FrancophonIA/ELRC3.0 huggingface dataset:
English: The Committee concluded that trimetazidine is associated with the occurrence of Parkinson syndrome and related symptoms.
Danish: Udvalget konkluderede, at trimetazidin er associeret med fremkomst af Parkinsons syndrom og beslægtede symptomer.
English: The improvement in the primary end point with trimetazidine was observed in the pooled analysis of patients receiving 35 and 70 mg twice daily and in the analysis of patients receiving either 35 mg twice daily or 70 mg twice daily.
Danish: Forbedringen af det primære effektmål med trimetazidin blev observeret i den samlede analyse af patienter, der fik 35 og 70 mg to gange dagligt, og i analysen af patienter, der fik enten 35 mg to gange dagligt eller 70 mg to gange dagligt.
English: No significant difference between groups could be found for the other secondary endpoints (total exercise duration, total workload and clinical endpoints).
Danish: Der sås ingen signifikant forskel mellem grupperne for de andre, sekundære effektmål (samlet arbejdsvarighed, samlet arbejdsbelastning og kliniske effektmål).
English: The CHMP considers that the revised indication is in line with the scientific evidence available at present for trimetazidine as add-on therapy and it is supported by trials that became available after the initial authorisation and considered to be of sufficient methodological quality and by meta-analyses that have come to similar conclusions.
Danish: CHMP finder, at den reviderede indikation stemmer overens med den nuværende, tilgængelige, videnskabelige evidens for trimetazidin som supplerende behandling, og dette understøttes af undersøgelser, der blev tilgængelige efter den første godkendelse, og som anses for at være af tilstrækkelig, metodologisk kvalitet, samt af metaanalyser, der er kommet til lignende konklusioner.
English: It is acknowledged that extrapyramidal symptoms reported in patients receiving TMZ have a low prevalence (incidence of 0.36/100,000 PY) and are generally reversible after TMZ withdrawal.
Danish: Det er anerkendt, at ekstrapyramidale symptomer rapporteret for patienter, der får trimetazidin, har en lav prævalens (forekomst på 0,36/100.000 patientår) og generelt er reversible efter seponering af trimetazidin.
English: • The Committee also recommended that trimetazidine can cause or worsen parkinsonian symptoms (tremor, akinesia, hypertonia).
Danish: • Udvalget tilkendegav også, at trimetazidin kan forårsage eller forværre parkinsonsymptomer (tremor, akinesi, hypertoni).
English: The clinical studies supporting ophthalmic field suffer from major methodological flaws.
Danish: De kliniske undersøgelser til støtte for det oftalmologiske område har alvorlige metodologiske fejl.
English: Three studies were conducted against betahistine (Haguenauer, 1980; Kluyskens, 1990; Martini, 1990) to demonstrate a clinical benefit of trimetazidine in the treatment of dizziness.
Danish: Der blev udført tre undersøgelser i forhold til betahistin (Haguenauer 1980, Kluyskens 1990, Martini 1990) med henblik på at påvise en klinisk fordel ved trimetazidin til behandling af svimmelhed.
English: The posthoc analysis of the study in 298 patients receiving trimetazidine in combination mainly with metoprolol is in line and it is considered useful to better assess the effect of trimetazidine in a population of patients that are often difficult to be treated with haemodynamic agents.
Danish: Post hoc-analysen af undersøgelsen hos 298 patienter, som fik trimetazidin i kombination med hovedsageligt metoprolol, stemmer overens, og det anses som nyttigt for en bedre vurdering af trimetazidins virkning hos en patientgruppe, der ofte er vanskelig at behandle med hæmodynamiske midler.
English: In response to the CHMP request regarding the re-evaluation of the risk/benefit ratio of trimetazidine (all forms and dosages) in the ENT indications, 9 clinical studies (Wayoff, 1984; Sterkers, 2001; Vitte, 2002; Haguenauer, 1980; Kluyskens, 1990; Martini, 1990; Morgon 1990; Coyas 1990 and France cochlea study, 2009 presented as support of safety since the efficacy objective was not reached) were submitted or presented as literature references.
Danish: Som svar på CHMP's anmodning om reevaluering af risk/benefit-forholdet for trimetazidin (alle former og doseringer) til øre-næse-hals-indikationer blev 9 kliniske undersøgelser (Wayoff 1984, Sterkers 2001, Vitte 2002, Haguenauer 1980, Kluyskens 1990, Martini 1990, Morgon 1990, Coyas 1990 og den franske cochlea-undersøgelse 2009 som støtte for sikkerheden, eftersom effektmålet ikke blev nået) indsendt eller fremlagt som litteraturhenvisninger.
English: The aim of the Sellier study (2003) was to assess the efficacy of the combination of trimetazidine MR 70 mg/day in patients suffering from angina pectoris who were insufficiently controlled on 50 mg/day of atenolol after two months of treatment.
Danish: Formålet med Sellier-undersøgelsen (2003) var at vurdere virkningen af kombinationen af trimetazidin 70 mg/dag depottabletter hos patienter, der led af angina pectoris, og som ikke var tilstrækkeligt kontrolleret på 50 mg/dag atenolol efter to måneders behandling.
English: Trimetazidine (TMZ) is a metabolic agent whose aim is to protect against ischemia by increasing glucose metabolism relative to that of fatty acids.
Danish: Trimetazidin (TMZ) er et metabolisk stof, hvis formål er at beskytte mod iskæmi ved at øge omdannelsen af glucose i forhold til omdannelsen af fedtsyrer.
English: Population pharmacokinetics data indicate that serious adverse events were more frequent in treated elderly patients with high trimetazidine plasma concentrations.
Danish: De farmakokinetiske data for denne population indikerer, at alvorlige bivirkninger forekom hyppigere hos behandlede, ældre patienter med høje plasmakoncentrationer af trimetazidin.
English: Based on the data submitted for the ophthalmologic indications, the CHMP considered that the evidence does not fulfill the requirements and criteria for the evaluation of efficacy currently requested in these pathologies.
Danish: Baseret på de indsendte data for de oftalmologiske indikationer fandt CHMP, at evidensen ikke opfylder de aktuelle, nødvendige krav og kriterier for evaluering af virkningen på disse patologier.
English: Grounds for the variation to the terms of the marketing authorisation
Danish: Begrundelser for ændring af betingelserne for markedsføringstilladelsen Følgende noteres:
English: In addition, the SmPC has to be amended to include a warning about trimetazidine induced parkinsonism, its diagnosis and management.
Danish: Derudover skal produktresuméet rettes, så det indeholder en advarsel om trimetazidin-induceret parkinsonisme samt diagnosticering og behandling af dette.
English: The three studies of short duration (up to 3 months) conducted against reference products of the time (e.g cinnarizine, piridoxilate ), included a small number of patients who presented very heterogeneous or poorly defined pathologies (n=19, n=24 and n=8 respectively for the Cornand (1982), Cordella (1982) and Perdriel (1988) studies).
Danish: De tre kortvarige undersøgelser (op til 3 måneder), der blev udført i forhold til daværende referenceprodukter (f.eks. cinnarizin, piridoxilat), omfattede et lille antal patienter med meget heterogene eller dårligt definerede patologier (n=19, n=24 og n=8 i undersøgelserne af hhv. Cornand (1982), Cordella (1982) og Perdriel (1988)).
English: Accordingly, the SmPC has been amended to include dose information in the elderly and in patients with moderate renal impairment (creatinine clearance [30-60] ml/min).
Danish: Følgelig er produktresuméet ændret til at omfatte doseringsinformation for ældre og for patienter med moderat nyreinsufficiens (creatinin-clearance [30-60] ml/min).
English: The CHMP agreed that trimetazidine can cause or worsen parkinsonian symptoms (tremor, akinesia, hypertonia), which should be regularly investigated, especially in elderly patients.
Danish: CHMP fandt, at trimetazidin kan forårsage eller forværre parkinsonsymptomer (tremor, akinesi, hypertoni), og at disse bør undersøges jævnligt, især hos ældre patienter.
English: Although the methodology followed by the MAH may be regarded as not totally compliant to the currently accepted standards, no major bias affecting the interpretation of study results appears evident and all analyses show a beneficial effect of trimetazidine combined with metoprolol on exercise tolerance, myocardial ischemia and clinical symptoms.
Danish: Selvom den metodologi, som indehaveren af markedsføringstilladelsen har anvendt, ikke kan anses som helt i overensstemmelse med de aktuelt godkendte standarder, er der ingen væsentlig bias, som påvirker fortolkningen af undersøgelsens resultater, og alle analyser viser en gavnlig virkning af trimetazidin kombineret med metoprolol på belastningstolerance, myokardiel iskæmi og kliniske symptomer.
English: It is considered that the study is only adequate to show the efficacy of trimetazidine with reference to the primary endpoint, time to onset of angina pectoris, as no significant difference between groups could be found for the other secondary endpoints (total exercise duration, total workload and clinical endpoints).
Danish: Det tages i betragtning, at undersøgelsen kun er tilstrækkeligt til at vise virkningen af trimetazidin i forhold til det primære effektmål, tid til fremkomst af angina pectoris, da der ikke sås nogen signifikante forskelle mellem grupperne for de andre, sekundære effektmål (samlet arbejdsvarighed, samlet arbejdsbelastning og kliniske effektmål).
English: In the overall population, including both asymptomatic and symptomatic patients, trimetazidine failed to demonstrate a benefit on both ergometric (total exercise duration, time to onset of 1mm ST and time to onset angina) and clinical endpoints.
Danish: I den samlede population, herunder både asymptomatiske og symptomatiske patienter, kunne der ikke påvises en fordel ved trimetazidin for hverken ergometriske (samlet arbejdsvarighed, tid til fremkomst af 1 mm ST-segment og tid til fremkomst af angina) eller kliniske effektmål.
English: The proposed multicentre, randomised, double-blind, placebo controlled long-term study in postpercutaneous coronary intervention (PCI) patients and the prospective and comparative cohort study to assess the prevalence of EPS in patients receiving trimetazidine may be adequate to solve the concerns on long-term efficacy and safety of trimetazidine.
Danish: Den foreslåede multicenterbaserede, randomiserede, dobbeltblinde, placebokontrollerede langtidsundersøgelse af patienter efter perkutan koronar intervention (PCI) samt det prospektive og komparative kohorteundersøgelse til vurdering af prævalensen af ekstrapyramidale symptomer hos patienter, der får trimetazidin, kan være tilstrækkelig til at løse problemerne ved trimetazidins langvarige virkning og sikkerhed.
English: Recent surveys in patients with coronary artery disease have shown that most patients with angina do not receive adequate anti-anginal therapy because of haemodynamic intolerance or chronotropic incompetence.
Danish: Nyere undersøgelser blandt patienter med koronararteriesygdom har vist, at de fleste patienter med angina ikke får tilstrækkelig antianginøs behandling på grund af hæmodynamisk intolerans eller kronotrop inkompetence.
English: These data support the efficacy of trimetazidine in add-on to beta-blockers.
Danish: Disse data understøtter virkningen af trimetazidin som supplement til betablokkere.
English: Indeed, it is well known that patients with proven coronary artery disease who are asymptomatic may not have inducible ischemia and that in these patients anti-anginal treatments are ineffective in improving exercise capacity.
Danish: Det er dog velkendt, at asymptomatiske patienter med påvist koronararteriesygdom ikke nødvendigvis har inducérbar iskæmi, og at antianginøs behandling ikke forbedrer belastningskapaciteten hos disse patienter.
English: Trimetazidine was shown to have an effect very similar to that of non-heart rate−lowering anti-anginal agents: nicorandil, ranolazine, long-acting nitrates and dihydropyridines, with less than a few seconds differences in exercise tolerance test (ETT) ergometric parameters.
Danish: Trimetazidin blev påvist at have en virkning, der meget ligner virkningen af ikke-hjertefrekvenssænkende antianginøse stoffer: nicorandil, ranolazin, langtidsvirkende nitrater og dihydropyridiner, med færre end et par sekunders forskel i ergometriske parametre fra test af belastningstolerans.
English: The main identified serious ADR is related to Parkinson syndrome and related symptoms.
Danish: Den vigtigste, identificerede, alvorlige bivirkning er tilknyttet Parkinsons syndrom og beslægtede symptomer.
English: Most of these studies included patients presenting very heterogeneous pathologies of various severities with absence of prior stratification on these pathologies, and of very limited duration of treatment (between 2 and 3 months) not in line with what is required by these pathologies that necessitate long term treatments.
Danish: De fleste af disse undersøgelser inkluderede patienter med meget heterogene patologier af forskellige sværhedsgrader med fravær af tidligere stratificering af disse patologier og meget begrænset behandlingsvarighed (mellem 2 og 3 måneder), hvilket ikke stemte overens med nødvendigheden af langvarig behandling af disse patologier.
English: Eight of them show inclusions of patients presenting very heterogeneous pathologies of various severities with absence of prior stratification on these pathologies, and short durations of treatment (between 2 and 6 months) while these pathologies are known to progress slowly and to require extended treatments.
Danish: Otte af dem inkluderede patienter med meget heterogene patologier af forskellige sværhedsgrader med fravær af tidligere stratificering af disse patologier og kort behandlingsvarighed (mellem 2 og 6 måneder), selvom disse patologier vides at udvikle sig langsomt med behov for langvarig behandling.
English: In a 1962 patients three-month randomised, double-blinded study (VASCO study, 2011) on top of atenolol 50 mg/d, two dosages of trimetazidine (70 mg/d and 140 mg/d) were tested versus placebo.
Danish: I en randomiseret, dobbeltblind undersøgelse fra 1962 over tre måneder (VASCO-undersøgelsen, 2011) blev der ud over atenolol 50 mg/dag undersøgt to doseringer af trimetazidin (70 mg/dag og 140 mg/dag) versus placebo.
English: This risk has been identified in post marketing setting and in literature based on: positive dechallenge of Parkinson symptoms after the only withdrawal of TMZ, positive rechallenge, significant higher coprescription of antiparkinson drugs in TMZ group compared to control group (IMS study) and significant higher number of patients that begin antiparkinson drugs after the introduction of TMZ compared to control group (IMS study).
Danish: Denne risiko er blevet identificeret efter markedsføringstilladelsen og i litteraturen på grundlag af: positiv dechallenge af Parkinsons symptomer efter seponering af trimetazidin, positiv rechallenge, signifikant flere ordinationer af samtidige antiparkinsonmidler i trimetazidin-gruppen, sammenlignet med kontrolgruppen (IMS-undersøgelsen), og et signifikant større antal patienter, der starter på antiparkinsonmidler efter introduktion af trimetazidin, sammenlignet med kontrolgruppen (IMS-studiet).
English: The CHMP concluded that following the assessment of all these studies the efficacy of trimetazidine is not proven on the ophthalmological indication.
Danish: Efter at have vurderet alle disse undersøgelser konkluderede CHMP, at trimetazidins virkning ikke er påvist ved den oftalmologiske indikation.
English: Caution should be exercised when prescribing trimetazidine to patients in whom an increased exposure is expected such as with moderate renal impairment and elderly patients older than 75 years old.
Danish: Der bør udvises forsigtighed ved ordinering af trimetazidin til patienter, hos hvem der forventes øget eksponering, såsom med moderat nyreinsufficiens, og ældre patienter over 75 år.
English: • The Committee is of the opinion that the benefits continue to outweigh the risks in patients with angina pectoris but that treatment should be restricted to add-on to existing treatments in patients who are not adequately controlled by or intolerant to other medicines for angina pectoris.
Danish: • Udvalget mener, at fordelene fortsat opvejer risiciene for patienter med angina pectoris, men at behandlingen bør begrænses til at være et supplement til eksisterende behandling af patienter, der ikke kan kontrolleres tilstrækkeligt med eller ikke kan tåle andre lægemidler mod angina pectoris.
English: However, in the subgroup of symptomatic patients (n= 1574) trimetazidine (140 mg) significantly improved total exercise duration (+23.8 s versus +13.1 s placebo; p=0.001) and time to onset of angina (+46.3 s versus +32.5 s placebo; p=0.005).
Danish: Men i undergruppen af symptomatiske patienter (n= 1574) forbedrede trimetazidin (140 mg) signifikant den samlede belastningsvarighed (+23,8 s versus +13,1 s placebo, p=0,001) og tiden til fremkomst af angina (+46,3 s versus +32,5 s placebo, p=0,005).
English: Therefore, considering these methodological weaknesses, the dossier is insufficient to conclude that trimetazidine has satisfactorily demonstrated a clinical benefit as adjuvant symptomatic treatment of dizziness, tinnitus or hearing loss.
Danish: Når man derfor tager disse metodologiske svagheder i betragtning, er dokumentationen ikke tilstrækkelig til at konkludere, at trimetazidin i tilfredsstillende grad giver en klinisk fordel som adjuverende, symptomatisk behandling af svimmelhed, tinnitus eller høretab.
English: Caution should be exercised when prescribing trimetazidine to patients in whom an increased exposure is expected moderate due to renal impairment, or in elderly patients older than 75 years old.
Danish: Der bør udvises forsigtighed ved ordinering af trimetazidin til patienter, hos hvem der forventes moderat øget eksponering på grund af nyreinsufficiens, eller til ældre patienter over 75 år.
English: study) to address all important, potential and identified risks, particularly Parkinsonism and a drug utilization study to verify the compliance of prescribers regarding the restricted indication after marketing authorisation changes was also agreed.
Danish: Det blev også vedtaget at udføre en PASS-undersøgelse for at håndtere alle vigtige, potentielle og identificerede risici, især parkinsonisme, og en undersøgelse af lægemiddelanvendelse med henblik på at bekræfte receptudstederes overholdelse af den indskrænkede indikation efter ændringerne til markedsføringstilladelsen.
English: The efficacy of trimetazidine is sufficiently demonstrated as add-on therapy in the shortmedium-term (weeks /months) treatment of symptomatic patients with angina who are inadequately controlled by or intolerant to first-line antianginal therapies.
Danish: Virkningen af trimetazidin er i tilstrækkelig grad påvist som supplerende kort- og mellemtidsbehandling (uger/måneder) af symptomatiske patienter med angina, som ikke kan kontrolleres tilstrækkeligt med eller ikke kan tåle antianginøse førstelinjebehandlinger.
English: The Emeriau PK study has shown high plasma concentrations of trimetazidine in old patients, receiving the usual dose of 35 mg twice daily.
Danish: Emeriaus farmakokinetiske undersøgelse har vist høje plasmakoncentrationer af trimetazidin hos ældre patienter, der fik den sædvanlige dosis på 35 mg to gange dagligt.
English: Results from this study did not highlight any clinical benefit of trimetazidine in comparison to the placebo to prevent the bilateralisation of choroidal neovascularisation in patients suffering from age-related macular degeneration, principal criterion of evaluation chosen to demonstrate the clinical benefit of trimetazidine 35 mg to slow the progression of age-related macular degeneration (ARMD).
Danish: Resultaterne fra denne undersøgelse påviste ingen klinisk fordel ved trimetazidin, sammenlignet med placebo som profylakse af bilateralisering af koroidal neurovaskularisering hos patienter med aldersbetinget maculadegeneration (AMD), som er det vigtigste kriterium for vurdering af den kliniske fordel ved trimetazidin 35 mg for så vidt angår nedsættelsen af udviklingen af aldersbetinget maculadegeneration (ARMD).
English: In a 426-patients randomised, double blind, placebo-controlled study (TRIMPOL-II), trimetazidine (60mg/day) added to metoprolol 100mg daily (50 mg b.i.d) for 12 weeks significantly improved statistically exercise tests parameters and clinical symptoms as compared to placebo: total exercise duration +20.1s, p= 0.023, total workload +0.54 METs, p=0.001, time to 1-mm ST-segment depression +33.4s, p=0.003, time to onset of angina +33.9s, p<0.001, angina attacks/week -0.73, p=0.014 and short acting nitrates consumption/week, -0.63, p=0.032, without hemodynamic changes.
Danish: I et randomiseret, dobbeltblindt, placebokontrolleret undersøgelse med 426 patienter (TRIMPOL-II) forbedrede trimetazidin (60 mg/dag) tilsat metoprolol 100 mg/dag (50 mg bid) i 12 uger signifikant statistiske parametre for arbejds-EKG samt kliniske symptomer sammenlignet med placebo: samlet arbejdsvarighed +20,1 s, p=0,023, samlet arbejdsbelastning +0,54 METs, p=0,001, tid til 1-mm ST-segment-depression +33,4 s, p=0,003, tid til fremkomst af angina +33,9 s, p<0,001, anginaanfald/uge -0,73, p=0,014 og forbrug af korttidsvirkende nitrater/uge, -0,63, p=0,032, uden hæmodynamiske ændringer.
English: Furthermore, these studies present other specific weaknesses: the Cordella study (versus cinnarizine) did not include inter-group comparison.
Danish: Disse undersøgelser har desuden andre specifikke svagheder: I Cordella-undersøgelsen (ift.
English: The submitted data comparing TMZ to either placebo or the other reference products or based on cohorts without comparator provide insufficient demonstration of a relevant clinical benefit of trimetazidine in the ancillary treatment of visual acuity decrease and visual field disturbances due to vascular reasons.
Danish: De indsendte data, der sammenlignede trimetazidin med enten placebo eller de andre referenceprodukter eller ud fra kohorter uden komparator, påviser i utilstrækkelig grad en relevant, klinisk fordel ved trimetazidin som supplerende behandling af nedsat synsskarphed og synsfeltforstyrrelser af vaskulære årsager.
English: In addition, a pharmacokinetics study was agreed with the MAH to investigate the effects of renal impairment and age on the trimetazidine safety profile.
Danish: Derudover blev der i overensstemmelse med indehaveren af markedsføringstilladelsen udført et farmakokinetisk undersøgelse for at vurdere indvirkningen af nyreinsufficiens og alderen på sikkerhedsprofilen for trimetazidin.
English: Favourable results from ‘Dizziness Handicap Inventory questionnaire' were suggested by the small Sterckers and Vitte studies.
Danish: De små Sterckers- og Vitteundersøgelser tydede på gunstige resultater fra spørgeskemaet »Dizziness Handicap Inventory«.
English: The occurrence of movement disorders such as parkinsonian symptoms, restless leg syndrome, tremors, gait instability should lead to definitive withdrawal of trimetazidine.
Danish: Fremkomsten af bevægelsesforstyrrelser som f.eks. parkinsonsymptomer, »Restless Legs Syndrome«, tremor og ganginstabilitet bør medføre definitiv seponering af trimetazidin.
English: The CHMP concluded that the limited data generated by the clinical trials submitted for the ENT indication, insufficiently support the demonstration of a relevant clinical benefit of trimetazidine for patients suffering from tinnitus, vertigo or hearing loss and that either the currently ENT registered indication or the newly claimed indications cannot be supported.
Danish: CHMP konkluderede, at de begrænsede data fra de indsendte, kliniske undersøgeler for øre-næsehals-indikationen ikke i tilstrækkelig grad understøtter påvisning af en relevant, klinisk fordel ved trimetazidin til patienter, der lider af tinnitus, vertigo eller høretab, og at hverken den aktuelt registrerede øre-næse-hals-indikation eller de nyangivne indikationer kan understøttes.