FrancophonIA/ELRC3.0 huggingface dataset:
English: Number of deaths
Croatian: Liječenje Broj umrlih
English: There are no clinical data in patients with moderate or severe hepatic impairment; therefore, the potential need for starting dose adjustment cannot be determined.
Croatian: Nema kliničkih podataka o primjeni u bolesnika s umjerenim ili teškim oštećenjem jetrene funkcije; stoga se ne može utvrditi moguća potreba za prilagodbom početne doze.
English: Adverse reactions are listed below by MedDRA body system organ class.
Croatian: Nuspojave u nastavku navedene su prema MedDRA klasifikaciji organskih sustava.
English: Treatment with trametinib monotherapy or in combination with dabrafenib should be used with caution in patients with risk factors for gastrointestinal perforation, including history of diverticulitis, metastases to the gastrointestinal tract and concomitant use of medicinal products with a recognised risk of gastrointestinal perforation.
Croatian: Liječenje trametinibom kao monoterapijom ili u kombinaciji s dabrafenibom treba primjenjivati uz oprez u bolesnika s rizičnim faktorima za gastrointestinalnu perforaciju, uključujući divertikulitis u anamnezi, metastaze u gastrointestinalnom sustavu i istodobnu primjenu lijekova s prepoznatim rizikom od gastrointestinalne perforacije.
English: For the primary endpoint of investigator-assessed ORR, the ORR in the first-line population was 61.1% (95% CI, 43.5%, 76.9%) and in the previously-treated population was 66.7% (95% CI, 52.9%, 78.6%).
Croatian: Za ORR kao primarnu mjeru ishoda prema procjeni ispitivača, ORR u populaciji na prvoj liniji terapije bio je 61,1% (95% CI, 43,5%, 76,9%), a u prethodno liječenoj populaciji bio je 66,7% (95% CI, 52,9%, 78,6%).
English: Chemotherapy (n=108)
Croatian: Kemoterapija (n=108)
English: If the LVEF recovers, treatment with trametinib may be restarted, but the dose should be reduced by one dose level with careful monitoring (see section 4.4).
Croatian: Ako se LVEF oporavi, liječenje trametinibom može se ponovno započeti, ali dozu treba smanjiti za jednu razinu, a bolesnika pomno nadzirati (vidjeti dio 4.4).
English: • Inflammation of hair follicles in the skin
Croatian: • upala folikula dlaka u koži
English: • Breakdown of muscle which can cause muscle pain and kidney damage (rhabdomyolysis)
Croatian: • razgradnja mišića koja može izazvati bol u mišićima i oštećenje bubrega (rabdomioliza)
English: Pyrexia has been reported in clinical trials with trametinib as monotherapy and in combination with dabrafenib; however, the incidence and severity of pyrexia are increased with the combination therapy.
Croatian: Pireksija je zabilježena u kliničkim ispitivanjima s trametinibom kao monoterapijom i u kombinaciji s dabrafenibom; međutim, incidencija i težina pireksije povećavaju se s kombiniranom terapijom.
English: No studies have been conducted to investigate the pharmacokinetics of trametinib in paediatric patients.
Croatian: Nisu provedena ispitivanja kojima bi se procijenila farmakokinetika trametiniba u pedijatrijskih bolesnika.
English: In clinical trials with the combination of trametinib and dabrafenib 11 patients reported trametinib overdose (4 mg); no SAEs were reported.
Croatian: U kliničkim ispitivanjima s kombinacijom trametiniba i dabrafeniba 11 bolesnika prijavilo je predoziranje trametinibom (4 mg); nije bio prijavljen nijedan ozbiljan štetni događaj.
English: Administration of a single dose of trametinib with a high-fat, high-calorie meal resulted in a 70% and 10% decrease in Cmax and AUC, respectively compared to fasted conditions (see sections 4.2 and 4.5).
Croatian: Primjena jedne doze trametiniba uz visokokaloričan obrok, s visokim udjelom masti smanjila je Cmax za 70%, a AUC za 10%, u odnosu na primjenu natašte (vidjeti dijelove 4.2 i 4.5).
English: Trametinib was phototoxic in an in vitro mouse fibroblast 3T3 Neutral Red Uptake (NRU) assay at significantly higher concentrations than clinical exposures (IC50 at 2.92 µg/ml, ≥130 times the clinical exposure based on Cmax), indicating that there is low risk for phototoxicity to patients taking trametinib.
Croatian: Neutral Red Uptake) testu fototoksičnosti na fibroblastima miševa, pri koncentracijama značajno višim od kliničkih izloženosti (IC50 pri 2.92 g/ml, ≥ 130 puta kliničke izloženosti na temelju Cmax), što upućuje na nizak rizik za fototoksičnost u bolesnika koji uzimaju trametinib.
English: Based on in vitro and in vivo data, trametinib is unlikely to significantly affect the pharmacokinetics of other medicinal products via interaction with CYP enzymes or transporters (see section 5.2).
Croatian: In vitro i in vivo podaci pokazuju da nije vjerojatno da bi trametinib mogao značajno utjecati na farmakokinetiku drugih lijekova putem interakcija s CYP enzimima ili prijenosnicima (vidjeti dio 5.2).
English: In patients with BRAF and NRAS mutation positive melanoma, administration of trametinib resulted in dose-dependent changes in tumour biomarkers including inhibition of phosphorylated ERK, inhibition of Ki67 (a marker of cell proliferation), and increases in p27 (a marker of apoptosis).
Croatian: U bolesnika s melanomom pozitivnim na BRAF i NSAR mutacije, primjena trametiniba izazvala je o dozi ovisne promjene tumorskih biokemijskih biljega, uključujući inhibiciju fosforiliziranog ERK, inhibiciju Ki67 (biljega stanične proliferacije) i povećanje razine p27 (biljega apoptoze).
English: ITT = Intent to Treat; PFS = Progression-free survival; CI = confidence interval.
Croatian: Progression-free survival) = preživljenje bez progresije bolesti; CI (engl. confidence interval) = interval pouzdanosti.
English: Table 4 Adverse reactions reported in the integrated safety population of trametinib monotherapy (n=329)
Croatian: Tablica 4 Nuspojave zabilježene u objedinjenoj populaciji u kojoj se ispitivala sigurnost monoterapije trametinibom (n=329)
English: If treatment-related toxicities occur when trametinib is used in combination with dabrafenib, then both treatments should be simultaneously dose reduced, interrupted or discontinued.
Croatian: Ako se pojave toksičnosti povezane s terapijom kada se trametinib primjenjuje u kombinaciji s dabrafenibom, u obje je terapije istovremeno potrebno smanjiti dozu, privremeno je prekinuti ili trajno obustaviti.
English: The bottle contains a desiccant.
Croatian: Bočica sadrži sredstvo za sušenje.
English: Mekinist in combination with dabrafenib is also used to treat a type of lung cancer called non-small cell lung cancer (NSCLC).
Croatian: Mekinist u kombinaciji s dabrafenibom koristi se i za liječenje vrste raka pluća koji se zove rak pluća nemalih stanica (NSCLC).
English: • Decreased red blood cells (anaemia), abnormal test related to creatine phosphokinase, an enzyme found mainly in heart, brain, and skeletal muscle
Croatian: • smanjen broj crvenih krvnih stanica (anemija), odstupanja u nalazima vrijednosti kreatin fosfokinaze, enzima koji se uglavnom nalazi u srcu, mozgu i mišićima kostura
English: 7 film-coated tablets 30 film-coated tablets
Croatian: Filmom obložena tableta 7 filmom obloženih tableta 30 filmom obloženih tableta
English: * The intensity of clinical adverse reactions graded by the Common Terminology Criteria for Adverse Events v4.0 (CTC-AE)
Croatian: Common Terminology Criteria for Adverse Events, CTC-AE, v4.0)
English: The trametinib 2 mg once daily and dabrafenib 150 mg twice daily combination demonstrated limited clinical activity in patients who had progressed on a BRAF inhibitor (see section 4.4).
Croatian: Kombinacija trametiniba 2 mg jedanput na dan i dabrafeniba 150 mg dvaput na dan pokazala je ograničenu kliničku aktivnost u bolesnika u kojih je došlo do progresije tijekom terapije BRAF inhibitorom (vidjeti dio 4.4).
English: Trametinib was not genotoxic in studies evaluating reverse mutations in bacteria, chromosomal aberrations in mammalian cells and micronuclei in the bone marrow of rats.
Croatian: Trametinib nije bio genotoksičan u ispitivanjima u kojima su se procjenjivale reverzne mutacije bakterija, kromosomske aberacije u stanicama sisavaca i mikronukleusi u koštanoj srži štakora.
English: As trametinib is metabolised predominantly via deacetylation mediated by hydrolytic enzymes (e.g. carboxyl-esterases), its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions (see section 5.2).
Croatian: Budući da se trametinib metabolizira prvenstveno deacetilacijom u kojoj posreduju hidrolitički enzimi (npr. karboksilesteraze), nije vjerojatno da bi drugi lijekovi mogli utjecati na njegovu farmakokinetiku putem metaboličkih interakcija (vidjeti dio 5.2).
English: In the integrated safety population of trametinib in combination with dabrafenib, decreased LVEF has been reported in 6% (65/1076) of patients, with most cases being asymptomatic and reversible.
Croatian: U objedinjenoj populaciji u kojoj se ispitivala sigurnost trametiniba u kombinaciji s dabrafenibom, smanjeni LVEF zabilježen je u 6% (65/1076) bolesnika pri čemu je većina slučajeva bila asimptomatska i reverzibilna.
English: For additional information on warnings and precautions associated with dabrafenib treatment, please refer to the dabrafenib SmPC.
Croatian: Za dodatne informacije o upozorenjima i mjerama opreza povezanima s liječenjem dabrafenibom, pogledajte Sažetak opisa svojstava lijeka za dabrafenib.
English: Baseline characteristics were balanced between treatment groups in the primary efficacy population and the ITT population.
Croatian: Početne značajke bile su ravnomjerno raspoređene među liječenim skupinama u primarnoj populaciji za ispitivanje djelotvornosti i ITT populaciji.
English: NE2 (8.3, NE) NE (6.9, NE)
Croatian: (8,3; NO) NO (6,9; NO)
English: Permanently discontinue trametinib.
Croatian: Trajno obustaviti primjenu trametiniba.
English: Taking Mekinist or the combination of Mekinist and dabrafenib may increase the risk of developing holes in the gut wall.
Croatian: Uzimanje Mekinista ili kombinacije Mekinista i dabrafeniba može povećati rizik od nastanka proboja u stijenci crijeva.
English: How to take Mekinist
Croatian: Kako uzimati Mekinist
English: 3) The following adverse reaction has occurred in MEK116513 and BRF115532 but not in MEK115306 and BRF113928: rhabdomyolysis (uncommon) b Cutaneous squamous cell carcinoma (cu SCC): SCC, SCC of the skin, SCC in situ (Bowen's disease) and keratoacanthoma c Papilloma, skin papilloma d
Croatian: 3) Sljedeća nuspojava se pojavila u MEK116513 i BRF115532, ali ne u MEK115306 i BRF113928: rabdomioliza (manje često) b Planocelularni karcinom kože (cu SCC): SCC, SCC kože, SCC in situ (Bowenova bolest) i keratoakantom c
English: Effects of trametinib on drug-metabolising enzymes and transporters: In vitro and in vivo data suggest that trametinib is unlikely to affect the pharmacokinetics of other medicinal products.
Croatian: Učinci trametiniba na enzime i prijenosnike koji metaboliziraju lijekove: In vitro i in vivo podaci pokazuju da nije vjerojatno da bi trametinib mogao utjecati na farmakokinetiku drugih lijekova.
English: Although trametinib exposure is unlikely to be affected by inhibition of BSEP, increased levels of trametinib upon strong inhibition of hepatic P-gp cannot be excluded (see section 4.5).
Croatian: Iako inhibicija BSEP-a vjerojatno ne utječe na izloženost trametinibu, povišene razine trametiniba kod jake inhibicije jetrenog P-gp-a ne mogu se isključiti (vidjeti dio 4.5).
English: The mean trametinib concentrations observed following repeat dose administration of 2 mg once daily exceeds the preclinical target concentration over the 24-hr dosing interval, thereby providing sustained inhibition of the MEK pathway.
Croatian: Srednja vrijednost koncentracija trametiniba primijećena nakon ponovljene primjene doze od 2 mg jedanput na dan premašuje ciljnu koncentraciju tijekom 24-satnog intervala doziranja u pretkliničkim ispitivanjima, čime omogućuju održanu inhibiciju MEK signalnog puta.
English: Unopened bottle
Croatian: Neotvorena bočica 2 godine
English: Fatal intracranial haemorrhages occurred in the integrated safety population of trametinib in combination with dabrafenib in <1% (8/1076) of patients.
Croatian: Smrtonosna intrakranijalna krvarenja u objedinjenoj populaciji u kojoj se ispitivala sigurnost trametiniba u kombinaciji s dabrafenibom javila su se u <1% (8/1076) bolesnika.
English: • passing blood in the stools or passing black stools
Croatian: • krv u stolici ili crnu stolicu
English: When trametinib and dabrafenib are taken in combination, the once-daily dose of trametinib should be taken at the same time each day with either the morning dose or the evening dose of dabrafenib.
Croatian: Kada se trametinib i dabrafenib uzimaju u kombinaciji potrebno je uzeti dozu trametiniba jedanput na dan u isto vrijeme svakoga dana bilo s jutarnjom ili s večernjom dozom dabrafeniba.
English: In repeat-dose studies the effects seen after trametinib exposure are found mainly in the skin, gastrointestinal tract, haematological system, bone and liver.
Croatian: U ispitivanjima s primjenom ponovljenih doza, učinci koji nastaju kao posljedica izloženosti trametinibu primijećeni su uglavnom na koži, u probavnom sustavu, hematološkom sustavu, na kostima i u jetri.
English: In more severe cases hospitalisation, interruption or permanent discontinuation of trametinib or trametinib and dabrafenib combination was required.
Croatian: U težim slučajevima hospitalizacije bio je potreban privremeni ili trajni prekid terapije trametinibom ili kombinacijom trametiniba i dabrafeniba.
English: Tell your doctor if you have any lung or breathing problems, including difficulty in breathing often accompanied by a dry cough, shortness of breath and fatigue.
Croatian: Obavijestite svog liječnika ako imate ikakve tegobe s plućima ili disanjem, uključujući poteškoće s disanjem koje su često popraćene suhim kašljem, nedostatkom zraka i umorom.
English: In adult rats, mineralisation of multiple organs was associated with increased serum phosphorus and was closely associated with necrosis in heart, liver and kidney and haemorrhage in the lung at exposures comparable to the human clinical exposure.
Croatian: U odraslih štakora se mineralizacija većeg broja organa povezivala s povišenom razinom fosfora u serumu te je bila usko povezana s nekrozom srca, jetre i bubrega te plućnim krvarenjem pri izloženostima koje su bile usporedive s kliničkom izloženošću u ljudi.
English: The median time to onset of the first occurrence of haemorrhagic events for the combination of trametinib and dabrafenib was 94 days in the melanoma Phase III studies and 75 days in the NSCLC study for the patients who had received prior anti-cancer therapy.
Croatian: Medijan vremena do prve pojave krvarenja bio je 94 dana za kombinaciju trametiniba i dabrafeniba u ispitivanjima faze III za melanom i 75 dana u ispitivanju za NSCLC u bolesnika koji su primili prethodnu antitumorsku terapiju.
English: Your doctor may advise an eye examination before you take Mekinist and while you are taking it.
Croatian: Vaš liječnik će Vam možda savjetovati da napravite pregled očiju prije početka liječenja lijekom Mekinist i za vrijeme njegove primjene.
English: Do not take Mekinist after the expiry date (EXP) which is stated on the bottle label and carton.
Croatian: Mekinist se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na naljepnici bočice i kutiji iza oznake „EXP“.
English: Resume trametinib at a lower dose (reduced by 0.5 mg) or discontinue trametinib in patients taking trametinib 1 mg daily.
Croatian: Nastaviti liječenje nižom dozom trametiniba (smanjenom za 0,5 mg) ili obustaviti njegovu primjenu u bolesnika koji primaju dozu od 1 mg na dan.
English: Most subjects had LDH ≤ULN (67%), ECOG performance status of 0 (70%), and visceral disease (78%) at baseline.
Croatian: Većina ispitanika imala je LDH ≤ GGN (67%), funkcionalni status ECOG 0 (70%) i visceralnu bolest (78%) na početku.
English: Following single and repeated doses of trametinib, trametinib as parent is the main circulating component in plasma.
Croatian: Nakon jednokratnog i ponovljenog doziranja trametiniba, glavni cirkulirajući spoj u plazmi je trametinib u obliku ishodišne tvari.
English: If RPED is diagnosed, the dose modification schedule in Table 3 should be followed (see section 4.2); if uveitis is diagnosed, please refer to dabrafenib SmPC section 4.4.
Croatian: Ako se dijagnosticira RPED, potrebno je slijediti korake za prilagodbu doze navedene u tablici 3 (vidjeti dio 4.2); ako se dijagnosticira uveitis, pogledajte Sažetak opisa svojstava lijeka za dabrafenib, dio 4.4.
English: Dose modifications are not recommended for adverse reactions of cutaneous squamous cell carcinoma (cuSCC) or new primary melanoma (see dabrafenib SmPC for further details).
Croatian: Prilagodbe doze ne preporučuje se kod nuspojava u obliku planocelularnog karcinoma kože (engl. cutaneous squamous cell carcinoma, cuSCC) ili novog primarnog melanoma (vidjeti Sažetak opisa svojstava lijeka za dabrafenib za dodatne pojedinosti).
English: In rats, hepatocellular necrosis and transaminase elevations were seen after 8 weeks at ≥0.062 mg/kg/day (approximately 0.8 times human clinical exposure based on AUC).
Croatian: U štakora su primijećene hepatocelularna nekroza i povišene vrijednosti transaminaza nakon 8 tjedana primjene doze ≥ 0,062 mg/kg/dan (približno 0,8 puta kliničke izloženosti u ljudi na temelju AUC-a).
English: Signs or symptoms of rhabdomyolysis should warrant an appropriate clinical evaluation and treatment as indicated (see section 4.4).
Croatian: Znakovi ili simptomi rabdomiolize zahtijevaju odgovarajuću kliničku procjenu i liječenje kako je indicirano (vidjeti dio 4.4).
English: Trametinib monotherapy has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy (see section 5.1).
Croatian: Trametinib kao monoterapija nije pokazao kliničku aktivnost u bolesnika u kojih je došlo do progresije tijekom prethodne terapije BRAF inhibitorom (vidjeti dio 5.1).
English: If the missed dose is more than12 hours late, skip that dose and take your next dose at the usual time.
Croatian: Ako je od propuštene doze prošlo više od 12 sati, preskočite tu dozu i uzmite sljedeću dozu u uobičajeno vrijeme.
English: P value f
Croatian: P vrijednost f
English: Left ventricular ejection fraction (LVEF) reduction/Left ventricular dysfunction Trametinib should be interrupted in patients who have an asymptomatic, absolute decrease of >10% in LVEF compared to baseline and the ejection fraction is below the institution's lower limit of normal (LLN) (see section 4.4).
Croatian: Smanjenje ejekcijske frakcije lijeve klijetke/disfunkcija lijeve klijetke Liječenje trametinibom treba prekinuti u bolesnika koji imaju asimptomatsko, apsolutno smanjenje ejekcijske frakcije lijeve klijetke (LVEF) za > 10% u odnosu na početnu vrijednost i u kojih je vrijednost ejekcijske frakcije ispod donje granice normale (DGN) za određenu ustanovu (vidjeti dio 4.4).
English: Trametinib plasma IV clearance is 3.21 L/hr.
Croatian: Klirens trametiniba iz plazme nakon intravenske primjene iznosi 3,21 l/h.
English: These melanomas are usually removed by surgery and treatment with Mekinist and dabrafenib can be continued without interruption.
Croatian: Ti se melanomi obično uklanjaju kirurškim zahvatom, a liječenje Mekinistom i dabrafenibom može se nastaviti bez prekida.
English: When an individual's adverse reactions are under effective management, dose re-escalation following the same dosing steps as de-escalation may be considered.
Croatian: Ako se bolesnikove nuspojave uspješno liječe, može se razmotriti ponovno povećanje doze prema istim koracima za doziranje kao i kod smanjenja.
English: Trametinib should be permanently discontinued in patients with Grade 3 or 4 left ventricular cardiac dysfunction or clinically significant LVEF reduction which does not recover within 4 weeks (see section 4.4).
Croatian: Liječenje trametinibom treba trajno obustaviti u bolesnika koji imaju disfunkciju lijeve srčane klijetke 3. ili 4. stupnja ili ako imaju klinički značajno smanjen LVEF koji se ne oporavi unutar 4 tjedna (vidjeti dio 4.4).
English: NR=not reached
Croatian: ND=nije dostignuto
English: Blood pressure should be measured at baseline and monitored during treatment with trametinib, with control of hypertension by standard therapy as appropriate.
Croatian: Krvni tlak se mora izmjeriti na početku i nadzirati tijekom liječenja trametinibom, a hipertenziju po potrebi kontrolirati standardnom terapijom.
English: Table 5 Adverse reactions reported in the integrated safety population of trametinib in combination with dabrafenib in the studies MEK115306, MEK116513
Croatian: Tablica 5 Nuspojave zabilježene u objedinjenoj populaciji u kojoj se ispitivala sigurnost za trametinib u kombinaciji s dabrafenibom u ispitivanjima MEK115306, MEK116513
English: If trametinib is being used in combination with dabrafenib then therapy with dabrafenib may be continued at the same dose.
Croatian: Ako se trametinib koristi u kombinaciji s dabrafenibom, terapija dabrafenibom može se nastaviti u istoj dozi.
English: Patients ≥65 years were more likely to experience ARs leading to permanent discontinuation of medicinal product, dose reduction and dose interruption than those <65 years.
Croatian: ≥ 65 godina imali su veću vjerojatnost za nastup nuspojava koje su zahtijevale trajnu obustavu lijeka, smanjenje doze ili privremeni prekid liječenja nego oni mlađi od 65 godina.
English: Mekinist, or the combination with dabrafenib, can cause problems with your liver which may develop into serious conditions such as hepatitis and liver failure, which may be fatal.
Croatian: Mekinist, ili kombinacija s dabrafenibom, može uzrokovati tegobe s jetrom koji se mogu razviti u ozbiljne bolesti kao što su hepatitis i zatajenje jetre, koje mogu biti smrtonosne.
English: Trametinib inhibits activation of MEK by BRAF and inhibits MEK kinase activity.
Croatian: Trametinib inhibira aktivaciju MEK proteina koju uzrokuje BRAF gen te inhibira aktivnost MEK kinaze.
English: High-density polyethylene (HDPE) bottle with child-resistant polypropylene closure.
Croatian: Bočica načinjena od polietilena visoke gustoće (HDPE) s polipropilenskim sigurnosnim zatvaračem za djecu.
English: Do not change your dose or stop Mekinist or dabrafenib unless your doctor, nurse or pharmacist tells you to.
Croatian: Ne mijenjajte dozu i ne prekidajte uzimanje Mekinista ili dabrafeniba ako Vam to ne kažu Vaš liječnik, medicinska sestra ili ljekarnik.
English: • Nail disorders such as nail bed changes, nail pain, infection and swelling of the cuticles
Croatian: • poremećaji noktiju, poput promjena na ležištu nokta, boli nokta, infekcije i oticanja zanoktica
English: Others may develop a type of skin cancer called basal cell carcinoma (BCC).
Croatian: U drugih se može razviti vrsta raka kože koji se zove karcinom bazalnih stanica (engl. basal cell carcinoma, BCC).
English: In patients receiving trametinib in combination with dabrafenib, there have been occasional reports of acute, severe left ventricular dysfunction due to myocarditis.
Croatian: U bolesnika koji su primali trametinib u kombinaciji s dabrafenibom bilo je povremenih prijava akutne, teške disfunkcije lijeve klijetke zbog miokarditisa.
English: Blood pressure should be measured at baseline and monitored during treatment, with control of hypertension by standard therapy as appropriate (see section 4.4).
Croatian: Krvni tlak treba izmjeriti na početku i nadzirati tijekom liječenja, a hipertenziju po potrebi kontrolirati standardnom terapijom (vidjeti dio 4.4).
English: When you take Mekinist and dabrafenib together you may get any of the side effects given in the lists above, although the frequency may change (increase or decrease).
Croatian: Kada uzimate zajedno Mekinist i dabrafenib mogli biste dobiti bilo koju od nuspojava navedenih na prethodnim popisima, iako bi njihova učestalost mogla biti drugačija (veća ili manja).