FrancophonIA/ELRC3.0 huggingface dataset:
English: • The Committee considered the procedure under Article 31 of Directive 2001/83/EC for ergot derivatives containing medicinal products.
Danish: • udvalget fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF for lægemidler indeholdende ergotderivater,
English: However, provision of information on these events is insufficient to avoid that some patients develop fibrosis and ergotism during treatment.
Danish: Oplysninger om disse hændelser af midlertidig ikke tilstrækkeligt til at undgå, at nogle patienter udvikler fibrose og ergotisme under behandlingen.
English: Moreover, recent cases were identified during the French survey conducted in 2011, which show that the risk minimisation measures currently in place are not sufficient to prevent the development of fibrotic reactions.
Danish: I den franske undersøgelse fra 2011 blev der desuden fundet nye tilfælde, der viser, at de nuværende risikominimeringsforanstaltninger ikke er tilstrækkelige til at forhindre udvikling af fibrotiske reaktioner.
English: • Adverse drug reaction with a substance marketed for a long time is generally less reported
Danish: • bivirkninger med et stof, der har været markedsført i lang tid, sædvanligvis indberettes mindre, og
English: Nicergoline was also given to 17 patients with migraines for prevention of attacks (Prusinski, Wiad.Lek, 1984).
Danish: Nicergolin blev desuden anvendt hos 17 patienter med migræne til forebyggelse af anfald (Prusinski, Wiad.Lek, 1984).
English: Improvements in visual acuity were also reported in Ganescu study (46 patients of various eye conditions) but this study was not comparative.
Danish: Der blev ligeledes fundet forbedret synsstyrke i Ganescu-undersøgelsen (46 patienter med forskellige øjensygdomme), men denne undersøgelse var ikke sammenlignende.
English: The CHMP noted that an under-notification of the adverse events can also be suspected given that:
Danish: CHMP bemærkede, at bivirkningerne også kan tænkes at være underindberettede, eftersom:
English: Regarding peritoneal and cardiac fibrosis, the CHMP was of the view that the causal role of nicergoline cannot be excluded.
Danish: Hvad angår peritoneal og kardial fibrose fandt CHMP, at en kausal rolle af nicergolin ikke kan udelukkes.
English: • The Committee is of the opinion that the evidence for clinically significant efficacy of nicergoline in the currently assessed indications is very limited, and therefore the potential benefit for patients in these indications is outweighed by the identified risk.
Danish: • udvalget finder, at dokumentationen for en væsentlig klinisk virkning af nicergolin til de aktuelt godkendte indikationer er meget begrænset, og at de potentielle fordele for patienter ved disse indikationer derfor ikke opvejer den konstaterede risiko,
English: Overall, the study designs were adequate (randomised, double-blind, placebo-controlled), diagnoses were established according classification criteria at the time of the studies, primary efficacy scales were defined a priori (MMSE, SCAG, ADAS-Cog).
Danish: Overordnet var undersøgelsernes design tilfredsstillende (randomiserede, dobbeltblindede placebokontrollerede), diagnoserne blev stillet i henhold til klassifikationskriterier på tidspunktet for undersøgelserne, og de primære skalaer for virkning var fastlagt a priori (MMSE, SCAG, ADAS-Cog).
English: • The Committee considered that the benefit-risk balance of nicergoline containing products:
Danish: • udvalget fandt, at benefit/risk-forholdet for lægemidler indeholdende nicergolin:
English: For the indication “prophylaxis of migraine headache” the available data in migraine headache are from open label studies in a small number of patients (40 and 17 patients).
Danish: For indikationen “forebyggelse af migræne ” er de foreliggende data om migræne baseret på åbne undersøgelser hos et lille antal patienter (40 og 17 patienter).
English: Following a national pharmacovigilance review held in 2011 new spontaneous notifications reported with some of those products identified serious cases of fibrosis and ergotism and France considered that this safety concern is not outweighed by the limited evidence of efficacy.
Danish: Ved en national gennemgang af lægemiddelovervågning i 2011 fandtes nye spontane indberetninger af alvorlige tilfælde af fibrose og ergotisme med nogle af disse produkter, og Frankrig fandt, at denne sikkerhedsmæssige betænkelighed ikke opvejes af den begrænsede dokumentation for virkning.
English: The majority of them had been previously treated with various anti-migraine drugs like dihydroergotamine, pizotifen and propranolol with unsatisfactory effects.
Danish: Størstedelen af dem var uden tilfredsstillende virkning tidligere blevet behandlet med forskellige migrænemidler såsom dihydroergotamin, pizotifen og propranolol.
English: Overall, the varying affinity for serotoninergic receptors with the different ergot derivatives and the therapeutic doses used may explain the differences observed for notification rates for the fibrotic reactions.
Danish: Overordnet kan den varierende affinitet for serotoninerge receptorer af de forskellige ergotderivater og de anvendte terapeutiske doser muligvis forklare de iagttagne forskelle i indberetningshyppigheden for fibrotiske reaktioner.
English: In addition, given that fibrosis is a serious life threatening reaction, observed after long duration of treatment with nicergoline (a drug used in indications requiring long duration of treatment), this has an impact on the benefit-risk profile of the products.
Danish: Da fibrose er en livstruende reaktion, som iagttages efter langtidsbehandling med nicergolin (et lægemiddel, der anvendes ved indikationer, som kræver langvarig behandling), har dette desuden indvirkning på produkternes benefit/risk-forhold.
English: Dementia and dementia related indications are excluded from the scope of this referral procedure.
Danish: Demens og demensrelaterede indikationer er ikke omfattet af denne indbringelse.
English: Fourty (40) patients with migraine were assessed in an open clinical study that became available after the initial marketing authorisation was granted (Prusinski, Wiad.Lek, 1984).
Danish: Fyrre (40) patienter med migræne blev vurderet i en åben klinisk undersøgelse, der blev til rådighed efter udstedelse af den oprindelige markedsføringstilladelse (Prusinski, Wiad.Lek, 1984).
English: Overall, the CHMP was of the opinion that no situation could justify exposing a patient to risk of fibrosis and ergotism considering the very limited data on efficacy.
Danish: Overordnet var CHMP at den opfattelse, at ingen situation kan berettige at udsætte en patient for risiko for fibrose og ergotisme på baggrund af de meget begrænsede data om virkning.
English: • The Committee considered that a potential causal association between fibrotic reactions or ergotism and nicergoline cannot be excluded.
Danish: • udvalget fandt, at der ikke kan udelukkes en potentiel årsagssammenhæng mellem nicergolin og fibrotiske reaktioner eller ergotisme.
English: • The Committee considered the overall submitted data provided by the MAHs and the outcome of the scientific advisory group.
Danish: • udvalget gennemgik alle data, der var forelagt af indehaverne af markedsføringstilladelse, og resultatet af mødet i den videnskabelige rådgivende gruppe,
English: • The suspension of the marketing authorisation for nicergoline containing medicinal products referred to in Annex I in the event that no other indications are approved as part of their marketing authorisation.
Danish: • suspendering af markedsføringstilladelsen for de i bilag I omhandlede lægemidler indeholdende nicergolin, når ingen andre indikationer er godkendt som en del af markedsføringstilladelsen.
English: Among the 21 remaining cases, an association between nicergoline and the fibrotic event or potential fibrotic event could not be excluded.
Danish: I de 21 resterende tilfælde kunne der ikke udelukkes en sammenhæng mellem nicergolin og den fibrotiske hændelse eller den potentielle fibrotiske hændelse.
English: This Cochrane review on efficacy of nicergoline was performed in patients with mild to moderate dementia and is therefore also outside the scope of the procedure.
Danish: Denne Cochrane-gennemgang af virkningen af nicergolin blev foretaget hos patienter med let til moderat demens og er derfor ikke omfattet af denne indbringelse.
English: In conclusion, the CHMP was of the opinion that a couple of studies have some positive findings in the populations tested but considering the inadequate methodology, the reliability and the clinical relevance of the results is questionable.
Danish: Som konklusion fandt CHMP, at et par undersøgelser har vist visse positive resultater hos de undersøgte populationer, men at resultaternes pålidelighed og kliniske relevans er tvivlsom i betragtning af den mangelfulde metodologi.
English: The studies submitted have assessed nicergoline for oral or parenteral use and had heterogeneous efficacy endpoints such as: sensitivity to cold, peripheral blood flow, walking distance, pain, quality of life.
Danish: De forelagte undersøgelser vurderede nicergolin til oral eller parenteral anvendelse og havde uensartede endepunkter for virkning såsom kuldefølsomhed, perifer blodgennemstrømning, gangdistance, smerter og livskvalitet.
English: The main localisation of fibrosis is preferentially pulmonary area and also retroperitoneal and cardiac area.
Danish: Fibrosen er hovedsagelig lokaliseret omkring lungerne og i det retroperitoneale og kardiale område.
English: Regarding cases of pulmonary reactions, the emerging number of cases and the improvement observed after nicergoline discontinuation in 10 cases with no confounding factor is in favour of a causal role of nicergoline, especially in 5 cases in which improvement was also confirmed by radiography or scanner.
Danish: For de pulmonale reaktioners vedkommende taler det stigende antal tilfælde og den iagttagne bedring ved seponering af nicergolin i 10 tilfælde uden konfunderende faktor for, at nicergolin har en kausal rolle, navnlig de fem tilfælde, hvor bedringen desuden bekræftedes ved radiografi eller skanning.
English: The CHMP has considered the totality of the available data on the safety and efficacy of nicergoline.
Danish: CHMP har vurderet samtlige tilgængelige data om sikkerheden og virkningen af nicergolin.
English: • The variation to the terms of the marketing authorisation for nicergoline containing medicinal products referred to in Annex I, to delete the below indications (specific wording of the indication may vary from product to product and from country to country) as well as any relevant reference to these indications, when there are other therapeutic indications approved as part of their marketing authorisation:
Danish: • ændring af betingelserne for markedsføringstilladelsen for de i bilag I anførte lægemidler indeholdende nicergolin, sletning af nedenstående indikationer (den konkrete ordlyd af indikationerne kan variere fra produkt til produkt og fra land til land) samt af enhver relevant omtale af disse indikationer, når andre terapeutiske indikationer er godkendt som en del af markedsføringstilladelsen:
English: For the indication “ancillary treatment of Raynaud's syndrome”, the submitted studies did not really assess nicergoline in patients with this specific indication, but were rather conducted in patients with peripheral arteriopathy.
Danish: For indikationen “supplerende behandling af Raynauds syndrom” vurderede de forelagte undersøgelser ikke reelt nicergolin til behandling af patienter med denne specifikke indikation, men snarere hos patienter med perifer arteriopati.
English: The improvement, when documented, was observed between 3 and 10 months after nicergoline discontinuation, without corticoid treatment in four cases.
Danish: Når bedringen blev beskrevet, iagttoges den mellem 3 og 10 måneder efter seponering af nicergolin, i fire tilfælde uden kortikoidbehandling.
English: The population was old and suffered from intermittent claudication.
Danish: Populationen var ældre patienter med claudicatio intermittens.
English: The CHMP considered the MAH's proposal for risk minimisation measures: the inclusion of information related to fibrosis and ergotism in section 4.4 of the Summary of Product Characteristics.
Danish: CHMP gennemgik markedsføringstilladelsesindehaverens forslag til risikominimeringsforanstaltninger: Indsættelse af oplysninger om fibrose og ergotisme i punkt 4.4 i produktresuméet.
English: To conclude, given the cases reported for a reaction difficult to early diagnose (delayed symptoms) and probably under reported, the use of the drug at an approved dosage, added to a plausible pharmacological profile, nicergoline is considered to be associated with a risk of fibrotic reactions.
Danish: Det konkluderes, at på baggrund af de indberettede tilfælde af en reaktion, der er vanskelig at diagnosticere tidligt (forsinket opståen af symptomer) og antagelig er underindberettet, og på baggrund af sin plausible farmakologiske profil anses nicergolin i godkendt dosering at være forbundet med risiko for fibrotiske reaktioner.
English: Nicergoline is a semisynthetic ergoline derivative that seems to have an action: (i) as an α1adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties.
Danish: Nicergolin er et halvsyntetisk ergolinderivat, der synes at have følgende virkning: (i) som α1adrenoceptorantagonist fremkalder det vasodilatation og øger den arterielle blodgennemstrømning; (ii) det forstærker funktionen af kolinerge og katekolaminerge neurotransmittere; (iii) det hæmmer trombocytaggregation; (iv) det forstærker den metaboliske aktivitet, resulterende i øget oxygen- og glukoseforbrug; og, (v), det har neurotrop og antioxiderende virkning.
English: Therefore, despite the positive conclusions of the authors regarding the progression of visual acuity under a treatment with nicergoline, the CHMP considered that, in the absence of a comparison to a placebo control, no reliable conclusion can be drawn from these clinical results which referred to heterogeneous data based on small series of patients of various eye conditions.
Danish: Trods forfatternes positive konklusioner om forbedret synsstyrke under behandlingen med nicergolin fandt CHMP, at der i mangel af placebokontrol ikke kan drages en pålidelig konklusion af disse kliniske resultater, som bygger på heterogene data hos en lille serie patienter med forskellige øjensygdomme.
English: From the approved indications of the nicergoline containing medicinal products the ones that are in the scope of this referral procedure and are approved in at least one Member State are the following (specific wording of the indication may vary from product to product):
Danish: For lægemidler indeholdende nicergolin omfatter denne indbringelsesprocedure følgende indikationer, som er godkendt i mindst én medlemsstat (den konkrete ordlyd af indikationen kan være forskellig for forskellige produkter):
English: The MAHs considers that the most comprehensive review of nicergoline efficacy was completed in a meta-analysis performed in 2008 by Winblad et al.
Danish: Indehaverne af markedsføringstilladelse finder, at den mest omfattende gennemgang af virkningen af nicergolin blev foretaget i en metaanalyse i 2008 udført af Winblad et al.
English: Regarding ergotism, there were no cases identified in the MAH's safety database reporting the preferred term ergotism associated with nicergoline.
Danish: Vedrørende ergotisme er der i markedsføringstilladelsesindehaverens sikkerhedsdatabase ikke fundet nogen tilfælde, hvor den foretrukne betegnelse ergotisme er blevet anvendt i forbindelse med nicergolin.
English: Ninety (90) cases were found to contain terms potentially indicative of symptoms or ergotism, such as paraesthesia, formication, tingling, intestinal/cerebrovascular/peripheral/tongue ischaemia, angina pectoris, coronaropathy, thoracic pain, nausea, vomiting, diarrhoea, abdominal pain, cold sensation, thrombosis, stroke, gangrene, necrosis, vasoconstriction/vasospasm, cyanosis, myalgia, muscular cramps, pain in extremities, vertigo, hypoaesthesia, numbness, headache, confusion, hallucinations.
Danish: Halvfems (90) tilfælde blev fundet at indeholde betegnelser, der potentielt tyder på symptomer på ergotisme såsom paræstesi, formikation, snurren, intestinal/cerebrovaskulær/perifer iskæmi eller iskæmi af tungen, angina pectoris, koronaropati, brystsmerter, kvalme, opkastning, diarré, abdominalsmerter, kuldefornemmelse, trombose, apopleksi, gangræn, nekrose, vasokonstriktion/vasospasme, cyanose, myalgi, muskelkramper, smerter i ekstremiteterne, vertigo, hypæstesi, følelsesløshed, hovedpine, konfusion og hallucinationer.
English: Therefore, the CHMP was of the opinion that these substantial methodological deficiencies preclude any conclusion on the efficacy of nicergoline (oral or parenteral) on Raynaud's syndrome, and more largely in peripheral circulation disorders.
Danish: CHMP var derfor den opfattelse, at disse væsentlige metodemæssige mangler udelukker en konklusion om virkningen af nicergolin (oralt eller parenteralt) ved Raynauds syndrom eller ved perifere kredsløbsforstyrrelser i bredere forstand.
English: However, the CHMP considered whether some of these studies could be used in support of the indication “ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease (PAOD Stage II)”.
Danish: CHMP vurderede fandt dog, om nogle af disse undersøgelser kunne anvendes til støtte for indikationen “supplerende behandling af claudicatio intermittens ved symptomatisk perifer arteriel okklusiv sygdom (PAOD stadium II)”.
English: The MAH further provided information on six clinical comparative studies in senile cerebral insufficiency and a short description of a non-comparative study and three observational studies in support of the efficacy of nicergoline in a specific indication “symptomatic treatment of mild cognitive impairment of vascular origin in the elderly”.
Danish: Indehaveren af markedsføringstilladelsen forelagde endvidere oplysninger om seks kliniske sammenlignende studier ved senil cerebral insufficiens og en kort beskrivelse af en ikkesammenlignende undersøgelse samt tre observationsundersøgelser til underbygning af virkningen af nicergolin ved den specifikke indikation “symptomatisk behandling af let kognitiv hæmning af vaskulær årsag hos ældre”.
English: In addition, a scientific advisory group (SAG) was convened in December 2012 at the request of the CHMP during which the experts discussed, based on their clinical experience, whether this substance plays a role in the prophylaxis of migraine headache.
Danish: Desuden blev der på anmodning af CHMP indkaldt en videnskabelig rådgivende gruppe, hvor eksperterne ud fra deres kliniske erfaring drøftede, om dette stof har en rolle i forebyggelse af migræne.
English: The group highlighted that the claimed indication is not used anymore in the clinical practice and that from a clinical viewpoint there is no evidence at present that there is a therapeutic need for this active substance in the treatment of cognitive and neurosensorial impairment in the elderly.
Danish: Gruppen fremhævede, at den påberåbte indikation ikke længere benyttes i klinisk praksis, og at der på nuværende tidspunkt ikke er evidens for et terapeutisk behov for nicergolin til behandling af kognitiv og neurosensorisk funktionsnedsættelse hos ældre.
English: The CHMP was of the opinion that overall based on these data there is some evidence of positive effects of nicergoline on cognition and behaviour in patients with senile cerebral insufficiency of different origins.
Danish: CHMP fandt, at der på grundlag af disse data overordnet er nogen evidens for, at nicergolin har positive virkninger på kognitiv funktion og adfærd hos patienter med senil cerebral insufficiens af forskellige årsager.
English: In addition, a scientific advisory group (SAG) was convened in December 2012 at the request of the CHMP during which the experts discussed, based on their clinical experience, whether this substance plays a role in the symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia).
Danish: Desuden blev der på anmodning af CHMP indkaldt en videnskabelig rådgivende gruppe, hvor eksperterne ud fra deres kliniske erfaring drøftede, om dette stof har en rolle i symptomatisk behandling af kronisk patologisk kognitiv og neurosensorisk funktionsnedsættelse hos ældre (undtagen Alzheimers sygdom og andre former for demens).
English: On the efficacy side for the indication “symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia)”, the efficacy data were mainly provided from study publications conducted in patients with dementia (Alzheimer disease, multi-infarct dementia, vascular dementia, Parkinson disease, etc), while dementia is excluded from the scope of this referral procedure.
Danish: For indikationen “symptomatisk behandling af kronisk patologisk kognitiv og neurosensorisk funktionsnedsættelse hos ældre (bortset fra Alzheimers sygdom og anden form for demens)” var data vedrørende virkning hovedsagelig udledt af publicerede undersøgelser hos patienter med demens (Alzheimers sygdom, multiinfarkt-demens, vaskulær demens, Parkinsons sygdom osv.), skønt demens ikke er omfattet af denne indbringelsesprocedure.
English: This does not exactly reflect the indication supported by the MAH.
Danish: Dette afspejler ikke nøjagtigt den indikation, der påberåbes af indehaveren af markedsføringstilladelsen.
English: The Committee concluded that the benefit-risk balance of nicergoline containing products is not favourable pursuant to Article 116 of Directive 2001/83/EC for symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia), for ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease (PAOD Stage II), for ancillary treatment of Raynaud's syndrome, for ancillary treatment of visual acuity decrease and visual field disturbances presumably of vascular origin, for acute retinopathies of vascular origin and for prophylaxis of migraine headache.
Danish: Udvalget konkluderede, at benefit/risk-forholdet for produkter indeholdende nicergolin ikke er gunstigt i henhold til artikel 116 i direktiv 2000/83/EF til symptomatisk behandling af kronisk patologisk kognitiv og neurosensorisk funktionsnedsættelse hos ældre (bortset fra Alzheimers sygdom og anden form for demens), til supplerende behandling af claudicatio intermittens ved symptomatisk perifer arteriel okklusiv sygdom (PAOD stadium II), til supplerende behandling af Raynauds syndrom, til supplerende behandling af nedsat synsstyrke og synsfeltforstyrrelser af formodet vaskulær årsag, til akutte retinopatier af vaskulær årsag eller til forebyggelse af migræne.
English: The CHMP noted that none of the studies was designed to address the specific indication under question (symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia)), and that the data is further weakened by publication biases and changes in the understanding of proper criteria for current diagnoses.
Danish: CHMP bemærkede, at ingen af undersøgelsernes design tog henblik på den konkrete indikation, der er under vurdering (symptomatisk behandling af kronisk patologisk kognitiv og neurosensorisk funktionsnedsættelse hos ældre (bortset fra Alzheimers sygdom og anden form for demens)), og at dataene yderligere svækkes af de publicerede undersøgelsers skævhed og forskelle i forhold til den nuværende opfattelse af korrekte diagnosekriterier.