natgillin/translations-raw huggingface dataset:
Pakningen indeholder en eller fire fyldt( e) pen( ne) med 100 µg Nespo injektionsvæske, opløsning i 0, 5 ml (200 µg/ ml).
Package containing one or four pre-filled pens of a 100 µg Nespo solution for injection in 0.5 ml (200 µg/ ml).
lg sa 6. 6 Regler for destruktion
312 6.6 Special precautions for disposal
EU/ 1/ 01/ 184/ 053 1- pakning EU/ 1/ 01/ 184/ 065 4- pakning id m
EU/ 1/ 01/ 184/ 053 1 pack EU/ 1/ 01/ 184/ 065 4 pack ct
314 Behandling med Nespo er delt i to trin – korrigerings - og vedligeholdelsesfase.
Treatment with Nespo is divided into two stages – correction and maintenance phase.
Voksne patienter med kronisk nyresvigt
314 Adult patients with chronic renal failure
315 Nespo (µg/ uge) kan bestemmes ved at dividere hele den ugentlige dosis af r- HuEPO (IE/ uge) med 200.
The initial weekly dose of Nespo (µg/ week) can be determined by dividing the total weekly dose of r-HuEPO (IU/ week) by 200.
På grund af individuel variation forventes titrering til optimal terapeutisk dosis for enkelte patienter.
315 individual variability, titration to optimal therapeutic doses is expected for individual patients.
316 Hvis stigningen i hæmoglobinniveauet er større end 2 g/ dl (1, 25 mmol/ l) i løbet af fire uger, skal dosis reduceres med cirka 25%, afhængigt af stigningshastigheden.
If the rise in haemoglobin is greater than 2 g/ dl (1.25 mmol/ l) in four weeks reduce the dose by approximately 25%, depending on the rate of increase.
25% lavere end den tidligere dosis.
316 increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
317 4. 3 Kontraindikationer
4.3 Contraindications
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
317 4.4 Special warnings and precautions for use
318 Nespo bør bruges med forsigtighed hos patienter med epilepsi.
Nespo should be used with caution in patients with epilepsy.
Hos disse patienter bør man tilstræbe en
318 In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
319 4. 5 Interaktion med andre lægemidler og andre former for interaktion
4.5 Interaction with other medicinal products and other forms of interaction
4. 6 Graviditet og amning
319 4.6 Pregnancy and lactation
320 Cancerpatienter
320 Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical studies are:
321 Darbepoetin alfa stimulerer erytropoiesen ved samme mekanisme som det endogene hormon.
321 in vivo activity.
322 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.
lg hæmoglobinkoncentration på under 13 g/ dl, fordi de medtagne data kun indeholder få patienter med
322 chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
323 farmakokinetiske parametre ved gentagen indgift over 12 uger (dosering hver uge eller hver anden uge).
change on multiple dosing over 12 weeks (dosing every week or every two weeks).
Der var bl. a. tale om
323 effect (decreased tissue perfusion due to increased blood viscosity).
324 6. 5 Emballagetype og pakningsstørrelser
6.5 Nature and contents of container M
Pakningen indeholder en eller fire fyldt( e) pen( ne) med 130 µg Nespo injektionsvæske, opløsning i 0, 65 ml (200 µg/ ml).
Package containing one or four pre-filled pens of a 130 µg Nespo solution for injection in 0.65 ml (200 µg/ ml).
lg sa 6. 6 Regler for destruktion
324 6.6 Special precautions for disposal
EU/ 1/ 01/ 184/ 072 1- pakning EU/ 1/ 01/ 184 / 4- pakning id m
EU/ 1/ 01/ 184/ 072 1 pack EU/ 1/ 01/ 184/ 073 4 pack ct
326 Behandling med Nespo er delt i to trin – korrigerings - og vedligeholdelsesfase.
Treatment with Nespo is divided into two stages – correction and maintenance phase.
Voksne patienter med kronisk nyresvigt
326 Adult patients with chronic renal failure
327 Nespo (µg/ uge) kan bestemmes ved at dividere hele den ugentlige dosis af r- HuEPO (IE/ uge) med 200.
The initial weekly dose of Nespo (µg/ week) can be determined by dividing the total weekly dose of r-HuEPO (IU/ week) by 200.
På grund af individuel variation forventes titrering til optimal terapeutisk dosis for enkelte patienter.
327 individual variability, titration to optimal therapeutic doses is expected for individual patients.
328 Hvis stigningen i hæmoglobinniveauet er større end 2 g/ dl (1, 25 mmol/ l) i løbet af fire uger, skal dosis reduceres med cirka 25%, afhængigt af stigningshastigheden.
If the rise in haemoglobin is greater than 2 g/ dl (1.25 mmol/ l) in four weeks reduce the dose by approximately 25%, depending on the rate of increase.
25% lavere end den tidligere dosis.
328 increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
329 4. 3 Kontraindikationer
4.3 Contraindications
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
329 4.4 Special warnings and precautions for use
330 Nespo bør bruges med forsigtighed hos patienter med epilepsi.
Nespo should be used with caution in patients with epilepsy.
Hos disse patienter bør man tilstræbe en
330 In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
331 4. 5 Interaktion med andre lægemidler og andre former for interaktion
4.5 Interaction with other medicinal products and other forms of interaction
4. 6 Graviditet og amning
331 4.6 Pregnancy and lactation
332 Cancerpatienter
332 Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical studies are:
333 Darbepoetin alfa stimulerer erytropoiesen ved samme mekanisme som det endogene hormon.
333 in vivo activity.
334 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.
lg hæmoglobinkoncentration på under 13 g/ dl, fordi de medtagne data kun indeholder få patienter med
334 chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
335 farmakokinetiske parametre ved gentagen indgift over 12 uger (dosering hver uge eller hver anden uge).
change on multiple dosing over 12 weeks (dosing every week or every two weeks).
Der var bl. a. tale om
335 effect (decreased tissue perfusion due to increased blood viscosity).
336 6. 5 Emballagetype og pakningsstørrelser
6.5 Nature and contents of container M
Pakningen indeholder en eller fire fyldt( e) pen( ne) med 150 µg Nespo injektionsvæske, opløsning i 0, 3 ml (500 µg/ ml).
Package containing one or four pre-filled pens of a 150 µg Nespo solution for injection in 0.3 ml (500 µg/ ml).
lg sa 6. 6 Regler for destruktion
336 6.6 Special precautions for disposal
EU/ 1/ 01/ 184/ 054 1- pakning le
EU/ 1/ 01/ 184/ 054 1 pack EU/ 1/ 01/ 184/ 066 4 pack ct
338 Behandling med Nespo er delt i to trin – korrigerings - og vedligeholdelsesfase.
Treatment with Nespo is divided into two stages – correction and maintenance phase.
Voksne patienter med kronisk nyresvigt
338 Adult patients with chronic renal failure
339 Nespo (µg/ uge) kan bestemmes ved at dividere hele den ugentlige dosis af r- HuEPO (IE/ uge) med 200.
The initial weekly dose of Nespo (µg/ week) can be determined by dividing the total weekly dose of r-HuEPO (IU/ week) by 200.
På grund af individuel variation forventes titrering til optimal terapeutisk dosis for enkelte patienter.
339 individual variability, titration to optimal therapeutic doses is expected for individual patients.
340 Hvis stigningen i hæmoglobinniveauet er større end 2 g/ dl (1, 25 mmol/ l) i løbet af fire uger, skal dosis reduceres med cirka 25%, afhængigt af stigningshastigheden.
If the rise in haemoglobin is greater than 2 g/ dl (1.25 mmol/ l) in four weeks reduce the dose by approximately 25%, depending on the rate of increase.
25% lavere end den tidligere dosis.
340 increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
341 4. 3 Kontraindikationer
4.3 Contraindications
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
341 4.4 Special warnings and precautions for use
342 Nespo bør bruges med forsigtighed hos patienter med epilepsi.
Nespo should be used with caution in patients with epilepsy.
Hos disse patienter bør man tilstræbe en
342 In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
343 4. 5 Interaktion med andre lægemidler og andre former for interaktion
4.5 Interaction with other medicinal products and other forms of interaction
4. 6 Graviditet og amning
343 4.6 Pregnancy and lactation
lg sa 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.
et administreres til ammende kvinder.
As there is no clinical experience with lactating women Nespo should not be administered to women who are breast-feeding.
er 4. 7 Påvirkning af evnen til at føre motorkøretøj eller betjene maskiner
ed 4.7 Effects on ability to drive and use machines
is Der er ikke foretaget undersøgelser af Nespos påvirkning af evnen til at føre motorkøretøj eller betjene
There have been no observed effects with Nespo on the ability to drive and use machines.
or maskiner.
is or 4.8 Undesirable effects
t 4. 8 Bivirkninger au e Generelt er
th General
Der har i sjældne tilfælde været rapporteret om alvorlige allergiske reaktioner, inklusiv anafylaktisk ng
au There have been reports of serious allergic reactions including anaphylactic reaction, angioedema, dyspnoea, skin rash and urticaria associated with darbepoetin alfa.
Patienter med kronisk nyresvigt e kk
Clinical Trial Experience er ng Chronic renal failure patients lo
Data præsenteret fra kontrollerede studier inkluderede 1357 patienter, hvoraf 766 modtog Nespo og 591 patienter modtog r- HuEPO.
Data presented from controlled studies included 1357 patients, 766 who received Nespo and 591 no
I Nespo- gruppen fik 83% dialyse, og 17% fik ikke dialyse. ri
In the Nespo group, 83% were receiving dialysis and 17% were not receiving dialysis. ct
Der blev rapporteret smerte ved injektionsstedet, som blev tilskrevet behandling i studier, hvor Nespo te
Injection site pain was reported as attributable to treatment in studies where Nespo was administered via subcutaneous injection.
Generne ved injektionsstedet var generelt milde, af forbigående karakter og optrådte hovedsageligt efter den første le
discomfort was generally mild and transient in nature and occurred predominantly after the first injection. ro
injektion. id
studies are: a
Forekomsten af bivirkninger, der betragtes som relateret til behandling med Nespo i kontrollerede m
MedDRA system organ class in
kliniske studier, er: ge
Subject Incidence
Medra systemorganklasse Hjerte Læ
Cardiac Disorders ic
Forekomst hos forsøgsperson Meget almindelig (≥ 1/ 10)
Very Common (≥ 1/ 10)
Bivirkning Hypertension
Hypertension
Hud og subkutane væv Vaskulære sygdomme
Skin and Subcutaneous Tissue Disorders ed
Almindelig (≥ 1/ 100 til < 1/ 10) Ikke almindelig (≥ 1/ 1. 000 til < 1/ 100)
Common (≥ 1/ 100 to < 1/ 10)
Udslæt/ erytem Tromboemboliske hændelser
Rash/ Erythema
344 De uønskede reaktioner blev fastlagt på baggrund af en datapulje fra syv randomiserede, dobbelt - blindede placebo- kontrollerede undersøgelser af Nespo, hvor i alt 2112 patienter deltog (Nespo 1200, placebo 912).
Adverse reactions were determined based on pooled data from seven randomised, double-blind, placebo-controlled studies of Nespo with a total of 2112 patients (Nespo 1200, placebo 912).
Forekomsten af bivirkninger, der betragtes som relaterede til behandling med Nespo udfra kontrollerede kliniske studier, er:
344 Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical studies are:
lg Vaskulære sygdomme
Vascular disorders
Tromboemboliske hændelser,
Thromboembolic events, including pulmonary embolism
sa herunder lungeembolisme Almene symptomer og reaktioner på
General Disorders and Administration Site Conditions
et er Erfaring efter markedsføring
ed Postmarketing Experience
is De følgende uønskede reaktioner blev identificeret ved brug af Nespo efter markedsføring:
is The following adverse reactions have been identified during postmarketing use of Nespo:
or • Erythroblastopenia.
or th • Pure Red Cell Aplasia.
t har medieret erythroblastopenia (PRCA) i forbindelse med behandling med Nespo, au hovedsageligt hos patienter med CRF, som blev behandlet subkutantsubkutant.
au patients with CRF treated subcutaneously.
I tilfælde af at PRCA diagnosticeres, skal behandling med Nespo afbrydes, og patienterne skal ikke skifte til et e andet gensplejset erytropoietisk protein (se afsnit 4. 4). er
In case PRCA is diagnosed, therapy with Nespo 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 ng
• er Allergic reactions, including anaphylactic reaction, angioedema, skin rash and urticaria. ng • Convulsions. lo
urticaria. læ
4.9 Overdose no
Selv ved meget høje plasmakoncentrationer er der ikke observeret nogle symptomer på overdosering. ri te
Even at very high serum levels, no symptoms of overdose have been observed. ct du
Hvis klinisk indiceret kan phlebotomi udføres. le id
If clinically indicated, phlebotomy may be performed. ro lp
FARMAKOLOGISKE EGENSKABER m
PHARMACOLOGICAL PROPERTIES a
5. 1 Farmakodynamiske egenskaber ge
5.1 Pharmacodynamic properties in
Læ
B03XA02. ic ed
Darbepoetin alfa har fem N- koblede kulhydratkæder, hvor det endogene hormon og recombinante 345 humane erytropoietiner (r- HuEPO) har tre.
345 in vivo activity.
I en prospektiv, randomiseret dobbeltblindt, placebokontrolleret undersøgelse med 314 lungecancerpatienter i platinkemoterapi, var der en signifikant reduktion i blodtransfusionsbehovet
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).
sa Kliniske studier har vist, at darbepoetin alfa havde lignende effekt, når denne blev givet som enkelt injektion enten én gang hver tredje uge, én gang hver anden uge eller ugentligt uden øgning i totalt
Clinical studies have demonstrated that darbepoetin alfa had similar effectiveness when administered as a single injection either once every three weeks, once every two weeks, or weekly without any increase in total dose requirements.
et Sikkerheden og effektiviteten af behandling med Nespo indgivet én gang hver tredje uge med det
ed The safety and effectiveness of once every three weeks dosing of Nespo therapy in reducing the requirement for red blood cell transfusions in patients undergoing chemotherapy was assessed in a
er formål at reducere behovet for transfusion af røde blodlegemer hos patienter, som får kemoterapi, blev undersøgt i en randomiseret, dobbeltblind multinational undersøgelse.
is randomised, double-blind, multinational study.
is anæmiske patienter med ikke- myeloide maligniteter, som modtog kemoterapi med flere cyklusser.
or non-myeloid malignancies receiving multi-cycle chemotherapy.
Patienterne blev randomiseret til at modtage en dosis på 500 μg Nespo én gang hver tredje uge eller
Patients were randomized to receive Nespo at 500 μ g once every three weeks or 2.25 μ g / kg once weekly.
t dosis (f. eks. var første dosisreduktion en reduktion til 300 μg i gruppen, der modtog dosis én gang au 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.
th 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
I gruppen, som modtog dosis e én gang om ugen, krævede 75% af patienterne dosisreduktioner.
In the once weekly group, 75% of patients required dose reductions.
Undersøgelsen understøtter er
This study supports 500 μ g once
gælder hyppigheden af forsøgspersonernes modtagelse af mindst én transfusion med røde blodlegemer i perioden fra uge 5 til slutningen af behandlingsforløbet. læ
er 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. ng In a prospective, randomised double-blind, placebo-controlled study conducted in 344 anaemic lo patients with lymphoproliferative malignancies receiving chemotherapy there was a significant reduction in transfusion requirements and an improvement in haemoglobin response (p < 0.001). no
I en prospektiv, randomiseret dobbeltblindt, placebokontrolleret studie hos 344 anæmiske patienter med lymfoproliferative maligniteter i kemoterapi, var der en signifikant reduktion i e
Improvement in fatigue, as measured by the Functional Assessment of Cancer Therapy-fatigue (FACT-fatigue) scale, was also observed. ct
Der blev ligeledes kk
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. du
fundet en reduktion i træthed, målt ved hjælp af ” Functional Assessment of Cancer Therapy- fatigue (FACT- fatigue) ” skala. ri
Survival and tumour progression have been examined in five large controlled studies involving a total ro
Erytropoietin er en vækstfaktor, der hovedsagelig stimulerer dannelsen af røde blodlegemer. te
of 2833 patients, of which four were double-blind placebo-controlled studies and one was an open- label study.
Erytropoietin- receptorer kan være udtrykt i overfladen på en række forskellige tumorceller. le
The lp
Heraf var de fire dobbeltblinde placebokontrollerede studier, mens ét var et id
In the open-label study there was no difference in overall survival between patients treated a
af hæmoglobin i to af studierne var > 13 g/ dl, og i de øvrige tre studier var den 12- 14 g/ dl.
In the four placebo-controlled studies the hazard in
med rekombineret humant erytropoietin og kontrolgruppen.
ratios for overall survival ranged between 1.25 and 2.47 in favour of controls.
Disse Læ
These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia ic
undersøgelser har påvist en konsekvent, men uforklarlig statistik signifikant overdødelighed hos patienter med anæmi, der er forbundet med forskellige almindelige former for cancer, og som modtog behandling med rekombineret humant erytropoietin sammenlignet med kontroller.
associated with various common cancers who received recombinant human erythropoietin compared ed
346 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:
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.
346 chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
lg 5. 2 Farmakokinetiske egenskaber
5.2 Pharmacokinetic properties
et er Patienter med kronisk nyresvigt
Chronic renal failure patients
is Darbepoetin alfas farmakokinetik er blevet klinisk undersøgt hos patienter med kronisk nyresvigt efter intravenøs og subkutan administration.
ed The pharmacokinetics of darbepoetin alfa has been studied clinically in chronic renal failure patients following intravenous and subcutaneous administration.
Darbepoetin alfas terminale halveringstid er 21 timer (SD 7, 5)
The terminal half-life of darbepoetin alfa is 21 hours (SD 7.5) when administered intravenously.
or ved intravenøs administration.
Clearance of darbepoetin alfa is 1.9 ml/ hr/ kg
t fordelingsvolumen (Vss) er omtrent lig plasmavolumen (50 ml/ kg).
is (SD 0.56) and the volume of distribution (Vss) is approximately equal to plasma volume (50 ml/ kg).
Biotilgængeligheden er 37% ved au subkutan administration.
or Bioavailability is 37% with subcutaneous administration.
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
Når darbepoetin alfa administreres subkutant, har det en længere terminal halveringstid, end når det administreres intravenøst, hvilket e skyldes den subkutane absorptionskinetik.
The longer terminal half-life of darbepoetin alfa administered subcutaneously compared to intravenously is due to subcutaneous absorption kinetics.
I kliniske forsøg blev der observeret minimal akkumulation er
In clinical studies, minimal
I prækliniske forsøg er det vist, at den renale clearance er minimal (op ng
au accumulation was observed with either route of administration.
til 2% af den totale clearance) og ikke påvirker serum halveringstiden.
In preclinical studies it has been shown that renal clearance is minimal (up to 2% of total clearance), and does not affect the serum half-life.
Resultater opnået ved indgift af Nespo til 809 patienter i kliniske undersøgelser i Europa blev læ
er Data from 809 patients receiving Nespo in European clinical studies were analysed to assess the dose ng required to maintain haemoglobin; no difference was observed between the average weekly dose administered via the intravenous or subcutaneous routes of injection. lo
Ved vurderingen af de farmakoninestiske egenskaber ved darbepoetin alfa hos børn (3- 16 år) med ri
Assessment of the pharmacokinetics of darbepoetin alfa in paediatric patients (3 to 16 years) with CRF no
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 te
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.
Sammenlignet med de farmakokinetiske data fra voksne med kronisk nyresvigt (CRF), hvor der blev brugt samme prøvevarighed, blev det påvist, at de farmakokinetiske egenskaber le
Compared with pharmacokinetic data from adults with CRF where the same sampling duration was used, the ct
Efter intravenøs administration blev der observeret en forskel på cirka 25% mellem børn og voksne i området under id
Following intravenous administration, an approximate 25% difference between du
Forskellen var dog mindre end det dobbelte m
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 ro
område i AUC( 0- ∞), der blev observeret hos børn.
pediatricpatients.
Halveringstiden var også næsten ge
Half-life was also similar between adult and paediatric patients with lp
Læ
CRF following both intravenous and subcutaneous administration. a