natgillin/translations-raw huggingface dataset:
In combination with capecitabine • For capecitabine dose modifications, see capecitabine summary of product characteristics. • For patients developing the first appearance of a Grade 2 toxicity, which persists at the time of the next docetaxel/ capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 100% of the original dose. • For patients developing the second appearance of a Grade 2 toxicity, or the first appearance of a Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1, then resume treatment with docetaxel 55 mg/ m². • For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel dose.
V kombinaciji s kapecitabinom • Za prilagoditve odmerka kapecitabina glejte povzetek glavnih značilnosti kapecitabina. • Pri bolnikih, pri katerih se prvič pojavijo toksični učinki 2. stopnje, ki trajajo še v času naslednjega zdravljenja z docetakselom/ kapecitabinom, zdravljenje odložite, dokler se ne zmanjšajo na stopnjo od 0 do 1 ter znova uporabite 100% izvirnega odmerka. • Pri bolnikih, pri katerih se drugič pojavijo toksični učinki 2. stopnje ali prvič učinki 3. stopnje kadarkoli med ciklusom zdravljenja, zdravljenje odložite, dokler se ne zmanjšajo na stopnjo od 0 do 1, nato zdravljenje nadaljujte z docetakselom 55 mg/ m2. • V primeru vsakega ponovnega pojava toksičnih učinkov ali pojava toksičnih učinkov 4. stopnje, odmerek docetaksela prekinite.
In combination with cisplatin and 5-fluorouracil If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/ m2.
V kombinaciji s cisplatinom in 5- fluorouracilom Če se kljub uporabi G- CSF pojavi febrilna nevtropenija, dolgotrajna nevtropenija ali nevtropenična okužba, je treba odmerek docetaksela zmanjšati s 75 na 60 mg/ m2.
If subsequent episodes of complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/ m2.
Če se pojavijo nadaljnje epizode zapletene nevtropenije, je treba odmerek docetaksela zmanjšati s 60 na 45 mg/ m2.
In case of Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/ m2.
V primeru trombocitopenije 4. stopnje je treba odmerek docetaksela zmanjšati s 75 na 60 mg/ m2.
Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level > 1,500 cells/ mm3 and platelets recover to a level > 100,000 cells/ mm3.
Bolniki ne smejo znova dobiti ciklusov docetaksela, dokler se število nevtrofilcev ne poveča na > 1. 500 celic/ mm3 in število trombocitov na > 100. 000 celic/ mm3.
(See section 4.4).
Če ti toksični učinki trajajo, zdravljenje prekinite (glejte poglavje 4. 4).
Recommended dose modifications for toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):
Priporočene prilagoditve odmerka v primeru toksičnih učinkov na prebavilih pri bolnikih, ki prejemajo Docetaxel Winthrop v kombinaciji s cisplatinom in 5- fluorouracilom (5- FU):
Diarrhea grade 3
driska 3. stopnje
First episode: reduce 5-FU dose by 20%.
Prvi pojav: zmanjšajte odmerek 5- FU za 20%.
Second episode: then reduce docetaxel dose by 20%.
Drugi pojav: zmanjšajte odmerek docetaksela za 20%.
Diarrhea grade 4
driska 4. stopnje
First episode: reduce docetaxel and 5-FU doses by 20%.
Prvi pojav: zmanjšajte odmerka docetaksel in 5- FU za 20%.
Stomatitis/ mucositis grade 3
Stomatitis/ mukoziti s 3. stopnje
Second episode: stop 5-FU only, at all subsequent cycles.
Drugi pojav: med vsemi naslednjimi ciklusi opustite le 5- FU.
Third episode: reduce docetaxel dose by 20%.
Tretji pojav: zmanjšajte odmerek docetaksel za 20%.
Stomatitis/ mucositis grade 4
Stomatitis/ mukoziti s 4. stopnje
First episode: stop 5-FU only, at all subsequent cycles.
Prvi pojav: med vsemi naslednjimi ciklusi opustite le 5- FU.
Second episode: reduce docetaxel dose by 20%.
Drugi pojav: zmanjšajte odmerek docetaksel za 20%.
For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product characteristics.
Za prilagoditve odmerjanja cisplatina in 5- fluorouracila glejte ustrezen povzetek glavnih značilnosti obeh zdravil.
In the pivotal SCCHN trials patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 6-15) in all subsequent cycles.
V ključnem SCCHN preskušanju pri bolnikih, pri katerih se je pojavila komplicirana nevtropenija (ki vključuje dolgotrajno nevtropenijo, fibrilno nevtropenijo ali okužbo), je bilo priporočeno, naj se v vseh naslednjih ciklih za profilaktično kritje (na primer med 6. in 15. dnem) uporablja G- CSF.
5 Special populations
5 Posebne skupine bolnikov:
Patients with hepatic impairment Based on pharmacokinetic data with docetaxel at 100 mg/ m² as single agent, patients who have both elevations of transaminase (ALT and/ or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/ m2 (see sections 4.4 and 5.2).
Bolniki z okvaro jeter Glede na farmakokinetične podatke o monoterapiji z docetakselom v odmerku 100 mg/ m2 je priporočljivi odmerek docetaksela za bolnike, ki imajo transaminazi (ALT, AST ali obe) zvišani nad 1, 5- kratno zgornjo mejo normalnega območja (ULN) in alkalno fosfatazo nad 2, 5- kratno ULN, 75 mg/ m2 (glejte poglavji 4. 4 in 5. 2).
For those patients with serum bilirubin > ULN and/ or ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose- reduction can be recommended and docetaxel should not be used unless strictly indicated.
Pri bolnikih, ki imajo serumski bilirubin > ULN in/ ali ALT in AST > 3, 5- kratno ULN ter hkrati alkalno fosfatazo > 6- kratno ULN, ni mogoče priporočiti zmanjšanja odmerka; pri teh bolnikih se docetaksela ne sme uporabljati, če ni strogo indiciran.
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial excluded patients with ALT and/ or AST > 1.5 × ULN associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated.
V ključnem kliničnem preskušanju docetaksela v kombinaciji s cisplatinom in 5- fluorouracilom pri bolnikih z adenokarcinomom želodca so izključili bolnike z ALT in/ ali AST > 1, 5 x ULN ter hkrati alkalno fosfatazo > 2, 5 x ULN in bilirubinom > 1 x ULN; pri teh bolnikih ni mogoče priporočiti zmanjšanja odmerka in docetaksela se ne sme uporabljati, če ni strogo indiciran.
Children and adolescents The experience in children is limited.
Otroci in mladostniki Izkušnje pri otrocih so omejene.
Elderly Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly.
Starostniki Za uporabo pri starostnikih glede na analizo farmakokinetike na populaciji ni posebnih navodil.
In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics).
V kombinaciji s kapecitabinom je priporočljivo začetni odmerek kapecitabina pri bolnikih, starejših od 60 let, zmanjšati na 75% (glejte povzetek glavnih značilnosti kapecitabina).
Docetaxel must not be used in patients with baseline neutrophil count of < 1,500 cells/ mm3.
Docetaksela se ne sme uporabljati pri bolnikih z izhodiščnim številom nevtrofilcev < 1. 500 celic/ mm3.
Docetaxel must not be used in pregnant or breast-feeding women.
Docetaksela ne smejo dobivati nosečnice in doječe ženske.
Docetaxel must not be used in patients with severe liver impairment since there is no data available (see sections 4.2 and 4.4).
Docetaksela se ne sme uporabljati pri bolnikih s hudo okvaro jeter, ker o uporabi pri njih ni podatkov (glejte poglavji 4. 2 in 4. 4).
For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e. g.
Pri zdravljenju raka dojke in nedrobnoceličnega pljučnega raka lahko 3- dnevna premedikacija s peroralnim kortikosteroidom, npr. deksametazonom 16 mg na dan (npr.
8 mg BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.
8 mg 2- krat na dan), ki se začne 1 dan pred aplikacijo docetaksela, zmanjša pogostnost in izrazitost zastajanja tekočine ter izrazitost preobčutljivostnih reakcij, če ni kontraindicirana.
For prostate cancer, the premedication is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2).
Pri zdravljenju raka prostate je premedikacija peroralni deksametazon 8 mg, 12 ur, 3 ure in 1 uro pred infuzijo docetaksela (prosimo, glejte poglavje 4. 2).
Patients should be retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/ mm3 (see section 4.2).
Bolniki smejo docetaksel spet dobiti, šele ko se število nevtrofilcev znova zveča na vrednost ≥ 1. 500 celic/ mm3 (glejte poglavje 4. 2).
In the case of severe neutropenia (< 500 cells/ mm3 for seven days or more) during a course of docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate symptomatic measures are recommended (see section 4.2).
Če se med zdravljenjem z docetakselom pojavi huda nevtropenija (< 500 celic/ mm3 sedem dni ali več), je med naslednjimi ciklusi priporočljivo zmanjšati odmerek ali uporabiti ustrezne simptomatske ukrepe (glejte poglavje 4. 2).
6 In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF.
6 Med bolniki, ki so docetaksel prejemali v kombinaciji s cisplatinom in 5- fluorouracilom (TCF), sta se febrilna nevtropenija in nevtropenična okužba redkeje pojavili pri bolnikih, ki so profilaktično prejemali G- CSF.
Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection).
Bolniki, ki prejemajo TCF, morajo profilaktično prejemati G- CSF za zmanjšanje tveganja za zapleteno nevtropenijo (febrilno nevtropenijo, dolgotrajno nevtropenijo ali nevtropenično okužbo).
Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8).
Bolnike, ki prejemajo TCF, je treba natančno nadzirati (glejte poglavji 4. 2 in 4. 8).
However, severe reactions, such as severe hypotension, bronchospasm or generalised rash/ erythema require immediate discontinuation of docetaxel and appropriate therapy.
V primeru hudih reakcij, npr. hude hipotenzije, bronhospazma ali generaliziranega izpuščaja oz. eritema, pa je treba zdravljenje z docetakselom takoj prekiniti in uporabiti ustrezno terapijo.
Severe symptoms such as eruptions followed by desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see section 4.2).
Opisani so hudi simptomi, npr. izpuščaji s poznejšo deskvamacijo, zaradi katerih je bilo treba zdravljenje z docetakselom prekiniti ali opustiti (glejte poglavje 4. 2).
In patients treated with docetaxel at 100 mg/ m2 as single agent who have serum transaminase levels (ALT and/ or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia.
Pri bolnikih, zdravljenih s 100 mg docetaksela/ m2 v monoterapiji, ki imajo serumski transaminazi (ALT, AST ali obe) zvišani nad 1, 5- kratno ULN in hkrati zvišano serumsko alkalno fosfatazo nad 2, 5 - kratno ULN, obstaja večja nevarnost hudih neželenih učinkov, kot so smrti zaradi zastrupitve, vključno s sepso in gastrointestinalno krvavitvijo, ki sta lahko usodni, febrilne nevtropenije, okužb, trombocitopenije, stomatitisa in astenije.
Therefore, the recommended dose of docetaxel in those patients with elevated liver function test (LFTs) is 75 mg/ m2 and LFTs should be measured at baseline and before each cycle (see section 4.2).
Zato je pri bolnikih z zvišanimi vrednostmi testov jetrne funkcije priporočeni odmerek docetaksela 75 mg/ m2, teste jetrne funkcije pa je treba opraviti na začetku in pred vsakim ciklusom zdravljenja (glejte poglavje 4. 2).
For patients with serum bilirubin levels > ULN and/ or ALT and AST > 3.5 times the ULN concurrent with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended and docetaxel should not be used unless strictly indicated.
Pri bolnikih, ki imajo serumski bilirubin > ULN in/ ali ALT in AST > 3, 5- kratno ULN ter hkrati alkalno fosfatazo > 6- kratno ULN, ni mogoče priporočiti zmanjšanja odmerka; pri teh bolnikih se docetaksela ne sme uporabljati, če ni strogo indiciran.
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial excluded patients with ALT and/ or AST > 1.5 × ULN associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated.
V ključnem kliničnem preskušanju docetaksela v kombinaciji s cisplatinom in 5- fluorouracilom pri bolnikih z adenokarcinomom želodca so izključili bolnike z ALT in/ ali AST > 1, 5 × ULN ter hkrati alkalno fosfatazo > 2, 5 × ULN in bilirubinom > 1 x ULN; pri teh bolnikih ni mogoče priporočiti zmanjšanja odmerka in docetaksela se ne sme uporabljati, če ni strogo indiciran.
The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2).
Če se pojavijo hudi periferni nevrotoksični učinki, je treba odmerek zmanjšati (glejte poglavje 4. 2).
7 Cardiac toxicity
7 Kardiotoksičnost
This may be moderate to severe and has been associated with death (see section 4.8).
Le- to je lahko zmerne do hude narave in je bilo povezano s smrtjo (glejte poglavje 4. 8).
Cardiac function should be further monitored during treatment (e. g. every three months) to help identify patients who may develop cardiac dysfunction.
Srčno funkcijo je med zdravljenjem potrebno nadalje nadzorovati (npr. vsake tri mesece), da bi prepoznali bolnice, ki bi se jim lahko razvila srčna okvara.
Contraceptive measures must be taken during and for at least three months after cessation of therapy.
Med zdravljenjem in vsaj še tri mesece po njegovem koncu je treba uporabljati kontracepcijsko zaščito.
Additional cautions for use in adjuvant treatment of breast cancer Complicated neutropenia For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or infection), G-CSF and dose reduction should be considered (see section 4.2).
Dodatna opozorila pri uporabi adjuvantne terapije raka dojke Komplicirana nevtropenija Pri bolnicah, ki doživijo komplicirano nevtropenijo (podaljšano nevtropenijo, febrilno nevtropenijo ali okužbo) je potrebno razmisliti o G- CSF in zmanjšanju odmerka (glejte poglavje 4. 2).
Gastrointestinal reactions Symptoms such as early abdominal pain and tenderness, fever, diarrhea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.
Gastrointestinalne reakcije Simptomi kot so: abdominalne bolečine in občutljivost, zvišana telesna temperatura, driska z ali brez nevtropenije, so lahko zgodnja manifestacija resne gastrointestinalne toksičnosti ter jih je potrebno nemudoma ovrednotiti in zdraviti.
Congestive heart failure Patients should be monitored for symptoms of congestive heart failure during therapy and during the follow up period.
Kongestivno srčno popuščanje Bolnice je med terapijo in v obdobju nadzora po terapiji potrebno kontrolirati glede simptomov kongestivnega srčnega popuščanja.
Leukemia In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires haematological follow-up.
Levkemija Pri bolnikih, ki se zdravijo z docetakselom, doksorubicinom in ciklofosfamidom (TAC), je zaradi tveganja mieolodisplazije ali mieloične levkemije potrebno hematološko spremljanje.
Patients with 4+ nodes The benefit/ risk ratio for TAC in patients with 4+ nodes was not defined fully at the interim analysis (see section 5.1).
Bolnice s 4+ bezgavkami Pri bolnicah s 4+ bezgavkami razmerje korist/ tveganje za TAC v vmesnih analizah ni bilo docela definirano (glejte poglavje 5. 1).
Elderly There are no data available in patients > 70 years of age on docetaxel use in combination with doxorubicin and cyclophosphamide.
Starejši Ni podatkov o uporabi docetaksela v kombinaciji z doksorubicinom in ciklofosfamidom pri bolnicah > 70 let.
In patients treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in patients who were 65 years of age or greater compared to younger patients.
Pri bolnikih, zdravljenih z docetakselom vsake tri tedne, ki so bili starejši od 65 let, je bila incidenca pojavljanja z zdravljenjem povezanih sprememb na nohtih ≥ 10% večja v primerjavi z mlajšimi bolniki.
The incidence of related fever, diarrhea, anorexia, and peripheral edema occurred at rates ≥ 10% higher in patients who were 75 years of age or greater versus less than 65 years.
Incidenca z zdravljenjem povezane zvišane telesne temperature, diareje, anoreksije in perifernih edemov se je pojavljala ≥ 10% večkrat pri bolnikih nad 75 let v primerjavi z mlajšimi od 65 let.
Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer study, 74 were 65 years of age or older and 4 patients were 75 years of age or older.
Med 300 bolniki (221 bolnikov v III. fazi študije in 79 bolnikov v II. fazi študije), ki so jih zdravili z docetakselom v kombinaciji s cisplatinom in 5- fluorouracilom v študiji raka želodca, je bilo 74 bolnikov starih 65 let ali več, 4 pa so bili stari 75 let ali več.
The incidence of the following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates ≥ 10% higher in patients who were 65 years of age or older compared to younger patients.
Incidenca naslednjih neželenih učinkov (vse stopnje) – letargije, stomatitisa in nevtropenične okužbe – je bila pri bolnikih, starih 65 let ali več, ≥ 10% večja kot pri mlajših bolnikih.
8 4.5 Interaction with other medicinal products and other forms of interaction
8 4. 5 Medsebojno delovanje z drugimi zdravili in druge oblike interakcij
In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as ciclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin.
Študije in vitro so pokazale, da lahko presnovo docetaksela spremeni sočasna uporaba zdravil, ki inducirajo ali inhibirajo citokrom P450- 3A ali se z njim presnavljajo (in ga tako lahko kompetitivno inhibirajo), kot so ciklosporin, terfenadin, ketokonazol, eritromicin in troleandomicin.
Docetaxel is highly protein bound (> 95%).
Docetaksel je v veliki meri (> 95%) vezan na beljakovine.
Although the possible in vivo interaction of docetaxel with concomitantly administered medication has not been investigated formally, in vitro interactions with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of docetaxel.
Možna medsebojna delovanja docetaksela s sočasno uporabljanimi zdravili in vivo sicer niso bila formalno raziskana, a medsebojno delovanje z učinkovinami, močno vezanimi na beljakovine – npr. eritromicinom, difenhidraminom, propranololom, propafenonom, fenitoinom, salicilati, sulfametoksazolom in natrijevim valproatom – in vitro ni vplivalo na vezavo docetaksela na beljakovine.
When combined to docetaxel, the clearance of carboplatin was about 50% higher than values previously reported for carboplatin monotherapy.
V kombinaciji z docetakselom je bil očistek karboplatina približno 50% večji od vrednosti, opisanih med monoterapijo s karboplatinom.
Docetaxel should be administered with caution in patients concomitantly receiving potent CYP3A4 inhibitors (e. g. protease inhibitors like ritonavir, azole antifungals like ketoconazole or itraconazole).
Docetaksel se mora uporabljati pazljivo pri pacientih, ki sočasno jemljejo močne zaviralce CYP3A4 (npr. zaviralce proteaze kot je ritonavir, antimikotike derivate azola kot je ketokonazol ali itrakonazol).
A drug interaction study performed in patients receiving ketoconazole and docetaxel showed that the clearance of docetaxel was reduced by half by ketoconazole, probably because the metabolism of docetaxel involves CYP3A4 as a major (single) metabolic pathway.
V študiji interakcije z zdravili izvajane pri bolnikih, ki so jemali ketokonazol in docetaksel, je ketokonazol za polovico zmanjšal očistek docetaksela, verjetno zato ker metabolizem docetaksela vključuje CYP3A4 kot glavno (edino) metabolično pot.
Therefore, docetaxel must not be used during pregnancy.
Zato se docetaksela med nosečnostjo ne sme uporabljati.
The adverse reactions considered to be possibly or probably related to the administration of docetaxel have been obtained in: • 1312 and 121 patients who received 100 mg/ m² and 75 mg/ m² of docetaxel as a single agent respectively. • 258 patients who received docetaxel in combination with doxorubicin. • 406 patients who received docetaxel in combination with cisplatin. • 92 patients treated with docetaxel in combination with trastuzumab.
Podatki o neželenih učinkih, ki so morda ali verjetno povezani z uporabo zdravila docetaksel, so bili zbrani pri: • 1312 bolnikih, ki so v monoterapiji prejemali 100 mg/ m² zdravila docetaksel, 121 pa jih je prejemalo 75 mg/ m². • 258 bolnikih, ki so prejemali docetaksel v kombinaciji z doksorubicinom. • 406 bolnikih, ki so prejemali docetaksel v kombinaciji s cisplatinom. • 92 bolnicah, ki so prejemale docetaksel v kombinaciji s trastuzumabom. • 255 bolnikih, ki so prejemali docetaksel v kombinaciji s kapecitabinom.