natgillin/translations-raw huggingface dataset:
Tasigna demonstrated efficacy in patients harboring a variety of BCR-ABL mutations associated with imatinib resistance, except T315I.
Tasigna je pokazala djelotvornost u bolesnika koji su razvili različite Bcr-Abl mutacije povezane s rezistencijom na imatinib, osim T315I.
In addition, tell your doctor or pharmacist before taking Tasigna if you are taking any antacids, which are medicines against heartburn.
Osim toga, obavijestite svojeg liječnika ili ljekarnika prije nego što uzmete Tasignu ako uzimate bilo koje antacide, odnosno lijekove protiv žgaravice.
The absolute bioavailability of nilotinib has not been determined.
Apsolutna bioraspoloživost nilotiniba nije utvrđena.
Progression to accelerated phase (AP) or blast crisis (BC) on treatment is defined as the time from the date of randomisation to the first documented disease progression to accelerated phase or blast crisis or CML-related death.
Progresija do ubrzane faze ili blastične krize pri terapiji definira se kao vrijeme od datuma randomizacije do prve dokumentirane progresije bolesti do ubrzane faze ili blastične krize ili smrti povezane s KML-om.
Table 9 Best CCyR rate
Tablica 9 Najbolja stopa CCyR
Chronic phase
Kronična faza
Repeated-dose toxicity studies in dogs of up to 4 weeks' duration and in cynomolgus monkeys of up to 9 months' duration revealed the liver as the primary target organ of toxicity of nilotinib.
Ispitivanja toksičnosti ponovljenih doza u pasa u trajanju do 4 tjedna i u cinomolgus majmuna do 9 mjeseci pokazala su da je jetra primarni ciljni organ toksičnosti nilotiniba.
Randomisation was stratified by Sokal risk score at the time of diagnosis.
Randomizacija je bila stratificirana po pokazatelju rizika prema Sokalu u vrijeme postavljanja dijagnoze.
H2 blockers should be taken approximately 10 hours before and approximately 2 hours after you take Tasigna; - antacids such as those containing aluminium hydroxide, magnesium hydroxide and simethicone, which neutralise high acidity in the stomach.
Blokatore H2 receptora potrebno je uzimati približno 10 sati prije i približno 2 sata nakon uzimanja Tasigne; - antacidi kao što su oni koji sadrže aluminij hidroksid, magnezij hidroksid i simetikon, koji neutraliziraju visoku kiselost želuca.
If clinically significant moderate or severe non-haematological toxicity develops, dosing should be interrupted, and patients should be monitored and treated accordingly.
Ako se razvije klinički značajna umjerena ili teška nehematološka toksičnost, doziranje treba prekinuti, a bolesnike pratiti i odgovarajuće liječiti.
Bioavailability/bioequivalence studies
Ispitivanja bioraspoloživosti/bioekvivalencije
The MMR rate at 12, 24, 36, 48, 60 and 72 months is presented in Table 7.
Stopa MMR-a u 12., 24., 36., 48., 60. i 72. mjesecu prikazana je u Tablici 7.
Since nilotinib and its metabolites are not renally excreted, a decrease in total body clearance is not anticipated in patients with renal impairment.
Budući da se nilotinib i njegovi metaboliti ne izlučuju putem bubrega, ne očekuje se pad ukupnog tjelesnog klirensa u bolesnika s oštećenjem bubrega.
The MCyR rate in 321 CP patients was 51%.
Stopa MCyR-a u 321 bolesnika u kroničnoj fazi bila je 51%.
Animal studies did not show an effect on fertility in male and female rats (see section 5.3).
Ispitivanja u životinja nisu pokazala učinak na plodnost muških i ženskih štakora (vidjeti dio 5.3).
If you are taking any of these, your doctor might prescribe other alternative medicines.
Ako uzimate neki od navedenih lijekova, liječnik Vam može propisati neki drugi lijek.
Table 10 Duration of exposure with nilotinib
Tablica 10 Trajanje izloženosti nilotinibu
If you are pregnant or think that you may be, tell your doctor who will discuss with you whether you can take this medicine during your pregnancy.
Ako ste trudni ili mislite da ste možda trudni, obavijestite svog liječnika koji će s Vama procijeniti možete li uzimati ovaj lijek tijekom Vaše trudnoće.
After a single dose of radiolabelled nilotinib in healthy subjects, more than 90% of the dose was eliminated within 7 days, mainly in faeces (94% of the dose).
Nakon jednokratne doze radiooznačenog nilotiniba u zdravih ispitanika, više od 90% doze eliminiralo se unutar 7 dana, prvenstveno stolicom (94% doze).
Of these patients 30/36 (83%) were treatment resistant not intolerant.
Od ovih bolesnika, u njih 30/36 (83%) razvila se rezistencija na liječenje, ali ga podnose.
Resistant (n=226)
Rezistencija (n=226)
Hypokalaemia or hypomagnesaemia must be corrected prior to Tasigna administration and should be monitored periodically during therapy.
Hipokalijemija ili hipomagnezijemija moraju se korigirati prije primjene Tasigne i trebaju se periodički pratiti tijekom liječenja.
Reproductive toxicity and fertility studies
Ispitivanja reproduktivne toksičnosti i plodnosti
The median TFS has not yet been reached (Figure 5); 74 of 126 patients (58.7%) did not have a TFS event.
Medijan TFS-a nije još dostignut (Slika 5); 74 od 126 bolesnika (58,7%) nije imalo TFS događaj.
No patient had a LVEF of <45% during treatment nor an absolute reduction in LVEF of more than
Tijekom liječenja, niti jedan bolesnik nije imao LVEF <45% niti potpuno smanjenje LVEF za više od 15%.
150 mg twice a day.
150 mg dva puta na dan.
Overall, 73% of patients were imatinib-resistant, while 27% were imatinib-intolerant.
Ukupno gledajući, u 73% bolesnika bila je prisutna rezistencija na imatinib, a u 27% bolesnika intolerancija na imatinib.
200 mg twice a day.
200 mg dva puta na dan.
Resistant (n=109)
Rezistencija (n=109)
Based on a reduction in body weight in both genders and a delayed preputial separation in males (which may be associated with the reduction in weight), the No-Observed-Effect-Level in juvenile rats was considered to be 6 mg/kg/day.
Na temelju sniženja tjelesne težine u oba spola i odgođenog odvajanja prepucija u mužjaka (što može biti povezano sa sniženjem tjelesne težine), doza od 6 mg/kg/dan se smatrala dozom bez opaženog učinka (No-Observed-Effect-Level) u mladih štakora.
In vitro, nilotinib is a relatively strong inhibitor of CYP3A4, CYP2C8, CYP2C9, CYP2D6 and UGT1A1, with Ki value being lowest for CYP2C9 (Ki=0.13 microM).
In vitro je nilotinib relativno snažan inhibitor CYP3A4, CYP2C8, CYP2C9, CYP2D6 i UGT1A1, uz najnižu Ki vrijednost za CYP2C9 (Ki=0,13 mikroM).
The highest prior imatinib dose was 600 mg/day in 74% of all patients, with 40% of patients receiving imatinib doses 800 mg/day.
Najveća prethodna doza imatiniba bila je 600 mg/dan u 74% svih bolesnika, a 40% bolesnika primao je doze imatiniba 800 mg/dan.
Contains lactose - see the package leaflet for further information.
Sadrži laktozu - za dodatne informacije vidjeti uputu o lijeku.
If a woman who is being treated with nilotinib is considering pregnancy, treatment discontinuation may be considered based on the eligibility criteria for discontinuing treatment as described in sections 4.2 and 4.4.
Ako žena liječena nilotinibom razmatra trudnoću, može se uzeti u obzir prekid liječenja temeljem kriterija koji trebaju biti ispunjeni za prekid liječenja kako je opisano u dijelovima 4.2 i 4.4.
If any of these apply to you or your child, tell your doctor.
Ako se bilo što od navedenog odnosi na Vas ili Vaše dijete, obavijestite svog liječnika.
Hypophosphataemia (including blood phosphorus decreased)
Hipofosfatemija (uključujući sniženje fosfora u krvi)
Eligibility for discontinuation of treatment
Ispunjavanje uvjeta za prekid liječenja
None of the metabolites contribute significantly to the pharmacological activity of nilotinib.
Niti jedan od metabolita ne utječe značajno na farmakološku aktivnost nilotiniba.
Cumulative incidence of MMR, %
Kumulativna incidencija MMR-a, %
The rates of response for the two treatment arms are reported in Table 12.
Stope odgovora u oba kraka liječenja prikazane su u Tablici 12.
The blood-to-plasma ratio of nilotinib is 0.71.
Omjer nilotiniba u krvi i plazmi je 0,71.
Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated.
Tasigna se može primijeniti u kombinaciji s hematopoetskim faktorima rasta kao što su eritropoetin ili faktor stimulacije granulocitnih kolonija (G-CSF) ako je klinički indicirano.
Pancreatitis, gastritis, sensitivity of teeth
Pankreatitis, gastritis, osjetljivost zuba
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Bolesnici s rijetkim nasljednim poremećajem nepodnošenja galaktoze, potpunim nedostatkom laktaze ili malapsorpcijom glukoze i galaktoze ne bi smjeli uzimati ovaj lijek.
Women of childbearing potential have to use highly effective contraception during treatment with nilotinib and for up to two weeks after ending treatment.
Žene reproduktivne dobi moraju koristiti visoko učinkovite mjere kontracepcije tijekom liječenja nilotinibom i do dva tjedna nakon završetka liječenja.
This study suggests that a clinically meaningful drug-drug interaction between nilotinib and warfarin is less likely up to a dose of 25 mg of warfarin.
Ovo ispitivanje ukazuje da je značajna interakcija između nilotiniba i varfarina manje vjerojatna do doze od 25 mg varfarina.
The long-term effects of treating children with Tasigna for long periods of time are not known.
Dugoročni učinci liječenja djece Tasignom tijekom duljih razdoblja nisu poznati.
Your doctor will regularly monitor your condition to check that the treatment is having the desired effect.
Vaše stanje da bi utvrdio ima li liječenje željeni učinak.
Nilotinib was shown to absorb light in the UV-B and UV-A range, is distributed into the skin and showed a phototoxic potential in vitro, but no effects have been observed in vivo.
Nilotinib apsorbira svjetlo u UV-B i UV-A rasponu, distribuira se u kožu te pokazuje fototoksični potencijal in vitro, bez zabilježenog učinka in vivo.
However, it is recommended that patients experiencing dizziness, fatigue, visual impairment or other undesirable effects with a potential impact on the ability to drive or use machines safely should refrain from these activities as long as the undesirable effects persist (see section 4.8).
Međutim, preporučuje se da bolesnici s omaglicom, umorom, poremećajima vida ili drugim nuspojavama koje mogu utjecati na sposobnost sigurnog upravljanja vozilom ili rada sa strojevima prestanu s tim aktivnostima sve dok traju nuspojave (vidjeti dio 4.8).
Patients with BCR-ABL levels ≤10% at 3 months of treatment show a greater overall survival at 72 months compared to those who did not achieve this molecular response level (94.5% vs. 77.1% respectively [p=0.0005]).
Bolesnici s razinama BCR-ABL ≤10% nakon 3 mjeseca liječenja imaju veće ukupno preživljavanje u 72. mjesecu u usporedbi s onima koji nisu postigli tu razinu molekularnog odgovora (94,5% u odnosu na 77,1% [p=0,0005]).
It is unknown whether nilotinib is excreted in human milk.
Nije poznato izlučuje li se nilotinib u majčino mlijeko u ljudi.
For patients who fail to achieve MMR after three months of treatment re-initiation, BCR-ABL kinase domain mutation testing should be performed.
U bolesnika koji nisu postigli MMR tri mjeseca nakon ponovnog započinjanja liječenja potrebno je obaviti testiranje na mutaciju kinazne domene BCR-ABL.
- if you have a heart disorder, such as an abnormal electrical signal called “prolongation of the QT interval”.
- ako patite od srčanog poremećaja, kao što je poremećaj provođenja električnih impulsa pod nazivom „produženje QT intervala“.
Patients should be tested for HBV infection before initiating treatment with nilotinib.
Bolesnike je potrebno testirati na infekciju HBV-om prije početka liječenja nilotinibom.
It may increase the amount of Tasigna in the blood, possibly to a harmful level.
To može povećati količinu Tasigne u krvi, moguće do razine koja Vam može naškoditi.
- Obligation to conduct post-authorisation measures
• Obveza provođenja mjera nakon davanja odobrenja
Median duration of therapy in days (25th-75th percentiles)
Medijan trajanja liječenja u danima (25.-75. percentila)
The median highest prior imatinib dose had been 600 mg/day.
Medijan najveće prethodne doze imatiniba bio je 600 mg/dan.
During treatment with Tasigna - if you faint (loss of consciousness) or have an irregular heart beat while taking this medicine, tell your doctor immediately as this may be a sign of a serious heart condition.
Tijekom liječenja Tasignom - ako se onesvijestite (izgubite svijest) ili imate nepravilne otkucaje srca dok uzimate ovaj lijek, odmah obavijestite svog liječnika, jer to može biti znak ozbiljne srčane bolesti.
The KM estimate of median treatment-free survival (TFS) has not yet been reached (Figure 4); 99 of 190 patients (52.1%) did not have a TFS event.
KM procjena medijana preživljenja bez liječenja (engl. treatment-free survival, TFS) nije još dostignuta (Slika 4); 99 od 190 bolesnika (52,1%) nije imalo TFS događaj.
If you stop taking Tasigna
Ako prestanete uzimati Tasignu
Resistance to imatinib included failure to achieve a complete haematological response (by 3 months), cytogenetic response (by 6 months) or major cytogenetic response (by 12 months) or progression of disease after a previous cytogenetic or haematological response.
Rezistencija na imatinib uključivala je neuspjeh u postizanju kompletnog hematološkog odgovora (do 3. mjeseca), citogenetskog odgovora (do 6. mjeseca) ili velikog citogenetskog odgovora (do 12. mjeseca), ili progresiju bolesti nakon prethodnog citogenetskog ili hematološkog odgovora.
The cardiovascular status of patients should be evaluated and cardiovascular risk factors monitored and actively managed during nilotinib therapy according to standard guidelines.
Potrebno je ocijeniti kardiovaskularni status bolesnika i pratiti čimbenike kardiovaskularnog rizika te ih aktivno zbrinjavati tijekom terapije nilotinibom u skladu sa standardnim smjernicama.
Due to lack of steady-state data, control of warfarin pharmacodynamic markers (INR or PT) following initiation of nilotinib therapy (at least during the first 2 weeks) is recommended.
Zbog nedostatka podataka u stanju dinamičke ravnoteže, preporučuje se nadzor farmakodinamičkih parametara varfarina (INR ili PV) nakon početka terapije nilotinibom (najmanje tijekom prva 2 tjedna).
dihydroergotamine).
dihidroergotamin).
Most responders achieved their MCyR rapidly within 3 months (median 2.8 months) of starting nilotinib treatment and these were sustained.
Većina bolesnika u kojih je postignut odgovor dosegli su svoj MCyR brzo unutar 3 mjeseca (medijan 2,8 mjeseca) nakon početka liječenja nilotinibom i to se zadržalo.
The bioavailability of nilotinib is increased by food.
Bioraspoloživost nilotiniba povećava se uzimanjem hrane.
If transient interruption of treatment is not possible, close monitoring of the individual for prolongation of the QT interval is indicated (see sections 4.2, 4.5 and 5.2).
Ako se ne može privremeno prekinuti liječenje, potrebno je pažljivo pratiti svakog pojedinog bolesnika zbog mogućeg produženja QT intervala (vidjeti dijelove 4.2, 4.5 i 5.2).
Nilotinib absorption following oral administration was approximately 30%.
Apsorpcija nilotiniba nakon peroralne primjene je približno 30%.
- Breast-feeding is not recommended during treatment with Tasigna and for two weeks after the last dose.
- Dojenje se ne preporučuje tijekom liječenja Tasignom i tijekom dva tjedna nakon posljednje doze.
In a pre- and postnatal development study in rats, maternal exposure to nilotinib caused reduced pup body weight with associated changes in physical development parameters as well as reduced mating and fertility indices in the offspring.
U pre- i postnatalnim ispitivanjima u štakora, izloženost majke nilotinibu uzrokovala je sniženje tjelesne težine mladunčadi povezane s promjenama u parametrima fizičkog razvoja, kao i smanjeno parenje i plodnost potomaka.
There is no experience with treatment of paediatric patients below 2 years of age.
Nema iskustva s liječenjem pedijatrijskih bolesnika mlađih od 2 godine.
It is therefore crucial to perform frequent monitoring of BCR-ABL transcript levels and complete blood count with differential in order to detect possible loss of remission (see section 4.2).
Stoga je presudno obavljati učestalo praćenje razina BCR-ABL transkripcija i kompletne krvne slike s diferencijalnom krvnom slikom kako bi se otkrio mogući gubitak remisije (vidjeti dio 4.2).
Imatinib intolerance included patients who discontinued imatinib because of toxicity and were not in major cytogenetic response at time of study entry.
Intolerancija na imatinib obuhvaćala je bolesnike koji su prestali uzimati imatinib zbog toksičnosti te koji nisu postigli veliki citogenetski odgovor u vrijeme ulaska u ispitivanje.
The primary endpoint was the percentage of patients in MMR at 48 weeks after starting the TFR phase (considering any patient who required re-initiation of treatment as non-responder).
Mjera primarnog ishoda bila je postotak bolesnika s MMR-om u 48. tjednu nakon početka TFR faze (pri čemu se svaki bolesnik kojem je bilo potrebno ponovno započinjanje liječenja smatrao bolesnikom bez odgovora).
No major differences were observed for safety and efficacy in patients ≥65 years of age as compared to adults aged 18 to 65 years.
Sigurnost i djelotvornost u bolesnika u dobi od ≥65 godina u usporedbi s odraslima u dobi od 18 do 65 godina nije se značajno razlikovala.
It may be given with hydroxyurea or anagrelide if clinically indicated.
Može se primijeniti s hidroksiurejom ili anagrelidom ako je klinički indicirano.
If a HMG-CoA reductase inhibitor (a lipid-lowering agent) is required, please refer to section 4.5 before initiating treatment since certain HMG-CoA reductase inhibitors are also metabolised by the CYP3A4 pathway.
Ako je potreban inhibitor HMG-CoA reduktaze (lijek za snižavanje lipida), vidjeti dio 4.5 prije početka liječenja budući da se određeni inhibitori HMG-CoA reduktaze također metaboliziraju putem CYP3A4.
MMR rates by different time points (including patients who achieved MMR at or before those time points as responders) are presented in the cumulative incidence of MMR (see Figure 1).
Stope MMR-a prema različitim vremenskim točkama (uključujući bolesnike koji su postigli MMR u vrijeme ili prije spomenutih vremenskih točaka kao osobe s odgovorom) prikazane su u kumulativnoj incidenciji MMR-a (vidjeti Sliku 1).
Forty-eight of these 51 patients (94.1%) regained MR4.0 and 47 patients (92.2%) regained MR4.5 by the time of the cut-off date.
Četrdeset osam od tih 51 bolesnika (94,1%) ponovo je postiglo MR4,0, a 47 bolesnika (92,2%) ponovo je postiglo MR4,5 do isključnog datuma.
The primary endpoint was the proportion of patients without confirmed loss of MR4.0 or loss of MMR within 48 weeks following treatment discontinuation.
Mjera primarnog ishoda bila je udio bolesnika bez potvrđenog gubitka MR4,0 ili gubitka MMR-a unutar 48 tjedana nakon prekida liječenja.
Patients must have typical BCR-ABL transcripts to allow quantitation of BCR-ABL, evaluation of the depth of molecular response, and determination of a possible loss of molecular remission after discontinuation of treatment with nilotinib.
Bolesnici moraju imati tipične BCR-ABL transkripcije kako bi bila moguća kvantifikacija BCR-ABL, ocjenjivanje dubine molekularnog odgovora i utvrđivanje mogućeg gubitka molekularne remisije nakon prekida liječenja nilotinibom.
Nilotinib has little or no effect against the majority of other protein kinases examined, including Src, except for the PDGF, KIT and Ephrin receptor kinases, which it inhibits at concentrations within the range achieved following oral administration at therapeutic doses recommended for the treatment of CML (see Table 6).
Nilotinib ima mali ili nikakav učinak na većinu ispitivanih protein kinaza, uključujući Src, osim na PDGF, Kit i Ephrin receptor kinaze, koje inhibira u koncentracijama unutar raspona koji se postiže nakon peroralne primjene terapijskih doza preporučenih za liječenje KML-a (vidjeti Tablicu 6).
Nilotinib absorption (relative bioavailability) might be reduced by approximately 48% and 22% in patients with total gastrectomy and partial gastrectomy, respectively.
Apsorpcija nilotiniba (relativna bioraspoloživost) mogla je biti snižena za otprilike 48% u bolesnika s potpunom gastrektomijom i 22% u bolesnika s djelomičnom gastrektomijom.
If you are told to discontinue Tasigna, your doctor will continue to carefully monitor your CML before, during and after you have discontinued Tasigna and may tell you to re-start Tasigna if your condition indicates that this is necessary.
Ako Vam kaže da prestanete uzimati Tasignu, liječnik će nastaviti pažljivo pratiti Vaš KML prije, za vrijeme i nakon što prestanete uzimati Tasignu i može Vam reći da ponovo počnete uzimati Tasignu ako Vaše stanje bude ukazivalo da je to potrebno.
Besides standard study parameters, evaluations of developmental landmarks, CNS effects, mating and fertility were performed.
Uz standardne parametre ispitivanja, napravljene su procjene razvojnih oznaka, učinaka na središnji živčani sustav, parenje i plodnost.
No episodes of torsade de pointes were observed in clinical studies.
Nisu zapažene epizode torsade de pointes u kliničkim ispitivanjima.
Total gastrectomy
Potpuna gastrektomija
Hyperbilirubinaemia (including blood bilirubin increased)
Hiperbilirubinemija (uključujući povišenje bilirubina u krvi)
Due to possible occurrence of tumour lysis syndrome (TLS) correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to initiating nilotinib therapy (see section 4.8).
Zbog mogućeg nastanka sindroma lize tumora preporučuje se korekcija klinički značajne dehidracije i liječenje visokih razina mokraćne kiseline prije početka liječenja nilotinibom (vidjeti dio 4.8).
Steady-state conditions were essentially achieved by day 8.
Stanje dinamičke ravnoteže je u biti postignuto do 8. dana.
Clinical studies have not been performed in patients with impaired renal function.
Nisu provedena klinička ispitivanja u bolesnika s oštećenom funkcijom bubrega.
The long-term effects of prolonged treatment with nilotinib in paediatric patients are unknown.
Dugoročni učinci produljenog liječenja nilotinibom u pedijatrijskih bolesnika nisu poznati.
If you experience side effects (such as dizziness or visual disorders) with a potential impact on the ability to safely drive or use any tools or machines after taking this medicine, you should refrain from these activities until the effect has disappeared.
U slučaju da ste nakon uzimanja ovog lijeka imali nuspojave (kao što su omaglica ili poremećaj vida) koje mogu utjecati na sposobnost sigurnog upravljanja vozilima ili strojevima ili korištenja nekog alata, trebate se suzdržati od tih aktivnosti dok taj utjecaj ne nestane.
Should treatment with any of these agents be required, it is recommended that nilotinib therapy be interrupted if possible (see section 4.5).
Ako je potrebno liječenje bilo kojim od ovih lijekova, preporučuje se prekinuti primjenu nilotiniba ako je moguće (vidjeti dio 4.5).
Serious cardiovascular events including problems with the blood flow to the leg (peripheral arterial occlusive disease), ischaemic heart disease and problems with the blood supply to the brain (ischaemic cerebrovascular disease) have been reported in patients taking Tasigna.
Ozbiljni srčanožilni događaji, uključujući probleme s dotokom krvi u nogu (okluzivna bolest periferne arterije), ishemijsku bolest srca i probleme s dotokom krvi u mozak (ishemijska cerebrovaskularna bolest), zabilježeni su u bolesnika koji su uzimali Tasignu.
Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong the QT interval, and/or food (see section 4.5).
Značajno produženje QT intervala može se pojaviti ako se nilotinib primjenjuje na neodgovarajući način zajedno sa snažnim CYP3A4 inhibitorima i/ili lijekovima za koje se zna da produžuju QT interval i/ili s hranom (vidjeti dio 4.5).