FrancophonIA/ELRC3.0 huggingface dataset:
English: It is used specifically in adults with a type of MS known as relapsing-remitting MS, where the patient has flare-ups of symptoms (relapses) followed by periods of recovery (remissions).
Bulgarian: Tecfidera се използва специално при възрастни с тип MС, известен като пристъпно-ремитентна МС, при която пациентът има обостряния на симптомите (пристъпи), последвани от периоди на възстановяване (ремисии).
English: In a main study involving 1,234 patients, the proportion of patients who experienced a relapse over the course of two years was significantly lower with Tecfidera treatment than with placebo (a dummy treatment): 27% versus 46%.
Bulgarian: В едно основно проучване при 1234 пациенти процентът на пациентите, които са имали пристъп в течение на две години, е значително по-нисък при лечение с Tecfidera в сравнение с плацебо (сляпо лечение):
English: The dose may be reduced temporarily in patients experiencing side effects of flushing and gastrointestinal problems.
Bulgarian: Дозата може временно да се намали при пациенти с нежелани лекарствени реакции на зачервяване и стомашно-чревни проблеми.
English: The European Commission granted a marketing authorisation valid throughout the European Union for Tecfidera on 30 January 2014.
Bulgarian: Европейската комисия издава разрешение за употреба на Tecfidera, валидно в Европейския съюз.
English: Tecfidera has been shown to be effective in reducing the number of relapses in patients with relapsingremitting MS and in reducing the number of patients who have relapses during treatment.
Bulgarian: Доказано е, че Tecfidera е ефективен за намаляване броя на пристъпите при пациенти с пристъпно-ремитентна МС и за намаляване на броя на пациентите, които имат пристъпи по време на лечението.
English: Why is Tecfidera approved?
Bulgarian: Защо Tecfidera е разрешен за употреба?
English: How does Tecfidera work?
Bulgarian: Как действа Tecfidera?
English: How is Tecfidera used?
Bulgarian: Как се използва Tecfidera?
English: Tecfidera has been shown to reduce the number of relapses in patients with relapsing-remitting MS and to reduce the number of patients who have them.
Bulgarian: Доказано е, че Tecfidera намалява броя на пристъпите при пациенти с пристъпно-ремитентна МС и броя на пациентите, които имат такива пристъпи.
English: Those data can be summarised as follows:
Bulgarian: Disse data kan sammenfattes således:
English: Therefore, its use as the positive control is in line with existing guidance and is considered legitimate.
Bulgarian: Dets anvendelse som positiv kontrol er derfor i overensstemmelse med de eksisterende retningslinjer og anses for berettiget.
English: Direct therapeutic benefits
Bulgarian: Direkte terapeutiske fordele
English: The application was submitted to Ireland as reference Member State and Belgium, Denmark, France, Germany, Greece, Italy, Luxembourg, the Netherlands, Portugal, Spain and the United Kingdom as concerned Member States.
Bulgarian: Ansøgningen blev indgivet med Irland som referencemedlemsstat og Belgien, Danmark, Frankrig, Tyskland, Grækenland, Italien, Luxembourg, Nederlandene, Portugal, Spanien og Det Forenede Kongerige
English: Add the following text in the relevant sections of the product information:
Bulgarian: Tilføj nedenstående tekst i de relevante sektioner af produktinformationen:
English: Sheep:
Bulgarian: Får:
English: Assessment of the data submitted
Bulgarian: Vurdering af de forelagte data
English: The adequacy of the treatment interval was one of the main points of discussion during the referral procedure.
Bulgarian: Tilstrækkeligheden af behandlingsperioden var et af hovedpunkterne i drøftelsen under indbringelsesproceduren.
English: There appears to be no advantage to increasing the dose to 30 mg/kg.
Bulgarian: Der synes ikke at være fordel ved at øge dosis til 30 mg/kg.
English: Having considered all data submitted in writing and in the oral explanation the CVMP concluded that:
Bulgarian: Efter gennemgang af alle de oplysninger, der er fremlagt skriftligt og ved den mundtlige forklaring, konkluderede CVMP, at:
English: None.
Bulgarian: Ingen.
English: Pharmacokinetics/pharmacodynamics data (PK/PD)
Bulgarian: Farmakokinetiske/farmakodynamiske data (PK/PD)
English: Additional benefits
Bulgarian: Supplerende fordele
English: The selected dose and between treatment interval was in line with the PK/PD conclusions.
Bulgarian: Den valgte dosis og intervallet mellem behandlingerne var på linje med konklusionerne af PK/PDdataene.
English: Name
Bulgarian: Navn
English: During the decentralised procedure two concerned Member States identified potential serious risks regarding the proposed indications (France) and the efficacy of the product (Denmark).
Bulgarian: Under den decentrale procedure påpegede to berørte medlemsstater potentielle alvorlige risici, dels vedrørende de ansøgte indikationer (Frankrig), dels vedrørende produktets virkning (Danmark).
English: The concern relating to the high failure rate and assumed lack of efficacy has been addressed under benefit assessment.
Bulgarian: Betænkelighederne vedrørende høj andel af behandlingssvigt og formodet manglende virkning er omhandlet under vurdering af fordele.
English: List of the names, pharmaceutical form, strength of the veterinary medicinal product, animal species, routes of administration, applicant in the Member States
Bulgarian: Liste over navne, lægemiddelform, styrke på det veterinærmedicinske produkt, dyrearter, administrationsmåde, ansøger
English: Belgium Intervet International B.V. Wim de Körverstraat 35
Bulgarian: Grækenland Intervet International B.V. Wim de Körverstraat 35
English: • A variety of studies are available on the distribution of florfenicol in bronchial secretions in man and various animal species (pigs and calves).
Bulgarian: Der foreligger en række undersøgelser af fordelingen af florfenicol i bronkiesekret hos mennesket og forskellige dyrearter (svin og kalve).
English: The valid Summary of Product Characteristics, Labelling and Package Leaflet are the final versions achieved during the Coordination Group procedure with the following amendments:
Bulgarian: Det gældende produktresumè, etikettering og indlægsseddel er de endelige versioner opnået via Koordinations Gruppens procedure med nedenstående tilføjelser:
English: Based on the available pharmacodynamic data, it is accepted that a dose selected on the basis of this study should also be predictive of likely efficacy against P. multocida.
Bulgarian: Baseret på de foreliggende farmakodynamiske data godtages det, at en dosis valgt på grundlag af denne undersøgelse også anses for prædiktiv for virkningen mod P. multocida.
English: For the objecting Member State, this gave rise to concerns that there was the potential for underdosing and that there may be an increase in risk for development of florfenicol resistance.
Bulgarian: Den indsigende medlemsstat fandt, at dette gav anledning til betænkelighed ved muligheden for underdosering og dermed øget risiko for resistensudvikling over for florfenicol.
English: The isolates on which the MIC data are based were collected from sheep with respiratory tract disease between 2006 and 2010.
Bulgarian: MIC-dataene er baseret på isolater indsamlet mellem 2006 og 2010 fra får med luftvejssygdom.
English: Conclusion
Bulgarian: Konklusion
English: The applicant provided detailed pharmacodynamic and pharmacokinetic data to justify the proposed dose for the claimed indication.
Bulgarian: Ansøgeren fremlagde detaljerede farmakodynamiske og farmakokinetiske data til underbygning af den ansøgte indikation.
English: Risk assessment
Bulgarian: Risikovurdering
English: In order to address the concerns raised by the referral, the applicant presented all available efficacy data for sheep.
Bulgarian: Til imødekommelse af de betænkeligheder, der var rejst i forbindelse med indbringelsen, fremlagde ansøgeren alle foreliggende data vedrørende produktets virkning hos får.
English: • The MIC90 values of florfenicol are in the range 0.5 - 1 μg/ml for target pathogens M. haemolytica and P. multocida.
Bulgarian: MIC90-værdierne for florfenicol ligger i området 0,5-1 μg/ml for de patogene målorganismer M. haemolytica og P. multocida.
English: These issues remained unsolved and therefore a referral under Article 33(1) of Directive 2001/82/EC to the CMD(v) was started.
Bulgarian: Disse spørgsmål forblev uafklarede, hvorfor der blev indledt en indbringelsesprocedure i henhold til artikel 33, stk. 1, i direktiv 2001/82/EF, til CMD(v) (koordinationsgruppen for gensidig anerkendelse og decentrale procedurer - veterinære anliggender).
English: In support of the proposed recommended treatment dose, the applicant conducted a comprehensive dose finding study using an experimental model of respiratory disease where test animals were challenged with M. haemolytica.
Bulgarian: Til støtte for den ansøgte anbefalede behandlingsdosis udførte ansøgeren en omfattende dosisfastlæggelsesundersøgelse, hvor der blev anvendt en eksperimentel model for luftvejssygdomme med belastning af forsøgsdyrene med M. haemolytica.
English: Secondary variables (e.g. mortality, pathogen recover, lung weight, lesion weight) confirm that 20 mg/kg is superior to a dose of 10 mg/kg.
Bulgarian: De sekundære variabler (f.eks. dødelighed, antal patogene, lungevægt, vægt af væv med forandringer) bekræfter superioriteten af en dosis på 20 mg/kg i forhold til 10 mg/kg.
English: Risk management or mitigation measures
Bulgarian: til risikostyring eller risikonedsættelse
English: Scientific conclusions and grounds for amendment of the summary of product characteristics, labelling and package leaflet
Bulgarian: Videnskabelige konklusioner og begrundelse for ændringen af produktresuméet, etiketteringen og indlægssedlen
English: Quality, User safety, Environmental risk and Residues were not assessed in this referral procedure.
Bulgarian: Kvalitet, brugersikkerhed, miljørisiko og restkoncentrationer er
English: The warnings in the product literature remain appropriate with the change indicated in section 2.4 below.
Bulgarian: i produktinformationen gælder fortsat med den ændring, der er angivet i afsnit 2.4 nedenfor. Der er ikke behov for yderligere foranstaltninger
English: While similar data have not been generated for sheep, it is reasonable to assume that that florfenicol concentrations achieved in plasma reflect what will be achieved in the lung.
Bulgarian: som de, der er påvist i serum. Der findes ikke tilsvarende data for får, men det er rimeligt at antage, at de opnåede koncentrationer i plasma afspejler dem, der opnås i lungerne.
English: Furthermore, the treatment failure rates in the clinical field study submitted by the applicant were considered too high.
Bulgarian: tilfælde med behandlingssvigt i den kliniske feltundersøgelse forelagt af ansøgeren.
English: The active substance is included in veterinary medicinal products currently licensed in several countries in the European Union for use in cattle and pigs for the treatment of respiratory disease.
Bulgarian: som aktivt stof indeholdt i veterinærmedicinske produkter, der er godkendt i flere EU-lande til behandling af luftvejssygdom hos kvæg og svin.
English: Therefore, the CVMP concluded that the objections raised by Denmark should not prevent the granting of the marketing authorisation for Nuflor 300 mg/ml solution for injection for cattle and sheep as the overall benefit-risk balance of the product is positive, subject to the recommended changes in the product information set out in annex III.
Bulgarian: CVMP konkluderede derfor, at de indvendinger, der er rejst af Danmark, ikke bør være til hinder for udstedelse af markedsføringstilladelse for Nuflor 300 mg/ml injektionsvæske, opløsning, til kvæg og får, da det overordnede benefit/risk-forhold for produktet er positivt, forudsat at der foretages de anbefalede ændringer i produktoplysningerne, som fremgår af bilag III.
English: Pharmaceutical form Strength Animal species Route of administration
Bulgarian: Lægemiddelform Styrke Dyrearter
English: Repeat administration of 20 mg/kg once daily for three days (proposed posology) resulted in some accumulation (accumulation factor of 1.48).
Bulgarian: til 13,76 + 6,42 timer. Gentagen administration af 20 mg/kg én gang dagligt i tre dage (den ansøgte dosering) resulterede i nogen akkumulation (akkumulationsfaktor 1,48).
English: It is noted that, currently, for ovine respiratory disease pathogens there is no internationally agreed breakpoint for florfenicol sensitivity.
Bulgarian: Det bemærkes, at der på nuværende tidspunkt ikke findes en internationalt vedtaget tærskelværdi for følsomheden af ovine luftvejspatogener over for florfenicol.
English: No further risk management or mitigation measures are required as a consequence of this referral procedure.
Bulgarian: til risikostyring eller risikonedsættelse i konsekvens af denne procedure for indbringelse af sager.
English: The applicant Intervet International BV submitted an application for a decentralised procedure (DCP) for an extension (Article 19 of Regulation (EC) 1234/2008) of the existing marketing authorisation of Nuflor 300 mg/ml solution for injection for cattle to add sheep as a target species.
Bulgarian: Ansøgeren, Intervet International BV, har indgivet en ansøgning via den decentrale procedure (DCP) om udvidelse (i henhold til artikel 19 i forordning (EF) nr. 1234/2008) af den eksisterende markedsføringstilladelse for Nuflor 300 mg/ml injektionsvæske, opløsning, til kvæg med tilføjelse af får som måldyreart.
English: The benefit of florfenicol is that ovine respiratory disease associated with susceptible M. haemolytica and P. multocida can effectively be treated.
Bulgarian: Fordelen ved florfenicol er, at ovin luftvejssygdom forbundet med følsomme stammer af M. haemolytica og P. multocida kan behandles effektivt.
English: Grounds for amendment of the summary of product characteristics
Bulgarian: Begrundelse for ændring af produktresuméet
English: Overall summary of the scientific evaluation of Nuflor 300 mg/ml solution for injection for cattle and sheep
Bulgarian: Samlet resumé af den videnskabelige vurdering af Nuflor 300 mg/ml injektionsvæske, opløsning, til kvæg og får
English: DOSAGE FOR EACH SPECIES, ROUTES AND METHOD OF ADMINISTRATION
Bulgarian: DOSERING FOR HVER DYREART, ANVENDELSESMÅDE OG INDGIVELSESVEJ(E)
English: The concerns raised for this referral procedure related to the efficacy of the product.
Bulgarian: sager vedrørte betænkeligheder omkring produktets virkning.
English: During the procedure the applicant provided additional data and the issues raised by France regarding the proposed indications were resolved.
Bulgarian: Under proceduren fremlagde ansøgeren supplerende oplysninger, hvilket førte til afklaring af de spørgsmål, der var rejst af Frankrig vedrørende de ansøgte indikationer. De betænkeligheder, der var rejst af Danmark, var fortsat uafklarede.
English: Introduction
Bulgarian: Indledning
English: • The proposed dosing schedule is supported by a dose finding study using an experimental model of respiratory disease where test animals were challenged with Mannheimia haemolytica, and
Bulgarian: den ansøgte doseringsplan støttes af en dosisfastlæggelsesundersøgelse med en eksperimentel model for luftvejssygdom, hvor forsøgsdyrene blev belastet med Mannheimia haemolytica
English: The study was conducted at multiple sites in Germany and Spain.
Bulgarian: til får med naturligt erhvervede luftvejsinfektioner. Forsøget blev udført på flere centre i Tyskland og Spanien.
English: Mean florfenicol concentration in serum remained above 1 μg/ml (MIC90) for up to 18 hours following administration of the product at the recommended treatment dose.
Bulgarian: Den gennemsnitlige serumkoncentration af florfenicol var vedholdende over 1 μg/ml (MIC90) i indtil 18 timer efter administration af den anbefalede behandlingsdosis.
English: (Clinical breakpoint is a MIC value used by clinicians to classify bacteria as susceptible or resistant to a certain antimicrobial and is therefore a measure of clinical efficacy.)
Bulgarian: (Den kliniske tærskelværdi er en MIC-værdi, der af klinikere anvendes til at klassificere bakterier
English: Amendments in the relevant sections of the summary of product characteristics, labelling and package leaflet
Bulgarian: til de relevante sektioner af produktresumè, etikettering og indlægsseddel
English: Based on the data presented in relation to the concerns notified for this referral procedure, the Committee for Medicinal Products for Veterinary Use (CVMP) concluded that the benefit-risk balance was favourable.
Bulgarian: På grundlag af de fremlagte oplysninger vedrørende de anmeldte betænkeligheder ved denne procedure for indbringelse af sager, konkluderede Udvalget for Lægemidler
English: Based on available data, it would appear that florfenicol concentrations achieved in lung tissue/bronchial secretions are at least as high as those detected in serum.
Bulgarian: De foreliggende data synes at vise, at koncentrationerne af florfenicol i lungevæv/bronkiesekret er mindst lige så høje
English: The concerns raised by Denmark remained unsolved and consequently the matter was referred to the CVMP on 21 September 2011.
Bulgarian: Sagen blev derfor henvist til CVMP den 21.
English: 4.9 Amounts to be administered and administration route
Bulgarian: 4.9 Dosering og indgivelsesmåde
English: France
Bulgarian: Frankrig
English: While there were some reservations about the use of oxytetracycline as the positive control, it is accepted that the chosen comparator product has a claim for ovine respiratory disease and is commonly used as a first-line therapy that will most likely be administered without any information on the sensitivity of causal organisms.
Bulgarian: til behandling af ovin luftvejssygdom og almindeligt anvendt som førstevalgsbehandling, og som må antages at blive administreret, uden at følsomheden af de pågældende patogene organismer er undersøgt.
English: There was a concern that a dose of 20 mg florfenicol/kg administered intramuscularly every 24 hours would not maintain an active/effective concentration of florfenicol at the infection site for the between treatment interval (that is, 24 hours).
Bulgarian: time muligvis ikke ville opretholde en aktiv/effektiv koncentration af florfenicol på infektionsstedet i tidsrummet mellem behandlingerne (dvs. 24 timer).
English: Evaluation of the benefit-risk balance
Bulgarian: Vurdering af benefit/risk-forholdet
English: This part of the dossier was not assessed in this referral procedure as no concern was notified by the reference Member State nor was any concern raised during the procedure as the dose remains as proposed and concluded by the reference Member State.
Bulgarian: ikke er rejst betænkelighed i løbet af proceduren, og da dosis forbliver
English: • Although some concentration dependency trends were observed for M. haemolytica strains, the killing effect/kinetic does not increase dramatically with the concentration of the antibiotic over the MIC or twice the MIC.
Bulgarian: Der var nogen tendens til koncentrationsafhængighed for stammer af M. haemolytica, men den baktericide virkning/kinetik stiger ikke dramatisk med koncentrationen af dette antibiotikum, når denne er over MIC eller den dobbelte af MIC. Den baktericide effekt af florfenicol er derfor i det væsentlige tidsafhængig.
English: The application in question, submitted via the decentralised procedure, is an extension of the existing marketing authorisation of Nuflor 300 mg/ml solution for injection for cattle to add sheep as a target species.
Bulgarian: Ansøgeren har via den decentrale procedure (DCP) indgivet en ansøgning om udvidelse af den eksisterende markedsføringstilladelse for Nuflor 300 mg/ml injektionsvæske, opløsning, til kvæg, med tilføjelse af får som måldyreart.
English: The available data suggest, therefore, that for this antibiotic the most relevant parameter for prediction of efficacy is time above MIC.
Bulgarian: De foreliggende data tyder således på, at den mest relevante parameter
English: Field study
Bulgarian: Feltundersøgelse
English: • The MIC and pharmacokinetic data, taken together with what is known about florfenicol kill kinetics and post-antibiotic effect, support the recommended treatment interval (24 hours) for target respiratory tract pathogens with MIC up to 1 μg/ml when the product is administered to sheep at the proposed dose of 20 mg florfenicol/kg bodyweight,
Bulgarian: MIC-dataene og de farmakokinetiske data sammen med florfenicols celledrabkinetik og postantibiotiske effekt (PAE) underbygger det anbefalede behandlingsinterval (24 timer) for patogene målorganismer med MIC op til 1 μg/ml, når produktet administreres til får i den ansøgte dosis på 20 mg florfenicol/kg kropsvægt
English: The results of this study demonstrated that florfenicol administered once daily at a dose of either 10, 20 or 30 mg/kg was effective for the treatment of pneumonia in sheep induced by M. haemolytica.
Bulgarian: Undersøgelsen viste, at florfenicol, administreret én gang dagligt ved en dosis på enten 10, 20 eller 30 mg/kg, var effektivt
English: Target animal safety
Bulgarian: Sikkerhed hos måldyrearten
English: From the M. haemolytica data, it can be seen that time to achieve a 3-Log reduction decreased with increasing florfenicol concentration; and, after only two hours exposure, florfenicol exhibits a post-antibiotic effect (ranging from 1 - 3 hours at concentrations >1 μg/ml).
Bulgarian: Florfenicol har postantibiotisk effekt efter kun to timers eksponering (fra 1-3 timer ved koncentrationer >1 μg/ml).
English: The Netherlands
Bulgarian: Holland
English: • A field study conducted in line with EMA/CVMP guideline recommendations showed that Nuflor, administered in accordance with the proposed dosing schedule, was non-inferior to the authorised reference product, Terramycin 100 mg/ml, when used for the treatment of respiratory disease in sheep associated with either Mannheimia haemolytica or Pasteurella multocida.
Bulgarian: • en feltundersøgelse, der blev udført i overensstemmelse med EMA's/CVMP's retningslinjer, viste non-inferioritet af Nuflor i forhold til det godkendte sammenligningsprodukt, Terramycin 100
English: The data suggest that if florfenicol concentrations in plasma/tissue are above the MIC for in excess of two hours, there is likely to be a marked post-antibiotic effect.
Bulgarian: Disse data viser, at hvis koncentrationen af florfenicol i plasma/væv overstiger MIC
English: The overall conclusion is that the efficacy dataset as a whole is adequate to support the efficacy of Nuflor 300 mg/ml solution for injection for cattle and sheep at the dose of 20 mg/kg daily via the intramuscular route of administration for three consecutive days in the treatment of Ovine Respiratory Disease associated with M. haemolytica and P. multocida.
Bulgarian: Udvalget konkluderede, at de foreliggende data tilfredsstillende dokumenterer virkningen af Nuflor 300 mg/ml injektionsvæske, opløsning, til kvæg og får i en dosis på 20 mg/kg dagligt, givet intramuskulært i tre på hinanden følgende dage, til behandling af ovin luftvejssygdom forbundet med M. haemolytica og P. multocida.
English: However, the CVMP agreed that section 4.9 of the Summary of Product Characteristics should be amended to clarify that the recommended treatment dose and treatment interval for sheep is based on the time mean florfenicol concentrations are maintained above MIC90 (see Annex III).
Bulgarian: skal ændres, så det præciserer, at den dosis og det behandlingsinterval, der anbefales for får, forudsætter, at gennemsnitskoncentrationen af florfenicol vedholdende overstiger MIC90 (se bilag III).
English: Based on dossier data concerning Minimum Inhibitory Concentrations (MICs) for florfenicol (MIC90= 1 µg/ml) and considering its pharmacokinetic/pharmacodynamic (PK/PD) plasma profile, the period of exposure to the MIC90 strength was believed by the objecting Member State to be too short.
Bulgarian: Den indsigende medlemsstat mente, at eksponeringen for MIC90 var for kortvarig, dels ud fra dokumentationens oplysninger om mindste hæmmende koncentrationer (MIC) for florfenicol (MIC90= 1 µg/ml), dels på baggrund af stoffets farmakokinetiske og farmakodynamiske (PK/PD) plasmaprofil.