natgillin/translations-raw huggingface dataset:
In the majority of patients (8/ 10), the pericardial effusion and pericarditis were deemed to be asymptomatic and of little or no clinical significance on echocardiographic assessment.
Pri večini bolnikov (8/ 10) so perikardni izliv in perikarditis ocenili kot asimptomatična in kot klinično nepomembna ali malo pomembna za ehokardiografske preiskave.
However, the pericardial effusion was clinically significant in 2 patients with some associated haemodynamic compromise.
Vendar pa je bil perikardni izliv klinično pomemben pri 2 bolnikih, pri katerih je bil povezan z ogroženo hemodinamiko.
Vascular disorders adverse events:
Žilne bolezni:
Fifty eight percent of patients experienced at least one vascular disorders adverse event.
Pri 58% bolnikov je prišlo do vsaj enega dogodka žilnega neželenega učinka.
Twenty six events in 24/ 132 patients were considered to be related to clofarabine, the most frequently reported being flushing (15 events; not serious) and hypotension (5 events; one of which was considered to be serious; see section 4.4).
Najpogosteje so poročali o vročinskih oblivih (15 dogodkov; niso bili resni) in hipotenziji (5 dogodkov; enega so ocenili kot resnega; glejte poglavje 4. 4).
However, the majority of these hypotensive events were reported in patients who had confounding severe infections.
Poleg tega je imelo 9/ 132 bolnikov, ki so prejemali klofarabin, vsaj hudo povečan kreatinin (vsaj 3. stopnje po CTC NCI v
7 Renal and urinary disorders adverse events:
7 ZDA).
In addition, 9/ 132 patients receiving clofarabine had at least severely elevated creatinine (at least US NCI CTC Grade 3 elevated creatinine) and increased blood creatinine was reported as an adverse event that was not related to clofarabine on 2 occasions (see sections 4.3 and 4.4).
O povečanem kreatininu v krvi kot o neželenem učinku, ki ni povezan z uporabo klofarabina, so poročali v dveh dogodkih (glejte poglavji 4. 3 in 4. 4).
Hepato-biliary disorders adverse events:
Bolezni jeter, žolčnika in žolčevodov:
The liver is a potential target organ for clofarabine toxicity and 26% of patients experienced at least one hepato-biliary disorders adverse event (see sections 4.3 and 4.4).
Jetra so morebitna tarča za toksične učinke klofarabina ter pri 26% bolnikov je prišlo do vsaj ene bolezni jeter, žolčnika in žolčevodov (glejte poglavji 4. 3 in 4. 4).
Fourteen events in 10/ 132 patients were considered to be related to clofarabine of which acute cholecystitis (1 event), cholelithiasis (1 event), hepatocellular damage (1 event; patient died (see above)) and hyperbilirubinaemia (2 events; patients discontinued therapy (see above)) were considered to be serious.
Za 14 dogodkov pri 10/ 132 bolnikih so menili, da so povezani z uporabo klofarabina, med njimi so akutni holecistitis (1 dogodek), holelitiaza (1 dogodek), poškodbe hepatocitov (1 dogodek; bolnik je umrl (glejte zgoraj)) in hiperbilirubinemijo (2 dogodka; bolnika sta prekinila zdravljenje (glejte zgoraj)) ocenili kot resne.
In addition, 55/ 129 patients receiving clofarabine had at least severely (at least US NCI CTC Grade 3) elevated ALT, 38/ 102 elevated AST and 19/ 131 elevated bilirubin levels.
Poleg tega je 55/ 129 bolnikov, ki so prejemali klofarabin, imelo vsaj hudo (vsaj 3. stopnje po CTC NCI v ZDA 3) povečane vrednosti ALT, 38/ 102 povečane vrednosti AST, 19/ 131 pa povečane vrednosti bilirubina.
Increased ALT and increased AST were reported as an adverse event on 2 occasions each and increased blood bilirubin was reported as an adverse event on 1 occasion; all 5 events were considered to be severe and related to clofarabine.
O povečanih vrednostih ALT in AST so poročali kot o neželenih učinkih v dveh primerih za vsak encim, o povečani vrednosti bilirubina pa v enem primeru; vseh 5 dogodkov so ocenili kot hude in povezane z uporabo klofarabina.
The majority of elevations in ALT and AST occurred within 1 week of clofarabine administration and were transient (typically of < 2 weeks duration).
Do večine pojavov povečanih vrednosti ALT in AST je prišlo v enem tednu od uporabe klofarabina, ta povečanja pa so bila prehodna (navadno so trajala < 2 tedna).
Although less common, elevations in bilirubin appeared to be more persistent.
Povečanja bilirubina so bila manj pogosta, vendar so trajala dlje.
However, possible symptoms of overdose are expected to include nausea, vomiting, diarrhoea and severe bone marrow depression.
Med možnimi simptomi prevelikega odmerjanja so navzeja, bruhanje, driska in huda supresija kostnega mozga.
To date, the highest daily dose administered to human beings is 70 mg/ m2 for 5 consecutive days (2 paediatric ALL patients).
Največji odmerek, ki so ga odmerili pri človeku, je 70 mg/ m2 5 dni zaporedoma (2 pediatrična bolnika z ALL).
The toxicities observed in these patients included vomiting, hyperbilirubinaemia, elevated transaminase levels and maculo-papular rash.
Med toksičnimi učinki, ki so jih opazili pri teh bolnikih, so bili bruhanje, hiperbilirubinemija, povečane vrednosti transaminaz in makulo- papularni izpuščaj.
Immediate discontinuation of therapy, careful observation and initiation of appropriate supportive measures are recommended.
Priporočeni so prekinitev zdravljenja, pozorno spremljanje bolnika in izvajanje ustreznih podpornih ukrepov.
Antineoplastic agents
Pripravki za zdravljenje novotvorb
This medicinal product has been authorised under “ Exceptional Circumstances”.
Zdravilo je pridobilo dovoljenje za promet v "izjemnih okoliščinah".
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
Evropska agencija za zdravila (EMEA) bo vsako leto ponovno pregledala vse nove podatke, ki bodo na voljo, in posodobila povzetek glavnih značilnosti zdravila, če bo potrebno.
Mechanism of action:
Način delovanja:
Its antitumour activity is believed to be due to 3 mechanisms: • DNA polymerase α inhibition resulting in termination of DNA chain elongation and/ or DNA synthesis / repair. • Ribonucleotide reductase inhibition with reduction of cellular deoxynucleotide triphosphate (dNTP) pools.
Njegovo protitumorsko delovanje je zasnovano na treh mehanizmih: • Inhibicija DNA polimeraze α, zaradi katere pride do terminacije elongacije verige DNA in/ ali sinteze/ popravljanja DNA. • Inhibicija ribonukleotid reduktaze z zmanjšanjem zalog celičnih deoksinukleotid trifosfatov (dNTP). • Motnje integritete mitohondrijske membrane s sproščanjem citokroma C in drugih proapoptotičnih faktorjev, kar povzroči programirano celično smrt, tudi pri limfocitih, ki se ne delijo.
8 • Disruption of mitochondrial membrane integrity with the release of cytochrome C and other proapoptotic factors leading to programmed cell death even in non-dividing lymphocytes.
Klofarabin mora najprej difundirati, da bi se lahko transportiral v ciljne celice, kjer ga znotrajcelične kinaze zaporedno fosforilirajo v mono - in difosfate, in na koncu v aktivni konjugat, klofarabin 5 ’ - trifosfat.
Clofarabine must first diffuse or be transported into target cells where it is sequentially phosphorylated to the mono- and bi-phosphate by intracellular kinases, and then finally to the active conjugate, clofarabine 5’ -triphosphate.
Klofarabin ima veliko afiniteto do enega izmed aktivirajočih fosforilirajočih encimov, deoksicitidin kinaze.
Clofarabine has high affinity for one of the activating phosphorylating enzymes, deoxycytidine kinase, which exceeds that of the natural substrate, deoxycytidine.
Ta afiniteta je večja od afinitete naravnega substrata, deoksicitidina.
In addition, clofarabine possesses greater resistance to cellular degradation by adenosine deaminase and decreased susceptibility to phosphorolytic cleavage than other active substances in its class whilst the affinity of clofarabine triphosphate for DNA polymerase α and ribonucleotide reductase is similar to or greater than that of deoxyadenosine triphosphate.
Poleg tega je klofarabin odpornejši na razgradnjo z adenozin deaminazo v celici in je manj dovzeten na fosforolitično cepljenje kot druge zdravilne učinkovine v tej skupini zdravil, medtem ko je afiniteta klofarabin trifosfata za DNA- polimerazo α in ribonukleotid- reduktazo podobna ali večja kot pri deoksiadenozin trifosfatu.
In addition, clofarabine delayed tumour growth and, in some cases, caused tumour regression in an assortment of human and murine tumour xenografts implanted in mice.
Poleg tega je klofarabin upočasnil rast tumorjev ter, v nekaterih primerih, povzročil regresijo tumorjev pri različnih človeških in mišjih ksenograftih, presajenih na miši.
To enable systematic evaluation of the responses seen in patients, an unblinded Independent Response Review Panel (IRRP) determined the following response rates based on definitions produced by the Children’ s Oncology Group:
Da bi omogočili sistematično oceno odzivov pri bolnikih, so v neodvisni panelni raziskavi odzivov (Independent Response Review Panel – IRRP) določili naslednje stopnje odziva, glede na opredelitve Skupine za otroško onkologijo (Children’ s Oncology Group):
CR = Complete Remission
Bolniki, ki izpolnjujejo vsa naslednja merila:
Patients who met each of the following criteria: • No evidence of circulating blasts or extramedullary disease • An M1 bone marrow (≤ 5% blasts) • Recovery of peripheral counts (platelets ≥ 100 x 109/ l and ANC ≥ 1.0 x 109/ l)
PR = Popolna remisija • ni znakov blastov v krvnem obtoku ali ekstramedularne bolezni • kostni mozeg M1 (≤ 5% blastov) • periferna obnovitev števila krvnih celic (trombociti ≥ 100 x 109/ l in ANC ≥ 1, 0 x 109/ l) • Bolniki, ki izpolnjujejo vsa merila za PR, razen PRt = Popolna remisija brez popolne obnovitve števila trombocitov na > 100 x 109/ l obnovitve števila trombocitov Bolniki, ki izpolnjujejo vsa naslednja merila:
• Patients who met all of the criteria for a CR except for recovery of platelet counts to > 100 x 109/ l Patients who met each of the following criteria: • Complete disappearance of circulating blasts • An M2 bone marrow (≥ 5% and ≤ 25% blasts) and appearance of normal progenitor cells • An M1 marrow that did not qualify for CR or CRp
DR = Delna remisija • popolno izginotje blastov v krvnem obtoku • kostni mozeg M2 (≥ 5% in ≤ 25% blastov) in pojav normalnih progenitornih celic • kostni mozeg M1, ki ni izpolnil pogojev za PR ali PRt • (število bolnikov s PR + število bolnikov s PRt) ÷ Stopnja skupne remisije (SR) število primernih bolnikov, ki so prejemali klofarabin
The safety and efficacy of clofarabine were evaluated in a phase I, open-label, non-comparative, dose-escalation study in 25 paediatric patients with relapsed or refractory leukaemia (17 ALL; 8 AML) who had failed standard therapy or for whom no other therapy existed.
Varnost in učinkovitost klofarabina so ocenili v odprti, neprimerjalni študiji s povečevanjem odmerka 1. faze, pri 25 pediatričnih bolnikih s ponovljeno ali refraktarno levkemijo (17 ALL; 8 AML), pri katerih standardno zdravljenje ni bilo uspešno ali pri katerih ni bilo drugega zdravljenja.
Dosing commenced at 11.25 with escalation to 15, 30, 40, 52 and 70 mg/ m2/ day by intravenous infusion for 5 days every 2 to 6 weeks depending on toxicity and response.
Odmerjanje se je začelo pri 11, 25, odmerek pa so nato povečevali na 15, 30, 40, 52 in 70 mg/ m2/ dan z intravensko infuzijo 5 dni zaporedoma, vsakih 2 do 6 tednov, glede na toksične učinke in odziv.
Thirteen of these patients (9 ALL, 4 AML) were treated with the 52 mg/ m2/ day clofarabine regimen.
13 izmed bolnikov (9 ALL, 4 AML) je prejemalo 52 mg klofarabina/ m2/ dan.
Of the 17 ALL patients, 4 achieved a complete remission (24%; CR) and 1 a partial remission (6%; PR) at varying doses.
Od 17 bolnikov z ALL je pri različnih odmerkih prišlo do popolne remisije pri 4 (24%; PR), do delne remisije pa pri enem (6%; DR).
Dose-limiting toxicities in this study were hyperbilirubinaemia, elevated transaminase levels and maculo-papular rash experienced at 70 mg/ m2/ day (2 ALL patients; see section 4.9).
Toksični učinki, ki so omejevali odmerjanje v tej študiji, so bili hiperbilirubinemija, povečane ravni transaminaz in makulo- papularni izpuščaj, ki so se pojavili pri odmerku 70 mg/ m2/ dan (2 bolnika z ALL; glejte poglavje 4. 9).
A multi-centre, phase II, open-label, non-comparative study of clofarabine was conducted to determine the overall remission (OR) rate in heavily pretreated patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL defined using the French-American-British classification.
Za določanje stopnje skupne remisije (SR) pri bolnikih, ki so prejemali intenzivno predhodno zdravljenje (starih ≤ 21 let ob prvi diagnozi) s ponovljeno ali refraktarno ALL, opredeljeno po francosko- ameriško- britanski klasifikaciji, so opravili večcentrično, odprto, neprimerjalno študijo klofarabina 2. faze.
The maximum tolerated dose identified in the phase I study described above of 52 mg/ m2/ day clofarabine was
Največji odmerek klofarabina, ki so ga bolniki prenašali, določen v zgoraj opisani študiji 1. faze, 52 mg/ m2/ dan, so dajali z intravensko infuzijo 5 dni zaporedoma, vsakih 2 do 6 tednov.
9 administered by intravenous infusion for 5 consecutive days every 2 to 6 weeks.
V tabeli spodaj je povzetek ključnih rezultatov učinkovitosti, pridobljenih v tej študiji.
Patients with ALL must not have been eligible for therapy of higher curative potential and must have been in second or subsequent relapse and/ or refractory i. e. failed to achieve remission after at least two prior regimens.
Bolniki z ALL niso smeli biti primerni za zdravljenje z večjo možnostjo ozdravitve in so morali biti najmanj v drugem relapsu in/ ali imeti refraktarno bolezen, tj. pri njih ni prišlo do remisije po najmanj dveh prejšnjih zdravljenjih.
Before enrolling in the trial, 58 of the 61 patients (95%) had received 2 to 4 different induction regimens and 18/ 61 (30%) of these patients had undergone at least 1 prior haematological stem cell transplant (HSCT).
Pred sodelovanjem v preskušanju je 58 od 61 bolnikov (95%) prejelo 2 do 4 različna indukcijska zdravljenja, 18/ 61 (30%) teh bolnikov pa je imelo vsaj 1 predhodno presaditev krvnih zarodnih celic (HSCT – haematological stem cell transplant).
Administration of clofarabine resulted in a dramatic and rapid reduction in peripheral leukaemia cells in 31 of the 33 patients (94%) who had a measurable absolute blast count at baseline.
Uporaba klofarabina je dramatično in hitro zmanjšala število perifernih levkemičnih celic pri 31 od 33 bolnikov (94%), ki so na začetku zdravljenja imeli merljivo absolutno število blastov.
The 12 patients who achieved an overall remission (CR + CRp) had a median survival time of 66.6 weeks as of the data collection cut-off date.
Pri 12 bolnikih, pri katerih je prišlo do skupne remisije (PR + PRt), je bila mediana časa preživetja 66, 6 tednov od datuma zbiranja podatkov.
Responses were seen in different immunophenotypes of ALL, including pre-B cell and T-cell.
Odzive so videli pri vseh imunofenotipih ALL, vključno s pre- B - in T- celično.
Although transplantation rate was not a study endpoint, 10/ 61 patients (16%) went on to receive a HSCT after treatment with clofarabine (3 after achieving a CR, 2 after a CRp, 3 after a PR, 1 patient that was considered a treatment failure by the IRRP and 1 that was considered not evaluable by the IRRP).
Čeprav stopnja transplantacije ni bila končna točka študije, je po zdravljenju s klofarabinom 10/ 61 bolnikov (16%) prejelo HSCT (3 po PR, 2 po PRt, 3 po DR, zdravljenje 1 bolnika je bilo ocenjeno kot neuspelo po IRRP, zdravljenje enega po so pri IRRP označili kot zdravljenje, ki ga ni mogoče oceniti).
Efficacy results from the pivotal study in patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL after at least two prior regimens Response
Rezultati učinkovitosti iz ključne študije pri bolnikih (starih ≤ 21 let ob prvi diagnozi) s ponovljeno ali refraktarno ALL po vsaj dveh predhodnih zdravljenjih Kategorija
ITT*
Bolniki
Median duration of
Mediana skupnega
Median time to
remisije (tedni)
Median overall
napredovanja bolezni
category
preživetja (tedni)
remission (weeks) (95% CI)
95%)
progression (weeks)** (95% CI)
(interval zaupanja 95%)
survival (weeks) (95% CI)
95%)
Overall remission (CR + CRp) CR
Skupna remisija
28.6 (9.7 to 58.6) 47.9 (6.1 to -)
%) 7
37.0 (15.4 to 61.9) 56.1 (13.7 to -)
(53, 7
66.6 (53.7 to 89.4) 66.6 (66.6 to 89.4)
do 89, 4) 66, 6
CRp
(12
28.6 (4.6 to 35.4)
(6, 1 do -) 28, 6
37.0 (9.1 to 39.4)
(13, 7 do -) 37, 0
53.7 (9.1 to -)
do 89, 4) 53, 7
PR
(8
5.2 (2.3 to -)
(2, 3 do -)
8.6 (6.3 to -)
(6, 3 do -)
33.0 (18.1 to -)
(18, 1 do -)
CR + CRp + PR Treatment failure
PR + PRt + DR
11.7 (6.1 to 47.9) N/ A
(30%) 33
20.4 (10.6 to 56.1) 4.0
(6, 1 do 47, 9) ni na voljo
66.6 (42.0 to 89.4) 7.6
(10, 6 do 56, 1)
Not evaluable
zdravljenje
10 (16%)
(54%) 10
N/ A
(6, 7
(3.4 to 5.1)
7, 6 do 12, 6)
(6.7 to 12.6)
(16%)
5.4 (4.0 to 6.1)
(4, 0 do 6, 1)
12.9 (7.9 to 18.1)
(7, 9 do 18, 1)
*ITT = intention to treat. **Patients alive and in remission at the time of last follow up were censored at that time point for the analysis.
* ITT = namera zdravljenja (angl. intention to treat). ** Podatke o bolnikih, ki so bili ob času zadnjega sledenja živi in v remisiji, so ob času analize cenzurirali.
Clinical safety:
Klinična varnost:
See section 4.8.
Glejte poglavje 4. 8.
The pharmacokinetics of clofarabine were studied in 40 patients aged between 2 to 19 years old with relapsed or refractory ALL or AML.
Farmakokinetiko klofarabina so preučevali pri 40 bolnikih, starih od 2 do 19 let s ponovljeno ali refraktarno ALL ali AML.
The patients were enrolled into a single phase I (n = 12) or two phase II (n = 14 / n = 14) safety and efficacy studies, and received multiple doses of clofarabine by intravenous infusion (see section 5.1).
Bolniki so sodelovali v eni študiji varnosti in učinkovitosti 1. faze (n = 12) ali dveh študijah varnosti in učinkovitosti 2. faze (n = 14 / n = 14), kjer so z intravensko infuzijo prejeli več odmerkov klofarabina (glejte poglavje 5. 1).
10 Pharmacokinetics in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML following administration of multiple doses of clofarabine by intravenous infusion Parameter
1 Farmakokinetika pri bolnikih, starih od 2 do 19 let s ponovljeno ali refraktarno ALL ali AML po intravenskem infundiranju več odmerkov klofarabina Parameter
Estimates based on
Ocena, ki temelji na
Estimates based on other
Ocena, ki temelji na drugi
non-compartmental analysis (n = 14 / n = 14)
Volumen porazdelitve (ravnotežno stanje)
172 l/ m2
nekompartmentalni analizi (n = 14/ n = 14) 172 l/ m2
47.1% 27.0%
analizi
β half-life of clofarabine
Vezava na beljakovine v plazmi Serumski albumin Izločanje:
5.2 hours
47, 1% 27, 0%
Half-life of clofarabine triphosphate
β- razpolovni čas klofarabina razpolovni čas klofarabin trifosfata
2
5, 2 ure 2
Systemic clearance
Sistemski očistek Ledvični očistek
28.8 l/ h/ m
28, 8 l/ h/ m 10, 8 l/ h/ m2
Renal clearance Dose excreted in urine
Odmerek izločen z urinom
Multivariate analysis showed that the pharmacokinetics of clofarabine are weight dependent and although white blood cell (WBC) count was identified as having an impact on clofarabine pharmacokinetics, this did not appear sufficient to individualise a patient’ s dosage regimen based on their WBC count.
Multivariantna analiza je pokazala, da je farmakokinetika klofarabina odvisna od telesne mase in čeprav so ugotovili, da število belih krvnih celic vpliva na farmakokinetiko klofarabina, ta učinek ni bil zadosten, da bi odmerjanje za posameznega bolnika določili na podlagi števila belih krvnih celic.
Intravenous infusion of 52 mg/ m2 clofarabine produced equivalent exposure across a wide range of weights.
Pri intravenskem infundiranju 52 mg klofarabina/ m2 je bila izpostavljenost pri bolnikih z zelo različno telesno maso enaka.
However, Cmax is inversely proportional to patient weight and, therefore, small children may have a higher Cmax at the end of infusion than a typical 40 kg child given the same dose of clofarabine per m2.
Vendar je vrednost Cmax obratno sorazmerna s telesno maso bolnika, zato je pri majhnih otrocih vrednost Cmax na koncu infundiranja lahko večja kot pri tipičnem 40- kilogramskem otroku, ki prejme enak odmerek klofarabina na m2.
Accordingly, longer infusion times should be considered in children weighing < 20 kg (see section 4.2).
Temu ustrezno je treba pri otrocih, ki tehtajo < 20 kg, razmisliti o daljšem času infundiranja (glejte poglavje 4. 2).
After 24 hours, about 60% of the dose is excreted unchanged in the urine.
Po 24 urah se 90% odmerka izloči z urinom v nespremenjeni obliki.
However, as clofarabine is not detectably metabolised by the cytochrome P450 (CYP) enzyme system, pathways of non-renal elimination currently remain unknown.
Vendar se klofarabin ne presnavlja s citokromskim encimskim sistemom P450 (CYP) v količini, ki bi jo bilo mogoče odkriti, zato pot neledvičnega izločanja ostaja neznana.
Adults (> 21 and < 65 years old):
Odrasli (stari > 21 in < 65 let):
There are currently insufficient data to establish the safety and efficacy of clofarabine in adult patients.
Na voljo ni dovolj podatkov, da bi ocenili varnost in učinkovitost klofarabina pri odraslih bolnikih.
However, the pharmacokinetics of clofarabine in adults with relapsed or refractory AML following administration of a single dose of 40 mg/ m2 clofarabine by intravenous infusion over 1 hour were comparable to those described above in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML following administration of 52 mg/ m2 clofarabine by intravenous infusion over 2 hours for 5 consecutive days.
Farmakokinetika pri odraslih bolnikih s ponovljeno ali refraktarno ALL ali AML po intravenskem infundiranju enkratnega odmerka klofarabina 40 mg/ m2 v 1 uri je bila primerljiva z zgoraj opisano farmakokinetiko pri bolnikih, starih od 2 do 19 let, s ponovljeno ali refraktarno ALL ali AML po intravenskem infundiranju 52 mg klofarabina/ m2 v 2 urah 5 dni zaporedoma.
Elderly patients (≥ 65 years old):
Starejši bolniki (≥ 65 let):
There are currently insufficient data to establish the safety and efficacy of clofarabine in elderly patients.
Na voljo ni dovolj podatkov, da bi ocenili varnost in učinkovitost klofarabina pri starejših bolnikih.
There is no experience in patients with renal insufficiency (serum creatinine ≥ 2 x ULN for age) and clofarabine is predominately excreted via the kidneys (see sections 4.3 and 4.4).
Z uporabo pri bolnikih z oslabljenim delovanjem ledvic (serumski kreatinin ≥ 2 x ULN za starost bolnika) ni izkušenj, klofarabin pa se večinoma izloča skozi ledvice (glejte poglavji 4. 3 in 4. 4).
To date, there are limited data on the pharmacokinetics of clofarabine in patients with decreased creatinine clearance.
Do sedaj še ni dovolj podatkov o farmakokinetiki klofarabina pri bolnikih z zmanjšanim kreatininskim očistkom.
However, these data indicate that clofarabine may accumulate in such patients (see figure below and sections 4.2 and 4.4).
Vendar ti podatki kažejo, da se lahko klofarabin pri teh bolnikih kopiči (glejte poglavji 4. 2 in 4. 4).
11 Clofarabine AUC0-24 hours by baseline estimated creatinine clearance in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML (n = 11 / n = 12) following administration of multiple doses of clofarabine by intravenous infusion (Creatinine clearance estimated using Schwartz formula) 3000
11 AUC0– 24 ur klofarabina po ocenjenem izhodiščnem kreatininskem očistku pri bolnikih, starih 2 do 19 let s ponovljeno ali refraktarno ALL ali AML (n = 11/ n = 12) po intravenskem infundiranju več odmerkov klofarabina (kreatininski očistek je bil ocenjen po Schwartzovi formuli)
(ng*h/ ml)
AUC 0– 24 ur klorafabina (ng* h/ ml)
Estimated creatinine clearance (ml/ min)
Ocenjen kreatininski očistek (ml/ min)
There is no experience in patients with hepatic impairment (serum bilirubin > 1.5 x ULN plus AST and ALT > 5 x ULN) and the liver is a potential target organ for toxicity (see sections 4.3 and 4.4).
Izkušenj z uporabo pri bolnikih z okvarjenim delovanjem jeter (serumski bilirubin > 1, 5 x ULN, AST in ALT > 5 x ULN) ni, poleg tega so jetra lahko morebitna tarča za toksične učinke (glejte poglavji 4. 3 in 4. 4).