FrancophonIA/ELRC3.0 huggingface dataset:
English: No effect of Ceplene and interleukin-2 was seen in patients in second or later remission.
Danish: Der sås ingen effekt af Ceplene og interleukin-2 hos patienter i anden eller senere bedringsperiode.
English: Each Ceplene injection must be given slowly over five to 15 minutes, in a different site from the interleukin-2 injection, and preferably in the thigh or abdomen (belly).
Danish: Hver Ceplene-injektion skal indgives langsomt over 5-15 minutter, og det skal ske et andet sted end interleukin-2-injektionen, helst i låret eller maven.
English: Ceplene contains the active substance histamine dihydrochloride.
Danish: Ceplene indeholder det aktive stof histamindihydrochlorid.
English: How is Ceplene used?
Danish: Hvordan anvendes Ceplene?
English: For the full list of side effects of Ceplene, see the package leaflet.
Danish: Den fuldstændige liste over bivirkninger ved Ceplene fremgår af indlægssedlen.
English: Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ceplene have been included in the summary of product characteristics and the package leaflet.
Danish: Der er anført anbefalinger og forholdsregler i produktresuméet og indlægssedlen, som patienter og sundhedspersonale skal følge for at sikre risikofri og effektiv anvendelse af Ceplene.
English: The active substance in Ceplene, histamine dihydrochloride, is an immune modulator.
Danish: Det aktive stof i Ceplene, histamindihydrochlorid, et en såkaldt immunmodulator.
English: How does Ceplene work?
Danish: Hvordan virker Ceplene?
English: For patients who were into their first remission the combination of Ceplene and interleukin-2 was more effective than no treatment in increasing the time until AML came back or the patient died from any cause: the average time without disease increased from 291 days with no treatment to 450 days after treatment with Ceplene and interleukin-2.
Danish: Hos patienter, der var i deres første bedringsperiode, var kombinationen af Ceplene og interleukin-2 mere effektiv end ingen behandling til at forlænge den sygdomsfri periode frem til tilbagefald af AML eller patientens død uanset årsag.
English: What benefit of Ceplene have been shown in studies?
Danish: Hvilke fordele viser studierne, at der er ved Ceplene?
English: Hence no safety margin could be calculated.
Danish: Der kunne derfor ikke beregnes en sikkerhedsmargin.
English: • four cases of spontaneous abortion,
Danish: • fire tilfælde af spontanabort,
English: Subsequent safety assessments focusing on genotoxic potential were issued in 20012 and 20033 .
Danish: Efterfølgende blev der udsendt sikkerhedsvurderinger med fokus på genotoksisk potentiale i 20012 og 20033.
English: Carcinogenicity is an important potential risk.
Danish: Karcinogenicitet er en vigtig potentiel risiko.
English: • Teratogenicity is classified as an important identified risk.
Danish: • Teratogenicitet er klassificeret som en vigtig identificeret risiko.
English: However it is still controversial if aneuploidy is a contributing cause or merely a consequence of neoplastic transformation.
Danish: Det er imidlertid stadig omdiskuteret, om aneuploidi er en medvirkende årsag til eller blot en konsekvens af neoplastisk omdannelse.
English: The package size should be adapted to new recommended treatment-days.
Danish: Pakningsstørrelsen skal tilpasses det nye anbefalede antal behandlingsdage,
English: The corresponding product information sections were updated accordingly.
Danish: De tilsvarende afsnit i produktinformationen blev ajourført i henhold hertil.
English: Aneuploidy is a common characteristic of cancer cells.
Danish: Aneuploidi er et fælles kendetegn for kræftceller.
English: Case review reports from 2004 up to 29 April 2013 from the second database reported 23 cases secondary to exposure during pregnancy and / or exposition in utero:
Danish: Gennemgang af case-rapporter fra 2004 frem til den 29. april 2013 fra den anden database viste 23 tilfælde sekundært til eksponering under graviditet og/eller in utero:
English: In the first database, 11 cases secondary to exposure during pregnancy were reported:
Danish: I den første database indberettedes 11 tilfælde sekundært til eksponering under graviditet:
English: The CHMP also considered that the use of TCC should be avoided during puberty (12 to 16-18 years) due to potential risk on fertility.
Danish: CHMP fandt desuden, at anvendelse af TCC skulle undgås i puberteten (12 til 16-18 år) på grund af den potentielle risiko for fertiliteten.
English: The CHMP also recommended further changes to the product information including information on fertility.
Danish: CHMP anbefalede derudover yderligere ændringer af produktinformationen, herunder oplysninger om fertilitet,
English: • Lastly, evidence for carcinogenicity of aneugens is limited.
Danish: • Endelig er der begrænset evidens for karcinogeniciteten af aneugene stoffer.
English: The CHMP was asked to give its opinion on whether the indication of TCC containing medicinal products should be restricted and/or other regulatory measures should be taken.
Danish: CHMP blev anmodet om at udtale sig om, hvorvidt indikationerne for lægemidler indeholdende TCC burde begrænses og/eller der burde foretages andre regulerende indgreb.
English: Clinical Safety
Danish: Klinisk sikkerhed
English: Overall summary of the scientific evaluation of thiocolchicoside containing medicinal products for systemic use (see Annex I)
Danish: Samlet resumé af den videnskabelige vurdering af lægemidler indeholdende thiocolchicosid til systemisk anvendelse (se bilag I)
English: On 21 February 2013, the CHMP started a referral procedure for TCC containing medicinal products.
Danish: Den 21. februar 2013 indledte CHMP en indbringelsesprocedure for lægemidler indeholdende TCC.
English: For the purpose of the review of this risk, the MAHs provided an analysis of this genotoxic potential for each systemic route of administration, together with an analysis of possible risk factors, including relevant criteria such as dose and duration of treatment.
Danish: Med henblik på gennemgangen af denne risiko fremlagde indehaveren af markedsføringstilladelse en analyse af dette genotoksiske potentiale for hver systemisk administrationsvej sammen med en analyse af mulige risikofaktorer, herunder relevante kriterier såsom dosis og behandlingsvarighed.
English: In addition males and females showed only a slight gender difference in exposure.
Danish: Desuden var kun lille kønsforskel i eksponeringen.
English: The CHMP also noted that the limited number of cases of malformations/embryo-foetal toxicities may be due to the fact that, in most of the Member States, the medicine is contraindicated in pregnancy.
Danish: CHMP bemærkede også, at det begrænsede antal tilfælde af misdannelser/embryoføtal toksicitet kan skyldes, at lægemidlet i størstedelen af medlemsstaterne er kontraindiceret ved graviditet.
English: This DUS should be conducted over a three year period.
Danish: Undersøgelsen af lægemiddelanvendelse skal udføres i en treårig periode.
English: Widely used by prescribers in the concerned Member States (see Annex I), the benefits of TCC containing medicinal products are recognised in clinical practice.
Danish: TCC ordineres i stort omfang i de berørte medlemsstater (se bilag I), og fordelene ved lægemidler indeholdende TCC er anerkendt i klinisk praksis.
English: A risk management plan (RMP) will be submitted to national competent authorities in accordance with agreed timelines and periodic safety update reports (PSURs) will be submitted every 3 years.
Danish: Der skal inden for de aftalte frister forelægges en risikostyringsplan for de nationale kompetente myndigheder, og der skal indsendes periodiske opdaterede sikkerhedsrapporter (PSUR) hvert tredje år.
English: In addition, the lack of evidence for the correlation between the use of TCC and cancer could be due to the difficulty of establishing a causal relationship between the medicine and the effect, which may occur years after intake.
Danish: Desuden kan den manglende evidens for korrelation mellem anvendelse af TCC og kræft skyldes vanskelighed ved at fastslå en årsagssammenhæng mellem lægemidlet og virkningen, da denne muligvis først optræder år efter indtagelsen.
English: Amendments to the warnings and pregnancy and lactation sections of the product information were also endorsed.
Danish: Der blev ligeledes godkendt ændringer af advarslerne og af afsnittene om graviditet og amning i produktinformationen.
English: A relevant summary is presented hereinafter.
Danish: De er sammenfattet i det følgende.
English: In view of the above, on 15 February 2013, Italy requested the CHMP, under Article 31 of Directive 2001/83/EC, to assess the above concerns regarding aneuploidy and its impact on the benefit-risk balance for TCC containing medicinal products for systemic use.
Danish: På denne baggrund anmodede Italien den 15. februar 2013 i henhold til artikel 31 i direktiv 2001/83/EF CHMP om at vurdere de nævnte betænkeligheder vedrørende aneuploidi og betydningen heraf for benefit/risk-forholdet for lægemidler indeholdende TCC til systemisk anvendelse.
English: No case was registered for neonatal effects related to exposure occurred in late pregnancy or during childbirth.
Danish: Der blev ikke registreret tilfælde af virkninger på den nyfødte ved eksponering sent i graviditeten eller under fødslen.
English: TCC is indicated for the treatment of painful muscular contractures in different settings.
Danish: TCC er indiceret til behandling af smertefulde kontrakturer i forskellig sammenhæng.
English: In females, a positive response was observed at doses of 25, 50, 70 and 100 mg/kg/d based on group mean and individual data.
Danish: Hos hundyrene sås positiv respons ved doser på 25, 50, 70 og 30 og 100 mg/kg/d baseret på gruppegennemsnit og individuelle data.
English: • The Committee considered the procedure under Article 31 of Directive 2001/83/EC for thiocolchicoside containing medicinal products for systemic use (see annex I).
Danish: • udvalget fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF for lægemidler indeholdende thiocolchicosid til systemisk anvendelse (se bilag I),
English: • one case of threat of premature delivery.
Danish: • et tilfælde af truende for tidlig fødsel
English: Postmarketing spontaneous cases were collected based on the reports recorded in two MAHs' global pharmacovigilance databases (cut-off dates of 15 February 2013 and 29 April 2013 respectively).
Danish: Der blev indsamlet spontane indberetninger efter markedsføring fra to markedsføringstilladelsesindehaveres globale databaser over lægemiddelovervågning (afskæringsdato hhv. 15. februar 2013 og 29. april 2013).
English: Therefore, on the basis of the above-mentioned available data, the CHMP considered the safety margins and benefit/risk for TCC and SL18.0740 (M1) acceptable.
Danish: På grundlag af de nævnte foreliggende data kunne CHMP derfor acceptere sikkerhedsmarginerne og benefit/risk-forholdet for TCC og SL18.0740 (M1).
English: After parenteral use, the plasma concentration of M2 is expected to be much lower as the M2 transformation occurs after oral administration mainly by intestinal metabolism.
Danish: Efter parenteral anvendelse forventes langt lavere plasmakoncentration af M2, da omdannelsen til M2 efter oral administration hovedsagelig sker ved metabolisering i tarmen.
English: However, more concern was raised in relation to the potential risk of foetal anomalies due to elevated sperm aneuploidy rather than to the male infertility per se.
Danish: Der var imidlertid større betænkelighed ved den potentielle risiko for fosteranomalier som følge af forhøjet forekomst af aneuploidi af sædceller end ved den mandlige infertilitet i sig selv.
English: However a follow-up study (in vivo micronucleus test) defined a no-effect level of 39.6 mg/kg.
Danish: I en opfølgende undersøgelse (in vivo-mikronukleustest) bestemtes nulvirkningsniveauet imidlertid til 39,6 mg/kg.
English: • The CHMP also agreed on the need of a RMP.
Danish: • CHMP fastslog endvidere, at der behøvedes en risikostyringsplan.
English: The CHMP considered that a Direct healthcare professional communication (DHPC) was needed to inform on the outcome of the present review, including the updated indication, the clinical use for these products (short-term) and to highlight the genotoxic risk.
Danish: CHMP fandt, at der behøvedes en direkte henvendelse til sundhedspersoner (DHPC) med information om udfaldet af nærværende gennemgang, herunder den opdaterede indikation, produkternes kliniske anvendelse (kortvarig) og understregning af den genotoksiske risiko.
English: In addition the CHMP reviewed the PSUR frequency for TCC containing medicines for systemic use and requested PSURs to be submitted on a three-yearly basis (instead of a 13-yearly basis as it is currently recommended).
Danish: Desuden overvejede CHMP hyppigheden af PSUR for systemiske lægemidler indeholdende TCC og anmodede om indsendelse af PSUR hvert 3. år (i stedet for den nuværende anbefalede hyppighed på hvert 13. år).
English: Taking the totality of data into account, the CHMP considered that causality cannot be excluded and that aneuploidy should be considered as a cancer risk factor on theoretical grounds.
Danish: Baseret på den samlede mængde data fandt CHMP, at en årsagssammenhæng ikke kan udelukkes, og at aneuploidi at teoretiske grunde bør regnes som en risikofaktor for kræft.
English: In most cases the treatment is for short-term use and not associated with the perception of increased cancer risk for both physicians and patients, therefore a causal relationship between cancer occurrence and treatment is difficult to establish.
Danish: I de fleste tilfælde er behandlingen kortvarig og opfattes af læger eller patienter ikke som værende forbundet med øget kræftrisiko, hvorfor det er vanskeligt at fastslå en årsagssammenhæng mellem behandlingen og forekomst af kræft.
English: Thiocolchicoside (TCC) is a semi-synthetic sulfurated colchicoside derivative with a muscle relaxant pharmacological activity.
Danish: Thiocolchicosid (TCC) er et halvsyntetisk svovlholdigt colchicosidderivat med muskelafslappende farmakologisk virkning.
English: • The Committee considered also that thiocolchicoside containing medicinal products for systemic use should be contraindicated during the entire pregnancy period.
Danish: • udvalget bestemte desuden, at systemiske lægemidler indeholdende thiocolchicosid skal være kontraindiceret i hele graviditetsperioden.
English: Given the treatment conditions with TCC (short-term, potentially aneugenic at maximum doses) effects on male fertility will be low and a rapid recover to normal levels can be expected.
Danish: I betragtning af betingelserne ved behandling med TCC (kortvarig, potentielt aneugen ved maksimale doser) forventes den mandlige fertilitet kun at blive påvirket i ringe grad og hurtigt at ville vende tilbage til et normalt niveau.
English: A significantly increased cancer risk would in general be dependent on long-term/chronic exposure/dosing with the aneugen.
Danish: Sædvanligvis vil væsentligt forhøjet kræftrisiko forudsætte langvarig/kronisk eksponering /dosering med det aneugene stof.
English: • The Committee concluded that there was a need for further risk minimisation measures such as a drug utilisation study to characterise the prescribing practices during typical clinical use, as well as adequate educational materials to be developed for patients and prescribers.
Danish: • udvalget konkluderede, at der er behov for yderligere risikominimeringsforanstaltninger såsom en undersøgelse af lægemiddelanvendelse til karakterisering af den typiske kliniske ordinationspraksis og tilstrækkeligt informationsmateriale til patienter og ordinerende læger.
English: The preclinical development of TCC was mainly performed during the 1980s, and then complemented in the 1990s to be compliant with the European guidelines on the non-clinical documentation for mixed marketing authorisation applications (CPMP/SWP/799/95) and to investigate a new active metabolite SL18.0740 (M1) identified at that time.
Danish: Den prækliniske udvikling af TCC fandt hovedsagelig sted i 1980'erne og suppleredes i 1990'erne dels for at bringe den i overensstemmelse med de europæiske retningslinjer for ikke-klinisk dokumentation for kombinerede ansøgninger om markedsføringstilladelse (CPMP/SWP/799/95), dels for at undersøge en ny aktiv metabolit, SL18.0740 (M1), der var blevet påvist på daværende tidspunkt.
English: In the two in vitro and in vivo preclinical studies conducted, the findings (increase in the incidence of micronucleated cells) were observed at concentrations/exposures close to the exposures measured in human at therapeutic doses.
Danish: I de to prækliniske in vitro- og in vivo-undersøgelser blev resultaterne (stigning i forekomsten af celler med mikronuklei) observeret ved koncentrationer/eksponeringer tæt på den eksponering, der er målt ved terapeutiske doser hos mennesker.
English: Muscle relaxants are one of the many treatments currently employed in the management of non-specific low back pain.
Danish: Muskelrelaksantia hører til de mange midler, der anvendes til behandling af uspecifikke lænderygsmerter.
English: However, whether the exposure to M2 would be below a threshold of aneugenicity (including a sufficient safety margin) is unknown since M2 has not been analysed in the available clinical kinetic studies.
Danish: Det vides imidlertid ikke, om eksponeringen for M2 vil være under tærsklen for aneugen virkning (inklusive en tilstrækkelig sikkerhedsmargin), da der ikke er foretaget bestemmelse af M2 i de foreliggende klinisk kinetiske undersøgelser.
English: The use of the product should therefore be limited to acute conditions in patients over 16 years old; an updated SmPC with restriction for use and duration therapy was endorsed accordingly.
Danish: Produktets anvendelse skal derfor begrænses til akutte tilstande hos patienter over 16 år; der godkendtes et opdateret produktresumé, hvor anvendelse og behandlingsvarighed var begrænset i henhold hertil.
English: Furthermore the CHMP requested a drug utilisation study (DUS) to be conducted in order to better characterise prescribing practices for these medicinal products during typical clinical use in representative groups of prescribers and to assess main reasons for prescription.
Danish: Derudover anmodede CHMP om, at der udføres en undersøgelse af lægemiddelanvendelse for at opnå en bedre karakterisering af den typiske kliniske ordinationspraksis for disse lægemidler hos repræsentative grupper af læger og vurdere de vigtigste grunde til, at de ordineres.
English: No cases of cancer, congenital abnormalities, spontaneous abortion and impaired male fertility were retrieved from a review of clinical trials and literature.
Danish: Der fandtes ingen tilfælde af kræft, medfødte misdannelser, spontanabort eller nedsat mandlig fertilitet ved gennemgang af kliniske undersøgelser og litteraturen.
English: These measures are to be included in the RMP.
Danish: Disse foranstaltninger skal ligeledes indgå i risikostyringsplanen,
English: It was concluded that M1 (SL18.0740) is devoid of mutagenic (gene mutations) and clastogenic (structural chromosome damage) potential, but is able to induce aneuploidy (numerical chromosome damage).
Danish: Det konkluderedes, at M1 (SL18.0740) er uden potentiale som mutagen (genmutationer) eller som clastogen (strukturel kromosombeskadigelse), men kan inducere aneuploidi (numeriske kromosomafvigelser).
English: An amendment to the product information was agreed to address this concern.
Danish: Der blev vedtaget en ændring af produktinformationen vedrørende dette punkt.
English: Since no relevant genetic toxicology studies were previously performed with the aglycone metabolite SL59.0955, complementary studies (chromosome damage assays) were performed in order to investigate the genotoxic profile of this metabolite and its ability to induce aneuploidy in nonclinical in vitro (up to 600 µg/mL) and in vivo (up to 150 mg/kg):
Danish: Da der er ikke tidligere var udført relevante genotoksikologiske undersøgelser med aglyconmetabolitten SL59.0955, blev der udført supplerende undersøgelser (kromosomskade-assay) til karakterisering af den toksiske profil af denne metabolit og dens evne til at inducere aneuploidi i ikkekliniske undersøgelser in vitro (op til 600 µg/ml) og in vivo (op til 150 mg/kg):
English: In addition, the CHMP was of the view that the package size should be restricted according to the new treatment-days scheme recommended (up to 30 tablets or capsules/4 mg pack, up to 14 tablets or capsules/8 mg pack and up to 10 vials/ampoules).
Danish: Derudover fandt CHMP, at den nye anbefaling om antal behandlingsdage skulle ledsages af en tilsvarende begrænsning af pakningsstørrelsen (til 30 tabletter eller kapsler for 4 mg pakningen, til 14 tabletter eller kapsler for 8 mg pakningen, og til ti hætteglas/ampuller).
English: These products should also be contraindicated in women of childbearing potential not using contraception and during lactation.
Danish: Produkterne skal også være kontraindiceret til kvinder i den fertile alder, der ikke anvender sikker kontraception, samt under amning.
English: Continuous monitoring of any safety signal correlated with aneuploidy (i.e. teratogenicity, embryo-foetal toxicity / spontaneous abortion, impaired male fertility and cancer) and pregnancy reporting to collect structured data on accidental exposure to the drug should be performed.
Danish: Der skal foretages løbende overvågning af alle sikkerhedssignaler, der er korreleret med aneuploidi (dvs. teratogenicitet, embryoføtal toksicitet/spontanabort, nedsat mandlig fertilitet og kræft) og indberetning om graviditeter med henblik på at indsamle strukturerede data om accidentel eksponering for lægemidlet.
English: To address the risks of teratogenicity and embryo-toxicity/spontaneous abortions the CHMP agreed on contraindicating TCC during the entire pregnancy period, during lactation, and in women of childbearing potential not using contraception.
Danish: Til imødegåelse af risiciene for teratogenicitet og embryotoksicitet/spontanabort vedtog CHMP en kontraindikation for TCC i hele graviditeten og ammeperioden samt hos kvinder i den fødedygtige alder, der ikke anvender antikonception.
English: • six cases of congenital abnormalities (i.e. one multiple malformations leading to abortion, one pulmonary hypoplasia, one cleft palate, one spina bifida, one Poland's syndrome, one patent ductus arteriosus),
Danish: • seks tilfælde af medfødte misdannelser (et af multiple misdannelser medførende abort, et af pulmonal hypoplasi, et af ganespalte, et af spina bifida, et af Polands syndrom, og et af persisterende ductus arteriosus),
English: Genotoxicity data on aglycone metabolite SL59.0955 (M2)
Danish: Genotoksicitetsdata for aglycon-metabolitten SL59.0955 (M2)
English: • and 2 cases with unknown exposure period: o 1 case of teratogenic effects (malformations) associated with exposure in early pregnancy, o 1 case with an unknown evolution of the pregnancy due to lack of documentation.
Danish: • og 2 tilfælde med ukendt eksponeringsperiode: o 1 tilfælde af teratogene virkninger (misdannelser) ved eksponering tidligt i graviditeten, o 1 tilfælde, hvor udviklingen af graviditeten var usikker som følge af manglende dokumentation.
English: The CHMP reviewed all available data from pre-clinical and clinical studies, literature and post-marketing experience on aneuploidy for TCC containing medicinal products for systemic use.
Danish: CHMP gennemgik alle foreliggende data fra prækliniske og kliniske undersøgelser, den publicerede litteratur og erfaringer efter markedsføring vedrørende aneuploidi for lægemidler indeholdende TCC til systemisk brug.
English: This was associated with M1 plasma AUC of 4073 ng.h/mL, which is more than 20 times higher than M1 exposure observed in human after a 8 mg bid oral dose of TCC (175 ng.h/mL at 30 min).
Danish: Dette skete ved et AUC af M1 i plasma på 4 073 ngh/ml, som er over 20 gange mere end den observerede eksponering for M1 af mennesker efter en oral dosis af TCC på 8 mg to gange dagligt (175 ngh/ml ved 30 min).