natgillin/translations-raw huggingface dataset:
Caution should be exercised in patients with relevant cardiac disorders (see section 4.4).
Nužan je oprez u bolesnika sa značajnim srčanim poremećajima (vidjeti dio 4.4).
N/R
N/D
Hypertension (including Blood pressure increased, Blood pressure systolic increased, Essential hypertension, Hypertensive crisis) Respiratory, thoracic and mediastinal disorders Very common Dyspnoea, Cough Common
Hipertenzija (uključujući povišeni krvni tlak, povišeni sistolički tlak, esencijalnu hipertenziju, hipertenzivnu krizu) Poremećaji dišnog sustava, prsišta i sredoprsja Vrlo često
In CML patients at steady state, Cmax (geometric mean, coefficient of variation [CV]%) was 145 (14) ng/mL, and AUCss (geometric mean, CV%) was 2,700 (16) ng•h/mL after daily administration of bosutinib at 400 mg with food.
U bolesnika s KML-om u stanju dinamičke ravnoteže Cmax (geometrijska sredina, koeficijent varijacije [CV]%) bio je 145 (14) ng/ml, a AUCss (geometrijska sredina, CV%) bio je 2700 (16) ng•h/ml nakon svakodnevne primjene bosutiniba u dozi od 400 mg s hranom.
Newly-diagnosed CP Ph+ CML The recommended dose is 400 mg bosutinib once daily.
Novodijagnosticirani Ph+ KML u kroničnoj fazi Preporučena doza je 400 mg bosutiniba jedanput dnevno.
• newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukaemia (Ph+ CML).
• novodijagnosticiranom kroničnom mijeloičnom leukemijom s pozitivnim Philadelphia kromosomom (Ph+ KML) u kroničnoj fazi (engl. chronic phase, CP)
Tell your doctor if you develop any of the following signs and symptoms of fluid retention during Bosulif treatment such as swelling of the ankles, feet or legs; difficulty breathing chest pain or a cough (these may be signs of fluid retention in the lungs or chest).
Obavijestite svog liječnika ako imate bilo koji od sljedećih znakova i simptoma zadržavanja tekućine tijekom liječenja lijekom Bosulif kao što su oticanje gležnjeva, stopala ili nogu; otežano disanje, bol u prsnom košu ili kašalj (to mogu biti znakovi zadržavanja tekućine u plućima ili prsnom košu).
Dizziness, Dysgeusia Ear and labyrinth disorders Common
Omaglica, disgeuzija Poremećaji uha i labirinta Često
The trial randomised 536 patients (268 in each treatment group) with Ph+ or Ph- newly-diagnosed CP CML (intent-to-treat population [ITT]) including 487 patients with Ph+ CML harbouring b2a2 and/or b3a2 transcripts and baseline BCR-ABL copies > 0 (modified intent-to-treat [mITT] population).
U ispitivanju je randomizirano 536 bolesnika (268 u svakoj liječenoj skupini) s Ph+ ili Ph- novodijagnosticiranim KML-om u u kroničnoj fazi (populacija planirana za liječenje [engl. intent-to-treat population, ITT]) uključujući 487 bolesnika s Ph+ KML-om koji imaju transkripte b2a2 i/ili b3a2 i broj kopija BCR-ABL na početku > 0 (modificirana populacija planirana za liječenje [engl. modified intent-to-treat population, mITT]).
All 3 metabolites exhibited activity that was  5% that of bosutinib in a Src-transformed fibroblast anchorage-independent proliferation assay.
Sva 3 metabolita pokazala su aktivnost koja je bila  5% od aktivnosti bosutiniba u analizi proliferacije fibroblasta koje je transformirao Src i koji nisu bili vezani za čvrstu podlogu.
Reactivation of hepatitis B (HBV) in patients who are chronic carriers of this virus has occurred after these patients received BCR-ABL TKIs.
U bolesnika koji su kronični nositelji virusa hepatitisa B (HBV) pojavila se ponovna aktivacija tog virusa nakon što su primili inhibitore BCR-ABL tirozin kinaze.
After a minimum of 12 months of follow-up in the mITT population, discontinuations due to disease progression to AP or BP CML for bosutinib-treated patients were 0.4% compared to 1.7% for imatinib-treated patients.
Nakon najmanje 12 mjeseci praćenja u mITT populaciji prekidi primjene lijeka zbog progresije bolesti do ubrzane faze ili blastične faze KML-a u bolesnika liječenih bosutinibom iznosili su 0,4% naspram 1,7% u bolesnika liječenih imatinibom.
The elimination half-life of bosutinib in subjects with renal impairment was similar to that in healthy subjects.
Poluvijek eliminacije bosutiniba u ispitanika s oštećenjem bubrega sličan je poluvijeku eliminacije u zdravih ispitanika.
Caution should be exercised when administering bosutinib concomitantly with PPIs.
Nužan je oprez kada se bosutinib primjenjuje istodobno s IPP.
If transaminase elevations ≥ 3 × ULN occur concurrently with bilirubin elevations > 2 × ULN and alkaline phosphatase < 2 × ULN, bosutinib should be discontinued (see section 4.4).
Ako se javi porast transaminaza ≥ 3 × GGN istodobno s porastom bilirubina > 2 × GGN i alkalne fosfataze < 2 × GGN, mora se prekinuti liječenje bosutinibom (vidjeti dio 4.4).
The maximum toxicity of diarrhoea was Grade 1 or 2 in 88% of patients, Grade 3 in 12% of patients; 1 patient (< 1%) experienced a Grade 4 event.
Maksimalna toksičnost proljeva bila je 1. ili 2. stupnja u 88% bolesnika, 3. stupnja u 12% bolesnika, a 1 bolesnik (< 1%) imao je događaj 4. stupnja.
If you have any further questions on the use of this medicine ask your doctor or pharmacist.
U slučaju bilo kakvih pitanja u vezi s primjenom ovog lijeka, obratite se liječniku ili ljekarniku.
Sample size (N) includes patients with a valid baseline haematological ass essment.
Veličina uzorka (N) uključuje bolesnike s važećom početnom hematološkom procjenom.
The Grade 3 or Grade 4 adverse reactions reported for  5% of patients were thrombocytopenia (20.3%), anaemia (10.2%), neutropenia (10.5%), ALT increased (12.7%), diarrhoea (9.6%), rash (5.0%), lipase increased (8.2%), and AST increased (5.8%).
Nuspojave 3. stupnja ili 4. stupnja prijavljene u  5% bolesnika bile su trombocitopenija (20,3%), anemija (10,2%), neutropenija (10,5%), porast ALT (12,7%), proljev (9,6%), osip (5,0%), porast lipaze (8,2%) i porast AST (5,8%).
However, bosutinib did not demonstrate a potential for phototoxicity of the skin or eyes in pigmented rats exposed to bosutinib in the presence of UV radiation at bosutinib exposures up to 3-times and 2-times the human exposure resulting from the clinical dose of 400 or 500 mg, respectively (based on unbound Cmax in the respective species).
Međutim, bosutinib nije pokazao potencijal za fototoksičnost kože ili očiju u pigmentiranih štakora koji su izloženi bosutinibu u prisutnosti UV zračenja pri izloženostima bosutinibu do 3 puta odnosno 2 puta većoj od izloženosti u ljudi nakon kliničke doze od 400 mg odnosno 500 mg (na temelju Cmax nevezanog spoja u odgovarajućim vrstama).
Bosutinib displays pH-dependent aqueous solubility in vitro.
Bosutinib pokazuje in vitro topljivost u vodi u ovisnosti o pH.
Carriers of HBV who require treatment with bosutinib should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy (see section 4.8).
Nositelje virusa HBV kojima je potrebno liječenje bosutinibom potrebno je pozorno nadzirati radi utvrđivanja eventualnih znakova i simptoma aktivne infekcije HBV-om tijekom terapije te nekoliko mjeseci nakon završetka terapije (vidjeti dio
The maximum toxicity of Grade 3 neutropenia was experienced in 90 (46%) patients and of Grade 4 in 44 (22%) patients.
Neutropenija maksimalne toksičnosti 3. stupnja pojavila se u 90 (46%) bolesnika, a 4. stupnja u 44 (22%) bolesnika.
Hepatotoxicity (including Hepatitis, Hepatitis toxic, Liver disorder), Hepatic function abnormal (including Liver function test abnormal, Liver function test increased, Transaminases increased), Blood bilirubin increased (including Hyperbilirubinaemia), Gamma-glutamyltransferase increased Uncommon Liver injury (including Drug-induced liver injury) Skin and subcutaneous tissue disorders
Hepatotoksičnost (uključujući hepatitis, toksični hepatitis, poremećaj jetre), poremećaj jetrene funkcije (uključujući odstupanja u rezultatima testova jetrene funkcije, povećanja vrijednosti u testovima jetrene funkcije, povišene transaminaze), porast bilirubina u krvi (uključujući hiperbilirubinemiju), porast gama glutamiltransferaze
Anti-arrhythmic medicinal products and other substances that may prolong QT Bosutinib should be used with caution in patients who have or may develop prolongation of QT, including those patients taking anti-arrhythmic medicinal products such as amiodarone, disopyramide, procainamide, quinidine and sotalol or other medicinal products that may lead to QT prolongation such as chloroquine, halofantrine, clarithromycin, domperidone, haloperidol, methadone, and moxifloxacin (see section 4.4).
Antiaritmici i ostale tvari koje mogu produljiti QT interval Bosutinib se mora oprezno primjenjivati u bolesnika koji imaju ili mogu razviti produljeni QT interval, uključujući bolesnike koji uzimaju antiaritmike kao što su amiodaron, dizopiramid, prokainamid, kinidin i sotalol ili druge lijekove koji mogu dovesti do produljenja QT intervala kao što su klorokin, halofantrin, klaritromicin, domperidon, haloperidol, metadon i moksifloksacin (vidjeti dio
Table 2 - Adverse reactions for bosutinib
Tablica 2 - Nuspojave bosutiniba
In the Phase 1/2 clinical study in patients with CML who were resistant or intolerant to prior therapy who started treatment at ≤ 500 mg, 93 (93/558; 16.7%) patients had dose escalations to 600 mg daily.
U kliničkom ispitivanju faze 1/2 na bolesnicima s KML-om koji su bili otporni ili nisu podnosili prethodnu terapiju te koji su započeli liječenje s ≤ 500 mg, doza se postupno povećavala do 600 mg na dan u 93 (93/558; 16,7%) bolesnika.
Of the 994 (78%) patients that experienced diarrhoea, 10 patients discontinued bosutinib due to this event.
Od 994 (78%) bolesnika koji su imali proljev, 10 bolesnika prekinulo je liječenje bosutinibom zbog tog događaja.
In a study of the central nervous system (CNS), bosutinib treated rats displayed decreased pupil size and impaired gait.
U ispitivanju središnjeg živčanog sustava, štakori liječeni bosutinibom imali su smanjene zjenice i poremećeni hod.
In the Phase 1/2 clinical study in patients with CML who were resistant or intolerant to prior therapy, dose escalations from 500 mg to 600 mg once daily with food were allowed in patients who failed to demonstrate complete haematological response (CHR) by Week 8 or complete cytogenetic response (CCyR) by Week 12 and did not have Grade 3 or higher adverse events possibly-related to the investigational product.
U kliničkom ispitivanju faze 1/2 na bolesnicima s KML-om koji su bili otporni ili nisu podnosili prethodnu terapiju, postupna povećavanja doze s 500 mg na 600 mg jedanput na dan s hranom bila su dozvoljena u bolesnika koji nisu uspjeli postići potpun hematološki odgovor (engl. complete haematological response, CHR) do 8. tjedna ili potpun citogenetski odgovor (engl. complete cytogenetic response, CCyR) do 12. tjedna i nisu imali štetne događaje 3. ili većeg stupnja za koje postoji mogućnost da su povezani s ispitivanim lijekom.
Complete cytogenetic response was defined as the absence of Ph+ metaphases in chromosome banding analysis of ≥ 20 metaphases derived from bone marrow aspirate or MMR if an adequate cytogenetic assessment was unavailable.
Potpun citogenetski odgovor definiran je kao odsutnost Ph+ metafaza u analizi tehnikom pruganja kromosoma ≥ 20 metafaza dobivenih iz aspirata koštane srži ili MMR ako odgovarajuća citogenetska procjena nije bila dostupna.
Hepatitis B reactivation has been reported in association with BCR-ABL TKIs.
Ponovna aktivacija hepatitisa B zabilježena je u vezi s inhibitorima BCR-ABL tirozin kinaze.
The median time to first event was 59 days (range: 27 to 505 days), and the median duration per event was 15 days (range: 1 to 913 days).
Medijan vremena do prvog događaja bio je 59 dana (raspon: 27 do 505 dana), a medijan trajanja po događaju bio je 15 dana (raspon: 1 do 913 dana).
Bosutinib treatment reduced the size of CML tumours growing in nude mice and inhibited growth of murine myeloid tumours expressing imatinib-resistant forms of BCR-ABL. Bosutinib also inhibits receptor tyrosine kinases c-Fms, EphA and B receptors, Trk family kinases, Axl family kinases, Tec family kinases, some members of the ErbB family, the non-receptor tyrosine kinase Csk, serine/threonine kinases of the Ste20 family, and 2 calmodulin-dependent protein kinases.
Nadalje, bosutinib inhibira receptorske tirozin-kinaze c-Fms, receptore EphA i B, obitelj Trk kinaza, obitelj Axl kinaza, obitelj Tec kinaza, određene članove obitelji ErbB kinaza, nereceptorsku tirozinkinazu Csk, serin/treonin kinaze obitelji Ste20 i 2 proteinske kinaze ovisne o kalmodulinu.
Nine (0.8%) patients experienced QTcF increase from baseline exceeding 60 ms.
Devet (0,8%) bolesnika imalo je porast QTcF intervala u odnosu na početne vrijednosti preko 60 ms.
The most frequent adverse reactions reported for  20% of patients were diarrhoea (78.1%), nausea (40.8%), thrombocytopenia (34.9%), abdominal pain (34.0%), vomiting (33.0%), rash (31.5%), anaemia (25.6%), pyrexia (21.8%), fatigue (21.4%), and ALT increased (25.0%).
Najčešće prijavljivane nuspojave u  20% bolesnika bile su proljev (78,1%), mučnina (40,8%), trombocitopenija (34,9%), bol u abdomenu (34,0%), povraćanje (33,0%), osip (31,5%), anemija (25,6%), pireksija (21,8%), umor (21,4%) i porast ALT (25,0%).
These medicines should be taken with caution during your treatment with Bosulif.
Ti se lijekovi moraju uzimati uz oprez za vrijeme liječenja lijekom Bosulif.
Subjects with moderate and severe renal impairment had an increase in AUC over healthy volunteers of 35% and 60%, respectively.
Ispitanici s umjerenim i teškim oštećenjem bubrega imali su 35%-tno, odnosno 60%-tno povećanje AUC-a u odnosu na zdrave ispitanike.
In a rat fertility study, fertility was slightly decreased in males.
U ispitivanju plodnosti na štakorima plodnost je bila nešto smanjena u mužjaka.
The efficacy results for Ph+ CP CML patients previously treated with imatinib and at least 1 additional TKI (minimum follow-up 48 months, median treatment duration of 9 months and 24.4% still on-treatment at 48 months) and the results for Ph+ CP CML patients previously treated with only imatinib (minimum follow-up 60 months, median treatment duration of 26 months and 40.5% still on-treatment at 60 months) are presented in Table 5.
Rezultati djelotvornosti u bolesnika s Ph+ CP KML-om koji su prethodno liječeni imatinibom i najmanje 1 dodatnim TKI-om (minimalno praćenje 48 mjeseci, medijan trajanja liječenja od 9 mjeseci i 24,4% bolesnika koji još primaju terapiju nakon 48 mjeseci) i rezultati djelotvornosti u bolesnika s Ph+ CP KML-om koji su prethodno liječeni samo imatinibom (minimalno praćenje 60 mjeseci, medijan trajanja liječenja od 26 mjeseci i 40,5% bolesnika koji još primaju terapiju nakon 60 mjeseci) prikazani su u Tablici 5.
The concomitant use of bosutinib with strong or moderate CYP3A inhibitors should be avoided, as an increase in bosutinib plasma concentration will occur (see section 4.5).
Nužno je izbjegavati istodobnu primjenu bosutiniba sa snažnim ili umjerenim inhibitorima CYP3A jer će doći do porasta koncentracije bosutiniba u plazmi (vidjeti dio 4.5).
Other efficacy endpoints include the cumulative MCyR rate, time to and duration of MCyR, and time to and duration of CHR, in patients with CP CML previously treated with only 1 prior TKI (imatinib).
Druge mjere ishoda djelotvornosti uključuju kumulativnu stopu MCyR-a, vrijeme do MCyR-a i njegovo trajanje, vrijeme do CHR-a i njegovo trajanje u bolesnika s CP KML-om koji su prethodno liječeni samo 1 TKI-om (imatinib).
Experts in liver disease and in the treatment of HBV should be consulted before treatment is initiated in patients with positive HBV serology (including those with active disease) and for patients who test positive for HBV infection during treatment.
Prije početka liječenja bolesnika s pozitivnim serološkim nalazima na HBV (uključujući one s aktivnom bolešću) te za bolesnike za koje se pokaže da su pozitivni na HBV tijekom liječenja, potrebno je savjetovati se sa stručnjacima za bolesti jetre i liječenje HBV infekcije.
The maximum toxicity of thrombocytopenia of Grade 3 was experienced in 161 (36%) patients and Grade 4 in 98 (22%) patients.
Trombocitopenija maksimalne toksičnosti 3. stupnja pojavila se u 161 (36%) bolesnika, a 4. stupnja u 98 (22%) bolesnika.
The median time to MMR for responders was 24.7 weeks versus 36.3 weeks for the bosutinib treatment and imatinib treatment groups, respectively, in the mITT population.
Medijan vremena do MMR-a u bolesnika s odgovorom na terapiju iznosio je 24,7 tjedana naspram 36,3 tjedana za skupinu liječenu bosutinibom, odnosno skupinu liječenu imatinibom u mITT populaciji.
Caution should be exercised if mild CYP3A inhibitors are used concomitantly with bosutinib.
Nužan je oprez ako se istodobno s bosutinibom koriste blagi inhibitori CYP3A.
Hold bosutinib until ANC  1.0 × 109/L and platelets 9/L.
Obustaviti bosutinib sve do ABN-a  1,0×10
Infections and infestations Very common Respiratory tract infection (including Lower respiratory tract infection, Respiratory tract infection viral, Upper respiratory tract infection, Viral upper respiratory tract infection), Nasopharyngitis
Infekcija dišnih puteva (uključujući infekciju donjih dišnih putova, virusnu infekciju dišnih putova, infekciju gornjih dišnih putova, virusnu infekciju gornjih dišnih putova), nazofaringitis
A 2-arm, Phase 3, open-label, multicentre superiority trial was conducted to investigate the efficacy and safety of bosutinib 400 mg once daily alone compared with imatinib 400 mg once daily alone in adult patients with newly-diagnosed Ph+ CP CML.
Otvoreno, multicentrično ispitivanje superiornosti faze 3 s dvije skupine bolesnika provedeno je kako bi se ispitale djelotvornost i sigurnost primjene samo bosutiniba u dozi od 400 mg jedanput na dan u usporedbi s primjenom samo imatiniba u dozi od 400 mg jedanput na dan u odraslih bolesnika s novodijagnosticiranim Ph+ KML-om u kroničnoj fazi.
In an oral study of bosutinib in dogs, bosutinib did not produce changes in blood pressure, abnormal atrial or ventricular arrhythmias, or prolongation of the PR, QRS, or QTc of the ECG at exposures up to 3-times the human exposure resulting from the clinical dose of 400 mg and 2-times the human exposure resulting from the clinical dose of 500 mg (based on unbound Cmax in the respective species).
U ispitivanju peroralne primjene bosutiniba u pasa bosutinib nije izazvao promjene u krvnom tlaku, abnormalne atrijske ili ventrikularne aritmije, ili produljenje PR, QRS ili QTc u EKG-u kod izloženosti do 3 puta većoj od izloženosti u ljudi nakon kliničke doze od 400 mg i 2 puta većoj od izloženosti u ljudi nakon kliničke doze od 500 mg (na temelju Cmax nevezanog spoja u odgovarajućim vrstama).
There were 570 patients treated with bosutinib in this trial including CP CML patients previously treated with only 1 prior TKI (imatinib), CP CML patients previously treated with imatinib and at least 1 additional TKI (dasatinib and/or nilotinib), CML patients in accelerated or blast phase previously treated with at least 1 TKI (imatinib) and patients with Ph+ ALL previously treated with at least 1 TKI (imatinib).
U navedenom ispitivanju sudjelovalo je 570 bolesnika liječenih bosutinibom, uključujući bolesnike s CP KML-om prethodno liječene samo 1 TKI-om (imatinib), bolesnike s CP KML-om prethodno liječene imatinibom i najmanje 1 dodatnim TKI-om (dasatinib i/ili nilotinib), bolesnike s KML-om u ubrzanoj ili blastičnoj fazi prethodno liječene najmanje 1 TKI-om (imatinib) i bolesnike s Ph+ ALLom prethodno liječene najmanje 1 TKI-om (imatinib).
In a renal impairment study, bosutinib exposures were increased in subjects with moderately and severely impaired renal function.
U ispitivanju oštećenja bubrega, izloženost bosutinibu bila je povećana kod ispitanika s umjerenim i teškim oštećenjem funkcije bubrega.
Following administration of single or multiple doses of bosutinib (400 or 500 mg) to humans, the major circulating metabolites appeared to be oxydechlorinated (M2) and N-desmethylated (M5) bosutinib, with bosutinib N-oxide (M6) as a minor circulating metabolite.
Nakon primjene jedne ili višekratnih doza bosutiniba (400 ili 500 mg) u ljudi, čini se da su glavni cirkulirajući metaboliti bili oksidekloriniran (M2) i N-desmetiliran (M5) bosutinib, a bosutinib
The concomitant use of bosutinib with strong CYP3A inhibitors (including, but not limited to itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, nefazodone, mibefradil, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, boceprevir, telaprevir, grapefruit products including grapefruit juice) or moderate CYP3A inhibitors (including, but not limited to fluconazole, ciprofloxacin, erythromycin, diltiazem, verapamil, amprenavir, atazanavir, darunavir/ritonavir, fosamprenavir, aprepitant, crizotinib, imatinib) should be avoided, as an increase in bosutinib plasma concentration will occur.
Nužno je izbjegavati istodobnu primjenu bosutiniba sa snažnim inhibitorima CYP3A (uključujući, između ostalog itrakonazol, ketokonazol, posakonazol, vorikonazol, klaritromicin, telitromicin, nefazodon, mibefradil, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, sakvinavir, boceprevir, telaprevir, proizvode od grejpa uključujući sok od grejpa) ili umjerenim inhibitorima CYP3A (uključujući, između ostalog flukonazol, ciprofloksacin, eritromicin, diltiazem, verapamil, amprenavir, atazanavir, darunavir/ritonavir, fosamprenavir, aprepitant, krizotinib, imatinib) jer će doći do porasta koncentracije bosutiniba u plazmi.
Whereas, in the Phase 3 study in patients with newly-diagnosed CP CML treated with bosutinib 400 mg, dose escalations by 100 mg increments to a maximum of 600 mg once daily with food were permitted if the patient failed to demonstrate breakpoint cluster region-Abelson (BCR-ABL) transcripts ≤ 10% at Month 3, did not have a Grade 3 or 4 adverse reaction at the time of escalation, and all Grade 2 non-haematological toxicities were resolved to at least Grade 1.
Naprotiv, u ispitivanju faze 3 na bolesnicima s novodijagnosticiranim KML-om u kroničnoj fazi liječenim bosutinibom u dozi od 400 mg, bila su dopuštena postupna povećavanja doze u koracima od 100 mg do maksimalne doze od 600 mg jedanput na dan s hranom ako u bolesnika nisu ustanovljeni transkripti BCR-ABL (engl. breakpoint cluster region-Abelson) ≤ 10% u 3. mjesecu, ako bolesnik nije imao nuspojavu 3. ili 4. stupnja u vrijeme postupnog povećavanja doze te ako su se sve nehematološke toksičnosti 2. stupnja povukle barem na 1. stupanj.
The primary efficacy endpoint of the study was the major cytogenetic response (MCyR) rate at Week 24 in patients with imatinib-resistant CP CML previously treated with only 1 prior TKI (imatinib).
Primarna mjera ishoda djelotvornosti u navedenom ispitivanju bila je stopa velikog citogenetskog odgovora (engl. major cytogenetic response, MCyR) u 24. tjednu u bolesnika s CP KML-om rezistentnim na imatinib, koji su prethodno liječeni 1 TKI-om (imatinib).
Transformation to AP/BPf On--treatment transformation, n
Transformacija u AP/BP
The exposure camparison across species indicates that exposures that did not elicit adverse events in the 6- and 9-month toxicity studies in rats and dogs, respectively, were similar to the human exposure resulting from a clinical dose of 400 mg or 500 mg (based on unbound AUC in the respective species).
Usporedba izloženosti među vrstama upućuje da su izloženosti koje nisu izazvale štetne događaje u 6-mjesečnom i 9-mjesečnom ispitivanju toksičnosti u štakora i u pasa bile slične izloženosti u ljudi nakon kliničke doze od 400 mg ili 500 mg (na temelju AUC-a nevezanog spoja u odgovarajućim vrstama).
The effect of bosutinib 500 mg administration on corrected QTc was evaluated in a randomised, single-dose, double-blind (with respect to bosutinib), crossover, placebo- and open-label moxifloxacin-controlled study in healthy subjects.
Učinak primjene bosutiniba 500 mg na korigirani QTc procijenjen je u randomiziranom, dvostruko slijepom (što se tiče bosutiniba) ispitivanju s jednokratnom dozom i križnom zamjenom skupina, kontrolirano placebom i moksifloksacinom kao poznatim lijekom u zdravih ispitanika.