natgillin/translations-raw huggingface dataset:
However the case for a lack of significant difference in efficacy concerns due to lower exposure is not adequately addressed in both the expert reports.
V nobenem izmed strokovnih poročil pa odsotnost pomembne razlike glede pomislekov o učinkovitosti zaradi nižje izpostavljenosti ni zadovoljivo obravnavana.
• the provided data does not show that Loraxin is similar to the product used in the pivotal clinical studies described in the submitted bibliography.
• Predloženi podatki ne izkazujejo, da je zdravilo Loraxin podobno zdravilu, ki je bilo uporabljeno v ključnih kliničnih študijah, opisanih v predloženi bibliografiji.
Although the other report contained some information on doseresponse this only referred to urticaria.
Drugo poročilo je sicer vsebovalo nekaj informacij o povezavi med odmerkom in odzivom, vendar so se nanašali samo na urtikarijo.
The results show that the 90% confidence interval of the AUCt (0.727-0.967) and Cmax (0.727-0.945) of the test product (Loraxin) to the product Clarityn did not conform to the acceptance interval of 0.81.25.
Rezultati kažejo, da 90-odstotni interval zaupanja za primerjavo AUCt (0,727-0,967) in Cmax (0,7270,945) testnega zdravila (Loraxin) z zdravilom Clarityn ne ustreza razponu sprejemljivosti 0,8-1,25.
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.
Poleg tega je navedeno, da se glede na Smernico o opredelitvi morebitnega resnega tveganja za javno zdravje lahko šteje, da pri določenem zdravilu obstaja morebitno resno tveganje za javno zdravje, če predloženi podatki za potrditev terapevtske učinkovitosti niso dovolj trdna podlaga za trditve o učinkovitosti in/ali podatki o klinični varnosti ne podpirajo dovolj ugotovitve, da so bila vsa morebitna vprašanja o varnosti obravnavana ustrezno in zadovoljivo.
Loraxin 10 mg is a conventional compressed immediate release tablet with loratadine as the active substance.
Loraxin 10 mg je klasična stisnjena tableta s takojšnjim sproščanjem, ki vsebuje zdravilno učinkovino loratadin.
In these studies pharmacokinetic parameters have been studied after single dose as well as after 10 days (40 mg/day) administration of loratadine.
V predloženih študijah so preučevali farmakokinetične parametre po enkratnem odmerku kot tudi po 10-dnevnem prejemanju loratadina (40 mg/dan).
The application for Loraxin 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 Loraxin torej temelji na javno dostopnih bibliografskih podatkih, saj je mogoče rezultate predkliničnih in kliničnih preskušanj nadomestiti z natančnimi sklicevanji na objavljeno znanstveno literaturo (javno dostopne informacije), če je mogoče dokazati, da so zdravilne učinkovine v zdravilu že vsaj deset let dobro uveljavljene v medicinski uporabi v Skupnosti, z znano učinkovitostjo ter sprejemljivo ravnjo varnosti.
With regard to the additional clinical data to support the efficacy and safety of Loraxin, the MAH has submitted two expert reports.
Kar zadeva dodatne klinične podatke, s katerimi bi podprli učinkovitost in varnost Loraxina, je imetnik dovoljenja za promet z zdravilom predložil dve strokovni poročili.
Re-examination of these data and also taking into account the two expert reports submitted by the MAH, confirmed that the results of the pharmacokinetic study are not reliable for loratadine.
Ob ponovnem pregledu teh podatkov in tudi upoštevanju dveh strokovnih poročil, ki ju je predložil imetnik dovoljenja za promet z zdravilom, je bilo potrjeno, da rezultati farmakokinetične študije niso zanesljivi za loratadin.
The use of loratidine is wide in clinical practice and a number of published papers have been submitted in support of efficacy and safety.
Loratadin se splošno uporablja v klinični praksi in predloženih je bilo več objavljenih strokovnih člankov o njegovi učinkovitosti in varnosti.
• The Committee considered the notification of the referral triggered by Finland under Article 29(4)
• Odbor je preučil obvestilo o napotitvenem postopku, ki ga je sprožila Finska, v skladu s členom 29(4) Direktive 2001/83/ES.
The MAH 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.
Imetnik dovoljenja za promet z zdravilom je izrazil nestrinjanje z nekaterimi postopkovnimi vidiki postopka z medsebojnim priznavanjem, postopkom CMDh in napotitvenim postopkom v skladu s členom 29(4) Direktive 2001/83/ES.
Part II.1.d) of Annex I of Directive 2001/83/EC is 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.
V delu II(1)(d) Priloge I k Direktivi 2001/83/ES je navedeno, da je treba „v pregledih neklinične in/ali klinične dokumentacije obrazložiti pomembnost vseh predloženih podatkov o zdravilu, ki se razlikuje od zdravila, namenjenega za trženje.
The experts reports submitted during the referral procedure suggest that that there could be a slightly lower exposure to loratadine, based on the results of the supportive pharmacokinetic study provided by the MAH.
Strokovna poročila, ki so bila predložena med napotitvenim postopkom, kažejo, da bi bila izpostavljenost loratadinu lahko nekoliko nižja, in sicer na podlagi rezultatov podporne farmakokinetične študije, ki jo je zagotovil imetnik dovoljenja za promet z zdravilom.
the CHMP has recommended the refusal of the granting of the marketing authorisation for Loraxin and associated names (see Annex I).
CHMP je priporočil, da se izdaja dovoljenja za promet z zdravilom Loraxin in povezanimi imeni zavrne (glej Prilogo I).
During the re-examination procedure, the MAH did not demonstrate adequately that the published literature of loratadine is directly applicable to Loraxin.
Imetnik dovoljenja za promet z zdravilom med postopkom ponovnega pregleda ni zadovoljivo dokazal, da se objavljena literatura o loratadinu lahko neposredno uporablja za Loraxin.
Loratadine is not a BCS class I (high solubility-high permeability) or III ((high solubility-low permeability) substance, which might otherwise have supported an extrapolation based on the pharmaceutical data.
Loratadin ni snov, ki bi se po klasifikaciji BCS uvrščala v razred I (dobra topnostdobra permeabilnost) ali III (dobra topnost-slaba permeabilnost), s čimer bi bilo sicer mogoče utemeljiti ekstrapolacijo na podlagi farmacevtskih podatkov.
Instead, as it is a BCS class II (low solubility-high permeability) or IV (low solubility-low permeability) substance additional data would be needed to support the relevance of the bibliographic data to demonstrate efficacy and safety of Loraxin.
Ker se snov po klasifikaciji BCS uvršča v razred II (slaba topnost-dobra permeabilnost) ali IV (slaba topnost-slaba permeabilnost), so potrebni dodatni podatki, s katerimi bi bilo mogoče podpreti pomembnost bibliografskih podatkov za dokazovanje učinkovitosti in varnosti Loraxina.
As it could not be established whether a potentially lower or higher exposure to loratidine compared to the exposure obtained following administration of the product used in the pivotal clinical studies described in the submitted literature would constitute any efficacy or safety concerns, the CHMP therefore maintained its concern that this is a potential serious risk to public health.
Ker ni bilo mogoče ugotoviti, ali bi lahko morebitna nižja ali višja izpostavljenost loratadinu v primerjavi z izpostavljenostjo, ki je bila dosežena po aplikaciji zdravila, uporabljenega v temeljnih kliničnih študijah, opisanih v predloženi literaturi, vzbudila pomisleke glede učinkovitosti ali varnosti, je CHMP vztrajal pri svojem pomisleku, da to lahko pomeni resno tveganje za javno zdravje.
The MAH expressed its disagreement with the CHMP opinion, focusing its scientific grounds on the following points, for which the MAH argues that clear justifications or evidence have not been presented to explain:
Imetnik dovoljenja za promet z zdravilom se ni strinjal z mnenjem CHMP v okviru znanstvenih utemeljitev glede naslednjih dejstev, za katera navaja, da niso bili predstavljeni jasni razlogi ali dokazi:
The mutual recognition marketing authorisation application presented for the medicinal product Loraxin 10 mg tablets is a well-established use (WEU) application according to Article 10a of Directive 2001/83/EC.
Vloga za pridobitev dovoljenja za promet s tabletami Loraxin 10 mg na podlagi medsebojnega priznavanja temelji na dejstvu, da je raba zdravila že dobro uveljavljena v skladu s členom 10(a) Direktive 2001/83/ES.
In several plasma samples the concentration of loratadine was below the lowest level of quantification (LLOQ).
V več vzorcih plazme koncentracija loratadina ni dosegla spodnje meje določanja.
• Pharmacokinetic data
• Farmakokinetični 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 in relation to the product under application.
Kot je bilo že navedeno, je v Prilogi I k Direktivi 2001/83/ES navedeno, da je treba s pregledi neklinične in/ali klinične dokumentacije pojasniti pomembnost vseh podatkov o zdravilu, za katero je bila podana vloga.
The marketing authorisation for Loraxin and associated names will have to be suspended in the reference Member State, where the product is currently authorised, until such time as adequate data is presented, which will allow a judgment to be made that in spite of the existing formulation differences, Loraxin and the products included in the literature references are considered similar, such that the data generated with these products may be considered relevant to Loraxin, and therefore address the potential serious risk to public health identified by Sweden and Poland.
Dovoljenje za promet z zdravilom Loraxin in povezanimi imeni bo treba začasno umakniti v referenčnih državah članicah, v katerih je promet z zdravilom trenutno dovoljen, dokler ne bodo predloženi ustrezni podatki, ki bodo omogočali presojo, da se zdravilo Loraxin in zdravila, na katera se sklicuje literatura, kljub obstoječim razlikam v farmacevtski obliki štejejo za podobna, tako da je mogoče podatke, ki so bili pridobljeni s temi zdravili, šteti za pomembne za Loraxin, in s tem obravnavati morebitno resno tveganje za javno zdravje, ki je bilo ugotovljeno na Švedskem in Poljskem.
Overall, the CHMP was still of the view that due to its limitations, the study could not confirm the relevance of the bibliographic data submitted to demonstrate safety and efficacy of Loraxin.
CHMP je na splošno še vedno menil, da s študijo zaradi njenih omejitev ni bilo mogoče potrditi primernosti bibliografskih podatkov, ki so bili predloženi za dokazovanje varnosti in učinkovitosti Loraxina.
The report of a pharmacokinetic study (Report V-808) submitted by the MAH in support of the marketing authorisation application was considered by the CHMP, since the inclusion of pharmacokinetic data in support of a well-established use application could be considered, if it is intended to show the relevance of the literature used to demonstrate safety and efficacy as regards the product concerned.
CHMP je preučil poročilo farmakokinetične študije (poročilo V-808), ki ga je imetnik dovoljenja za promet z zdravilom kot dokazilo priložil vlogi za pridobitev dovoljenja za promet z zdravilom, saj je mogoče upoštevati vključitev farmakokinetičnih podatkov, ki so kot dokazilo priloženi vlogi na podlagi dobro uveljavljene rabe, če se z njimi dokazuje pomembnost uporabljene literature za dokazovanje varnosti in učinkovitosti zadevnega zdravila.
Therefore the CHMP was of the view that the submitted pharmacokinetic study report V-808 did not confirm the relevance of the bibliographic data submitted to demonstrate safety and efficacy of Loraxin.
CHMP je tako menil, da predloženo poročilo farmakokinetične študije V-808 ni potrdilo primernosti predloženih bibliografskih podatkov za dokazovanje varnosti in učinkovitosti Loraxina.
Based on the pharmacokinetic study results used to bridge Loraxin to the published literature, there is a potential for difference in exposure after Loraxin administration as compared to the product Clarityn, and the MAH has not adequately justified why this potential difference in exposure is unlikely to have a clinically significant difference in efficacy or safety.
Iz rezultatov farmakokinetične študije, ki je bila uporabljena za povezavo zdravila Loraxin z objavljeno literaturo, je razvidno, da lahko nastanejo razlike v izpostavljenosti po aplikaciji zdravila Loraxin v primerjavi z zdravilom Clarityn, imetnik dovoljenja za promet z zdravilom pa ni zadovoljivo utemeljil, zakaj ta morebitna razlika v izpostavljenosti ne bo povzročila klinično pomembne razlike v učinkovitosti ali varnosti.
Based on the published literature and the pharmacokinetic study results used to bridge Loraxin to the published literature, the relevance of the literature data submitted which concern a product different from the product intended for marketing was not addressed satisfactorily.
Na podlagi objavljene literature in rezultatov farmakokinetične študije, ki so bili uporabljeni za povezavo zdravila Loraxin z objavljeno literaturo, pomembnost predloženih podatkov iz literature, ki se nanašajo na drugačno zdravilo od tega, ki je namenjeno za promet, ni bila zadovoljivo obravnavana.
Therefore the CHMP considered the provided clinical data to be very limited and not strong enough to address what a potential difference in exposure, compared to the exposure obtained following administration of the product used in the pivotal clinical studies described in the submitted bibliography, could mean for efficacy and safety for each indication.
CHMP je zaradi tega menil, da so predloženi klinični podatki zelo omejeni in ne kažejo dovolj zanesljivo, kako lahko morebitna razlika med izpostavljenostjo, v primerjavi z izpostavljenostjo po aplikaciji zdravila iz ključnih kliničnih študij, ki so opisane v predloženi bibliografiji, vpliva na učinkovitost in varnost pri vsaki indikaciji.
As discussed previously a pharmacokinetic study was provided to bridge Loraxin to the published literature and the AUCt and Cmax of Loraxin to the product Clarityn did not conform to the acceptance interval of 0.8-1.25 for the parent compound, loratadine.
Kot je bilo že navedeno, predložena farmakokinetična študija, ki naj bi povezala Loraxin z objavljeno literaturo, ter AUCt in Cmax, ki naj bi Loraxin povezala z zdravilom Clarityn, niso ustrezali razponu sprejemljivosti 0,81,25 za izhodno sestavino loratadin.
In view of the above, the CHMP considered that the pharmaceutical, pharmacokinetic and clinical data/documentation referred to by the MAH was not considered sufficient to establish the relevance of the bibliographic data to Loraxin.
CHMP je glede na navedeno menil, da farmacevtski, farmakokinetični in klinični podatki/dokumentacija, ki jih je navedel imetnik dovoljenja za promet z zdravilom, ne zadoščajo za dokazovanje pomembnosti bibliografskih podatkov za Loraxin.
On the basis of the bibliographic data submitted, taken together with the pharmaceutical, pharmacokinetic and clinical documentation, the MAH failed to establish the relevance of these data to demonstrate safety and efficacy of Loraxin.
Na podlagi predloženih bibliografskih podatkov, ob upoštevanju farmacevtske, farmakokinetične in klinične dokumentacije, imetnik dovoljenja za promet z zdravilom ni mogel dokazati pomembnosti teh podatkov za dokazovanje varnosti in učinkovitosti zdravila Loraxin.
why the applied loratadine 10 mg product would cause a potential serious risk to public health how the applied loratadine 10 mg product would cause a potential serious risk to public health
zakaj bi aplikacija zdravila, ki vsebuje 10 mg loratadina, lahko resno ogrozila javno zdravje;
Furthermore, there were extensive inter-subject variabilities in the absorption parameters of loratadine.
Poleg tega so se pri parametrih absorpcije loratadina pokazala velika nihanja med posameznimi poskusnimi osebami.
The Marketing Authorisation Holder is requested to present adequate data, which will allow a judgment to be made that in spite of the existing formulation differences, Loraxin and the products included in the literature references are considered similar, such that the data generated with these products may be considered relevant to Loraxin.
Imetnik dovoljenja za promet z zdravilom mora predložiti ustrezne podatke, ki bodo omogočali presojo, da se Loraxin in zdravila, na katera se sklicuje literatura, kljub obstoječim razlikam v farmacevtski obliki štejejo za podobna, tako da je mogoče podatke, ki so bili pridobljeni s temi zdravili, šteti za pomembne za Loraxin.
It is also noted that the case for the safety concerns due to potentially higher exposures has not been adequately addressed by the MAH.
Navedeno je bilo tudi, da imetnik dovoljenja za promet z zdravilom ni ustrezno obravnaval varnostnih pomislekov zaradi morebitne višje izpostavljenosti.
• The data referred to by the MAH is not considered sufficient to address what a potential difference in exposure, compared to the exposure obtained following administration of the product used in the pivotal clinical studies described in the submitted bibliography, could mean for efficacy and safety for each indication.
• Podatki, na katere se je skliceval imetnik dovoljenja za promet z zdravilom, ne kažejo dovolj zanesljivo, kako lahko morebitna razlika med izpostavljenostjo, v primerjavi z izpostavljenostjo po aplikaciji zdravila iz ključnih kliničnih študij, ki so opisane v predloženi bibliografiji, vpliva na učinkovitost in varnost pri vsaki indikaciji.
The MAH's argument that the literature on the originator product is relevant for their product on the basis of the submitted pharmaceutical data is not considered scientifically valid by CHMP.
Imetnik dovoljenja za promet z zdravilom se sklicuje na literaturo o originalnem zdravilu in svoje navedbe podpre s predloženimi farmacevtskimi podatki, vendar ta argument po mnenju CHMP ni znanstveno veljaven.
• Pharmaceutical data
• Farmacevtski podatki
Therefore, a scientifically valid approach such as the demonstration of comparable kinetics may be necessary to bridge Loraxin to a similar product.
Zaradi tega je za povezavo zdravila Loraxin s podobnim zdravilom morda mogoče treba uporabiti znanstveno veljaven pristop, na primer dokaz o primerljivi kinetiki.
In order to show the relevance of the bibliographic data used in support of the application for Loraxin, the MAH referred to pharmaceutical, pharmacokinetic and clinical data.
Imetnik dovoljenja za promet z zdravilom je dokazoval pomembnost bibliografskih podatkov, ki jih je navedel v vlogi za Loraxin, s sklicevanjem na farmacevtske, farmakokinetične in klinične podatke.
Denmark
Danski
The median age was 64 years.
Mediana starost je bila 64 let.
● if you are pregnant.
● če ste noseči.
It is therefore not authorised to be used in this way.
Zato tudi ni odobreno za tovrstno uporabo.
Treatment comparison Other factor
Primerjava zdravljenj Drug dejavnik
25-75 percentile (months)
25-75 percentilov (meseci)
The incidence varied between 10% (4/40) and 20% (3/15).
Pojavnost se je gibala med 10 % (4/40) in 20 % (3/15).
Both co-primary objectives were met:
Dosegli so oba sočasna primarna cilja:
Please consult your doctor, even if these above statements were only applicable to you in the past.
Posvetujte se z zdravnikom, tudi če je zgoraj navedeno za vas veljalo samo v preteklosti.
These results have been confirmed through an independent radiological review.
Te rezultate je potrdil tudi neodvisen radiološki pregled.
If indicated, therapy should either be permanently discontinued or temporarily suspended as described in section 4.4.
Če je indicirano, je treba zdravljenje trajno ali začasno prekiniti, kot je opisano v poglavju 4.4.
Patients older than 65 years have an increased risk of experiencing the following side effects:
Pri bolnikih, starejših od 65 let, obstaja povečano tveganje za naslednje neželene učinke:
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 14 February 2019
Datum prve odobritve: 14. februar 2019
Discuss with your doctor to make sure that you do not combine these medicine.
Posvetujte se z zdravnikom in se tako prepričajte, da ne boste prejemali kombinacije teh zdravil.
It has not been developed or made for injection into the eye.
Niso ga razvili in izdelali za injiciranje v oko.
There were no objective (partial or complete) radiological responses (MacDonald criteria).
Objektivnih (delnih ali popolnih) radioloških odzivov (merila po MacDonaldu) ni bilo.
System organ class (SOC)
Organski sistem (SOC - system organ class)
Please consult your doctor for more information.
Za več informacij se posvetujte z zdravnikom.
These results were consistent with those from various sensitivity analyses and in clinically relevant subgroups.
Ti rezultati so bili skladni z rezultati iz različnih občutljivostnih analiz in rezultati v klinično ustreznih podskupinah.
In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Za izboljšanje sledljivosti bioloških zdravil je treba lastniško ime in številko serije uporabljenega zdravila jasno zabeležiti (oziroma navesti) v bolnikovo kartoteko.
In Part II, treatment assignment was double-blind with respect to bevacizumab.
V 2. delu je bila dodelitev zdravljenja dvojno slepa glede bevacizumaba.
Women of childbearing potential have to use effective contraception during (and up to 6 months after) treatment.
Ženske v rodni dobi morajo med zdravljenjem (in do 6 mesecev po njem) uporabljati učinkovito kontracepcijo.
Adjuvant taxane therapy was allowed only if it was completed at least 12 months prior to trial entry.
Adjuvantno zdravljenje s taksani so dovolili le, če so ga bolniki zaključili najmanj 12 mesecev pred vstopom v preskušanje.
Objective response rate was low in both treatment arms and the difference was not significant.
Objektivni odziv na zdravljenje je bil nizek pri obeh zdravljenih skupinah in razlika ni bila pomembna.
• abnormal urine test (protein in the urine),
• nenormalne izvide urinskih preiskav (beljakovine v urinu),
● you may develop a severe migraine.
● lahko dobite hudo migreno.
Please consult your doctor if you or your family tend to suffer from bleeding problems or you are taking medicines to thin the blood for any reason.
Posvetujte se z zdravnikom, če ste vi ali vaša družina nagnjeni k težavam zaradi krvavitev ali če jemljete zdravila za redčenje krvi iz kakršnihkoli razlogov.
(See section 4.2 for information on paediatric use).
(Za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
For further information as to human epidermal growth factor receptor 2 (HER2) status, please refer to section 5.1.
Za dodatne informacije glede statusa receptorja humanega epidermalnega rastnega faktorja 2 (HER2) glejte poglavje 5.1.
Please discuss with your doctor if you noticed this previously.
Pogovorite se z zdravnikom, če ste to že kdaj opazili.