natgillin/translations-raw huggingface dataset:
With longer treatment and follow-up (median of 24 months), MCyR was achieved in 53% of the dasatinib-treated patients (CCyR in 44%) and 33% of the imatinib-treated patients (CCyR in 18%) prior to crossover.
Pri daljšem zdravljenju in spremljanju (v povprečju 24 mesecev) je bil dober citogenetski odziv dosežen pri 53% bolnikov, ki so se zdravili z dasatinibom (popoln citogenetski odziv pri 44%), in 33% bolnikov, ki so se zdravili z imatinibom (popoln citogenetski odziv pri 18%) pred zamenjavo zdravljenja.
Based on the Kaplan-Meier estimates, the proportion of patients who maintained MCyR for 1 year was 92% (95% CI:
14 Na osnovi Kaplan- Meierjeve ocene se je pri zdravljenju z dasatinibom dober citogenetski odziv ohranil 1 leto pri 92% bolnikov (95% interval zaupanja:
[85%-100%]) for dasatinib (CCyR 97%, 95% CI:
[85% - 100%]) (popoln citogenetski odziv pri 97% bolnikov, 95% interval zaupanja:
[92%-100%]) and 74% (95% CI:
[92% - 100%]), pri zdravljenju z imatinibom pa pri 74% bolnikov (95% interval zaupanja:
[49%-100%]) for imatinib (CCyR 100%).
[49% - 100%]) (popoln citogenetski odziv pri 100% bolnikov).
The proportion of patients who maintained MCyR for 18 months was 90% (95% CI:
Pri zdravljenju z dasatinibom se je dober citogenetski odziv ohranil 18 mesecev pri 90% bolnikov (95% interval zaupanja:
[82%-98%]) for dasatinib (CCyR 94%, 95% CI:
[82% - 98%]) (popoln citogenetski odziv pri 94% bolnikov, 95% interval zaupanja:
[87%-100%]) and 74% (95% CI:
[87% - 100%]), pri zdravljenju z imatinibom pa pri 74% bolnikov (95% interval zaupanja:
Based on the Kaplan-Meier estimates, the proportion of patients who had progression-free survival (PFS) for 1 year was 91% (95% CI:
Na osnovi Kaplan- Meierjeve ocene je bil pri zdravljenju z dasatinibom delež bolnikov z 1- letnim preživetjem brez progresije bolezni 91% (95% interval zaupanja:
[85%-97%]) for dasatinib and 73% (95% CI:
[85% - 97%]), pri zdravljenju z imatinibom pa 73% (95% interval zaupanja:
[54%-91%]) for imatinib.
[54% - 91%]).
The proportion of patients who had PFS at 2 years was 86% (95% CI:
Delež bolnikov z 2- letnim preživetjem brez progresije bolezni je bil pri zdravljenju z dasatinibom 86% (95% interval zaupanja:
[78%-93%]) for dasatinib and 65% (95% CI:
[78% - 93%]), pri zdravljenju z imatinibom pa 65% (95% interval zaupanja:
[43%-87%]) for imatinib.
[43% - 87%]).
A total of 43% of the patients in the dasatinib arm, and 82% in the imatinib arm had treatment failure, defined as disease progression or cross-over to the other treatment (lack of response, study drug intolerance, etc.).
Neuspeh zdravljenja je bil definiran kot napredovanje bolezni ali prehod na drugo obliko zdravljenja (pomanjkanje odziva, neprenašanje študijskega zdravila, itd.).
The rate of major molecular response (defined as BCR-ABL/ control transcripts ≤ 0.1% by RQ-PCR in peripheral blood samples) prior to crossover was 29% for dasatinib and 12% for imatinib.
Delež dobrega molekularnega odziva (definiran z vrednostjo prepisa BCR- ABL/ kontrola ≤ 0, 1% pri kvantitativni polimerazni verižni reakciji v realnem času (RQ- PCR) v vzorcu periferne krvi) pred zamenjavo zdravljenja je bil pri uporabi dasatiniba 29%, pri uporabi imatiniba pa 12%.
14 2- An open-label, single-arm, multicenter study was conducted in patients resistant or intolerant to imatinib (i. e. patients who experienced significant toxicity during treatment with imatinib that precluded further treatment).
2 - Pri bolnikih, ki so bili odporni na imatinib ali ga niso prenašali (to je pri bolnikih, pri katerih se je med zdravljenjem z imatinibom pojavila znatnejša toksičnost, ki je preprečila nadaljnje zdravljenje), je bila izvedena odprta, enoskupinska (“ single- arm ”), multicentrična študija.
Efficacy results are reported in Table 5.
Rezultati učinkovitosti so predstavljeni v tabeli 5.
With a minimum of 24 months follow-up, 21 of the 240 patients who had achieved a MCyR had progressed and the median duration of MCyR had not been reached.
Pri spremljanju, ki je trajalo najmanj 24 mesecev je do napredovanja bolezni prišlo pri 21 od 240 bolnikov, pri katerih je bil dosežen dober citogenetski odziv.
Based on the Kaplan-Meier estimates, 95% (95% CI:
[92% - 98%]).
[92%-98%]) of the patients maintained MCyR for 1 year and 88% (95% CI:
Dober citogenetski odziv se je 2 leti ohranil pri 88% bolnikov (95% interval zaupanja:
The proportion of patients who maintained CCyR for 1 year was 97% (95% CI:
Popoln citogenetski odziv se je 1 leto ohranil pri 97% bolnikov (95% interval zaupanja:
[94%-99%]) and for 2 years was 90% (95% CI:
[94% - 99%]), 2 leti pa pri 90% bolnikov (95% interval zaupanja:
Fifty-five percent of the imatinib-resistant patients with no prior MCyR to imatinib (n= 288) achieved a MCyR with dasatinib.
Pri uporabi dasatiniba je bil dober citogenetski odziv dosežen pri 55% bolnikov, odpornih na imatinib, pri katerih dober citogenetski odziv na zdravljenje z imatinibom (n= 288) ni bil dosežen.
There were 45 different BCR-ABL mutations in 38% of patients enrolled in this trial.
Pri 38% bolnikov, vključenih v to preskušanje, je bilo ugotovljenih 45 različnih mutacij BCR- ABL.
Complete haematologic response or MCyR was achieved in patients harboring a variety of BCR-ABL mutations associated with imatinib resistance except T315I.
Popoln hematološki odziv ali dober citogenetski odziv je bil dosežen pri bolnikih, pri katerih so bile prisotne različne mutacije BCR- ABL, povezane z odpornostjo na imatinib, razen mutacije T315I.
The rates of MCyR at 2 years were similar whether patients had any baseline BCR-ABL mutation, P-loop mutation, or no mutation (63%, 61% and 62%, respectively).
Po 2 letih so bili deleži dobrega citološkega odziva podobni ne glede na to, če je bila v izhodišču prisotna katerakoli mutacija BCR- ABL, P- loop mutacija ali pa mutacija ni bila prisotna (63%, 61% oziroma 62%).
Among imatinib-resistant patients, the estimated rate of PFS was 88% (95% CI:
Pri na imatinib odpornih bolnikih je bil ocenjen delež preživetja brez progresije bolezni po 1 letu 88% (95% interval zaupanja:
[84%-92%]) at 1 year and 75% (95% CI:
[84% - 92%]), po 2 letih pa 75% (95% interval zaupanja:
[69%-81%]) at 2 years.
Pri
Among imatinib-intolerant patients, the estimated rate of PFS was 98% (95% CI:
15 bolnikih, ki imatiniba niso prenašali je bil ocenjen delež preživetja brez progresije bolezni po 1 letu 98% (95% interval zaupanja:
[95%-100%]) at 1 year and 94% (95% CI:
[95% - 100%]), po 2 letih pa 94% (95% interval zaupanja:
Accelerated Phase CML:
KML v obdobju pospešenega poteka:
An open-label, single-arm, multicenter study was conducted in patients intolerant or resistant to imatinib.
Pri bolnikih, ki imatiniba niso prenašali ali so bili nanj odporni, je bila izvedena odprta, enoskupinska (“ single- arm ”), multicentrična študija.
Further efficacy results are reported in Table 5.
Nadaljni rezultati učinkovitosti so predstavljeni v tabeli 5.
Myeloid Blast Phase CML:
KML v obdobju mieloblastne preobrazbe:
Median duration of treatment on dasatinib was 3.5 months with 12% of patients treated for > 24 months to date.
Zdravljenje z dasatinibom je v povprečju trajalo 3, 5 mesece, pri 12% bolnikov je zdravljenje do danes trajalo dlje kot 24 mesecev.
Clinical trials in Lymphoid Blast Phase CML and Ph+ ALL:
Klinična preskušanja pri KML v obdobju limfoblastne preobrazbe in pri Ph+ ALL:
An open-label, single-arm, multicenter study was conducted in patients with lymphoid blast phase CML or Ph+ ALL who were resistant or intolerant to prior imatinib therapy.
Pri bolnikih s KML v obdobju limfoblastne preobrazbe ali s Ph+ ALL, ki imatiniba niso prenašali ali pa so bili na predhodno zdravljenje z imatinibom odporni, je bila izvedena odprta, enoskupinska (“ single- arm ”), multicentrična študija.
Median duration of
Od diagnoze do začetka zdravljenja je v povprečju minilo 18 mesecev.
15 treatment on dasatinib was 3 months with 7% of patients treated for > 24 months to date.
Zdravljenje z dasatinibom je v povprečju trajalo 3 mesece, pri 7% bolnikov je zdravljenje do danes trajalo dlje kot 24 mesecev.
Table 5:
16 Tabela 5:
Efficacy in Phase II SPRYCEL Single-Arm
Učinkovitost zdravila SPRYCEL v enoskupinskih (“ single arm ”) kliničnih preskušanjih II. fazea Obdobje Obdobje Obdobje pospešenega mieloidne limfoblastne Kronično
Clinical Studiesa Myeloid Lymphoid
obdobje poteka preobrazbe preobrazbe (n= 387) (n= 174) (n= 109) (n= 48) b
Haematologic Response Rateb (%) MaHR (95% CI)
Delež hematološkega odziva (%) Dober hematološki odziv (95% IZ) Popoln
CHR (95% CI) NEL (95% CI)
levkemije (95% IZ)
Duration of MaHR (%; Kaplan-Meier Estimates)
Trajanje dobrega hematološkega odziva (%; Kaplan- Meierjeva ocena)
1 Year 2 Year
1 leto 2 leti
Cytogenetic Response (%) MCyR (95% CI) CCyR (95% CI)
Citogenetski odziv (%) Dober citogenetski odziv (95% IZ) Popoln
Survival (%; Kaplan-Meier Estimates) Progression-Free
Preživetje (%; Kaplan- Meierjeva ocena) Brez progresije
Overall a
Skupno a
Major haematologic response:
Številke v krepkem tisku so rezultati primarnih opazovanih dogodkov. b Kriteriji hematološkega odziva (vsi odzivi potrjeni po 4 tednih):
(MaHR) = complete haematologic response (CHR) + no evidence of leukemia (NEL).
Dober hematološki odziv = popoln hematološki odziv + brez znakov levkemije.
WBC ≤ institutional ULN, platelets < 450,000/ mm3, no blasts or promyelocytes in peripheral blood, < 5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood < 20%, and no extramedullary involvement.
Popoln hematološki odziv (KML v kroničnem obdobju): število belih krvnih celic ≤ zgornje meje referenčnih vrednosti, trombociti < 450. 000/ mm3, brez blastov ali promielocitov v periferni krvi, < 5% mielocitov in metamielocitov v periferni krvi, < 20% bazofilcev v periferni krvi in brez ekstramedularne vpletenosti.
WBC ≤ institutional ULN, ANC ≥ 1000/ mm3, platelets ≥ 100,000/ mm3, no blasts or promyelocytes in peripheral blood, bone marrow blasts ≤ 5%, < 5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood < 20%, and no extramedullary involvement.
Popoln hematološki odziv (KML v obdobju pospešenega poteka/ Ph+ ALL): število belih krvnih celic ≤ zgornje meje referenčnih vrednosti, absolutno število nevtrofilcev ≥ 1. 000/ mm3, trombociti ≥ 100. 000/ mm3, brez blastov ali promielocitov v periferni krvi, blasti v kostnem mozgu ≤ 5%, < 5% mielocitov in metamielocitov v periferni krvi, < 20% bazofilcev v periferni krvi in brez ekstramedularne vpletenosti.
NEL: same criteria as for CHR but ANC ≥ 500/ mm3 and< 1000/mm3, or platelets ≥ 20,000/mm3 and ≤ 1 00,000/mm3. c Cytogenetic response criteria: complete (0% Ph+ metaphases) or partial (> 0%– 35%).
Brez znakov levkemije: isti kriteriji kot za popoln hematološki odziv, vendar absolutno število nevtrofilcev ≥ 500/ mm3 in < 1. 000/ mm3 in/ ali trombocitov ≥ 20. 000/ mm3 in ≤ 100. 000/ mm3. c Kriteriji citogenetskega odziva: popolni (0% Ph+ metafaze) ali delni (> 0% – 35%).
MCyR (0% – 35%) combines both complete and partial responses. n/ a = not applicable CI = confidence interval ULN = upper limit normal range.
Dober citogenetski odziv (0% - 35%) je kombinacija obeh, popolnega in delnega odziva. n/ a = ni pomembno; IZ = interval zaupanja
Phase III Clinical Trials Two randomised, open-label studies were conducted to evaluate the efficacy of dasatinib administered once daily compared with dasatinib administered twice daily:
Klinična preskušanja III. faze Izvedeni sta bili dve randomizirani, odprti študiji, ki sta vrednotili učinkovitost uporabe dasatiniba enkrat na dan v primerjavi z uporabo dasatiniba dvakrat na dan:
1- In the study of chronic phase CML, the primary endpoint was MCyR in imatinib-resistant patients.
1 - V študiji KML v kroničnem obdobju je bil primarni opazovani dogodek dober citogenetski odziv pri bolnikih z odpornostjo na imatinib.
The main secondary endpoint was MCyR by total daily dose level in the imatinib-resistant patients.
Drugi sekundarni
Other secondary endpoints included duration of MCyR, progression-free survival, and overall survival.
17 opazovani dogodki so vključevali trajanje dobrega citogenetskega odziva, preživetje brez progresije bolezni in skupno preživetje.
A total of 670 patients, of whom 498 were imatinib-resistant, were randomised to the dasatinib 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily group.
Na dasatinib v odmerku 100 mg enkrat na dan, 140 mg enkrat na dan, 50 mg dvakrat na dan ali 70 mg dvakrat na dan je bilo skupaj randomiziranih 670 bolnikov, od katerih jih je bilo 498 odpornih na imatinib.
Median duration of treatment was approximately 8 months (range < 1– 15 months).
Zdravljenje je v povprečju trajalo približno 8 mesecev (razpon od < 1 do 15 mesecev).
16 Response rates are presented in Table 6.
Odstotki odziva so predstavljeni v tabeli 6.
Efficacy was achieved across all dasatinib treatment groups with the once daily schedule demonstrating comparable efficacy (non-inferiority) to the twice daily schedule on the primary efficacy endpoint (difference in MCyR 2.8%; 95% confidence interval [-6% - 11.6%]).
Pri režimu odmerjanja enkrat na dan je bila učinkovitost pri primarnem opazovanem dogodku primerljiva (enakovredna) z učinkovitostjo pri režimu odmerjanja dvakrat na dan (razlika pri dobrem citogenetskem odzivu 2, 8%; 95% interval zaupanja [- 6% - 11, 6%]).
The main secondary endpoint of the study also showed comparable efficacy (non-inferiority) between the 100 mg total daily dose and the 140 mg total daily dose (difference in MCyR -0.8%; 95% confidence interval [-9.6% - 8.0%]).
Primerljiva (enakovredna) učinkovitost med 100 mg skupnim dnevnim odmerkom in 140 mg skupnim dnevnim odmerkom je bila ugotovljena tudi pri glavnem sekundarnem opazovanem dogodku (razlika pri dobrem citogenetskem odzivu - 0, 8%; 95% interval zaupanja [- 9, 6% - 8, 0%]).
Durations of MCyR, progression-free survival, and overall survival were similar across the four treatment groups.
Trajanje dobrega citogenetskega odziva, preživetja brez progresije bolezni in skupnega preživetja je bilo podobno v vseh štirih skupinah.
The median overall survival had not been reached for any of the four treatment groups.
Mediana vrednost skupnega preživetja ni bila dosežena v nobeni od štirih skupin.
Efficacy of SPRYCEL in Phase III Dose-Optimisation Study: Chronic 100 mg once daily 50 mg twice daily 140 mg once daily n = 167 n = 168 n = 167
100 mg enkrat na 50 mg dvakrat na 140 mg enkrat na 70 mg dvakrat dan dan dan
Phase CML 70 mg twice daily n = 168
n = 167 n = 168 n = 167 n
Percent (%) of Patients a Haematologic Response Rate (%) CHR
Delež hematološkega odziva (%) Popoln hematološki odziv
Cytogenetic Response (%) MCyR All Patients (95% CI) Imatinib-
Citogenetski odziv Dober citogenetski odziv Vsi bolniki (95%
resistant patients (n/ N) CCyR
imatinib (n/ N)
All Patients Imatinib-
Vsi bolniki Bolniki, odporni na
resistant patients (n/ N) a
imatinib (n/ N)
Haematologic response criteria (all responses confirmed after 4 weeks):
Kriteriji hematološkega odziva:
CHR (chronic CML):
(vsi odzivi potrjeni po 4 tednih):
WBC ≤ institutional ULN, platelets < 450,000/ mm3, no blasts or promyelocytes in peripheral blood, < 5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood< 20%, and no extramedullary involvement. b Cytogenetic response criteria: complete (0% Ph+ metaphases) or partial (> 0%–35%).
Popoln hematološki odziv (KML v kroničnem obdobju): število belih krvnih celic ≤ zgornje meje referenčnih vrednosti, trombociti < 450. 000/ mm3, brez blastov ali promielocitov v periferni krvi, < 5% mielocitov in metamielocitov v periferni krvi, < 20% bazofilcev v periferni krvi in brez ekstramedularne vpletenosti. b Kriteriji citogenetskega odziva: popolni (0% Ph+ metafaze) ali delni (> 0% – 35%).
MCyR (0% – 35%) combines both complete and partial responses.
Dober citogenetski odziv (0% – 35%) je kombinacija obeh, popolnega in delnega odziva.
2- In the study of advanced phase CML and Ph+ALL, the primary endpoint was MaHR.
2 - V študiji KML v napredovalem obdobju in Ph+ ALL je bil primarni opazovani dogodek dober hematološki odziv.
Median duration of treatment was approximately 6 months (range < 1-16 months).
Zdravljenje je v povprečju trajalo približno 6 mesecev (razpon od < 1 do 16 mesecev).
The once daily schedule demonstrated comparable efficacy (non-inferiority) to the twice daily schedule on the primary efficacy endpoint (difference in MaHR 0.2%; 95% confidence interval [-7.8% - 8.1%]).
Režim
Therefore 70 mg twice daily remains the recommended dose schedule in imatinib-resistant or intolerant patients with advanced phase CML and Ph+ALL.
18 odmerjanja 70 mg dvakrat na dan tako ostaja priporočeni režim odmerjanja pri bolnikih s KML v napredovalem obdobju ali Ph+ ALL, ki so odporni na imatinib ali imatiniba ne prenašajo.
Dasatinib is rapidly absorbed in patients following oral administration, with peak concentrations between 0.5-3 hours.
Pri bolnikih je absorpcija dasatiniba po peroralnem dajanju hitra.
Following oral administration, the increase in the mean exposure (AUC τ) is
Največje koncentracije so dosežene v  0, 5 do 3 urah.
17 approximately proportional to the dose increment across doses ranging from 25 mg to 120 mg twice daily.
Po peroralnem dajanju se srednja izpostavljenost (AUCτ) povečuje približno sorazmerno s povečevanjem odmerka v razponu odmerkov od 25 mg do 120 mg dvakrat na dan.
Data from healthy subjects administered a single, 100 mg dose of dasatinib 30 minutes following a high-fat meal indicated a 14% increase in the mean AUC of dasatinib.
Podatki pri zdravih osebah, ki so prejele enkraten 100 mg odmerek dasatiniba 30 minut po obroku z visoko vsebnostjo maščob kažejo, da se je srednja vrednost AUC povečala za 14%.
In patients, dasatinib has a large apparent volume of distribution (2,505 l) suggesting that the medicinal product is extensively distributed in the extravascular space.
Dasatinib ima pri bolnikih velik navidezni volumen porazdelitve (2505 l), kar kaže na ekstenzivno porazdelitev zdravila v ekstravaskularni prostor.
Dasatinib is extensively metabolized in humans with multiple enzymes involved in the generation of the metabolites.
Pri nastanku presnovkov so vključeni številni encimi.
Following a single oral dose of [14C]-labelled dasatinib, approximately 89% of the dose was eliminated within 10 days, with 4% and 85% of the radioactivity recovered in the urine and faeces, respectively.
4% radioaktivnosti so zasledili v urinu, 85% pa v blatu.
Unchanged dasatinib accounted for 0.1% and 19% of the dose in urine and faeces, respectively, with the remainder of the dose as metabolites.
Nespremenjeni dasatinib predstavlja 0, 1% z urinom izločenega odmerka in 19% z blatom izločenega odmerka; preostali del odmerka predstavljajo presnovki.
Exposure to dasatinib may be expected to increase if liver function is impaired (see section 4.4).
V primeru okvare delovanja jeter lahko pričakujemo povečano izpostavljenost dasatinibu (glejte poglavje 4. 4).
The non-clinical safety profile of dasatinib was assessed in a battery of in vitro and in vivo studies in mice, rats, monkeys, and rabbits.
Predklinični varnostni profil dasatiniba je bil ovrednoten z vrsto in vitro in in vivo študij na miših, podganah, opicah in kuncih.
Renal changes in monkeys treated for up to 9 months were limited to an increase in background kidney mineralization.
Pri opicah, ki so zdravilo prejemale do 9 mesecev, so bile spremembe v ledvicah omejene na mineralizacijo.
Cutaneous haemorrhage was observed in an acute, single-dose oral study in monkeys but was not observed in repeat-dose studies in either monkeys or rats.
Pri opicah so pri akutni študiji z enim peroralnim odmerkom opazili kožne krvavitve, vendar pa pri študijah s ponavljajočimi se odmerki kožnih krvavitev pri opicah ali podganah niso
However, in an in vivo single-dose study in conscious telemetered monkeys, there were no changes in QT interval or ECG wave form.
Aktivnost dasatiniba pri hERG testih in testih na Purkynjevih vlaknih in vitro kaže na možnost podaljšanja repolarizacije ventriklov (Q- T interval), vendar pa in vivo pri študiji z enkratnim odmerkom na zavestnih opicah niso opazili sprememb Q- T intervala ali oblike zobcev na elektrokardiogramu.
18 Dasatinib was not mutagenic in in vitro bacterial cell assays (Ames test) and was not genotoxic in an in vivo rat micronucleus study.
Pri in vitro testih na bakterijskih celicah (Amesov test) dasatinib ni deloval mutageno in tudi ni bil genotoksičen pri in vivo študiji s podganjimi mikronukleusi.
In embryofoetal development studies, dasatinib likewise induced embryolethality with associated decreases in litter size in rats, as well as foetal skeletal alterations in both rats and rabbits.
Pri podganah in kuncih so zasledili tudi spremembe na skeletu plodov.
These effects occurred at doses that did not produce maternal toxicity, indicating that dasatinib is a selective reproductive toxicant from implantation through the completion of organogenesis.
Ti učinki so se pojavili pri odmerkih, ki niso bili toksični za mater, kar kaže, da je dasatinib selektivno toksičen v obdobju reprodukcije in sicer v obdobju od vgnezditve do zaključka organogeneze.
In mice, dasatinib induced immunosuppression, which was dose-related and effectively managed by dose reduction and/ or changes in dosing schedule.
Pri miših je dasatinib povzročil imunosupresijo, ki je bila odvisna od odmerka in se je lahko učinkovito nadzirala z zmanjšanjem odmerka in/ ali spremembo odmerne sheme.
Dasatinib had phototoxic potential in an in vitro neutral red uptake phototoxicity assay in mouse fibroblasts.
Pri in vitro testu “ neutral red uptake phototoxicity ” na mišjih fibroblastih je imel dasatinib fototoksični potencial.
Dasatinib was considered to be non-phototoxic in vivo after a single oral administration to female hairless mice at exposures up to 3-fold the human exposure following administration of the recommended therapeutic dose (based on AUC).
Izpostavljenost je ustrezala do 3- kratni izpostavljenosti človeka po prejetju priporočenega terapevtskega odmerka (na osnovi AUC).
No carcinogenesis studies were conducted with dasatinib.
Študije karcinogenosti dasatiniba niso bile izvedene.
Lactose monohydrate Cellulose, microcrystalline Croscarmellose sodium Hydroxypropyl cellulose Magnesium stearate
Jedro tablete: laktoza monohidrat mikrokristalna celuloza premreženi natrijev karmelozat hidroksipropilceluloza magnezijev stearat
Hypromellose Titanium dioxide Macrogol 400
Filmska obloga: hipromeloza titanov dioksid makrogol 400
Alu/ Alu blisters (calendar blisters and unit dose blisters) and high-density polyethylene (HDPE) bottle with child resistant closure of polypropylene.
Alu/ alu pretisni omoti (koledarski pretisni omoti in enoodmerni pretisni omoti) in plastenka iz polietilena visoke gostote (HDPE) z za otroke varno polipropilensko zaporko.
Cartons containing 56 film-coated tablets in 4 blisters of 14 film-coated tablets each.
En pretisni omot vsebuje 14 filmsko obloženih tablet.
Cartons containing 60 film-coated tablets in perforated unit dose blisters.
Škatle s 60 filmsko obloženimi tabletami v perforiranih enoodmernih pretisnih omotih.
19 Cartons containing one bottle with 60 film-coated tablets.
Škatle z eno plastenko s 60 filmsko obloženimi tabletami.
The tablets consist of a core tablet, surrounded by a film coating to prevent exposure of health care professionals to the active substance.
Slednja zdravstveno osebje sicer varuje pred stikom z zdravilno učinkovino, vendar pa se tablete pri rokovanju lahko nenamerno zdrobijo ali kakorkoli drugače poškodujejo.
However, if the tablets are unintentionally crushed or broken, health care professionals should wear disposable chemotherapy gloves for appropriate disposal in order to minimize the risk of dermal exposure.
Da bi se tveganje za izpostavljenost kože zdravilni učinkovini zmanjšalo na minimum, mora zdravstveno osebje uporabljati rokavice, ki so namenjene rokovanju s kemoterapevtiki in jih nato ustrezno zavreči.