FrancophonIA/ELRC3.0 huggingface dataset:
English: Clinical data however indicate that the overall incidence of adverse events is increased if patients are simultaneously exposed to tasonermin and interferon-gamma.
Danish: Ikke desto mindre tyder visse kliniske data på, at den generelle sandsynlighed for ugunstige hændelser stiger, hvis patienterne samtidig udsættes for tasonermin og interferon-gamma.
English: Furthermore, blood pressure, urine output and electrocardiographic monitoring should be routinely undertaken in the first 24 to 48 hours post-ILP, or longer if indicated.
Danish: Derudover bør monitorering af blodtryk, diurese samt elektrokardiografi foretages løbende de første 24-48 timer efter ILP, eller længere hvis indikeret.
English: The circulatory changes included decreased blood pressure and, in some studies, increased heart rate and decreased contractility.
Danish: De kredsløbsmæssige ændringer omfattede faldende blodtryk, og i visse undersøgelser, øget hjertefrekvens og nedsat kontraktilitet.
English: Mechanism of action In vivo antitumour activity is probably based on direct and indirect effects:
Danish: Antitumoraktiviteten in vivo er sandsynligvis baseret på direkte og indirekte virkninger.
English: Intraarterial use
Danish: Intraarteriel brug
English: - The active substance is tasonermin.
Danish: - Aktivt stof: tasonermin.
English: It is important that it does not reach other parts of your body, because this so-called systemic leakage could cause serious side effects on the main organs of the body.
Danish: Det er vigtigt, at stoffet ikke kommer ud i andre dele af kroppen, da denne såkaldte systemiske lækage kan give alvorlige bivirkninger i kroppens organer.
English: ILP allows the administration of high and fairly stable concentrations of tasonermin to the limb.
Danish: ILP tillader administration af høje og relativt stabile tasonerminkoncentrationer til ekstremiteten.
English: 2, Rue Albert 1er L-1117 Luxembourg Grand Duchy of Luxembourg
Danish: 2, Rue Albert 1er L-1117 Luxembourg Storhertugdømmet Luxembourg
English: Patients in whom the blood supply to the extremity distal to the tumour is suspected to be highly dependent on tumour associated blood vessels.
Danish: Patienter hos hvilke blodforsyningen til ekstremiteten distalt for tumoren er mistænkt for i høj grad at være afhængig af tumorassocierede blodkar.
English: For administration by ILP Intraarterial use
Danish: Til administration via ILP Intraarteriel anvendelse
English: Hand and foot, if not affected, should be protected by Esmarch (expulsion) bandages.
Danish: Såfremt hænder og fødder ikke er afficerede skal de beskyttes med ”Esmarch expulsion bandager”.
English: Melphalan dose should be calculated according to the litre-volume method of Wieberdink (Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthius GAA.
Danish: Melfalandosis bør beregnes i overensstemmelse med Wieberdinks litervolumemetode (Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthuis GAA).
English: These changes in turn lead to a procoagulant state, resulting in microvascular thrombosis.
Danish: Disse ændringer fører igen til et prokoagulant stadie, som resulterer i mikrovaskulær trombose.
English: Tasonermin does not cross the intact blood-brain barrier to a significant extent in mice.
Danish: Tasonermin passerer ikke den intakte blod-hjernebarriere i væsentlig grad hos mus.
English: A matched-pair survival analysis of patients treated by Beromun and melphalan ILP as compared to a historical control failed to demonstrate any survival difference (p=0.5).
Danish: En ”matched-pair” overlevelsesanalyse af patienter behandlet med Beromun og melfalan ILP sammenlignet med en historisk kontrol kunne ikke vise en overlevelsesdifference (p=0,5).
English: Surgical resection of the tumour remnant should be undertaken whenever possible.
Danish: Kirurgisk resektion af tumorresten skal foretages, når det er muligt.
English: *tumor necrosis factor alfa-1a (TNFα-1a) produced by recombinant DNA technology in E. coli.
Danish: * tumornekrosefaktor alfa-1a (TNFα-1a) fremstillet ved hjælp af rekombinant DNA teknologi i E. coli.
English: Artificial respiratory support may be required if ARDS develops.
Danish: Respiratorbehandling kan være påkrævet, hvis ARDS opstår.
English: It is important to maintain a constant level of anaesthesia in order to prevent large fluctuations in systemic blood pressure, which can affect leakage between systemic circulation and perfusion circuit.
Danish: Det er vigtigt at opretholde et konstant anæstesiniveau for at undgå store udsving i det systemiske blodtryk, som kan påvirke lækagen mellem det systemiske kredsløb og perfusionskredsløbet.
English: Night sweats
Danish: Natlige svedeture.
English: The toxicological profile of tasonermin has been investigated in preclinical studies using mice, rats, rabbits, dogs and monkeys.
Danish: Tasonermin‘s toksikologiske profil har været undersøgt i prækliniske studier med mus, rotter, kaniner, hunde og aber.
English: Colloids and hydroxyethyl starch fluids are preferred, as they are less likely to leak out of the vascular system.
Danish: Kolloider og hydroxyethylstivelsesesvæsker foretrækkes, idet disse er mindst tilbøjelige til at sive ud i det vaskulære system.
English: Doses of up to 6 mg of other TNFα preparations have been administered via ILP, but this dose was found to be unacceptable in terms of loco-regional toxicity.
Danish: Doser på op til 6 mg af andre TNFα præparater er blevet administreret via ILP, men sådanne doser har vist sig at være uacceptable hvad angår lokalregional toksicitet.
English: Renal and hepatic function should be closely monitored.
Danish: Nyre- og leverfunktion bør nøje monitoreres.
English: Melphalan:
Danish: Melfalan:
English: A dose-dependency has been observed as indicated by a decrease in clearance and an increase in half-life at increasing doses.
Danish: En dosisafhængighed er blevet observeret ved et fald i clearance og en forøgelse af halveringstiden ved øgede doser.
English: Prophylaxis and treatment of fever, chills and other influenza-like symptoms associated with Beromun administration can be achieved by pre-ILP administration of paracetamol (oral or by suppository) or an alternative analgesic/antipyretic.
Danish: Profylakse og behandling af feber, kulderystelser og andre influenzalignende symptomer associeret med Beromun administration kan opnås ved præ-ILP administration af paracetamol (oralt eller med suppositorie) eller et alternativt analgetikum/antipyretikum.
English: Animal studies are insufficient with respect to effects on pregnancy, embryonal development and postnatal development (see section 5.3).
Danish: Data fra dyreforsøg er utilstrækkelige med hensyn til virkningerne på drægtighed samt den embryonale og postnatale udvikling (se pkt.
English: The systemic application of tasonermin is limited by its toxic effects, the effective dose predicted from preclinical studies being substantially higher than the observed human maximum tolerated dose.
Danish: Den systemiske administration af tasonermin er begrænset pga. toksiske virkninger, den effektive dosis beregnet ud fra prækliniske studier er betydeligt højere end den observerede humane maksimalt tolererede dosis.
English: Once the temperature in the distal subcutaneous tissue of the limb has reached >38°C, (but not exceeding 39°C), and pH of the perfusate is between 7.2 and 7.35, Beromun should be injected as a bolus into the arterial line of the circuit.
Danish: Når temperaturen i det distale subkutane væv er nået op på >38 °C (men må ikke overstige 39 °C), og perfusatets pH-værdi er mellem 7,2 og 7,35, bør Beromun injiceres som en bolus i kredsløbets arterielle forbindelse.
English: Beromun should only be administered if leakage is less than 10 %.
Danish: Der må kun gives Beromun, såfremt lækagen udgør mindre end 10 %.
English: Simultaneous treatment with cardiotoxic substances (e.g. anthracyclines).
Danish: Samtidig behandling med kardiotoksiske midler (f.eks. antracyklin).
English: In approximately 2% of cases, Beromun may cause tissue damage in your affected arm or leg which is severe enough to require amputation.
Danish: I ca. 2 % af tilfældene kan Beromun forårsage vævsskader i den syge arm eller ben, der er så alvorlige, at amputation bliver nødvendig.
English: Indirect and direct immunomodulation: Tasonermin has profound effects on cellular components of the immune system.
Danish: Indirekte og direkte immunmodulering: Tasonermin har en kraftig effekt på immunsystemmets cellulære komponenter.
English: If you get any side effects , talk to your doctor.
Danish: Hvis du oplever bivirkninger, bør du tale med din læge.
English: Adverse reactions are either local, affecting the limb treated with ILP, or systemic.
Danish: Bivirkningerne er enten lokale, påvirkede ekstremiteterne behandlet med ILP eller systemiske.
English: The addition of interferon-gamma to the tasonermin perfusate seems not to be associated with significant increases in endogenous production of tasonermin or other inflammatory cytokines as shown in patients with severe trauma.
Danish: Tilsætningen af interferon-gamma til tasonerminperfusatet synes ikke at være knyttet til en væsentlig forøgelse af den endogene produktion af tasonermin eller til andre inflammatoriske cytokiner, således som det ses hos patienter med alvorligt trauma.
English: Altered renal function comprised increased water and sodium excretion as well as increased urea and creatinine.
Danish: Ændret nyrefunktion omfattede forøget udskillelse af vand og natrium såvel som forhøjet urea og kreatinin.
English: Beromun is contraindicated in pregnancy (see section 4.3).
Danish: Beromun er kontraindiceret under graviditet (se pkt.
English: If there is any risk of serious side effects, your doctor will immediately transfer you to an intensive care unit to closely monitor you and start adequate treatment.
Danish: Hvis der er risiko for alvorlige bivirkninger, vil din læge omgående overføre dig til en intensivafdeling på hospitalet for at overvåge dig nøje og starte passende behandling.
English: A number of therapeutic measures are routinely used during the ILP and in the immediate post-operative period.
Danish: En række terapeutiske foranstaltninger anvendes rutinemæssigt under ILP-proceduren og i den umiddelbart efterfølgende postoperative periode.
English: In order to minimise the risk of leakage of the perfusate into the systemic circulation, the perfusion flow rate should not exceed 40 ml/litre limb volume/minute.
Danish: Med henblik på at minimere risikoen for lækage af perfusatet til den systemiske cirkulation, bør perfusionshastigheden ikke overstige 40 ml/l ekstremitetsvolumen/min.
English: Compartment syndrome, myalgia
Danish: Kompartmentsyndrom, myalgi
English: The terminal half-life at the maximum tolerated intravenous dose (150 µg/m2) was 15-30 min.
Danish: tolererede intravenøse dosis (150 µg/m2) var 15-30 min.
English: No late detrimental effects of tasonermin were seen.
Danish: Ingen forsinket ufordelagtig effekt fra tasonermin blev observeret.
English: Nerve injury, peripheral neurotoxicity, altered state of consciouness, headache
Danish: Nerveskade, perifer neurotoksicitet, ændret bevidsthed, hovedpine.
English: To cover the intended clinical use of Beromun, ILP experiments were performed in hind legs of healthy rats using different doses in the same tasonermin concentration as in the clinical situation in the human.
Danish: For at dække den påtænkte kliniske anvendelse af Beromun er ILP-eksperimenter blevet udført i bagbenene af raske rotter med forskellige doser af den samme tasonerminkoncentration som i den kliniske situation i mennesker.
English: Washout should be continued until the colour of the perfusate is clear pink, transparent (see section 4.4).
Danish: Udvaskning bør fortsættes, indtil farven på perfusatet er klar lyserødt, gennemsigtigt (se pkt.
English: Blood creatinine increased Surgical and medical procedures Common:
Danish: Forhøjet blodcreatininniveau Kirurgiske og medicinske procedurer Almindelig:
English: After 30 minutes perfusion of Beromun alone, melphalan should be added as a bolus into the reservoir of the circuit, or slowly into the arterial line of the circuit.
Danish: Efter 30 min Beromun-perfusion alene tilsættes melfalan som en bolus i kredsløbets reservoir eller langsomt i kredsløbets arterielle forbindelse.
English: If Beromun dry powder or reconstituted solution should come into contact with the skin or mucous membranes, they should be washed thoroughly with water.
Danish: Hvis Beromun-pulver eller rekonstitueret opløsning kommer i kontakt med hud eller slimhinder, skal der vaskes grundigt med vand.
English: MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER (S) RESPONSIBLE FOR BATCH RELEASE
Danish: A. FREMSTILLER AF DET BIOLOGISK AKTIVE STOF OG FREMSTILLER(E) ANSVARLIG(E) FOR BATCHFRIGIVELSE
English: Perfusate samples of several ILPs showed plateau levels of tasonermin (as measured by ELISA) up to 100 minutes after start of perfusion, with no decay attributable to degradation.
Danish: Perfusatprøver af flere ILP'er har vist plateauniveauer af tasonermin (målt ved hjælp af ELISA) på op til 100 min. efter perfusionsstart uden henfald, som kan tilskrives nedbrydning.
English: After that, melphalan will be added and the ILP continued for another 60 minutes.
Danish: Herefter indgives også melfalan, og ILP-behandlingen vil fortsætte i yderligere 60 minutter.
English: This is to ensure optimal haemodynamic conditions and ensure a high urinary output, especially after the perfusion, to allow for rapid clearance of any residual tasonermin.
Danish: Dette er for at sikre optimale hæmodynamiske betingelser og høj diurese, især efter perfusionen for at muliggøre en hurtig clearance af eventuel overskydende tasonermin.
English: Except for slight aggravation of ischaemic effects in higher doses, standard histological examinations of the skin, muscle, bone, nerves and vessels revealed no difference in findings between tasonermin-treated and control animals.
Danish: Bortset fra en svag forværring af iskæmiske påvirkninger i højere doser viste histologiske standardundersøgelser af hud, muskler, knogler, nerver og kar ingen forskel mellem tasonerminbehandlede dyr og kontroldyr.
English: Because of the unknown risk to the infant, breast-feeding is contraindicated within 7 days of ILP (see section 4.3).
Danish: Pga. den ukendte risiko for spædbarnet er amning kontraindiceret indtil 7 dage efter ILP (se pkt.
English: Beromun has been co-administered with interferon-gamma in the ILP setting but no added value has been demonstrated.
Danish: Beromun har været anvendt i kombination med interferon-gamma i ILP-opsætningen, men der er ikke påvist nogen yderligere værdi af denne kombination.
English: After reconstitution in 0.9 % physiological sodium chloride solution the amount is 37.82 mg (1.64 mmol) sodium.
Danish: Efter rekonstitution i 0,9 % fysiologisk natriumchloridopløsning er mængden 37,82 mg (1,64 mmol) natrium.
English: When necessary a second ILP can be considered 6-8 weeks after the first ILP.
Danish: Om nødvendigt kan en yderligere ILP overvejes 6-8 uger efter den første ILP.
English: Measures should be taken to ensure that the periods of interrupted oxygen supply to the limb are as brief as possible (20 minutes maximum).
Danish: Man bør sikre, at perioder med afbrudt ilttilførelse til ekstremiteten er så korte som muligt (maks.
English: Venous thrombosis, arterial thrombosis, shock, hypotension
Danish: Venøs trombose, arteriel trombose, shock, hypotension.
English: Tasonermin did not cross the placenta or pass into necrotic tumour.
Danish: Tasonermin krydsede ikke placenta og penetrerede ikke nekrotisk tumor.
English: Fertility No data on the possible effect of this medicinal product on male and female fertility are available.
Danish: Fertilitet Der foreligger ingen data om lægemidlets mulige indvirkning på fertiliteten hos hanner eller hunner.
English: A homogeneous solution will be obtained by shaking gently.
Danish: En homogen opløsning opnås ved forsigtig omrystning.
English: In the Rhesus monkey, whole body radiography following administration of radiolabelled tasonermin indicated no specific distribution pattern.
Danish: I Rhesus-aben viste en radiografi af hele kroppen efter behandling med radioaktivt mærket tasonermin intet specifikt distributionsmønster.
English: Side effects may be caused by Beromun, melphalan, the ILP technique or a combination of these factors.
Danish: Bivirkningerne kan forårsages af Beromun, af melfalan, af ILP-teknikken eller en kombination af disse.
English: In the event of severe shock before the end of the ILP, the limb perfusion should be discontinued and appropriate therapy administered.
Danish: I tilfælde af alvorligt shock inden afslutningen af ILP bør ekstremitetsperfusionen afbrydes og passende behandling påbegyndes.
English: Potential leakage should be measured by radioactively labelled albumin or erythrocytes injected into the perfusion circuit, with appropriate measures for continuous monitoring of radioactivity leakage into the systemic circulation.
Danish: Potentiel lækage bør måles med radioaktivt mærket albumin eller erytrocytter injiceret i perfusionskredsløbet med passende metoder til kontinuerlig monitorering af radioaktivitetslækage til den systemiske cirkulation.
English: To be taken into consideration by patients on a controlled sodium diet.
Danish: Dette bør tages i betragtning hos patienter på saltfattig diæt.
English: Several lines of evidence suggest that these immunomodulatory activities are of relevance for the antitumour effects; e.g. the antitumour activities of tasonermin are much less pronounced in immunodeficient animals.
Danish: Meget tyder på, at disse immunomudulerende aktiviteter har betydning for antitumoreffekt f.eks. er tasonermin‘s antitumoraktivitet mindre udtalt i immundefekte dyr.
English: Haematological and circulatory changes, decreased well-being and weight gain as well as alterations in the function of liver and kidneys were the main adverse effects observed on repeated tasonermin administration.
Danish: Hæmatologiske og kredsløbsmæssige ændringer, nedsat velvære og vægtforøgelse såvel som ændringer i lever- og nyrefunktion var de væsentligste bivirkninger, som blev observeret efter gentagen tasonerminadministration.
English: Beromun contains the active substance tasonermin (tumor necrosis factor alfa-1a), produced by recombinant DNA technology.
Danish: Beromun indeholder det aktive stof tasonermin (tumornekrosefaktor alfa-1a), der fremstilles ved hjælp af rekombinant DNA-teknologi.
English: However, should this occur, your doctor will immediately wash out your affected limb to remove Beromun, and the ILP will be stopped.
Danish: Skulle det imidlertid ske, vil lægen straks skylle årerne i armen/benet igennem for at fjerne Beromun, og ILP vil blive bragt til ophør.
English: Further, adherence and extravasation of leukocytes is increased, leading to infiltration of the tumour by lymphocytes, monocytes, and granulocytes.
Danish: Desuden er adhæsion og ekstravasation af leukocytter øget, hvilket fører til infiltration af tumoren af lymfocytter, monocytter og granulocytter.
English: Beromun should be administered by mild hyperthermic ILP.
Danish: Beromun bør administreres via let hypertermisk ILP.
English: If a second ILP is indicated, physicians should take into account the leakage rate of the previous ILP.
Danish: Hvis der er indikationer for yderligere en ILP bør lægerne medtage lækagehastigheden fra den tidligere ILP i deres overvejelser.
English: This technique ensures that Beromun is kept within the affected arm or leg.
Danish: Denne teknik sørger for, at Beromun forbliver i den syge arm eller det syge ben.
English: MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS VIAL LABEL FOR BEROMUN
Danish: MINDSTEKRAV TIL MÆRKNING PÅ SMÅ INDRE EMBALLAGER HÆTTEGLASETIKET TIL BEROMUN
English: ILP allows that tumour cells in your limb can be exposed to a very high dose of Beromun and melphalan, enhancing their anti-tumour effect, but without reaching the rest of the body, where they could cause serious side effects.
Danish: ILP-teknikken gør, at tumorcellerne i armen eller benet kan udsættes for en meget høj dosis Beromun og melfalan, hvilket øger deres anti-tumor-virkning, og det på en sådan måde, at stofferne ikke kommer ud i resten af kroppen, hvor de kunne forårsage alvorlige bivirkninger.
English: Beromun will be administered by a doctor who is experienced and skilled in isolated limb perfusion (ILP).
Danish: Beromun vil blive givet af en læge, som har viden og erfaring i isoleret ekstremitetsperfusion (ILP).
English: The perfusion circuit (roller pump, oxygenator with integrated reservoir, heat exchanger, connecting tubing) should be prepared prior to surgery and primed with 700 to 800 ml of perfusate, with haematocrit of 0.25 to 0.30.
Danish: Perfusionskredsløbet (rullepumpe, iltmaske med integreret reservoir, varmeveksler, tilsluttende slangesystem) bør gøres klart inden operation og være forberedt med 700-800 ml perfusat med en hæmatokrit på 0,25-0,30.
English: After lower limb perfusion, 3 to 6 litres should be used, and after upper limb perfusion, 1 to 2 litres.
Danish: Efter perfusion af underekstremitet bør 3-6 l anvendes og efter perfusion af overekstremitet bør 1-2 l anvendes.
English: At ILP, no incompatibilities with other constituents of the perfusate, with hyperthermia or with the membrane oxygenator and the silicone tubing are known.
Danish: Ved ILPer ingen uforligeligheder med andre bestanddele af perfusatet, med hypertermi eller med membranoxygenatoren og siliconeslangerne kendt.
English: Under conditions of greater than 2 % systemic leakage (observed in 13 of 51 patients) maximum systemic concentrations of tasonermin were still at least ten times lower than in the perfusion circuit.
Danish: I de tilfælde hvor den systemiske lækage var større end 2 % (observeret hos 13 ud af 51 patienter) var de systemiske koncentrationer af tasonermin stadig mindst 10 x mindre end i perfusionskredsløbet.
English: Pharmacokinetics in ILP
Danish: Farmakodynamiske forhold ved ILP
English: Therefore, whenever there is significant systemic leakage of tasonermin, serious undesirable effects are to be expected.
Danish: Derfor må det altid forventes, at der ved væsentlige systemiske lækager af tasonermin kan opstå alvorlige bivirkninger.
English: Further, in addition to its direct effects, tasonermin modulates immune responses by inducing production of cytokines as well as low molecular weight mediators (prostaglandins, platelet activating factor).
Danish: Foruden dets direkte virkninger modulerer tasonermin immunresponset ved at inducere produktionen af cytokiner og lavmolekylære mediatorer (prostaglandiner, blodpladeaktiveringsfaktor).
English: Each pack contains 4 vials of powder.
Danish: Hver pakning indeholder 4 hætteglas med pulver.
English: Each vial contains 1 mg tasonermin.
Danish: Hvert hætteglas indeholder 1 mg tasonermin.
English: Precautions to be taken before handling or administering the medicinal product When preparing and handling Beromun solutions, the use of gloves is recommended.
Danish: Sikkerhedsforanstaltninger, der skal tages før håndtering og administration af lægemidlet Det anbefales at bruge handsker ved tilberedning og håndtering af Beromun injektionsvæske.
English: Systemic pharmacokinetics
Danish: Systemisk farmakokinetik
English: Beromun contains sodium
Danish: Beromun indeholder natrium
English: Adverse reactions have been ranked under headings of frequency using the following convention:
Danish: Bivirkningerne er blevet inddelt efter hyppighed efter følgende inddelinger:
English: During the ILP, central venous pressure and arterial pressure monitoring is strongly recommended.
Danish: Under ILP anbefales monitorering af centralt venøst tryk og arterielt tryk.
English: The loco-regional application of Beromun, along with melphalan, has been shown to be highly effective for local control of irresectable soft tissue sarcomas of the limbs.
Danish: Den lokalregionale administration af Beromun sammen med melfalan har vist sig at være meget effektiv til lokal kontrol af irresektable bløddelssarkomer i ekstremiteterne.
English: EXP For single use only.
Danish: EXP Kun til éngangsbrug.