FrancophonIA/ELRC3.0 huggingface dataset:
English: The trials submitted with active arm comparators (Gate 1, Nava 2007, Addolorato 1999 and Nimmerrichter 2002) had several methodological flaws such as open label, small sample size, heterogeneity in the studies' population, lack of protocol or defined primary endpoints, assessment of large number of outcomes, and long enrolment period, which lead to conclusions based on post-hoc analysis that do not provide sufficient evidence to establish the efficacy for the use of sodium oxybate granules in the treatment of AWS.
Danish: De undersøgelser i ansøgningen, der omfatter aktive sammenligningspræparater (Gate 1, Nava 2007, Addolorato 1999 og Nimmerrichter 2002), havde adskillige metodemæssige mangler (ikkeblindet, lille stikprøvestørrelse, heterogenitet i undersøgelsespopulationen, ingen protokol eller ingen definerede primære endepunkter, vurdering af et stort antal udfald samt lang inklusionsperiode), som førte til konklusioner baseret på post hocanalyser, der ikke giver tilstrækkelig evidens til klarlæggelse af lægemidlets effekt ved anvendelse af natriumoxybat-granulat til behandling af alkoholabstinenser.
English: In conclusion, further to the initial assessment and the re-examination procedure, the CHMP maintains its initial opinion that the benefit-risk balance of this medicinal product is not favourable in both of the proposed indications.
Danish: I forlængelse af den første vurdering og revurderingen fastholder CHMP afslutningsvis sin første udtalelse og mener fortsat, at benefit/risk-forholdet for lægemidlet er ugunstig i de to ansøgte indikationer.
English: These data are therefore considered insufficient to establish the efficacy of Alcover, granules in sachets, in the proposed indications;
Danish: Disse data vurderes derfor som værende utilstrækkelige til at klarlægge effekten af Alcover-granulat i brev i de ansøgte indikationer.
English: • With regards to the identified and potential risks related to the use of Alcover granules in sachets, the Committee considered the proposed risk minimisation measures, mainly to mitigate the potential risk of abuse, switch of addiction/ dependence and withdrawal in the light of the proposed indications;
Danish: • Hvad angår de identificerede risici ved brug af Alcover-granulat i brev, gennemgik udvalget under hensyn til de ansøgte indikationer de foreslåede risikominimeringsforanstaltninger, primært med henblik på at mindske den potentielle risiko for misbrug, ny afhængighed og abstinenser.
English: CHMP discussion on grounds for re-examination
Danish: CHMP's gennemgang af ansøgerens begrundelse for revurdering
English: Overall, the CHMP maintains its initial opinion that the results of the submitted clinical studies are not sufficient to establish the efficacy of Alcover (sodium oxybate) granules in the maintenance of alcohol abstinence and treatment of alcohol withdrawal syndrome (AWS) as there are several drawbacks in the design of these clinical studies, including open-label designs, small sample size, choice of patient population and absence of clearly defined, statistically significant outcomes, DRL not being recorded at baseline, low dose of comparator, and lack of assessment of effects on seizures or delirium as the most concerning events in alcohol withdrawal.
Danish: CHMP fastholder samlet set sin udtalelse og mener fortsat ikke, at resultaterne af de kliniske undersøgelser i ansøgningen er tilstrækkelige til at klarlægge effekten af Alcover-granulat (natriumoxybat) til vedligeholdelse af alkoholafholdenhed og behandling af alkoholabstinenser, da der er adskillige mangler ved undersøgelsernes udformning (ikkeblindet, lille stikprøvestørrelse, uhensigtsmæssigt valg af patientpopulation og fravær af tydeligt definerede, statistisk signifikante resultater, manglende baseline-registrering af DRL, lav dosis af sammenligningspræparat samt manglende vurdering af indvirkningen på krampeanfald og delirium (de mest bekymrende hændelser i forbindelse med alkoholabstinenser).
English: The meta-analysis that included GATE 2, SMO032/10/03, Gallimberti 1992 and Di Bello 1995 have several methodological flaws and quality concerns such as GATE 2 did not evaluate the population of interest; SMO032/10/03 trial included only a subset of High/Very High DRL patients and failed to meet its primary endpoint; Gallimberti trial did not report primary endpoint or follow-up time; Di Bello had a very small sample size (total n=17) and failed to specify the primary endpoint.
Danish: GATE 2 evaluerede ikke den relevante population, SMO032/10/03-undersøgelsen omfattede kun en undergruppe af patienter med meget høj DRLværdi og opfyldte ikke det primære endepunkt, Gallimberti-undersøgelsen rapporterede ikke det primære endepunkt eller opfølgningsperioden, og Di Bello havde en meget lille populationsstørrelse (total n=17) og anførte ikke det primære endepunkt.
English: • The Committee reviewed the totality of the data provided by the applicant in writing and in the oral explanations and related to the efficacy and safety of Alcover and associated names, 750 mg, 1250 mg, 1750 mg granules in sachets in the proposed indications for the maintenance of alcohol abstinence and the treatment of alcohol withdrawal syndrome; The Committee also considered the grounds submitted by the applicant within the re-examination procedure, and the views from an ad-hoc expert group.
Danish: • Udvalget har gennemgået alle de data, som ansøgeren har fremlagt skriftligt og i sin mundtlige redegørelse vedrørende sikkerhed og effekt af Alcover-granulat (og relaterede navne) i brev 750 mg, 1 250 mg, 1 750 mg i de ansøgte indikationer, dvs. til vedligeholdelse af alkoholafholdenhed og behandling af alkoholabstinenser.
English: The Committee concluded that in the absence of demonstration of efficacy for Alcover granules in sachets, the benefit-risk balance of this medicinal product is not favourable in the proposed indications.
Danish: Udvalget konkluderede, at benefit/risk-forholdet for dette lægemiddel ikke er gunstigt i de ansøgte indikationer, da effekten af Alcover-granulat i brev ikke er påvist.
English: Talk to your doctor.
Danish: Tal med lægen.
English: Second induction (if required)
Danish: Anden induktion (hvis nødvendig)
English: Day 1 (as per standard medical practice)
Danish: Dag 1 (som ved almindelig medicinsk praksis)
English: • Infections (including serious infections)
Danish: • Infektioner (herunder alvorlige infektioner)
English: g. Based on Fisher's exact test.
Danish: Baseret på Fishers eksakte test.
English: It is essentially ‘sodium-free'.
Danish: Det er i det væsentlige 'natriumfrit'
English: Age, race, and gender
Danish: Alder, race og køn
English: • Your doctor or nurse will decide on the correct dose.
Danish: • Lægen eller sygeplejersken vil fastsætte den korrekte dosis.
English: Contact your doctor immediately if you or your partner becomes pregnant while taking this medicine.
Danish: Kontakt straks lægen, hvis du eller din partner bliver gravid, mens du tager dette lægemiddel.
English: Not reported
Danish: Ikke rapporteret
English: Frequency unknown (frequency cannot be estimated from the available data):
Danish: Hyppighed ikke ukendt (kan ikke estimeres ud fra forhåndenværende data):
English: See section 5.2 for available data from in vitro studies.
Danish: 5.2 for tilgængelige data fra in vitro-studier.
English: The primary endpoint was event-free survival (EFS).
Danish: Det primære endepunkt var hændelsesfri overlevelse (EFS).
English: The median study size was 15 patients, with a range of 5-105 patients.
Danish: Den mediane studiestørrelse var 15 patienter med et interval på 5-105 patienter.
English: There is no information on fertility in patients.
Danish: Der foreligger ingen information om patienters fertilitet.
English: Previously untreated AML
Danish: Tidligere ubehandlet AML
English: • Postpone start of consolidation course.
Danish: • Udsættelse af konsolideringsforløbets start.
English: Pharmacokinetics in specific groups of subjects or patients
Danish: Farmakokinetik i specifikke grupper af forsøgspersoner eller patienter
English: MYLOTARG should not be given if you:
Danish: MYLOTARG må ikke gives, hvis du:
English: MYLOTARG will be stored by the health professionals at the hospital or clinic.
Danish: MYLOTARG opbevares af sundhedspersonalet på hospitalet eller klinikken.
English: This includes the time required for reconstitution, dilution, and administration.
Danish: Dette inkluderer den påkrævede tid for rekonstitution, fortynding og administration.
English: Therefore, caution should be exercised when driving or operating machines.
Danish: Derfor bør der udvises forsigtighed, når man fører motorkøretøj eller betjener maskiner.
English: Immediately contact your doctor if you experience any of the following serious side effects (see also section 2 “What you need to know before you are given MYLOTARG”):
Danish: Kontakt straks din læge, hvis du oplever nogen af de følgende alvorlige bivirkninger (se også afsnit 2 'Det skal du vide, før du får MYLOTARG'):
English: Some infections may be serious and may be life-threatening.
Danish: Visse infektioner kan være alvorlige og livstruende.
English: Routine clinical and laboratory surveillance testing during and after treatment is indicated.
Danish: Rutinemæssige kliniske og laboratorieovervågningstests under og efter behandling, er indiceret.
English: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Danish: Da der ikke er udført forligelighedsstudier, må dette lægemiddel ikke blandes med andre lægemidler.
English: Monitoring only total bilirubin may not identify all patients at risk of VOD/SOS.
Danish: Hvis man kun kontrollerer totalbilirubin, vil man måske ikke identificere alle patienter med risiko for VOD/SOS.
English: d: Within 30 days from the last dose of MYLOTARG.
Danish: d: Inden for 30 dage efter den sidste dosis af MYLOTARG.
English: Patients who experienced remission were also eligible for allogeneic transplantation.
Danish: Patienter, der oplevede remission, kvalificerede sig også til allogen transplantation.
English: Grade 3/4
Danish: Grad 3/4
English: Total bilirubin > 2 × ULN and AST and/or ALT > 2.5 × ULN
Danish: Total bilirubin > 2 × ULN og ASAT og/eller ALAT > 2,5 × ULN
English: An interval of at least 2 months between the last dose of MYLOTARG and transplantation was recommended.
Danish: Der anbefaledes et interval på mindst to måneder mellem den sidste dosis MYLOTARG og transplantation.
English: b. For patients experiencing a complete remission (CR) following induction.
Danish: Hos patienter, der oplever en komplet remission (CR) efter induktion.
English: Treatment of MYLOTARG overdose should consist of general supportive measures.
Danish: Behandling af en MYLOTARG overdosis skal bestå af generelle støtteforanstaltninger.
English: One of these patients experienced VOD 25 days after the subsequent HSCT.
Danish: Denne ene af patienterne oplevede VOD 25 dage efter den efterfølgende HSCT.
English: • High blood sugar
Danish: • Højt blodsukker
English: There are no or limited amount of data from the use of gemtuzumab ozogamicin in pregnant women.
Danish: Der er ingen eller en meget begrænset mængde data fra brugen af gemtuzumab ozogamicin hos gravide kvinder.
English: Single doses higher than 9 mg/m2 in adults were not tested.
Danish: Der blev ikke testet enkeltdoser højere end 9 mg/m hos voksne.
English: Complete blood counts should be monitored prior to each dose of MYLOTARG.
Danish: Komplette blodtal skal monitoreres før hver dosis med MYLOTARG.
English: As with all therapeutic proteins, there is potential for immunogenicity.
Danish: Immunogenicitet Som ved alle terapeutiske proteiner er der risiko for immunogenicitet.
English: MYLOTARG must not be used during pregnancy unless the potential benefit to the mother outweighs the potential risks to the foetus.
Danish: MYLOTARG må ikke anvendes under graviditeten, medmindre den potentielle fordel for moderen opvejer de potentielle risici hos fosteret.
English: There is no information regarding the presence of gemtuzumab ozogamicin or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production.
Danish: Der foreligger ingen data om tilstedeværelse af gemtuzumab ozogamicin eller dets metabolitter i human mælk, virkningerne på det ammede spædbarn eller virkningerne på mælkeproduktionen.
English: Most studies were in the compassionate use setting (70.6%).
Danish: De fleste studier blev gennemført i en kontekst med compassionate use (70,6 %).
English: MYLOTARG was given as induction treatment in most studies (82.4%).
Danish: MYLOTARG blev givet som induktionsbehandling i de fleste studier (82,4 %).
English: Some of the side effects could be serious and may occur during or after treatment with MYLOTARG.
Danish: Nogle af disse bivirkninger kan være alvorlige og kan opstå under og efter behandlingen med MYLOTARG.
English: Warnings and precautions When you first receive this medicine and during the course of treatment, tell your doctor or nurse if you:
Danish: Advarsler og forsigtighedsregler Første gang du får dette lægemiddel og under behandlingsforløbet, bør du fortælle din læge, hvis du:
English: Determination of PK parameters for unconjugated calicheamicin was limited due to the low systemic concentration levels.
Danish: Bestemmelse af PKparametre for ukonjugeret calicheamicin var begrænset grundet de lave systemiske koncentrationsniveauer.
English: Definitive conclusions cannot be drawn between the presence of antibodies and potential impact on efficacy and safety due to the limited number of patients with positive ADAs.
Danish: Der kan ikke drages afgørende konklusioner mellem tilstedeværelsen af antistoffer og mulig indvirkning på virkning og sikkerhed, da antallet af patienter med positive ADA'er var begrænset.
English: When MYLOTARG was given in combination, a cytarabine based regimen was used in 8 of the 9 studies.
Danish: Når MYLOTARG blev givet i kombination, blev der anvendt et cytarabinbaseret regime i 8 ud af de 9 studier.
English: The detection of ADAs is highly dependent on the sensitivity and specificity of the assay.
Danish: Påvisning af ADA'er afhænger i høj grad af analysens følsomhed og nøjagtighed.
English: DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 19 April 2018
Danish: Dato for første markedsføringstilladelse: 19. april 2018
English: Gemtuzumab ozogamicin is a CD33-targeted ADC.
Danish: Gemtuzumab ozogamicin er et CD33-målrettet ADC.
English: Because of this limited data collection, laboratory data from the combination therapy study are included in Table 5.
Danish: På grund af denne begrænsede dataindsamling bliver laboratoriedata fra kombinationsbehandlingsstudiet inkluderet i skema 5.
English: • Your doctor may change your dose, interrupt, or completely stop treatment with MYLOTARG if you have certain side effects.
Danish: • Lægen vil muligvis ændre din dosis, afbryde eller helt stoppe behandlingen med MYLOTARG, hvis du får bivirkninger.
English: N per study (range)
Danish: N per studie (interva l)
English: Few patients (13.7%) had low CD33 expression (less than 30% of blasts).
Danish: Få patienter (13,7 %) havde lav CD33-ekspression (færre end 30 % blaster).
English: The activity (cytotoxicity) of the resultant metabolites is expected to be significantly attenuated.
Danish: De resulterende metabolitters aktivitet (cytotoksicitet) forventes at være væsentligt svækket.
English: For these reasons, comparison of incidence of antibodies to gemtuzumab ozogamicin with the incidence of antibodies to other products may be misleading.
Danish: Af disse grunde kan en sammenligning af forekomst af antistoffer mod gemtuzumab ozogamicin med forekomst af antistoffer mod andre produkter være misvisende.
English: • Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose according to patient body surface area.
Danish: • Beregn det rekonstituerede opløsningsvolumen, der er nødvendig for at opnå den korrekte dosis i forhold til patientens legemsoverflade.
English: Treatment-related death due to septic shock was reported in 1 (0.8%) patients.
Danish: Behandlingsrelaterede dødsfald grundet septisk shock blev indberettet for 1 (0,8 %) patient.
English: The overall minimum and maximum ages range from 0 years to 22.3 years, with an overall median age of 8.7 years at the time of treatment.
Danish: Det samlede interval for minimum- og maksimumalder var 0 til 22,3 år, med en samlet medianalder på 8,7 år på behandlingstidspunktet.
English: Based on the primary definition of EFS: event dates (induction failure, relapse, or death) determined by investigator assessment.
Danish: På grundlag af den primære definition på EFS: hændelsesdatoer (induktionssvigt, tilbagefald eller dødsfald) bestemt ved investigators vurdering.
English: **Only selected safety data were collected in this study of newly diagnosed AML.
Danish: Der blev kun indsamlet udvalgte sikkerhedsdata i dette studie med nyligt diagnosticeret AML.
English: Limitations of this analysis include the small sample size of some studies, heterogeneity of the studies, and the lack of control data in this setting.
Danish: Begrænsninger ved denne analyse omfatter den lille populationsstørrelse i nogle af studierne, studiernes heterogenitet og manglen på kontroldata i denne kontekst.
English: f. Overall response difference; CI based on Santner and Snell method.
Danish: Samlet responsdifference; CI baseret på Santner og Snell-metoden.
English: Overall, 59.0% and 65.3% of patients had documented favourable/intermediate-risk disease by the National Comprehensive Cancer Network (NCCN) and European LeukaemiaNet (ELN) 2010 risk classifications, respectively.
Danish: Generelt havde 59,0 % og 65,3 % af patienterne dokumenteret gunstig/middel sygdomsrisiko ifølge henholdsvis National Comprehensive Cancer Network (NCCN) og European LeukaemiaNet (ELN) 2010 risikoklassifikationen.
English: c: Rates across studies were estimated using inverse variance weighting with fixed effects.
Danish: c: Rater på tværs af studierne blev estimeret ved brug af invers varians vægtning med faste effekter.
English: Almost all patients (>90 %) experienced myelosuppression across studies a: When MYLOTARG was given in combination, cytarabine was part of the combination studied in 8 out of the 9 studies.
Danish: Næsten alle patienter (> 90 %) oplevede myelosuppression på tværs af studierne a: Når MYLOTARG blev givet i kombination, var cytarabin en del af den undersøgte kombination i 8 ud af de 9 studier.
English: The mITT population included all patients who were randomised, unless withdrawal of consent prior to start of treatment and were analysed according to initial randomisation arm.
Danish: mITT-populationen omfattede alle patienter, der var randomiserede, medmindre samtykke var tilbagekaldt før behandlingsstart, og blev analyseret i henhold til den oprindelige randomiseringsarm.
English: ***Frequency is based on laboratory values (Grade per NCI CTCAE v4.03).
Danish: Hyppighed er baseret på laboratorieværdier (grad pr. NCI CTCAE v. 4.03).
English: If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.
Danish: Hvis du er gravid eller ammer, har mistanke om, at du er gravid, eller planlægger at blive gravid, skal du spørge din læge eller apotekspersonalet til råds, før du får dette lægemiddel.
English: If you feel unusually tired, dizzy or have a headache (these are very common side effects of MYLOTARG) you should not drive or use machines.
Danish: Hvis du føler dig usædvanligt træt, svimmel eller har hovedpine (det er meget almindelige bivirkninger af MYLOTARG), bør du ikke føre køretøjer eller betjene maskiner.
English: The infusion line does not need to be protected from light.
Danish: Infusionsslangen behøver ikke at være beskyttet mod lys.
English: Nervous system effects have not been observed in animals after administration of MYLOTARG.
Danish: Der er ikke observeret virkninger på nervesystemet hos dyr efter administration af MYLOTARG.
English: See section 2, “MYLOTARG contains sodium”.
Danish: Se afsnit 2, ”Mylotarg indeholder natrium”
English: • are allergic to gemtuzumab ozogamicin or any of the other ingredients of this medicine (listed in section 6).
Danish: • er allergisk over for gemtuzumab ozogamicin eller et af de øvrige indholdsstoffer (angivet i afsnit 6).
English: Increased embryolethality was also observed in the presence of maternal toxicity.
Danish: Der blev også observeret forhøjet embryomortalitet med maternel toksicitet.
English: Other severe or life-threatening non-haematologic toxicities
Danish: Andre alvorlige eller livstruende ikkehæmatologiske toksiciteter
English: For patients who proceed to HSCT, close monitoring of liver tests is recommended during the post-HSCT period, as appropriate.
Danish: Hos patienter, der går videre til HSCT, anbefales nøje overvågning af levertests i post-HSCT-perioden, hvis det er relevant.
English: • Your doctor will do blood tests during the treatment to check for side effects and for response to treatment.
Danish: • Lægen vil tage blodprøver under behandlingen for at undersøge, om du har bivirkninger, og om du reagerer på behandlingen.
English: Consider omitting scheduled dose if delayed more than 2 days between sequential infusions.
Danish: Overvej at undlade planlagt dosering, hvis der er mere end en 2 dages forsinkelse mellem sekventielle infusioner.
English: • During the infusion, the intravenous bag or syringes needs to be protected from light using a light (including ultraviolet light) blocking cover.
Danish: • Under infusionen skal den intravenøse pose eller sprøjter beskyttes mod lys (også ultraviloet lys) ved hjælp af et lysblokerende dække.
English: Probability (%) calculated by the product-limit method; CI calculated from the log log transformation of survival probability using a normal approximation and the Greenwood formula.
Danish: Sandsynlighed (%) beregnet med produktgrænsemetoden; CI beregnet ud fra log-log transformation af sandsynlighed for overlevelse ved hjælp af normalfordeling samt Greenwood-formlen.
English: Overall, the incidence rate of ADA development after MYLOTARG treatment was < 1% across the 4 clinical studies with ADA data.
Danish: Overordnet set var incidensraten for udvikling af ADA efter MYLOTARG-behandling <1 % på tværs af de 4 kliniske studier med data om ADA.
English: • Reduced number of white blood cells which may result in general weakness and a tendency to develop infections
Danish: • Nedsat antal hvide blodlegemer, hvilket kan medføre generel svækkelse og tendens til at udvikle infektioner
English: In the combination therapy study, VOD and hepatic laboratory abnormalities were collected.
Danish: I kombinationsbehandlingsstudiet blev VOD og hepatiske laboratorieabnormiteter indsamlet.
English: Number of studies
Danish: Antal studi er
English: The median time from the last gemtuzumab ozogamicin dose to onset of VOD was 9 days (range: 2-298 days).
Danish: Den gennemsnitlige tid fra sidste dosis gemtuzumab ozogamicin til indtræden af VOD var 9 dage (interval: 2-298 dage).
English: • Filtration of the diluted solution is required.
Danish: • Det er nødvendigt at filtrere den fortyndede opløsning.
English: No clinical PK data have been collected using the fractionated regimen; however, the PK have been simulated using the population PK model.
Danish: Der er ikke indsamlet nogen kliniske PK-data fra den fraktionerede doseringsplan; PK er dog blevet simuleret ved hjælp PK populationsmodellen.
English: MYLOTARG should be administered under the supervision of a physician experienced in the use of anticancer medicinal products and in an environment where full resuscitation facilities are immediately available.
Danish: MYLOTARG skal administreres under tilsyn af en læge med erfaring i behandling med lægemidler mod kræft og i omgivelser med komplet genoplivningsudstyr umiddelbart til rådighed.
English: Patients should be monitored for signs and symptoms of TLS and treated according to standard medical practice.
Danish: Patienten bør overvåges for symptomer på TLS og behandles i henhold til almindelig medicinsk praksis.