natgillin/translations-raw huggingface dataset:
CHMP var på tidspunktet for tilbagetrækningen derfor af den opfattelse, at resultaterne af studiet ikke ansås for pålidelige, og konkluderede, at lægemidlet ikke kunne være blevet godkendt på baggrund af de oplysninger, som virksomheden havde fremlagt.
Therefore, at the time of the withdrawal, the CHMP was of the opinion that the results of the study were not considered to be reliable and the Committee concluded that the change to the use of the medicine could not have been approved based on the data presented by the company.
I sit brev til agenturet om tilbagekaldelse af ansøgningen anførte virksomheden, at tilbagetrækningen bygger på CHMP's udtalelse om, at de forelagte data ikke giver udvalget mulighed for at godkende anvendelse ved myelodysplastisk syndrom.
In its letter notifying the Agency of the withdrawal of application, the company stated that the withdrawal is based on the CHMP's opinion that the data provided do not allow the Committee to authorise use in myelodysplastic syndromes.
På baggrund af gennemgangen af de data, der forelå på tilbagetrækningstidspunktet, havde CHMP visse betænkeligheder og var af den foreløbige opfattelse, at Aranesp ikke kunne være blevet godkendt til behandling af anæmi hos voksne patienter med myelodysplastisk syndrom.
Based on the review of the data, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Aranesp could not have been approved for the treatment of anaemia in adult patients with myelodysplastic syndromes.
Hvad sker der med Aranesp til de godkendte indikationer?
What is happening with Aranesp in its authorised uses?
Da Aranesp virker på samme måde som erythropoietin, stimulerer det kroppen til at danne flere røde blodlegemer, hvorved det modvirker anæmi.
By acting in the same way as erythropoietin, Aranesp stimulates the body to make more red blood cells and so treats anaemia.
Darbepoetin alfa, det aktive stof i Aranesp, virker fuldstændig som det naturlige hormon erythropoietin, der produceres af nyrerne for at stimulere dannelsen af røde blodceller, men dets struktur er en anelse anderledes.
Aranesp, acts exactly like a natural hormone called erythropoietin that is made by the kidneys to stimulate red blood cell production, but it is very slightly different in its structure.
Hvordan virker Aranesp?
How does Aranesp work?
Aranesp forventedes desuden anvendt til behandling af anæmi hos patienter med knoglemarvssygdomme af typen myelodysplastisk syndrom.
Aranesp was also expected to be used to treat anaemia in patients with myelodysplastic syndromes, a group of bone marrow disorders.
officielt Udvalget for Lægemidler til Mennesker (CHMP), at virksomheden ønsker at trække sin ansøgning tilbage om at tilføje anvendelse til behandling af anæmi hos voksne patienter med myelodysplastisk syndrom til den eksisterende markedsføringstilladelse.
On 21 February 2018, Amgen Europe B.V. officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wished to withdraw its application to add treatment of anaemia in adult patients with myelodysplastic syndromes to the existing marketing authorisation.
Tidsplanen for gennemførelse af aftalen er angivet i bilag IV.
The timetable for the implementation of the agreement is set out in Annex IV.
En gennemgang viste, at fire af disse tilfælde fik fatalt udfald.
A review of these cases indicated that, four cases had a fatal outcome.
De resterende var alle livstruende, men endte med fuld restitution.
The remaining cases were all life-threatening but resulted in full recovery.
Dette er derfor fortsat en varierende sikkerhedsrisiko i alle pædiatriske aldersgrupper.
Therefore, this continues to represent a variable safety risk across all paediatric age groups.
Børnene var i alderen 17 dage til 6 år.
The children's age ranged from 17 days to 6 years.
Symptomerne på morfintoksicitet kan forstærkes under disse omstændigheder.
The symptoms of morphine toxicity may be increased in these settings.
I denne kliniske sammenhæng kan kodein ikke forventes at tilføre nævneværdig fordel, hvorimod de konstaterede risici kan have alvorlige konsekvenser.
In such clinical settings it is not expected that codeine use brings any significant benefit, while the risks identified can be of serious consequences.
Størstedelen (38/50) af tilfældene vedrørte børn under 12 år, og der var 6 fatale tilfælde.
Overall, the majority (38/50) of the cases were in patients younger than 12 years of age and 6 were fatal cases.
Kodein omdannes i kroppen til morfin af cytokrom P450 2D6 (CYP2D6), et enzym, der udviser genetisk polymorfi.
Codeine is converted into morphine in the body by cytochrome P450 2D6 (CYP2D6), an enzyme which shows genetic polymorphism.
Sædvanligvis inddeles personer i dårlige (PM), ekstensive (EM) og ultrahurtige metabolisatorer (UM), afhængigt af enzymaktiviteten.
Individuals are normally classified as poor (PM), extensive (EM) or ultrarapid metabolisers (UM), depending on the activity of the enzyme.
Hoste er en refleksreaktion på mekanisk, kemisk eller inflammatorisk irritation af det trakeobronkiale træ.
Cough is a reflex response to mechanical, chemical, or inflammatory irritation of the tracheobronchial tree.
Risikoen for opioidtoksicitet er særlig udtalt hos ultrahurtige metabolisatorer pga. de alvorlige følger af respirationsdepression.
The risk of opioid toxicity is especially pronounced among UMs due to its serious consequences of respiratory depression.
PRAC gennemgik desuden data fra den europæiske lægemiddelovervågningsdatabase (Eudravigilance) og en undersøgelse af ordinationsmønstrene for kodein, og rådførte sig med faglige organisationer i sundhedssektoren og med det pædiatriske udvalg (PDCO).
The PRAC also considered data from the European Pharmacovigilance database (Eudravigilance), a drug utilisation study of the patterns of prescription of codeine and performed a consultation with European healthcare professional organisations and with the Paediatric Committee (PDCO).
I Eudravigilance-databasen fandtes der i alt 50 case-rapporter, som kunne sættes i forbindelse med opiattoksicitet, hvoraf 31 vedrørte børn under 6 år (herunder 4 fatale tilfælde), og 7 tilfælde vedrørte børn over 6, men under 12 år (herunder 1 fatalt tilfælde), mens de tilbageværende 12 tilfælde vedrørte børn over 12, men under 18 år (herunder 1 fatalt tilfælde).
Data analyses from the Eudravigilance database identified a total of 50 case reports that could be related to opiate toxicity, of which 31 cases were in those younger than 6 years (including 4 fatal cases), 7 cases in older than 6 years and younger than 12 years (including 1 fatal case) and the remaining 12 cases were on those older than 12 and younger than 18 years (including 1 fatal case).
Markedsføringstilladelsesindehaverne for orale kodeinholdige lægemidler bør derfor drøfte med medlemsstaternes nationale kompetente myndigheder, om denne minimeringsforanstaltning kan anvendes i den pågældende stat.
Therefore, the marketing authorisation holders of codeine containing medicinal products in oral formulations should discuss with the National Competent Authorities in the Member States the applicability of this minimisation measure in their territory.
Heri indgik besvarelserne fra markedsføringstilladelsesindehaverne, litteraturdata, der var blevet tilgængelige siden udstedelsen af de oprindelige markedsføringstilladelser, og rådgivning fra sundhedspersoner og andre eksperter,
This included MAH responses, published literature data which became available since the initial granting of the marketing authorisations and consultation of healthcare professionals and other experts.
PRAC tog i betragtning, at de enzymatiske systemer, der metaboliserer kodein, hos børn over 12 år kan betragtes som sammenlignelige med voksnes.
The PRAC took into account that the enzymatic systems responsible for the metabolism of codeine in children older than 12 years of age can be considered comparable to that of adults.
Den overvejende del af luftvejsinfektioner hos børn med hoste skyldes virusinfektioner, som er selvbegrænsende og kun varer få dage, mens behandlingen ved kronisk hoste bør rettes mod den underliggende sygdom2,3 (American Academy of Paediatrics Committee on Drugs 1997, American Academy of Paediatrics, AAP publications retired or reaffirmed 2006).
The large majority of childhood respiratory infections with cough are caused by viral infections, which are self-limiting and only last for a few days whereas in the case of chronic cough, treatment should be directed at the underlying disease2,3 (American Academy of Paediatrics Committee on Drugs 1997, American Academy of Paediatrics, AAP publications retired or reaffirmed 2006).
I tilslutning til PRAC's anbefaling om ændring af markedsføringstilladelserne vedtog CMDh derfor, at hvis en markedsføringstilladelse ikke kan ændres i overensstemmelse med betingelserne i CMDhaftalen, kan medlemsstaterne overveje at inddrage markedsføringstilladelsen.
Therefore, in addition to the PRAC recommendation to vary the marketing authorisations, the CMDh also agreed that if a marketing authorisation cannot be varied in line with the terms of the CMDh agreement, member states may consider the revocation of that marketing authorisation.
Nærværende indbringelse i henhold til artikel 31 i direktiv 2001/83/EF vedrørende anvendelse af kodein til behandling af hoste og/eller forkølelse hos børn blev indledt den 2. april 2014 af den tyske kompetente myndighed (BfArM) i konsekvens af, at ovennævnte risikominimeringsforanstaltninger også bør kunne anvendes ved disse indikationer.
The present referral under Article 31 of Directive 2001/83/EC concerns the use of codeine in paediatric patients for the cough and/or cold indications as triggered on 02 April 2014 by the German National Competent Authority (BfArM) due to the applicability of the above risk measures also to these indications.
En gennemgang af alvorlige og fatale tilfælde hos børn baseret på oplysninger fra litteraturen, globale lægemiddelovervågningsdatabaser og regulerende myndigheder tyder på, at kodeins respirationsdeprimerende virkning kan have betydning for forekomsten af respirationskomplikationer.
A review of serious and fatal cases in paediatric patients from the literature, global pharmacovigilance databases and regulatory authorities suggests that the respiratory depressant effects of codeine may influence the occurrence of respiratory complications.
Overalt hvor kodein omtales i disse punkter i et produktresumé for en kombination af kodein og andre aktive stoffer, ændres ordlyden derfor, således at produktets særnavn anvendes i stedet for INN-navnet “kodein”.
Therefore, whenever reference to codeine is made in these SmPC sections and the product is a combination of codeine and other active substances, the wording is amended to include the invented name of these products instead of the INN “codeine”.
PRAC gennemgik alle foreliggende data fra forskellige kilder: kliniske undersøgelser, observationsundersøgelser, metaanalyser, data efter markedsføring og yderligere litteraturdata om brug af kodeinholdige produkter hos børn til behandling af hoste og/eller forkølelse.
The PRAC reviewed all available data from different sources: clinical trials, observational studies, metaanalyses, post-marketing data and further published literature data on the use of codeine containing products in children for treatment of cough and/or cold.
Kodein, der også kaldes methylmorphin, bindes til μ-opioidreceptorerne og bevirker analgesi og eufori samt respirationsdepression, miosis og nedsat gastrisk motilitet.
Codeine, also known as methylmorphine, binds to µ-opioid receptors to produce analgesia and euphoria, as well as respiratory depression, miosis, and reduced gastric motility.
Den uforudsigelige og varierende metabolisering af kodein hos børn som følge af polymorfi af CYP2D6 kan hos nogle børn medføre alvorlige morfinrelaterede bivirkninger såsom vejrtrækningsbesvær eller respirationsdepression, også inden for de anbefalede doser.
The unpredictable and variable metabolism of codeine in children, governed by CYP2D6 polymorphism, may cause some children to exhibit morphine-related serious adverse events such as breathing difficulties or respiratory depression even within the recommended doses.
• PRAC tog stilling til den procedure, der i medfør af artikel 31 i direktiv 2001/83/EF var foranlediget af lægemiddelovervågningsdata for kodeinholdige lægemidler til behandling af hoste og/eller forkølelse hos børn,
• The PRAC considered the procedure under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data for codeine containing medicinal products for the treatment of cough and/or cold in children.
Der blev i alt kun fundet fire publicerede undersøgelser af brugen af kodeinholdige lægemidler til behandling af hoste hos børn.
Overall, only four published studies investigating the use of codeine-containing medicines for the treatment of cough in children could be identified.
PRAC bemærkede desuden, at øvre luftvejsinfektioner er den dominerende årsag til hoste hos børn.
The PRAC also noted that cough associated with upper respiratory tract infections is the dominating cause of cough in children.
En randomiseret klinisk undersøgelse (Jaffe G et al, 1983) og en epidemiologisk undersøgelse (De Blasio F et al, 2012) viste ingen nævneværdig virkning af kodein på hoste og/eller forkølelse hos børn.
A randomised clinical trial (Jaffe G et al, 1983) and an epidemiological study (De Blasio F et al, 2012) did not show a significant effect of the treatment with codeine in cough and/or cold in children.
I 2012 indgik undersøgelsen af Taylor et al i en Cochrane-gennemgang af håndkøbsmedicin mod akut hoste hos børn og voksne i ambulant regi; ved denne gennemgang blev der fundet yderligere to randomiserede, kontrollerede undersøgelser, hvor kodein var testet hos voksne (Eccles et al, 1992; Freestone C, 1997): Kodein fandtes ikke at være mere effektivt end placebo.
In 2012, the Taylor et al study was included in a Cochrane review of non-prescription/over-the-counter (OTC) medications for acute cough in children and adults in ambulatory settings; this review additionally identified two randomised controlled trials where codeine was tested in adults (Eccles et al, 1992; Freestone C, 1997): codeine was found to be no more effective than placebo.
Dataene vedrørende virkningen er derfor begrænsede, og der er ikke nyere veldokumenterede, kontrollerede videnskabelige undersøgelser, som viser klar fordel af kodein til de godkendte indikationer hoste og/eller forkølelse hos børn.
Efficacy data is therefore limited, with no recent and well-established controlled scientific studies to clearly support the benefit of codeine in the approved indications for cough and/or cold for the paediatric population.
Desuden anbefalede PRAC, at de relevante risikominimeringsforanstaltninger fra den tidligere indbringelse ligeledes burde gælde anvendelse af kodein til symptomatisk behandling af hoste og/eller forkølelse.
In addition, the PRAC also recommended that the relevant risk minimisation measures from the previous referral should also apply to the use of codeine in the symptomatic treatment of cough and/or cold.
Kodein undertrykker hosterefleksen gennem direkte påvirkning af hostecentret i hjernestammen.
Codeine suppresses the cough reflex through a direct effect on the cough centre in the medulla.
To af undersøgelserne (Kelly et al, 1963 og Jaffe et al, 1983), hvor der ikke var nogen placebokontrolgruppe, viste, at kodein ikke havde større virkning end andre antitussive midler, men at forekomsten af bivirkninger i kodeingruppen var højere end i gruppen med sammenligningspræparatet.
Two studies (Kelly et al, 1963 and Jaffe et al, 1983), which did not include a placebo control group, suggested that efficacy was no greater for codeine than the other antitussives but that the incidence of side effects in the codeine group was higher than in the comparator group.
Behandlingsretningslinjerne anbefaler, at behandlingen af persisterende kronisk hoste hos børn baseres på ætiologien,
Treatment guidelines recommend treatment of persistent chronic cough in paediatric patients based on aetiology.
PRAC foreslår derfor, at de nationale kompetente myndigheder i EU's medlemsstater træffer de indvendige foranstaltninger til, at kodeinprodukter, der kun er godkendt til anvendelse hos voksne, føres ajour med disse kontraindikationer.
Therefore, the PRAC suggests that National Competent Authorities of the EU Members States to take the necessary actions to have the labelling of codeine products approved only for adults updated with the contraindications.
I fortsættelse af gennemgangen af de på daværende tidspunkt foreliggende data konkluderede PRAC, at kodein fortsat var et effektivt analgetikum hos børn over 12 år ved akutte, moderate smerter, der ikke kunne afhjælpes med andre analgetika.
Further to consideration of all data available at that time, the PRAC concluded that codeine remained an effective analgesic for the treatment of acute moderate pain in children above 12 years of age which is not considered to be relieved by other analgesics.
Hostens fysiologiske funktion er at befri luftvejene for obstruktivt eller irriterende materiale og advare om giftige stoffer i den indåndede luft.
Cough serves as a physiologic function to clear airways of obstructive or irritating material or to warn of noxious substances in inspired air.
• PRAC fandt, at der kun er begrænset evidens for virkningen af kodein ved hoste og forkølelse, og at disse sygdomme sædvanligvis er selvbegrænsende.
• The PRAC considered that there is limited evidence that support the efficacy of codeine in cough and cold and that these are generally self-limiting conditions.
I overensstemmelse med anbefalingen fra PRAC bemærkede CMDh desuden, at kontraindikationen for kvinder uanset alder, som ammer, ligeledes skal gælde alle kodeinholdige produkter, der er godkendt til voksne, uanset indikation.
Moreover, the CMDh noted as advised by the PRAC that the contraindication in women of all ages who are breastfeeding should also apply to all codeine containing products approved for adults and regardless of the indication.
Kodein var i 2013 genstand for en artikel 31-indbringelse for PRAC1 vedrørende analgetisk anvendelse hos den pædiatriske population (herefter omtalt som “børn”), idet der var rejst betænkeligheder vedrørende opioidtoksicitet og manglende konsekvente risikominimeringsforanstaltninger efter litteraturbeskrivelser af tilfælde af fatal eller livstruende respirationsdepression ved brug af kodein hos børn efter adenodektomi/tonsillektomi til behandling af obstruktiv søvnapnø.
Codeine was subject of an Article 31 referral to the PRAC in 20131, when used for pain relief in the paediatric population (hereafter refer as “children”) due to concerns regarding opioid toxicity and the lack of consistent risk minimisation measures raised following cases described in the literature of fatal or life-threatening respiratory depression, when codeine was given to children after adenoidectomy/tonsillectomy for obstructive sleep apnoea.
CMDh fandt desuden, at risikoen for accidentel overdosering (fire tilfælde konstateret) kunne minimeres gennem børnesikret emballage til alle flydende orale kodeinholdige lægemidler.
The CMDh also considered that the risk of accidental overdose (four cases identified) could be minimised by the use of child resistant containers (CRC) for all oral liquid codeine containing medicinal products.
Videnskabelige konklusioner og begrundelse for ændringen af betingelserne for markedsføringstilladelserne
Overall conclusion and grounds for the variation to the terms of the marketing authorisations Whereas
Foruden som analgetikum anvendes det til symptomatisk behandling af hoste og/eller forkølelse.
Apart from its use as an analgesic for relief of pain, it is also used for the symptomatic treatment of cough and/or cold.
PRAC fandt, at børn under 12 år er særligt udsat for livstruende respirationsdepression, og gjorde derfor anvendelse af kodein kontraindiceret hos børn under 12 år.
The PRAC considered that children below 12 years are at special risk of life-threatening respiratory depression and therefore, contraindicated the use of codeine in children below 12 years.
På baggrund af alt det ovennævnte konkluderede PRAC, at benefit/risk-forholdet for kodeinholdige produkter fortsat er positivt til hoste og/eller forkølelse hos børn under forudsætning af de vedtagne begrænsninger, kontraindikationer, advarsler og andre ændringer i produktinformationen, som fremgår af bilag III til udtalelsen.
Having noted all of the above, the PRAC concluded that the benefit-risk balance of codeine-containing products indicated in cough and/or cold in children remains favourable, subject to the agreed restrictions, contraindications, warnings and other changes to the product information as set out in Annex III to the opinion.
1 Artikel 31-indbringelse vedrørende lægemiddelovervågning for kodein til analgetisk behandling af børn (EMA/H/A31/1342) http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Codeinecontaining_medicines/human_referral_prac_000008.jsp&mid=WC0b01ac05805c516f
1 Article 31 pharmacovigilance referral for codeine used for management of pain in paediatric patients (EMA/H/A-31/1342) http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Codeinecontaining_medicines/human_referral_prac_000008.jsp&mid=WC0b01ac05805c516f symptomatic treatment of cough and/or cold as current evidence does not find codeine to be more effective than placebo for acute cough in children.
Gennemgangen omfatter alle kodeinholdige lægemidler, der er godkendt til behandling af hoste og eller forkølelse hos børn, herunder monokomponent- og kombinationsprodukter godkendt i EU.
All codeine containing medicinal products approved for the treatment of cough and/or cold in paediatric population, including single and combination products authorised in the European Union are included in this review.
• PRAC fandt desuden, at den nuværende evidens viser, at børn under 12 år er særligt udsat for livstruende respirationsdepression, og konkluderede derfor, at kodeinholdige lægemidler til behandling af hoste og/eller forkølelse er kontraindiceret hos børn under 12 år.
• In addition, the PRAC considered that the current evidence suggests that children below 12 years are at special risk of life-threatening respiratory depression and therefore, concluded that the use of codeine containing medicinal products for the treatment of cough and/or cold is contraindicated in children below 12 years.
• PRAC gennemgik de foreliggende data om sikkerheden og virkningen af kodeinholdige lægemidler til behandling af hoste og/eller forkølelse hos børn vedrørende risikoen for opioidtoksicitet.
• The PRAC considered available data on the safety and the efficacy of the codeine containing medicinal products for the treatment of cough and/or cold in children in relation to the risk of opioid toxicity.
Hertil hører kontraindikation hos patienter, der uanset alder vides at være ultrahurtige CYP2D6-metabolisatorer, og hos kvinder uanset alder, som ammer.
This included contraindication in patients of any age known to be CYP2D6 ultra-rapid metabolisers and in women of all ages who are breastfeeding.
PRAC fandt derudover, at analgetisk anvendelse af kodein kunne være forbundet med opioidtoksiske hændelser som følge af den variable og uforudsigelige metabolisering af kodein til morfin, navnlig hos børn under 12 år, og at kodein derfor ikke burde anvendes hos denne patientgruppe.
The PRAC also considered that the use of codeine in pain relief could be associated with serious adverse events of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine, in particular in the paediatric population below 12 years of age and therefore codeine should not be used in this population.