natgillin/translations-raw huggingface dataset:
Brugen af TYSABRI er blevet associeret med en øget risiko for PML.
Use of TYSABRI has been associated with an increased risk of PML.
Inden behandling med TYSABRI påbegyndes, skal en nylig gennemført (sædvanligvis inden for 3 måneder) MR- scanning være tilgængelig.
Before initiation of treatment with TYSABRI, a recent (usually within 3 months) Magnetic Resonance Image should be available.
Patienter skal med regelmæssige intervaller monitoreres for nye neurologiske symptomer, for forværring i bestående neurologiske symptomer og/ eller tegn, der kunne tyde på PML.
Patients must be monitored at regular intervals for any new or worsening neurological symptoms or signs that may be suggestive of PML.
Hvis der er mistanke om PML, skal yderligere administration suspenderes, indtil PML er blevet udelukket.
If PML is suspected, further dosing must be suspended until PML has been excluded.
Lægen bør evaluere patienten for at fastslå, om symptomerne er tegn på neurologisk dysfunktion, og i så fald, hvorvidt disse symptomer er typiske for MS, eller om de kan være tegn på PML.
The clinician should evaluate the patient to determine if the symptoms are indicative of neurological dysfunction, and if so, whether these symptoms are typical of MS or possibly suggestive of PML.
Hvis der er tvivl, bør yderligere evaluering overvejes, herunder MR- scanning helst med kontrast (sammenlignes med MR inden behandlingen), analyse af cerebrospinalvæsken for JC DNA samt gentagen neurologisk vurdering, som beskrevet i informationen til lægen og i behandlingsvejledningen (se afsnittet Rådgivende vejledning).
If any doubt exists, further evaluation, including MRI scan preferably with contrast (compared with pre- treatment MRI), CSF testing for JC Viral DNA and repeat neurological assessments, should be considered as described in the Physician Information and Management Guidelines (see educational guidance).
Så snart lægen har udelukket PML (om nødvendigt ved gentagelse af kliniske undersøgelser, scanning og/ eller laboratorieundersøgelser, hvis der stadig er klinisk mistanke om PML), kan behandling med natalizumab genoptages.
Once the clinician has excluded PML (if necessary, by repeating clinical, imaging and/ or laboratory investigations if clinical suspicion remains), dosing of natalizumab may resume.
Lægen bør være særlig på vagt over for symptomer, der kunne tyde på PML, og som patienten muligvis ikke lægger mærke til (f. eks. kognitive eller psykiatriske symptomer).
The physician should be particularly alert to symptoms suggestive of PML that the patient may not notice (e. g. cognitive or psychiatric symptoms).
Efter genetablering af immunsystemet hos immunkompromitterede patienter med PML har man observeret stabilisering eller bedring hos patienterne (se pkt.
Following reconstitution of the immune system in immunocompromised patients with PML, stabilisation or improved outcome has been seen (see section 5.2).
Man ved ikke, om tidlig påvisning af PML og suspendering af TYSABRI kan føre til lignende stabilisering eller bedring.
It remains unknown if early detection of PML and suspension of TYSABRI therapy may lead to similar stabilisation or improved outcome.
Andre opportunistiske infektioner
Other Opportunistic Infections
Hos patienter uden disse co- morbiditeter kan en øget risiko for andre opportunistiske infektioner i forbindelse med brug af TYSABRI dog ikke udelukkes på nuværende tidspunkt.
Other opportunistic infections have been reported with use of TYSABRI, primarily in patients with Crohn’ s disease who were immunocompromised or where significant co-morbidity existed, however increased risk of other opportunistic infections with use of TYSABRI in patients without these co- morbidities cannot currently be excluded.
4. 8).
Opportunistic infections were also detected in MS patients treated with TYSABRI as a monotherapy (see section 4.8).
Ordinerende læger bør være opmærksomme på muligheden for, at der kan optræde andre opportunistiske infektioner under TYSABRI behandlingen og bør inkludere disse i differential diagnostiseringen af infektioner, der optræder hos TYSABRI behandlede patienter.
Prescribers should be aware of the possibility that other opportunistic infections may occur during TYSABRI therapy and should include them in the differential diagnosis of infections that occur in TYSABRI-treated patients.
Hvis der er mistanke om opportunistisk infektion skal behandling med TYSABRI suspenderes, indtil mistanken er afkræftet ved yderligere evalueringer.
If an opportunistic infection is suspected, dosing with TYSABRI is to be suspended until such infections can be excluded through further evaluations.
Hvis en patient, der behandles med TYSABRI, udvikler en opportunistisk infektion, skal behandlingen med TYSABRI afbrydes permanent.
If a patient receiving TYSABRI develops an opportunistic infection, dosing of TYSABRI must be permanently discontinued.
4 Læger skal diskutere fordele og risici ved TYSABRI behandlingen med patienten og de skal give patienten et patientinformationskort.
Physicians must discuss the benefits and risks of TYSABRI therapy with the patient and provide them with a Patient Alert Card.
Lægerne bør informere patienterne om vigtigheden af at behandlingen ikke afbrydes, især i de første måneder af behandlingen (se Overfølsomhed).
4 Physicians should counsel patients on the importance of uninterrupted dosing, particularly in the early months of treatment (see hypersensitivity).
Overfølsomhedsreaktioner er blevet associeret med TYSABRI, herunder alvorlige systemiske reaktioner (se sektion 4. 8).
Hypersensitivity reactions have been associated with TYSABRI, including serious systemic reactions (see section 4.8).
Risikoen for overfølsomhed var størst i forbindelse med de første infusioner og hos patienter re- eksponeret for TYSABRI efter en indledende kortvarig eksponering (en eller to infusioner) og en længerevarende periode (tre måneder eller mere) uden behandling.
The risk for hypersensitivity was greatest with early infusions and in patients re-exposed to TYSABRI following an initial short exposure (one or two infusions) and extended period (three months or more) without treatment.
Patienterne skal observeres under infusionen og i 1 time efter at infusionen er tilendebragt (se sektion 4. 8).
Patients are to be observed during the infusion and for 1 hour after the completion of the infusion (see section 4.8).
Samtidig eller tidligere behandling med immunosuppressive midler
Concurrent or prior treatment with immunosuppressants
4. 3).
Concurrent use of these agents with TYSABRI may increase the risk of infections, including opportunistic infections, and is contraindicated (see section 4.3).
Patienter med en behandlingsanamnese med immunosuppresive lægemidler, herunder cyclophosphamid og mitoxantron, kan opleve langvarig immunosuppression og kan derfor have øget risiko for at udvikle PML.
Patients with a treatment history of immunosuppressant medications, including cyclophosphamide and mitoxantrone, may experience prolonged immunosuppression and therefore may be at increased risk for PML.
Der bør udvises forsigtighed hos patienter, som tidligere har modtaget immunosuppresive midler, så der gives tilstrækkelig tid til, at immunsystemets funktion genetableres.
Care should be taken with patients who have previously received immunosuppressants to allow sufficient time for immune function recovery to occur.
Læger skal evaluere hvert enkelt tilfælde for at fastslå, hvorvidt der er tegn på en immunkompromitteret tilstand, inden behandling med TYSABRI påbegyndes (se pkt 4. 3).
Physicians must evaluate each individual case to determine whether there is evidence of an immunocompromised state prior to commencing treatment with TYSABRI (see section 4.3).
I kliniske fase III studier hos MS- patienter var en samtidig kort kortikosteroid behandling af attakker ikke associeret med en øget hyppighed af infektioner.
In Phase 3 MS clinical trials, concomitant treatment of relapses with a short course of corticosteroids was not associated with an increased rate of infection.
Korte kortikosteroid behandlinger kan anvendes i kombination med TYSABRI.
Short courses of corticosteroids can be used in combination with TYSABRI.
4. 8).
In these cases the presence of antibodies should be evaluated and if these remain positive in a confirmatory test after 6 weeks, treatment should be discontinued, as persistent antibodies are associated with a substantial decrease in efficacy of TYSABRI and an increased incidence of hypersensitivity reactions (see section 4.8).
Da patienter, der har fået en indledende kortvarig eksponering for TYSABRI, og derefter havde en længerevarende periode uden behandling, er mere udsatte for overfølsomhed ved readministration, bør tilstedeværelsen af antistoffer evalueres, og hvis disse forbliver positive ved en bekræftende test efter 6 uger, bør behandling ikke genoptages.
Since patients who have received an initial short exposure to TYSABRI and then had an extended period without treatment are more at risk for hypersensitivity upon redosing, the presence of antibodies should be evaluated and if these remain positive in a confirmatory test after 6 weeks treatment should not be resumed.
Hepatiske bivirkninger
Hepatic Events
5 Spontane, alvorlige bivirkninger med leverskade er blevet rapporteret i post- marketing fasen.
Spontaneous serious adverse reactions of liver injury have been reported during the post marketing phase.
I nogle tilfælde forekom reaktionen igen, når TYSABRI blev re- introduceret.
Some patients with a past
Nogle patienter, som tidligere har haft en abnorm levertest, har oplevet en forværring af de abnorme leverværdier, mens de fik TYSABRI.
5 medical history of an abnormal liver test have experienced an exacerbation of abnormal liver test while on TYSABRI.
Hvis det besluttes at standse behandlingen med natalizumab, bør lægen erindre, at natalizumab forbliver i blodet og har farmakodynamiske virkninger (f. eks. forhøjet lymfocyttal) i cirka 12 uger efter den sidste dosisindgift.
If a decision is made to stop treatment with natalizumab, the physician needs to be aware that natalizumab remains in the blood, and has pharmacodynamic effects (e. g increased lymphocyte counts) for approximately 12 weeks following the last dose.
For lægemidler som interferon og glatiramer acetat blev samtidig eksponering af denne varighed i kliniske forsøg ikke associeret med sikkerhedsrisici.
For drugs such as interferon and glatiramer acetate, concomitant exposure of this duration was not associated with safety risks in clinical trials.
Der er ingen tilgængelige data fra MS- patienter vedrørende samtidig eksponering med immunosuppresive lægemidler.
No data are available in MS patients regarding concomitant exposure with immunosuppressant medication.
Brugen af sådanne lægemidler kort tid efter afbrydelse af behandling med natalizumab kan føre til additive immunosuppressive virkninger.
Use of these medicines soon after the discontinuation of natalizumab may lead to an additive immunosuppressive effect.
4. 3
See section 4.3.
Data for anvendelse af TYSABRI til gravide er utilstrækkelige.
There are no adequate data from the use of natalizumab in pregnant women.
Dyreforsøg har påvist reproduktionstoksicitet (se sektion 5. 3).
Studies in animals have shown reproductive toxicity (see section 5.3).
Natalizumab bør kun anvendes på tvingende indikation til gravide.
Natalizumab should not be used during pregnancy unless clearly necessary.
Hvis en kvinde bliver gravid, mens hun får TYSABRI, bør det overvejes at afbryde behandlingen med TYSABRI.
If a woman becomes pregnant while taking TYSABRI, discontinuation of TYSABRI should be considered.
Det vides ikke, hvorvidt TYSABRI udskilles i modermælk, men det er observeret i dyreforsøg (se pkt.
It is not known whether TYSABRI is excreted in human milk, but it has been observed in animal studies (see section 5.3).
Patienter der får TYSABRI bør ikke amme.
Patients receiving TYSABRI should not breastfeed their infants.
Baseret på den farmakologiske virkningsmekanisme af natalizumab forventes brugen af TYSABRI ikke af have indflydelse på patientens evne til at føre bil eller betjene maskiner.
Based on the pharmacological mechanism of action of natalizumab, the use of TYSABRI is not expected to affect patient's ability to drive and use machines.
I placebo- kontrollerede forsøg med 1. 617 MS- patienter, der blev behandlet med natalizumab i op til 2 år (placebo:
In placebo-controlled trials in 1,617 MS patients treated with natalizumab for up to 2 years (placebo:
1. 135), forekom der hos 5, 8% af de natalizumab- behandlede patienter (placebo:
1,135), adverse events leading to discontinuation of therapy occurred in 5.8% of patients treated with natalizumab (placebo:
4, 8%) bivirkninger, der førte til afbrydelse af behandlingen.
4.8%).
I løbet af forsøgenes 2 års varighed rapporterede 43, 5% af de patienter, der blev behandlet med natalizumab, bivirkninger (placebo:
Over the 2-year duration of the studies, 43.5% of patients treated with natalizumab reported adverse drug reactions (placebo:
Bivirkninger, som blev indberettet i forbindelse med natalizumab med en incidens på 0, 5% højere end indberettet for placebo, er vist nedenfor.
Adverse drug reactions reported with natalizumab with an incidence of 0.5% greater than reported with placebo are shown below.
Reaktionerne er listet som foretrukne termer i henhold til MedDRA' s primære systemorganklasser.
The reactions are reported as MedDRA preferred terms under the MedDRA primary system organ class.
Almindelig (≥ 1/ 100 til < 1/ 10), usædvanlig (≥ 1/ 1. 000 til < 1/ 100).
Common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100).
1 En bivirkning som af den undersøgende læge blev vurderet som relateret til behandlingen.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
De alvorligste bivirkninger skal anføres først.
1 An adverse event judged related to therapy by the investigating physician.
Nervesystemet Almindelig
6 Nervous system disorders Common
Mave- tarm- kanalen Almindelig
Gastrointestinal disorders Common
Urinvejsinfektion Nasofaryngitis
Urinary tract infection Nasopharyngitis
Almene symptomer og reaktioner på administrationsstedet Almindelig
and administration site conditions
Rigor Pyreksi Fatigue
Common
Immunsystemet
Rigors Pyrexia Fatigue
Almindelig Usædvanlig
Immune system disorders Common Uncommon
Urticaria Overfølsomhed
Urticaria Hypersensitivity
I 2- års kontrollerede kliniske forsøg med MS- patienter var en infusionsrelateret reaktion defineret som en uønsket hændelse, der opstod under infusionen eller inden for én time efter, at infusionen var tilendebragt.
In 2-year controlled clinical trials in MS patients, an infusion-related event was defined as an adverse event occurring during the infusion or within 1 hour of the completion of the infusion.
Sådanne reaktioner optrådte hos 23, 1% af de MS- patienter, der blev behandlet med natalizumab (placebo:
These occurred in 23.1% of MS patients treated with natalizumab (placebo:
I 2- års kontrollerede kliniske forsøg med MS- patienter forekom der overfølsomhedsreaktioner hos op til 4% af patienterne.
In 2-year controlled clinical trials in MS patients, hypersensitivity reactions occurred in up to 4% of patients.
Anafylaktiske/ anafylaktoide reaktioner forekom hos mindre end 1% af de patienter, der fik TYSABRI.
Anaphylactic/ anaphylactoid reactions occurred in less than 1% of patients receiving TYSABRI.
4. 4).
Hypersensitivity reactions usually occurred during the infusion or within the 1-hour period after the completion of the infusion (See section 4.4).
Hos 10% af patienterne blev der påvist antistoffer mod natalizumab i 2- års kontrollerede kliniske forsøg med MS- patienter.
In 10% of patients antibodies against natalizumab were detected in 2-year controlled clinical trials in MS patients.
Cirka 6% af patienterne udviklede persisterende anti- natalizumab antistoffer (én positiv test bekræftet ved gentagelse af testen mindst 6 uger senere).
Persistent anti-natalizumab antibodies (one positive test reproducible on retesting at least 6 weeks later) developed in approximately 6% of patients.
Enkeltstående tilfælde af antistofpåvirkning sås hos yderligere 4% af patienterne.
Antibodies were detected on only one occasion in an additional 4% of patients.
4. 4).
Additional infusion-related reactions associated with persistent antibodies included rigors, nausea, vomiting and flushing (see section 4.4).
7 Hvis der, efter cirka 6 måneders behandling, er mistanke om persisterende antistoffer, enten på grund af nedsat effekt eller på grund af forekomsten af infusionsrelaterede bivirkninger, kan de påvises og bekræftes ved en efterfølgende test 6 uger efter den første positive test.
If, after approximately 6 months of therapy, persistent antibodies are suspected, either due to reduced efficacy or due to occurrence of infusion-related events, they may be detected and confirmed with a subsequent test 6 weeks after the first positive test.
Infektioner, inklusive PML og opportunistiske infektioner
7 Infections, including PML and opportunistic infections
I 2- års kontrollerede kliniske forsøg med MS- patienter var infektionshyppigheden cirka 1, 5 per patient- år hos både natalizumab - og placebo- behandlede patienter.
In 2-year controlled clinical trials in MS patients, the rate of infection was approximately 1.5 per patient-year in both natalizumab- and placebo-treated patients.
Typen af infektioner hos natalizumab- behandlede patienter lignede generelt typen af infektioner hos placebo- behandlede patienter.
The nature of the infections was generally similar in natalizumab- and placebo-treated patients.
Et tilfælde af cryptosporidium diaré blev indberettet i kliniske forsøg med MS- patienter.
A case of cryptosporidium diarrhoea was reported in MS clinical trials.
I andre kliniske forsøg er der indberettet tilfælde af yderligere opportunistiske infektioner, hvoraf nogle var fatale.
In other clinical trials, cases of additional opportunistic infections have been reported, some of which were fatal.
I kliniske afprøvninger forekom herpesinfektioner (Varicella- Zoster virus, Herpes- simplex virus) en anelse hyppigere hos patienter behandlet med natalizumab end hos placebo- behandlede patienter.
In clinical trials, herpes infections (Varicella-Zoster virus, Herpes-simplex virus) occurred slightly more frequently in natalizumab-treated patients than in placebo-treated patients.
Efter markedsføring er der rapporteret om alvorlige tilfælde, inklusive ét fatalt tilfælde af herpes encephalitis.
In post marketing experience, there have been reports of serious cases, including one fatal case of herpes encephalitis.
Størstedelen af patienterne fortsatte natalizumab- behandlingen under infektioner, og patienterne restitueredes med passende behandling.
The majority of patients did not interrupt natalizumab therapy during infections and recovery occurred with appropriate treatment.
I kliniske forsøg er tilfælde af PML blevet rapporteret.
In clinical trials, cases of PML have been reported.
PML fører sædvanligvis til funktionstab eller dødsfald (se sektion 4. 4).
PML usually leads to severe disability or death (see section 4.4).
I pivotale kliniske forsøg forekom der hos MS- patienter, der samtidig blev behandlet med interferon beta- 1a terapi gennem mere end 2 år, to tilfælde, hvoraf det ene var med dødelig udgang.
In pivotal clinical trials, two cases, including one fatality, occurred in MS patients who were being treated with concomitant interferon beta-1a therapy for more than 2 years.
I et andet forsøg udviklede én patient med Crohn’ s sygdom, som havde en lang anamnese med behandling med immunosuppressive midler og associeret lymfopeni, ligeledes PML og døde.
In another trial, one patient with Crohn’ s disease, who had a long history of treatment with immunosuppressants and associated lymphopenia also developed PML and died.
Efter markedsføringen er der indberettet PML hos patienter i TYSABRI- monoterapi.
PML has been reported in post-marketing experience in patients treated with TYSABRI monotherapy.
4. 4).
Spontaneous cases of serious liver injuries, increased liver enzymes, hyperbilirubinaemia have been reported during the post marketing phase (see section 4.4).
Der blev ikke observeret forskel i hyppighed eller art af malignitet mellem natalizumab - og placebo- behandlede patienter i løbet af 2 års behandling.
No differences in incidence rates or the nature of malignancies between natalizumab- and placebo-treated patients were observed over 2 years of treatment.
4. 3.
See section 4.3.
Behandling med TYSABRI blev associeret med forøgelse af cirkulerende lymfocytter, monocytter, eosinofile granulocytter, basofile granulocytter og kerneholdige røde blodlegemer.
TYSABRI treatment was associated with increases in circulating lymphocytes, monocytes, eosinophils, basophils and nucleated red blood cells.
Der blev ikke observeret stigninger i neutrofile granulocytter.
Elevations in neutrophils were not seen.
Forøgelse fra baseline for lymfocytter, monocytter, eosinofile granulocytter og basofile granulocytter varierede inden for området fra 35% til 140% for individuelle celletyper.
Increases from baseline for lymphocytes, monocytes, eosinophils and basophils ranged from 35% to 140% for individual cell types but mean cell counts remained within normal ranges.
Under behandling med TYSABRI blev der observeret mindre reduktioner i hæmoglobinniveauet (gennemsnitlig reduktion 0, 6 g/ dl), hæmatokrit (gennemsnitlig reduktion 2%) og antallet af røde blodlegemer (gennemsnitlig reduktion 0, 1 x 106/ l).
During treatment with TYSABRI, small reductions in haemoglobin (mean decrease 0.6 g/ dl), haematocrit (mean decrease 2%) and red blood cell counts (mean decrease 0.1 x 106/ l) were seen.
Alle ændringer i hæmatologiske parametre vendte sædvanligvis tilbage til niveauerne før behandlingen inden for 16 uger efter den sidste indgivelse af TYSABRI, og ændringerne var ikke associerede med kliniske symptomer.
All changes in haematological variables returned to pre-treatment values, usually within 16 weeks of last dose of TYSABRI and the changes were not associated with clinical symptoms.
Selektivt immunosuppressivt middel, ATC- kode:
Selective Immunosuppressive Agent, ATC code:
Disse er kraftigt udtrykt på overfladen af alle leukocytter med undtagelse af neutrofile granulocytter.
8 Natalizumab is a selective adhesion-molecule inhibitor and binds to the α 4-subunit of human integrins, which is highly expressed on the surface of all leukocytes, with the exception of neutrophils.
Natalizumab binder sig specifikt til α4β1 integrinet og blokerer derved interaktionen med dets kognate receptor, vaskulært celleadhæsionsmolekyle- 1 (VCAM- 1) og ligand osteopontin, og et variant domæne (alternatively spliced) af fibronektin, connecting segment- 1 (CS- 1).
Specifically, natalizumab binds to the α 4β 1 integrin, blocking the interaction with its cognate receptor, vascular cell adhesion molecule-1 (VCAM-1), and ligands osteopontin, and an alternatively spliced domain of fibronectin, connecting segment-1 (CS-1).
Natalizumab blokerer interaktionen af α4β7 integrinet med det mukosale addressin celleadhæsionsmolekyle- 1 (MadCAM- 1).
Natalizumab blocks the interaction of α 4β 7 integrin with the mucosal addressin cell adhesion molecule-1 (MadCAM-1).
En yderligere virkningsmekanisme af natalizumab kan være at undertrykke igangværende inflammatoriske reaktioner i de syge væv ved at hæmme interaktionen af α4- udtrykkende leukocytter med deres respektive ligander i den ekstracellulære matrix og på parenkymceller.
A further mechanism of action of natalizumab may be to suppress ongoing inflammatory reactions in diseased tissues by inhibiting the interaction of α 4-expressing leukocytes with their ligands in the extracellular matrix and on parenchymal cells.
I MS menes det, at læsioner opstår, når aktiverede T- lymfocytter krydser blodhjernebarrieren (blood- brain barrier - BBB).
In MS, lesions are believed to occur when activated T-lymphocytes cross the blood-brain barrier (BBB).