natgillin/translations-raw huggingface dataset:
• CHMP fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF for lægemidler indeholdende methysergid
• The CHMP considered the procedure under Article 31 of Directive 2001/83/EC for methysergide containing medicinal products.
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.
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.
Methysergid bindes med forskellig affinitet til en række serotonerge receptorer (5-HT-receptorer).
Methysergide binds with varying affinities to a range of serotonergic receptors (5-HT receptors).
Indikationen bør indskrænkes til patienter med funktionel invaliditet efter forudgående svigt af andre behandlinger.
The indication should be restricted to patients with functional disability in whom other treatments have failed.
Desuden kan der indføres foranstaltninger til minimering af risikoen for fibrose
In addition, risk minimisation measures can be put in place to minimise the risk of fibrosis.
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.
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.
Krabbe A. Limited efficacy of methysergid in cluster headache.
Krabbe A. Limited efficacy of methysergide in cluster headache.
I en nyere oversigtsartikel14 blev methysergid og verapamil beskrevet som de nyttigste behandlinger til den episodiske form af klyngehovedpine.
In a more recent review14, methysergide and verapamil were cited as the most useful treatments of the episodic form of cluster headache.
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).
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).
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.
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.
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.).
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.).
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.
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.
forbehold, da de i undersøgelserne anvendte metoder til påvisning af fibrose ikke er tilstrækkeligt følsomme, navnlig for valvulær fibrose.
with caution as methods of detection of fibrosis used in these studies are not sensitive enough, in particular for valvular fibrosis.
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.
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.
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.
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.
• udvalget gennemgik alle foreliggende data om virkningen og sikkerheden af lægemidler indeholdende methysergid, navnlig vedrørende risikoen for fibrotiske reaktioner
• 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.
Clinical trial of methysergid and other preparations in the management of migraine.
Clinical trial of methysergide and other preparations in the management of migraine.
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.
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.
På grund af den påviste fibroserisiko bør der imidlertid indføres passende risikominimeringsforanstaltninger.
However, in view of the demonstrated risk of fibrosis, adequate risk minimisation measures should be put in place.
For retroperitoneal fibrose er der evidens for øget risiko ved behandling med methysergid (200 mod 1,3 pr. 100 000 patienter)23,24.
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.
Til vurdering af sikkerheden af methysergid gennemgik CHMP data fra litteraturen og sikkerhedsdatabaser, herunder spontane indberetninger og videnskabelige artikler.
In order to evaluate the safety of methysergide, the CHMP considered data from literature and safety database including spontaneous and literature reports.
Whewell J. methysergid in prophylaxis of migraine: a clinical trial in general practice.
7 Whewell J. Methysergide in prophylaxis of migraine: a clinical trial in general practice.
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.
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.
Alvorlig intolerans over for eller kontraindikation af førstevalgslægemidlet sidestilles med behandlingssvigt.
Serious intolerance or contra-indication to a first line drug is regarded as treatment failure.
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.
In 2011, a French national pharmacovigilance review reported serious cases of valvulopathy, pulmonary, pleural and retroperitoneal fibrosis associated with methysergide containing medicinal products.
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.
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.
12 Lovshin LL. Use of methysergid in the treatment of extracranial vascular headache.
Lovshin LL. Use of methysergide in the treatment of extracranial vascular headache.
I betragtning af antallet af indberettede tilfælde af fibrose og den sandsynlige underindberetning kan risikoen for fibrotiske reaktioner i forbindelse med methysergid ikke udelukkes.
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.
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.
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.
• udvalget fandt det sandsynligt, at der er kausal sammenhæng mellem methysergid og fibrotiske reaktioner, baseret på de foreliggende data (hovedsagelig for retroperitoneal fibrose).
• The Committee considered that a causal association between methysergide and fibrotic reactions is likely based on available data (mainly relating to retroperitoneal fibrosis).
Foranstaltningerne består i begrænset behandlingsvarighed, optimal behandlingsdosis, overvågning ved speciallæge og information til ordinerende læger og patientorganisationer.
These included restricted duration of treatment, optimal dose of treatment, specialist supervision and information for prescribing physicians and patients' organisation.
CHMP anbefalede desuden, at behandling med methysergid bør indledes og overvåges af specialiserede læger med erfaring i behandling af migræne og klyngehovedpine.
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.
• CHMP fandt derfor, at benefit/risk-forholdet for lægemidler indeholdende methysergid:
• Therefore the CHMP was of the opinion that the benefit-risk balance of methysergide containing products:
Begrundelse for ændring af betingelserne for markedsføringstilladelserne
Grounds for variation to the terms of the marketing authorisations Whereas
Der kan derfor ikke udelukkes en kausal sammenhæng mellem methysergid og fibrotiske reaktioner.
Therefore, the potential causal association between fibrotic reactions and methysergide cannot be excluded.
CHMP bemærkede yderligere, at eksperter anbefaler methysergid som redningsbehandling, der er forbeholdt patienter, hos hvem andre behandlinger har slået fejl.
In addition, the CHMP noted that methysergide is recommended by experts as a rescue treatment, reserved for patients in whom other treatments have failed.
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.
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.
Der skal have været forudgående behandlingssvigt af mindst to klasser lægemidler, før behandling med methysergid påbegyndes.
Patients should have failed at least 2 classes of drugs before starting methysergide.
• 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
• 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.
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.
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.
Respir Crit Care Med 2006;174(7):810-6.
Am J Respir Crit Care Med 2006;174(7):810-6.
Southwell N, Williams J, Mackenzie I. methysergid In The Prophylaxis Of Migraine.
Southwell N, Williams J, Mackenzie I. Methysergide In The Prophylaxis Of Migraine.
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.
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.
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.
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.
CHMP har vurderet samtlige foreliggende data om sikkerheden og virkningen af methysergid.
The CHMP has considered the totality of the available data on the safety and efficacy of methysergide.
23 Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associated with methysergid therapy for headache.
23 Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associated with methysergide therapy for headache.
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.
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.
Det bindes navnlig til 5HT2B-receptoren og virker antagonistisk på denne.
In particular, it binds to and is an antagonist of the 5HT2B receptor.
Efter gennemgang af alle data, der er forelagt skriftligt af markedsføringstilladelsesindehaveren, konkluderede CHMP, at benefit/risk-forholdet for produkter indeholdende methysergid er positivt til:
Having considered the overall data provided by the MAH in writing, the CHMP concluded that the benefit-risk balance of methysergide is favourable in:
4 Shekelle RB, Ostfeld AM. methysergid in the migraine syndrome.
Shekelle RB, Ostfeld AM. Methysergide in the migraine syndrome.
Bana DS, MacNeal PS, LeCompte PM. Cardiac murmurs and endocardial fibrosis associated with methysergid therapy.
19 Bana DS, MacNeal PS, LeCompte PM. Cardiac murmurs and endocardial fibrosis associated with methysergide therapy.
Samlet fandt CHMP, at methysergid synes at være til fordel for en lille patientpopulation med migræne og klyngehovedpine.
Overall, the CHMP considered that methysergide seems to benefit a small patient population of migraine and cluster headache patients.
• udvalget fandt, at der er nogen evidens for, at methysergid har en klinisk betydningsfuld virkning til profylaktisk behandling af svær invaliderende migræne og klyngehovedpine, for hvilke der kun findes begrænsede behandlingsalternativer.
• The Committee considered that there is some evidence for clinically significant efficacy of methysergide in the prophylactic treatment of severe, debilitating migraine and cluster headache for which therapeutic alternatives are limited.
Efter gennemgang af samtlige foreliggende data finder CHMP, at der er nogen evidens for klinisk betydningsfuld virkning af methysergid til profylaktisk behandling af svær og invaliderende migræne.
Considering the overall data available, the CHMP is of the opinion that there is some evidence of clinically significant efficacy of methysergide in the prophylactic treatment of severe and debilitating migraine.
− er gunstigt til profylaktisk behandling af svær intraktabel migræne (med eller uden forvarsel) med funktionel invaliditet hos voksne.
− Is favourable for the prophylactic treatment of severe intractable migraine (with or without aura) with functional disability in adults.
• profylaktisk behandling af svær intraktabel migræne (med eller uden forvarsel) med funktionel invaliditet hos voksne.
• the prophylactic treatment of severe intractable migraine (with or without aura) with functional disability in adults.
− er gunstigt til profylaktisk behandling af episodisk og kronisk klyngehovedpine hos voksne.
− Is favourable for the prophylactic treatment of episodic and chronic cluster headache in adults.
Pedersen E, Møller CE. methysergid in migraine prophylaxis.
2 Pedersen E, Møller CE. Methysergide in migraine prophylaxis.
• profylaktisk behandling af episodisk og kronisk klyngehovedpine hos voksne.
• the prophylactic treatment of episodic and chronic cluster headache in adults.
− ikke er gunstigt til behandling af diarré af forårsaget af karcinoid sygdom anbefaler CHMP i medfør af artikel 116 i direktiv 2001/83/EF ændring af betingelserne for markedsføringstilladelserne for de i bilag I omhandlede lægemidler, der indeholder methysergid.
Therefore, in accordance with Article 116 of Directive 2001/83/EC, the CHMP recommends the variation to the terms of the marketing authorisation for methysergide containing medicinal products referred to in Annex I.
Nogle af dem viste virkning af methysergid sammenlignet med placebo til denne indikation5,6,7.
In addition, further trials comparing methysergide with placebo or comparators were also presented, some of which also showed efficacy of methysergide compared to placebo in this indication5,6,7.
Methysergid er ikke effektivt til behandling af et manifest migræneanfald.
Methysergide is not effective for treating a migraine attack that is already present.
Migraine, Tension-Type, Cluster and Medication-Overuse Headache.
Guidelines for All Healthcare Professionals in the Diagnosis and Management of Migraine, Tension-Type, Cluster and Medication-Overuse Headache.
For indikationen “klyngehovedpine” henviste ansøgeren til en oversigtsartikel11, der pegede på profylaktisk virkning af methysergid, navnlig ved den episodiske form af klyngehovedpine, og til en
With regard to the indication “cluster headache”, the applicant referred to a review11 which suggested the prophylactic efficacy of methysergide, particularly for the episodic form of cluster headache and to a study12 where 69% of cluster headache patients reported to have good to excellent results.
Disse undersøgelser tyder på, at methysergid i sammenligning med placebo har profylaktisk virkning mod migræne.
The results of these studies are suggestive of the efficacy of methysergide compared to placebo in the prophylaxis of migraine.
An evaluation of methysergid in the prevention of migraine and other vascular headaches.
Lance JW et al. An evaluation of methysergide in the prevention of migraine and other vascular headaches.
Behandlingen skal have haft en varighed af mindst to måneder, før det kan konkluderes, om der er behandlingssvigt.
The minimal duration of treatment before concluding failure is 2 months.
Således underbygger nogle data, at dets antagonistiske virkning på 5-HT2B-receptoren spiller en rolle i profylakse af migræne.
There are a number of pharmacological pathways by which methysergide may be effective in preventing migraine, for instance some data support the role of antagonism of the 5-HT2B receptor in the prophylaxis of migraine.
Bendtsen L, Birk S, Kasch H et al.
18 Bendtsen L, Birk S, Kasch H et al. Reference programme: Diagnosis and treatment of headache disorders and facial pain.
Den samlede reduktion var 54 %.
The overall reduction was 54%.
Dato for første markedsføringstilladelse: 16. august 2016.
Date of first authorisation: 16 August 2016.
● Risikostyringsplan (RMP)
● Risk management plan (RMP)
En opdateret RMP skal fremsendes: ● på anmodning fra Det Europæiske Lægemiddelagentur
An updated RMP should be submitted: ● At the request of the European Medicines Agency;
I denne korte periode kan en risiko for det ammede barn ikke udelukkes.
In this short period, a risk to the suckling child cannot be excluded.
Over 52 uger
Over 52 weeks
Lægen vil beregne den rette dosis for dig.
Your doctor will work out the right dose for you.
% reduktion
% reduction
Over 16 uger
Over 16 weeks
Dette er ikke usædvanligt for proteinholdige opløsninger.
This is not unusual for proteinaceous solutions.
Infusionstiden kan variere, afhængigt af det totale volumen, der skal gives.
Infusion time may vary depending on the total volume to be infused.
Vedligeholdelsesbehandling med OCS var ikke tilladt.
Maintenance OCS was not allowed.
Dette er især vigtigt: - hvis du får andre lægemidler, som påvirker dit immunsystem - hvis du er blevet vaccineret for nylig, eller hvis det er sandsynligt, at du har behov for at blive vaccineret.
This is particularly important: - if you are receiving other medicines which affect your immune system; - if you have recently received a vaccination or if you are likely to need a vaccination.
Disse tilfælde medførte seponering af behandlingen.
These cases resulted in the discontinuation of treatment.
Der er ingen eller utilstrækkelige data (færre end 300 graviditetsudfald) fra anvendelse af reslizumab til gravide kvinder.
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of reslizumab in pregnant women.
Resultaterne blev støttet af de sekundære virkningsendepunkter og stemte overens med resultaterne for den samlede population.
Results were supported by the secondary efficacy endpoints and were in line with the overall population.
Inter-individuel variabilitet i maksimal og samlet eksponering er ca. 20-30 %.
Inter-individual variability in peak and overall exposure is approximately 20-30%
Der foreligger ingen data for børn i alderen op til 11 år.
No data are available for children aged up to 11 years.
Du må IKKE stoppe behandlingen med CINQAERO, medmindre lægen fortæller dig det, heller ikke selv om du får det bedre.
Do NOT stop treatment with CINQAERO unless your doctor tells you to, even if you feel better.