natgillin/translations-raw huggingface dataset:
Det gældende produktresumé, mærkning og indlægsseddel er de endelige versioner udarbejdet under den koordinerende gruppeprocedure. 
The valid summary of product characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure.
Bemærk: Produktresume, etikettering og indlægsseddel herunder er den gældende version på tidspunktet for Kommissionens beslutning. 
Note: This SPC, labelling and packages leaflet is the version valid at the time of Commission decision.
Doseringspumpe (PP/LDPE) 
Transdermal use metering pump (PP/LDPE);
doseringspumpe 
1 metering pump
Der er ingen klar sammenhæng mellem formuleringer og indikationer. 
There is no clear correlation between formulations and indications.
Retrieved from http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Paediatric_Regulation/Assessment_Reports/ Article_45_work-sharing/Metoclopramid_Art.45_PdAR_Update.pdf 
Retrieved from http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Paediatric_Regulation/Assessment_Reports/Articl e_45_work-sharing/Metoclopramid_Art.45_PdAR_Update.pdf
I dette tilfælde vil en dosisreduktion på 75 % være påkrævet. 
As such, a dose reduction of 75% would be necessary.
Orale flydende formuleringer 
Oral liquid formulations
Der findes ikke kliniske data, der giver mulighed for diskussion af dette punkt. 
There is no clinical data available to allow for a discussion on this point.
De franske kompetente myndigheder fandt det navnlig vigtigt, at de terapeutiske indikationer og sikkerhedsoplysninger blev bragt i indbyrdes overensstemmelse i alle medlemsstater. 
The French Competent Authority considered it particularly important that the therapeutic indications and safety information be made consistent across Member States.
Metoclopramid har været godkendt i EU siden 1960'erne og er omfattet af markedsføringstilladelser i alle medlemsstaterne foruden Norge og Island. 
Metoclopramide has been authorised in the European Union since the 1960's and marketing authorisations currently exist in all Member States as well as in Norway and Iceland.
Sikkerhedsdata 
Safety data
Til denne indikation og population anses det for særlig vigtigt at råde over orale formuleringer. 
For this indication and population, it is considered particularly important that oral formulations are available.
Desuden omfattede de eksisterende undersøgelser kun et meget lille antal patienter og en kort behandlingsperiode. 
Furthermore, existing studies included a very small number of patients and focused on a small duration of treatment.
For børn er der desuden indberettet et betydeligt antal tilfælde af overdosering. 
In children there is also a significant number of reported cases of overdose.
• udvalget fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF for lægemidler indeholdende metoclopramid, 
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for metoclopramide-containing medicinal products.
Denne dosering gælder alle orale formuleringer og er ikke afhængig af legemsvægt. 
This posology applies to all oral formulations and is not dependent on body weight.
Når en egnet doseringsanordning anvendes som anbefalet, er det ikke nødvendigt at tælle dråber. 
If an appropriate measuring device is used as recommended, there will be no need to count drops.
Også kombinationsprodukter er godkendt, men ved denne procedure omfatter vurderingen kun monokomponentprodukterne. 
Combination products are also approved, but this procedure focused on the assessment of the monocomponent products.
De godkendte indikationer for de berørte produkter er forskellige, man kan bredt inddeles således: 
The authorised indications for the concerned products are different but can broadly be grouped in the following way:
Udvalget konstaterede, at en formulering som suppositorier med styrken 20 mg er godkendt i visse medlemsstater. 
It was noted by the Committee that a formulation of suppositories dosed at 20mg is currently approved in some Member States.
• Kontraindikation hos nyfødte 
• Contraindication in neonates;
Samlet resumé af den videnskabelige vurdering af lægemidler med metoclopramid som eneste aktive indholdsstof (se bilag I) 
Overall summary of the scientific evaluation of metoclopramide-only containing medicinal products (see Annex I)
Til denne særlige indikation hos den pædiatriske population kan både de parenterale og orale lægemiddelformer være egnede. 
For this particular indication in the paediatric population, both the parenteral and the oral pharmaceutical forms may be appropriate.
Metoclopramid kan derfor anvendes under graviditet, hvis det er klinisk begrundet. 
Metoclopramide can therefore be used during pregnancy, if clinically justified.
• Begrænsning af den maksimale koncentration/dosering for visse formuleringer for at sikre, at patienterne ikke utilsigtet udsættes for højere doser end den anbefalede enkeltdosis af produktet. 
• Limiting the maximum concentration/dosing in certain formulations to ensure that patients are not unintentionally exposed to doses higher than the single recommended dose for the product.
Skønt den kliniske betydning heraf er usikker, bør patienterne overvåges for bivirkninger. 
Although the clinical significance is uncertain, patients should be monitored for adverse reactions.
Langsom intravenøs administration af dosis som en bolus i løbet af mindst 3 minutter mindsker risikoen for alle dystoniske reaktioner. 
The slow administration of intravenous doses as a slow bolus over at least 3 minutes lowers the risk of all dystonic reactions.
I dette scenarie, hvor utilsigtet fejlanvendelse allerede finder sted, vil tilføjelse af en kontraindikation i produktinformationen sammen med en anvisning i mærkningen næppe være tilstrækkelig til at ændre administrationsmønsteret. 
In this scenario where the unintended misuse is already taking place, to include a contraindication in the product information alongside a statement in the labelling is unlikely to be sufficient to change administration habits.
Derfor bør anvendelsen af metoclopramid forbeholdes situationer, hvor andre behandlinger ikke har været effektive eller ikke kan anvendes. 
Therefore use of metoclopramide should be reserved for situations where alternative treatments have not been effective or cannot be administered.
Ved svær leverfunktionsnedsættelse er den eksisterende anbefaling om 50 % dosisreduktion passende. 
For severe hepatic impairment, the existing recommendation for 50% dose reduction is appropriate.
For patienter med moderat til svær nyrefunktionsnedsættelse (ClCr 15-60 ml/min) vil en reduktion på 50 % dog fortsat være passende. 
However, for patients with moderate to severe impairment (ClCr 15-60 ml/min), a 50% reduction remains appropriate.
Risiko for nyfødte kan derfor ikke udelukkes, og metoclopramid bør undgås i den sidste del af graviditeten. 
Therefore the risk to newborns cannot be excluded and metoclopramide should be avoided at the end of pregnancy.
Dette var baseret på utilstrækkeligheden af evidensen for virkning hos børn til de berørte indikationer og sikkerhedsproblemet bestående i neurologiske symptomer. 
This was based on insufficient evidence of efficacy in children in the concerned indications and on the safety issue of neurological symptoms.
Adjuvans til kirurgiske og radiologiske procedurer 
Adjuvant to surgical and radiological procedures
Trods de indberettede alvorlige kardiovaskulære reaktioner med metoclopramid (hovedsagelig ved intravenøs administration) er der ikke er registreret nye signaler af betydning. 
Although serious cardiovascular reactions have been reported with metoclopramide (mainly associated to the intravenous administration), no new significant signals have been identified.
Bilag II Videnskabelige konklusioner og begrundelse for inddragelse af markedsføringstilladelserne/ændring af betingelserne for markedsføringstilladelserne 
Annex II Scientific conclusions and grounds for revocation / variation to the terms of the Marketing Authorisations
I sin udtalelse fra juli 2013 anbefalede CHMP for alle indikationer til voksne en enkeltdosis på 10 mg op til tre gange dagligt. 
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.
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. 
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.
CHMP godkendte en direkte meddelelse til sundhedspersoner (DHPC) med henblik på en hurtig formidling af resultatet af denne gennemgang. 
The CHMP endorsed a communication i.e. Dear Healthcare Professional Communication (DHPC), to rapidly communicate the outcome of the present review.
metoclopramid kan anvendes i kombination med orale analgetika for at forbedre absorptionen af analgetika ved akut migræne” (ved oral administration) 
Metoclopramide can be used in combination with oral analgesics to improve the absorption of analgesics in acute migraine' (oral route)
Næsten samtlige data vedrører intravenøs administration af metoclopramid, og i størstedelen af de vurderede undersøgelser blev der anvendt en dosis på 10 mg. 
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.
De forelagte data er begrænsede og blev genereret i forskellige scenarier, hvor der kan optræde kvalme og opkastning. 
The data presented is limited and was generated in different settings during which nausea and vomiting may occur.
Desuden kan metoclopramid på grund af sine prokinetiske egenskaber også spille en rolle, når det gives oralt i kombination med analgetika. 
In addition, due to its prokinetic properties, metoclopramide may also play a role when given orally in combination with analgesics.
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. 
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.
Derimod øges risikoen for alvorlige neurologiske bivirkninger. 
However, the risk of serious neurological adverse reactions is increased.
Det har parasympatomimetisk aktivitet og er desuden en dopaminreceptor- (D2-) antagonist med direkte virkning på kemoreceptorens aktiveringsområde. 
It possesses parasympathomimetic activity as well as being a dopamine-receptor (D2) antagonist with a direct effect on the chemoreceptor trigger zone.
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. 
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.
En oral bioækvivalensundersøgelse af metoclopramid-tabletter sammenlignet med væske viste, at Cmax og Tmax ikke afviger væsentligt mellem de to orale formuleringer. 
An oral bioequivalence study of metoclopramide tablets compared to liquid showed that Cmax and Tmax are not significantly different for the two oral formulations.
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. 
Following the adoption of the CHMP opinion in July 2013, a request for re-examination was received from one MAH concerned by the procedure.
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. 
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.
Metoclopramid er et substitueret benzamid, der anvendes på grund af sine prokinetiske og antiemetiske egenskaber. 
Metoclopramide is a substituted benzamide used for its prokinetic and antiemetic properties.
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. 
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.
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. 
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
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. 
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.
Risiciene øges ved anvendelse af høje doser eller ved langvarig behandling, og navnlig for ekstrapyramidale symptomer er risikoen for børn større end for voksne, 
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.
Ældre synes ved lang tids behandling at være særlig udsat for at udvikle tardiv dyskinesi, som i nogle tilfælde kan være irreversibel. 
The elderly appear to be at particular risk of developing tardive dyskinesia following long-term treatment, which in some cases may be irreversible.
Manifest nyresvigt er defineret som ClCr < 15 ml/min, hvorfor dette afskæringspunkt bør indgå i alle doseringsanbefalinger. 
Established renal failure is defined as ClCr < 15 ml/min, therefore this cut-off should be included in any dosing recommendations.
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. 
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.
En oversigtsartikel af Lee et al. giver en dækkende sammenfatning af evidensen for virkningen ved diabetisk gastroparese. 
The review by Lee et al. provides a complete overview of the evidence of efficacy in diabetic gastroparesis.
Det har derudover egenskaber som serotoninreceptor- (5-HT3-) antagonist. 
It also has serotonin-receptor (5-HT3) antagonist properties.
Suppositorier 
Suppositories
Udvalget fandt derfor, at den foreliggende evidens ikke støtter antagelsen om, at orale flydende formuleringer har hurtigere indsættende virkning end tabletter. 
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.
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. 
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.
Metoclopramid udskilles i modermælk, og skønt de foreliggende data ikke giver grund til betænkelighed, kan påvirkning af brystbarnet ikke udelukkes. 
Metoclopramide is excreted in breast milk, and although the available data does no raise concerns, effects in the breast fed infant cannot be excluded.
Benefit/risk-forhold 
Benefit-risk balance
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: 
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:
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. 
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.
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. 
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.
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. 
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.
Det dispenseres som en række forskellige lægemiddelformer (f.eks. tablet, depottablet, oral opløsning, suppositorium, injektionsvæske). 
It is available in a variety of pharmaceutical forms (e.g. tablet, prolonged-release tablet, oral solution, suppository, solution for injection).
• 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”, 
• 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'.
• udvalget tog i betragtning, at risikoen for alvorlige neurologiske bivirkninger kan minimeres ved at anvende lavere doser af metoclopramid og begrænse behandlingsvarigheden. 
• The Committee considered that the risk of serious neurological adverse events can be minimised by using lower doses of metoclopramide and limiting treatment duration.
Desuden tyder dataene på, at bivirkningsbelastningen øges med dosis. 
In addition, data is indicative that the burden of adverse reactions is increased with dose.
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. 
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.
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. 
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.
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. 
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.
Desuden kan virkningen være hurtigere indsættende med opløsningen end med tabletterne, da tabletterne først skal opløses i mavetarmkanalen. 
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.
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. 
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.
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. 
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.
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. 
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.