natgillin/translations-raw huggingface dataset:
t gælder hyppigheden af forsøgspersonernes modtagelse af mindst én transfusion med røde blodlegemer i perioden fra uge 5 til slutningen af behandlingsforløbet. au I en prospektiv, randomiseret dobbeltblindt, placebokontrolleret studie hos 344 anæmiske patienter e med lymfoproliferative maligniteter i kemoterapi, var der en signifikant reduktion i er
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
Der blev ligeledes ng
Improvement in fatigue, as measured by the Functional Assessment of Cancer Therapy-fatigue (FACT-fatigue) scale, was also observed. ct
fundet en reduktion i træthed, målt ved hjælp af ” Functional Assessment of Cancer Therapy- fatigue (FACT- fatigue) ” skala. læ
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. du
Erytropoietin er en vækstfaktor, der hovedsagelig stimulerer dannelsen af røde blodlegemer.
Survival and tumour progression have been examined in five large controlled studies involving a total ro
Overlevelse og tumorprogression er blevet undersøgt i fem store kontrollerede studier, som omfatter i alt 2. 833 patienter.
of 2833 patients, of which four were double-blind placebo-controlled studies and one was an open- label study.
Heraf var de fire dobbeltblinde placebokontrollerede studier, mens ét var et ri
The lp
To af studierne omhandlede patienter, som modtog kemoterapi.
target haemoglobin concentration in two studies was > 13 g/ dl; in the remaining three studies it was 12-14 g/ dl.
Det te
In the open-label study there was no difference in overall survival between patients treated a
ublindede studiet viste ingen forskel i den samlede overlevelsesrate hos patienter, der blev behandlet med rekombineret humant erytropoietin og kontrolgruppen.
with recombinant human erythropoietin and controls.
I de fire placebokontrollerede studier lå le
In the four placebo-controlled studies the hazard in
hazard ratioen for den samlede overlevelse på mellem 1, 25 og 2, 47 i kontrolgruppens favør.
ratios for overall survival ranged between 1.25 and 2.47 in favour of controls.
Disse undersøgelser har påvist en konsekvent, men uforklarlig statistik signifikant overdødelighed hos id
These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia ic
patienter med anæmi, der er forbundet med forskellige almindelige former for cancer, og som modtog m
associated with various common cancers who received recombinant human erythropoietin compared ed
behandling med rekombineret humant erytropoietin sammenlignet med kontroller.
to controls.
Resultaterne for den samlede overlevelsesrate i forsøgene kan ikke på tilfredsstillende måde forklares ud fra ge
Overall survival outcome in the trials could not be satisfactorily explained by differences in the incidence of thrombosis and related complications between those given recombinant human M
Læ
erythropoietin and those in the control group.
Det er uklart, i hvor høj grad disse resultater berører indgivelsen af rekombineret humant
The extent to which these outcomes might apply to the administration of recombinant human erythropoietin to patients with cancer, treated with
10 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.
lg sa Patienter med kronisk nyresvigt
Chronic renal failure patients
til intravenøs og subkutan administration.
ed The pharmacokinetics of darbepoetin alfa has been studied clinically in chronic renal failure patients following intravenous and subcutaneous administration.
Clearance for darbepoetin alfa er 1, 9 ml/ t/ kg (SD 0, 56) og
Clearance of darbepoetin alfa is 1.9 ml/ hr/ kg
et 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
or Bioavailability is 37% with subcutaneous administration.
Når darbepoetin alfa administreres
Following monthly administration of darbepoetin alfa, at subcutaneous doses ranging from 0.6 to 2.1 µg/ kg, the terminal half-life was
is subkutant, har det en længere terminal halveringstid, end når det administreres intravenøst, hvilket 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
In clinical studies, minimal
or for begge administrationsveje.
au accumulation was observed with either route of administration.
I prækliniske forsøg er det vist, at den renale clearance er minimal (op
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.
t til 2% af den totale clearance) og ikke påvirker serum halveringstiden. au Resultater opnået ved indgift af Nespo 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; e der blev ikke observeret nogen forskel på den gennemsnitlige ugentlige dose uanset om injektionen er
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 kronisk nyresvigt (CRF), som enten var eller ikke var i dialysebehandling, blev der fastlagt læ
Assessment of the pharmacokinetics of darbepoetin alfa in paediatric patients (3 to 16 years) with CRF no
Sammenlignet med de farmakokinetiske data fra voksne med kronisk nyresvigt e
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.
(CRF), hvor der blev brugt samme prøvevarighed, blev det påvist, at de farmakokinetiske egenskaber kk
Compared with pharmacokinetic data from adults with CRF where the same sampling duration was used, the ct
ved darbepoetin alfa var de samme hos børn og voksne med kronisk nyresvigt (CRF).
comparison showed that the pharmacokinetics of darbepoetin alfa were similar for paediatric and adult patients with CRF.
Efter intravenøs administration blev der observeret en forskel på cirka 25% mellem børn og voksne i området under ri
Following intravenous administration, an approximate 25% difference between du
AUC( 0- ∞) var næsten det samme hos børn og te
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
voksne med kronisk nyresvigt (CRF) efter subkutan administration.
pediatricpatients.
Halveringstiden var også næsten den samme hos børn og voksne med kronisk nyresvigt (CRF) efter både intravenøs og subkutan le
Half-life was also similar between adult and paediatric patients with lp
administration. id
CRF following both intravenous and subcutaneous administration. a
Cancerpatienter i kemoterapi m
Cancer patients receiving chemotherapy in
Efter subkutan indgift af 2, 25 μg/ kg til voksne cancerpatienter, opnåedes en gennemsnitlig ge
Following subcutaneous administration of 2.25 µg/ kg to adult cancer patients a mean peak ic
peakkoncentration på 10, 6 ng/ ml (SD 5, 9) darbepoietin alfa i løbet af en gennemsnitstid på 91 timer (SD 19, 7).
concentration of 10.6 ng/ ml (SD 5.9) of darbepoetin alfa was reached at a mean time of 91 hours ed
dosisinterval (0, 5 til 8 μg/ kg ugentlig og 3 til 9 μg/ kg hver anden uge).
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).
Der var ingen ændring i de 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).
Bivirkninger ved meget høje doser, blev alle vurderet at være relateret til en forhøjet farmakologisk effekt (nedsat vævsperfusion pga. øget blodviskositet).
Adverse events at very high doses were all considered to be related to an exaggerated pharmacological
Nespo vist ikke noget genotoksisk potentiale, og ej heller havde det nogen effekt på celledelingen af
11 effect (decreased tissue perfusion due to increased blood viscosity).
lg ikke- hæmatologiske celler hverken in vitro eller in vivo.
Nespo did not reveal any genotoxic potential nor did it have any effect on the proliferation of non- haematological cells in vitro or in vivo.
I de kroniske toksicitets undersøgelser
In the chronic toxicity studies no tumourigenic or unexpected mitogenic responses were observed in any tissue type.
til I undersøgelser udført på rotter og kaniner blev der ikke observeret nogen kliniske relevante beviser for skadelig effekt hverken hvad angår graviditet, fosterudvikling, fødsel eller postnatal udvikling.
In studies performed in rats and rabbits no clinically relevant evidence of harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development was observed.
et Transporten over placenta var minimal.
Placental transfer was minimal.
er is 6.
ed is 6.
or 6. 1 Hjælpestoffer
th Sodium phosphate monobasic Sodium phosphate dibasic
t Natriumfosfat enkelbasisk natriumfosfat dobbelbasisk au natriumchlorid e polysorbat 80 er
au Sodium chloride Polysorbate 80
vand til injektionsvæsker ng
er Water 6.2
6. 2 Uforligeligheder læ
for injections Incompatibilities
Da der ikke foreligger undersøgelser vedrørende eventuelle uforligeligheder, bør Nespo ikke blandes eller administreres som en infusion sammen med andre lægemidler. e kk
In the absence of incompatibility studies, Nespo should not be mixed or administered as an infusion with other medicinal products. no
6. 3 Opbevaringstid ri
6.3 Shelf life ct
2 år. te
2 years. du
6. 4 Særlige opbevaringsforhold le
6.4 Special precautions for storage ro
Må ikke nedfryses. id
Do not freeze. lp
Opbevar beholderen i den ydre karton for at beskytte mod lys. m
Keep the container in the outer carton, in order to protect from light. a
Ved ambulant brug tillades det, at Nespo fjernes én gang fra opbevaringen i en enkelt periode på højst ge
For the purpose of ambulatory use, Nespo may be removed from storage once for a maximum single in
7 dage ved stuetemperatur (op til 25°C).
period of seven days at room temperature (up to 25°C).
Læ
refrigerator and has reached room temperature (up to 25°C) it must either be used within 7 days or disposed of. ed
6. 5 Emballagetype og pakningsstørrelser
6.5 Nature and contents of container M
Pakning med en eller fire fyldt( e) injektionssprøjte( r) indeholdende 10 µg Nespo injektionsvæske, opløsning i 0, 4 ml (25 µg/ ml).
Package containing one or four pre-filled syringe(s) of a 10 µg Nespo solution for injection in 0.4 ml (25 µg/ ml).
12 Injektionssprøjten er produceret af glas af type 1 med 27 gauge nåle af rustfrit stål.
The syringes are made from type 1 glass with stainless steel 27 gauge needles.
lg sa Før administration skal Nespo opløsningen undersøges for synlige partikler.
Before administration the Nespo solution should be inspected for visible particles.
til Benyt forskellige injektionssteder og injicer langsomt for at undgå ubehag ved injektionsstedet.
Rotate the injection sites and inject slowly to avoid discomfort at the site of injection.
et er Ikke anvendte lægemidler samt affald heraf bør destrueres i henhold til lokale retningslinier.
ed Any unused product or waste material should be disposed of in accordance with local requirements.
is 7.
is 7.
Via San Martino 12 I- 20122 Milan Italien
th Via San Martino 12 I-20122 Milan
or
au Italy
EU/ 1/ 01/ 184/ 002 4- pakning blister EU/ 1/ 01/ 184/ 033 1- pakning e kk
MARKETING AUTHORISATION NUMBERS er ng EU/ 1/ 01/ 184/ 001 1 Pack Blister lo EU/ 1/ 01/ 184/ 002 4 Pack Blister EU/ 1/ 01/ 184/ 033 1 Pack Unblistered no
DATO FOR FØRSTE TILLADELSE/ FORNYELSE AF TILLADELSEN ri
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION ct
Dato for første godkendelse:
Date of first authoristion:
08. juni 2001 te
8 June 2001 du
19. maj 2006 le
19 May 2006 ro
DATO FOR ÆNDRING AF TEKSTEN id m
DATE OF REVISION OF THE TEXT
De kan finde yderligere oplysninger om dette medicinalprodukt på webstedet for Det Europæiske Agentur for Lægemiddelvurdering (EMEA) http: // www. emea. europa. eu / ge Læ
Agency (EMEA) http: / /www. emea. europa. eu/ ed M
14 Voksne patienter med kronisk nyresvigt
14 Adult patients with chronic renal failure
15 grund af individuel variation forventes titrering til optimal terapeutisk dosis for enkelte patienter.
15 individual variability, titration to optimal therapeutic doses is expected for individual patients.
18 Hos patienter med kronisk nyresvigt og klinisk tegn på iskæmisk hjertesygdom eller kronisk hjertesvigt skal hæmoglobinniveauet fastsættes individuelt.
18 In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
lg Cancerpatienter
Cancer patients
sa Virkning på tumorprogression
ed Effect on tumour growth
til Epoetiner er vækstfaktorer, der hovedsageligt stimulerer dannelsen af røde blodlegemer.
Erythropoietin
Erytropoietin- receptorer kan være udtrykt i overfladen på en række forskellige tumorceller.
is receptors may be expressed on the surface of a variety of tumour cells.
Som ved
As with all growth factors,
et alle vækstfaktorer, er der frygt for at epoetiner kan stimulere væksten af tumorceller.
or there is a concern that epoetins could stimulate the growth of tumours.
Flere
In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression
er kontrollerede studier har vist, at epoetiner ikke i væsentlig grad øger overlevelsesraten eller væsentligt mindsker udbredelsen af tumorer hos patienter, der har anæmi associeret med cancer.
th in patients with anaemia associated with cancer.
is I kontrollerede kliniske studier har brugen af Nespo og andre erytropoiesestimulerende midler (ESAer)
au In controlled clinical studies, use of Nespo and other erythropoiesis-stimulating agents (ESAs) have shown:
ESAer er ikke indiceret til brug i denne patientpopulation. e er
• er shortened time to tumour progression in patients with advanced head and neck cancer receiving ng 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. lo
• kortere samlet overlevelsestid og overdødelighed som følge af sygdomsudvikling efter 4 ng
• shortened overall survival and increased deaths attributed to disease progression at 4 months in no
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). læ
patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/ dl (7.5-8.7 mmol/ l) ct
• øget risiko for dødsfald, når det indgives for at behandle en hæmoglobinkoncentration på 12 g/ dl (7, 5 mmol/ l) hos patienter med aktiv malign sygdom, som hverken modtager kemoterapi e
• 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 du
ESAer er ikke indiceret til brug i denne patientpopulation. kk
therapy. ESAs are not indicated for use in this patient population. ro
I lyset af ovenstående bør blodtranfusion i nogle kliniske situationer være den foretrukne behandling ri
In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer.
Beslutningen om at administrere rekombinante erythropoietiner bør være baseret på en vurdering af fordele versus risici med den enkelte patients deltagelse og under te
Factors that should be considered a
De faktorer, som bør overvejes i forbindelse med denne vurdering, er tumortype og tumorstadie, anæmiens udstrækning, forventet levetid, le
in this assessment should include the type of tumour and its stage; the degree of anaemia; life- in
patientens behandlingsmiljø og patientens ønsker (se afsnit 5. 1). id
expectancy; the environment in which the patient is being treated; and patient preference (see section ic
Hvis hæmoglobin værdier overskrider 12 g/ dl (7, 5 mmol/ l) hos patienter med solide tumorer eller m
5.1). ed
Blodpladeværdier og ge
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 M
Læ
Platelet counts and haemoglobin level should also be monitored at regular intervals.
19 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.
Forekomsten af bivirkninger, der betragtes som relaterede til behandling med Nespo udfra kontrollerede kliniske studier, er:
20 Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical studies are:
Medra systemorganklasse Hud og subkutane væv
MedDRA system organ class Skin and Subcutaneous Tissue Disorders
Forekomst hos forsøgsperson Almindelig (≥ 1/ 100 til < 1/ 10)
Subject Incidence Common (≥ 1/ 100 to < 1/ 10)
Bivirkning Udslæt- erytem
Adverse Drug Reaction Rash/ Erythema
20 Vaskulære sygdomme
Vascular disorders
Erfaring efter markedsføring
ed Postmarketing Experience
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:
lg sa • Erythroblastopenia.
or th • Pure Red Cell Aplasia.
I tilfælde af at
In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Nespo therapy have been reported predominantly in
til PRCA diagnosticeres, skal behandling med Nespo afbrydes, og patienterne skal ikke skifte til et andet gensplejset erytropoietisk protein (se afsnit 4. 4).
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).
et er • Overfølsomhedsreaktioner, herunder anafylaktiske reaktioner, angioødem, hududslæt og urticaria.
• er Allergic reactions, including anaphylactic reaction, angioedema, skin rash and urticaria. ng • Convulsions. lo
is or • Krampeanfald.
4.9 Overdose no
t 4. 9 Overdosering au Det terapeutiske indeks for Nespo er meget bredt.
The therapeutic margin of Nespo is very wide.
Selv ved meget høje plasmakoncentrationer er der e ikke observeret nogle symptomer på overdosering. er
Even at very high serum levels, no symptoms of overdose have been observed. ct du
Hvis klinisk indiceret kan ng
In the event of polycythaemia, Nespo should be temporarily withheld (see section 4.2).
phlebotomi udføres. læ
If clinically indicated, phlebotomy may be performed. ro lp
FARMAKOLOGISKE EGENSKABER e
PHARMACOLOGICAL PROPERTIES a
5. 1 Farmakodynamiske egenskaber kk
5.1 Pharmacodynamic properties in
B03XA02. ri
B03XA02. ic ed
Humant erytropoietin er et endogent glykoprotein hormon, der fungerer som den primære regulator af te
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.
erytropoiesen gennem specifik interaktion med erytropoietin- receptoren på den erythroide stamcelle i knoglemarven.
The production of erythropoietin primarily occurs in and is regulated by the M
ændringer i iltningen af vævet.
kidney in response to changes in tissue oxygenation.
kronisk nyresvigt og den primære årsag til deres anæmi er erytropoietinmangel.
Production of endogenous erythropoietin is impaired in patients with chronic renal failure and the primary cause of their anaemia is due to erythropoietin deficiency.
For disse patienter bidrager både erytropoietinmanglen m
In patients with cancer receiving chemotherapy the etiology of anaemia is multifactorial.
og det nedsatte respons på erythroide stamceller af endogent erytropoietin, betydeligt til deres anæmi. ge
In these patients, erythropoietin deficiency and a reduced response of erythroid progenitor cells to endogenous erythropoietin both contribute significantly towards their anaemia.
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.
21 Cancerpatienter i kemoterapi
21 in vivo activity.
22 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.
22 chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
Nespo vist ikke noget genotoksisk potentiale, og ej heller havde det nogen effekt på celledelingen af
23 effect (decreased tissue perfusion due to increased blood viscosity).
Pakning med en eller fire fyldt( e) injektionssprøjte( r) indeholdende 15 µg Nespo injektionsvæske, opløsning i 0, 375 ml (40 µg/ ml).
Package containing one or four pre-filled syringe(s) of a 15 µg Nespo solution for injection in 0.375 ml (40 µg/ ml).
24 Injektionssprøjten er produceret af glas af type 1 med 27 gauge nåle af rustfrit stål.
The syringes are made from type 1 glass with stainless steel 27 gauge needles.
EU/ 1/ 01/ 184/ 004 4- pakning blister EU/ 1/ 01/ 184/ 034 1- pakning e kk
MARKETING AUTHORISATION NUMBERS er ng EU/ 1/ 01/ 184/ 003 1 Pack Blister lo EU/ 1/ 01/ 184/ 004 4 Pack Blister EU/ 1/ 01/ 184/ 034 1 Pack Unblistered no
26 Voksne patienter med kronisk nyresvigt
26 Adult patients with chronic renal failure
lg Hvis hæmoglobinstigningen er større end 2 g/ dl (1, 25 mmol/ l) på fire uger reduceres dosis med ca.
If the rise in haemoglobin is greater than 2 g/ dl (1.25 mmol/ l) in four weeks reduce the dose by approximately 25%.
sa 25%.
ed considered.
27 grund af individuel variation forventes titrering til optimal terapeutisk dosis for enkelte patienter.
27 individual variability, titration to optimal therapeutic doses is expected for individual patients.
29 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
29 4.4 Special warnings and precautions for use
30 Hos patienter med kronisk nyresvigt og klinisk tegn på iskæmisk hjertesygdom eller kronisk hjertesvigt skal hæmoglobinniveauet fastsættes individuelt.
30 In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
31 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.