natgillin/translations-raw huggingface dataset:
Udvalget anbefalede udstedelse af markedsføringstilladelse for Avonex.
The Committee recommended that Avonex be given marketing authorisation.
2/ 3 Avonex blev oprindeligt godkendt under ” særlige omstændigheder ”, da der på godkendelsestidspunktet af videnskabelige årsager ikke forelå tilstrækkelige oplysninger, da sygdommen er sjælden.
2/ 3 Other information about Avonex:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Avonex den 13. marts 1997.
The European Commission granted a marketing authorisation valid throughout the European Union for Avonex on 13 March 1997.
Markedsføringstilladelsen blev fornyet den 13. marts 2002 og den 13. marts 2007.
The marketing authorisation was renewed on 13 March 2002 and 13 March 2007.
Den fuldstændige EPAR for Avonex findes her.
The full EPAR for Avonex is available here.
Hvert BIO- SET hætteglas indeholder 30 mikrogram (IE) interferon beta- 1a.
Each BIO-SET vial contains 30 micrograms (6 million IU) of interferon beta-1a.
Efter rekonstitution med solvens (vand til injektioner) indeholder hætteglasset 1, 0 ml opløsning.
Following reconstitution with the solvent (water for injections) the vial contains 1.0 ml of solution.
Ifølge Verdenssundhedsorganisationen WHO International Standard for Interferon, indeholder 30 mikrogram AVONEX 6 millioner IE antiviral aktivitet.
Using the World Health Organisation (WHO) International Standard for Interferon, 30 micrograms of AVONEX contains 6 million IU of antiviral activity.
Hætteglasset indeholder en hvid til off- white tablet.
The vial contains a white to off-white cake.
AVONEX bremser handikapudviklingen og reducerer antallet af attakker.
In clinical trials, this was characterised by two or more acute exacerbations (relapses) in the previous three years without evidence of continuous progression between relapses; AVONEX slows the progression of disability and decreases the frequency of relapses.
5. 1)
• Patients with a single demyelinating event with an active inflammatory process, if it is severe enough to warrant treatment with intravenous corticosteroids, if alternative diagnoses have been excluded, and if they are determined to be at high risk of developing clinically definite multiple sclerosis (see section 5.1).
6. 6).
The recommended dosage for the treatment of relapsing MS is 30 micrograms (1 ml solution), administered by intramuscular (IM) injection once a week (see section 6.6).
Der er ikke udført formaliserede kliniske forsøg eller farmakokinetiske studier blandt børn eller unge.
No formal clinical trials or pharmacokinetic studies have been conducted in children or adolescents.
Imidlertid antyder begrænsede publicerede data, at sikkerhedsprofilen hos unge fra 12 til 16 år, der modtager AVONEX 30 mikrogram i. m. én gang om ugen, ligner den, der ses hos voksne.
However, limited published data suggest that the safety profile in adolescents
2 Der er ingen information om brugen af AVONEX hos børn under 12 år, og derfor bør AVONEX ikke anvendes til denne population.
There is no information on the use of AVONEX in children under 12 years of age and therefore AVONEX should not be used in this population.
Kliniske studier omfattede ikke et tilstrækkeligt antal patienter i alderen 65 år og derover til at påvise, hvorvidt de responderer forskelligt fra yngre patienter.
Clinical studies did not include a sufficient number of patients aged 65 and over to determine whether they respond differently than younger patients.
5. 3).
The intramuscular injection site should be varied each week (see section 5.3).
Før injektionen og i op til 24 timer efter hver injektion, anbefales det at tage et analgetikum med antipyretisk virkning for at begrænse de influenza- lignende symptomer, der opstår i forbindelse med injektion af AVONEX.
Prior to injection and for an additional 24 hours after each injection, an antipyretic analgesic is advised to decrease flu-like symptoms associated with AVONEX administration.
4. 6).
- Initiation of treatment in pregnancy (see section 4.6).
- Patienter med en anamnese med overfølsomhed overfor naturligt eller rekombinant interferon- ß,
- Patients with a history of hypersensitivity to natural or recombinant interferon -ß, human
humant albumin eller overfor et eller flere af hjælpestofferne.
albumin or to any excipients.
4. 4 og 4. 8).
- Patients with current severe depression and/ or suicidal ideation (see sections 4.4 and 4.8).
Dette gælder især patienter, der tidligere har haft selvmordstanker (se pkt.
AVONEX should be administered with caution to patients with previous or current depressive disorders, in particular to those with antecedents of suicidal ideation (see section 4.3).
Patienterne bør rådes til straks at rapportere ethvert tegn på depression og/ eller selvmordstanker til den behandlende læge.
Patients should be advised to immediately report any symptoms of depression and/ or suicidal ideation to their prescribing physician.
4. 3 og 4. 8).
Cessation of therapy with AVONEX should be considered (see also sections 4.3 and 4.8).
4. 5 og 4. 8).
AVONEX should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled with anti-epileptics (see sections 4.5 and 4.8).
Der bør udvises forsigtighed ved brug af AVONEX til patienter med stærkt nedsat nyre - og leverfunktion, og til patienter med stærkt nedsat knoglemarvsfunktion.
Caution should be used and close monitoring considered when administering AVONEX to patients with severe renal and hepatic failure and to patients with severe myelosuppression.
4. 8).
Hepatic injury including elevated serum hepatic enzyme levels, hepatitis, autoimmune hepatitis and hepatic failure has been reported with interferon beta in post-marketing (see section 4.8).
Muligheden for additive virkninger af lægemidler eller andre hepatotoksiske stoffer (f. eks. alkohol) er ikke blevet påvist.
The potential of additive effects from multiple medicinal products or other hepatotoxic agents (e. g. alcohol) has not been determined.
Patienter med hjertesygdomme, såsom angina, kongestivt hjertesvigt eller arytmier, bør nøje observeres for forværring af deres kliniske tilstand under behandling med AVONEX.
3 Patients with cardiac disease, such as angina, congestive heart failure or arrhythmia, should be closely monitored for worsening of their clinical condition during treatment with AVONEX.
3 Influenza- lignende symptomer, der kan forekomme under en behandling med AVONEX, kan være belastende for patienter med underliggende hjerteproblemer.
Flu-like symptoms associated with AVONEX therapy may prove stressful to patients with underlying cardiac conditions.
Hos nogle af disse patienter kan antistofferne reducere aktiviteten af interferon beta- 1a in vitro (neutraliserende antistoffer).
The antibodies of some of those patients reduce the activity of interferon beta-1a in vitro (neutralising antibodies).
8% danner neutraliserende antistoffer.
Data from patients treated up to two years with AVONEX suggests that approximately 8% develop neutralising antibodies.
Anvendelsen af skiftende metoder til at måle serum- antistoffer mod interferoner begrænser muligheden for at sammenligne anti- geniciteten mellem de forskellige præparater.
The use of various assays to detect serum antibodies to interferons limits the ability to compare antigenicity among different products.
Påvirkningen af den del af lever- metaboliseringen, der er afhængig af cytokrom P- 450, er undersøgt hos aber efter indgift af høje doser AVONEX, og der blev ikke observeret ændringer i leverens evne til metabolisering.
The effect of high-dose AVONEX administration on P450-dependent metabolism in monkeys was evaluated and no changes in liver metabolising capabilities were observed.
Der bør udvises forsigtighed, når AVONEX gives i kombination med lægemidler, der har et snævert terapeutisk index og hvis clearance overvejende er afhængig af cytokrom P- 450 systemet, f. eks. antiepileptika og visse klasser af antidepressiva.
Caution should be exercised when AVONEX is administered 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. 3).
Initiation of treatment is contraindicated during pregnancy (see section 4.3).
Kvinder i den fødedygtige alder bør benytte passende antikonception.
Women of child-bearing potential have to take appropriate contraceptive measures.
5. 3).
If the patient becomes pregnant or plans to become pregnant while taking AVONEX she should be informed of the potential hazards and discontinuation of therapy should be considered (see section 5.3).
4 Amning
4 Lactation
Det vides ikke, om AVONEX udskilles i modermælken.
It is not known whether AVONEX is excreted in human milk.
På grund af risikoen for alvorlige bivirkninger hos ammede børn, bør det besluttes enten at stoppe amningen eller at afbryde behandlingen med AVONEX.
Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue breast-feeding or AVONEX therapy.
Der er ikke foretaget undersøgelser af virkningen af AVONEX på evnen til at føre motorkøretøj eller betjene maskiner.
No studies on the effects of AVONEX on the ability to drive and use machines have been performed.
4. 8).
Central nervous system-related adverse reactions may have a minor influence on the ability to drive and use machines in susceptible patients (see section 4.8).
Den største hyppighed af bivirkninger forbundet med AVONEX- behandlingen er relateret til influenza- lignende symptomer.
The highest incidence of adverse reactions associated with AVONEX therapy is related to flu-like symptoms.
De hyppigst rapporterede influenza- lignende symptomer er muskelsmerter, feber, kulderystelser, svedudbrud, asteni, hovedpine og kvalme.
The most commonly reported flu-like symptoms are myalgia, fever, chills, sweating, asthenia, headache and nausea.
Influenza- lignende symptomer har en tendens til at være mest fremtrædende i starten af en behandling og falder i hyppighed ved fortsat behandling.
Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment.
Forbigående episoder med hypertoni og/ eller svær muskelsvaghed, der besværliggør frivillige bevægelser, kan forekomme når som helst under behandlingen.
Transient episodes of hypertonia and/ or severe muscular weakness that prevent voluntary movements may occur at any time during treatment.
I nogle tilfælde associeres disse symptomer til influenza- lignende symptomer.
In some cases these symptoms are associated with flu-like symptoms.
Bivirkningernes hyppighed udtrykkes i patient- år jævnfør nedenstående kategorier:
The frequencies of adverse reactions are expressed in patient-years, according to the following categories:
Meget almindelig (≥1/ 10 patient- år); Almindelig (≥1/ 100 til, < 1/ 10 patient- år); Ikke almindelig (≥1/ 1. 000 til, < 1/ 100 patient- år); Sjælden (≥1/ 10. 000 til, < 1/ 1. 000 patient- år); Meget sjælden (< 1/ 10. 000 patient- år); Ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Very common (≥ 1/ 10 patient-years); Common (≥ 1/ 100 to < 1/ 10 patient-years); Uncommon (≥ 1/ 1, 000 to < 1/ 100 patient-years); Rare (≥ 1/ 10, 000 to < 1/ 1,000 patient-years); Very rare (< 1/ 10,000 patient-years); Not known (cannot be estimated from the available data).
Patient- tid er summen af individuelle tidsenheder, hvor patienten i studiet er blevet eksponeret for AVONEX, inden patienten oplevede bivirkningen.
Patient-time is the sum of individual units of time that the patient in the study has been exposed to AVONEX before experiencing the adverse reaction.
For eksempel, 100 person- år kunne observeres hos 100 patienter, som var i behandling i ét år eller hos 200 patienter, som var i behandling i et halvt år.
For example, 100 person-years could be observed in 100 patients who were on treatment for one year or in 200 patients who were on treatment for half a year.
5 Undersøgelser
5 Investigations
nedsat trombocyttal
platelet count decreased
4. 4), palpitationer, arytmi, takykardi
cardiomyopathy, congestive heart failure (see section 4.4), palpitations, arrhythmia, tachycardia
meget almindelig almindelig
very common
hovedpine2 muskelspasticitet, hypoæstesi neurologiske symptomer, synkope3,
muscle spasticity, hypoesthesia
hypertoni, svimmelhed, paræstesi, krampeanfald, migræne
neurological symptoms, syncope3, hypertonia, dizziness, paraesthesia, seizures, migraine
rhinorrhoea
rhinorrhoea
dyspnø
dyspnoea
udslæt, øget svedafsondring, kontusion
rash, sweating increased, contusion
alopeci
alopecia
angioneurotisk ødem, pruritus, vesikulært udslæt, urticaria, forværring af psoriasis
angioneurotic oedema, pruritus, rash vesicular, urticaria, aggravation of psoriasis
6 Knogler, led, muskler og bindevæv
6 Musculoskeletal and connective tissue disorders
muskelkrampe, nakkesmerte, myalgi 2, artralgi, smerte i ekstremiteter, rygsmerte, muskelstivhed, muskel/ knoglestivhed
muscle cramp, neck pain, myalgia2, arthralgia, pain in extremity, back pain, muscle stiffness, musculoskeletal stiffness
anoreksi
anorexia
hedeture
flushing
vasodilatation
vasodilatation
meget almindelig
very common
influenzalignende symptomer, pyreksi 2, kulderystelser2, svedudbrud2
flu-like symptoms, pyrexia2, chills2, sweating2
smerte ved injektionssted, erytem ved injektionssted, blå mærker ved injektionssted, asteni2, smerte, træthed2, ubehag, natlige svedudbrud
injection site pain, injection site erythema,
ikke almindelig
common
brændende fornemmelse ved injektionssted
injection site bruising, asthenia2, pain, fatigue2, malaise, night sweats
ikke kendt
injection site burning uncommon injection site reaction, injection site not known
reaktion ved injektionssted, inflammation ved injektionssted, cellulitis ved injektionssted1, nekrose ved injektionssted, blødning ved injektionssted, brystsmerte
inflammation, injection site cellulitis1, injection site necrosis, injection site bleeding, chest pain
7 Lever og galdeveje
7 Hepatobiliary disorders
4. 4), hepatitis, autoimmun hepatitis
hepatic failure (see section 4.4), hepatitis, autoimmune hepatitis
4. 4), insomni
depression (see section 4.4), insomnia
1 Der er rapporter om reaktioner ved injektionsstedet, inklusive smerte, inflammation og meget sjældne tilfælde af absces eller cellulitis, der kan kræve kirurgisk indgriben.
1 Injection site reactions including pain, inflammation and very rare cases of abscess or cellulitis that may require surgical intervention have been reported.
2 Hyppigheden af forekomsten er højere ved behandlingens start.
2 The frequency of occurrence is higher at the beginning of treatment.
Normalt er det en enkeltstående episode, der sædvanligvis forekommer ved behandlingens start og ikke optræder igen ved efterfølgende injektioner.
3 A syncope episode may occur after AVONEX injection, it is normally a single episode that usually appears at the beginning of the treatment and does not recur with subsequent injections.
Farmakoterapeutisk klassifikation: interferoner, ATC- kode:
Interferons, ATC code:
L03 AB07
L03 AB07.
Interferonerne alfa og beta klassificeres som type I- interferoner, og interferon gamma er et type II- interferon.
Interferons alpha and beta are classified as Type I interferons and interferon gamma is a Type II interferon.
Naturlig interferon beta og AVONEX (interferon beta- 1a) er glykosylerede og har en enkelt N- bundet kompleks kulhydratfraktion.
Natural interferon beta and AVONEX (interferon beta-1a) are glycosylated and have a single N-linked complex carbohydrate moiety.
Denne binding starter en kompleks kaskade af intracellulære reaktioner, der fører til ekspression af talrige interferon- inducerede genprodukter og markører.
This binding initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers.
Disse forbindelser omfatter MHC klasse I, Mx protein, 2 '/ 5' - oligoadenylat syntetase, β2- mikroglobulin og neopterin.
These include MHC Class I, Mx protein, 2’ / 5’ -oligoadenylate synthetase, β 2-microglobulin, and neopterin.
Nogle af disse forbindelser er blevet målt i serum og i cellulære fraktioner af blod fra patienter behandlet med 8 AVONEX.
Some of these products have been 8 measured in the serum and cellular fractions of blood collected from patients treated with AVONEX.
Virkninger af frysetørret AVONEX i behandlingen af patienter med MS blev påvist i en placebo- kontrolleret afprøvning med 301 patienter med recidiverende MS (AVONEX n=158, placebo n=143) defineret som mindst 2 attakker inden for de seneste 3 år eller mindst ét attak pr. år, hvis sygdomsforløbet havde været kortere end 3 år ved studiestart.
The effects of lyophilised AVONEX in the treatment of MS were demonstrated in a placebo- controlled study of 301 patients (AVONEX n=158, placebo n=143) with relapsing MS characterised by at least 2 exacerbations in the previous 3 years or at least one exacerbation per year prior to entry when the duration of the disease was less than 3 years.
Patienter med EDSS på 1, 0 – 3, 5 ved studiestart blev inkluderede.
Patients with an EDSS of 1.0 to 3.5 at entry were included in the clinical trial.
150 AVONEX- behandlede patienter gennemførte behandlingen i ét år, og 85 patienter gennemførte behandlingen i to år.
150 AVONEX-treated patients completed one year on study and 85 completed two years on study.
I undersøgelsen var den kumulative del af patienter, som udviklede progression af invaliditeten (målt med “ Kaplan- Meier life table ” analyse) ved slutningen af de to år 35% for patienter i placebo- gruppen og 22% for patienter i AVONEX- gruppen.
In the study, the cumulative percentage of patients who developed disability progression (by Kaplan-Meier life table analysis) by the end of two years was 35% for placebo-treated patients and 22% for AVONEX-treated patients.
Progression af invaliditeten blev målt som en stigning i Expanded Disability Status Scale (EDSS) på 1, 0 point, bestående over mindst seks måneder.
Disability progression was measured as an increase in the Expanded Disability Status Scale (EDSS) of 1.0 point, sustained for at least six months.
Et dobbeltblindt randomiseret dosis- sammenligningsstudie med 802 patienter med recidiverende MS (AVONEX 30 mikrogram n=402, AVONEX 60 mikrogram n=400) har vist, at der ikke er signifikante forskelle eller trends mellem 30 mikrogram og 60 mikrogram doseringerne af AVONEX på kliniske og generelle MRI parametre.
A double-blind randomised dose comparison study of 802 relapsing MS patients (AVONEX 30 micrograms n=402, AVONEX 60 micrograms n=400) has shown no statistically significant differences or trends between the 30 micrograms and the 60 micrograms doses of AVONEX in clinical and general MRI parameters.
Den anslåede risiko for et nyt anfald var 50% over tre år og 39% over to år i placebo- gruppen og 35% (tre år) og 21% (to år) i AVONEX- gruppen.
The estimated risk of a second event was 50% in three years and 39% in two years in the placebo group and 35% (three years) and 21% (two years) in the AVONEX group.
I en post- hoc analyse havde patienter med en baseline MRI med mindst én Gd- forstærket læsion og ni T2 læsioner en to- årig risiko på 56% for at få et nyt attak i placebo- gruppen og 21% i gruppen, der blev behandlet med AVONEX.
In a post-hoc analysis, those patients with a baseline MRI with at least one Gd-enhancing lesion and nine T2 lesions had a two-year risk of suffering a second event of 56% in the placebo group and 21% in the AVONEX treatment group.
Imidlertid er virkningen af tidlig behandling med AVONEX uvis selv i denne høj- risiko undergruppe, da studiet hovedsageligt var designet til at bestemme tidspunktet for et nyt anfald frem for langtidsudviklingen af sygdommen.
However, the impact of early treatment with AVONEX is unknown even in this high-risk subgroup as the study was mainly designed to assess the time to the second event rather than the long term evolution of the disease.
Der findes endnu ikke nogen veletableret definition af høj- risiko patienter, men en konservativ holdning vil være at anvende mindst ni T2 hyperintense læsioner på den første MRI efterfulgt af mindst én ny T2 eller én ny Gd- forstærket læsion på den efterfølgende MRI foretaget minimum tre måneder efter den første.
Furthermore, for the time-being there is no well established definition of a high risk patient although a more conservative approach is to accept at least nine T2 hyperintense lesions on the initial scan and at least one new T2 or one new Gd-enhancing lesion on a follow-up scan taken at least three months after the initial scan.
Den farmakokinetiske profil af AVONEX er blevet undersøgt indirekte med et forsøg, der måler den antivirale aktivitet af interferon.
The pharmacokinetic profile of AVONEX has been investigated indirectly with an assay that measures interferon antiviral activity.
Denne målemetode begrænses af, at den er følsom for interferon, men mangler specificiteten for interferon beta.
This assay is limited in that it is sensitive for interferon but lacks specificity for interferon beta.
Alternative prøveteknikker er ikke tilstrækkeligt følsomme.
Alternative assay techniques are not sufficiently sensitive.
Efter en intramuskulær injektion af AVONEX når det antivirale aktivitetsniveau i serum et toppunkt mellem fem og femten timer efter injektionen, og det aftager med en halveringstid på ca. ti timer.
Following intramuscular administration of AVONEX, serum antiviral activity levels peak between 5 and 15 hours post-dose and decline with a half-life of approximately 10 hours.
40%.
With appropriate adjustment for the rate of absorption from the injection site, the calculated bioavailability is approximately 40%.
Den intramuskulære biotilgængelighed er 3 gange større end den subkutane biotilgængelighed.
Intramuscular bioavailability is three-fold higher than subcutaneous bioavailability.
Subkutan indgift kan derfor ikke erstatte intramuskulær indgift.
Subcutaneous administration cannot be substituted for intramuscular administration.
9 5. 3 Prækliniske sikkerhedsdata
9 5.3 Preclinical safety data
Carcinogenicitet:
Carcinogenesis:
Der findes ingen carcinogenicitetsdata for interferon beta- 1a, hverken for dyr eller mennesker.
No carcinogenicity data for interferon beta-1a are available in animals or humans.
Kronisk toksicitet:
Chronic Toxicity:
I et 26- ugers gentagen dosis toksicitetsstudie i rhesusaber med intramuskulær administration én gang ugentlig, og givet i kombination med en anden immunmodulerende substans, et anti- CD40 ligand monoklonalt antistof, blev der ikke påvist noget immunrespons over for interferon- beta- 1a, og der var ingen tegn på toksicitet.
In a 26-week, repeated-dose toxicity study in rhesus monkeys by intramuscular route once per week, administered in combination with another immunomodulating agent, an anti CD40 ligand monoclonal antibody, no immune response toward interferon beta-1a and no signs of toxicity were demonstrated.
Lokal tolerance: intramuskulær irritation er ikke evalueret hos forsøgsdyr efter gentagne intramuskulære injektioner på samme injektionssted.
Intramuscular irritation has not been evaluated in animals following repeated administration to the same injection site.
Mutagenicitet:
Mutagenesis:
Begrænsede, men relevante tests for mutagenicitet er gennemført.
Limited but relevant mutagenesis tests have been carried out.
Nedsat fertilitet:
Impairment of Fertility:
Hos rhesusaber er der foretaget undersøgelser over fertilitet og fosterudvikling med et interferon, der er beslægtet med interferon beta- 1a.
Fertility and developmental studies in rhesus monkeys have been carried out with a related form of interferon beta-1a.
Lignende dosis- afhængige virkninger på reproduktionen er også observeret med andre former af alfa og beta interferoner.
Similar reproductive dose-related effects have also been observed with other forms of alpha and beta interferons.