FrancophonIA/ELRC3.0 huggingface dataset:
English: Farydak should be used with caution in patients who already have or who are at significant risk of developing QTc prolongation.
Croatian: Farydak se mora oprezno primjenjivati u bolesnika koji već imaju produljenje QTc-a ili su izloženi značajnom riziku od razvoja produljenja QTc-a.
English: Blood and lymphatic system disorders a
Croatian: Poremećaji krvi i limfnog sustava a
English: Adverse reactions leading to permanent discontinuation occurred in 30%, 44% and 47% of patients aged <65 years, 65-75 years and ≥75 years, respectively.
Croatian: Nuspojave koje su dovele do trajnog prekida primjene pojavile su se u 30%, 44% odnosno 47% bolesnika u dobi od redom <65 godina, 65-75 godina odnosno ≥75 godina.
English: While many patients developed neutropenia, febrile neutropenia only occurred in a fraction of treated patients (1.0%, both for CTC all grades and for grades 3 and 4).
Croatian: Dok se u mnogo bolesnika razvila neutropenija, febrilna neutropenija javila se samo u malom dijelu liječenih bolesnika (1,0%, kako za sve stupnjeve prema CTC-u tako i za 3. i 4. stupanj).
English: This could potentially lead to slightly decreased exposure to sensitive CYP3A4 substrates.
Croatian: To bi potencijalno moglo dovesti do blago povišene izloženosti osjetljivim CYP3A4 supstratima.
English: Farydak is an anti-cancer medicine that contains the active substance panobinostat, which belongs to a group of medicines called pan-deacetylase inhibitors.
Croatian: Farydak je lijek protiv raka koji sadrži djelatnu tvar panobinostat, koji pripada skupini lijekova koji se nazivaju inhibitorima pan-deacetilaze.
English: The recommended dose of bortezomib is 1.3 mg/m2 given as an injection.
Croatian: Preporučena doza bortezomiba je 1,3 mg/m2 u obliku injekcije.
English: Relapsed or refractory multiple myeloma patients are at risk of infections.
Croatian: Bolesnici s rekurentnim ili refraktornim multiplim mijelomom izloženi su riziku od infekcija.
English: Fatalities involving either pneumonia or sepsis were reported.
Croatian: Prijavljeni su smrtni slučajevi koji su uključivali ili pneumoniju ili sepsu.
English: • CTC grade 3 or 4 toxicity recurrence - a further dose reduction may be considered once the adverse event has resolved to CTC grade <1.
Croatian: • Ponovna pojava toksičnosti 3. ili 4. stupnja prema CTC-u - može se razmotriti daljnje smanjenje doze nakon što se štetni događaj riješi do <1. stupnja prema CTC-u.
English: Day 10 Day 11 Day 12 Day 13 Day 14 Day 15 Day 16 Day 17 Day 18 Day 19 Day 20 Day 21
Croatian: 10. dan 11. dan 12. dan 13. dan 14. dan 15. dan 16. dan 17. dan 18. dan 19. dan 20. dan 21. dan
English: Tell your doctor straight away if your partner becomes pregnant while you are taking Farydak or during the six months following your treatment with Farydak.
Croatian: Odmah se obratite svom liječniku ako Vaša partnerica zatrudni dok uzimate Farydak ili tijekom šest mjeseci nakon liječenja Farydakom.
English: After a single oral dose of [14C] panobinostat in patients, 29 to 51% of administered radioactivity is excreted in the urine and 44 to 77% in the faeces.
Croatian: Nakon jednokratne doze [14C] panobinostata u bolesnika, 29 do 51% primijenjene radioaktivnosti izlučuje se u mokraći, a 44 do 77% u stolici.
English: The effects of panobinostat on labour and post-natal growth and maturation were not evaluated in animal studies.
Croatian: Učinci panobinostata na porod i postnatalni rast i sazrijevanje nisu bili ocjenjivani u ispitivanjima na životinjama.
English: In addition, it is currently unknown whether panobinostat may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should additionally use a barrier method of contraception.
Croatian: Uz to, trenutačno nije poznato može li panobinostat smanjiti učinkovitost hormonskih kontraceptiva, pa stoga žene koje koriste hormonske kontraceptive moraju uz to koristiti i kontracepcijsku metodu barijere.
English: Farydak is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs at nanomolar concentrations.
Croatian: Farydak je inhibitor histonske deacetilaze (HDAC) koji inhibira enzimsku aktivnost HDAC-a u nanomolarnim koncentracijama.
English: In case of concomitant use of agents that may increase panobinostat plasma concentrations, such as strong CYP3A4 inhibitors, dose adjustment is required (see sections 4.5 and 4.2).
Croatian: U slučaju istodobne primjene tvari koje mogu povećati koncentracije panobinostata u plazmi, kao što su snažni CYP3A4 inhibitori, potrebno je prilagoditi dozu (vidjeti dijelove 4.5 i 4.2).
English: There are no clinical studies on the use of Farydak in pregnant patients.
Croatian: Nema kliničkih ispitivanja primjene Farydaka u trudnih bolesnica.
English: Panobinostat may be started at a dose of 15 mg, and if tolerated in the first cycle escalated to 20 mg in the second cycle.
Croatian: Primjena panobinostata može se započeti u dozi od 15 mg, a ako se podnosi u prvom ciklusu može se povećati do 20 mg u drugom ciklusu.
English: - Do not take this medicine after the expiry date, which is stated on the carton and blister foil.
Croatian: - Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na kutiji i foliji blistera.
English: Resume at the same dose
Croatian: Nastaviti u istoj dozi
English: Some of these infections (e.g. pneumonia) have been severe (e.g. leading to sepsis, or respiratory or multi-organ failure) and have had fatal outcomes (see section 4.8).
Croatian: Neke od tih infekcija (npr. pneumonija) bile su teške (npr. dovele do sepse, ili respiratornog ili multiorganskog zatajenja) te su imale smrtne ishode (vidjeti dio 4.8).
English: If this is unavoidable, patients should be closely monitored and further dose reduction or discontinuation may be considered as clinically indicated (see section 4.5).
Croatian: Ako je to neizbježno, bolesnike treba pažljivo pratiti te razmotriti dodatno smanjenje doze ili prekid terapije ako je to klinički indicirano (vidjeti dio 4.5).
English: Cycles 1-8 (3-week cycles)
Croatian: 1.-8. ciklus (3-tjedni ciklusi)
English: These medicines should be used with care or may need to be avoided during your treatment with Farydak.
Croatian: Ti se lijekovi moraju koristiti oprezno ili ćete ih možda trebati izbjegavati tijekom liječenja Farydakom.
English: Due to the potential risk of death or malformation to the foetus, you should use the following methods of contraception while taking Farydak:
Croatian: Zbog potencijalnog rizika od smrti ili anomalije fetusa, morate koristiti sljedeće metode kontracepcije dok uzimate Farydak:
English: Pertinent metabolic pathways involved in the biotransformation of panobinostat are reduction, hydrolysis, oxidation and glucuronidation processes.
Croatian: Relevantni metabolički putevi uključeni u biotransformaciju panobinostata su procesi redukcije, hidrolize, oksidacije i glukuronidacije.
English: Hard capsule 6 capsules 12 capsules 24 capsules
Croatian: 12 kapsula 24 kapsule
English: • difficulty in breathing with blueness around the mouth, which could lead to loss of consciousness (sign of serious lung problems)
Croatian: • poteškoće s disanjem uz plavilo oko usana, što može dovesti do gubitka svijesti (znak ozbiljnih problema s plućima)
English: All 55 patients were previously treated with bortezomib and at least one IMiD (lenalidomide: 98.2%, thalidomide: 69.1%).
Croatian: Svih 55 bolesnika prethodno je bilo liječeno bortezomibom i najmanje jednim imunomodulacijskim lijekom (lenalidomid: 98,2%, talidomid: 69,1%).
English: • The patient compliance card shall contain instructions on the following key messages: o How to become familiar with the compliance card: this section provides a general overview of the compliance card and its purpose.
Croatian: • Kartica za praćenje suradljivosti bolesnika treba sadržavati upute za sljedeće ključne poruke: o Kako se upoznati s karticom za praćenje suradljivosti: taj dio pruža opće informacije o kartici za praćenje suradljivosti i navodi njezinu svrhu.
English: Treatment with Farydak should be initiated by a physician experienced in the use of anti-cancer therapies.
Croatian: Liječenje Farydakom treba započeti liječnik koji ima iskustva u primjeni terapija protiv raka.
English: - Store in the original package in order to protect from moisture.
Croatian: - Čuvati u originalnom pakiranju radi zaštite od vlage.
English: Grade on day of treatment
Croatian: Stupanj neutropenije na dan liječenja
English: Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation.
Croatian: Inhibicija aktivnosti HDAC-a rezultira povećanom acetilacijom histonskih proteina, epigenetskom promjenom koja rezultira opuštanjem kromatina, što dovodi do transkripcijske aktivacije.
English: Panobinostat is rapidly and almost completely absorbed with Tmax reached within 2 hours of oral administration in patients with advanced cancer.
Croatian: Panobinostat se brzo i gotovo potpuno apsorbira pri čemu se Tmax postiže u roku od 2 sata od peroralne primjene u bolesnika s uznapredovalim rakom.
English: Gastrointestinal toxicity, primarily diarrhoea, nausea and vomiting, is among the most frequently reported adverse reactions.
Croatian: Gastrointestinalna toksičnost, prvenstveno proljev, mučnina i povraćanje, među najčešće su prijavljenim nuspojavama.
English: In vitro, panobinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells.
Croatian: In vitro je panobinostat uzrokovao akumulaciju acetiliranih histona i drugih proteina, uključujući zaustavljanje staničnog ciklusa i/ili apoptozu nekih transformiranih stanica.
English: - The active substance of Farydak is panobinostat.
Croatian: - Djelatna tvar Farydaka je panobinostat.
English: For patients >75 years of age, depending on the patient's general condition and concomitant diseases, an adjustment of the starting doses or schedule of the components of the combination regimen may be considered.
Croatian: >75 godina, ovisno o bolesnikovom općem stanju i istodobno prisutnim bolestima, može se razmotriti prilagođavanje početnih doza ili rasporeda komponenti kombiniranog režima.
English: Panobinostat may increase the QTc interval (see section 4.4).
Croatian: Panobinostat bi mogao produljiti QTc interval (vidjeti dio 4.4).
English: The primary endpoint of the study was to assess overall response rate (ORR) after 8 cycles of therapy
Croatian: Primarni ishod ispitivanja bio je procijeniti ukupnu stopu odgovora (eng. overall response rate, ORR)
English: Patients should be monitored for signs and symptoms of infections during treatment with panobinostat; if a diagnosis of infection is made, appropriate anti-infective treatment should be instituted promptly and interruption or discontinuation of Farydak considered.
Croatian: U bolesnika treba pratiti postoje li znakovi i simptomi infekcija tijekom liječenja panobinostatom; ako se utvrdi dijagnoza infekcije, potrebno je odmah započeti odgovarajuće antiinfekcijsko liječenje te razmotriti privremeni ili trajni prekid primjene Farydakom.
English: • palpitations
Croatian: • palpitacije
English: Patients should be instructed to avoid star fruit, grapefruit, grapefruit juice, pomegranates and pomegranate juice, as these are known to inhibit cytochrome P450 3A enzymes and may increase the bioavailability of panobinostat.
Croatian: Bolesnike treba uputiti da izbjegavaju karambolu (zvjezdano voće), grejp, sok od grejpa, šipak (nar) i sok od nara, budući da je za njih poznato da inhibiraju enzime citokroma P450 3A i mogu povećati bioraspoloživost panobinostata.
English: CTC grade 3 fatigue was reported in 15.7% of the patients, and grade 4 in 1.3%.
Croatian: Umor 3. stupnja prema CTC-u bio je prijavljen u 15,7% bolesnika, a 4. stupnja u 1,3%.
English: Talk to your doctor or pharmacist before taking Farydak: - if you have liver problems or have ever had liver disease.
Croatian: Obratite se svom liječniku ili ljekarniku prije nego uzmete Farydak: - ako imate problema s jetrom ili ako ste ikada imali bolest jetre.
English: Gastrointestinal toxicity is very common in patients treated with panobinostat.
Croatian: Gastrointestinalna toksičnost vrlo je česta u bolesnika liječenih panobinostatom.
English: Therefore a complete blood count must be performed before initiating therapy with panobinostat, with frequent monitoring during treatment (in particular before each injection of bortezomib as per bortezomib SmPC).
Croatian: Stoga se mora napraviti kompletna krvna slika prije početka terapije panobinostatom, uz učestalo praćenje tijekom liječenja (osobito prije svake injekcije bortezomiba u skladu sa Sažetkom opisa svojstava lijeka za bortezomib).
English: The bortezomib and dexamethasone prescribing information should be consulted prior to the start of the combination treatment to assess whether a dose reduction is required.
Croatian: Potrebno je pročitati informacije o propisivanju za bortezomib i deksametazon prije početka kombiniranog liječenja kako bi se procijenilo je li potrebno smanjenje doze.
English: If you are a sexually active man, you should use condoms during treatment with Farydak.
Croatian: Ako ste seksualno aktivan muškarac, morate koristiti kondome tijekom liječenja Farydakom.
English: Panobinostat shows more cytotoxicity towards tumour cells compared to normal cells.
Croatian: Panobinostat pokazuje više citotoksičnosti prema tumorskim stanicama u usporedbi s normalnim stanicama.
English: Frequency of monitoring of these patients should be increased during treatment with panobinostat, particularly during the dose escalation phase.
Croatian: Učestalost praćenja tih bolesnika treba povećati tijekom liječenja panobinostatom, osobito tijekom faze povećanja doze.
English: How to use the Farydak blister
Croatian: Kako koristiti Farydak blister
English: In addition, increased expression of the tumour suppressor gene p21CDKNIA (cyclin dependent kinase inhibitor 1/p21) gene, a key mediator of G1 arrest and differentiation, was triggered with panobinostat exposure.
Croatian: Uz to, povećana ekspresija tumor supresorskog gena p21CDKNIA (inhibitor kinaze 1/p21 ovisan o ciklinu), ključnog posrednika zaustavljanja i diferencijacije G1 faze, bila je potaknuta izloženošću panobinostatu.
English: The median PFS (95% CI) was 12.0 months (10.3, 12.9) and 8.1 months (7.6, 9.2), respectively.
Croatian: Medijan PFS-a (95% CI) bio je 12,0 mjeseci (10,3, 12,9) odnosno 8,1 mjesec
English: • increased blood level of the waste product creatinine
Croatian: • povećana razina otpadnog proizvoda kreatinina u krvi
English: Liver function should be monitored prior to treatment and regularly during treatment.
Croatian: Funkciju jetre treba pratiti prije liječenja te redovito tijekom liječenja.
English: Unchanged panobinostat accounted for <2.5% of the dose in urine and <3.5% of the dose in faeces.
Croatian: Nepromijenjeni panobinostat činio je <2,5% doze u mokraći i <3,5% doze u stolici.
English: Carcinogenicity studies have not been performed with panobinostat.
Croatian: Ispitivanja kancerogenosti nisu provođena s panobinostatom.
English: The median time to onset for grade 3 and 4 thrombocytopenia was one month and the median time to recovery was 12 days.
Croatian: Medijan vremena do nastupa trombocitopenije 3. i 4. stupnja bio je mjesec dana, a medijan vremena do oporavka bio je 12 dana.
English: - Do not take this medicine if you notice any damage to the packaging or if there are any signs of tampering.
Croatian: - Ovaj lijek se ne smije upotrijebiti ako primijetite da je pakiranje oštećeno ili postoje vidljivi znakovi neovlaštenog otvaranja.
English: Censoring Times PAN+BTZ+Dex (n/N=44/73) PBO+BTZ+Dex (n/N=54/74)
Croatian: Vremena cenzuriranja PAN+BTZ+Dex (n/N=44/73) PBO+BTZ+Dex (n/N=54/74)
English: Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal infections such as aspergillosis or candidiasis, and viral infections including hepatitis B virus and herpes simplex, have been reported in patients taking panobinostat.
Croatian: Lokalizirane i sistemske infekcije, uključujući upalu pluća, druge bakterijske infekcije, invazivne gljivične infekcije kao što su aspergiloza ili kandidijaza, te virusne infekcije uključujući hepatitis B virus i herpes simplex, prijavljene su u bolesnika koji su uzimali panobinostat.
English: In the event of grade 3 nausea or grade 3 or 4 vomiting despite administration of an anti-emetic, panobinostat should be temporarily discontinued and resumed at a reduced dose on recovery to grade 1.
Croatian: U slučaju mučnine 3. stupnja ili povraćanja 3. ili 4. stupnja usprkos primjeni antiemetika, potrebno je privremeno prekinuti primjenu panobinostata te nastaviti u smanjenoj dozi nakon oporavka do 1. stupnja.
English: Adverse drug reactions are listed according to system organ classes in MedDRA.
Croatian: Nuspojave na lijek su navedene prema klasifikaciji organskih sustava u MedDRA-i.
English: Based on preclinical and clinical data, panobinostat has the potential to prolong the QT interval.
Croatian: Na temelju pretkliničkih i kliničkih podataka, panobinostat ima potencijal produljivanja QT intervala.
English: Pooled clinical data from over 500 patients treated with panobinostat alone in multiple indications and at different dose levels have shown that the incidence of CTC grade 3 QTc prolongation (QTcF >500 msec) was approximately 1% overall and 5% or more at a dose of 60 mg or higher; no episodes of torsades de pointes were observed.
Croatian: Objedinjeni klinički podaci dobiveni od više od 500 bolesnika liječenih samo panobinostatom za više indikacija i u različitim dozama pokazali su da je incidencija produljenja QTc-a 3. stupnja prema CTC-u (QTcF >500 msec) bila otprilike 1% ukupno te 5% ili više pri dozi od 60 mg ili većoj; nisu bile uočene epizode torsades de pointes.
English: There is no relevant use of panobinostat in paediatric patients below the age of 18 years in the indication multiple myeloma (see section 5.2).
Croatian: Nema relevantne primjene panobinostata u pedijatrijskih bolesnika mlađih od 18 godina za indikaciju multiplog mijeloma (vidjeti dio 5.2).
English: Gastrointestinal toxicity
Croatian: Gastrointestinalna toksičnost
English: QTcF should be <480 msec prior to initiation of treatment with Farydak.
Croatian: QTcF treba biti <480 msec prije početka liječenja Farydakom.
English: HDACs catalyse the removal of acetyl groups from the lysine residues of histones and some non-histone proteins.
Croatian: HDAC-i kataliziraju uklanjanje acetilnih skupina iz lizinskih ostataka histona i nekih nehistonskih proteina.
English: Overall panobinostat exposure and inter-patient variability remained unchanged with or without food, whereas Cmax was reduced by <45% and Tmax prolonged by 1 to 2.5 hours with food (i.e. both normal and high-fat breakfasts).
Croatian: Ukupna izloženost panobinostatu i varijabilnost među bolesnicima ostale su nepromijenjene uz obrok ili bez njega, dok se Cmax smanjio za <45%, a Tmax produljio za 1 do 2,5 sata uz obrok (tj. i uz normalan doručak i uz doručak bogat masnoćama).
English: However, thrombocytopenia is reversible (median time to recovery of 12 days) and can usually be managed by dose adjustment and interruption with or without platelet transfusion (see section 4.4).
Croatian: Međutim, trombocitopenija je reverzibilna (medijan vremena do oporavka od 12 sati) i obično se može zbrinuti prilagođavanjem doze i privremenim prekidom terapije uz transfuziju trombocita ili bez nje (vidjeti dio 4.4).
English: Panobinostat has demonstrated mutagenic potential in the Ames assay, endo-reduplication effects in human peripheral blood lymphocytes in vitro, and DNA damage in an in vivo COMET study in mouse lymphoma L5178Y cells, that are attributed to the pharmacological mode of action.
Croatian: Panobinostat je pokazao mutageni potencijal u Amesovom testu, endoreduplikacijske učinke u limfocitima ljudske periferne krvi in vitro i oštećenje DNK u in vivo ispitivanju COMET na stanicama L5178Y mišjeg limfoma, koji se pripisuju farmakološkom načinu djelovanja.
English: Your doctor may need to change your dose, temporarily stop or completely stop your treatment with Farydak in case you experience side effects.
Croatian: Liječnik će Vam možda morati promijeniti dozu, privremeno ili trajno prekinuti liječenje Farydakom ako osjetite nuspojave.
English: In the phase III study, thrombocytopenia typically recovered to baseline by the start of the next 21-day cycle (see Figure 1).
Croatian: U ispitivanju faze III trombocitopenija se obično oporavila na početnu vrijednost do početka sljedećeg 21-dnevnog ciklusa (vidjeti Sliku 1).
English: Potential contributing factors may include prior history of chemotherapy, stem cell transplant, the nature of the disease and neutropenia or lymphopenia associated with Farydak treatment.
Croatian: Potencijalni čimbenici koji tome doprinose mogu uključivati prethodnu kemoterapiju, transplantaciju matičnih stanica, prirodu bolesti te neutropeniju ili limfopeniju povezanu s liječenjem Farydakom.
English: If you accidentally take more capsules than you should, or if someone else accidentally takes your medicine, talk to a doctor or go to a hospital straight away.
Croatian: Ako slučajno uzmete više kapsula nego što ste trebali, ili ako netko drugi slučajno uzme
English: • The dose should be omitted, if QTcF is ≥480 msec or above 60 msec from baseline.
Croatian: • Dozu treba propustiti ako je QTcF ≥480 msec ili iznad 60 msec u odnosu na početnu vrijednost.
English: • swollen ankles (a sign of a low level of albumin in the blood which is known as hypoalbuminaemia)
Croatian: • otečeni gležnjevi (znak niske razine albumina u krvi koja se naziva hipoalbuminemija)
English: Bortezomib may be started at 1.3 mg/m2 once weekly on days 1 and 8, and dexamethasone at 20 mg on days 1 and 8.
Croatian: Bortezomib se može započeti u dozi od 1,3 mg/m2 jedanput na tjedan i to 1. i 8. dana, a deksametazon u dozi od 20 mg 1. i 8. dana.
English: Sexually active men taking Farydak and their female partners should use a highly effective method of contraception during the man's treatment and for six months after his last dose of Farydak.
Croatian: Seksualno aktivni muškarci koji uzimaju Farydak i njihove partnerice trebaju koristiti vrlo učinkovitu metodu kontracepcije tijekom liječenja muškarca te šest mjeseci nakon njegove zadnje doze Farydaka.
English: The primary target organs of toxicity following administration of panobinostat in rats and dogs were identified as the erythropoietic, myelopoietic and lymphatic systems.
Croatian: Primarni ciljni organi toksičnosti nakon primjene panobinostata u štakora i pasa utvrđeni su kao eritropoetski, mijelopoetski i limfni sustav.
English: Prostatic atrophy accompanied by reduced secretory granules, testicular degeneration, oligospermia and increased epididymal debris were observed in dogs at exposures corresponding to 0.41-0.69 of the human clinical AUC and not fully reversible after a 4 week recovery period.
Croatian: Atrofija prostate popraćena smanjenim sekretornim granulama, degeneracijom testisa, oligospermijom i povećanim ostacima u epididimisu bila je uočena u pasa pri izloženostima koje odgovaraju 0,41-0,69 klinički uočenog AUC-a kod ljudi i nije bila potpuno reverzibilna nakon razdoblja oporavka od 4 tjedna.
English: Prophylactic anti-emetics should be administered at the discretion of the physician and in accordance with local medical practice (see section 4.4).
Croatian: Profilaktičke antiemetike treba primjenjivati prema odluci liječnika te u skladu s lokalnom medicinskom praksom (vidjeti dio 4.4).
English: Due to its cytostatic/cytotoxic mode of action, panobinostat can influence the quality of sperm formed during treatment.
Croatian: Zbog svog citostatičnog/citotoksičnog načina djelovanja, panobinostat može utjecati na kvalitetu sperme koja nastaje za vrijeme liječenja.