natgillin/translations-raw huggingface dataset:
Der bør udvises forsigtighed, når der gives Rebif i forbindelse med medicinske produkter, der har et snævert terapeutisk indeks og i høj grad er afhængig af det hepatiske cytokrom P450- system for clearence, f. eks. antiepileptika og nogle typer antidepressiva.
Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e. g. antiepileptics and some classes of antidepressants.
4 Interaktionen af Rebif og kortikosteroider eller adrenokortikotropt hormon (ACTH) er ikke studeret systematisk.
4 The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically.
Kliniske studier indikerer, at multipel sklerose- patienter kan modtage Rebif og kortikosteroider eller ACTH under et recidiv.
Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses.
Der findes begrænset information om anvendelse af Rebif under graviditet.
There is limited information on the use of Rebif in pregnancy.
Tilgængelige data indikerer, at der er en øget risiko for spontan abort.
Available data indicates that there may be an increased risk of spontaneous abortion.
4. 3).
Therefore initiation of treatment is contraindicated during pregnancy (see section 4.3).
Hvis patienten bliver gravid eller planlægger at blive gravid under behandlingen med Rebif, skal hun informeres om den potentielle risiko, og ophør af behandlingen bør overvejes (se pkt.
If the patient becomes pregnant or plans to become pregnant while taking Rebif she should be informed of the potential hazards and discontinuation of therapy should be considered (see section 5.3).
Hos patienter med høj attakfrekvens før behandlingsstart skal risikoen for alvorlige attakker, som følge af behandlingsophør ved graviditet, opvejes mod den eventuelt forøgede risiko for spontan abort.
In patients with a high relapse rate before treatment has started, the risk of a severe relapse following discontinuation of Rebif in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion.
Det vides ikke, hvorvidt Rebif udskilles i modermælken.
It is not known whether Rebif is excreted in human milk.
På grund af den potentielle risiko for bivirkninger hos det diende barn bør der tages stilling til enten at afbryde amningen eller Rebif - behandlingen.
Because of the potential for serious adverse reactions in breast-fed infants, a decision should be made whether to discontinue breast-feeding or Rebif therapy.
4. 8).
Central nervous system-related adverse events associated with the use of interferon beta (e. g. dizziness) might influence the patient's ability to drive or use machines (see section 4.8).
Den hyppigste forekomst af bivirkninger, som er forbundet/ associeret med behandling med Rebif, er relateret til influenzalignende syndrom.
The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome.
Influenzalignende symptomer har en tendens til at være mest udtalte i starten af behandlingen og aftager i frekvens ved fortsat behandling.
Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment.
70% af patienterne, som behandles med Rebif, kan forvente at opleve det typiske influenzalignende interferon- symptom inden for de første seks måneder efter start af behandlingen.
Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment.
30% af patienterne vil ligeledes opleve reaktioner ved injektionsstedet, overvejende mild inflammation eller erythema.
Approximately 30% of patients will also experience reactions at the injection site, predominantly mild inflammation or erythema.
Asymsymtomatisk forhøjelse af laboratorieleverparameterne og formindskelse af leukocyttal er også almindelig.
Asymptomatic increases in laboratory parameters of hepatic function and decreases in white blood cells (WBC) are also common.
Flertallet af bivirkninger, der er observeret med IFN beta- 1a, er normalt milde og reversible og responderer godt ved reduktion af dosis.
The majority of adverse reactions observed with IFN beta-1a are usually mild and reversible, and respond well to dose reductions.
I tilfælde af alvorlige eller vedvarende uønskede bivirkninger må dosis af Rebif midlertidigt sættes ned eller midlertidigt afbrydes efter lægens skøn.
In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician.
Følgende bivirkninger er angivet i henhold til hyppigheden af hændelser:
The adverse reactions reported below are classified according to frequency of occurrence as follows:
Meget almindelig Almindelig Usædvanlig Sjælden Meget sjælden Ikke kendt
Very Common Common Uncommon Rare
≥1/ 10 ≥1/ 100 til < 1/ 10 ≥1/ 1. 000 til < 1/ 100 ≥1/ 10. 000 til < 1/ 1. 000 < 1/ 10. 000 Kan ikke estimeres ud fra de tilgængelige data
≥ 1/ 10 ≥ 1/ 100 to < 1/ 10 ≥ 1/ 1,000 to < 1/ 100 ≥ 1/ 10,000 to < 1/ 1,000
Inden for hver enkelt frekvensgruppe skal bivirkningerne opstilles efter, hvor alvorlige de er.
Cannot be estimated from the available data
De præsenterede data er indsamlet fra flere kliniske studier af multipel sklerose (placebo = 824 patienter; Rebif 22 mikrogram 3 gange om ugen = 398 patienter; Rebif 44 mikrogram 3 gange om ugen = 727 patienter) og viser hyppigheden af bivirkninger, der er observeret seks måneder efter start af behandling (mere end placebo).
The data presented is obtained from pooled clinical studies in multiple sclerosis (placebo=824 patients; Rebif 22 micrograms three times per week (TIW)=398 patients; Rebif 44 micrograms TIW=727 patients) and shows the frequency of adverse reactions observed at six months (excess over
5 Organklasser
5 placebo).
Meget almindelig
System Organ Class Infections and infestations
Ikke kendt *
Common
Infektioner og parasitære sygdomme Blod og lymfesystem
Uncommon Injection site abscess
Neutropeni, lymfopeni, leukopeni, trombocyto - peni, anæmi
Not known* Injection site infections, including cellulitis
Absces på injektionsstedet
Blood and lymphatic system disorders
Infektioner på injektionsstedet inklusive cellulitis
Neutropenia, lymphopenia, leucopenia, thrombocytopenia, anaemia
Skjoldbruskkirtel - dysfunktion oftest i form af hypotyreoidisme eller hypertyreoidisme
Thyroid dysfunction most often presenting as hypothyroidism or hyperthyroidism
Nervesyste - met
Nervous system disorders
Kløe, hududslæt, erytematøs kløe, maculo - papular kløe
Pruritus, rash, erythematous rash, maculo-papular rash
Angioødem, nældefeber, erytema multiforme, erytema multiforme - lignende hudreaktion, hårtab
Angioedema, urticaria, erythema multiforme, erythema multiforme-like skin reactions, Stevens-Johnson syndrome, hair loss
Muskelsmerte og ledsmerte
Myalgia, arthralgia
Almene symptomer og reaktioner på administra - tionsstedet
General disorders and administration site conditions
Betændelse ved injektions - stedet, reaktion ved injektions - stedet, influenzaligne nde symptomer
Injection site inflammation, injection site reaction, influenza-like symptoms
Smerter ved injektionssted et, træthed, stivhed, feber
Injection site pain, fatigue, rigors, fever
Nekrose og hævelse på injektionsstedet
Injection site necrosis, injection site mass
Undersøg - elser
Investigations
Forhøjelse af symptomfri transaminase
Asymptomatic transaminase increase
Immun - systemet
Immune system disorders Vascular disorders
Anafylaktiske reaktioner
Anaphylactic reactions Thromboembolic events
Vaskulære sygdomme Lever og galdeveje
Hepatobiliary disorders
Tromboemboliske reaktioner Hepatitis med eller uden gulsot
Hepatitis with or without icterus
* Bivirkninger, der er observeret ved post- marketing- undersøgelser (frekvens ikke kendt)
6 *Adverse reactions identified during post marketing surveillance (frequency not known)
6 Interferon- beta har risiko for at fremkalde alvorlige leverskader.
Interferon beta has a potential for causing severe liver injury.
Mekanismen for den sjældne symptomatiske hepatiske funktionsfejl er ikke kendt.
The mechanism for the rare symptomatic hepatic dysfunction is not known.
Flertallet af tilfældene af svære leverskader forekommer inden for de første seks måneders behandling.
The majority of the cases of severe liver injury occurred within the first six months of treatment.
Der er ikke identificeret specifikke risikofaktorer.
No specific risk factors have been identified.
4. 4).
Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (see section 4.4).
Administration af interferoner har været forbundet med anoreksi, svimmelhed, angst, vasodilatation arrhythmia, hjertebanken, menoragi og metroragi.
The administration of interferons has been associated with anorexia, dizziness, anxiety, arythmias, vasodilation and palpitation, menorrhagia and metrorrhagia.
Der kan forekomme en forøgelse i dannelsen af autoantistof med IFN- beta- 1a- behandling.
An increased formation of auto-antibodies may occur during treatment with interferon beta.
Patienten bør i tilfælde af overdosering indlægges til observation med passende understøttende behandling.
In case of overdose, patients should be hospitalised for observation and appropriate supportive treatment should be given.
Immunostimulanter, Interferoner, ATC- kode:
Immunostimulants, Interferons, ATC code:
Interferoner (IFNs) er en gruppe endogene glykoproteiner, der er udrustet med immunmodulerende, antivirale og antipoliferative egenskaber.
Interferons (IFNs) are a group of endogenous glycoproteins endowed with immunomodulatory, antiviral and antiproliferative properties.
Rebif (interferon beta- 1a) indeholder samme aminosyresekvenser som endogent, humant interferon beta.
Rebif (interferon beta-1a) shares the same amino acid sequence with endogenous human interferon beta.
Det produceres i celler hos pattedyr (ovariet hos kinesiske hamstere) og er derfor glykosyleret som det naturlige protein.
It is produced in mammalian cells (Chinese hamster ovary) and is therefore glycosylated like the natural protein.
Sikkerheden og effekten af Rebif er blevet evalueret hos patienter med recidiverende- remitterende multipel sklerose ved dosering fra 11 til 44 mikrogram (3- 12 millioner IE), administreret subkutant 3 gange om ugen.
The safety and efficacy of Rebif has been evaluated in patients with relapsing-remitting multiple sclerosis at doses ranging from 11 to 44 micrograms (3-12 million IU), administered subcutaneously three times per week.
30% over 2 år) og sværhedsgraden af kliniske attakker hos patienter med mindst 2 attakker i de foregående to år og med en EDSS på 0- 5, 0 ved start.
At licensed posology, Rebif 22 micrograms has been demonstrated to decrease the incidence (approximately 30% over 2 years) and severity of clinical relapses in patients with at least 2 exacerbations in the previous 2 years and with an EDSS of 0-5.0 at entry.
Forværret førlighed defineres som mindst 1 points øgning på EDSS - skalaen og bekræftes efter 3 måneder.
The proportion of patients with disability progression, as defined by at least one point increase in EDSS confirmed three months later, was reduced from 39% (placebo) to 30% (Rebif 22 micrograms).
I over 4 år var reduktionen af den gennemsnitlige eksacerbationsrate 22% hos patienter, der blev behandlet med Rebif 22 mikrogram, og 29% hos patienter, der blev behandlet med Rebif 44 mikrogram, sammenlignet med en gruppe patienter, der blev behandlet med placebo i to år og derefter med enten Rebif 22 eller Rebif 44 mikrogram i to år.
Over 4 years, the reduction in the mean exacerbation rate was 22% in patients treated with Rebif 22 micrograms, and 29% in patients treated with Rebif 44 micrograms group compared with a group of patients treated with placebo for 2 years and then either Rebif 22 or Rebif 44 micrograms for 2 years.
30%.
In a 3-year study in patients with secondary progressive multiple sclerosis (EDSS 3-6.5) with evidence of clinical progression in the preceding two years and who had not experienced relapses in the preceding 8 weeks, Rebif had no significant effect on progression of disability, but relapse rate was reduced by approximately 30%.
Hvis man delte patientgruppen i to undergrupper (med og uden attakker i 2- års perioden før studiestart), fandt man ingen effekt på førligheden hos patienter uden attakker, men hos patienter med attakker blev andelen med forværret førlighed i slutningen af studiet reduceret fra 70% (placebo) til 57% (Rebif 22 mikrogram og 44 mikrogram kombineret).
If the patient population was divided into 2 subgroups (those with and those without relapses in the 2-year period prior to study entry), there was no effect on disability in patients without relapses, but in patients with relapses, the proportion with progression in disability at the end of the study was reduced from 70% (placebo) to 57% (Rebif 22 micrograms and 44 micrograms combined).
Rebif er endnu ikke afprøvet på patienter med primær progressiv MS og bør ikke anvendes til denne patientgruppe.
Rebif has not yet been investigated in patients with primary progressive multiple sclerosis, and should not be used in such patients.
7 5. 2 Farmakokinetiske egenskaber
7 5.2 Pharmacokinetic properties
Efter intravenøs injektion hos raske frivillige forsøgspersoner udviser interferon beta- 1a et brat multi - eksponentialt fald, med et serumniveau, der er proportionalt med dosis.
In healthy volunteers after intravenous administration, interferon beta-1a exhibits a sharp multi-exponential decline, with serum levels proportional to the dose.
Den initiale halveringstid er i størrelsesordenen minutter og den terminale halveringstid er adskillige timer, med mulig tilstedeværelse af et perifert fordelingsrum.
The initial half-life is in the order of minutes and the terminal half-life is several hours, with the possible presence of a deep compartment.
Når stoffet gives subkutant eller intramuskulært forbliver serumniveauet af interferon beta lavt, men er stadig målbart i op til 12 til 24 timer efter dosis.
When administered by the subcutaneous or intramuscular routes, serum levels of interferon beta remain low, but are still measurable up to 12 to 24 hours post-dose.
Subkutane og intramuskulære injektioner af Rebif producerer ækvivalente billeder af interferon beta.
Subcutaneous and intramuscular administrations of Rebif produce equivalent exposure to interferon beta.
Efter en enkel dosis på 60 mikrogram fremkommer en maksimal spidskoncentration på omkring 6 til 10 IE/ ml, målt ved immunoassay, gennemsnitligt 3 timer efter injektionen.
Following a single 60 microgram dose, the maximum peak concentration, as measured by immunoassay, is around 6 to 10 IU/ ml, occurring on average around 3 hours after the dose.
2, 5 x for AUC).
After subcutaneous administration at the same dose repeated every 48 hours for 4 doses, a moderate accumulation occurs (about 2.5 x for AUC).
Efter en enkel dosis stiger den intracellulære aktivitet og serumaktiviteten af 2- 5A synthetase og serumkoncentrationen af beta2- mikroglobulin og neopterin inden for 24 timer og begynder at aftage inden for 2 dage.
After a single dose, intracellular and serum activity of 2-5A synthetase and serum concentrations of beta-2 microglobulin and neopterin increase within 24 hours, and start to decline within 2 days.
Intramuskulære og subkutane injektioner producerer fuldstændigt sammenlignelige responser.
Intramuscular and subcutaneous administrations produce fully superimposable responses.
Efter subkutane injektioner med den samme dosis 4 gange med 48 timers mellemrum forbliver de biologiske responser forhøjet uden nogen tegn på toleranceudvikling.
After repeated subcutaneous administration every 48 hours for 4 doses, these biological responses remain elevated, with no signs of tolerance development.
Interferon beta- 1a metaboliseres og udskilles hovedsageligt gennem lever og nyrer.
Interferon beta-1a is mainly metabolised and excreted by the liver and the kidneys.
De prækliniske data viser ingen særlig risiko for mennesker vurderet ud fra konventionelle undersøgelser af sikkerhedsfarmakologi, toksicitet efter gentagne doser og genotoksicitet.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, and genotoxicity.
Rebif er ikke blevet undersøgt for carcinogenicitet.
Rebif has not been investigated for carcinogenicity.
Et studie af fostertoksicitet hos aber viste intet bevis på reproduktive forstyrrelser.
A study on embryo/ foetal toxicity in monkeys showed no evidence of reproductive disturbances.
Ud fra observationer med andre alfa - og beta- interferoner kan en øget risiko for abort ikke udelukkes.
Based on observations with other alpha and beta interferons, an increased risk of abortions cannot be excluded.
Der er ingen tilgængelige informationer om effekten af interferon beta- 1a på den mandlige fertilitet.
No information is available on the effects of the interferon beta-1a on male fertility.
Mannitol Poloxamer 188 L- methionin Benzylalkohol Natriumacetat Eddikesyre til justering af pH Natriumhydroxid til justering af pH Vand til injektionsvæsker.
Mannitol Poloxamer 188 L-methionine Benzyl alcohol Sodium acetate Acetic acid for pH adjustment Sodium hydroxide for pH adjustment Water for injections
8 6. 4 Særlige opbevaringsforhold
8 6.4 Special precautions for storage
Opbevares i køleskab (2 °C – 8 °C) så langt fra fryserummet som muligt.
Store in a refrigerator (2°C – 8°C) away from the cooling element.
1 ml type 1 glas injektionssprøjte med en rustfri stålkanyle indeholder 0, 5 ml opløsning.
One ml type 1glass syringe, with a stainless steel needle, containing 0.5 ml solution.
Injektionsvæsken i fyldte injektionssprøjter er klar til brug.
The solution for injection in a pre-filled syringe is ready for use.
Injektionssprøjterne kan også anvendes med en egnet antoinjektor.
It may also be administered with a suitable auto-injector.
Kan kun anvendes til én patient.
For single use only.
Der må kun anvendes en klar opløsning uden partikler og synlig tegn på forringelse.
Only clear to opalescent solution without particles should be used and without visible signs of deterioration.
SERONO EUROPE Limited 56, Marsh Wall London E14 9TP Storbritannien
Serono Europe Limited 56, Marsh Wall London E14 9TP United Kingdom
MARKEDSFØRINGSTILLADELSESNUMRER (NUMRE)
MARKETING AUTHORISATION NUMBERS
4. maj 1998 Dato for første fornyelse:
4th May 1998 Date of first renewal:
4. maj 2003 Dato for sidste fornyelse:
4th May 2003 Date of latest renewal:
20. maj 2008
20th May 2008
Rebif 44 mikrogram injektionsvæske, opløsning i en fyldt injektionssprøjte.
Rebif 44 micrograms solution for injection in pre-filled syringe
Hver fyldt injektionssprøjte (0, 5 ml) indeholder 44 mikrogram (12 MIE *) interferon beta- 1a **.
Each pre-filled syringe (0.5 ml) contains 44 micrograms (12 MIU*) of interferon beta-1a**.
Produceret i kinesiske hamsteres ovarieceller (CHO- K1) ved rekombinant DNA- teknologi.
* Million International Units, measured by cytopathic effect (CPE) bioassay against the in house IFN beta-1a standard which is calibrated against the current international NIH standard (GB-23-902-531). ** produced in Chinese hamster ovary Cells (CHO-K1) by recombinant DNA technology.
Rebif er indikeret til behandling af patienter med attakvis multipel sklerose.
Rebif is indicated for the treatment of relapsing multiple sclerosis.
I kliniske studier, var dette karakteriseret ved to eller flere akutte attakker i de foregående to år (se punkt 5. 1)
In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1).
5. 1.
Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapsing activity (see section 5.1).
En lavere dosis på 22 mikrogram tre gange ugentlig ved subkutan injektion, anbefales til patienter som ikke kan tolerere den højere dosis ifølge behandlende læge.
A lower dose of 22 micrograms, also given three times per week by subcutaneous injection, is recommended for patients who cannot tolerate the higher dose in view of the treating specialist.
Ved opstart af Rebif- behandlingen skal dosis øges gradvist med henblik på udvikling af takyfylakse, og dermed en reduktion af bivirkningerne.
When first starting treatment with Rebif, dose should be gradually escalated in order to allow tachyphylaxis to develop thus reducing adverse reactions.
På nuværende tidspunkt vides det ikke, hvor lang behandlingsperioden bør være.
10 At the present time, it is not known for how long patients should be treated.
Derefter tager den behandlende læge en individuel beslutning om langtidsbehandling.
It is recommended that patients should be evaluated at least every second year in the 4-year period after initiation of treatment with Rebif and a decision for longer term treatment should then be made on an individual basis by the treating
Begrænsede publicerede data tyder dog på, at bivirkningsprofilen hos unge fra 12 til 16 år, der behandles med Rebif 22 mikrogram subkutant tre gange om ugen, er tilsvarende den, der ses hos voksne.
However, limited published data suggest that the safety profile in adolescents from 12 to 16 years of age receiving Rebif 22 micrograms subcutaneous three times per week is similar to that seen in adults.
Influenzalignende symptomer i forbindelse med injektion af interferon beta- 1a, kan virke stressende på patienter med hjertesygdomme.
Symptoms of the flu-like syndrome associated with interferon beta-1a therapy may prove stressful to patients with cardiac conditions.
For at minimere risikoen for nekrose på injektionsstedet anbefales patienter at: • bruge en aseptisk injektionsteknik, • skifte injektionssted ved hver dosering
To minimise the risk of injection site necrosis patients should be advised to: • use an aseptic injection technique, • rotate the injection sites with each dose.
Hvis patienten har adskillige læsioner, skal Rebif behandlingen ophøre, indtil der har fundet opheling sted.
If the patient has multiple lesions, Rebif should be discontinued until healing has occurred.
I kliniske forsøg med Rebif var en asymptomatisk forhøjelse af hepatisk transaminase (især ALT) almindelig, og 1- 3% af patienterne fik forhøjelser af hepatisk transaminase fem gange over den øvre normalgrænse (ULN).
11 In clinical trials with Rebif, asymptomatic elevations of hepatic transaminases (particularly alanine aminotransferase (ALT)) were common and 1-3% of patients developed elevations of hepatic transaminases above 5 times the upper limit of normal (ULN).
Hvis ALT stiger til mere end fem gange
In the absence of clinical symptoms, serum ALT levels should be monitored prior to the start of therapy, at months 1, 3 and 6 on therapy and periodically thereafter.
11 den øvre normalgrænse, bør det overvejes at reducere dosis af Rebif og herefter trappe langsomt op, når enzymniveauet er normaliseret.
Dose reduction of Rebif should be considered if ALT rises above 5 times the ULN, and gradually re-escalated when enzyme levels have normalized.
Behandlingen med Rebif bør stoppes, hvis der forekommer gulsot eller andre kliniske symptomer på leverpåvirkning (se 4. 8 Bivirkninger).
Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (see section 4.8).
Rebif, ligesom andre interferon- beta- præparater, har mulighed for at fremkalde alvorlige leverskader (se 4. 8 Bivirkninger) inklusive akut hepatisk svigt.
Rebif, like other interferons beta, has a potential for causing severe liver injury (see section 4.8) including acute hepatic failure.
Der er ikke blevet identificeret specifikke risikofaktorer.
No specific risk factors have been identified.