natgillin/translations-raw huggingface dataset:
* protein, som fremstilles ved rekombinant DNA- teknologi i ovarieceller fra kinesisk hamster og konjugeres kovalent til et lineært methoxypolyethylenglycol (PEG).
*Protein produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells and covalently conjugated to a linear methoxy-polyethylene glycol (PEG).
Virkningsgraden af methoxypolyethylenglycol- epoetin beta bør ikke sammenlignes med andre pegylerede eller ikke- pegylerede proteiner i den samme terapeutiske klasse.
The potency of methoxy polyethylene glycol-epoetin beta should not be compared to the one of another pegylated or non-pegylated protein of the same therapeutic class.
5. 1.
For more information, see section 5.1.
Behandling af symptomatisk anæmi forårsaget af kronisk nyreinsufficiens.
Treatment of symptomatic anaemia associated with chronic kidney disease (CKD).
Sikkerheden og effekten af behandling med MIRCERA ved andre indikationer er ikke undersøgt.
The safety and efficacy of MIRCERA therapy in other indications has not been established.
Behandling af symptomatisk anæmi hos voksne patienter med kronisk nyreinsufficiens Behandling med MIRCERA skal påbegyndes under supervision af en læge med erfaring med behandling af patienter med kronisk nyreinsufficiens.
Treatment of symptomatic anaemia in adult chronic kidney disease patients Treatment with MIRCERA has to be initiated under the supervision of a physician experienced in the management of patients with renal impairment.
Det er nødvendigt, at en læge vurderer hver enkelt patients kliniske forløb og tilstand.
Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’ s evaluation of the individual patient’ s clinical course and condition is necessary.
MIRCERA bør administreres enten subkutant eller intravenøst for at øge hæmoglobinniveaut til højst 12 g/ dl (7, 45 mmol/ l).
MIRCERA should be administered either subcutaneously or intravenously in order to increase haemoglobin to not greater than 12 g/ dl (7.45 mmol/ l).
MIRCERA kan injiceres subkutant i abdomen, arm eller lår.
MIRCERA can be injected subcutaneously in the abdomen, arm or thigh.
På grund af intra- patientvariabilitet kan der til tider observeres individuelle hæmoglobinværdier over og under det ønskede hæmoglobinniveau.
Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed.
Hæmoglobinvariabilitet bør håndteres ved at styre dosis, med det ønskede hæmoglobininterval på 10 g/ dl (6, 21 mmol/ l) til 12 g/ dl (7, 45 mmol/ l) taget i betragtning.
Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/ dl (6.21 mmol/ l) to 12 g/ dl (7.45 mmol/ l).
Vejledning for passende dosisjustering, når hæmoglobinværdier over 12 g/ dl (7, 45 mmol/ l) er observeret, er beskrevet nedenfor.
A sustained haemoglobin level of greater than 12 g/ dl (7.45 mmol/ l) should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 12 g/ dl (7.45 mmol/ l) are observed are described below.
En stigning i hæmoglobin på mere en 2 g/ dl (1, 24 mmol/ l) over en 4 ugers periode bør undgås.
A rise in haemoglobin of greater than 2 g/ dl (1.24 mmol/ l) over a four-week period should be avoided.
2 Patienter bør nøje monitoreres for at sikre, at den lavest godkendte dosis MIRCERA anvendes til at sørge for tilstrækkelig kontrol af de anæmiske symptomer.
2 Patients should be monitored closely to ensure that the lowest approved dose of MIRCERA is used to provide adequate control of the symptoms of anaemia.
Patienter, som ikke i øjeblikket er i behandling med et erythropoiese- stimulerende agens (ESA):
Patients not currently treated with an erythropoiesis stimulating agent (ESA):
Den anbefalede startdosis er 0, 6 mikrogram/ kg legemsvægt, administreret én gang hver 2. uge som en intravenøs eller subkutan injektion for at øge hæmoglobinkoncentrationen til over 10 g/ dl (6, 21 mmol/ l).
The recommended starting dose is 0.6 microgram/ kg body weight, administered once every two weeks as a single intravenous or subcutaneous injection in order to increase haemoglobin levels to greater than 10 g/ dl (6.21 mmol/ l).
25% af den tidligere dosis, hvis hæmoglobinkoncentrationen øges med mindre end 1, 0 g/ dl (0, 621 mmol/ l) på en måned.
The dose may be increased by approximately 25% of the previous dose if the rate of rise in haemoglobin is less than 1.0 g/ dl (0.621 mmol/ l) over a month.
25% kan foretages med månedlige intervaller, indtil det individuelle mål for hæmoglobin er nået.
Further increases of approximately 25% may be made at monthly intervals until the individual target haemoglobin level is obtained.
Derefter påbegyndes behandlingen igen med ca.
If the rate of rise in haemoglobin is greater than 2 g/ dl (1.24 mmol/ l) in one month or if the haemoglobin level is increasing and approaching 12 g/ dl (7.45 mmol/ l), the dose is to be reduced by approximately 25%.
25% af den tidligere administrerede dosis.
If the haemoglobin level continues to increase, therapy should be interrupted until the haemoglobin level begins to decrease, at which point therapy should be restarted at a dose approximately 25% below the previously administered dose.
0, 35 g/ dl (0, 22 mmol/ l) pr. uge.
After dose interruption a haemoglobin decrease of approximately 0.35 g/ dl (0.22 mmol/ l) per week is expected.
Når der er nået en hæmoglobinkoncentration på over 10 g/ dl (6, 21 mmol/ l) for den enkelte patient, kan MIRCERA administreres én gang månedlig i en dosis, som er dobbelt så stor som den dosis, der tidligere blev givet hver 2. uge.
If the haemoglobin concentration above 10 g/ dl (6.21 mmol/ l) is reached for the individual patient, MIRCERA may be administered once-monthly using the dose equal to twice the previous once-every– two-weeks dose.
Patienter, som i øjeblikket er i behandling med et ESA, kan omstilles til MIRCERA administreret én gang månedlig som en enkelt intravenøs eller subkutan injektion.
Patients currently treated with an ESA can be switched to MIRCERA administered once a month as a single intravenous or subcutaneous injection.
Startdosis af methoxypolyethylenglycol- epoetin beta baseres på den tidligere beregnede ugentlige dosis af darbepoetin alfa eller epoetin på tidspunktet for udskiftningen, som beskrevet i tabel 1.
The starting dose of methoxy polyethylene glycol- epoetin beta is based on the calculated previous weekly dose of darbepoetin alfa or epoetin at the time of substitution as described in Table 1.
MIRCERA startdosis
MIRCERA starting doses
Tidligere ugentlig dosis Tidligere ugentlig af darbepoetin alfa, dosis af epoetin, intravenøst eller intravenøst eller subkutant subkutant
Previous weekly Previous weekly
Månedlig dosis af MIRCERA, intravenøst eller subkutant
Monthly MIRCERA
(mikrogram/ uge)
epoetin alfa epoetin
(IE/ uge)
intravenous or
(mikrogram/ én gang månedligt)
intravenous or intravenous or
< 40 40- 80 > 80
subcutaneous dose (microgram/ week )< 40 40-80 > 80
25%.
If a dose adjustment is required to maintain the target haemoglobin concentration above 10 g/ dl (6.21 mmol/ l), the monthly dose may be increased by approximately 25%.
Derefter påbegyndes behandlingen igen med ca.
If the rate of rise in haemoglobin is greater than 2 g/ dl (1.24 mmol/ l) over a month or if the haemoglobin level is increasing and approaching 12 g/ dl (7.45 mmol/ l), the dose is to be reduced by approximately 25%.
Det er derfor nødvendigt med regelmæssig hæmoglobinkontrol og streng overholdelse af vejledningen for justering af dosis hos denne patientgruppe.
3 Since the treatment experience is limited in patients on peritoneal dialysis, regular haemoglobin monitoring and strict adherence to dose adjustment guidance is recommended in these patients.
Afbrydelse af behandlingen Behandlingen med MIRCERA er normalt en langtidsbehandling.
Treatment interruption Treatment with MIRCERA is normally long-term.
Den kan dog om nødvendigt afsluttes når som helst.
However, it can be interrupted at any time, if necessary.
Glemte doser Hvis en dosis MIRCERA glemmes, skal den glemte dosis administreres så hurtigt som muligt, og administrationen af MIRCERA skal påbegyndes igen med den foreskrevne doseringshyppighed.
Missed dose If one dose of MIRCERA is missed, the missed dose is to be administered as soon as possible and administration of MIRCERA is to be restarted at the prescribed dosing frequency.
Anvendelse til børn MIRCERA bør ikke anvendes til børn under 18 år på grund af manglende dokumentation for sikkerhed og virkning.
Paediatric use MIRCERA is not recommended for use in children and adolescents below 18 years due to a lack of safety and efficacy data.
Ældre patienter I de kliniske studier var 24% af de MIRCERA- behandlede patienter mellem 65 og 74 år, mens 20% var 75 år og derover.
Elderly patients In clinical studies 24% of patients treated with MIRCERA were aged 65 to 74 years, while 20% were aged 75 years and over.
5. 2).
Patients with hepatic impairment No adjustments of the starting dose nor of the dose modification rules are required in patients with hepatic impairment (see section 5.2).
Ukontrolleret hypertension.
Uncontrolled hypertension
Supplerende jernbehandling anbefales til alle patienter med serumferritinværdier under 100 mikrogram/ l eller med transferrinmætning under 20%.
Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 microgram/ l or with transferrin saturation below 20%.
For at sikre effektiv erythropoiese skal jernstatus kontrolleres hos alle patienter før og under behandlingen.
To ensure effective erythropoiesis, iron status has to be evaluated for all patients prior to and during treatment.
Manglende respons på behandling med MIRCERA bør give anledning til en undersøgelse af kausale årsager.
Failure to respond to MIRCERA therapy should prompt for a search for causative factors.
Tilstødende infektioner, inflammatoriske eller traumatiske episoder, okkult blodtab, hæmolyse, svær aluminiumtoksicitet, underliggende hæmatologiske sygdomme eller knoglemarvsfibrose kan også kompromittere det erythropoietiske respons.
Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases, or bone marrow fibrosis may also compromise the erythropoietic response.
Hvis alle nævnte tilstande kan udelukkes, og patienten har et pludseligt fald i hæmoglobin ledsaget af reticulocytopeni og anti- erythropoietinantistoffer, bør undersøgelse af knoglemarven for diagnosen Pure Red Cell Aplasia (PRCA) overvejes.
If all the conditions mentioned are excluded and the patient has a sudden drop of haemoglobin associated with reticulocytopenia and anti-erythropoietin antibodies, examination of the bone marrow for the diagnosis of Pure Red Cell Aplasia (PRCA) should be considered.
Der er rapporteret om Pure Red Cell Aplasia forårsaget af anti- erythropoietinantistoffer i forbindelse med ESAs.
Pure Red Cell Aplasia caused by anti-erythropoietin antibodies has been reported in association with ESAs.
Det er vist, at disse antistoffer krydsreagerer med alle ESAs, og patienter, som mistænkes for eller vides at have disse antistoffer over for erythropoietin, bør derfor ikke skiftes over til MIRCERA.
These antibodies have been shown to cross-react with all ESAs, and patients suspected or confirmed to have antibodies to erythropoietin should not be switched to MIRCERA.
4 Hæmoglobinkoncentration:
Haemoglobin concentration:
Hos patienter med kronisk nyreinsufficiens bør opretholdelse af hæmoglobinkoncentrationen ikke overskride den øvre grænse for den ønskede hæmoglobinkoncentration, som anbefalet under pkt.
In patients with chronic kidney disease, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration recommended in section 4.2.
I kliniske studier blev der observeret en øget risiko for dødsfald og alvorlige kardiovaskulære hændelser, når erythropoietinstimulerende stoffer (ESAs) blev administreret for at opnå en hæmoglobinkoncentration over 12 g/ dl (7, 45 mmol/ l).
In clinical trials, an increased risk of death and serious cardiovascular events was observed when erythropoiesis stimulating agents (ESAs) were administered to target a haemoglobin of greater than 12g/ dl (7.5 mmol/ l).
Blodtrykskontrol:
4 Blood pressure monitoring:
Som for andre ESAs kan blodtrykket stige under behandlingen med MIRCERA.
As with other ESAs, blood pressure may rise during treatment with MIRCERA.
Blodtrykket skal kontrolleres hos alle patienter før, ved starten af og under behandlingen med MIRCERA.
Blood pressure should be adequately controlled in all patients before, at initiation of, and during treatment with MIRCERA.
4. 2).
If high blood pressure is difficult to control by medical treatment or dietary measures, the dose must be reduced or administration discontinued (see section 4.2).
Virkningen på tumorvækst:
Effect on tumour growth:
MIRCERA er, ligesom andre ESAs, en vækstfaktor, som primært stimulerer produktionen af røde blodlegemer.
MIRCERA, like other ESAs, is a growth factor that primarily stimulates red blood cell production.
Erythropoietinreceptorer kan udtrykkes på overfladen af mange slags tumorceller.
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.
To kontrollerede, kliniske studier, i hvilke epoetiner blev administreret til patienter med forskellige kræfttyper, inklusive hoved- halskræft og brystkræft, viste en uforklaret øget mortalitet.
Two controlled clinical studies in which epoetins were administered to patients with various cancers including head and neck cancers, and breast cancer, have shown an unexplained excess mortality.
MIRCERA er ikke godkendt til behandling af anæmi hos patienter med kræft.
MIRCERA is not approved for the treatment of anaemia in patients with cancer.
Sikkerhed og virkning af behandling med MIRCERA er ikke dokumenteret hos patienter med hæmoglobinopatier, kramper, blødning eller nylig blødning, som kræver tranfusion, eller hos patienter med trombocyttal over 500 x 109/ l.
The safety and efficacy of MIRCERA therapy has not been established in patients with haemoglobinopathies, seizures, bleeding or a recent history of bleeding requiring transfusions or with platelet levels greater than 500 x 109/ l.
5. 3).
Animal studies do not indicate direct harmful effects with respect to pregnancy, embryofoetal development, parturition or postnatal development but indicate a class-related reversible reduction in foetal weight (see section 5.3).
Det vides ikke, om methoxypolyethylenglycol- epoetin beta udskilles i human brystmælk.
It is unknown whether methoxy polyethylene glycol-epoetin beta is excreted in human breast milk.
Et dyreforsøg har vist, at methoxypolyethylenglycol- epoetin beta udskilles i modermælk.
One animal study has shown excretion of methoxy polyethylene glycol-epoetin beta in maternal milk.
Beslutningen om at fortsætte eller stoppe amningen eller om at fortsætte eller afbryde behandlingen med MIRCERA skal træffes ved at afveje fordelen ved amning af barnet med fordelen ved at behandle kvinden med MIRCERA.
A decision on whether to continue or discontinue breast-feeding or to continue or discontinue therapy with MIRCERA should be made taking into account the benefit of breast-feeding to the child and the benefit of MIRCERA therapy to the woman.
MIRCERA påvirker ikke eller i ubetydelig grad evnen til at føre motorkøretøj eller betjene maskiner.
MIRCERA has no or negligible influence on the ability to drive and use machines.
Sikkerhedsdatabasen fra de kliniske studier omfatter 2737 kronisk nyreinsufficiente patienter, inklusive 1789 patienter behandlet med MIRCERA og 948 behandlet med et andet ESA.
The safety data base from clinical trials comprised 2’ 737 CKD patients, including 1’ 789 patients treated with MIRCERA and 948 with another ESA.
6% af de patienter, som behandles med MIRCERA, forventes at få bivirkninger.
Approximately 6% of patients treated with MIRCERA are expected to experience adverse reactions.
Meget almindelig (≥1/ 10); almindelig (≥1/ 100 til < 1/ 10); ikke almindelig (≥1/ 1. 000 til < 1/ 100); sjælden (≥1/ 10. 000 til < 1/ 1. 000); meget sjælden (< 1/ 10. 000).
The frequencies are defined as follows: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000)
Tabel 2:
5 Table 2:
Bivirkninger, som kan tilskrives behandling med MIRCERA i kontrollerede, kliniske studier
Adverse reactions attributed to the treatment with MIRCERA in controlled clinical trials in CKD patients
Systemorganklasse Nervesystemet
System organ class Nervous system disorders
Hyppighed Ikke almindelig
Frequency Uncommon
Bivirkning Hovedpine
Adverse reaction Headache
Makulo- papuløst udslæt
Rash, maculo-papular
Trombose efter anlæggelse af karadgang
Vascular access thrombosis
Alle andre bivirkninger, som kunne tilskrives MIRCERA, var sjældne, og de fleste var af let til moderat sværhedsgrad.
All other events attributed to MIRCERA were reported with rare frequency and the majority were mild to moderate in severity.
Bivirkningerne var konsistente med kendte ko- morbiditeter i populationen.
These events were consistent with comorbidities known in the population.
I de kliniske studier blev der under behandlingen med MIRCERA set et let fald i trombocyttallene, som var inden for referenceintervallet.
During treatment with MIRCERA, a slight decrease in platelet counts remaining within the normal range was observed in clinical studies.
Trombocyttal under 100 x 109/ l blev set hos 7% af de patienter, som blev behandlet med MIRCERA og hos 4% af de patienter, som blev behandlet med andre ESAs.
Platelet counts below 100 x 109/ l were observed in 7% of patients treated with MIRCERA and 4% of patients treated with other ESAs.
En overdosis kan medføre manifestationer på en overdreven farmakodynamisk virkning, fx excessiv erythropoiese.
Overdose can result in manifestations of an exaggerated pharmacodynamic effect, e. g. excessive erythropoiesis.
4. 2).
In case of excessive haemoglobin levels, treatment with MIRCERA should be temporarily discontinued (see section 4.2).
Andre midler mod anæmi, ATC- kode:
Other antianemic preparations, ATC code:
En langsommere binding til og hurtigere adskillelse fra receptoren, en reduceret, specifik in vitro aktivitet med en forøget aktivitet in vivo, og desuden en forlænget halveringstid i modsætning til erythropoetin.
Methoxy polyethylene glycol-epoetin beta, the active substance of MIRCERA, is a continuous erythropoietin receptor activator that shows a different activity at the receptor level characterized by a slower association to and faster dissociation from the receptor, a reduced specific activity in vitro with an increased activity in vivo, as well as an increased half-life, in contrast to erythropoietin.
30 kDA.
The average molecular mass is approximately 60 kDa of which the protein moiety plus the carbohydrate part constitutes approximately 30 kDa.
MIRCERA stimulerer erythropoiesen ved interaktion med erythropoietinreceptoren på progenitorceller i knoglemarven.
MIRCERA stimulates erythropoiesis by interaction with the erythropoietin receptor on progenitor cells in the bone marrow.
Som primær vækstfaktor for erythroid- udvikling dannes det naturlige hormon erythropoietin i nyrerne og udskilles i blodet som respons på hypoxi.
As primary growth factor for erythroid development, the natural hormone erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia.
Det naturlige hormon erythropoeitin interagerer med erythroide progenitorceller som respons på hypoxi, hvorved produktionen af røde blodceller stiger.
Data from correction studies show that the haemoglobin response rates in the MIRCERA group at the end of the correction period were high (93.3% and 97.5% in the studies in patients on dialysis and not
Data fra korrektionsstudier viser at hæmoglobin responsraterne i MIRCERA armen var høje (93, 3% og 97, 5% i studier med patienter henholdsvis i dialyse og ikke i dialyse) sammenlignet med komparator (henholdsvis 91, 3% og 96, 3%).
6 on dialysis, respectively) and comparable to comparators (91.3% and 96.3%, respectively).
0, 2 g/ dl/ uge og 0, 3 g/ dl/ uge.
The median time to response was 43 days in the MIRCERA arm and 29 days in the comparator arm, with increases of haemoglobin within the first 6 weeks of 0.2 g/ dl/ week and 0.3 g/ dl/ week, respectively.
Der er udført fire randomiserede, kontrollerede studier med dialysepatienter, som ved studiestart blev behandlet med enten darbepoetin alfa eller epoetin.
Four randomized controlled studies were performed in dialysis patients treated with darbepoetin alfa or epoetin at the time of enrollment.
I evalueringsperioden (uge 29- 36) var middel - og mediankoncentrationerne af hæmoglobin hos de MIRCERA- behandlede patienter praktisk talt identiske med hæmoglobinkoncentrationerne ved baseline.
At the evaluation period (week 29-36), the mean and median level of haemoglobin in patients treated with MIRCERA was virtually identical to their baseline haemoglobin level.
Erythropoietinreceptorer kan være udtrykket på overfladen af diverse tumorceller.
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.
Heraf var fire studier dobbelt- blindede placebo- kontrollerede studier, og et studie var et ublindet studie.
Survival and tumour progression have been examined in five large controlled studies involving a total of 2’ 833 patients, of which four were double-blind placebo-controlled studies and one was an open- label study.
Den ønskede hæmoglobinkoncentration i to studier var > 13 g/ dl; i de øvrige 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 det ublindede studie var der ingen forskel på total ovelevelse for patienter, der blev behandlet med rekombinant human erythropoietin og kontrolgruppen.
In the open-label study there was no difference in overall survival between patients treated with recombinant human erythropoietin and controls.
I de fire placebo- kontrollerede studier var hazard ratio for total overlevelse 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.
En systematisk gennemgang har også været foretaget af 57 kliniske studier, som har involveret mere end 9000 cancerpatienter.
A systematic review has also been performed involving more than 9’ 000 cancer patients participating in 57 clinical trials.
En meta- analyse af data for total overlevelse viste en estimeret hazard ratio på 1. 08 i kontrolgruppens favør (95% konfidensinterval:
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 studier og 8167 patienter).
0.99, 1.18; 42 trials and 8’ 167 patients).
1. 67; 95% konfidensinterval:
An increased relative risk of thromboembolic events (RR 1.67, 95% CI:
1. 35, 2. 06; 35 studier og 6769 patienter).
1.35, 2.06, 35 trials and 6’ 769 patients) was observed in patients treated with recombinant human erythropoietin.
Der er derfor konsistent evidens for at formode, at der kan være signifikant skadelig virkning hos patienter, som har cancer, og som bliver behandlet med rekombinant human erythropoietin.
There is therefore consistent evidence to suggest that there may be significant harm to patients with cancer who are treated with recombinant human erythropoietin.
Det er uklart i hvilket omfang disse resultater også kan forbindes med administration af rekombinant human erythropoietin til patienter med cancer, som bliver behandlet med kemoterapi for at opnå hæmoglobinkoncentrationer på mindre end 13 g/ dl, fordi få patienter med disse karakteristika var inkluderet i de gennemgåede data.
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.