FrancophonIA/ELRC3.0 huggingface dataset:
English: • the contraindications of pregnancy and breastfeeding, genital bleeding of unknown aetiology or for reasons other than uterine fibroids, and uterine, cervical, ovarian or breast cancer as well as underlying hepatic disorder.
Croatian: • Kontraindikacije: trudnoću i dojenje, krvarenje iz rodnice nepoznate etiologije ili iz razloga koji nisu fibroidi maternice te karcinom maternice, cerviksa, jajnika ili dojke, kao i podležeći poremećaj jetre.
English: - Herbal remedies containing St John's wort (Hypericum perforatum) used for depression or anxiety.
Croatian: - Biljni lijekovi koji uključuju gospinu travu (Hypericum perforatum) koja se koristi za liječenje depresije ili tjeskobe.
English: No pharmacokinetic studies with ulipristal acetate have been performed in women with impaired renal or hepatic function.
Croatian: Nisu provedena farmakokinetička ispitivanja s ulipristalacetatom u žena s oštećenom bubrežnom ili jetrenom funkcijom.
English: Should the excessive bleeding persist, patients should notify their physician.
Croatian: Ako je obilno krvarenje i dalje prisutno, bolesnica treba obavijestiti svog liječnika.
English: Ulipristal acetate and its active mono-N-demethylated metabolite are excreted in breast milk with a mean AUCt milk/plasma ratio of 0.74 ± 0.32 for ulipristal acetate.
Croatian: Ulipristalacetat i njegov aktivni mono-N-demetilirani metabolit izlučuju se u majčino mlijeko sa srednjom vrijednosti omjera za AUCt mlijeko/plazma od 0,74 ± 0,32 za ulipristalacetat.
English: The direct action on the endometrium results in class-specific changes in histology termed PAEC.
Croatian: Izravno djelovanje na endometrij rezultira u klasno specifičnim histološkim promjenama koje se nazivaju PAEC.
English: If you have been prescribed several courses of Esmya 3-month treatment, you should start each course at the earliest during the second menstrual period following the previous treatment completion.
Croatian: Ako Vam je propisano nekoliko ciklusa 3-mjesečnog liječenja lijekom Esmya, svaki ciklus trebate početi najranije tijekom razdoblja druge menstruacije koja nastupi nakon završetka prethodnog ciklusa liječenja.
English: Among these 1,053 women, the safety of repeated intermittent treatment courses (each limited to 3 months) has been evaluated in 551 women with uterine fibroids treated with 5 or 10 mg ulipristal acetate in two phase III studies (including 446 women exposed to four intermittent treatment courses of whom 53 were exposed to eight intermittent treatment courses) and demonstrated a similar safety profile to that observed for one treatment course.
Croatian: Od tih 1053 žena, sigurnost ponovljenih intermitentnih ciklusa liječenja (od kojih je svaki ograničen na 3 mjeseca) procijenjena je u 551 žene s fibroidima maternice koje su liječene s 5 ili 10 mg ulipristalacetata u dva ispitivanja faze III (uključujući 446 žena izloženih četirima intermitentnim ciklusima liječenja od kojih su 53 žene bile izložene osam intermitentnih ciklusa liječenja) i pokazala je sigurnosni profil sličan onome uočenom kod jednog ciklusa liječenja.
English: Ulipristal acetate is highly bound (>98%) to plasma proteins, including albumin, alpha-l-acid glycoprotein, high density lipoprotein and low density lipoprotein.
Croatian: Ulipristalacetat se znatno veže (> 98%) na proteine plazme, uključujući albumin, alfa-1-kiseli glikoprotein te na lipoproteine visoke i niske gustoće.
English: In vitro data indicate that this is predominantly mediated by the cytochrome P450 3A4 isoform (CYP3A4).
Croatian: Podaci iz in vitro ispitivanja pokazuju da je ta pretvorba posredovana uglavnom izooblikom citokroma P450 3A4 (CYP3A4).
English: Marketing Authorisation Holder Gedeon Richter Plc.
Croatian: Nositelj odobrenja za stavljanje lijeka u promet Gedeon Richter Plc.
English: Potential for ulipristal acetate to affect other medicinal products:
Croatian: Mogućnost utjecaja ulipristalacetata na djelovanje drugih lijekova:
English: When comparing repeated treatment courses, overall adverse reactions rate was less frequent in subsequent treatment courses than during the first one and each adverse reaction was less frequent or remained in the same frequency category (except for dyspepsia which was classified as uncommon in treatment course 3 based on one patient occurence).
Croatian: Usporedba ponovljenih ciklusa liječenja pokazuje da je sveukupna učestalost nuspojava bila manja u slučaju uzastopnih ciklusa liječenja nego u prvom ciklusu liječenja, a svaka je nuspojava imala manju učestalost ili je ostala u istoj kategoriji učestalosti (osim dispepsije koja je razvrstana kao manje česta u 3. ciklusu liječenja na temelju pojave u jedne bolesnice).
English: Due to the CYP-mediated metabolism, hepatic impairment is expected to alter the elimination of ulipristal acetate, resulting in increased exposure.
Croatian: Zbog metabolizma posredovanog enzimima CYP očekuje se da će oštećenje jetrene funkcije izmijeniti eliminaciju ulipristalacetata što može uzrokovati povećanu izloženost lijeku.
English: For further treatment courses, liver function must be tested once before each new treatment course and when clinically indicated.
Croatian: Za daljnje cikluse liječenja testovi jetrene funkcije se moraju napraviti jednom prije svakog novog ciklusa liječenja i kad je klinički indicirano.
English: Thus administration of ulipristal acetate is unlikely to alter the clearance of medicinal products that are metabolised by these enzymes.
Croatian: Stoga nije vjerojatno da će primjena ulipristalacetata promijeniti klirens lijekova koje metaboliziraju ovi enzimi.
English: In study 2, the reduction in menstrual blood loss was comparable for the patients treated with ulipristal acetate and the gonadotrophin releasing hormone-agonist (leuprorelin).
Croatian: U ispitivanju 2, smanjenje količine menstrualne krvi bilo je podjednako u bolesnica liječenih ulipristalacetatom i onih liječenih agonistom gonadotropin oslobađajućeg hormona (leuprorelin).
English: Uterine haemorrhage
Croatian: • tamnu mokraću
English: Experience with ulipristal acetate overdose is limited.
Croatian: Iskustvo s predoziranjem ulipristalacetatom je ograničeno.
English: What Esmya contains - The active substance is ulipristal acetate.
Croatian: Što Esmya sadrži - Djelatna tvar je ulipristalacetat.
English: The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent updates of the RMP.
Croatian: Nositelj odobrenja obavljat će zadane farmakovigilancijske aktivnosti i intervencije, detaljno objašnjene u dogovorenom Planu upravljanja rizikom (RMP), koji se nalazi u Modulu 1.8.2
English: White to off-white, round biconvex tablet of 7 mm engraved with “ES5” on one face.
Croatian: Bijela do bjelkasta, okrugla bikonveksna tableta promjera 7 mm s utisnutim znakom “ES5” na jednoj strani.
English: Myoma size reduction was generally maintained during this follow-up period in patients originally treated with ulipristal acetate but some re-growth occurred in patients treated with leuprorelin.
Croatian: Smanjenje veličine mioma općenito se održalo tijekom ovog razdoblja praćenja u bolesnica koje su početno liječene ulipristalacetatom, ali neki su miomi opet počeli rasti u bolesnica liječenih leuprorelinom.
English: A majority of women taking a therapeutic dose of ulipristal acetate have anovulation, however, the level of fertility while taking multiple doses of ulipristal acetate has not been studied.
Croatian: Većina žena koja uzima terapijsku dozu ulipristalacetata ne ovulira, međutim, razina plodnosti za vrijeme uzimanja višestrukih doza ulipristalacetata nije proučavana.
English: Esmya can cause side effects although not everybody gets them.
Croatian: Lijek Esmya može uzrokovati nuspojave, iako se one neće javiti kod svakoga.
English: Patients who develop transaminase levels (ALT or AST) > 3 times the upper limit of normal during treatment should stop treatment and be closely monitored.
Croatian: Bolesnice čije razine transaminaza (ALT ili AST) tijekom liječenja premašuju trostruku vrijednost gornje granice normale moraju prestati uzimati lijek te ih treba pomno pratiti.
English: Adverse reactions during treatment course 1 Very common Common
Croatian: Nuspojave tijekom 1. ciklusa liječenja Vrlo često
English: Drug hypersensitivity symptoms such as generalised oedema, pruritus, rash, swelling face or urticaria were reported by 0.4% of patients in Phase III trials.
Croatian: Simptomi preosjetljivosti na lijek kao što su generalizirani edem, pruritus, osip, oticanje lica ili urtikarija zabilježeni su u 0,4% bolesnica u ispitivanjima faze III.
English: • Educational material for prescribers (gynaecologists) which contains: o Cover letter o SmPC o Physician's guide to prescribing Esmya
Croatian: • Edukacijskog materijala za propisivače (ginekologe) koji sadrži: o Popratno pismo o Sažetak opisa svojstava lijeka o Vodič za liječnika za propisivanje lijeka Esmya
English: Co-administration of moderate or potent CYP3A4 inhibitors and ulipristal acetate is not recommended (see section 4.4).
Croatian: Istovremena primjena umjerenih ili snažnih inhibitora CYP3A4 i ulipristalacetata nije preporučljiva (vidjeti dio 4.4).
English: These were always in favour of ulipristal acetate.
Croatian: Te su razlike uvijek išle u prilog ulipristalacetata.
English: Median change in myoma volume from baseline a Treatment course 2 assessment corresponds to Treatment course 2 plus one menstrual bleeding.
Croatian: Medijan promjene u volumenu mioma u odnosu na početne vrijednosti a Procjena 2. ciklusa liječenja odgovara 2. ciklusu liječenja plus jedno menstrualno krvarenje.
English: Depending on the result of these tests your doctor will decide if treatment with Esmya is suitable for you.
Croatian: Ovisno o rezultatima tih pretraga, Vaš liječnik odlučit će je li liječenje lijekom Esmya prikladno za Vas.
English: Depending on the result of these tests, the doctor will decide if treatment with Esmya is suitable for you.
Croatian: Ovisno o rezultatima tih pretraga, liječnik će odlučiti je li liječenje lijekom Esmya prikladno za Vas.
English: Treatment must not be initiated if transaminases (alanine transaminase (ALT) or aspartate aminotransferase (AST)) exceed 2 x ULN (isolated or in combination with bilirubin >2 x ULN).
Croatian: Liječenje se ne smije započeti ako transaminaze (alanin transaminaza (ALT) ili aspartat aminotransferaza (AST)) premašuju dvostruku vrijednost gornje granice normale (GGN) (izolirano ili u kombinaciji s bilirubinom >2 x GGN).
English: Do not use this medicine after the expiry date which is stated on the carton and on the blister after EXP.
Croatian: Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na kutiji i blisteru iza „Rok valjanosti“.
English: Bleeding pattern
Croatian: Uzorak krvarenja
English: Treatments should only be initiated when menstruation has occurred: - The first treatment course should start during the first week of menstruation.
Croatian: Liječenje treba početi tek kada nastupi menstruacija: - Prvi ciklus liječenja treba početi tijekom prvog tjedna menstruacije.
English: Although a majority of women taking a therapeutic dose of ulipristal acetate have anovulation, a non hormonal contraceptive method is recommended during treatment (see sections 4.4 and 4.5).
Croatian: Iako većina žena koja uzima terapijsku dozu ulipristalacetata ne ovulira, tijekom liječenja se preporučuje nehormonska metoda kontracepcije (vidjeti dijelove 4.4 i 4.5).
English: Menstrual periods generally return within 4 weeks after the end of each treatment course.
Croatian: Menstrualni ciklus se obično uspostavlja unutar 4 tjedna nakon završetka pojedinog ciklusa liječenja.
English: • detailed recommendations for management of endometrial thickening.
Croatian: • detaljne preporuke za liječenje zadebljanja endometrija
English: If hysterectomy or endometrial biopsy specimens are sent for histology, then the pathologist should be informed that the patient has taken ulipristal acetate (see sections 4.4 and 5.1).
Croatian: Pri histološkoj analizi bioptata endometrija ili tkiva maternice nakon histerektomije, potrebno je patologu napomenuti da je bolesnica uzimala ulipristalacetat (vidjeti dijelove 4.4 i 5.1).
English: The safety of ulipristal acetate has been evaluated in 1,053 women with uterine fibroids treated with 5 mg or 10 mg ulipristal acetate during Phase III studies.
Croatian: Sigurnost ulipristalacetata procijenjena je u 1053 žene s fibroidima maternice koje su liječene s 5 mg ili 10 mg ulipristalacetata tijekom ispitivanja faze III.
English: Ulipristal acetate is readily converted to its mono-N-demethylated and subsequently to its di-N-demethylated metabolites.
Croatian: Ulipristalacetat se brzo pretvara u svoj mono-N-demetilirani metabolit te naknadno u svoje di-Ndemetilirane metabolite.
English: Ulipristal acetate exerts a direct action on fibroids reducing their size through inhibition of cell proliferation and induction of apoptosis.
Croatian: Ulipristalacetat ima izravni učinak na fibroide smanjujući njihovu veličinu putem inhibicije proliferacije stanica i indukcije apoptoze.
English: - Certain medicines used to treat depression (e.g. nefazodone).
Croatian: - Određeni lijekovi koji se koriste za liječenje depresije (primjerice nefazodon).
English: For further treatment courses, your liver will be checked once before each new treatment course and if you experience any of the symptoms described below.
Croatian: Vaša jetra provjeravat će se jednom prije svakog novog ciklusa liječenja i ako osjetite bilo koji od simptoma navedenih u nastavku.
English: It is therefore recommended that co-administration of ulipristal acetate and P-gp substrates (e.g. dabigatran etexilate, digoxin, fexofenadine) should be separated in time by at least 1.5 hours.
Croatian: Stoga se preporučuje odvojiti uzimanje ulipristalacetata i supstrata P-gp-a (npr. dabigatran-etaksilat, dikosin, feksofenadin) za barem 1,5 sat.
English: If you forget to take Esmya
Croatian: Ako ste zaboravili uzeti Esmyu
English: In vivo results show that ulipristal acetate (administered as a single 10 mg tablet) 1.5 hour before administration of the P-gP substrate fexofenadine (60 mg) has no clinically relevant effects on the pharmacokinetic of fexofenadine.
Croatian: Podaci iz in vivo istraživanja pokazuju kako uzimanje ulipristalacetata (u jednoj tableti od 10 mg) 1,5 sat prije uzimanja supstrata P-gp-a feksofenadina (60 mg) nema klinički relevantnih učinaka na farmakokinetičko djelovanje feksofenadina.
English: Ulipristal acetate has a specific pharmacodynamic action on the endometrium: Changes in the histology of the endometrium may be observed in patients treated with ulipristal acetate.
Croatian: Ulipristalacetat ima specifično farmakodinamičkodjelovanje na endometrij: U bolesnica liječenih ulipristalacetatom mogu se primijetiti histološke promjene endometrija.
English: • inform the patients on the need to warn their physicians on any liver problems they may have.
Croatian: • informirati bolesnice da moraju upozoriti svoje liječnike ako imaju bilo kakvih problema s jetrom.
English: Endometrium
Croatian: Endometrij
English: This includes annual ultrasound to be performed after resumption of menstruation during off-treatment period.
Croatian: To uključuje godišnji ultrazvučni pregled nakon ponovne pojave menstrualnog krvarenja tijekom razdoblja bez liječenja.
English: Very common (may affect more than 1 in 10 people) side effects: - reduction or absence of menstrual bleeding (amenorrhea) - thickening of the lining of the womb (endometrial thickening).
Croatian: Vrlo česte nuspojave (mogu se javiti u više od 1 na 10 osoba): - smanjenje ili odsutnost menstrualnog krvarenja (amenoreja) - zadebljanje stijenke maternice (zadebljanje endometrija).
English: One tablet contains 5 mg of ulipristal acetate.
Croatian: Jedna tableta sadrži 5 mg ulipristalacetata.
English: The vast majority spontaneously reversed to normal endometrium after resumption of menstruation during the off-treatment period.
Croatian: U većini slučajeva endometrij se spontano vratio na normalnu debljinu nakon ponovne pojave menstrualnog krvarenja tijekom razdoblja bez liječenja.
English: In the first 3-month treament course of the two long term Phase III trials, the frequency was 5.3% and 5.8% for ulipristal acetate, respectively.
Croatian: U prvom 3-mjesečnom ciklusu liječenja u dva dugotrajna ispitivanja faze III učestalost za ulipristalacetat bila je 5,3% odnosno 5,8%.
English: Adverse reactions listed below are classified according to frequency and system organ class.
Croatian: Nuspojave navedene u nastavku klasificirane su prema učestalosti i organskim sustavima.
English: If during the treatment you experience any liver related signs such as feeling of being sick (nausea or vomiting), fatigue, severe tiredness, jaundice (yellowing of the eyes or skin), dark urine, itching or upper stomach ache, you should stop treatment and immediately contact a doctor, who will check the functioning of your liver and decide if you can continue the treatment.
Croatian: Ako tijekom liječenja primijetite bilo kakve znakove koji mogu biti povezani s jetrom kao što su mučnina ili povraćanje, umor, teški zamor, žutica (žutilo očiju ili kože), tamna mokraća, svrbež ili bol u gornjem dijelu trbuha, prestanite uzimati lijek i odmah obavijestite liječnika, koji će provjeriti funkciju Vaše jetre i odlučiti možete li nastaviti liječenje.
English: A daily dose of ulipristal acetate 5 mg partially suppresses FSH levels but serum oestradiol levels are maintained in the mid-follicular range in the majority of patients and are similar to levels in patients who received placebo.
Croatian: Dnevna doza ulipristalacetata od 5 mg djelomično potiskuje razine FSH, ali razine serumskog estradiola održane su u srednje folikularnom rasponu u većine bolesnica te su slične razinama u bolesnica koje su primale placebo.
English: Ulipristal acetate has a steroid structure and acts as a selective progesterone receptor modulator with predominantly inhibitory effects on the progesterone receptor.
Croatian: Ulipristalacetat ima steroidnu strukturu i djeluje kao selektivni modulator progesteronskih receptora s prevladavajućim inhibitornim učincima.
English: carbamazepine, oxcarbazepine, primidone).
Croatian: fenobarbital, karbamazepin, okskarbazepin, primidon).
English: nausea or vomiting, severe tiredness, jaundice (yellowing of the eyes or skin), dark urine, itching or upper stomach ache.
Croatian: - mučnina ili povraćanje, teški zamor, žutica (žutilo očiju ili kože), tamna mokraća, svrbež ili bol u gornjem dijelu trbuha.
English: - Re-treatment courses should start at the earliest during the first week of the second menstruation following the previous treatment course completion.
Croatian: - Ponovne cikluse liječenja treba početi najranije tijekom prvog tjedna druge menstruacije koja nastupi nakon završetka prethodnog ciklusa liječenja.
English: Experience with Esmya when several doses are taken at once is limited.
Croatian: Iskustva s višestrukim dozama Esmye uzetim istovremeno su ograničena.
English: Keep the blisters in the outer carton in order to protect from light.
Croatian: Čuvati blistere u vanjskom pakiranju radi zaštite od svjetlosti.
English: Therefore, hormonal contraceptives are not recommended and you should use an alternative reliable barrier contraceptive method, such as a condom, during Esmya treatment.
Croatian: Stoga se hormonski kontraceptivi ne preporučuju te tijekom liječenja lijekom Esmya treba koristiti alternativnu pouzdanu metodu barijerne kontracepcije poput kondoma.
English: In Study 2, a double-dummy method was used to maintain the blind.
Croatian: U ispitivanju 2 koristila se metoda dvostrukog placeba za održavanje stanja slijepog ispitivanja.
English: Concomitant use of progestagen-only pills, a progestagen-releasing intrauterine device or combined oral contraceptive pills is not recommended (see section 4.5).
Croatian: Istovremena primjena pilula koje sadrže samo progesteron, intrauterinih uređaja koji otpuštaju progesteron ili kombiniranih oralnih kontraceptiva se ne preporučuje (vidjeti dio 4.5).
English: In vitro data indicate that ulipristal acetate may be an inhibitor of P-gp at clinically relevant concentrations in the gastrointestinal wall during absorption.
Croatian: Podaci iz in vitro ispitivanja pokazuju da je ulipristalacetat mogući inhibitor P-gp-a pri klinički relevantnim koncentracijama u stijenci probavnog sustava prilikom apsorpcije.
English: Ulipristal acetate may interfere with the action of hormonal contraceptive medicinal products (progestagen only, progestagen releasing devices or combined oral contraceptive pills) and progestagen administered for other reasons.
Croatian: Ulipristalacetat može interferirati s djelovanjem lijekova iz skupine hormonskih kontraceptiva (lijekova koji sadrže samo progestagen, proizvoda koji otpuštaju progestagen ili pilula kombiniranih oralnih kontraceptiva) te progestagena koji se primjenjuje iz drugih razloga.
English: The terminal half-life of ulipristal acetate in plasma following a single dose of 5 or 10 mg is estimated to be about 38 hours, with a mean oral clearance (CL/F) of about 100 l/h.
Croatian: Terminalni poluvijek ulipristalacetata u plazmi nakon pojedinačne doze od 5 ili 10 mg procijenjen je na približno 38 sati s prosječnim peroralnim klirensom (CL/F) od približno 100 l/h.
English: • reminder of the effect of ulipristal acetate on the endometrium.
Croatian: • podsjetnik na učinke ulipristalacetata na endometrij
English: Following oral administration of a single dose of 5 or 10 mg, ulipristal acetate is rapidly absorbed, with a Cmax of 23.5 ± 14.2 ng/ml and 50.0 ± 34.4 ng/ml occurring approximately 1 h after ingestion, and with an AUC0-∞ of 61.3 ± 31.7 ng.h/ml and 134.0 ± 83.8 ng.h/ml, respectively.
Croatian: Nakon oralne primjene pojedinačne doze od 5 ili 10 mg, ulipristalacetat se brzo apsorbira s Cmax od 23,5 ± 14,2 ng/ml i 50,0 ± 34,4 ng/ml koja se događa približno 1 sat nakon gutanja, i s AUC0-∞ od 61,3 ± 31,7 ng/ml odnosno s 134,0 ± 83,8 ng.h/ml.
English: Ulipristal acetate is rapidly transformed into a pharmacologically active metabolite with a Cmax of 9.0 ± 4.4 ng/ml and 20.6 ± 10.9 ng/ml also occurring approximately 1 h after ingestion, and with an AUC0-∞ of 26.0 ± 12.0 ng.h/ml and 63.6 ± 30.1 ng.h/ml respectively.
Croatian: Ulipristalacetat se brzo transformira u farmakološki aktivan metabolit s Cmax od 9,0 ± 4,4 ng/ml i 20,6 ± 10,9 ng/ml koji se također pojavljuje 1 sat nakon gutanja te s AUC0-∞ od 26,0 ± 12,0 ng/ml odnosno 63,6 ± 30,1 ng.h/ml.
English: This effect of medicinal products that increase gastric pH is not expected to be of clinical relevance for daily administration of ulipristal acetate tablets.
Croatian: Ne očekuje se da će ovaj učinak lijeka koji povećava želučani pH biti klinički značajan u dnevnoj primjenu tableta ulipristalacetata.
English: In a 39-week study in cynomolgus monkeys, histological changes resembling PAEC were noted at low doses.
Croatian: U ispitivanju na makaki majmunima u trajanju od 39 tjedana pri nižim dozama zabilježene su histološke promjene koje podsjećaju na PAEC.
English: Keep the blister in the outer carton in order to protect from light.
Croatian: Blistere čuvajte u vanjskoj kutiji radi zaštite od svjetlosti.
English: Ulipristal acetate may have minor influence on the ability to drive or use machines as mild dizziness has been observed after ulipristal acetate intake.
Croatian: Ulipristalacetat malo utječe utjecaj na sposobnost upravljanja vozilima i rada sa strojevima budući da je primijećena blaga omaglica nakon primjene ulipristalacetata.
English: These symptoms may be signs of liver injury (frequency not known).
Croatian: To su mogući znakovi oštećenja jetre (učestalost nepoznata).
English: Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Croatian: Unutar svake skupine učestalosti nuspojave su navedene prema opadajućoj ozbiljnosti.
English: Esmya is contraindicated in patients with hepatic disorder (see section 4.3 and 4.4).
Croatian: Lijek Esmya kontraindiciran je u bolesnica s poremećajem jetre (vidjeti dijelove 4.3 i 4.4).