natgillin/translations-raw huggingface dataset:
• The Committee considered that in this context, the narrow therapeutic index of buflomedil is of major concern, as patients with peripheral vascular disease treated with buflomedil are inherently likely to experience decreased renal function, due to the nature of their condition. 
• odbor je upošteval, da je v zvezi s tem ozek terapevtski indeks buflomedila glavna skrb, saj je pri bolnikih s periferno žilno boleznijo, zdravljenih z buflomedilom, verjetnost za zmanjšano delovanje ledvic inherentna zaradi narave njihove bolezni;
According to the approved indication, the injection formulation of buflomedil is used to initiate PAOD therapy, to be followed by a switch to oral therapy. 
V skladu z odobreno indikacijo se injekcijska formulacija buflomedila uporablja za začetek zdravljenja BOPA, nato pa bolnik preide na peroralno zdravljenje.
While acknowledging the iatrogenic nature of the reported cases, the CHMP considered that these cases provide supportive evidence of the cardiovascular and neurological risks of buflomedil, as adverse events were noted in patients administered twice the daily dosage, which suggests that the risks are associated with overdoses of relatively small magnitudes. 
Ob priznavanju iatrogene narave sporočenih primerov je CHMP menil, da ti primeri ustrezno podpirajo dokaze o kardiovaskularnih in nevroloških tveganjih buflomedila, saj so neželene učinke opazili pri bolnikih, ki so prejemali odmerke dvakrat na dan, kar kaže, da je obseg tveganj, povezan s prevelikim odmerjanjem, relativno majhen.
Although the 12 cases were complicated by underlying clinical conditions and other concomitant medications, the CHMP considered them to confirm the risk of serious adverse events associated with the use of buflomedil under normal conditions of use. 
Čeprav se je 12 primerov zapletlo zaradi osnovnih kliničnih boleznih in sočasne uporabe drugih zdravil, jih je CHMP upošteval pri potrditvi tveganja resnih neželenih učinkov, povezanih z uporabo buflomedila v običajnih pogojih uporabe.
As a result, when addressing the risk-benefit of buflomedil under normal conditions for use, the CHMP assumed a switch to oral formulations and therefore considered that the risk/benefit of buflomedil injectable needs to be considered within the overall discussion of the risk-benefit of buflomedil. 
Posledično CHMP ob obravnavanju razmerja med tveganji in koristmi uporabe buflomedila v običajnih pogojih uporabe predvideva prehod na peroralno formulacijo, zato meni, da je treba razmerje med tveganji in koristmi injekcije buflomedila upoštevati v okviru splošne razprave o razmerju med tveganji in koristmi buflomedila.
The CHMP concluded that due to the similarities between the proposed RMMs and the ones implemented in France, it is possible to conclude on the effectiveness of the proposed RMMs, despite the lack of implementation in all member states and that these measures are inadequate to prevent the occurrence of serious adverse events with buflomedil. 
CHMP je zaključil, da je zaradi podobnosti med predlaganimi ukrepi za obvladovanje tveganj in tistimi, ki so v Franciji že uvedeni, mogoče sklepati o učinkovitosti predlaganih ukrepov za obvladovanje tveganja, čeprav še niso bili vpeljani v vseh državah članicah, in da ti ukrepi ne zadoščajo za preprečevanje hudih neželenih učinkov z buflomedilom.
Following a European PSUR assessment and a full benefit-risk assessment completed by the MAH in January 2010, the MAH proposed a number of measures to address the identified concerns. 
Po evropskem redno posodobljenem poročilu o varnosti zdravila (PSUR) in celoviti oceni razmerja med tveganji in koristmi, ki ga je imetnik dovoljenja za promet z zdravilom izvedel januarja 2010, je imetnik dovoljenja za promet z zdravilom predlagal številne ukrepe za rešitev opredeljenih težav.
The reported ADRs were mainly related to serious neurological and cardiovascular ADRs. 
Neželeni učinki, o katerih so poročali, so bili večinoma povezani z resnimi nevrološkimi in kardiovaskularnimi neželenimi učinki.
The CHMP noted that according to the French experience (including the results of the Thalès study and the publication by Bruhat et al.), cases of non-compliance with the recommended dose, nonadjustment of dose in patients with renal impairment and lack of monitoring of renal function persist, resulting in cases of serious adverse events, which is unacceptable for a product for which the only benefit is a limited level of efficacy in the lower limb peripheral vascular disease indication. 
CHMP je na podlagi francoskih izkušenj (vključno z rezultati Thalesove študije in publikacije Bruhat in dr.) uvidel, da še naprej prihaja do neusklajenosti s priporočenim odmerkom, neprilagojevanja odmerka pri bolnikih z okvaro ledvic, velikokrat izostane tudi spremljanje delovanja ledvic, vse skupaj pa povzroči primere hudih neželenih učinkov, kar je za zdravilo, katerega edina korist je omejena raven učinkovitosti za indikacijo periferna žilna bolezen spodnjih okončin, nesprejemljivo.
The CHMP was of the opinion that this data showed the risks associated with buflomedil in view of its narrow therapeutic margin. 
Po mnenju CHMP ta podatek kaže na tveganje, povezano z uporabo buflomedila glede na njegovo ozko terapevtsko mejo.
The CHMP also considered a review of the individual case safety reports (ICSR) database conducted by the MAH, to identify cases of cardiological or neurological adverse events under normal conditions of use, i.e. cases where the dose did not exceed the maximum daily dose of 600mg, cases with accidental overdoses or cases including patients with known renal impairment requiring dose adjustment. 
CHMP je upošteval tudi pregled podatkovne baze posamičnih poročil o škodljivih neželenih učinkih (individual case safety reports, ICSR), ki ga je opravil imetnik dovoljenja za promet z zdravilom za opredelitev primerov kardioloških ali nevroloških neželenih učinkov v običajnih pogojih uporabe, tj. v primerih, kjer odmerek ni presegel največjega dnevnega odmerka 600 mg, primere nenamernega prevelikega odmerjanja ali primere, ki vključujejo bolnike z znano okvaro ledvic, pri katerih je treba odmerek prilagoditi.
The CHMP also noted the MAH proposal to reduce the pack size, to minimise the consequences of an intentional overdose. 
CHMP je opazil tudi predlog imetnika dovoljenja za promet z zdravilom za zmanjšanje velikosti pakiranja in s tem posledic nenamernega prevelikega odmerjanja.
• The Committee therefore concluded, in view of the available data, that the risks of serious cardiac and neurological adverse events associated with the use of buflomedil-containing medicinal products in the symptomatic treatment of chronic peripheral vascular disease, under normal conditions of use, outweigh the limited benefits. 
• odbor je zato v okviru razpoložljivih podatkov sklenil, da je tveganje resnih neželenih učinkov na srce in nevroloških neželenih učinkov ob uporabi zdravil, ki vsebujejo buflomedil, pri simptomatskem zdravljenju kronične periferne vaskularne bolezni v običajnih pogojih uporabe, večje od omejenih koristi;
• The Committee considered that a number of serious cardiac and neurological adverse events have been reported with the use of buflomedil under normal conditions of use, particularly in elderly patients. 
• odbor je upošteval, da so bila predložena številna poročila o resnih neželenih učinkih na srce in nevroloških neželenih učinkih pri uporabo buflomedila v običajnih pogojih uporabe, zlasti pri starejših bolnikih;
These reported 188 and 26 patients respectively who experienced AEs. 
Prva poroča o 188, druga pa o 26 bolnikih, ki so imeli neželene učinke.
In addition, the CHMP noted the evidence of limited clinical efficacy of buflomedil, as demonstrated in recent clinical trials. 
CHMP je upošteval tudi dokaze glede omejene klinične učinkovitosti buflomedila, ki so jih dala novejša klinična preskušanja.
In conclusion, taking into account the serious cardiac and neurological adverse events associated with the use of buflomedil-containing medicinal products under normal conditions of use, the evidence of limited clinical efficacy which is insufficient to compensate for the risks associated with the use of buflomedil and the established concerns regarding the effectiveness of the risk minimisation measures, the CHMP considered that the risk-benefit balance of buflomedil-containing medicinal products is not positive under normal conditions of use. 
CHMP je zato ob upoštevanju resnih neželenih učinkov na srce in nevroloških neželenih učinkov, povezanih z zdravili, ki vsebujejo buflomedil, ob običajnih pogojih uporabe, in dokazov omejene klinične učinkovitosti, ki ne nadomestijo tveganj, povezanih z uporabo buflomedila, in zaradi ugotovljenih skrbi glede učinkovitosti ukrepov za zmanjšanje tveganj, sklenil, da razmerje med tveganji in koristmi zdravil, ki vsebujejo buflomedil, v običajnih pogojih uporabe ni pozitivno.
However, the CHMP considered that the risk minimisation measures proposed by the MAH are unlikely to reduce the serious cardiac and neurological adverse events associated with the use of buflomedil to a clinically acceptable level. 
CHMP je kljub temu menil, da ni verjetno, da bi ukrepi za zmanjševanje tveganj, ki jih je predlagal imetnik dovoljenja za promet z zdravilom, zmanjšali resne neželene učinke na srce in nevrološke neželene učinke, povezane z uporabo buflomedila, na klinično sprejemljivo raven.
Consequently, while the efficacy remains largely unchanged since the granting of the initial MA, the CHMP was of the opinion that the available evidence is not supportive of a significant clinical efficacy of buflomedil on cardiovascular events and on walking distance. 
Posledično je CHMP menil, da ostaja učinkovitost od podelitve prvega dovoljenja za promet z zdravilom v veliki meri enaka in da z razpoložljivimi dokazi značilna klinična učinkovitosti buflomedila pri kardiovaskularnih dogodkih in prehojeni razdalji ni prepričljivo dokazana.
The CHMP considered the proposal for a website dedicated to buflomedil to be unlikely to significantly improve the awareness of prescribers, as previous communication tools already implemented in France were insufficient to improve compliance with indications and renal monitoring. 
CHMP je opazil, da imetnik dovoljenja za promet z zdravilom ni predlagal umika formulacije tablet s 300 mg. CHMP je menil, da ni verjetno, da bi predlagana spletna stran, posvečena buflomedilu, znatno izboljšala zavedanje zdravnikov, ki zdravilo predpisujejo, saj prejšnje komunikacijsko orodje, uvedeno v Franciji, ni zadoščalo za izboljšanje skladnosti z indikacijami in ni povečalo nadzora delovanja ledvic.
This is of particular concern as patients with peripheral vascular disease are inherently likely to experience decreased renal function due to the nature of their condition. 
To je še zlasti zaskrbljujoče zaradi bolnikov s periferno žilno boleznijo, pri katerih je verjetnost za zmanjšano delovanje ledvic inherentna zaradi narave njihove bolezni.
In these enquires, the reported nervous system SAEs consisted mainly of convulsions, myoclonia and status epilepticus while the cardiac SAEs consisted mainly of tachycardia, hypotension, ventricular rhythm disorders and cardiac arrest. 
V teh preiskavah so sporočeni resni neželeni dogodki živčnega sistema obsegali predvsem krče, mioklonijo in epileptični status, resni neželeni dogodki srca pa so obsegali predvsem tahikardijo, hipotenzijo, ventrikularno motnjo ritma in srčni zastoj.
Regarding risk minimisation measures, the CHMP noted the MAH proposals but considered that these are unlikely to be sufficient to prevent the occurrence of serious cardiac and neurological adverse events under normal conditions of use nor reduce the well identified risks of accidental overdoses and non-compliance with renal function monitoring associated with the use of buflomedil to an acceptable level. 
Glede ukrepov za zmanjšanje tveganj je CHMP upošteval predloge imetnika dovoljenja za promet z zdravilom, vendar je menil, da verjetno ne bodo zadoščali za preprečevanje pojava resnih neželenih učinkov za srce in nevroloških neželenih učinkov pri običajnih pogojih uporabe ali za zmanjšanje dobro znanih tveganj nenamernega prevelikega odmerjanja in tudi ne bodo privedli do rutinskega nadziranja delovanja ledvic, povezanega z uporabo buflomedila.
With regards to safety, the CHMP concluded that the use of buflomedil is associated with a number of serious cardiological (mainly tachycardia, hypotension, ventricular rhythm disorders and cardiac arrest) and neurological (mainly convulsions, myoclonia and status epilepticus) adverse events, which occur under normal conditions of use, particularly in elderly patients, who are predominantly the patient population relevant to the approved indication. 
Glede varnosti je CHMP zaključil, da je uporaba buflomedila povezana s številnimi resnimi kardiološkimi (predvsem tahikardijo, hipotenzijo, ventrikularno motnjo ritma in srčnim zastojem) in nevrološkimi (predvsem krči, mioklonijo in epileptičnim statusom) neželenimi učinki, ki so se pojavili v običajnih pogojih uporabe, zlasti pri starejših bolnikih, ki predstavljajo pretežno populacijo bolnikov za odobreno indikacijo.
In summary, the CHMP concluded that the use of buflomedil is associated with a number of serious cardiological (mainly tachycardia, hypotension, ventricular rhythm disorders and cardiac arrest) and neurological (mainly convulsions, myoclonia and status epilepticus) adverse events, which occur under normal conditions of use, particularly in elderly patients, who are predominantly the patient population relevant to the approved indication. 
Povzetek sklepa CHMP je, da je uporaba buflomedila povezana s številnimi resnimi kardiološkimi (predvsem tahikardijo, hipotenzijo, ventrikularno motnjo ritma in srčnim zastojem) in nevrološkimi (predvsem krči, mioklonijo in epileptičnim statusom) neželenimi učinki, ki so se pojavili v običajnih pogojih uporabe, zlasti pri starejših bolnikih, ki predstavljajo pretežno populacijo bolnikov za odobreno indikacijo.
The MAH review of the ICSR database identified 33 cases involving the use of a maximum daily dose of 600 mg. From these, a total of 21 cases of neurological adverse events were retrieved. 
V pregledu podatkovne baze ICSR je imetnik dovoljenja za promet z zdravilom opredelil 33 primerov z uporabo največjega dnevnega odmerka 600 mg.
Having assessed the risk minimisation measures proposed by the MAH, the CHMP concluded that given the high risk with buflomedil, notably in patients with advanced vascular disease and/or diabetes and metabolic syndrome, in patients with impaired renal function and in elderly patients, no adequate or sufficient measures could be identified to reduce the risks associated with buflomedil to an acceptable level. 
Po ocenitvi ukrepov za zmanjšanje tveganj, ki jih je predlagal imetnik dovoljenja za promet z zdravilom, je CHMP zaključil, da ustreznih ali zadostnih ukrepov za zmanjšanje tveganj, povezanih z buflomedilom, na sprejemljivo raven, zlasti pri bolnikih z napredovalo žilno boleznijo in/ali sladkorno boleznijo in presnovnim sindromom pri bolnikih z okvarjenim delovanjem ledvic in pri starejših bolnikih, ni bilo mogoče opredeliti.
Having assessed the totality of the risk minimisation measures proposed by the MAH, the CHMP concluded that given the high risk with buflomedil, notably in patients with impaired renal function and in elderly patients, no measures could be identified to reduce the risks associated with buflomedil to an acceptable level. 
Po ocenitvi vseh ukrepov za zmanjšanje tveganj, ki jih je predlagal imetnik dovoljenja za promet z zdravilom, je CHMP zaključil, da noben od ukrepov za zmanjšanje tveganj, povezanih z buflomedilom, na sprejemljivo raven, zlasti pri bolnikih z okvarjenim delovanjem ledvic in pri starejših bolnikih, ni zadosten.
(Invente d) name 
(Izmiљlje no) ime
MA (EU) Number 
Љtevilka (EU) dovoljenja za promet
Strength Pharmaceuti cal form 
Farmacevtska oblika
Route of administratio n 
Pot uporabe Stična ovojnina
This procedure ended on 28 November 2006. 
Ta postopek se je zaključil 28. novembra 2006.
This conclusion is accepted. 
Tak zaključek je bil sprejet.
Schepenveld 41 3891 ZK Zeewolde The Netherlands fs@ace-pharm.nl 
Schepenveld 41 3891 ZK Zeewolde Nizozemska fs@ace-pharm.nl
The Netherlands, Belgium, Germany, France, Italy, Spain and the United Kingdom. 
Nizozemska, Belgija, Nemčija, Francija, Italija, Španija in Združeno kraljestvo
Considering safety, the product seems not to create a considerable risk to young and healthy animals. 
Kar se tiče varnosti, ni videti, da bi zdravilo povzročilo pomembno tveganje za mlade in zdrave živali.
Since 1998 post-marketing studies have been performed as well as regular monitoring of adverse effects by FAQ system. 
Od leta 1998 so se izvajale postmarketinške raziskave in redno spremljanje neželenih učinkov s sistemom FAQ.
Indeed, treatment is not successful in all animals, but the level of efficacy is such that there is an advantage in treatment. 
Zdravljenje torej ni uspešno pri vseh živalih, vendar je raven učinkovitosti takšna, da zdravljenje prinaša prednosti.
Enurace 50 was first authorised in The Netherlands on 15 September 2000. 
Dovoljenje za promet z zdravilom Enurace 50 je bilo najprej izdano na Nizozemskem 15. septembra 2000.
Enurace has been officially authorised since 2000 (since 1995 available in the Netherlands). 
Dovoljenje za promet z zdravilom Enurace je bilo izdano leta 2000 (od leta 1995 je na voljo na Nizozemskem).
At Day 90 of the MRP, 27 September 2006, France and Italy could not agree to the granting of a marketing authorization as they consider there are potentially serious risks for animal health. 
Francija in Italija se na 90. dan postopka medsebojnega priznavanja, 27. septembra 2006, nista strinjali z odobritvijo dovoljenja za promet, saj sta menili, da obstajajo potencialno resna tveganja za zdravje živali.
However, in Europe ovariohysterectomy is most frequently performed in middle aged and old bitches. 
Vendar se v Evropi ovariohisterektomija najpogosteje opravlja pri psicah srednjih let ali starih psicah.
A Mutual Recognition Procedure started on 29 June 2006 with The Netherlands as Reference Member State and Belgium, Germany, Spain, France, Italy and the United Kingdom as Concerned Member States. 
Dne 29. junija 2006 se je začel postopek medsebojnega priznavanja (MRP), pri čemer je bila Nizozemska referenčna država članica, Belgija, Nemčija, Španija, Francija, Italija, in Združeno kraljestvo pa zadevne države članice.
CMD(v) could not reach an agreement by day 60 of this procedure, as France and Italy maintained their concerns. 
V CMD(v) do 60. dne tega postopka ni bilo doseženo soglasje, saj sta Francija in Italija vztrajala pri svojih zadržkih.
Possible risk connected with the use of ephedrine in this group of animals can be reduced by appropriate management measures. 
Možna tveganja zaradi uporabe efedrina v tej skupini živali lahko zmanjšamo z ustreznimi ukrepi pri obravnavi.
These figures seem highly convincing when compared to the 20 % placebo treated animals that became continent in study ACE129801. 
Te številke so zelo prepričljive v primerjavi z 20 % živalih, ki so dobivale placebo in postale kontinenčne v raziskavi ACE129801.
The raw outcome shows good effect in both test and control groups (87% vs 85.5%), an effect that might be somewhat higher in treatment naïve animals (93.7% vs 88.9%). 
Neobdelani podatki o rezultatih kažejo dober učinek v testni in kontrolni skupini (87 % proti 85,5 %), ki pa je še boljši pri zdravljenju prej nezdravljenih živali (93,7 % napram 88,9 %).
However, the study where Enurace 50 is compared to Propaline (ACE129802) is convincing although a non-inferiority analysis has not been performed. 
Vendar je raziskava, kjer so primerjali zdravilo Enurace 50 z zdravilom Propaline (ACE129802) prepričljiva, čeprav analiza neinferiornosti ni bila opravljena.
The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination Group procedure with the following amendment: 
Veljavni Povzetek glavnih značilnosti zdravila, označevanje in navodilo za uporabo so zadnje različice, ki so bile pripravljene v postopku koordinacijske skupine z naslednjo dopolnitvijo:
The Marketing Authorisation Holder should provide all supporting data (preclinical and clinical documentation, including the expert reports, efficacy and tolerance studies conducted), to justify a positive benefit-risk ratio for the treated animal. 
Imetnik dovoljenja za promet z zdravilom (MAH) mora predložiti vse podporne podatke (predklinično in klinično dokumentacijo, vključno s strokovnimi poročili, opravljenimi raziskavami učinkovitosti in tolerance) za utemeljitev pozitivnega razmerja med koristmi/tveganji za zdravljeno žival.
3 Conclusion and Recommendation 
Zaključki in priporočila
The CVMP has concluded that the risk/benefit for this product is favourable. 
CVMP meni, da je razmerje med tveganji koristmi za to zdravilo ugodno.
Taking into account that urinary incontinence may occur even several years after the operation it can be suspected that Enurace would be used mostly in older animals, more frequently suffering form cardiovascular, liver, renal and other diseases. 
Ob upoštevanju, da se urinska inkontinenca lahko pojavi celo več let po operaciji, lahko sklepamo, da bi se zdravilo Enurace uporabljalo večinoma pri starejših živalih, ki imajo pogosteje srčno-žilne, jetrne, ledvične in druge bolezni.
Proposed dose of 1 - 3 mg Ephedrine HCl /kg/day, divided in two oral doses is effective and safe, but some animals may need a higher dose, which is associated with individual variation in the response to ephedrine. 
Predlagani odmerek 1 - 3 mg efedrina HCl/kg/dan, ki ga razdelimo v dva peroralna odmerka, je učinkovit in varen, vendar nekatere živali potrebujejo višji odmerek, ki je povezan z individualno variacijo odziva na efedrin.
The application was made in accordance with Article 12.3 of Directive 2001/82/EC as a stand alone application. 
Vloga je bila predložena v skladu s členom 12(3) Direktive 2001/82/ES kot samostojna vloga.
At the recommended dose level, which according to the suggested SPC should be individually adjusted, safety is ensured to a reasonable level. 
Pri priporočenem odmerku, ki ga je treba skladno s predlogom Povzetka glavnih značilnosti zdravila individualno prilagoditi, je varnost zagotovljena do primerne ravni.
Although the influence of age was not reflected in the tolerance studies, it was taken into account in the efficacy and post- marketing studies. 
V študijah tolerance niso preverjali vpliva starosti živali, upoštevali pa so ga v študijah učinkovitosti in postmarketinških raziskavah.
A starting dose of 2 mg Ephedrine HCl per kg of bodyweight per day, divided in two oral doses is recommended. 
Priporočeni začetni odmerek je 2 mg efedrina HCl na kg telesne mase dnevno, razdeljen v dva peroralna odmerka.
Strength Animal species 
Jakost Živalsk a vrsta
Regarding cardiac dysfunction, this was one of the exclusion criteria so the studies give no information on use of the product in animals with such a condition but there is also no data suggesting that the cardiac patients must not be treated with the substance. 
Glede srčne disfunkcije Odbor ugotavlja, da je slednja bila eden od izključitvenih kriterijev, zato raziskave niso prinesle podatkov o uporabi zdravila pri živalih s takšnim stanjem, vendar tudi ni podatkov, da srčnih bolnikov ne smemo zdraviti z efedrinom.
The CVMP during its meeting of December 2006 started a referral procedure under Article 33(4) of Directive 2001/82/EC as amended for Enurace 50. 
CVMP je na seji decembra 2006 za zdravilo Enurace 50 začel napotitveni postopek po členu 33(4) Direktive 2001/82/ES, kakor je bila spremenjena.
France considers the risk/benefit analysis unfavourable for the animal when the adverse effects (in very rare cases atrium fibrillation and tachycardia) are weighed against the potential benefits of effective treatment of incontinence. 
Francija meni, da je razmerje med tveganji in koristmi neugodno za živali, če tehtamo neželene učinke (atrijska fibrilacija in tahikardija v zelo redkih primerih) in potencialne koristne učinke učinkovitega zdravljenja inkontinence.