FrancophonIA/ELRC3.0 huggingface dataset:
English: It was also noted that not all products mentioned the adverse events confusion and hyperhidrosis in the product information and that this should be harmonised.
Danish: Det blev også bemærket, at ikke alle produkter nævnte bivirkningerne forvirring og hyperhidrose i produktoplysningerne, og at dette bør harmoniseres.
English: The CHMP was therefore requested to give its opinion on whether the marketing authorisations for medicinal products containing tolperisone, and associated names should be maintained, varied, suspended or withdrawn.
Danish: CHMP blev derfor anmodet om at udtale sig om, hvorvidt markedsføringstilladelserne for lægemidler, der indeholder tolperison, og tilknyttede navne burde opretholdes, ændres, suspenderes eller inddrages.
English: Annex II Scientific conclusions and grounds for Variation to the terms of the Marketing Authorisations (oral formulations) and Revocation of the Marketing Authorisations (parenteral formulations)
Danish: Bilag II Videnskabelige konklusioner og begrundelse for ændring af betingelserne for markedsføringstilladelserne (orale formuleringer) og tilbagekaldelse af markedsføringstilladelserne (parenterale formuleringer)
English: The mechanism of tolperisone-related hypersensitivity is unknown.
Danish: Mekanismen i tolperisonrelateret overfølsomhed er ukendt.
English: The data available on this indication comes from two observational studies (1986 and 1989) with a total of 166 patients, where 450 mg tolperisone were given daily for a few weeks.
Danish: De tilgængelige data om denne indikation stammer fra to observationsundersøgelser (1986 og 1989) med i alt 166 patienter, hvor 450 mg tolperison blev indgivet dagligt i nogle få uger.
English: However, as hypersensitivity is a characteristic of the active substance rather than of the formulation, the concerns identified with the oral formulations are also relevant for the parenteral formulation.
Danish: Eftersom overfølsomhed er et kendetegn for det aktive stof snarere end for formuleringen, er de bekymringer, der er identificeret i forbindelse med de orale formuleringer, imidlertid også relevante for den parenterale formulering.
English: Validation of new parameters needs to be done beforehand if proof of efficacy is to be derived from a study.
Danish: Nye parametre skal valideres på forhånd, hvis virkningen skal dokumenteres i en undersøgelse.
English: Very limited information exists on the efficacy of tolperisone in this indication.
Danish: Der findes meget begrænset information om virkningen af tolperison i denne indikation.
English: Tolperisone is a centrally acting muscle relaxant first synthesized in 1956, and used in clinical practice since the 1960's.
Danish: Tolperison er et centralt virkende muskelafslappende middel, der blev syntetiseret for første gang i 1956 og har været anvendt i klinisk praksis siden 1960'erne.
English: The actively controlled study was open label, used pentoxyphyllin as control and involved a total of 70 patients.
Danish: Den aktivt kontrollerede undersøgelse var åben, anvendte pentoxyfyllin som kontrollægemiddel og involverede i alt 70 patienter.
English: Neurolahyrism affects predominantly young adult males at time of famine and generally does not occur in European countries, therefore generalisation of the study results to the existing indication is questionable.
Danish: Neurolatyrisme rammer primært unge voksne mænd i forbindelse med hungersnød og forekommer generelt ikke i europæiske lande, hvorfor en generalisering af undersøgelsesresultaterne til den eksisterende indikation er tvivlsom.
English: Finally, the Hodinka 2001 study also failed to demonstrate a relevant difference in the primary endpoint, and the only transient significant difference observed was in the Roland-Morris Disability Scale at day 7, having disappeared at day 14.
Danish: Endelig påviste Hodinkaundersøgelsen (2001) ikke en relevant forskel i det primære endepunkt, og den eneste observerede forbigående signifikante forskel blev registreret på Roland-Morris Disability-skalaen på dag syv og var forsvundet på dag 14.
English: In contrast, the prematurely terminated Avigen study AV650-018 (2007) failed to demonstrate any effect in the multiple sclerosis population.
Danish: Avigen-undersøgelsen AV650-018 (2007), der blev afsluttet før tid, påviste derimod ingen virkning hos populationen med multipel sklerose.
English: Relevant studies also exist in the locomotor indication, the majority of which failed to demonstrate the efficacy of the product.
Danish: Der findes også relevante undersøgelser inden for den lokomotoriske indikation, hvoraf størstedelen ikke dokumenterede lægemidlets virkning.
English: However, it only included patients with spasticity caused by neurolathyrism.
Danish: Den omfattede dog kun patienter med spasticitet som følge af neurolatyrisme.
English: • The Committee considered that the risk of hypersensitivity reactions is more significant than previously identified.
Danish: • udvalget vurderede, at risikoen for overfølsomhedsreaktioner er mere signifikant end hidtil dokumenteret
English: It is also noted that the reporting rates in Germany appear to be significantly higher than those calculated through the MAH's database.
Danish: Det bemærkes endvidere, at indberetningstallene i Tyskland lader til at være væsentligt højere end dem, der er beregnet via databasen hos indehaveren af markedsføringstilladelsen.
English: Mean maximum walking distance per 2 minutes at final visit was approx. 70 meters in the tolperisone and 40 meters in the placebo group.
Danish: Den gennemsnitlige maksimale gåafstand på to minutter ved det sidste besøg var på ca. 70 m i tolperisongruppen og 40 m i placebogruppen.
English: There is a discrepancy between the patterns of spontaneous reports and the reports from studies.
Danish: Der er forskel på mønstrene for henholdsvis de spontane indberetninger og indberetningerne fra undersøgelser.
English: In particular, the CHMP re-assessed 4 pooled analyses (Alken-2005, Farkas-2011, Varga2011a and Varga-2011b) of randomised clinical trials (Pratzel 1995, Struck 2002 and Struck 2004) and requested the Biostatistics Working Party (BSWP) to give its view on the pooled analyses data.
Danish: CHMP vurderede herunder fire samlede analyser (Alken-2005, Farkas-2011, Varga-2011a og Varga-2011b) af randomiserede kliniske undersøgelser (Pratzel 1995, Struck 2002 og Struck 2004) igen og anmodede arbejdsgruppen vedrørende biostatistik (BSWP) om at udtale sig om de samlede analysedata.
English: In both studies, tolperisone is given to a very heterogeneous population as part of a rehabilitation program, so it is not possible to isolate the effect of tolperisone from the effect of other interventions and therefore this data does not support the evidence of efficacy in this particular indication.
Danish: I begge undersøgelser indgives tolperison til en meget heterogen population som led i et revalideringsprogram, hvorfor det ikke er muligt at isolere virkningen af tolperison fra virkningen af andre indgreb, og dataene støtter derfor ikke dokumentationen af virkningen i denne specifikke indikation.
English: The only study in this indication with a positive outcome contains significant methodological deficiencies which preclude any conclusion on the efficacy of the product.
Danish: Den eneste undersøgelse inden for denne indikation med et positivt resultat er forbundet med væsentlige metodologiske mangler, hvilket udelukker enhver konklusion om lægemidlets virkning.
English: The currently approved product information does not seem to adequately reflect the risk or communicate it to patients in order to allow early identification of signs of hypersensitivity.
Danish: De godkendte produktoplysninger lader ikke til korrekt at afspejle risikoen eller formidle den til patienterne med henblik på at gøre det muligt at identificere tegn på overfølsomhed på et tidligt tidspunkt.
English: It is therefore considered that efficacy in these indications has not been demonstrated.
Danish: Det vurderes derfor, at virkningen inden for disse indikationer ikke er dokumenteret.
English: It can therefore be concluded that of the four main studies in this indication, which became available after the initial marketing authorisation was granted, one suffers from substantial deficiencies and the remaining 3 failed to demonstrate an effect on the efficacy outcome.
Danish: Det kan således konkluderes, at af de fire største undersøgelser inden for denne indikation, som blev publiceret, efter at den oprindelige markedsføringstilladelse var udstedt, var én behæftet med alvorlige mangler, og de resterende tre dokumenterede ingen effekt på virkningsresultatet.
English: Tolperisone reduces the reticulo-spinal facilitation in the brainstem and has been shown to be effective in alleviating experimental gamma-rigor of reticular origin.
Danish: Tolperison reducerer den retikulospinale facilitering i hjernestammen og har vist sig effektivt til lindring af eksperimental gamma rigor af retikulær oprindelse.
English: • Central-spinal level - tolperisone reduces the increased mono- and polysynaptic reflex activity in a dose-dependent manner to the physiological level.
Danish: • Centralt spinalt niveau - tolperison reducerer den øgede mono- og polysynaptiske refleksaktivitet på en dosisafhængig måde til det fysiologiske niveau.
English: While only a small number of reports of hypersensitivity reactions were observed in the studies submitted, they represent more than half of all spontaneous reports.
Danish: Kun et lavt antal indberetninger af overfølsomhedsreaktioner blev observeret i de indsendte undersøgelser, mens de tegnede sig for mere end halvdelen af de spontane indberetninger.
English: The product information should also be updated so that all products contain consistent and updated information on interactions, effects on ability to drive and use machines, the effect of food on bioavailability, influence of renal or hepatic function and adverse reactions.
Danish: Produktoplysningerne bør endvidere ajourføres, således at alle produkter indeholder konsekvent og ajourført information om interaktioner, virkning på evnen til at føre motorkøretøj eller betjene maskiner, fødevarers virkning på biotilgængelighed, indflydelse på nyre- eller leverfunktion og bivirkninger.
English: The only studies that exist are of observational nature, were conducted in a heterogeneous population and contain extremely limited information.
Danish: De eneste undersøgelser er observationsundersøgelser, som blev gennemført hos en heterogen population og indeholder ekstremt begrænset information.
English: • Peripheral level - stabilises the membrane of neurons, and consequently supresses the amplitude and frequency of the action potentials.
Danish: • Perifert niveau - stabiliserer neuroners membran og hæmmer dermed amplituden og frekvensen af aktionspotentialer.
English: However, efficacy results of the subgroup treated with a daily tolperisone dose of up to 450 mg/day were consistent with the results of the whole ITT population.
Danish: Resultater for virkning i den undergruppe, der blev behandlet med en tolperisondosis på 450 mg/dag, var imidlertid i overensstemmelse med resultaterne for den samlede ITT-population.
English: It was noted that information in the Summary of Product Characteristics regarding interactions, effects on ability to drive and use machines and effect of food on pharmacokinetic parameters was not reflecting the latest available data.
Danish: Det blev bemærket, at oplysningerne i produktresuméet om interaktioner, virkning på evnen til at føre motorkøretøj eller betjene maskiner og fødevarers virkning på farmakokinetiske parametre ikke afspejlede de senest tilgængelige data.
English: The Struck 2002 study failed to demonstrate a significant improvement in the primary endpoint, and the two secondary parameters for which a statistically significant improvement could be seen are subjective, and not considered clinically meaningful given that they were not accompanied by commensurate improvements in clinically relevant parameters such as pain intensity, pain at movement and motility.
Danish: Struck-undersøgelsen (2002) påviste ikke en signifikant forbedring i det primære endepunkt, og de to sekundære parametre, for hvilke der kunne ses en statistisk signifikant forbedring, er subjektive og vurderes ikke som værende af klinisk relevans, da de ikke blev ledsaget af proportionale forbedringer i klinisk relevante parametre, såsom smerteintensitet, smerte ved bevægelse og motilitet.
English: The SAG was also of the opinion that it is not possible to derive any conclusion regarding the efficacy of tolperisone, nor was it possible to identify any specific patient subgroups that could benefit from treatment with tolperisone compared to other treatments.
Danish: SAG var desuden af den opfattelse, at der ikke kan drages konklusioner om virkningen af tolperison, og at det ligeledes ikke var muligt at udpege bestemte patientundergrupper, der kunne have gavn af behandling med tolperison sammenlignet med andre behandlinger.
English: The improvement in Ashworth scale was accompanied by a statistically significant difference in the investigator's overall assessment of efficacy in favour of tolperisone.
Danish: Forbedringen på Ashworth-skalaen blev ledsaget af en statistisk signifikant forskel i undersøgerens generelle vurdering af virkningen til fordel for tolperison.
English: Gedeon Richter PLC proposed to restrict the indication to “Short-term treatment of muscle spasms in adult patients with acute non-specific low back pain”, with a maximum duration of treatment of 7 days.
Danish: Gedeon Richter PLC foreslog at begrænse indikationen til kortvarig behandling af muskelspasmer hos voksne patienter med akutte uspecifikke lænderygsmerter med en maksimal behandlingsvarighed på syv dage.
English: • Central-reticular level - An imbalance between supraspinal facilitatory and inhibitory control can also lead to an enhanced reflex activity and an increased muscle tone.
Danish: • Centralt retikulært niveau - en ubalance mellem supraspinal faciliterende og inhiberende kontrol kan også føre til øget refleksaktivitet og øget muskeltonus.
English: The interim analysis results indicated that it failed to achieve statistical significance in any evaluated efficacy endpoint.
Danish: De foreløbige analyseresultater indikerer, at undersøgelsen ikke opnåede statistisk signifikans i nogen af de undersøgte effektendepunkter.
English: In the Melka study (1997), the reduction in muscle tone (as measured by the Ashworth scale) was accompanied by a consistent improvement in functional parameters indicative of clinical relevance.
Danish: I Melka-undersøgelsen (1997) blev den reducerede muskeltonus (som målt på Ashworth-skalaen) ledsaget af en konsekvent forbedring i funktionelle parametre, hvilket indikerer klinisk relevans.
English: It is therefore not plausible how the reduction of a triggered PPT could have been translated into a clinically relevant effect in patients with painful reflex muscle spasm.
Danish: Det er derfor ikke sandsynliggjort, hvordan reduktionen i en udløst PPT kan tolkes som en klinisk relevant virkning hos patienter med smertefulde reflektoriske muskelspasmer.
English: The Feher study (1985) used the Rivermead scale, which has shown high validity and reliability in assessment of motor function in stroke patients.
Danish: Feher-undersøgelsen (1985) anvendte Rivermead-skalaen, der har vist høj validitet og pålidelighed i vurderingen af den motoriske funktion hos patienter med postapopleksi.
English: Hypotheses include structural similarity to the local anaesthetic lidocaine, so the risk for cross-reactions needs to be consistently described in the product information.
Danish: Hypoteser omfatter strukturel lighed med det lokalbedøvende middel lidocain, og risikoen for krydsreaktioner skal derfor konsekvent være beskrevet i produktoplysningerne.
English: A causal relationship with tolperisone was assessed as at least possible in 90% of all hypersensitivity reactions.
Danish: En årsagssammenhæng med tolperison blev vurderet som i det mindste mulig ved 90 % af alle overfølsomhedsreaktionerne.
English: The Ashworth scale used in this study is a validated instrument generally accepted for the clinical evaluation of degree of spasticity.
Danish: Ashworth-skalaen, der blev anvendt i undersøgelsen, er et valideret instrument, som er generelt accepteret til klinisk evaluering af spasticitetsgraden.
English: These are mostly observational and extremely limited documentation is available.
Danish: Der er overvejende tale om observationsundersøgelser, og dokumentationen er yderst begrænset.
English: The chemical structure of tolperisone is similar to that of lidocaine and, similarly to lidocaine, tolperisone has membrane stabilising effects.
Danish: Tolperisons kemiske struktur ligner den kemiske struktur for lidocain, og ligesom lidocain har tolperison membranstabiliserende virkninger.
English: However, the Committee considered the proposed study to be inadequate to provide conclusive evidence regarding the potential efficacy of tolperisone in the proposed indication, in particular due to the short treatment duration proposed.
Danish: Udvalget fandt imidlertid den foreslåede undersøgelse utilstrækkelig til at kunne give afgørende evidens for den potentielle virkning af tolperison ved den ansøgte indikation, navnlig på grund af den foreslåede korte behandlingsvarighed.
English: Hypotheses include tolperisone metabolites as hapten formations activating the patient's immune system through covalent modification of proteins, or structural similarity to the local anaesthetic lidocaine.
Danish: Hypoteser omfatter tolperisonmetabolitter som haptenformationer, der aktiverer patientens immunsystem gennem kovalent modifikation af proteiner, eller strukturel lighed med det lokalbedøvende middel lidocain.
English: Hypersensitivity can be a significant event and cases of anaphylactic reactions/anaphylactic shock have been reported.
Danish: Overfølsomhed kan være en alvorlig hændelse, og der er indberettet tilfælde af anafylaktiske reaktioner/anafylaktisk chok.
English: In the Stamenova study, patients could be titrated up to 900 mg per day, thus only a subgroup (35%) of tolperisone patients was treated within the dose range currently approved in the SPC (150-450 mg).
Danish: I Stamenova-undersøgelsen kunne patienters dosis titreres op til 900 mg/dag, hvilket betød, at kun en undergruppe (35 %) af tolperisonpatienterne blev behandlet inden for det dosisinterval, der på nuværende tidspunkt er godkendt i produktresuméet (150-450 mg).
English: Overall, the SAG considered that the analyses has not been performed appropriately and that the provided data did not allow an assessment of how the various population and treatment characteristics were taken into account for the analyses.
Danish: Overordnet fandt SAG, at analyserne ikke var udført tilfredsstillende, og at det ikke på baggrund af de forelagte data var muligt at vurdere, hvordan der i analyserne var taget hensyn til de forskellige karakteristika af populationer og behandlinger.
English: In the only study in this indication where superiority of tolperisone over placebo in the primary outcome was shown (Pratzel 1995), this was achieved using a new parameter in the formula for calculation which was not pre-determined but rather introduced in post-hoc efficacy analysis.
Danish: I den eneste undersøgelse af denne indikation, hvor tolperisons overlegenhed i forhold til placebo blev dokumenteret i det primære resultat (Pratzel 1995), blev resultatet opnået ved at anvende en ny parameter i beregningsformlen, som ikke var forudbestemt, men nærmere indført i efterfølgende virkningsanalyser.
English: The CHMP therefore carried out a new assessment of the available efficacy data in the concerned indication.
Danish: CHMP foretog derfor en ny vurdering af de foreliggende data om virkning ved den pågældende indikation.
English: Germany considered that the numerous reports of hypersensitivity reactions received in the post authorisation phase are indicative of a safety concern which is not balanced by the limited evidence of efficacy.
Danish: Tyskland vurderede, at de mange indberetninger af overfølsomhedsreaktioner, der blev modtaget i fasen efter godkendelsen, tyder på et sikkerhedsmæssigt problem, der ikke opvejes af den begrænsede dokumentation for virkningen.
English: It is capable of inhibiting the pathological peripheral impulse condition induced by pain, which could start various motoric or vegetative reflexes that would lead to increased muscular tone.
Danish: Tolperison er i stand til at inhibere den patologiske perifere impulsmekanisme, der induceres af smerte, og som kan udløse forskellige motoriske eller vegetative reflekser, der ville føre til øget muskeltonus.
English: The mean improvement in the Ashworth score found in the Stamenova study was 32% in the overall ITT (intention-to-treat) population and 42% in the subgroup of patients receiving 300-450 mg/day).
Danish: Den gennemsnitlige forbedring på Ashworthskalaen i Stamenova-undersøgelsen var på 32 % hos den samlede ITT-population (»Intention-ToTreat«) og 42 % hos undergruppen af patienter, der modtog 300-450 mg/dag.
English: Having noted the BSWP assessment, the CHMP concluded that there are serious concerns regarding the appropriateness of the statistical methodology used for the pooled analyses, mainly because they have been based on fixed effects models in the presence of evident heterogeneity but in particular because the main grounds for the refusal of the evidence relate to the lack of compliance with the key criteria detailed in the CHMP Points to consider document (CPMP/EWP/2330/99).
Danish: Efter gennemgang af vurderingen fra BSWP konkluderede CHMP, at der er alvorlig betænkelighed ved egnetheden af den statistiske metode, der blev anvendt til de samlede analyser, hovedsagelig fordi de er baseret på en model med faste effekter i tilstedeværelse af åbenlys heterogenitet, men specielt fordi hovedbegrundelsen for afvisningen af evidensen er manglende overholdelse af hovedkriterierne i CHMP's dokument vedrørende spørgsmål, der skal tages i betragtning (CPMP/EWP/2330/99).
English: Further functional secondary parameters (i.e. the modified Barthel Index (assessing activities of daily living), capacity to perform routine activities and walking endurance) consistently favoured tolperisone over placebo.
Danish: Yderligere funktionelle sekundære parametre (modificerede Barthel-indeks (der vurderer dagligdags aktiviteter), evne til at udføre rutineaktiviteter og udholdenhed ved gang) placerede konsekvent tolperison højere end placebo.
English: Tolperisone reduces the sodium influx through the isolated nerve membrane in a dose dependent way, thus amplitude and frequency of action potentials are reduced.
Danish: Tolperison reducerer natriuminflux gennem den isolerede nervemembran på en dosisafhængig måde, hvilket betyder, at amplituden og frekvensen af aktionspotentialer reduceres.
English: Furthermore, inhibitory effects on voltage dependent Ca2+ channels have been demonstrated, suggesting that tolperisone might also reduce the transmitter release in addition to its membrane stabilising effect.
Danish: Endvidere er der påvist inhiberende virkninger på spændingsafhængige Ca2+-kanaler, hvilket tyder på, at tolperison ud over sin membranstabiliserende virkning muligvis også reducerer transmitterfrigørelsen.
English: • The variation to the terms of the marketing authorisation for the oral formulations of medicinal products referred to in Annex I, for which the relevant sections of the summary of product characteristics and package leaflet are set out in Annex III to the opinion.
Danish: • ændring af markedsføringstilladelsen for de orale formuleringer af de i bilag 1 omhandlede lægemidler, for hvilke de relevante afsnit af produktresuméet og indlægssedlen fremgår af bilag III til udtalelsen,
English: The MAHs also disagreed with the CHMP assessment of the safety profile of tolperisone.
Danish: Indehaverne af markedsføringstilladelserne var ligeledes uenige i CHMP's vurdering af sikkerhedsprofilen for tolperison.