natgillin/translations-raw huggingface dataset:
MINIMUM PARTICULARS TO APPEAR ON BLISTERS BLISTER - 1.875 mg
PRETISNI OMOT S 7 TABLETAMI S - 1,875 mg
Treatment duration
ZDRAVILA
MINIMUM PARTICULARS TO APPEAR ON BLISTERS BLISTER - 3.75 mg
PRETISNI OMOT S 7 TABLETAMI S - 3,75 mg
NAME OF THE VETERINARY MEDICINAL PRODUCT Ypozane 3.75 mg tablets for dogs Osaterone acetate
IME ZDRAVILA ZA UPORABO V VETERINARSKI MEDICINI Ypozane 3,75 mg tablete za pse
MARKETING AUTHORISATION NUMBER(S) EU/2/06/068/001
ŠTEVILKA(E) DOVOLJENJ(A) ZA PROMET EU/2/06/068/001
MINIMUM PARTICULARS TO APPEAR ON BLISTERS BLISTER - 15 mg
PRETISNI OMOT S 7 TABLETAMI S - 15 mg
Lactose monohydrate
Laktoza monohidrat Škrob, predgelirani Kalcijev karmelozat Koruzni škrob Smukec
MARKETING AUTHORISATION NUMBER(S) EU/2/06/068/004
ŠTEVILKA(E) DOVOLJENJ(A) ZA PROMET EU/2/06/068/004
MARKETING AUTHORISATION NUMBER(S) EU/2/06/068/002
ŠTEVILKA(E) DOVOLJENJ(A) ZA PROMET EU/2/06/068/002
Carmellose calcium
4.11 Karenca
MARKETING AUTHORISATION NUMBER(S) EU/2/06/068/003
ŠTEVILKA(E) DOVOLJENJ(A) ZA PROMET EU/2/06/068/003
MINIMUM PARTICULARS TO APPEAR ON BLISTERS BLISTER - 7.5 mg
PRETISNI OMOT S 7 TABLETAMI S - 7,5 mg
Divergent positions are presented in Appendix III.
Različna stališča so predstavljena v Prilogi III.
Particular attention was dedicated to the issue of hepatotoxicity.
Posebno pozornost so namenili vprašanju hepatotoksičnosti.
It was also considered that no restrictive use could be adequately substantiated.
Prav tako je menil, da ni mogoče zadostno utemeljiti nobene omejene uporabe.
Moreover, these cases were derived from old publications (from 1980 to 1986) while changes could be expected in the management of patients over more than 25 years.
Ti primeri izhajajo iz starih publikacij (od 1980 do 1986), medtem ko se pričakuje, da je v več kot 25 letih prišlo do sprememb v obravnavi bolnikov.
In parallel, on 1 July 2011, France triggered a referral under Article 31of Directive 2001/83/EC, as amended.
Vzporedno je Francija 1. julija 2011 sprožila napotitveni postopek v skladu s členom 31 Direktive 2001/83/ES, kot je bila spremenjena.
Positive rechallenge was noted in some cases.
V nekaterih primerih so opazili pozitivno provokacijo.
In Europe, oral formulations of ketoconazole are currently approved in 20 Member States as well as in Iceland and Norway.
V Evropi so peroralne formulacije ketokonazola trenutno odobrene v 20 državah članicah ter na Islandiji in Norveškem.
Several potential mechanisms for this toxicity have been identified but uncertainties still remain.
Ugotovili so več potencialnih mehanizmov za to toksičnost, vendar so še vedno prisotne nejasnosti.
This was followed by the registration of topical pharmaceutical forms such as cream /ointment/shampoo.
Temu je sledila registracija topičnih farmacevtskih oblik, kot so krema/mazilo/zdravilni šampon.
The level of risk appears to be higher than that observed with other antifungal agents.
Stopnja tveganja je videti večja kot pri drugih antimikotikih.
Therefore, pursuant to Article 116 of Directive 2001/83/EC, the CHMP recommends the suspension of the Marketing Authorisations for all medicinal product(s) referred to in Annex I. The conditions for the lifting of the suspension of the Marketing Authorisation(s) are set out in Annex III.
Skladno s členom 116 Direktive 2001/83/ES je CHMP priporočil začasni umik dovoljenj za promet z vsemi zdravili iz Priloge I. Pogoji za preklic začasnega umika dovoljenj za promet z zdravilom so navedeni v Prilogi III.
However, the experts unanimously agreed that these cases were anecdotal and that there was no scientific evidence available to support this claim.
Vendar so se strokovnjaki soglasno strinjali, da so ti primeri anekdotični in da ni nobenih znanstvenih dokazov, ki bi podprli to trditev.
Dosing recommendations in adults are largely consistent across Member States, at 200 mg per day which can be increased to 400 mg in cases where there is no adequate response.
Priporočila za odmerjanje pri odraslih so večinoma usklajena v vseh državah članicah, tj. 200 mg na dan, kar se lahko poveča na 400 mg, če ne pride do zadostnega odziva.
Ketoconazole 20mg/ml oral suspension and ketoconazole 100mg tablet formulations are no longer authorised in any EEA Member State.
Ketokonazol 20 mg/ml peroralna suspenzija in ketokonazol 100 mg tableta nista več odobreni v nobeni državi članici EGP.
Overall summary of the scientific evaluation of ketoconazole-containing products for oral use (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravil za peroralno uporabo, ki vsebujejo ketokonazol (glejte Prilogo I)
Ketoconazole was first registered as tablets and oral suspension in December 1980.
Ketokonazol je bil prvič registriran decembra 1980 v obliki tablet in peroralne suspenzije.
Finally, the SAG recognised that ketoconazole could potentially be used as a last treatment option in some very rare cases.
Na koncu je skupina potrdila, da bi lahko ketokonazol uporabljali kot zadnjo možnost zdravljenja pri nekaterih zelo redkih primerih.
In the literature, incidence of acute injuries is variable and ranged from 1/2000 patients exposed to 12%.
V literaturi je incidenca akutnih poškodb različna, saj je bil njen razpon od 1/2000 izpostavljenih bolnikov do 12 %.
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for ketoconazole-containing products for oral use;
• odbor je obravnaval napotitveni postopek v skladu s členom 31 Direktive 2001/83/ES za zdravila za peroralno uporabo, ki vsebujejo ketokonazol;
The marketing authorisation holder extensively discussed the mechanism of hepatotoxicity, widely supported with literature data from 1986 to 2007.
Imetnik dovoljenja za promet z zdravilom je izčrpno preučil mehanizem hepatotoksičnosti, kar je obširno podprl s podatki iz literature, objavljene med letoma 1986 in 2007.
In general, the clinical studies submitted to support the efficacy of oral ketoconazole were limited and not conducted in line with the current guidelines.
Na splošno so bile klinične študije, predložene kot podpora za učinkovitost peroralnega ketokonazola, omejene in niso bile izvedene v skladu s trenutnimi smernicami.
Within the EU, the indications approved for ketoconazole-containing products vary amongst Members States.
V EU se indikacije, odobrene za zdravila, ki vsebujejo ketokonazol, med državami članicami lahko razlikujejo.
The CHMP was requested to give its opinion on whether the marketing authorisations for medicinal products containing ketoconazole for oral use, and associated names should be maintained, varied, suspended or withdrawn.
Odbor CHMP je zaprosila, naj poda svoje mnenje o tem, ali naj se dovoljenja za promet z zdravili za peroralno uporabo, ki vsebujejo ketokonazol, in povezanimi imeni, ohranijo, spremenijo, začasno umaknejo ali ukinejo.
Seven fatal/life-threatening cases were reported with event dates after 2006 i.e., after the CCDS update that contained substantial hepatotoxicity-related revisions.
O sedmih smrtnih/smrtno nevarnih primerih so poročali po letu 2006, tj. po posodobitvi CCDS, ki je vsebovala obsežne revizije glede hepatotoksičnosti.
Topical forms have not been considered in the present review.
Topične oblike niso vključene v pričujoči pregled.
In 2011, a review performed by the French National Competent Authority concluded that spontaneous reports and literature data indicate that oral ketoconazole is associated with a high level of liver toxicity.
Leta 2011 je pregled, ki ga je opravil francoski nacionalni pristojni organ, pokazal, da spontana poročila in podatki iz literature kažejo, da je peroralni ketokonazol povezan s visoko stopnjo jetrne toksičnosti.
In addition, a literature review retrieved more than 100 publications related to hepatotoxicity of ketoconazole.
Poleg tega je pregled literature odkril več kot 100 publikacij, povezanih s hepatotoksičnostjo ketokonazola.
Marketing authorisations have been withdrawn by the MAH in several Member States for commercial reasons and only the 200mg tablet formulation is still available in the EEA.
Imetnik dovoljenja za promet z zdravilom je umaknil dovoljenja za promet z zdravilom v več državah članicah zaradi poslovnih razlogov, zato je v prostoru EGP na voljo samo še formulacija 200-miligramske tablete.
This issue has not been mitigated because ketoconazole has not been used as an active comparator for newer drugs since 2001.
Težave niso zmanjšali, saj ketokonazol ni uporabljan kot primerjalna zdravilna učinkovina pri novejših zdravilih od leta 2001.
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.
Študije učinkovitosti ketokonazola proti Malassezia folliculitis, Pityriasis versicolor, Tinea Capitis ter Tinea Barbae, Tinea Corporis, Tinea Cruris, Tinea Pedis in Tinea Manuum so omejene.
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.
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.
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.
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.
Moreover, tests for susceptibility to ketoconazole are not commercially available.
Poleg tega preiskave za občutljivost na ketokonazol niso na voljo na tržišču.
Characteristics of acute injuries mainly included cytolysis and may lead to serious outcomes including liver transplantation.
Za akutne poškodbe je bila večinoma značilna citoliza, ki lahko povzroči resne izide, vključno s presaditvijo jeter.
Of note, while ketoconazole was available since 1982, fluconazole and itraconazole became later available in the 1990's.
Treba je omeniti, da je ketokonazol na voljo od leta 1982, flukonazol in itrakonazol pa so začeli tržiti v 90. letih 20. stoletja.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The experts unanimously agreed that there was no scientific evidence to support the MAH's revised indication proposal.
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.
Treatment duration ranges from 5 consecutive days (vaginal candidosis) to up to 6 months for systemic fungal infections such as paracoccidioidomycosis and histoplasmosis.
Trajanje zdravljenja je od 5 zaporednih dni (vaginalna kandidoza) do 6 mesecev pri sistemskih glivičnih okužbah, kot sta južnoameriška blastomikoza in histoplazmoza.
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.
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.
In addition, based on the literature review, ketoconazole seemed to be the only antifungal agent associated with development of chronic hepatitis and cirrhosis.
Poleg tega je bilo na podlagi pregleda literature videti, da je ketokonazol edini antimikotik, povezan z razvojem kroničnega hepatitisa in ciroze.
Based on those conclusions, the Committee recommended the suspension of the marketing authorisations for all ketoconazole-containing products for oral use.
Na podlagi teh zaključkov je odbor priporočil začasni umik dovoljenj za promet z vsemi zdravili za peroralno uporabo, ki vsebujejo ketokonazol.
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.
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.
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.
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.
Results from non-clinical toxicity studies indicated the liver and endocrine system as primary target organs.
Rezultati iz predkliničnih študij toksičnosti so pokazali, da sta primarna ciljna organa jetra in endokrini sistem.
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.
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.
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.
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.
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.
Upoštevajoč celotno zgornje besedilo odbor CHMP ni ugotovil nobene okoliščine, ki bi upravičila izpostavitev bolnika stopnji hepatotoksičnosti ketokonazola za peroralno uporabo.
All but 5 tinea capitis (no case of Malassezia folliculitis) corresponded to Chronic Mucocutaneous Candidiasis (n=16).
Vsi primeri, razen 5 primerov tinea capitis, so ustrezali kronični mukokutani kandidozi (n = 16) (primera Malassezia folliculitis ni bilo).
Overall, although hepatotoxicity is a class effect of azoles, the quantitative and qualitative aspects of the hepatotoxicity of ketoconazole are of particular concern.
Čeprav je hepatotoksičnost učinek razreda azolnih antimikotikov, so predvsem problematični količinski in kakovostni vidiki hepatotoksičnosti ketokonazola.
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.
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.
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.
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.
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.
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.
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).
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).
The MAH provided a detailed report examining efficacy of oral ketoconazole by approved indication.
Imetnik dovoljenja za promet z zdravilom je predložil podrobno poročilo o učinkovitosti peroralnega ketokonazola pri odobrenih indikacijah.
• 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;
• 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;
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.
Od 1 505 primerov zanimanja jih je bilo 880 (58 %) medicinsko validiranih kot resnih.
Indeed, the SAG considered that the activity of the newer systemic antifungals is expected to be superior to ketoconazole.
Skupina je celo menila, da je pričakovati, da bo učinkovitost novih sistemskih antimikotikov boljša kot pri ketokonazolu.
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.
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
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.
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.