FrancophonIA/ELRC3.0 huggingface dataset:
English: Bleeding events were more frequent in patients receiving concurrent heparin while undergoing PCI, when ACT exceeded 350 seconds (see section 4.4, heparin use).
Croatian: Krvarenje je bilo češće u bolesnika koji su istodobno primali heparin i bili podvrgnuti PCI, kad je ACT premašio 350 sekundi (vidjeti dio 4.4., Primjena heparina).
English: INTEGRILIN is indicated for the prevention of early myocardial infarction in adults presenting with unstable angina or non-Q-wave myocardial infarction, with the last episode of chest pain occurring within 24 hours and with electrocardiogram (ECG) changes and/or elevated cardiac enzymes.
Croatian: INTEGRILIN je indiciran za sprječavanje ranog infarkta miokarda u odraslih osoba koji imaju nestabilnu anginu ili infarkt miokarda bez Q-zupca, u kojih se posljednja epizoda boli u prsima dogodila u posljednja 24 sata i koji imaju promjene u elektrokardiogramu (EKG) i/ili povišene srčane enzime.
English: Toxicology studies conducted with eptifibatide include single and repeated dose studies in the rat, rabbit and monkey, reproduction studies in the rat and rabbit, in vitro and in vivo genetic toxicity studies, and irritation, hypersensitivity and antigenicity studies.
Croatian: Toksikološka ispitivanja provedena s eptifibatidom uključuju ispitivanja s pojedinačnim ili ponavljanim dozama na štakorima, kunićima i majmunima, ispitivanja utjecaja na reprodukciju štakora i kunića, in vitro i in vivo ispitivanja genotoksičnosti, te ispitivanja iritacije, preosjetljivosti i antigenosti.
English: INTEGRILIN is an antithrombotic agent that acts by inhibition of platelet aggregation; therefore the patient must be observed carefully for indications of bleeding during treatment (see section 4.8).
Croatian: INTEGRILIN je antitrombotik koji djeluje inhibicijom agregacije trombocita; stoga bolesnika treba pomno nadzirati zbog naznaka krvarenja tijekom liječenja (vidjeti dio 4.8.).
English: Unfractionated heparin was administered intravenously or subcutaneously at the physician's discretion, most commonly as an intravenous bolus of 5,000 U followed by a continuous infusion of 1,000 U/h.
Croatian: Nefrakcionirani heparin je primijenjen intravenski ili supkutano prema odluci liječnika, najčešće u obliku intravenskog bolusa od 5000 jedinica, nakon koje je slijedila kontinuirana infuzija od 1000 jedinica na sat.
English: The need for blood transfusions was increased modestly by Integrilin treatment (11.8% versus 9.3% for placebo).
Croatian: neznatno je povećalo potrebu za transfuzijom krvi (11,8 % prema 9,3 % za placebo).
English: The primary endpoint of the trial was death (D), MI, urgent target vessel revascularisation (UTVR), and acute antithrombotic rescue with GP IIb/IIIa inhibitor therapy (RT) within 48 hours of randomisation.
Croatian: Primarna mjera ishoda ispitivanja bila je smanjenje incidencije smrti (D), infarkta miokarda, hitne revaskularizacije ciljne krvne žile (UTVR) i akutne antitrombotske hitne intervencije inhibitorom GP IIb/IIIa (RT) unutar 48 sati od randomizacije.
English: Integrilin is given into the vein by direct injection followed by an infusion (drip solution).
Croatian: Kako primjenjivati Integrilin Integrilin se daje u venu direktnom injekcijom nakon koje slijedi infuzija (drip otopina).
English: Marketing Authorisation Holder and manufacturer Marketing Authorisation Holder:
Croatian: Nositelj odobrenja za stavljanje lijeka u promet i proizvođač Nositelj odobrenja:
English: 4.5 Interaction with other medicinal products and other forms of interaction
Croatian: 4.5 Interakcije s drugim lijekovima i drugi oblici interakcija Varfarin i dipiridamol
English: However, treatment with eptifibatide was associated with antibodies that recognise GPIIb/IIIa occupied by eptifibatide, suggesting an immune-mediated mechanism.
Croatian: Naime, liječenje eptifibatidom je bilo povezano s pojavom antitijela koja prepoznaju GPIIb/IIIa receptore koje je zauzeo eptifibatid, što upućuje na imunološki posredovan mehanizam.
English: Major bleeding was also very common and reported more frequently with Integrilin than with placebo in the PURSUIT study (>1/10 or 10.8% versus 9.3%), but it was infrequent in the vast majority of patients who did not undergo CABG within 30 days of inclusion in the study.
Croatian: Veliko krvarenje bilo je također vrlo često, a zabilježeno je češće u bolesnika liječenih lijekom INTEGRILIN nego onih koji su primali placebo u ispitivanju PURSUIT (>1/10 ili 10,8 % prema 9,3 %), no bilo je manje često zabilježeno u većini bolesnika koji nisu bili podvrgnuti CABG-u unutar 30 dana od uključenja u ispitivanje.
English: GUSTO moderate or severe/life threatening bleeding occurred significantly more often with early routine eptifibatide (7.4% vs. 5.0% in delayed provisional eptifibatide group; p <0.001).
Croatian: Prema GUSTO kriterijima umjereno ili jako/životno ugrožavajuće krvarenje se javljalo značajno češće uz ranu rutinsku primjenu eptifibatida (7,4 % naspram 5,0 % pri odgođenoj privremenoj primjeni eptifibatida; p <0,001).
English: − if you have or have had bleeding problems.
Croatian: − ako ste imali ili imate problema s krvarenjima.
English: 4.4 Special warnings and precautions for use
Croatian: 4.4 Posebna upozorenja i mjere opreza pri uporabi Krvarenje
English: Data are limited on the use of INTEGRILIN in patients receiving thrombolytic agents.
Croatian: Ograničeni su podaci o primjeni lijeka INTEGRILIN u bolesnika koji primaju trombolitike.
English: Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Croatian: embriofetalni razvoj, porod i postnatalni razvoj (vidjeti dio 5.3).
English: LIST OF EXCIPIENTS Citric acid monohydrate, sodium hydroxide, water for injections.
Croatian: Citratna kiselina hidrat, natrijev hidroksid, voda za injekcije.
English: In patients undergoing CABG, the incidence of bleeding was not increased by Integrilin compared to the patients treated with placebo.
Croatian: U bolesnika podvrgnutih CABG-u, incidencija krvarenja nije bila povišena primjenom lijeka INTEGRILIN u usporedbi s ispitanicima na placebu.
English: If you are breast-feeding a baby, breast-feeding should be interrupted during the treatment period.
Croatian: Ako dojite, morat ćete prekinuti dojenje tijekom perioda liječenja.
English: These plasma concentrations are achieved rapidly when the infusion is preceded by a 180 microgram/kg bolus.
Croatian: Te koncentracije u plazmi se postižu vrlo brzo kada infuziji prethodi bolus injekcija od 180 mikrograma/kg eptifibatida.
English: Integrilin should not be used if it is noticed that particulate matter or discoloration is present.
Croatian: Integrilin se ne smije upotrijebiti ako primijetite čestice ili promjenu boje otopine.
English: Therefore, it is not recommended to administer eptifibatide in patients who have previously experienced immune mediated thrombocytopenia with GP IIb/IIIa inhibitors, including eptifibatide.
Croatian: Prema tome, ne preporučuje se primjena eptifibatida u bolesnika koji su već doživjeli imunološki posredovanu trombocitopeniju nakon primjene inhibitora GP IIb/IIIa, uključujući eptifibatid.
English: GlaxoSmithKline Manufacturing S.P.A., Strada Provinciale Asolana No. 90, San Polo di Torrile 43056, Parma, Italy
Croatian: GlaxoSmithKline Manufacturing S.P.A., Strada Provinciale Asolana No. 90, San Polo di Torrile 43056, Parma, Italija
English: INTEGRILIN infusion should be stopped immediately if circumstances arise that necessitate thrombolytic therapy or if the patient must undergo an emergency CABG surgery or requires an intraortic balloon pump.
Croatian: Infuziju lijeka INTEGRILIN treba odmah prekinuti ako nastupe okolnosti koje zahtijevaju primjenu trombolitičke terapije ili ako bolesnik mora pristupiti hitnoj ugradnji premosnice koronarne arterije
English: The combination of reduced dose tenecteplase and eptifibatide compared to placebo and eptifibatide significantly increased the risk of both major and minor bleeding when administered concomitantly in an acute ST-elevation myocardial infarction study.
Croatian: Kombinacija smanjene doze tenekteplaze i eptifibatida u usporedbi s placebom i eptifibatidom značajno je povisila rizik i velikog i manjeg krvarenja kada je primjenjivana istodobno u ispitivanju na bolesnicima s akutnim infarktom miokarda sa ST-elevacijom.
English: Before infusion of INTEGRILIN, the following laboratory tests are recommended to identify preexisting haemostatic abnormalities: prothrombin time (PT) and aPTT, serum creatinine, platelet count, haemoglobin and haematocrit levels.
Croatian: Prije infuzije lijeka INTEGRILIN, preporučuju se sljedeći laboratorijski testovi u cilju otkrivanja postojećih hemostatskih poremećaja: protrombinsko vrijeme (PV) i aPTT, serumski kreatinin, broj trombocita, razina hemoglobina i hematokrita.
English: No apparent differences were observed between patients treated with eptifibatide or with placebo in values for liver function (SGOT/AST, SGPT/ALT, bilirubin, alkaline phosphatase) or renal function (serum creatinine, blood urea nitrogen).
Croatian: Između bolesnika koji su dobivali eptifibatid ili placebo nisu uočene vidljive razlike u vrijednostima pretraga jetrene funkcije (SGOT/AST, SGPT/ALT, bilirubin, alkalna fosfataza) ili bubrežne funkcije (serumski kreatinin, dušik iz ureje u krvi).
English: diazepam, digoxin, diltiazem, diphenhydramine, enalapril, fentanyl, furosemide, heparin, lidocaine, lisinopril, metoprolol, midazolam, morphine, nitrates, nifedipine, and warfarin.
Croatian: cefazolina, diazepama, digoksina, diltiazema, difenhidramina, enalaprila, fentanila, furosemida, heparina, lidokaina, lizinoprila, metoprolola, midazolama, morfija, nitratia, nifedipina i varfarina.
English: Any unused medicine after opening should be thrown away.
Croatian: Nakon otvaranja, neupotrijebljeni lijek treba baciti.
English: − serious bleeding (for example, bleeding inside the abdomen, inside the brain, and into the lungs).
Croatian: − ozbiljno krvarenje (na primjer krvarenje u trbušnoj šupljini, u mozgu i u plućima).
English: Citric acid monohydrate
Croatian: Citratna kiselina hidrat
English: − heart failure
Croatian: − zatajenje srca.
English: − persistent or recurrent ischemic cardiac pain
Croatian: − perzistentna ili ponavljajuća ishemična bol u predjelu srca
English: If the patient weighs < 70 kg, a bolus dose of 60 units/kg is recommended, followed by an infusion of 12 units/kg/hr.
Croatian: Ako bolesnik ima < 70 kg, treba dati dozu od 60 jedinica/kg u bolusu, nakon koje treba uslijediti infuzija od 12 jedinica/kg/h.
English: There is no experience with INTEGRILIN and low molecular weight heparins.
Croatian: Nema iskustava s primjenom lijeka INTEGRILIN i heparina male molekulske težine.
English: What Integrilin looks like and contents of the pack Integrilin solution for infusion: 100 ml vial, pack of one vial.
Croatian: Kako Integrilin izgleda i sadržaj pakiranja Integrilin otopina za infuziju: bočica sa 100 ml, kutija s jednom bočicom.
English: ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with eptifibatide Therapy) was a double-blind, randomised, placebo-controlled trial (n= 2,064) for nonurgent PCI with intracoronary stenting.
Croatian: Enhanced Suppression of the Platelet IIb/IIIa Receptor with eptifibatide Therapy) je bilo dvostruko slijepo, randomizirano, placebom kontrolirano ispitivanje (n= 2064) za neurgentne PCI s ugradnjom intrakoronarnog stenta.
English: INTEGRILIN-treated patients who had a prothrombin time (PT) > 14.5 seconds and received warfarin concomitantly did not appear to be at an increased risk of bleeding.
Croatian: INTEGRILIN, koji su imali protrombinsko vrijeme (PV) > 14,5 sekundi i istodobno primali varfarin,
English: How to use Integrilin
Croatian: Kako primjenjivati Integrilin
English: INTEGRILIN solution for infusion must be used in conjunction with INTEGRILIN solution for injection.
Croatian: INTEGRILIN otopina za infuziju mora se primjenjivati zajedno s INTEGRILIN otopinom za injekciju.
English: Patients most likely to benefit from INTEGRILIN treatment are those at high risk of developing myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA (Percutaneous Transluminal Coronary Angioplasty) (see section 5.1).
Croatian: INTEGRILIN će najviše koristiti bolesnicima pod visokim rizikom od razvoja infarkta miokarda tijekom prva 3-4 dana nakon nastupa simptoma angine, uključujući, na primjer, one kojima je potrebna rana perkutana transluminalna koronarna angioplastika (PTCA) (vidjeti dio 5.1).
English: For a particular adverse reaction, if data was available from both PURSUIT and ESPRIT, then the highest reported incidence was used to assign adverse reaction frequency.
Croatian: Za pojedine nuspojave, ako su podaci bili dostupni i iz ispitivanja PURSUIT i ESPRIT, za procjenu učestalosti nuspojave korištena je najviša prijavljena incidencija.
English: What Integrilin looks like and contents of the pack Integrilin solution for injection: 10 ml vial, pack of one vial.
Croatian: Kako Integrilin izgleda i sadržaj pakiranja Integrilin otopina za injekcije: bočica s 10 ml, kutija s jednom bočicom.
English: To avoid the possibility of interactions with other medicines please tell your doctor or hospital pharmacist if you are taking or have recently taken or might take any other medicines, including medicines obtained without a prescription.
Croatian: Kako biste izbjegli mogućnost pojave interakcije s drugim lijekovima, obavijestite liječnika ili bolničkog ljekarnika ako uzimate, nedavno ste uzeli ili biste mogli uzeti bilo koje druge lijekove,
English: If percutaneous coronary intervention (PCI) is performed during Integrilin therapy, the intravenous solution may be continued for up to 96 hours.
Croatian: Ako se tijekom liječenja lijekom Integrilin provede perkutana koronarna intervencija (PCI), infuzija intravenske otopine može se nastaviti davati i do 96 sati.
English: Eptifibatide appeared to increase the risk of bleeding when administered with streptokinase in an acute myocardial infarction study.
Croatian: Čini se, međutim, da je eptifibatid povećao rizik od krvarenja kad se primjenjivao sa streptokinazom u istraživanjima na bolesnicima s akutnim infarktom miokarda.
English: Heparin administration is recommended unless a contraindication (such as a history of thrombocytopenia associated with use of heparin) is present.
Croatian: Preporučuje se primjena heparina ako za to ne postoje kontraindikacije (kao što je pojava trombocitopenije inducirane heparinom).
English: Physical and chemical compatibility testing indicate that INTEGRILIN may be administered through an intravenous line with atropine sulfate, dobutamine, heparin, lidocaine, meperidine, metoprolol, midazolam, morphine, nitroglycerin, tissue plasminogen activator, or verapamil.
Croatian: Ispitivanje fizikalne i kemijske kompatibilnosti pokazuje da se INTEGRILIN može primijeniti intravenskom linijom zajedno s atropin sulfatom, dobutaminom, heparinom, lidokainom, meperidinom, metoprololom, midazolamom, morfijem, nitroglicerinom, aktivatorom tkivnog plazminogena ili verapamilom.
English: • either ST-segment changes: ST depression > 0.5 mm of less than 30 minutes or persistent ST
Croatian: • promjene ST-segmenta: depresiju ST segmenta > 0,5 mm u trajanju manjem od 30 minuta ili perzistentnu elevaciju ST segmenta > 0,5 mm koja ne zahtijeva reperfuzijsku terapiju ili trombolitike, inverziju T-vala (> 1 mm)
English: Similar differences were noted for TIMI major haemorrhage (118 [2.5%] in early routine use vs. 83 [1.8%] in delayed provisional use; p=0.016).
Croatian: Slične su razlike zamijećene za velika krvarenja prema TIMI kriterijima (118 [2,5 %] u ranoj rutinskoj primjeni naspram 83 [1,8 %] pri odgođenoj privremenoj primjeni; p= 0,016).
English: The placebo arm was comparable (aspirin 99.7 %, clopidogrel 95.9 %, ticlopidin 2.6 %).
Croatian: Placebo skupina je bila usporediva (aspirin 99,7 %,klopidogrel 95,9 %, tiklopidin 2,6 %).
English: INTEGRILIN solution for injection must be used in conjunction with INTEGRILIN solution for infusion.
Croatian: INTEGRILIN otopina za injekcije mora se primjenjivati zajedno s INTEGRILIN otopinom za infuziju.
English: − The other ingredients are citric acid monohydrate, sodium hydroxide and water for injections.
Croatian: Pomoćne tvari su citratna kiselina hidrat, natrijev hidroksid i voda za injekcije.
English: Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu
Croatian: Detaljnije informacije o ovom lijeku dostupne su na internetskoj stranici Europske agencije za lijekove: http://www.ema.europa.eu, i na internetskoj stranici www.halmed.hr.
English: Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product Characteristics, 4.2)
Croatian: Lijek se izdaje na ograničeni recept (Vidjeti Prilog I.: Sažetak opisa svojstava lijeka, dio 4.2.).
English: INTEGRILIN did not appear to increase the risk of major and minor bleeding associated with concomitant use of warfarin and dipyridamole.
Croatian: Nema pokazatelja da INTEGRILIN povećava rizik od većeg i manjeg krvarenja povezanog s istodobnom primjenom varfarina i dipiridamola.
English: The primary endpoint event rate was 11.9 % in patients who received a reduced dose (1microgram/kg/min) vs 11.2% in patients who received the standard dose (2microgram/kg/min) when eptifibatide was administered in the early routine fashion (p=0.81).
Croatian: Stopa događaja primarnog ishoda je iznosila 11,9 % u bolesnika koji su primili smanjenu dozu (1 mikrogram/kg/min) naspram 11,2 % u bolesnika koji su primili standardnu dozu (2 mikrograma/kg/min), kada je eptifibatid primijenjen kao rana rutinska terapija (p=0,81).
English: DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 01.07.1999
Croatian: Datum prvog odobrenja: 01.07.1999.
English: Glaxo Operations UK Ltd., (Trading as Glaxo Wellcome Operations), Harmire Road, Barnard Castle, Co. Durham, DL12 8DT, United Kingdom
Croatian: Glaxo Operations UK Ltd., (posluje kao Glaxo Wellcome Operations), Harmire Road, Barnard Castle, Co.
English: The recommended dose is 180 microgram/kg administered as a bolus (rapid intravenous injection), followed by an infusion (drip solution) of 2 microgram/kg/minute for up to 72 hours.
Croatian: Preporučena doza iznosi 180 mikrograma/kg primijenjena u bolusu (brza intravenska injekcija), nakon koje slijedi infuzija (drip otopina za infuziju) u dozi od 2 mikrograma/kg/min u trajanju do 72 sata.
English: In ESPRIT, bleeding events were reported at 48 hours, and non-bleeding events were reported at 30 days.
Croatian: U ispitivanju ESPRIT krvarenja su procjenjivana nakon 48 sati, a nuspojave nevezane uz krvarenja 30. dana.
English: Minor bleeding was defined in the PURSUIT trial as spontaneous gross haematuria, spontaneous haematemesis, observed blood loss with a haemoglobin decrease of more than 3 g/dl, or a haemoglobin decrease of more than 4 g/dl in the absence of an observed bleeding site.
Croatian: Manje krvarenje definirano je u ispitivanju PURSUIT kao spontana teška hematurija, spontana hematemeza, vidljiv gubitak krvi sa smanjenjem hemoglobina za više od 3 g/dl, ili smanjenje hemoglobina za više od 4 g/dl kad mjesto krvarenja nije vidljivo.
English: Concurrent administration of heparin is recommended unless this is contraindicated for reasons such as a history of thrombocytopenia associated with use of heparin (see ‘Heparin administration', section 4.4).
Croatian: Preporučuje se istodobna primjena heparina ako za to ne postoje kontraindikacije poput anamnestičkog podatka o trombocitopeniji povezanoj s primjenom heparina (vidjeti dio 4.4 'Primjena heparina').
English: − if you have or have had severe kidney or liver problems.
Croatian: − ako ste imali ili imate ozbiljnih problema s bubrezima ili jetrom.
English: All patients received routine standard of care and were randomised to either placebo or eptifibatide (2 bolus doses of 180 microgram/kg and a continuous infusion until discharge from hospital or a maximum of 18-24 hours).
Croatian: Svi bolesnici primali su rutinsku standardnu njegu i bili su randomizirani u skupinu koja je primala placebo ili u skupinu koja je primala eptifibatid (2 bolus doze od 180 mikrograma/kg i zatim kontinuirana infuzija do otpusta iz bolnice ili do maksimalno 18-24 sata).
English: PURSUIT: This was a randomised, double-blind evaluation of the efficacy and safety of Integrilin versus placebo for reducing mortality and myocardial (re)infarction in patients with unstable angina or non-Q-wave myocardial infarction.
Croatian: PURSUIT: randomizirana, dvostruka slijepa procjena djelotvornosti i sigurnosti primjene lijeka INTEGRILIN u odnosu na placebo, u smanjenju smrtnosti i (re)infarkta miokarda u bolesnika s nestabilnom anginom ili infarktom miokarda bez Q-zupca.
English: The mechanism, whether immune- and/or non-immune-mediated, by which eptifibatide may induce thrombocytopaenia is not fully understood.
Croatian: Mehanizam kojim eptifibatid može inducirati trombocitopeniju, bez obzira je li ona imunološki ili ne imunološki posredovana, nije u potpunosti razjašnjen.
English: Because INTEGRILIN inhibits platelet aggregation, caution must be employed when it is used with other medicinal products that affect haemostasis, including ticlopidine, clopidogrel, thrombolytics, oral anticoagulants, dextran solutions, adenosine, sulfinpyrazone, prostacyclin, non-steroidal antiinflammatory agents, or dypyridamole (see section 4.5).
Croatian: Budući da INTEGRILIN inhibira agregaciju trombocita, treba ga pažljivo primjenjivati s drugim lijekovima koji djeluju na hemostazu, uključujući tiklopidin, klopidogrel, trombolitike, oralne antikoagulanse, otopine dekstrana, adenozin, sulfinpirazon, prostaciklin, nesteroidne protuupalne lijekove ili dipiridamol (vidjeti dio 4.5).
English: ESPRIT: This was a double-blind, multicentre, randomised, parallel-group, placebo-controlled trial evaluating the safety and efficacy of eptifibatide therapy in patients scheduled to undergo nonemergent percutaneous coronary intervention (PCI) with stent implantation.
Croatian: ESPRIT: dvostruko slijepo, multicentrično, randomizirano, placebom kontrolirano ispitivanje paralelnih grupa o sigurnosti i djelotvornosti terapije eptifibatidom bolesnika predviđenih za ne-hitnu perkutanu koronarnu intervenciju (PCI) s implantacijom stenta.
English: INTEGRILIN is compatible with 0.9 % sodium chloride solution for infusion and with dextrose 5 % in Normosol R with or without potassium chloride.
Croatian: INTEGRILIN je kompatibilan s 0,9 %- tnom otopinom natrijevog klorida i 5 %- tnom glukozom u Normosolu R, s ili bez kalijevog klorida.
English: The primary endpoint analysis [quadruple composite of death, MI, urgent target vessel revascularisation (UTVR) and thrombolytic bail-out (TBO) at 48 hours] showed a 37 % relative and 3.9 % absolute reduction in the eptifibatide group (6.6 % events versus 10.5 %, p = 0.0015).
Croatian: Analiza primarne mjere ishoda[kompozitna mjera sastavljena od četiri komponente: smrti, infarkta miokarda, hitne revaskularizacije ciljne krvne žile i tzv. 'bail-out' trombolize tijekom 48 sati] pokazala je 37 % relativno, te 3,9 % apsolutno smanjenje u skupini koja je primala eptifibatid (6,6 % događaja vs 10,5 %, p = 0,0015).
English: • Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
Croatian: • na zahtjev Europske agencije za lijekove; • prilikom svake izmjene sustava za upravljanje rizikom, a naročito kada je ta izmjena rezultat primitka novih informacija koje mogu voditi ka značajnim izmjenama omjera korist/rizik,