natgillin/translations-raw huggingface dataset:
Resultater fra dyrereproduktionsundersøgelser indicerer, at rekombinant interferon alfa- 2b ikke var teratogent hos rotter eller kaniner, ej heller påvirkede det i skadelig grad graviditet, fosterudvikling eller reproduktionsevne i efterkommere af behandlede rotter.
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of treated rats.
Interferon alfa- 2b er vist til at have abortfremkaldende virkninger hos Macaca mulatta (rhesus aber) ved 90 og 180 gange den anbefalede intramuskulære eller subkutane dosis på 2 millioner IE/ m2.
Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2.
Abort blev observeret i alle dosis grupper (7, 5 millioner, 15 millioner og 30 millioner IE/ kg), og var statistisk signifikant mod kontrolgruppen for medium - og højdosisgrupperne (svarende til 90 og 180 gange den anbefalede intramuskulære eller subkutane dosis på 2 millioner IE/ m2).
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2).
Høje doser af andre former af interferon alfa og beta er kendt for at producere dosisrelateret anovulatorisk og abortfremkaldende virkning hos rhesus aber.
High doses of other forms of interferons alpha and beta are known to produce dose- related anovulatory and abortifacient effects in rhesus monkeys.
Mutagenicitetsundersøgelser med interferon alfa- 2b afslørede ingen bivirkninger.
Mutagenicity studies with interferon alfa-2b revealed no adverse events.
4. 4 og produktresumeet for Rebetol hvis IntronA skal gives i kombination med ribavirin).
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if IntronA is to be administered in combination with ribavirin).
Glycin, Dinatriumphosphat, vandfri, Natriumdihydrogenphosphatmonohydrat, Human albumin.
Glycine, Disodium phosphate anhydrous, Sodium dihydrogen phosphate monohydrate,
Solvens:
 20 Human albumin solution.
Færdigtilberedt produkt:
After reconstitution:
Det anbefales, at produktet anvendes med det samme.
An immediate use is recommended.
Fysisk- kemisk stabilitet under brug er imidlertid vist i 24 timer ved 25C.
However, the chemical and physical in-use stability has been demonstrated for 24 hours at 25ºC.
Inden for holdbarhedsperioden, under transport og/ eller for at lette ambulant brug, kan det ikke færdigtilberedte produkt opbevares ved stuetemperatur (op til 25°C) i op til 4 uger inden anvendelse.
Within its shelf-life, for the purpose of transport and/or to facilitate ambulatory use the non- reconstituted product can be kept at or below 25°C for a period up to four weeks before use.
Pakningsstørrelse á 1 eller 12.
Pack sizes of 1 or 12.
Færdigtilberedning af IntronA, pulver til injektionsvæske eller til infusionsvæske, opløsning til parenteral indgift:
Reconstitution of IntronA, powder for solution for injection or infusion, for parenteral administration:
IntronA leveres som et pulver i styrker på 1 million IE/ ml til éndosisbrug.
IntronA is supplied as a powder at strengths of 1 million IU/ml for single-dose use.
Med en steril injektionssprøjte og kanyle indsprøjtes 1 ml vand til injektionsvæsker i hætteglasset med IntronA.
Using a sterilised injection syringe and injection needle, inject 1 ml water for injections into the vial of IntronA.
Det færdigtilberedte lægemiddel bør i lighed med alle parenterale lægemidler undersøges visuelt for partikler og misfarvning før brugen.
As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and discolouration prior to administration.
Detaljerede instruktioner til den subkutane brug af præparatet følger med indlægsseddelen (se ” Hvordan injicerer De selv IntronA ”).
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to “How to self inject IntronA”).
Tilberedning af IntronA til intravenøs infusion:
 21 Preparation of IntronA for intravenous infusion:
Infusionsvæsken bør tilberedes umiddelbart før brug.
The infusion must be prepared immediately prior to use.
Den frysetørrede pulverform af IntronA skal færdigtilberedes ved tilsætning af 1 ml vand til injektionsvæsker til hætteglasset.
The lyophilised powder form of IntronA is to be reconstituted by adding 1 ml of water for injections to the vial.
Den beregnede mængde interferon til den passende dosis skal derefter trækkes op af hætteglasset (glassene), tilsættes til 100 ml 9 mg/ ml (0, 9%) natriumchlorid injektionsvæske, opløsning og indgives over 20 minutter.
The calculated amount of interferon for the appropriate dose then is withdrawn from the vial(s), added to 100 ml of 9 mg/ml (0.9%) sodium chloride solution for injection and administered over 20 minutes.
Slutkoncentrationen af interferon i natriumchloridopløsning må ikke være mindre end 1 x 105 IE/ ml.
Final concentration of interferon in sodium chloride solution must not be less than 1 x 105 IU/ml.
INTET ANDET LÆGEMIDDEL MÅ INFUNDERES SAMTIDIG MED INTRONA.
NO OTHER MEDICINAL PRODUCT CAN BE INFUSED CONCOMITANTLY WITH INTRONA.
21 Ikke anvendt lægemiddel skal kasseres efter udtrækning af dosis.
Any unused product must be discarded after withdrawal of the dose.
SP Europe 73, rue de Stalle B- 1180 Bruxelles Belgien
SP Europe 73, rue de Stalle B-1180 Bruxelles Belgium
9. marts 2000 Dato for seneste fornyelse:
9 March 2000 Date of last renewal:
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMEAs) hjemmeside http: // www. emea. europa. eu /
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu/
IntronA 3 millioner IE/ ml pulver og solvens til injektionsvæske eller til infusionsvæske, opløsning
IntronA 3 million IU/ml powder and solvent for solution for injection or infusion
Et hætteglas med pulver indeholder 3 millioner IE interferon alfa- 2b produceret i E. coli ved rekombinant DNA- teknologi.
One vial of powder contains 3 million IU of interferon alfa-2b produced in E.coli by recombinant DNA technology.
Efter rekonstitution, indeholder 1 ml 3 millioner IE interferon alfa- 2b
After reconstitution, 1 ml contains 3 million IU of interferon alfa-2b.
Behandling af voksne patienter med kronisk hepatitis B forbundet med tegn på hepatitis B virusreplikation (tilstedeværelse af HBV- DNA og HBeAg), forhøjet alaninaminotransferase (ALAT) og histologisk påvist aktiv leverinflammation og/ eller fibrose.
Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and histologically proven active liver inflammation and/or fibrosis.
Den bedste måde at anvende IntronA ved denne indikation er i kombination med ribavirin.
The best way to use IntronA in th is indication is in combination with ribavirin.
Behandling af voksne patienter med Philadelphia kromosom eller bcr/ abl translokationspositiv kronisk myeloid leukæmi.
Treatment of adult patients with Philadelphia chromosome or bcr/abl translocation positive chronic myelogenous leukaemia.
Klinisk erfaring indikerer, at et hæmatologisk og cytogenetisk større/ mindre respons er opnåeligt hos størstedelen af behandlede patienter.
Clinical experience indicates that a haematological and cytogenetic major/minor response is obtainable in the majority of patients treated.
23 leukæmiske celler i knoglemarven, mens et mindre respons er  34%, men < 90% Ph+ celler i marven.
A major cytogenetic response is defined by < 34% Ph+ leukaemic cells in the bone marrow, whereas a minor response is  34%, but < 90% Ph+ cells in the marrow.
Kombinationsbehandling:
 23 Combination therapy:
Den givne dosis skal reduceres med 50% i tilfælde af forekomst af hæmatologiske lidelser (hvide blodlegemer < 1. 500/ mm3, granulocytter < 1. 000/ mm3, thrombocytter < 100. 000/ mm3).
The administered dose should be reduced by 50% in case of occurrence of haematological disorders (white blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3).
Behandlingen skal seponeres i tilfælde af svær leukopeni (< 1. 200/ mm3), svær neutropeni (< 750/ mm3) eller svær thrombocytopeni (< 70. 000/ mm3).
Treatment should be discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe thrombocytopaenia (< 70,000/mm3).
Interferon alfa- 2b 3 millioner IE/ m2 indgives subkutant 3 gange om ugen (hver anden dag) i kombination med ribavirin kapsler eller oral opløsning indgivet oralt fordelt på to daglige doser til et måltid (morgen og aften).
Interferon alfa-2b 3 MIU/m2 is administered subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution administered orally in two divided doses daily with food (morning and evening).
24 (Se produktresume for ribavirin kapsler med henblik på dosis af ribavirin kapsler og retningslinierne for dosisindstilling ved kombinationsbehandling.
 24 (See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
Behandling bør fortsættes i yderligere en 6- måneders periode (det vil sige i alt 12 måneder) hos patienter, der udviser negativ HCV- RNA ved 6 måneder, og ved viral genotype 1 (bestemt ved en prøve før behandling) og høj virusmængde før behandling.
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and high pre-treatment viral load.
Genotype 2/ 3:
Genotype 2/3:
Virologisk respons efter 1 års behandling og 6 måneders opfølgning var 36% for genotype 1 og 81% for genotype 2/ 3/ 4.
Virological responses after 1 year of treatment and 6 months of follow-up were 36% for genotype 1 and 81% for genotype 2/3/4.
Den anbefalede dosering er 2 millioner IE/ m2 givet subkutant tre gange om ugen (hver anden dag) for både splenektomerede og ikke splenektomerede patienter.
The recommended dosage is 2 million IU/m2 administered subcutaneously three times a week (every other day) for both splenectomised and non-splenectomised patients.
25 Kronisk myeloid leukæmi:
 25 Chronic Myelogenous Leukaemia:
Den anbefalede dosering af IntronA er 4 til 5 millioner IE/ m2 givet dagligt subkutant.
The recommended dosage of IntronA is 4 to 5 million IU/m2 administered daily subcutaneously.
Nogle patienter har vist at have gavn af IntronA 5 millioner IE/ m2 indgivet dagligt subkutant i forbindelse med cytarabin (Ara- C) 20 mg/ m2 indgivet dagligt subkutant i 10 dage per måned (op til en maksimal daglig dosis på 40 mg).
Some patients have been shown to benefit from IntronA 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg).
Når leucocyttallet er under kontrol, bør den maksimalt tolererede dosis IntronA (4 til 5 millioner IE/ m2 daglig) indgives for at vedligeholde den hæmatologiske remission.
When the white blood cell count is controlled, administer the maximum tolerated dose of IntronA (4 to 5 million IU/m2 daily) to maintain haematological remission.
Hos patienter, som er i plateaufase (mere end 50% reduktion af myelom- protein) efter initial induktionskemoterapi, kan interferon alfa- 2b gives som monoterapi, subkutant i en dosering på 3 millioner IE/ m2 tre gange om ugen (hver anden dag).
In patients who are in the plateau phase (more than 50% reduction of myeloma protein) following initial induction chemotherapy, interferon alfa-2b may be administered as monotherapy, subcutaneously, at a dose of 3 million IU/m2 three times a week (every other day).
6. 6).
As induction therapy, interferon alfa-2b is administered intravenously at a dose of 20 million IU/m2 daily for five days a week for a four-week period; the calculated interferon alfa-2b dose is added to sodium chloride 9 mg/ml (0.9%) solution for injection and administered as a 20- minute infusion (see section 6.6).
Som vedligeholdelsesbehandling er den anbefalede dosis 10 millioner IE/ m2 indgivet subkutant tre gange om ugen (hver anden dag) i 48 uger.
As maintenance treatment, the recommended dose is 10 million IU/m2 administered subcutaneously three days a week (every other day) for 48 weeks.
Hvis der udvikles alvorlige bivirkninger under interferon alfa- 2b behandlingen, især hvis granulocyttallet falder til < 500/ mm3 eller alaninaminotransferase/ aspartataminotransferase (ALAT/ ASAT) stiger til > 5 gange den øvre normalgrænse, skal behandlingen midlertidigt afbrydes, indtil bivirkningen aftager.
If severe adverse events develop during interferon alfa-2b treatment, particularly if granulocytes decrease to < 500/mm3 or alanine aminotransferase/aspartate aminotransferase (ALT/AST) rises to > 5 x upper limit of normal, discontinue treatment temporarily until the adverse event abates.
Hvis intolerance vedvarer efter dosisjustering, eller hvis granulocyttallet falder til < 250/ mm3 eller ALAT/ ASAT stiger til > 10 gange den øvre normalgrænse, skal interferon alfa- 2b behandling afbrydes.
If intolerance persists after dose adjustment or if granulocytes decrease to < 250/mm3 or ALT/AST rises to > 10 x upper limit of normal, discontinue interferon alfa-2b therapy.
- Anamnese med alvorlig tidligere hjertesygdom, såsom ukontrolleret hjerteinsufficiens, nylig
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure,
4. 4).
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4).
26 Børn og unge:
 26 Children and adolescents:
Akutte overfølsomhedsreaktioner (såsom urticaria, angioødem, bronkokonstriktion, anafylaksi) over for interferon alfa- 2b har sjældent været observeret under IntronA behandling.
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon alfa-2b have been observed rarely during IntronA therapy.
Lungeinfiltrat, pneumonitis og pneumonia, undertiden resulterende i dødsfald, er sjældent blevet observeret hos interferon- alfa behandlede patienter, inklusive de, som er behandlet med IntronA.
 27 Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Voksne patienter med tidligere hjerteinsufficiens, myokardieinfarkt og/ eller tidligere eller eksisterende arytmisygdomme, som kræver IntronA- behandling, skal følges tæt.
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current arrhythmic disorders, who require IntronA therapy, must be closely monitored.
De patienter, som har haft hjerteanomalier og/ eller er i fremskreden cancerstadie, skal have taget elektrokardiogram før og under behandling.
It is recommended that those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have electrocardiograms taken prior to and during the course of treatment.
Passende vaccination (hepatitis A og B) bør overvejes hos patienter, der regelmæssigt/ gentagne gange får humant albumin udvundet fra plasma.
 28 Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived albumin.
Standardmetoder til forebyggelse af infektioner, der stammer fra anvendelse af lægemidler fremstillet fra humant blod eller plasma, omfatter udvælgelse af donorer, screening af individuelle donationer og 28 plasmapools for specifikke markører for infektion og inklusion af effektive fremstillingstrin for inaktivering/ fjernelse af vira.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses.
Børn og unge patienter bør monitoreres hver 3. måned for tegn på thyreoideadysfunktion (f. eks.
Children and adolescents should be monitored every 3 months for evidence of thyroid dysfunction (e.g.
Baseret på foreløbige data fra en langsigtet opfølgningsundersøgelse, havde 12 (14%) af 84 børn dog en > 15 procent nedgang i hastigheden af linear vækst, af hvilke 5 (6%) børn havde en > 30 procent nedgang på trods af, at behandlingen havde været afbrudt i mere end et år.
However, based on interim data from a long-term follow-up study, 12 (14%) of 84 children had a > 15 percentile decrease in rate of linear growth, of whom 5 (6%) children had a > 30 percentile decrease despite being off treatment for more than 1 year.
Det anbefales at læger monitorerer væksten af børn, der tager ribavirin i kombination med interferon alfa - 2b.
Therefore, the risk/benefit of the combined use of interferon alfa-2b and
29 Samtidig infektion med HCV/ HIV:
 29 ribavirin should be assessed in young children prior to the initiation of therapy.
Indgift af IntronA i kombination med andre kemoterapeutika (såsom Ara- C, cyclophosphamid, doxorubicin, teniposid) kan føre til forøget risiko for toksicitet (sværhedsgrad og varighed), som kan være livstruende eller fatal som et resultat af det samtidigt indgivne lægemiddel.
Administration of IntronA in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration), which may be life-threatening or fatal as a result of the concomitantly administered medicinal product.
30 Interferoner kan påvirke den oksidative metaboliske proces.
Interferons may affect the oxidative metabolic process.
Dette skal tages i betragtning ved samtidig behandling med præparater, der metaboliseres på denne måde, såsom xanthin- derivaterne theophyllin eller aminophyllin.
This must be considered during concomitant therapy with medicinal products metabolised by this route, such as the xanthine derivatives
4. 4).
Administration of IntronA in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration) (see section 4.4).
I kliniske undersøgelser foretaget i en lang række indikationer og i et bredt dosisområde (fra 6 MIE/ m2/ uge ved hårcelleleukæmi op til 100 MIE/ m2/ uge ved melanom) var de mest almindeligt rapporterede bivirkninger feber, træthed, hovedpine og myalgi.
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable effects were fever, fatigue, headache and myalgia.
Dette bygger på kliniske undersøgelser af naive patienter, der blev behandlet i et år.
In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from clinical trials in naïve patients treated for one year.
De bivirkninger, der er listet i Tabel 1, er baseret på erfaringer fra kliniske undersøgelser og post- marketing.
The adverse reactions listed in Table 1 are based on experience from clinical trials and post-
Indenfor systemorganklasserne, er bivirkningerne listet under overskrifter efter hyppighed under anvendelse af følgende kategorier: meget almindelig (≥1/ 10); almindelig (≥1/ 100, < 1/ 10); ikke almindelig (≥1/ 1. 000, < 1/ 100); sjælden (≥1/ 10. 000, < 1/ 1. 000); meget sjælden (< 1/ 10. 000); ikke kendt.
Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (≥1/10); common (≥1/100, < 1/10); uncommon (≥1/1,000, < 1/100); rarely (≥1/10,000, < 1/1,000); very rarely (< 1/10,000); not known.
32 Øjne Meget almindelig:
Very common:
Retinal blødning§, retinopatier (inklusive makulært ødem), retinal arterie - eller veneobstruktion§, optisk neuritis, papilødem, tab af synsskarphed eller synsfelt, slørede pletter§
Retinal haemorrhages§, retinopathies (including macular oedema), retinal artery or vein obstruction§, optic neuritis, papilloedema, loss of visual acuity or visual field, cotton-
Almindelig:
wool spots§ Ear and labyrinth Common:
33 Almene symptomer og reaktioner på administrationsstedet Meget almindelig:
Very common:
4. 4
*These events were only common with IntronA alone § See section 4.4
4. 4).
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
4. 4)
Cardiomyopathy, that may be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior evidence of cardiac disease (see section 4.4).
Derudover forekom lidelser på injektionsstedet, feber, anoreksi, opkastning og emotionel labilitet hyppigere hos 34 børn og unge sammenlignet med voksne patienter.
In addition, injection site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and adolescents compared to adult patients.
Bivirkninger rapporteret som værende meget almindelige eller almindelige i kliniske undersøgelser hos børn Meget almindelig (≥1/ 10) - Almindelig (≥1/ 100, < 1/ 10) Systemorganklasser Infektioner og parasitære sygdomme
Table 2 Adverse reactions very commonly and commonly reported in paediatric clinical trials Very common (≥1/10) - Common (≥1/100, < 1/10) System Organ Class  Infection and infestations
Almindelig: § Psykiske forstyrrelser
Psychiatric disorders§
35 Lever og galdeveje Almindelig:
Common:
36 Interferoner er en familie af små proteinmolekyler med molekylevægte på cirka 15. 000- 21. 000 daltons.
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 21,000 daltons.
Resultaterne af adskillige undersøgelser antyder, at når interferon er bundet til cellemembranen starter en kompleks sekvens af intracellulære reaktioner, som omfatter induktion af visse enzymer.
 36 The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
37 IntronA blev indgivet i en dosis på 3 MIE 3 gange om ugen som monoterapi eller i kombination med ribavirin.
IntronA was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with ribavirin.
Uafhængigt af genotype havde patienter, som fik IntronA i kombination med ribavirin og fik  80% af deres behandling, et højere vedvarende respons 6 måneder efter 1 års behandling end dem, der anvendte < 80% af deres behandling (56% mod 32% i undersøgelse C/ I98- 580).
Regardless of genotype, patients who received IntronA in combination with ribavirin and received  80% of their treatment had a higher
Behandlingsvarigheden var 48 uger med en opfølgningsperiode på 6 måneder med undtagelse
The duration of therapy was 48 weeks with a follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load < 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.
38 af de patienter, der var inficeret med genotype 2 og 3 og viral load < 800. 000 IE/ ml (Amplicor), som blev behandlet i 24 uger med en opfølgningsperiode på 6 måneder.
after IntronA in combination with combination with ribavirin in
Tabel 4
value a