natgillin/translations-raw huggingface dataset:
Der er rapporteret om pure red cell- aplasi forårsaget af neutraliserende antistoffer mod erytropoietin i forbindelse med rekombinante erytropoietiske proteiner, herunder darbepoetin alfa.
Pure red cell aplasia caused by neutralising anti-erythropoietin antibodies has been reported in association with recombinant erythropoietic proteins, including darbepoetin alfa.
Disse antistoffer har vist sig at krydsreagere med alle erytropoietinproteiner, og patienter der er under mistanke for at have eller som har fået bekræftet tilstedeværelsen af neutraliserende antistoffer mod erytropoietin, bør ikke overgå til behandling med darbepoetin alfa (se afsnit 4. 8).
These antibodies have been shown to cross-react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to darbepoetin alfa (see section 4.8).
Derfor findes der ingen data fra patienter med nedsat leverfunktion.
Active liver disease was an exclusion criteria in all studies of Aranesp, therefore no data are available from patients with impaired liver function.
Da leveren antages at være den primære eliminationsvej for Aranesp og r- HuEPO, bør Aranesp altid anvendes med forsigtighed af patienter med leversygdom.
Since the liver is thought to be the principal route of elimination of Aranesp and r-HuEPO, Aranesp should be used with caution in patients with liver disease.
Aranesp bør også benyttes med forsigtighed hos patienter med seglcelleanæmi eller epilepsi.
Aranesp should also be used with caution in those patients with sickle cell anaemia or epilepsy.
Hos patienter med kronisk nyresvigt må vedligeholdelseskoncentrationen af hæmoglobin ikke overstige den øvre grænse for den målkoncentration af hæmoglobin, der en anbefalet i afsnit 4. 2.
In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration recommended in section 4.2.
I kliniske studier er der observeret en øget risiko for dødsfald, alvorlige hjertekarhændelser og trombose med vaskulær adgang ved indgivelse af erytropoiesestimulerende midler (ESAer) med det formål at opnå en hæmoglobinkoncentration på mere end 12 g/ dl (7, 5 mmol/ l).
In clinical studies, an increased risk of death, serious cardiovascular events, and vascular access thrombosis was observed when erythropoiesis-stimulating agents (ESAs) were administered to target a haemoglobin of greater than 12 g/ dl (7.5 mmol/ l).
6 Aranesp bør bruges med forsigtighed hos patienter med epilepsi.
Aranesp should be used with caution in patients with epilepsy.
Supplerende jerntilskud anbefales til alle patienter med serum ferritin- værdier på under 100 μg/ l eller til de patienter, hvis transferrinmætning er under 20%.
Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 µg/ l or whose transferrin saturation is below 20%.
Hos patienter med kronisk nyresvigt og klinisk tegn på iskæmisk hjertesygdom eller kronisk hjertesvigt skal hæmoglobinniveauet fastsættes individuelt.
6 In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
Hos disse patienter bør man tilstræbe en øvre grænse på 12 g/ dl (7, 5 mmol/ l), hvis ikke alvorlige symptomer (f. eks. angina) dikterer andet.
In these patients an upper limit of 12 g/ dl (7.5 mmol/ l) should be aimed for, unless severe symptoms (e. g. angina) dictate otherwise.
Kaliumforhøjelse er blevet rapporteret i nogle få patienter i behandling med Aranesp, selvom årsagssammenhæng ikke er blevet påvist.
Potassium elevation has been reported in a few patients receiving Aranesp, though causality has not been established.
Hvis et forhøjet eller stigende kaliumniveau observeres, bør det overvejes at standse Aranesp, indtil niveauet er blevet korrigeret.
If an elevated or rising potassium level is observed then consideration should be given to ceasing Aranesp administration until the level has been corrected.
I kontrollerede kliniske studier har brugen af Aranesp og andre erytropoiesestimulerende midler (ESAer) givet følgende resultater:
In controlled clinical studies, use of Aranesp and other erythropoiesis-stimulating agents (ESAs) have shown:
ESAer er ikke indiceret til brug i denne patientpopulation.
• shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/ dl (8.7 mmol/ l), ESAs are not indicated for use in this patient population.
• kortere samlet overlevelsestid og overdødelighed som følge af sygdomsudvikling efter 4 måneder hos patienter med metastatisk brystcancer, som modtager kemoterapi, når det indgives for at behandle en hæmoglobinkoncentration på 12- 14 g/ dl (7, 5- 8, 7 mmol/ l).
• shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/ dl (7.5-8.7 mmol/ l)
ESAer er ikke indiceret til brug i denne patientpopulation.
• increased risk of death when administered to target a haemoglobin of 12 g/ dl (7.5 mmol/ l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for use in this patient population.
De faktorer, som bør overvejes i forbindelse med denne vurdering, er tumortype og tumorstadie, anæmiens udstrækning, forventet levetid, patientens behandlingsmiljø og patientens ønsker (se afsnit 5. 1).
Factors that should be considered in this assessment should include the type of tumour and its stage; the degree of anaemia; life- expectancy; the environment in which the patient is being treated; and patient preference (see section 5.1).
Hvis hæmoglobin værdier overskrider 12 g/ dl (7, 5 mmol/ l) hos patienter med solide tumorer eller lymfoproliferative maligniciteter, skal dosistilpasningen ske i overensstemmelse med afsnit 4. 2, for at minimere den potentielle risiko for tromboemboliske hændelser.
In patients with solid tumours or lymphoproliferative malignancies, if the haemoglobin value exceeds 12 g/ dl (7.5 mmol/ l), the dosage adaptation described in section 4.2 should be closely respected, in order to minimise the potential risk of thromboembolic events.
7 4. 5 Interaktion med andre lægemidler og andre former for interaktion
4.5 Interaction with other medicinal products and other forms of interaction
De kliniske resultater opnået til nu indikerer ingen interaktion mellem Aranesp og andre stoffer.
The clinical results obtained so far do not indicate any interaction of Aranesp with other substances.
Der er risiko for interaktioner med lægemidler som er tæt bundet til røde blodlegemer, f. ex. ciclosporin og tacrolimus.
However, there is potential for an interaction with drugs that are highly bound to red blood cells e. g. cyclosporin, tacrolimus.
4. 6 Graviditet og amning
7 4.6 Pregnancy and lactation
Der foreligger ikke kliniske data om eksponering for Aranesp under graviditet.
For Aranesp no clinical data on exposed pregnancies are available.
Dyreforsøg viser ikke direkte skadelige virkninger for graviditet, embryoets/ fostrets udvikling, fødslen eller den postnatale udvikling.
Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development.
Da der ikke er klinisk erfaring med brug af Aranesp hos ammende kvinder, bør Aranesp ikke administreres til ammende kvinder.
As there is no clinical experience with lactating women Aranesp should not be administered to women who are breast-feeding.
Når Aranesp er absolut påkrævet, skal kvinden stoppe med at amme.
When Aranesp therapy is absolutely indicated women must stop breast- feeding.
4. 7 Påvirkning af evnen til at føre motorkøretøj eller betjene maskiner
4.7 Effects on ability to drive and use machines
Der er ikke foretaget undersøgelser af Aranesps påvirkning af evnen til at føre motorkøretøj eller betjene maskiner.
There have been no observed effects with Aranesp on the ability to drive and use machines.
Data præsenteret fra kontrollerede studier inkluderede 1357 patienter, hvoraf 766 modtog Aranesp og 591 patienter modtog r- HuEPO.
Data presented from controlled studies included 1357 patients, 766 who received Aranesp and 591 patients who received r-HuEPO.
I Aranesp- gruppen fik 83% dialyse, og 17% fik ikke dialyse.
In the Aranesp group, 83% were receiving dialysis and 17% were not receiving dialysis.
Der blev rapporteret smerte ved injektionsstedet, som blev tilskrevet behandling i studier, hvor Aranesp blev administreret via subkutan injektion.
Injection site pain was reported as attributable to treatment in studies where Aranesp was administered via subcutaneous injection.
Dette sås oftere end ved r- HuEPO.
This was seen more frequently than with r-HuEPO.
Forekomsten af bivirkninger, der betragtes som relateret til behandling med Aranesp i kontrollerede kliniske studier, er:
Incidence of undesirable effects considered related to treatment with Aranesp from controlled clinical studies are:
Medra systemorganklasse Hjerte Hud og subkutane væv Vaskulære sygdomme
MedDRA system organ class Cardiac Disorders Skin and Subcutaneous Tissue Disorders
Forekomst hos forsøgsperson Meget almindelig (≥ 1/ 10) Almindelig (≥ 1/ 100 til < 1/ 10) Ikke almindelig (≥ 1/ 1. 000 til < 1/ 100)
Subject Incidence Very Common (≥ 1/ 10) Common (≥ 1/ 100 to < 1/ 10)
Bivirkning Hypertension Udslæt/ erytem Tromboemboliske hændelser
Adverse Drug Reaction Hypertension Rash/ Erythema
Almene symptomer og reaktioner på administrationsstedet
Vascular disorders
Almindelig (≥ 1/ 100 til < 1/ 10)
Uncommon (≥ 1/ 1,000 to < 1/ 100)
8 Cancerpatienter
Cancer patients
De uønskede reaktioner blev fastlagt på baggrund af en datapulje fra syv randomiserede, dobbelt - blindede placebo- kontrollerede undersøgelser af Aranesp, hvor i alt 2112 patienter deltog (Aranesp 1200, placebo 912).
Adverse reactions were determined based on pooled data from seven randomised, double-blind, placebo-controlled studies of Aranesp with a total of 2112 patients (Aranesp 1200, placebo 912).
I de kliniske undersøgelser indgik patienter med solide tumorer (f. eks. lunge -, bryst -, tyktarms -, ovariekræft) og lymfoide maligne sygdomme (f. eks. lymfom, multipelt myeloma).
Patients with solid tumours (e. g., lung, breast, colon, ovarian cancers) and lymphoid malignancies (e. g., lymphoma, multiple myeloma) were enrolled in the clinical studies.
Forekomsten af bivirkninger, der betragtes som relaterede til behandling med Aranesp udfra kontrollerede kliniske studier, er:
8 Incidence of undesirable effects considered related to treatment with Aranesp from controlled clinical studies are:
Medra systemorganklasse Hud og subkutane væv Vaskulære sygdomme
MedDRA system organ class Skin and Subcutaneous Tissue Disorders
Forekomst hos forsøgsperson Almindelig (≥ 1/ 100 til < 1/ 10) Almindelig (≥ 1/ 100 til < 1/ 10)
Subject Incidence Common (≥ 1/ 100 to < 1/ 10)
Bivirkning Udslæt- erytem Tromboemboliske hændelser, herunder lungeembolisme
Thromboembolic events, including pulmonary embolism
Meget almindelig (≥ 1/ 10)
Very Common (≥ 1/ 10)
Almindelig (≥ 1/ 100 til < 1/ 10)
Common (≥ 1/ 100 to < 1/ 10)
De følgende uønskede reaktioner blev identificeret ved brug af Aranesp efter markedsføring:
The following adverse reactions have been identified during postmarketing use of Aranesp:
• Erythroblastopenia.
• Pure Red Cell Aplasia.
Det er i enkelte tilfælde set, at neutraliserende antistoffer mod erytropoietin har medieret erythroblastopenia (PRCA) i forbindelse med behandling med Aranesp, hovedsageligt hos patienter med CRF, som blev behandlet subkutant.
In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Aranesp therapy have been reported predominantly in patients with CRF treated subcutaneously.
I tilfælde af at PRCA diagnosticeres, skal behandling med Aranesp afbrydes, og patienterne skal ikke skifte til et andet gensplejset erytropoietisk protein (se afsnit 4. 4).
In case PRCA is diagnosed, therapy with Aranesp must be discontinued and patients should not be switched to another recombinant erythropoietic protein (see section 4.4).
• Overfølsomhedsreaktioner, herunder anafylaktiske reaktioner, angioødem, hududslæt og urticaria.
• Allergic reactions, including anaphylactic reaction, angioedema, skin rash and urticaria.
• Krampeanfald.
• Convulsions.
Det terapeutiske indeks for Aranesp er meget bredt.
The therapeutic margin of Aranesp is very wide.
I tilfælde af polycytæmi bør Aranesp midlertidigt seponeres (se afsnit 4. 2).
In the event of polycythaemia, Aranesp should be temporarily withheld (see section 4.2).
Anti- anæmisk, ATC- kode:
Anti-anaemic ATC Code:
Humant erytropoietin er et endogent glykoprotein hormon, der fungerer som den primære regulator af erytropoiesen gennem specifik interaktion med erytropoietin- receptoren på den erythroide stamcelle i knoglemarven.
Human erythropoietin is an endogenous glycoprotein hormone that is the primary regulator of erythropoiesis through specific interaction with the erythropoietin receptor on the erythroid progenitor cells in the bone marrow.
9 Darbepoetin alfa stimulerer erytropoiesen ved samme mekanisme som det endogene hormon.
Darbepoetin alfa stimulates erythropoiesis by the same mechanism as the endogenous hormone.
Darbepoetin alfa har fem N- koblede kulhydratkæder, hvor det endogene hormon og recombinante humane erytropoietiner (r- HuEPO) har tre.
Darbepoetin alfa has five N-linked carbohydrate chains whereas the endogenous hormone and recombinant human erythropoietins (r-HuEPO) have three.
På grund af dets øgede kulhydratindhold har darbepoetin alfa en længere terminal halveringstid end r- HuEPO og som konsekvens heraf en større in vivo- aktivitet.
Due to its increased carbohydrate content darbepoetin alfa has a longer terminal half-life than r-HuEPO and consequently a greater
På trods af disse molekylære ændringer bibeholder darbepoetin alfa en meget præcis specificitet for erytropoietin - receptoren.
Despite these molecular changes, darbepoetin alfa retains a very narrow specificity for the erythropoietin receptor.
I en prospektiv, randomiseret dobbeltblindt, placebokontrolleret undersøgelse med 314 lungecancerpatienter i platinkemoterapi, var der en signifikant reduktion i blodtransfusionsbehovet (p < 0, 001).
In a prospective, randomised double-blind, placebo-controlled study conducted in 314 lung cancer patients receiving platinum containing chemotherapy there was a significant reduction in transfusion requirements (p < 0.001).
Sikkerheden og effektiviteten af behandling med Aranesp indgivet én gang hver tredje uge med det formål at reducere behovet for transfusion af røde blodlegemer hos patienter, som får kemoterapi, blev undersøgt i en randomiseret, dobbeltblind multinational undersøgelse.
The safety and effectiveness of once every three weeks dosing of Aranesp therapy in reducing the requirement for red blood cell transfusions in patients undergoing chemotherapy was assessed in a randomised, double-blind, multinational study.
Undersøgelsen omfattede 705 anæmiske patienter med ikke- myeloide maligniteter, som modtog kemoterapi med flere cyklusser.
This study was conducted in 705 anaemic patients with non-myeloid malignancies receiving multi-cycle chemotherapy.
Patienterne blev randomiseret til at modtage en dosis på 500 μg Aranesp én gang hver tredje uge eller 2, 25 μg/ kg én gang om ugen.
Patients were randomized to receive Aranesp at 500 μ g once every three weeks or 2.25 μ g / kg once weekly.
I begge grupper blev dosis reduceret med 40% i forhold til den tidligere dosis (f. eks. var første dosisreduktion en reduktion til 300 μg i gruppen, der modtog dosis én gang hver tredje uge, og til 1, 35 μg/ kg i gruppen, der modtog dosis én gang om ugen), hvis hæmoglobintallet steg med mere end 1 g/ dl over en periode på 14 dage.
In both groups, the dose was reduced by 40% of the previous dose (e. g., for first dose reduction, to 300 μ g in the once every three weeks group and 1.35 μ g / kg in the once weekly group) if haemoglobin increased by more than 1 g/ dl in a 14-day period.
I gruppen, som modtog dosis én gang hver tredje uge, krævede 72% af patienterne dosisreduktioner.
In the once every three weeks group, 72% of patients required dose reductions.
I gruppen, som modtog dosis én gang om ugen, krævede 75% af patienterne dosisreduktioner.
In the once weekly group, 75% of patients required dose reductions.
Undersøgelsen understøtter antagelsen om, at 500 μg én gang hver tredje uge er sammenlignelig med en ugentlig dosis, når det gælder hyppigheden af forsøgspersonernes modtagelse af mindst én transfusion med røde blodlegemer i perioden fra uge 5 til slutningen af behandlingsforløbet.
This study supports 500 μ g once every three weeks being comparable to once weekly administration with respect to the incidence of subjects receiving at least one red blood cell transfusion from week 5 to the end of treatment phase.
I en prospektiv, randomiseret dobbeltblindt, placebokontrolleret studie hos 344 anæmiske patienter med lymfoproliferative maligniteter i kemoterapi, var der en signifikant reduktion i blodtransfusionsbehovet og en forbedring af hæmoglobinrespons (p < 0, 001).
In a prospective, randomised double-blind, placebo-controlled study conducted in 344 anaemic patients with lymphoproliferative malignancies receiving chemotherapy there was a significant reduction in transfusion requirements and an improvement in haemoglobin response (p < 0.001).
Der blev ligeledes fundet en reduktion i træthed, målt ved hjælp af ” Functional Assessment of Cancer Therapy- fatigue (FACT- fatigue) ” skala.
Improvement in fatigue, as measured by the Functional Assessment of Cancer Therapy-fatigue (FACT-fatigue) scale, was also observed.
Heraf var de fire dobbeltblinde placebokontrollerede studier, mens ét var et ublindet- studie.
Survival and tumour progression have been examined in five large controlled studies involving a total of 2833 patients, of which four were double-blind placebo-controlled studies and one was an open- label study.
Målkoncentrationen af hæmoglobin i to af studierne var > 13 g/ dl, og i de øvrige tre studier var den 12- 14 g/ dl.
The target haemoglobin concentration in two studies was > 13 g/ dl; in the remaining three studies it was 12-14 g/ dl.
I de fire placebokontrollerede studier lå hazard ratioen for den samlede overlevelse på mellem 1, 25 og 2, 47 i kontrolgruppens favør.
In the four placebo-controlled studies the hazard ratios for overall survival ranged between 1.25 and 2.47 in favour of controls.
10 Der er også foretaget en systematisk gennemgang af flere end 9. 000 cancerpatienter, som deltog i 57 kliniske forsøg.
A systematic review has also been performed involving more than 9000 cancer patients participating in 57 clinical trials.
En metaanalyse af de samlede overlevelsesdata viste en vurderet hazard ratio på 1. 08 i kontrolgruppens favør (95% CI:
Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.08 in favour of controls (95% CI:
0, 99, 1, 18; 42 forsøg og 8. 167 patienter).
0.99, 1.18; 42 trials and 8167 patients).
Der blev observeret en øget relativ risiko for tromboemboliske hændelser (RR 1, 67, 95% CI:
An increased relative risk of thromboembolic events (RR 1.67, 95% CI:
1, 35, 2, 06, 35 forsøg og 6. 769 patienter) blev observeret hos patienter, der modtog behandling med rekombineret humant erytropoietin.
1.35, 2.06, 35 trials and 6769 patients) was observed in patients treated with recombinant human erythropoietin.
Det er uklart, i hvor høj grad disse resultater berører indgivelsen af rekombineret humant erytropoietin til patienter med cancer, som modtager kemoterapi med det formål at opnå en hæmoglobinkoncentration på under 13 g/ dl, fordi de medtagne data kun indeholder få patienter med disse karakteristika.
10 chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
Dette tillader en sjældnere administration af darbepoetin alfa for at opnå samme biologiske respons.
Due to its increased carbohydrate content the level of darbepoetin alfa in the circulation remains above the minimum stimulatory concentration for erythropoiesis for longer than the equivalent molar dose of r-HuEPO, allowing darbepoetin alfa to be administered less frequently to achieve the same biological response.
Darbepoetin alfas terminale halveringstid er 21 timer (SD 7, 5) ved intravenøs administration.
The terminal half-life of darbepoetin alfa is 21 hours (SD 7.5) when administered intravenously.
Clearance for darbepoetin alfa er 1, 9 ml/ t/ kg (SD 0, 56) og fordelingsvolumen (Vss) er omtrent lig plasmavolumen (50 ml/ kg).
Clearance of darbepoetin alfa is 1.9 ml/ hr/ kg (SD 0.56) and the volume of distribution (Vss) is approximately equal to plasma volume (50 ml/ kg).
Efter månedlig administration af darbepoetin alfa ved subkutane doser fra 0, 6 til 2, 1 µg/ kg var den terminale halveringstid 73 timer (SD 24).
Following monthly administration of darbepoetin alfa, at subcutaneous doses ranging from 0.6 to 2.1 µg/ kg, the terminal half-life was 73 hours (SD 24).
Resultater opnået ved indgift af Aranesp til 809 patienter i kliniske undersøgelser i Europa blev analyseret med henblik på at kunne fastsætte den dosis, som er påkrævet for at fastholde hæmoglobin; der blev ikke observeret nogen forskel på den gennemsnitlige ugentlige dose uanset om injektionen skete intravenøst eller subkutant.
Data from 809 patients receiving Aranesp in European clinical studies were analysed to assess the dose required to maintain haemoglobin; no difference was observed between the average weekly dose administered via the intravenous or subcutaneous routes of injection.
Ved vurderingen af de farmakoninestiske egenskaber ved darbepoetin alfa hos børn (3- 16 år) med kronisk nyresvigt (CRF), som enten var eller ikke var i dialysebehandling, blev der fastlagt farmakokinetiske profiler for prøverperioder op til 1 uge (168 timer) efter en enkelt subkutan eller intravenøs dosis.
Assessment of the pharmacokinetics of darbepoetin alfa in paediatric patients (3 to 16 years) with CRF who were either receiving or not receiving dialysis determined pharmacokinetic profiles for sampling periods up to 1 week (168 hours) after a single subcutaneous or intravenous dose.
Forskellen var dog mindre end det dobbelte område i AUC( 0- ∞), der blev observeret hos børn.
Following intravenous administration, an approximate 25% difference between paediatric and adult patients in the area under the curve from time 0 to infinity (AUC[0-∞]) was observed; however, this difference was less than the 2-fold range in AUC(0-∞) observed for the pediatricpatients.
AUC( 0- ∞) var næsten det samme hos børn og voksne med kronisk nyresvigt (CRF) efter subkutan administration.
AUC(0-∞) was similar between adult and paediatric patients with CRF following subcutaneous administration.
Efter subkutan indgift af 2, 25 μg/ kg til voksne cancerpatienter, opnåedes en gennemsnitlig peakkoncentration på 10, 6 ng/ ml (SD 5, 9) darbepoietin alfa i løbet af en gennemsnitstid på 91 timer (SD 19, 7).
Following subcutaneous administration of 2.25 µg/ kg to adult cancer patients a mean peak concentration of 10.6 ng/ ml (SD 5.9) of darbepoetin alfa was reached at a mean time of 91 hours (SD 19.7).
Der var ingen ændring i de
These parameters were consistent with dose linear pharmacokinetics over a wide dose range (0.5 to 8 µg/ kg weekly and 3 to 9 µg/ kg every two weeks).
11 farmakokinetiske parametre ved gentagen indgift over 12 uger (dosering hver uge eller hver anden uge).
Pharmacokinetic parameters did not change on multiple dosing over 12 weeks (dosing every week or every two weeks).