natgillin/translations-raw huggingface dataset:
This increase expends to three fold in both moderate and severe hepatic impairment when considering unbound binimetinib exposure (see section 4.2). 
Povećanje postaje trostruko u bolesnika s umjerenim i teškim oštećenjem jetrene funkcije ako se uzme u obzir izloženost nevezanom binimetinibu (vidjeti dio 4.2).
LVD led to treatment discontinuation in 0.4% (1/274) of patients and led to dose interruptions or dose reductions in 6.6 % (18/274) of patients. 
LVD je doveo do trajnog prekida liječenja u 0,4% (1/274) bolesnika i doveo do privremenog obustavljanja ili smanjenja doze u 6,6% (18/274) bolesnika.
• muscle pain, cramps, stiffness or spasm 
• bol u mišićima, grčeve, ukočenost ili spazam
Binimetinib is not recommended in patients with a history of RVO. 
Binimetinib se ne preporučuje u bolesnika s anamnezom RVO-a.
Depending on the severity of symptoms, degree of CK elevation or creatinine elevation, dose reduction, dose interruption or permanent discontinuation of binimetinib may be required (see Table 1 in section 4.2). 
Ovisno o težini simptoma, stupnju povišenja kreatin kinaze ili povišenja kreatinina, može biti potrebno smanjiti dozu, prekinuti dozu ili trajno obustaviti binimetinib (vidjeti Tablicu 1 u dijelu 4.2).
If one of these toxicities occurs, see section 4.2. of encorafenib Summary of Product Characteristics (SmPC) for dose modification instructions for encorafenib. 
Ako dođe do jedne od ovih toksičnosti, vidjeti dio 4.2 sažetka opisa svojstava lijeka za enkorafenib za upute o prilagodbi doze enkorafeniba.
Most events were Grade 1-2, with Grade 3 reported in 0.4 % (1/274) of patients and no event led to discontinuation. 
Većina je nuspojava bila stupnja 1-2, dok je stupanj 3 zabilježen u 0,4% (1/274) bolesnika i nijedan slučaj nije doveo do trajne obustave liječenja.
Additionally, the combination of encorafenib and binimetinib prevented the emergence of treatment resistance in BRAF V600E mutant human melanoma xenografts in vivo. 
Također, kombinacija enkorafeniba i binimetiniba sprečava pojavu rezistencije na liječenje u ljudskih ksenografta melanoma s BRAF V600E mutacijom in vivo.
Constipation occurred in 24.1 % (66/274) of patients and was Grade 1 or 2. 
Konstipacija se javila u 24,1% (66/274) bolesnika i bila je stupnja 1 ili 2.
Muscle problems: Mektovi can cause breakdown of muscles (rhabdomyolysis) which can lead to kidney damage and can be fatal; signs and symptoms can include: 
Problemi s mišićima: Lijek Mektovi može uzrokovati razgradnju mišića (rabdomioliza) koja može prouzročiti oštećenje bubrega koje može uzrokovati smrt ; znakovi i simptomi mogu uključivati:
Polyvinyl alcohol (E1203) Macrogol 3350 (E1521) Titanium dioxide (E171) Talc (E533b) Iron oxide yellow (E172) Iron oxide black (E172) 
Film-ovojnica poli(vinilni alkohol) (E1203) makrogol 3350 (E1521) titanijev dioksid (E171) talk (E533b) željezov oksid, žuti (E172) željezov oksid, crni (E172)
• some medicines typically used to treat epilepsy such as phenobarbital, phenytoin, 
• lijekovi koji se koriste za liječenje epilepsije kao što su fenobarbital, fenitoin, karbamazepin
Gamma-glutamyl transferase increased* 
Povišenje gama-glutamil transferaze* vrlo često povišenje kreatinina u krvi*
Grade 3 events occurred in 1.1 % (3/274) of patients. 
Događaji stupnja 3 javili su se u 1,1% (3/274) bolesnika.
Dry skin* 
vrlo često suha koža*
Binimetinib in combination with encorafenib in patients with brain metastases 
Binimetinib u kombinaciji s enkorafenibom u bolesnika s metastazama u mozgu
There are limited efficacy data with the combination of binimetinib and encorafenib in patients with a BRAF V600 mutant melanoma which have metastasised to the brain (see section 5.1). 
Ograničeni su podaci o djelotvornosti kombinacije binimetiniba i enkorafeniba u bolesnika s melanomom s BRAF V600 mutacijom koji je metastazirao u mozak (vidjeti dio 5.1).
Skin and subcutaneous tissue disorders 
Poremećaji kože i potkožnog tkiva hiperkeratoza*
Effects of binimetinib on other medicinal products 
Učinak binimetiniba na druge lijekove
In the pooled Combo 450 population, photosensitivity was observed in 4.0 % (11/274) of patients. 
U ukupnoj populaciji kombinirane terapije 450, fotoosjetljivost je zapažena u 4,0% (11/274) bolesnika.
Following a single oral dose of 45 mg [14C] binimetinib in healthy subjects, the apparent volume of distribution (Vz/F) of binimetinib is 374 L. 
Nakon jednokratne doze od 45 mg [14C] binimetiniba u zdravih ispitanika, prividni volumen raspodjele (Vz/F) binimetiniba iznosi 374 L.
For additional information on warnings and precautions associated with encorafenib treatment, see section 4.4 of encorafenib SmPC. 
Za dodatne informacije o upozorenjima i mjerama opreza povezanim s liječenjem enkorafenibom, vidjeti dio 4.4 sažetka opisa svojstava lijeka za enkorafenib.
Following a single oral dose of 45 mg [14C] binimetinib in healthy subjects, at least 50 % of the binimetinib dose was absorbed. 
Nakon jednokratne doze od 45 mg [14C] binimetiniba u zdravih ispitanika, apsorbiralo se najmanje 50% doze binimetiniba.
Binimetinib in combination with encorafenib should not be used in patients with wild type BRAF malignant melanoma. 
Binimetinib u kombinaciji s enkorafenibom se ne smije primjenjivati u bolesnika koji imaju maligni melanom s divljim tipom BRAF gena.
Dermatologic evaluations should be performed prior to initiation of therapy with binimetinib in combination with encorafenib, every 2 months while on therapy and for up to 6 months following discontinuation of the combination. 
Prije započinjanja liječenja binimetinibom u kombinaciji s enkorafenibom, potrebno je napraviti dermatološki pregled, zatim svaka 2 mjeseca tijekom terapije te u razdoblju do 6 mjeseci nakon prestanka liječenja kombinacijom.
• Tablet film-coat: polyvinyl alcohol (E1203), macrogol 3350 (E1521), titanium dioxide (E171), talc (E533b), iron oxide yellow (E172) and iron oxide black (E172). 
• Film-ovojnica tablete: poli(vinilni alkohol) (E1203), makrogol 3350 (E1521), titanijev dioksid (E171), talk (E533b), žuti željezov oksid (E172) i crni željezov oksid (E172).
No effects were observed at 3times the human therapeutic exposure. 
Nisu primijećeni nikakvi učinci pri izloženosti tri puta većoj od one u ljudi pri terapijskim dozama.
The incidence of Grade 3 or 4 adverse reactions was 5.8 % (16/274). 
Incidencija nuspojava stupnja 3 ili 4 bila je 5,8% (16/274) bolesnika.
Binimetinib should be used with caution in patients who are at risk for, or who have a history of VTE. 
Binimetinib se mora s oprezom davati bolesnicima kod kojih prijeti pojava ili koji imaju anamnezu VTE-a.
Binimetinib should be withheld until improved to Grade 0 or 1 and resumed at the same dose if first occurrence or resumed at a reduced dose if recurrent Grade 3. 
Treba prekinuti binimetinib dok se ne postigne poboljšanje na stupanj 0 ili 1, a potom nastaviti s istom dozom ako se nuspojava pojavila prvi put ili nastaviti sa smanjenom dozom u slučaju da se radi o ponovljenoj pojavi stupnja 3.
Each film-coated tablet contains 15 mg binimetinib. 
Jedna filmom obložena tableta sadrži 15 mg binimetiniba.
QTc prolongation of > 60 ms compared to pre-treatment values was observed in 4.9 % (13/268) patients in the encorafenib plus binimetinib group, and in 3.4 % (7/204) in the encorafenib single agent group (see section 5.1 of encorafenib SmPC). 
Povećanje QTc-a > 60 ms u odnosu na početnu vrijednost primijećeno je u 4,9% (13/268) bolesnika iz skupine koja je liječena enkorafenibom s binimetinibom i u 3,4% (7/204) u skupini liječenoj enkorafenibom u monoterapiji (vidjeti dio 5.1
Very Common 
vrlo često
There are no data on the effect on fertility in humans for binimetinib. 
Plodnost Nema podataka o utjecaju binimetinibom na plodnost u ljudi.
VTE led to dose interruptions or dose modifications in 1.1 % (3/274) patients and to additional therapy in 4.7 % (13/274) of patients. 
VTE je doveo do privremenog prekida ili prilagodbe doze u 1,1% (3/274) bolesnika i do dodatnog liječenja u 4,7% (13/274) bolesnika.
The tablets also contain lactose. 
POPIS POMOĆNIH TVARI Tablete također sadrže laktozu.
Mektovi film-coated tablets are yellow/dark yellow, unscored biconvex, oval film-coated tablets debossed with “A” on one side and “15” on the other side. 
Lijek Mektovi su obložene tablete žute do tamnožute boje, bez ureza, bikonveksne, ovalne filmom obložene tablete, s oznakom „A” utisnutom s jedne strane tablete i „15” s druge strane.
The most frequent haemorrhagic events were haematuria in 3.3 % (9/274) of patients, rectal haemorrhage in 2.9 % (8/274) and haematochezia in 2.9 % (8/274) of patients. 
Najčešći događaji krvarenja obuhvaćali su hematuriju u 3,3% (9/274) bolesnika, rektalno krvarenje u 2,9% (8/274) bolesnika i hematohezija u 2,9% (8/274) bolesnika.
New primary malignancies, cutaneous and non-cutaneous, have been observed in patients treated with BRAF inhibitors and can occur when binimetinib is administered in combination with encorafenib (see section 4.8). 
Nove primarne zloćudne bolesti, koje su na koži i one koje nisu, zabilježene su u bolesnika liječenih BRAF inhibitorima i mogu se javiti tijekom primjene binimetiniba u kombinaciji s enkorafenibom (vidjeti dio 4.8).
• a particular change (mutation) in a gene responsible for producing a protein called BRAF, and 
• koji ima određenu promjenu (mutaciju) gena pod nazivom BRAF, odgovornog za stvaranje proteina, i • koji se proširio na druge dijelove tijela ili se ne može ukloniti kirurškim zahvatom.
When encorafenib was used at a dose of 300 mg once daily in combination with binimetinib 45 mg twice daily (Combo 300) in study CMEK162B2301-Part 2, the frequency category was lower compared to the pooled Combo 450 population for the following adverse reactions: anemia, peripheral neuropathy, haemorrhage, hypertension, pruritus (common) and colitis, increased amylase and increased lipase (uncommon). 
Pri korištenju enkorafeniba jedanput dnevno u dozi od 300 mg u kombinaciji s binimetinibom u dozi od 45 mg dvaput dnevno (kombinirana terapija 300), u ispitivanju CMEK162B2301, dio 2, kategorije učestalosti su bile niže u usporedbi s ukupnom populacijom kombinirane terapije 450 za sljedeće nuspojave: anemija, periferna neuropatija, krvarenje, hipertenzija, pruritus (često) i kolitis, povišenje vrijednosti amilaze i lipaze (manje često).
Binimetinib dose should be maintained. 
Treba održavati dozu binimetiniba.
• If the LVEF does not recover within 4 weeks, binimetinib should be permanently discontinued. 
• Ako se LVEF ne povrati unutar 4 tjedna, treba trajno obustaviti binimetinib.
Serious side effects Mektovi may cause serious side effects. 
Ozbiljne nuspojave Lijek Mektovi može izazvati ozbiljne nuspojave.
The Functional Assessment of Cancer Therapy-Melanoma (FACT-M), the European Organisation for Research and Treatment of Cancer's core quality of life questionnaire (EORTC QLQ-C30) and the EuroQoL-5 Dimension-5 Level examination (EQ-5D-5L) were used to explore patient-reported outcomes (PRO) measures of health-related Quality of Life, functioning, melanoma symptoms, and treatment-related adverse reaction. 
Patient Reported Outcomes, PRO) a vezane su uz mjerenja kvalitete života povezane sa zdravljem, funkcioniranjem, simptomima melanoma i nuspojava povezanih s liječenjem korišteni su FACT-M upitnik (The Functional Assessment of Cancer Therapy-Melanoma), EORTC QLQ-C30 upitnik (European Organization for Research and Treatment of Cancer's core quality of life questionnaire,) i EQ-5D-5L (EuroQoL-5 Dimension-5 Level examination).
• Grade 3 or Grade 4 
• Stupanj 3 ili stupanj 4
Treatment with binimetinib should be withheld in patients with suspected pneumonitis or ILD, including patients presenting new or progressive pulmonary symptoms or findings such as cough, dyspnoea, hypoxia, reticular opacities or pulmonary infiltrates (see Table 1 in section 4.2). 
ILD, uključujući bolesnike koji pokazuju nove ili progresivne simptome plućne bolesti ili nalaze, kao što su kašalj, dispneja, hipoksija, retikularna opacifikacija ili plućni infiltrat (vidjeti Tablicu 1 u dijelu 4.2).
The median time to onset of the first event of RPED (all grades) was 1.5 month (range 0.03 to 17.5 months). 
Medijan vremena do prvog pojavljivanja RPED-a (za sve stupnjeve) iznosio je 1,5 mjeseci (u rasponu od 0,03 do 17,5 mjeseci).
If you take more tablets than you should, contact your doctor, pharmacist or nurse straightaway. 
Ako uzmete više tableta nego što ste trebali, odmah se obratite svom liječniku, ljekarniku ili medicinskoj sestri.
Ocular toxicities 
Okularna toksičnost
In the pooled Combo 450 population, LVD was reported in 8.4 % (23/274) of patients. 
U ukupnoj populaciji kombinirane terapije 450, LVD je prijavljen u 8,4% (23/274) bolesnika.
Exceptions where dose reductions are necessary for encorafenib only (adverse reactions primarily related to encorafenib) are: palmar-plantar erythrodysaesthesia syndrome (PPES), uveitis including iritis and iridocyclitis and QTc prolongation. 
Iznimke u kojima su smanjenja doze potrebna samo za enkorafenib (nuspojave prvenstveno povezane s enkorafenibom) su: sindrom palmarno-plantarne eritrodizestezije (engl.
• Grade 3 or 4 LVEF decrease or symptomatic left ventricular dysfunction (LVD) 
• Smanjenje ejekcijske frakcije lijevog ventrikula stupnja 3 ili 4 ili simptomatska disfunkcija lijevog ventrikula
Dose modification was reported in 0.7 % (2/274) of patients. 
Prilagodba doze zabilježena je u 0,7% (2/274) bolesnika.
Study CMEK162B2301, Part 1: Progression-free survival and confirmed overall response results (independent central review) 
Tablica 4: Ispitivanje CMEK162B2301, dio 1: Preživljenje bez progresije i potvrđeni rezultati ukupnog odgovora (neovisna središnja procjena)
In the safety analysis of pooled studies of encorafenib 450 mg once daily in combination with 45 mg binimetinib twice daily (Combo 450), the incidence of new QTc prolongation > 500 ms was 0.7 % (2/268) in the encorafenib 450 mg plus binimetinib group, and 2.5 % (5/203) in the encorafenib single agent group. 
Na temelju analize podataka o sigurnosti iz objedinjenih kliničkih ispitivanja primjene enkorafeniba 450 mg jedanput dnevno u kombinaciji s 45 mg binimetiniba dvaput dnevno (kombinirana terapija 450), incidencija novih produljenja intervala QTc > 500 ms bila je 0,7% (2/268) u skupine bolesnika liječenih enkorafenibom u dozi od 450 mg s binimetinibom, i 2,5% (5/203) u skupini bolesnika liječenih enkorafenibom u monoterapiji.
• High blood pressure: Mektovi can raise blood pressure. 
• Visok krvni tlak: lijek Mektovi može povećati krvni tlak.
Vomiting occurred in 15.2% (39/257) of patients with Grade 3 reported in 0.4% (1/257) of patients. 
Povraćanje se javilo u 15,2% (39/257) bolesnika, a stupanj 3 prijavljen je kod 0,4% (1/257) bolesnika.
Binimetinib in combination with encorafenib in patients who have progressed on a BRAF inhibitor 
Binimetinib u kombinaciji s enkorafenibom u bolesnika u kojih je došlo do progresije tijekom terapije BRAF inhibitorom
An interim OS analysis of study CMEK162B2301 Part 1, (cut-off date 07 November 2017) demonstrated a statistically significant improvement in OS for Combo 450 compared with vemurafenib (see Table 5 and Figure 2). 
Interim analize ukupnog preživljenja (OS) ispitivanja CMEK162B2301, dio 1 (datum prestanka prikupljanja podataka 7. studenoga 2017), pokazale su statistički značajno poboljšanje OS-a u skupini kombinirane terapije 450 u usporedbi sa skupinom liječenom vemurafenibom (vidjeti Tablicu 5 i sliku 2).
Hepatic impairment No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh A). 
U bolesnika s blagim oštećenjem jetrene funkcije nije potrebna prilagodba doze (Child-Pugh A).
Following a single oral dose of 45 mg [14C] binimetinib in healthy subjects, a mean of 62.3 % of the radioactivity was eliminated in the feces while 31.4 % was eliminated in the urine. 
Nakon jednokratne peroralne doze od 45 mg [14C] binimetiniba u zdravih ispitanika, srednja vrijednost od 62,3% radioaktivnosti eliminirana je putem stolice, a 31,4% putem mokraće.
There are limited data for use of the combination of binimetinib with encorafenib in patients who have progressed on a prior BRAF inhibitor given for the treatment of unresectable or metastatic melanoma with BRAF V600 mutation. 
Postoje ograničeni podaci o primjeni kombinirane terapije binimetinibom i enkorafenibom u bolesnika u kojih je došlo do progresije tijekom prethodne terapije BRAF inhibitorom korištenim za liječenje neoperabilnog ili metastatskog melanoma s BRAF V600 mutacijom.
Dose interruption or dose modification was reported in 0.4 % (1/274) of patients. 
Privremeni prekid ili prilagodba doze zabilježeni su u 0,4% (1/274) bolesnika.
• First occurrence of Grade 3 (AST or ALT > 5x ULN and blood bilirubin > 2x ULN) 
• Prva pojava stupnja 3 (AST ili ALT > 5x GGN i bilirubin u krvi > 2x GGN)
In the pooled Combo 450 population, mostly mild asymptomatic blood CK elevation was reported in 27.0 % (74/274) of patients. 
U ukupnoj populaciji kombinirane terapije 450 prijavljeno je uglavnom blago asimptomatsko povišenje kreatin kinaze u krvi u 27,0% (74/274) bolesnika.
• First occurrence of Grade 4 (AST or ALT > 20 ULN) 
• Prva pojava stupnja 4 (AST ili ALT > 20x GGN)
• If resolved within 4 weeks, binimetinib should be resumed at a reduced dose, or 
• Ako se riješi unutar 4 tjedna, treba nastaviti sa smanjenom dozom binimetiniba ili
The safety of encorafenib (300 mg orally once daily) in combination with binimetinib (45 mg orally twice daily) was evaluated in 257 patients with BRAF V600 mutant unresectable or metastatic melanoma (hereafter referred to as the Combo 300 population), based on the Phase III study (CMEK162B2301, Part 2). 
Sigurnost enkorafeniba (300 mg peroralno jedanput dnevno) u kombinaciji s binimetinibom (45 mg peroralno dvaput dnevno) procijenjena je u 257 bolesnika s neoperabilnim ili metastatskim melanomom s pozitivnom mutacijom BRAF V600 (u daljnjem tekstu: populacija kombinirane terapije 300), na temelju ispitivanja faze III (CMEK162B2301, dio 2).
• Tablet core: lactose monohydrate, cellulose microcrystalline (E460i), silica colloidal anhydrous (E551), croscarmellose sodium (E468) and magnesium stearate (E470b). 
• Jezgra tablete: laktoza hidrat, mikrokristalična celuloza (E460i), bezvodni koloidni silicijev dioksid (E551), umrežena karmelozanatrij (E468) i magnezijev stearat (E470b).
Median DOR for confirmed responses per BIRC was 12.7 months [95% CI: 9.3, 15.1] for Combo 300 and 12.9 months [95 % CI: 8.9, 15.5] for Enco 300. 
Medijan trajanja odgovora (DoR) za potvrđene odgovore prema ocjeni BIRC-a iznosio je 12,7 mjeseci (95% CI: 9,3; 15,1) za kombiniranu terapiju 300 i 12,9 mjeseci (95% CI: 8,9; 15,5) za enkorafenib 300.
If encorafenib is permanently discontinued, then binimetinib should be discontinued. 
Ako je enkorafenib trajno obustavljen, onda se mora obustaviti i binimetinib.
Diarrhoea led to dose discontinuation in 0.4 % of patients and to dose interruption or dose modification in 4.4 % of patients. 
Proljev je doveo do trajne obustave liječenja u 0,4% bolesnika i privremenog prekida liječenja ili prilagodbe doze u 4,4% bolesnika.
Lactose monohydrate Cellulose microcrystalline (E460i) Silica colloidal anhydrous (E551) Croscarmellose sodium (E468) Magnesium stearate (E470b) 
Jezgra tablete laktoza hidrat mikrokristalična celuloza (E460i) silicijev dioksid, koloidni, bezvodni (E551) karmelozanatrij, umrežena (E468) magnezijev stearat (E470b)
Blood and lymphatic system disorders 
Poremećaji krvi i limfnog sustava anemija vrlo često
Uncommon (may affect up to 1 in 100 people) - weakness and paralysis of face muscles - inflammation of the pancreas (pancreatitis) causing severe abdominal pain 
Manje često (može se javiti u 1 na 100 osoba) - slabost ili paraliza mišića lica
In the pooled Combo 450 population, RPED was reported in 29.6 % (81/274) of patients. 
U ukupnoj populaciji kombinirane terapije 450 RPED je prijavljen u 29,6% (81/274) bolesnika.
In part 1, patients in the study were randomised to receive binimetinib 45 mg orally twice daily plus encorafenib 450 mg orally daily (Combo 450, n = 192), encorafenib 300 mg orally daily (hereafter referred to as Enco 300, n = 194), or vemurafenib 960 mg orally twice daily (hereafter referred to as Vem, n = 191). 
U dijelu 1, bolesnici su randomizirani na liječenje binimetinibom 45 mg peroralno, dvaput dnevno i enkorafenibom 450 mg peroralno, jedanput dnevno (kombinirana terapija 450, n = 192), enkorafenibom 300 mg peroralno, jedanput dnevno (u daljnjem tekstu: enkorafenib 300, n=194), ili vemurafenibom 960 mg peroralno, dvaput dnevno (u daljnjem tekstu: vemurafenib, n = 191).
Abdominal pain was reported in 27.4 % (75/274) of patients and was Grade 3 in 2.6 % (7/274) patients. 
Bol u abdomenu prijavljena je u 27,4% (75/274) bolesnika i bila je stupnja 3 u 2,6% (7/274) bolesnika.
BRAF V600 mutant unresectable or metastatic melanoma The safety and efficacy of binimetinib in combination with encorafenib were evaluated in a 2-part Phase III, randomised (1:1:1) active-controlled, open-label, multicenter study in patients with unresectable or metastatic BRAF V600 E or K mutant melanoma (Study CMEK162B2301), as detected using a BRAF assay. 
Neoperabilni ili metastatski melanom s mutacijom BRAF V600 Sigurnost i djelotvornost binimetiniba u kombinaciji s enkorafenibom procijenjena je u dvodjelnom randomiziranom (1:1:1), aktivno kontroliranom, otvorenom, multicentričnom ispitivanju faze III u bolesnika s neoperabilnim ili metastatskim melanomom s mutacijom BRAF V600 E ili K
Binimetinib inhibits activation of MEK by BRAF and inhibits MEK kinase activity. 
BRAF-a i inhibira aktivnost MEK kinaze.
The median age of patients was 56 years (range 20-89), 58 % were male, 90 % were Caucasian, and 72 % of patients had baseline ECOG performance status of 0. 
Medijan dobi bolesnika bio je 56 godina (raspon 20 - 89), 58% ispitivane populacije bili su muškarci,
After oral administration, binimetinib is rapidly absorbed with a median Tmax of 1.5 hours. 
Binimetinib se brzo apsorbira uz medijan Tmax od približno 1,5 sati nakon peroralne primjene u bolesnika.
A two-fold increase in total binimetinib exposure (AUC) was observed in patients with moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment (see section 4.2). 
Dvostruko povećanje ukupnog izlaganja binimetinibu (AUC) primijećeno je u bolesnika s umjerenim (Child-Pugh B) i teškim (Child
Binimetinib pharmacokinetics have been shown to be approximately dose-linear. 
Ispitivanje je pokazalo da binimetinib pokazuje linearnu farmakokinetiku proporcionalnu dozu.
Visual impairment* 
Poremećaji oka poremećaj vida*
Study CMEK162B2301, Part 1: Kaplan-Meier plot of interim overall survival (cut-off date: 7 November 2017) 
Ispitivanje CMEK162B2301, dio 1: Kaplan-Meierove krivulje interim rezultata ukupnog preživljenja (datum prestanka prikupljanja podataka: 7. studenoga 2017.)
Binimetinib treatment in combination with encorafenib should be initiated and supervised under the responsibility of a physician experienced in the use of anticancer medicinal products. 
4.2 Doziranje i način primjene Liječenje binimetinibom u kombinaciji s enkorafenibom mora započeti i nadzirati liječnik s iskustvom u primjeni antitumorskih lijekova.
In rats, lower gestational body weight gain and fetal body weights and a decreased number of ossified fetal sternebrae were noted. 
Kod fetusa štakora je primijećeno manje dobivanje na težini, manja težina fetusa te smanjen broj okoštanih sternebri kod fetusa.
Cutaneous reactions • Grade2 
Kožne reakcije • Stupanj 2
Part 2 of study CMEK162B2301 was designed to assess the contribution of binimetinib to the encorafenib and binimetinib combination. 
Ispitivanje CMEK162B2301, dio 2 Dio 2 ispitivanja CMEK162B2301 ustrojen je za procjenu doprinosa binimetiniba u kombiniranom liječenju enkorafenibom i binimetinibom.
Tell your doctor immediately if you get severe headache, feel dizzy or lightheaded or if your blood pressure measured on a home blood pressure device is much higher than usual. 
Odmah obavijestite liječnika budete li imali jake glavobolje, osjećali omaglicu, ošamućenost ili ukoliko vam je tlak izmjeren kućnim tlakomjerom mnogo viši nego inače.
Median, months (95 % CI) 
Medijan, mjeseci (95% CI)