FrancophonIA/ELRC3.0 huggingface dataset:
English: • Acute streptococcal tonsillitis and pharyngitis (infections of the tonsils and throat).
Danish: • Akut tonsillitis og faryngitis forårsaget af streptokokker (infektioner i mandlerne og halsen)
English: Zinnat was identified as needing harmonisation by the Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh).
Danish: Koordinationsgruppen vedrørende gensidig anerkendelse og decentrale godkendelsesprocedurerhuman (CMD(h)) fandt, at der er behov for harmonisering for Zinnat.
English: • Acute bacterial sinusitis (infection of the sinuses).
Danish: • Akut bakteriel sinusitis (bihulebetændelse)
English: Withdrawal period
Danish: Tilbageholdelses -tid
English: However, these results should be taken
Danish: Disse resultater må dog tages med
English: Methysergide.
Danish: methysergid.
English: Such adverse effects may be serious and in some cases irreversible and potentially fatal.
Danish: Sådanne bivirkninger kan være alvorlige og i nogle tilfælde irreversible og potentielt fatale
English: Methysergide containing products are currently authorised in the following EU countries: Belgium, France, the Netherlands and the United Kingdom.
Danish: Lægemidler, der indeholder methysergid, er på nuværende tidspunkt godkendt i følgende EU-lande: Belgien, Frankrig, Nederlandene og Det Forenede Kongerige.
English: 1 ed. Oxford: Oxford University Press; 1980.
Danish: Vi 1 ed. Oxford: Oxford University Press, 1980:
English: Overall summary of the scientific evaluation of methysergide containing medicinal products (see Annex I)
Danish: Samlet resumé af den videnskabelige vurdering af lægemidler, der indeholder methysergid (se bilag I)
English: The CHMP highlighted that these results should be taken with caution as these studies are old and generally not carried out with the current upto-date methodology8.
Danish: CHMP understregede, at disse resultater bør tages med forbehold, da undersøgelserne er gamle og sædvanligvis ikke udført med tidssvarende, moderne metoder8.
English: Existing data seems to show that fibrosis development is not related to patient age.
Danish: De foreliggende data synes at vise, at fibroseudvikling ikke er relateret til patientens alder.
English: Annex II Scientific conclusions and grounds for the variation of the marketing authorisations
Danish: Bilag II Videnskabelige konklusioner og begrundelse for ændring af markedsføringstilladelserne
English: Two studies, one observational and one prospective, reported less convincing evidence13 where around 26% patients had satisfactory, good or excellent outcomes.
Danish: To undersøgelser, nemlig en observationsundersøgelse og en prospektiv undersøgelse, gav mindre overbevisende evidens13, idet ca. 26 % af patienterne fik et tilfredsstillende, godt eller udmærket udfald.
English: The real incidence rate might be under-estimated and the risk of fibrosis is probably higher.
Danish: Den faktiske incidensrate kan være undervurderet, og risikoen for fibrose er antagelig højere.
English: The majority of patients (92.4%) who developed fibrosis received daily doses of methysergide within the currently recommended (≤ 6 mg/day).
Danish: Størstedelen af de patienter (92,4 %), der udviklede fibrose, fik daglige doser af methysergid inden for de gældende anbefalinger (≤ 6 mg/dag).
English: However, cases have also been reported with treatment duration up to six months, so occurrence of fibrosis with short-term treatment cannot be excluded.
Danish: Der er imidlertid også indberettet tilfælde med en behandlingsvarighed på under seks måneder, hvorfor forekomst af fibrose ved korttidsbehandling ikke kan udelukkes.
English: This is subject to the agreed warnings, other changes to the product information and additional risk minimisation measures.
Danish: Dette er betinget af de vedtagne begrænsninger, advarsler og andre ændringer i produktinformationen samt supplerende risikominimeringsforanstaltninger.
English: Based on this, France considered that the benefit risk balance of methysergide containing products should be reviewed and triggered a referral under Article 31 of Directive 2001/83/EC.
Danish: På denne baggrund fandt Frankrig, at benefit/risk-forholdet for lægemidler indeholdende methysergid burde gennemgås, og indledte en indbringelse i medfør af artikel 31 af direktiv 2001/83/EF.
English: For the indication “prophylaxis of migraine”, data were submitted from randomised, double-blind, placebo-controlled studies1,2,3,4.
Danish: Til indikationen “profylakse af migræne” blev der forelagt data fra randomiserede, dobbeltblindede, placebokontrollerede undersøgelser1,2,3,4.
English: In addition, development of fibrosis appears to be correlated to treatment duration, as most patients developed fibrotic events after long-term therapy (at least one year).
Danish: Desuden synes udvikling af fibrose at være korreleret med behandlingsvarigheden, idet de fleste patienter udviklede fibrotiske hændelser efter langvarig behandling (mindst et år).
English: Methysergide is to be used only following unsuccessful treatment with other standard classes of drugs after sufficient treatment duration (at least 4 months) at the maximal tolerated dose.
Danish: Methysergid bør kun anvendes efter fejlslagen behandling med andre sædvanlige klasser af lægemidler i tilstrækkelig lang tid (mindst 4 måneder) ved den maksimale tolererede dosis.
English: In this respect, the CHMP took note of the fact that one of the marketing authorisation holders of the products for which this indication is approved informed the CHMP of their intention to voluntarily withdraw the indication “diarrhoea caused by carcinoid syndrome”.
Danish: I denne forbindelse tog CHMP til efterretning, at en af markedsføringstilladelsesindehaverne for de produkter, som denne indikation er godkendt for, underrettede CHMP om, at virksomheden havde til hensigt frivilligt at trække indikationen “diarré forårsaget af karcinoid syndrom” tilbage.
English: This is provided that the recommended risk minimisation measures are implemented;
Danish: Dette forudsætter, at de anbefalede risikominimeringsforanstaltninger anvendes
English: Methysergide is an ergot alkaloid, first described in clinical practice in 1959.
Danish: Methysergid er et ergotalkaloid, der første gang er beskrevet i klinisk praksis i 1959.
English: • The CHMP considered the procedure under Article 31 of Directive 2001/83/EC for methysergide containing medicinal products.
Danish: • CHMP fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF for lægemidler indeholdende methysergid
English: The incidence rates of valvular and pulmonary fibrosis in patients treated with methysergide was shown to be similar to those of the general population19,20,21,22.
Danish: Incidensraterne af valvulær og pulmonal fibrose hos patienter, der behandles med methysergid, blev påvist at svare til raterne i den almindelige befolkning19,20,21,22.
English: Methysergide binds with varying affinities to a range of serotonergic receptors (5-HT receptors).
Danish: Methysergid bindes med forskellig affinitet til en række serotonerge receptorer (5-HT-receptorer).
English: The indication should be restricted to patients with functional disability in whom other treatments have failed.
Danish: Indikationen bør indskrænkes til patienter med funktionel invaliditet efter forudgående svigt af andre behandlinger.
English: In addition, risk minimisation measures can be put in place to minimise the risk of fibrosis.
Danish: Desuden kan der indføres foranstaltninger til minimering af risikoen for fibrose
English: Warnings on the risk of fibrosis should be included in the product information, alongside measures to monitor patients for development of fibrosis, and these should also be communicated to prescribers and patients using educational material.
Danish: Der bør indsættes advarsler om risikoen for fibrose i produktinformationen samt foranstaltninger til overvågning af patienten for fibroseudvikling, og dette bør desuden formidles gennem oplysningsmateriale til ordinerende læger og patienter.
English: Krabbe A. Limited efficacy of methysergide in cluster headache.
Danish: Krabbe A. Limited efficacy of methysergid in cluster headache.
English: In a more recent review14, methysergide and verapamil were cited as the most useful treatments of the episodic form of cluster headache.
Danish: I en nyere oversigtsartikel14 blev methysergid og verapamil beskrevet som de nyttigste behandlinger til den episodiske form af klyngehovedpine.
English: Methysergide is currently indicated in the prophylaxis of migraine headache, cluster headache and also in the treatment of diarrhoea caused by carcinoid disease (specific wording of the indication may vary from product to product).
Danish: Methysergid er aktuelt indiceret til profylakse af migræne og klyngehovedpine samt til behandling af diarré forårsaget af karcinoid sygdom (den konkrete ordlyd af indikationen kan være forskellig fra produkt til produkt).
English: The CHMP noted that the mechanistic basis for the fibrosis appears to be well-founded, and fits with the known association between methysergide use and fibrosis, which has been reported with respect of valvular heart disease since the mid-1960s.
Danish: CHMP bemærkede, at det mekanistiske grundlag for fibrose synes at være velunderbygget og er i overensstemmelse med den kendte sammenhæng mellem anvendelse af methysergid og fibrose, som er indberettet i forbindelse med valvulær hjertesygdom siden midten af 1960'erne.
English: The CHMP noted that fibrosis can be a life-threatening event and that some of the retroperitoneal fibrotic reactions reported are very severe (ureter fibrosis, bilateral uretic stenting, bilateral nephrostomy etc.).
Danish: CHMP bemærkede, at fibrose kan være livstruende, og at nogle af de indberettede retroperitoneale fibrotiske reaktioner er meget svære (ureterfibrose, bilateral stentindlæggelse, bilateral nefrostomi mv.).
English: Since fibrotic reactions are believed to be associated with persistent agonist activation of the 5-HT2B receptor, long-term treatment with methysergide will expose patients to the potential for tissue fibrosis mediated by its principal active metabolite, methylergometrine.
Danish: Da fibrotiske reaktioner menes at have sammenhæng med vedholdende agonistisk aktivering af 5-HT2B-receptoren, vil langtidsbehandling med methysergid udsætte patienterne for potentialet for vævsfibrose medieret af den vigtigste aktive metabolit, methylergometrin.
English: with caution as methods of detection of fibrosis used in these studies are not sensitive enough, in particular for valvular fibrosis.
Danish: forbehold, da de i undersøgelserne anvendte metoder til påvisning af fibrose ikke er tilstrækkeligt følsomme, navnlig for valvulær fibrose.
English: Clin Pharmacol Ther 19667(4):520-526 3 Ryan RE. Double-blind crossover comparison of BC-105, methysergide, and placebo in the prophylaxis of migraine headache.
Danish: Clin Pharmacol Ther 19667(4):520-526 3 Ryan RE. Double-blind crossover comparison of BC-105, methysergid, and placebo in the prophylaxis of migraine headache.
English: The CHMP also noted that methysergide is included in the latest recommendations of migraine preventive treatments of the European Federation of Neurological Societies (EFNS; 2009)9 as drug of third choice for migraine prophylaxis for short-term use only, and in the latest French recommendations of 2013 as Grade B or C (probably effective) for migraine prophylaxis10.
Danish: CHMP bemærkede desuden, at methysergid i de nyeste anbefalinger for profylaktisk behandling af migræne fra European Federation of Neurological Societies (EFNS; 2009)9 kun er medtaget som tredjevalg til kortvarig profylakse, og i de seneste franske anbefalinger fra 2013 som grad B eller C (formodentlig effektivt) til migræneprofylakse10.
English: • The Committee reviewed all available data on the efficacy and safety of methysergide containing medicinal products, in particular with regard to the risk of fibrotic reactions.
Danish: • udvalget gennemgik alle foreliggende data om virkningen og sikkerheden af lægemidler indeholdende methysergid, navnlig vedrørende risikoen for fibrotiske reaktioner
English: Clinical trial of methysergide and other preparations in the management of migraine.
Danish: Clinical trial of methysergid and other preparations in the management of migraine.
English: The CHMP further noted that methysergide is included as second choice treatment in the latest recommendations of cluster headache preventive treatments of the EFNS (2006)15 and is also included in the list of preventive therapies for cluster headache in recently published guidelines16,17,18.
Danish: CHMP bemærkede endvidere, at methysergid er medtaget som en andetvalgsbehandling i de seneste anbefalinger for forebyggende behandling af klyngehovedpine fra EFNS (2006)15 og desuden er opført på listen over forebyggende behandlinger af klyngehovedpine i nyligt offentliggjorte vejledninger16,17,18.
English: However, in view of the demonstrated risk of fibrosis, adequate risk minimisation measures should be put in place.
Danish: På grund af den påviste fibroserisiko bør der imidlertid indføres passende risikominimeringsforanstaltninger.
English: Regarding the risk of retroperitoneal fibrosis, there is evidence of increased risk in patients treated with methysergide (200 versus 1.3 per 100 000 patients)23,24.
Danish: For retroperitoneal fibrose er der evidens for øget risiko ved behandling med methysergid (200 mod 1,3 pr. 100 000 patienter)23,24.
English: In order to evaluate the safety of methysergide, the CHMP considered data from literature and safety database including spontaneous and literature reports.
Danish: Til vurdering af sikkerheden af methysergid gennemgik CHMP data fra litteraturen og sikkerhedsdatabaser, herunder spontane indberetninger og videnskabelige artikler.
English: 7 Whewell J. Methysergide in prophylaxis of migraine: a clinical trial in general practice.
Danish: Whewell J. methysergid in prophylaxis of migraine: a clinical trial in general practice.
English: The CHMP acknowledged the advice of the Scientific Advisory Group (SAG) which was convened in September 2013 during which the experts discussed, based on their clinical experience, whether it is possible to define a population for which there is a therapeutic need for oral methysergide-containing products when standard treatment for these indications have been ineffective.
Danish: CHMP henholdt sig til rådgivningen fra den videnskabelige rådgivende gruppe, der blev indkaldt til et møde i september 2013, hvor eksperterne ud fra deres kliniske erfaringer drøftede, om der kan fastlægges en population, der har et behandlingsbehov for orale produkter indeholdende methysergid, når standardbehandlingen ved disse indikationer har været ineffektiv.
English: Serious intolerance or contra-indication to a first line drug is regarded as treatment failure.
Danish: Alvorlig intolerans over for eller kontraindikation af førstevalgslægemidlet sidestilles med behandlingssvigt.
English: In 2011, a French national pharmacovigilance review reported serious cases of valvulopathy, pulmonary, pleural and retroperitoneal fibrosis associated with methysergide containing medicinal products.
Danish: I 2011 blev der ved en national fransk gennemgang af lægemiddelovervågningsdata fundet alvorlige tilfælde af valvulopati og pulmonal, pleural og retroperitoneal fibrose, der havde sammenhæng med lægemidler indeholdende methysergid.
English: The CHMP further took note of third party interventions received from patients and healthcare professionals during the assessment, highlighting the importance of maintaining availability of this product to a population that, albeit small, has few or no therapeutic alternatives for a debilitating condition.
Danish: CHMP henholdt sig desuden til tredjepartsindlæg fra patienter og sundhedspersoner, der blev modtaget under vurderingen, og understregede vigtigheden af fortsat at råde over dette produkt til en population, der er lille, men har få eller slet ingen behandlingsalternativer ved en invaliderende sygdom.
English: Lovshin LL. Use of methysergide in the treatment of extracranial vascular headache.
Danish: 12 Lovshin LL. Use of methysergid in the treatment of extracranial vascular headache.
English: Taking into account the number of fibrosis cases reported and the probable under reporting, the risk of fibrotic reactions associated with methysergide cannot be excluded.
Danish: I betragtning af antallet af indberettede tilfælde af fibrose og den sandsynlige underindberetning kan risikoen for fibrotiske reaktioner i forbindelse med methysergid ikke udelukkes.
English: Regarding the indication “treatment of diarrhoea caused by carcinoid disease”, the CHMP concluded that the benefit-risk balance is negative as there is a clearly demonstrated risk of fibrosis but no evidence of benefit.
Danish: For indikationen “behandling af diarré forårsaget af karcinoid sygdom” konkluderede CHMP, at benefit/risk-forholdet er negativt, da der klart er påvist fibroserisiko, men ikke gavnlig virkning.
English: • The Committee considered that a causal association between methysergide and fibrotic reactions is likely based on available data (mainly relating to retroperitoneal fibrosis).
Danish: • udvalget fandt det sandsynligt, at der er kausal sammenhæng mellem methysergid og fibrotiske reaktioner, baseret på de foreliggende data (hovedsagelig for retroperitoneal fibrose).
English: These included restricted duration of treatment, optimal dose of treatment, specialist supervision and information for prescribing physicians and patients' organisation.
Danish: Foranstaltningerne består i begrænset behandlingsvarighed, optimal behandlingsdosis, overvågning ved speciallæge og information til ordinerende læger og patientorganisationer.
English: The CHMP also recommended that methysergide treatment should be initiated and supervised by specialised physicians with experience in the treatment of migraine and cluster headache.
Danish: CHMP anbefalede desuden, at behandling med methysergid bør indledes og overvåges af specialiserede læger med erfaring i behandling af migræne og klyngehovedpine.
English: • Therefore the CHMP was of the opinion that the benefit-risk balance of methysergide containing products:
Danish: • CHMP fandt derfor, at benefit/risk-forholdet for lægemidler indeholdende methysergid:
English: Grounds for variation to the terms of the marketing authorisations Whereas
Danish: Begrundelse for ændring af betingelserne for markedsføringstilladelserne
English: Therefore, the potential causal association between fibrotic reactions and methysergide cannot be excluded.
Danish: Der kan derfor ikke udelukkes en kausal sammenhæng mellem methysergid og fibrotiske reaktioner.
English: In addition, the CHMP noted that methysergide is recommended by experts as a rescue treatment, reserved for patients in whom other treatments have failed.
Danish: CHMP bemærkede yderligere, at eksperter anbefaler methysergid som redningsbehandling, der er forbeholdt patienter, hos hvem andre behandlinger har slået fejl.
English: The SAG also considered that patients should be monitored at baseline and every six months while on treatment (heart ultrasound, abdominal magnetic resonance imaging (MRI), pulmonary function tests) in order to be able to identify all fibrosis before severe and potentially irreversible reactions have occurred.
Danish: Den rådgivende videnskabelige gruppe fandt det desuden nødvendigt at overvåge patienterne ved baseline og hver sjette måned under behandlingen (ultralydsundersøgelse af hjertet, MR-scanning af abdomen, lungefunktionstest) med henblik på at opdage al fibrose, før der er indtrådt svære og potentielt irreversible reaktioner.
English: J Neurol Neurosurg Psychiatry 1964; 27:463-9.
Danish: Neurosurg Psychiatry 1964; 27:463-9.
English: Patients should have failed at least 2 classes of drugs before starting methysergide.
Danish: Der skal have været forudgående behandlingssvigt af mindst to klasser lægemidler, før behandling med methysergid påbegyndes.
English: • The Committee noted that there is no evidence of efficacy of methysergide in the treatment of diarrhoea caused by carcinoid disease, and therefore the potential benefit for patients in this indication is outweighed by the identified risk.
Danish: • udvalget bemærkede, at der ikke er evidens for virkningen af methysergid til behandling af diarré forårsaget af karcinoid sygdom, og at de potentielle fordele for patienter ved denne indikation derfor ikke opvejer den påviste risiko
English: The CHMP considered the view of the SAG which recommended some measures to be taken in order to minimise the risk of fibrotic reactions when prescribing methysergide.
Danish: CHMP henholdt sig til den videnskabelige rådgivende gruppes udtalelse, der anbefalede indførelse af visse foranstaltninger til minimering af risikoen for fibrotiske reaktioner ved ordination af methysergid.
English: Am J Respir Crit Care Med 2006;174(7):810-6.
Danish: Respir Crit Care Med 2006;174(7):810-6.
English: Southwell N, Williams J, Mackenzie I. Methysergide In The Prophylaxis Of Migraine.
Danish: Southwell N, Williams J, Mackenzie I. methysergid In The Prophylaxis Of Migraine.
English: No data was submitted in support of efficacy of methysergide in the “treatment of diarrhoea caused by carcinoid disease”, and it is therefore considered that efficacy in this indication has not been demonstrated.
Danish: Der blev ikke forelagt data til underbygning af virkningen af methysergid til “behandling af diarré forårsaget af karcinoid sygdom”, og virkningen ved denne indikation anses derfor ikke for at være påvist.
English: The CHMP noted that the clinical trial evidence for the efficacy of methysergide as a prophylactic treatment for cluster headache is less robust compared to the evidence for migraine prophylaxis and that the majority of studies have a number of limitations.
Danish: CHMP bemærkede, at evidensen fra kliniske undersøgelser af virkningen af methysergid til profylaktisk behandling af klyngehovedpine er mindre fyldestgørende end evidensen for migræneprofylakse, og at størstedelen af undersøgelserne har en række begrænsninger.
English: The CHMP has considered the totality of the available data on the safety and efficacy of methysergide.
Danish: CHMP har vurderet samtlige foreliggende data om sikkerheden og virkningen af methysergid.
English: 23 Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associated with methysergide therapy for headache.
Danish: 23 Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associated with methysergid therapy for headache.
English: Based on the clinical experience of headache experts, the SAG considered that there is a small proportion of the populations suffering from migraine and from cluster headache that seems to benefit from treatment with methysergide, when previous treatments have failed.
Danish: Med baggrund i kliniske erfaringer hos eksperter i hovedpine fandt den videnskabelige rådgivende gruppe, at en lille andel af de populationer, der lider af migræne og af klyngehovedpine, synes at have fordel af behandling med methysergid, når tidligere behandlinger har slået fejl.
English: In particular, it binds to and is an antagonist of the 5HT2B receptor.
Danish: Det bindes navnlig til 5HT2B-receptoren og virker antagonistisk på denne.
English: Having considered the overall data provided by the MAH in writing, the CHMP concluded that the benefit-risk balance of methysergide is favourable in:
Danish: Efter gennemgang af alle data, der er forelagt skriftligt af markedsføringstilladelsesindehaveren, konkluderede CHMP, at benefit/risk-forholdet for produkter indeholdende methysergid er positivt til:
English: Shekelle RB, Ostfeld AM. Methysergide in the migraine syndrome.
Danish: 4 Shekelle RB, Ostfeld AM. methysergid in the migraine syndrome.
English: 19 Bana DS, MacNeal PS, LeCompte PM. Cardiac murmurs and endocardial fibrosis associated with methysergide therapy.
Danish: Bana DS, MacNeal PS, LeCompte PM. Cardiac murmurs and endocardial fibrosis associated with methysergid therapy.