natgillin/translations-raw huggingface dataset:
Based on a population pharmacokinetic analysis in 183 patients with cancer (50 male and 133 female patients, age ranging from 22 to 89 years, and body weight ranging from 38 to 123 kg), gender had no effect on the exposure of palbociclib, and age and body weight had no clinically important effect on the exposure of palbociclib.
Na podlagi populacijske farmakokinetične analize podatkov 183 bolnikov z rakom (50 moških in 133 ženskih bolnic, starih od 22 do 89 let in s telesno maso od 38 do 123 kg) spol ni imel nobenega učinka na izpostavljenost palbociklibu, starost in telesna masa pa nista imela klinično pomembnega učinka na izpostavljenost palbociklibu.
Effects of other medicinal products on the pharmacokinetics of palbociclib
Učinki drugih zdravil na farmakokinetiko palbocikliba
Palbociclib was foetotoxic in pregnant animals.
Palbociklib je bil fetotoksičen pri brejih živalih.
Laboratory abnormalities observed in pooled dataset from 3 randomised studies (N=872)
Laboratorijske nenormalnosti, opažene v združeni zbirki podatkov 3 randomiziranih preskušanj (n = 872)
IBRANCE 75 mg, 100 mg, and 125 mg are available in blister packs of 21 or 63 hard capsules and in plastic bottles of 21 hard capsules.
Zdravilo IBRANCE 75mg, 100mg in 125mg je na voljo v pretisnih omotihz21 ali 63trdimi kapsulami in plastenkah z 21 trdimi kapsulami.
OR [% (95% CI)]
OR [% (95 % IZ)]
The primary endpoint of the study was progression-free survival (PFS) evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, as assessed by investigator.
Primarni opazovani dogodek preskušanja je bilo preživetje brez napredovanja bolezni (PFSProgression-Free Survival), ki ga je raziskovalec ocenjeval v skladu z merili RECIST (Response Evaluation Criteria in Solid Tumours), različica 1.1.
The capsule length is 18.0 ± 0.3 mm.
Kapsula je dolga 18,0 ± 0,3 mm.
Randomised Phase 3 Study PALOMA-2: IBRANCE in combination with letrozole
Randomizirano preskušanje 3. faze PALOMA-2: zdravilo IBRANCE v kombinaciji z letrozolom
c Neutropenia includes the following PTs: Neutropenia, Neutrophil count decreased.
c. Nevtropenija vključuje naslednje PT: nevtropenija, zmanjšanje števila nevtrofilcev.
IBRANCE is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer: - in combination with an aromatase inhibitor; - in combination with fulvestrant in women who have received prior endocrine therapy (see section 5.1).
Zdravilo IBRANCE je indicirano za zdravljenje lokalno napredovalega ali metastatskega na hormonske receptorje (HR - Hormone Receptors) pozitivnega in na receptorje humanega epidermalnega rastnega faktorja 2 (HER2 - Human Epidermal growth factor Receptor 2) negativnega raka dojk: - v kombinaciji z zaviralcem aromataze, - v kombinaciji s fulvestrantom pri ženskah, ki so prejele predhodno endokrino zdravljenje (glejte poglavje 5.1).
HDPE bottle with a PP closure containing 21 hard capsules.
Plastenka iz HDPE z zaporko iz polipropilena, ki vsebuje 21 trdih kapsul.
The mean fraction unbound (fu) of palbociclib in human plasma in vivo increased incrementally with worsening hepatic function.
Srednja vrednost nevezane frakcije (fu) palbocikliba v človeški plazmi in vivo se je postopoma povečevala s slabšanjem delovanja jeter.
At the time of the updated analyses, the median time from randomisation to second subsequent therapy was 38.8 months in the palbociclib + letrozole arm and 28.8 months in the placebo + letrozole arm, HR 0.73 (95% CI: 0.58, 0.91).
Ob času posodobljenih analiz je bil mediani čas od randomizacije do drugega naknadnega zdravljenja 38,8 meseca v skupini s palbociklibom in letrozolom in 28,8 meseca v skupini s placebom in letrozolom, HR 0,73 (95 % IZ: 0,58; 0,91).
Palbociclib works by blocking proteins called cyclin-dependent kinase 4 and 6, which regulate cell growth and division.
Palbociklib deluje tako, da blokira beljakovini, imenovani od ciklina odvisna kinaza 4 in 6, ki uravnavata rast in delitev celic.
The concomitant use of strong CYP3A inhibitors including, but not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided (see sections 4.2 and 4.4).
Sočasni uporabi močnih zaviralcev CYP3A, med drugim klaritromicina, indinavirja, itrakonazola, ketokonazola, lopinavirja/ritonavirja, nefazodona, nelfinavirja, posakonazola, sakvinavirja, telaprevirja, telitromicina, vorikonazola in grenivke ali grenivkinega soka, se je treba izogibati (glejte poglavji 4.2 in 4.4).
Data from a pharmacokinetic trial in subjects with varying degrees of renal function indicate that total palbociclib exposure (AUCinf) increased by 39%, 42%, and 31% with mild (60 mL/min≤CrCl<90 mL/min), moderate (30 mL/min≤CrCl <60 mL/min), and severe (CrCl <30 mL/min) renal impairment, respectively, relative to subjects with normal (CrCl ≥90 mL/min) renal function.
Podatki iz farmakokinetičnega preskušanja pri preskušancih z različnimi stopnjami delovanja ledvic kažejo, da se je skupna izpostavljenost palbociklibu (AUCinf) povečala za 39 % pri blagi (60 ml/min ≤ CrCl < 90 ml/min), 42 % pri zmerni (30 ml/min ≤ CrCl < 60 ml/min) in 31 % pri hudi (CrCl < 30 ml/min) okvari ledvic v primerjavi s preskušanci z normalnim (CrCl ≥ 90 ml/min) delovanjem ledvic.
IBRANCE dose modification and management - Non-haematological toxicities CTCAE Grade
Prilagajanje in uravnavanje odmerkov zdravila IBRANCE - nehematološka toksičnost Stopnja CTCAE
Palbociclib is a reversible inhibitor of cyclin-dependent kinases 4 and 6, which are both involved in regulating the cell cycle.
Palbociklib je reverzibilni zaviralec od ciklina odvisnih kinaz 4 in 6, ki sodelujeta pri regulaciji celičnega cikla.
The geometric mean apparent oral clearance (CL/F) of palbociclib was 63 L/h, and the mean plasma elimination half-life was 28.8 hours in patients with advanced breast cancer.
Pri bolnikih z napredovalim rakom dojk je bil geometrični srednji navidezni peroralni očistek (CL/F) palbocikliba 63 l/h, srednji razpolovni čas izločanja iz plazme pa je bil 28,8 ur.
Final overall survival (OS) (13 April 2018 cutoff) Number of events (%) Median [months (95% CI)] Hazard ratio (95% CI) and p-value†
Končno celokupno preživetje (OS) (datum zaključka 13. april 2018) število dogodkov (%) mediana [meseci (95 % IZ)] razmerje ogroženosti (95 % IZ) in vrednost p p = 0,0429
In addition, based on a population pharmacokinetic analysis that included 183 patients with advanced cancer, where 40 patients had mild hepatic impairment based on National Cancer Institute (NCI) classification (total bilirubin ≤ Upper Limit of Normal (ULN) and Aspartate Aminotransferase (AST) > ULN, or total bilirubin >1.0 to 1.5 × ULN and any AST), mild hepatic impairment had no effect on the pharmacokinetics of palbociclib.
Poleg tega, na podlagi populacijske farmakokinetične analize podatkov 183 bolnikov z napredovalim rakom, od katerih je 40 bolnikov imelo blago okvaro jeter po merilih Nacionalnega inštituta za rakava obolenja (NCI - National Cancer Institute) (skupni bilirubin ≤ zgornja meja normalnih vrednosti [ZMN] in vrednost aspartat-aminotransferaze [AST] > ZMN, ali skupni bilirubin > 1,0 do 1,5 × ZMN in katerakoli vrednost AST), blaga okvara jeter ni imela nobenega učinka na farmakokinetiko palbocikliba.
Binding of palbociclib to human plasma proteins in vitro was ~85%, with no concentration dependence.
In vitro vezava palbocikliba na humane plazemske beljakovine je bila približno 85 %, neodvisno od koncentracije zdravila.
Updated Analysis (31 May 2017 Cutoff)
Posodobljena analiza (datum zaključka 31. maj 2017)
Effect of CYP3A inhibitors
Učinek zaviralcev CYP3A
IBRANCE is an anticancer medicine containing the active substance palbociclib.
Zdravilo IBRANCE je zdravilo za zdravljenje rakavih bolezni, ki vsebuje učinkovino palbociklib.
The capsule length is 19.4 ± 0.3 mm.
Kapsula je dolga 19,4 ± 0,3 mm.
Printing ink: shellac, titanium dioxide (E171), ammonium hydroxide (28% solution), propylene glycol, simeticone (see section 2 “IBRANCE contains lactose”).
Črnilo za napis na kapsuli: šelak, titanov dioksid (E171), amonijev hidroksid (28 % raztopina), propilenglikol, simetikon (glejte poglavje 2, ''Zdravilo IBRANCE vsebuje laktozo'').
Similarly, a reduction in the risk of disease progression or death in the palbociclib plus letrozole arm was observed in 512 patients whose tumour tested positive for Rb protein expression by immunohistochemistry (IHC) (HR of 0.543 [95% CI: 0.433, 0.681], mPFS 27.4 months versus 13.7 months).
Podobno so zmanjšanje tveganja za napredovanje bolezni ali smrt v skupini s palbociklibom in letrozolom opazili pri 512 bolnicah, pri katerih so za tumor imunohistokemijsko (IHC) potrdili ekspresijo beljakovine Rb (HR 0,543 [95 % IZ: 0,433; 0,681], mPFS 27,4 meseca v primerjavi s 13,7 meseca)].
It is unknown whether palbociclib is excreted in human milk.
Ni znano, ali se palbociklib izloča v materino mleko.
Note: Laboratory results are graded according to the NCI CTCAE version 4.0 severity grade.
Opomba: Laboratorijski rezultati so razvrščeni glede na stopnjo resnosti v skladu z merili NCI za poenoteno terminologijo neželenih dogodkov (National Cancer Institute Common Terminology Criteria for Adverse Events), različica 4.0.
Effects on glucose metabolism were associated with findings in the pancreas and secondary effects on eye, teeth, kidney, and adipose tissue in studies ≥15 weeks duration in rats only and bone changes were observed in rats only following 27 weeks of dosing.
V študijah samo na podganah, ki so trajale ≥ 15 tednov, so bili učinki na presnovo glukoze povezani z ugotovitvami glede trebušne slinavke in sekundarnimi učinki na oči, zobe, ledvice in maščobno tkivo, po 27 tednih odmerjanja samo pri podganah pa so opazili spremembe v kosteh.
A total of 521 pre/peri- and postmenopausal women who had progressed on or within 12 months from completion of adjuvant endocrine therapy or on or within 1 month from prior endocrine therapy for advanced disease, were randomised 2:1 to palbociclib plus fulvestrant or placebo plus fulvestrant and stratified by documented sensitivity to prior hormonal therapy, menopausal status at study entry (pre/peri- versus postmenopausal), and presence of visceral metastases.
Skupno 521 žensk v pred-, peri- in postmenopavzi, ki so napredovale v 12 mesecih od zaključka adjuvantnega endokrinega zdravljenja ali v 1 mesecu po predhodnem endokrinem zdravljenju napredovale bolezni, so randomizirali v razmerju 2:1 v skupino s palbociklibom in fulvestrantom ali v skupino s placebom in fulvestrantom ter jih stratificirali glede na dokumentirano občutljivost na predhodno hormonsko zdravljenje, menopavzalni status ob vključitvi v preskušanje (pred-/peri- v primerjavi s postmenopavzalnim) in prisotnost visceralnih metastaz.
Effect of tamoxifen on palbociclib exposure
Učinek tamoksifena na izpostavljenost palbociklibu
The concomitant use of strong CYP3A inducers including, but not limited to: carbamazepine, enzalutamide, phenytoin, rifampin, and St. John's Wort should be avoided (see sections 4.3 and 4.4).
Sočasni uporabi močnih induktorjev CYP3A, med drugim karbamazepina, enzalutamida, fenitoina, rifampicina in šentjanževke, se je treba izogibati (glejte poglavji 4.3 in 4.4).
WBC-white blood cells; AST-aspartate aminotransferase; ALT-alanine aminotransferase; N-number of patients; N/A-not applicable.
BKC = bele krvne celice; AST = aspartat-aminotransferaza; ALT = alanin-aminotransferaza; n = število bolnikov; N/V = ni na voljo.
The median time to first episode of any grade neutropenia was 15 days (12-700 days) and the median duration of Grade ≥3 neutropenia was 7 days across 3 randomised clinical studies.
V 3 randomiziranih kliničnih preskušanjih je bil mediani čas do prve epizode nevtropenije katerekoli stopnje 15 dni (12-700 dni), mediano trajanje nevtropenije stopnje ≥ 3 pa je bilo 7 dni.
The most common (≥20%) adverse reactions of any grade reported in patients receiving palbociclib in randomised clinical studies were neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anaemia, diarrhoea, alopecia and thrombocytopenia.
Najpogostejši (> 20 %) neželeni učinki katerekoli stopnje, o katerih so poročali v randomiziranih kliničnih preskušanjih pri bolnikih, ki so prejemali palbociklib, so bili nevtropenija, okužbe, levkopenija, utrujenost, navzea, stomatitis, anemija, diareja, alopecija in trombocitopenija.
Palbociclib-related findings in the testis, epididymis, prostate, and seminal vesicle included decreased organ weight, atrophy or degeneration, hypospermia, intratubular cellular debris, lower sperm motility and density, and decreased secretion.
S palbociklibom povezani učinki na moda, epididimis, prostato in semenjaka so vključevali zmanjšano maso organov, atrofijo ali degeneracijo, hipospermijo, intratubularni celični drobir, manjšo gibljivost in gostoto semenčic ter zmanjšano izločanje.
DDI studies of palbociclib with oral contraceptives have not been conducted (see section 4.6).
Študij medsebojnega delovanja med palbociklibom in peroralnimi kontraceptivi niso izvedli (glejte poglavje 4.6).
Addition of palbociclib to fulvestrant resulted in a symptom benefit by significantly delaying time-to-deterioration in pain symptom compared with placebo plus fulvestrant (median 8.0 months versus 2.8 months; HR of 0.64 [95% CI: 0.49, 0.85]; p<0.001).
V primerjavi s placebom in fulvestrantom je dodajanje palbocikliba fulvestrantu povzročilo izboljšanje simptomov tako, da je pomembno podaljšalo čas do poslabšanja simptomov bolečine (mediana 8,0 mesecev v primerjavi z 2,8 meseci, HR 0,64 [95 % IZ: 0,49; 0,85]; p < 0,001).
Absolute neutrophil counts (ANC) of ≥1000/mm3 and platelet counts of ≥50,000/mm3 are recommended to receive IBRANCE.
Za prejemanje zdravila IBRANCE je priporočeno absolutno število nevtrofilcev (ANC - Absolute Neutrophil Counts) ≥ 1.000/mm in število trombocitov ≥ 50.000/mm
Grade 4
stopnja 4
Coadministration of multiple doses of palbociclib with midazolam increased the midazolam AUCinf and Cmax values by 61% and 37%, respectively, as compared with administration of midazolam alone.
Sočasna uporaba večkratnih odmerkov palbocikliba z midazolamom je povečala vrednosti AUCinf in cmax midazolama za 61 % oziroma 37 % v primerjavi s samostojno uporabo midazolama.
Based on the 31-May-2017 data cutoff date, this reduction in risk continued to be observed in the following subgroups: (1) patients with either visceral metastases (HR of 0.62 [95% CI: 0.47, 0.81], median progression-free survival [mPFS] 19.3 months versus 12.3 months) or without visceral metastases (HR of 0.50 [95% CI: 0.37, 0.67], mPFS 35.9 months versus 17.0 months) and (2) patients with either bone only disease (HR of 0.41 [95% CI: 0.26, 0.63], mPFS 36.2 months versus 11.2 months) or without bone-only disease (HR of 0.62 [95% CI: 0.50, 0.78], mPFS 24.2 months versus 14.5 months).
Na datum zaključka zajema podatkov 31. maja 2017 so to zmanjšanje tveganja še naprej opažali pri naslednjih podskupinah: (1) pri bolnicah z visceralnimi metastazami (HR 0,62 [95 % IZ: 0,47; 0,81], mediano preživetje brez napredovanja bolezni [mPFS] 19,3 meseca v primerjavi z 12,3 meseca) ali brez visceralnih metastaz (HR 0,50 [95 % IZ: 0,37; 0,67], mPFS 35,9 meseca v primerjavi s 17,0 meseca) in (2) pri bolnicah z boleznijo samo v kosteh (HR 0,41 [95 % IZ: 0,26; 0,63], mPFS 36,2 meseca v primerjavi z 11,2 meseca) ali brez bolezni samo v kosteh (HR 0,62 [95 % IZ: 0,50; 0,78], mPFS 24,2 meseca v primerjavi s 14,5 meseca).
Palbociclib-related neoplastic finding in rats included an increased incidence of microglial cell tumours in the central nervous system of males at 30 mg/kg/day; there were no neoplastic findings in female rats at any dose up to 200 mg/kg/day.
S palbociklibom povezan pojav neoplastičnih sprememb pri podganah je vključeval povečano incidenco tumorjev mikroglialnih celic v osrednjem živčevju pri samcih pri odmerku 30 mg/kg/dan; pri samicah podgan neoplastičnih sprememb niso ugotovili pri nobenem odmerku do 200 mg/kg/dan.
Permanent discontinuation due to an adverse reaction occurred in 5.2% of patients receiving IBRANCE in randomised clinical studies regardless of the combination.
V randomiziranih kliničnih preskušanjih je do trajne prekinitve zdravljenja zaradi neželenega učinka prišlo pri 5,2 % bolnikov, ki so prejemali zdravilo IBRANCE, ne glede na kombinacijo.
The dose of sensitive CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) may need to be reduced when coadministered with IBRANCE as IBRANCE may increase their exposure.
Pri sočasni uporabi z zdravilom IBRANCE bo morda treba zmanjšati odmerek občutljivih substratov CYP3A z ozkim terapevtskim indeksom (npr. alfentanil, ciklosporin, dihidroergotamin, ergotamin, everolimus, fentanil, pimozid, kinidin, sirolimus in takrolimus), saj zdravilo IBRANCE lahko poveča izpostavljenost tem zdravilom.
In vitro and in vivo studies indicate that palbociclib undergoes extensive hepatic metabolism in humans.
Študije in vitro in in vivo kažejo, da je palbociklib pri ljudeh podvržen obsežni jetrni presnovi.
Kaplan-Meier plot of progression-free survival (investigator assessment, intent-to-treat population) - PALOMA-3 study (23 October 2015 cutoff)
Kaplan-Meierjev graf preživetja brez napredovanja bolezni (ocena raziskovalca, populacija z namenom zdravljenja) - preskušanje PALOMA-3 (datum zaključka 23. oktober 2015)
Patients with advanced symptomatic, visceral spread, that were at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement), were not eligible for enrolment into the study.
Bolnice z napredovalim simptomatskim, visceralno razširjenim rakom, pri katerih je obstajalo kratkoročno tveganje za življenjsko ogrožajoče zaplete (vključno z bolnicami z masivnimi neobvladanimi izlivi [plevralni, perikardni ali peritonealni], pljučnim limfangiitisom in več kot 50 % prizadetostjo jeter), niso bile primerne za vključitev v preskušanje.
Patients with advanced/metastatic, symptomatic, visceral spread, that were at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement), were not eligible for enrolment into the study.
Bolnice z napredovalim/metastatskim, simptomatskim, visceralno razširjenim rakom, pri katerih je obstajalo kratkoročno tveganje za življenjsko ogrožajoče zaplete (vključno z bolnicami z masivnimi neobvladanimi izlivi [plevralni, perikardni ali peritonealni], pljučnim limfangiitisom in več kot 50 % prizadetostjo jeter), niso bile primerne za vključitev v preskušanje.
No dose adjustment of IBRANCE is necessary in patients ≥65 years of age (see section 5.2).
Pri bolnikih, starih ≥ 65 let, prilagajanje odmerka zdravila IBRANCE ni potrebno (glejte poglavje 5.2).
WBC decreased Neutrophils decreased Anaemia
zmanjšanje števila BKC zmanjšanje števila nevtrofilcev 95,6 anemija
No dose adjustment of IBRANCE is required for patients with mild, moderate or severe renal impairment (creatinine clearance [CrCl] ≥15 mL/min).
Pri bolnikih z blago, zmerno ali hudo okvaro ledvic (očistek kreatinina [CrCl - Creatinine Clearance] ≥ 15 ml/min) prilagajanje odmerka zdravila IBRANCE ni potrebno.
Grade 3
stopnja 3
Palbociclib may decrease fertility in men.
Plodnost Palbociklib lahko poslabša plodnost pri moških.
IBRANCE dose modification and management - Haematological toxicities CTCAE Grade
Prilagajanje in uravnavanje odmerkov zdravila IBRANCE - hematološka toksičnost Stopnja po CTCAE
There was no obvious trend in the mean palbociclib fu in human plasma in vivo with worsening renal function.
Očitnega trenda gibanja srednje vrednosti fu palbocikliba v človeški plazmi in vivo, povezanega s slabšanjem delovanja ledvic, niso opazili.
The reversibility of the effects on glucose homeostasis, pancreas, eye, kidney, and bone was not established following a 12-week nondosing period, whereas partial to full reversal of effects on the haematolymphopoietic and male reproductive systems, teeth, and adipose tissue was observed.
Po 12-tedenskem obdobju brez odmerjanja niso ugotovili reverzibilnosti učinkov na homeostazo glukoze, trebušno slinavko, oči, ledvice in kosti, vendar pa so opazili delni ali popolni preobrat učinkov na hematolimfopoetske in moške reprodukcijske organe, zobe in maščobno tkivo.
Palbociclib did not affect mating or fertility in female rats at any dose tested up to 300 mg/kg/day (approximately 3 times human clinical exposure based on AUC), and no adverse effects were observed in female reproductive tissues in repeat-dose toxicity studies up to 300 mg/kg/day in the rat and 3 mg/kg/day in the dog (approximately 5 and 3 times human clinical exposure based on AUC, respectively).
Palbociklib ni vplival na parjenje ali plodnost samic podgan pri nobenem testiranem odmerku do 300 mg/kg/dan (približno 3-kratnik klinične izpostavljenosti pri ljudeh na osnovi vrednosti AUC) prav tako v študijah toksičnosti ponavljajočih se odmerkov do 300 mg/kg/dan pri podganah in 3 mg/kg/dan pri psih (približno 5- oziroma 3-kratnik klinične izpostavljenosti pri ljudeh na osnovi vrednosti AUC) niso opazili nobenih neželenih učinkov na reproduktivna tkiva samic.
A total of 666 postmenopausal women were randomised 2:1 to the palbociclib plus letrozole arm or placebo plus letrozole arm and were stratified by site of disease (visceral versus nonvisceral), disease-free interval from the end of (neo)adjuvant treatment to disease recurrence (de novo metastatic versus 12 months versus >12 months), and by the type of prior (neo)adjuvant anticancer therapies (prior hormonal therapy versus no prior hormonal therapy).
Skupno 666 žensk v postmenopavzi so randomizirali v razmerju 2:1 v skupino s palbociklibom in letrozolom ali v skupino s placebom in letrozolom in jih stratificirali glede na mesto bolezni (visceralna v primerjavi z nevisceralno), interval brez bolezni od konca (neo)adjuvantnega zdravljenja do ponovitve bolezni (metastatska bolezen de novo v primerjavi z  12 meseci v primerjavi z > 12 meseci) in glede na vrsto predhodnega (neo)adjuvantnega zdravljenja raka (predhodno hormonsko zdravljenje v primerjavi z odsotnostjo predhodnega hormonskega zdravljenja).
Use of preparations containing St. John's Wort (see section 4.5).
Uporaba pripravkov s šentjanževko (glejte poglavje 4.5).
Placebo plus fulvestrant (N=174)
Placebo in fulvestrant (n = 174)
Data from a pharmacokinetic trial in subjects with varying degrees of hepatic function indicate that palbociclib unbound exposure (unbound AUCinf) decreased by 17% in subjects with mild hepatic impairment (Child-Pugh class A), and increased by 34% and 77% in subjects with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic impairment, respectively, relative to subjects with normal hepatic function.
Podatki iz farmakokinetičnega preskušanja pri preskušancih z različnimi stopnjami delovanja jeter kažejo, da se je izpostavljenost nevezanemu palbociklibu (nevezana AUCinf) zmanjšala za 17 % pri preskušancih z blago (razred A po klasifikaciji Child-Pugh) okvaro jeter ter povečala za 34 % pri preskušancih z zmerno (razred B po klasifikaciji Child-Pugh) in za 77 % pri preskušancih s hudo (razred C po klasifikaciji Child-Pugh) okvaro jeter v primerjavi s preskušanci z normalnim delovanjem jeter.