FrancophonIA/ELRC3.0 huggingface dataset:
English: For the primary endpoint, which was incidence of cataract development or progression at 12 months (defined as an increase of ≥ 0.3 in the LOCS III score), a greater proportion of subjects experienced cataract development in the palifermin group compared with the placebo group (28.6 % in the placebo group vs 48.1% in the palifermin group).
Croatian: Primarni ishod, tj. incidencija razvoja ili progresije katarakte tijekom 12 mjeseci (definirana kao povećanje ≥ 0,3 prema ljestvici LOCS III), razmjerno je bila veća u skupini koja je primala palifermin (48,1%) nego u placebo skupini (28,6%).
English: OTHER CONDITIONS AND REQUIREMENTS OF THE
Croatian: OSTALI UVJETI I ZAHTJEVI ZA STAVLJANJE
English: KGF is a protein that targets epithelial cells by binding to specific cell-surface receptors thereby stimulating proliferation, differentiation, and upregulation of cytoprotective mechanisms (e.g., induction of antioxidant enzymes).
Croatian: Čimbenik rasta keratinocita je protein koji se ciljano veže na epitelne stanice putem specifičnih receptora na površini stanica i tako potiče proliferaciju, diferencijaciju i aktivaciju zaštitnih staničnih mehanizama (npr. indukciju antioksidativnih enzima).
English: Mild to moderate renal impairment (creatinine clearance 30-80 ml/min) did not influence palifermin pharmacokinetics.
Croatian: Blago do umjereno oštećenje funkcije bubrega (klirens kreatinina 30-80 ml/min) nije utjecalo na farmakokinetiku palifermina.
English: 6.25 mg of powder in a vial (Type I glass) with a rubber stopper, an aluminium seal and a plastic flip
Croatian: 6,25 mg praška u bočici (staklo tipa I) s gumenim čepom, aluminijskim prstenom i plastičnom
English: These no observed adverse effect level (NOAEL) doses were associated with systemic exposures up to 2.5 times greater than anticipated clinical exposure.
Croatian: Te doze pri kojima nisu uočeni štetni učinci povezane su sa sustavnim izlaganjima do 2,5 puta većim od očekivane kliničke izloženosti.
English: Safety data are based on patients with haematological malignancies enrolled in randomised, placebocontrolled clinical studies, including one pharmacokinetic study, and post marketing experience.
Croatian: Podaci o sigurnosti temelje se na bolesnicima s hematološkim malignim bolestima koji su bili uključeni u randomizirana, placebom kontrolirana klinička ispitivanja, uključujući jedno fakmakokinetičko ispitivanje te na iskustvima nakon stavljanja lijeka u promet.
English: Kepivance should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of cytotoxic chemotherapy.
Croatian: Kepivance se ne smije primjenjivati unutar 24 sata prije, tijekom ili unutar 24 sata nakon primjene citotoksične kemoterapije.
English: Rash, pruritus and erythema Skin hyperpigmentation Palmar-plantar erythrodysaesthesia syndrome (dysaesthesia, erythema, oedema on the palms and soles)
Croatian: Osip, svrbež i crvenilo kože Hiperpigmentacija kože Palmarno-plantarna eritrodizestezija (dizestezija, eritem, edem na dlanovima i tabanima)
English: Kepivance is used to reduce the frequency, duration and severity of oral mucositis symptoms.
Croatian: Kepivance se koristi za smanjenje učestalosti, trajanja i težine simptoma oralnog mukozitisa.
English: Other endpoints included the incidence, duration and severity of oral mucositis and the requirement for opioid analgesia.
Croatian: Drugi ciljevi bili su incidencija, trajanje i težina oralnog mukozitisa i potreba za opioidnom analgezijom.
English: In a clinical trial, administration of Kepivance within 24 hours of chemotherapy resulted in an increased severity and duration of oral mucositis.
Croatian: U kliničkom je ispitivanju primjena Kepivancea unutar 24 sata nakon kemoterapije uzrokovala teži oblik i dulje trajanje oralnog mukozitisa.
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)
Croatian: • Uoči svake izmjene sustava za upravljanje rizicima, a naročito kada je ta izmjena rezultat primitka novih informacija koje mogu voditi ka značajnim izmjenama omjera korist/rizik,
English: The duration between last dose of Kepivance before myeloablative radiochemotherapy and the first dose of Kepivance after myeloablative radiochemotherapy should be at least seven days.
Croatian: Razmak između posljednje doze Kepivancea prije mijeloablativne radiokemoterapije i prve doze Kepivancea nakon mijeloablativne radiokemoterapije treba iznositi najmanje sedam dana.
English: You will be given Kepivance for three days in a row before chemotherapy and radiotherapy and for three days in a row after chemotherapy and radiotherapy for a total of six doses.
Croatian: Kepivance ćete dobivati tri dana zaredom prije kemoterapije i zračenja i tri dana zaredom nakon kemoterapije i zračenja, ukupno šest doza.
English: In patients with severe renal impairment (creatinine clearance < 30 ml/min), clearance was decreased by 22% (n = 5).
Croatian: U bolesnika s teškim oštećenjem funkcije bubrega (klirens kreatinina < 30 ml/min) klirens je bio smanjen za 22% (n = 5).
English: Non-haematological malignancies
Croatian: Nehematološke maligne bolesti
English: Kepivance should not be used during pregnancy unless clearly
Croatian: Kepivance se ne smije primjenjivati u trudnoći, osim ako je to neophodno.
English: Epithelial cell proliferation was assessed by Ki67 immunohistochemical staining in healthy subjects.
Croatian: Proliferacija epitelnih stanica procjenjivana je imunohistokemijskim bojenjem na Ki67 u zdravih ispitanika.
English: Hypersensitivity, including Anaphylactic reactions, has also been associated with palifermin.
Croatian: uključujući anafilaktičke reakcije, također se povezuje s paliferminom.
English: - if you are allergic to palifermin, Escherichia coli derived proteins or any other ingredients of
Croatian: - ako ste alergični na palifermin, proteine dobivene iz Escherichie coli ili druge sastojke ovog lijeka (navedene u dijelu 6).
English: The efficacy and safety of palifermin have only been established in association with conditioning regimens for autologous haematopoietic stem cell support that comprise total body irradiation and high dose chemotherapy (cyclophosphamide and etoposide) (see section 5.1).
Croatian: Djelotvornost i sigurnost palifermina utvrđena je samo za režime kondicioniranja za terapiju autolognim krvotvornim matičnim stanicama koji uključuju ozračivanje cijelog tijela i visoke doze kemoterapije (ciklofosfamid i etopozid) (vidjeti dio 5.1).
English: Systemic toxicity (clinical signs and/or changes in body weight) and adverse effects on male and female fertility parameters were seen at doses ≥ 300 micrograms/kg/day (5-fold higher than the recommended human dose).
Croatian: Sistemska toksičnost (klinički znakovi i/ili promjene tjelesne težine) i štetni učinci na muške i ženske parametre plodnosti primijećeni su pri dozama ≥ 300 mikrograma/kg/dan (peterostruko viša doza od preporučene doze za ljude).
English: No overt cases of pancreatitis have been reported in this patient population.
Croatian: U ovoj populaciji bolesnika nisu prijavljeni očiti slučajevi pankreatitisa.
English: The diluent should be injected slowly into the Kepivance vial.
Croatian: Otapalo treba polako injicirati u bočicu s lijekom Kepivance.
English: Do not shake or vigorously agitate the vial.
Croatian: Bočicu ne tresti niti snažno mućkati.
English: There was no evidence of a delay in time to haematopoietic recovery in patients who received palifermin as compared to patients who received placebo.
Croatian: Nije dokazan odgođeni hematopoetski oporavak u bolesnika koji su primali palifermin u usporedbi s ispitanicima koji su primali placebo.
English: Kepivance is used to treat oral mucositis (soreness, dryness and inflammation of the mouth) which has occurred as a side effect of treatments for your blood cancer.
Croatian: Kepivance se koristi za liječenje oralnog mukozitisa (bol, suhoća i upala usta) koji nastaje kao nuspojava u liječenju raka krvi.
English: In patients with end-stage renal disease (requiring dialysis) palifermin clearance was decreased by 10% (n = 6).
Croatian: U bolesnika u terminalnoj fazi bolesti bubrega (koja zahtijeva dijaliza), klirens palifermina bio je manji za 10% (n = 6).
English: Kepivance is indicated to decrease the incidence, duration and severity of oral mucositis in adult patients with haematological malignancies receiving myeloablative radiochemotherapy associated with a high incidence of severe mucositis and requiring autologous haematopoietic stem cell support.
Croatian: Kepivance je indiciran za smanjenje incidencije, trajanja i težine oralnog mukozitisa u odraslih bolesnika s hematološkim malignim bolestima koji primaju mijeloablativnu radiokemoterapiju povezanu s visokom stopom incidencije teškog mukozitisa i kojima je potrebna terapija autolognim krvotvornim matičnim stanicama.
English: Kepivance contains the active substance palifermin which is a protein produced by biotechnology in a bacteria called Escherichia coli.
Croatian: Kepivance sadrži djelatnu tvar palifermin, protein proizveden biotehnologijom u bakteriji
English: The pharmacokinetics of palifermin were studied in healthy volunteers and patients with haematological malignancies.
Croatian: 5.2 Farmakokinetička svojstva Farmakokinetička svojstva palifermina ispitivana su u zdravih dobrovoljaca i bolesnika s hematološkim malignim bolestima.
English: • swelling (oedema) of the face or mouth;
Croatian: • oticanje (edem) lica ili usta;
English: Kepivance has not been tested in pregnant women.
Croatian: Trudnoća i dojenje Kepivance nije ispitivan na trudnicama.
English: Fractionation of increased levels of amylase revealed the increase to be predominantly salivary in origin.
Croatian: Frakcioniranjem povišenih razina amilaze utvrđeno je da se uglavnom radi o amilazi iz sline.
English: It is not known whether Kepivance is present in human milk.
Croatian: Nije poznato izlučuje li se Kepivance u majčino mlijeko.
English: • change in colour of the mouth or tongue;
Croatian: • promjena boje usne šupljine ili jezika;
English: Kepivance should not be administered if discolouration or particulates are observed.
Croatian: Kepivance se ne smije primijeniti ako uočite promjenu boje ili čestice.
English: The last of the three doses given before chemotherapy andradiotherapy, must be given at least 24 to 48 hours before the chemotherapy and radiotherapy starts.
Croatian: Posljednja od tri doze koja se daje prije kemoterapije i zračenja mora se dati najmanje 24 do 48 sati prije početka kemoterapije i zračenja.
English: Haematopoietic recovery following PBPC infusion was similar between patients who received Kepivance or placebo, and there were no observed differences in disease progression or survival.
Croatian: Hematopoetski oporavak nakon infuzije progenitornih stanica iz periferne krvi bio je sličan u bolesnika koji su primili Kepivance i onih koji su primili placebo te nisu ustanovljene razlike u napredovanju bolesti ili preživljenju.
English: Pain and arthralgia are other common adverse reactions, consistent with Kepivance treated patients having received less opioid analgesia than placebo-treated patients (see Table 2).
Croatian: Bol i artralgija su česte nuspojave u bolesnika liječenih Kevipanceom koji su primili manje opioidnih analgetika od bolesnika liječenih placebom (vidjeti Tablicu 2.).
English: In a single dose study the clearance of palifermin was approximately 30% lower in 8 healthy subjects aged 66-73 years after a dose of 90 micrograms/kg than in younger subjects (≤ 65 years) after a dose of 180 micrograms/kg.
Croatian: U ispitivanju jednokratne doze klirens palifermina bio je približno 30% niži u 8 zdravih ispitanika u dobi od 66 do 73 godine koji su primili dozu od 90 mikrograma/kg u odnosu na mlađe ispitanike (≤ 65 godina) koji su primili dozu od 180 mikrograma/kg.
English: p-value*
Croatian: SZO**
English: The first three doses should be administered prior to myeloablative therapy, with the third dose 24 to 48 hours before myeloablative radiochemotherapy.
Croatian: Prve 3 doze treba primijeniti prije mijeloablativnog liječenja, tako da se 3. doza primijeni 24 do 48 sati prije mijeloablativne radiokemoterapije.
English: Palifermin was administered as a daily intravenous injection of 60 micrograms/kg for 3 consecutive days prior to initiation of cytotoxic therapy and for 3 consecutive days following infusion of peripheral blood progenitor cells with nine days between the last pre dose and first post dose.
Croatian: Palifermin je primijenjen u obliku dnevne intravenske injekcije od 60 mikrograma/kg kroz 3 uzastopna dana prije početka citotoksične terapije i kroz 3 uzastopna dana nakon infuzije progenitornih stanica iz periferne krvi s devet dana razmaka između posljednje doze prije i prve doze nakon terapije.
English: L-histidine, mannitol, sucrose, polysorbate 20 and diluted hydrochloric acid
Croatian: L-histidin, manitol, saharoza, polisorbat 20 i razrijeđena kloridna kiselina
English: Very common (affects more than 1 user in 10) side effects are:
Croatian: Vrlo često (mogu se javiti u više od 1 od 10 osoba):
English: Do not use this medicine after the expiry date which is stated on the carton and vial label, after EXP.
Croatian: Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na pakiranju i naljepnici bočice iza Rok valjanosti/EXP.
English: No adverse effects on reproductive/fertility parameters were observed at doses of up to 100 micrograms/kg/day.
Croatian: Nisu utvrđeni štetni učinci na parametre reprodukcije/plodnosti pri dozama do 100 mikrograma/kg/dan.
English: No gender-related differences were observed in the pharmacokinetics of palifermin.
Croatian: U farmakokinetici palifermina nisu primjećene razlike s obzirom na spol.
English: In a small multiple-dose study in paediatric patients (1 to 16 years old) receiving 40, 60 or 80 micrograms/kg/day for 3 days pre- and post- HSCT, there was no effect of age on the pharmacokinetics of palifermin although a large variability was observed in the estimated parameters.
Croatian: U ispitivanju višestrukih doza provedenom na malom broju pedijstrijskih bolesnika (u dobi od 1 do 16 godina) koji su primali 40, 60 ili 80 mikrograma/kg/dan 3 dana prije i nakon transplantacije krvotvornih matičnih stanica, dob nije utjecala na farmakokinetiku palifermina iako su primijećene velike razlike u procijenjenim parametrima.
English: If heparin is used to maintain an intravenous line, sodium chloride solution should be used to rinse the line prior to and after Kepivance administration (see section 6.2).
Croatian: Ako se heparin primjenjuje za održavanje venskog puta, potrebno je prije i nakon primjene Kepivancea venski put isprati otopinom natrijeva klorida (vidjeti dio 6.2).
English: Safety and efficacy has not been evaluated in patients with hepatic impairment (see section 5.2).
Croatian: Sigurnost i djelotvornost u bolesnika s oštećenjem funkcije jetre nije procijenjena (vidjeti dio 5.2).
English: There was a lower incidence of severe oral mucositis in patients receiving 80 micrograms/kg/day but no effect on the incidence of acute graft-versus-host disease (GVHD).
Croatian: U bolesnika koji su primali dozu od 80 mikrograma/kg/dan bila je niža incidencija teškog oralnog mukozitisa, ali nije bilo učinka na incidenciju akutne reakcije presatka protiv primatelja (GVHD).
English: The frequency listed below is defined using the following convention: very common (> 1/10), common (≥ 1/100 to < 1/10), not known (frequency cannot be estimated from available data).
Croatian: (≥ 1/100 i < 1/10), nepoznato (ne može se procijeniti iz dostupnih podataka).
English: A randomised, placebo-controlled, double-blind study was conducted post-approval to evaluate the efficacy of palifermin given pre- or pre- and post- chemotherapy (CT).
Croatian: Nakon stavljanja lijeka u promet provedeno je randomizirano, placebom kontrolirano, dvostruko slijepo ispitivanje radi ocjenjivanja djelotvornosti palifermina primijenjenog prije ili i prije i nakon kemoterapije.
English: The incidence of severe (grades 3 and 4) oral mucositis in the 3 groups was 36.8%, 38.3% and 23.9% for the placebo, pre/post CT and pre-CT groups respectively, with no statistical significance being demonstrated.
Croatian: Incidencija teškog (stupnjevi 3 i 4) oralnog mukozitisa u te 3 skupine iznosila je 36,8% za placebo skupinu, 38,3% u skupini koja je lijek primila prije i nakon kemoterapije te 23,9% u skupini koja je lijek primila prije kemoterapije, bez statističke značajnosti.
English: The first of the three doses given after the chemotherapy and radiotherapy must be given at least 7 days after the most recent
Croatian: Prva od tri doze koja se daje nakon kemoterapije i zračenja mora se dati najmanje 7 dana nakon posljednje doze Kepivancea.
English: No accumulation of palifermin occurred after 3 consecutive daily doses of 20 and 40 micrograms/kg (healthy volunteers) or 60 micrograms/kg (adult patients) or 40 to 80
Croatian: Nije došlo do nakupljanja palifermina nakon uzimanja dnevnih doza od 20 do 40 mikrograma/kg (zdravi dobrovoljci) ili 60 mikrograma/kg (odrasli bolesnici) ili 40 do 80 mikrograma/kg (pedijatrijski bolesnici) kroz 3 uzastopna dana.
English: • redness, bumps or swelling of the tongue;
Croatian: • crvenilo, kvržice ili oticanje jezika;
English: Kepivance left at room temperature for more than 1 hour should be discarded.
Croatian: Ako Kepivance ostane na sobnoj temperaturi dulje od 1 sata, treba ga baciti.
English: Once reconstituted, Kepivance contains 5 mg/ml of palifermin.
Croatian: Nakon pripreme za primjenu, Kepivance sadrži 5 mg/ml palifermina
English: Palifermin should therefore not be given to patients with known or suspected non-haematological malignancies.
Croatian: Palifermin se stoga ne smije primjenjivati u bolesnika u kojih se je potvrđena ili postoji sumnja na nehematološku malignu bolest.
English: - The other ingredients are mannitol, sucrose, L-histidine, polysorbate 20 and diluted
Croatian: - Ostali sastojci su manitol, saharoza, L-histidin, polisorbat 20 i razrijeđena kloridna kiselina.
English: Reconstituted Kepivance should not be left at room temperature for more than one hour, and should be protected from light.
Croatian: Kepivance se nakon pripreme ne smije čuvati dulje od sat vremena na sobnoj temperaturi te ga je potrebno zaštititi od svjetla.
English: Kepivance treatment should be supervised by a physician experienced in the use of anti-cancer
Croatian: Liječenje Kepivanceom treba nadzirati liječnik s iskustvom u primjeni onkološkog liječenja.
English: If heparin is used to maintain an intravenous line, sodium chloride solution should be used to rinse the line prior to and after Kepivance administration, since palifermin has been shown to bind to heparin
Croatian: Ako se heparin primjenjuje za održavanje venskog puta, venski put je prije i nakon primjene lijeka Kepivance potrebno isprati otopinom natrijeva klorida, budući da je utvrđeno da se u in vitro uvjetima palifermin veže za heparin.
English: Endogenous KGF is an epithelial cell specific growth factor which is produced by mesenchymal cells and is naturally upregulated in response to epithelial tissue injury.
Croatian: Endogeni čimbenik rasta keratinocita je specifičani čimbenik rasta epitelnih stanica kojeg proizvode mezenhimalne stanice, a prirodno se aktivira pri ozljedi epitelnog tkiva.
English: In a postmarketing clinical trial investigating multiple myeloma patients receiving melphalan 200 mg/m2 as conditioning regimen, palifermin administration with four days between the last pre dose and the first post dose did not show a therapeutic benefit in the frequency or duration of severe oral mucositis compared to placebo.
Croatian: U kliničkom ispitivanju nakon stavljanja lijeka u promet koje je uključivalo bolesnike s multiplim mijelomom koji su u sklopu protokola kondicioniranja primali melfalan u dozi od 200 mg/m2 ustanovljeno je da, u usporedbi s placebom, primjena palifermina s četiri dana razmaka između posljednje doze prije i prve doze nakon liječenja ne pokazuje terapijsku korist po pitanju učestalosti ili trajanja teškog oralnog mukozitisa.
English: KGF receptors are known to be expressed on the lens of the eye. Cataractogenic effects of palifermin cannot be excluded (see section 5.1).
Croatian: Kataraktogeni učinci palifermina ne mogu se isključiti (vidjeti dio 5.1).
English: Renal impairment Dose adjustment in patients with renal impairment is not necessary (see section 5.2).
Croatian: Nije potrebna prilagodba doze u bolesnika s oštećenjem funkcije bubrega (vidjeti dio 5.2).
English: The pharmacokinetic profile in patients with hepatic insufficiency has not been assessed.
Croatian: Farmakokinetički profil u bolesnika s oštećenom funkcijom jetre nije procijenjivan.
English: The incidence of ulcerative oral mucositis was 57.9% in the placebo arm, 68.7% in the pre/post CT group and 51.4% in the pre-CT group.
Croatian: Incidencija ulcerativnog oralnog mukozitisa iznosila je 57,9% u placebo skupini, 68,7% u skupini koja je lijek primala prije i nakon kemoterapije te 51,4% u skupini koja je lijek primila prije kemoterapije.
English: For storage conditions after reconstitution of the medicinal product, see section 6.3.
Croatian: Uvjete čuvanja nakon pripreme lijeka za primjenu vidjeti u dijelu 6.3.
English: It is not known whether Kepivance is excreted in human milk, therefore Kepivance should not be administered to women who are breast-feeding.
Croatian: Nije poznato izlučuje li se Kepivance u majčino mlijeko te se stoga ne preporučuje primjena
English: Dose limiting toxicities were observed in 36% (5 of 14) patients receiving 6 doses of 80 micrograms/kg/day administered intravenously over 2 weeks (3 doses preceding and three doses following myeloablative therapy).
Croatian: Toksičnost ovisna o dozi primijećena je u 36% (5 od 14) bolesnika koji su u razdoblju od 2 tjedna intravenski primili 6 doza od 80 mikrograma/kg/dan (3 doze prije i 3 doze nakon mijeloablativnog liječenja).
English: There is no experience with Kepivance doses greater than 80 micrograms/kg/day administered intravenously in patients over 2 weeks (3 doses preceding and 3 doses following myeloablative
Croatian: Nema iskustva u primjeni doza Kepivancea većih od 80 mikrograma/kg/dan primijenjenih intravenski u bolesnika u razdoblju od 2 tjedna (3 doze prije i 3 doze nakon mijeloablativnog liječenja).
English: Cataractogenic effects of palifermin cannot be excluded following results of ophthalmologic examinations in a subset of patients (n = 66; 14 in the placebo group, 52 in the palifermin group) who were followed for 12 months after the acute phase of the above post-approval study.
Croatian: Prema rezultatima oftalmoloških pregleda u podskupini ispitanika (n = 66; 14 u skupini koja je primala placebo, 52 u skupini koja je primala palifermin) koja je praćena tijekom 12 mjeseci nakon akutne faze spomenutog ispitivanja provedenog nakon registracije lijeka, ne mogu se isključiti kataraktogeni učinci palifermina.
English: Post- myeloablative radiochemotherapy:
Croatian: Prije mijeloablativne radiokemoterapije:
English: The safety and efficacy of Kepivance has not been established in patients with KGF receptor expressing non-haematological malignancies.
Croatian: Sigurnost i djelotvornost Kepivancea nije utvrđena u bolesnika s nehematološkim malignim bolestima koje izražavaju receptore za čimbenike rasta keratinocita.
English: The palifermin clinical program in the setting of myelotoxic therapy requiring haematopoietic stem cell (HSC) support included 650 patients with haematologic malignancies enrolled in 3 randomised, placebo-controlled clinical studies and a pharmacokinetic study.
Croatian: Klinička djelotvornost i sigurnost U klinički program primjene palifermina u ustanovama za mijelotoksičnu terapiju s potpornom primjenom krvotvornih matičnih stanica bilo je uključeno 650 bolesnika s hematološkim malignim bolestima koji su sudjelovali u 3 randomizirana, placebom kontrolirana klinička ispitivanja te jedno farkmakokinetičko ispitivanje.