natgillin/translations-raw huggingface dataset:
In a 39-week monkey study, no NOAEL (no observed adverse effect level) was established at the lowest dose of 15 mg/ kg, approximately one-third the maximum human dose of 800 mg based on body surface.
V 39- tedenski študiji na opicah pri najmanjšem odmerku 15 mg/ kg, kar je približno ena tretjina največjega odmerka za človeka (ki je 800 mg, izračunan na podlagi telesne površine), niso našli NOAEL (odmerek brez opaženih neželenih učinkov).
In a study of fertility, in male rats dosed for 70 days prior to mating, testicular and epididymal weights and percent motile sperm were decreased at 60 mg/ kg, approximately equal to the maximum clinical dose of 800 mg/ day, based on body surface area.
V študiji plodnosti na podganjih samcih, ki so dobivali zdravilo 70 dni pred parjenjem, se je pri odmerku 60 mg/ kg, ki je približno enakovreden največjemu kliničnemu odmerku 800 mg/ dan, izračunanemu na podlagi telesne površine, zmanjšala masa mod in obmodkov in odstotek gibljivih semenčic.
This was not seen at doses ≤ 20 mg/ kg.
Pri odmerkih ≤ 20 mg/ kg tega niso opazili.
A slight to moderate reduction in spermatogenesis was also observed in the dog at oral doses ≥ 30 mg/ kg.
Pri psu so pri peroralnih odmerkih ≥ 30 mg/ kg opazili tudi rahlo do zmerno zmanjšanje spermatogeneze.
At a dose of 60 mg/ kg, female rats had significant post- implantation foetal loss and a reduced number of live foetuses.
Pri odmerku 60 mg/ kg je prišlo pri samicah do znatne izgube plodov po vgnezditvi in do zmanjšanja števila živorojenih plodov.
This was not seen at doses ≤ 20 mg/ kg.
Tega pri odmerkih ≤ 20 mg/ kg niso opazili.
In an oral pre- and postnatal development study in rats, red vaginal discharge was noted in the 45 mg/ kg/ day group on either day 14 or day 15 of gestation.
V peroralni študiji predporodnega in poporodnega razvoja pri podganah so pri skupini s 45 mg/ kg/ dan 14. ali 15. dne brejosti opazili rdeč izcedek iz nožnice.
F1 fertility was not affected, while an increased number of resorptions and a decreased number of viable foetuses was noted at 45 mg/ kg/ day.
Plodnost F1 ni bila prizadeta, pač pa se je pri odmerku 45 mg/ kg/ dan povečalo število resorpcij in zmanjšalo število za življenje sposobnih plodov.
The no observed effect level (NOEL) for both the maternal animals and the F1 generation was 15 mg/ kg/ day (one quarter of the maximum human dose of 800 mg).
Odmerek brez opaženega učinka (NOEL) tako na samice- matere kot na generacijo F1 je bil 15 mg/ kg/ dan (ena četrtina največjega odmerka za človeka, ki je 800 mg).
Imatinib was teratogenic in rats when administered during organogenesis at doses ≥ 100 mg/ kg, approximately equal to the maximum clinical dose of 800 mg/ day, based on body surface area.
Imatinib je bil teratogen pri podganah, če so ga dobivale med organogenezo v odmerkih ≥ 100 mg/ kg,
Teratogenic effects included exencephaly or encephalocele, absent/ reduced frontal and absent parietal bones.
24 kar je približno enako največjemu kliničnemu odmerku 800 mg/ dan, izračunanemu na podlagi telesne površine.
These effects were not seen at doses ≤ 30 mg/ kg.
Teh učinkov pri odmerkih ≤ 30 mg/ kg niso opazili.
23 In the 2-year rat carcinogenicity study administration of imatinib at 15, 30 and 60 mg/ kg/ day resulted in a statistically significant reduction in the longevity of males at 60 mg/ kg/ day and females at ≥ 30 mg/ kg/ day.
V 2- letni študiji karcinogenosti pri podganah je odmerjanje imanitiba 15, 30 in 60 mg/ kg/ dan povzročilo statistično značilno skrajšanje življenjske dobe samcev pri 60 mg/ kg/ dan in samic pri ≥ 30 mg/ kg/ dan.
Papilloma/ carcinoma of the preputial/ clitoral gland were noted from 30 mg/ kg/ day onwards, representing approximately 0.5 or 0.3 times the human daily exposure (based on AUC) at 400 mg/ day or 800 mg/ day, respectively, and 0.4 times the daily exposure in children (based on AUC) at 340 mg/ m2/ day.
Papilome/ karcinome prepucijske/ klitorisne žleze so opazili pri odmerkih od 30 mg/ kg/ dan naprej, kar predstavlja približno 0, 5- kratnik oziroma 0, 3- kratnik dnevne izpostavljenosti človeka (na podlagi AUC) pri odmerku 400 mg/ dan oziroma 800 mg/ dan, in 0, 4- kratnik dnevne izpostavljenosti otrok (na podlagi AUC) pri 340 mg/ m2/ dan.
The no observed effect level (NOEL) was 15 mg/ kg/ day.
Odmerek brez opaženega učinka (NOEL) je bil 15 mg/ kg/ dan.
The renal adenoma/ carcinoma, the urinary bladder and urethra papilloma, the small intestine adenocarcinomas, the parathyroid glands adenomas, the benign and malignant medullary tumours of the adrenal glands and the non-glandular stomach papillomas/ carcinomas were noted at 60 mg/ kg/ day, representing approximately 1.7 or 1 times the human daily exposure (based on AUC) at 400 mg/ day or 800 mg/ day, respectively, and 1.2 times the daily exposure in children (based on AUC) at 340 mg/ m2/ day.
Adenome/ karcinome ledvic, papilome sečnega mehurja in sečnice, adenokarcinome tankega črevesa, adenome obščitničnih žlez, benigne in maligne medularne tumorje nadlevičnih žlez in papilome/ karcinome ne- žleznega dela želodca so opazili pri odmerku 60 mg/ kg/ dan, kar predstavlja približno 1, 7 do 1- kratnik dnevne izpostavljenosti človeka (na podlagi AUC) pri odmerku 400 mg/ dan oziroma 800 mg/ dan in 1, 2- kratnik dnevne izpostavljenosti otrok (na podlagi AUC) pri 340 mg/ m2/ dan.
The no observed effect level (NOEL) was 30 mg/ kg/ day.
Odmerek brez opaženega učinka (NOEL) je bil 30 mg/ kg/ dan.
Non-neoplastic lesions not identified in earlier preclinical studies were the cardiovascular system, pancreas, endocrine organs and teeth.
Ne- neoplastične lezije organov, ki jih v prejšnjih predkliničnih študijah niso opazili, obsegajo srčnožilni sistem, pankreas, endokrine organe in zobe.
Cellulose microcrystalline Crospovidone Magnesium stearate Silica colloidal, anhydrous
Vsebina kapsule: mikrokristalna celuloza krospovidon magnezijev stearat brezvodni koloidni silicijev dioksid
Gelatin Iron oxide, yellow (E172) Titanium dioxide (E171)
Ovojnica kapsule: želatina rumeni železov oksid (E172) titanov dioksid (E171)
Printing ink:
Tiskarska barva:
Iron oxide, red (E172) Shellac Soya lecithin
rdeči železov oksid (E172) šelak sojin lecitin
6.2 Incompatibilities
25 6. 2 Inkompatibilnosti
24 6.4 Special precautions for storage
6. 4 Posebna navodila za shranjevanje
PVC/ aluminium blisters
Pretisni omoti iz PVC/ aluminija.
Packs containing 30 capsules.
Škatle, ki vsebujejo po 30 kapsul.
Novartis Europharm Limited Wimblehurst Road Horsham West Sussex, RH12 5AB UNITED KINGDOM
Novartis Europharm Limited Wimblehurst Road Horsham West Sussex, RH12 5AB VELIKA BRITANIJA
07.11.2001 Date of first renewal:
07. 11. 2001 Datum podaljšanja dovoljenja za promet:
Each capsule contains 100 mg imatinib (as mesilate).
Vsaka kapsula vsebuje 100 mg imatiniba (v obliki mesilata).
White to yellow powder in an orange to greyish-orange opaque capsule, marked “ NVR SI”.
Bel do rumen prašek v oranžni do sivkastooranžni neprozorni kapsuli, označeni z “ NVR SI ”.
Glivec is indicated for the treatment of • adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment. • adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. • adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy. • adult patients with relapsed or refractory Ph+ ALL as monotherapy. • adult patients with myelodysplastic/ myeloproliferative diseases (MDS/ MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements. • adult patients with advanced hypereosinophilic syndrome (HES) and/ or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement.
Glivec je indiciran za zdravljenje • odraslih in pediatričnih bolnikov z na novo diagnosticirano kronično mieloično levkemijo (CML), s prisotnim kromosomom Philadelphia (bcr- abl) (Ph+), pri katerih presaditev kostnega mozga kot zdravljenje prve izbire ne pride v poštev. • odraslih in pediatričnih bolnikov s Ph+ CML v kronični fazi po neuspelem zdravljenju z interferonom alfa, ali v pospešeni fazi ali blastni krizi. • odraslih bolnikov z na novo diagnosticirano akutno limfoblastno levkemijo, s prisotnim kromosomom Philadelphia (Ph+ ALL) skupaj s kemoterapijo; • odraslih bolnikov z relapsom ali neodzivno Ph+ ALL v monoterapiji. • odraslih bolnikov z mielodisplastičnimi/ mieloproliferativnimi boleznimi (MDS/ MPD) v povezavi s preureditvijo genov za receptor za rastni faktor iz trombocitov (PDGFR – platelet derived growth factor receptor); • odraslih bolnikov z napredovalim hipereozinofilnim sindromom (HES) ali kronično eozinofilno levkemijo (CEL) s premestitvijo FIP1L1- PDGFRα ali obojim.
Therapy should be initiated by a physician experienced in the treatment of patients with
27 Zdravljenje mora začeti zdravnik, izkušen v zdravljenju bolnikov s hematološkimi malignimi boleznimi oziroma z malignimi sarkomi.
Posology for Ph+ ALL The recommended dose of Glivec is 600 mg/ day for patients with Ph+ ALL.
28 Odmerjanje pri Ph+ ALL Priporočeni odmerek zdravila Glivec pri bolnikih s Ph+ ALL je 600 mg/ dan.
27 Treatment schedule:
Razpored zdravljenja:
If elevations in bilirubin > 3 x institutional upper limit of normal (IULN) or in liver transaminases > 5 x IULN occur, Glivec should be withheld until bilirubin levels have returned to < 1.5 x IULN and transaminase levels to < 2.5 x IULN.
Nato se lahko
Treatment with Glivec may then be continued at a reduced daily dose.
29 zdravljenje z zdravilom Glivec nadaljuje z zmanjšanim dnevnim odmerkom.
Haematological adverse reactions Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are 28 recommended as indicated in the table below.
Hematološke neželene reakcije Pri hudi nevtropeniji in trombocitopeniji je priporočljivo zmanjšanje odmerka ali prekinitev zdravljenja, kot kaže spodnja preglednica.
Paediatric accelerated phase CML and blast
pospešena faza CML in
ANC < 0.5 x 109/ l and/ or
Preverite, ali je citopenija povezana z
1.
30
Check whether cytopenia is related to leukaemia (marrow aspirate or biopsy).
levkemijo (aspirat ali biopsija kostnega
29 DFSP
1.
ANC <
in/ ali trombocitov < 50 x 109/ l
Stop Glivec until ANC ≥ 1.5 x 109/ l and
trombociti ≥ 75 x 109/ l.
Elderly patients:
31 Starejši bolniki:
If either is abnormal, follow-up with a cardiology specialist and the prophylactic use of systemic steroids (1– 2 mg/ kg) for one to two weeks concomitantly with imatinib should be considered at the initiation of therapy.
V primeru nenormalnega izvida katere od teh preiskav je potrebno razmisliti o kontrolnem pregledu pri kardiologu in sočasni profilaktični uporabi steroidov s sistemskim delovanjem (1- 2 mg/ kg) ob uvedbi zdravljenja z imatinibom, v obdobju enega do dveh tednov.
In the GIST clinical trial, both gastrointestinal and intra-tumoural haemorrhages were reported (see section 4.8).
32 V kliničnem preskušanju GIST so poročali tako o gastrointestinalnih kot o intratumorskih krvavitvah (glejte poglavje 4. 8).
31 recommended in section 4.2.
Zdravljenje z zdravilom Glivec lahko prekinemo ali odmerek zmanjšamo, kot je priporočeno v poglavju 4. 2.
Because warfarin is metabolised by CYP2C9, patients who require anticoagulation should receive low-molecular-weight or standard heparin.
33 Ker varfarin presnavlja CYP2C9, naj bolniki, pri katerih je potrebna antikoagulantna terapija, dobivajo nizkomolekularni ali standardni heparin.
In clinical trials in CML, drug discontinuation for drug-related adverse reactions was observed in 2.4% of newly diagnosed patients, 4% of patients in late chronic phase after failure of interferon therapy, 4% of patients in accelerated phase after failure of interferon therapy and 5% of blast crisis patients after failure of interferon therapy.
Pri GIST so
In GIST the study drug was discontinued for drug-related adverse reactions in 4% of patients.
34 preskušano zdravilo ukinili zaradi neželenih reakcij, povezanih z zdravilom, pri 4% bolnikov.
33 When imatinib was combined with high dose chemotherapy in Ph+ ALL patients, transient liver toxicity in the form of transaminase elevation and hyperbilirubinaemia were observed.
Kadar so imatinib uporabljali v kombinaciji z visokoodmerno kemoterapevtsko shemo pri bolnikih s Ph+ ALL, je prišlo do prehodne toksičnosti za jetra v obliki zvišanja transaminaz in hiperbilirubinemije.
Uncommon:
35 glavobol2 zelo pogosti: pogosti: občasni:
Herpes zoster, herpes simplex, nasopharyngitis, pneumonia7, sinusitis, cellulites, upper respiratory tract infection, influenza, urinary tract infection, gastroenteritis, sepsis
Infekcijske in parazitske bolezni herpes zoster, herpes simpleks, nazofaringitis, pljučnica7, sinuzitis, flegmona, občasni: okužba zgornjih dihal, gripa, okužba sečil, gastroenteritis, sepsa redki:
Common:
36
Table 2
37 Preglednica 2
36 Laboratory test abnormalities Haematology In CML, cytopenias, particularly neutropenia and thrombocytopenia, have been a consistent finding in all studies, with the suggestion of a higher frequency at high doses ≥ 750 mg (phase I study).
Podatki kažejo, da so lahko citopenije pogostejše pri velikih odmerkih ≥ 750 mg (študija prve faze), vendar pa je pojavljanje citopenij tudi nedvomno odvisno od stadija bolezni.
Treatment was discontinued permanently because of liver laboratory abnormalities in less than 1% of CML patients.
38 manj kot 1% bolnikov s CML.
WBC < 10 x 109/ l, platelet < 450 x 109/ l, myelocyte+metamyelocyte < 5% in blood, no blasts and promyelocytes in blood, basophils < 20%, no extramedullary involvement Cytogenetic response criteria: complete (0% Ph+ metaphases), partial (1– 35%), minor (36– 65%) or minimal (66– 95%).
40 promielocitov v krvi, bazofilci < 20%, brez ekstramedularne prizadetosti Kriteriji citogenetičnega odziva: popolni (0% Ph+ metafaz), delni (1– 35%), manjši (36– 65%) ali minimalni (66– 95%).
40 response was also higher in the patients treated at 600 mg (33%) as compared to the patients treated at 400 mg (16%, p=0.0220).
Stopnja odziva je bila tudi večja pri bolnikih, zdravljenih s 600 mg (33%), kot pri bolnikih, zdravljenih s 400 mg (16%, p=0, 0220).
Table 4
42 Preglednica 4
Response in adult CML studies
Odziv pri odraslih bolnikih s CML v kliničnih študijah
Study 0109
Študija 0110 Študija 0109 podatki pri podatki pri 37 mesecih 40, 5 meseca
37-month data
1
Accelerated phase (n=235)
pospešena faza (n=235) bolnikov (CI95%)
% of patients (CI95%) 1 Haematological response Complete haematological response (CHR)
Hematološki odziv popolni hematološki odziv (CHR)
28% (22.0– 33.9) 20%
28%
(Confirmed3) [95% CI] Partial
(43%) [38, 6 – 47, 2]
(43%) [38.6– 47.2] (16%) [11.3– 21.0] 12% 7%
(16%)
A major response combines both complete and partial responses: complete (0% Ph+ metaphases), partial (1– 35%) 3 Complete cytogenetic response confirmed by a second bone marrow cytogenetic evaluation performed at least one month after the initial bone marrow study.
Pomemben odziv združuje tako popolne kot delne odzive: popoln (0% Ph+ metafaz), delen (1 – 35%) 3 Popoln citogenetični odziv, potrjen z drugo citogenetično oceno kostnega mozga, opravljeno vsaj en mesec po prvi študiji kostnega mozga.
41 majority of patients who achieved a CCyR developed the CCyR between months 3 and 10 with a median time to response based on the Kaplan-Meier estimate of 5.6 months.
Večina bolnikov, ki je dosegla popolni citogenetični odziv, ga je dosegla med 3. in 10. mesecem s povprečnim časom do odziva 5, 6 meseca glede na Kaplan- Meierjevo oceno.
Clinical studies in Ph+ ALL Newly diagnosed Ph+ ALL:
43 Klinične študije pri Ph+ ALL Novo odkrita Ph+ ALL:
As expected on the basis of the study design, no difference was observed in remission duration, disease-free survival or overall survival, although patients with complete molecular response and remaining in minimal residual disease had a better outcome in terms of both remission duration (p=0.01) and disease-free survival (p=0.02).
Kot je bilo pričakovati glede na načrt študije, ni bilo nobene razlike v trajanju remisij, preživetju brez bolezni ali preživetju nasploh, čeprav so imeli bolniki s popolnim molekularnim odzivom in tisti z minimalno rezidualno boleznijo boljši izid glede trajanja remisije (p=0, 01) in preživetja brez bolezni (p=0, 02)
Consolidation (de novo Ph+ ALL) Study ADE04
odkrita Ph+ ALL) Študija ADE04 predhodna faza indukcijsko zdravljenje I indukcijsko zdravljenje II
(1 h), days 28-31, 35-38, 42-45; 6-MP 60 mg/ m2 oral, days 26-46
(1 ura), 28. - 31., 35. - 38., 42. - 45. dan; 6- MP 60 mg/ m2 peroralno, 26. - 46. dan
DEX 10 mg/ m2 oral, days 1-5; vindesine 3 mg/ m2 i. v., day 1; MTX 1.5 g/ m2 i. v.
44 DEX 10 mg/ m2 peroralno, 1. - 5. dan; vindezin 3 mg/ m2 i. v., 1. dan; MTX konsolidacijsko 1, 5 g/ m2 i. v.
(3 h, q 12 h), day 5
(1 ura) 4. - 5. dan; zdravljenje Ara- C 2x 2 g/ m2 i. v.
CP 1.2 g/ m2 i. v.
(3 ure, na 12 ur), 5. dan Študija AJP01 CP 1, 2 g/ m2 i. v.
(1 h), days 1-3; vincristine 1.3 mg/ m2 i. v., days 1, 8, 15, 21; prednisolone 60 mg/ m2/ day oral
(1 ura), 1. - indukcijsko 3. dan; vinkristin 1, 3 mg/ m2 i. v., 1., 8., 15., 21. dan; prednizolon zdravljenje 60 mg/ m2/ dan peroralno izmenična kemoterapija: visokoodmerna kemoterapija z MTX 1 g/ m2 i. v. konsolidacijsko (24 ur), 1. dan in Ara- C 2 g/ m2 i. v.
VCR 1.3 g/ m2 i. v., day 1; prednisolone 60 mg/ m2 oral, days 1-5
(na 12 ur), 2. - 3. dan, v 4 ciklusih zdravljenje VCR 1, 3 g/ m2 i. v., 1. dan; prednizolon 60 mg/ m2 peroralno, 1. - 5. dan vzdrževanje Študija AUS01 hyper- CVAD shema:
Eleven patients achieved rapid CHR; ten had complete resolution of cytogenetic abnormalities and a decrease
11 bolnikov je doseglo hiter popolni hematološki odziv, pri desetih je prišlo do popolne normalizacije citogenetičnih nepravilnosti in zmanjšanja oziroma izginotja fuzijskih transkriptov, kot so izmerili z verižno reakcijo s polimerazo v
43 or disappearance of fusion transcripts as measured by RT-PCR.
45 realnem času (RT- PCR).
n (%) 1(0.7)
n (%) 1 (0, 7) 98 (66, 7) 23 (15, 6)
44 In two clinical studies (study B2222 and an intergroup study S0033) the daily dose of Glivec was escalated to 800 mg in patients progressing at the lower daily doses of 400 mg or 600 mg.
46 V dveh kliničnih študijah (študija B2222 in študija med skupinami S0033) so pri bolnikih, pri katerih je pri manjših dnevnih odmerkih 400 mg ali 600 mg, bolezen napredovala zvečali dnevni odmerek zdravila Glivec na 800 mg.
Of a panel of potential comedications (acetaminophen, aciclovir, allopurinol, amphotericin, cytarabine, erythromycin, fluconazole, hydroxyurea, norfloxacin, penicillin V) only erythromycin (IC50 50 µM) and fluconazole (IC50 118 µM) showed inhibition of imatinib metabolism which could have clinical relevance.
47 sta samo eritromicin (IC50 50 µM) in flukonazol (IC50 118 µM) pokazala inhibicijo presnove imatiniba, ki bi bila lahko klinično pomembna.
45 Imatinib was shown in vitro to be a competitive inhibitor of marker substrates for CYP2C9, CYP2D6 and CYP3A4/ 5.
In vitro so pokazali, da je imatinib kompetitiven inhibitor markerskih substratov za CYP2C9, CYP2D6 in CYP3A4/ 5.
The free drug clearance of imatinib is probably similar between patients with renal impairment and those with normal renal function, since renal excretion represents only a minor elimination pathway for imatinib (see sections 4.2 and 4.4).
Očistek nevezane učinkovine je pri imatinibu verjetno podoben pri bolnikih z okvaro ledvic in pri tistih z normalnim delovanjem ledvic, saj predstavlja izločanje skozi ledvice manj pomemben način izločanja
Although the results of pharmacokinetic analysis showed that there is considerable inter-subject variation, the mean exposure to imatinib did not increase in patients with varying degrees of liver dysfunction as compared to patients with normal liver function (see sections 4.2, 4.4 and 4.8).
Čeprav so rezultati farmakokinetične analize pokazali, da so razlike med posamezniki precejšnje, se povprečna izpostavljenost imatinibu pri bolnikih z različnimi stopnjami disfunkcije jeter v primerjavi z bolniki z normalno funkcijo jeter ni povečala (glejte poglavja 4. 2, 4. 4 in 4. 8).
46 5.3 Preclinical safety data
5. 3 Predklinični podatki o varnosti
Imatinib was teratogenic in rats when administered during organogenesis at doses ≥ 100 mg/ kg, approximately equal to the maximum clinical dose of 800 mg/ day, based on body surface area.
49 Imatinib je bil teratogen pri podganah, če so ga dobivale med organogenezo v odmerkih ≥ 100 mg/ kg, kar je približno enako največjemu kliničnemu odmerku 800 mg/ dan, izračunanemu na podlagi telesne površine.
Teratogenic effects included exencephaly or encephalocele, absent/ reduced frontal and absent parietal bones.
Teratogeni učinki so obsegali eksencefalijo ali encefalokelo, odsotnost ali zmanjšanje frontalnih kosti ter odsotnost parietalnih kosti.
47 In the 2-year rat carcinogenicity study administration of imatinib at 15, 30 and 60 mg/ kg/ day resulted in a statistically significant reduction in the longevity of males at 60 mg/ kg/ day and females at ≥ 30 mg/ kg/ day.
V 2- letni študiji karcinogenosti pri podganah je odmerjanje imanitiba 15, 30 in 60 mg/ kg/ dan povzročilo statistično značilno skrajšanje življenjske dobe samcev pri 60 mg/ kg/ dan in samic pri ≥ 30 mg/ kg/ dan.
Papilloma/ carcinoma of the preputial/ clitoral gland were noted from 30mg/ kg/ day onwards, representing approximately 0.5 or 0.3 times the human daily exposure (based on AUC) at 400 mg/ day or 800 mg/ day, respectively, and 0.4 times the daily exposure in children (based on AUC) at 340 mg/ m2/ day.
Papilome/ karcinome prepucijske/ klitorisne žleze so opazili pri odmerkih od 30 mg/ kg/ dan naprej, kar predstavlja približno 0, 5- kratnik oziroma 0, 3- kratnik dnevne izpostavljenosti človeka (na podlagi AUC) pri odmerku 400 mg/ dan oziroma 800 mg/ dan, in 0, 4- kratnik dnevne izpostavljenosti otrok (na podlagi AUC) pri 340 mg/ m2/ dan.
Gelatin Iron oxide, red (E172) Iron oxide, yellow (E172) Titanium dioxide (E171)
Ovojnica kapsule: želatina rdeči železov oksid (E172) rumeni železov oksid (E172) titanov dioksid (E171)
2 years
50 2 leti
48 6.4 Special precautions for storage
6. 4 Posebna navodila za shranjevanje
Very dark yellow to brownish-orange film-coated tablet, round with “ NVR” on one side and “ SA” and score on the other side.
Zelo temno rumena do rjavkastooranžna filmsko obložena tableta, okrogla in z oznako “ NVR ” na eni ter “ SA ” in zarezo na drugi strani.
50 4.2 Posology and method of administration
52 4. 2 Odmerjanje in način uporabe
Dose increases from 340 mg/ m2 daily to 570 mg/ m2 daily (not to exceed the total dose of 800 mg) may be considered in children in the absence of severe adverse drug reaction and severe non-leukaemia- related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any 51 time); failure to achieve a satisfactory haematological response after at least 3 months of treatment; failure to achieve a cytogenetic response after 12 months of treatment; or loss of a previously achieved haematological and/ or cytogenetic response.
Povečanje odmerka s 340 mg/ m2 dnevno na 570 mg/ m2 (ne sme preseči celotnega odmerka 800 mg) pride v poštev pri otrocih, ki nimajo hudih neželenih učinkov na zdravilo in hude nevtropenije ali trombocitopenije, ki bi bila povezana z levkemijo, in sicer v sledečih okoliščinah: napredovanje bolezni (kadarkoli); odsotnost zadovoljivega hematološkega odziva po najmanj 3 mesecih zdravljenja; odsotnost citogenetičnega odziva po 12 mesecih zdravljenja; ali izguba že prej doseženega
Posology for Ph+ ALL The recommended dose of Glivec is 600 mg/ day for patients with Ph+ ALL.
Odmerjanje pri Ph+ ALL Priporočeni odmerek zdravila Glivec pri bolnikih s Ph+ ALL je 600 mg/ dan.