natgillin/translations-raw huggingface dataset:
CHMP fandt imidlertid, at de af indehaveren af markedsføringstilladelsen foreslåede foranstaltninger til risikominimering næppe vil kunne reducere de alvorlige kardiale og neurologiske bivirkninger, der er forbundet med brug af buflomedil, til et klinisk acceptabelt niveau.
However, the CHMP considered that the risk minimisation measures proposed by the MAH are unlikely to reduce the serious cardiac and neurological adverse events associated with the use of buflomedil to a clinically acceptable level.
Alt i alt anså the CHMP de forelagte kliniske data til dokumentation af virkningen af buflomedil for at være begrænsede.
Overall, the CHMP considered the clinical data submitted in support of the efficacy of buflomedil to be limited.
Skønt disse indberettede tilfælde er iatrogene, fandt CHMP, at de giver støttende evidens for de kardiovaskulære og neurologiske risici ved buflomedil, eftersom der blev konstateret bivirkninger ved det dobbelte af dagsdosis, hvad der tyder på, at der er risici ved forholdsvis små overdoser.
While acknowledging the iatrogenic nature of the reported cases, the CHMP considered that these cases provide supportive evidence of the cardiovascular and neurological risks of buflomedil, as adverse events were noted in patients administered twice the daily dosage, which suggests that the risks are associated with overdoses of relatively small magnitudes.
• udvalget fandt, at buflomedils smalle terapeutiske indeks giver anledning til stor betænkelighed, da patienter med perifere kredsløbsforstyrrelser, der behandles med buflomedil, under alle omstændigheder kan forventes at ville udvikle nedsat nyrefunktion på grund af deres sygdom,
• The Committee considered that in this context, the narrow therapeutic index of buflomedil is of major concern, as patients with peripheral vascular disease treated with buflomedil are inherently likely to experience decreased renal function, due to the nature of their condition.
Dette giver anledning til særlig betænkelighed, fordi patienter med perifere kredsløbsforstyrrelser under alle omstændigheder kan forventes at udvikle nedsat nyrefunktion på grund af deres sygdom.
This is of particular concern as patients with peripheral vascular disease are inherently likely to experience decreased renal function due to the nature of their condition.
Som konklusion fandt CHMP - i betragtning af de alvorlige kardiologiske og neurologiske bivirkninger, der er forbundet med brug af lægemidler indeholdende buflomedil under normale anvendelsesbetingelser, dokumentationen for den kliniske virkning, der er utilstrækkelig til at opveje risiciene ved anvendelse af buflomedil samt de fundne betænkeligheder vedrørende effektiviteten af foranstaltningerne til risikominimering - at risk/benefit-forholdet for lægemidler indeholdende buflomedil til oral indgivelse ikke er positivt under normale anvendelsesbetingelser.
In conclusion, taking into account the serious cardiac and neurological adverse events associated with the use of buflomedil-containing medicinal products under normal conditions of use, the evidence of limited clinical efficacy which is insufficient to compensate for the risks associated with the use of buflomedil and the established concerns regarding the effectiveness of the risk minimisation measures, the CHMP considered that the risk-benefit balance of buflomedil-containing medicinal products is not positive under normal conditions of use.
Disse betingelser anses for at være normale anvendelsesbetingelser for buflomedil.
Usage of buflomedil according to these conditions is considered to be under normal conditions of use.
CHMP vurderede virkningen af de foranstaltninger til risikominimering, der tidligere var indført i Frankrig og hovedsagelig bestod i en revision af produktresumé og kommunikation.
The CHMP assessed the impact of the risk minimisation measures previously implemented in France, consisting mainly of revisions to the SmPC and communication and noted the proposed extension of these measures to other member states.
CHMP konstaterede desuden, at lægemiddelovervågningsdata og toksikologiske overvågningsdata viser, at sikkerhedsprofilen af buflomedil ikke er blevet bedre trods implementeringen af risikostyringsplanen i Frankrig i 2006.
The CHMP also noted the pharmacovigilance and toxicovigilance data which show no improvement of the safety profile of buflomedil despite the implementation of the RMP in France in 2006; instead, a two fold increase of misuse compared to the previous period was observed.
Efter at have gennemgået alle de af indehaveren af markedsføringstilladelsen foreslåede foranstaltninger til risikominimering konkluderede CHMP, at på baggrund af den høje risiko ved buflomedil, navnlig for patienter med nedsat nyrefunktion og ældre patienter, har det ikke været muligt at udpege foranstaltninger, der kan mindske risiciene relateret til buflomedil til et acceptabelt niveau.
Having assessed the totality of the risk minimisation measures proposed by the MAH, the CHMP concluded that given the high risk with buflomedil, notably in patients with impaired renal function and in elderly patients, no measures could be identified to reduce the risks associated with buflomedil to an acceptable level.
Undersøgelserne viste, at de indberettede alvorlige neurologiske bivirkninger hovedsagelig var krampeanfald, myokloni og status epilepticus, og at de kardiale bivirkninger hovedsagelig var takykardi, hypotension, ventrikulære arytmier og hjertestop.
In these enquires, the reported nervous system SAEs consisted mainly of convulsions, myoclonia and status epilepticus while the cardiac SAEs consisted mainly of tachycardia, hypotension, ventricular rhythm disorders and cardiac arrest.
Ændringerne begrænsede populationen gennem yderligere indskrænkning af indikationen PAOD og gennem en revideret ordlyd af kontraindikationen svær nyrefunktionsnedsættelse med henblik på at forbedre efterlevelsen af ordinationsreglerne ved nyreinsufficiens.
The CHMP noted the proposed additional revisions to the SmPC, restricting the population by further narrowing the PAOD indication and revising the wording of the contraindication in severe renal impairment in order to improve compliance to prescribing in the event of renal insufficiency.
CHMP konstaterede, at de franske erfaringer (herunder resultaterne af Thalès-undersøgelsen og publikationen af Bruhat et al.) viser, at der fortsat forekommer eksempler på manglende overholdelse af den anbefalede dosis, manglende dosisjustering hos patienter med nedsat nyrefunktion og manglende overvågning af nyrefunktionen.
The CHMP noted that according to the French experience (including the results of the Thalès study and the publication by Bruhat et al.), cases of non-compliance with the recommended dose, nonadjustment of dose in patients with renal impairment and lack of monitoring of renal function persist, resulting in cases of serious adverse events, which is unacceptable for a product for which the only benefit is a limited level of efficacy in the lower limb peripheral vascular disease indication.
CHMP gennemgik de af indehaveren af markedsføringstilladelsen trufne foranstaltninger til risikominimering og konkluderede, at det på baggrund af den høje risiko forbundet med buflomedil - navnlig hos patienter med fremskreden vaskulær sygdom og/eller diabetes og metabolisk syndrom, patienter med nedsat nyrefunktion og ældre patienter - ikke har været muligt at udpege foranstaltninger, der kan mindske de med buflomedil forbundne risici til et acceptabelt niveau.
Having assessed the risk minimisation measures proposed by the MAH, the CHMP concluded that given the high risk with buflomedil, notably in patients with advanced vascular disease and/or diabetes and metabolic syndrome, in patients with impaired renal function and in elderly patients, no adequate or sufficient measures could be identified to reduce the risks associated with buflomedil to an acceptable level.
Ved den af indehaveren af markedsføringstilladelsen foretagne gennemgang af ICSR-databasen fandtes 33 tilfælde, hvor der var anvendt en maksimal daglig dosis på 600 mg.
The MAH review of the ICSR database identified 33 cases involving the use of a maximum daily dose of 600 mg. From these, a total of 21 cases of neurological adverse events were retrieved.
Formålet var at kortlægge forekomsten af kardiologiske eller neurologiske bivirkninger under normale anvendelsesbetingelser, dvs. tilfælde, hvor den maksimale daglige dosis på 600 mg ikke var overskredet, tilfælde med accidentel overdosering og tilfælde med kendt nyrefunktionsnedsættelse, der havde nødvendiggjort dosisjustering.
The CHMP also considered a review of the individual case safety reports (ICSR) database conducted by the MAH, to identify cases of cardiological or neurological adverse events under normal conditions of use, i.e. cases where the dose did not exceed the maximum daily dose of 600mg, cases with accidental overdoses or cases including patients with known renal impairment requiring dose adjustment.
Den risikostyringsplan, der blev foreslået i henhold til denne artikel 107procedure, svarer til den franske risikostyringsplan, der blev implementeret i 2006.
As the Risk Management Plan (RMP) proposed in the scope of this Article 107 procedure is equivalent to the French RMP implemented in 2006, the CHMP was therefore of the opinion that it is possible to conclude on the effectiveness of the proposed RMMs, despite the lack of implementation in all member states.
Vedrørende sikkerheden konkluderede CHMP, at brug af buflomedil er forbundet med en række alvorlige kardiale bivirkninger (hovedsagelig takykardi, hypotension, ventrikulære arytmier og hjertestop) og neurologiske bivirkninger (hovedsagelig kramper, myokloni og status epilepticus).
With regards to safety, the CHMP concluded that the use of buflomedil is associated with a number of serious cardiological (mainly tachycardia, hypotension, ventricular rhythm disorders and cardiac arrest) and neurological (mainly convulsions, myoclonia and status epilepticus) adverse events, which occur under normal conditions of use, particularly in elderly patients, who are predominantly the patient population relevant to the approved indication.
Sammenfattende konkluderede CHMP, at brug af buflomedil er forbundet med en række alvorlige kardiologiske bivirkninger (hovedsagelig takykardi, hypotension, ventrikulære arytmier og hjertestop) og neurologiske bivirkninger (hovedsagelig kramper, myokloni og status epilepticus).
In summary, the CHMP concluded that the use of buflomedil is associated with a number of serious cardiological (mainly tachycardia, hypotension, ventricular rhythm disorders and cardiac arrest) and neurological (mainly convulsions, myoclonia and status epilepticus) adverse events, which occur under normal conditions of use, particularly in elderly patients, who are predominantly the patient population relevant to the approved indication.
Udvalget fandt det usandsynligt, at foranstaltningerne vil være tilstrækkelige til at forebygge alvorlige kardiale og neurologiske bivirkninger under normale anvendelsesforhold eller til at mindske de veldefinerede risici ved accidentel overdosering eller manglende overvågning af nyrefunktionen til et acceptabelt niveau.
Regarding risk minimisation measures, the CHMP noted the MAH proposals but considered that these are unlikely to be sufficient to prevent the occurrence of serious cardiac and neurological adverse events under normal conditions of use nor reduce the well identified risks of accidental overdoses and non-compliance with renal function monitoring associated with the use of buflomedil to an acceptable level.
Ved gennemgangen af EudraVigilance fandtes 74 tilfælde med bivirkninger relateret til buflomedil.
The EudraVigilance review identified 74 cases of adverse events associated with buflomedil, with a total of 35 cases recording cardiac adverse and 39 cases recording neurological adverse events.
CHMP konkluderede, at lighederne mellem de foreslåede risikostyringsforanstaltninger og dem, der er gennemført i Frankrig, gør det muligt at drage konklusioner om effektiviteten af de foreslåede risikostyringsforanstaltninger, selv om de ikke er gennemført i alle medlemsstaterne.
The CHMP concluded that due to the similarities between the proposed RMMs and the ones implemented in France, it is possible to conclude on the effectiveness of the proposed RMMs, despite the lack of implementation in all member states and that these measures are inadequate to prevent the occurrence of serious adverse events with buflomedil.
Formålet var at kortlægge tilfælde af kardiale og neurologiske reaktioner ved normale terapeutiske doser (dvs. maksimalt 600 mg dagligt for den orale tabletformulering).
The CHMP noted a review of French Eudravigilance data analysing spontaneous reports associated with treatment with buflomedil, to identify cases where cardiac and neurological reactions occurred under normal therapeutic doses (i.e. maximum of 600 mg daily for the oral tablet formulation).
Udvalget begrundede dette med, at de kommunikationsredskaber, der allerede var taget i brug i Frankrig, var utilstrækkelige til at forbedre overholdelsen af indikationerne og overvågningen af nyrefunktionen.
The CHMP considered the proposal for a website dedicated to buflomedil to be unlikely to significantly improve the awareness of prescribers, as previous communication tools already implemented in France were insufficient to improve compliance with indications and renal monitoring.
De indberettede bivirkninger var hovedsagelig af alvorlig neurologisk og kardiovaskulær art. Ud over disse fem tilfælde var der to tilfælde med nedsat nyrefunktion, hvor dosis var ukendt.
In addition to these 5 cases, a further two cases related to renal impairment were identified, where the dose was unknown.
Styrke Lжgemiddelform
Strength Pharmaceuti cal form
Emballage Pakningsstшrrele
Immediate Packaging
(Sжrnavn) Navn
(Invente d) name
Denne procedure blev afsluttet den 28. november 2006.
This procedure ended on 28 November 2006.
Denne konklusion godtages.
This conclusion is accepted.
Enurace 50 Tabletter
Enurace 50 Tablets
Enurace 50 blev første gang godkendt i Nederlandene den 15. september 2000.
Enurace 50 was first authorised in The Netherlands on 15 September 2000.
Nederlandene, Belgien, Tyskland, Frankrig, Italien, Spanien og Det Forenede Kongerige.
The Netherlands, Belgium, Germany, France, Italy, Spain and the United Kingdom.
Enurace har været officielt godkendt siden 2000 (i Nederlandene siden 1995).
Enurace has been officially authorised since 2000 (since 1995 available in the Netherlands).
3 Konklusion og anbefaling
3 Conclusion and Recommendation
3891 ZK Zeewolde Nederlandene fs@ace-pharm.nl
Schepenveld 41 3891 ZK Zeewolde The Netherlands fs@ace-pharm.nl
Hvad angår sikkerheden synes brug af produktet ikke at indebære nogen nævneværdig risiko hos unge, raske dyr.
Considering safety, the product seems not to create a considerable risk to young and healthy animals.
Italien kunne godtage ansøgningen med en revideret ordlyd i produktresuméet.
Italy could accept the application with revised wording in the SPC .
En gensidig anerkendelsesprocedure blev indledt den 29. juni 2006 med Nederlandene som referencemedlemsstat og Belgien, Tyskland, Spanien, Frankrig, Italien og Det Forenede Kongerige som berørte medlemsstater.
A Mutual Recognition Procedure started on 29 June 2006 with The Netherlands as Reference Member State and Belgium, Germany, Spain, France, Italy and the United Kingdom as Concerned Member States.
CVMP konkluderede, at benefit/risk-forholdet for produktet er gunstigt.
The CVMP has concluded that the risk/benefit for this product is favourable.
Siden 1998 er der udført undersøgelser efter markedsføringen samt regelmæssig overvågning af bivirkninger med FAQsystemet.
Since 1998 post-marketing studies have been performed as well as regular monitoring of adverse effects by FAQ system.
CMD(v) var på dag 60 af proceduren ikke nået til enighed, da Frankrig og Italien fastholdt deres betænkeligheder.
CMD(v) could not reach an agreement by day 60 of this procedure, as France and Italy maintained their concerns.
I Europa foretages ovariohysterektomi dog oftest hos midaldrende og gamle tæver.
However, in Europe ovariohysterectomy is most frequently performed in middle aged and old bitches.
Resultatet viser umiddelbart god virkning hos både test- og kontrolgruppe (87 % mod 85,5 %), en virkning, der måske er større hos behandlingsnaive dyr (93,7 % mod 88,9 %).
The raw outcome shows good effect in both test and control groups (87% vs 85.5%), an effect that might be somewhat higher in treatment naïve animals (93.7% vs 88.9%).
Disse tal synes yderst overbevisende i sammenligning med de 20 % placebobehandlede dyr, der blev kontinente i undersøgelse ACE129801.
These figures seem highly convincing when compared to the 20 % placebo treated animals that became continent in study ACE129801.
På dag 90 af den gensidige anerkendelsesprocedure, den 27. september 2006, kunne Frankrig og Italien ikke tilslutte sig udstedelse af en markedsføringstilladelse, da de fandt, at produktet frembyder alvorlige potentielle risici for dyrs sundhed.
At Day 90 of the MRP, 27 September 2006, France and Italy could not agree to the granting of a marketing authorization as they consider there are potentially serious risks for animal health.
Den undersøgelse, hvor Enurace 50 sammenlignes med Propalin (ACE129802), er imidlertid overbevisende, skønt der ikke er udført en non-inferiority analyse.
However, the study where Enurace 50 is compared to Propaline (ACE129802) is convincing although a non-inferiority analysis has not been performed.
Den mulige risiko ved anvendelse af ephedrin hos denne gruppe af dyr kan mindskes gennem passende foranstaltninger.
Possible risk connected with the use of ephedrine in this group of animals can be reduced by appropriate management measures.
De gældende tekster til produktresumé, etikettering og indlægsseddel er de endelige versioner, der er fastlagt ved behandlingen i koordinationsgruppen, med følgende ændring:
The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination Group procedure with the following amendment:
Ansøgningen blev indgivet i overensstemmelse med artikel 12, stk. 3, i direktiv 2001/82/EF som en selvstændig ansøgning.
The application was made in accordance with Article 12.3 of Directive 2001/82/EC as a stand alone application.
Ved den anbefalede dosis, der ifølge det foreslåede produktresumé bør justeres individuelt, er sikkerheden rimeligt garanteret.
At the recommended dose level, which according to the suggested SPC should be individually adjusted, safety is ensured to a reasonable level.
Skønt alderens betydning ikke er afspejlet i toleranceundersøgelserne, blev den taget i betragtning i undersøgelserne af virkningen og i undersøgelserne efter markedsføringen.
Although the influence of age was not reflected in the tolerance studies, it was taken into account in the efficacy and post- marketing studies.
ACE Pharmaceuticals BV Schepenveld 41
ACE Pharmaceuticals BV
Data vedrørende virkningen er behæftet med adskillige mangler og er sparsomme.
Efficacy data are connected to several shortcomings and the amount of data available is sparse.
I betragtning af, at urininkontinens kan optræde selv flere år efter operationen, kan Enurace formodes hovedsagelig at ville blive anvendt hos ældre dyr, der oftere lider af hjerte-kar-, lever- og nyresygdomme samt andre sygdomme.
Taking into account that urinary incontinence may occur even several years after the operation it can be suspected that Enurace would be used mostly in older animals, more frequently suffering form cardiovascular, liver, renal and other diseases.
Indehaveren af markedsføringstilladelsen skulle forelægge alle oplysninger, (præklinisk og klinisk dokumentation, herunder ekspertrapporterne og de udførte undersøgelser af virkning og tolerance) med henblik på at godtgøre, at benefit/risk-forholdet for behandlede dyr er positivt.
The Marketing Authorisation Holder should provide all supporting data (preclinical and clinical documentation, including the expert reports, efficacy and tolerance studies conducted), to justify a positive benefit-risk ratio for the treated animal.
Sagen blev indbragt for koordinationsgruppen vedrørende gensidig anerkendelse og decentraliserede godkendelsesprocedurer, (CMD(v)) med henblik på en 60dages-procedure i overensstemmelse med artikel 33, stk. 1, i direktiv 2001/82/EF, med senere ændringer.
The matter was referred to the Co-ordination Group for Mutual Recognition and Decentralised Procedures CMD(v) for a 60 day procedure in accordance with Article 33(1) of Directive 2001/82/EC, as amended.
Til besvarelse af spørgsmålene vedrørende toksicitet gør ansøgeren gældende, at der som følge af den farmakologiske virkning af ephedrin og den individuelle variation i receptortæthed ikke kan fastlægges en sikkerhedsmargen, og at stigende doser vil være forbundet med stigende intensitet og hyppighed af velkendte bivirkninger.
In response to the questions related to toxicity, the applicant argues that due to the pharmacologic effect of ephedrine and the individual variation in receptor density no safety margin can be determined and increasing doses will be associated to increased intensity and frequency of well known adverse effects.
Der er ingen tvivl om, at behandling af hunde med Enurace kan medføre bivirkninger som følge af ephedrins særlige aktivitet.
There is no doubt that treatment of the dog with Enurace may involve an occurrence of adverse reactions due to peculiar activity of ephedrine.
De af ansøgeren forelagte oplysninger viser, at Enurace 50 er et effektivt middel til behandling af urininkontinens hos ovariohysterektomerede tæver.
The data provided by the applicant show that Enurace 50 is an effective medicinal product for treatment of urinary incontinence in ovariohysterectomised bitches.
Punkt 4.5 i produktresuméet og punkt 12 i indlægssedlen:
Section 4.5 of the SPC and Section 12 of the Package Leaflet:
Frankrig anser benefit/risk-forholdet for at være ugunstigt for dyret, når bivirkningerne (meget sjældne tilfælde af atrieflimren og takykardi) opvejes mod de mulige fordele ved effektiv behandling af inkontinens.
France considers the risk/benefit analysis unfavourable for the animal when the adverse effects (in very rare cases atrium fibrillation and tachycardia) are weighed against the potential benefits of effective treatment of incontinence.
CVMP indledte på sit møde i december 2006 en indbringelsesprocedure for Enurace 50 i overensstemmelse med artikel 33, stk. 4, i direktiv 2001/82/EF, med senere ændringer.
The CVMP during its meeting of December 2006 started a referral procedure under Article 33(4) of Directive 2001/82/EC as amended for Enurace 50.
Den anbefalede startdosering er 2 mg ephedrinhydrochlorid pr. kg kropsvægt pr. dag, fordelt på to orale doser.
A starting dose of 2 mg Ephedrine HCl per kg of bodyweight per day, divided in two oral doses is recommended.
Den foreslåede dosis på 1-3 mg ephedrinhydrochlorid pr. kg kropsvægt pr. dag, fordelt på to doser oralt, er effektiv og sikker, men nogle dyr kan have behov for større dosis som følge af den individuelle variation i responsen på ephedrin.
Proposed dose of 1 - 3 mg Ephedrine HCl /kg/day, divided in two oral doses is effective and safe, but some animals may need a higher dose, which is associated with individual variation in the response to ephedrine.
Kardial dysfunktion var blandt eksklusionskriterierne, hvorfor undersøgelserne ikke indeholder oplysninger om anvendelse af produktet hos dyr med sådanne lidelser, men de foreliggende oplysninger tyder ikke på, at det bør undgås at behandle hunde med hjertelidelser med stoffet.
Regarding cardiac dysfunction, this was one of the exclusion criteria so the studies give no information on use of the product in animals with such a condition but there is also no data suggesting that the cardiac patients must not be treated with the substance.