natgillin/translations-raw huggingface dataset:
With a median follow-up of 12.9 months (range, 0.6 to 20.1), the primary endpoint of confirmed best overall response rate (CR + PR) as assessed by an independent review committee (IRC) was 53% (95% CI: 44%, 62%).
Mediana spremljanja je bila 12,9 meseca (razpon: od 0,6 do 20,1 meseca), primarni cilj študije je bil potrjen najboljši celokupni odziv (popolni in delni odziv (CR + PR)) po oceni odbora za neodvisni pregled (ICR, independent review committee); ta delež je znašal 53 % (95-% interval zaupanja: 44 %; 62 %).
Nine of the 132 patients enrolled into NP22657 had V600K mutation-positive tumours according to retrospective Sanger sequencing.
Devet od 132 bolnikov, vključenih v študijo NP22657, je imelo tumorje z V600K pozitivno mutacijo glede na retrospektivno določanje zaporedja po metodi Sanger.
● Change in liver tests results (ALT, alkaline phosphatase and bilirubin increase)
• spremembe v izvidih jetrnih testov (zvišanje ALT, alkalne fosfataze in bilirubina),
Previous history of cancer
Anamneza raka
Progression of pre-existing pancreatic adenocarcinoma with KRAS mutation.
Napredovanje že obstoječega adenokarcinoma trebušne slinavke z mutacijo KRAS.
There were no increases to Grade 4 ALT, alkaline phosphatase or bilirubin.
Zvišanja ALT, alkalne fosfataze ali bilirubina do stopnje 4 ni bilo.
It is not known whether vemurafenib is excreted in human milk.
Ni znano, ali se vemurafenib izloča v materino mleko.
Occasional intake of vemurafenib on an empty stomach is expected to have limited influence on steady state exposure due to the high accumulation of vemurafenib at steady state.
Občasno jemanje vemurafeniba na prazen želodec naj bi imelo majhen vpliv na izpostavljenost v stanju dinamičnega ravnovesja zaradi visoke akumulacije vemurafeniba v stanju dinamičnega ravnovesja.
The effect of food on steady state vemurafenib exposure is currently unknown.
Vpliv hrane na izpostavljenost vemurafenibu v stanju dinamičnega ravnovesja trenutno ni znan.
Best overall confirmed response rate as assessed by independent review committee, number of responders n (%) b Two-sided 95% Clopper-Pearson Confidence Interval (CI) c Duration of response as assessed by an Independent Review Committee d Kaplan-Meier estimate e Assessed by investigator
d a Delež najboljšega potrjenega celokupnega odziva po oceni odbora za neodvisni pregled, število odzivnih bolnikov n (%) b Dvostranski 95-% Clopper-Pearsonov interval zaupanja (IZ) c Trajanje odziva po oceni odbora za neodvisni pregled d
● Skin problems including warts
• težave s kožo, vključno z bradavicami,
Most lesions classified as “other” (43%) were benign skin lesions (e.g. verruca vulgaris, actinic keratosis, benign keratosis, cyst/benign cyst).
Večina sprememb, opredeljenih kot "drugo" (43 %), so bile benigne kožne spremembe (npr. navadna bradavica, aktinična keratoza, benigna keratoza, cista/benigna cista).
In addition, patients should undergo a chest Computerised Tomography (CT) scan, prior to treatment and every 6 months during treatment.
Poleg tega morajo bolniki pred zdravljenjem in na 6 mesecev med zdravljenjem opraviti računalniško tomografijo (CT) prsnega koša.
Mild induction of CYP2B6 by vemurafenib was noted in vitro at a vemurafenib concentration of 10 µM.
Blaga indukcija CYP2B6 z vemurafenibom je bila opažena in vitro, pri 10 µM koncentraciji vemurafeniba.
PFS - overall Median (months)e
PFS - celokupno mediana (meseci)e
Stop taking Zelboraf and get medical help immediately if you have any symptoms of an allergic reaction such as swelling of the face, lips or tongue, difficulty breathing, rash, or fainting sensation.
Prenehajte z jemanjem zdravila Zelboraf in takoj poiščite medicinsko pomoč, če se pri vas pojavi kateri koli od simptomov alergijske reakcije, kot so oteklost obraza, ust ali jezika, težko dihanje, kožni izpuščaj ali omedlevica.
The recommended dose of vemurafenib is 960 mg (4 tablets of 240 mg) twice daily (equivalent to a total daily dose of 1,920 mg).
Priporočeni odmerek vemurafeniba je 960 mg (4 tablete po 240 mg) dvakrat na dan (to ustreza celotnemu dnevnemu odmerku 1920 mg).
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.
Rezultati študije faze III (NO25026) pri predhodno nezdravljenih bolnikih Odprta, multicentrična, randomizirana mednarodna študija faze III podpira uporabo vemurafeniba pri predhodno nezdravljenih bolnikih z neresektabilnim ali metastatskim melanomom s pozitivno mutacijo BRAF V600E.
There is no information about the safety of Zelboraf in pregnant women.
O varnosti zdravila Zelboraf pri nosečnicah ni podatkov.
This can occur on the area that was treated with radiation, such as the skin, esophagus, bladder, liver, rectum, and lungs.
To se lahko pojavi na delu, ki so ga zdravili z obsevanjem, kot je koža, požiralnik, sečni mehur, jetra, danka in pljuča.
The pharmacokinetic parameters for vemurafenib were determined using non-compartmental analysis in a phase I and phase III studies (20 patients after 15 days of dosing at 960 mg twice daily, and 204 patients in steady state day 22) as well as by population PK analysis using pooled data from 458 patients.
Farmakokinetične parametre vemurafeniba so določili z nerazdelčno analizo v študijah faze I in faze III (pri 20 bolnikih po 15 dneh odmerjanja 960 mg dvakrat na dan in 204 bolnikih v stanju dinamičnega ravnovesja 22. dan), kot tudi s populacijsko farmakokinetično analizo, v kateri so bili uporabljeni kumulativni podatki 458 bolnikov.
Renal toxicity
Ledvična toksičnost
Management of adverse drug reactions or QTc prolongation may require dose reduction, temporary interruption and/or treatment discontinuation (see tables 1 and 2).
Za obvladovanje neželenih učinkov ali ob podaljšanju intervala QTc je potrebno zmanjšanje odmerka, začasna prekinitev in/ali dokončno prenehanje zdravljenja (glejte preglednici 1 in 2 spodaj).
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:
Nenormalnosti jetrnih encimov, zabeležene v klinični študiji faze III, so izražene spodaj kot delež bolnikov, ki so se jim nenormalnosti jetrnih encimov spremenile od izhodišča do stopnje 3 ali 4:
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).
Učinki vemurafeniba na transportne sisteme zdravil Študije in vitro so pokazale, da je vemurafenib zaviralec izločevalnih prenašalcev, P-glikoproteina (P-gp) in proteina pri odpornosti raka dojk (BCRP, breast cancer resistance protein).
● Abnormal kidney blood test results (creatinine increased).
• nenormalni rezultati krvnih preiskav delovanja ledvic (zvišan kreatinin),
In addition ADRs originating from safety reports across all clinical trials and post-marketing sources are reported.
Navedeni so tudi neželeni učinki iz varnostnih poročil vseh kliničnih preskušanj in obdobja po prihodu zdravila na trg.
Accumulation occurs upon multiple twice daily dosing of vemurafenib.
Kopičenje se pojavi v primeru večkratnega odmerjanja vemurafeniba dvakrat na dan.
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).
Ker se vemurafenib izloča skozi jetra, so bolniki z zmerno do hudo okvaro jeter lahko bolj izpostavljeni in jih je treba pozorno spremljati (glejte poglavji 4.4 in 5.2).
Cohort 2 Previously treated n = 56
2. skupina Predhodno zdravljeni bolniki n = 56
Patients with severe renal impairment should be closely monitored (see sections 4.4 and 5.2).
Bolnike s hudo okvaro ledvic je tako treba pozorno spremljati (glejte poglavji 4.4 in 5.2).
A clinical drug interaction study demonstrated that multiple oral doses of vemurafenib (960 mg twice daily) increased the exposure of a single oral dose of the P-gp substrate digoxin, approximately 1.8 and 1.5 fold for digoxin AUClast and Cmax, respectively.
Klinična študija medsebojnega delovanja med zdravili je pokazala, da so večkratni peroralni odmerki vemurafeniba (960 mg dvakrat dnevno) povečali izpostavljenost substratu P-gp digoksinu po uporabi enkratnega peroralnega odmerka, AUCzadnja digoksina se je povečala približno 1,8-krat, njegova Cmax pa približno 1,5-krat.
The incidence of cuSCC in vemurafenib-treated patients across studies was approximately 20%.
V študijah je bila incidenca ploščatoceličnega karcinoma kože pri bolnikih, zdravljenih z vemurafenibom, približno 20-%.
Cohort 1 No previous treatment n = 90
1. skupina Predhodno nezdravljeni bolniki n = 90
Co-administration of itraconazole, a strong CYP3A4/Pgp inhibitor, increased steady state vemurafenib AUC by approximately 40%.
Sočasno dajanje itrakonazola, močnega zaviralca CYP3A4/P-gp, je povečalo AUC vemurafeniba v stanju dinamičnega ravnovesja za približno 40 %.
Stratification variable
Stratifikacijska spremenljivka
● Pain in the extremities
• bolečine v okončinah,
Cases of renal toxicity have been reported with vemurafenib ranging from creatinine elevations to acute interstitial nephritis and acute tubular necrosis, some observed in the setting of dehydration events.
Med uporabo vemurafeniba so poročali o primerih ledvične toksičnosti v razponu od zvišanega kreatinina do akutnega intersticijskega nefritisa in akutne tubulne nekroze; nekatere so opazili pri obravnavi dogodkov dehidracije.
● Tingling or burning feelings in hands and feet
• mravljinčenje ali pekoč občutek v dlaneh in stopalih,
Based on these preliminary data, the concurrent administration of ipilimumab and vemurafenib is not recommended.
Glede na te preliminarne podatke sočasna uporaba ipilimumaba in vemurafeniba ni priporočljiva.
No data are available in patients with melanoma harbouring rare BRAF V600 mutations other than V600E and V600K.
Na voljo ni podatkov o bolnikih z melanomom, ki imajo BRAF V600 mutacije, ki niso V600E ali V600K.
Table 1: Dose modification schedule based on the grade of any Adverse Events (AEs)
Preglednica 1: Shema prilagajanja odmerka glede na stopnjo katerega koli neželenega dogodka Stopnja neželenega dogodka
However, in repeat-dose toxicity studies in rats and dogs, no histopathological findings were noted in reproductive organs in males and females (see section 5.3).
Pri študijah toksičnosti s ponavljajočimi se odmerki pri podganah in psih niso opazili histopatoloških sprememb na reproduktivnih organih samcev in samic (glejte poglavje 5.3).
Stop taking Zelboraf and talk to your doctor immediately if you get a skin rash with any of the following symptoms: blisters on your skin, blisters or sores in your mouth, peeling of your skin, fever, redness or swelling of your face, hands, or soles of your feet.
Prenehajte z jemanjem zdravila Zelboraf in se takoj posvetujte z zdravnikom, če se pri vas pojavi kožni izpuščaj s katerim koli izmed naslednjih simptomov: mehurji na koži, mehurji ali razjede v ustih, luščenje kože, zvišana telesna temperatura, rdečica ali oteklost obraza, rok ali podplatov.
The population apparent volume of distribution for vemurafenib in metastatic melanoma patients is estimated to be 91 L (with 64.8% between patient variability).
Ocenjeni populacijski navidezni volumen porazdelitve vemurafeniba pri bolnikih z metastatskim melanonom je 91 l (s 64,8-% variabilnostjo med bolniki).
Recommended dose modification
Priporočena prilagoditev odmerka
On this basis, the efficacy of contraceptive pills metabolized by CYP3A4 used concomitantly with vemurafenib might be decreased.
Tako je lahko učinkovitost kontracepcijskih tablet, ki se presnavljajo s CYP3A4 in se uporabljajo sočasno z vemurafenibom, zmanjšana.
Laboratory abnormalities should be managed with dose reduction, treatment interruption or with treatment discontinuation (see sections 4.2 and 4.8).
Laboratorijske nepravilnosti je treba obvladati z zmanjšanjem odmerka, prekinitvijo zdravljenja ali prenehanjem zdravljenja (glejte poglavji 4.2 in 4.8).
For photosensitivity grade 2 (intolerable) or greater, dose modifications are recommended (see section
V primeru fotosenzibilnosti stopnje 2 (neprenosljivo) ali več so priporočljive prilagoditve odmerka (glejte poglavje 4.2).
The study was terminated due to low enrollment.
Študija je bila prekinjena zaradi počasnega vključevanja bolnikov.
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).
V kliničnih preskušanjih faze II in III so primerne bolnike identificirali s testom verižne reakcije s polimerazo v realnem času (cobas 4800 BRAF V600 Mutation Test).
• Problem with the nerves that can produce pain, loss of sensation and/or muscle weakness
• težave z živci, ki lahko povzročijo bolečino, otrplost in/ali mišično oslabelost (periferna nevropatija),
Conjugation metabolites (glucuronidation and glycosylation) were also identified in humans.
Pri ljudeh so ugotovili tudi prisotnost metabolitov konjugacij (glukuronidacije in glikozilacije).
If co-administration cannot be avoided, it needs to be considered that vemurafenib may decrease plasma concentrations of CYP3A4 substrates and thereby their efficacy may be impaired.
Če se sočasnemu dajanju ne moremo izogniti, moramo upoštevati, da vemurafenib lahko zmanjša plazemske koncentracije zdravil, ki so substrati CYP3A4, zato se njihova učinkovitost lahko zmanjša.
Cases of cuSCC were typically managed with simple excision, and patients generally continued on treatment without dose modification (see sections 4.2 and 4.4).
Primere ploščatoceličnega karcinoma kože so praviloma obvladali s preprosto ekscizijo in bolniki so v glavnem nadaljevali zdravljenje brez prilagoditve odmerka (glejte poglavji 4.2 in 4.4).
● Difficulty or pain when swallowing, chest pain, heartburn or acid reflux (esophagitis).
• težave ali bolečine pri požiranju, bolečina v prsnem košu, zgaga ali kislinski refluks (ezofagitis).
Repeat-dose toxicology studies identified the liver and bone marrow as target organs in the dog.
Študije toksičnosti ponavljajočih se odmerkov so pokazale, da sta pri psih ciljna organa jetra in kostni mozeg.
The most common (≥ 5%) Grade 3 ADRs were cuSCC, keratoacanthoma, rash, arthralgia and gamma-glutamyltransferase (GGT) increased.
Najbolj pogosti (≥ 5 %) neželeni učinki stopnje 3 so bili ploščatocelični karcinom kože, keratoakantom, izpuščaj, artralgija in zvišana gama-glutamiltransferaza (GGT).
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).
Ocenjeni populacijski navidezni očistek vemurafeniba pri bolnikih z metastatskim melanonom je 29,3 l/dan (z 31,9-% variabilnostjo med bolniki).
There are no data in patients with severe renal impairment (see sections 4.2 and 4.4).
Podatkov o bolnikih s hudo okvaro ledvic ni (glejte poglavji 4.2 in 4.4).
Based on its mechanism of action, vemurafenib could cause fetal harm when administered to a pregnant woman.
Na podlagi mehanizma delovanja lahko vemurafenib, če ga jemlje nosečnica, povzroči škodo plodu.
The intensity of clinical adverse events graded by the Common Terminology Criteria for Adverse Events v4.0 (CTC-AE).
(a)Izrazitost kliničnih neželenih dogodkov je ocenjena po CTC-AE (Common Terminology Criteria for Adverse
(z) As of February 01, 2012, a total of 675 patients were evaluable for the post-hoc analysis update of PFS.
Do 1. februarja 2012 so skupno 675 bolnikom ponovno ocenili preživetje brez napredovanja bolezni v okviru post-hoc analize.
Common ≥ 1/100 to < 1/10
Pogosti: ≥ 1/100 do < 1/10
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).
V populacijski farmakokinetični analizi podatkov pridobljenih iz kliničnih preskušanj bolnikov z metastastkim melanomom, blaga in zmerna okvara ledvic ni vplivala na navidezni očistek vemurafeniba (očistek kreatinina > 40 ml/min).
Anticipated frequency in V600 mutation-positive melanoma (t)
Pričakovana pogostnost melanomov s pozitivno mutacijo V600
For patients treated with stereotactic radiotherapy (SRT) or surgery, a new RECIST-assessable brain lesion must have developed following this prior therapy.
Da bi bolniki, ki so bili zdravljeni s stereotaktično radioterapijo (SRT) ali operacijo, zadostili temu kriteriju, se je morala pri njih po tem predhodnem zdravljenju razviti nova lezija v možganih, ki jo je bilo mogoče oceniti po kriterijih RECIST (Response Evaluation Criteria in Solid Tumors).
Aluminium/Aluminium perforated unit dose blisters.
Aluminij/aluminijski perforirani pretisni omoti za enkratni odmerek.
The majority of cases were mild to moderate, but severe, disabling cases of Dupuytren's contracture have also been reported (see section 4.8).
Večina primerov je bila blagih do zmernih, poročali pa so tudi o hudih primerih Dupuytrenove kontrakture, ki je bolnike onesposobila (glejte poglavje 4.8).
• Common: ALT, alkaline phosphatase, bilirubin
• pogosti: ALT (alanin aminotransferaza), alkalna fosfataza, bilirubin;
Monitoring of these lesions occurs as outlined above for cutaneous squamous cell carcinoma.
Spremljanje takšnih lezij poteka, kot je opisano zgoraj pri ploščatoceličnem karcinomu kože.
Do not use Zelboraf after the expiry date which is stated on the carton and the blister after EXP.
Tega zdravila ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na škatli in pretisnem omotu poleg oznake Uporabno do/EXP.
Treatment with vemurafenib is not recommended in patients with uncorrectable electrolyte abnormalities (including magnesium), long QT syndrome or who are taking medicinal products known to prolong the QT interval.
Z vemurafenibom ni priporočljivo zdraviti bolnikov z elektrolitskimi motnjami (vključno z magnezijem), ki jih ni mogoče odpraviti, bolnikov s sindromom dolgega intervala QT in bolnikov, zdravljenih z zdravili, ki podaljšajo interval QT.
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).
V tem poglavju navedeni neželeni učinki temeljijo na rezultatih 468 bolnikov, vključenih v randomizirano, odprto študijo faze III pri odraslih bolnikih z neresektabilnim melanomom ali melanomom stadija IV s pozitivno mutacijo BRAF V600 ter študijo faze II z eno skupino pri bolnikih z melanomom stadija IV s pozitivno mutacijo BRAF V600, pri katerih vsaj eno predhodno sistemsko zdravljenje ni bilo uspešno (glejte poglavje 5.1).
This leaflet was last revised in <{MM/YYYY}> Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.
DATUM ZADNJE REVIZIJE BESEDILA Podrobne informacije o zdravilu so objavljene na spletni strani Evropske agencije za zdravila http://www.ema.europa.eu.
Dose adjustments for CYP3A4 substrates with narrow therapeutic window may be considered, if clinically indicated (see sections 4.4 and 4.6).
Pri substratih CYP3A4, ki imajo ozko terapevtsko okno, se lahko razmisli o prilagoditvi odmerka, če je klinično indicirano (glejte poglavji 4.4 in 4.6).
Name and address of the manufacturer(s) responsible for batch release
Ime in naslov proizvajalca, odgovornega za sproščanje serije
Effects of vemurafenib on Drug Metabolizing Enzymes Results from an in vivo drug-drug interaction study in metastatic melanoma patients demonstrated that vemurafenib is a moderate CYP1A2 inhibitor and a CYP3A4 inducer.
Vplivi vemurafeniba na encime, ki presnavljajo zdravila Rezultati študije medsebojnega delovanja zdravil in vivo pri bolnikih z metastatskim melanomom so pokazali, da je vemurafenib zmeren zaviralec CYP1A2 in induktor CYP3A4.
Retinal vein occlusion, iridocyclitis
Očesne bolezni uveitis zapora mrežnične vene, iridociklitis
Patients should be carefully monitored for safety and dose modifications applied if clinically indicated (see Table 1 in section 4.2).
Bolnike je treba skrbno spremljati glede varnosti in prilagoditi odmerek, če je klinično indicirano (glejte preglednico 1 v poglavju 4.2).
In vitro studies have demonstrated that vemurafenib is a substrate of the efflux transporters P-gp and BCRP.
Študije in vitro so pokazale, da je vemurafenib substrat izločevalnih prenašalcev, P-gp in BCRP.
● Tell your doctor if you have had, or are going to have radiotherapy, as Zelboraf may worsen radiation treatment side effects.
• Zdravniku povejte, če ste se zdravili z obsevanjem ali pa se boste v prihodnosti, ker lahko zdravilo Zelboraf poslabša neželene učinke, ki jih povzroča obsevanje.
In another clinical trial, vemurafenib increased Cmax and AUC of a single 2 mg dose of tizanidine (CYP1A2 substrate) approximately 2.2-fold and 4.7-fold, respectively.
V drugem kliničnem preskušanju je vemurafenib povečal Cmax in AUC enkratnega 2-mg odmerka tizanidina (substrata CYP1A2): Cmax približno 2,2-krat in AUC približno 4,7-krat.
Injury, Poisoning, and Procedural Complications
Poškodbe in zastrupitve in zapleti pri posegih povečanje toksičnosti obsevanja
● medicines for heart rhythm problems (e.g. quinidine, amiodarone)
• zdravila proti težavam s srčnim ritmom (npr. kinidin, amiodaron),
These cases were managed with excision, and patients continued treatment without dose adjustment.
Takšni primeri so bili obvladani z ekscizijo, bolniki pa so nadaljevali z zdravljenjem brez prilagoditve odmerka.
Table 8: Overall survival in previously untreated patients with BRAF V600 mutation-positive melanoma by LDH, tumour stage and ECOG status (post hoc analysis, December 20, 2012 cutoff, censored results at time of cross over)
Preglednica 8: Celokupno preživetje pri predhodno nezdravljenih bolnikih z melanomom s pozitivno BRAF V600 mutacijo glede na LDH, stadij tumorja in status ECOG (post hoc analiza, podatki, zbrani do 20. decembra 2012; rezultati so bili krnjeni ob času prehoda na vemurafenib)
In a clinical trial, co-administration of vemurafenib decreased the AUC of midazolam (CYP3A4 substrate) by an average 39% (maximum decrease up to 80%).
V kliničnem preskušanju je sočasno dajanje vemurafeniba z midazolamom zmanjšalo AUC midazolama (substrata CYP3A4) za povprečno 39 % (in največ do
All patients were required to have advanced melanoma with BRAF V600 mutations according to the cobas 4800 BRAF V600 Mutation Test.
Vsi bolniki so morali imeti napredovali melanom z BRAF V600 pozitivno mutacijo glede na cobas 4800 BRAF V600 Mutation Test.
Warnings and precautions Talk to your doctor before taking Zelboraf.
Opozorila in previdnostni ukrepi Pred začetkom jemanja zdravila Zelboraf se posvetujte z zdravnikom.
Vemurafenib should be used with caution in patients with severe renal impairment and patients should be closely monitored.
Pri bolnikih s hudo ledvično okvaro je treba vemurafenib uporabljati previdno ter jih pozorno spremljati.
Sarcoidosis (1)(2)(j)
Bolezni imunskega sistema sarkoidoza(1)(2)(j)
Preclinical data generated in biochemical assays demonstrated that vemurafenib can potently inhibit BRAF kinases with activating codon 600 mutations (table 6).
Predklinični podatki, pridobljeni iz biokemičnih analiz, kažejo, da lahko vemurafenib močno zavira BRAF kinaze z aktivacijo mutacij kodona 600 (preglednica 6).
Monitoring for skin lesions should occur as outlined in section 4.4.
Bolnika je treba spremljati zaradi možnega pojava kožnih lezij, kot je navedeno v poglavju 4.4.
Vemurafenib moderately inhibited CYP2C8 in vitro.
Vemurafenib je in vitro zmerno zaviral CYP2C8.
Monitoring for skin lesions should occur as outlined above for cutaneous squamous cell carcinoma.
Nadzor nad pojavom kožnih lezij je treba izvajati, kot je navedeno zgoraj pri ploščatoceličnem karcinomu kože.