FrancophonIA/ELRC3.0 huggingface dataset:
English: There was a significant difference in the occurrence of clinical seizures (P = .021).
Danish: Der var signifikant forskel i forekomsten af kliniske anfald (p = 0,021).
English: However this was not accepted due to the risk of dosing errors.
Danish: Dette blev dog ikke accepteret på grund af risikoen for doseringsfejl.
English: • The Committee considered the notification of the referral triggered by the United Kingdom under Article 29(4) of l Directive 2001/83/EC.
Danish: • Udvalget behandlede anmeldelsen af den indbringelse, der var indledt af Det Forenede Kongerige i henhold til artikel 29, stk. 4, i direktiv 2001/83/EF.
English: Overall summary of the scientific evaluation of Levothyroxine Alapis and associated names (see Annex I)
Danish: Samlet resumé af den videnskabelige vurdering af Levothyroxine Alapis og relaterede navne (se bilag I)
English: Scientific conclusions and grounds for refusal
Danish: Videnskabelige konklusioner og begrundelse for afslag
English: Grounds for refusal
Danish: Begrundelse for afslag
English: • The Committee concluded that the risk-benefit balance of Levothyroxine Alapis is therefore not considered to be favourable.
Danish: • Udvalget konkluderede, at benefit/risk-forholdet for Levothyroxine Alapis derfor ikke anses for gunstigt.
English: It is also noted that the proposed package leaflet (PL) recommends that the drops are not administered directly to the patient, but should first be delivered to a spoon.
Danish: Desuden bemærkes det, at det i den foreslåede indlægsseddel anbefales, at dråberne ikke administreres direkte til patienten, men først dryppes i en ske.
English: Levothyroxine Alapis contains 200mg/ml of ethanol per dose.
Danish: Levothyroxine Alapis indeholder 200 mg/ml ethanol pr. dosis.
English: • The Committee was of the opinion that there was an unacceptable risk of medication error due to the dropper insert, where the inappropriate orientation of the dropper insert would result in inaccurate and variable drop volume.
Danish: • Udvalget fandt, at der var en uacceptabel risiko for medicineringsfejl som følge af dråbetælleren, idet uhensigtsmæssig orientering af dråbetælleren ville medføre unøjagtigt og varierende
English: Despite the shortcomings of this study the data suggest a dose-dependent trend towards a higher incidence of seizures with higher doses of propylene glycol.
Danish: Trods undersøgelsens mangler viser dataene en dosisafhængig tendens til større forekomst af anfald ved højere doser af propylenglycol.
English: The guidance “Guideline on the excipients in the label and the package leaflet of medicinal products for human use” states that if the content of ethanol is 100 mg - 3g per dose, the following should be stated in the PL: ‘This medicinal product contains < > vol % ethanol (alcohol), i.e. up to < > mg per dose, equivalent to < > ml beer, < > ml wine per dose.
Danish: Vejledningen “Guideline on the excipients in the label and the package leaflet of medicinal products for human use” foreskriver, at der, hvis ethanolindholdet er mellem 100 mg og 3 g pr. dosis, skal stå følgende i indlægssedlen: “Dette lægemiddel indeholder < > vol % ethanol (alkohol), dvs. op til < > mg pr. dosis, svarende til < > ml øl, < > ml vin pr. dosis.
English: • The Committee reviewed all the data that was available to address the potential serious risk to public health, in particular with regard to the safety of Levothyroxine Alapis 100 microgram/ml oral drops solution.
Danish: • Udvalget gennemgik alle de tilgængelige data vedrørende den potentielle alvorlige risiko for den offentlige sundhed, navnlig sikkerheden af Levothyroxine Alapis, orale dråber, opløsning, 100 µg/ml.
English: To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.'
Danish: Dette skal tages i betragtning hos kvinder, der er gravide eller ammer, samt hos børn og højrisikogrupper, såsom patienter med leversygdom eller epilepsi.”
English: This represents an impractical means of dosing babies and small infants, and will result in further variability in dosing volumes associated with use of a second administration device.
Danish: Dette er en upraktisk doseringsmåde til spædbørn og mindre børn og vil medføre yderligere variabilitet i det doserede volumen gennem anvendelse af endnu en indgivelsesanordning.
English: Inaccuracies due to miscounting
Danish: Unøjagtighed som følge af fejltælling
English: This is a bibliographic application that refers to literature concerning several levothyroxin tablet formulations and solutions and thus no reference is made to a single unique formulation.
Danish: Ansøgningen er bibliografisk og henviser til litteratur vedrørende en række tabletformuleringer og opløsninger af levothyroxin; der henvises således ikke til nogen enkelt bestemt formulering.
English: The possible medication errors caused by the dropper insert were discussed by the CHMP:
Danish: CHMP drøftede de mulige medicineringsfejl som følge af dråbetælleren:
English: Therefore any deviation from vertical orientation, such as an attempt to slow the drop rate will result in inaccurate drop volume.
Danish: Enhver afvigelse fra lodret, såsom et forsøg på at nedbringe dråbehastigheden, vil derfor medføre, at dråbevolumen bliver unøjagtigt.
English: The decentralised marketing authorisation application for the medicinal product Levothyroxine is a well-established use application according to Article 10(a) of Directive 2001/83/EC.
Danish: Ansøgningen om markedsføringstilladelse via den decentrale procedure for lægemidlet Levothyroxine Alapis vedrører en almindelig anerkendt anvendelse i henhold til artikel 10, stk. 1, litra a), i direktiv 2001/83/EF.
English: Deviation from a vertical position is more likely in situations where the patient / carer is attempting to manage / slow the drop rate to enable a relatively high number of drops to be counted.
Danish: Afvigelser fra lodret position af flasken er mere sandsynlig i situationer, hvor patienten/omsorgsgiveren forsøger at styre/nedsætte dråbehastigheden for at tælle et forholdsvis stort antal dråber.
English: The absence of robust user testing with representative members of the general public provides no reassurance that this dropper device will prove manageable and accurate in practice.
Danish: Uden en fyldestgørende brugertest med repræsentative personer fra den almindelige befolkning er der ikke sikkerhed for, at dråbetælleren vil vise sig at være anvendelig og nøjagtig i praktisk brug.
English: Based on the above, the CHMP considers that the safety concerns relating to Levothyroxine Alapis that were raised during the decentralised procedure and the CMDh referral procedure have not been sufficiently addressed.
Danish: På ovenstående grundlag finder CHMP, at de sikkerhedsmæssige betænkeligheder vedrørende Levothyroxine Alapis, der blev rejst under den decentrale procedure og CMD(h)indbringelsesproceduren, ikke er imødekommet tilstrækkeligt.
English: More seizures occurred with the higher dose of propylene glycol, where 33% of the infants had seizures, vs only 14% of infants who received the lower dose of propylene glycol.
Danish: Ved den højere dosis af propylenglycol forekom der anfald hos 33 % af børnene, mod kun 14 % ved den lavere dosis af propylenglycol.
English: The proposed patient populations are: adults, children over 12 years (in the treatment of diffuse non-toxic goitre), and neonates and infants (with congenital hypothyroidism).
Danish: De foreslåede patientpopulationer er: voksne, børn over 12 år (ved behandling af diffus ikketoksisk struma) samt nyfødte og børn (med medfødt hypotyroidisme).
English: The dosing errors due to the difficulty in accurately counting a large number of drops per dose (up to 20 drops) of Levothyroxine Alapis solution also remain a concern.
Danish: Der er endvidere fortsat betænkelighed ved doseringsfejl som følge af vanskeligheden ved nøjagtigt at tælle et stort antal dråber (op til 20) af opløsningen af Levothyroxine Alapis pr. dosis.
English: Published literature highlights the potential for significant variability in both drop rate and volume for low viscosity solutions such as this product, where bottle orientation is not vertical.
Danish: I litteraturen1 understreges potentialet for betydelig variabilitet i både dråbehastighed og dråbevolumen for lavviskøse opløsninger som dette produkt, når flasken ikke holdes lodret.
English: Medication errors caused by the administration device (dropper insert) Initially two different dropper inserts resulting in different drop sizes that would count up to 40 drops was proposed by the Applicant.
Danish: Medicineringsfejl forårsaget af doseringsanordningen (dråbetæller) Oprindeligt omfattede ansøgningen to forskellige dråbetællere, som resulterede i forskellige dråbestørrelser og skulle tælle op til 40 dråber.
English: In light of the failure to provide responses to the CHMP list of questions, , the available information was not considered to be sufficient to address the safety concerns of the chronic use of ethanol and the propylene glycol, in particular in the paediatric population.
Danish: På grund af den manglende besvarelse af CHMP's liste med spørgsmål blev oplysningerne ikke anset for at være tilstrækkelige til at imødekomme de sikkerhedsmæssige betænkeligheder ved kronisk anvendelse af ethanol og propylenglycol, navnlig hos den pædiatriske population.
English: The study by MacDonald et al2, seems relevant as daily doses of propylene glycol similar to what can be expected from Levothyroxine Alapis were studied in one of the study arms.
Danish: Undersøgelsen af MacDonald et al2 forekommer relevant, da der i den ene af undersøgelsens arme blev anvendt daglige doser af propylenglycol svarende til dem, der kan forventes fra Levothyroxine Alapis.
English: In light of the Applicant's failure to provide responses to the CHMP list of questions during the Article 29(4) referral procedure, the assessment was carried out on the data made available during the decentralised procedure and the CMDh referral procedure.
Danish: Som følge af ansøgerens manglende besvarelse af CHMP's spørgsmål under proceduren for indbringelse af sager i overensstemmelse med artikel 29, stk. 4, fandt vurderingen sted på grundlag af de oplysninger, der blev stillet til rådighed under den decentrale procedure og CMD(h)indbringelsesproceduren.
English: And therefore the CHMP recommended the refusal of the granting of the marketing authorisation for Levothyroxine Alapis and associated names (see Annex I).
Danish: anbefalede CHMP afslag på ansøgningen om markedsføringstilladelse og suspendering af de markedsføringstilladelser, der er udstedt for Levothyroxine Alapis og relaterede navne (se bilag I).
English: Two groups of infants were treated with two doses of propylene glycol; 0.3 g/day and 3 g/day in an IV multivitamin solution, during two consecutive 19month periods in a retrospective design.
Danish: To grupper børn blev behandlet med propylenglycol i to doseringer (0,3 g/dag og 3 g/dag) i en intravenøs multivitaminopløsning.
English: Alcohol dehydrogenase preferentially metabolises ethanol prior to metabolising other alcohols, including propylene glycol.
Danish: Alkoholdehydrogenase metaboliserer fortrinsvis ethanol før andre alkoholer, herunder propylenglycol.
English: • The Committee was of the opinion that the chronic co-administration of the proposed quantities of the excipients ethanol and propylene glycol in children remains a safety concern.
Danish: • Udvalget fandt, at kronisk samtidig indgivelse af de ansøgte mængder af hjælpestofferne ethanol og propylenglycol hos børn fortsat giver anledning til sikkerhedsmæssige betænkeligheder.
English: As there is limited information on safe ethanol concentrations in paediatric formulations intended for chronic use, there are concerns with regard to chronic use of Levothyroxine Alapis in neonates/children, as ethanol represents an additional insult to brain development that is already compromised by congenital hypothyroidism.
Danish: Da der kun findes begrænset viden om sikre koncentrationer af ethanol i pædiatriske formuleringer til kronisk anvendelse, er der betænkelighed forbundet med kronisk anvendelse af Levothyroxine Alapis til nyfødte/børn, idet ethanol medfører en yderligere skadelig påvirkning af hjernens udvikling, hvor denne i forvejen er belastet ved medfødt hypotyroidisme.
English: In conclusion given that Levothyroxine Alapis is a highly concentrated solution containing 100 mcg/ml the dropper device is considered to be unsuitable due to inaccuracies resulting from improper dropper orientation and miscounting, especially for paediatric initial doses less than 25 mcg.
Danish: På baggrund af at Levothyroxine Alapis er en stærkt koncentreret opløsning, der indeholder 100 µg/ml, konkluderes det, at dråbetælleren må anses for uegnet på grund af de unøjagtigheder, der bevirkes af uhensigtsmæssig orientering af dråbetælleren og fejltælling, navnlig når den anvendes til pædiatriske startdoser på mindre end 25 µg.
English: As ethanol is used to solubilise levothyroxine, its use is not considered to be essential in this formulation, based on the relatively poor solubility of levothyroxine in ethanol when compared to propylene glycol.
Danish: Da ethanol anvendes til at bringe levothyroxin i opløsning, anses det ikke for uundværligt i denne formulering i betragtning af levothyroxins forholdsvis ringe opløselighed i ethanol i forhold til opløseligheden i propylenglycol.
English: Levothyroxine Alapis is a solution with low viscosity, which gives a fast drop rate.
Danish: Levothyroxine Alapis er en opløsning med lav viskositet, hvilket medfører hurtig dråbeafgivelse.
English: Inaccuracies due to improper dropper orientation
Danish: Unøjagtighed som følge af uhensigtsmæssig orientering af dråbetælleren
English: Therefore there are major safety concerns due to the chronic use of the combination of ethanol and propylene glycol in neonates/children.
Danish: Dette giver anledning til alvorlige sikkerhedsmæssige betænkeligheder ved kronisk anvendelse af kombinationen af ethanol og propylenglycol hos nyfødte/børn.
English: In addition there are also concerns in patients with hepatic impairment, epilepsy and in vulnerable adults such as those suffering from alcoholism.
Danish: Desuden er der betænkeligheder ved anvendelse hos patienter med nedsat leverfunktion og epilepsi samt hos udsatte voksne, såsom alkoholikere.
English: Although propylene glycol is widely used as an excipient in oral and injectable medicines, literature data on its safety in children when administered chronically is sparse.
Danish: Skønt propylenglycol har udbredt anvendelse som hjælpestof i orale og parenterale lægemidler, findes der kun sparsomme litteraturdata om dets sikkerhed ved kronisk indgivelse til børn.
English: The excipients are glycerol, propylene glycol, ethanol and purified water, which comply with the respective Ph.Eur monographs.
Danish: Hjælpestofferne er glycerol, propylenglycol, ethanol og renset vand, der alle er i overensstemmelse med de pågældende monografier i Ph.Eur.
English: The proposed indications for Levothyroxine Alapis are for: the treatment of hypothyroidism (congenital or acquired, including diffuse non-toxic goiter), hypothyroidism forms of Hashimoto's thyroiditis and thyroid carcinoma.
Danish: De foreslåede indikationer for Levothyroxine Alapis er: behandling af hypotyroidisme (medfødt eller erhvervet, herunder diffus ikketoksisk struma), Hashimotos tyroiditis med hypotyroidisme samt thyreoideakarcinom.
English: Levothyroxine Alapis is an oral drop solution containing levothyroxine sodium as active substance (100 mcg/ml).
Danish: Levothyroxine Alapis er orale dråber, opløsning, med levothyroxinnatrium som det aktive indholdsstof (100 µg/ml).
English: The applicant then proposed to use: - a dropper insert for doses between 12.5 µg and 50 µg (5 to 20 drops) and - a 3 mL oral syringe for doses between 50 µg and 200 µg (0.5 to 2 mL) According to the proposed Summary of Product Characteristics (SmPC), the dropper insert will be mainly used for administration to paediatric patients as well as for initial dosing of adults and children over 12 years.
Danish: Ansøgeren foreslog derefter anvendelse af: - en dråbetæller til doser mellem 12,5 µg og 50 µg (5-20 dråber) og - en 3 ml oral sprøjte til doser mellem 50 µg og 200 µg (0,5-2 ml).
English: Since no consensus could be reached on the issues relating to medication errors due to the method of administration of the oral drops and the safety of excipients ethanol and propylene glycol in the paediatric population, the CMDh referred the matter to the CHMP under Article 29(4) of Directive
Danish: Da det ikke var muligt at nå til enighed om problemerne vedrørende medicineringsfejl som følge af indgivelsesmåden for de orale dråber og vedrørende sikkerheden af hjælpestofferne ethanol og propylenglycol hos den pædiatriske population, indbragte koordinationsgruppen vedrørende gensidig anerkendelse og decentraliseret procedure - lægemidler til mennesker (CMD(h)) sagen for CHMP i henhold til artikel 29, stk. 4, i direktiv 2001/83.
English: The active substance levothyroxine, is an established active substance described in the European Pharmacopoeia.
Danish: Det aktive stof i Levothyroxine Alapis, levothyroxin, er velkendt og beskrevet i Den Europæiske Farmakopé.
English: Therefore, co-administration of ethanol and propylene glycol can lead to raised and potentially toxic levels of the latter.
Danish: Samtidig indgivelse af ethanol og propylenglycol kan derfor medføre forhøjede og potentielt toksiske koncentrationer af propylenglycol.
English: Since both propylene glycol and ethanol share a common metabolic pathway the combination of ethanol and propylene glycol is a concern.
Danish: Da propylenglycol og ethanol metaboliseres ad samme vej, er der betænkelighed ved kombinationen af ethanol og propylenglycol.
English: Safety of excipients (ethanol / propylene glycol) in paediatric population The excipients used in Levothyroxine Alapis are ethanol, propylene glycol, glycerol and water and comply with the Ph. Eur monographs.
Danish: Sikkerheden af hjælpestofferne (ethanol/propylenglycol) hos den pædiatriske population Hjælpestofferne i Levothyroxine Alapis er ethanol, propylenglycol, glycerol og vand, der alle opfylder monografierne i Ph.Eur.
English: Combination of ethanol and propylene glycol
Danish: Ethanol og propylenglycol i kombination
English: Both ethanol and propylene glycol are initially metabolised by alcohol dehydrogenase.
Danish: Både ethanol og propylenglycol metaboliseres initialt af alkoholdehydrogenase.
English: As mentioned previously, both ethanol and propylene glycol are initially metabolised by alcohol dehydrogenase.
Danish: Som nævnt metaboliseres ethanol og propylenglycol begge initialt af alkoholdehydrogenase.
English: In addition there are concerns in vulnerable adults such as those suffering from alcoholism, as well as in patients with hepatic impairment and epilepsy.
Danish: Desuden er der betænkeligheder ved behandling af udsatte voksne, såsom personer med alkoholisme, nedsat leverfunktion eller epilepsi.
English: Newborn infants, and children are not able to metabolize ethanol as efficiently as adults; as a consequence, they may be at higher risk of both acute and chronic alcohol-related toxicities.
Danish: Nyfødte og børn kan ikke metabolisere ethanol lige så effektivt som voksne.
English: Inaccuracy due to the miscounting of the large number of drops administered also contributes to the risk of medication error.
Danish: Risikoen for medicineringsfejl øges endvidere af unøjagtighed som følge af fejltælling af det store antal indgivne dråber.
English: Levothyroxine Alapis, which is a highly concentrated solution of a highly potent medicinal product, is associated with adverse events with chronic over-dosing - particularly cardiovascular events.
Danish: Levothyroxine Alapis er formuleret som en stærkt koncentreret opløsning af et meget potent lægemiddel og er ved kronisk overdosering forbundet med bivirkninger, navnlig kardiovaskulære hændelser, mens kronisk underdosering har konsekvenser for den normale udvikling af hjernen hos børn.
English: Levothyroxine Alapis, which is formulated as a highly concentrated solution of a very potent active substance, is associated with adverse events with chronic over-dosing - particularly cardiovascular.
Danish: Levothyroxine Alapis er formuleret som en stærkt koncentreret opløsning af et meget potent aktivt stof, og kronisk overdosering er forbundet med bivirkninger, navnlig kardiovaskulære, mens kronisk underdosering medfører konsekvenser for den normale udvikling af hjernen hos de pågældende børn.
English: To be determined by Member States following EC decision
Danish: Fastsættes af medlemsstaterne efter Kommissionens afgørelse.
English: The national competent authorities, coordinated by the reference Member State, if applicable, shall ensure that the following conditions are fulfilled by the marketing authorisation holders:
Danish: De kompetente nationale myndigheder sikrer, i givet fald med referencemedlemsstaten som koordinerende instans, at indehaverne af markedsføringstilladelse opfylder følgende betingelser:
English: The MAHs should circulate a DHPC in accordance with the agreed key messages.
Danish: Indehaverne af markedsføringstilladelse udsender en direkte henvendelse til sundhedspersoner (DHPC) i overensstemmelse med de vedtagne hovedpunkter.
English: 0.5ml (1mg/ml) 14 Vials
Danish: Hætteglas (glas) 0,5 ml (1 mg/ml)
English: These findings have since been verified.
Danish: Disse resultater er siden verificeret.
English: Special media and atmosphere are required and the incubation period is long (7-10 days).
Danish: Der kræves specialmedier og specialatmosfære, og inkubationstiden er lang (7-10 dage).
English: Furthermore, this indication should not be granted for the pending marketing authorisation applications (see Annex I).
Danish: Desuden bør denne indikation ikke godkendes for de ansøgninger om markedsføringstilladelse, der er under behandling (se bilag I).
English: should be granted, maintained, varied or removed from the product information of the aforementioned products.
Danish: bør godkendes, bibeholdes, ændres eller slettes i produktinformationen for de nævnte produkter.
English: The clinical signs vary but the milk loss is usually significant.
Danish: De kliniske symptomer varierer, men tabet af mælk er sædvanligvis betydeligt.
English: (or Mycoplasma bovis) which are currently authorised or pending authorisations in the European Union.
Danish: (eller Mycoplasma bovis) og aktuelt er godkendt eller afventer godkendelser i EU.
English: Monitoring the lack of efficacy is a part of the veterinary pharmacovigilance system.
Danish: Overvågning af manglende virkning indgår i ordningen til veterinær lægemiddelovervågning.
English: Infected cows may remain externally normal with few clinical signs, even in severe cases.
Danish: Smittede køer kan udadtil forblive normale med få kliniske symptomer, selv i svære tilfælde.
English: INN Pharmaceutical form
Danish: INN Lægemiddelform Styrke
English: Details of the treatment experiments are scarce, but altogether he described the results as unrewarding.
Danish: Der er ikke mange detaljer om behandlingsforsøgene, men overordnet beskrev han resultaterne som utilfredsstillende.
English: 29% of the composite samples (81/280) and 43% of the quarter milk samples (433/1008) did not yield growth of Mycoplasma.
Danish: 29 % af de kombinerede prøver (81/280) og 43 % af prøverne fra de enkelte mælkekirtler (433/1008) medførte ikke vækst af Mycoplasma.
English: The dose 3 g/cow/day is within the dose range widely authorised in Europe i.e. 4-10 mg/kg/day i.m.
Danish: En dosis på 3 g/ko/dag er inden for det dosisområde, der er bredt godkendt i Europa, dvs. 4-10 mg/kg/dag im.
English: Often more than one quarter is affected and there is a marked drop in milk production.
Danish: Ofte er mere end én kirtel angrebet, og der er et udtalt fald i mælkeproduktionen.
English: Current technologies such as Polymerase Chain Reaction (PCR) have enabled significantly quicker identification of M. bovis.
Danish: De nuværende teknikker såsom polymerasekædereaktion (PCR) har muliggjort hurtigere identifikation af M. bovis.