natgillin/translations-raw huggingface dataset:
52 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.
54 ustanovo (IULN- institutional upper limit of normal) ali zvišanja jetrnih transaminaz na > 5- kratno IULN, je treba zdravljenje z zdravilom Glivec prekiniti, dokler se koncentracija bilirubina ne vrne na < 1, 5- kratno IULN oziroma koncentracija transaminaz na < 2, 5- kratno IULN.
Haematological adverse reactions Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are 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.
Dose adjustments for neutropenia and thrombocytopenia:
Prilagajanje odmerkov zaradi nevtropenije in trombocitopenije
If cytopenia persists for 4 weeks and is still unrelated to leukaemia, stop Glivec until ANC ≥ 1 x 109/ l and platelets ≥ 20 x 109/ l, then resume treatment at 300 mg.
Če citopenija vztraja 4 tedne in še vedno ni povezana z levkemijo, prekinite zdravljenje z zdravilom Glivec, dokler ni ANC ≥ 1 x 109/ l in trombociti
Paediatric accelerated phase CML and blast
zdravljenje z odmerkom 300 mg. pospešena faza CML in aANC blastna kriza pri
ANC < 0.5 x 109/ l and/ or
< 0, 5 x 109/ l in/ ali trombocitov < 10 x 109/ l
If cytopenia persists for 4 weeks and is still unrelated to leukaemia, stop Glivec until ANC ≥ 1 x 109/ l and platelets ≥ 20 x 109/ l, then resume treatment at
Če citopenija vztraja 4 tedne in še vedno ni povezana z levkemijo, prekinite zdravljenje z zdravilom Glivec, dokler ni ANC ≥ 1 x 109/ l in trombociti ≥ 20 x 109/ l, nato spet začnite zdravljenje z odmerkom 200 mg/ m2.
DFSP (at dose 800 mg)
(ob odmerku 800 mg)
ANC < 1.0 x 109/ l and/ or platelets < 50 x 109/ l
in/ ali trombocitov < 50 x 109/ l
The dose can be reduced if not tolerated, or increased for lack of efficacy (see sections 4.4 and 5.2).
56 znižati, če ga bolnik ne prenaša dobro, ali zvišati v primerih nezadostnega učinka (glejte poglavji 4. 4 in 5. 2).
Concomitant use of imatinib and medicinal products that induce CYP3A4 (e. g. dexamethasone,
Sočasna uporaba imatiniba in zdravil, ki inducirajo CYP3A4 (na primer deksametazon, fenitoin, karbamazepin, rifampicin, fenobarbital ali Hypericum perforatum, znan tudi kot šentjanževka), lahko pomembno zmanjša izpostavljenost zdravilu Glivec, kar potencialno poveča tveganje za neuspešnost zdravljenja.
Evaluation by a cardiology specialist, performance of an echocardiogram and determination of serum troponin should therefore be considered in patients with HES/ CEL, and in patients with MDS/ MPD associated with high eosinophil levels before imatinib is administered.
Zato je pri bolnikih s HES/ CEL in bolnikih z visokimi koncentracijami eozinofilcev v povezavi z MDS/ MPD pred uporabo imatiniba potrebno razmisliti o pregledu pri specialistu kardiologu, izvedbi ehokardiograma in
However, the occurrence of these cytopenias is likely to be related to the stage of the disease being treated and they were more frequent in patients with accelerated phase CML or blast crisis as compared to patients with
Vendar je pojavljanje teh citopenij verjetno v zvezi s stadijem bolezni, ki jo zdravimo.
55 chronic phase CML.
Pogostejše so pri bolnikih s pospešeno fazo CML ali blastno krizo kot pri bolnikih s kronično fazo CML.
Treatment with Glivec may be interrupted or the dose may be reduced, as recommended in section 4.2.
Zdravljenje z zdravilom Glivec lahko prekinemo ali odmerek zmanjšamo, kot je priporočeno v poglavju 4. 2.
Glivec may increase plasma concentration of other CYP3A4 metabolised drugs (e. g. triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, i. e. statins, etc.).
58 CYP3A4 (na primer triazolo- benzodiazepinov, dihidropiridinskih blokatorjev kalcijevih kanalčkov, nekaterih zaviralcev reduktaze HMG- CoA, tj. statinov, itn.).
Because warfarin is metabolised by CYP2C9, patients who require anticoagulation should receive low-molecular-weight or standard heparin.
Ker varfarin presnavlja CYP2C9, naj bolniki, pri katerih je potrebna antikoagulantna terapija, dobivajo nizkomolekularni ali standardni heparin.
56 Caution should therefore be exercised when using Glivec and paracetamol concomitantly, especially with high doses of paracetamol.
Zato je pri sočasni uporabi zdravila Glivec in paracetamola potrebna previdnost, posebno pri velikih odmerkih paracetamola.
4.7 Effects on ability to drive and use machines
59 4. 7 Vpliv na sposobnost vožnje in upravljanja s stroji
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.
V kliničnih preskušanjih pri CML so prekinitev dajanja zdravila zaradi neželenih reakcij, povezanih z zdravilom, zabeležili pri 2, 4% na novo diagnosticiranih bolnikov, 4% bolnikov v pozni kronični fazi po neuspelem zdravljenju z interferonom, 4% bolnikov v pospešeni fazi po neuspelem zdravljenju z interferonom in 5% bolnikov v blastni krizi po neuspelem zdravljenju z interferonom.
57 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.
Table 1
60 Preglednica 1
Haemolytic anaemia
hemolitična anemija glavobol2
Ear and labyrinth disorders Uncommon:
Ušesne bolezni vključno z motnjami labirinta občasni:
Respiratory, thoracic and mediastinal disorders
Bolezni dihal, prsnega koša in mediastinalnega prostora pogosti: občasni:
Uncommon:
dispneja, krvavitev iz nosu, kašelj plevralni izliv3, bolečine v žrelu in grlu, vnetje žrela
Renal and urinary disorders Uncommon:
Bolezni kože in podkožja
Metabolism and nutrition Common:
otekanje sklepov okorelost sklepov in mišic oslabelost mišic, artritis
Uncommon:
Presnovne in prehranske motnje pogosti: občasni:
Joint swelling Joint and muscle stiffness Muscular weakness, arthritis disorders Anorexia Hypokalaemia, increased appetite, hypophosphataemia, decreased appetite, dehydration, gout, hyperuricaemia, hypercalcaemia, hyperglycaemia, hyponatraemia
anoreksija hipokaliemija, povečan tek, hipofosfatemija, zmanjšan tek, dehidracija, protin, hiperurikemija, hiperkalciemija, hiperglikemija, hiponatriemija
1 On a patient-year basis, cardiac events including congestive heart failure were more commonly observed in patients with transformed CML than in patients with chronic CML.
leto pogosteje opažali pri bolnikih s transformacijo CML kot pri bolnikih s kroničnim potekom CML.
This includes spontaneous case reports as well as serious adverse events from ongoing studies, the expanded access programmes, clinical pharmacology studies and exploratory studies in unapproved indications.
To vključuje tako spontano sporočene primere kot tudi resne neželene dogodke iz študij v teku, iz programov razširjene uporabe, študij klinične farmakologije in raziskovalnih študij
60 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.
Zaradi jetrnih laboratorijskih nenormalnosti so zdravljenje trajno prekinili pri manj kot 1% bolnikov s CML.
Three large, international, open-label, non-controlled phase II studies were conducted in patients with Philadelphia chromosome positive (Ph+) CML in advanced, blast or accelerated phase disease, other Ph+ leukaemias or with CML in the chronic phase but failing prior interferon-alpha (IFN) therapy.
64 Opravili so tri velike mednarodne odprte nekontrolirane študije druge faze pri bolnikih s CML, s prisotnim kromosomom Philadelphia (Ph+), v napredovali, blastni ali pospešeni fazi bolezni, z drugimi Ph+ levkemijami ali s CML v kronični fazi, a po predhodnem neuspešnem zdravljenju z interferonom alfa (IFN).
One large, open-label, multicentre, international randomised phase III study has been conducted in patients with newly diagnosed Ph+ CML.
Eno veliko odprto, multicentrično, mednarodno randomizirano študijo tretje faze so opravili na bolnikih z na novo diagnosticirano Ph+ CML.
Molecular response Major response at 12 months (%) Major response at 24 months (%) * p < 0.001, Fischer’ s exact test
Molekularni odziv pomemben odziv pri 12 mesecih (%) pomemben odziv pri 24 mesecih (%)
** insufficient data, only two patients available with samples Haematological response criteria (all responses to be confirmed after ≥ 4 weeks):
65 * p < 0, 001, Fischerjev eksaktni test ** premalo podatkov, na voljo sta samo dva bolnika z vzorci Kriteriji hematološkega odziva (vsi odzivi morajo biti potrjeni po ≥ 4 tednih):
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%).
WBC < 10 x 109/ l, trombociti < 450 x 109/ l, mielociti+metamielociti < 5% v krvi, brez blastov in 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%).
In this study, dose escalations were allowed from 400 mg daily to 600 mg daily, then from 600 mg daily to 800 mg daily.
V tej študiji so bila dovoljena zvišanja odmerka s 400 mg na dan na 600 mg na dan, nato s 600 mg na 66 dan na 800 mg na dan.
Of these 11 patients, 4 patients escalated up to 800 mg daily, 2 of whom regained a cytogenetic response (1 partial and 1 complete, the latter also achieving a molecular response), while of the 7 patients who did not escalate the dose, only one regained a complete cytogenetic response.
Od teh 11 bolnikov so 4 bolnikom zvečali odmerek na 800 mg na dan, od njih sta 2 spet dobila citogenetični odziv (1 delnega in 1 popolnega, le- ta je dosegel tudi molekularni odziv), medtem ko je od 7 bolnikov, pri katerih odmerka niso zvečali, le eden spet dobil popolni citogenetični odziv.
64 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
67 Preglednica 4
65 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.
DEX 10 mg/ m2 oral, days 1-5; vindesine 3 mg/ m2 i. v., day 1; MTX 1.5 g/ m2 i. v.
69 1, 5 g/ m2 i. v.
Haematological and cytogenetic responses have been sustained for a median of 49 months (range 19-60) and 47 months (range 16-59), respectively.
70 citogenetični odzivi pa 47 mesecev (od 16 do 59).
68 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.
71 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.
Absorption Mean absolute bioavailability for imatinib is 98%.
Absorpcija Povprečna absolutna biološka uporabnost imatiniba je 98%.
69 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.
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).
73 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).
70 5.3 Preclinical safety data
5. 3 Predklinični podatki o varnosti
Renal toxicity was observed in monkeys treated for 2 weeks, with focal mineralisation and dilation of the renal tubules and tubular nephrosis.
Pri opicah, ki so dobivale zdravilo po 2 tedna, je bila opažena toksičnost za ledvice z žariščno mineralizacijo in razširitvijo ledvičnih tubulov in tubulno nefrozo.
In rats, hyperplasia of the transitional epithelium in the renal papilla and in the urinary bladder was observed at doses ≥ 6 mg/ kg in the 13-week study, without changes in serum or urinary parameters.
Pri podganah so v 13- tedenski raziskavi pri odmerkih ≥ 6 mg/ kg našli hiperplazijo prehodnega epitela v ledvični papili in v sečnem mehurju, brez sprememb serumskih ali urinskih parametrov.
Teratogenic effects included exencephaly or encephalocele, absent/ reduced frontal and absent parietal bones.
74 kar je približno enako največjemu kliničnemu odmerku 800 mg/ dan, izračunanemu na podlagi telesne površine.
71 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.
Iron oxide, red (E172) Iron oxide, yellow (E172) Macrogol Talc Hypromellose
Obloga tablete: rdeči železov oksid (E172) rumeni železov oksid (E172) makrogol smukec hipromeloza
72 6.4 Special precautions for storage
75 6. 4 Posebna navodila za shranjevanje
PVC/ alu blisters
Pretisni omoti iz PVC/ aluminija.
11.11.2003 Date of first renewal:
11. 11. 2003 Datum podaljšanja dovoljenja za promet:
Each film-coated tablet contains 400 mg imatinib (as mesilate).
Vsaka filmsko obložena tableta vsebuje 400 mg imatiniba (v obliki mesilata).
Very dark yellow to brownish-orange, ovaloid, biconvex film-coated tablet with bevelled edges, debossed with “ NVR” on one side and “ SL” on the other side.
Zelo temno rumena do rjavkastooranžna, ovalna filmsko obložena tableta z izbočenimi stranicami in z oznako “ NVR ” na eni ter “ SL ” na drugi strani.
74 4.2 Posology and method of administration
77 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 75 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
76 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.
79 ustanovo (IULN- institutional upper limit of normal) ali zvišanja jetrnih transaminaz na > 5- kratno IULN, je treba zdravljenje z zdravilom Glivec prekiniti, dokler se koncentracija bilirubina ne vrne na < 1, 5- kratno IULN oziroma koncentracija transaminaz na < 2, 5- kratno IULN.
77
9
The dose can be reduced if not tolerated, or increased for lack of efficacy (see sections 4.4 and 5.2).
81 znižati, če ga bolnik ne prenaša dobro, ali zvišati v primerih nezadostnega učinka (glejte poglavji 4. 4 in 5. 2).
Cases of liver injury, including hepatic failure and hepatic necrosis, have been observed with imatinib.
Pri uporabi imatiniba so opažali poškodbe jeter, vključno z odpovedjo in nekrozo jeter.
79 chronic phase CML.
Pogostejše so pri bolnikih s pospešeno fazo CML ali blastno krizo kot pri bolnikih s kronično fazo CML.
Glivec may increase plasma concentration of other CYP3A4 metabolised drugs (e. g. triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, i. e. statins, etc.).
83 CYP3A4 (na primer triazolo- benzodiazepinov, dihidropiridinskih blokatorjev kalcijevih kanalčkov, nekaterih zaviralcev reduktaze HMG- CoA, tj. statinov, itn.).
80 Caution should therefore be exercised when using Glivec and paracetamol concomitantly, especially with high doses of paracetamol.
Zato je pri sočasni uporabi zdravila Glivec in paracetamola potrebna previdnost, posebno pri velikih odmerkih paracetamola.
4.7 Effects on ability to drive and use machines
84 4. 7 Vpliv na sposobnost vožnje in upravljanja s stroji
81 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.
Table 1
85 Preglednica 1
84 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.
Three large, international, open-label, non-controlled phase II studies were conducted in patients with Philadelphia chromosome positive (Ph+) CML in advanced, blast or accelerated phase disease, other Ph+ leukaemias or with CML in the chronic phase but failing prior interferon-alpha (IFN) therapy.
89 Opravili so tri velike mednarodne odprte nekontrolirane študije druge faze pri bolnikih s CML, s prisotnim kromosomom Philadelphia (Ph+), v napredovali, blastni ali pospešeni fazi bolezni, z drugimi Ph+ levkemijami ali s CML v kronični fazi, a po predhodnem neuspešnem zdravljenju z interferonom alfa (IFN).
** insufficient data, only two patients available with samples Haematological response criteria (all responses to be confirmed after ≥ 4 weeks):
90 * p < 0, 001, Fischerjev eksaktni test ** premalo podatkov, na voljo sta samo dva bolnika z vzorci Kriteriji hematološkega odziva (vsi odzivi morajo biti potrjeni po ≥ 4 tednih):
In this study, dose escalations were allowed from 400 mg daily to 600 mg daily, then from 600 mg daily to 800 mg daily.
V tej študiji so bila dovoljena zvišanja odmerka s 400 mg na dan na 600 mg na dan, nato s 600 mg na 91 dan na 800 mg na dan.
88 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
92 Preglednica 4
89 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:
93 Klinične študije pri Ph+ ALL Novo odkrita Ph+ ALL:
DEX 10 mg/ m2 oral, days 1-5; vindesine 3 mg/ m2 i. v., day 1; MTX 1.5 g/ m2 i. v.
94 DEX 10 mg/ m2 peroralno, 1. - 5. dan; vindezin 3 mg/ m2 i. v., 1. dan; MTX konsolidacijsko 1, 5 g/ m2 i. v.
91 or disappearance of fusion transcripts as measured by RT-PCR.
95 realnem času (RT- PCR).
92 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.
96 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.
97 sta samo eritromicin (IC50 50 µM) in flukonazol (IC50 118 µM) pokazala inhibicijo presnove imatiniba, ki bi bila lahko klinično pomembna.
93 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.
94 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.
99 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.
95 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.
3 years
100 3 leta
96 6.4 Special precautions for storage
6. 4 Posebna navodila za shranjevanje
PVDC/ alu blisters
Pretisni omoti iz PVDC/ aluminija.
97 ANNEX II
101 DODATEK II