FrancophonIA/ELRC3.0 huggingface dataset:
English: The experts were asked to discuss any restricted indication where the benefit/risk could be regarded as positive in the current armamentarium, and particularly the restricted indication proposed by the MAH.
Slovenian: Znanstveno svetovalna skupina za protivnetna sredstva je na pobudo odbora CHMP 3. septembra 2012 sklicala sestanek, na katerem so strokovnjaki razpravljali o omejenih indikacijah, pri katerih bi bilo lahko razmerje med tveganji in koristmi pozitivno v sklopu trenutnega armamentarija, in predvsem o omejeni indikaciji, ki jo je predlagal imetnik dovoljenja za promet z zdravilom.
English: • Chronic mucocutaneous candidosis
Slovenian: • kronična mukokutana kandidoza,
English: • Orapharyngeal and esophageal candidosis
Slovenian: • orofaringealna in ezofagealna kandidoza,
English: - hepatotoxicity with ketoconazole has been reported at a daily dose of 200 mg (median) which is the recommended daily dose; - the incidence and seriousness of hepatotoxicity associated with the use of oral ketoconazole is higher than with the use of other antifungals in the treatment of superficial, sub-cutaneous and systemic fungal infections, with the highest crude incidence rate per 10 000 patients for acute liver injury among other oral antifungals and with its use associated with the development of chronic hepatitis and cirrhosis (Chien et al, 1997; Garcia et al, 1999); - the onset of hepatotoxicity with ketoconazole usually occurs between 1 and 6 months after initiation of treatment (55% of the cases when the time to onset was documented) but has also be reported earlier than 1 month (including few days) after initiation of treatment (35% of the cases when the time to onset was documented);
Slovenian: Pregled podatkov iz literature in obdobja trženja zdravila, ki ga je predložil imetnik dovoljenja za promet z zdravilom, je pokazal, da - so o hepatotoksičnosti ob uporabi ketokonazola poročali pri dnevnem odmerku 200 mg (mediana), ki je priporočeni dnevni odmerek; - sta incidenca in resnost hepatotoksičnosti, povezane z uporabo peroralnega ketokonazola, večji kot pri uporabi drugih antimikotikov pri zdravljenju površinskih, subkutanih in sistemskih glivičnih okužb, z največjo grobo incidenco na 10 000 bolnikov za akutno jetrno poškodbo med drugimi peroralnimi antimikotiki, njegova uporaba pa je prav tako povezana z razvojem kroničnega hepatitisa in ciroze (Chien in sod.
English: • Chronic, recurrent vaginal candidosis
Slovenian: • kronična, ponavljajoča se vaginalna kandidoza, sistemske glivične okužbe,
English: Uncertainties still remain about the liver toxicity mechanism of ketoconazole.
Slovenian: Mehanizem hepatotoksičnosti pri uporabi ketokonazola je še vedno nejasen.
English: Therefore, fungal meningitis should not be treated with oral ketoconazole.
Slovenian: Ketokonazol slabo prodira v osrednje živčevje, zato se glivični meningitis ne sme zdraviti s peroralnim ketokonazolom.
English: Grounds for suspension of the marketing authorisations
Slovenian: Podlaga za začasni umik dovoljenj za promet z zdravilom Ob upoštevanju naslednjega:
English: Amongst other risk minimisation activities proposed by the MAH were the restriction of prescribing by physicians experienced in treating rare fungal skin disease and rare sub-sets of common fungal disease, Limitation of the use: short treatment periods and treatment of susceptible infecting pathogens only (Candida) and enhanced communication on the risks.
Slovenian: Med drugimi aktivnostmi za zmanjšanje tveganja, ki jih je predlagal imetnik dovoljenja za promet z zdravilom, je bila omejitev predpisovanja na zdravnike z izkušnjami z zdravljenjem redkih glivičnih kožnih bolezni in redkih podskupin pogostih glivičnih bolezni.
English: • The Committee could not identify any further adequate measures to reduce the risks of ketoconazole for oral use as antifungal treatment to an acceptable level.
Slovenian: • odbor ni ugotovil nobenih dodatnih primernih ukrepov, ki bi zmanjšali tveganje pri ketokonazolu za peroralno uporabo, ki se uporablja za antimikotično zdravljenje, na sprejemljivo stopnjo; zato je odbor sklenil, da razmerje med tveganji in koristmi zdravil za peroralno uporabo, ki vsebujejo ketokonazol, pri zdravljenju glivičnih okužb ni ugodno.
English: In addition, the claimed indications concern superficial fungal infections which are mainly confined to skin involvement (also mucous membranes for CMC), and while the social burden/inconvenience of this type of infections is not denied, the fact that they are mostly benign is also per se to be balanced with the level of hepatotoxicity of the drug.
Slovenian: Medtem ko so upoštevali družbeno breme/nadležnost te vrste okužb, je jasno tudi, da so te večinoma benigne, zato korist zdravila ne odtehta stopnje hepatotoksičnosti zdravila.
English: • Cutaneous candidosis
Slovenian: • kandidoza kože,
English: However additional measures must be implemented to minimise potential risks in these patients.
Slovenian: Vendar pa je treba izvajati dodatne ukrepe za zmanjšanje možnih tveganj pri teh bolnikih.
English: Details of this recommendation are presented hereafter.
Slovenian: Podrobnosti omenjenega priporočila so predstavljene v nadaljevanju.
English: Benefit risk balance
Slovenian: Razmerje med koristmi in tveganji
English: New results from CRYSTAL have also become available.
Slovenian: Na voljo so postali tudi rezultati iz študije CRYSTAL.
English: Monitoring of renal function in patients is recommended for at least 90 days.
Slovenian: Priporočeno je spremljanje ledvične funkcije pri bolnikih v obdobju najmanj 90 dni.
English: While the re-examination was ongoing some Member States decided to suspend or limit the marketing or use of these medicines in their territories.
Slovenian: V času, ko je potekal ponoven pregled, so se nekatere države članice odločile, da bodo začasno ustavile ali omejile trženje oziroma uporabo omenjenih zdravil na svojih ozemljih.
English: An European drug utilisation study will also be conducted to evaluate the effectiveness of the recommended risk minimisation measures.
Slovenian: Prav tako bo izvedena evropska študija uporabe zdravil za oceno učinkovitosti priporočenih ukrepov za zmanjšanje tveganja.
English: Protocols and results of these studies will be submitted to national competent authorities according to agreed timelines.
Slovenian: Protokoli in rezultati teh študij bodo v dogovorjenih rokih predloženi pristojnim nacionalnim organom.
English: In accordance with the EU legislation, this type of action required that an EU review procedure be carried out.
Slovenian: V skladu z zakonodajo EU je morala EU zaradi tega ukrepa sprožiti revizijski postopek.
English: Additional expert advice was sought from an ad-hoc expert group.
Slovenian: Odbor je zaprosil tudi za izvedensko svetovanje ad hoc skupine izvedencev.
English: Having reviewed the PRAC recommendation, the CMDh agreed with the overall scientific conclusions and grounds for recommendation.
Slovenian: Potem ko je pregledala priporočilo, ki ga je izdal odbor PRAC, se je skupina CMDh strinjala s splošnimi znanstvenimi zaključki in podlago za priporočilo.
English: • The PRAC also concluded that there was need for further risk minimisation measures such as information to patients and healthcare professionals.
Slovenian: • odbor PRAC je zaključil tudi, da so potrebni dodatni ukrepi za zmanjšanje tveganja, na primer informacije za bolnike in zdravstvene delavce.
English: Companies had been encouraged to submit core elements of the risk management plan, but the CMDh considered that this should be a condition.
Slovenian: Družbam so priporočili, naj predložijo ključne dele načrta obvladovanja tveganj, vendar je skupina CMDh menila, da bi to moral biti pogoj.
English: The product information will be updated to reflect these restrictions and warnings.
Slovenian: Informacije o zdravilu bodo posodobljene v skladu s temi omejitvami in opozorili.
English: The first review was initially started under the framework of Article 31 of Directive 2001/83/EC.
Slovenian: Prvi pregled se je najprej začel v okviru člena 31 Direktive 2001/83/ES.
English: This is subject to restrictions, warnings and other changes to the product information.
Slovenian: To velja, če se upoštevajo omejitve, opozorila in druge spremembe informacij o zdravilu;
English: The experts suggested that benefit of HES may be seen in particular in perioperative bleeding.
Slovenian: Izvedenci so menili, da je koristi HES mogoče opaziti predvsem pri perioperativnih krvavitvah.
English: In hypovolaemic patients with normal pulmonary function, the use of colloids to maintain colloid-osmotic pressure may limit the development of peripheral as well as pulmonary oedema (Vincent JL 2000).
Slovenian: Pri hipovolemičnih bolnikih z normalno pljučno funkcijo lahko uporaba koloidov za vzdrževanje koloidno-osmotskega tlaka omeji razvoj tako perifernega kot tudi pljučnega edema (Vincent JL, 2000).
English: In addition, in the BaSES study, the hospitalisation time was significantly reduced in patients treated with 6% HES 130/0.4 compared to 0.9% NaCl.
Slovenian: Poleg tega je bil v študiji BaSES čas bolnišničnega zdravljenja pri bolnikih, ki so jih zdravili s 6-odstotnim HES 130/0,4, znatno krajši kot pri bolnikih, ki so prejemali 0,9-odstotni NaCl.
English: Consequently the CMDh decided that synopsis were not required in advance of the recommended scientific advice.
Slovenian: Posledično je CMDh sklenila, da povzetkov ni treba predložiti pred pridobitvijo priporočenega znanstvenega mnenja.
English: Hamaji et al 2013 also showed that significantly fewer red blood cell transfusions were required in the HES group.
Slovenian: Hamaji et al. (2013) pa so pokazali, da je bilo v skupini s HES potrebnih veliko manj transfuzij rdečih krvnih celic.
English: Some publications also suggest that colloids might help to prevent positive fluid balance and/or overinfusion of fluids (Wills 2005, Naing CM and Win DK 2010).
Slovenian: Nekatere publikacije tudi navajajo, da bi lahko koloidi pomagali preprečiti pozitivno razmerje tekočin in/ali infundiranje prevelikih količin tekočin (Wills, 2005; Naing, CM in Win DK, 2010).
English: Although 90-day mortality was lower among patients receiving colloids, this requires further investigations.
Slovenian: Kljub temu da je bila smrtnost v 90 dneh manjša med bolniki, ki so prejemali koloide, je treba zgornjo ugotovitev podrobneje raziskati.
English: Some of authors argue that a positive net fluid balance is associated with a decrease in organ perfusion and an increased mortality (e.g. Sadaka F et al. 2013, Payen D et al. 2008).
Slovenian: Nekateri avtorji trdijo, da je neto pozitivno ravnovesje tekočin povezano z zmanjšano perfuzijo organov in povečano smrtnostjo (npr. Sadaka, F. et al., 2013, Payen, D. et al., 2008).
English: The MAHs are also encouraged to submit risk management plans to national competent authorities.
Slovenian: Imetnikom dovoljenja za promet z zdravilom so tudi priporočili, naj pristojnim nacionalnim organom predložijo načrte obvladovanja tveganj.
English: The experts agreed that the benefits may be observed in severe hypovolaemia in short duration only at the beginning i.e. perioperative setting and disappearing faster with patient's stabilisation.
Slovenian: Ti so se strinjali, da je pri hudi hipovolemiji mogoče opaziti kratkotrajne koristi samo na začetku, tj. v perioperativnem okolju, saj hitro izginejo, ko se stanje bolnika stabilizira.
English: • The PRAC noted the conclusions of a review under article 31 of Directive 2001/83/EC.
Slovenian: • odbor PRAC je upošteval zaključke iz pregleda po členu 31 Direktive 2001/83/ES.
English: In view of the above and considering that the study protocols of the drug utilisation study and of the two randomised clinical trials are conditions to the marketing authorisation, the CMDh noted that these elements should be reflected in a risk management plan.
Slovenian: Na podlagi vsega zgoraj omenjenega in ob upoštevanju, da so protokol študije uporabe zdravila in protokola dveh randomiziranih kliničnih preskušanj pogoji za pridobitev dovoljenja za promet z zdravilom, je skupina CMDh izpostavila, da morajo biti ti deli vključeni v načrt obvladovanja tveganj.
English: Hydroxyethyl starch (HES) solutions for infusion include products with starch derived from potato or corn with different molecular weights and substitution ratios.
Slovenian: Raztopine za infundiranje, ki vsebujejo hidroksietil škrob (HES), vključujejo zdravila z vsebnostjo škroba, pridobljenega iz krompirja ali koruze, z različnimi molekulskimi masami in stopnjami substituiranosti.
English: The PRAC considered that the use of HES must be discontinued at the first sign of renal injury.
Slovenian: Odbor PRAC je menil, da je treba uporabo HES prekiniti ob prvih znakih okvare ledvic.
English: Particular caution should be exercised when treating patients with impaired hepatic function or in patients with blood coagulation disorders.
Slovenian: Posebna previdnost je potrebna pri zdravljenju bolnikov z okvarjenim delovanjem jeter in bolnikov z motnjami strjevanja krvi.
English: HES containing solutions for infusion were indicated mainly for the treatment and prophylaxis of hypovolaemia and hypovolemic shock.
Slovenian: Raztopine za infundiranje, ki vsebujejo hidroksietil škrob, so bile v glavnem indicirane za zdravljenje in profilakso hipovolemije ter hipovolemičnega šoka.
English: Core elements of a direct healthcare professional communication were agreed, together with the timelines for distribution, and that studies should be conducted.
Slovenian: Opredeljeni so bili ključni deli neposrednega obvestila zdravstvenim delavcem in roki za njegovo razdelitev ter zahteva po izvedbi študije.
English: However, it must be noted that new evidence was considered in the procedure under Article 107i of Directive 2001/83/EC.
Slovenian: Treba je poudariti, da so v postopku po členu 107i Direktive 2001/83/ES proučili nove dokaze.
English: Overall summary of the scientific evaluation of solutions for infusion containing hydroxyethyl starch medicinal products by PRAC
Slovenian: Splošni povzetek znanstvenega vrednotenja zdravil v obliki raztopin za infundiranje, ki vsebujejo hidroksietil škrob, s strani odbora PRAC
English: Some benefit for elective surgical patients has also been shown in short-term surrogate hemodynamic outcomes along with a modest volume sparing effect (Hartog et al. 2011).
Slovenian: Določena korist za bolnike, pri katerih je predviden kirurški poseg, se je pokazala tudi s kratkotrajnim izboljšanjem nadomestnih hemodinamskih kazalcev skupaj z majhnim učinkom na ohranitev volumna (Hartog et al., 2011).
English: Results from the RaFTinG registry in intensive care units, an observational, non-randomised study aiming to gather more information in ‘real-life' clinical practice showed no statistically significant differences between patients treated with crystalloids only (n=2482) and those treated with colloids (all HES preparations and gelatin, n=2063) for the endpoints of 90-day mortality.
Slovenian: Rezultati iz registra študije RaFTinG, opazovalne, nerandomizirane študije, opravljene na oddelkih za intenzivno nego, s katero so želeli pridobiti več informacij v „resnični“ klinični praksi, niso pokazali statistično pomembnih razlik med bolniki, zdravljenimi s samimi kristaloidi (n = 2482), in tistimi, ki so jih zdravili s koloidi (vsi pripravki s HES in želatina, n = 2063), pri izidih smrtnosti v 90 dneh.
English: The CMDh also considered that the direct healthcare professional communication (DHPC) should be submitted to the NCAs where HES products are marketed, within one week of the CMDh adopted position as per agreed communication plan.
Slovenian: Skupina CMDh je prav tako menila, da je treba pristojnim nacionalnim organom v državah, kjer se tržijo zdravila, ki vsebujejo HES, predložiti neposredno obvestilo zdravstvenim delavcem (DHPC), in sicer v enem tednu od sprejetja stališča skupine CMDh v skladu z dogovorjenim načrtom obveščanja.
English: In addition, special warnings in surgery and trauma patients have been included.
Slovenian: Poleg tega je vključil posebna opozorila za kirurške bolnike in bolnike s poškodbami;
English: Despite the studies' limitations which were noted, the results from the CRYSTAL study comparing colloids to crystalloids showed that in patients with hypovolaemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality.
Slovenian: Kljub ugotovljenim omejitvam študije so rezultati iz študije CRYSTAL, v kateri so primerjali koloide s kristaloidi, pokazali, da pri uporabi koloidov oziroma kristaloidov pri bolnikih s hipovolemijo ni bilo pomembnih razlik v smrtnosti v 28 dneh.
English: The PRAC issued a recommendation on available data for this review in June 2013, concluding that HES solutions should be suspended in all patient populations.
Slovenian: Odbor PRAC je na podlagi podatkov, ki so bili na voljo za ta pregled, junija 2013 izdal priporočilo o začasni ukinitvi uporabe raztopin, ki vsebujejo HES, pri vseh skupinah bolnikov.
English: To this end the MAHs were strongly advised to seek scientific advice with the European Medicines Agency, in time for the submission of the study protocols to the national competent authorities (NCAs) within 6 months of the European Commission Decision.
Slovenian: V ta namen so imetnikom dovoljenj za promet z zdravili izrecno svetovali, naj pridobijo znanstveno mnenje Evropske agencije za zdravila, preden se izteče rok za predložitev protokolov študij pristojnim nacionalnim organom, ki je 6 mesecev od sklepa Evropske komisije.
English: The PRAC also considered that studies should be conducted to provide more evidence on the efficacy and safety of hydroxyethyl starch in the perioperative setting and trauma.
Slovenian: Prav tako je menil, da so potrebne študije za zagotovitev dodatnih dokazov o učinkovitosti in varnosti hidroksietil škroba v perioperativnem okolju in pri poškodbah.
English: Therefore, the PRAC agreed that the therapeutic indication of hydroxyethyl starch containing products should be restricted to treatment of hypovolaemia due to acute blood loss when crystalloids alone are not considered sufficient.
Slovenian: Odbor PRAC je zato sklenil, da bi bilo treba terapevtsko indikacijo zdravil, ki vsebujejo hidroksietil škrob, omejiti na zdravljenje hipovolemije zaradi akutne izgube krvi, kadar sami kristaloidi ne zadoščajo.
English: Whilst recognising the limitations of these studies which included limited size and short duration of follow-up, the PRAC noted that some volume sparing effect was reported in Madi-Jebara et al. 2008, that suggested that HES 130/0.4 6% seems to have benefits over twice the volume of Ringer's lactate in preventing spinal anaesthesia induced hypotension.
Slovenian: Čeprav je odbor PRAC ugotovil, da so imele omenjene študije določene omejitve, na primer omejen obseg in kratko trajanje spremljanja, je upošteval, da so v študiji, ki so jo objavili Madi-Jebara et al. (2008), opazili določen učinek na ohranitev volumna, ki kaže, da ima 6-odstotni HES 130/0,4 večje koristi od dvakrat večje količine Ringerjevega laktata pri preprečevanju hipotenzije po spinalni anesteziji.
English: Following requests for re-examination by marketing authorisation holders (MAHs), the PRAC confirmed its previous position under the Article 31 in October 2013.
Slovenian: Potem ko so imetniki dovoljenj za promet z zdravili zahtevali ponoven pregled mnenja, je odbor PRAC oktobra 2013 potrdil svoje prvotno mnenje na podlagi člena 31.
English: On the basis of the available data, in particular results from VISEP, 6S and CHEST studies, the PRAC concluded that HES is associated with an increased risk of mortality and renal failure in patients with sepsis, in critically ill and burn patients and that the benefits of HES do not outweigh the risks in these patient populations.
Slovenian: Na podlagi razpoložljivih podatkov, zlasti rezultatov iz študij VISEP, 6S in CHEST, je odbor PRAC zaključil, da je HES povezan s povečanim tveganjem za smrtnost in odpoved ledvic pri bolnikih s sepso, kritično bolnih ter bolnikih z opeklinami in da koristi HES ne odtehtajo več tveganj pri teh skupinah bolnikov.
English: The PRAC therefore acknowledged the results of this studies which shows no risk of mortality associated with the use of HES but considered that given the limitations of this study its findings could not negate the findings from 6S and VISEP studies that had shown an increased risk of mortality in critically ill patients.
Slovenian: Odbor PRAC je upošteval rezultate te študije, ki so pokazali, da uporaba HES ni povezana s povečanim tveganjem za smrtnost, vendar je menil, da zaradi omejitev omenjene študije njeni rezultati ne morejo ovreči ugotovitev iz študij 6S in VISEP, ki so pokazale povečano tveganje za smrtnost pri kritično bolnih.
English: Although the mechanisms by which increased renal injury and mortality occur is not well established, it is possible that the degree of inflammatory processes seen in sepsis and critically ill patients is greater and associated with significant capillary leakage compared with other patient populations such as the perioperative setting after elective surgery or un-complicated trauma where the systematic inflammatory process and the extent of capillary leak may be lower.
Slovenian: Čeprav mehanizmi, zaradi katerih se povečajo okvare jeter in smrtnost, niso povsem raziskani, obstaja možnost, da je stopnja vnetnih procesov pri septičnih in kritično bolnih bolnikih višja in povezana z večjim prepuščanjem kapilar kot pri drugih skupinah bolnikov, na primer bolnikih v perioperativnem okolju po načrtovanem kirurškem posegu ali nezapleteni poškodbi, ko sta stopnja sistemskega vnetnega procesa in obseg prepuščanja kapilar lahko manjša.
English: • The PRAC considered, in view of the new evidence which includes data from clinical trials, further expert advice, new proposals for additional risk minimisation measures, including restrictions on use and a commitment from the MAHs to perform additional studies in patients with trauma and in elective surgery, that the benefit of hydroxyethyl starch containing products outweighs the risk in the treatment of hypovolaemia due to acute blood loss when crystalloids alone are not considered sufficient.
Slovenian: • odbor PRAC je na podlagi novih dokazov, vključno s podatki iz kliničnih študij, dodatnega izvedenskega mnenja, novih predlogov za dodatne ukrepe za zmanjšanje tveganja, ki vključujejo omejitve glede uporabe in obvezo imetnikov dovoljenj za promet z zdravili, da bodo izvedli dodatne študije na bolnikih s poškodbami in bolnikih, pri katerih je predviden kirurški poseg, menil, da so koristi zdravil, ki vsebujejo hidroksietil škrob, večje od tveganj pri zdravljenju hipovolemije zaradi akutne izgube krvi, kadar sami kristaloidi ne zadoščajo.
English: In addition, two phase IV randomised clinical trials with an appropriate control and clinically meaningful endpoints will need to be conducted to provide more evidence on the efficacy and safety, including the risk of 90-day mortality and renal failure, in perioperative and trauma populations.
Slovenian: Poleg tega je treba izvesti dve randomizirani klinični preskušanji IV. faze z ustrezno kontrolo in klinično relevantnimi opazovanimi dogodki za pridobitev dodatnih dokazov o učinkovitosti in varnosti, vključno s podatki o tveganju za smrtnost in odpoved ledvic v 90 dneh, pri bolnikih v perioperativnem obdobju in bolnikih s poškodbami.
English: Detailed explanation for the differences from the PRAC recommendation
Slovenian: Podrobna obrazložitev odstopanj od priporočila odbora PRAC
English: Scientific conclusions and grounds for the variation to the terms of the marketing authorisations subject to conditions and detailed explanation for the differences from the PRAC recommendation
Slovenian: Znanstveni zaključki in podlaga za spremembo pogojev dovoljenj za promet z zdravili pod določenimi pogoji ter podrobna obrazložitev odstopanj od priporočila odbora PRAC