natgillin/translations-raw huggingface dataset:
The national competent authorities, coordinated by the reference Member State, shall ensure that the following conditions are fulfilled by the marketing authorisation holders: 
Pristojni nacionalni organi, ki jih usklajuje referenčna država članica, morajo zagotoviti, da imetniki dovoljenja za promet z zdravilom izpolnijo naslednje pogoje:
4. part III, pharmacovigilance plan: category 1 should be added for the PASS and the DUS. 
4. del III, načrt farmakovigilance: kategorija 1 se mora dodati za študijo PASS in študijo o uporabi zdravila.
The applicant shall conduct a PASS to evaluate the long-term safety profile of dexamfetamine in children with ADHD, specifically targeting key issues such as cardiovascular events, growth and psychiatric related adverse events. 
Predlagatelj mora izvesti študijo PASS za ovrednotenje profila dolgoročne varnosti deksamfetamina pri otrocih z ADHD, s posebnim poudarkom na ključnih problemih, kot so srčno-žilni dogodki, rast in psihiatrični neželeni dogodki.
As part of this study the MAH shall actively obtain reports of abuse, misuse, diversion and dependence in children with ADHD from poison centres, drug monitoring centres, other databases, publicly available information in the literature and online. 
V okviru te študije mora imetnik dovoljenja za promet z zdravilom aktivno zbirati poročila o zlorabi, napačni uporabi, uporabi za rekreativne namene in odvisnosti pri otrocih z ADHD iz centrov za zastrupitve, centrov za spremljanje drog, drugih podatkovnih zbirk, javno dostopnih informacij iz literature in spleta.
3. annex 7: should include the text of a proposed follow up form to be used for specific adverse event follow-up. 
3. priloga 7 mora vsebovati besedilo predlaganega obrazca za spremljanje, ki se bo uporabljal za spremljanje določenih neželenih dogodkov;
The applicant shall undertake a DUS to follow the use of prescribed dexamfetamine in the European Union using multiple data sources. 
Predlagatelj mora izvesti študijo o uporabi zdravila, namenjeno spremljanju uporabe predpisanega deksamfetamina v Evropski uniji s pomočjo različnih virov podatkov.
The applicant shall submit an updated RMP taking into consideration the following recommendations: 1. section VI.2.5 Documentation for public summary should include a summary of risk minimisation measures by safety concern. 
1. poglavje VI.2.5 Dokumentacija za povzetek za javnost mora vsebovati povzetek ukrepov za zmanjšanje tveganja po varnostnih tveganjih;
2. annex 2 should include the proposed text of the package leaflet in addition to the proposed SmPC. 
2. priloga 2 mora poleg predlaganega povzetka glavnih značilnosti zdravila vsebovati tudi predlagano besedilo navodila za uporabo;
This opinion supersedes the opinion on temporary measures adopted on 4 July 2011. 
To mnenje nadomesti mnenje o začasnih ukrepih, sprejeto 4. julija 2011.
The mean age was 70.2 and 71.6 years, respectively. 
Povprečna starost je bila 70,2 oziroma 71,6 let.
years of age). 
stopnje)“.
As a result, a procedure under Article 107 of Directive 2001/83/EC, as amended was automatically initiated. 
Samodejno je bil sprožen postopek iz člena 107 Direktive 2001/83/ES, v skladu s spremembami le-te.
The need to consider renal function was also introduced. 
Uvedena je bila tudi potreba po upoštevanju ledvične funkcije.
Safety of the injectable formulations of buflomedil 
Varnost injekcijskih formulacij buflomedila
The CHMP also noted the two French pharmacovigilance enquiries covering the period 1998 to 2004 and 2006 to 2009. 
CHMP je upošteval tudi dve francoski farmakovigilančni poizvedbi, ki pokrivata obdobji od leta 1998 do 2004 in od leta 2006 do 2009.
The procedure started during the February 2011 CHMP meeting. 
Postopek se je začel februarja 2011 med sejo Odbora za zdravila za uporabo v humani medicini (CHMP).
Thalès observational drug utilisation study 
Thalèsova opazovalna študija o uporabi zdravil
Overall summary of the scientific evaluation of buflomedil-containing medicinal products (see Annex I) 
Splošni povzetek znanstvenega vrednotenja zdravil, ki vsebujejo buflomedil (glejte Prilogo I)
Buflomedil-containing medicines are authorised and marketed in 12 EU countries by national procedures and were first authorised in France in 1974. 
Zdravila, ki vsebujejo buflomedil, so odobrena z nacionalnimi postopki in prisotna na trgu v 12 državah EU, prvič pa so bila odobrena leta 1974 v Franciji.
Discussion on efficacy 
Razprava o učinkovitosti
Overall summary on safety and on risk minimisation measures 
Splošni povzetek o varnosti in o ukrepih za zmanjšanje tveganj
Annex II Scientific conclusions and grounds for the suspension of the marketing and use of the products presented by the EMA 
Priloga II Znanstveni zaključki in podlaga za začasni preklic prometa z zdravilom in uporabe proizvodov, ki jih kje predstavila agencija EMA
Overall conclusions on safety 
Splošni zaključki o varnosti
In addition to these 5 cases, a further two cases related to renal impairment were identified, where the dose was unknown. 
Poleg teh 5 primerov so opredelili še dva primera, povezana z okvaro ledvic, pri čemer je bil odmerek neznan.
In addition, 32 cardiological adverse events were retrieved; the most frequent reactions were tachycardia, hypertension, flushing and hypotension. 
Poleg tega je bilo opaženih 32 kardioloških neželenih učinkov; najpogostejše reakcije so bile tahikardija, hipertenzija, oblivanje in hipotenzija.
Risk minimisation measures 
Ukrepi za zmanjšanje tveganj
Usage of buflomedil according to these conditions is considered to be under normal conditions of use. 
Uporaba buflomedila v skladu s temi pogoji velja za uporabo v okviru običajnih pogojev uporabe.
Regarding the proposed additional pharmacovigilance activities, the CHMP was of the opinion that signal detection is no longer a priority, given that the risks associated with buflomedil are now identified and confirmed. 
Glede predlaganih dodatnih farmakovigilančnih dejavnosti je CHMP menil, da dodatno zaznavanje signalov ni več prednostna naloga, saj so sedaj tveganja, povezana z buflomedilom, opredeljena in potrjena.
Discussion on safety 
Razprava o varnosti
The study compared a reference period of 6 months before the 2006 French evaluation with two 6-months evaluation periods following the implementation of the resulting RMMs and the circulation of a DHPC. 
V študiji so primerjali referenčno obdobje 6 mesecev pred francosko ocenitvijo iz leta 2006 z dvema 6-mesečnima ocenitvenima obdobjema po uvedbi posledičnih ukrepov za obvladovanje tveganj in kroženjem neposrednega sporočila med zdravstvenim osebjem.
However, the CHMP noted that the analysis did not demonstrate statistical significance and that the results therefore did not allow to conclude on a statistically significant reduction in the combined primary endpoint compared to placebo. 
Vendar pa je CHMP opazil, da analiza ni pokazala statistične značilnosti, zato na podlagi rezultatov ni bilo mogoče sklepati na statistično značilno zmanjšanje kombiniranega primarnega izida v primerjavi s placebom.
In 70% of the cases, the dose of buflomedil received by the patients was inappropriate because of underlying renal failure. 
V 70 % primerov je bil odmerek buflomedila, ki so ga bolniki prejeli, neustrezen zaradi osnovne odpovedi ledvic.
Grounds for the suspension of the Marketing Authorisations 
Razlog za začasni preklic dovoljenja za promet z zdravilom
The CHMP was of the opinion that despite this reduction, the percentage of patients at risk remained unacceptably high. 
CHMP je bil mnenja, da ostaja odstotek bolnikov, izpostavljenih tveganju, kljub temu zmanjšanju nesprejemljivo visok.
Consequently, the CHMP recommended to the European Commission the suspension of the Marketing Authorisations of buflomedil-containing medicinal products listed in Annex I of the Opinion in all concerned EU Member States. 
Posledično je CHMP Evropski komisiji predlagal začasni preklic dovoljenja za promet z zdravili, ki vsebujejo buflomedil, naštetimi v Prilogi I tega mnenja, v vseh zadevnih državah članicah EU.
The approved maximum daily dose in patients with normal renal function is 600 mg and 300 mg in patients with renal impairment. 
Odobren največji dnevni odmerek pri bolnikih z normalnim delovanjem ledvic je 600 mg, pri bolnikih z okvaro ledvic pa 300 mg.
For the lifting of the suspension, the Marketing Authorisation Holders should provide convincing data to identify a population in which the benefits of buflomedil clearly outweigh its identified risks (see Annex III). 
Za odpravo začasnega preklica dovoljenja za promet mora imetnik dovoljenja za promet predložiti prepričljive podatke z opredelitvijo populacije, v kateri koristi zdravljenja z buflomedilom jasno odtehtajo opredeljena tveganja (glejte Prilogo III).
In December 2010, a further French benefit-risk evaluation of buflomedil was carried out, following which the French National Competent Authority suspended all French Marketing Authorisations for buflomedil-containing products. 
V decembru leta 2010 so v Franciji opravili dodatno oceno razmerja med koristmi in tveganji uporabe buflomedila, po kateri je pristojni francoski nacionalni organ začasno umaknil vsa francoska dovoljenja za promet z zdravili, ki vsebujejo buflomedil.
In addition, review of all available individual case safety data related to buflomedil identified 28 cases of overdoses in elderly patients (over 65 
Poleg tega je pregled vseh razpoložljivih podatkov o varnosti iz posamičnih primerov, povezanih z buflomedilom, opredelil 28 primerov prevelikega odmerjanja pri starejših bolnikih (starih 65 let ali več).
There were 6 cases of cardiovascular and 6 cases of neurological serious adverse events. 
6 primerov je navajalo kardiovaskularne in 6 primerov nevrološke resne neželene učinke.
Buflomedil is an α1-, α2-adrenolytic agent with vasoactive and haemorheologic properties, improving the blood flow in the microcirculation as well as tissue oxygenation. 
Buflomedil je adrenolitično α1-, α2-sredstvo z vazoaktivnim in hemoreološkim delovanjem, ki izboljšuje krvni pretok na mikrocirkulatorni ravni in oskrbo tkiva s kisikom.
Following an oral explanation held in July 2011, the MAH was requested to propose further risk minimisation measures and asked whether a restricted population could be identified. 
Po ustni razlagi v juliju 2011 so imetnika dovoljenja za promet z zdravilom zaprosili za dodatne ukrepe za zmanjšanje tveganj in za opredelitev populacije z omejeno uporabo.
The study showed that about 30% of patients with renal failure still receive an excessive dose, although it was noted that this had decreased from 75% prior to the DHPC. 
Študija je pokazala, da je približno 30 % bolnikov z ledvično odpovedjo še vedno prejelo prevelik odmerek, čeprav je bilo zabeleženo, da se je to zmanjšalo s 75 % pred neposrednim sporočilom za zdravstveno osebje.
One patient experienced convulsions after taking two 300 mg tablets at the same time instead of two tablets BID. 
Pri enem bolniku so se pojavili krči po sočasnem vnosu dveh 300 mg tablet namesto dveh tablet dvakrat na dan.
The CHMP noted that of the 24 reported cases (about 5% of all adverse drug reactions recorded in the MAH database), a majority (13 out of 24) were cases of accidental overdose. 
CHMP je opazil, da je bila od 24 sporočenih primerov (približno 5 % vseh neželenih učinkov na zdravilo, zabeleženih v podatkovni bazi imetnika dovoljenja za promet z zdravilom), večina (13 od 24) primerov nenamernega prevelikega odmerjanja.
Various indications previously registered across the EU were deleted and the indication was restricted to the Symptomatic treatment of chronic peripheral vascular disease (stage 2) (intermittent claudication), bringing it in line with the French SmPC. 
Izbrisane so bile različne indikacije, ki so bile pred tem registrirane po vsej EU, indikacija pa je bila omejena na Simptomatsko zdravljenje kronične periferne žilne bolezni (2. stopnje) (intermitentna klavdikacija) v skladu s francoskim povzetkom glavnih značilnosti zdravila.
Buflomedil is currently approved in France in the treatment of ”symptomatic peripheral arterial occlusive disease (PAOD Stage II) symptoms”. 
Buflomedil je v Franciji trenutno odobren za zdravljenje „simptomov bolezni sistemske okluzije perifernih arterij (BOPA II.
As the Risk Management Plan (RMP) proposed in the scope of this Article 107 procedure is equivalent to the French RMP implemented in 2006, the CHMP was therefore of the opinion that it is possible to conclude on the effectiveness of the proposed RMMs, despite the lack of implementation in all member states. 
Ker je načrt za obvladovanje tveganja, predlagan v okviru postopka iz člena 107, enakovreden francoskemu RMP, ki je bil uveden leta 2006, CHMP meni, da je možno zaključiti o učinkovitosti predlaganih ukrepov za zmanjševanje tveganj, čeprav še niso bili vpeljani v vseh državah članicah.
If dose-adaptation is not done correctly, this leads to serious and lifethreatening toxicity. 
Nepravilna prilagoditev odmerka lahko povzroči hudo do življenjsko nevarno toksičnost.
In addition, the CHMP observed with concern that an initial assessment of renal function was only carried out in 20% of patients and that measurements of creatinine clearance were only performed in 17% of patients, despite the SmPC recommendations. 
CHMP je z zaskrbljenostjo opazoval tudi, da so začetno ocenitev delovanja ledvic opravili le pri 20 % bolnikov in da so očistek kreatinina izmerili le pri 17 % bolnikov, kljub priporočilom v povzetku glavnih značilnosti zdravila.
The CHMP acknowledged that variations to implement the European harmonisation of the SmPC are still ongoing in some countries but noted that the RMP proposed by Amdipharm in May 2010 was largely equivalent to the RMPs already implemented in France. 
CHMP priznava, da so spremembe za uvedbo evropske uskladitve povzetka glavnih značilnosti zdravila v nekaterih državah še vedno v teku, vendar je opazil, da se načrt za obvladovanje tveganja, ki ga je maja 2010 predlagalo podjetje Amdipharm, v veliki meri ujema z načrtom za obvladovanje tveganja, ki se v Franciji že uporablja.
The CHMP also examined a review of all available individual case safety data related to buflomedil, conducted by the MAH, based on post-marketing safety data from Abbott Laboratories' global safety database and Amdipharm's safety database, published medical literature (worldwide) and from a number of other sources, including Toxicology/Poison Control Centres and Regulatory Authorities. 
CHMP je proučila tudi pregled vseh razpoložljivih posamičnih poročil o škodljivih neželenih učinkih, povezanih z buflomedilom, ki ga je opravil imetnik dovoljenja za promet z zdravilom na podlagi podatkov o varnosti v obdobju po začetku trženja, iz svetovne baze podatkov o varnosti podjetja Abbott Laboratories in baze podatkov o varnosti podjetja Amdipharm, objavljene medicinske literature (po vsem svetu) in podatke številnih drugih virov, vključno s podatki centrov za toksikologijo/nadzor zastrupitev in regulatornih organov.
Serious cardiovascular and neurological adverse events under normal conditions of use 
Resni kardiovaskularni in nevrološki neželeni učinki v običajnih pogojih uporabe
The CHMP also noted the pharmacovigilance and toxicovigilance data which show no improvement of the safety profile of buflomedil despite the implementation of the RMP in France in 2006; instead, a two fold increase of misuse compared to the previous period was observed. 
CHMP je opazil tudi, da podatki o farmakovigilanci in toksikovigilanci ne kažejo na izboljšanje varnostnega profila buflomedila kljub uvedbi načrta za obvladovanje tveganja v Franciji leta 2006; nasprotno, opazili so dvakratno povečanje napačne uporabe v primerjavi s prejšnjim obdobjem.
From these cases, a total of 12 cases were identified in which patients were treated within the maximum therapeutic range (i.e. up to 600 mg daily) of buflomedil. 
Ugotovljeno je bilo, da so v skupaj 12 od teh primerov bolnike zdravili znotraj največjega terapevtskega razpona (tj. do 600 mg na dan) za uporabo buflomedila.
Overall, the CHMP considered the clinical data submitted in support of the efficacy of buflomedil to be limited. 
Na splošno je bil CHMP mnenja, da so klinični podatki, predloženi v podporo učinkovitosti buflomedila, omejeni.
Serious cardiovascular and neurological adverse events in elderly patients and patients with renal impairment 
Resni kardiovaskularni in nevrološki neželeni učinki pri starejših bolnikih in bolnikih z okvaro ledvic
The CHMP assessed the impact of the risk minimisation measures previously implemented in France, consisting mainly of revisions to the SmPC and communication and noted the proposed extension of these measures to other member states. 
CHMP je ocenil vpliv ukrepov za zmanjšanje tveganj, ki so bili pred tem uvedeni v Franciji, in ki so bili v glavnem sestavljeni iz popravkov povzetka glavnih podrobnosti zdravila in komunikacij, ter predlagana podaljšanja teh ukrepov sporočil drugim državam članicam.
The MAH review of the ICSR database identified 5 cases with known dosage occurring in elderly patients for whom dosage adjustment was required. 
Pregled podatkovne baze ICSR, ki ga je opravil imetnik dovoljenja za promet z zdravilom, je razkril 5 primerov z znanim odmerjanjem, ki so se pojavili pri starejših bolnikih, za katere je bilo treba odmerek prilagoditi.
Following these enquiries, France took a number of national regulatory actions to minimise the risk of adverse events associated with buflomedil. 
Po teh poročilih je Francija sprejela več nacionalnih regulativnih ukrepov za zmanjšanje tveganja resnih neželenih učinkov, povezanih z uporabo buflomedila.
France previously conducted two pharmacovigilance and toxicovigilance investigations following reports of nervous system and cardiac serious adverse events (SAEs) associated with the use of buflomedil. 
Francija je doslej izvedla dve preiskavi farmakovigilance in toksikovigilance po prejemu poročil o resnih neželenih dogodkih (SAE) živčnega sistema in srca, povezanih z uporabo buflomedila.
The CHMP also noted the results of the Thalès observational drug utilisation study, including 300 000 patients and conducted to assess the impact of the RMMs implemented in France on prescription patterns. 
CHMP je upošteval tudi rezultate Thalsove opazovalne študije o uporabi zdravila, v katero je bilo vključenih 300 000 bolnikov, in ocenil vpliv ukrepov za obvladovanje tveganj v Franciji z vzorci predpisovanja zdravila.
The CHMP concluded that the impact of the implemented measures was very weak and that the expected impact of the proposed measures was insufficient to adequately address the identified risks observed with buflomedil. 
CHMP je zaključil, da je bil učinek uvedenih ukrepov zelo šibak in da pričakovani učinek predlaganih ukrepov ne zadošča, da bi lahko opredeljena tveganja, ki so jih opazili pri uporabi buflomedila, ustrezno odpravili.
• The Committee considered, based on the assessment of the impact of risk minimisation measures already implemented in some Member States and on the published literature, that the risk minimisation measures proposed by the Marketing Authorisation Holder would not be able to adequately reduce the risks of serious adverse events to a clinically acceptable level. 
• odbor je menil, da na podlagi ocene vpliva ukrepov za zmanjševanje tveganj, ki so bili v nekaterih državah članicah že uvedeni, in na podlagi objavljene literature, ukrepi za zmanjšanje tveganja, ki jih je predlagal imetnik dovoljenja za promet z zdravilom, ne bi zadoščali za ustrezno zmanjšanje tveganja resnih neželenih učinkov na klinično sprejemljivo raven;
The concerns regarding the rapid deterioration of renal function in these patients, requiring regular and frequent monitoring were also reiterated. 
Poudarjena je bila tudi zaskrbljenost zaradi naglega slabšanja delovanja ledvic pri teh bolnikih, zaradi česar jih je treba redno in pogosto spremljati.
• The Committee considered that buflomedil-containing medicinal products showed only limited clinical efficacy in the symptomatic treatment of chronic peripheral vascular disease. 
• odbor je menil, da so pokazala zdravila z buflomedilom samo omejeno klinično učinkovitost pri simptomatskem zdravljenju kronične periferne žilne bolezni;
The EudraVigilance review identified 74 cases of adverse events associated with buflomedil, with a total of 35 cases recording cardiac adverse and 39 cases recording neurological adverse events. 
S pregledom sistema EudraVigilance je bilo ugotovljenih 74 primerov neželenih učinkov, povezanih z uporabo buflomedila, s skupaj 35 primeri zabeleženih neželenih dogodkov srca in 39 primeri zabeleženih nevroloških neželenih dogodkov.
The CHMP also carried out a separate assessment of the safety of the parenteral formulations of buflomedil, which are used in the hospital setting for the treatment of severe chronic ischaemia of the lower limbs. 
CHMP je ločeno ocenil varnost parenteralnih formulacij buflomedila, ki se uporabljajo v bolnišnicah za zdravljenje hude kronične ishemije spodnjih udov.
Regarding the LIMB study, the results indicated a trend of a decrease in symptoms (symptomatic deterioration of PAOD, amputations) although there was an increase in cardiovascular events (MI, stroke, CV deaths). 
Rezultati v zvezi s študijo LIMB kažejo na trend zmanjšanja simptomov (zmanjšanje simptomov BOPA, manj amputacij), vendar se je število kardiovaskularnih dogodkov povečalo (miokardni infarkt, kap, smrt zaradi kardiovaskularnih bolezni).
Overall benefit-risk assessment 
Splošna ocena razmerja med koristmi in tveganji
• The Committee raised concerns regarding the rapid deterioration of renal function in patients with peripheral vascular disease, requiring regular and frequent monitoring. 
• odbor je izrazil skrb glede hitrega slabšanja delovanja ledvic pri bolnikih s periferno žilno boleznijo, zaradi česar jih je treba redno in pogosto nadzirati;
The CHMP noted a review of French Eudravigilance data analysing spontaneous reports associated with treatment with buflomedil, to identify cases where cardiac and neurological reactions occurred under normal therapeutic doses (i.e. maximum of 600 mg daily for the oral tablet formulation). 
CHMP je upošteval pregled francoskih podatkov v sistemu Eudravigilance, ki analizirajo spontana poročila, povezana z zdravljenjem z buflomedilom, da opredeli primere, v katerih so se kardiološke in nevrološke reakcije pojavile z običajnimi terapevtskimi odmerki (tj. največ 600 mg na dan za formulacijo peroralnih tablet).
The CHMP noted the efficacy data submitted by the MAH, including the relatively recent large placebocontrolled LIMB (Limbs International Medicinal Buflomedil) study. 
CHMP je upošteval podatke o učinkovitosti, ki jih je predložil imetnik dovoljenja za promet z zdravilom, tudi relativno novo in obširno s placebom kontrolirano študijo LIMB (Limbs International Medicinal Buflomedil).
• The Committee therefore considered that the risk-benefit balance of buflomedil-containing medicinal products is not positive under normal conditions of use. 
• zato je odbor menil, da razmerje med tveganji in koristmi uporabe zdravil, ki vsebujejo buflomedil, v običajnih pogojih uporabe ni pozitivno.
These risks are compounded by the fact that buflomedil is a substance with a narrow therapeutic index and that buflomedil treatment requires dose-adaptation to adjust for renal function. 
Ta tveganja še zaostruje dejstvo, da je buflomedil snov z ozkim terapevtskim indeksom, in da je treba pri zdravljenju z buflomedilom odmerek ustrezno prilagoditi glede na delovanje ledvic.
The CHMP noted the proposed additional revisions to the SmPC, restricting the population by further narrowing the PAOD indication and revising the wording of the contraindication in severe renal impairment in order to improve compliance to prescribing in the event of renal insufficiency. 
CHMP je zaznal predlagane dodatne popravke povzetka glavnih značilnosti zdravila, ki omejujejo populacijo z dodatnim zoženjem indikacije BOPA in popravljenim besedilom za kontraindikcije pri hudi okvari ledvic z namenom izboljšati skladnost pri predpisovanju v primeru ledvične insuficience.