FrancophonIA/ELRC3.0 huggingface dataset:
English: The use of effective contraception without interruption during the all course of treatment should be included as well as a reminder for annual re-assessment.
Danish: Brugen af sikker prævention uden afbrydelse under hele behandlingen bør også nævnes, ligesom der bør være en påmindelse om årlig revurdering.
English: The potential impact of paternal use of valproate, the potential effect on the third generation offspring and the potential effects on mitochondria (mitochondrial toxicity) were discussed.
Danish: Den mulige indvirkning af paternel brug af valproat, den mulige indvirkning på tredjegenerationsefterkommere og den mulige indvirkning på mitokondrier (mitokondriel toksicitet) blev drøftet.
English: In addition, the PRAC considered the views of patient organisations, patients, families and carers, and the views of healthcare professionals in a public hearing and dedicated meeting.
Danish: Derudover vurderede PRAC de synspunkter, som patientorganisationer, patienter, pårørende og omsorgspersoner samt sundhedspersoner havde givet udtryk for i en offentlig høring og på et særligt møde.
English: The epigenetic mechanism refers to the possibility that changes in the gene expression in the gametes are transmitted to the gene expression in the embryo (for example by changes in DNA methylation).
Danish: Den epigenetiske mekanisme henviser til muligheden for, at forandringer i genekspressionen i gameterne overføres til genekspressionen i embryoet (f.eks. gennem forandringer i dna-metylering).
English: The PRAC therefore recommends that other tests could be performed (e.g. in vitro mouse lymphoma assay) to further explore this hypothesis.
Danish: PRAC anbefaler derfor, at der gennemføres andre test (f.eks. in vitro-muselymfomtest) for at undersøge denne hypotese yderligere.
English: Every effort should be made to switch to appropriate alternative treatment prior to conception, and before contraception is discontinued.
Danish: Det bør så vidt muligt tilstræbes at skifte til en relevant alternativ behandling før undfangelse og før ophør af brug af prævention.
English: As the injectable formulations are indicated only for short use, the patient card is most likely to be of limited value.
Danish: Da de injicérbare formuleringer kun er indiceret til kortvarig brug, vil patientkortet formentlig være af begrænset værdi.
English: In addition to the measures to increase awareness about risks of valproate, the different expert consultations provided clear recommendations to restrict the use of valproate.
Danish: I tillæg til de tiltag, der var beregnet på at øge bevidstheden om risiciene ved valproat, fremsatte de forskellige eksperter klare anbefalinger om at begrænse brugen af stoffet.
English: Core elements of a direct healthcare professional communication were agreed, together with the timelines for its distribution.
Danish: Hovedelementerne i et direkte brev til sundhedspersoner blev vedtaget tillige med en tidsplan for udsendelsen heraf.
English: Consequently, the annual risk acknowledgment form is not required for the injectable formulations.
Danish: Den årlige risikoerklæringsblanket er derfor ikke påkrævet for injicérbare formuleringer.
English: • The PRAC concluded that the risk minimisation measures in place have not been sufficiently effective to prevent unintended in utero exposure to valproate and related substances in all indications.
Danish: • PRAC konkluderede, at de iværksatte risikominimerende foranstaltninger ikke har været tilstrækkeligt effektive til at forebygge utilsigtet in utero-eksponering for valproat og relaterede stoffer i alle indikationer.
English: In the course of the consultations that PRAC had in this procedure, some additional concerns have arisen, other than the well-known and documented harm to the foetus during in utero exposure.
Danish: I løbet af de høringer, som PRAC har haft i denne procedure, er der fremkommet yderligere betænkeligheder i tillæg til den velkendte og dokumenterede skade på fostre ved in utero-eksponering.
English: Regarding exposure via seminal fluid, estimation was made of the area under curve (AUC) for valproate in a woman following vaginal exposure to valproate via seminal fluid of a man treated with valproate.
Danish: Hvad angår eksponering via sædvæske, foretog man et skøn af arealet under kurven (AUC) for valproat hos en kvinde efter vaginal eksponering for valproat via sædvæske fra en mand, der blev behandlet med valproat.
English: • For their use in pregnancy for the treatment of epilepsy, the PRAC concluded that these medicinal products are contraindicated unless there is no suitable alternative treatment option.
Danish: • For så vidt angår brugen af disse lægemidler under graviditet til behandling af epilepsi, konkluderede PRAC, at de er kontraindicerede, medmindre der ikke findes nogen egnet alternativ behandling.
English: The MAHs are strongly encouraged to collaborate on the requested measures and to perform joint studies.
Danish: Indehaverne af markedsføringstilladelse opfordres til at samarbejde om de krævede foranstaltninger og gennemføre fælles studier.
English: The guide should explain the pregnancy prevention programme and the conditions to be met prior to starting treatment with valproate.
Danish: Vejledningen bør forklare graviditetsforebyggelsesprogrammet og de betingelser, der skal opfyldes før iværksættelse af behandling med valproat.
English: • The Pharmacovigilance Risk Assessment Committee (PRAC) considered the procedure under Article 31 of Directive 2001/83/EC for medicinal products containing substances related to valproate.
Danish: • Udvalget for Risikovurdering inden for Lægemiddelovervågning (PRAC) gennemførte proceduren vedrørende lægemidler indeholdende stoffer, der er relateret til valproat, i henhold til artikel 31 i direktiv 2001/83/EF.
English: The MAHs are encouraged to collaborate and liaise with the national competent authorities to facilitate the dissemination of the agreed educational material.
Danish: Indehaverne af markedsføringstilladelse opfordres til at samarbejde og tage kontakt til de nationalt kompetente myndigheder med henblik på at fremme udbredelsen af det aftalte informationsmateriale.
English: It was shown in a transgenerational experiment in mice that administration of valproate during pregnancy (day 10) produced autism-like symptoms and increased expression of several proteins in the brains up to the third generation offspring.
Danish: Det blev i et transgenerationelt forsøg hos mus påvist, at administration af valproat under drægtighed (dag 10) medførte autisme-lignende symptomer og øget ekspression af adskillige proteiner i hjernen op til tredjegenerationsafkommet.
English: Information on the patient card should be brief and concise regarding the efficacy of the product but also the harm to an unborn child when taken during pregnancy.
Danish: Oplysningerne på patientkortet skal være kortfattede og præcise vedrørende virkningen af lægemidlet, men også om skaden på et ufødt barn, hvis det tages under graviditet.
English: In one experiment it was shown that a change in gene expression (one gene) in male mice after exposure to a histone deacetylases (HDAC) inhibitor (not valproate) was observed also in the offspring of these mice (Jia et al, 2015)1, so possible in principle.
Danish: I et forsøg blev det påvist, at en forandring i genekspressionen (ét gen) hos hanmus efter eksponering for en histondeacetylase-hæmmer (ikke valproat) også kunne ses hos afkommet af disse mus (Jia et al, 2015)1, så det er i princippet muligt.
English: To obtain additional robust information on the switch and discontinuation of valproate, the PRAC requested the conduct of an observational study to identify and evaluate the best practices for switching of valproate in clinical practice.
Danish: Med henblik på at indhente yderligere solide oplysninger om skift fra og seponering af valproat anmodede PRAC om gennemførelse af et observationsstudie for at identificere og evaluere bedste praksis for skift fra valproat i klinisk praksis.
English: Nevertheless, as shown in the data reviewed in this procedure educational measures did not reach the targeted audience in a satisfactory rate in order to have any significant impact on prescriptions.
Danish: Ikke desto mindre viser oplysningerne fra den nye gennemgang af data i denne procedure, at informationstiltagene ikke nåede målgruppen i tilstrækkelig grad til at have en betydelig indvirkning på ordinationerne.
English: The information through the DHPC about risks and the new contraindications and other risk minimization measures is applicable to all formulations.
Danish: Oplysningerne i det direkte brev om risiciene, de nye kontraindikationer og øvrige risikominimerende foranstaltninger gælder for alle formuleringer.
English: For the female patients, there may be situations in which valproate treatment is initiated with the IV formulation (before discharge on valproate oral administration).
Danish: Hvad angår kvindelige patienter, kan der være tilfælde, hvor valproat-behandlingen påbegyndes med den intravenøse formulering (før udskrivning med oral administration af valproat).
English: Genetic changes can be divided in gene mutations and chromosome aberrations.
Danish: Genetiske forandringer kan opdeles i genmutationer og kromosomafvigelser.
English: It is unknown whether slight chromosome damage might be transmitted to the offspring.
Danish: Det vides ikke, om små kromosomskader kan blive overført til afkommet.
English: The PRAC also reviewed the annual risk acknowledgement form which should be used and documented at initiation and during each annual review of valproate treatment by a specialist.
Danish: PRAC gennemgik også den årlige risikoerklæringsblanket, der bør anvendes og dokumenteres ved behandlingsstart og ved hver årlige gennemgang af valproat-behandlingen hos speciallægen.
English: The PRAC taking into account all the evidence as well the areas where information is limited requested several measures in order to further characterise the risks, increase the awareness of the risks, restrict the use and measure the effectiveness of the currently proposed measures.
Danish: Under hensyn til al evidens samt de områder, hvor der er begrænsede oplysninger, opfordrede PRAC til iværksættelse af adskillige tiltag med henblik på at undersøge risiciene, øge bevidstheden om risiciene, begrænse brugen og måle virkningen af de aktuelt foreslåede tiltag.
English: It seems theoretically possible that gene mutations in sperm cells could be transmitted to the offspring.
Danish: Det synes teoretisk muligt, at genmutationer i sædceller kan overføres til afkommet.
English: Therefore, it is considered that the patient card is not required for injectable formulations products containing valproate and related substances.
Danish: Det vurderes derfor, at patientkortet ikke er nødvendigt for injicérbare formuleringer af lægemidler indeholdende valproat og relaterede stoffer.
English: If switching is not possible, the woman should receive further counselling regarding the valproate risks for the unborn child to support her informed decision making regarding family planning.
Danish: Hvis det ikke er muligt at skifte, bør kvinden rådgives yderligere vedrørende risiciene for det udfødte barn ved fortsat brug af valproat med henblik på at understøtte hendes informerede beslutningstagning i forhold til familieplanlægning.
English: PRAC also recommended postauthorisation studies to assess the effectiveness of the risk minimisation measures.
Danish: PRAC anbefalede også iværksættelse af studier efter markedsføring for at vurdere virkningen af de risikominimerende foranstaltninger.
English: Further, an observational study to evaluate and identify the best practice for discontinuation and switching of valproate treatment will be conducted.
Danish: Der vil desuden blive gennemført et observationsstudie for at evaluere og identificere bedste praksis for seponering og skift fra valproatbehandling.
English: In view of the safety issues in discussion and the whole set of conditions for the risk minimisation aiming at minimising exposure in pregnancy, all MAHs need to have in place a risk management plan.
Danish: I betragtning af de sikkerhedsmæssige betænkeligheder og rækken af betingelser for risikominimering, der skal reducere eksponering under graviditet, skal alle indehavere af markedsføringstilladelse iværksætte en risikostyringsplan.
English: A pregnancy prevention programme will be implemented accordingly to prevent valproate exposure during pregnancy given that significant risk of lifelong harm is associated with its use.
Danish: Et graviditetsforebyggelsesprogram vil blive gennemført for at forebygge eksponering for valproat under graviditet, eftersom brugen af lægemidlet er forbundet med betydelig risiko for livsvarig skade.
English: Furthermore, in a literature overview regarding effects on mitochondria, known side effects were described such as liver toxicity, Reye-like syndrome, pancreatitis and immune deficiency (leukopenia).
Danish: I en gennemgang af litteratur vedrørende påvirkning af mitokondrierne blev kendte bivirkninger som levertoksicitet, Reye-lignende symptomer, pankreatitis og nedsat immunforsvar (leukopeni) beskrevet.
English: A wide consultation was done on the request of PRAC to gather all the latest information in terms of scientific and clinical knowledge with the consultation of two scientific groups (neurology and psychiatry), and to collect information from healthcare professionals, female patients themselves as well their families, from patient organisations (public hearing, stake holders meeting) who are advocating to better characterise and increase the awareness on the risk of harm to the foetus when using valproate during pregnancy.
Danish: På PRAC's anmodning blev der gennemført en bred høring for at samle alle de nyeste oplysninger med hensyn til videnskabelig og klinisk viden med deltagelse af to videnskabelige grupper (neurologi og psykiatri) og for at indsamle oplysninger fra sundhedspersoner, de kvindelige patienter og deres familier samt patientorganisationer (offentlig høring, møde med interessenter), som ønsker en bedre karakterisering af og øget bevidsthed om risikoen for skade på fosteret ved brug af valproat under graviditet.
English: With regards to the other pharmacovigilance activities and the studies are required to further investigate potential risks with products containing valproate and related substances and to measure the effectiveness of the RMMs, the CMDh clarified that these studies would not be relevant for the injectable products as the information that could be collected for these products would be limited and unlikely to be meaningful in view of the short duration of use, often in urgent situations and only when the oral formulations cannot be administered.
Danish: Hvad angår de andre lægemiddelovervågningsaktiviteter og de studier, der er nødvendige for nærmere at undersøge de mulige risici ved lægemidler, der indeholder valproat og relaterede stoffer, og for at måle virkningen af de risikominimerende foranstaltninger, præciserede CMDh, at disse studier ikke ville være relevante for de injicérbare lægemidler, da de oplysninger, der kan indsamles for disse produkter, ville være begrænsede og formentlig ikke være meningsfulde i lyset af den kortvarige brug (ofte i akutte situationer og kun, når orale formuleringer ikke kan administreres).
English: The PRAC recommended that a patient card to be made available in all MSs and for all patients who receive valproate.
Danish: PRAC anbefalede, at der i alle medlemsstater udleveres et patientkort til alle patienter, der behandles med valproat.
English: • In addition, the PRAC recommended other changes to the product information such as warnings and precautions for use and updated information on the risks related to exposure during pregnancy to better inform the healthcare professionals and patients.
Danish: • PRAC anbefalede derudover en række andre ændringer af produktinformationen som f.eks. advarsler og forsigtighedsregler og opdaterede oplysninger om risiciene ved eksponering under graviditet med henblik på at informere sundhedspersoner og patienter bedre.
English: • The PRAC concluded that the minimisation measures for medicinal products containing valproate or related substances should be strengthened through contraindication in all indications (epilepsy, bipolar disorders and prophylaxis of migraine) in women/girls of childbearing potential unless the conditions of the pregnancy prevention programme are complied with.
Danish: • PRAC konkluderede, at de risikominimerende foranstaltninger for lægemidler indeholdende valproat eller relaterede stoffer bør styrkes gennem kontraindikation i alle indikationer (epilepsi, bipolær sindslidelse og forebyggelse af migræne) hos fertile piger/kvinder, medmindre betingelserne i graviditetsforebyggelsesprogrammet overholdes.
English: In addition in an effort to increase the knowledge on the association between paternal exposure to valproate and the risk of congenital anomalies and neurodevelopmental disorders including autism in offspring, a retrospective observational study is recommended.
Danish: Ud over indsatsen for at øge viden om sammenhængen mellem paternel eksponering for valproat og risikoen for medfødte misdannelser og udviklingsmæssige sygdomme i nervesystemet, herunder autisme hos afkommet, anbefales det at gennemføre et retrospektivt observationsstudie.
English: Usage data from the ongoing joint drug utilisation study (DUS) as well as other data (surveys, national surveys, anecdotal evidence etc.) that have been evaluated in the current referral indicate that valproate is still used by a considerable proportion of WCBP in different MSs for both epilepsy and bipolar disorder indications.
Danish: Data fra det fælles studie af lægemiddelanvendelse (DUS) samt andre data (undersøgelser, nationale undersøgelser, anekdotisk evidens osv.), som er blevet evalueret i den igangværende indbringelsesprocedure, indikerer, at valproat stadig anvendes af en betragtelig andel af fertile kvinder i forskellige medlemsstater i indikationerne epilepsi og bipolær sindslidelse.
English: The PRAC agreed that such visual reminder on the outer carton is important to warn the patient on the risk and to prompt to consult a physician and requested the inclusion of a visual reminder on the outer packaging.
Danish: PRAC var enig i, at en sådan visuel påmindelse på den ydre æske er vigtig for at advare patienterne om risikoen og tilskynde dem til at gå til lægen, og anbefalede medtagelse af en visuel påmindelse på yderemballagen.
English: Advice on non-interruption of treatment as well as the need to contact the doctor when a pregnancy is planned or suspected should also be included.
Danish: Råd om ikke at afbryde behandling og om behovet for at kontakte lægen, når en graviditet skal planlægges, eller når der er mistanke om graviditet, bør også fremgå af patientkortet.
English: The CMDh therefore clarified that the amendments to the product information and the other routine measures to inform on the risk to the foetus when valproate is taken in pregnancy to all Healthcare professionals (HCP) and patients are applicable to all medicinal products containing valproate and related substances, irrespective of the route of administration.
Danish: CMDh præciserede derfor, at ændringerne af produktinformationen og de andre almindelige informationstiltag vedrørende risikoen for fosteret ved brug af valproat under graviditet, som er rettet mod alle sundhedspersoner og patienter, gælder for alle lægemidler indeholdende valproat og relaterede stoffer, uanset administrationsvej.
English: With regards to the educational materials (i.e. HCP guide and patient guide), these are also considered relevant for the injectable forms of products containing valproate and related substances and therefore should be implemented.
Danish: Med hensyn til informationsmaterialet (dvs. vejledningen til sundhedspersoner og vejledningen til patienter) vurderes også disse at være relevante for de injicérbare formuleringer indeholdende valproat og relaterede stoffer, og de bør derfor gennemføres.
English: For the following risk minimisation measures, the CMDh clarified that:
Danish: CMDh præciserede følgende vedrørende de risikominimerende foranstaltninger:
English: Theoretically this is possible by changes to the gene expression in sperm cells of adult males or by changes to the developing germ cells in the embryo.
Danish: Teoretisk set er dette muligt gennem forandringer i genekspressionen i sædceller hos voksne mænd eller forandringer i udviklende kimceller i embryoet.
English: The visual reminder is considered important and required to be implemented on the outer packaging of any valproate formulation and presentation.
Danish: Den visuelle påmindelse skønnes at være vigtig, og det er nødvendigt, at den implementeres på yderemballagen for alle valproat-formuleringer.
English: The current ongoing drug utilisation study (DUS) should be adapted and continued to assess the effectiveness of the updated risk minimisation measures including the pregnancy prevention programme conditions and to further characterise the prescribing patterns for valproate.
Danish: Det igangværende studie af lægemiddelanvendelse (DUS) bør tilpasses og fortsættes for at vurdere virkningen af de opdaterede risikominimerende foranstaltninger, herunder betingelserne i graviditetsforebyggelsesprogrammet, og for yderligere at undersøge ordinationsmønstret for valproat.
English: This may be particularly important as the prescribers of IV formulations of valproate are expected to be different from the usual prescribers targeted during the implementation of additional risk minimisation measures.
Danish: Dette kan være særligt vigtigt, da de læger, der ordinerer intravenøse formuleringer af valproat, forventes at være andre end de sædvanlige ordinerende læger, der er målgruppen for de yderligere risikominimeringsforanstaltninger.
English: Regarding pregnancy/family planning in epilepsy, the PRAC also highlighted that, a specialist experienced in the management of epilepsy, must reassess valproate therapy and consider alternative treatment options.
Danish: Hvad angår graviditet/familieplanlægning hos epileptiske patienter, fremhævede PRAC desuden, at en speciallæge med erfaring i behandling af epilepsi bør revurdere valproat-behandling og overveje alternative behandlingsmuligheder.
English: At least annual re-assessment of the need for valproate therapy and consideration of alternative treatment options in female children who experienced menarche and women of childbearing potential should be included.
Danish: Dette bør som minimum omfatte en årlig revurdering af behovet for valproat-behandling og overvejelse af alternative behandlingsmuligheder hos piger, der har fået menstruation, og fertile kvinder.
English: Among the requests from the patients and family members who were consulted was the implementation of a visual reminder on the outer package to warn the women on the harm to the unborn baby and to also promptly advise them to use effective contraception.
Danish: De patienter og pårørende, som blev hørt, havde blandt andet et ønske om implementering af en visuel påmindelse på den ydre emballage for at advare kvinderne om risikoen for skade på det ufødte barn og for også at tilskynde dem til at bruge sikker prævention.