natgillin/translations-raw huggingface dataset:
Exposure-response relationship in paediatric population On the basis of clinical trial data in patients with JIA (pJIA and ERA), an exposure-response relationship was established between plasma concentrations and PedACR 50 response.
Razmerje med izpostavljenostjo in odzivom pri pediatrični populaciji Na podlagi podatkov iz kliničnih preskušanj pri bolnikih z juvenilnim idiopatskim artritisom (JIA)
• Keep this container out of the sight and reach of children
• Ta vsebnik shranjujte nedosegljivo otrokom.
It is important to tell your doctor if your child gets symptoms of infections, such as fever, wounds, feeling tired or dental problems.
Pomembno je, da zdravniku poveste, če se pri vašem otroku razvijejo znaki okužbe, kot so zvišana telesna temperatura, rane, utrujenost ali problemi z zobmi.
Erectile dysfunction
Ocena erozij
• haematoma;
• nevropatija;
Deafness, tinnitus
KG Knollstrasse
a 20
Preglednica 20
If a faster response is required, the doctor may prescribe a first dose of 160 mg (two 80 mg injections in one day or one 80 mg injection per day for two consecutive days), followed by 80 mg (one 80 mg injection) two weeks later.
Če je potreben hitrejši odziv na zdravljenje, lahko uporabite shemo 160 mg 0. teden (odmerek lahko aplicirate z dvema 80 mg injiciranjema na en dan ali z enim 80 mg injiciranjem na dan dva dni zapored) in 80 mg 2. teden.
p-value a p-value b p-value
b 2-stranska vrednost p testa log-rank.
33.5% respectively, p < 0.001) and Humira monotherapy (50.7%, p < 0.002 and 44.5%, p < 0.001 respectively).
(30,6 % proti 4,3 %, v tem zaporedju [P = 0,014]).
Squeeze the skin at your child's injection site with your other hand to make a raised area and hold it firmly.
Z drugo roko stisnite otrokovo kožo na mestu injiciranja,
One 0.8 ml pre-filled syringe with needle guard contains 40 mg adalimumab.
Ena 0,8 ml napolnjena injekcijska brizga vsebuje 40 mg adalimumaba.
Whereas
Ker
Furosemide has been authorised in the EU for more than 40 years.
Furosemid ima dovoljenje za promet v EU že več kot 40 let.
1 Dormans et al.
Dormans in sod.
Scientific conclusions and grounds for refusal presented by the European Medicines Agency
Znanstveni zaključki in razlogi za zavrnitev, ki jih je predstavila Evropska agencija za zdravila
The detailed grounds for re-examination were submitted on 21 December 2012.
Podrobne razloge za ponovni pregled je predlagatelj predložil 21. decembra 2012.
• Detailed grounds for re-examination submitted by the applicant
• Podrobni razlogi za ponovni pregled, ki jih je predložil predlagatelj
The results have shown that furosemide absorption is highly variable (AUC value varies from 793.8 to 3953 ng*h/ml, Cmax from 283,6 to 2636 ng/ml and ln Cmax values are almost a tenfold difference).
Rezultati so pokazali, da je absorpcija furosemida zelo različna (vrednost AUC niha od 793,8 do 3953 ng*h/ml, vrednost Cmax od 283,6 do 2636 ng/ml, vrednosti ln Cmax pa so skoraj desetkratno različne).
However, it is noted that the CHMP is a scientific committee and that while it operates within the legal framework, it cannot discuss the specific merits of procedural and legal aspects of administrative procedures laid down in the legislation.
Upošteva se, da je CHMP znanstveni odbor in da kljub delovanju v pravnem okviru ne more razpravljati o konkretnih prednostih postopkovnih in pravnih vidikov administrativnih postopkov, opredeljenih z zakonodajo.
The decentralised procedure was closed on day 210, with most of the Concerned Member States agreeing with the conclusions of the Reference Member State's assessment report except Poland and Lithuania which raised a potential serious risk to public health (PSRPH).
Decentralizirani postopek se je končal na 210. dan, ko je večina zadevnih držav članic soglašala z zaključki poročila o oceni referenčne države članice z izjemo Poljske in Litve, ki sta izrazili zaskrbljenost zaradi možnega resnega tveganja za javno zdravje (PSRPH).
At the request of the applicant, an ad-hoc expert meeting was convened.
Na zahtevo predlagatelja je bila sklicana ad-hoc seja strokovnjakov.
Overall summary of the scientific evaluation of Furosemide Vitabalans and associated names (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravila Furosemide Vitabalans in povezanih imen (glejte Prilogo I)
The applicant expressed its disagreement on some procedural aspects of the mutual recognition procedure, the CMDh procedure and the referral procedure under Article 29(4) of Directive 2001/83/EC.
Predlagatelj je izrazil nestrinjanje z nekaterimi postopkovnimi vidiki postopka medsebojnega priznavanja, postopkom CMDh in napotitvenim postopkom v skladu s členom 29(4) Direktive 2001/83/ES.
• It has not been sufficiently demonstrated by the applicant that a potentially lower or higher exposure to furosemide would not influence the efficacy or safety.
• predlagatelj ni zadovoljivo prikazal, da potencialno manjša ali večja izpostavljenost furosemidu ne vpliva na učinkovitost ali varnost;
Considering the foreseeable high variability of the product, the main risk with furosemide would be a lack of efficacy.
Glede na predvideno veliko spremenljivost zdravila bi bilo glavno tveganje s furosemidom pomanjkanje učinkovitosti.
Furosemide is a loop diuretic which acts along the entire nephron with the exception of the distal exchange site.
Furosemid je diuretik zanke, ki deluje vzdolž celotnega nefrona z izjemo distalnega mesta izmenjave.
It cannot be excluded that the bioavailability of the applied product may be lower or higher than the bioavailability of these products.
Ni mogoče izključiti, da bo morda biološka uporabnost zdravila, za katerega je vloga predložena, manjša ali večja od biološke uporabnosti teh zdravil.
In view of this lack of evidence the Committee found merit on the concerns raised by the Member States on the potential serious risk to public health.
Zaradi tega pomanjkanja dokazov je Odbor ugotovil utemeljenost zadržkov, ki sta jih izpostavili državi članici glede potencialno resnega tveganja za javno zdravje.
The applicant expressed its disagreement with the CHMP opinion, focusing its scientific grounds on the following points, for which the applicant argued that clear justification or evidence had not been presented to explain:
Predlagatelj je izrazil nestrinjanje z mnenjem CHMP in pri tem svoje znanstvene utemeljitve osredotočal na spodaj navedene točke, glede katerih predlagatelj meni, da niso bili predstavljeni zadostni dokazi ali utemeljitve, da bi razložili naslednje:
Following the adoption of the CHMP opinion and recommendations during the October 2012 CHMP meeting, a request for a re-examination was received from the applicant Vitabalans Oy on 12
Po sprejetju mnenja in priporočil odbora CHMP na srečanju Odbora oktobra 2012 je predlagatelj Vitabalans Oy 12. novembra prosil za ponovni pregled.
As a result, procedural and legal considerations are outside the remit of the CHMP, and therefore the re-examination of the referral procedure under Article 29(4) of Directive 2001/83/EC focussed only on the scientific points addressed in the grounds for reexamination.
Iz tega sledi, da postopkovni in pravni zadržki niso v pristojnosti odbora CHMP, zato se je ponovni pregled napotitvenega postopka v skladu s členom 29(4) Direktive 2001/83/ES osredotočal samo na znanstvene točke, opredeljene v razlogih za ponovni pregled.
• CHMP conclusion on grounds for re-examination
• Sklep odbora CHMP na osnovi ponovnega pregleda
In addition, it is also noted that according to the Guideline on the Definition of a Potential Serious Risk to Public Health, a potential serious risk to public health in relation to a particular medicinal product can be considered to exist if the data submitted to support therapeutic efficacy do not provide sound justification for the claims of efficacy and/or the clinical safety data does not provide adequate support for the conclusion that all potential safety issues have been appropriately and adequately addressed.
Prav tako je ugotovljeno, da je v skladu s smernico o potencialno resnih tveganjih za javno zdravje mogoče sklepati o potencialno resnem tveganju za javno zdravje v povezavi z določenim zdravilom samo, če predloženi podatki za podporo terapevtske učinkovitosti ne zagotavljajo ustrezne utemeljitve za zahtevke o učinkovitosti in/ali če klinični varnostni podatki ne zagotavljajo ustrezne podpore za sklep, da so bila vsa potencialna vprašanja o varnosti ustrezno in primerno pojasnjena.
The clinical part of the dossier referred to 77 publications up to 2009 supporting the effect of furosemide in the treatment of oedema associated with congestive heart failure, cirrhosis of the liver and renal disease, including nephrotic syndrome and mild to moderate hypertension.
Klinični del dokumentacije se je nanašal na 77 objav do leta 2009, ki podpirajo učinek furosemida pri zdravljenju edema, povezanega s kongestivnim srčnim popuščanjem, cirozo jeter in boleznijo ledvic, vključno z nefrotskim sindromom in blago do zmerno hipertenzijo.
The decentralised marketing authorisation application for Furosemide Vitabalans was made in accordance with Article 10(a) of Directive 2001/83/EC, which is a well-established use application.
Vloga za pridobitev dovoljenja za promet z zdravilom Furosemide Vitabalans po decentraliziranem postopku je bila predložena v skladu s členom 10(a) Direktive 2001/83/ES, ki predstavlja vlogo na osnovi dobro uveljavljene rabe.
• Ad-hoc expert meeting
• Ad-hoc seja strokovnjakov
The application for Furosemide Vitabalans is therefore based on publicly available bibliographic data as it is possible to replace results of the pre-clinical and clinical trials by detailed references to published scientific literature (information available in the public domain) if it can be demonstrated that the active substances of a medicinal product have been in well-established medicinal use within the Community for at least ten years, with recognized efficacy and an acceptable level of safety.
Vloga za zdravilo Furosemide Vitabalans tako temelji na javno dostopnih bibliografskih podatkih, saj je mogoče nadomestiti rezultate predkliničnih in kliničnih preskušanj s podrobnimi sklici na objavljeno znanstveno literaturo (informacije, ki so v splošni rabi), če je mogoče dokazati, da so zdravilne učinkovine zdravila v dobro uveljavljeni medicinski uporabi v Skupnosti vsaj deset let, s priznano učinkovitostjo in sprejemljivo stopnjo varnosti.
The non-clinical overview referred to 29 publications up to year 2010 describing pharmacodynamics, general pharmacology, pharmacokinetic and toxicology studies.
Pregled predklinične dokumentacije se je nanašal na 29 objav do leta 2010, ki opisujejo študije farmakodinamike, splošne farmakologije, farmakokinetike in toksikologije.
Indeed, furosemide is an active substance with low solubility and low permeability (BCS class IV) which does not support an extrapolation based on pharmaceutical data.
Dejansko je furosemid zdravilna učinkovina z nizko topnostjo in majhno prepustnostjo (razred BCS IV), kar ne podpira ekstrapolacije na podlagi farmacevtskih podatkov.
One of the factors influencing furosemide's pharmacokinetic variability is precisely the absorption process which is dependent on the intrinsic properties of this substance/low solubility, low permeability associated with unknown formulation effects.
Eden od dejavnikov, ki vpliva na spremenljivost farmakokinetike furosemida, je prav proces absorpcije, ki je odvisen od bistvenih lastnosti te snovi / nizke topnosti, nizke prepustnosti, povezane z neznanimi učinki te oblike.
It is agreed that the manufacturing method is adequately described, however a robust manufacturing process is only a basis for further investigations on efficacy and safety of the applied product, and cannot be accepted as proof of equivalence to an authorised product.
Odbor se strinja, da je metoda izdelave ustrezno opisana, vendar je robusten postopek izdelave zgolj osnova za nadaljnje preiskave učinkovitosti in varnosti zdravila, za katerega je vloga predložena, in ga ni mogoče upoštevati kot dokaz enakovrednosti z odobrenim zdravilom.
The lack of data regarding the bioavailibity of the product could lead to unforeseeable changes in the pharmacodynamics response and therapeutic failure, as well as the occurrence of toxic effects.
Pomanjkanje podatkov v zvezi z biološko uporabnostjo zdravila bi lahko povzročilo nepredvidljive spremembe v farmakodinamičnem odzivu, neuspešnost zdravljenja in pojav toksičnih učinkov.
Furthermore, the group considered that there is a safety concern to put a product on the market for such indication (heart failure) when the efficacy has not been demonstrated.
Skupina je bila tudi mnenja, da obstaja pri dajanju zdravila na trg za tovrstne indikacije (srčna odpoved) brez prikazane učinkovitosti varnostni zadržek.
In addition, for highly variables drugs, as it is the product under application, it is considered necessary to investigate the pharmacokinetics behaviour in order to exclude any other potential product-related variations.
Poleg tega je treba za zelo spremenljiva zdravila, kot je to zdravilo, za katero je vloga predložena, raziskati farmakokinetično obnašanje, da se izključijo vsakršne druge potencialne spremembe, povezane z zdravilom.
During the decentralised procedure, Poland and Lithuania were of the opinion that bibliographic data on pharmacokinetics of furosemide, presented in the marketing authorisation dossier cannot be applied to Furosemide Vitabalans and should be regarded as not sufficient.
V času decentraliziranega postopka sta bili Poljska in Litva mnenja, da bibliografskih podatkov o farmakokinetiki furosemida, ki so bili predstavljeni v dokumentaciji dovoljenja za promet, ni mogoče uporabiti za zdravilo Furosemide Vitabalans in jih je treba smatrati za nezadostne.
Therefore, the CHMP concluded that the efficacy of Furosemide Vitabalans has not been demonstrated in the applied indications, and this constitutes a potential serious risk to public health.
Zato je odbor CHMP zaključil, da učinkovitost zdravila Furosemide Vitabalans v indikacijah, za katere predlagatelj vlaga vlogo, ni bila prikazana, kar predstavlja potencialno resno tveganje za javno zdravje.
The use of furosemide is wide in clinical practice and a number of published papers have been submitted in support of efficacy and safety during the decentralised procedure.
Uporaba furosemida v klinični praksi je široka in v času decentraliziranega postopka so bili v podporo njegovi učinkovitosti ter varnosti predloženi številni objavljeni članki.
• why the pharmacokinetics parameters of the applied furosemide 40 mg product would be different than the pharmacokinetics parameters in other furosemide products described in literature and to what extent they would be expected to be different, and how this difference would cause a concrete potential serious risk to public health.
• zakaj in v kakšnem obsegu bi bili farmakokinetični parametri zdravila furosemid 40 mg, za katerega je vloga predložena, drugačni od farmakokinetičnih parametrov drugih izdelkov s furosemidom, opisanih v literaturi, in kako bi ta razlika povzročila konkretno potencialno resno tveganje za javno zdravje.
• how the applied furosemide 40 mg product would cause a potential serious risk to public health
• kako bi zdravilo furosemid 40 mg, za katerega je vloga predložena, povzročilo potencialno resno tveganje za javno zdravje;
• why the safety and efficacy of the applied furosemide 40 mg product would be effectively different than in other furosemide 40 mg products
• zakaj bi bili varnost in učinkovitost zdravila furosemid 40 mg, za katerega je vloga predložena, učinkovito drugačni od drugih zdravil s 40 mg furosemida;
Part II.1.d) of Annex I of Directive 2001/83/EC states that “the non-clinical and/or clinical overviews must explain the relevance of any data submitted which concern a product different from the product intended for marketing.
Del II.1.d) Priloge I Direktive 2001/83/ES navaja, da „morajo pregledi predklinične in/ali klinične dokumentacije pojasniti pomen vsakršnih predloženih podatkov, ki zadevajo drugačno zdravilo od zdravila, namenjenega za trženje.
The CHMP is of the opinion that the comparability of the bioavailability between the applied product and a product included in the submitted literature should have been shown in order to claim the same indication.
Odbor CHMP meni, da bi bilo treba prikazati primerljivost biološke uporabnosti med zdravilom, za katerega je vloga predložena, in zdravilom, vključenim v predloženo literaturo, da bi lahko sklepali na enake indikacije.
The CHMP has recommended the refusal of the granting of the marketing authorisation for Furosemide Vitabalans and associated names (see Annex I).
Odbor CHMP je priporočil zavrnitev izdaje dovoljenja za promet z zdravilom Furosemide Vitabalans in povezanimi imeni (glejte Prilogo I).
A judgement must be made whether the product studied can be considered as similar to the product for which application for marketing authorisation has been made in spite of existing differences”.
Presoditi je treba, ali je preučevano zdravilo mogoče obravnavati kot podobno zdravilu, za katerega je bila podana vloga za pridobitev dovoljenja za promet kljub obstoječim razlikam“.
It was considered necessary to have in vivo data especially with a drug exhibiting such wide range of pharmacokinetic values.
Podatki in vivo so zlasti potrebni pri zdravilu, ki kaže tako širok razpon farmakokinetičnih vrednosti.
• Pharmaceutical data
• farmacevtske podatke
• Clinical data
• klinične podatke
Therefore, it not possible to conclude that the efficacy and safety of Furosemide Vitabalans will be the same as that of the products containing furosemide included in the submitted literature.
Zato ni mogoče zaključiti, da bo učinkovitost in varnost zdravila Furosemide Vitabalans enaka kot pri drugih zdravilih s furosemidom, ki so vključena v predloženo literaturo.
Furthermore, in vitro data cannot be sole proof that the clinical data from the submitted studies are applicable to Furosemide Vitabalans.
Poleg tega podatki in vitro ne morejo biti edini dokaz, da klinični podatki iz predloženih študij veljajo za zdravilo Furosemide Vitabalans.
Furthermore, the applicant provided a set of dissolution profiles comparing Furosemide Vitabalans with nine other furosemide 40 mg tablets.
Poleg tega je predlagatelj predložil niz profilov raztapljanja, ki primerjajo zdravilo Furosemide Vitabalans z devetimi drugimi tabletami s 40 mg furosemida.
In order to show the relevance of the bibliographic data used in support of the application for Furosemide Vitabalans, the applicant made reference to:
Z namenom prikaza pomena bibliografskih podatkov, ki so bili uporabljeni za podporo vlogi za pridobitev dovoljenja za promet z zdravilom Furosemide Vitabalans, je predlagatelj navedel:
Diuretic efficacy of high dose furosemide pharmacokinetics and pharmacodynamics in health and diseasean update.
Diuretic efficacy of high dose furosemide pharmacokinetics and pharmacodynamics in health and disease - an update (Diuretska učinkovitost farmakokinetike in farmakodinamike furosemida v velikih odmerkih na zdravje in bolezni - posodobitev).
• Pharmacokinetics data
• farmakokinetične podatke
Furthermore, given that furosemide is a highly variable compound, the submission of in vivo data was considered necessary in order to characterise the PK of the product together with justification that would allow establishing a bridge to the published data.
Ker je furosemid zelo spremenljiva sestavina, se je predložitev podatkov in vivo smatrala za potrebno zaradi karakterizacije farmakokinetike zdravila skupaj z utemeljitvijo, ki bi omogočila povezavo z objavljenimi podatki.
As mentioned previously, Annex I of Directive 2001/83/EC states that the non-clinical and/or clinical overviews must explain the relevance of any data submitted which concern a product different from the product intended for marketing.
Kot je navedeno zgoraj, Priloga I Direktive 2001/83/ES navaja, da morajo pregledi predklinične in/ali klinične dokumentacije pojasniti pomen vsakršnih predloženih podatkov, ki zadevajo drugačno zdravilo od zdravila, namenjenega za trženje.
The CHMP considered that a wide range of pharmacokinetic values for different furosemide 40 mg products did not prove that the pharmacokinetic parameters of Furosemide Vitabalans will be within the same range.
Odbor CHMP je presodil, da širok razpon farmakokinetičnih vrednosti za različna zdravila s 40 mg furosemida dokazuje, da bodo farmakokinetični parametri zdravila Furosemide Vitabalans znotraj istega razpona.
The study in support of the safety of furosemide (Dormans et al.1) presented by the applicant, was not considered as relevant by the CHMP, as furosemide in this study was used intravenously and Furosemide Vitabalans is intended to be used in oral administration as a 40mg tablet.
Študije v podporo varnosti furosemida (Dormans in sod.1), ki jo je predložil predlagatelj, odbor CHMP ni upošteval za ustrezno, saj je bil v tej študiji furosemid uporabljan intravensko, zdravilo Furosemide Viatabalans pa je namenjeno za peroralno uporabo v obliki 40 mg tablet.
In response to the CHMP, the applicant further referred to published pharmacokinetics data presenting PK parameters of similar tablets formulations to Furosemide Vitabalans as well as different formulations (e.g. tablet 20mg).
Kot odgovor odboru CHMP je predlagatelj nadalje navedel objavljene farmakokinetične podatke, ki predstavljajo farmakokinetične parametre tablet, podobnih zdravilu Furosemide Vitabalans, kot tudi drugačnih formulacij (npr. 20-miligramske tablete).
The pharmacokinetic parameters available in the literature are not sufficient to claim that Furosemide Vitabalans would have a similar bioavailability.
Farmakokinetični parametri, ki so na voljo v literaturi, niso zadostni za potrditev, da ima zdravilo Furosemide Vitabalans podobno biološko uporabnost.
The group considered that manufacturing methods or dissolution data could not predict how the product would behave in vivo.
Skupina je bila prav tako mnenja, da z metodami izdelave ali s podatki o raztapljanju ni mogoče predvideti obnašanja zdravila in vivo.
The CHMP is of the opinion that the applicant has not adequately demonstrated that the submitted published literature on furosemide was directly applicable to Furosemide Vitabalans.
Odbor CHMP meni, da predlagatelj ni ustrezno predstavil, da je mogoče predloženo objavljeno literaturo o furosemidu neposredno uporabiti za zdravilo Furosemide Vitabalans.
A judgement must be made whether the product studied can be considered as similar to the products, for which application for a marketing authorisation has been made in spite of the existing differences.
Presoditi je treba, ali je preučevano zdravilo mogoče obravnavati kot podobno zdravilu, za katerega je bila predložena vloga za pridobitev dovoljenja za promet kljub obstoječim razlikam.
As discussed previously, in vitro data demonstrating similarity of dissolution profiles between Furosemide Vitabalans and other products containing furosemide do not prove that the bioavailability of these products would be similar, in particular, with a BCS class IV drug substance (low solubility, low permeability).
Kot je bilo predhodno obravnavano, podatki in vitro za prikaz podobnosti profilov raztapljanja med zdravilom Furosemide Vitabalans z drugimi zdravili s furosemidom ne dokazujejo podobnosti biološke uporabnosti, zlasti z biofarmacevtskim zdravilom razreda IV (nizka topnost, nizka prepustnost).
The applicant also argued that dissolution behaviour together with evident pharmaceutical equivalence proves bridging between Furosemide Vitabalans and other authorised furosemide 40mg products.
Predlagatelj je prav tako trdil, da obnašanje pri raztapljanju skupaj z evidentno farmacevtsko enakovrednostjo dokazuje povezavo med zdravilom Furosemide Vitabalans z drugimi zdravili s 40 mg furosemida.
An ad-hoc expert meeting was convened on 13 February 2013 at the request of the applicant.
Na zahtevo predlagatelja je bila 13. februarja sklicana adhoc seja strokovnjakov.