natgillin/translations-raw huggingface dataset:
On 15 July 2011, Germany triggered a referral under Article 31 of Directive 2001/83/EC. 
Nemčija je 15. julija 2011 sprožila napotitveni postopek v skladu s členom 31 Direktive 2001/83/ES.
This effect is well demonstrated in several animal models. 
Učinek je bil dokazan na različnih živalskih modelih.
Tolperisone-containing products are currently approved in the following EU countries: Bulgaria, Cyprus, Czech Republic, Germany, Hungary, Latvia, Lithuania, Poland, Romania and Slovak Republic. 
Zdravila, ki vsebujejo tolperizon, so trenutno odobrena v naslednjih državah EU: v Bolgariji, na Cipru, v Češki republiki, Nemčiji, na Madžarskem, v Latviji, Litvi, na Poljskem, v Romuniji ter v Slovaški republiki.
The precise mechanism of action is not fully known. 
Natančen mehanizem njegovega delovanja ni povsem znan.
Therefore, in accordance with Article 32(4)(d) of Directive 2001/83/EC, the CHMP recommended: 
CHMP je torej v skladu s členom 32(4)(d) Direktive 2001/83/ES priporočil:
There are a few studies where a parenteral formulation was used. 
Obstaja nekaj študij, v katerih je bila uporabljena parenteralna oblika.
The CHMP also consulted its Neurology Scientific Advisory Group (SAG). 
CHMP se je posvetoval tudi s svojo znanstveno svetovalno skupino za nevrologijo (SAG).
It is well known that the safety profile of a product may vary depending on the formulation. 
Splošno znano je, da je varnostni profil zdravila lahko različen glede na formulacijo.
In addition, all patients started by receiving doses above the approved dose. 
Poleg tega so vsi bolniki na začetku prejemali odmerke, višje od odobrenih.
Tolperisone exerts its action at 3 levels: 
Tolperizon deluje na 3 ravneh:
The following indications have been approved in at least one Member State (specific wording of the indication may vary from product to product): 
Najmanj ena od držav članic je potrdila indikacije, naštete v nadaljevanju (besedilo indikacije se lahko od zdravila do zdravila razlikuje):
In contrast, the prematurely terminated Avigen study AV650-018 (2007) failed to demonstrate any effect in the multiple sclerosis population. 
Po drugi strani predčasno zaključena študija AV650-018 podjetja Avigen (2007) ni pokazala nobenih učinkov pri populaciji bolnikov z multiplo sklerozo.
This indication is mainly supported by the Stamenova (2005) study, which is of acceptable quality. 
Ta indikacija pretežno temelji na študiji, ki jo je izvedla Stamenova (2005), in je sicer sprejemljive kakovosti.
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. 
Zato je bil CHMP zaprošen za mnenje, ali naj se dovoljenja za promet z zdravili, ki vsebujejo tolperizon, in povezanimi imeni ohranijo, spremenijo, začasno umaknejo ali prekličejo.
The CHMP therefore carried out a new assessment of the available efficacy data in the concerned indication. 
CHMP je torej opravil novo oceno razpoložljivih podatkov o učinkovitosti pri zadevni indikaciji.
The conditions affecting the marketing authorisations are set out in Annex IV. 
Pogoji za dovoljenja za promet z zdravilom so določeni v Prilogi IV.
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. 
Zlasti je znova ocenil štiri združene analize (Alken 2005, Farkas 2011, Varga 2011a in Varga 2011b) randomiziranih kliničnih preskušanj (Pratzel 1995, Struck 2002 in Struck 2004) ter zaprosil delovno skupino za biostatistiko (BSWP), naj poda svoje mnenje o podatkih združenih analiz.
Overall summary of the scientific evaluation of tolperisone-containing products (see Annex I) 
Splošni povzetek znanstvenega vrednotenja zdravil, ki vsebujejo tolperizon (glejte Prilogo I)
It is therefore considered that efficacy in these indications has not been demonstrated. 
Zato velja, da učinkovitost zdravila v zvezi s temi indikacijami ni dokazana.
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. 
Podatke, na voljo v zvezi s to indikacijo, sta zagotovili dve opazovalni študiji (1986 in 1989), ki sta skupaj zajeli 166 bolnikov, ki so nekaj tednov dnevno prejemali 450 mg tolperizona.
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. 
Na splošno je menila, da analize niso bile ustrezno izvedene in da na podlagi predloženih podatkov ni mogoče oceniti, kako so bile pri analizah upoštevane značilnosti različnih populacij in zdravljenja.
Tolperisone is a centrally acting muscle relaxant first synthesized in 1956, and used in clinical practice since the 1960's. 
Tolperizon je mišični relaksant, ki deluje na osrednje živčevje in je bil prvič sintetiziran leta 1956, v klinični praksi pa so ga začeli uporabljati v 60. letih prejšnjega stoletja.
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) 
Priloga II Znanstveni zaključki in podlaga za spremembo pogojev dovoljenj za promet z zdravilom (peroralne oblike) ter preklic dovoljenj za promet z zdravilom (parenteralne oblike)
Hypotheses include structural similarity to the local anaesthetic lidocaine, so the risk for cross-reactions needs to be consistently described in the product information. 
Ena izmed hipotez je, da obstaja strukturna podobnost z lokalnim anestetikom lidokainom, zato mora biti tveganje za navzkrižne reakcije dosledno opisano v informacijah o zdravilu.
The interim analysis results indicated that it failed to achieve statistical significance in any evaluated efficacy endpoint. 
Vmesni rezultati analiz so pokazali, da učinki niso dosegli statistične značilnosti v nobenem od zaključenih opazovanih dogodkov učinkovitosti.
It is also noted that the reporting rates in Germany appear to be significantly higher than those calculated through the MAH's database. 
Ugotovljeno je bilo tudi, da je stopnja pogostosti poročanja v Nemčiji verjetno znatno višja, kot kažejo izračuni na podlagi podatkovne baze imetnika dovoljenja za promet z zdravilom.
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. 
Ugotovljeno je bilo, da informacije v povzetku glavnih značilnosti zdravila o medsebojnem delovanju zdravil, vplivu na sposobnost vožnje in upravljanje s stroji ter vplivu hrane na farmakokinetične parametre ne odražajo najnovejših razpoložljivih podatkov.
Due to lack of adequate data, no firm conclusions on the influence of renal or hepatic function can be drawn, although the existing data does not raise cause for concern. 
Zaradi pomanjkanja ustreznih podatkov ni mogoče podati zanesljivih zaključkov glede vpliva na delovanje ledvic in jeter, vendar pa na podlagi obstoječih podatkov ni razloga za skrb.
The actively controlled study was open label, used pentoxyphyllin as control and involved a total of 70 patients. 
Aktivno nadzorovana študija je bila odprtega tipa, za kontrolno sredstvo je bil uporabljen pentoksifilin, skupno pa je bilo vključenih 70 bolnikov.
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. 
Poleg tega je treba informacije o zdravilu posodabljati, da se zagotovi, da vsi izdelki vsebujejo dosledne in posodobljene informacije o medsebojnem delovanju zdravil, vplivu na sposobnost vožnje in upravljanje s stroji, vplivu hrane na biološko uporabnost, vplivu na delovanje ledvic in jeter ter o neželenih učinkih.
The CHMP also considered a recently conducted meta-analysis presented during the October 2012 oral explanation but raised concerns with regard to the methodology of the analysis and the quality of the included individual studies and therefore concluded that this meta-analysis did provide any additional support of the efficacy of tolperisone. 
CHMP je upošteval tudi nedavno izvedeno metaanalizo, predstavljeno med ustno razlago oktobra 2012, vendar je izrazil pomisleke v zvezi z metodologijo analize in kakovostjo vključenih posamičnih študij ter zato sklenil, da ta metaanaliza ne zagotavlja nobene dodatne potrditve učinkovitosti tolperizona.
The mechanism of tolperisone-related hypersensitivity is unknown. 
Mehanizem preobčutljivosti, povezane s tolperizonom, ni znan.
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. 
Prav tako je bilo ugotovljeno, da nista bila pri vseh izdelkih v informacije o zdravilu vključena neželena dogodka zmedenost in hiperhidroza, kar bi bilo treba poenotiti.
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. 
Zdi se, da trenutno odobrene informacije o zdravilu neustrezno odražajo tveganja oziroma jih bolnikom ne posredujejo na način, ki bi omogočal zgodnje prepoznavanje znakov preobčutljivosti.
The Ashworth scale used in this study is a validated instrument generally accepted for the clinical evaluation of degree of spasticity. 
Ashworthova lestvica, uporabljena v študiji, je potrjen instrument, ki se splošno uporablja za klinično vrednotenje stopnje spastičnosti.
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. 
Nevrolatirizem pretežno prizadene mlajše odrasle moške ob pomanjkanju hrane in se načeloma ne pojavlja v evropskih državah, zato je vprašljivo, ali je rezultate študije mogoče posplošiti in vključiti v obstoječe indikacije.
There is a discrepancy between the patterns of spontaneous reports and the reports from studies. 
Med vzorcema spontanih poročil in poročil, ki so jih zagotovile študije, obstajajo določena razhajanja.
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. 
Pomaga lahko zavirati patološko vzdraženost perifernih receptorjev, ki jo sproži bolečina in lahko povzroči različne motorične ali vegetativne reflekse, ki bi vodili do povišanega mišičnega tonusa.
However, it only included patients with spasticity caused by neurolathyrism. 
Vendar pa je študija zajela samo bolnike s spastičnostjo, ki jo povzroča nevrolatirizem.
• The Committee considered that the risk of hypersensitivity reactions is more significant than previously identified. 
• da je odbor ocenil, da je tveganje za preobčutljivostne reakcije večje, kot je bilo sprva ugotovljeno;
The only studies that exist are of observational nature, were conducted in a heterogeneous population and contain extremely limited information. 
Edine obstoječe študije so opazovalne narave, poleg tega pa so zajele heterogeno populacijo bolnikov in so ponudile izjemno omejene informacije.
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). 
Ob upoštevanju ocene BSWP je sklenil, da obstajajo resni pomisleki glede ustreznosti statistične metodologije, ki se je uporabila za združene analize, predvsem ker so temeljile na modelu fiksnih učinkov v prisotnosti očitne heterogenosti, zlasti pa zato, ker se glavni razlogi za zavrnitev dokazov nanašajo na pomanjkanje skladnosti s ključnimi merili, podrobno določenimi v dokumentu CHMP Points to consider (CPMP/EWP/2330/99).
Analysis of spontaneous reports suggests that hypersensitivity reactions are more frequent in women, patients with previous or current allergic disease or those using NSAIDs or other analgesics concomitantly. 
Analiza spontanih poročil je razkrila, da so preobčutljivostne reakcije pogostejše pri ženskah, bolnikih s preteklimi ali trenutnimi alergijskimi boleznimi in pri ljudeh, ki istočasno jemljejo nesteroidna protivnetna zdravila (NSAID) ali druge analgetike.
A causal relationship with tolperisone was assessed as at least possible in 90% of all hypersensitivity reactions. 
Podane so bile ocene, da je bila vzročna povezava s tolperizonom vsaj možen vzrok za 90 % vseh preobčutljivostnih reakcij.
Van Denburg et al. (2008) have found a 33% change in the Ashworth Scale to correlate with a 1-point change in the Physician's global assessment score in patients with post-stroke spasticity, indicating clinical relevance. 
Van Denburg et al. (2008) so ugotovili, da 33-odstotno izboljšanje na Ashworthovi lestvici sovpada z izboljšanjem za 1 točko pri zdravnikovi splošni oceni bolnika s spastičnostjo, ki je posledica možganske kapi, kar kaže na klinično pomembnost zdravila.
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. 
Družba Gedeon Richter PLC je predlagala, naj se indikacija omeji na „kratkoročno zdravljenje mišičnih spazmov pri odraslih bolnikih z akutno nespecifično bolečino v križu“, pri čemer zdravljenje traja največ sedem dni.
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. 
Zaključimo lahko, da je izmed štirih glavnih študij v zvezi z navedeno indikacijo, ki so postale dostopne po izdaji prvotnega dovoljenja za promet z zdravilom, ena študija precej pomanjkljiva, preostale tri pa niso uspele dokazati vpliva zdravila na rezultate učinkovitosti.
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. 
Prav tako je menila, da ni mogoče niti izpeljati nobenega zaključka glede učinkovitosti tolperizona niti opredeliti nobenih podskupin bolnikov, ki bi lahko imeli koristi od zdravljenja s tolperizonom v primerjavi z drugimi zdravljenji.
There are no GCPcompliant studies, there is 1 actively-controlled trial and a few observational studies. 
Izvedena ni bila nobena študija, ki bi bila skladna z dobro klinično prakso, obstajajo pa ena aktivno nadzorovana preiskava in nekaj opazovalnih študij.
The CHMP has considered the totality of the available data on the safety and efficacy of tolperisone. 
CHPM je upošteval vse razpoložljive podatke glede varnosti in učinkovitosti tolperizona.
The chemical structure of tolperisone is similar to that of lidocaine and, similarly to lidocaine, tolperisone has membrane stabilising effects. 
Kemijska zgradba tolperizona je podobna zgradbi lidokaina, poleg tega pa tako kot lidokain tudi tolperizon sodeluje pri stabilizaciji membrane.
The improvement in Ashworth scale was accompanied by a statistically significant difference in the investigator's overall assessment of efficacy in favour of tolperisone. 
Poleg izboljšanja na Ashworthovi lestvici velja omeniti tudi statistično pomembno razliko pri raziskovalčevi splošni oceni učinkovitosti, ki je bila v korist tolperizona.
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. 
Študija, ki jo je leta 2002 izvedel Struck, ni pokazala nobenega omembe vrednega izboljšanja pri primarnem opazovanem dogodku, dva sekundarna parametra, kjer je bilo opaženo statistično pomembno izboljšanje, pa sta subjektivna in klinično nepomembna, saj bi morala biti zabeležena tudi ustrezna izboljšanja pri klinično pomembnih parametrih, kot so intenzivnost bolečin, bolečine pri gibanju in gibljivost.
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. 
Vendar pa so bili rezultati učinkovitosti pri podskupini, ki je prejemala dnevni odmerek do 450 mg, skladni z rezultati pri celotni populaciji vključenih bolnikov (ITT).
Very limited information exists on the efficacy of tolperisone in this indication. 
O učinkovitosti tolperizona v zvezi s to indikacijo je na voljo zelo omejeno število informacij.
• 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. 
• spremembo pogojev dovoljenja za promet z zdravilom za peroralne oblike zdravil iz Priloge I, za katere so zadevni razdelki povzetka glavnih značilnosti zdravila in navodilo za uporabo navedeni v Prilogi III k mnenju;
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. 
Tudi drugi funkcionalni sekundarni parametri (npr. spremenjen Barthelov indeks (instrument za ocenjevanje dnevnih aktivnosti), zmožnost opravljanja rutinskih dejavnosti in vzdržljivost pri hoji) so dosledno kazali na večjo učinkovitost tolperizona v primerjavi s placebom.
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. 
Tudi študija, ki jo je leta 2001 izvedel Hodinka, ni pokazala omembe vrednih sprememb pri primarnem opazovanem dogodku, kratkotrajno izboljšanje pa je 7. dan sicer bilo opaženo na Roland-Morrisovi lestvici prizadetosti, vendar so učinki 14. dan izginili.
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. 
Vendar je odbor menil, da predlagana študija ne zadostuje za zagotovitev prepričljivih dokazov o možni učinkovitosti tolperizona v zvezi s predlagano indikacijo, zlasti zaradi predlaganega kratkega trajanja zdravljenja.
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. 
Študija Melke (1997) je poleg znižanja mišičnega tonusa (glede na Ashworthovo lestvico) zabeležila tudi sistematično izboljšanje funkcionalnih parametrov, kar kaže na klinično pomembnost zdravila.
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. 
Ker pa je preobčutljivost bolj značilnost zdravilne učinkovine kot formulacije zdravila, so pomisleki, ki so se pojavili v zvezi s peroralnimi oblikami, pomembni tudi za parenteralne oblike.
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. 
Nemčija je menila, da številna poročila o preobčutljivostnih reakcijah, ki jih je prejela po odobritvi zdravila, kažejo na nekatera varnostna tveganja, ki niso uravnotežena z omejenim številom dokazov o učinkovitosti zdravila.
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. 
V predloženih študijah so namreč zabeležili majhno število poročil o preobčutljivostnih reakcijah, medtem ko je med spontanimi poročili takih več kot polovica.
It possesses high affinity for nervous tissue, reaching the highest concentrations in the brain stem, spinal cord and peripheral nerve tissue. 
Tolperizon ima veliko afiniteto do živčnega tkiva, najvišje koncentracije pa doseže v možganskem deblu, hrbtenjači in perifernem živčevju.
Following the adoption of the CHMP opinion and recommendations during the June 2012 CHMP meeting, re-examination requests were received from Gedeon Richter PLC and PP Nature Balance Lizenz GmbH, as they considered that there is adequate data supporting the efficacy of tolperisone in the “treatment of muscular hypertonicity and muscle spasms associated with locomotor diseases” indication. 
Po sprejetju mnenja CHMP in priporočil na sestanku CHMP junija 2012 sta družbi Gedeon Richter PLC in PP Nature Balance Lizenz GmbH poslali zahtevka za ponovni pregled, saj po njunem mnenju obstajajo zadostni podatki, ki potrjujejo učinkovitost tolperizona pri indikaciji „zdravljenje mišične hipertonije in mišičnih spazmov, povezanih z obolenji lokomotornega sistema“.
The Struck 2004 study also failed to demonstrate a significant improvement in the primary endpoint. 
Študija, ki jo je Struck opravil leta 2004, prav tako ni pokazala omembe vrednega izboljšanja pri primarnem opazovanem dogodku.
Mean maximum walking distance per 2 minutes at final visit was approx. 70 meters in the tolperisone and 40 meters in the placebo group. 
Povprečna najdaljša prehojena razdalja v 2 minutah pri zadnjem obisku je znašala približno 70 metrov pri bolnikih, ki so prejemali tolperizon, in 40 metrov pri bolnikih, ki so prejemali placebo.
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). 
Študija Stamenove je dopuščala titracijo dnevnih odmerkov do 900 mg, tako da je samo podskupina (35 %) bolnikov, zdravljenih s tolperizonom, dobivala odmerek, ki je v povzetku glavnih značilnosti zdravila trenutno naveden kot odobren (150-450 mg).
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. 
V obeh študijah je tolperizon prejemala izredno heterogena populacija bolnikov, vključenih v rehabilitacijski program, zato je nemogoče ločiti učinke tolperizona od učinkov drugih dejavnikov, kar pomeni, da podatki študij ne morejo podpreti dokazov o učinkovitosti v zvezi z omenjeno indikacijo.
Tolperisone reduces the reticulo-spinal facilitation in the brainstem and has been shown to be effective in alleviating experimental gamma-rigor of reticular origin. 
Tolperizon zmanjša retikulospinalni spodbujevalni vpliv v možganskem deblu in dokazano učinkovito lajša okorelost receptorjev gama retikularnega izvora.