FrancophonIA/ELRC3.0 huggingface dataset:
English: The Marketing Authorisation Holder should submit the result of a properly conducted bioequivalence study, in compliance with the Questions & Answers document of the CHMP EWP subgroup on pharmacokinetics on the Bioavailability and Bioequivalence Guideline.
Slovenian: Imetnik dovoljenja za promet z zdravilom mora predložiti rezultat pravilno izvedene študije biološke enakovrednosti, ki je skladen z dokumentom Vprašanja in odgovori podskupine EWP za farmakokinetiko pri CHMP o priporočilih glede biološke razpoložljivosti in biološke enakovrednosti.
English: In accordance with the Questions & Answers document of the CHMP EWP subgroup on pharmacokinetics on the bioavailability and bioequivalence guideline, exclusion of data is not justified and cannot be accepted on the basis of statistical analysis or for pharmacokinetic reasons alone, because it is impossible to distinguish between formulation effects and pharmacokinetic effects.
Slovenian: Skladno z dokumentom Vprašanja in odgovori podskupine EWP za farmakokinetiko pri CHMP o priporočilih glede biološke razpoložljivosti in biološke enakovrednosti izključevanje podatkov ni upravičeno in ni sprejemljivo na podlagi statistične analize ali zaradi vzrokov, ki izvirajo iz farmakokinetike, ker ni mogoče razlikovati med učinki formulacije in učinki farmakokinetike.
English: The Applicant submitted Cmax, AUCt and AUCinf values for all the volunteers and stated that the design of the study included sampling times in the absorption and late elimination phases in order to use results not exceeding the limit of quantification.
Slovenian: Predlagatelj je predložil vrednosti Cmax, AUCt in AUCinf za vse prostovoljce ter navedel, da je zasnova študije vključevala čase vzorčenja v fazah absorbcije in pozne eliminacije, da bi uporabili rezultate, ki ne presegajo meje kvantifikacije.
English: However, the CHMP noted that the Applicant did not properly determine the LOQ limits and did not provide detailed information on the choice of points for the calculation of the terminal phase, nor on the points chosen for the individual profile and segments.
Slovenian: Vendar je CHMP ugotovil, da predlagatelj ni pravilno določil vrednosti LOQ ter ni predložil podrobnih podatkov niti o izbiri točk za izračun terminalne faze niti o točkah, ki jih je izbral za posamezni profil in segmente.
English: With regards to the terminal phase being derived from Cmax in certain volunteers, this could be a matter of concern if the pharmacokinetic analysis applied had been compartmental, as it would suggest that a fast disposition phase did not exist in those cases compared with the remaining ones.
Slovenian: Izpeljava terminalne faze iz Cmax pri določenih prostovoljcih bi lahko predstavljala težavo, če bi se uporabila kompartmentalizirana farmakokinetična analiza, saj bi pokazala, da pri teh preiskovancih ni bilo hitre dispozicijske faze v primerjavi z ostalimi preiskovanci.
English: One of the metabolites is hydroxy-itraconazole, which has in vitro antifungal activity comparable to itraconazole.
Slovenian: Eden izmed presnovkov je hidroksiitrakonazol, katerega protiglivna aktivnost in vitro je primerljiva z itrakonazolom.
English: Regarding the statement that elimination phase was not achieved in some volunteers, the Applicant considered that the assessment of whether a volunteer has achieved elimination phase needs to take into account the experimental sample points and the concentrations values obtained.
Slovenian: Predlagatelj glede izjave, da faza eliminacije ni bila dosežena pri nekaterih prostovoljcih, meni, da je treba pri vrednotenju začetka faze eliminacije pri prostovoljcu upoštevati eksperimentalne točke vzorčenja in pridobljene vrednosti koncentracij.
English: Volunteer number 24 showed a decreased absorption with 52% of the sampling points BLQ, and only one sampling point with quantifiable values from his maximum concentration.
Slovenian: Prostovoljec št. 24 je kazal zmanjšano absorpcijo, saj je bilo 52 % vzorčnih točk pod mejo kvantifikacije in le ena vzorčna točka je imela vrednosti največje koncentracije, ki jih je bilo možno kvantificirati.
English: The Applicant included data on Clast, providing the last quantified concentration for each volunteer and formulation and the individual semi-logarithm pharmacokinetic figures.
Slovenian: Predlagatelj je priložil podatke o vrednosti Clast, ki je zadnja kvantificirana koncentracija za vsakega prostovoljca in formulacijo, ter posamezne pollogaritemske farmakokinetične številke.
English: No valid arguments were provided to justify the lack of credible pharmacokinetic calculations, as the LOQ value used in analytical method was not determined by a validation process, but arbitrarily accepted as 5 ng/ml (the lowest calibrator).
Slovenian: Veljavni argumenti za utemeljitev odsotnosti verodostojnih farmakokinetičnih izračunov niso bili predloženi, saj v analitični metodi uporabljena vrednost LOQ ni bila določena s postopkom validacije, ampak arbitrarno sprejeta kot 5 ng/ml (najnižji kalibracijski standard).
English: Czech Republic PRO.MED.CS Praha a.s. Tel ská 1
Slovenian: Češka republika PRO.MED.CS Praha a.s.
English: The Applicant stated that because the method to calculate the area under the curve is not described in the European guide (EMA), the method described in the FDA guide (page 9, paragraph III.A.8c) was used, applying the software WinNonlin which uses the module NCA (“Non compartmental Analysis”).
Slovenian: Predlagatelj je navedel, da metoda za izračun površine pod krivuljo ni opisana v Evropskih priporočilih (EMA), zato so uporabili metodo, opisano v priporočilu FDA (stran 9, odstavek III.A.8c), in programsko opremo WinNonlin z modulom NCA („nekompartmentalizirana analiza“).
English: The CHMP considered that the applied methods for calculating the AUCt and AUCinf and the ‘last exponential elimination constant' are standard and general accepted methods and noted that the requested data were provided, with at least 3 data points being used for estimation of the elimination phase.
Slovenian: CHMP je menil, da so uporabljene metode za izračun AUCt in AUCinf ter „zadnje konstante eksponentne eliminacije“ standardne in splošno priznane metode, ter potrdil, da so bili predloženi želeni podatki, iz katerih so bile za oceno faze eliminacije uporabljene vsaj 3 podatkovne točke.
English: Strength Pharmaceutical
Slovenian: Farmacevtska oblika
English: The correctness of the estimator point calculations could not be assessed and there is no summary of the specification calculations for the analysis of variance and intra- and inter-variability, individual ratios and differences for pharmacokinetic parameters.
Slovenian: Pravilnosti točk, uporabljenih za ocene, ni bilo mogoče vrednotiti, saj ni povzetka izračunov specifikacij za analizo variance ter intra- in intervariabilnosti, posameznih razmerij ter razlik za farmakokinetične parametre.
English: The CHMP expressed doubts on the quality of LOQ, noting the lack of summary specifications and concluded that similar problems of residual areas are likely to affect further subjects beyond the five already identified.
Slovenian: CHMP je izrazil dvome o kakovosti LOQ, opozoril na pomanjkanje povzetih specifikacij ter zaključil, da podobne težave rezidualnih površin verjetno vplivajo na druge preiskovance, ne le na odkritih pet preiskovancev.
English: The algorithm used to calculate the “last exponential elimination constant” in the NCA module is based on least squares regression and adjustment by the determination coefficient (square R) as a function of the number of points employed in the calculations.
Slovenian: Algoritem za izračun „zadnje konstante eksponentne eliminacije“ v modulu NCA temelji na regresiji z najmanjšimi kvadrati ter korekciji z določitvijo koeficienta (kvadriran R) kot funkcijo števila točk, uporabljenih v izračunih.
English: Itraconazole shows a rather long tmax (about 6 h) as a result of the long elimination half-life, however estimation of AUC was at least 4 times the tmax, indicating that in these subjects the drug has been absorbed from the gastrointestinal-tract, and that the drug in the body is not dependent on differences between the 2 formulations.
Slovenian: Itrakonazol ima zaradi dolge razpolovne dobe eliminacije precej dolg tmax (približno 6 ur), vendar je bila ocena AUC najmanj štirikratnik tmax, kar kaže, da se je pri teh preiskovancih zdravilo absorbiralo iz prebavil ter da zdravilo v telesu ni odvisno od razlik med formulacijama.
English: The applicant is asked to justify the results of the presented bioequivalence study, mainly the calculation of the AUCinf and z (last exponential elimination constant) as well as to provide all AUCt data.
Slovenian: Predlagatelja so prosili za utemeljitev rezultatov predstavljene študije biološke enakovrednosti, zlasti izračuna AUCinf in λz (zadnja konstanta eksponentne eliminacije), ter za predložitev vseh podatkov AUCt.
English: The CHMP considered that the bioequivalence between the test and reference product has not been sufficiently proven, and that as such the product is not considered approvable for the sought indications.
Slovenian: CHMP je menil, da biološka enakovrednost med preskusnim in referenčnim zdravilom ni bila zadostno dokazana in da zdravila kot takega ni mogoče odobriti za predlagane indikacije.
English: Disagreement remained between the concerned member states regarding the bioequivalence of Prokanazol to the originator, as no agreement could be reached with regards to the limits of quantification (LOQ) of itraconazole, the validation of calculation method of Cx/ z ratio (Cx being the last evaluable concentration and z being the last exponential elimination constant) or the justification of values of AUC residual above 20% of AUC total.
Slovenian: Zadevne države članice se niso strinjale glede biološke enakovrednosti zdravila Prokanazol in originatorja, saj niso dosegle soglasja o meji kvantifikacije (LOQ) itrakonazola, validaciji metode izračuna razmerja Cx/λz (pri čemer je Cx zadnja koncentracija, ki jo je mogoče ovrednotiti, λz pa zadnja konstanta eksponentne eliminacije) ali utemeljitvi vrednosti ostanka površine pod krivuljo plazemske koncentracije v odvisnosti od časa (AUC) nad 20 % skupne AUC.
English: In conclusion, the Applicant did not provide sufficient information on the sample size, the power test or the coefficients of inter- and intra-variability.
Slovenian: CHMP je zaključil, da predlagatelj ni predložil zadostnih podatkov o velikosti vzorca, moči testa ali koeficientih inter- in intravariabilnosti.
English: The CHMP noted that no values were used below the estimated LOQ of 5 ng/ml and that the last value above the LOQ was used for the estimation of AUCinf.
Slovenian: CHMP je ugotovil, da predlagatelj ni uporabil nobene vrednosti pod ocenjenim LOQ 5 ng/ml in da je za oceno AUCinf uporabil zadnjo vrednost nad LOQ.
English: Slovak Republic
Slovenian: Slovaška republika
English: The analytical centre gives only numerical results when the concentration is not BLQ, so is not possible to perform any calculations with these results.
Slovenian: Ko koncentracija ni bila pod mejo kvantifikacije, je analitični center podajal le številske rezultate, zato s temi rezultati ni možno opraviti izračunov.
English: Due to these outstanding concerns and the lack of documentation, the CHMP was unable to consider Prokanazol as being bioequivalent to the reference product and considered that more data was needed before an opinion could be provided.
Slovenian: CHMP zaradi nerešenih zadržkov in pomanjkljive dokumentacije ni mogel šteti zdravila Prokanazol za biološko enakovrednega referenčnemu zdravilu, ter je menil, da je za mnenje potrebnih več podatkov.
English: the CHMP has recommended the refusal of the granting of the Marketing Authorisations in the Concerned Member States and the suspension of the Marketing Authorisation in the Reference Member State, where the product is currently authorised, for Prokanazol and associated names (see Annex I).
Slovenian: CHMP je za zdravilo Prokanazol in z njim povezana imena (glejte Dodatek I) priporočil zavrnitev odobritve dovoljenj za promet z zdravilom v zadevnih državah članicah ter umik dovoljenja za promet z zdravilom v referenčni državi članici, kjer je zdravilo trenutno odobreno.
English: The pharmacokinetic analysis applied, following the recommendations from the regulatory agencies, was non-compartmental amodelistic.
Slovenian: Uporabljena pa je bila nekompartmentalizirana amodelistična farmakokinetična analiza skladno s priporočili regulativnih agencij.
English: EU/EEA
Slovenian: Država članica EU/EGP
English: Form
Slovenian: Jakost
English: Route of administration
Slovenian: Pot uporabe zdravila
English: This overview was last updated in 10-2019.
Slovenian: Povzetek je bil nazadnje posodobljen 10-2019.
English: Treatment should last for at least 3 weeks and continue until the patient no longer has symptoms.
Slovenian: Zdravljenje mora trajati vsaj tri tedne in se nadaljevati, dokler simptomi pri bolniku ne izzvenijo.
English: What measures are being taken to ensure the safe and effective use of Defitelio?
Slovenian: Kateri ukrepi se izvajajo za zagotovitev varne in učinkovite uporabe zdravila Defitelio?
English: Defitelio (defibrotide)
Slovenian: Defitelio (defibrotid)
English: Every year, the Agency will review any new information that becomes available and this overview will be updated as necessary.
Slovenian: Agencija bo vsako leto ponovno pregledala vse nove podatke, ki bodo na voljo.
English: Defitelio is used in adults and in children from one month of age.
Slovenian: Zdravilo Defitelio se lahko uporablja pri odraslih in otrocih, starejših od enega meseca.
English: Further information on Defitelio can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
Slovenian: Nadaljnje informacije o zdravilu Defitelio so na voljo na spletni strani agencije: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
English: The European Medicines Agency decided that Defitelio's benefits are greater than its risks and it can be authorised for use in the EU.
Slovenian: Evropska agencija za zdravila je zaključila, da so koristi zdravila Defitelio večje od z njim povezanih tveganj in da se lahko odobri za uporabo v EU.
English: Further information on the orphan designation can be found here: ema.europa.eu/Find medicine/Human medicines/Rare disease designation.
Slovenian: Nadaljnje informacije glede določitve zdravila sirote lahko najdete tukaj: ema.europa.eu/Find medicine/Human medicines/Rare disease designation.
English: Severe VOD has a high mortality rate of 75% or higher.
Slovenian: Stopnja umrljivosti zaradi hude venookluzivne bolezni je visoka in znaša 75 % ali več.
English: Defitelio received a marketing authorisation valid throughout the European Union on 18 October 2013.
Slovenian: Za zdravilo Defitelio je bilo 18. oktobra 2013 izdano dovoljenje za promet, veljavno po vsej Evropski uniji.
English: As for all medicines, data on the use of Defitelio are continuously monitored.
Slovenian: Tako kot za vsako zdravilo se tudi podatki o uporabi zdravila Defitelio stalno spremljajo.
English: Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Defitelio have been included in the summary of product characteristics and the package leaflet.
Slovenian: Priporočila in previdnostni ukrepi, ki jih morajo za varno in učinkovito uporabo zdravila Defitelio upoštevati zdravstveni delavci in bolniki, so vključeni v povzetek glavnih značilnosti zdravila in navodilo za uporabo.
English: Defitelio lowered the mortality rate to 62% at 100 days after transplantation, and 24% of patients had no symptoms of severe VOD after 100 days.
Slovenian: Zdravilo Defitelio je po 100 dneh po presaditvi zmanjšalo stopnjo umrljivosti na 62 %, 24 % bolnikov pa po 100 dneh ni imelo nobenih simptomov hude venookluzivne bolezni.
English: Benefits of Defitelio were also seen in data from a United States patient registry (information about patients collected in a standard way), where patients with severe VOD after blood stem cell transplantation who received Defitelio plus standard care had better outcomes than those given standard care alone, including a higher 100-day survival rate (39% versus 31%) and a higher proportion of patients whose VOD resolved (51% versus 29%).
Slovenian: Koristi zdravila Defitelio so bile opažene tudi pri podatkih iz registra bolnikov v ZDA (informacije o bolnikih, zbrane na standarden način), na podlagi katerih so imeli bolniki s hudo venookluzivno boleznijo, ki so po presaditvi krvotvornih matičnih celic prejemali zdravilo Defitelio v kombinaciji s standardnim zdravljenjem, boljše izide kot tisti, ki so prejemali samo standardno zdravljenje, vključno z višjo stopnjo preživetja po 100 dneh (39 % v primerjavi z 31 %) in višjim odstotkom bolnikov, pri katerih so simptomi venookluzivne bolezni izginili (51 % v primerjavi z 29 %).
English: Why is Defitelio authorised in the EU?
Slovenian: Zakaj je zdravilo Defitelio odobreno v EU?
English: Although it was not possible to conduct a study directly comparing Defitelio with placebo (dummy treatment), the company had provided sufficient data to show that patients treated with the medicine had improved chances of survival.
Slovenian: Čeprav ni bilo mogoče izvesti študije, v kateri bi zdravilo Defitelio neposredno primerjali s placebom (zdravilom brez učinkovine), je podjetje priskrbelo dovolj podatkov, da je dokazalo, da so imeli bolniki, ki so se zdravili z zdravilom, večje možnosti preživetja.
English: An overview of Defitelio and why it is authorised in the EU
Slovenian: Pregled zdravila Defitelio in zakaj je odobreno v EU
English: The side effects seen, such as bleeding, were considered manageable and it was not possible to determine with certainty whether they were caused by Defitelio.
Slovenian: Neželeni učinki, kot je krvavitev, so se šteli za obvladljive, poleg tega pa ni bilo mogoče z gotovostjo trditi, da jih je povzročilo zdravilo Defitelio.
English: What benefits of Defitelio have been shown in studies?
Slovenian: Kakšne koristi zdravila Defitelio so se pokazale v študijah?
English: What is Defitelio and what is it used for?
Slovenian: Kaj je zdravilo Defitelio in za kaj se uporablja?
English: VOD is rare, and Defitelio was designated an ‘orphan medicine' (a medicine used in rare diseases) on 29 July 2004.
Slovenian: Venookluzivna bolezen je redka, zato je bilo zdravilo Defitelio 29. julija 2004 določeno kot „zdravilo sirota“ (zdravilo za zdravljenje redkih bolezni).
English: What are the risks associated with Defitelio?
Slovenian: Kakšna tveganja so povezana z zdravilom Defitelio?
English: For more information about using Defitelio, see the package leaflet or contact your doctor or pharmacist.
Slovenian: Za več informacij glede uporabe zdravila Defitelio glejte navodilo za uporabo ali se posvetujte z zdravnikom ali farmacevtom.
English: Side effects reported with Defitelio are carefully evaluated and any necessary action taken to protect patients.
Slovenian: Neželeni učinki, o katerih so poročali pri zdravilu Defitelio, se skrbno ovrednotijo in po potrebi se sprejmejo ukrepi za zaščito bolnikov.
English: Defitelio has been authorised under ‘exceptional circumstances'.
Slovenian: Zdravilo Defitelio je pridobilo dovoljenje za promet „v izjemnih okoliščinah“.
English: Defitelio must not be used together with other medicines that break down blood clots.
Slovenian: Zdravilo Defitelio se ne sme uporabljati skupaj z drugimi zdravili za razgrajevanje krvnih strdkov.
English: The most common side effects with Defitelio are hypotension (low blood pressure) and bleeding.
Slovenian: Najpogostejša neželena učinka zdravila Defitelio sta hipotenzija (nizek krvni tlak) in krvavitev.
English: In one main study involving 102 patients with severe VOD following blood stem cell transplantation, Defitelio was compared with past records of patients who had received standard supportive care.
Slovenian: V eni glavni študiji, v katero sta bila vključena 102 bolnika s hudo venookluzivno boleznijo, ki je bila posledica presaditve krvotvornih matičnih celic, so zdravilo Defitelio primerjali z zdravniškimi izvidi bolnikov iz preteklosti, ki so prejeli standardno podporno zdravljenje.
English: This is because it has not been possible to obtain complete information about Defitelio due to the rarity of the disease.
Slovenian: To pomeni, da zaradi redkosti bolezni ni bilo mogoče pridobiti vseh podatkov o zdravilu.
English: Since Defitelio has been authorised under exceptional circumstances, the company that markets the medicine is required to provide results of an ongoing study on safety of the medicine when used for prevention of VOD in adults and children undergoing hematopoietic stem cell transplantation.
Slovenian: Ker je zdravilo Defitelio pridobilo dovoljenje za promet v izjemnih okoliščinah, mora podjetje, ki ga trži, predložiti rezultate potekajoče študije o varnosti zdravila, kadar se to uporablja za preprečevanje venookluzivne bolezni pri odraslih in otrocih, ki so prestali presaditev krvotvornih matičnih celic.
English: Myeloablative chemotherapy is used to clear the patient's bone marrow of cells before receiving healthy stem cells.
Slovenian: Mieloablativna kemoterapija se uporablja zato, da se iz kostnega mozga bolnika izločijo celice, preden ta prejme zdrave matične celice.
English: The company will also analyse data on transplant outcomes in VOD patients who have and have not been treated with Defitelio.
Slovenian: Podjetje bo tudi analiziralo podatke o izidih presaditev pri bolnikih z venookluzivno boleznijo, ki so bili zdravljeni z zdravilom Defitelio, in pri tistih, ki s tem zdravilom niso bili zdravljeni.
English: Other information about Defitelio
Slovenian: Druge informacije o zdravilu Defitelio
English: Defitelio had been shown to improve survival in patients with severe VOD.
Slovenian: Zdravilo Defitelio je dokazano izboljšalo stopnjo preživetja pri bolnikih s hudo venookluzivno boleznijo.
English: The active substance in Defitelio, defibrotide, works by increasing the breakdown of clots in the blood.
Slovenian: Učinkovina v zdravilu Defitelio, defibrotid, deluje tako, da pospešuje razgrajevanje strdkov v krvi.
English: Defitelio can only be obtained with a prescription and it must be prescribed and given by a doctor experienced in the management of complications of blood stem cell transplantation.
Slovenian: Predpisovanje in izdaja zdravila Defitelio je le na recept, zdravljenje pa mora predpisati in izvajati zdravnik, ki ima izkušnje z zdravljenjem zapletov pri presaditvi krvotvornih matičnih celic.
English: The medicines used for this treatment can damage the lining of the blood vessels in the liver, leading to the formation of clots and obstruction of the vessels seen in VOD.
Slovenian: Zdravila, ki se uporabijo pri tem zdravljenju, lahko poškodujejo notranje plasti krvnih žil v jetrih, to pa lahko povzroči nastanek strdkov in zaporo žil, ki se pojavita pri venookluzivni bolezni.
English: VOD is usually a complication resulting from a treatment known as ‘myeloablative chemotherapy' given before blood stem cell transplantation.
Slovenian: Venookluzivna bolezen je običajno zaplet, ki je posledica zdravljenja, imenovanega „mieloablativna kemoterapija“, ki se bolniku daje pred presaditvijo krvotvornih matičnih celic.
English: What information is still awaited for Defitelio?
Slovenian: Katere informacije o zdravilu Defitelio še pričakujemo?
English: How does Defitelio work?
Slovenian: Kako zdravilo Defitelio deluje?
English: Defitelio is a medicine used to treat severe veno-occlusive disease (VOD) in patients undergoing haematopoietic (blood) stem cell transplantation.
Slovenian: Defitelio je zdravilo, ki se uporablja za zdravljenje hude venookluzivne bolezni (VOB) pri bolnikih, ki so prestali presaditev hematopoetskih (krvotvornih) matičnih celic.
English: For the full list of side effects of Defitelio, see the package leaflet.
Slovenian: Za celoten seznam neželenih učinkov, o katerih so poročali pri uporabi zdravila Defitelio, glejte navodilo za uporabo.
English: How is Defitelio used?
Slovenian: Kako se zdravilo Defitelio uporablja?