FrancophonIA/ELRC3.0 huggingface dataset:
English: Data unstable due to the limited duration of response.
Croatian: b Podaci nestabilni zbog ograničenog trajanja odgovora.
English: Prior to launch of OPDIVO in each Member State the Marketing Authorisation Holder (MAH) must agree about the content and format of the educational programme, including communication media, distribution modalities, and any other aspects of the programme, with the National Competent Authority.
Croatian: Prije stavljanja lijeka OPDIVO u promet, nositelj odobrenja za stavljanje lijeka u promet mora u svakoj državi članici s nacionalnim nadležnim tijelom dogovoriti sadržaj i format edukacijskog programa, uključujući medije komunikacije, modalitete distribucije i sve druge aspekte programa.
English: There was no statistically significant difference between nivolumab and chemotherapy in the final OS analysis.
Croatian: Nije primijećena statistički značajna razlika između nivolumaba i kemoterapije u završnoj analizi OS-a.
English: A decision must be made whether to discontinue breast-feeding or to discontinue from nivolumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Croatian: Potrebno je odlučiti da li prekinuti dojenje ili prekinuti liječenje nivolumabom uzimajući u obzir korist dojenja za dijete i korist liječenja za ženu.
English: Reported also in studies outside the pooled dataset.
Croatian: Prijavljeno i u ispitivanjima izvan objedinjenog skupa podataka.
English: The MAH shall ensure that in each Member State where OPDIVO is marketed, all healthcare professionals and patients/carers who are expected to prescribe and use OPDIVO have access to/are provided with the following educational package:
Croatian: Nositelj odobrenja pobrinut će se da u svakoj zemlji članici u kojoj će OPDIVO biti na tržištu svi zdravstveni radnici i bolesnici/njegovatelji za koje se očekuje da će propisivati i primjenjivati lijek OPDIVO imaju pristup/dobiju sljedeći edukacijski paket:
English: • Signs or symptoms of the safety concern and when to seek attention from a HCP
Croatian: • Znakove i simptome pojedinih sigurnosnih problema i naputak o tome kada potražiti pomoć zdravstvenog radnika
English: RFS, assessed by investigator, was defined as the time between the date of randomisation and the date of first recurrence (local, regional, or distant metastasis), new primary melanoma, or death due to any cause, whichever occurred first.
Croatian: RFS je ocjenjivao ispitivač, a definirao se kao vrijeme od datuma randomizacije do datuma prvog recidiva (lokalnog, regionalnog ili udaljene metastaze), novog primarnog melanoma ili smrti zbog bilo kojeg uzroka, ovisno o tome što je nastupilo prvo.
English: Reported in clinical studies and in the post-marketing setting.
Croatian: Prijavljeno u kliničkim ispitivanjima i nakon stavljanja lijeka u promet.
English: With a minimum of 62.6 months follow-up, OS benefit remains consistently demonstrated across subgroups.
Croatian: Uz praćenje od minimalno 62,6 mjeseca, korisni učinci na OS i dalje se dosljedno primjećuju u svim podskupinama.
English: Complete response (CR) Partial response (PR) Stable disease (SD)
Croatian: Potpun odgovor (CR) Djelomičan odgovor (PR) Stabilna bolest (SD)
English: RFS results are shown in Table 13 and Figure 7 (all randomised population).
Croatian: Rezultati za RFS prikazani su u Tablici 13 i na Slici 7 (populacija svih randomiziranih bolesnika).
English: Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that nivolumab does not adversely affect them.
Croatian: Zbog mogućih nuspojava poput umora (vidjeti dio 4.8), bolesnicima treba savjetovati da budu oprezni kada upravljaju vozilima ili rade sa strojevima dok ne budu sigurni da nivolumab ne utječe štetno na njih.
English: Efficacy from both studies was evaluated by the same IRRC.
Croatian: Podatke o djelotvornosti iz oba ispitivanja ocjenjivao je isti IRRC.
English: The average EQ-VAS increased over time for both treatment groups, indicating better overall health status for patients remaining on treatment.
Croatian: Prosječni EQ-VAS rezultat s vremenom se povećavao u obje liječene skupine, što je ukazivalo na bolji ukupan zdravstveni status bolesnika koji su nastavili liječenje.
English: OS results at an additional analysis undertaken at a minimum follow-up of 36 months show outcomes consistent with the original analysis.
Croatian: Rezultati za OS dobiveni u dodatnoj analizi provedenoj nakon minimalnog praćenja od 36 mjeseci pokazuju ishode koji odgovaraju prvobitnoj analizi.
English: Confidence interval for ORR calculated using the Clopper-Pearson method.
Croatian: Interval pouzdanosti za ORR izračunat je Clopper-Pearsonovom metodom.
English: Bristol-Myers Squibb Company 6000 Thompson Road East Syracuse, New York 13057 USA
Croatian: Bristol-Myers Squibb Company 6000 Thompson Road East Syracuse, New York 13057 SAD
English: Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed.
Croatian: Primijećeni su netipični odgovori (tj. početno prolazno povećanje veličine tumora ili male nove lezije unutar prvih nekoliko mjeseci, nakon čega se tumor smanjuje).
English: In terms of ORR, increasing PD-L1 expression was associated with larger ORR.
Croatian: S obzirom na ORR, povećana ekspresija PD-L1 bila je povezana s većim ORR-om.
English: Not known aseptic meningitish
Croatian: Nepoznato aseptički meningitish
English: Grade 2 elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin
Croatian: Povišenje razina aspartat aminotransferaze (AST), alanin aminotransferaze (ALT) ili ukupnog bilirubina 2. stupnja
English: OPDIVO acts on your immune system and may cause inflammation in parts of your body.
Croatian: OPDIVO djeluje na imunosni sustav i može uzrokovati upalu u nekim dijelovima tijela.
English: Treatment should be continued in the presence of hormone replacement therapyb as long as no symptoms are present
Croatian: Liječenje treba nastaviti uz hormonsku nadomjesnu terapijub, pod uvjetom da nema nikakvih simptoma
English: Rare cases of SJS and TEN some of them with fatal outcome have been observed (see sections 4.2 and 4.4).
Croatian: Primijećeni su rijetki slučajevi SJS-a i TEN-a, od kojih su neki završili smrtnim ishodom (vidjeti dijelove 4.2 i 4.4).
English: Use of nivolumab in melanoma patients with rapidly progressing disease
Croatian: Primjena nivolumaba u bolesnika s melanomom u kojih bolest brzo progredira
English: Until further data become available, careful consideration to the potential benefits of HSCT and the possible increased risk of transplant related complications should be made case-by-case (see section 4.8).
Croatian: Dok ne bude dostupno više podataka, potrebno je pažljivo razmotriti potencijalne koristi HSCT-a i mogući povećan rizik od komplikacija povezanih s transplantacijom u svakom pojedinom slučaju (vidjeti dio 4.8).
English: PD-L1+ TAIC in the tumour microenvironment were qualitatively assessed, and characterised as “numerous”, “intermediate”, and “rare” based on pathologist assessments.
Croatian: Ekspresija PD-L1+ TAIC u tumorskom mikrookruženju ocijenjena je kvalitativno i okarakterizirana kao „brojna“, „srednja“ i „rijetka“ na temelju ocjene patologa.
English: Withdraw the required volume of OPDIVO concentrate using an appropriate sterile syringe.
Croatian: Izvucite potrebni volumen koncentrata lijeka OPDIVO odgovarajućom sterilnom štrcaljkom.
English: - It is important that you keep the Alert Card with you during treatment.
Croatian: Važno je da tijekom liječenja sa sobom nosite Karticu s upozorenjima.
English: It is important that you also read the package leaflet for this medicine.
Croatian: Važno je da pročitate i uputu o tom lijeku.
English: Patients with cardiac or cardiopulmonary symptoms should be assessed for potential myocarditis.
Croatian: Bolesnike sa srčanim ili srčano-plućnim simptomima treba ocijeniti zbog mogućeg miokarditisa.
English: Confirmed objective response (BICR)
Croatian: Potvrđen objektivan odgovor (BICR)
English: All patients had either progressed, were censored, or lost to follow-up
Croatian: Svi su bolesnici ili doživjeli progresiju bolesti, bili cenzurirani ili su izgubljeni tijekom praćenja.
English: Sixteen percent of patients had received prior adjuvant therapy; the most common adjuvant treatment was interferon (9%).
Croatian: Šesnaest posto bolesnika prethodno je primalo adjuvantnu terapiju; najčešća adjuvantna terapija bila je liječenje interferonom (9%).
English: The majority of patients (72%) were treated with one prior anti-angiogenic therapy.
Croatian: Većina bolesnika (72%) prethodno je bila liječena jednom antiangiogenom terapijom.
English: The preliminary results show that systemic immunosuppression after starting nivolumab treatment does not appear to preclude the response on nivolumab.
Croatian: Preliminarni rezultati pokazuju da sistemska imunosupresija nakon uvođenja liječenja nivolumabom ne isključuje odgovor na nivolumab.
English: Rapid tapering may lead to worsening or recurrence of the adverse reaction.
Croatian: Naglo smanjenje doze može dovesti do pogoršanja ili ponovne pojave nuspojave.
English: Based on a stratified log-rank test.
Croatian: Na temelju stratificiranog log-rang testa.
English: The PD-1 receptor is a negative regulator of T-cell activity that has been shown to be involved in the control of T-cell immune responses.
Croatian: Receptor PD-1 je negativan regulator aktivnosti T-stanica za koji se pokazalo da sudjeluje u kontroli imunih odgovora T-stanica.
English: “Numerous” and “intermediate” groups were combined to define the “abundant” group.
Croatian: Kategorije „brojna“ i „srednja“ objedinjene su u skupinu „obilna“.
English: Transfer the concentrate into a sterile, evacuated glass bottle or intravenous container (PVC or polyolefin).
Croatian: Prenesite koncentrat u sterilnu, praznu staklenu bocu ili spremnik za intravensku primjenu (PVC ili poliolefin).
English: Before you are given OPDIVO, tell your doctor if you are taking any medicines that suppress your immune system, such as corticosteroids, since these medicines may interfere with the effect of OPDIVO.
Croatian: Prije nego što primite OPDIVO, obavijestite svog liječnika ako uzimate bilo kakve lijekove koji potiskuju imunosni sustav, poput kortikosteroida, jer ti lijekovi mogu utjecati na djelovanje lijeka OPDIVO.
English: Among these 37 patients, treatment with nivolumab resulted in an ORR of 59.5% (22/37).
Croatian: Među tih 37 bolesnika, liječenje nivolumabom rezultiralo je ORR-om od 59,5% (22/37).
English: With appropriate medical therapy, immune-related adverse reactions resolved in most cases.
Croatian: Uz odgovarajuće medicinsko liječenje, imunološki uzrokovane nuspojave u većini su se slučajeva povukle.
English: Updated analysis (24-month follow-up)
Croatian: Ažurirana analiza (nakon 24 mjeseca praćenja)
English: Prior adjuvant or neoadjuvant therapy was allowed if it was completed at least 6 weeks prior to randomisation.
Croatian: Prethodna adjuvantna ili neoadjuvantna terapija bila je dopuštena ako je završila najmanje 6 tjedana prije randomizacije.
English: No Grade 5 endocrinopathy was reported.
Croatian: Nije prijavljen nijedan slučaj endokrinopatije 5. stupnja.
English: The effects of OPDIVO in pregnant women are not known, but it is possible that the active substance, nivolumab, could harm an unborn baby.
Croatian: Učinci lijeka OPDIVO u trudnica nisu poznati, ali moguće je da djelatna tvar, nivolumab, naškodi nerođenu djetetu.
English: Infectious and other aetiologies of diarrhoea should be ruled out, therefore appropriate laboratory tests and additional examinations must be performed.
Croatian: Potrebno je isključiti infektivne i druge etiologije proljeva te se stoga moraju provesti odgovarajuće laboratorijske pretrage i dodatni pregledi.
English: All prescribers of OPDIVO must be familiar with the Physician Information and Management Guidelines.
Croatian: Svi liječnici koji propisuju OPDIVO moraju poznavati Informacije za liječnike i Smjernice za zbrinjavanje.
English: Most patients present with asymptomatic increases in serum creatinine.
Croatian: U većine bolesnika prisutno je asimptomatsko povećanje razine kreatinina u serumu.
English: The OS analysis was not adjusted to account for subsequent therapies received.
Croatian: Analiza OS-a nije bila prilagođena za uključivanje kasnijih terapija.
English: OS and PFS were estimated using Kaplan-Meier method.
Croatian: OS i PFS procijenjeni su uz pomoć Kaplan-Meierove metode.
English: Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
Croatian: Stevens-Johnsonov sindrom (SJS) ili toksična epidermalna nekroliza (TEN)
English: Safety was the primary endpoint and efficacy was a secondary endpoint.
Croatian: Sigurnost je bila primarna mjera ishoda, dok je djelotvornost bila jedna od sekundarnih mjera ishoda.
English: Based on modelling of dose/exposure efficacy and safety relationships, there are no clinically significant differences in efficacy and safety between a nivolumab dose of 240 mg every 2 weeks or 3 mg/kg every 2 weeks.
Croatian: Temeljem rezultata modeliranja djelotvornosti i sigurnosti povezanih s određenom dozom/izloženošću, nema klinički značajnih razlika u djelotvornosti i sigurnosti između nivolumaba u dozi od 240 mg svaka 2 tjedna i u dozi od 3 mg/kg svaka 2 tjedna.
English: (16.56, NR)
Croatian: (16,56; NP)
English: c included 4 drug-related deaths: 1 pneumonitis, 1 acute respiratory failure, 1 respiratory failure, and 1 cardiovascular failure.
Croatian: c Uključena su 4 smrtna slučaja povezana s lijekom: 1 pneumonitis, 1 akutno zatajenje disanja, 1 zatajenje disanja i 1 zatajenje kardiovaskularnog sustava.
English: 31st March 2019
Croatian: 31. ožujka 2019.
English: For instructions on the preparation and handling of the medicinal product before administration, see section 6.6.
Croatian: Za upute o pripremi i rukovanju lijekom prije primjene vidjeti dio 6.6.
English: Efficacy results for the intermediate/poor risk patients from the primary analysis (minimum follow-up 17.5 months) are shown in Table 19.
Croatian: Rezultati za djelotvornost u bolesnika s umjerenim/visokim rizikom iz primarne analize (minimalno praćenje od 17,5 mjeseci) prikazani su u Tablici 19.
English: The unopened vial can be stored at controlled room temperature up to 25°C with room light for up to 48 hours.
Croatian: Neotvorena bočica može se čuvati na kontroliranoj sobnoj temperaturi do 25°C i pri sobnom osvjetljenju tijekom najviše 48 sati.
English: investigator's choice (n = 121)
Croatian: Izbor ispitivača (n = 121)
English: OPDIVO is for intravenous use only.
Croatian: OPDIVO je namijenjen samo za intravensku primjenu.
English: At the time of this final ORR analysis, results from 120 nivolumab-treated patients and 47 chemotherapy-treated patients who had a minimum of 6 months of follow-up were analysed.
Croatian: U trenutku ove završne analize ORR-a analizirani su rezultati prikupljeni u 120 bolesnika liječenih nivolumabom i 47 bolesnika liječenih kemoterapijom koji su bili praćeni tijekom najmanje 6 mjeseci.
English: Nivolumab was continued beyond progression in 44% of patients.
Croatian: Liječenje nivolumabom nakon progresije nastavilo se u 44% bolesnika.
English: Patients should be monitored continuously (at least up to 5 months after the last dose) as an adverse reaction with nivolumab or nivolumab in combination with ipilimumab may occur at any time during or after discontinuation of therapy.
Croatian: Bolesnike je potrebno kontinuirano nadzirati (najmanje 5 mjeseci nakon posljednje doze) jer kod primjene nivolumaba ili nivolumaba u kombinaciji s ipilimumabom nuspojava može nastupiti u bilo kojem trenutku tijekom ili nakon prekida terapije.
English: Baseline characteristics were similar across the two studies and cohorts (see Table 20 below).
Croatian: Početne značajke bile su slične u oba ispitivanja i svim kohortama (vidjeti Tablicu 20 u nastavku).
English: Randomisation was stratified by tumour PD-L1 status and M stage (M0/M1a/M1b versus M1c).
Croatian: Randomizacija je bila stratificirana prema tumorskom PD-L1 statusu i metastatskom stadiju (M0/M1a/M1b naspram M1c).
English: This observation was maintained with the OS results with a minimum followup of 36 months.
Croatian: Ovi su se opaženi rezultati za OS održali i nakon minimalnog praćenja od 36 mjeseci.
English: Patients were stratified by IMDC prognostic score and region.
Croatian: Bolesnici su bili stratificirani prema prognostičkom rezultatu na temelju IMDC kriterija i regiji.
English: In subgroup analyses, survival benefit compared to docetaxel was not shown for patients who were never-smokers or whose tumours harboured EGFR activating mutations; however, due to the small numbers of patients, no definitive conclusions can be drawn from these data.
Croatian: U analizama podskupina, korisni učinci na preživljenje u odnosu na docetaksel nisu primijećeni u bolesnika koji nikada nisu pušili niti u onih čiji je tumor imao aktivirajuće mutacije EGFR-a; međutim, zbog malog broja bolesnika ne mogu se donijeti konačni zaključci na temelju tih podataka.
English: The median time to onset of objective response was 3.5 months (range: 1.4-24.8 months) after the start of nivolumab treatment.
Croatian: Medijan vremena do nastupa objektivnog odgovora iznosio je 3,5 mjeseci (raspon: 1,4-24,8 mjeseci) nakon početka liječenja nivolumabom.
English: There are no data on adjuvant treatment in patients with melanoma with the following risk factors (see sections 4.5 and 5.1
Croatian: Nema podataka o adjuvantnom liječenju u bolesnika s melanomom i sljedećim faktorima rizika (vidjeti dijelove 4.5 i 5.1):
English: What OPDIVO contains
Croatian: Što OPDIVO sadrži
English: Rare cases of SJS and TEN some of them with fatal outcome have been observed.
Croatian: Primijećeni su rijetki slučajevi SJS-a i TEN-a, od kojih neki sa smrtnim ishodom.
English: Sixty-four percent of patients were men and 98% were white.
Croatian: Šezdeset i četiri posto bolesnika bili su muškarci, a 98% bili su bijelci.
English: Changes in test results
Croatian: Promjene u nalazima pretraga
English: 75 28.88 (18.10, NR)
Croatian: 75 28,88 (18,10; NP)
English: The educational programme is aimed at increasing the awareness about the potential immune mediated adverse events associated with OPDIVO use, how to manage them and to enhance the awareness of patients or their caregivers on the signs and symptoms relevant to the early recognition/identification of those adverse events.
Croatian: Cilj edukacijskog programa je povećati svijest o mogućim imunološki uzrokovanim nuspojavama povezanima s primjenom lijeka OPDIVO, o tome kako ih zbrinuti i povećati svijest bolesnika ili njihovih njegovatelja o znakovima i simptomima koji su važni za rano prepoznavanje/utvrđivanje tih nuspojava.
English: Nivolumab attaches to a target protein called programmed death-1 receptor (PD-1) that can switch off the activity of T cells (a type of white blood cell that forms part of the immune system, the body's natural defences).
Croatian: Nivolumab se vezuje za ciljni protein koji se naziva receptorom programirane stanične smrti (engl. programmed death-1 receptor, PD-1) i koji može zaustaviti aktivnost T-stanica (jedne vrste bijelih krvnih stanica koje čine dio imunosnog sustava, prirodnog obrambenog sustava tijela).
English: From a microbiological point of view, once opened, the medicinal product should be infused or diluted and infused immediately.
Croatian: S mikrobiološkog stanovišta, lijek se nakon otvaranja mora odmah infundirati ili razrijediti i infundirati.
English: Use separate infusion bags and filters for each infusion.
Croatian: Za svaku infuziju moraju se upotrijebiti zasebne infuzijske vrećice i filtri.
English: After 28 months of follow-up, median OS was not reached in either of the nivolumab containing arms regardless of BRAF status.
Croatian: Nakon 28 mjeseci praćenja, medijan OS-a nije postignut ni u jednoj skupini čija je terapija uključivala nivolumab, neovisno o BRAF statusu.
English: Updated analysis Minimum follow-up: 62.7 months a Post-hoc analysis; results should be interpreted with caution as the subgroup samples sizes are small and, at the time of the analysis, the PD-L1 IHC 28-8 pharmDx assay was not analytically validated at the 10% or 50% expression levels.
Croatian: Ažurirana analiza Minimalno praćenje: 62,7 mjeseci a Post-hoc analiza; rezultate treba tumačiti uz oprez zbog male veličine uzoraka u podskupinama i činjenice da u trenutku provedbe analize test za određivanje ekspresije PD-L1 IHC 28-8 pharmDx nije bio analitički validiran za razine ekspresije od 10% i 50%.
English: Due to the small numbers of patients in the subgroups, and exploratory nature of the analysis, no definitive conclusions can be drawn from these data.
Croatian: Zbog malog broja bolesnika u podskupinama i eksploracijske naravi ove analize, na temelju tih podataka ne mogu se donijeti konačni zaključci.
English: Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available post-marketing data).
Croatian: Učestalost je definirana kao: vrlo često (≥ 1/10); često (≥ 1/100 i < 1/10); manje često (≥ 1/1000 i < 1/100); rijetko (≥ 1/10 000 i < 1/1000); vrlo rijetko (< 1/10 000); nepoznato (ne može se procijeniti iz dostupnih podataka nakon stavljanja lijeka u promet).
English: Data available indicate that the onset of nivolumab effect is delayed such that benefit of nivolumab above chemotherapy may take 2-3 months.
Croatian: Dostupni podaci pokazuju da je nastup učinka nivolumaba odgođen, pa će se korist od liječenja nivolumabom u odnosu na kemoterapiju možda primijetiti tek za 2-3 mjeseca.
English: Not reached (2.9-20.5+)
Croatian: nije postignut (2,9-20,5+)
English: The ORR and PFS were assessed by IRRC per RECIST version 1.1.
Croatian: ORR i PFS ocijenio je IRRC prema verziji 1.1 RECIST kriterija.
English: Study CA209017 included a limited number of patients ≥ 75 years (11 in the nivolumab group and 18 in the docetaxel group).
Croatian: U ispitivanje CA209017 bio je uključen ograničen broj bolesnika u dobi od ≥ 75 godina (11 u skupini liječenoj nivolumabom i 18 u skupini liječenoj docetakselom).
English: Adjuvant treatment of melanoma
Croatian: Adjuvantno liječenje melanoma
English: Dublin 15, D15 H6EF
Croatian: Dublin 15, D15 T867
English: Incidence rates per 100 person-years of exposure were 9.3 vs. 0; serious cardiac events were reported by 4.9% patients in the nivolumab group vs. 0 in the investigator´s choice group.
Croatian: Stopa incidencije na 100 bolesnik-godina izloženosti iznosila je 9,3 naspram 0; ozbiljne srčane događaje prijavilo je 4,9% bolesnika u skupini liječenoj nivolumabom naspram 0 bolesnika u skupini koja je primala lijek po izboru ispitivača.
English: To be taken into consideration when treating patients on a controlled sodium diet.
Croatian: To treba uzeti u obzir u liječenju bolesnika koji su na dijeti s kontroliranim unosom natrija.
English: Assessment according to discrete PD-L1 expression intervals were not included in the prespecified analyses due to the small sample sizes within the intervals.
Croatian: Ocjena prema pojedinačnim rasponima ekspresije PD-L1 nije bila uključena u unaprijed specificirane analize zbog male veličine uzoraka unutar tih raspona.
English: No dose adjustment is required for elderly patients (≥ 65 years) (see section 5.2).
Croatian: Nije potrebno prilagođavati dozu u starijih bolesnika (≥ 65 godina) (vidjeti dio 5.2).
English: Please refer to the package leaflet of ipilimumab in order to understand the use of this medicine.
Croatian: Pročitajte uputu o lijeku za ipilimumab da biste shvatili za što se taj lijek koristi.
English: Permanently discontinue treatment (see section 4.4)
Croatian: Trajno prekinuti liječenje (vidjeti dio 4.4)