FrancophonIA/ELRC3.0 huggingface dataset:
English: Fatigue/ weakness (G3/4: 5%); Oedema peripheral (G3/4: 1%)
Danish: Erytematøst udslæt (G3/4: < 1 %); Misfarvning af negle; Onycholysis (G3/4: 1 %)
English: Anaemia (G3/4: 9.2%); Thrombocytopenia
Danish: Anæmi (G3/4: 8,9 %); Febril neutropeni
English: • one vial of 1.28 ml solvent (water for injections).
Danish: et hætteglas a 0,72 ml koncentrat (20 mg docetaxel), et hætteglas a 1,28 ml solvens (vand til injektionsvæsker).
English: There are no active patients;
Danish: Der er ingen aktive patienter.
English: It was noted that three Clinical studies are currently ongoing:
Danish: Det blev bemærket, at der i øjeblikket er tre igangværende kliniske undersøgelser:
English: National competent authorities competent for the regulatory oversight of these clinical studies should act accordingly.
Danish: De nationale kompetente myndigheder med ansvar for det regulatoriske tilsyn med disse kliniske undersøgelser bør handle i overensstemmelse hermed.
English: This is potentially a plausible mechanism which needs to be further investigated.
Danish: Dette er muligvis en tænkelig mekanisme, som skal undersøges nærmere.
English: In addition, the European Commission requested the Agency to give its opinion, as soon as possible, as to whether provisional measures were necessary to protect public health
Danish: Desuden anmodede Europa-Kommissionen agenturet om snarest muligt at afgive en udtalelse om, hvorvidt det er nødvendigt at iværksætte midlertidige foranstaltninger af hensyn til folkesundheden.
English: It is administered as 150 mg dose subcutaneously once a month.
Danish: Det gives som en 150 mg-dosis subkutant en gang om måneden.
English: Zinbryta (daclizumab beta) has been authorised in the European Union (EU) since 1 July 2016.
Danish: Zinbryta (daclizumab beta) har været godkendt i Den Europæiske Union (EU) siden den 1. juli 2016.
English: The PRAC considered the alternative treatment options for the different stages or manifestations of the disease.
Danish: PRAC vurderede de alternative behandlingsmuligheder for de forskellige stadier eller manifestationer af sygdommen.
English: The postmarketing exposure in the European Economic Area (EEA) is estimated at 3,290 patients (of which around 2,890 patients in Germany) and worldwide at 5,086 patients.
Danish: Eksponeringen efter markedsføringen i Det Europæiske Økonomiske Samarbejdsområde (EØS) anslås til 3.290 patienter (heraf ca. 2.890 patienter i Tyskland) og 5.086 patienter på verdensplan.
English: EXTEND: extension study to assess efficacy and safety in patients from the pivotal studies.
Danish: EXTEND: forlængelsesundersøgelse til vurdering af virkning og sikkerhed hos patienter fra de centrale undersøgelser.
English: ZEUS: non-interventional study in Germany with 609 patients enrolled currently.
Danish: ZEUS: ikke-interventionel undersøgelse i Tyskland med p.t. 609 inkluderede patienter.
English: In the European Union, as of 30 November 2017, daclizumab beta has been marketed in Austria, Belgium, Denmark, Finland, Germany, Ireland, Italy, Netherlands, Norway, Poland, Slovenia, Sweden and United Kingdom.
Danish: I Den Europæiske Union er daclizumab beta siden den 30. november 2017 blevet markedsført i Østrig, Belgien, Danmark, Finland, Tyskland, Irland, Italien, Nederlandene, Norge, Polen, Slovenien, Sverige og Storbritannien.
English: All cases were spontaneous reports, except for the Spanish case which came from an extension of a clinical trial.
Danish: Alle tilfælde var spontane indberetninger, undtagen det spanske tilfælde, som kom fra en forlængelse af en klinisk undersøgelse.
English: This adverse reaction appears unpredictable and no measure to minimize the risk has been identified at this stage.
Danish: Denne bivirkning kan tilsyneladende ikke forudses, og der er endnu ikke identificeret nogen måde at minimere risikoen på.
English: As of November 2017, 2,251 patients had received Zinbryta in the clinical development program.
Danish: Siden november 2017 har 2.251 patienter fået Zinbryta gennem det kliniske udviklingsprogram.
English: In addition, no new patients should start treatment with Zinbryta.
Danish: Desuden bør nye patienter ikke starte på behandling med Zinbryta.
English: These cases concerned 10 females, 1 male (and 1 unknown), aged between 30 and 69 years-old; 9 cases occurred in Germany, 2 in USA and 1 in Spain.
Danish: Tilfældene omfattede 10 kvinder, 1 mand og 1 person af uoplyst køn i alderen 30-69 år; 9 af tilfældene skete i Tyskland, 2 i USA og 1 i Spanien.
English: It was initially indicated in adult patients for the treatment of relapsing forms of multiple sclerosis (RMS).
Danish: Det var oprindeligt indiceret til voksne patienter til behandling af tilbagevendende former af multipel sklerose (RMS).
English: Patients stopping treatment must be followed up for at least 6 months, as symptoms may appear after discontinuation of Zinbryta treatment.
Danish: Patienter, der afbryder behandling, skal følges i mindst 6 måneder, da symptomer kan forekomme efter seponering af Zinbryta-behandling.
English: On 26 February 2018, pursuant to Article 20 of Regulation (EC) No 726/2004, the European Commission requested the opinion of the Agency on whether the marketing authorisation of Zinbryta should be maintained, varied, suspended or revoked.
Danish: Den 26. februar 2018 anmodede Europa-Kommissionen i henhold til artikel 20 i forordning (EF) nr. 726/2004 agenturet om at udtale sig om, hvorvidt markedsføringstilladelsen for Zinbryta bør opretholdes, ændres, suspenderes eller inddrages.
English: The MAH plans to terminate the study as a result of the product suspension in the EU.
Danish: Indehaveren af markedsføringstilladelse har planlagt at stoppe undersøgelsen som følge af suspenderingen af produktet i EU.
English: SUSTAIN: A phase 3b open label study to assess efficacy and safety of daclizumab beta in patients switching from natalizumab in 5 countries, 3 in EU (DE, IT and UK).
Danish: SUSTAIN: En åben fase 3B-undersøgelse af virkningen og sikkerheden ved daclizumab beta hos patienter, der skifter fra natalizumab, i 5 lande, heraf 3 i EU (Tyskland, Italien og Det Forenede Kongerige).
English: These cases are characterized by torpid progression and potentially fatal or disabling outcome.
Danish: Disse tilfælde var karakteriseret ved langsom udvikling og potentielt dødelig eller invaliderende udfald.
English: Furthermore, the analysis of PSUR data indicated that a range of immune-mediated disorders were reported in other organs than the brain and liver following the use of Zinbryta.
Danish: Desuden viste analysen af PSUR-dataene, at en række immunmedierede sygdomme blev indberettet i andre organer end hjernen og leveren efter brug af Zinbryta.
English: Activation and expansion of NK cells may lead to a higher cytotoxic response that may be involved in the pathogenesis of autoimmune hepatitis and other autoimmune diseases.
Danish: Aktivering og ekspansion af NK-celler kan medføre et højere cytotoksisk respons, som kan være involveret i patogenesen ved autoimmun hepatitis og andre autoimmune sygdomme.
English: On 20 February 2018, the Paul Ehrlich Institute (PEI) informed the EMA about five patients who were treated in 2016 and 2017 with daclizumab beta in Germany, and experienced worsening of disease after initiation of therapy.
Danish: Den 20. februar 2018 informerede Paul Ehrlich-instituttet Det Europæiske Lægemiddelagentur om fem patienter, der i 2016 og 2017 var blevet behandlet med daclizumab beta i Tyskland, og som havde oplevet en forværring af deres sygdom efter påbegyndelse af behandling.
English: The number of doses received before the event was reported in all but two cases; it ranged between 1 and 8 doses, except for the Spanish patient who had received daclizumab beta for 4 years.
Danish: Antallet af doser, der var administreret, før hændelsen indtraf, var kendt i alle tilfælde på nær to og drejede sig om 1-8 doser, bortset fra det spanske tilfælde, hvor patienten havde fået daclizumab beta for 4 år siden.
English: The use and the marketing authorisation for Zinbryta should be suspended and the product should be recalled from the market at the level of pharmacies and hospitals.
Danish: Brugen af og markedsføringstilladelsen for Zinbryta bør suspenderes, og produktet bør tilbagekaldes fra markedet (fra apoteker og hospitaler).
English: From the third PSUR (period from 27 May 2017 - 26 November 2017), there have also been some cases of unexpected deaths, attributed to cerebrovascular accidents, but with no detailed information on them that would conclusive allow for the exclusion of encephalitis.
Danish: I den tredje PSUR (vedrørende perioden 27. maj 201726. november 2017) er der også indberettet en række tilfælde af uventede dødsfald, relateret til cerebrovaskulære hændelser, dog uden detaljerede oplysninger, som gør det muligt konklusivt at udelukke encefalitis.
English: Overall, 12 cases of encephalitis or encephalopathy in patients treated with daclizumab beta for multiple sclerosis have been identified.
Danish: I alt er der identificeret 12 tilfælde af encefalitis eller encefalopati hos patienter, der er blevet behandlet med daclizumab beta mod multipel sklerose.
English: Healthcare professionals should contact patients currently being treated with Zinbryta and should stop their treatment and consider alternatives as a matter of urgency.
Danish: Sundhedspersoner bør øjeblikkeligt kontakte patienter, der aktuelt bruger Zinbryta, og seponere deres behandling og overveje alternative behandlinger.
English: Whilst the absolute numbers for each disorder is low, this raises concerns that these disorders could be induced by immune-mediated effects and could be causally associated with Zinbryta.
Danish: Selvom det absolutte antal er lavt for hver enkelt sygdom, giver dette grund til bekymring for, at disse sygdomme kan være induceret af immunmedierede effekter, og at de kan have en årsagssammenhæng til Zinbryta.
English: • In addition, PRAC also considered the known serious immune-mediated liver toxicity associated with Zinbryta as well as potential other immune-mediated disorders affecting other organs than the brain or the liver.
Danish: • Derudover overvejede PRAC også den kendte alvorlige immunmedierede levertoksicitet, der er forbundet med Zinbryta, samt andre mulige immunmedierede sygdomme, der påvirker andre organer end hjernen og leveren.
English: It is plausible that the immunomodulatory effects of the drug are involved in immune-mediated adverse effects, such as autoimmune hepatitis, and could be related to the reported cases of encephalitis and/or meningoencephalitis.
Danish: Det er tænkeligt, at lægemidlets immunmodulerende effekter er involveret i immunmedierede bivirkninger som f.eks. autoimmun hepatitis, og at de kan være relateret til de indberettede tilfælde af encefalitis og/eller meningoencefalitis.
English: Although the absolute number of the individual reports for each disorder was low, cumulatively there were a significant number of autoimmune events possibly related to daclizumab beta treatment.
Danish: Selvom det absolutte antal individuelle rapporter for hver sygdom er lavt, blev der kumulativt observeret et betydeligt antal autoimmune tilfælde, der muligvis er relateret til behandling med daclizumab beta.
English: In the second PSUR (period from 27 November 2016 - 26 May 2017), the review of autoimmune encephalitis cases and other immune-related disorders cases showed that there was a wide variety of immune-mediated disorders reported (such as encompassed seronegative arthritis, blood dyscrasias, thyroid disorders, glomerulonephritis and skin and subcutaneous disorders).
Danish: I den anden PSUR-periode (27. november 2016-26. maj 2017) viste gennemgangen af tilfælde af autoimmun encefalitis og andre immunrelaterede sygdomme, at der var indberettet en bred vifte af immunmedierede sygdomme (f.eks. encompassed seronegativ artritis, bloddyskrasier, thyroideasygdomme, glomerulonefritis og sygdomme i hud og subkutane væv).
English: In light of all of the above and having carefully assessed all available data, PRAC considered at this stage that the benefit-risk balance of the product is no longer favourable and that urgent measures in accordance with Article 20(3) of Regulation (EC) No 726/2004, taking into account the grounds set out in Articles 116 and 117 of Directive 2001/83/EC, are needed to protect patients.
Danish: I lyset af ovenstående og efter at have omhyggeligt vurderet alle tilgængelige data er det på nuværende tidspunkt PRAC's opfattelse, at benefit/risk-forholdet for produktet ikke længere er positivt, og at det er nødvendigt at træffe øjeblikkelige foranstaltninger for at beskytte patienterne i overensstemmelse med artikel 20, stk. 3, i forordning (EF) nr. 726/2004 under hensyn til begrundelserne i artikel 116 og 117 i direktiv 2001/83/EF.
English: A PRAC review concluded on 31 October 2017 (due to cases of immune-mediated liver injury) led to the restriction of indication to the treatment of adult patients with relapsing forms of multiple sclerosis who have had an inadequate response to at least two disease modifying therapies (DMTs) and for whom treatment with any other DMT is contraindicated or otherwise unsuitable.
Danish: En gennemgang fra PRAC, der blev afsluttet den 31. oktober 2017 (på grund af tilfælde af immunmedieret leverskade), medførte, at indikationen blev begrænset til behandling af voksne patienter med tilbagevendende former af multipel sklerose, som ikke har reageret tilstrækkeligt på mindst to sygdomsmodificerende behandlinger, og hos hvem en anden sygdomsmodificerende behandling er kontraindiceret eller på anden måde uegnet.
English: • In view of the above, the PRAC considered that the benefit-risk balance of Zinbryta is no longer favourable and that urgent measures are needed to protect patients.
Danish: • På grundlag af dette konkluderede PRAC, at benefit/risk-forholdet for Zinbryta ikke længere er positivt, og at det er nødvendigt øjeblikkeligt at indføre foranstaltninger for at beskytte patienter.
English: Further, the PRAC took into consideration that interrupting treatment in patients whose disease is well-controlled with daclizumab beta may induce relapses, but considered that the serious risk of auto-immune or immune-mediated reactions outweighs the benefit that daclizumab beta may bring to relapsed patients eligible to the authorised indication.
Danish: Desuden tog PRAC i betragtning, at afbrydelse af behandlingen hos patienter, hvis sygdom er velreguleret med daclizumab beta, kan medføre recidiv, men fandt, at den alvorlige risiko for autoimmune eller immunmedierede reaktioner opvejer den fordel, som daclizumab beta kan medføre for patienter med recidiv, der er egnede til den godkendte indikation.
English: Three of these cases had a fatal outcome, 2 cases are still intubated, 1 has an Expanded Disability Status Scale (EDSS) score 9.5, 1 recovered with sequelae, 1 partially recovered, and the remaining cases had an unknown outcome.
Danish: I tre af disse tilfælde døde patienten, i 2 tilfælde er patienten stadig intuberet, 1 patient har en score på 9,5 på EDSS-skalaen (Expanded Disability Status Scale), 1 patient er kommet sig med sequelae, 1 patient er kommet sig delvist, og i de øvrige tilfælde kendes udfaldet ikke.
English: • The PRAC reviewed the totality of the available data, including data provided by the marketing authorisation holder in writing and in an oral explanation on the 12 cases of serious encephalitis and meningo-encephalitis (of which three fatal) reported since the initial marketing authorisation and safety data from clinical trials, in relation to the overall risk of immune-mediated disorders with CNS involvement during treatment with Zinbryta.
Danish: • PRAC gennemgik alle tilgængelige data, herunder de oplysninger, som indehaveren af markedsføringstilladelse havde givet skriftligt og mundtligt om de 12 tilfælde af alvorlig encefalitis og meningoencefalitis (hvoraf tre var fatale), der er indberettet siden den oprindelige markedsføringstilladelse og sikkerhedsdata fra kliniske undersøgelser, i forhold til den samlede risiko for immunmedierede sygdomme med påvirkning af centralnervesystemet under Zinbryta-behandling.
English: • The PRAC considered the procedure under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance data for Zinbryta, in particular the need for provisional measures in accordance with Article 20(3) of Regulation (EC) No 726/2004, taking into account the grounds set out in Articles 116 and 117 of Directive 2001/83/EC.
Danish: • På baggrund af lægemiddelovervågningsdata for Zinbryta gennemførte PRAC en procedure i henhold til artikel 20 i forordning (EF) nr. 726/2004, navnlig med hensyn til behovet for midlertidige foranstaltninger, jf. artikel 20, stk. 3, under hensyn til begrundelserne i artikel 116 og 117 i direktiv 2001/83/EF.
English: This effect is probably mediated through excess of IL-2 produced by activated T cells that cannot bind to high affinity IL-2 receptors, but is available to bind to intermediate IL-2 receptors.
Danish: Denne virkning er formentlig medieret af et overskud af IL-2, som er dannet af aktiverede T-celler, der ikke kan binde til højaffinitets-IL-2-receptorer, men som kan binde til intermediære IL-2receptorer.
English: More information concerning these immune-mediated events had been requested to the MAH to be submitted in the third PSUR.
Danish: Indehaveren af markedsføringstilladelse blev bedt om at fremskaffe flere oplysninger om disse immunmedierede hændelser i forbindelse med den tredje PSUR.
English: Key effects of this IL-2 pathway modulation potentially related to the therapeutic effects of daclizumab beta in multiple sclerosis (MS) include selective antagonism of activated T-cell responses, and expansion of immunoregulatory CD56bright natural killer (NK) cells, which have been shown to selectively decrease activated T-cells.
Danish: Hovedeffekterne af denne modulering af IL-2-signaleringen, der potentielt er relateret til daclizumab betas terapeutiske virkninger ved multipel sklerose (MS), inkluderer selektiv antagonisering af aktiverede T-celleresponser og ekspansion af immunregulerende CD56bright naturlige dræberceller (NK-celler), som er vist selektivt at reducere aktiverede T-celler.
English: Autoimmune haemolytic anemia is already known to be related to daclizumab beta treatment.
Danish: Det er allerede kendt, at autoimmun hæmolytisk anæmi er relateret til behandling med daclizumab beta.
English: • Furthermore, PRAC recommended that a healthcare professional communication should be disseminated to inform healthcare professionals about the risks related to Zinbryta and provide instructions related to the cessation of the treatment and the follow-up of patients having received Zinbryta.
Danish: • PRAC anbefalede også, at der udsendes et brev til sundhedspersoner om risiciene ved Zinbryta og med en vejledning i seponering af behandlingen og opfølgning af patienter, der har fået Zinbryta.
English: Together, these immunomodulatory effects of daclizumab beta are believed to reduce central nervous system (CNS) pathology in MS and thereby reduce the occurrence of relapses and disability progression.
Danish: Tilsammen menes disse immunmodulerende virkninger af daclizumab at reducere de centralnervesystem-patologiske træk ved MS og derved reducere forekomsten af attakker og sygdomsprogression.
English: At least 5 of these patients had clinical symptoms compatible with ‘drug rash with eosinophilia and systemic symptoms' (DRESS) syndrome, one of which was confirmed with skin biopsy and one highly suspected.
Danish: Mindst 5 af disse patienter havde kliniske symptomer, der var kompatible med medikamentelt udslæt med eosinofiler og systemiske symptomer (DRESS), hvoraf ét blev bekræftet ved hudbiopsi og ét formodedes i meget høj grad at være DRESS.
English: • The PRAC recommended to suspend the use and the marketing authorisation for Zinbryta, and to recall all the batches of the medicinal product from the market up to the level of pharmacies and hospitals.
Danish: • PRAC anbefalede at suspendere brugen af og markedsføringstilladelsen for Zinbryta og at tilbagekalde alle batcher af lægemidlet fra markedet (fra apoteker og hospitaler).
English: In summary, 12 cases of serious and potentially fatal immune-mediated events involving CNS, with symptoms initially compatible with relapse of MS and later on explained by unexpected findings in the neuropathology, with a predominantly inflammatory process and eosinophilic granulocytes, were reported.
Danish: I alt er der indberettet 12 tilfælde af alvorlige og potentielt dødelige immunmedierede hændelser, der påvirkede centralnervesystemet, og som omfattede symptomer, der indledningsvist var kompatible med MS-recidiv og senere blev forklaret ved uventede fund i neuropatologien, med en overvejende inflammatorisk proces og eosinofile granulocytter.
English: Some of these patients did not improve despite treatment with corticosteroids and/or plasmapheresis in these patients brain biopsies were obtained, which showed an unexpected finding of massive inflammation with eosinophilic granulocytes.
Danish: Nogle af disse patienter fik det ikke bedre på trods af behandling med kortikosteroider og/eller plasmaferese; hos disse patienter blev der udtaget hjernebiopsier, som viste et uventet fund af massiv inflammation med eosinofile granulocytter.
English: Immune-mediated or autoimmune conditions such as type I diabetes, colitis, autoimmune thyroiditis, pancreatitis, glomerulonephritis, among other, were reported in low numbers.
Danish: Antallet af indberettede tilfælde af immunmedierede eller autoimmune sygdomme som f.eks. type 1diabetes, kolitis, autoimmun tyroiditis, pankreatitis og glomerulonefritis er lavt.
English: Administration of acute corticosteroids and/or plasmapheresis did not improve the clinical situation, brain biopsies were obtained, which showed an unexpected finding of massive inflammation with eosinophilic granulocytes (unexpected in MS patients).
Danish: Administration af akutte kortikosteroider og/eller plasmaferese forbedrede ikke den kliniske situation, og der blev udtaget hjernebiopsier, som viste et uventet fund af massiv inflammation med eosinofile granulocytter (uventet hos MS-patienter).
English: Daclizumab beta binds to the alpha-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor.
Danish: Daclizumab beta binder til alfa-underenheden (CD25) af højaffinitets-interleukin-2 (IL-2)-receptoren.
English: PRAC concluded that these adverse reactions could be causally associated with Zinbryta.
Danish: PRAC konkluderede, at der kan være en årsagssammenhæng mellem disse bivirkninger og Zinbryta.
English: PRAC has considered carefully the above described cases, the probable mechanism of action for these adverse events, along with the potential for auto-immune or immune-mediated reactions that appears associated with Zinbryta, the product mechanism of action, the biological plausibility, and that no risk minimisation measures (RMMs) can be foreseeable to prevent occurrence of these risks in patients on treatment with daclizumab beta at this stage.
Danish: PRAC har foretaget en grundig vurdering af de ovenfor beskrevne tilfælde, den mulige virkningsmekanisme for bivirkningerne samt potentialet for autoimmune eller immunmedierede reaktioner, der synes at være forbundet med Zinbryta, produktets virkningsmekanisme, den biologiske årsagssammenhæng og det faktum, at der på nuværende tidspunkt ikke kan forudses nogen risikominimerende foranstaltninger, som kan forebygge disse bivirkninger hos patienter i behandling med daclizumab beta.
English: Four of the five patients experienced also fever, leukocytosis, exanthema/skin reactions, thus potentially meeting the criteria for DRESS.
Danish: Fire ud af de fem patienter oplevede også feber, leukocytose og eksantem/hudreaktioner og opfyldte derfor muligvis kriterierne for medikamentelt udslæt med eosinofili og systemiske symptomer gemiddelinduceret (DRESS).