FrancophonIA/ELRC3.0 huggingface dataset:
English: Efficacy studies of ketoconazole on Malassezia folliculitis, Pityriasis versicolor, Tinea Capitis and Tinea Barbae, Tinea Corporis, Tinea Cruris, Tinea Pedis, and Tinea Manuum were scarce.
Slovenian: Študije učinkovitosti ketokonazola proti Malassezia folliculitis, Pityriasis versicolor, Tinea Capitis ter Tinea Barbae, Tinea Corporis, Tinea Cruris, Tinea Pedis in Tinea Manuum so omejene.
English: The CHMP, having considered the data submitted by the MAH, was of the opinion that the proposed risk minimisation activities were not appropriate to reduce the risks to an acceptable level taking into account the restrictions and warnings already in place.
Slovenian: Odbor CHMP je obravnaval podatke, ki jih je predložil imetnik dovoljenja za promet z zdravilom, in menil, da predlagane aktivnosti za zmanjševanje tveganja niso primerne za zmanjšanje tveganja na sprejemljivo stopnjo, pri čemer je upošteval že veljavne omejitve in opozorila.
English: Since no additional study was provided, the hypothesis that high cumulative dose of ketoconazole is a possible risk factor for the development of serious hepatotoxicity could not be supported at this stage.
Slovenian: Ker ni bila predložena nobena dodatna študija, hipoteze, da je velik kumulativni odmerek ketokonazola morebitni dejavnik tveganja za razvoj resne hepatotoksičnosti, v tej fazi ni bilo mogoče potrditi.
English: Moreover, tests for susceptibility to ketoconazole are not commercially available.
Slovenian: Poleg tega preiskave za občutljivost na ketokonazol niso na voljo na tržišču.
English: Characteristics of acute injuries mainly included cytolysis and may lead to serious outcomes including liver transplantation.
Slovenian: Za akutne poškodbe je bila večinoma značilna citoliza, ki lahko povzroči resne izide, vključno s presaditvijo jeter.
English: Of note, while ketoconazole was available since 1982, fluconazole and itraconazole became later available in the 1990's.
Slovenian: Treba je omeniti, da je ketokonazol na voljo od leta 1982, flukonazol in itrakonazol pa so začeli tržiti v 90. letih 20. stoletja.
English: Given its level of efficacy and its poor distribution in the central nervous system, the use of ketoconazole in systemic mycoses might expose patients to sub-optimal management, as translated in the therapeutic guidelines.
Slovenian: Glede na stopnjo učinkovitosti in slabo porazdelitev v osrednjem živčevju lahko uporaba ketokonazola pri sistemskih mikozah bolnike izpostavi suboptimalni obravnavi, kot je razloženo v terapevtskih smernicah.
English: In addition, the use of ketoconazole in those cases would likely require a long term or repeated treatment which would be of concern for the SAG given the hepatotoxicity profile of the compound.
Slovenian: Poleg tega bi uporaba ketokonazola pri teh primerih verjetno zahtevala dolgotrajno ali večkratno zdravljenje, kar je za skupino predstavljalo težavo zaradi hepatotoksičnega profila te spojine.
English: In children, dosing recommendations are also broadly consistent with 100 mg daily for children weighing 15-30 kg and the same dose as for adults in children weighing more than 30 kg.
Slovenian: Tudi pri otrocih so priporočila za odmerjanje splošno usklajena, tj. 100 mg na dan pri otrocih s telesno maso od 15 do 30 kg, odmerek pri otrocih s telesno maso, večjo od 30 kg, pa je enak kot pri odraslih.
English: The SAG was also of the opinion that the pharmacokinetics / pharmacodynamics profile of ketoconazole presents similar limitations as the other systemic antifungal treatments (i.e. limited absorption, distribution) and the drug-drug interaction profile could be even worse.
Slovenian: Skupina je prav tako menila, da farmakokinetični/farmakodinamični profil ketokonazola pomeni podobne omejitve kot druge oblike sistemskega antimikotičnega zdravljenja (tj. omejena absorpcija, porazdelitev), profil medsebojnega delovanja med zdravili pa bi bil lahko še slabši.
English: In view of the above, the French Agency considered in June 2011 that the benefit-risk balance of oral ketoconazole was negative, suspended the existing marketing authorisations in France and informed the healthcare professionals and the public of its conclusions.
Slovenian: Glede na zgornje podatke je francoska agencija leta 2011 menila, da je razmerje med tveganji in koristmi peroralnega ketokonazola negativno, začasno umaknila obstoječa dovoljenja za promet z zdravilom v Franciji in zdravstvene delavce in javnost obvestila o svojih sklepih.
English: Based on this analysis, the point-estimate risk, in terms of the commonly-used Frequency Categories in the Summary of Product Characteristics (SmPCs), was “Common” (≥ 1/100 to < 1/10) for any Hepatic Function Test result being abnormal, and “Rare” (≥ 1/10,000 to < 1/1,000) for Hepatitis and/or Jaundice.
Slovenian: Na podlagi te analize je bilo tveganje pri ocenjeni vrednosti v skladu z običajnimi kategorijami za pogostnost v povzetku glavnih značilnosti zdravila „pogosto“ (≥ 1/100 do < 1/10) za kateri koli nenormalni rezultat preiskave jetrnega delovanja ter „redko“ (≥ 1/10 000 do < 1/1 000) za hepatitis in/ali zlatenico.
English: The experts unanimously agreed that there was no scientific evidence to support the MAH's revised indication proposal.
Slovenian: Strokovnjaki so se soglasno strinjali, da ni znanstvenih dokazov, ki bi podprli predlog revidirane indikacije, ki ga je predložil imetnik dovoljenja za promet z zdravilom.
English: Treatment duration ranges from 5 consecutive days (vaginal candidosis) to up to 6 months for systemic fungal infections such as paracoccidioidomycosis and histoplasmosis.
Slovenian: Trajanje zdravljenja je od 5 zaporednih dni (vaginalna kandidoza) do 6 mesecev pri sistemskih glivičnih okužbah, kot sta južnoameriška blastomikoza in histoplazmoza.
English: The SAG was of the opinion that there are no data to support the efficacy of ketoconazole when other treatments (including other azoles) have failed or resistance has been detected.
Slovenian: Skupina je menila, da ni podatkov, ki bi podprli učinkovitost ketokonazola, kadar so bile druge oblike zdravljenja neuspešne (vključno z drugimi azoli) ali kjer so zaznali odpornost.
English: In addition, based on the literature review, ketoconazole seemed to be the only antifungal agent associated with development of chronic hepatitis and cirrhosis.
Slovenian: Poleg tega je bilo na podlagi pregleda literature videti, da je ketokonazol edini antimikotik, povezan z razvojem kroničnega hepatitisa in ciroze.
English: Based on those conclusions, the Committee recommended the suspension of the marketing authorisations for all ketoconazole-containing products for oral use.
Slovenian: Na podlagi teh zaključkov je odbor priporočil začasni umik dovoljenj za promet z vsemi zdravili za peroralno uporabo, ki vsebujejo ketokonazol.
English: In order to assess the general safety of ketoconazole, relevant information from pre-clinical studies, clinical trials, post-marketing spontaneous case reports, pharmaco-epidemiological studies and published literature was assessed.
Slovenian: Za namene vrednotenja splošne varnosti ketokonazola so ocenili zadevne podatke iz predkliničnih študij, kliničnih preskušanj, spontanih poročil o primerih v obdobju trženja zdravila, farmakoepidemioloških študij in objavljene literature.
English: The clinical safety of oral ketoconazole was evaluated in 4735 subjects in 92 company-sponsored clinical trials of ketoconazole tablets (or suspension), administered either to treat a variety of fungal infections in patients or to healthy-volunteer subjects.
Slovenian: Klinično varnost peroralnega ketokonazola so ocenili pri 4 735 preskušancih v 92 kliničnih preskušanjih, ki jih je financirala farmacevtska družba, s tabletami (ali suspenzijo) ketokonazola, ki so se uporabljale za zdravljenje različnih glivičnih okužb pri bolnikih ali zdravih prostovoljcih.
English: Results from non-clinical toxicity studies indicated the liver and endocrine system as primary target organs.
Slovenian: Rezultati iz predkliničnih študij toksičnosti so pokazali, da sta primarna ciljna organa jetra in endokrini sistem.
English: The demonstrate the effectiveness of ketoconazole in these indications, the MAH provided a total of 40 cases, 19 cases based on clinical visits of two clinicians who kept a registry of such patients and 21 cases based on a review of the literature.
Slovenian: Kot dokaz za učinkovitost ketokonazola pri teh indikacijah je imetnik dovoljenja za promet z zdravilom predložil skupno 40 primerov, od katerih jih je 19 temeljilo na kliničnih obiskih pri dveh zdravnikih, ki sta vodila register teh bolnikov, 21 pa na pregledu literature.
English: Although the efforts of the company to substantiate the use of ketoconazole in rescue therapy of other azoles in superficial fungal infections was acknowledged, the cases series were limited and could not adequately ascertain the benefit of the drug in rescue therapy as claimed by the company.
Slovenian: Čeprav je skupina priznala prizadevanja farmacevtske družbe za utemeljitev uporabe ketokonazola kot reševalnega zdravljenja namesto drugih azolov pri površinskih glivičnih okužbah, so bili nizi primerov omejeni in niso zadostno dokazali koristi tega zdravila pri reševalnem zdravljenju, kot je trdila farmacevtska družba.
English: Taking into account all the above, the CHMP could not identify any situation that could justify exposing a patient to the level of hepatotoxicity of ketoconazole for oral use.
Slovenian: Upoštevajoč celotno zgornje besedilo odbor CHMP ni ugotovil nobene okoliščine, ki bi upravičila izpostavitev bolnika stopnji hepatotoksičnosti ketokonazola za peroralno uporabo.
English: All but 5 tinea capitis (no case of Malassezia folliculitis) corresponded to Chronic Mucocutaneous Candidiasis (n=16).
Slovenian: Vsi primeri, razen 5 primerov tinea capitis, so ustrezali kronični mukokutani kandidozi (n = 16) (primera Malassezia folliculitis ni bilo).
English: Overall, although hepatotoxicity is a class effect of azoles, the quantitative and qualitative aspects of the hepatotoxicity of ketoconazole are of particular concern.
Slovenian: Čeprav je hepatotoksičnost učinek razreda azolnih antimikotikov, so predvsem problematični količinski in kakovostni vidiki hepatotoksičnosti ketokonazola.
English: The experts all concurred that ketoconazole safety profile was worse than the other systemic antifungal treatments, and there's no evidence that it would represent an option when other azoles are not tolerated.
Slovenian: Vsi strokovnjaki so se strinjali, da je varnostni profil ketokonazola slabši kot pri drugih oblikah sistemskega antimikotičnega zdravljenja in da ni dokazov, ki bi podprli to možnost, kadar bolniki ne prenašajo drugih azolnih antimikotikov.
English: The analysis also showed that the use of oral ketoconazole was associated with the highest crude incidence rate per 10 000 patients for acute liver injury among other oral antifungals as well as with the development of chronic hepatitis and cirrhosis.
Slovenian: Analiza je prav tako pokazala, da je bila uporaba peroralnega ketokonazola povezana 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.
English: In addition, the experts would not easily foresee the utility of ketoconazole when resistance to agent(s) of the class is detected as cross resistance is frequent and there is a lack of evidence around the potential susceptibility to ketoconazole when resistance to other azoles occurs.
Slovenian: Poleg tega strokovnjaki niso predvideli uporabe ketokonazola, kadar se ugotovi odpornost na učinkovine tega razreda, saj je navzkrižna odpornost pogosta, dokazi za morebitno občutljivost na ketokonazol, če se pojavi odpornost na druge azolne antimikotike, pa so pomanjkljivi.
English: A cumulative search through 15 July 2011 for adverse events coded to the MedDRA (version 14.0) Preferred Terms (PTs) listed in the Standardised MedDRA Queries (SMQ) Hepatic disorders (broad terms) retrieved 1,512 cases, of which 1,505 cases were part of the sub-SMQ Drug related hepatic disorders (comprehensive search excluding non-drug related events such as congenital, infection, alcohol and pregnancy related events).
Slovenian: Kumulativna preiskava za neželene učinke, razvrščene po prednostnih izrazih MedDRA (različici 14.0), navedenih pri jetrnih boleznih (razširjen pojem) po SMQ (Standardised MedDRA Queries), ki je vključevala čas do 15. julija 2011, je ugotovila 1 512 primerov, od katerih jih je bilo 1 505 z zdravilom povezanih jetrnih bolezni po pod-SMQ (izčrpna preiskava, ki je izključila dogodke, ki niso povezani z zdravilom, kot so kongenitalni dogodki, okužba ter z alkoholom in nosečnostjo povezani dogodki).
English: The MAH provided a detailed report examining efficacy of oral ketoconazole by approved indication.
Slovenian: Imetnik dovoljenja za promet z zdravilom je predložil podrobno poročilo o učinkovitosti peroralnega ketokonazola pri odobrenih indikacijah.
English: • The Committee reviewed all the available data on the efficacy and safety of ketoconazolecontaining medicines for oral use, in particular data in relation to the risk of hepatotoxicity provided by the MAHs in writing and in the oral explanations;
Slovenian: • odbor je pregledal vse razpoložljive podatke o učinkovitosti in varnosti zdravil za peroralno uporabo, ki vsebujejo ketokonazol, predvsem podatke, povezane s tveganjem hepatotoksičnosti, ki jih je v pisni obliki in z ustno obrazložitvijo predložil imetnik dovoljenja za promet z zdravilom;
English: Of the 1,505 cases of interest; 880 (58%) were medically validated serious of which 18 life-threatening cases did not present any confounding factors and therefore are supportive of a causal role of ketoconazole.
Slovenian: Od 1 505 primerov zanimanja jih je bilo 880 (58 %) medicinsko validiranih kot resnih.
English: Indeed, the SAG considered that the activity of the newer systemic antifungals is expected to be superior to ketoconazole.
Slovenian: Skupina je celo menila, da je pričakovati, da bo učinkovitost novih sistemskih antimikotikov boljša kot pri ketokonazolu.
English: From 1985 to 2010, around a hundred cases of hepatic disorders with oral ketoconazole were reported to the French Pharmacovigilance Regional Centres network, including hepatitis NOS, toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, hepatic failure.
Slovenian: Od leta 1985 do 2010 so francoskim regionalnim centrom za farmakovigilanco poročali o približno sto primerih jetrnih bolezni, povezanih s peroralnim ketokonazolom, vključno s hepatitisom
English: The Committee could not identify a fungal infection where the level of hepatotoxicity of the drug could be balanced by an adequately substantiated benefit and therefore concluded that the benefits of oral ketoconazole in the treatment of all antifungal indications listed above do not outweigh the risks.
Slovenian: Odbor ni ugotovil nobene glivične okužbe, pri kateri bi zadostno utemeljena korist odtehtala stopnjo hepatotoksičnosti zdravila, zato je zaključil, da koristi peroralnega ketokonazola pri zdravljenju vseh zgoraj navedenih antimikotičnih indikacijah niso večje od tveganj.
English: The benefits and the risks of oral ketoconazole in dermatophytosis (Tinea Capitis, Tinea Barbae, Tinea Corporis, Tinea Cruris, Tinea Pedis, and Tinea Manuum) Pityriasis Versicolor, Malassezia folliculitis, Infections Due to Candida Species, Cutaneous candidiasis, Chronic Mucocutaneous Candidosis, Oropharyngeal Candidosis, Oesophageal Candidosis, Chronic Recurrent Vulvovaginal Candidosis, Systemic Mycoses (Paracoccidioidomycosis, Histoplasmosis, Coccidioidomycosis, Blastomycosis) were reviewed by the MAH which concluded that ketoconazole had an acceptable safety profile when used at low dose for short periods in benign diseases, but that its use at high doses for extended periods could only be supported where there was good efficacy and the risks of hepatotoxicity were outweighed by the mortality and serious morbidity of the disease.
Slovenian: Imetnik dovoljenja za promet je pregledal koristi in tveganja peroralnega ketokonazola pri dermatofitiji (Tinea Capitis, Tinea Barbae, Tinea Corporis, Tinea Cruris, Tinea Pedis in Tinea Manuum), Pityriasis Versicolor, Malassezia folliculitis, okužbah zaradi vrst kandide, kandidozi kože, kronični mukokutani kandidozi, orofaringealni kandidozi, ezofagealni kandidozi, kronični ponavljajoči se vulvovaginalni kandidozi, sistemskih mikozah (južnoameriški blastomikozi, histoplazmozi, kokcidioidomikozi, blastomikozi) in ugotovil, da ima ketokonazol sprejemljiv varnostni profil, če se uporablja kratkotrajno in z majhnim odmerkom pri benignih boleznih, njegova dolgotrajna uporaba v velikih odmerkih pa je upravičena samo, če je učinkovitost velika, tveganje hepatotoksičnosti pa je manjše od tveganja umrljivosti in resne obolevnosti zaradi bolezni.
English: The potential for hepatotoxicity is a class effect of azole antifungals and has been long reported for ketoconazole in numerous nonclinical and clinical references.
Slovenian: Potencial za hepatotoksičnost je učinek razreda azolnih antimikotikov, o njem pa že dolgo poročajo tudi v številnih predkliničnih in kliničnih študijah s ketokonazolom.
English: • The Committee considered that available data from pre-clinical studies, clinical trials, postmarketing spontaneous case reports, pharmaco-epidemiological studies and published literature have shown that the use of oral ketoconazole-containing products is associated with a high risk of serious hepatotoxicity, best demonstrated by the causality assessments of fatal/life-threatening hepatotoxicity cases;
Slovenian: • odbor je menil, da so razpoložljivi podatki iz predkliničnih študij, kliničnih preskušanj, spontanih poročil o primerih v obdobju trženja zdravila, farmakoepidemioloških študij in objavljene literature pokazali, da je uporaba peroralnih zdravil, ki vsebujejo ketokonazol, povezana z velikim tveganjem resne hepatotoksičnosti, ki se je najbolje pokazala z ocenami vzročnosti pri smrtnih/smrtno nevarnih primerih hepatotoksičnosti;
English: The incidence of symptomatic hepatic reactions in the setting of treatment with oral ketoconazole was estimated in several epidemiology studies to be between 1/10,000 and 1/15,000 patients.
Slovenian: V številnih epidemioloških študijah so ocenili, da je incidenca simptomatskih jetrnih reakcij pri zdravljenju s peroralnim ketokonazolom od 1/10 000 do 1/15 000 bolnikov.
English: • The Committee could not identify a fungal infection where the level of hepatotoxicity of the drug could be balanced by an adequately substantiated benefit; the Committee noted that there are currently alternatives available for the treatment of fungal infections;
Slovenian: • odbor ni odkril nobene glivične okužbe, pri kateri bi zadostno utemeljena korist odtehtala stopnjo hepatotoksičnosti zdravila; odbor je izpostavil, da so trenutno na voljo druge oblike zdravljenja glivičnih okužb;
English: • Blastomycosis
Slovenian: • blastomikoza.
English: There was also insufficient evidence to claim or refute a benefit for any antifungal agent in treating candidiasis and the studies presented by the MAHs on the efficacy of ketoconazole on other Candida spp.
Slovenian: Prav tako ni zadostnih dokazov, s katerimi bi lahko potrdili ali ovrgli korist katerega koli antimikotika pri zdravljenju kandidoze, študije o učinkovitosti ketokonazola proti Candida spp., ki jih je predložil imetnik dovoljenja za promet z zdravilom, pa so omejene.
English: • Dermatophytosis
Slovenian: • dermatofitija,
English: • Histoplasmosis
Slovenian: • histoplazmoza,
English: Systemic fungal infections.
Slovenian: antimikotično zdravljenje.
English: In order to minimise the risks, the MAH has proposed to eliminate all indications that require prolonged treatment at higher dosages, e.g., systemic mycoses requiring treatment for 6 months or longer, taking into account that hepatotoxicity has usually been reported after extensive cumulative exposure to ketoconazole, and to limit indications to Malassezia folliculitis, Tinea capitis and chronic mucocutaneous candidiasis in patients who had either developed intolerance or failed to respond to alternative oral and/or IV antifungal therapy.
Slovenian: Da bi zmanjšal tveganje, je imetnik dovoljenja za promet z zdravilom je predlagal umik vseh indikacij, ki zahtevajo dolgotrajno zdravljenje z velikimi odmerki, npr. sistemske mikoze, ki zahtevajo vsaj 6mesečno zdravljenje, pri čemer je upošteval, da so o hepatotoksičnosti navadno poročali po obsežni kumulativni izpostavitvi ketokonazolu, in da se indikacije omejijo na Malassezia folliculitis, Tinea capitis ter kronično mukokutano kandidozo pri bolnikih, pri katerih se je razvila intoleranca ali pa se niso odzvali na drugo peroralno in/ali i.v.
English: It was concluded that the results of the current analysis of all cases of potential hepatotoxicity with oral ketoconazole-containing medicinal product confirm the risk of serious hepatotoxicity associated with the use of oral ketoconazole, best demonstrated by the causality assessments of fatal/lifethreatening hepatotoxicity cases.
Slovenian: Sklenili so, da rezultati trenutne analize vseh primerov morebitne hepatotoksičnosti ob uporabi peroralnih zdravil, ki vsebujejo ketokonazol, potrjujejo tveganje resne hepatotoksičnosti, povezane z uporabo peroralnega ketokonazola, kar je najbolje pokazala ocena vzročnosti smrtnih/smrtno nevarnih primerov hepatotoksičnosti.
English: The results of the current analysis of all cases of potential hepatotoxicity with oral ketoconazolecontaining medicinal product confirmed the risk of serious hepatotoxicity associated with the use of oral ketoconazole, best demonstrated by the causality assessments of fatal/life-threatening hepatotoxicity cases.
Slovenian: Rezultati trenutne analize vseh primerov morebitne hepatotoksičnosti ob uporabi peroralnih zdravil, ki vsebujejo ketokonazol, potrjujejo tveganje resne hepatotoksičnosti, povezane z uporabo peroralnega ketokonazola, kar je najbolje pokazala ocena vzročnosti smrtnih/smrtno nevarnih primerov hepatotoksičnosti.
English: The MAH proposed to withdraw all indications that require prolonged treatment at higher dosages, e.g., systemic mycoses requiring treatment for 6 months or longer taking into account the fact that hepatotoxicity has usually been reported after extensive cumulative exposure to ketoconazole and to limit indications to Malassezia folliculitis, Tinea capitis and chronic mucocutaneous candidiasis in patients who had either developed intolerance or failed to respond to alternative oral and/or IV antifungal therapy.
Slovenian: Imetnik dovoljenja za promet z zdravilom je predlagal umik vseh indikacij, ki zahtevajo dolgotrajno zdravljenje z velikimi odmerki, npr. sistemske mikoze, ki zahtevajo vsaj 6-mesečno zdravljenje, pri čemer je upošteval, da so o hepatotoksičnosti navadno poročali po obsežni kumulativni izpostavitvi ketokonazolu, in omejitev indikacij na Malassezia folliculitis, Tinea capitis ter kronično mukokutano kandidozo pri bolnikih, pri katerih se je razvila intoleranca ali pa se niso odzvali na drugo peroralno in/ali i.v.
English: Infections of the skin, hair, and mucosa, induced by dermatophytes and/or yeasts that cannot be treated topically because of the site or the extent of the lesion or deepinfection of the skin.
Slovenian: Terapevtske indikacije, vključene v trenutno različico krovnega dokumenta farmacevtske družbe (Company Core Data Sheet - CCDS) za originatorsko zdravilo, so naslednje: okužbe kože, las in sluznice, ki jih povzročajo dermatofiti in/ali glivice, ki jih ni mogoče zdraviti topično zaradi mesta ali obsega lezije ali globoke kožne okužbe.