af patienterne i placeboarmen tidligere fået systemisk behandling for MCD, og 30 % af patienterne i siltuximabarmen og 31 % i placeboarmen anvendte kortikokosteroider. 
At baseline, 55% of patients in the siltuximab arm and 65% of patients in the placebo arm had received prior systemic therapies for MCD and 30% of patients in the siltuximab arm and 31% in the placebo arm were using corticosteroids.
Kvinder i den fertile alder skal anvende sikker kontraception under behandlingen og i op til 3 måneder efter behandlingen (se pkt. 
Women of childbearing potential must use effective contraception during and up to 3 months after treatment (see section 4.5).
• hvis du har en leversygdom eller leverændringer, som kan påvises i blodprøver. 
• you have liver disease or changes that show up in blood tests of the liver.
Intravenøs infusion efter rekonstitution og fortynding. 
Intravenous infusion after reconstitution and dilution.
Der er indberettet to tilfælde af reaktiveret hepatitis B, hvor SYLVANT blev administreret samtidig med en høj dosis af dexamethason og bortezomib, melphalan og prednison hos patienter med myelomatose. 
Two cases of reactivated hepatitis B have been reported when SYLVANT was administered concomitantly with high dose dexamethasone, and bortezomib, melphalan and prednisone in multiple myeloma patients.
Du kan være mere tilbøjelig til at få infektioner, mens du er i behandling med SYLVANT. 
You may be more likely to get infections while you are being treated with SYLVANT.
Totalscoren for alle symptomer (omtalt som den samlede score for symptomer relateret til MCD) er summen af sværhedsgraderne (NCI-CTCAE-grader) for symptomer relateret til MCD [generelle symptomer relateret til MCD (træthed, utilpashed, hyperhidrose, natlige svedeture, feber, vægttab, anoreksi, tumorsmerter, dyspnø og pruritus), autoimmune fænomener, væskeretention, neuropati og hudsygdomme]. 
A total score of all symptoms (referred to as the MCD-related Overall Symptom Score) is the sum of the severity grades (NCI-CTCAE grade) of the MCD-related signs and symptoms [general MCD-related (fatigue, malaise, hyperhidrosis, night sweats, fever, weight loss, anorexia, tumour pain, dyspnea, and pruritus), autoimmune phenomena, fluid retention, neuropathy, and skin disorders].
• SYLVANT fås i pakninger, der indeholder 1 hætteglas. 
• SYLVANT is available in packs containing 1 vial.
Hvis du tror, at du har fået for meget SYLVANT, skal du omgående fortælle det til lægen eller sundhedspersonalet. 
If you think you have been given too much SYLVANT, tell your doctor or nurse straight away.
For hver systemorganklasse angives bivirkningerne efter hyppighed inden for følgende kategorier: meget almindelig (≥ 1/10); almindelig (≥ 1/100 til < 1/10); 
Within the system organ class, adverse reactions are listed under headings of frequency using the following categories: very common (≥ 1/10); common (≥ 1/100 to
Ud fra de begrænsede erfaringer med siltuximab tyder de foreliggende data ikke på en øget risiko for maligne sygdomme. 
On the basis of limited experience with siltuximab the present data do not suggest any increased risk of malignancy.
SYLVANT er et lægemiddel, der indeholder det aktive stof siltuximab. 
SYLVANT is a medicine that contains the active substance siltuximab.
Du vil kun få SYLVANT af en læge eller sygeplejerske på hospitalet eller en klinik. 
SYLVANT will be given to you by your doctor or nurse, in a hospital or clinic only.
Kontakt straks lægen, hvis du får tegn på infektion under behandlingen med SYLVANT. 
Tell your doctor straight away if you get any signs of infection during treatment with SYLVANT.
Behandlingskriterier 
Treatment criteria
Analyser af både primære og sekundære endepunkter for forskellige undergrupper inklusive alder (< 65 år og ≥ 65 år), race (hvid/ikke-hvid), region (Nordamerika, Europa, Mellemøsten og Afrika samt Asien og Stillehavsområdet), brug af kortikosteroider ved baseline (ja/nej), tidligere behandling (ja/nej) og MCD histologi (plasma og blandet histologi) viste konsekvent, at virkningen af behandlingen var størst i siltuximabarmen undtagen i den hyaline vaskulære subtype, hvor ingen af patienterne opnåede definitionen af det primære endepunkt. 
Analyses for both primary and secondary endpoints on various subgroups including age (< 65 years and ≥ 65 years); race (White and Non-White); region (North America, Europe, Middle East and Africa, and Asia Pacific); baseline corticosteroid use (yes and no); prior therapy (yes and no); and MCD histology (plasmatic and mixed histology) consistently showed that the treatment effect favoured the siltuximab arm except for the hyaline vascular subgroup in which no patient achieved the definition of the primary endpoint.
Kontakt straks din læge, hvis du bemærker følgende alvorlige bivirkninger, da lægen kan være nødt til at stoppe behandlingen: 
Tell your doctor straight away if you notice the following side effects, as he or she may need to stop your treatment:
De mulige bivirkninger af at få for meget SYLVANT kendes ikke. 
It is not known what the possible side effects could be from having too much SYLVANT.
Det kan derfor ikke helt udelukkes, at der er en øget modtagelighed over for specifikke tumorer. 
Therefore, an increased susceptibility to specific tumours cannot be entirely ruled out.
Håndteringen af svære reaktioner på infusionen afhænger af symptomerne på reaktionen. 
The management of severe infusion reactions should be dictated by the signs and symptoms of the reaction.
En histopatologisk undersøgelse af lymfevæv fra GD140-fostre viste ingen morfologiske anomalier i udviklingen af immunsystemet. 
Histopathological examination of lymphoid tissues from GD140 fetuses showed no morphological abnormalities in the development of the immune system.
Patienter med MCD frembringer for meget IL6, og det menes at bidrage til unormal vækst af visse celler i lymfeknuderne. 
Patients with MCD produce too much IL-6 and this is thought to contribute to the abnormal growth of certain cells in lymph nodes.
Clearance af siltuximab steg med stigende legemsvægt, men der er ikke behov for dosisjustering pga. legemsvægten, da doseringen er baseret på mg/kg. 
Siltuximab clearance increased with increasing body weight; however, no dose adjustment is required for body weight since administration is on an mg/kg basis.
- hvis du har en alvorlig allergi over for siltuximab eller et af de øvrige indholdsstoffer i dette lægemiddel (angivet i punkt 6). 
You are severely allergic to siltuximab or any of the other ingredients of this medicine (listed in section 6).
Pædiatrisk population Der er ikke udført interaktionsstudier. 
Paediatric population No interaction studies have been performed in this population.
Behandling med siltuximab for MCD resulterer i et hurtigt og vedvarende fald i serumkoncentrationen af CRP. 
Siltuximab treatment in MCD results in rapid and sustained decreases in CRP serum concentrations.
Yderligere immunogenicitetsanalyser blev udført for alle positive prøver fra de 4 patienter med påviselige anti-siltuximab-antistoffer. 
Further immunogenicity analyses were conducted for all positive samples from the 4 patients with detectable anti-siltuximab antibodies.
SYLVANT kan maskere symptomer på akut inflammation inklusive suppression af feber og af akutfase-reaktanter såsom C-reaktivt protein (CRP). 
SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute-phase reactants, such as C-reactive protein (CRP).
I prækliniske studier er interleukin-6 (IL-6) kendt for at nedsætte aktiviteten af cytokrom P450 (CYP450). 
In non-clinical studies, interleukin-6 (IL-6) is known to decrease the activity of cytochrome P450 (CYP450).
• SYLVANT gives som intravenøs infusion - dvs. som drop i en vene, sædvanligvis i armen. 
• SYLVANT will be given as an “intravenous infusion” (a drip into a vein, usually in your arm).
Infektioner (inklusive øvre luftvejsinfektioner), pruritus, udslæt, artralgi og diarré var de mest almindelige bivirkninger, som forekom hos > 20 % af de patienter, der fik siltuximab under kliniske studier af Castlemans sygdom (CD). 
Infections (including upper respiratory tract infections), pruritus, rash, arthralgia, and diarrhoea were the most common adverse reactions , occurring in > 20% of siltuximab-treated patients in Castleman's disease (CD) clinical studies.
SYLVANT indeholder ikke konserveringsmidler, og ikke anvendt infusionsopløsning må derfor ikke gemmes til senere brug. 
SYLVANT does not contain preservatives; therefore do not store any unused portion of the infusion solution for re-use.
Farmakoterapeutisk klassifikation: immunsuppressiva, interleukinhæmmere, ATC-kode: L04AC11. 
Pharmacotherapeutic group: Immunosuppresants, interleukin inhibitors, ATC code: L04AC11.
Hvis patienten får en svær reaktion relateret til infusionen, anafylaksi, en svær allergisk reaktion eller cytokin-frigivelsessyndrom relateret til infusionen, skal yderligere administration af SYLVANT seponeres. 
If the patient develops a severe infusion related reaction, anaphylaxis, severe allergic reaction, or cytokine release syndrome related to the infusion, further administration of SYLVANT should be discontinued.
Efter en enkelt administration i den anbefalede dosering (11 mg/kg en gang hver 3. uge) var clearance 3,54 ± 0,44 ml/kg/dag og halveringstiden 16,3 ± 4,2 dage. 
Following the single dose administration at the recommended dose regimen (11 mg/kg given once every 3 weeks), the clearance was 3.54 ± 0.44 mL/kg/day and half-life was 16.3 ± 4.2 days.
• theophyllin til behandling af astma 
• theophylline, used to treat asthma
Din læge vil måske vælge at stoppe behandlingen med SYLVANT med det samme. 
Your doctor may stop your treatment with SYLVANT straight away.
Du og din læge bør sammen tage stilling til, om du skal fortsætte med at bruge SYLVANT eller amme og stoppe med SYLVANT. 
You and your doctor should decide if you will continue to take SYLVANT, or breast-feed and discontinue SYLVANT.
BILAG II A. FREMSTILLERE AF DET BIOLOGISK AKTIVE STOF OG FREMSTILLER ANSVARLIG FOR BATCHFRIGIVELSE B. BETINGELSER ELLER BEGRÆNSNINGER VEDRØRENDE UDLEVERING OG ANVENDELSE C. ANDRE FORHOLD OG BETINGELSER FOR MARKEDSFØRINGSTILLADELSEN D. BETINGELSER ELLER BEGRÆNSNINGER MED HENSYN TIL SIKKER OG EFFEKTIV ANVENDELSE AF LÆGEMIDLET 
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
Den ordinerende læge skal derfor omhyggeligt monitorere patienter, der behandles med SYLVANT, med henblik på at opdage alvorlige infektioner. 
Therefore, prescribers should diligently monitor patients receiving treatment in order to detect serious infections.
Der foreligger dog også materiale, der indikerer, at IL6-hæmning kan undertrykke immunrespons og immunovervågning og nedsætte forsvaret mod udviklede tumorer. 
However, there is also evidence to suggest that IL-6 inhibition may suppress immune responses, immune surveillance and lower defense against established tumours.
Den største samlede mængde siltuximab, der hidtil er administreret i et klinisk studie, var 2.190 mg (11 mg/kg). 
The highest total amount of siltuximab administered in any clinical trial so far per dose was 2,190 mg (11 mg/kg).
Alle kliniske studier med SYLVANT ekskluderede patienter med klinisk signifikante infektioner, herunder patienter med påviselig hepatitis B-overfladeantigen (HbsAg positive). 
All clinical studies with SYLVANT excluded patients with clinically significant infections, including those known to be hepatitis B surface antigen positive.
Den mest alvorlige bivirkning associeret med anvendelse af siltuximab var anafylaktisk reaktion. 
The most serious adverse reaction associated with the use of siltuximab was anaphylactic reaction.
Efter den første administration af siltuximab (i doser fra 0,9 til 15 mg/kg) steg arealet under kurven for plasmakoncentration over tid (AUC) og maksimal serumkoncentration (Cmax) dosisproportionalt, og clearance (CL) var uafhængigt af dosis. 
Following the first administration of siltuximab (doses ranging from 0.9 to 15 mg/kg), the area under the concentration-time curve (AUC) and maximal serum concentration (Cmax) increased in a dose-proportional manner and clearance (CL) was independent of dose.
Dosisjustering er ikke nødvendig (se pkt. 
No dose adjustment is required (see section 5.2).
Siltuximab påvirker ikke eller kun i ubetydelig grad evnen til at føre motorkøretøj og betjene maskiner. 
Siltuximab has no or negligible influence on the ability to drive and use machines.
• luftvejsinfektioner - f.eks. i næse, bihuler eller svælg 
• respiratory infections - such as of the nose, sinuses or throat
Studiets primære endepunkt var varigt tumor- og symptomatisk respons, defineret som tumorrespons vurderet ved uvildig gennemgang og komplet resolution eller stabilisering af prospektivt indsamlede symptomer på MCD i mindst 18 uger uden behandlingssvigt. 
The primary endpoint of the study was durable tumour and symptomatic response, defined as tumour response assessed by independent review and complete resolution or stabilisation of prospectively collected MCD symptoms, for at least 18 weeks without treatment failure.
Et åbent, ikke-randomiseret fase 2-multicenterstudie vurderede sikkerhed og virkning ved længerevarende behandling med siltuximab hos 60 patienter med MCD, som tidligere havde deltaget i studie 1 (41 patienter) eller studie 2 (19 patienter). 
An open-label, multicentre, non-randomised Phase 2 study assessed the safety and efficacy of extended treatment with siltuximab in 60 patients with MCD who were previously enrolled in Study 1 (41 patients) or Study 2 (19 patients).
Hæmoglobinrespons defineredes som en ændring fra baseline på ≥ 15 g/l (0,9 mmol/l) i uge 13. 
Haemoglobin response was defined as a change from baseline of ≥ 15 g/L (0.9 mmol/L) at Week 13.
Inspicer hætteglassene for partikelindhold og misfarvning før tilberedning af dosis. 
Inspect the vials for particulate matter and discolouration prior to dose preparation.
De vigtigste resultater for virkning fra studie 1 fremgår af tabel 3. 
Key efficacy results from Study 1 are summarised in Table 3.
• Aktivt stof: siltuximab. 
• The active substance is siltuximab.
• Den anbefalede dosis er 11 mg pr. kg legemsvægt, der gives en gang hver 3. uge. 
• The recommended dose is 11 milligrams per kilogram of body weight, given once every
Infusionen skal afsluttes inden for 6 timer efter tilsætning af den rekonstituerede opløsning til infusionsposen. 
The infusion should be completed within 6 hours of the addition of the reconstituted solution to the infusion bag.
Tegn omfatter: hoste, influenzalignende symptomer, utilpashed, rød eller varm hud, feber. 
Signs include: cough, flu-like symptoms, feeling unwell, red or hot skin, fever.
Siltuximab (9,2 og 46 mg/kg/uge) medførte ikke toksicitet i reproduktionsorganerne hos cynomolgusaber. 
Siltuximab (9.2 and 46 mg/kg/week) did not produce any toxicity of the reproductive tract in cynomolgus monkeys.
Gennem binding til IL6 blokerer siltuximab dets aktivitet og stopper unormal cellevækst. 
By binding to IL-6, siltuximab blocks its activity and stops abnormal cell growth.
• hvis du har en sygdom som f.eks. et mavesår eller betændelse i en eller flere divertikler (divertikulitis), der kan øge risikoen for at få en rift i din mave eller tarm (gastrointestinal perforering). 
• you have a condition such as stomach ulcer or diverticulitis that may increase the risk of getting a tear in the stomach or gut (gastrointestinal perforation).
Den procentvise ændring fra baseline i MCD-relaterede symptomer og den samlede symptomscore relateret til sygdommen for hver behandlingscyklus blev beregnet. 
The percent change from baseline in MCD-related signs and symptoms and MCD-related overall symptom score at each cycle was calculated.
Symptomer relateret til MCD blev indsamlet prospektivt. 
MCD-related signs and symptoms were prospectively collected.
Overproduktion af IL-6 i kroniske inflammatoriske sygdomme og maligniteter er sat i forbindelse med anæmi og kakeksi og der er fremsat en hypotese om, at det spiller en central rolle ved fremning af proliferation af plasmaceller og systemiske manifestationer hos patienter med CD. 
Overproduction of IL-6, in chronic inflammatory diseases and malignancies has been linked to anaemia and cachexia and has been hypothesised to play a central role in driving plasma cell proliferation and systemic manifestations in patients with CD.
Siltuximabs immunogenicitet blev evalueret ved hjælp af metoderne antigen-bridging enzym-immunoassay (EIA) og elektrokemiluminiscens- (ECL-) baseret immunoassay (ECLIA). 
The immunogenicity of siltuximab has been evaluated using antigen-bridging enzyme immunoassay (EIA) and electrochemiluminescence (ECL)-based immunoassay (ECLIA)
Det er veldokumenteret, at IL-6 stimulerer eksprimering af C-reaktivt protein (CRP) i akutfasen. 
It is well established that IL-6 stimulates the acute-phase expression of C-reactive protein (CRP).
(IR; IR)b 
(N/A; N/A)b
• SYLVANT udleveres i et hætteglas af glas, der indeholder et hvidt pulver til koncentrat til infusionsvæske, opløsning (pulver til koncentrat). 
• SYLVANT is supplied as a glass vial containing a white powder for concentrate for solution for infusion (powder for concentrate).
Symptomerne på denne sygdom kan omfatte træthed, natlige svedudbrud, en prikkende fornemmelse og manglende appetit. 
Symptoms of this disease may include feeling tired, sweating at night, having a tingling feeling, and loss of appetite.
Den ordinerende læge bør også udvise forsigtighed ved samtidig administration af siltuximab og lægemidler, der er substrater for CYP3A4, hvis en nedsættelse af virkningen ville være uønsket (f.eks. orale kontraceptiva). 
Prescribers should also exercise caution when siltuximab is co-administered with medicinal products that are CYP3A4 substrates where a decrease in effectiveness would be undesirable (e.g., oral contraceptives).
* Bedste understøttende behandling a 95 % konfidensinterval for forskellen i procentdele b IR = “Ikke relevant”, der var ingen respondere, hvorfor 95 % CI ikke er relevant c 95 % konfidensinterval for hazard ratio d Fuldstændigt symptomatisk respons defineres som 100 % reduktion i den samlede symptomscore for MCD ved baseline, der blev opretholdt i mindst 18 uger før behandlingssvigt 
* Best Supportive Care a 95% confidence interval for the for the difference in proportions b N/A = “Not applicable”, there were no responders therefore 95% CI is not applicable c 95% confidence interval for the hazard ratio d Complete symptomatic response is defined as a 100% reduction in the baseline MCD overall symptom score sustained for at least 18 weeks prior to treatment failure
Behandlingen med SYLVANT bør pauseres, hvis patienten har en svær infektion eller en svær ikke-hæmatologisk bivirkning, og den kan genoptages med samme dosis, når patienten er kommet sig. 
The SYLVANT therapy should be withheld if the patient has a severe infection or any severe non-haematological toxicity and can be restarted at the same dose after recovery.
I overensstemmelse med halveringstiden efter den første dosis nåede serumkoncentrationer steady state ved den sjette infusion (med 3 ugers interval) med gennemsnitlige (± SD) maksimale og bundkoncentrationer på henholdsvis 332 ± 139 og 84 ± 66 mikrog/ml. 
Consistent with half-life after the first dose, serum concentrations reached steady-state levels by the sixth infusion (intervals every 3 weeks) with mean (± SD) peak and trough concentrations of 332 ± 139 and 84 ± 66 mcg/mL, respectively.
Der er rapporteret gastrointestinal (GI) perforering med siltuximab i kliniske studier, omend ikke i studier af MCD. 
Gastrointestinal (GI) perforation has been reported in siltuximab clinical trials although not in MCD trials.
Siltuximabs populationsfarmakokinetik blev analyseret for at evaluere virkningerne af demografiske kendetegn. 
The population PK of siltuximab were analysed to evaluate the effects of demographic characteristics.
I kliniske studier blev siltuximab associeret med en infusionsrelaret reaktion eller overfølsomhedsreaktion hos 5,1 % (svær reaktion hos 0,8 %) af de patienter, der fik siltuximab som monoterapi. 
In clinical studies, siltuximab was associated with an infusion related reaction or hypersensitivity reaction in 5.1% (severe reaction in 0.8%) of patients treated with siltuximab monotherapy.
Siltuximabs påvirkning af fertilitet er ikke evalueret hos mennesket. 
Effects of siltuximab on fertility have not been evaluated in humans.
Det skal besluttes, om amning skal ophøre eller behandling med siltuximab seponeres, idet der tages højde for fordelene ved amning for barnet i forhold til de terapeutiske fordele for moderen. 
A decision must be made whether to discontinue breast-feeding or discontinue/abstain from siltuximab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Indehaveren af markedsføringstilladelsen skal fremsende data i tabelform til CHMP hver 12. måned i lighed med cyklus for fremsendelse af periodiske, opdaterede sikkerhedsberetninger (PSUR'er), og tabellen må kun omfatte data for de patienter, der er kandidater til behandling med siltuximab. 
The MAH should provide tabulated data to the CHMP every 12 months in line with the periodic safety update report (PSUR) cycle including data for only those patients who are candidates for treatment with siltuximab.
IL-6 har vist sig at være involveret i forskellige normale fysiologiske processer såsom induktion af produktion af immunoglobulin, initiering af akutfase proteinsyntese i leveren og stimulering af den hæmatopoietiske prækursor for cellevækst og -differentiering. 
IL-6 has been shown to be involved in diverse normal physiologic processes such as induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation.
Siltuximab virker gennem neutralisering af IL-6-bioaktivitet, som kan måles indirekte ved suppression af CRP. 
The mechanism of action of siltuximab is neutralisation of IL-6 bioactivity, which can be measured indirectly by suppression of CRP.
Under intravenøs infusion af SYLVANT kan der opnås bedring af lette til moderate infusionsreaktioner, hvis infusionen gives langsommere eller stoppes helt. 
During intravenous infusion of SYLVANT, mild to moderate infusion reactions may improve following slowing of or stopping the infusion.
Under eller efter infusionen bør behandling seponeres hos patienter, der har svære overfølsomhedsreaktioner relateret til infusionen (f.eks. anafylaksi). 
During or following infusion, treatment should be discontinued in patients who have severe infusion related hypersensitivity reactions (e.g., anaphylaxis).
Ligesom med andre immunglobulin G-antistoffer passerer siltuximab placenta, hvilket er observeret i studier med aber. 
As with other immunoglobulin G antibodies, siltuximab crosses the placenta as observed in studies in monkeys.
Efter administration af gentagne doser i den anbefalede dosering var clearance af siltuximab tidsuafhængigt, og der sås moderat systemisk akkumulering (et akumulationsindeks på 1,7). 
Following the repeat dose administration at the recommended dose, siltuximab clearance was found to be time-invariant, and systemic accumulation was moderate (accumulation index of 1.7).
Kriterier for genbehandling 
Retreatment criteria
Dokumentation fra studier udført med siltuximab og andre IL6-hæmnere indikerer, at siltuximab har et lavt potentiale for karcinogenicitet. 
Evidence from studies conducted with siltuximab and other IL-6 inhibitors suggest that the potential for siltuximab to cause carcinogenicity is low.
Ud over studie 1 foreligger der også effektdata for patienter med CD fra et fase 1-studie med en enkelt arm (studie 2). 
Study 2 In addition to Study 1, efficacy data are available in patients with CD from a single arm Phase 1 study