natgillin/translations-raw huggingface dataset:
For information on preparation and administration of Kepivance, please see information for healthcare professionals at the end of this leaflet.
Za informacije o pripremi i primjeni Kepivancea pročitajte informacije za zdravstvene djelatnike na kraju ove upute.
If you are pregnant you should not use Kepivance unless clearly necessary.
Ako ste trudni, ne smijete primati Kepivance, osim ako je to neophodno.
Once reconstituted, store in a refrigerator and use within 24 hours.
Nakon pripreme za primjenu, čuvati u hladnjaku i primijeniti unutar 24 sata.
These events were consistent with those observed at the recommended dose but were generally more severe.
Te nuspojave odgovaraju onima primijećenim pri preporučenoj dozi, ali su općenito bile ozbiljnije.
Studies in animals have shown reproductive and developmental toxicity (see section 5.3).
Ispitivanja na životinjama pokazala su reproduktivnu i razvojnu toksičnost (vidjeti dio 5.3).
These reactions were primarily mild to moderate in severity and were reversible.
Te reakcije bile su uglavnom blage do umjerene i reverzibilne.
Adverse reactions from clinical trials and spontaneous reporting
Nuspojave iz kliničkih ispitivanja i spontanog prijavljivanja
• increase in lipase and amylase levels (digestive enzymes) in the blood (which do not require treatment and usually return to normal after stopping treatment with Kepivance).
• povišene razine lipaze i amilaze (probavnih enzima) u krvi (koje ne zahtijevaju liječenje i obično se vrate na normalnu razinu po završetku liječenja Kepivanceom).
Based on these limited data no recommendation on dose adjustment can be
Na temelju ovih ograničenih podataka nije moguće dati preporuku za prilagodbu doze.
Peri- and postnatal development has not been studied.
Nisu provedena ispitivanja peri- i postnatalnog razvoja.
Kepivance will be given to you by a doctor or nurse with experience in cancer treatment.
Kepivance će Vam dati liječnik ili medicinska sestra s iskustvom u liječenju raka.
Pharmacotherapeutic group: Detoxifying agents for antineoplastic treatment, ATC code: V03A F08.
Farmakoterapijska skupina: Detoksikacijsko sredstvo pri liječenju antineoplastičnim lijekovima, ATK oznaka: V03A F08.
Safety and efficacy has not been evaluated in older people.
Starije osobe Sigurnost i djelotvornost u starijih osoba nije procijenjena.
In this study, 212 patients were randomised and received either palifermin or placebo.
U ovom ispitivanju 212 bolesnika je randomizirano i primilo ili palifermin, ili placebo.
Although palifermin was safe at all doses tested the incidence of skin reactions increased with the dose.
Iako je palifermin bio siguran pri svim ispitivanim dozama, incidencija kožnih reakcija povećavala se s dozom.
Other medicines and Kepivance
Drugi lijekovi i Kepivance
As a protein therapeutic, the risk for Kepivance to interact with other medicinal products is low.
Budući da se radi o terapijskom proteinu, rizik od interakcije Kepivancea s drugim lijekovima je nizak.
After reconstitution: 24 hours at 2 °C - 8 °C, protected from light.
Nakon pripreme za primjenu: 24 sata na temperaturi 2°C-8°C, zaštićen od svjetlosti.
Kepivance might interact with a medicine called heparin.
Može doći do interakcije lijeka Kepivance s lijekom koji se zove heparin.
Anaphylactic reaction/Hypersensitivity
Anafilaktička reakcija/preosjetljivost
Each pack contains 6 vials.
Svako pakiranje sadrži 6 bočica.
There are no adequate data from the use of Kepivance in pregnant women.
Nema odgovarajućih podataka o primjeni Kepivancea u trudnica.
Blood amylase increased and Lipase Increased1
Povišena amilaza u krvi i povišena lipaza1
Palifermin is a 140 amino acid protein with a molecular weight of 16.3 kilodaltons.
Palifermin je protein koji se sastoji od 140 aminokiselina i ima molekularnu težinu od 16,3 kilodaltona.
However, the administration of palifermin did not affect heparin´s anticoagulant effect in the experimental conditions (single dose, subtherapeutic dose regimen).
Međutim, primjena palifermina nije utjecala na antikoagulacijski učinak heparina u eksperimentalnim uvjetima (jednokratna doza, primjena supterapijske doze).
Very common: Common:
Vrlo često:
Neither of the two dosing regimens demonstrated statistically significant results versus placebo.
U niti jednom od dva protokola doziranja nisu utvrđeni statistički značajni rezultati u usporedbi s placebom.
Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu
Detaljnije informacije o ovom lijeku dostupne su na web stranici Europske agencije za lijekove http://www.ema.europa.eu.
Palifermin should not be used in association with myeloablative chemotherapy-only conditioning.
Palifermin se ne smije upotrebljavati pri kondicioniranju samo mijeloablativnom kemoterapijom.
A phase I dose escalation study was conducted in paediatric patients aged 1-16 years.
Ispitivanje faze I s povišenjem doze provedeno je u pedijatrijskih bolesnika u dobi od 1 do 16 godina.
In a study to assess potential carcinogenicity in transgenic rasH2 mice, no treatment related increases in the incidence of neoplastic lesions were observed.
U ispitivanju provedenom radi procjene potencijalne kancerogenosti u transgeničnih rasH2 miševa nije došlo do povećanja incidencije neoplastičnih lezija povezanih s liječenjem.
Kepivance should be reconstituted with 1.2 ml water for injections.
Kepivance treba pripremiti za primjenu pomoću 1,2 ml vode za injekcije.
One of the side effects of these treatments is oral mucositis.
Jedna od nuspojava tih liječenja je oralni mukozitis.
Lack of efficacy and risk of infection with high dose melphalan conditioning regimen
Nedostatna djelotvornost i rizik od infekcije u slučaju protokola kondicioniranja visokom dozom melfalana
Inter-subject variability is high with a CV% of about 50% for CL and 60% for Vss.
Varijabilnost među ispitanicima bila je visoka, s koeficijentom varijacije od oko 50% za klirens i 60% za volumen Vss.
Visual acuity was not affected at 6 or 12 months in either treatment group.
Oštrina vida nije se u 6 ili 12 mjeseci pogoršala niti u jednoj od skupina.
The usual dose of Kepivance is 60 micrograms of Kepivance per kilogram of bodyweight per day.
Uobičajena doza Kepivancea je 60 mikrograma po kilogramu tjelesne težine dnevno.
Median time to onset was approximately 6 days following the first of 3 consecutive daily doses of Kepivance, with a median duration of approximately 5 days.
Medijan vremena do pojave bio je oko 6 dana nakon prve od 3 uzastopne dnevne doze Kepivancea s medijanom trajanja od oko 5 dana.
1 Kepivance may cause increased lipase and amylase levels in some patients with or without symptoms of abdominal pain or backache.
1 Kepivance može uzrokovati povišene razine lipaze i amilaze u nekih bolesnika s ili bez simptoma boli u trbuhu ili leđima.
- The active substance is palifermin.
- Djelatna tvar je palifermin.
Face oedema, oedema mouth
Edem lica, edem usne šupljine
The long-term safety of Kepivance has not been fully evaluated with respect to overall survival, progression free survival and secondary malignancies.
Dugoročna sigurnost Kepivancea s obzirom na ukupno preživljenje, preživljenje bez progresije bolesti i sekundarne maligne bolesti još nije u potpunosti istražena.
The contents should be swirled gently during dissolution.
Sadržaj je tijekom otapanja potrebno lagano miješati.
Kepivance should not be administered subcutaneously due to poor local tolerability.
Kepivance se ne smije primjenjivati supkutano zbog loše lokalne podnošljivosti lijeka.
Dysgeusia Paraesthesia oral
Dizgeuzija Oralne parestezije
The pharmacodynamic effect of palifermin, as measured by the change in Ki67 expression, tended to be lower when administered with heparin but the clinical relevance of this finding is unclear.
Farmakodinamički učinak palifermina, mjeren promjenama u ekspresiji antigena Ki67, bio je manji kada se primjenjivao s heparinom, no klinički značaj ove pojave nije jasan.
For information on dose limiting toxicities see section 4.8.
Za informacije o toksičnosti ovisnoj o dozi vidjeti dio 4.8.
In addition, there was a higher incidence of infections in patients administered palifermin pre- and post-chemotherapy (49.5%) compared with patients who received placebo (24.6%).
Osim toga, incidencija infekcija bila je veća u bolesnika koji su palifermin primili prije i poslije kemoterapije (49,5%) u usporedbi s bolesnicima koji su primali placebo (24,6%).
In-vitro and in-vivo data suggest that palifermin binds to unfractionated as well as low molecular weight heparins.
In vitro i in vivo podaci pokazuju da se palifermin veže za nefrakcionirani heparin kao i za heparine niske molekularne mase.
A single dose of 250 micrograms/kg has been administered intravenously to 8 healthy volunteers without severe or serious adverse effects.
Jednokratna doza od 250 mikrograma/kg primijenjena je intravenski u 8 zdravih dobrovoljaca bez teških ili ozbiljnih nuspojava.
In this Phase 3 clinical study, palifermin treated patients demonstrated significant benefits in patient-reported outcomes of mouth and throat soreness and its impact on swallowing, drinking, eating and talking.
U ovom kliničkom ispitivanju faze 3 bolesnici liječeni paliferminom prijavili su značajno poboljšanje po pitanju nadraženosti usne šupljine i grla i njenog utjecaja na gutanje, pijenje, jedenje i pričanje.
In two studies in healthy volunteers, co-administration of Kepivance and heparin resulted in approximately 5 times higher systemic exposure to palifermin, due to a lower volume of distribution.
U dva ispitivanja provedena na zdravim dobrovoljcima, istovremena primjena Kepivancea i heparina dovela je do približno 5 puta većeg sustavnog izlaganja paliferminu zbog smanjenog volumena raspodjele.
The main efficacy endpoint of the study was the number of days during which patients experienced severe oral mucositis (grade 3/4 on the World Health Organisation (WHO) scale).
Primarni ishod ispitivanja bio je broj dana tijekom kojih su bolesnici imali težak oblik oralnog mukozitisa (stupnja 3/4 prema ljestvici Svjetske zdravstvene organizacije (SZO)).
Do not use Kepivance if you are breast
Nemojte primjenjivati Kepivance ako dojite.
Kepivance is a sterile but unpreserved product and is intended for single use only.
Kepivance je sterilan lijek, ali ne sadrži konzervanse te je namijenjen za jednokratnu uporabu.
The most commonly reported adverse drug reactions (reported in > 1/10 patients) are reactions consistent with the pharmacologic action of Kepivance on skin and oral epithelium, e.g. oedema, including peripheral oedema, and hypertrophia of oral structures.
Najčešće nuspojave na lijek (u >1/10 bolesnika) su reakcije koje odgovaraju farmakološkom djelovanju Kepivancea na kožu i oralni epitel, npr. edem, uključujući periferni edem i hipertrofiju oralnih struktura.
• darkening of an area of skin (hyperpigmentation);
• trnci u usnoj šupljini; • tamnjenje dijela kože (hiperpigmentacija);
Currently available data are described in section 5.2 but no recommendation on dose adjustment can be made.
Trenutno dostupni podaci opisani su u dijelu 5.2, međutim nije moguće dati preporuku o doziranju.
However, patients treated with chemotherapy and/or radiotherapy are at higher risk of developing secondary tumours some of which may express KGF receptors, and theoretically, be stimulated by KGF receptor ligands.
Međutim, u bolesnika liječenih kemoterapijom i/ili radioterapijom postoji veći rizik od razvoja sekundarnih tumora od kojih neki mogu izražavati receptore za čimbenike rasta keratinocita i teoretski mogu biti stimulirani ligandima receptora za čimbenike rasta keratinocita.
Common (affects 1 to 10 users in 100) side effects are:
Često (mogu se javiti u 1 do 10 osoba na 100 osoba):
Treatment with these doses was also associated with maternal effects (clinical signs and/or changes in body weight/food consumption), suggesting that palifermin was not selectively toxic to development in either species.
Liječenje ovim dozama također je bilo povezano s učincima na majku (klinički pokazatelji i/ili promjene tjelesne težine/uzimanja hrane), što znači da u tim vrstama palifermin nije bio selektivno toksičan za razvoj.
There was an imbalance in age distribution with more elderly (> 65 years) patients in the palifermin group.
Skupine su bile dobno neuravnotežene, s više starijih ispitanika (> 65 godina) u skupini koja je primala palifermin.
Due to limited data in patients, heparins should be used with care in patients receiving palifermin and appropriate blood coagulation tests should be carried out to monitor their treatment.
Zbog ograničenih podataka u bolesnika, heparine treba upotrebljavati oprezno u bolesnika koji primaju palifermin te treba provoditi odgovarajuće testove zgrušavanja krvi radi praćenja liječenja.
Palifermin stimulates the growth of specific cells called epithelial cells that form the tissue lining of your mouth and digestive tract, as well as other tissues such as skin.
Palifermin potiče rast posebnih stanica koje se nazivaju epitelne stanice, a oblikuju tkivo kojim su obložena Vaša usta i probavna cijev, kao i druga tkiva poput kože.
Salient findings in toxicology studies in rat and monkey were generally attributable to the pharmacological activity of palifermin, specifically, proliferation of epithelial tissues.
Glavni rezultati toksikoloških ispitivanja na štakorima i majmunima uglavnom su bili u skladu s farmakološkom aktivnošću palifermina, osobito proliferacijom epitelnog tkiva.
Compared with the placebo group, the pre/post-chemotherapy group had a higher incidence of herpes virus infection (9% vs 0%), oral fungal infection (7% vs 2%) and sepsis/septic shock (12% vs 2%).
U usporedbi sa skupinom koja je primala placebo, u skupini koja je lijek primila prije i poslije kemoterapije bila je viša incidencija infekcija virusom herpesa (9% naspram 0%), oralnih gljivičnih infekcija (7% naspram 2%) i sepse/septičkog šoka (12% naspram 2%).
** WHO Oral Mucositis Scale: Grade 1 = soreness/erythema; Grade 2 = erythema, ulcers, can eat solids; Grade 3 = ulcers, requires liquid diet only; Grade 4 = alimentation not possible
** Ljestvica SZO-a za oralni mukozitis: stupanj 1 = osjetljivost/crvenilo; stupanj 2 = crvenilo, ulkusi, može jesti krutu hranu; stupanj 3 = ulkusi, samo tekuća hrana; stupanj 4 = nije moguće uzimanje hrane
MARKETING AUTHORISATION HOLDER Swedish Orphan Biovitrum AB (publ) SE-112 76 Stockholm
Swedish Orphan Biovitrum AB (publ) SE-112 76 Stockholm Švedska
To treat your blood cancer you may be receiving chemotherapy, radiotherapy and autologous hematopoietic stem cell transplantation (cells from your own body that produce blood cells).
Za liječenje raka krvi možete primati kemoterapiju, zračenje ili presađivanje vlastitih krvotvornih matičnih stanica (stanice iz Vašeg tijela koje proizvode druge krvne stanice).
Before injection‚ Kepivance may be allowed to reach room temperature for a maximum of 1 hour but should be protected from light.
Prije injiciranja, Kepivance se može ostaviti maksimalno 1 sat da postigne sobnu temperaturu, ali ga je potrebno zaštititi od svjetlosti.
Vaginal oedema and vulvovaginal erythema
Vaginalni edem i vulvovaginalni eritem
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).
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%).
OTHER CONDITIONS AND REQUIREMENTS OF THE
OSTALI UVJETI I ZAHTJEVI ZA STAVLJANJE
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).
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).
Mild to moderate renal impairment (creatinine clearance 30-80 ml/min) did not influence palifermin pharmacokinetics.
Blago do umjereno oštećenje funkcije bubrega (klirens kreatinina 30-80 ml/min) nije utjecalo na farmakokinetiku palifermina.
6.25 mg of powder in a vial (Type I glass) with a rubber stopper, an aluminium seal and a plastic flip
6,25 mg praška u bočici (staklo tipa I) s gumenim čepom, aluminijskim prstenom i plastičnom
These no observed adverse effect level (NOAEL) doses were associated with systemic exposures up to 2.5 times greater than anticipated clinical exposure.
Te doze pri kojima nisu uočeni štetni učinci povezane su sa sustavnim izlaganjima do 2,5 puta većim od očekivane kliničke izloženosti.
Safety data are based on patients with haematological malignancies enrolled in randomised, placebocontrolled clinical studies, including one pharmacokinetic study, and post marketing experience.
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.
Kepivance should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of cytotoxic chemotherapy.
Kepivance se ne smije primjenjivati unutar 24 sata prije, tijekom ili unutar 24 sata nakon primjene citotoksične kemoterapije.
Rash, pruritus and erythema Skin hyperpigmentation Palmar-plantar erythrodysaesthesia syndrome (dysaesthesia, erythema, oedema on the palms and soles)
Osip, svrbež i crvenilo kože Hiperpigmentacija kože Palmarno-plantarna eritrodizestezija (dizestezija, eritem, edem na dlanovima i tabanima)
Kepivance is used to reduce the frequency, duration and severity of oral mucositis symptoms.
Kepivance se koristi za smanjenje učestalosti, trajanja i težine simptoma oralnog mukozitisa.
Other endpoints included the incidence, duration and severity of oral mucositis and the requirement for opioid analgesia.
Drugi ciljevi bili su incidencija, trajanje i težina oralnog mukozitisa i potreba za opioidnom analgezijom.
In a clinical trial, administration of Kepivance within 24 hours of chemotherapy resulted in an increased severity and duration of oral mucositis.
U kliničkom je ispitivanju primjena Kepivancea unutar 24 sata nakon kemoterapije uzrokovala teži oblik i dulje trajanje oralnog mukozitisa.
• 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)
• 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,
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.
Razmak između posljednje doze Kepivancea prije mijeloablativne radiokemoterapije i prve doze Kepivancea nakon mijeloablativne radiokemoterapije treba iznositi najmanje sedam dana.
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.
Kepivance ćete dobivati tri dana zaredom prije kemoterapije i zračenja i tri dana zaredom nakon kemoterapije i zračenja, ukupno šest doza.
In patients with severe renal impairment (creatinine clearance < 30 ml/min), clearance was decreased by 22% (n = 5).
U bolesnika s teškim oštećenjem funkcije bubrega (klirens kreatinina < 30 ml/min) klirens je bio smanjen za 22% (n = 5).
Non-haematological malignancies
Nehematološke maligne bolesti
Kepivance should not be used during pregnancy unless clearly
Kepivance se ne smije primjenjivati u trudnoći, osim ako je to neophodno.
Epithelial cell proliferation was assessed by Ki67 immunohistochemical staining in healthy subjects.
Proliferacija epitelnih stanica procjenjivana je imunohistokemijskim bojenjem na Ki67 u zdravih ispitanika.
Hypersensitivity, including Anaphylactic reactions, has also been associated with palifermin.
uključujući anafilaktičke reakcije, također se povezuje s paliferminom.
- if you are allergic to palifermin, Escherichia coli derived proteins or any other ingredients of
- ako ste alergični na palifermin, proteine dobivene iz Escherichie coli ili druge sastojke ovog lijeka (navedene u dijelu 6).
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).
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).
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).
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).
No overt cases of pancreatitis have been reported in this patient population.
U ovoj populaciji bolesnika nisu prijavljeni očiti slučajevi pankreatitisa.
The diluent should be injected slowly into the Kepivance vial.
Otapalo treba polako injicirati u bočicu s lijekom Kepivance.
Do not shake or vigorously agitate the vial.
Bočicu ne tresti niti snažno mućkati.
There was no evidence of a delay in time to haematopoietic recovery in patients who received palifermin as compared to patients who received placebo.
Nije dokazan odgođeni hematopoetski oporavak u bolesnika koji su primali palifermin u usporedbi s ispitanicima koji su primali placebo.
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.
Kepivance se koristi za liječenje oralnog mukozitisa (bol, suhoća i upala usta) koji nastaje kao nuspojava u liječenju raka krvi.
In patients with end-stage renal disease (requiring dialysis) palifermin clearance was decreased by 10% (n = 6).
U bolesnika u terminalnoj fazi bolesti bubrega (koja zahtijeva dijaliza), klirens palifermina bio je manji za 10% (n = 6).
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.
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.
Kepivance contains the active substance palifermin which is a protein produced by biotechnology in a bacteria called Escherichia coli.
Kepivance sadrži djelatnu tvar palifermin, protein proizveden biotehnologijom u bakteriji
The pharmacokinetics of palifermin were studied in healthy volunteers and patients with haematological malignancies.
5.2 Farmakokinetička svojstva Farmakokinetička svojstva palifermina ispitivana su u zdravih dobrovoljaca i bolesnika s hematološkim malignim bolestima.
• swelling (oedema) of the face or mouth;
• oticanje (edem) lica ili usta;
Kepivance has not been tested in pregnant women.
Trudnoća i dojenje Kepivance nije ispitivan na trudnicama.