FrancophonIA/ELRC3.0 huggingface dataset:
English: The PRAC further noted that in view of the low safety margin calculated at doses below the therapeutic effect dose, reducing the dose would not permit to reduce the risk to an acceptable level.
Croatian: PRAC je nadalje napomenuo da, s obzirom na nisku sigurnosnu granicu izračunatu pri dozama koje su niže od terapijski učinkovite doze, smanjenje doze ne bi omogućilo smanjenje rizika na prihvatljivu razinu.
English: These very low margins may have also been overestimated (i.e. plasma concentrations corresponding to the maximum daily doses were not determined, not clear whether the analysis was performed at steady state plasma concentrations or not).
Croatian: Moguće je da su te vrlo niske granice također bile precijenjene (tj. nisu utvrđene koncentracije u plazmi koje odgovaraju maksimalnim dnevnim dozama, nije jasno je li analiza provedena pri plazmatskim koncentracijama u stanju dinamičke ravnoteže ili ne).
English: However, some risk factors of TdP like congenital long QT syndrome are usually silent and unpredictable.
Croatian: Međutim, neki čimbenici rizika TdP-a poput kongenitalnog sindroma dugog QT intervala obično su neprimjetni i nepredvidivi.
English: It is noted that lack of ECG diagnosis is common in these cases, which generates significant uncertainty on the actual incidence of TdP.
Croatian: Primijećeno je da je u tim slučajevima uobičajen izostanak EKG dijagnoze, što stvara značajnu nesigurnost u pogledu stvarne incidencije TdP-a.
English: • The PRAC considered the procedure under Article 107i of Directive 2001/83/EC, for fenspiridecontaining medicinal products (see Annex I).
Croatian: • PRAC je razmotrio postupak proveden u skladu s člankom 107.i Direktive 2001/83/EZ za lijekove koji sadrže fenspirid (vidjeti Prilog I.).
English: On 8 February 2019 the French Competent Authority (ANSM) therefore triggered an urgent Union procedure under Article 107i of Directive 2001/83/EC resulting from pharmacovigilance data, and requested the PRAC to assess the impact of the above concerns on the benefit-risk balance of fenspiride containing medicinal products and to issue a recommendation on whether the relevant marketing authorisations should be maintained, varied, suspended or revoked.
Croatian: Dana 8. veljače 2019. francusko nadležno tijelo (ANSM) pokrenulo je hitan postupak na razini Europske unije u skladu s člankom 107.i Direktive 2001/83/EZ koji je proizašao iz podataka o farmakovigilanciji, te je od PRAC-a zatražilo procjenu učinka navedenih problema na omjer koristi i rizika za lijekove koji sadrže fenspirid i izdavanje preporuke o tome treba li odgovarajuća odobrenja za stavljanje u promet zadržati, izmijeniti, privremeno obustaviti ili oduzeti.
English: Considering the seriousness of TdP which can lead to fatal outcome, a thorough risk analysis would be essential for each individual patient prior to treatment initiation with fenspiride.
Croatian: S obzirom na ozbiljnost TdP-a, koji može dovesti do smrtnog ishoda, neophodna je temeljita analiza rizika za svakog pojedinog bolesnika prije početka liječenja fenspiridom.
English: This included the results of the above-mentioned requested non-clinical study (Aptuit), two other non-clinical studies and post-marketing case-reports as well as published efficacy studies.
Croatian: To je uključivalo rezultate prethodno navedenog nekliničkog ispitivanja (Aptuit), dvaju drugih nekliničkih ispitivanja i izvješća o slučajevima nakon stavljanja lijeka u promet, kao i objavljena ispitivanja djelotvornosti.
English: There is a possibility that the IC50 value is overestimated (i.e. experiments performed at room temperature, external K+ concentration in the milieu unknown, no DMSO cells perfusion before adding fenspiride in DMSO yet substracting DMSO effect) and fenspiride could be a more potent blocker of hERG channels than shown in vitro.
Croatian: Postoji mogućnost da je vrijednost IC50 precijenjena (tj. eksperimenti su provedeni na sobnoj temperaturi, vanjska koncentracija K+ u okruženju nije poznata, izostanak perfuzije DMSO-a u stanice prije dodavanja fenspirida u DMSO dok se učinak DMSO-a oduzima) te bi fenspirid mogao biti snažniji blokator hERG kanala nego što je utvrđeno in vitro.
English: The calculated safety margins between the hERG IC50 obtained and the effective therapeutic plasma concentration for fenspiride, was below the lowest acceptable safety margin proposed in the literature (between 6 and 26, depending on the pharmaceutical form/dose administered and on the administration schedule).
Croatian: Izračunate granice sigurnosti između dobivene vrijednosti hERG IC50 i učinkovite terapijske koncentracije fenspirida u plazmi bile su ispod najniže prihvatljive sigurnosne granice predložene u literaturi (između 6 i 26, ovisno o farmaceutskom obliku / primijenjenoj dozi i rasporedu primjene).
English: The PRAC considered all data submitted by the MAHs, received from stakeholders and provided by EMA.
Croatian: PRAC je razmotrio sve podatke koje su podnijeli nositelji odobrenja za stavljanje u promet, koje je primio od interesnih skupina i koje je dostavila EMA.
English: The French Competent Authority (ANSM) considered that these results taken together with pharmacovigilance data support the risk of prolongation of the QTc interval in these patients.
Croatian: Francusko nadležno tijelo (ANSM) smatralo je da ti rezultati uzeti zajedno s podatcima o farmakovigilanciji potvrđuju postojanje rizika od produljenja QTc intervala u tih bolesnika.
English: The PRAC considered that in view of the available data the generation of additional evidence via an ICH E14 thorough QT/QTc clinical study would not be justified and would not allow identifying defined patient population in whom the benefits could outweigh the risks.
Croatian: PRAC je zaključio da, s obzirom na dostupne podatke, dobivanje dodatnih dokaza putem temeljitog kliničkog ispitivanja QT/QTc u skladu sa smjernicama ICH E14 ne bi bilo opravdano i ne bi omogućilo utvrđivanje populacije bolesnika u kojoj bi koristi mogle nadmašiti rizike.
English: In addition, no effect of fenspiride was observed on the PR or QRS complex of the ECG, suggesting that fenspiride has no significant effect on other cardiac channels and no compensatory action of hERG blockade in vivo.
Croatian: Osim toga, nije uočen učinak fenspirida na PR ili QRS kompleks na EKG-u, što upućuje na to da fenspirid nema značajan učinak na druge kanale u srcu te da nema kompenzacijskog djelovanja hERG blokade in vivo.
English: Fenspiride has been shown in the Aptuit study to block hERG channels at supratherapeutic doses in vitro in a heterologous expression system, with an IC50 value of 15.14 µM.
Croatian: U ispitivanju Aptuit dokazano je da fenspirid blokira hERG kanale u dozama koje premašuju terapijske doze in vitro u sustavu heterologne ekspresije, uz IC50 vrijednost od 15,14 µM.
English: Fenspiride-containing medicinal products are authorised nationally for the treatment of symptoms (e.g. cough and expectoration) related to bronchopulmonary diseases.
Croatian: Lijekovi koji sadrže fenspirid odobreni su na nacionalnoj razini za liječenje simptoma (npr. kašalj i iskašljavanje) koji su povezani s bronhopulmonalnim bolestima.
English: In addition, no protective effects regarding the triggering of TdP arrhythmias (blockade of Nav1.5 and cardiac L-type Ca2+ channels) was shown for fenspiride.
Croatian: Osim toga, nisu dokazani zaštitni učinci fenspirida povezani s izazivanjem TdP aritmija (blokada Nav1.5 i Ca2+ kanala tipa L u srcu).
English: QT/QTc interval prolongation was not accompanied by any events of arrhythmia or contracture on the guinea pig heart model at any assay concentration.
Croatian: Produljenje QT/QTc intervala nije bilo popraćeno događajima aritmije ili kontrakture na modelu srca zamorca ni u jednoj testiranoj koncentraciji.
English: Calculated safety margins between the hERG inhibition concentration and the effective therapeutic plasma concentration were below the lowest acceptable margin proposed in the literature for administration in humans.
Croatian: Izračunate granice sigurnosti između koncentracije koja dovodi do inhibicije hERG i učinkovite terapijske koncentracije u plazmi bile su ispod najniže prihvatljive granice koja je u literaturi predložena za primjenu u ljudi.
English: In in silico models, fenspiride induced QT prolongation and “early afterdepolarizations” (EADs; arrhythmic makers) in specific cardiovascular disease state models.
Croatian: Na temelju in silico modeliranja, fenspirid uzrokuje produljenje QT-a i „ranu naknadnu depolarizaciju” (EAD-ovi, uzročnici aritmije) u specifičnim modelima stanja za kardiovaskularne bolesti.
English: • Taking into account that these medicinal products are only used to treat benign symptoms, the PRAC considered that no feasible and proportionate measures would effectively allow identifying patients with risk factors for QT prolongation and TdP, and that therefore any related risk minimisation measures could not be implemented in clinical practice.
Croatian: • Uzimajući u obzir činjenicu da se ti lijekovi primjenjuju samo za liječenje benignih simptoma, PRAC je zaključio da nijedna izvediva i proporcionalna mjera ne bi učinkovito omogućila identificiranje bolesnika u kojih su prisutni čimbenici rizika od produljenja QT intervala i TdP-a te se stoga u kliničkoj praksi ne može provesti nijedna povezana mjera minimizacije rizika.
English: Additionally, unspecific terms of syncope, loss of consciousness, tachycardia and palpitations that may (among others) be signs and symptoms of TdP were present in a significant number of cases.
Croatian: Osim toga, u značajnom broju slučajeva zabilježeni su neodređena razdoblja sinkope, gubitka svijesti, tahikardije i palpitacije, koji mogu (među ostalim) biti znakovi i simptomi TdP-a.
English: This included the results of non-clinical studies and post-marketing case reports as well as published efficacy studies submitted by the MAHs, by stakeholders and provided by EMA.
Croatian: To je uključivalo rezultate nekliničkih ispitivanja i izvješća o slučajevima nakon stavljanja lijeka u promet, kao i objavljena ispitivanja djelotvornosti koje su podnijeli nositelji odobrenja, interesne skupine i koje je dostavila EMA.
English: In addition, performing ECG or measurements of potassium or magnesium levels is neither considered proportionate in pre-treatment screening for a medicinal product solely used to treat benign symptoms of generally self-limiting conditions, nor feasible in clinical practice.
Croatian: Osim toga, obavljanje EKG-a ili mjerenje razine kalija ili magnezija ne smatra se razmjernim kod probira prije liječenja za lijek koji se primjenjuje isključivo za liječenje benignih simptoma općenito samoograničavajućih stanja, ni izvedivim u kliničkoj praksi.
English: • The PRAC reviewed the totality of the data available for fenspiride-containing medicinal products in relation to the risk of QT prolongation.
Croatian: • PRAC je pregledao sve dostupne podatke za lijekove koji sadrže fenspirid koji se odnose na rizik od produljenja QT intervala.
English: It has also been shown in a recent ex vivo study on isolated guinea pig hearts that the hERG blockade exerted by fenspiride may translate into QT prolongation in a similar concentration range as observed in the hERG study.
Croatian: U nedavno provedenom ex vivo ispitivanju na izoliranim srcima zamoraca također je dokazano da hERG blokada izazvana fenspiridom može rezultirati produljenjem QT-a u sličnom koncentracijskom rasponu koji je zabilježen u hERG ispitivanju.
English: • The PRAC considered that the use of fenspiride is associated with a risk of QT prolongation, and therefore it has proarrhythmic potential and present a risk of Torsade de Pointes (TdP).
Croatian: • PRAC je smatrao da je primjena fenspirida povezana s rizikom od produljenja QT intervala, te stoga ima proaritmijski potencijal i predstavlja rizik za pojavu torsades de pointes (TdP).
English: QT prolongation and TdP are unpredictable and potentially life-threatening conditions that constitute a major safety concern, particularly given the benign symptoms for which fenspiride-containing medicinal products are used to treat.
Croatian: Produljenje QT intervala i TdP nepredvidiva su i potencijalno po život opasna stanja koja predstavljaju ozbiljan razlog za zabrinutost, osobito s obzirom na to da se lijekovi koji sadrže fenspirid primjenjuju za liječenje benignih simptoma.
English: Taking into account that fenspiride is indicated to treat benign symptoms and the seriousness of the risk of unpredictable QT prolongation leading to proarrhythmic potential in human, the ANSM concluded that the benefit-risk balance of fenspiride-containing medicinal products was no longer favourable in the treatment of symptoms related to bronchopulmonary diseases, and suspended the marketing authorisations of these products.
Croatian: Uzimajući u obzir činjenicu da je fenspirid indiciran za liječenje benignih simptoma i ozbiljnost rizika od nepredvidivog produljenja QT-a koje u ljudi dovodi do proaritmijskog potencijala, ANSM je zaključio da omjer koristi i rizika lijekova koji sadrže fenspirid nije više povoljan za liječenje simptoma povezanih s bronhopulmonalnim bolestima, te je privremeno obustavio odobrenja za stavljanje u promet tih lijekova.
English: • Further, the PRAC could not identify condition(s) to the marketing authorisation which if fulfilled would demonstrate a positive benefit-risk balance for these products in a defined patient population.
Croatian: • Nadalje, PRAC nije mogao utvrditi uvjete odobrenja za stavljanje lijeka u promet koji bi, kada bi bili ispunjeni, pokazali pozitivan omjer koristi i rizika za te lijekove u utvrđenoj populaciji bolesnika.
English: Newly available results of two non-clinical studies showed that fenspiride can induce an inhibition of hERG tail current in vitro, and increase the corrected QT (QTc) intervals in isolated and perfused guinea pig heart.
Croatian: Rezultati dvaju nekliničkih ispitivanja koji su nedavno postali dostupni pokazali su da fenspirid in vitro može izazvati inhibiciju terminalnog toka hERG kanala i povećati korigirane QT (QTc) intervale u izoliranom i perfundiranom srcu zamorca.
English: Therefore, the PRAC concluded that the risk of QT prolongation, the proarrhythmic potential and associated risk of TdP outweighs the benefits of fenspiride in its authorised indication(s).
Croatian: Stoga je PRAC zaključio da rizik od produljenja QT intervala, proaritmijskog potencijala i povezanog rizika od TdP-a nadmašuje koristi fenspirida u odobrenim indikacijama.
English: Regarding clinical data, analysis of post-marketing cases reported since the marketing authorisation showed evidence to support a causal association between occurrence of QT prolongation/TdP in patients, mostly with risk factors for these events, and the treatment with fenspiride-containing medicinal products.
Croatian: U pogledu kliničkih podataka, rezultati analize slučajeva prijavljenih nakon izdavanja odobrenja za stavljanje lijeka u promet podupiru uzročnu povezanost između produljenja QT intervala / TdP-a u bolesnika, uglavnom s čimbenicima rizika za te događaje, i liječenja lijekovima koji sadrže fenspirid.
English: Consequently, the PRAC recommended the revocation of the marketing authorisations for fenspiride-containing medicinal products.
Croatian: Zbog toga je PRAC preporučio ukidanje odobrenja za stavljanje u promet lijekova koji sadrže fenspirid.
English: Further, the PRAC could not identify condition(s) which if fulfilled would demonstrate a positive benefitrisk balance for these products in a defined patient population.
Croatian: Nadalje, PRAC nije mogao utvrditi uvjete koji bi, kada bi bili ispunjeni, pokazali pozitivan omjer koristi i rizika za te lijekove u utvrđenoj populaciji bolesnika.
English: The observed prolongation may be underestimated in this study due to the necessary QT correction formula of the observed dose-dependent QTc augmentations, in view of the method used.
Croatian: S obzirom na primijenjenu metodu, moguće je da je produljenje zabilježeno u tom ispitivanju umanjeno zbog formule za neophodnu korekciju QT intervala za promatrano QTc povećanje ovisno o dozi.
English: Therefore, pursuant to Article 116 of Directive 2001/83/EC, the CMDh recommends the revocation of the marketing authorisations for fenspiride-containing medicinal products.
Croatian: Direktive 2001/83/EZ, CMDh preporučuje ukidanje odobrenja za stavljanje u promet lijekova koji sadrže fenspirid.
English: Therefore, pursuant to Article 116 of Directive 2001/83/EC, the Committee recommends the revocation of the marketing authorisations for fenspiride-containing medicinal products.
Croatian: Direktive 2001/83/EZ, Odbor preporučuje ukidanje odobrenja za stavljanje u promet lijekova koji sadrže fenspirid.
English: The PRAC noted that this conclusion was also reached by the MAH of the originator.
Croatian: PRAC je zamijetio da je i nositelj odobrenja za izvorni lijek došao do istog zaključka.
English: The CMDh considered the arguments presented in writing by one MAH (Aflofarm Farmacja Polska Sp. Z O.O.)
Croatian: CMDh je razmotrio obrazloženja koja je jedan nositelj odobrenja za stavljanje lijeka u promet (Aflofarm Farmacja Polska Sp. Z O.O.) podnio u pisanom obliku te je zaključio da je PRAC već razmotrio sve relevantne elemente.
English: The CMDh, as a consequence, considers that the benefit-risk balance of fenspiride-containing medicinal products is not favourable.
Croatian: Slijedom toga, CMDh smatra da omjer koristi i rizika lijekova koji sadrže fenspirid nije povoljan.
English: The Committee, as a consequence, considers that the benefit-risk balance of fenspiride-containing medicinal products is no longer favourable.
Croatian: Slijedom toga, Odbor smatra da omjer koristi i rizika lijekova koji sadrže fenspirid više nije povoljan.
English: In summary based on non-clinical assays of the accepted surrogate markers of TdP, i.e. blockade of hERG tail current and prolongation of the QT/QTc interval, and on post-marketing spontaneous reports of confirmed cases of TdP, QT prolongation and ventricular fibrillation/arrhythmia, the risk of QT prolongation, a proarrhythmic potential and associated risk of TdP is considered confirmed with fenspiride use.
Croatian: Ukratko, na temelju nekliničkih ispitivanja prihvaćenih zamjenskih markera TdP-a, tj. blokade terminalnog toka hERG kanala i produljenja QT/QTc intervala, te na temelju spontanih prijava potvrđenih slučajeva
English: The strength and number of pipettes used depends on the weight of the cat being treated.
Croatian: Jačina i broj pipeta koje se upotrebljavaju ovise o težini tretirane mačke.
English: This small volume of liquid is absorbed through the skin and has an effect throughout the animal's body.
Croatian: Ta mala količina tekućine upije se kroz kožu i djeluje po cijelom tijelu životinje.
English: On the day of treatment, treated cats must not be allowed to sleep in the same bed as their owner, especially children.
Croatian: Na dan primjene VMP-a tretirane mačke ne smiju spavati u istom krevetu sa svojim vlasnikom, posebno s djecom.
English: This overview was last updated in February 2019.
Croatian: Ovaj pregled informacija posljednji je put ažuriran u 02. 2019.
English: Treated animals must not be touched until the application area is dry.
Croatian: Tretirane životinje ne smiju se dirati sve dok se mjesto nanošenja VMP-a ne osuši.
English: Further information on Felisecto Plus can be found on the Agency's website: ema.europa.eu/medicines/veterinary/EPAR/felisecto-plus.
Croatian: Više informacija o VMP-u Felisecto Plus nalazi se na internetskim stranicama Agencije: ema.europa.eu/medicines/veterinary/EPAR/felisecto-plus.
English: Sarolaner is effective against ticks and fleas.
Croatian: Sarolaner je učinkovit protiv krpelja i buha.
English: Hands should be washed after use and any product in contact with the skin should be washed off immediately with soap and water.
Croatian: Ruke treba oprati nakon primjene, a svaki proizvod koji je došao u dodir s kožom mora se odmah isprati sapunom i vodom.
English: In order to be exposed to selamectin and sarolaner, fleas and ticks must commence feeding on the cat's blood.
Croatian: Kako bi ih se izložilo selamektinu i sarolaneru, buhe i krpelji moraju se početi hraniti krvlju mačke.
English: In case of skin or eye contact, the affected area should be rinsed immediately with water.
Croatian: U slučaju kontakta s kožom ili očima, zahvaćeno se područje treba odmah isprati vodom.
English: It is recommended to treat cats in the evening.
Croatian: Preporučuje se da se VMP na mačkama primijeni navečer.
English: Felisecto Plus received a marketing authorisation valid throughout the EU on 26 April 2019.
Croatian: Felisecto Plus dobio je odobrenje za stavljanje u promet koje je na snazi u EU-u od 26/04/2019.
English: The medicine must be kept in its packaging until use, in order to prevent access by children.
Croatian: VMP se mora čuvati u originalnom pakiranju do uporabe kako bi se spriječilo da VMP-u pristupe djeca.
English: Because ticks must start feeding on the cat in order to be killed by the medicine, the risk of transmission of diseases that they may carry cannot be excluded.
Croatian: Budući da se krpelji moraju početi hraniti krvlju mačke da bi ih se moglo iskorijeniti VMP-om, ne može se isključiti rizik od prijenosa bolesti koje oni mogu nositi.
English: Felisecto Plus kills fleas and some ticks within 24 hours and it continues to work for 5 weeks against fleas and 4 to 5 weeks against ticks (depending on the type).
Croatian: Felisecto Plus ubija buhe i neke krpelje u roku od 24 sata i nastavlja djelovati protiv buha tijekom 5 tjedana te protiv krpelja od 4 do 5 tjedana (ovisno o vrsti krpelja).
English: It can also be used as part of a treatment for flea allergy dermatitis (an allergic reaction to flea bites)
Croatian: Može se primjenjivati i kao dio liječenja alergijskog dermatitisa uzrokovanog buhama (alergijske reakcije na ugrize buha)
English: Felisecto Plus (selamectin / sarolaner)
Croatian: Felisecto Plus (selamektin / sarolaner)
English: The medicine can be used:
Croatian: Ovaj se VMP može upotrijebiti za:
English: Felisecto Plus is highly flammable and should be kept away from heat, sparks, any open flame or other sources of ignition.
Croatian: Felisecto Plus vrlo je zapaljiv i treba ga držati podalje od izvora topline, iskrenja, bilo kakvog otvorenog plamena ili nekog drugog izvora zapaljenja.
English: This results in uncontrolled activity of the nervous system and the paralysis and death of the parasites.
Croatian: To rezultira nekontroliranim djelovanjem živčanog sustava i paralizom te uginućem parazita.
English: Children must not be allowed to play with treated cats for 4 hours after treatment.
Croatian: Djeca se ne smiju igrati tretiranim mačkama još 4 sata nakon primjene VMP-a.
English: Used pipettes of the medicine must be disposed of immediately.
Croatian: Upotrijebljene pipete treba odmah baciti.
English: People with sensitive skin or who are hypersensitive (allergic) to selamectin or sarolaner should handle Felisecto Plus with caution.
Croatian: Osobe osjetljive kože ili one koje su preosjetljive (alergične) na selamektin ili sarolaner moraju pažljivo rukovati VMP-om Felisecto Plus.
English: Felisecto Plus must not be used in cats suffering from other diseases or in cats that are weak and underweight (for their age).
Croatian: Felisecto Plus ne smije se primjenjivati u mačaka oboljelih od drugih bolesti ili u mačaka koje su oslabljene i premale tjelesne težine (za svoju dob).
English: This medicine is the same as Stronghold Plus, which is already authorised in the European Union (EU).
Croatian: Ovaj VMP isti je kao i VMP Stronghold Plus koji je već odobren u Europskoj uniji (EU).
English: The company that makes Stronghold Plus has agreed that its scientific data can be used for Felisecto Plus (‘informed consent').
Croatian: Proizvođač VMPa Stronghold Plus pristao je na to da se njegovi znanstveni podatci upotrebljavaju za VMP Felisecto Plus (tzv. „informirani pristanak”).