natgillin/translations-raw huggingface dataset:
Baseret på den til dato tilgængelige information medfører korrektion af anæmi med erytropoietin hos voksne patienter med renal insufficiens, som endnu ikke er i dialyse, ikke en stigning af progressionsraten for den renale insufficiens.
Based on information available to date, correction of anaemia with erythropoietin in adult patients with renal insufficiency not yet undergoing dialysis does not accelerate the rate of progression of renal insufficiency.
Ved vurderingen af om Retacrit- terapi er hensigtsmæssig hos cancerpatienter i kemoterapi (risiko for, at patienten transfunderes), bør det tages i betragtning, at der går 2- 3 uger, fra administration af erytropoietin påbegyndes, til der viser sig erytropoietin- fremkaldte røde blodceller.
In cancer patients receiving chemotherapy, the 2-3 week delay between erythropoietin administration and the appearance of erythropoietin-induced red cells should be taken into account when assessing if Retacrit therapy is appropriate (patient at risk of being transfused).
4. 2)
If the rate of increase in haemoglobin exceeds 2 g/ dl (1.25 mmol/ l) per month or the haemoglobin level exceeds 12 g/ dl (7.5 mmol/ l), the dose adjustment detailed in section 4.2 should be thoroughly performed to minimise the risk of thrombotic events (see section 4.2).
Dette er især vigtigt hos cancerpatienter med forhøjet risiko for vaskulær trombose, fx ved ovevægt, og patienter, som tidligere har oplevet TVE' er (fx dyb venetrombose eller pulmonal embolisme).
As an increased incidence of thrombotic vascular events (TVEs) has been observed in cancer patients receiving erythropoietic agents (see section 4.8), this risk should be carefully weighed against the benefit to be derived from treatment (with Retacrit) particularly in cancer patients with an increased risk of thrombotic vascular events, such as obesity and patients with a prior history of TVEs (e. g. deep venous thrombosis or pulmonary embolism).
Der kan ske ekspression af erytropoietinreceptorer på overfladen af en række forskellige tumorceller.
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.
I kontrollerede kliniske forsøg har brug af epoetin alfa og andre erytropoiese- stimulerende stoffer (ESA' er) vist: • kortere tid til tumorprogression hos patienter med fremskreden hoved - og halscancer, som får strålebehandling, når stofferne administreres for at tilstræbe et hæmoglobinniveau, som er højere end 14 g/ dl (8, 7 mmol/ l), • kortere samlet overlevelse og flere dødsfald, som tilskrives sygdomsprogression ved 4
In controlled clinical studies, use of Epoetin alfa and other erythropoiesis-stimulating agents (ESAs) have shown:
øget risiko for død, når stofferne gives for at tilstræbe et hæmoglobinniveau på 12 g/ dl (7, 5 mmol/ l) hos patienter med aktiv malign sygdom, som hverken får kemoterapi eller strålebehandling.
8 • 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), • 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), 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.
Beslutningen om at administrere rekombinante erytropoietiner bør bygge på en vurdering af fordele og ulemper og med inddragelse af den enkelte patient, og der skal tages højde for den specifikke kliniske kontekst.
The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context.
Der eksisterer ingen beviser for, at behandling med erytropoietin ændrer andre lægemidlers metabolisme.
There is no evidence to indicate that treatment with erythropoietin alters the metabolism of other medicinal products.
Da ciclosporin er bundet til RBC’ er, er der imidlertid en mulighed for interaktion med andre lægemidler.
However, since ciclosporin is bound by red blood cells there is potential for interactions with other medicinal products.
Hvis erytropoietin gives sideløbende med ciclosporin, bør ciclosporinniveauet i blodet monitoreres, og ciclosporindosis skal justeres, efterhånden som hæmatokritten stiger.
If erythropoietin is given concomitantly with ciclosporin, blood levels of ciclosporin should be monitored and the dose of ciclosporin adjusted as the haematocrit rises.
Der findes ingen tilstrækkelige og velkontrollerede undersøgelser af virkningerne hos gravide.
There are no adequate and well-controlled studies in pregnant women.
Undersøgelser med dyr har påvist reproduktionstoksicitet (se pkt.
Studies in animals have shown reproduction toxicity (see section 5.3).
Erytropoietin bør derfor kun anvendes under graviditet og amning, hvis den potentielle bedring opvejer den potentielle risiko for barnet.
Consequently, erythropoietin should generally be used during pregnancy and lactation only if the potential benefit outweighs the potential risk to the foetus.
4. 7 Virkning på evnen til at føre motorkøretøj og betjene maskiner.
4.7 Effects on ability to drive and use machines
Retacrit er et biologisk lægemiddel.
Retacrit is a biological medicinal product.
Data fra kliniske undersøgelser med Retacrit stemmer overens med sikkerhedsprofilen for andre godkendte erytropoietiner.
Data from clinical studies with Retacrit are in line with the safety profile of other authorized erythropoietins.
8% af de patienter, der behandles med erytropoietin, oplever bivirkninger.
Based on the results from clinical trials with other authorized erythropoietins approximately 8% of patients treated with erythropoietin are expected to experience adverse reactions.
Bivirkninger under behandlingen med erytropoietin er især observeres hos patienter med kronisk nyresvigt eller underliggende maligniteter.
Undesirable effects during treatment with erythropoietin are observed predominantly in patients with chronic renal failure or underlying malignancies.
Disse bivirkninger er typisk hovedpine og dosisafhængig forhøjelse af blodtrykket.
These undesirable effects are most commonly headache and a dose dependent increase in blood pressure.
Hududslæt (ikke specificeret) har været beskrevet i forbindelse med epoetin alfa- behandlingen.
General Non-specific skin rashes have been described with epoetin alfa.
4. 4).
9 Thrombocytosis has been observed but its occurrence is very rare (see section 4.4).
Der er rapporteret om trombotiske/ vaskulære hændelser, f. eks. myokardieiskæmi, myokardieinfarkt, cerebrovaskulær hændelse (cerebral blødning og cerebral infarkt), forbigående iskæmiske anfald, dyb
Thrombotic/ vascular events, such as myocardial ischaemia, myocardial infarction, cerebrovascular accidents (cerebral haemorrhage and cerebral infarction), transient ischaemic attacks, deep vein thrombosis, arterial thrombosis, pulmonary emboli, aneurysms, retinal thrombosis, and clotting of an artificial kidney have been reported in patients receiving erythropoietic agents.
4. 3 og 4. 4).
In most of these patients, antibodies to erythropoietins have been observed (see sections 4.3 and 4.4)
Voksne og pædiatriske hæmodialysepatienter, voksne peritoneal- dialysepatienter og voksne med nyreinsufficiens, der endnu ikke er i dialyse
Adult and paediatric haemodialysis patients, adult peritoneal dialysis patients and adult patients with renal insufficiency not yet undergoing dialysis
Uafhængigt af erytropoietinbehandling kan der opstå trombotiske og vaskulære hændelser hos operationspatienter med underliggende hjerte- karsygdom efter gentagne flebotomier.
Independent of erythropoietin treatment, thrombotic and vascular events may occur in surgical patients with underlying cardiovascular disease following repeated phlebotomy.
Den terapeutiske margin for erytropoietin er meget bred.
The therapeutic margin of erythropoietin is very wide.
Overdosering af erytropoietin kan fremkalde virkninger, som er udvidelser af hormonets farmakologiske virkninger.
Overdose of erythropoietin may produce effects that are extensions of the pharmacological effects of the hormone.
Antianæmiske præparater, erytropoietin ATC- kode:
Antianaemic preparations, erythropoietin ATC code:
Erytropoietin er et glykoprotein, der som mitosestimulerende faktor og differentierende hormon stimulerer dannelsen af erytrocytter ved at stimulere forstadier i knoglemarven.
Erythropoietin is a glycoprotein that stimulates, as a mitosis-stimulating factor and differentiating hormone, the formation of erythrocytes from precursors of the stem cell compartment.
11 Erytropoietins tilsyneladende molekylvægt er 32000- 40000 Dalton.
The apparent molecular weight of erythropoietin is 32,000-40,000 Dalton.
58% af den samlede molekylvægt og består af 165 aminosyrer.
The protein moiety of the molecule contributes about 58% of total molecular weight and consists of 165 amino acids.
De fire kulhydratkæder er bundet til proteinet via tre N- glykosidbindinger og en O- glykosidbinding.
The four carbohydrate chains are attached via three N-glycosidic bonds and one O-glycosidic bond to the protein.
Epoetin zeta er med hensyn til aminosyresekvens og kulhydratsammensætning identisk med endogent humant erytropoietin, som er isoleret fra urin fra anæmipatienter.
Epoetin zeta is identical in its amino acid sequence and similar in carbohydrate composition to endogenous human erythropoietin that has been isolated from the urine of anaemic patients.
Erytropoietins biologiske effektivitet er påvist hos forskellige forsøgsdyr in vivo (normale og anæmiske rotter, polycytæmiske mus).
The biological efficacy of erythropoietin has been demonstrated in various animal models in vivo (normal and anaemic rats, polycythaemic mice).
Efter administration af erytropoietin stiger såvel erytrocyttal, Hb- værdier og reticulocyttal som 59Fe- optagelsesrate.
After administration of erythropoietin, the number of erythrocytes, the Hb values and reticulocyte counts increase as well as the 59Fe-incorporation rate.
En øget optagelse af 3H- thymidin i de erytroide kerneholdige miltceller er fundet in vitro (kultur af miltceller fra mus) efter inkubering med erytropoietin.
An increased 3H-thymidine incorporation in the erythroid nucleated spleen cells has been found in vitro (mouse spleen cell culture) after incubation with erythropoietin.
Ved hjælp af cellekulturer fra human knoglemarv kunne det vises, at erytropoietin specifikt stimulerer erytropoiesen og ikke indvirker på leukopoiesen.
It could be shown with the aid of cell cultures of human bone marrow cells that erythropoietin stimulates erythropoiesis specifically and does not affect leucopoiesis.
Der kunne ikke detekteres cytotoksiske virkninger af erytropoietin på knoglemarvsceller.
Cytotoxic actions of erythropoietin on bone marrow cells could not be detected.
Ligesom andre hæmatopoietiske vækstfaktorer har erytropoietin vist sig at stimulere humane endotelceller in vitro.
As with other haematopoietic growth factors, erythropoietin has shown in vitro stimulating properties on human endothelial cells.
721 cancerpatienter, i behandling med ikke– platinbaseret kemoterapi indgik i tre placebokontrollerede undersøgelser, 389 patienter med hæmatologiske maligniteter (221 med multipelt myelom, 144 med ikke- Hodgkin- lymfom og 24 med andre hæmatologiske maligniteter) og 332 med massive tumorer (172 med bryst -, 64 med gynækologiske, 23 med lunge -, 22 med prostata -, 21 med gastrointestinale og 30 med andre typer tumorer).
721 cancer patients receiving non-platinum chemotherapy were included in three placebo-controlled studies, 389 patients with haematological malignancies (221 multiple myeloma, 144 non-Hodgkin's lymphoma, and 24 other haematological malignancies) and 332 with solid tumours (172 breast, 64 gynaecological, 23 lung, 22 prostate, 21 gastrointestinal, and 30 other tumour types).
I to store åbne undersøgelser deltog 2697 cancerpatienter i behandling med ikke- platinbaseret kemoterapi, heraf 1895 med massive tumorer (683 med bryst -, 260 med lunge -, 174 med gynækologiske, 300 med gastrointetinale og 487 med andre typer tumorer) og 802 med hæmatologiske maligniteter.
In two large, open-label studies, 2697 cancer patients receiving non-platinum chemotherapy were included, 1895 with solid tumours (683 breast, 260 lung, 174 gynaecological, 300 gastrointestinal, and 478 other tumour types) and 802 with haematological malignancies.
I en prospektiv, randomiseret, dobbeltblind, placebokontrolleret afprøvning, med 375 anæmipatienter med forskellige non- myeloide maligniteter, der var i behandling med ikke- platinbaseret kemoterapi, sås en signifikant reduktion af anæmirelaterede sequelae (fx træthed, nedsat energi og nedsat aktivitetsniveau), målt med anvendelse af følgende instrumenter og skalaer:
In a prospective, randomised, double-blind, placebo-controlled trial conducted in 375 anaemic patients with various non-myeloid malignancies receiving non-platinum chemotherapy, there was a significant reduction of anaemia-related sequelae (e. g. fatigue, decreased energy, and activity reduction), as measured by the following instruments and scales:
Functional Assessment of Cancer Therapy- Anaemia (FACT- An) generel skala, FACT- An træthedsskala og Cancer Linear Analogue Scale (CLAS).
Functional Assessment of Cancer Therapy-Anaemia (FACT-An) general scale, FACT-An fatigue scale, and Cancer Linear Analogue Scale (CLAS).
EORTC- QLQ- C30- skalaen og CLAS- skalaen.
Two other smaller, randomized, placebo-controlled trials failed to show a significant improvement in quality of life parameters on the EORTC-QLQ-C30 scale or CLAS, respectively.
Erytropoietin er en vækstfaktor, som primært stimulerer produktionen af røde blodceller.
Erythropoietin is a growth factor that primarily stimulates red cell production.
Forsøgene rekrutterede enten patienter, som var i behandling med kemoterapi (to forsøg) eller benyttede patientpopulationer, hvor erytropoiese- stimulerende stoffer ikke er indiceret: anæmi hos patienter med cancer, som ikke fik kemoterapi, og hoved - og halscancer hos patienter, som fik strålebehandling.
The studies either recruited patients who were being treated with chemotherapy (two studies) or used patient populations in which erythropoiesis stimulating agents are not indicated: anaemia in patients with cancer not receiving chemotherapy, and head and neck cancer patients receiving radiotherapy.
Den tilstræbte hæmoglobinkoncentration i to forsøg var > 13 g/ dl, og i de øvrige tre forsøg 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 det åbne forsøg var der ingen forskel i den samlede overlevelse på patienter behandlet med rekombinant humant erytropoietin og kontrolgruppen.
In the open-label study there was no difference in overall survival between patients treated with recombinant human erythropoietin and controls.
Disse forsøg har vist en vedvarende uforklarlig statistisk signifikant overdødelighed hos patienter, som har anæmi i forbindelse med forskellige almindelige cancertyper, og som fik rekombinant humant erytropoietin sammenlignet med kontrolgrupper.
11 mortality in patients who have anaemia associated with various common cancers who received recombinant human erythropoietin compared to controls.
Den samlede overlevelsesrate i undersøgelserne kunne ikke forklares tilfredsstillende med forskellen i incidens af trombose og relaterede komplikationer imellem dem, som fik rekombinant humant erytropoietin og dem i kontrolgruppen.
Overall survival outcome in the trials could not be statisfactorily explained by differences in the incidence of thrombosis and related complications between those given recombinant human erythropoietin and those in the control group.
12 fordel for kontrolgruppen (95% konfidensinterval:
Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.08 in favour of controls (95% CI:
1, 35, 2, 06, 35 undersøgelser og 6769 patienter) sås hos patienter behandlet med rekombinant humant erytropoietin.
1.35, 2.06, 35 trials and 6769 patients) was observed in patients treated with recombinant human erythropoietin.
Der er en øget risiko for tromboemboliske hændelser hos patienter med cancer, som behandles med rekombinant humant erytropoietin, og en negativ virkning på samlet overlevelse kan ikke udelukkes.
There is an increased risk for thromboembolic events in patients with cancer treated with recombinant human erythropoietin and a negative impact on overall survival cannot be excluded.
Hvorvidt disse rater også gælder for administration af rekombinant humant erytropoietin til patienter med cancer, som behandles med kemoterapi, for at opnå hæmoglobinkoncentrationer på mindre end 13 g/ dl, er uklart, fordi der i de gennemgåede data kun var få patienter med disse karakteristika.
The extent to which these outcomes might apply to the administration of recombinant human erythropoietin to patients with cancer, treated with chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
5 timer.
Intravenous route Measurement of erythropoietin following multiple dose intravenous administration revealed a half-life of approximately 4 hours in healthy volunteers and a somewhat more prolonged half-life of approximately 5 hours in renal failure patients.
6 timer er rapporteret hos børn.
A half-life of approximately 6 hours has been reported in children.
Subkutan indgivelse Efter subkutan injektion er serumniveauerne af erytropoietin meget lavere end de niveauer, der er opnået efter intravenøs injektion; niveauerne stiger langsomt og når et højdepunkt mellem 12 og 18 timer efter indgivelse af dosis.
Subcutaneous route Following subcutaneous injection, serum levels of erythropoietin are much lower than the levels achieved following intravenous injection, the levels increase slowly and reach a peak between 12 and 18 hours postdose.
Niveauerne er de samme, uanset om de bestemmes 4 timer efter første injektion eller 24 timer efter sidste injektion.
There is no accumulation: the levels remain the same, whether they are determined 24 hours after the first injection or 24 hours after the last injection.
24 timer.
The half-life is difficult to evaluate for the subcutaneous route and is estimated to be about 24 hours.
20%.
The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenous medicinal product and is approximately 20%.
I nogle prækliniske toksikologiske undersøgelser med hunde og rotter, men ikke aber, blev erytropoietin- terapien associeret med subklinisk knoglemarvsfibrose (knoglemarvsfibrose er en kendt komplikation ved kronisk nyresvigt hos mennesker og kan relateres til sekundær hyperparatyroidisme eller ukendte faktorer.
In some pre-clinical toxicological studies in dogs and rats, but not in monkeys, erythropoietin therapy was associated with subclinical bone marrow fibrosis (bone marrow fibrosis is a known complication of chronic renal failure in humans and may be related to secondary hyperparathyroidism or unknown factors.
Forekomsten af knoglemarvsfibrose blev ikke forøget i en undersøgelse af hæmodialysepatienter, som blev behandlet med erytropoietin i 3 år, sammelignet med en tilsvarende kontrolgruppe af dialysepatienter, som ikke var blevet behandlet med erytropoietin).
The incidence of bone marrow fibrosis was not increased in a study of haemodialysis patients who were treated with erythropoietin for 3 years compared to a matched control group of dialysis patients who had not been treated with erythropoietin).
20 gange den ugentlige dosis, der anbefales til mennesker.
In animal studies, erythropoietin has been shown to decrease foetal body weight, delay ossification and increase foetal mortality when given in weekly doses of approximately 20 times the recommended human weekly dose.
Erytropoietin viste ingen ændringer ved mutagenicitetstest af bakterie - og mammalcellekulturer eller ved in vivo- mikronukleustest af mus.
Erythropoietin did not show any changes in bacterial and mammalian cell culture mutagenicity tests and an in vivo micronucleus test in mice.
Der er ikke foretaget langtids- karcinogenicitetsforsøg.
Long-term carcinogenicity studies have not been carried out.
I litteraturen foreligger der rapporter, som er modstridende med hensyn til, om erytropoietin kan spille en større rolle som tumorproliferator.
There are conflicting reports in the literature regarding whether erythropoietin may play a major role as tumour proliferator.
Disse rapporter er baseret på in vitro- resultater fra humane tumorprøver, men det er usikkert, om de har betydning i den kliniske situation.
These reports are based on in vitro findings from human tumour samples, but are of uncertain significance in the clinical situation.
6. 1 Hjælpestoffer
6.1 List of Excipients
Dinatriumfosfat- dihydrat Natriumdihydrogenfosfat- dihydrat Natriumklorid Kalciumklorid- dihydrat
Disodium phosphate dihydrate Sodium dihydrogen phosphate dihydrate Sodium chloride Calcium chloride dihydrate Polysorbate 20 Glycine Leucine Isoleucine Threonine Glutamic acid Phenylalanine Water for injections Sodium hydroxide (pH adjuster) Hydrochloric acid (pH adjuster)
Fyldte injektionssprøjter (Type I glas) med fast stål injektionsnål og stempelprop med PTFE - belægning.
Pre-filled syringe Type I glass with a fixed steel injection needle and a plunger stopper with PTFE coating.
Hver fyldt injektionssprøjte indeholder 0, 3 ml injektionsvæske, opløsning.
Each pre-filled syringe contains 0.3 ml solution for injection.
Retacrit må ikke bruges, hvis • blisterpakningens forsegling er brudt, eller blisterpakningen på nogen måde er beskadiget • væsken har farve, eller man kan se partikler flyde omkring i den • Der er sivet væske ud af den fyldte sprøjte, eller der er synlig kondens indeni den forseglede blisterpakning • det ved et uheld er blevet frosset
Retacrit must not be used if • The blister sealing is broken or the blister is damaged in any way. • The liquid is coloured or you can see particles floating in it. • Any liquid has leaked out of the pre-filled syringe or condensation is visible within the sealed blister. • It may have been accidentally frozen.
14 Må ikke rystes.
Do not shake.
Taurusavenue 19- 21 NL- 2132 LS HOOFDDORP Nederlandene
Taurusavenue 19-21 NL-2132 LS HOOFDDORP The Netherlands
EU/ 1 / 07/ 431/ 001 EU/ 1 / 07/ 431/ 002
EU/ 1/ 07/ 431/ 001 EU/ 1/ 07/ 431/ 002
Retacrit 2000 IU/ 0, 6 ml injektionsvæske, opløsning i en fyldt injektionssprøjte
Retacrit 2000 IU/ 0.6ml solution for injection in pre-filled syringe
1 fyldt injektionssprøjte med 0, 6 ml injektionsvæske, opløsning indeholder 2000 internationale enheder (IU) epoetin zeta * (rekombinant humant erytropoietin).
1 pre-filled syringe with 0.6 ml solution for injection contains 2000 international units (IU) epoetin zeta* (recombinant human erythropoietin).
Hver fyldt injektionssprøjte indeholder 0, 30 mg fenylalanin
Each pre-filled syringe contains 0.30 mg phenylalanine.
− Behandling af symptomatisk anæmi hos voksne og pædiatriske patienter med kronisk nyreinsufficiens
Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patientsIn patients with chronic renal failure the medicinal product has to be administered intravenously (see section 4.4)
16 Der tilstræbes en hæmoglobinkoncentration på mellem 10 og 12 g/ dl (6, 2- 7, 5 mmol/ l) undtaget hos pædiatriske patienter, hvis hæmoglobinkoncentration bør ligge mellem 9, 5 og 11 g/ dl (5, 9 - 6, 8 mmol/ l).
15 The haemoglobin concentration aimed for is between 10 and 12 g/ dl (6.2-7.5 mmol/ l), except in paediatric patients in whom the haemoglobin concentration should be between 9.5 and 11 g/ dl (5.9-6.8 mmol/ l).
Vægt (kg)
Dose (IU/ kg given 3x week)
< 10 10- 30 > 30
Weight (kg )< 10 10-30 > 30
75- 150 60- 150 30- 100
Usual maintenance dose 75-150 60-150 30-100