FrancophonIA/ELRC3.0 huggingface dataset:
English: The CHMP recommends amendments to the product information and in view of the limitations of the currently available efficacy data for Symbioflor2 in the treatment of irritable bowel syndrome (IBS), the CHMP is of the view that a post-authorisation efficacy study should be conducted.
Croatian: CHMP preporučuje izmjene informacija o lijeku te s obzirom na ograničenja trenutačno dostupnih podataka o djelotvornosti lijeka Symbioflor 2 u liječenju sindroma iritabilnog crijeva (IBS), CHMP smatra da bi trebalo provesti ispitivanje djelotvornosti lijeka nakon dobivanja odobrenja za stavljanje lijeka u promet.
English: The CHMP concluded that this study cannot be regarded as adequately supporting an indication for Symbioflor 2 in this age group.
Croatian: CHMP je zaključio da se ne može smatrati da ovo ispitivanje na primjeren način podupire indikaciju za lijek Symbioflor 2 za tu dobnu skupinu.
English: The CHMP agreed with the MAH's proposal to amend the product information to include the information of this review and concluded that, considering its long presence on the market with limited adverse drug reactions reporting, the safety profile of Symbioflor 2 is generally expected to be benign.
Croatian: CHMP se složio s prijedlogom nositelja odobrenja za stavljanje lijeka u promet da se izmijene informacije o lijeku kako bi se uvrstile informacije iz ovog pregleda te je zaključio da bi, s obzirom na dugotrajnu prisutnost na tržištu i mali broj izvješća o nuspojavama lijeka, sigurnosni profil lijeka Symbioflor 2 općenito trebao biti povoljan.
English: In the clinical development program, there were respectively 50 adverse drug reactions reported in the Symbioflor 2 group, and 44 in the placebo group for Study S2 in 79 patients.
Croatian: U programu kliničkog razvoja u okviru ispitivanja S2 provedenog na 79 bolesnika zabilježeno je 50 nuspojava lijeka u skupini koja je primala lijek Symbioflor 2 i 44 u skupini koja je primala placebo.
English: The newly defined primary endpoints in this re-evaluation were evaluated with adequate statistical methodology and were strict with regards to treatment success, because only patients completely free of symptoms were counted as “responders”.
Croatian: Ishodi su bili strogi u pogledu uspješnosti liječenja jer se smatralo da su bolesnici „koji su reagirali” samo oni koji više nisu imali nikakve simptome.
English: In 2005, based on the evaluation of the available evidence at that time in the claimed indications ("functional gastrointestinal disorders'', "irritable bowel syndrome"), the application was refused by the German National Competent Authority on the ground that a positive benefit-risk had not been adequately established.
Croatian: Njemačko nacionalno nadležno tijelo odbilo je zahtjev u 2005. na temelju ocjene tada dostupnih dokaza za navedene indikacije („funkcionalni gastrointestinalni poremećaji”, „sindrom iritabilnog crijeva”) s obrazloženjem da pozitivan omjer koristi i rizika nije utvrđen na odgovarajući način.
English: In addition, in the absence of valid statistical evaluations and given the paucity of elements contributing to support the robustness and the strength of the results, the CHMP was, neither able to draw reliable conclusions with regards to the efficacy of Symbioflor 2, nor to establish whether Symbioflor 2 is efficacious in IBS in general or any sub-type of IBS.
Croatian: Osim toga, u nedostatku valjanih statističkih ocjena i s obzirom na manjak elemenata koji doprinose pouzdanosti i snazi rezultata, CHMP nije mogao izvesti pouzdane zaključke u pogledu djelotvornosti lijeka Symbioflor 2 niti utvrditi je li lijek djelotvoran u liječenju sindroma iritabilnog crijeva općenito ili bilo kojeg podtipa IBS-a.
English: In the absence of relevant data submitted by the MAH and in view of the uncertainties about proof of efficacy in Study S2, the CHMP concluded that these results cannot be extrapolated from adults to children or to adolescents.
Croatian: U nedostatku mjerodavnih podataka dobivenih od nositelja odobrenja za stavljanje lijeka u promet i s obzirom na nesigurnosti u vezi dokazivanja djelotvornosti u ispitivanju S2, CHMP je zaključio da se ti rezultati ne mogu ekstrapolirati s odraslih osoba na djecu ili adolescente.
English: Two reports in support of the claimed indication in the treatment of irritable bowel syndrome (IBS) were submitted in the context of this referral procedure:
Croatian: U kontekstu ovog postupka upućivanja dostavljena su dva izvješća koja podupiru navedenu indikaciju u liječenju sindroma iritabilnog crijeva (IBS):
English: • Acknowledging the limitations of the established efficacy profile of Symbioflor 2, the CHMP requested the MAH to conduct a well-designed and adequately powered multi-centre, double blind, randomised, placebo controlled post approval efficacy study allowing for relevant subpopulation analyses to confirm the efficacy of Symbioflor 2 in the treatment of IBS in general versus subtypes of the disease such as IBS C and IBS D, gender, disease severity and address the sustainability of efficacy to confirm the efficacy of Symbioflor 2 in IBS;
Croatian: • Potvrđujući ograničenja utvrđenog profila djelotvornosti lijeka Symbioflor 2, CHMP je od nositelja odobrenja za stavljanje lijeka u promet zatražio da provede ispitivanje djelotvornosti nakon dobivanja odobrenja koje je dobro izvedeno, primjerene snage, multicentrično, dvostruko slijepo, randomizirano i placebom kontrolirano te omogućava analize odgovarajućih podpopulacija kako bi se potvrdila općenita djelotvornost lijeka Symbioflor 2 u liječenju IBS-a nasuprot djelotvornosti u liječenju podtipova bolesti kao što su sindrom iritabilnog crijeva sa zatvorom (IBS-C) i sindrom iritabilnog crijeva s proljevom (IBS-D), prema spolu, težini bolesti te kako bi se riješilo pitanje održivosti djelotvornosti i potvrdila djelotvornost lijeka Symbioflor 2 u liječenju IBS-a;
English: In summary, in the absence of valid statistical evaluation and given the risk of bias and the paucity of elements contributing to support the robustness and the strength of the results (the evidence being based on a single pivotal trial), the CHMP was not able to confidently draw a conclusion with regards to the efficacy of Symbioflor 2 in IBS or a sub-type of IBS.
Croatian: Ukratko, u nedostatku valjane statističke ocjene i s obzirom na rizik od pristranosti i manjak elemenata koji doprinose pouzdanosti i snazi rezultata (dokazi se temelje na jednom glavnom ispitivanju), CHMP nije mogao sa sigurnošću izvesti zaključak u pogledu djelotvornosti lijeka Symbioflor 2 u liječenju sindroma iritabilnog crijeva ili podtipova te bolesti.
English: • The CHMP also noted that results of the observational study in children older than 4 years with IBS suggested a possible efficacy of Symbioflor 2.
Croatian: • CHMP je također napomenuo da su rezultati opservacijskog ispitivanja na djeci u dobi iznad četiri godine sa sindromom iritabilnog crijeva ukazali na moguću djelotvornost lijeka Symbioflor 2.
English: In the absence of relevant data submitted by the MAH to support the paediatric use and in view of the uncertainties about the benefit-risk in Study S2 conducted in adult patients only, the CHMP concluded that extrapolation of the results from adults to children or adolescents was not justified.
Croatian: U nedostatku mjerodavnih podataka dobivenih od nositelja odobrenja za stavljanje lijeka u promet koji podupiru pedijatrijsku primjenu i s obzirom na nesigurnosti u pogledu omjera koristi i rizika u ispitivanju S2 provedenom samo na odraslim bolesnicima, CHMP je zaključio da ekstrapolacija rezultata s odraslih osoba na djecu ili adolescente nije opravdana.
English: The CHMP also noted that results of the observational study in children older than 4 years with IBS suggested a possible efficacy of Symbioflor 2.
Croatian: CHMP je također napomenuo da su rezultati opservacijskog ispitivanja na djeci u dobi iznad četiri godine sa sindromom iritabilnog crijeva ukazali na moguću djelotvornost lijeka Symbioflor 2.
English: In addition, the CHMP was of the opinion that the adequacy of a global evaluation criterion defined by the MAH for the assessment of the efficacy of Symbioflor 2 in the treatment of IBS was questionable in comparison to the specific, better measurable and less subjective evaluation of changes in stool related abnormalities and pain.
Croatian: Osim toga, CHMP-a je smatrao da je upitna primjerenost kriterija opće procjene koji je nositelj odobrenja za stavljanje lijeka u promet utvrdio radi ocjene djelotvornosti lijeka Symbioflor 2 u liječenju sindroma iritabilnog crijeva u odnosu na specifičnu, lakše mjerljivu i u manjoj mjeri subjektivnu ocjenu promjena u poremećajima stolice i jačini boli.
English: In general, the CHMP was of the opinion that, although the reporting might have been suboptimal and uncertainties remain with regards to the nature and frequency of the adverse events occurring with Symbioflor 2 in order to fully characterize its safety profile and notably its long term safety profile, the analysis of the safety data did not raise particular concerns.
Croatian: Općenito, CHMP je smatrao da analiza podataka o sigurnosti ne izaziva posebnu zabrinutost, iako je izvještavanje možda bilo ispod optimalne razine, te su preostale nesigurnosti u pogledu prirode i učestalosti nuspojava kod primjene lijeka Symbioflor 2 povezane s provedbom potpune karakterizacije sigurnosnog profila lijeka, a posebno dugoročnog sigurnosnog profila.
English: The SmPC was amended to reflect that efficacy in children has not been established.
Croatian: Sažetak opisa svojstava lijeka izmijenjen je kako bi se navelo da nije utvrđena djelotvornost u djece.
English: • The CHMP was of the opinion that, although the results of Study S2 seemed to suggest possible efficacy of Symbioflor 2 in IBS in adult patients, the possibility that significant bias had been introduced compromising the validity of the results could not be ruled out.
Croatian: • Iako se činilo da rezultati ispitivanja S2 ukazuju na moguću djelotvornost lijeka Symbioflor 2 u liječenju sindroma iritabilnog crijeva u odraslih bolesnika, CHMP je smatrao da se ne može isključiti mogućnost značajne pristranosti koja je ugrozila valjanost rezultata.
English: Furthermore, the CHMP requested that the MAH conduct a well-designed and adequately powered multi-centre, double blind, randomised, placebo controlled post approval efficacy study allowing for relevant subpopulation analyses to assess the efficacy of Symbioflor 2 in the treatment of IBS in general versus subtypes of the disease such as IBS C and IBS D, gender, disease severity and address the sustainability of efficacy to confirm the efficacy of Symbioflor 2 in IBS.
Croatian: Nadalje, CHMP je zatražio da nositelj odobrenja za stavljanje lijeka u promet provede ispitivanje djelotvornosti nakon dobivanja odobrenja koje je dobro izvedeno, primjerene snage, multicentrično, dvostruko slijepo, randomizirano i placebom kontrolirano te omogućava analize odgovarajućih podpopulacija kako bi se ocijenila općenita djelotvornost lijeka Symbioflor 2 u liječenju IBS-a nasuprot djelotvornosti u liječenju podtipova bolesti kao što su sindrom iritabilnog crijeva sa zatvorom (IBS-C) i sindrom iritabilnog crijeva s proljevom (IBS-D), prema spolu, težini bolesti te kako bi se riješilo pitanje održivosti djelotvornosti i potvrdila djelotvornost lijeka Symbioflor 2 u liječenju IBS-a.
English: Data were not controlled and did thus not account for the contribution of spontaneous fluctuations of IBS symptoms or for a placebo response in the assessment of the benefit-risk of Symbioflor 2.
Croatian: Nije provedena kontrola podataka, koji stoga u ocjeni omjera koristi i rizika za lijek Symbioflor 2 nisu odrazili doprinos spontanih fluktuacija simptoma sindroma iritabilnog crijeva ili reagiranja na placebo.
English: In this regards, the SmPC is amended to reflect that efficacy in children has not been established;
Croatian: U tom je smislu izmijenjen sažetak opisa svojstava lijeka kako bi se navelo da nije utvrđena djelotvornost u djece.
English: Additional bias might have been introduced by various other deficiencies encountered in the conduct of Study S2, including the fact that the endpoint was solely based on the rating by the investigator on a weekly basis rather than selfassessed by the patient closer to the administration of Symbioflor 2.
Croatian: Moguće je da su razni drugi nedostatci zamijećeni u provođenju ispitivanja S2 doveli do dodatne pristranosti, uključujući činjenicu da se ishod temeljio isključivo na ocjeni ispitivača na tjednoj osnovi, umjesto na samostalnoj ocjeni bolesnika s osobnim iskustvom primjene lijeka Symbioflor 2. U odsustvu faze uvođenja terapije i posebnih kriterija uključenosti također nisu postojala dostatna jamstva o tome da je populacija bolesnika bila pogođena sindromom iritabilnog crijeva.
English: The CHMP was of the opinion that a significant number of adverse events would have been expected to be reported in this study due to the underlying disease regardless of the safety profile of Symbioflor 2.
Croatian: CHMP je smatrao da se zbog popratne bolesti mogao očekivati znatan broj zabilježenih nuspojava u ovom ispitivanju, bez obzira na sigurnosni profil lijeka Symbioflor 2. Stoga se ne može zaključiti da ovo ispitivanje dodatno doprinosi utvrđivanju sigurnosnog profila lijeka Symbioflor 2.
English: Grounds for CHMP opinion
Croatian: Obrazloženje mišljenja CHMP-a Budući da:
English: If you notice any of the following:
Croatian: Ako primijetite bilo što od navedenog:
English: Keep the bottle tightly closed.
Croatian: Bočicu držati čvrsto zatvorenom.
English: Signs that your liver may not be working properly may include:
Croatian: Znakovi da Vaša jetra možda ne radi kako treba mogu uključivati:
English: Mekinist with food and drink
Croatian: Mekinist s hranom i pićem
English: Tell your doctor immediately if you get a temperature above 38.5ºC while you are taking this medicine.
Croatian: Odmah obavijestite svog liječnika ako dobijete temperaturu iznad 38,5ºC dok uzimate ovaj lijek.
English: You need to know about important symptoms to look out for.
Croatian: Morate biti upoznati s važnim simptomima na koje treba pripaziti.
English: At 1 year At 2 years At 3 years At 4 years At 5 years
Croatian: Na 1 godinu Na 2 godine Na 3 godine Na 4 godine Na 5 godina
English: - The other ingredients are
Croatian: - Drugi sastojci su
English: You may also have blood tests.
Croatian: Možda ćete obaviti i krvne pretrage.
English: Mekinist can harm the unborn baby.
Croatian: Mekinist može naškoditi nerođenu djetetu.
English: This means that:
Croatian: To znači da:
English: Store in a refrigerator in the original bottle.
Croatian: Čuvati u hladnjaku u originalnoj bočici.
English: Do not take a double dose to make up for a missed dose.
Croatian: Nemojte uzeti dvostruku dozu kako biste nadoknadili propuštenu dozu.
English: Do not throw away medicines in wastewater or household waste.
Croatian: Nikada nemojte nikakve lijekove bacati u otpadne vode ili kućni otpad.
English: Store in a refrigerator (2°C to 8°C).
Croatian: Čuvati u hladnjaku (2ºC - 8ºC).
English: Full recovery was observed when stopping treatment.
Croatian: Potpuni oporavak je zapažen kod prekida liječenja.
English: Table 12 Survival data from the primary and post-hoc analyses
Croatian: Tablica 12 Podaci o preživljenju iz primarne i post-hoc analize
English: Do not take Mekinist:
Croatian: Nemojte uzimati Mekinist:
English: The safety and efficacy of trametinib have not been established in children and adolescents (<18 years).
Croatian: Sigurnost i djelotvornost trametiniba u djece i adolescenata (< 18 godina) nisu ustanovljene.
English: May 20,
Croatian: 20. svibnja
English: Take Mekinist at about the same time each day.
Croatian: Mekinist uzmite svakoga dana u približno isto vrijeme.
English: Descriptions of these effects can be found in other sections (see sections 2 and 4).
Croatian: Opise tih nuspojava možete pronaći u drugim dijelovima (pogledajte dijelove 2 i 4).
English: You need to use another effective method of birth control so you do not become pregnant while you are taking this medicine.
Croatian: Morate koristiti dodatnu učinkovitu kontracepcijsku metodu kako ne biste zatrudnili dok uzimate ovaj lijek.
English: • if you are allergic to trametinib or any of the other ingredients of this medicine (listed in section 6).
Croatian: • ako ste alergični na trametinib ili neki drugi sastojak ovog lijeka (naveden u dijelu 6).
English: Women of childbearing potential/Contraception in females
Croatian: Žene reproduktivne dobi/Kontracepcija u žena
English: Do not stop unless your doctor advises you to.
Croatian: Nemojte prestati uzimati lijek, osim ako Vam to ne savjetuje Vaš liječnik.
English: The deacetylation is mediated by the carboxyl-esterases 1b, 1c and 2, with possible contributions by other hydrolytic enzymes.
Croatian: Deacetilacija je posredovana karboksilesterazama 1b, 1c i 2,s mogućim doprinosima drugih hidrolitičkih enzima.
English: Other medicines and Mekinist
Croatian: Drugi lijekovi i Mekinist
English:  Read the information “Possible serious side effects” in section 4 of this leaflet.
Croatian: Pročitajte informacije u odlomku „Moguće ozbiljne nuspojave“ u dijelu 4 ove Upute.
English: The increase in exposure (Cmax and AUC) was dose-proportional following repeat dosing.
Croatian: Povećanje izloženosti (Cmax i AUC) nakon ponovljenog doziranja bilo je proporcionalno dozi.
English: Oncogenic mutations in BRAF lead to constitutive activation of the RAS/RAF/MEK/ERK pathway.
Croatian: Onkogene mutacije u BRAF-u dovode do konstitutivne aktivacije puta RAS/RAF/MEK/ERK.
English: The desiccant must be kept inside the bottle and must not be eaten.
Croatian: Sredstvo za sušenje mora ostati u bočici i ne smije se pojesti.
English: Binding of trametinib to human plasma proteins is 97.4%.
Croatian: Vezanje trametiniba za ljudske proteine plazme iznosi 97,4%.
English: 1/10,000 to <1/1,000
Croatian:  1/10 000 i < 1/1000
English: What Mekinist is and what it is used for
Croatian: Što je Mekinist i za što se koristi
English: The potential for these events in patients with low platelet counts (<75,000) has not been established as such patients were excluded from clinical trials.
Croatian: Potencijal za te događaje u bolesnika s niskom razinom trombocita (< 75 000) nije utvrđen budući da su takvi bolesnici bili isključeni iz kliničkih ispitivanja.
English: Conditions you need to look out for
Croatian: Bolesti na koje morate pripaziti
English: • If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Croatian: • Ako ste trudni, mislite da biste mogli biti trudni ili planirate imati dijete, obratite se svom liječniku za savjet prije nego uzmete ovaj lijek.
English: Once opened, the bottle may be stored for 30 days at not more than 30°C.
Croatian: Nakon otvaranja bočica se može čuvati 30 dana na temperaturi od najviše 30°C.
English: What Mekinist is and what it is used for What you need to know before you take Mekinist How to take Mekinist
Croatian: Što je Mekinist i za što se koristi Što morate znati prije nego počnete uzimati Mekinist Kako uzimati Mekinist
English: Grade 1 or Grade 2 (Tolerable)
Croatian: 1. stupanj ili 2. stupanj (podnošljivo)
English: Then carry on taking your tablets at regular times as usual.
Croatian: Zatim nastavite uzimati tablete prema uobičajenom rasporedu.
English: It is important to take Mekinist on an empty stomach because food affects the way the medicine is absorbed into your body (see section 3).
Croatian: Važno je uzimati Mekinist na prazan želudac jer hrana utječe na način na koji se lijek apsorbira u tijelu (pogledajte dio 3).
English: For trametinib monotherapy, more than 90% of these liver events occurred within the first 6 months of treatment.
Croatian: Kod monoterapije trametinibom više od 90% tih jetrenih događaja javilo se unutar prvih 6 mjeseci liječenja.
English: Talk to your doctor before taking your medicine.
Croatian: Obratite se svom liječniku prije nego uzmete ovaj lijek.
English: Mekinist is not recommended for children and adolescents since the effects of Mekinist in people younger than 18 years old are not known.
Croatian: Mekinist se ne preporučuje za djecu i adolescente jer nisu poznati učinci lijeka Mekinist u osoba mlađih od 18 godina.
English: Chemotherapy a
Croatian: Kemoterapija a
English: There are no adequate and well-controlled studies of trametinib in pregnant women.
Croatian: Nisu provedena odgovarajuća i dobro kontrolirana ispitivanja trametiniba u trudnica.
English: October 26,
Croatian: 26. listopada
English: Avoid driving or using machines if you feel tired or weak, if you have problems with your vision or if your energy levels are low.
Croatian: Izbjegavajte upravljanje vozilima ili rad sa strojevima ako se osjećate umorno ili slabo, ako imate tegoba s vidom ili ako osjećate da nemate energije.
English: Therefore, before starting treatment your doctor will test for this mutation.
Croatian: Stoga će Vaš liječnik prije početka liječenja napraviti test na tu mutaciju.
English: Pelvic examinations (for women) and anal examinations are also recommended before and at the end of your treatment.
Croatian: Pregled zdjelice (za žene) i analni pregled također se preporučuju prije i na kraju Vašeg liječenja.
English: Mekinist can affect how well your heart pumps blood.
Croatian: Mekinist može utjecati na to koliko će dobro srce izbacivati krv.
English: Steady state was achieved by Day 15.
Croatian: Stanje dinamičke ravnoteže postignuto je do 15. dana.
English: In the first-line population, 68% of patients had not progressed after 9 months.
Croatian: U populaciji na prvoj liniji terapije, 68% bolesnika nije imalo progresiju nakon 9 mjeseci.
English: o If it is less than 6 hours to your next scheduled dose of dabrafenib, which is taken twice daily.
Croatian: o Ako ima manje od 6 sati do Vaše sljedeće planirane doze dabrafeniba, koji se uzima dvaput na dan.
English: Grade 2 (Intolerable) or Grade 3
Croatian: 2. stupanj (nepodnošljivo) ili 3. stupanj
English: Your doctor will check your skin before you start taking dabrafenib, then check it again every month while you are taking this medicine and for 6 months after you stop taking it.
Croatian: Liječnik će Vam provjeriti kožu prije nego počnete uzimati dabrafenib i zatim je provjeravati ponovo svaki mjesec dok uzimate ovaj lijek te 6 mjeseci nakon što ga prestanete uzimati.
English: Before starting treatment, tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines.
Croatian: Prije početka liječenja obavijestite svog liječnika, medicinsku sestru ili ljekarnika ako uzimate, nedavno ste uzeli ili biste mogli uzeti bilo koje druge lijekove.
English: • after eating, you must wait at least 2 hours before taking Mekinist.
Croatian: • nakon jela morate pričekati najmanje 2 sata prije uzimanja lijeka Mekinist.
English: Your doctor will also check your head, neck, mouth and lymph glands and you will have scans of your chest and stomach area (called CT scans) regularly.
Croatian: Liječnik će Vam također provjeriti glavu, vrat, usta i limfne žlijezde, a redovito će Vam se raditi i snimke grudnog koša i područja trbuha (takozvane CT snimke).
English: Your doctor or nurse should check your blood pressure during treatment with Mekinist.
Croatian: Vaš liječnik ili medicinska sestra moraju Vam kontrolirati krvni tlak tijekom liječenja lijekom Mekinist.
English: What Mekinist looks like and contents of the pack
Croatian: Kako Mekinist izgleda i sadržaj pakiranja
English: Name and address of the manufacturers responsible for batch release Glaxo Wellcome, S.A.
Croatian: Nazivi i adrese proizvođača odgovornih za puštanje serije lijeka u promet Glaxo Wellcome, S.A.
English: The trametinib dose should not exceed 2 mg once daily.
Croatian: Doza trametiniba ne smije biti viša od 2 mg jedanput na dan.
English: Prior to starting treatment with dabrafenib, talk to your doctor about options to improve your chances to have children in the future.
Croatian: Prije nego što započnete liječenje dabrafenibom, razgovarajte sa svojim liječnikom o tome kako možete povećati svoje mogućnosti da imate djecu u budućnosti.