FrancophonIA/ELRC3.0 huggingface dataset:
English: As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the tipranavir/ritonavir co-administration (a separate formulation of dolutegravir is available for this dose adjustment, see section 4.2).
Slovenian: Zdravilo Dovato je v obliki tablet s fiksnim odmerkom, zato je potrebno v času sočasnega zdravljenja s tipranavirjem/ritonavirjem približno 12 ur po uporabi zdravila Dovato vzeti dodatno 50 mg tableto z dolutegravirjem (za prilagoditev odmerka je na voljo ločena farmacevtska oblika z dolutegravirjem, glejte poglavje 4.2).
English: As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the nevirapine co-administration (a separate formulation of dolutegravir is available for this dose adjustment, see section 4.2).
Slovenian: Zdravilo Dovato je v obliki tablet s fiksnim odmerkom, zato je potrebno v času sočasnega zdravljenja z nevirapinom približno 12 ur po uporabi zdravila Dovato vzeti dodatno 50 mg tableto z dolutegravirjem (za prilagoditev odmerka je na voljo ločena farmacevtska oblika z dolutegravirjem, glejte poglavje 4.2).
English: Sorbitol
Slovenian: laktacidoza
English: • numbness, tingly feelings in the skin (pins and needles)
Slovenian: • odrevenelost, občutek mravljinčenja v koži
English: • stomach ache
Slovenian: • tesnoba
English: Do not take an antacid during the 6 hours before you take Dovato, or for at least 2 hours after you take it. You can take other acid-lowering medicines like ranitidine and omeprazole at the same time as Dovato.
Slovenian: V 6 urah pred jemanjem zdravila Dovato ali vsaj 2 uri po tem, ko ste ga vzeli, ne jemljite antacida.
English: Dolutegravir ↓ AUC ↓ 59% Cmax ↓ 47% Cτ ↓ 76%
Slovenian: tipranavir + ritonavir/ dolutegravir dolutegravir  AUC  59 % Cmax  47 %
English: Table 1:
Slovenian: Preglednica 1: Interakcije
English: Package leaflet: Information for the patient
Slovenian: Vsebina pakiranja in dodatne informacije Kaj vsebuje zdravilo Dovato
English: Dolutegravir ↔ AUC ↑ 1% Cmax ↓ 3% Cτ ↓ 8% Tenofovir ↔
Slovenian: Cτ  22 % rilpivirin  Nukleozidni zaviralci reverzne transkriptaze (NRTIs) dizoproksiltenofovirat emtricitabin, didanozin, stavudin, tenofovir alafenamid, zidovudin dolutegravir  AUC  1 % Cmax  3 % Cτ  8 % tenofovir 
English: • muscle or joint aches.
Slovenian: • bolečine v mišicah ali sklepih.
English: Re-examination procedure under Article 32(4) of Directive 2001/83/EC, as amended
Slovenian: Ponovni pregled postopka v skladu s členom 32(4) Direktive 2001/83/ES, kakor je bila spremenjena
English: The company presented no new data but reiterated the previous arguments.
Slovenian: Družba ni predstavila novih podatkov, ampak ponovila prejšnje argumente.
English: For generics, including this i.v.
Slovenian: Za generična zdravila, vključno s to i.v.
English: The originator product Targocid 400mg is registered in Germany since 10th March 1992.
Slovenian: Originatorsko zdravilo Targocid 400 mg je registrirano v Nemčiji od 10. marca 1992.
English: A number of guidelines support monitoring.
Slovenian: Spremljanje podpirajo številne smernice.
English: The procedure was therefore referred to the CHMP.
Slovenian: Postopek je bil zato napoten na CHMP.
English: Non-clinical study results
Slovenian: Rezultati neklinične študije
English: However, the exact level of activity, which must be determined in order to propose the recommendations for use, has not been established.
Slovenian: Vendar natančna raven aktivnosti, ki mora biti določena za predlog priporočila uporabe, ni bila določena.
English: GROUNDS FOR REFUSAL
Slovenian: PODLAGE ZA ZAVRNITEV
English: Content (concentration)
Slovenian: Pot uporabe Vsebina (koncentracija)
English: ANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR REFUSAL
Slovenian: DODATEK II ZNANSTVENI ZAKLJUČKI IN PODLAGA ZA ZAVRNITEV
English: The Applicant concluded that no additional clinical data are required.
Slovenian: Predlagatelj je zaključil, da dodatni klinični podatki niso potrebni.
English: Most MIC values were identical for the two preparations, and the remaining 10.2% of the results were within one twofold dilution.
Slovenian: Večina vrednosti MIC je bila enaka pri obeh pripravkih, preostalih 10,2 % rezultatov je znotraj dvakratne razredčine.
English: OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF TEICOPLANIN HOSPIRA AND ASSOCIATED NAMES (SEE ANNEX I)
Slovenian: SPLOŠNI POVZETEK ZNANSTVENEGA VREDNOTENJA ZDRAVILA TEICOPLANIN HOSPIRA IN Z NJIM POVEZANIH IMEN (GLEJTE DODATEK I)
English: ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTES OF ADMINISTRATION, APPLICANTS IN THE MEMBER STATES
Slovenian: DODATEK I SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVIL, POTI UPORABE ZDRAVILA, PREDLAGATELJEV V DRŽAVAH ČLANICAH
English: Question 5- The post hoc analysis conducted by the Applicant as a response to the concerned member state Day 145 comments was based on the individual Cmax/MIC or AUC/MIC ratios, determined for each subcomponent and then summed.
Slovenian: Vprašanje 5 - Post hoc analiza, ki jo je opravil predlagatelj kot odziv na pripombe zadevne države članice na 145. dan, je temeljila na posameznih razmerjih Cmax/MIK ali AUC/MIK, ki so bila določena za vsako podkomponento in nato sešteta.
English: The Applicant should provide data (e.g. guidance documents) demonstrating that adjustment of the dose to the clinical course is generally accepted and practised.
Slovenian: Predlagatelj mora predložiti podatke (npr. smernice), ki dokazujejo, da je prilagoditev odmerka kliničnemu poteku na splošno sprejemljiva in izvajana.
English: Ground 2: Bioequivalence was not demonstrated for each subcomponent.
Slovenian: Podlaga 2: Biološka enakovrednost ni bila dokazana za vse podkomponente.
English: Question 2 - The Applicant is requested to fully justify why the Phase I study submitted should not be considered a failed study.
Slovenian: Vprašanje 2 - Predlagatelja prosimo, da popolnoma utemelji, zakaj predložene študije faze I ne moremo šteti za neuspeh.
English: Taking into consideration the legal basis of the application, a clear negative trend was observed at the CHMP.
Slovenian: Ob upoštevanju pravne osnove vloge za pridobitev dovoljenja je CHMP opazil jasen negativen trend.
English: Ground 1: The Applicant has not sufficiently justified why the specifications of the innovator were not met.
Slovenian: Podlaga 1: Predlagatelj ni zadostno utemeljil, zakaj ni izpolnil specifikacije inovatorskega zdravila.
English: In 2005 Hospira UK submitted applications for Decentralised Procedure for Teicoplanin Hospira 200 mg & 400 mg powder and solvent for solution for injection in the framework of Article 28 of Directive 2001/83/EC, as amended.
Slovenian: Leta 2005 je družba Hospira UK predložila vlogi za decentraliziran postopek za zdravilo Teicoplanin Hospira 200 mg in 400 mg prašek in vehikel za raztopino za injiciranje v okvirih člena 28 Direktive 2001/83/ES, kakor je bila spremenjena.
English: The study was stopped early due to safety reasons, but the available pharmacokinetics data of teicoplanin was still assessed to the extent the data would allow.
Slovenian: Študijo so prekinili zgodaj zaradi varnostnih razlogov, vendar so razpoložljive podatke o farmakokinetiki teikoplanina še vedno ocenjevali, dokler so podatki to dopuščali.
English: Apart from the difference in levels of the TA2 subcomponents, there are no concerns over the manufacturing process used, particularly in terms of impurities.
Slovenian: Razen razlik v ravneh podkomponent TA2 ni zadržkov glede uporabljenega proizvodnega postopka, zlasti z vidika nečistoč.
English: The CHMP noted the Applicant response, and the summary of advice received from national agencies.
Slovenian: CHMP je upošteval predlagateljev odgovor in povzetek nasvetov iz nacionalnih agencij.
English: However, although these monographs ensure acceptable quality, they do not establish therapeutic equivalence.
Slovenian: Vendar pa te monografije zagotavljajo sprejemljivo kakovost in ne terapevtske enakovrednosti.
English: The Applicant should provide an analysis based on whole (total) teicoplanin plasma concentrations.
Slovenian: Predlagatelj naj predloži analizo za celotne (skupne) plazemske koncentracije teikoplanina.
English: Overall the total numbers of adverse events observed were similar for both treatments.
Slovenian: Skupno število neželenih učinkov je bilo podobno pri obeh zdravljenjih.
English: From a GCP perspective and in terms of the data generated which support the CMC and non-clinical data, TEC062 cannot be considered a failed study.
Slovenian: Z vidika GCP in v smislu pridobljenih podatkov, ki podpirajo CMC in neklinične podatke, študije TEC062 ne moremo šteti za neuspešno.
English: 200 mg/vial (66,7 mg/ml)
Slovenian: 200 mg/vialo (66,7 mg/ml)
English: In addition, the evaluation of free drug AUC also failed to demonstrate equivalence.
Slovenian: Poleg tega vrednotenje AUC prostega zdravila ni dokazalo enakovrednosti.
English: On this basis, the Applicant concluded that small variations in the composition of the active fractions are unlikely to affect the safety and efficacy of the drug in vivo.
Slovenian: Predlagatelj je zaključil, da s tega stališča majhne razlike v sestavi aktivnih frakcij malo verjetno vplivajo na varnost in učinkovitost zdravila in vivo.
English: The CHMP adopted a list of questions to be addressed by the Applicant.
Slovenian: CHMP je pripravil seznam vprašanj, na katera naj bi predlagatelj odgovoril.
English: The Applicant claimed essential similarity to the innovator product Targocid, despite acknowledging differences in the profile of glycopeptides.
Slovenian: Predlagatelj je uveljavljal osnovno podobnost z inovatorskim zdravilom Targocid kljub priznavanju razlik v profilu glikopeptidov.
English: The CHMP acknowledged that safety and efficacy were established, as well as the general equivalence.
Slovenian: CHMP je potrdil dokaze o varnosti in učinkovitosti ter splošni enakovrednosti.
English: Question 4 - The Applicant states that in clinical practice, the dose of teicoplanin is adjusted to the clinical course and the trough serum concentrations especially in severe infections.
Slovenian: Vprašanje 4 - Predlagatelj navaja, da je v klinični praksi odmerek teikoplanina prilagojen kliničnemu poteku in najnižjim serumskim koncentracijam, zlasti pri hudih okužbah.
English: In conclusion, irrespective of the legal basis, the Applicant believes that the product is developed in accordance with all appropriate specifications for teicoplanin and that no additional nonclinical studies are necessary.
Slovenian: Torej, predlagatelj ne glede na pravno osnovo meni, da je zdravilo razvito skladno z vsemi zadevnimi specifikacijami za teikoplanin in da dodatne neklinične študije niso potrebne.
English: The Applicant stated that appropriate loading doses of teicoplanin must be considered mandatory for all patients regardless of their renal function in order to achieve therapeutically relevant concentrations early in the treatment period.
Slovenian: Predlagatelj je navedel, da morajo biti ustrezni začetni odmerki teikoplanina obvezni za vse bolnike, ne glede na njihovo ledvično funkcijo, da se dosežejo terapevtsko relevantne koncentracije zgodaj v poteku zdravljenja.
English: The Applicant considers it relevant to measure free drug AUC (as the sum of the major active drug components).
Slovenian: Predlagatelj meni, da je smiselno meriti AUC prostega zdravila (kot vsote poglavitnih komponent aktivnega zdravila).
English: The Applicant responded that the Phase I study (TEC062) provided in support of this application, should not be considered as a failed study, as it was conducted in accordance with the relevant guidelines and that an inspection identified no major findings specifically related to the conduct of the study.
Slovenian: Predlagatelj je odgovoril, da se študija faze I (TEC062), predložena v podporo vlogi za pridobitev dovoljenja, ne sme šteti za neuspešno, saj je bila izvedena skladno z ustreznimi smernicami, in da inšpekcija ni odkrila poglavitnih težav, specifično povezanih z izvedbo študije.
English: The CHMP agreed with the Applicant response and considered the issue to be resolved.
Slovenian: CHMP se je strinjal s predlagateljevim odgovorom in menil, da je vprašanje rešeno.
English: 400 mg/vial (133,4 mg/ml)
Slovenian: 400 mg/vialo (133,4 mg/ml)
English: In particular, the non-protein bound kinetics of the sub-components of teicoplanin that contribute to its activity (TA21-5) was examined.
Slovenian: Zlasti je pregledal kinetiko podkomponent teikoplanina, ki niso vezane na beljakovine in ki prispevajo k njegovi aktivnosti (TA21-5).
English: teicoplanin formulation, bioequivalence should be shown as the supporting clinical data is not sensitive enough to detect differences between formulations.
Slovenian: formulacijo teikoplanina, je treba dokazati biološko enakovrednost, saj podporni klinični podatki niso dovolj občutljivi za odkrivanje razlik med formulacijama.
English: The Applicant believes that the sum of the individual ratios determined for each subcomponent is essentially the same as for the total teicoplanin.
Slovenian: Predlagatelj meni, da vsota posameznih razmerij, ki je določeno za vsako podkomponento v osnovi enaka kot za skupni teikoplanin.
English: The Applicant further discussed the supporting pre-clinical data in detail, describing the studies submitted (two MIC studies using a number of organisms, a neutropenic mouse thigh infection model and a repeated dose toxicity study in rats).
Slovenian: Predlagatelj je dodatno podrobno razpravljal o podpornih predkliničnih podatkih in opisoval predložene študije (dve študiji MIK s številnimi organizmi, model okužbe stegna nevtropeničnih mišk ter študijo toksičnosti ponavljajočih se odmerkov na podganah).
English: The Applicant discussed the legal basis of their application, stating that it was accepted as such by the RMS and all other member states and considering that the requirements of this legal basis have been met.
Slovenian: Predlagatelj je razpravljal o pravni osnovi svoje vloge in navedel, da so jo sprejele referenčna država članica in vse druge države članice, ter štel zahteve omenjene pravne osnove za izpolnjene.
English: The Applicant therefore conducted a series of preclinical studies and reviewed the published literature on the biological activity of the individual subcomponents of teicoplanin.
Slovenian: Predlagatelj je zato izvedel niz predkliničnih študij ter opravil pregled objavljene literature o biološki aktivnosti posameznih podkomponent teikoplanina.
English: The variability seen in the subcomponent composition is inherent to a fermentation product, and both products show variability for all individual components, although remaining well within the JP and European specifications.
Slovenian: Variabilnost sestave podkomponent je inherentna fermentacijskemu produktu in obe zdravili kažeta variabilnost vseh posameznih komponent, ki pa ostaja precej znotraj japonske in evropske specifikacije.
English: These differences are indicative that Teicoplanin Hospira is not a generic of Targocid and the potential impact on the safety of the drug is still not clear.
Slovenian: Te razlike kažejo, da zdravilo Teicoplanin Hospira ni generično zdravilo zdravila Targocid in da potencialni vpliv na varnost zdravila še vedno ni jasen.
English: Regarding safety, the data from study TEC062 showed no differences between Teicoplanin Hospira and Targocid, however, the premature termination of the study does not allow solid conclusions to be drawn, although there were no suggestions of any differential safety profile between the two products.
Slovenian: Glede varnosti pa podatki iz študije TEC062 niso pokazali razlik med zdraviloma Teicoplanin Hospira in Targocid, vendar prezgodnja prekinitev študije ne omogoča trdnih zaključkov, čeprav ni znakov razlik v varnostnem profilu med zdraviloma.
English: Question 6 - The MIC values used in the calculations for each sub-component have not been approved by the EUCAST.
Slovenian: Vprašanje 6 - Vrednosti MIC, uporabljene v izračunih posameznih podkomponent, ni odobril Evropski odbor za testiranje občutljivosti za protibakterijske učinkovine (EUCAST).
English: The CHMP acknowledges that the specifications of the innovator are confidential however, analysing innovator product batches will provide insight into the variability of innovator subcomponent levels and achieving specifications within this variability range would ensure equivalence.
Slovenian: CHMP priznava, da so specifikacije inovatorja zaupne, vendar analiza serij inovatorskega zdravila omogoča vpogled v variabilnost ravni podkomponent v inovatorskem zdravilu in da doseganje specifikacije v tem razponu variabilnosti zagotovi enakovrednost.
English: Accidental overdosing showed no adverse events or abnormalities.
Slovenian: Nenamerno preveliko odmerjanje ni imelo neželenih učinkov ali nenormalnosti.
English: Question 1 - The differences in composition between the two products and the resulting differences between the AUC values do not clearly demonstrate that Teicoplanin Hospira and the reference product Targocid are essentially similar.
Slovenian: Vprašanje št. 1 - Različna sestava obeh zdravil in posledične razlike vrednosti AUC ne dokazujejo jasno, da sta zdravilo Teicoplanin Hospira in referenčno zdravilo Targocid v osnovi podobni.
English: The majority of the adverse events observed were mild in intensity and not considered related to drug administration.
Slovenian: Večina opaženih neželenih učinkov je bila blagih po intenzivnosti in se ni štela za posledico dajanja zdravila.
English: The Applicant concluded that all the studies support the efficacy and safety of Teicoplanin Hospira and that the results were similar to those obtained with the originator.
Slovenian: Predlagatelj je zaključil, da vse študije podpirajo učinkovitost in varnost zdravila Teicoplanin Hospira in da so bili rezultati podobni rezultatom originatorskega zdravila.
English: The Applicant stated that generic applicants do not have access to the specifications of the originator products and that it therefore attempted to develop an API containing subcomponents at levels similar to that seen in Targocid.
Slovenian: Predlagatelj je navedel, da predlagatelji generičnih zdravil nimajo dostopa do specifikacij originatorskih zdravil in da je zato poskušal razviti zdravilno učinkovino, ki vsebuje podkomponente v podobnih ravneh kot v zdravilu Targocid.
English: The CHMP noted the Applicant data and agreed that free drug is more important for biological activity and is thus the better parameter to demonstrate “pharmacodynamic”-equivalence.
Slovenian: CHMP je upošteval podatke predlagatelja in se strinjal, da je prosto zdravilo pomembnejše za biološko aktivnost in zaradi tega boljši parameter za dokaz „farmakodinamične“ enakovrednosti.
English: The Applicant is, therefore, requested to fully justify whether or not additional clinical data is required in the form of a comparative safety and efficacy study with the innovator product in advance of the product being granted a Marketing Authorisation.
Slovenian: Predlagatelja zato prosimo, da popolnoma utemelji, ali so pred odobritvijo dovoljenja za promet z zdravilom potrebni dodatni klinični podatki v obliki primerjalne študije varnosti in učinkovitosti z inovatorskim zdravilom.
English: Question 3 - The Applicant should discuss the scientific basis for the post hoc analysis on the free AUC instead of the total AUC.
Slovenian: Vprašanje 3 - Predlagatelj naj razpravlja o znanstveni osnovi za post hoc analizo AUC prostega zdravila namesto AUC skupnega zdravila.
English: According to the Applicant, this indicates essentially similar therapeutic outcome.
Slovenian: Predlagatelj to razlaga kot pokazatelja osnovne podobnosti terapevtskega izida.
English: The CHMP noted the data comparing the PK, PDD and safety of Teicoplanin Hospira and the originator.
Slovenian: CHMP je upošteval podatke primerjave farmakokinetike, PDD in varnosti zdravila Teicoplanin Hospira ter originatorskega zdravila.
English: While EUCAST approved subcomponent MICs are not available for any antibacterial, this should not constitute an argument against their use.
Slovenian: Čeprav EUCAST ni odobril vrednosti MIK za podkomponente pri nobenem protibakterijskem zdravilu, to še ne pomeni, da jih ne smemo uporabljati.
English: Due to the differences in systemic exposure between Teicoplanin Hospira and Targocid and because the effect of the subcomponent differences on tissue drug concentrations was not measured, the CHMP concluded that bioequivalence could not be demonstrated.
Slovenian: Zaradi razlik v sistemski izpostavljenosti med zdraviloma Teicoplanin Hospira in Targocid in ker učinek razlik v podkomponentah na koncentracije zdravila v tkivu ni bil izmerjen, CHMP meni, da biološke enakovrednosti ni mogoče dokazati.
English: Comparable free AUC/MIC activity cannot waive potential PK differences or the outcome of the bioequivalence study.
Slovenian: Primerljive aktivnosti AUC/MIK prostega zdravila ne morejo mimo možnih razlik v farmakokinetiki ali izidu študije biološke enakovrednosti.
English: The CHMP therefore adopted the following List of Outstanding Issues to be addressed by the Applicant: “Following discussion and considering the differences in the composition and the demonstrated PK differences, the CHMP was of the opinion that it was not sufficiently demonstrated that Teicoplanin Hospira is a generic of Targocid.
Slovenian: CHMP je zato pripravil naslednji seznam nerešenih vprašanj, na katera naj bi odgovoril predlagatelj: „CHMP je po razpravi in upoštevanju razlik v sestavi ter dokazanih razlik v farmakokinetiki menil, da ni dovolj dokazov, da je zdravilo Teicoplanin Hospira generično zdravilo zdravila Targocid.
English: The Applicant did not further discuss the outcomes of the partially completed bioequivalence studies evaluating AUC and Cmax, as the CHMP considered that due to the nature of this drug, the whole drug (total) AUC is not appropriate to demonstrate bioequivalence.
Slovenian: Predlagatelj ni dodatno razpravljal o izidih delno opravljenih študij biološke enakovrednosti, v katerih so vrednotili AUC in Cmax, saj je CHMP menil, da za dokazovanje biološke enakovrednosti AUC za celotno (skupno) zdravilo ni primerna zaradi narave zdravila.
English: The Applicant also provided a briefing document stating that other endpoints, including pharmacodynamics, protein binding and analysis of the PK and PD of the principal sub-components, were measured in the study as it is believed that only free drug (non-protein bound teicoplanin) contributes to pharmacodynamic activity.
Slovenian: Predlagatelj je predložil tudi navodila, ki kažejo, da so v študiji merili druge končne točke, vključno s farmakodinamiko, vezavo na beljakovine in analizo farmakokinetike in farmakodinamike glavnih podkomponent, saj so menili, da le prosto zdravilo (na beljakovine nevezani teikoplanin) prispeva k farmakodinamični aktivnosti.
English: Safety data obtained from clinical study and non-clinical toxicity study The Applicant stated that the dosing regimen of teicoplanin is predictable, therefore dose-dependent toxicity is not of concern under standard clinical use.
Slovenian: Podatki o varnosti, pridobljeni iz klinične študije in neklinične študije toksičnosti Predlagatelj je navedel, da je režim odmerjanja napovedljiv, zato od odmerka odvisna toksičnost ni zadržek pri standardni klinični rabi.
English: The CHMP considered that similarity with regards to the free drug is important and that with regards to free AUC, the sum of all free TA2 subcomponents is 13% higher for Teicoplanin Hospira.
Slovenian: CHMP je menil, da je podobnost v smislu prostega zdravila pomembna in da je pri AUC prostega zdravila vsota vseh prostih podkomponent TA2 13 % večja pri zdravilu Teicoplanin Hospira.