FrancophonIA/ELRC3.0 huggingface dataset:
English: In the non-compartmental analysis, after dosing with 960 mg vemurafenib twice daily the Day 15 / Day 1 ratio ranged from 15- to 17-fold for AUC, and 13to 14-fold for Cmax, yielding AUC0-8h and Cmax of 380.2 ± 143.6 µg⋅h/mL and 56.7 ± 21.8 µg/mL, respectively, under steady-state conditions.
Croatian: U nekompartmentalnoj analizi nakon primjene doze od 960 mg dvaput na dan, 15. su dana vrijednosti AUC-a bile 15 do 17 puta, a vrijednosti Cmax 13 do 14 puta veće nego 1. dana, što daje AUC0-8h od 380,2 ± 143,6 µg⋅h/ml i Cmax od 56,7 ± 21,8 µg/ml u stanju dinamičke ravnoteže.
English: Retinal vein occlusion, iridocyclitis
Croatian: Poremećaji oka uveitis okluzija retinalne vene, iridociklitis
English: 2nd occurrence of any grade 4 AE or persistence of any grade 4 AE after 1st dose reduction
Croatian: Drugi nastup bilo koje nuspojave stupnja 4, ili trajanje bilo koje nuspojave stupnja 4 nakon prvog sniženja doze
English: ● Rash, itching, dry or scaly skin
Croatian: • osip, svrbež, suha ili ljuskava koža
English: Hypersensitivity reaction
Croatian: Reakcije preosjetljivosti
English: Results from the Phase III study (NO25026) in previously untreated patients An open-label, multicentre, international, randomised phase III study supports the use of vemurafenib in previously untreated patients with BRAF V600E mutation-positive unresectable or metastatic melanoma.
Croatian: Rezultati ispitivanja faze III (NO25026) u prethodno neliječenih bolesnika Otvoreno, multicentrično, međunarodno, randomizirano kliničko ispitivanje faze III podupire primjenu vemurafeniba u prethodno neliječenih bolesnika s neresektabilnim ili metastatskim melanomom s pozitivnom BRAF mutacijom V600E.
English: ● It is not known whether the ingredients in Zelboraf pass into human milk.
Croatian: • Nije poznato izlučuju li se sastojci lijeka Zelboraf u majčino mlijeko.
English: ● Tell your doctor if you have had a different type of cancer than melanoma, as Zelboraf may cause progression of certain types of cancers.
Croatian: • Obavijestite liječnika ako ste bolovali od neke druge vrste raka osim melanoma jer
English: ● Change in liver tests results (GGT increase)
Croatian: • promjene rezultata testova jetrene funkcije (povišen GGT)
English: The relative proportions of vemurafenib and its metabolites were characterised in a human mass balance study with a single dose of 14C-labeled vemurafenib administered orally.
Croatian: Relativni udjeli vemurafeniba i njegovih metabolita određeni su u ispitivanju masene bilance u ljudi, uz peroralnu primjenu jednokratne doze vemurafeniba označenog radioizotopom 14C.
English: Infections and infestations
Croatian: Infekcije i infestacije folikulitis
English: The primary efficacy objective of the study was best overall response rate (BORR) in the brain of metastatic melanoma patients with previously untreated brain metastases, as assessed by an independent review committee (IRC).
Croatian: Primarna mjera ishoda za djelotvornost u ispitivanju bila je stopa najboljeg ukupnog odgovora (engl. best overall response rate, BORR) u mozgu bolesnika s metastatskim melanomom i prethodno neliječenim moždanim metastazama, prema ocjeni neovisnog ocjenjivačkog povjerenstva.
English: As vemurafenib is cleared by the liver, patients with moderate to severe hepatic impairment may have increased exposure and should be closely monitored (see sections 4.4 and 5.2).
Croatian: Budući da se vemurafenib uklanja putem jetre, u bolesnika s umjerenim do teškim oštećenjem jetrene funkcije izloženost lijeku može biti povećana te ih treba pomno nadzirati (vidjeti dijelove 4.4 i 5.2).
English: In this section, ADRs are based on results in 468 patients from a phase III randomised open label study in adult patients with BRAF V600 mutation-positive unresectable or stage IV melanoma, as well as a phase II single-arm study in patients with BRAF V600 mutation-positive stage IV melanoma who had previously failed at least one prior systemic therapy (see section 5.1).
Croatian: Nuspojave na lijek prikazane u ovom dijelu temelje se na rezultatima 468 bolesnika iz otvorenog, randomiziranog ispitivanja faze III, provedenog u odraslih bolesnika s inoperabilnim ili melanomom stadija IV s pozitivnom BRAF mutacijom V600, te iz ispitivanja faze II s jednom skupinom bolesnika s melanomom stadija IV s pozitivnom BRAF mutacijom V600 koji prethodno nisu uspješno odgovorili na najmanje jednu sistemsku terapiju (vidjeti dio 5.1).
English: ● medicines for heart rhythm problems (e.g. quinidine, amiodarone)
Croatian: • lijekove za tegobe sa srčanim ritmom (npr. kinidin, amiodaron)
English: Change ≥ 1 grade from baseline to any grade Change ≥ 1 grade from baseline to grade 3 or higher
Croatian: Promjena za ≥ 1 stupanj od početne vrijednosti do 3. ili višeg stupnja
English: Co-administration of vemurafenib resulted in an 18% increase in AUC of S-warfarin (CYP2C9 substrate).
Croatian: Istodobna primjena vemurafeniba dovela je do povećanja AUC-a S-varfarina (supstrata CYP2C9) za 18%.
English: It cannot be excluded that vemurafenib pharmacokinetics could be affected by such medicines through influence on P-gp (e.g. verapamil, cyclosporine, quinidine) or BCRP (e.g. cyclosporine, gefitinib).
Croatian: Ne može se isključiti mogućnost da takvi lijekovi utječu na farmakokinetiku vemurafeniba djelovanjem na P-gp (npr. verapamil, ciklosporin, kinidin) ili BCRP (npr. ciklosporin, gefitinib).
English: Table 7: Overall survival in previously untreated patients with BRAF V600 mutation-positive melanoma by study cut-off date (N=338 dacarbazine, N=337 vemurafenib) Cut-off dates
Croatian: Tablica 7: Ukupno preživljenje u prethodno neliječenih bolesnika s melanomom s pozitivnom BRAF mutacijom V600 prema zaključnim datumima za prikupljanje podataka za analizu (N=338 dakarbazin, N=337 vemurafenib)
English: Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates (e.g. aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, everolimus, fexofenadine, lapatinib, maraviroc, nilotinib, posaconazole, ranolazine, sirolimus, sitagliptin, talinolol, topotecan) and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.
Croatian: Potreban je oprez kad se vemurafenib primjenjuje istodobno sa supstratima P-gp-a (npr. aliskirenom, ambrisentanom, kolhicinom, dabigatraneteksilatom, digoksinom, everolimusom, feksofenadinom, lapatinibom, maravirokom, nilotinibom, posakonazolom, ranolazinom, sirolimusom, sitagliptinom, talinololom, topotekanom) te se može razmotriti smanjenje doze istodobno primijenjenog lijeka, ako je to klinički indicirano.
English: Patients with severe renal impairment should be closely monitored (see sections 4.4 and 5.2).
Croatian: Bolesnike s teškim oštećenjem bubrežne funkcije treba pomno nadzirati (vidjeti dijelove 4.4 i 5.2).
English: ● Progression of a type of pre-existing cancers with RAS mutations (Chronic Myelomonocytic
Croatian: • pogoršanje već postojećih vrsta raka s mutacijama gena RAS (kronične mijelomonocitne leukemije, adenokarcinoma gušterače)
English: Posology adjustments
Croatian: Prilagodbe doziranja
English: Breast-feeding is not recommended during treatment with Zelboraf.
Croatian: Tijekom liječenja lijekom Zelboraf dojenje se ne preporučuje.
English: ● Allergic reactions can happen while taking Zelboraf and may be severe.
Croatian: • Dok uzimate Zelboraf mogu nastupiti alergijske reakcije, koje mogu biti teške.
English: In the population pharmacokinetic analysis using data from clinical trials in patients with metastatic melanoma, mild and moderate renal impairment did not influence the apparent clearance of vemurafenib (creatinine clearance >40 ml/min).
Croatian: U populacijskoj farmakokinetičkoj analizi u kojoj su korišteni podaci iz kliničkih ispitivanja u bolesnika s metastatskim melanomom, blago i umjereno oštećenje bubrežne funkcije nije utjecalo na prividni klirens vemurafeniba (klirens kreatinina > 40 ml/min).
English: The prescriber should examine the patient monthly during and up to six months after treatment for cuSCC.
Croatian: Liječnik koji propisuje lijek mora mjesečno kontrolirati bolesnika tijekom, te do šest mjeseci po završetku liječenja planocelularnog karcinoma kože.
English: Patients should be carefully monitored for safety and dose modifications applied if clinically indicated (see Table 1 in section 4.2).
Croatian: Bolesnike je potrebno pažljivo nadzirati zbog sigurnosti te prilagoditi dozu ako je to klinički indicirano (vidjeti Tablicu 1 u dijelu 4.2).
English: Ophthalmologic reactions
Croatian: Oftalmološke reakcije
English: A risk for increased exposure in patients with severe renal impairment cannot be excluded.
Croatian: Ne može se isključiti rizik od povećane izloženosti lijeku u bolesnika s teškim oštećenjem bubrežne funkcije.
English: Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates.
Croatian: Potreban je oprez kada se vemurafenib primjenjuje istodobno sa supstratima P-gp-a.
English: In the phase II and phase III clinical trials, eligible patients were identified using a real-time polymerase chain reaction assay (the cobas 4800 BRAF V600 Mutation Test).
Croatian: U kliničkim ispitivanjima faze II i faze III bolesnici primjereni za uključivanje, određeni su pomoću testa lančane reakcije polimerazom u stvarnom vremenu (cobas 4800 BRAF V600 Mutation Test).
English: Effects of vemurafenib on other medicinal products Vemurafenib may increase the plasma exposure of medicinal products predominantly metabolised by CYP1A2 and decrease the plasma exposure of medicines predominantly metabolised by CYP3A4.
Croatian: Vemurafenib može povećati izloženost u plazmi lijekova koji se pretežno metaboliziraju putem CYP1A2, a smanjiti izloženost u plazmi lijekova koji se pretežno metaboliziraju putem CYP3A4.
English: Vemurafenib is indicated in monotherapy for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma (see section 5.1).
Croatian: Vemurafenib je indiciran kao monoterapija u liječenju odraslih bolesnika s neoperabilnim ili metastatskim melanomom s pozitivnom mutacijom BRAF V600 (vidjeti dio 5.1).
English: In an in vitro bone marrow cytotoxicity study, slight cytotoxicity was observed in some lympho-haematopoietic cell populations of rat, dog and human at clinically relevant concentrations.
Croatian: U istraživanju citotoksičnosti za koštanu srž in vitro opažena je neznatna citotoksičnost za neke populacije limfo- i hematopoetskih stanica u štakora, pasa i u ljudi pri klinički značajnim koncentracijama.
English: The efficacy and safety of vemurafenib in patients with tumours expressing rare BRAF V600 mutations other than V600E and V600K have not been convincingly established (see section 5.1).
Croatian: Djelotvornost i sigurnost primjene vemurafeniba nisu s dovoljnom sigurnošću utvrđene u bolesnika koji imaju tumor s rijetkim BRAF V600 mutacijama koje nisu V600E i V600K (vidjeti dio 5.1).
English: ● You may develop new melanoma lesions while taking Zelboraf.
Croatian: • Dok uzimate Zelboraf, mogu se razviti novi melanomi.
English: Amongst these patients, 3 had a PR, 3 had SD, 2 had PD and one was not evaluable.
Croatian: Od njih su 3 imala djelomičan odgovor na liječenje, 3 stabilnu bolest, 2 progresivnu bolest, a jedan bolesnik nije bio raspoloživ za analizu.
English: Acute kidney injury cases associated with dehydration events
Croatian: Slučajevi akutnog oštećenja tkiva bubrega* Slučajevi akutnog oštećenja tkiva bubrega povezani s događajima dehidracije
English: There are no data regarding the use of vemurafenib in pregnant women.
Croatian: Nema podataka o primjeni vemurafeniba u trudnica.
English: Manufacturer Roche Pharma AG Emil-Barell-Strasse 1 D-79639
Croatian: Proizvođač Roche Pharma AG Emil-Barell-Strasse 1 D-79639
English: ● You should have your eyes examined by your doctor while you are taking Zelboraf.
Croatian: • Dok uzimate Zelboraf, liječnik Vam mora pregledati oči.
English: All patients were required to have advanced melanoma with BRAF V600 mutations according to the cobas 4800 BRAF V600 Mutation Test.
Croatian: Svi su bolesnici morali imati uznapredovali melanom s BRAF mutacijom V600, potvrđenom testom cobas 4800 BRAF V600 Mutation Test.
English: The population apparent volume of distribution for vemurafenib in metastatic melanoma patients is estimated to be 91 L (with 64.8% between patient variability).
Croatian: Prividni volumen distribucije vemurafeniba u populaciji bolesnika s metastatskim melanomom procjenjuje se na 91 l (uz varijabilnost između bolesnika od 64,8%).
English: Vemurafenib should be used with caution when given concomitantly or sequentially with radiation treatment.
Croatian: Potreban je oprez kod istodobne ili sekvencijske primjene vemurafeniba s radioterapijom.
English: Median (months) (95% CI)d
Croatian: Medijan (mjeseci)e (95% CI)d
English: Effects of vemurafenib on drug transport systems In vitro studies have demonstrated that vemurafenib is an inhibitor of the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
Croatian: Ispitivanja in vitro pokazala su da je vemurafenib inhibitor efluksnih prijenosnika P-glikoproteina (P-gp) i proteina rezistencije raka dojke (BCRP).
English: The study was terminated due to low enrollment.
Croatian: Ispitivanje je prekinuto zbog slabog uključivanja bolesnika.
English: Patients co-treated with such agents should be carefully monitored for safety and dose modifications applied if clinically indicated (see Table 1 in section 4.2).
Croatian: Bolesnike istodobno liječene tim lijekovima treba pažljivo nadzirati zbog sigurnosti te prilagoditi dozu ako je to klinički indicirano (vidjeti Tablicu 1 u dijelu 4.2).
English: Radiation therapy reactions
Croatian: Reakcije na terapiju zračenjem
English: Recommended dose modification
Croatian: Preporučena prilagodba doze
English: Resume dosing at 720 mg twice daily (or 480 mg twice daily if the dose has already been lowered).
Croatian: Nastaviti liječenje dozom od 720 mg dvaput na dan (ili 480 mg dvaput na dan ako je doza već smanjena).
English: How to store Zelboraf
Croatian: Kako čuvati Zelboraf
English: In vitro studies have demonstrated that vemurafenib is a substrate of the efflux transporters P-gp and BCRP.
Croatian: Ispitivanja in vitro pokazala su da je vemurafenib supstrat efluksnih prijenosnika P-gp-a i BCRP-a.
English: In patients who develop cuSCC, it is recommended to continue the treatment without dose adjustment.
Croatian: U bolesnika koji razviju planocelularni karcinom kože preporučuje se nastaviti liječenje bez prilagođavanja doze.
English: Monitoring for skin lesions should occur as outlined above for cutaneous squamous cell carcinoma.
Croatian: Kontrole kožnih lezija potrebno je provoditi kako je prethodno navedeno za planocelularni karcinom kože.
English: Hazard Ratio (95% CI)
Croatian: Omjer hazarda (HR) (95% CI)
English: ● A type of skin cancer (cutaneous squamous cell carcinoma)
Croatian: • jedna vrsta raka kože (planocelularni karcinom kože)
English: A phase I dose-escalation study evaluating the use of vemurafenib in six adolescent patients with stage IIIC or IV BRAF V600 mutation positive melanoma was conducted.
Croatian: Provedeno je ispitivanje povećanja doze faze I u kojem se ocjenjivala primjena vemurafeniba u šest adolescentnih bolesnika s melanomom stadija IIIC ili IV pozitivnim na BRAF mutaciju V600.
English: Genital examinations (for women) and anal examinations are also recommended before and at the end of your treatment.
Croatian: Također se prije početka i na kraju liječenja preporučuje pregled spolnih organa (za žene) i čmara.
English: ● Medicines that could be influenced by a protein called P-gp (e.g. aliskiren, colchicine, digoxin, everolimus, fexofenadine) or a protein called BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).
Croatian: • Lijekove na koje može djelovati protein pod nazivom P-gp (npr. aliskiren, kolhicin, digoksin, everolimus, feksofenadin) ili protein pod nazivom BCRP (npr. metotreksat, mitoksantron, rosuvastatin).
English: Vemurafenib has minor influence on the ability to drive and use machines.
Croatian: Vemurafenib malo utječe na sposobnost upravljanja vozilima i rada sa strojevima.
English: Exercise caution and consider additional INR (international normalized ratio) monitoring when vemurafenib is used concomitantly with warfarin (see section 4.4).
Croatian: Potrebno je postupati uz oprez i razmotriti dodatno praćenje INR-a kad se vemurafenib primjenjuje istodobno s varfarinom (vidjeti dio 4.4).
English: If co-administration cannot be avoided, exercise caution, as vemurafenib may increase plasma exposure of CYP1A2 substrate drugs.
Croatian: Ako se istodobna primjena ne može izbjeći, potreban je oprez jer vemurafenib može povećati plazmatsku izloženost lijekovima koji su supstrati CYP1A2.
English: The safety and efficacy of vemurafenib has not been established in non-Caucasian patients.
Croatian: Nisu ustanovljene sigurnost i djelotvornost vemurafeniba u bolesnika koji nisu bijele rase.
English: ● Medicines that are mainly eliminated by metabolising proteins called CYP1A2 (e.g caffeine, olanzapine, theophylline), CYP3A4 (e.g. some oral contraceptives) or called CYP2C8.
Croatian: • Lijekove koji se odstranjuju iz organizma uglavnom putem metaboličkih bjelančevina pod nazivom CYP1A2 (npr. kofein, olanzapin, teofilin), CYP3A4 (npr. pojedini oralni kontraceptivi) ili CYP2C8.
English: Concomitant administration of strong inducers of CYP3A4, P-gp and glucuronidation (e.g. rifampicin, rifabutin, carbamazepine, phenytoin or St John's Wort [hypericin]) might lead to decreased exposure of vemurafenib and should be avoided when possible (see section 4.5).
Croatian: Istodobna primjena snažnih induktora CYP3A4, P-gp-a i glukuronidacije (npr. rifampicina, rifabutina, karbamazepina, fenitoina ili gospine trave (Hypericum perforatum) [hipericin]) može dovesti do smanjene izloženosti vemurafenibu pa je treba izbjegavati kad god je moguće (vidjeti dio 4.5).
English: ● Fever
Croatian: • vrućica
English: Liver enzyme abnormalities reported in the phase III clinical study are expressed below as the proportion of patients who experienced a shift from baseline to a grade 3 or 4 liver enzyme abnormalities:
Croatian: Odstupanja od normalnih vrijednosti jetrenih enzima prijavljena u kliničkom ispitivanju faze III u daljnjem su tekstu izražena kao udio bolesnika u kojih je u odnosu na početne vrijednosti jetrenih enzima došlo do pomaka na stupanj 3 ili stupanj 4 odstupanja od normalnih vrijednosti:
English: Following oral dosing, the absorption rate constant for the population of metastatic melanoma patients is estimated to be 0.19 hr-1 (with 101% between patient variability).
Croatian: Procjenjuje se da nakon peroralne doze konstanta brzine apsorpcije za populaciju bolesnika s metastatskim melanomom iznosi 0,19 h-1 (uz varijabilnost između bolesnika od 101%).
English: The population apparent clearance of vemurafenib in patients with metastatic melanoma is estimated to be 29.3 L/day (with 31.9% between patient variability).
Croatian: Procjenjuje se da je prividni klirens vemurafeniba u populaciji bolesnika s metastatskim melanomom 29,3 l/dan (uz varijabilnost između bolesnika od 31,9%).
English: Vemurafenib was shown to be phototoxic, in vitro, on cultured murine fibroblasts after UVA irradiation, but not in vivo in a rat study at doses up to 450 mg/kg/day (at exposures below the anticipated clinical exposure (based on AUC comparison).
Croatian: Vemurafenib se pokazao fototoksičnim in vitro, u kulturi mišjih fibroblasta nakon ozračivanja UVA zrakama, ali ne i in vivo u ispitivanju na štakorima pri dozama do 450 mg/kg na dan (izloženost manja od izloženosti očekivane u kliničkoj primjeni, na temelju usporedbe AUC-a).
English: No cases of overdose have been observed with Zelboraf.
Croatian: Nisu zabilježeni slučajevi predoziranja lijekom Zelboraf.
English: What Zelboraf looks like and contents of the pack Zelboraf 240 mg film-coated tablets are pinkish white to orange white.
Croatian: Zelboraf 240 mg filmom obložene tablete su ružičasto-bijele do narančasto-bijele boje.
English: 3rd occurrence of any grade 2 or 3 AE or persistence after 2nd dose reduction
Croatian: Treći nastup bilo koje nuspojave stupnja 2 ili 3, ili trajanje nuspojave nakon drugog sniženja doze
English: A single-arm, multicentre study (N = 146) of vemurafenib was conducted in adult patients with histologically confirmed metastatic melanoma harbouring the BRAF V600 mutation (according to the cobas 4800 BRAF V600 Mutation Test) and with brain metastases.
Croatian: Provedeno je multicentrično ispitivanje vemurafeniba s jednom skupinom (N =146),odraslih bolesnika s histološki potvrđenim metastatskim melanomom pozitivnim na mutaciju BRAF V600 (potvrđeno testom cobas 4800 BRAF V600 Mutation Test) i moždanim metastazama.
English: A total of 57 patients out of 673 whose tumours were analysed retrospectively by sequencing were reported to have BRAF V600K mutation-positive melanoma in NO25026.
Croatian: U ispitivanju NO25026 je od ukupno 673 bolesnika čiji su tumori retrospektivno analizirani sekvencioniranjem u njih 57 utvrđen melanom s pozitivnom BRAF mutacijom V600K.
English: These cases were managed with excision, and patients continued treatment without dose adjustment.
Croatian: Kirurški su odstranjeni, a bolesnici su nastavili liječenje bez prilagođavanja doze.
English: Laboratory abnormalities should be managed with dose reduction, treatment interruption or with treatment discontinuation (see sections 4.2 and 4.8).
Croatian: Odstupanja od normalnih vrijednosti laboratorijskih testova potrebno je korigirati smanjenjem doze, privremenim prekidom ili trajnom obustavom liječenja (vidjeti dijelove 4.2 i 4.8).
English: Anticipated frequency in V600 mutation-positive melanoma (t)
Croatian: Očekivana učestalost u melanomu s pozitivnom mutacijom V600
English: Patients with moderate to severe hepatic impairment may have increased exposure (see section 5.2).
Croatian: U bolesnika s umjerenim do teškim oštećenjem jetrene funkcije može doći do veće izloženosti lijeku (vidjeti dio 5.2).
English: ● Joint or muscle pain, musculoskeletal pain
Croatian: • bol u zglobovima ili mišićima, mišićno-koštana bol
English: Effects of concomitant medicines on vemurafenib
Croatian: Učinci istodobno primijenjenih lijekova na vemurafenib
English: ● medicines for depression (e.g. amitriptyline, imipramine)
Croatian: • lijekove za liječenje depresije (npr. amitriptilin, imipramin)
English: Consider additional drug level monitoring for P-gp substrate medicinal products with a narrow therapeutic index (NTI) (e.g. digoxin, dabigatran etexilate, aliskiren) (see section 4.4).
Croatian: Potrebno je razmotriti dodatno praćenje razine lijekova koji su supstrati P-gp-a i imaju uzak terapijski indeks (npr. digoksin, dabigatraneteksilat, aliskiren) (vidjeti dio 4.4).
English: Your doctor will run tests to check that your heart is working properly before and during your treatment with Zelboraf.
Croatian: Liječnik će prije i tijekom liječenja lijekom Zelboraf obavljati pretrage kako bi provjerio radi li Vam srce pravilno.
English: However, in repeat-dose toxicity studies, no histopathological findings were noted on reproductive organs in males and females in rats and dogs at doses up to 450 mg/kg/day (at exposures below the anticipated clinical exposure based on AUC comparison).
Croatian: Međutim, u ispitivanju toksičnosti ponovljenih doza nisu opažene histopatološke promjene na reproduktivnim organima mužjaka ni ženki štakora i pasa pri dozama do 450 mg/kg na dan (izloženost manja od izloženosti očekivane u kliničkoj primjeni na temelju usporedbe AUC-a).
English: Renal elimination does not appear to be of importance for vemurafenib elimiation, whereas biliary excretion of unchanged compound may be an important route of elimination.. Vemurafenib is a substrate and inhibitor of P-gp in vitro.
Croatian: Čini se da izlučivanje putem bubrega nije značajno za eliminaciju vemurafeniba, dok izlučivanje nepromijenjenog spoja putem žuči može predstavljati važan put eliminacije.
English: ● Pain in the extremities
Croatian: • bol u udovima