natgillin/translations-raw huggingface dataset:
За практическа информация относно употребата на Tecfidera пациентите следва да прочетат листовката или да попитат своя лекар или фармацевт.
For practical information about using Tecfidera, patients should read the package leaflet or contact their doctor or pharmacist.
При МС имунната система на организма не функционира правилно и атакува части от централната нервна система (главния и гръбначния мозък), като по този начин причинява възпаление, увреждащо обвивките на нервите.
In MS, the body's immune system malfunctions and attacks parts of the central nervous system (the brain and spinal cord), causing the inflammation that damages the nerve sheaths.
За пълния списък на всички нежелани лекарствени реакции, съобщени при Tecfidera, вижте листовката.
For the full list of all side effects reported with Tecfidera, see the package leaflet.
Какви ползи от Tecfidera са установени в проучванията?
What benefits of Tecfidera have been shown in studies?
Какви са рисковете, свързани с Tecfidera?
What are the risks associated with Tecfidera?
Най-честите нежелани лекарствени реакции при Tecfidera (които е възможно да засегнат повече от 1 на 10 души) са зачервяване (почервеняване на кожата) и стомашно-чревни проблеми (като диария, гадене и болки в коремната област).
The most common side effects with Tecfidera (which may affect more than 1 in 10 people) are flushing (reddening of skin) and gastrointestinal problems (such as diarrhoea, nausea, and pain in the abdominal area).
Какво представлява Tecfidera и за какво се използва?
What is Tecfidera and what is it used for?
Tecfidera се отпуска по лекарско предписание и лечението трябва да се започне под наблюдение на лекар с опит в лечението на МС.
Tecfidera can only be obtained with a prescription and treatment should be started under the supervision of a doctor experienced in treating MS.
Основните рискове, идентифицирани с Tecfidera, се считат за управляеми и включват зачервяване и стомашно-чревни проблеми (най-често срещаните нежелани лекарствени реакции), както и по-ниски нива на белите кръвни клетки и белтък в урината.
The main risks identified with Tecfidera are considered to be manageable and include flushing and gastrointestinal problems (the most common side effects), as well as reduced levels of white blood cells and protein in the urine.
В проучванията е доказано е, че диметил фумарат намалява възпалението и модулира активността на имунната система.
Dimethyl fumarate, has been shown in studies to reduce the inflammation and modulate the activity of the immune system.
Това проучване доказва, че Tecfidera е поефективен от плацебо за намаляване на броя на пристъпите в продължение на две години: броят на пристъпите на пациент годишно е около 0,2 при лечение с Tecfidera в сравнение с 0,4 с плацебо.
This study showed Tecfidera to be more effective than placebo in reducing the number of relapses over the course of two years: the number of relapses per patient per year was around 0.2 with Tecfidera compared with 0.4 with placebo.
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).
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).
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):
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%.
Дозата може временно да се намали при пациенти с нежелани лекарствени реакции на зачервяване и стомашно-чревни проблеми.
The dose may be reduced temporarily in patients experiencing side effects of flushing and gastrointestinal problems.
Европейската комисия издава разрешение за употреба на Tecfidera, валидно в Европейския съюз.
The European Commission granted a marketing authorisation valid throughout the European Union for Tecfidera on 30 January 2014.
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.
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.
Защо Tecfidera е разрешен за употреба?
Why is Tecfidera approved?
Как действа Tecfidera?
How does Tecfidera work?
Как се използва Tecfidera?
How is Tecfidera used?
Доказано е, че Tecfidera намалява броя на пристъпите при пациенти с пристъпно-ремитентна МС и броя на пациентите, които имат такива пристъпи.
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.
Disse data kan sammenfattes således:
Those data can be summarised as follows:
Dets anvendelse som positiv kontrol er derfor i overensstemmelse med de eksisterende retningslinjer og anses for berettiget.
Therefore, its use as the positive control is in line with existing guidance and is considered legitimate.
Direkte terapeutiske fordele
Direct therapeutic benefits
Ansøgningen blev indgivet med Irland som referencemedlemsstat og Belgien, Danmark, Frankrig, Tyskland, Grækenland, Italien, Luxembourg, Nederlandene, Portugal, Spanien og Det Forenede Kongerige
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.
Tilføj nedenstående tekst i de relevante sektioner af produktinformationen:
Add the following text in the relevant sections of the product information:
Får:
Sheep:
Vurdering af de forelagte data
Assessment of the data submitted
Tilstrækkeligheden af behandlingsperioden var et af hovedpunkterne i drøftelsen under indbringelsesproceduren.
The adequacy of the treatment interval was one of the main points of discussion during the referral procedure.
Der synes ikke at være fordel ved at øge dosis til 30 mg/kg.
There appears to be no advantage to increasing the dose to 30 mg/kg.
Efter gennemgang af alle de oplysninger, der er fremlagt skriftligt og ved den mundtlige forklaring, konkluderede CVMP, at:
Having considered all data submitted in writing and in the oral explanation the CVMP concluded that:
Ingen.
None.
Farmakokinetiske/farmakodynamiske data (PK/PD)
Pharmacokinetics/pharmacodynamics data (PK/PD)
Supplerende fordele
Additional benefits
Den valgte dosis og intervallet mellem behandlingerne var på linje med konklusionerne af PK/PDdataene.
The selected dose and between treatment interval was in line with the PK/PD conclusions.
Navn
Name
Under den decentrale procedure påpegede to berørte medlemsstater potentielle alvorlige risici, dels vedrørende de ansøgte indikationer (Frankrig), dels vedrørende produktets virkning (Danmark).
During the decentralised procedure two concerned Member States identified potential serious risks regarding the proposed indications (France) and the efficacy of the product (Denmark).
Betænkelighederne vedrørende høj andel af behandlingssvigt og formodet manglende virkning er omhandlet under vurdering af fordele.
The concern relating to the high failure rate and assumed lack of efficacy has been addressed under benefit assessment.
Liste over navne, lægemiddelform, styrke på det veterinærmedicinske produkt, dyrearter, administrationsmåde, ansøger
List of the names, pharmaceutical form, strength of the veterinary medicinal product, animal species, routes of administration, applicant in the Member States
Grækenland Intervet International B.V. Wim de Körverstraat 35
Belgium Intervet International B.V. Wim de Körverstraat 35
Der foreligger en række undersøgelser af fordelingen af florfenicol i bronkiesekret hos mennesket og forskellige dyrearter (svin og kalve).
• A variety of studies are available on the distribution of florfenicol in bronchial secretions in man and various animal species (pigs and calves).
Det gældende produktresumè, etikettering og indlægsseddel er de endelige versioner opnået via Koordinations Gruppens procedure med nedenstående tilføjelser:
The valid Summary of Product Characteristics, Labelling and Package Leaflet are the final versions achieved during the Coordination Group procedure with the following amendments:
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.
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.
Den indsigende medlemsstat fandt, at dette gav anledning til betænkelighed ved muligheden for underdosering og dermed øget risiko for resistensudvikling over for florfenicol.
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.
MIC-dataene er baseret på isolater indsamlet mellem 2006 og 2010 fra får med luftvejssygdom.
The isolates on which the MIC data are based were collected from sheep with respiratory tract disease between 2006 and 2010.
Konklusion
Conclusion
Ansøgeren fremlagde detaljerede farmakodynamiske og farmakokinetiske data til underbygning af den ansøgte indikation.
The applicant provided detailed pharmacodynamic and pharmacokinetic data to justify the proposed dose for the claimed indication.
Risikovurdering
Risk assessment
Til imødekommelse af de betænkeligheder, der var rejst i forbindelse med indbringelsen, fremlagde ansøgeren alle foreliggende data vedrørende produktets virkning hos får.
In order to address the concerns raised by the referral, the applicant presented all available efficacy data for sheep.
MIC90-værdierne for florfenicol ligger i området 0,5-1 μg/ml for de patogene målorganismer M. haemolytica og P. multocida.
• The MIC90 values of florfenicol are in the range 0.5 - 1 μg/ml for target pathogens M. haemolytica and P. multocida.
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).
These issues remained unsolved and therefore a referral under Article 33(1) of Directive 2001/82/EC to the CMD(v) was started.
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.
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.
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.
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.
til risikostyring eller risikonedsættelse
Risk management or mitigation measures
Videnskabelige konklusioner og begrundelse for ændringen af produktresuméet, etiketteringen og indlægssedlen
Scientific conclusions and grounds for amendment of the summary of product characteristics, labelling and package leaflet
Kvalitet, brugersikkerhed, miljørisiko og restkoncentrationer er
Quality, User safety, Environmental risk and Residues were not assessed in this referral procedure.
i produktinformationen gælder fortsat med den ændring, der er angivet i afsnit 2.4 nedenfor. Der er ikke behov for yderligere foranstaltninger
The warnings in the product literature remain appropriate with the change indicated in section 2.4 below.
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.
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.
tilfælde med behandlingssvigt i den kliniske feltundersøgelse forelagt af ansøgeren.
Furthermore, the treatment failure rates in the clinical field study submitted by the applicant were considered too high.
som aktivt stof indeholdt i veterinærmedicinske produkter, der er godkendt i flere EU-lande til behandling af luftvejssygdom hos kvæg og svin.
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.
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.
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.
Lægemiddelform Styrke Dyrearter
Pharmaceutical form Strength Animal species Route of administration
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).
Repeat administration of 20 mg/kg once daily for three days (proposed posology) resulted in some accumulation (accumulation factor of 1.48).
Det bemærkes, at der på nuværende tidspunkt ikke findes en internationalt vedtaget tærskelværdi for følsomheden af ovine luftvejspatogener over for florfenicol.
It is noted that, currently, for ovine respiratory disease pathogens there is no internationally agreed breakpoint for florfenicol sensitivity.
til risikostyring eller risikonedsættelse i konsekvens af denne procedure for indbringelse af sager.
No further risk management or mitigation measures are required as a consequence of this referral procedure.
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.
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.
Fordelen ved florfenicol er, at ovin luftvejssygdom forbundet med følsomme stammer af M. haemolytica og P. multocida kan behandles effektivt.
The benefit of florfenicol is that ovine respiratory disease associated with susceptible M. haemolytica and P. multocida can effectively be treated.
Begrundelse for ændring af produktresuméet
Grounds for amendment of the summary of product characteristics
Samlet resumé af den videnskabelige vurdering af Nuflor 300 mg/ml injektionsvæske, opløsning, til kvæg og får
Overall summary of the scientific evaluation of Nuflor 300 mg/ml solution for injection for cattle and sheep
DOSERING FOR HVER DYREART, ANVENDELSESMÅDE OG INDGIVELSESVEJ(E)
DOSAGE FOR EACH SPECIES, ROUTES AND METHOD OF ADMINISTRATION
sager vedrørte betænkeligheder omkring produktets virkning.
The concerns raised for this referral procedure related to the efficacy of the product.
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.
During the procedure the applicant provided additional data and the issues raised by France regarding the proposed indications were resolved.
Indledning
Introduction
den ansøgte doseringsplan støttes af en dosisfastlæggelsesundersøgelse med en eksperimentel model for luftvejssygdom, hvor forsøgsdyrene blev belastet med Mannheimia haemolytica
• 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
til får med naturligt erhvervede luftvejsinfektioner. Forsøget blev udført på flere centre i Tyskland og Spanien.
The study was conducted at multiple sites in Germany and Spain.
Den gennemsnitlige serumkoncentration af florfenicol var vedholdende over 1 μg/ml (MIC90) i indtil 18 timer efter administration af den anbefalede behandlingsdosis.
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.
(Den kliniske tærskelværdi er en MIC-værdi, der af klinikere anvendes til at klassificere bakterier
(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.)
til de relevante sektioner af produktresumè, etikettering og indlægsseddel
Amendments in the relevant sections of the summary of product characteristics, labelling and package leaflet
På grundlag af de fremlagte oplysninger vedrørende de anmeldte betænkeligheder ved denne procedure for indbringelse af sager, konkluderede Udvalget for Lægemidler
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.
De foreliggende data synes at vise, at koncentrationerne af florfenicol i lungevæv/bronkiesekret er mindst lige så høje
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.
Sagen blev derfor henvist til CVMP den 21.
The concerns raised by Denmark remained unsolved and consequently the matter was referred to the CVMP on 21 September 2011.
4.9 Dosering og indgivelsesmåde
4.9 Amounts to be administered and administration route
Frankrig
France
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.
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.
time muligvis ikke ville opretholde en aktiv/effektiv koncentration af florfenicol på infektionsstedet i tidsrummet mellem behandlingerne (dvs. 24 timer).
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).
Vurdering af benefit/risk-forholdet
Evaluation of the benefit-risk balance
ikke er rejst betænkelighed i løbet af proceduren, og da dosis forbliver
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.
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.
• 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.
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.
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.
De foreliggende data tyder således på, at den mest relevante parameter
The available data suggest, therefore, that for this antibiotic the most relevant parameter for prediction of efficacy is time above MIC.
Feltundersøgelse
Field study
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
• 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,
Undersøgelsen viste, at florfenicol, administreret én gang dagligt ved en dosis på enten 10, 20 eller 30 mg/kg, var effektivt
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.
Sikkerhed hos måldyrearten
Target animal safety
Florfenicol har postantibiotisk effekt efter kun to timers eksponering (fra 1-3 timer ved koncentrationer >1 μg/ml).
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).
Holland
The Netherlands
• 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
• 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.
Disse data viser, at hvis koncentrationen af florfenicol i plasma/væv overstiger MIC
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.