FrancophonIA/ELRC3.0 huggingface dataset:
English: Although serious cardiovascular reactions have been reported with metoclopramide (mainly associated to the intravenous administration), no new significant signals have been identified.
Danish: Trods de indberettede alvorlige kardiovaskulære reaktioner med metoclopramid (hovedsagelig ved intravenøs administration) er der ikke er registreret nye signaler af betydning.
English: Annex II Scientific conclusions and grounds for revocation / variation to the terms of the Marketing Authorisations
Danish: Bilag II Videnskabelige konklusioner og begrundelse for inddragelse af markedsføringstilladelserne/ændring af betingelserne for markedsføringstilladelserne
English: In its July 2013 opinion, the CHMP recommended that for all indications in adults the single dose is 10 mg, up to three times daily.
Danish: I sin udtalelse fra juli 2013 anbefalede CHMP for alle indikationer til voksne en enkeltdosis på 10 mg op til tre gange dagligt.
English: The exception is the treatment of established post-operative nausea and vomiting, which had already been recommended to be maintained in a previous worksharing procedure under Article 45 of Regulation (EC) No 1901/2006.
Danish: Undtagelsen er behandling af manifest postoperativ kvalme og opkastning, der allerede anbefaledes opretholdt i en tidligere arbejdsdelingsprocedure i medfør af artikel 45 i forordning (EF) nr. 1901/2006.
English: The CHMP endorsed a communication i.e. Dear Healthcare Professional Communication (DHPC), to rapidly communicate the outcome of the present review.
Danish: CHMP godkendte en direkte meddelelse til sundhedspersoner (DHPC) med henblik på en hurtig formidling af resultatet af denne gennemgang.
English: Metoclopramide can be used in combination with oral analgesics to improve the absorption of analgesics in acute migraine' (oral route)
Danish: metoclopramid kan anvendes i kombination med orale analgetika for at forbedre absorptionen af analgetika ved akut migræne” (ved oral administration)
English: The almost totality of the data relates to the intravenous administration of metoclopramide, and in the majority of the studies assessed, a 10 mg dose was used.
Danish: Næsten samtlige data vedrører intravenøs administration af metoclopramid, og i størstedelen af de vurderede undersøgelser blev der anvendt en dosis på 10 mg.
English: The data presented is limited and was generated in different settings during which nausea and vomiting may occur.
Danish: De forelagte data er begrænsede og blev genereret i forskellige scenarier, hvor der kan optræde kvalme og opkastning.
English: In addition, due to its prokinetic properties, metoclopramide may also play a role when given orally in combination with analgesics.
Danish: Desuden kan metoclopramid på grund af sine prokinetiske egenskaber også spille en rolle, når det gives oralt i kombination med analgetika.
English: The majority of the efficacy data submitted during the current procedure had already been assessed during the previous paediatric worksharing procedure under Article 45 of Regulation (EC) No 1901/2006, and the new data did not add relevant new elements to the previous assessment.
Danish: Størstedelen af de data om virkning, der er forelagt under denne procedure, var i forvejen vurderet under den tidligere pædiatriske arbejdsdelingsprocedure i medfør af artikel 45 i forordning (EF) nr. 1901/2006, og de nye oplysninger bibragte ikke relevante nye elementer til den tidligere vurdering.
English: However, the risk of serious neurological adverse reactions is increased.
Danish: Derimod øges risikoen for alvorlige neurologiske bivirkninger.
English: It possesses parasympathomimetic activity as well as being a dopamine-receptor (D2) antagonist with a direct effect on the chemoreceptor trigger zone.
Danish: Det har parasympatomimetisk aktivitet og er desuden en dopaminreceptor- (D2-) antagonist med direkte virkning på kemoreceptorens aktiveringsområde.
English: Based on the risk of neurological and cardiovascular adverse events, as well as on the limited evidence of efficacy for all indications approved, the French Competent Authority triggered a referral under Article 31 of Directive 2001/83/EC and asked the CHMP to review the benefit-risk balance of metoclopramide-containing products in all populations, particularly in children and the elderly.
Danish: På baggrund af risikoen for neurologiske og kardiovaskulære bivirkninger og den begrænsede evidens for virkning ved alle godkendte indikationer indledte de franske kompetente myndigheder en indbringelse i medfør af artikel 31 i direktiv 2001/83/EF og anmodede CHMP om at gennemgå benefit/risk-forholdet for produkter indeholdende metoclopramid til alle populationer, navnlig børn og ældre.
English: An oral bioequivalence study of metoclopramide tablets compared to liquid showed that Cmax and Tmax are not significantly different for the two oral formulations.
Danish: En oral bioækvivalensundersøgelse af metoclopramid-tabletter sammenlignet med væske viste, at Cmax og Tmax ikke afviger væsentligt mellem de to orale formuleringer.
English: Following the adoption of the CHMP opinion in July 2013, a request for re-examination was received from one MAH concerned by the procedure.
Danish: Efter vedtagelsen af CHMP's udtalelse i juli 2013 modtoges en anmodning om fornyet overvejelse fra en af de markedsføringstilladelsesindehavere, som var involveret i proceduren.
English: From the data assessed, it appears that the risk of acute dystonias is increased when using high doses, and is higher in children than in adults.
Danish: Af de vurderede data fremgår det, at risikoen for akutte dystonier øges ved anvendelse af høje doser og er større hos børn end hos voksne.
English: Metoclopramide is a substituted benzamide used for its prokinetic and antiemetic properties.
Danish: Metoclopramid er et substitueret benzamid, der anvendes på grund af sine prokinetiske og antiemetiske egenskaber.
English: After finalisation of the procedure under Article 45 of Regulation (EC) No 1901/2006, the Marketing Authorisation Committee of the French Competent Authority performed a national assessment of the benefit-risk balance of metoclopramide in children and decided, in October 2011, to extend the contraindication to all children under 18 years old for all formulations.
Danish: Efter afslutning af proceduren i medfør af artikel 45 i forordning (EF) nr. 1901/2006 foretog de franske kompetente myndigheders udvalg vedrørende markedsføringstilladelser en national vurdering af benefit/risk-forholdet for metoclopramid hos børn og besluttede i oktober 2011 at udvide kontraindikationen til at omfatte alle børn under 18 år for alle formuleringer.
English: For this indication, only the intravenous formulation is of relevance, in line with the outcome of the procedure under Article 45 of Regulation (EC) No
Danish: Til denne indikation er kun den intravenøse formulering relevant, hvilket er på linje med udfaldet af proceduren i medfør af artikel 45 i forordning (EF) nr. 1901/2006.
English: The published epidemiological studies conducted in different countries on the safety of metoclopramide use during pregnancy consistently showed the absence of association between exposure during pregnancy and risk of major congenital malformations.
Danish: De publicerede epidemiologiske undersøgelser, der i en række lande er udført vedrørende sikkerheden af metoclopramid under graviditet, viste samstemmende, at der ikke var sammenhæng mellem eksponering under graviditet og risiko for alvorlige medfødte misdannelser.
English: The risks are increased when using high doses or during longterm treatment, and in particular for extrapyramidal symptoms the risk is higher in children than in adults.
Danish: Risiciene øges ved anvendelse af høje doser eller ved langvarig behandling, og navnlig for ekstrapyramidale symptomer er risikoen for børn større end for voksne,
English: The elderly appear to be at particular risk of developing tardive dyskinesia following long-term treatment, which in some cases may be irreversible.
Danish: Ældre synes ved lang tids behandling at være særlig udsat for at udvikle tardiv dyskinesi, som i nogle tilfælde kan være irreversibel.
English: Established renal failure is defined as ClCr < 15 ml/min, therefore this cut-off should be included in any dosing recommendations.
Danish: Manifest nyresvigt er defineret som ClCr < 15 ml/min, hvorfor dette afskæringspunkt bør indgå i alle doseringsanbefalinger.
English: However the safety data seems to indicate that methaemoglobinaemia occurs almost exclusively in children, and that children are also at higher risk of serious neurological adverse reactions.
Danish: Data vedrørende sikkerheden synes imidlertid at vise, at methæmoglobinæmi næsten udelukkende forekommer hos børn, og at børn også har højere risiko for alvorlige neurologiske bivirkninger.
English: The review by Lee et al. provides a complete overview of the evidence of efficacy in diabetic gastroparesis.
Danish: En oversigtsartikel af Lee et al. giver en dækkende sammenfatning af evidensen for virkningen ved diabetisk gastroparese.
English: It also has serotonin-receptor (5-HT3) antagonist properties.
Danish: Det har derudover egenskaber som serotoninreceptor- (5-HT3-) antagonist.
English: Suppositories
Danish: Suppositorier
English: Therefore, the Committee considered that the available evidence does not support the assumption that oral liquid formulations have a faster onset of action than tablets.
Danish: Udvalget fandt derfor, at den foreliggende evidens ikke støtter antagelsen om, at orale flydende formuleringer har hurtigere indsættende virkning end tabletter.
English: For the indications gastrointestinal motility disorders including gastroparesis and gastroesophageal reflux disease and dyspepsia, the Committee noted that these are essentially chronic conditions for which long term use is often required.
Danish: Vedrørende indikationerne gastrointestinale motilitetsforstyrrelser, herunder gastroparese og gastroøsofageal reflukssygdom og dyspepsi, bemærkede udvalget, at de i det væsentlige er kroniske tilstande, der ofte kræver langvarig behandling.
English: Metoclopramide is excreted in breast milk, and although the available data does no raise concerns, effects in the breast fed infant cannot be excluded.
Danish: Metoclopramid udskilles i modermælk, og skønt de foreliggende data ikke giver grund til betænkelighed, kan påvirkning af brystbarnet ikke udelukkes.
English: Benefit-risk balance
Danish: Benefit/risk-forhold
English: A paediatric worksharing procedure under Article 45 of Regulation (EC) No 1901/20061 to assess information from paediatric studies with metoclopramide has been concluded in 2010 with a recommendation that Member States should introduce the following changes to the product information:
Danish: En pædiatrisk arbejdsdelingsprocedure i henhold til artikel 45 i forordning (EF) nr. 1901/20061 til vurdering af oplysninger fra pædiatriske undersøgelser med metoclopramid blev afsluttet i 2010 med en anbefaling af, at medlemsstaterne indførte følgende ændringer i produktoplysningerne:
English: The Committee considered the proposal by one MAH to explicitly restrict intravenous administration to locations where resuscitation equipment is available, but noted that most places where intravenous drugs are administrated will already have such equipment.
Danish: Udvalget overvejede forslaget fra en markedsføringstilladelsesindehaver om eksplicit at begrænse intravenøs administration til centre, der råder over genoplivningsudstyr, men bemærkede, at sådant udstyr i forvejen forefindes på de fleste behandlingssteder, hvor der gives intravenøse lægemidler.
English: Much of the available data is derived from trials designed to investigate newer agents such as the 5-HT3 receptor antagonists, and therefore do not always allow for a definite conclusion of the effect of metoclopramide due to the absence of a comparison to placebo.
Danish: En stor del af de foreliggende data er udledt af undersøgelser med nyere midler såsom 5-HT3-receptorantagonister og giver derfor ikke altid mulighed for en endelig konklusion om virkningen af metoclopramid på grund af manglende sammenligning med placebo.
English: This therapeutic alternative may be of particular relevance due to the association between prolonged use of 5-HT3 receptor antagonists and adverse effects of constipation and headache, which may be severe and poorly tolerated.
Danish: Dette behandlingsalternativ kan være særlig relevant på grund af af sammenhængen mellem langvarig anvendelse af 5-HT3-receptorantagonister og bivirkninger i form af konstipation og hovedpine, som kan være svære og dårligt tolererede.
English: It is available in a variety of pharmaceutical forms (e.g. tablet, prolonged-release tablet, oral solution, suppository, solution for injection).
Danish: Det dispenseres som en række forskellige lægemiddelformer (f.eks. tablet, depottablet, oral opløsning, suppositorium, injektionsvæske).
English: • The Committee noted that the available data do not support clinically significant efficacy for the indications which require long term use (‘gastrointestinal motility disorders including gastroparesis', ‘gastroesophageal reflux disease and dyspepsia') and for the indication ‘adjuvant to surgical and radiological procedures'.
Danish: • udvalget bemærkede, at de foreliggende data ikke underbygger klinisk betydningsfuld virkning ved indikationer, der kræver langvarig anvendelse (“gastrointestinale motilitetsforstyrrelser, herunder gastroparese” og “gastroøsofageal reflukssygdom og dyspepsi”) eller ved indikationen “adjuvans til kirurgiske og radiologiske procedurer”,
English: • The Committee considered that the risk of serious neurological adverse events can be minimised by using lower doses of metoclopramide and limiting treatment duration.
Danish: • udvalget tog i betragtning, at risikoen for alvorlige neurologiske bivirkninger kan minimeres ved at anvende lavere doser af metoclopramid og begrænse behandlingsvarigheden.
English: In addition, data is indicative that the burden of adverse reactions is increased with dose.
Danish: Desuden tyder dataene på, at bivirkningsbelastningen øges med dosis.
English: This may be due to an issue of dose accuracy and reproducibility, unclear information on dosing and possibly difficulties measuring and administering the correct dose, particularly with high concentration formulations and poorly validated devices.
Danish: Dette problem kan skyldes, at doseringen er unøjagtig eller ikke reproducerbar, uklar information om doseringen og muligvis vanskelighed ved at måle og administrere den korrekte dosis, navnlig af formuleringer med høj koncentration og med utilstrækkeligt validerede doseringsanordninger.
English: Considering the recommendation for posology to be defined as 10mg three times a day and the fact that this pharmaceutical form does not allow for adjustment of dose, the Committee considered that the benefit-risk balance of the suppositories dosed at 20mg is negative.
Danish: I betragtning af, at den anbefalede dosering er 10 mg tre gange dagligt, og at denne lægemiddelform ikke giver mulighed for dosisjustering, fandt udvalget benefit/risk-forholdet for suppositorier i styrken 20 mg negativt.
English: However, it also took into consideration the recommendations of the British National Formulary for children (BNFc), which has been validated against emerging evidence, best practice guidelines and advice from a network of clinical experts.
Danish: Udvalget tog dog også anbefalingerne fra British National Formulary for children (BNFc) i betragtning, der er valideret i forhold til ny evidens, retningslinjer for bedste praksis og rådgivning fra et net af kliniske eksperter.
English: Also, the onset of action may be faster with the solution in comparison to that of tablets, as tablets have first to be dissolved in the gastrointestinal tract.
Danish: Desuden kan virkningen være hurtigere indsættende med opløsningen end med tabletterne, da tabletterne først skal opløses i mavetarmkanalen.
English: If however risk minimisation measures are put in place to allow accurate dosing and address the risk of overdose, oral liquid formulations remain an important and suitable alternative for the paediatric population.
Danish: Hvis der indføres tiltag til sikring af nøjagtig dosering og mindskelse af risikoen for overdosering, er orale flydende formuleringer imidlertid fortsat et vigtigt og velegnet alternativ til anvendelse hos den pædiatriske population.
English: Therefore, in order to minimise the risk of serious neurological adverse reactions such as acute extrapyramidal symptoms and irreversible tardive dyskinesia, the dose should be restricted to the minimum effective dose, which for adults is considered to be 10 mg three times daily.
Danish: For at minimere risikoen for alvorlige neurologiske bivirkninger såsom akutte ekstrapyramidale symptomer og irreversibel tardiv dyskinesi bør dosis derfor begrænses til den mindste effektive dosis, der for voksne anses at være 10 mg tre gange dagligt.
English: Using a device such as a graduated oral syringe may even be more convenient than counting drops and it ensures accurate and reproducible dosing in any situation, including when doses are reduced due to renal or hepatic impairment.
Danish: En anordning såsom en oral sprøjte med målestreger kan være endnu mere bekvem i brug end at tælle dråber og sikrer nøjagtig og reproducerbar dosering i enhver situation, herunder reduceret dosis ved nedsat nyre- eller leverfunktion.
English: It is also noted that there are other well-established agents available for this indication, including proton pump inhibitors and H2 receptor antagonists, for which a positive benefit-risk balance has been clearly demonstrated for acute and chronic use.
Danish: Det bemærkes endvidere, at der til denne indikation findes andre anerkendte midler, herunder protonpumpehæmmere og H2-receptorantagonister, for hvilke der er påvist et klart positivt benefit/risk-forhold ved akut og kronisk anvendelse.
English: Limited data exists on the onset of action of oral liquid formulations in comparison with tablets.
Danish: Der findes begrænsede data om virkningen af orale flydende formuleringer sammenlignet med tabletter.
English: • Oral liquid formulations intended to be used in children must be supplied with an appropriate measuring device (e.g. graduated oral syringe) to ensure accurate measuring of the dose and avoid accidental overdosing.
Danish: • Orale flydende formuleringer til anvendelse hos børn skal være forsynet med en egnet doseringsenhed (f.eks. en oral sprøjte med målestreger) for at sikre en nøjagtigt afmålt dosis og undgå accidentel overdosering.
English: In addition to the neurological risk, there is also a risk of occurrence of cardiovascular adverse events including rare but potentially serious reactions such as bradycardia, atrioventricular block, cardiac arrest, mainly reported with the formulations for intravenous use.
Danish: Ud over den neurologiske risiko er der risiko for kardiovaskulære bivirkninger, herunder sjældne, men potentielt alvorlige reaktioner som bradykardi, atrioventrikulært blok og hjertestop, der hovedsagelig beskrives i forbindelse med intravenøse formuleringer.
English: • Inclusion of specific warnings and precautions, mainly regarding the extrapyramidal adverse events.
Danish: • Indførelse af særlige advarsler og forsigtighedsregler, hovedsagelig vedrørende ekstrapyramidale bivirkninger
English: Of note, the review by Jantunen et al. describes the low metoclopramide doses used (20-80mg) as ‘inadequate' and concludes that this may not be an appropriate comparator for 5-HT3 receptor antagonists.
Danish: Det bemærkes, at oversigten udarbejdet af Jantunen et al. beskriver de anvendte lave doser af metoclopramid (20-80 mg) som “utilstrækkelige” og konkluderer, at dette muligvis ikke er velegnet som sammenligningsstof til 5-HT3-receptorantagonister.
English: There is no data submitted to support the efficacy of metoclopramide in the required treatment duration, but there is evidence that the above mentioned risks are increased with prolonged treatment.
Danish: Der er ikke forelagt data til dokumentation af virkningen af metoclopramid i den nødvendige behandlingstid, men der er evidens for, at ovennævnte risici øges ved langvarig behandling.
English: • The Committee considered the totality of the data submitted in support of the efficacy and safety of metoclopramide.
Danish: • udvalget vurderede samtlige forelagte data om virkningen og sikkerheden af metoclopramid,
English: This raises an issue of dose accuracy and reproducibility, particularly with high concentration formulations, and may explain at least partially the reason behind the reports of accidental overdose in the paediatric population.
Danish: Heraf fremgår, at doseringens nøjagtighed og reproducerbarhed er et problem navnlig ved formuleringer med høj koncentration og i det mindste delvis kan forklare indberetningerne om accidentel overdosering hos den pædiatriske population.
English: o Is not favourable for ‘gastrointestinal motility disorders, including gastroparesis'
Danish: o ikke er positivt til “forstyrrelser i den gastrointestinale motilitet, herunder gastroparese”
English: The doses, routes of administration and treatment durations of metoclopramide used in these studies are not always consistent, and only one specific dose-finding study was identified (in PONV).
Danish: Doser, administrationsveje og behandlingsvarigheder for metoclopramid i disse undersøgelser er ikke altid overensstemmende, og der blev kun fundet én særlig dosisfastsættelsesundersøgelse (ved postoperativ kvalme og opkastning).
English: For the indication adjuvant to surgical and radiological procedures, very limited efficacy data exists, and the existing data is not consistent.
Danish: For indikationen adjuvans til kirurgiske og radiologiske procedurer findes der kun meget begrænsede data om virkning, og de eksisterende data er ikke samstemmende.
English: While in some cases a high dose regimen (2-10mg/kg/day) is approved for prevention of acute RINV, studies have been conducted using 10 mg three times a day and the efficacy of this posology is not questioned.
Danish: Skønt der i nogle tilfælde er godkendt et højdosisregime (2-10 mg/kg/dag) til forebyggelse af akut stråleterapiinduceret kvalme og opkastning, er der også udført undersøgelser med en dosering på 10 mg tre gange dagligt, og virkningen af denne dosering bliver ikke betvivlet.
English: Both gastroesophageal reflux disease and dyspepsia may be chronic diseases, and therefore existing data cannot be considered sufficient to support the use in these indications.
Danish: Både gastroøsofagealt reflukssygdom og dyspepsi kan være kroniske sygdomme, hvorfor de eksisterende data ikke kan anses for fyldestgørende at underbygge anvendelsen ved disse indikationer.
English: Gastrointestinal motility disorders
Danish: Gastrointestinale motilitetsforstyrrelser
English: Grounds for the revocation / variation to the terms of the marketing authorisation
Danish: Begrundelse for inddragelse af markedsføringstilladelsen/ændring af betingelserne for markedsføringstilladelsen
English: The CHMP, having considered the data submitted, is of the opinion that in addition to product information amendments which include the use of the minimum effective dose and the limitation of treatment duration, the following risk minimisation activities are necessary for the safe and effective use of the medicinal product:
Danish: Efter gennemgang af de forelagte data finder CHMP, at der foruden ændringer af produktinformationen med henblik på anvendelse af mindste effektive dosis og begrænset behandlingsvarighed er behov for følgende tiltag for at sikre risikofri og effektiv anvendelse af lægemidlet:
English: As previously described, there is no evidence that doses above 10mg result in higher efficacy.
Danish: Som nævnt er der ingen evidens for, at doser over 10 mg resulterer i større virkning.