natgillin/translations-raw huggingface dataset:
STATEMENT OF ACTIVE SUBSTANCE(S) Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.35 mg pramipexole. 
NAVEDBA ENE ALI VEČ UČINKOVIN Ena tableta vsebuje 0,35 mg pramipeksola v obliki 0,5 mg pramipeksolijevega diklorida monohidrata.
Superiority of MIRAPEXIN prolonged-release tablets over placebo was demonstrated after 18 weeks of treatment on both the primary (UPDRS Parts II+III score) and the key secondary (CGI-I and PGI-I responder rates) efficacy endpoints in a double-blind placebo-controlled trial including a total of 539 patients with early Parkinson's disease. 
To je pokazalo dvojno slepo, s placebom nadzorovano preskušanje, ki je skupno zajela 539 bolnikov z zgodnjo Parkinsonovo boleznijo, ko so po 18 tednih jemanja z dvema lestvicama ocenili primarne (lestvica UPDRS, ocena II.
two MIRAPEXIN 0.52 mg prolonged-release tablets, OR four MIRAPEXIN 0.26 mg prolonged-release tablets. 
Število tablet ena MIRAPEXIN 0,26 mg tableta s podaljšanim sproščanjem ena MIRAPEXIN 0,52 mg tableta s podaljšanim sproščanjem ALI dve MIRAPEXIN 0,26 mg tableti s podaljšanim sproščanjem ena MIRAPEXIN 1,05 mg tableta s podaljšanim sproščanjem ALI dve MIRAPEXIN 0,52 mg tableti s podaljšanim sproščanjem ALI štiri MIRAPEXIN 0,26 mg tablete s podaljšanim sproščanjem
Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.35 mg pramipexole. 
MIRAPEXIN 0,35 mg tablete Ena tableta vsebuje 0,35 mg pramipeksola v obliki 0,5 mg pramipeksolijevega diklorida monohidrata.
Warnings and precautions Talk to your doctor before taking MIRAPEXIN. 
Pred začetkom jemanja zdravila MIRAPEXIN se posvetujte s svojim zdravnikom.
40 (1 cartridge x 40) tablets 
40 (1 vložek x 40) tablet
Immediate Packaging Pack size 
Jakost Farmacevtska oblika Pot uporabe Stična ovojnina Velikost pakiranja
EU number 
Številka EU Ime
Name 
Ovojnina
MA (EU) number (Invented) name Strength Pharmaceutical Form Route of Administration 
Številka (EU) dovoljenja za promet
All indications are not authorised in all EU MS. 
Vse indikacije niso odobrene v vseh državah članicah EU.
The CMDh position was forwarded to the European Commission. 
Stališče skupine CMDh je bilo posredovano Evropski komisiji.
2 - CMDh revised position 
2 - Revidirano stališče skupine CMDh
The PRAC noted that the worldwide estimated exposure of the originator's products alone is over 50 million patient-years and, in the EU over the last decade, around 6.8 million patient-years. 
Odbor PRAC je ugotovil, da je ocena globalne izpostavljenosti samo zdravilom originatorjem več kot 50 milijonov bolnikovih let, v zadnjem desetletju v EU pa približno 6,8 milijona bolnikovih let.
Further, the definition of the relevant clinical endpoints and the measurement of symptoms in these conditions are challenging (Rubin, 2007). 
Poleg tega sta opredelitev zadevnih kliničnih opazovanih dogodkov in meritev simptomov teh stanj težavna (Rubin, 2007).
These constitute the majority of the available evidence, in particular in the indications that were first authorised (e.g. secretolytic indication). 
Te študije sestavljajo večino razpoložljivih dokazov, zlasti pri indikacijah, ki so bile odobrene na začetku (npr. sekretolitična indikacija).
The level of evidence did not allow for further stratification by age group. 
Stopnja dokazov ni omogočala nadaljnje stratifikacije po starostnih skupinah.
This is not unexpected considering the methodological challenges inherent to this therapeutic area and evidential standards and requirements at the time when these products were first developed. 
To ni nepričakovano glede na metodološke izzive, povezane s tem terapevtskim področjem, in dokazne standarde ter zahteve v času prvega razvoja teh zdravil.
The PDCO was also of the view that these products are no longer the preferred treatment option in IRDS. 
Komisija PDCO je prav tako menila, da ta zdravila niso več prednostna možnost pri zdravljenju IRDS.
Of note, drugs started less than 4 days or more than 8 weeks before the onset of the reaction are unlikely to be responsible. 
Treba je omeniti, da zdravila, ki se uvedejo manj kot 4 dni ali več kot 8 tednov pred začetkom reakcije, niso verjetni povzročitelji.
Based on its clinical experience, the PDCO was of the view that there is no need for the use of these products in this indication in children below 2 years of age. 
Na podlagi kliničnih izkušenj je komisija PDCO menila, da ni potrebe po uporabi teh zdravil za to indikacijo pri otrocih, mlajših od dveh let.
However, prompt recognition of severe reactions and early withdrawal of the causative agent is the most important factor to minimise morbidity and mortality. 
Vendar sta takojšnje prepoznavanje hudih reakcij in zgodnja prekinitev jemanja povzročitelja najpomembnejša dejavnika pri zmanjševanju obolevnosti in umrljivosti.
The PRAC also considered the available data in the paediatric population. 
Odbor PRAC je prav tako upošteval razpoložljive podatke pri pediatrični populaciji.
1 - Overall summary of the scientific evaluation by the PRAC Safety issues 
1 - Splošni povzetek znanstvenega vrednotenja odbora PRAC
It is acknowledged that most of the indications are supported by old studies presenting limitations and deficiencies. 
Prav tako je upošteval, da je večina indikacij podprta s starimi študijami, kar pomeni omejitve in pomanjkljivosti.
During the decision making process, at a meeting of the Standing Committee on Medicinal Products for Human Use, some Member States raised new questions of technical nature which they considered had not been sufficiently addressed in the PRAC recommendation and CMDh position. 
Med odločanjem na sestanku Stalnega odbora za zdravila za uporabo v humani medicini so nekatere države članice sprožile nova vprašanja tehnične narave, za katere so menile, da v priporočilu odbora PRAC in stališču skupine CMDh niso bila obravnavana v zadostni meri.
Most often these patients receive a number of drugs concomitantly and causality assessment is difficult. 
Najpogosteje ti bolniki prejmejo številna sočasna zdravila, zato je ocena vzročnosti težavna.
In light of this, the PRAC recommendation and CMDh position was referred back to the Agency for further consideration. 
Na podlagi zgoraj navedenega sta bila priporočilo odbora PRAC in stališče skupine CMDh vrnjena Agenciji v ponovno preučitev.
It is recognised also that the limitations and uncertainties attached to the dataset hinder the ability to draw robust conclusions on the efficacy. 
Znano je tudi, da omejitve in negotovosti, povezane z naborom podatkom, ovirajo pripravo grobih zaključkov o učinkovitosti.
Ambroxol- and bromhexine-containing medicinal products have first been registered in a European Union (EU) Member State (MS) in 1978 and 1963, respectively, and are currently authorised in all EU MSs (as well as in Norway and Iceland) except the United Kingdom. 
Zdravila, ki vsebujejo ambroksol in bromheksin, so bila v državi članici Evropske unije prvič odobrena leta 1978 oziroma 1963, trenutno pa so odobrena v vseh državah članicah EU (vključno z Norveško in Islandijo), razen v Združenem kraljestvu.
However, the overall reporting rate is very low when the estimated exposure is considered and many confounders are present in these cases, the evidence supporting this risk is therefore weak. 
Vendar je splošni delež poročanja zelo majhen, če se upošteva ocena izpostavljenosti in obstaja prisotnost mnogih zavajajočih dejavnikov v teh primerih, zato so dokazi, ki podpirajo to tveganje, šibki.
Many drug reactions cannot be distinguished from naturally occurring or infection-induced eruptions, and thus misdiagnosis is common. 
Mnogih reakcij na zdravila ni mogoče razlikovati od naravnih reakcij ali izbruhov, ki jih povzroča okužba, zato je napačna diagnoza pogosta.
Consequently the PSUR cycle should be shortened to a 3-yearly cycle in order to periodically review these analyses. 
Posledično je treba cikel za predložitev poročila PSUR skrajšati na trikrat na leto, da bo mogoče pogosto pregledovati te analize.
Moreover SCARs cases should be analysed in details in future PSURs. 
Poleg tega je treba primere SCAR v prihodnjih poročilih PSUR podrobno analizirati.
However, a shorter PSUR cycle should be introduced to continue to review periodically data that becomes available on the benefit-risk balance of the products. 
Vendar pa je treba vpeljati krajši cikel za predložitev poročila PSUR, da se bodo še naprej redno pregledovali razpoložljivi podatki o razmerju med tveganji in koristmi zdravil.
For these reasons studies conducted after the initial marketing authorisation do not provide new significant scientific data on the efficacy of the products. 
Zato študije, opravljene po prvotnem dovoljenju za promet z zdravilom, ne zagotavljajo novih pomembnih znanstvenih podatkov o učinkovitosti zdravil.
However, when looking at the date of the reports, 40 reports, out of the 119 reported in total for the originator since the first marketing authorisation, appear to have been sent in two batches by the Chinese health authority to the MAH of the originator of these products. 
Pri pregledu datumov teh poročil pa so ugotovili, da je od prve odobritve dovoljenja za promet z zdravilom 40 od skupno 119 poročil za originator imetniku dovoljenja za promet z originatorjem teh zdravil v dveh serijah poslal kitajski zdravstveni organ.
In addition, the PRAC discussed the need to conduct post-authorisation studies, and concluded that such studies would likely not generate new robust information towards more definite conclusions. 
Poleg tega je odbor PRAC razpravljal o potrebi po izvedbi študij po izdaji dovoljenja za promet z zdravilom in zaključil, da iz tovrstnih študij verjetno ne bi pridobili novih grobih informacij, ki bi omogočile izpeljavo dokončnejših zaključkov.
The clinical studies performed during the development of bromhexine- and ambroxol-containing products between the 1950ies and 1980ies were considerably less standardised than would be necessary today, and would not completely fulfil contemporary requirements with regard to validated endpoints, statistical confirmation, or Good Clinical Practice (GCP). 
Klinične študije, izvedene med razvojem bromheksina in ambroksola v času med 50-imi in koncem 80-ih let prejšnjega stoletja, so bile precej manj standardizirane, kot je zahtevano danes, zato delno ne izpolnjujejo sodobnih zahtev glede validiranih opazovanih dogodkov, statistične potrditve ali dobre klinične prakse.
Some trials failed to show a significant difference between ambroxol or bromhexine and placebo and other only showed significant difference in some of the studied endpoints. 
Nekatera preskušanja niso uspela pokazati pomembne razlike med ambroksolom ali bromheksinom in placebom, druga pa so pomembno razliko pokazala samo pri nekaterih preiskovanih opazovanih dogodkih.
Therefore the PRAC concluded that the evidence available did not justify the introduction of further age specific restrictions in the product information. 
Odbor PRAC je zato zaključil, da razpoložljivi dokazi niso upravičili uvedbe dodatnih, za starost specifičnih omejitev v informacije o zdravilu.
This increase in reporting follows the implementation of a new pharmacovigilance regulation in China that might have influenced adverse reaction reporting and does not reflect a new safety concern. 
To povečanje poročanja je posledica uvedbe novega farmakovigilančnega predpisa na Kitajskem, ki je morda vplival na poročanje neželenih učinkov in ne predstavlja novega varnostnega zadržka.
On 25 February 2015, the CMDh, having considered the PRAC recommendation, dated 9 January 2015, reached by majority the position that the marketing authorisations for the concerned medicinal products should be varied. 
Po preučitvi priporočila odbora PRAC z dne 9. januarja 2015 je skupina CMDh 25. februarja 2015 z večino glasov sprejela stališče, da je treba dovoljenja za promet z zadevnimi zdravili spremeniti.
Taking into account these limitations, together with the weak evidence of a safety issue from the pharmacovigilance data, the PRAC could not conclude from the available evidence that risks outweighed benefits in the different indications. 
Upoštevajoč te omejitve skupaj s šibkimi dokazi o varnostnih zadržkih iz farmakovigilančnih podatkov odbor PRAC na podlagi razpoložljivih dokazov ni mogel zaključiti, ali so tveganja pri različnih indikacijah večja od koristi.
Four cases of SCARs retrieved from Eudravigilance and 3 others from the literature have been assessed as related to ambroxol. 
Štiri primere SCAR iz sistema Eudravigilance in tri druge primere iz literature so ocenili kot povezane z ambroksolom.
Overall conclusion and grounds for the revised PRAC recommendation 
Splošni zaključki in podlaga za revidirano priporočilo odbora PRAC Ob upoštevanju naslednjega:
In light of the above, on 4 April 2014, the FAMHP informed the European Medicines Agency, of their decision to notify a referral procedure to ask for the PRAC's recommendation pursuant to Article 31 of Directive 2001/83/EC, on whether the balance of benefits and risks for these products is still positive in the approved indications, and whether the marketing authorisations for ambroxol- and bromhexinecontaining medicinal products should be maintained, varied, suspended or withdrawn. 
Na podlagi zgornjih podatkov je organ FAMHP 4. aprila 2014 obvestil Evropsko agencijo za zdravila o svoji odločitvi, da bo sprožil napotitveni postopek in odbor PRAC v skladu s členom 31 Direktive 2001/83/ES zaprosil za priporočilo o tem, ali je razmerje med tveganji in koristmi teh zdravil pri odobrenih indikacijah še vedno pozitivno ter ali naj se dovoljenja za promet z zdravili, ki vsebujejo ambroksol in bromheksin, ohranijo, spremenijo, začasno umaknejo ali odvzamejo.
• The PRAC considered the procedure under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data for ambroxol- and bromhexine-containing medicinal products. 
• odbor PRAC je upošteval napotitev v skladu s členom 31 Direktive 2001/83/ES, ki je bila na podlagi farmakovigilančnih podatkov predložena za zdravila, ki vsebujejo ambroksol in bromheksin;
All the available data submitted, related to the safety and the efficacy of the medicinal products were reviewed by the PRAC to assess the potential impact of the new safety concerns identified on the established benefit-risk balance of the authorised medicinal products. 
Odbor PRAC je pregledal vse razpoložljive predložene podatke v zvezi z varnostjo in učinkovitostjo zdravil, da bi ocenil morebitni vpliv novih varnostnih zadržkov na ugotovljeno razmerje med tveganji in koristmi odobrenih zdravil.
The PRAC took note of the advice of the paediatric committee (PDCO) that the use of ambroxol and bromhexine varies significantly in paediatric clinical practice across the EU. 
Odbor PRAC je upošteval nasvet pediatrične komisije (PDCO), da se uporaba ambroksola in bromheksina v klinični praksi v EU precej razlikuje.
Efficacy issues 
Vprašanja glede učinkovitosti
As SCARs sometimes start with flu-like symptoms some patients might also start taking ambroxol or bromhexine to alleviate these symptoms whereas the typical skin reactions appear later and ambroxol or bromhexine might be considered as suspect drug. 
Ker se SCAR včasih začne z gripi podobnimi simptomi, lahko nekateri bolniki začnejo jemati tudi ambroksol ali bromheksin za lajšanje teh simptomov, čeprav se značilne kožne reakcije pojavijo pozneje, zato se morda ambroksol ali bromheksin obravnavata kot povzročitelja.
Based on these data it is considered that the susceptibility of all age groups (paediatric, adults and elderly) to putative hypersensitivity-related undesirable effects of ambroxol or bromhexine is likely similar. 
Na podlagi teh podatkov so menili, da je dovzetnost vseh starostnih skupin (pediatričnih, odraslih in starejših) za domnevne, s preobčutljivostjo povezane neželene učinke ambroksola ali bromheksina verjetno podobna.
Many patients with SCARs receive various mucolytic or secretolytic agents in the relevant time period before the onset of their adverse event. 
Mnogi bolniki s SCAR pred pojavom neželenega dogodka v zadevnem časovnem obdobju prejemajo različne mukolitične ali sekretolitične učinkovine.
However, these adverse reactions are already listed in the product information of most ambroxol- and bromhexinecontaining products and the analysis of the most frequently reported adverse events selected by the SMQ Hypersensitivity (broad) did not identify any new safety concerns. 
Vendar so ti neželeni učinki že navedeni v informacijah o zdravilu, ki veljajo za večino zdravil, ki vsebujejo ambroksol in bromheksin, analiza najpogosteje poročanih neželenih dogodkov, izbranih na podlagi (široke) opredelitve SMQ za preobčutljivost, pa ni pokazala novih zadržkov v zvezi z varnostjo.
The safety information submitted by the MAHs, from Eudravigilance and from the literature, comprises in total around 300 case reports of suspected SCARs, many of which have possible confounders. 
Varnostni podatki, ki so jih predložili imetniki dovoljenj za promet z zdravilom, iz sistema Eudravigilance in literature, vključujejo skupno približno 300 poročil o primerih suma na SCAR, od katerih jih ima mnogo morebitne zavajajoče dejavnike.
In addition the PRAC recommended harmonising the terms related to hypersensitivity reactions in the product information. 
Poleg tega je odbor PRAC priporočil, da se v informacijah o zdravilu izrazi, povezani s preobčutljivostnimi reakcijami, uskladijo.
• The PRAC reviewed the totality of the data submitted in support of the safety and efficacy of ambroxol- and bromhexine-containing products, including submissions from the marketing authorisation holders and expert input. 
• odbor PRAC je pregledal vse podatke, predložene v podporo varnosti in učinkovitosti zdravil, ki vsebujejo ambroksol in bromheksin, vključno z vlogami imetnikov dovoljenja za promet z zdravilom in mnenji strokovnjakov;
The PRAC, as a consequence, concluded that the benefit-risk balance of of ambroxol- and bromhexinecontaining medicinal products remains favourable, subject to the above detailed amendments to the product information. 
Posledično je odbor PRAC zaključil, da je razmerje med tveganji in koristmi zdravil, ki vsebujejo ambroksol in bromheksin, še naprej ugodno pod pogojem, da se upoštevajo zgornje podrobne spremembe informacij o zdravilu.
In addition, ambroxol formulations indicated in secretolytic therapy and prophylaxis or treatment of IRDS and PPC have been associated with delayed-onset hypersensitivity reactions without severe skin injury. 
Poleg tega so bile formulacije ambroksola, indicirane za sekretolitično terapijo in profilakso ali zdravljenje IRDS ter PPC, povezane z zapoznelimi preobčutljivostnimi reakcijami brez hude kožne poškodbe.
Taking all of the above into consideration, the PRAC concluded that the data reviewed supported amendments of the product information to reflect the risk of severe cutaneous adverse reactions, and that further age restrictions to reflect the concerns about the benefit-risk balance of ambroxol- and bromhexine-containing products are not justified on the basis of the data available. 
Upoštevajoč vse zgornje podatke je odbor PRAC zaključil, da pregledani podatki podpirajo spremembe informacij o zdravilu, in sicer tako, da se vanje vključi tveganje hudih kožnih neželenih učinkov, in da dodatne omejitve glede starosti, ki odražajo pomisleke o razmerju med tveganji in koristmi zdravil, ki vsebujejo ambroksol in bromheksin, niso upravičene na podlagi razpoložljivih podatkov.
An increase was observed in the reporting frequency of anaphylactic reactions over 2012-2014 linked to ambroxol. 
Med letoma 2012 in 2014 so opazili povečanje pogostosti poročanja o anafilaktičnih reakcijah, povezanih z ambroksolom.
Analysis of the safety information submitted by the MAH, from Eudravigilance and from the literature, demonstrates that ambroxol and bromhexine formulations in their different indications have been associated with reports of serious immediate hypersensitivity reactions. 
Analiza varnostnih podatkov, ki jih je predložil imetnik dovoljenja za promet z zdravilom, iz sistema Eudravigilance in literature, kaže, da so bile formulacije ambroksola in bromheksina pri različnih indikacijah povezane s poročili o takojšnjih resnih preobčutljivostnih reakcijah.
In addition, ambroxol and bromhexine have been approved in some EU MS in airway diseases indications in fixed dose combinations with various active substances. 
Poleg tega sta se ambroksol in bromheksin v nekaterih državah članicah EU odobrila za indikacijo bolezni dihal v kombinacijah z različnimi zdravilnimi učinkovinami s fiksnim odmerkom.
As ambroxol is a metabolite of bromhexine and hypersensitivity reactions are not dependent on the dose of the allergenic substance absorbed, the FAMHP considered that any confirmed risk with ambroxol could also be found in bromhexine-containing medicinal products with regards to these reactions. 
Ker je ambroksol presnovek bromheksina in preobčutljivostne reakcije niso odvisne od odmerka absorbiranega alergena, je organ FAMHP menil, da bi lahko potrjeno tveganje za te reakcije pri ambroksolu veljalo tudi za zdravila, ki vsebujejo bromheksin.
The authorised indications of bromhexine, as listed in the Company Core Data Sheet of the originator, are secretolytic therapy, alteration in the production or elimination of mucus (acute and chronic sinusitis) and Sjögren's syndrome. 
Odobrene indikacije za bromheksin, kot je navedeno v glavnem podatkovnem listu imetnika dovoljenja za originator, so sekretolitična terapija, spremembe v tvorbi ali izločanju sluzi (akutni in kronični sinusitis) ter Sjögrenov sindrom.
The PRAC was of the view that the possible risk of SCARs can be adequately addressed by the proposed amendments to the PI to inform caregivers and patients of the risk and allow early identification of signs of SCARs and immediate discontinuation of treatment should they occur. 
Odbor PRAC je menil, da se lahko morebitno tveganje za SCAR zadostno obravnava s predlaganimi spremembami informacij o zdravilu, ki bodo negovalce in bolnike obveščale o tveganju, omogočale zgodnje prepoznavanje znakov SCAR in opozarjale na takojšnjo prekinitev jemanja, če se taki znaki pojavijo.
It is acknowledged that clinical evidence from studies in children is weak due to their heterogeneity and to the lower number of children enrolled. 
Znano je, da so zaradi heterogenosti in manjšega števila vključenih otrok klinični dokazi iz študij pri otrocih šibkejši.
Based on the evaluation of the individual case reports, considering the nature of these events the PRAC was of the view that there is a reasonable possibility that all ambroxol and bromhexine-containing products are associated with an increased risk of SCARs including combination products. 
Na podlagi ocene posameznih poročil o primerih in glede na naravo teh dogodkov je odbor PRAC menil, da obstaja možnost, da so vsa zdravila, ki vsebujejo ambroksol in bromheksin, povezana s povečanim tveganjem za SCAR, vključno s kombiniranimi zdravili.
The PRAC however noted that the observed increase in reporting of anaphylactic reactions for ambroxol-containing products was likely an artefact resulting from the implementation of a new pharmacovigilance regulation in China and did not constitute a new safety concern. 
Vendar je sklepal, da je opaženo povečanje poročanja o anafilaktičnih reakcijah na zdravila, ki vsebujejo ambroksol, verjetno artefakt, ki je posledica uvedbe novega farmakovigilančnega predpisa na Kitajskem, in ne predstavlja novega varnostnega zadržka.
In relation to the efficacy of ambroxol- and bromhexine-containing products, the PRAC concluded that although modest positive results were reported, the evidence of efficacy of ambroxol and bromhexine suffered from a number of limitations and deficiencies. 
Glede učinkovitosti zdravil, ki vsebujejo ambroksol in bromheksin, je odbor PRAC zaključil, da imajo dokazi o učinkovitosti ambroksola in bromheksina kljub zmerno pozitivnim rezultatom mnoge omejitve in pomanjkljivosti.