FrancophonIA/ELRC3.0 huggingface dataset:
English: Written explanations were provided by the marketing authorisation holders on 12 August 2011 and 14 February 2012.
Danish: Indehaveren af markedsføringstilladelsen fremsendte skriftlige redegørelser den 12. august 2011 og den 14. februar 2012.
English: Oral explanations were given on 14 May 2012.
Danish: Mundtlige redegørelser blev afgivet den 14. maj 2012.
English: Due to divergent national decisions taken by Member States with respect to e.g. target species, indications, amounts to be administered and withdrawal periods concerning the authorisations of Baytril 10% oral solution and its associated names, on 15 October 2010 the United Kingdom referred the issue to the CVMP under Article 34(1) of Directive 2001/82/EC, in order to resolve divergences amongst the nationally authorised product information across the European Union.
Danish: Som følge af, at der var truffet divergerende nationale afgørelser af medlemsstaterne vedrørende f.eks. måldyrearter, indikationer, mængder som skal indgives, samt tilbageholdelsestider i forbindelse med godkendelserne af Baytril 10 % oral opløsning og relaterede navne, indbragte Det Forenede Kongerige den 15. oktober 2010 sagen for CVMP i henhold til artikel 34, stk. 1, i direktiv 2001/82/EF med henblik på at fjerne divergenserne mellem de nationalt godkendte produktinformationer i hele Den Europæiske Union.
English: Baytril 10% oral solution and its associated names contain 100 mg enrofloxacin per ml oral solution for use in drinking water.
Danish: Baytril 10 % oral opløsning og relaterede navne indeholder 100 mg enrofloxacin pr. ml oral opløsning til anvendelse i drikkevand.
English: and subject to a condition on the marketing authorisations.
Danish: markedsføringstilladelserne underlægges en betingelse.
English: The products are authorised for use in the target species chickens, turkeys and rabbits for treatment of the respiratory tract and of the digestive tract infections caused by bacteria susceptible to enrofloxacin.
Danish: Produkterne er godkendt til anvendelse i måldyrearterne kyllinger, kalkuner og kaniner til behandling af infektioner i luftvejene og mave-tarmkanalen forårsaget af enrofloxacin-følsomme bakterier.
English: Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolone carboxylic acid derivatives.
Danish: Enrofloxacin er et syntetisk kemoterapeutikum tilhørende klassen carboxylsyrederivater af fluorquinolon.
English: Based on the rapporteurs' assessment of the currently available data, the CVMP considered that the benefit-risk profile of Baytril 10% oral solution and its associated names remains positive, subject to variation of the marketing authorisations in accordance with the recommended product information,
Danish: På grundlag af rapportørernes vurdering af de foreliggende data var CVMP af den opfattelse, at benefit/risk-forholdet for Baytril 10 % oral opløsning og relaterede navne fortsat er positivt, forudsat at markedsføringstilladelserne ændres i overensstemmelse med den anbefalede produktinformation, og at
English: Opinion following an Article 341 referral for Baytril 10% oral solution and associated names
Danish: Udtalelse efter en artikel 341-indbringelse for Baytril 10 % oral opløsning og relaterede navne
English: The list of product names concerned is given in Annex I. The scientific conclusions are provided in Annex II, together with the amended Summary of Product Characteristics, labelling and package leaflet are in the Annex III.
Danish: Listen over de berørte produktnavne fremgår af bilag I. De videnskabelige konklusioner fremgår af bilag II.
English: Opinion following an Article 340F referral for Baytril 10% oral solution and associated names
Danish: Udtalelse efter en artikel 340F-indbringelse for Baytril 10 % oral opløsning og relaterede navne EMA/511421/2012
English: and concluded that all relevant elements had already been considered by PRAC.
Danish: og konstaterede, at alle relevante elementer allerede var gennemgået af PRAC.
English: These very low margins may have also been overestimated (i.e. plasma concentrations corresponding to the maximum daily doses were not determined, not clear whether the analysis was performed at steady state plasma concentrations or not).
Danish: Disse meget lave margener kan også have været overvurderet (dvs. plasmakoncentrationer svarende til de maksimale daglige doser blev ikke bestemt, det står ikke klart, om analysen blev udført ved steady state-plasmakoncentrationer eller ej).
English: No other appropriate measure was identified that would reduce the risk of QT prolongation to an acceptable level.
Danish: Der blev ikke identificeret andre relevante foranstaltninger, som kan reducere risikoen for QTforlængelse til et acceptabelt niveau.
English: The PRAC adopted a recommendation on 16 May 2019 which was then considered by the CMDh, in accordance with Article 107k of Directive 2001/83/EC.
Danish: PRAC vedtog den 16. maj 2019 en anbefaling, der efterfølgende er blevet vurderet af CMDh, jf. artikel 107k i direktiv 2001/83/EF.
English: In conclusion, no feasible and effective measures could be identified which would minimise this risk to an acceptable level.
Danish: Samlet set er der ikke identificeret nogen gennemførlige eller effektive foranstaltninger, der kan minimere denne risiko til et acceptabelt niveau.
English: Annex II
Danish: Bilag II Videnskabelige konklusioner
English: The observed prolongation may be underestimated in this study due to the necessary QT correction formula of the observed dose-dependent QTc augmentations, in view of the method used.
Danish: Den observerede forlængelse kan være underestimeret i dette studie som følge af den nødvendige QT-korrektionsformel for de observerede dosisafhængige QTc-forhøjelser, set i lyset af den anvendte metode.
English: However, some risk factors of TdP like congenital long QT syndrome are usually silent and unpredictable.
Danish: Imidlertid er nogle af risikofaktorerne for torsades de pointes, som f.eks. langt QT-syndrom, typisk tavse og uforudsigelige.
English: The CMDh considered the arguments presented in writing by one MAH (Aflofarm Farmacja Polska Sp. Z O.O.)
Danish: CMDh gennemgik de skriftlige argumenter fra en indehaver af markedsføringstilladelse (Aflofarm Farmacja Polska Sp. Z O.O.)
English: This included the results of the above-mentioned requested non-clinical study (Aptuit), two other non-clinical studies and post-marketing case-reports as well as published efficacy studies.
Danish: Det omfattede resultaterne af den førnævnte påkrævede ikke-kliniske undersøgelse (Aptuit), to andre ikke-kliniske studier og tilfælde, der er indberettet efter markedsføring samt offentliggjorte effektstudier.
English: It is noted that lack of ECG diagnosis is common in these cases, which generates significant uncertainty on the actual incidence of TdP.
Danish: Det bemærkes, at manglende ekg-diagnose er almindeligt forekommende i disse tilfælde, hvilket skaber betydelig usikkerhed om den aktuelle forekomst af torsades de pointes.
English: The PRAC considered that in view of the available data the generation of additional evidence via an ICH E14 thorough QT/QTc clinical study would not be justified and would not allow identifying defined patient population in whom the benefits could outweigh the risks.
Danish: PRAC vurderede i lyset af de tilgængelige data, at generering af yderligere evidens gennem et grundigt klinisk ICH E14-QT/QTc-studie ikke ville være berettiget og ikke ville gøre det muligt at identificere en patientpopulation, hvor fordelene ville opveje risiciene.
English: Therefore, the conclusions of the PRAC are not affected.
Danish: PRAC's konklusioner står derfor ved magt.
English: In addition, no protective effects regarding the triggering of TdP arrhythmias (blockade of Nav1.5 and cardiac L-type Ca2+ channels) was shown for fenspiride.
Danish: Desuden blev der ikke påvist nogen beskyttende virkning i forhold til udløsning af TdP-arytmier (blokade af Nav1.5- og kardielle L-type Ca1+kanaler) for fenspirid.
English: Fenspiride-containing medicinal products are authorised nationally for the treatment of symptoms (e.g. cough and expectoration) related to bronchopulmonary diseases.
Danish: Fenspirid-holdige lægemidler er godkendt nationalt til behandling af symptomer (f.eks. hoste og ekspektoration), der er relateret til bronkopulmonale sygdomme.
English: The French Competent Authority (ANSM) considered that these results taken together with pharmacovigilance data support the risk of prolongation of the QTc interval in these patients.
Danish: Den franske kompetente myndighed (ANSM) fandt, at disse resultater sammenholdt med data for lægemiddelovervågning indikerer en risiko for forlængelse af QTc-intervallet hos disse patienter.
English: On 8 February 2019 the French Competent Authority (ANSM) therefore triggered an urgent Union procedure under Article 107i of Directive 2001/83/EC resulting from pharmacovigilance data, and requested the PRAC to assess the impact of the above concerns on the benefit-risk balance of fenspiride containing medicinal products and to issue a recommendation on whether the relevant marketing authorisations should be maintained, varied, suspended or revoked.
Danish: På baggrund af lægemiddelovervågningsdata indledte den franske kompetente myndighed (ANSM) derfor den 8. februar 2019 en hastende EU-indbringelsesprocedure i henhold til artikel 107i i direktiv nr. 2001/83/EF og bad PRAC om at vurdere ovenstående problemstillings betydning for benefit/riskforholdet for fenspirid-holdige lægemidler og fremsætte en anbefaling om, hvorvidt de pågældende markedsføringstilladelser bør opretholdes, ændres, suspenderes eller tilbagekaldes.
English: Considering the seriousness of TdP which can lead to fatal outcome, a thorough risk analysis would be essential for each individual patient prior to treatment initiation with fenspiride.
Danish: I betragtning af alvoren af torsades de pointes, som kan være fatal, er en grundig risikoanalyse af afgørende betydning for den enkelte patient, før behandling med fenspirid påbegyndes.
English: The calculated safety margins between the hERG IC50 obtained and the effective therapeutic plasma concentration for fenspiride, was below the lowest acceptable safety margin proposed in the literature (between 6 and 26, depending on the pharmaceutical form/dose administered and on the administration schedule).
Danish: De beregnede sikkerhedsmargener mellem den opnåede hERG IC50 og den effektive terapeutiske plasmakoncentration for fenspirid var under den lavest acceptable sikkerhedsmargen, der er beskrevet i litteraturen (mellem 6 og 26, afhængigt af lægemiddelformen/den administrerede dosis og doseringsplanen).
English: There is a possibility that the IC50 value is overestimated (i.e. experiments performed at room temperature, external K+ concentration in the milieu unknown, no DMSO cells perfusion before adding fenspiride in DMSO yet substracting DMSO effect) and fenspiride could be a more potent blocker of hERG channels than shown in vitro.
Danish: Det er muligt, at IC50værdien er overvurderet (dvs. forsøg er udført ved stuetemperatur, den eksterne kalium-koncentration i miljøet er ikke kendt, ingen DMSO-celleperfusion før tilføjelse af fenspirid i DMSO, men alligevel er der korrigeret for en DSMO-effekt), og fenspirid kan være en mere potent hERG-kanalblokker end påvist in vitro.
English: Calculated safety margins between the hERG inhibition concentration and the effective therapeutic plasma concentration were below the lowest acceptable margin proposed in the literature for administration in humans.
Danish: De beregnede sikkerhedsmargener mellem hERGhæmningskoncentrationen og den effektive terapeutiske plasmakoncentration var under den lavest acceptable margen, som er beskrevet i litteraturen for administration til mennesker.
English: Fenspiride has been shown in the Aptuit study to block hERG channels at supratherapeutic doses in vitro in a heterologous expression system, with an IC50 value of 15.14 µM.
Danish: Det blev i Aptuit-studiet påvist, at fenspirid hæmmer hERG-kanaler ved supraterapeutiske doser in vitro i et heterologt ekspressionssystem med en IC50-værdi på 15,14 µM.
English: QT prolongation and TdP are unpredictable and potentially life-threatening conditions that constitute a major safety concern, particularly given the benign symptoms for which fenspiride-containing medicinal products are used to treat.
Danish: QTforlængelse og torsades de pointes er uforudsigelige og potentielt livstruende sygdomme, som udgør et stort sikkerhedsproblem, især i betragtning af de godartede symptomer, som fenspirid-holdige lægemidler anvendes til at behandle.
English: In addition, performing ECG or measurements of potassium or magnesium levels is neither considered proportionate in pre-treatment screening for a medicinal product solely used to treat benign symptoms of generally self-limiting conditions, nor feasible in clinical practice.
Danish: Desuden anses gennemførelse af målinger af ekg eller kalium- eller magnesiumniveauer hverken for at stå i rimeligt forhold ved screening før behandling for et lægemiddel, der kun anvendes til at behandle godartede symptomer af generelt selvbegrænsende sygdomme, eller for at være praktisk gennemførligt i klinisk praksis.
English: • Taking into account that these medicinal products are only used to treat benign symptoms, the PRAC considered that no feasible and proportionate measures would effectively allow identifying patients with risk factors for QT prolongation and TdP, and that therefore any related risk minimisation measures could not be implemented in clinical practice.
Danish: • Da disse lægemidler kun anvendes til at behandle godartede symptomer, vurderede PRAC, at det ikke ville være muligt at gennemføre rimelige foranstaltninger til effektiv identificering af patienter med risikofaktorer for QT-forlængelse og torsades de pointes, og at der derfor ikke kan gennemføres nogen relaterede risikominimerende foranstaltninger i klinisk praksis.
English: In addition, no effect of fenspiride was observed on the PR or QRS complex of the ECG, suggesting that fenspiride has no significant effect on other cardiac channels and no compensatory action of hERG blockade in vivo.
Danish: Derudover er der ikke observeret nogen effekt ved fenspirid på PR- eller QRSkomplekset i ekg'er, hvilket indikerer, at fenspirid ikke har nogen signifikant virkning på andre kardielle kanaler og ingen kompenserende virkning i form af hERG-blokade in vivo.
English: In in silico models, fenspiride induced QT prolongation and “early afterdepolarizations” (EADs; arrhythmic makers) in specific cardiovascular disease state models.
Danish: I in silico-modeller inducerede fenspirid QT-forlængelse og tidlige efterdepolariseringer (arytmiske markører) i specifikke modeller for kardiovaskulær sygdomsstatus.
English: QT/QTc interval prolongation was not accompanied by any events of arrhythmia or contracture on the guinea pig heart model at any assay concentration.
Danish: Forlængelse af QT/QTcintervallet blev ikke ledsaget af arytmier eller kontrakturer i marsvinhjerte-modellen ved nogen af de undersøgte koncentrationer.
English: Taking into account that fenspiride is indicated to treat benign symptoms and the seriousness of the risk of unpredictable QT prolongation leading to proarrhythmic potential in human, the ANSM concluded that the benefit-risk balance of fenspiride-containing medicinal products was no longer favourable in the treatment of symptoms related to bronchopulmonary diseases, and suspended the marketing authorisations of these products.
Danish: I betragtning af, at fenspirid er indiceret til behandling af godartede symptomer og alvoren af risikoen for uforudsigelig QT-forlængelse, der kan føre til pro-arytmisk potentiale hos mennesker, konkluderede ANSM, at benefit/risk-forholdet for fenspirid-holdige lægemidler ikke længere er gunstigt ved behandling af symptomer relateret til bronkopulmonale sygdomme, og suspenderede markedsføringstilladelserne for disse lægemidler.
English: Newly available results of two non-clinical studies showed that fenspiride can induce an inhibition of hERG tail current in vitro, and increase the corrected QT (QTc) intervals in isolated and perfused guinea pig heart.
Danish: Resultater fra to ikke-kliniske studier, der er blevet tilgængelige for nylig, viser, at fenspirid kan medføre hæmning af hERG-tail current in vitro og øge de korrigerede QT (QTc)-intervaller hos isolerede og perfunderede marsvinhjerter.
English: The PRAC further noted that in view of the low safety margin calculated at doses below the therapeutic effect dose, reducing the dose would not permit to reduce the risk to an acceptable level.
Danish: I lyset af den lave sikkerhedsmargen, der var beregnet ved doser under den terapeutisk virksomme dosis, bemærkede PRAC desuden, at reduktion af dosen ikke ville gøre det muligt at reducere risikoen til et acceptabelt niveau.
English: • The PRAC reviewed the totality of the data available for fenspiride-containing medicinal products in relation to the risk of QT prolongation.
Danish: • PRAC gennemgik alle tilgængelige data vedrørende fenspirid-holdige lægemidler i forhold til risikoen for QT-forlængelse.
English: This included the results of non-clinical studies and post-marketing case reports as well as published efficacy studies submitted by the MAHs, by stakeholders and provided by EMA.
Danish: Gennemgangen omfattede resultaterne af ikke-kliniske studier og indberetninger af tilfælde efter markedsføring samt offentliggjorte effektstudier, der var fremlagt af indehaverne af markedsføringstilladelse, interessenter og EMA.
English: Consequently, the PRAC recommended the revocation of the marketing authorisations for fenspiride-containing medicinal products.
Danish: PRAC anbefalede derfor tilbagekaldelse af markedsføringstilladelserne for fenspirid-holdige lægemidler.
English: It has also been shown in a recent ex vivo study on isolated guinea pig hearts that the hERG blockade exerted by fenspiride may translate into QT prolongation in a similar concentration range as observed in the hERG study.
Danish: Det er også påvist i et nyligt ex vivo-studie hos isolerede marsvin-hjerter, at den hERG-blokade, som fenspirid medfører, kan føre til QT-forlængelse i samme koncentrationsinterval som observeret i hERGstudiet.
English: • The PRAC considered the procedure under Article 107i of Directive 2001/83/EC, for fenspiridecontaining medicinal products (see Annex I).
Danish: • PRAC behandlede sagen vedrørende fenspirid-holdige lægemidler (se bilag I) i henhold til artikel 107i i direktiv 2001/83/EF.
English: • Further, the PRAC could not identify condition(s) to the marketing authorisation which if fulfilled would demonstrate a positive benefit-risk balance for these products in a defined patient population.
Danish: • PRAC kunne desuden ikke identificere nogen betingelser for markedsføringstilladelsen, der, selvom de blev opfyldt, kunne påvise et positivt benefit/risk-forhold for disse lægemidler i en defineret patientpopulation.
English: The Committee, as a consequence, considers that the benefit-risk balance of fenspiride-containing medicinal products is no longer favourable.
Danish: Udvalget vurderer som følge heraf, at benefit/risk-forholdet for fenspirid-holdige lægemidler ikke længere er positivt.
English: • The PRAC considered that the use of fenspiride is associated with a risk of QT prolongation, and therefore it has proarrhythmic potential and present a risk of Torsade de Pointes (TdP).
Danish: • PRAC bemærkede, at brugen af fenspirid er forbundet med en risiko for QT-forlængelse, og derfor har stoffet proarytmisk potentiale og udgør en risiko for torsades de pointes.
English: In summary based on non-clinical assays of the accepted surrogate markers of TdP, i.e. blockade of hERG tail current and prolongation of the QT/QTc interval, and on post-marketing spontaneous reports of confirmed cases of TdP, QT prolongation and ventricular fibrillation/arrhythmia, the risk of QT prolongation, a proarrhythmic potential and associated risk of TdP is considered confirmed with fenspiride use.
Danish: På grundlag af ikke-kliniske undersøgelser af de accepterede surrogat-markører for torsades de pointes, dvs. blokade af hERG-tail current og forlængelse af QT-/QTc-intervallet, og spontane indberetninger efter markedsføring af bekræftede tilfælde af torsades de pointes, QT-forlængelse og ventrikelflimren/arytmier kan det derfor sammenfattende anses for bekræftet, at der er en risiko for QT-forlængelse, et proarytmisk potentiale og en deraf følgende risiko for torsades de pointes forbundet med brug af fenspirid.
English: Regarding clinical data, analysis of post-marketing cases reported since the marketing authorisation showed evidence to support a causal association between occurrence of QT prolongation/TdP in patients, mostly with risk factors for these events, and the treatment with fenspiride-containing medicinal products.
Danish: Hvad angår kliniske data, har en analyse af tilfælde, der er indberettet efter markedsføring, vist evidens for en årsagssammenhæng mellem forekomsten af QT-forlængelse/torsades de pointes hos patienter (typisk med risikofaktorer for disse hændelser) og behandlingen med fenspirid-holdige lægemidler.
English: The PRAC noted that this conclusion was also reached by the MAH of the originator.
Danish: PRAC bemærkede, at indehaveren af markedsføringstilladelse for det originale lægemiddel også var nået til denne konklusion.
English: Therefore, pursuant to Article 116 of Directive 2001/83/EC, the Committee recommends the revocation of the marketing authorisations for fenspiride-containing medicinal products.
Danish: I henhold til artikel 116 i direktiv 2001/83/EF anbefaler udvalget derfor tilbagekaldelse af markedsføringstilladelserne for fenspirid-holdige lægemidler.
English: The PRAC considered all data submitted by the MAHs, received from stakeholders and provided by EMA.
Danish: PRAC gennemgik alle de data, som var blevet fremlagt af indehaverne af markedsføringstilladelser, interessenterne og EMA.
English: Therefore, the PRAC concluded that the risk of QT prolongation, the proarrhythmic potential and associated risk of TdP outweighs the benefits of fenspiride in its authorised indication(s).
Danish: PRAC konkluderede derfor, at risikoen for QTforlængelse, det proarytmiske potentiale og den forbundne risiko for torsades de pointes opvejer fordelene ved fenspirid i de godkendte indikationer.
English: The CMDh, as a consequence, considers that the benefit-risk balance of fenspiride-containing medicinal products is not favourable.
Danish: CMDh vurderer som følge heraf, at benefit/risk-forholdet for fenspirid-holdige lægemidler ikke er positivt.
English: Therefore, pursuant to Article 116 of Directive 2001/83/EC, the CMDh recommends the revocation of the marketing authorisations for fenspiride-containing medicinal products.
Danish: I henhold til artikel 116 i direktiv 2001/83/EF anbefaler CMDh derfor tilbagekaldelse af markedsføringstilladelserne for fenspirid-holdige lægemidler.
English: Further, the PRAC could not identify condition(s) which if fulfilled would demonstrate a positive benefitrisk balance for these products in a defined patient population.
Danish: PRAC kunne desuden ikke identificere nogen betingelser, der, selvom de blev opfyldt, kunne påvise et positivt benefit/risk-forhold for disse lægemidler i en defineret patientpopulation.
English: Additionally, unspecific terms of syncope, loss of consciousness, tachycardia and palpitations that may (among others) be signs and symptoms of TdP were present in a significant number of cases.
Danish: Desuden blev der i et betydeligt antal tilfælde anvendt uspecifikke termer som besvimelse, tab af bevidsthed, takykardi og palpitationer, der kan være nogle af tegnene og symptomerne på torsades de pointes.
English: The marketing authorisation was renewed on 20 September 2001 and on 20 September 2006.
Danish: Markedsføringstilladelsen blev forlænget den 20. september 2001 og den 20. september 2006.
English: The additional studies showed that the presence of antibodies was maintained for up to five years.
Danish: De yderligere undersøgelser viste, at tilstedeværelsen af antistoffer blev fastholdt i op til fem år.