natgillin/translations-raw huggingface dataset:
146 For at undgå beskadigelse af den forfyldte sprøjte, må den ikke nedfryses.
Do not freeze in order to prevent damage to the pre-filled syringe.
Anvend kun den forfyldte sprøjte, som leveret i æsken til opløsning.
Use only the pre-filled syringe provided in the box for reconstitution.
Andre sterile engangssprøjter kan anvendes til indgivelse.
Other sterile disposable syringes may be used for administration.
Hvert hætteglas indeholder nominelt 250, 500, 1000 eller 2000 IE nonacog alfa. − Øvrige indholdsstoffer:
contains nominally 250, 500, 1000 or 2000 IU of nonacog alfa.
Saccharose, glycin, L- histidin, polysorbat 80.
chloride solution) is also supplied for reconstitution.
En solvens (0, 234% natriumklorid) medfølger også til brug ved opløsning. − Efter opløsning i den medfølgende solvens (0, 234% natriumklorid) indeholder hvert hætteglas 50, 100, 200 eller 400 IE/ ml (se tabel 1).
- After reconstitution with the supplied solvent (0.234% sodium chloride solution), each vial contains
BeneFIX’ s styrke pr. ml færdig opløsning
50, 100, 200 or 400 IU/ ml (see Table 1).
Mængde BeneFIX per hætteglas
Strength of BeneFIX per ml prepared solution
Mængde BeneFIX per ml
Amount of BeneFIX per Vial
færdig opløsning til injection
Amount of BeneFIX per 1 ml of prepared solution for injection
1000 IE 2000 IE
250 IU 500 IU 1000 IU 2000 IU
200 IE 400 IE
50 IU 100 IU 200 IU 400 IU
BeneFIX leveres som pulver til injektionsvæske i et hætteglas og en solvens i en forfyldt sprøjte.
BeneFIX is provided as a powder for injection in a glass vial and a solvent provided in pre-filled syringe.
• et hætteglas med BeneFIX 250, 500, 1000 eller 2000 IE pulver • en forfyldt sprøjte med stempelstang, med solvens, 5 ml steril 0, 234% natriumklorid til opløsning til injektion • en steril hætteglasadapter til rekonstitution • et sterilt infusionssæt • to alkoholkompresser • et plaster • en gazetampon
• one vial of BeneFIX 250, 500 1000 or 2000 IU powder • one pre-filled syringe of solvent, 5 ml sterile 0.234% sodium chloride solution for injection for reconstitution, with one plunger rod • one sterile vial adapter reconstitution device • one sterile infusion set • two alcohol swabs • one plaster • one gauze pad
147 Wyeth Farma S. A.
161 Manufacturer
Hvis De/ du vil have yderligere oplysninger om BeneFIX, skal De/ du henvende Dem/ dig til den lokale repræsentant:
For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.
Denne indlægsseddel blev senest godkendt {MM/ ÅÅÅÅ}.
This leaflet was last approved in.
149
163
Samtidig holdes blodgennemstrømningen i lemmet isoleret (afbrudt) fra resten af kroppen.
Beromun is used in patients with soft tissue sarcoma (a type of cancer) of the limb (arm or leg), together with melphalan (an anticancer medicine), using a technique called ‘ isolated limb perfusion’ (ILP): both medicines are injected into the limb while the blood circulation in the limb is kept isolated (cut off) from the rest of the body.
Under fuld bedøvelse lægges der en stram bandage om øverste del af lemmet, så dets blodforsyning afbrydes og medicinen forhindres i at sprede sig til resten af kroppen.
Before Beromun is given, the limb is first isolated: while the patient is under general anaesthetic, a tight band is placed around the top of the limb to isolate its blood supply and prevent the medicine reaching the rest of the body.
Lemmet varmes op til en temperatur på 38- 39 °C.
The blood circulation in the limb is then replaced by the ‘ perfusion ’ of a special liquid and the limb is warmed to a temperature of between 38 and 39°C.
Denne dosis gives i løbet af 90 minutter.
Beromun is then injected into the perfusion solution at a dose of 3 mg for an arm and 4 mg for a leg, given over 90 minutes.
Melfalan gives under samme indgreb i løbet af 60 minutter, begyndende 30 minutter efter starten af perfusionen med Beromun, når temperaturen er blevet øget til 39- 40 °C.
Melphalan is given during the same operation over 60 minutes, beginning 30 minutes after the start of the Beromun perfusion, when the temperature should be increased to 39 to 40°C.
Den anvendte dosis af melfalan afhænger af armens eller benets størrelse.
The dose of melphalan depends on the size of the arm or leg.
Det aktive stof i Beromun, tasonermin, er en kopi af det menneskelige protein tumornekrosefaktor alfa- 1a (TNFα).
The active substance in Beromun, tasonermin, is a copy of the human protein tumour necrosis factor alfa-1a (TNF α).
Hvordan TNFα virker mod visse kræfttyper, vides ikke nøjagtigt, men det menes at kunne dræbe svulstceller direkte og desuden ødelægge de kar, der forsyner svulsterne, og stimulere immunsystemet til at angribe dem.
The exact way that TNF α works against certain types of cancer is not fully understood, but it is thought that it can kill tumour cells directly, as well as destroy the blood vessels supplying tumours and stimulate the immune system to attack them.
Det produceres af en bakterie, der har fået indsat et gen (dna), som gør den i stand til at producere TNFα.
The active substance in Beromun, tasonermin, is produced by a method known as ‘ recombinant DNA technology’: it is made by bacteria that have received a gene (DNA), which makes them able to produce TNFα.
De uafhængige bedømmere var enige om, at 62% af de patienter (90 af 145), der fik Beromun og melfalan, fik et bedre udfald end ventet, idet deres arm eller ben blev reddet, uden at de behøvede at blive opereret for at få fjernet svulsten, eller svulsten blev fjernet uden væsentligt funktionstab.
The independent reviewers agreed that 62% of the patients receiving Beromun and melphalan (90 out of 145) had a better outcome than predicted, since their limb was saved without surgery to remove the tumour or their tumour was removed without causing significant loss of function.
De patienter, der desuden fik interferon gamma, var for få til, at det kunne fastslås, om udfaldet for patienterne derved blev endnu bedre.
There were too few patients also receiving interferon-gamma to determine whether this improved the patients ’ outcome further.
Det må ikke anvendes hos patienter med hjerte - karsygdomme af væsentligt omfang, svære lungesygdomme, nyligt eller aktivt mavesår, svær væskeansamling i bughulen, blodsygdomme, nyre - eller leversygdom eller for højt kalciumindhold i blodet, eller hos kvinder, der er gravide eller ammer.
It must not be used in patients with significant cardiovascular (heart and blood vessel) disease, severe lung disease, a recent or active stomach ulcer, severe ascites (fluid accumulation in the abdomen), blood disorders, kidney or liver disease, or hypercalcaemia (high blood calcium levels), or in women who are pregnant or breast-feeding.
Beromun må ikke anvendes hos patienter, der ikke må få melfalan, eller hos patienter, der ikke må få ILP- behandling.
Beromun must not be used in patients who cannot receive melphalan or who cannot undergo ILP.
Udvalget for Humanmedicinske Lægemidler (CHMP) fandt, at fordelene ved Beromun opvejer risiciene som tillægsbehandling til operation med henblik på at forhindre eller forsinke amputation ved efterfølgende fjernelse af svulsten, samt til symptomlindrende behandling af ikke opererbart bløddelssarkom i lemmerne, anvendt i kombination med melfalan via let hypertermisk ILP.
The Committee for Medicinal Products for Human Use (CHMP) decided that Beromun’ s benefits are greater than its risks as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in the palliative situation, for irresectable soft tissue sarcoma of the limbs, used in combination with melphalan via mild hyperthermic ILP.
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Beromun til Boehringer Ingelheim International GmbH den 13. april 1999.
The European Commission granted a marketing authorisation valid throughout the European Union for Beromun to Boehringer Ingelheim International GmbH on 13 April 1999.
2/ 3 Den fuldstændige EPAR for Beromun findes her.
2/ 3 This summary was last updated in 04-2009.
1 mg Solvens:
1 mg Solvent:
Beromun 1 mg/ 5 ml, pulver og solvens til infusionsvæske, opløsning
Beromun 1 mg/ 5 ml powder and solvent for solution for infusion
Et hætteglas indeholder 1 mg tasonermin (tumornekrosefaktor alfa- 1a; TNFα- 1a) som udviser en aktivitet på 3, 0- 6, 0 x 107 IU.
One vial contains 1 mg tasonermin (Tumor Necrosis Factor alfa-1a; TNFα -1a) exhibiting an activity of 3.0-6.0 x 107 IU.
En ampul solvens indeholder 5 ml 0, 9% natriumchlorid opløsning.
One ampoule solvent contains 5 ml 0.9% sodium chloride solution.
Efter rekonstitution er styrken 0, 2 mg/ ml.
After reconstitution the strength is 0.2 mg/ ml.
Tasonermin er fremstillet ved rekombinant DNA teknologi i E. coli.
Tasonermin is produced by recombinant DNA technology in E. coli.
6. 1.
For excipients, see section 6.1.
Pulver og solvens til infusionsvæske, opløsning (til brug ved isoleret ekstremitetsperfusion; ILP).
Powder and solvent for solution for infusion (for isolated limb perfusion; ILP).
Bruges i kombination med melfalan via mild hypertermisk isoleret ekstremitetsperfusion (ILP).
As an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in the palliative situation, for irresectable soft tissue sarcoma of the limbs, used in combination with melphalan via mild hyperthermic isolated limb perfusion (ILP).
Øvre ekstremitet:
Upper limb:
3 mg total dosis ved isoleret ekstremitetsperfusion.
3 mg total dose by isolated limb perfusion Lower limb:
4 mg total dosis ved isoleret ekstremitetsperfusion.
4 mg total dose by isolated limb perfusion
Melfalandosis bør beregnes i overensstemmelse med Wieberdinks (Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthius GAA.
Melphalan dosage should be calculated according to the litre-volume method of Wieberdink (Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthius GAA.
905- 910.) litervolumemetode, til en maks. dosis på 150 mg.
905-910.), to a maximum dose of 150 mg.
10 mg/ l perfunderet nedre ekstremitetsvolume.
13 mg/ litre perfused upper limb volume 10 mg/ litre perfused lower limb volume
Denne behandling bør foretages på specialafdelinger af kirurgiske teams med erfaring i behandling af ekstremitetssarkomer og ILP- procedure, med en intensivafdeling til rådighed og med mulighed for kontinuerlig monitorering af lægemiddellækage til den systemiske cirkulation.
This treatment should be undertaken in specialised centres by surgical teams experienced in the management of limb sarcomas and ILP procedure, with an intensive care unit readily available and with the facilities for continuous monitoring for medicinal product leakage into the systemic circulation.
Beromun bør administreres via mild hypertermisk isoleret ekstremitetsperfusion.
Beromun should be administered by mild hyperthermic isolated limb perfusion.
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.
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.
2 Perfusionsniveauet skal fastsættes på passende vis således, at det kan dække hele det berørte væv (vena iliaca externa, femoralis, femoro- poplitea, poplitea, axilaris og brachialis kan benyttes som indgangsveje) og til introduktion af katetere.
2 Perfusion level should be chosen to adequately encompass affected tissue (external iliac, common femoral, femoro-popliteal, popliteal, axillary and brachial being accepted routes) and catheters introduced.
Såfremt hænder og fødder ikke er afficerede skal de beskyttes med ” Esmarch expulsion bandager ”.
Hand and foot, if not affected, should be protected by Esmarch (expulsion) bandages.
4. 4).
After connection of the limb to the isolated circuit, flow rate should be adjusted to 35 to 40 ml/ litre limb volume/ minute and leakage from limb to systemic circulation checked using a radioactive tracer technique (see section 4.4).
Justering af flowhastigheden og årepresse kan være nødvendigt for at sikre at lækage fra perfusionskredsløbet til det systemiske kredsløb er stabil (det systemiske radioaktivitetsniveau er nået op på et stabilt leje) og ikke overstiger 10%.
Adjustment of flow rate and tourniquet may be required to ensure leakage from perfusion circuit to systemic circulation is stable (systemic level of radioactivity has reached a plateau) and does not exceed 10%.
Der må kun gives Beromun, såfremt lækagen udgør mindre end 10%.
Beromun should only be administered if leakage is less than 10%.
Når temperaturen i det fjerneste 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 skal Beromun injiceres som en bolus i kredsløbets arterielle forbindelse.
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.
Beromun- perfusion alene, tilsættes melfalan som en bolus i kredsløbets reservoir, eller langsomt i kredsløbets arterielle forbindelse.
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.
Temperaturen skal herefter øges til > 39°C (men må ikke overstige 40°C) målt på 2 forskellige steder i tumorområdet.
The temperature should then be increased to > 39°C (but not exceeding 40°C) in two different sites of measurement in the tumour area.
Ved perfusionens afslutning skal perfusatet opsamles i reservoiret, alt imens udvaskningsvæskerne tilsættes kredsløbet og cirkulerer med samme kredsløbshastighed på 35- 40 ml/ l ekstremitetsvolume/ min.
At the end of the perfusion, the perfusate should be collected into the reservoir while washout fluid is added simultaneously to the circuit and circulated at the same flow rate of 35 to 40 ml/ litre limb volume/ minute.
4. 4).
Washout should be continued until the colour of the perfusate is clear (pink, transparent; see section 4.4).
Sikkerhed og effekt hos børn under 16 år er ikke undersøgt.
Safety and efficacy in children under the age of 16 has not been established.
Kirurgisk resektion af tumorresten skal foretages nårsomhelst det er muligt.
Surgical resection of the tumour remnant should be undertaken whenever possible.
Om nødvendigt kan en yderligere ILP overvejes 6- 8 uger efter den første ILP.
When necessary a second ILP can be considered 6-8 weeks after the first ILP.
Kontraindikationerne i forbindelse med Beromun ved isoleret ekstremitetsperfusion (ILP) angives herunder opdelt i henhold til procedurens faser:
Contraindications to Beromun isolated limb perfusion (ILP), subdivided by components of the procedure, are:
Kontraindikationer i forbindelse med Beromun:
Contraindications to Beromun:
Overfølsomhed over for det aktive stof eller et af hjælpestofferne.
Hypersensitivity to the active substance or to any of the excipients.
Udtalte kardiovaskulære sygdomme f. eks. hjerteinsuffiens (New York Heart Association Klassificering II, III eller IV), alvorlig angina pectoris, hjertearytmi, myokardieinfarkt inden for de seneste 3 mdr. forud for behandlingen, venetrombose, okklusiv perifer arteriesygdom, nylig lungeemboli.
Significant cardiovascular disease, e. g. congestive heart failure (New York Heart Association Class II, III or IV), severe angina pectoris, cardiac arrhythmias, myocardial infarction within a 3 month period prior to treatment, venous thrombosis, occlusive peripheral arterial disease, recent pulmonary embolism.
Alvorlig lungedysfunktion.
Severe pulmonary dysfunction.
Nyligt tilfælde af eller aktivt mavesår.
A recent history of, or active peptic ulcer.
Alvorlig hæmatologisk dysfunktion f. eks. leukocytter < 2, 5 x 109/ l hæmoglobin < 9 g/ dl, blodplader < 60 x 109/ l hæmoragisk diatese eller aktive blødningsforstyrrelser.
Significant haematological dysfunction, e. g. leucocytes < 2.5 x 109/ l, haemoglobin < 9 g/ dl, platelets < 60 x 109/ l, haemorrhagic diathesis or active bleeding disorder.
Alvorlig nyredysfunktion f. eks. nefrotisk syndrom, serumkreatinin > 150 µmol/ l eller kreatininclearance på < 50 ml/ min.
Significant renal dysfunction, e. g. nephrotic syndrome, serum creatinine > 150 µmol/ l, or creatinine clearance of < 50 ml/ minute.
3 Alvorlig hepatisk dysfunktion f. eks. > 2 x øvre grænse af normal værdi af aspartataminotransferase, alaninaminotransferase eller alkalisk fosfatase; eller et bilirubinniveau på > 1, 25 x den øvre grænse for normalen.
3 Significant hepatic dysfunction, e. g. > 2 x upper limits of normal levels of aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase; or bilirubin levels > 1.25 x upper limits of normal.
Hypercalcæmi > 12 mg/ dl (2, 99 mmol/ l).
Hypercalcaemia > 12 mg/ dl (2.99 mmol/ l).
Samtidig behandling med kardiotoksiske midler (f. eks. antracyklin).
Simultaneous treatment with cardiotoxic substances (eg anthracyclines).
4. 6).
Use in pregnancy and lactation (see section 4.6).
Kontraindikationer overfor melfalan:
Contraindications to melphalan:
Se venligst produktresuméet for melfalan.
Please refer to SPC for melphalan.
Kontraindikationer overfor ILP- proceduren:
Contraindications to the ILP procedure:
Alvorlig lymfeødem i ekstremiteten.
Severe lymphoedema of the limb.
Patienter, hos hvilke brug af karkontraherende midler er kontraindiceret
Patients with contra-indications to the use of vasopressor agents.
Graviditet og amning.
Use in pregnancy and lactation.
Isoleret ekstremitetsperfusion bør foretages på specialafdelinger af kirurgiske teams med erfaring i behandling af ekstremitetssarkomer og ILP- procedure, med en intensivafdeling til rådighed og med mulighed for kontinuerlig monitorering for lægemiddellækage til den systemiske cirkulation.
Isolated limb perfusion should be undertaken in specialised centres by surgical teams experienced in the management of limb sarcomas and ILP procedure, with an intensive care unit readily available and with the facilities for continuous monitoring for medicinal product leakage into the systemic circulation.
Før påbegyndelse af ILP- procedure se da venligst produktresuméet for melfalan.
Please refer to the SPC of melphalan prior to commencing an ILP procedure.
Derudover bør monitorering af blodtryk, diurese samt elektrokardiografi foretages løbende de første 24- 48 timer efter ILP, eller længere hvis indikeret.
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.
Et Swan- Ganz kateter bør overvejes til monitorering af pulmonalt arterielt tryk og ” wedge ” tryk under ILP samt postoperativt.
A Swan-Ganz catheter may be considered for monitoring pulmonary artery pressure and wedge pressure during the ILP and in the post-operative period.
4 Profylakse og behandling af feber, kulderystelser og andre influenzalignende symptomer associeret med Beromun administration, kan opnås ved præ- ILP administration af paracetamol (oralt eller rektalt) eller et alternativt analgetikum/ antipyretikum.
4 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.
Dette er for at sikre optimale hæmodynamiske betingelser og høj diurese, især efter perfusionen for at muliggøre en hurtig clearance af eventuel overskydende Beromun.
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 Beromun.
Supplerende genoplivningsvæsker (krystalloid - og kolloidopløsninger) bør være til rådighed til volumenudvidelse i tilfælde af et væsentligt fald i blodtrykket.
Additional resuscitation fluids (crystalloid and colloid solutions) should be available for volume expansion in case of a significant fall in blood pressure.
Kolloider og hydroxyethyl - stivelsesesvæsker foretrækkes, idet disse er mindst tilbøjelige til at sive ud i det vaskulære system.
Colloids and hydroxyethyl starch fluids are preferred, as they are less likely to leak out of the vascular system.
Endvidere og såfremt det skønnes klinisk nødvendigt kan administration af karkontraherende midler som f. eks. dopamin overvejes under ILP- proceduren og postoperativt.
In addition, as the clinical situation dictates, a vasopressor agent, e. g. dopamine, can be considered for administration during the ILP procedure, as well as in the post-operative period.
Med henblik på at minimere risikoen for lækage af perfusatet til den systemiske cirkulation, bør perfusionshastigheden ikke overstige 40 ml/ l ekstremitetsvolumen/ min.
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.
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 (Hoekstra HJ, Naujocks T, Schraffordt Koops H, Beekhuis H, van Groningen a Stuling R, ter Veen H, et. al..
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 (Hoekstra HJ, Naujocks T, Schraffordt Koops H, Beekhuis H, van Groningen a Stuling R, ter Veen H, et. al..
248- 253.).
248-253.).
Perfusionen bør afbrydes hvis den kumulative lækage til den systemiske cirkulation er > 10%.
The perfusion should be terminated if the cumulative leakage into the systemic circulation is > 10%.
Efter perfusion af underekstremitet bør 3- 6 l anvendes og efter perfusion af overekstremitet bør 1- 2 l anvendes.
After lower limb perfusion, 3 to 6 litres should be used, and after upper limb perfusion, 1 to 2 litres.
20 min.).
Measures should be taken to ensure that the periods of interrupted oxygen supply to the limb are as brief as possible (20 minutes maximum).
10 x den systemisk MTD.
The maximum tolerated dose (MTD) of Beromun for ILP is 4 mg, which is 10 times the systemic MTD.
Derfor må det altid forventes, at der ved væsentlige systemiske lækager af Beromun kan opstå alvorlige bivirkninger.
Therefore, whenever there is significant systemic leakage of Beromun, serious undesirable effects are to be expected.
Hvis der opstår tegn på systemisk toksicitet såsom f. eks. feber, hjertearytmi, shock/ hypotension, adult respiratory distress syndrome (ARDS) skal der anvendes normale hjælpeforanstaltninger, og patienten skal straks overføres til en intensiv afdeling til overvågning.
If signs of systemic toxicity appear for example fever, cardiac arrhythmias, shock/ hypotension, adult respiratory distress syndrome (ARDS), general supportive measures should be employed and the patient immediately transferred to an Intensive Care Unit for monitoring.
Nyre - og leverfunktion skal overvåges nøje.
Renal and hepatic function should be closely monitored.
Derfor bør
Cases of compartment syndrome characterised by pain, swelling and neurological symptoms, as well as muscle damage affecting the perfused limb have been observed in isolated patients treated with Beromun.
5 patienter monitoreres i de første tre dage efter ILP.
Therefore patients should be monitored during the first three days after the ILP.
Faciotomi af alle muskel områder af den berørte legemsdel.
Fasciotomy of all muscle compartments of the limb affected,
2.
5 2.
Ingen formelle interaktionsstudier er blevet udført med Beromun.
No formal interaction studies have been performed with Beromun.
Kombinationsbehandling udover standardbehandlingen med melfalan, kan ikke anbefales.
Co-administration, other than in the standard regimen with melphalan, is not recommended.