FrancophonIA/ELRC3.0 huggingface dataset:
English: The European Commission (EC) triggered a procedure under Article 20 of Regulation (EC) No 726/2004 on 15 April 2016; the PRAC was requested to assess the impact on the benefit-risk balance of canagliflozin containing medicinal products, to assess whether this is a class issue and to issue a recommendation by 31 March 2017 on whether the relevant marketing authorisations should be maintained, varied, suspended or revoked and whether provisional measures are necessary to ensure the safe and effective use of these medicinal products.
Slovenian: Ugotoviti je moral, ali gre za učinek razreda zdravil, in do 31. marca 2017 izdati priporočilo o tem, ali je treba zadevna dovoljenja za promet z zdravilom ohraniti, spremeniti, začasno preklicati ali ukiniti, in o tem, ali so potrebni začasni ukrepi za zagotovitev varne in učinkovite uporabe teh zdravil.
English: In March 2016 the EMA was informed by the Marketing authorization holder (MAH) of canagliflozin about an approximately 2-fold increase of lower limb amputations in canagliflozin-treated subjects compared to placebo in the MAH sponsored ongoing cardiovascular (CV) event study CANVAS.
Slovenian: Marca 2016 je imetnik dovoljenja za promet z zdravilom kanagliflozinom obvestil agencijo EMA o približno dvakratnem povečanju števila amputacij spodnjih okončin pri preiskovancih, zdravljenih s kanagliflozinom, v primerjavi s placebom v potekajoči študiji kardiovaskularnih dogodkov CANVAS, ki jo sponzorira imetnik dovoljenja za promet z zdravilom.
English: Annex IV Scientific conclusions
Slovenian: Priloga IV
English: The PRAC, as a consequence, concluded that the benefit-risk balance of the SGLT2 inhibitor containing products identified in Annex A remains favourable, subject to the agreed amendments to the product information and additional pharmacovigilance activities to be reflected in the RMP.
Slovenian: posledično je odbor PRAC zaključil, da je razmerje med tveganji in koristmi zdravil, ki vsebujejo zaviralec SGLT2 in so navedena v Prilogi A, še naprej ugodno, pod pogojem, da se upoštevajo dogovorjene spremembe informacij o zdravilu ter dodatne farmakovigilančne dejavnosti, vključene v načrt za obvladovanje tveganja.
English: The PRAC therefore recommended that the variation to the terms of the marketing authorisation for the above listed products referred to in Annex A, for which the relevant sections of the summary of product characteristics and package leaflet are set out in Annex III of the PRAC recommendation, was warranted.
Slovenian: Odbor PRAC je zato priporočil, da je potrebna sprememba pogojev dovoljenj za promet z zgornjimi zdravili, ki so navedena v Prilogi A, skladno z besedili ustreznih poglavij povzetka glavnih značilnosti zdravila in navodila za uporabo, opredeljenimi v Prilogi III k priporočilu odbora PRAC.
English: Therefore, having considered all the data submitted, in view of the above, the PRAC concluded that the benefit-risk balance of the bove listed products remains positive, but considered that changes to the product information of all authorised SGLT2 inhibitors adding information on the risk of lower limb amputations, as well as additional pharmacovigilance activities to be reflected in the RMP, are warranted.
Slovenian: Z upoštevanjem vseh predloženih podatkov in zgoraj navedenega je odbor PRAC zaključil, da razmerje med tveganji in koristmi zgoraj navedenih zdravil ostaja pozitivno, vendar je menil, da so potrebne spremembe informacij o zdravilu za vse odobrene zaviralce SGLT2, in sicer je treba dodati informacije o tveganju za amputacije na spodnjih okončinah, v načrt za obvladovanje tveganja pa je treba vključiti dodatne farmakovigilančne dejavnosti.
English: • The PRAC noted that data on amputation events from clinical trials and post-marketing surveillance for dapagliflozin and empagliflozin-containing medicines are either not available to the same extent as for canagliflozin-containing medicines or there were some limitations in the data collection of these events;
Slovenian: • odbor PRAC je opozoril, da podatki o amputacijah iz kliničnih preskušanj in nadzora v obdobju trženja za zdravila, ki vsebujejo dapagliflozin in empagliflozin, bodisi niso na voljo v takem obsegu kot podatki za zdravila, ki vsebujejo kanagliflozin, bodisi obstajajo določene omejitve pri zbiranju podatkov o teh dogodkih;
English: • The PRAC was of the view that it is currently not possible to identify an underlying cause for the observed imbalances in amputation risk that would be specifically attributable to canagliflozin-containing medicines and not to the other products of the class;
Slovenian: • odbor PRAC je menil, da trenutno ni mogoče določiti osnovnega vzroka za opaženo neravnovesje v tveganju za amputacijo, ki bi ga lahko pripisali samo zdravilom, ki vsebujejo kanagliflozin, in ne tudi drugim zdravilom iz istega razreda;
English: PRAC noted that an increased amputation risk has only become apparent with canagliflozin so far, but one large cardiovascular outcome study (DECLARE) is still on-going for dapagliflozin and amputation events were not been systematically captured within the completed large cardiovascular outcome study conducted with empagliflozin (EMPA-REG).
Slovenian: Za dapagliflozin še vedno poteka velika študija kardiovaskularnih izidov (DECLARE), v zaključeni veliki študiji kardiovaskularnih dogodkov z empagliflozinom (EMPA-REG) pa amputacij niso sistematično beležili.
English: The PRAC also considered that data on amputation events from clinical trials and postmarketing surveillance for dapagliflozin and empagliflozin-containing medicines are either not available to the same extent as for canagliflozin-containing medicines or here were some limitations in the data collection.
Slovenian: Odbor PRAC je menil tudi, da podatki o amputacijah iz kliničnih preskušanj in nadzora v obdobju trženja za zdravila, ki vsebujejo dapagliflozin in empagliflozin, bodisi niso na voljo v takem obsegu kot podatki za zdravila, ki vsebujejo kanagliflozin, bodisi obstajajo omejitve pri zbiranju podatkov.
English: The PRAC was also of the view that it is currently not possible to identify an underlying cause for the observed imbalances in amputation risk that would be specifically attributable to canagliflozincontaining medicines and not to the other products of the class.
Slovenian: Odbor PRAC je prav tako menil, da trenutno ni mogoče določiti osnovnega vzroka za opaženo neravnovesje v tveganju za amputacijo, ki bi ga lahko pripisali samo zdravilom, ki vsebujejo kanagliflozin, in ne tudi drugim zdravilom iz istega razreda.
English: A Direct Healthcare Professional Communication (DHPC) was circulated on 2 May 2016 to inform healthcare professionals that a two-fold higher incidence of lower limb amputation (primarily of the toe) had been seen in a clinical trial with canagliflozin; in addition, the need to counsel patients about the importance of routine preventative foot care was highlighted.
Slovenian: Dne 2. maja 2016 so z neposrednimi obvestili za zdravstvene delavce slednje obvestili, da so v kliničnem preskušanju s kanagliflozinom opazili dvakrat večjo pojavnost amputacij spodnjih okončin (zlasti prstov).
English: Having considered all available data, the PRAC was of the view that the growing data on amputation in the CANVAS and CANVAS-R trial confirm an increased amputation risk for canagliflozin; it is unlikely that the difference in amputation risk seen with canagliflozin compared to placebo is a finding by chance.
Slovenian: Potem ko je odbor PRAC pregledal vse razpoložljive podatke, je menil, da naraščajoče število podatkov o amputacijah v preskušanjih CANVAS in CANVAS-R potrjujejo obstoj povečanega tveganja za amputacije pri kanagliflozinu.
English: (Invented) Name
Slovenian: (Izmišljeno) ime
English: GROUNDS FOR NEGATIVE OPINION
Slovenian: PODLAGA ZA NEGATIVNO MNENJE
English: Tel ská 1
Slovenian: Telčská 1
English: It is thus impossible to calculate any AUC with a minimum robustness.
Slovenian: Zato ni mogoče izračunati AUC z najmanjšo robustnostjo.
English: Therefore the potential serious potential risk to public health due to the lack of bioequivalence remains unresolved.
Slovenian: Zato možnost resnega potencialnega tveganja za javno zdravje zaradi odsotnosti biološke enakovrednosti ostaja nerešena.
English: The Applicant argued that the fulfilment of both conditions is confirmed and that accuracy can be estimated.
Slovenian: Predlagatelj je trdil, da je izpolnjevanje obeh pogojev potrjeno ter da je mogoče točnost oceniti.
English: The procedure was therefore referred to the CHMP and a List of Questions was adopted:
Slovenian: Postopek je bil zato napoten na CHMP, pri čemer je bil sprejet seznam vprašanj:
English: The National Competent Authorities, coordinated by the Reference Member State, shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders:
Slovenian: Pristojni nacionalni organi, ki jih koordinira referenčna država članica, morajo zagotoviti, da imetniki dovoljenja za promet z zdravilom izpolnijo naslednje pogoje:
English: ANNEX II SCIENTIFIC CONCLUSIONS
Slovenian: DODATEK II ZNANSTVENI ZAKLJUČKI
English: ANNEX III CONDITIONS FOR THE LIFTING OF THE MARKETING AUTHORISATION SUSPENSION
Slovenian: DODATEK III POGOJI ZA PREKLIC UMIKA DOVOLJENJA ZA PROMET Z ZDRAVILOM
English: OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF PROKANAZOL AND ASSOCIATED NAMES (SEE ANNEX I)
Slovenian: SPLOŠNI POVZETEK ZNANSTVENEGA VREDNOTENJA ZDRAVILA PROKANAZOL IN Z NJIM POVEZANIH IMEN (GLEJTE DODATEK I)
English: The product was authorised in the reference member state under Article 10.1 of Directive 2001/83/EC and the application was submitted in the concerned member states under the Mutual recognition procedure.
Slovenian: Zdravilo je bilo odobreno v referenčni državi članici v skladu s členom 10.1 Direktive 2001/83/ES, v zadevnih državah članicah pa je bila predložena vloga po postopku medsebojnega priznavanja.
English: However, excluding subject 24 because of low itraconazole plasma concentrations is not acceptable.
Slovenian: Vendar izključitev preiskovanca št. 24 zaradi nizkih koncentracij itrakonazola v plazmi ni sprejemljiva.
English: As a consequence, all or almost all the volunteers had one or several points with values below the limit of quantification (BLQ).
Slovenian: Posledično so imeli vsi ali skoraj vsi prostovoljci eno ali več točk z vrednostmi pod mejo kvantifikacije.
English: Moreover, in certain volunteers (based on the submitted data) the terminal phase was derived from Cmax.
Slovenian: Poleg tega je bila pri določenih prostovoljcih (na podlagi predloženih podatkov) terminalna faza izpeljana iz Cmax.
English: Therefore, bioequivalence can be considered to be proven for the 35 subjects who were included in the analysis.
Slovenian: Zato lahko šteje, da je biološka enakovrednost dokazana za 35 preiskovancev, ki so bili vključeni v analizo.
English: Likewise it will be important to take into account the last quantified concentration in comparison with the value of the lower limit of quantification (LLOQ).
Slovenian: Podobno je treba upoštevati zadnjo kvantificirano koncentracijo v primerjavi z vrednostjo spodnje meje kvantifikacije (LLOQ).
English: The problem is thus not only the five subjects of the original dossier but also the absence of pharmacokinetic calculations.
Slovenian: Torej težava ni le zaradi petih preiskovancev v originalni dokumentaciji, ampak tudi zaradi odsotnosti farmakokinetičnih izračunov.
English: In the Applicant study, mean results of this pharmacokinetic parameter were 19.3 and 19.0 hours for the reference and the test compounds, respectively.
Slovenian: V študiji predlagatelja sta bila rezultata tega farmakokinetičnega parametra 19,3 ure za referenčno spojino in 19,0 ure za preskusno spojino.
English: It is therefore unknown how the terminal phase and the residual area were calculated.
Slovenian: Zato ni znan postopek izračuna terminalne faze in rezidualne površine.
English: Therefore, selecting the last sample point as being at +96 hours corresponds to more than 3 half-lives (based on the theoretical a priori information) and more than 5 half-lives (based on the experimental value obtained in the study).
Slovenian: Zato izbrana zadnja točka vzorčenja +96 ur ustreza več kot trikratniku razpolovne dobe (na podlagi teoretične apriorne informacije) ter več kot petkratniku razpolovne dobe (na podlagi eksperimentalne vrednosti, pridobljene v študiji).
English: Please provide the raw data of all volunteers used for calculations.
Slovenian: Prosimo, predložite neobdelane podatke vseh prostovoljcev, ki ste jih uporabili za izračune.
English: Using this approach, the regression with the best adjustment is retained from the experimental data in order to provide a reliable estimation of the elimination constant and thereby of the pharmacokinetic parameters derived from it.
Slovenian: S tem pristopom se ohrani regresija z najboljšo korekcijo iz eksperimentalnih podatkov, da bi dobili zanesljivo oceno konstante eliminacije in s tem iz nje izpeljanih farmakokinetičnih parametrov.
English: Please produce calculations of the following after removal of volunteers with values below the LOQ: a. AUCinf; b. AUCt; c. Cmax
Slovenian: Prosimo vas za izračune naslednjih vrednosti po izključitvi prostovoljcev z vrednostmi pod LOQ: a. AUCinf; b. AUCt; c. Cmax
English: The confidence intervals and the value of relative bioavailability for the 3 parameters (Cmax, AUCt and AUCinf) were provided.
Slovenian: Predloženi so bili intervali zaupanja in vrednost relativne biološke razpoložljivosti za 3 parametre (Cmax, AUCt in AUCinf).
English: - the exclusion of an outlier subject is not accepted, as the data must be interpreted in its totality,
Slovenian: - izključitev preiskovanca, ki je bil osamelec, ni sprejeta, saj je treba podatke interpretirati v njihovi celovitosti;
English: Itraconazole is an antimycoticum active against infections caused by dermatophytes, yeasts, Aspergillus spp, Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, and various other yeasts and fungi.
Slovenian: Itrakonazol je protiglivno sredstvo, aktivno proti okužbam, ki jih povzročajo dermatofiti, kvasovke, glive Aspergillus spp, Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis ter razne druge kvasovke in glive.
English: As a result, WinNonlin cannot calculate the portion of area until infinite and the AUCinf therefore appears to be missing.
Slovenian: Posledično WinNonlin ne more izračunati deleža površine do neskončnosti in zdi se, da vrednost AUCinf manjka.
English: The CHMP recalculated the 90% confidence intervals and obtained comparable results to those provided by the Applicant.
Slovenian: CHMP je znova izračunal 90-odstotne intervale zaupanja in dobil rezultate, ki so primerljivi s predlagateljevimi.
English: The CHMP therefore adopted a List of Outstanding Issues:
Slovenian: CHMP je zato sprejel seznam nerešenih zadržkov:
English: The Applicant also provided all the different pharmacokinetic parameters, among others the area under the curve until the last quantified concentration (AUCt).
Slovenian: Predlagatelj je predložil tudi vse različne farmakokinetične parametre, med drugim površino pod krivuljo do zadnje kvantificirane koncentracije (AUCt).
English: Therefore, pharmacokinetic and bioequivalence results were analysed with all the data available obtained from 35 of the 36 volunteers included in the study, after removing volunteer 24 who presented a clearly atypical absorption pattern that prevented evaluating the area under the curve.
Slovenian: Zato so bili rezultati farmakokinetike in biološke enakovrednosti analizirani z vsemi razpoložljivimi podatki, pridobljenimi pri 35 od 36 v študijo vključenih prostovoljcih, po izključitvi prostovoljca št. 24, ki je imel očitno atipičen vzorec absorpcije, kar je onemogočalo vrednotenje površine pod krivuljo.
English: The Applicant also provided the raw data for all volunteers as requested by the CHMP.
Slovenian: Predlagatelj je predložil tudi neobdelane podatke za vse prostovoljce, kakor je želel CHMP.
English: - the benefit risk of the generic product Prokanazol is considered to be negative,
Slovenian: - razmerje med koristmi in tveganji za generično zdravilo Prokanazol šteje za negativno.
English: When including the data for subject 24, bioequivalence cannot be proven, as the 90% confidence intervals for AUC and Cmax then fall outside the normal acceptance criteria of 80 - 125%.
Slovenian: Ob vključitvi podatkov za preiskovanca št. 24 biološke enakovrednosti ni mogoče dokazati, saj 90-odstotni intervali zaupanja za AUC in Cmax ležijo izven običajnih kriterijev sprejemljivosti 80 -125 %.
English: Peak plasma levels are reached within 3 to 4 hours following an oral dose.
Slovenian: Največje koncentracije v plazmi so dosežene 3 do 4 ure po peroralnem odmerku.
English: Some variability coefficients and data on the variability of the main pharmacokinetic parameters of the parent drug were provided but its origin could not be determined.
Slovenian: Predloženi so bili nekateri koeficienti variabilnosti in podatki o variabilnosti glavnih farmakokinetičnih parametrov starševskega zdravila, vendar njihovega porekla ni mogoče ugotoviti.
English: If the actual LOQ of the method is much lower than that assumed, this may result in a greater error factor, in particular for the determination of terminal phase of extrapolated line and residual area.
Slovenian: Če je dejanska vrednost LOQ metode precej nižja od te, predpostavljene vrednosti, je lahko faktor napake večji, zlasti pri določanju terminalne faze ekstrapolirane premice in rezidualne površine.
English: Regarding the arbitrary acceptance of the lower limit of quantification (LLOQ), the Applicant considered that the LLOQ is complying with the requirements recommended by the FDA in relation to “response compared to blank response” and “precision and accuracy”.
Slovenian: Predlagatelj je v zvezi z arbitrarno sprejemljivostjo spodnje meje kvantifikacije (LLOQ) upošteval, da je LLOQ v skladu z zahtevami, ki jih priporoča FDA v zvezi z „odzivom v primerjavi s slepim poskusom“ ter „natančnostjo in točnostjo“.
English: As it was stated in the protocol of the trial, the elimination half-life of the drug is about 26 hours.
Slovenian: V protokolu preskušanja je bila navedena razpolovna doba eliminacije zdravila približno 26 ur.
English: No volunteers had to be removed by misinterpretation or an incorrect use of values below the LOQ and furthermore, the Applicant provided the calculated 90% confidence intervals for all 36 subjects and by exclusion of subject 24.
Slovenian: Prostovoljcev ni bilo treba izključevati zaradi napačne interpretacije ali nepravilne uporabe vrednosti pod LOQ, poleg tega pa je predlagatelj predložil izračunane 90-odstotne intervale zaupanja za vseh 36 preiskovancev in po izključitvi preiskovanca št. 24.
English: ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM(S), STRENGTH(S) OF THE MEDICINAL PRODUCT(S), ROUTE(S) OF ADMINISTRATION, APPLICANT(S) / MARKETING AUTHORISATION HOLDER(S) IN THE MEMBER STATES
Slovenian: DODATEK I SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVILA, POTI UPORABE ZDRAVILA, PREDLAGATELJEV, IMETNIKOV DOVOLJENJA ZA PROMET Z ZDRAVILOM V DRŽAVAH ČLANICAH
English: Inter-patient variability in serum concentrations following oral administration of itraconazole has been described in the literature, and is most notable with the capsule formulation (up to 15-fold differences).
Slovenian: Variabilnost serumskih koncentracij med bolniki po peroralnem dajanju itrakonazola je opisana v literaturi in je najbolj izrazita pri kapsulah (do 15-kratne razlike).
English: The oral bioavailability of itraconazole is maximal when the capsules are taken immediately after a full meal.
Slovenian: Peroralna biološka razpoložljivost itrakonazola je največja, če bolnik kapsule vzame takoj po celotnem obroku.
English: Values for the pharmacokinetic parameters were presented, but without any documentation of their calculation, preventing verification.
Slovenian: Predložene so bile vrednosti farmakokinetičnih parametrov, vendar brez dokumentacije o njihovem izračunu, kar onemogoča preverjanje.
English: The calculation of AUCinf and z could be affected by the fact that the elimination phase was not achieved in some volunteers, mainly due to the arbitrary acceptance of the limit of quantification (LOQ).
Slovenian: Na izračun AUCinf in λz lahko vpliva dejstvo, da faza eliminacije pri nekaterih prostovoljcih ni bila dosežena, zlasti zaradi arbitrarne sprejemljivosti meje kvantifikacije (LOQ).
English: The Applicant provided both values (precision and accuracy) for both products (hidroxi-itraconazol and itraconazol) from the 6 chromatograms obtained.
Slovenian: Predlagatelj je za obe zdravili (hidroksiitrakonazol in itrakonazol) predložil obe vrednosti (natančnost in točnost) na podlagi pridobljenih šestih kromatogramov.
English: In nearly all cases (65/70), the obtained values were not higher than 3 times the LLOQ and in no cases was the last quantified sample higher than 4 times the LLOQ.
Slovenian: V skoraj vseh primerih (65/70) pridobljene vrednosti niso presegale trikratnika LLOQ, v nobenem primeru pa rezultat zadnjega kvantificiranega vzorca ni bil višji od štirikratnika LLOQ.
English: Prokanaz 100 mg ciet s kapsulas
Slovenian: Prokanaz 100 mg cietās kapsulas
English: Acceptable explanations to exclude pharmacokinetic data or to exclude a subject would be protocol violations, which are not observed in this study.
Slovenian: Sprejemljive razlage izključitve farmakokinetičnih podatkov ali preiskovanca bi bile kršitve protokola, ki niso ugotovljene v tej študiji.
English: - of the CHMP considered that bioequivalence could not be shown,
Slovenian: - CHMP je menil, da biološke enakovrednosti ni mogoče dokazati;
English: The confidence interval range for total and residual areas does not explain nor improve the credibility of the calculations, especially as no estimator points were provided.
Slovenian: Razpon intervala zaupanja za skupne in rezidualne površine ne pojasnjuje in ne poveča verodostojnosti izračunov, zlasti ker niso bile predložene točke, uporabljene za ocene.
English: The sampling schedule should cover the plasma concentration time curve long enough to provide a reliable estimate of the extent of exposure which is achieved if AUCt is at least 80% of the AUC .
Slovenian: Urnik vzorčenja mora pokrivati krivuljo plazemske koncentracije v odvisnosti od časa v tolikšni meri, da zagotovi zanesljivo oceno obsega izpostavitve, ki se doseže, če je AUCt najmanj 80 % vrednosti AUC∞.
English: The CHMP considers that the lack of assessment of the estimators of kinetic parameters analysis hampers the proper assessment of the data.
Slovenian: CHMP meni, da odsotnost vrednotenja točk, uporabljenih za ocene v analizi kinetičnih parametrov, onemogoča pravilno vrednotenje podatkov.
English: Furthermore, the elimination half-life of itraconazole is about 26 hours and blood samples were obtained over at least 3-times the elimination half-life.
Slovenian: Poleg tega je razpolovna doba eliminacije itrakonazola približno 26 ur, vzorci krvi pa so bili pridobljeni v razponu, ki je obsegal najmanj trikratnik razpolovne dobe eliminacije.
English: A more detailed analysis of the quantifiable determinations indicated that in the case of the reference formulation, 4 of 9 concentrations did not reach values above 4xLOQ and none reached these levels for the test formulation.
Slovenian: Podrobnejša analiza koncentracij, ki jih je bilo možno kvantificirati, je pokazala, da v primeru referenčne formulacije štiri koncentracije od devetih niso dosegle vrednosti nad 4xLOQ, v primeru preskusne formulacije pa nobena koncentracija ni dosegla teh ravni.
English: Based on the totality of the data from all 36 subjects, bioequivalence has not been proven and as such the benefit risk ratio for this generic product is considered negative.
Slovenian: Na podlagi celovitih podatkov za vseh 36 preiskovancev biološka enakovrednost ni bila dokazana, zato razmerje med koristmi in tveganji za to generično zdravilo šteje za negativno.