natgillin/translations-raw huggingface dataset:
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)
For information on the posology and recommended dose modifications of encorafenib, see section 4.2 of encorafenib SmPC.
Za informacije o doziranju i preporučenoj prilagodbi doze enkorafeniba, vidjeti dio 4.2 sažetka opisa svojstava lijeka za enkorafenib.
Fatal gastric ulcer haemorrhage with multiple organ failure as a concurrent cause of death, occurred in one patient.
Smrtonosno krvarenje čira na želucu i višeorgansko zatajenje kao dodatni uzrok smrti prijavljeni su u jednog bolesnika.
In the pooled Combo 450 population, anaemia was reported in 19.7 % (54/274) of patients; 4.7 % (13/274) of patients had Grade 3 or 4.
U ukupnoj populaciji kombinirane terapije 450, anemija je prijavljena u 19,7% (54/274) bolesnika; 4,7% (13/274) bolesnika je imalo nuspojave stupnja 3 ili 4.
• Bleeding problems: Mektovi may cause serious bleeding problems.
• Krvarenja: lijek Mektovi može prouzročiti ozbiljne probleme s krvarenjem.
• If not improved, binimetinib should be permanently discontinued.
• Ako nema poboljšanja, treba trajno obustaviti binimetinib.
CK elevation/rhabdomyolysis
Povišenje kreatin kinaze / rabdomioliza
27 patients (5 %) had received prior checkpoint inhibitors (antiPD1/PDL1 or ipilimumab) (8 patients in Combo 450 arm (4 %); 7 patients in vemurafenib arm (4 %); 12 patients in Enco 300 arm (6 %) including 22 patients in the metastatic setting (6 patients in Combo 450 arm; 5 patients in vemurafenib arm; 11 patients in Enco 300 arm) and 5 patients in the adjuvant setting (2 patients in Combo 450 arm; 2 patients in vemurafenib arm; 1 patient in Enco 300 arm.
bolesnika (5%) je prethodno primalo checkpoint inhibitore (anti-PD1/PDL1 ili ipilimumab) (8 bolesnika u skupini s kombiniranom terapijom 450 (4%); 7 bolesnika u skupini liječenoj vemurafenibom (4%); 12 bolesnika u skupini liječenih enkorafenibom 300 (6%) uključujući i 22
Survival at 24 months (95% CI)
Preživljenje nakon 24 mjeseca (95% CI)
Photosensitivity*
vrlo često fotoosjetljivost*
Duration of response Median, months (95 % CI)
Trajanje odgovora Medijan, mjeseci (95% CI)
It is important to take Mektovi for as long as your doctor prescribes it. Do not stop taking this medicine unless your doctor tells you to.
Važno je uzimati lijek Mektovi dokle god vam ga liječnik propisuje.
The occurrence of LVEF decrease can be managed with treatment interruption, dose reduction or with treatment discontinuation (see section 4.2).
Pojava smanjenja LVEF-a može se zbrinuti privremenim prekidom liječenja, smanjenjem doze ili trajnom obustavom liječenja (vidjeti dio 4.2).
In the pooled Combo 450 population, VTE was reported as Grade 1 or 2 in 3.6 % (10/274) of patients and Grade 3 or 4 in 1.1 % (3/274) of patients.
ukupnoj populaciji kombinirane terapije 450, VTE je prijavljen kao stupanj 1 ili 2 u 3,6% (10/274) bolesnika i kao stupanj 3 ili 4 u 1,1% (3/274) bolesnika.
• Recurrent Grade 3 (AST or ALT > 5x ULN and blood bilirubin > 2x ULN)
• Ponovna pojava stupnja 3 (AST ili ALT > 5x GGN i bilirubin u krvi > 2x GGN)
Study CMEK162B2301, Part 1: Kaplan-Meier plot of progression-free survival by independent central review (cut-off date 19 May 2016)
Slika 1: Ispitivanje CMEK162B2301, dio 1: Kaplan-Meierove krivulje preživljenja bez progresije prema neovisnoj središnjoj procjeni (datum prestanka prikupljanja podataka: 19. svibnja 2016.)
Your doctor will check that your heart is working properly before and during your treatment with this medicine.
Vaš će liječnik prije i tijekom liječenja ovim lijekom provjeriti radi li vaše srce ispravno.
Talk to your doctor immediately if you have any symptoms of heart problems such as feeling dizzy, tired, lightheaded, if you have shortness of breath, if you feel like your heart is pounding, racing, beating irregularly or if you have swelling in the legs.
Odmah obavijestite svog liječnika ako imate bilo kakve simptome srčanih tegoba, kao što su osjećaj omaglice, umora, ošamućenosti, nedostatak zraka, osjećaj lupanja srca, ubrzan puls, preskakanje srca ili ako su vam noge otečene.
If during treatment patient develops VTE or pulmonary embolism, it should be managed with dose interruption, reduction or treatment discontinuation (see Table 1 in section 4.2).
Ako se tijekom liječenja u bolesnika pojavi VTE ili plućna embolija, potrebno ju je zbrinuti prekidom doze, smanjenjem doze ili trajnom obustavom liječenja (vidjeti Tablicu 1 u dijelu 4.2).
Table 2: Recommended dose modifications for binimetinib (used in combination with encorafenib) for other adverse reactions
Tablica 2: Preporučeno prilagođavanje doze za binimetinib (kada se primjenjuje u kombinaciji s enkorafenibom) za druge nuspojave Težina nuspojava
Alopecia*
vrlo često alopecija*
Asymptomatic CK elevations are seen in patients treated with binimetinib (see section 4.8), and, rhabdomyolysis was uncommonly reported.
Asimptomatsko povišenje kreatin kinaze primijećeno je u bolesnika liječenih binimetinibom (vidjeti dio 4.8), a rjeđe je primijećena rabdomioliza.
Diarrhoea occurred in 28.4% (73/257) of patients with Grade 3 reported in 1.6% (4/257) of patients.
Proljev je zapažen u 28,4% (73/257) bolesnika, a stupanj 3 prijavljen je kod 1,6% (4/257) bolesnika.
Haemorrhagic events were observed in 17.9 % (49/274) of patients in the pooled Combo 450 population.
Krvarenje je zapaženo u 17,9% (49/274) bolesnika iz ukupne populacije kombinirane terapije 450.
• If not resolved within 4 weeks, binimetinib should be permanently discontinued.
• Ako se ne riješi unutar 4 tjedna, treba trajno obustaviti binimetinib.
Blood alkaline phosphatase increased Common Amylase increased
često povišenje alkalne fosfataze u krvi često povišenje amilaze često povišenje lipaze često
• If not improved to Grade 2, binimetinib should be permanently discontinued.
• Ako nije došlo do poboljšanja na stupanj 2, treba trajno obustaviti binimetinib.
Immune system disorders Hypersensitivityb
Poremećaji imunološkog sustava preosjetljivostb često
Mektovi 15 mg film-coated tablets
Mektovi 15 mg filmom obložene tablete
• Recurrent Grade 4 (AST or ALT > 20 ULN)
• Ponovna pojava stupnja 4 (AST ili ALT > 20x GGN )
Survival at 12 months (95% CI)
Preživljenje nakon 12 mjeseci (95% CI)
In the pooled Combo 450 population, rash occurred in 19.7 % (54/274) of patients.
U ukupnoj populaciji kombinirane terapije 450, osip se pojavio u 19,7% (54/274) bolesnika.
Nausea occurred in 41.6 % (114/274) with Grade 3 or 4 observed in 2.6 % (7/274) of patients.
Mučnina se javila u 41,6% (114/274) bolesnika, a stupanj 3 ili 4 prijavljen je u 2,6% (7/274)
As encorafenib is not recommended in patients with moderate (Child Pugh B) and severe hepatic impairment (Child Pugh C), administration of binimetinib is not recommended in these patients (see sections 4.2 and 5.2).
Kako se ne preporučuje uporaba enkorafeniba u bolesnika s umjerenim (Child-Pugh B) ili teškim oštećenjem jetrene funkcije (Child-Pugh C), u ovih bolesnika se ne preporučuje ni primjena binimetiniba (vidjeti dio 4.2 sažetka opisa svojstava lijeka za enkorafenib).
It should be considered to permanently discontinue binimetinib.
Treba razmotriti trajno obustavljanje binimetiniba.
If binimetinib is permanently discontinued, encorafenib should be discontinued.
Ako je binimetinib trajno obustavljen, onda se mora obustaviti i enkorafenib.
Binimetinib should be withheld until improved to Grade 0 or 1.
Treba prekinuti dozu binimetiniba dok se ne dosegne poboljšanje na stupanj 0 ili 1.
In the pooled Combo 450 population, headache occurred in 21.5% (59/274) of patients including Grade 3 in 1.5% (4/274) of patients.
U ukupnoj populaciji kombinirane terapije 450, glavobolja se javila u 21,5% (59/274) bolesnika uključujući i nuspojave stupnja 3 u 1,5% (4/274) bolesnika.
Rash led to treatment discontinuation in 0.4 % (1/274) of patients and to dose interruption or dose modification in 1.1 % (3/274) of patients.
Osip je doveo do trajne obustave liječenja u 0,4% (1/274) bolesnika i privremenog prekida ili prilagodbe doze u 1,1% (3/274) bolesnika.
• medicine used to treat depression such as duloxetine
• lijekovi koji se koriste za liječenje depresije, kao što je duloksetin • lijekovi kojima se obično liječi visok kolesterol, kao što je pravastatin
Effect of binimetinib on transporters
Učinak binimetiniba na transportne proteine