natgillin/translations-raw huggingface dataset:
• The PRAC considered the procedure under Article 20 of Regulation (EC) No 726/2004 for the products listed in Annex A;
• odbor PRAC je obravnaval postopek v skladu s členom 20 Uredbe (ES) št. 726/2004 za zdravila, navedena v Prilogi A;
All RMPs should be updated accordingly via an appropriate variation to be submitted no later than one month of the European Commission decision;
Vse načrte za obvladovanje tveganja je treba ustrezno posodobiti prek ustrezne vloge za spremembo, ki jo je treba predložiti najpozneje en mesec po sklepu Evropske komisije;
Hence, it is currently not possible to establish whether the increased amputation risk is a class effect or not.
Zato trenutno ni mogoče ugotoviti, ali je povečano tveganje za amputacijo učinek razreda zdravil ali ne.
The mechanism of action that would allow understanding which patients are at risk is therefore still unclear.
Mehanizem delovanja, ki bi omogočil razumevanje, kateri bolniki so ogroženi, torej še ni jasen.
• The PRAC therefore considered that the risk may constitute a possible class effect;
• odbor PRAC je zato menil, da je tveganje morda morebiten učinek razreda zdravil;
Consequently, the EC requested on 6 July 2016 to extend the current procedure to include all of the authorised products of the class of SGLT2 inhibitors.
Zato je Evropska komisija dne 6. julija 2016 zahtevala podaljšanje trenutnega postopka in vanj vključila vsa odobrena zdravila iz razreda zaviralcev SGLT2.
The CANVAS and CANVAS-R studies and the CREDENCE and DECLARE Studies are planned to be completed in 2017 and 2020, respectively.
V skladu z načrti bosta študiji CANVAS in CANVAS-R zaključeni leta 2017, študiji CREDENCE in DECLARE pa leta 2020.
• The PRAC was also of the opinion that a mechanism of action, allowing to understand which patients are at risk, is still unclear;
• odbor PRAC je prav tako menil, da mehanizem delovanja, ki bi omogočil razumevanje, kateri bolniki so ogroženi, še ni jasen;
In addition, an analysis of the ongoing renal study CANVAS-R with a similar population as CANVAS showed a numerical imbalance with regards to amputation events.
Poleg tega je analiza potekajoče ledvične študije CANVAS-R, ki vključuje podobno populacijo kot študija CANVAS, pokazala številčno neravnovesje v zvezi z amputacijami.
• Because no specific risk factors could be identified apart from general amputation risk factors potentially contributing to the events, the PRAC recommended that patients should be advised on routine preventative foot care and maintaining adequate hydration as a general advice to prevent amputation;
• ker poleg splošnih dejavnikov tveganja za amputacijo ni bilo mogoče določiti specifičnih dejavnikov tveganja, ki bi prispevali k dogodkom, je odbor PRAC priporočil, da je treba bolnikom svetovati rutinsko preventivno nego stopal in vzdrževanje primerne hidratacije kot splošen nasvet za preprečevanje amputacije;
All members of the class share the same mode of action and there is no confirmed underlying mechanism that is canagliflozin-specific.
Vsi člani razreda imajo enak način delovanja in osnovni mehanizem, ki bi bil specifičen za kanagliflozin, ni potrjen.
Therefore the CHMP recommends the variation to the terms of the marketing authorisations for Invokana, Vokanamet, Forxige, Edistride, Xigduo, Ebymect, Jardiance and Synjardy.
Zato priporoča spremembo pogojev dovoljenj za promet z zdravili Invokana, Vokanamet, Forxige, Edistride, Xigduo, Ebymect, Jardiance in Synjardy.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are used together with diet and exercise in patients with type 2 diabetes, either alone or in combination with other diabetes medicines.
Zaviralci natrijevih glukoznih koprenašalcev 2 (SGLT2) se uporabljajo poleg prehrane in telesne vadbe pri bolnikih s sladkorno boleznijo tipa 2, bodisi samostojno bodisi v kombinaciji z drugimi zdravili za sladkorno bolezen.
Further to the information received by the EMA, the Independent Data Monitoring Committee (IDMC) for the CANVAS and CANVAS-R studies, which has access to all un-blinded CV outcome and safety data, recommended that the study should continue, that action to minimize this potential risk should be taken and that participants should be informed adequately about this risk.
Glede na informacije, ki jih je prejela agencija EMA, je neodvisni odbor za spremljanje podatkov za študiji CANVAS in CANVAS-R, ki ima dostop do nezakritih kardiovaskularnih izidov in podatkov o varnosti, priporočil, da se študija nadaljuje, da je treba uvesti ukrepe za zmanjševanje tega morebitnega tveganja in da je treba udeležence o tveganju ustrezno obvestiti.
• The PRAC was therefore of the view that the risk of lower limb amputation should be included in the product information for all products listed in Annex A, with a warning highlighting to healthcare professional and patients the importance of routine preventative foot care.
• odbor PRAC je torej menil, da je treba tveganje za amputacijo spodnjih okončin vključiti v informacije o zdravilu za vsa zdravila, navedena v Prilogi A, z opozorilom za zdravstvene delavce in bolnike o pomenu rutinske preventivne nege stopal.
Final analysis of these studies, after un-blinding, will provide further information on the benefit/risk of SGLT2 inhibitors particularly of the risk of lower limb amputations.
Končna analiza teh študij bo po razkritju zagotovila več informacij o razmerju med tveganji in koristmi zaviralcev SGLT2, zlasti o tveganju za amputacije spodnjih okončin.
The warning for canagliflozin also includes information that, in patients developing amputation preceding events, consideration may be given to discontinue treatment.
Opozorilo za kanagliflozin vključuje tudi informacije o tem, da je treba pri bolnikih, pri katerih se pojavijo znaki, ki napovedujejo amputacijo, razmisliti o prekinitvi zdravljenja.
• The PRAC reviewed the totality of the data submitted by the marketing authorisation holders in relation to the risk of lower limb amputation in patients treated with Sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes mellitus;
• odbor PRAC je proučil vse podatke, ki so jih predložili imetniki dovoljenj za promet z zdravilom v povezavi s tveganjem za amputacijo spodnjih okončin pri bolnikih, zdravljenih z zaviralci natrijevih glukoznih koprenašalcev 2 (SGLT2) zaradi sladkorne bolezni tipa 2;
• The PRAC also considered that additional information on amputation events should be collected through appropriate case report forms (CRFs) for clinical trials, follow-up questionnaires for post-marketing cases, use of common MedDRA preferred term (PT) lists for amputation preceding events, and appropriate meta-analyses of large studies including cardiovascular outcome studies.
• odbor PRAC je menil tudi, da je treba zbrati dodatne informacije o amputacijah, in sicer z ustreznimi obrazci za poročila o primerih v kliničnih preskušanjih, vprašalniki za spremljanje primerov v obdobju trženja, uporabo seznamov prednostnih izrazov MedDRA za znake, ki napovedujejo amputacijo, in ustreznimi metaanalizami velikih študij, vključno s študijami kardiovaskularnih izidov.
Furthermore, the PRAC considered that a class effect could not be excluded, as all SGLT2 inhibitors share the same mechanism of action, as the potential mechanism leading to an increased amputation risk is not known, and as an underlying cause specific to canagliflozin containing medicines only cannot be identified at the moment.
Nadalje je odbor PRAC menil, da učinka razreda zdravil ni mogoče izključiti, ker imajo vsi zaviralci SGLT2 enak mehanizem delovanja, ker morebitni mehanizem, ki vodi do povečanega tveganja za amputacijo, ni znan in ker osnovnega vzroka, značilnega samo za zdravila, ki vsebujejo kanagliflozin, ta trenutek ni mogoče določiti.
The CHMP, as a consequence, considers that the benefit-risk balance of Invokana, Vokanamet, Forxige, Edistride, Xigduo, Ebymect, Jardiance and Synjardy remain favourable subject to the amendments to the product information described above.
Odbor CHMP posledično meni, da je razmerje med tveganji in koristmi zdravil Invokana, Vokanamet, Forxige, Edistride, Xigduo, Ebymect, Jardiance in Synjardy še naprej ugodno, pod pogojem, da se upoštevajo zgoraj opisane spremembe informacij o zdravilu.
• The PRAC considered that the available data on amputation in the CANVAS and CANVAS-R trials confirm that treatment with canagliflozin may contribute to an increased risk of amputation of the lower limb, mainly of the toe;
• odbor PRAC je menil, da razpoložljivi podatki o amputacijah iz preskušanj CANVAS in CANVAS-R potrjujejo, da zdravljenje s kanagliflozinom lahko prispeva k povečanemu tveganju za amputacijo spodnjih okončin, predvsem prstov;
The communication also asked healthcare professionals to consider treatment discontinuation in patients who develop amputation preceding events.
V sporočilu so zdravstvene delavce prosili, naj pri bolnikih, pri katerih se pojavijo znaki, ki napovedujejo amputacijo, razmislijo o prekinitvi zdravljenja.
For canagliflozin, lower limb amputations (mainly of the toe) have been also included, as an adverse drug reaction, in the product information;
Za kanagliflozin so bile amputacije spodnjih okončin (zlasti prstov) kot neželeni učinek že vključene v informacije o zdravilu;
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.
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.
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.
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.
Annex IV Scientific conclusions
Priloga IV
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.
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.
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.
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.
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.
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.
• 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;
• 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;
• 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;
• 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;
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).
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.
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.
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.
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.
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.
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.
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).
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.
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.
(Invented) Name
(Izmišljeno) ime
GROUNDS FOR NEGATIVE OPINION
PODLAGA ZA NEGATIVNO MNENJE
It is thus impossible to calculate any AUC with a minimum robustness.
Zato ni mogoče izračunati AUC z najmanjšo robustnostjo.
Therefore the potential serious potential risk to public health due to the lack of bioequivalence remains unresolved.
Zato možnost resnega potencialnega tveganja za javno zdravje zaradi odsotnosti biološke enakovrednosti ostaja nerešena.
The Applicant argued that the fulfilment of both conditions is confirmed and that accuracy can be estimated.
Predlagatelj je trdil, da je izpolnjevanje obeh pogojev potrjeno ter da je mogoče točnost oceniti.
The procedure was therefore referred to the CHMP and a List of Questions was adopted:
Postopek je bil zato napoten na CHMP, pri čemer je bil sprejet seznam vprašanj:
The National Competent Authorities, coordinated by the Reference Member State, shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders:
Pristojni nacionalni organi, ki jih koordinira referenčna država članica, morajo zagotoviti, da imetniki dovoljenja za promet z zdravilom izpolnijo naslednje pogoje:
ANNEX II SCIENTIFIC CONCLUSIONS
DODATEK II ZNANSTVENI ZAKLJUČKI
ANNEX III CONDITIONS FOR THE LIFTING OF THE MARKETING AUTHORISATION SUSPENSION
DODATEK III POGOJI ZA PREKLIC UMIKA DOVOLJENJA ZA PROMET Z ZDRAVILOM
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF PROKANAZOL AND ASSOCIATED NAMES (SEE ANNEX I)
SPLOŠNI POVZETEK ZNANSTVENEGA VREDNOTENJA ZDRAVILA PROKANAZOL IN Z NJIM POVEZANIH IMEN (GLEJTE DODATEK I)
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.
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.
However, excluding subject 24 because of low itraconazole plasma concentrations is not acceptable.
Vendar izključitev preiskovanca št. 24 zaradi nizkih koncentracij itrakonazola v plazmi ni sprejemljiva.
As a consequence, all or almost all the volunteers had one or several points with values below the limit of quantification (BLQ).
Posledično so imeli vsi ali skoraj vsi prostovoljci eno ali več točk z vrednostmi pod mejo kvantifikacije.
Moreover, in certain volunteers (based on the submitted data) the terminal phase was derived from Cmax.
Poleg tega je bila pri določenih prostovoljcih (na podlagi predloženih podatkov) terminalna faza izpeljana iz Cmax.
Therefore, bioequivalence can be considered to be proven for the 35 subjects who were included in the analysis.
Zato lahko šteje, da je biološka enakovrednost dokazana za 35 preiskovancev, ki so bili vključeni v analizo.
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).
Podobno je treba upoštevati zadnjo kvantificirano koncentracijo v primerjavi z vrednostjo spodnje meje kvantifikacije (LLOQ).
The problem is thus not only the five subjects of the original dossier but also the absence of pharmacokinetic calculations.
Torej težava ni le zaradi petih preiskovancev v originalni dokumentaciji, ampak tudi zaradi odsotnosti farmakokinetičnih izračunov.
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.
V študiji predlagatelja sta bila rezultata tega farmakokinetičnega parametra 19,3 ure za referenčno spojino in 19,0 ure za preskusno spojino.
It is therefore unknown how the terminal phase and the residual area were calculated.
Zato ni znan postopek izračuna terminalne faze in rezidualne površine.
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).
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).
Please provide the raw data of all volunteers used for calculations.
Prosimo, predložite neobdelane podatke vseh prostovoljcev, ki ste jih uporabili za izračune.
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.
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.
Please produce calculations of the following after removal of volunteers with values below the LOQ: a. AUCinf; b. AUCt; c. Cmax
Prosimo vas za izračune naslednjih vrednosti po izključitvi prostovoljcev z vrednostmi pod LOQ: a. AUCinf; b. AUCt; c. Cmax
The confidence intervals and the value of relative bioavailability for the 3 parameters (Cmax, AUCt and AUCinf) were provided.
Predloženi so bili intervali zaupanja in vrednost relativne biološke razpoložljivosti za 3 parametre (Cmax, AUCt in AUCinf).
- the exclusion of an outlier subject is not accepted, as the data must be interpreted in its totality,
- izključitev preiskovanca, ki je bil osamelec, ni sprejeta, saj je treba podatke interpretirati v njihovi celovitosti;
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.
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.
As a result, WinNonlin cannot calculate the portion of area until infinite and the AUCinf therefore appears to be missing.
Posledično WinNonlin ne more izračunati deleža površine do neskončnosti in zdi se, da vrednost AUCinf manjka.
The CHMP recalculated the 90% confidence intervals and obtained comparable results to those provided by the Applicant.
CHMP je znova izračunal 90-odstotne intervale zaupanja in dobil rezultate, ki so primerljivi s predlagateljevimi.
The CHMP therefore adopted a List of Outstanding Issues:
CHMP je zato sprejel seznam nerešenih zadržkov:
The Applicant also provided all the different pharmacokinetic parameters, among others the area under the curve until the last quantified concentration (AUCt).
Predlagatelj je predložil tudi vse različne farmakokinetične parametre, med drugim površino pod krivuljo do zadnje kvantificirane koncentracije (AUCt).