natgillin/translations-raw huggingface dataset:
Of the total number of patients in the integrated safety population of dabrafenib monotherapy (n=578), 22% were 65 years of age and older, and 6% were 75 years of age and older. 
Od ukupnog broja ispitanika u objedinjenoj populaciji u kojoj se ispitivala sigurnost monoterapije dabrafenibom (n=578), 22% je imalo 65 i više godina, a 6% imalo je 75 godina i više.
• Cardiac glycosides (e.g. digoxin, see section 4.4) 
• Glikozide digitalisa (npr. digoksin, vidjeti dio 4.4)
P-value is obtained from the two-sided stratified logrank test (stratification factors were disease stage - IIIA vs. IIIB vs. IIIC - and BRAF V600 mutation type - V600E vs. V600K) NE = not estimable 
P-vrijednost je dobivena iz dvostranog stratificiranog logrank testa (faktori stratifikacije bili su stadij bolesti - IIIA naspram IIIB naspram IIIC - i tip BRAF V600 mutacije - V600E naspram V600K)
Effects of dabrafenib on substance transport systems 
Učinci dabrafeniba na sustave prijenosa tvari
Dabrafenib in combination with trametinib should be used with caution in patients with conditions that could impair left ventricular function. 
Dabrafenib u kombinaciji s trametinibom treba primjenjivati s oprezom u bolesnika sa stanjima koja mogu oštetiti funkciju lijevog ventrikula.
In a clinical drug interaction study, Cmax and AUC of oral midazolam (a CYP3A4 substrate) decreased by 47% and 65%, respectively with co-administration of repeat-dose dabrafenib. 
U kliničkom ispitivanju interakcija lijekova, snizile su se vrijednosti Cmax i AUC za oralni midazolam (supstrat CYP3A4) za 47% i 65%, pri istodobnom ponavljanom doziranju dabrafeniba.
(22.6, NR) 
(22,6; ND)
Pancreatitis has been reported in <1% of patients treated with dabrafenib as monotherapy and in combination with trametinib in unresectable or metastatic melanoma clinical trials and about 4% of patients treated with dabrafenib in combination with trametinib in the NSCLC clinical trial. 
Pankreatitis je zabilježen u < 1% bolesnika koji su primali dabrafenib kao monoterapiju i u kombinaciji s trametinibom u kliničkim ispitivanjima neoperabilnog ili metastatskog melanoma i u oko 4% bolesnika koji su primali dabrafenib u kombinaciji s trametinibom u kliničkom ispitivanju NSCLC-a.
Patients with brain metastases 
Bolesnici s metastazama u mozgu
• Analgesics (e.g. fentanyl, methadone) 
• Analgetike (npr. fentanil, metadon)
Granulomatous nephritis has been reported (see section 4.8). 
Prijavljen je granulomatozni nefritis (vidjeti dio 4.8).
Figure 4 Kaplan-Meier RFS curves for Study BRF115532 (ITT population, updated results) 
Slika 4 Kaplan-Meier RFS krivulje za ispitivanje BRF115532 (ITT populacija, ažurirani rezultati)
If possible, show them the Tafinlar and trametinib pack with each leaflet. 
Ako je moguće, pokažite im pakiranja Tafinlara i trametiniba s uputama o lijeku.
Neither dabrafenib nor its 3 main metabolites were demonstrated to be inhibitors of Pgp in vitro. 
In vitro nije dokazano da su dabrafenib i njegova 3 glavna metabolita inhibitori Pgp-a.
In the integrated safety population for dabrafenib in combination with trametinib, 2% of patients developed cuSCC and the events occurred later than with dabrafenib monotherapy with a median time to onset of 18-31 weeks. 
U objedinjenoj populaciji u kojoj se ispitivala sigurnost dabrafeniba u kombinaciji s trametinibom, u 2% bolesnika razvio se cuSCC, a do događaja je došlo kasnije nego uz monoterapiju dabrafenibom, s medijanom vremena do prve pojave od 18-31 tjedan.
How should you take Tafinlar in combination with trametinib 
Kako uzimati Tafinlar u kombinaciji s trametinibom
The population pharmacokinetic analysis showed no significant differences in the pharmacokinetics of dabrafenib between Asian and Caucasian patients. 
Analiza populacijske farmakokinetike nije pokazala značajne razlike u farmakokinetici dabrafeniba između bolesnika azijskog podrijetla i bijelaca.
Most patients (94%) enrolled in the combination therapy treated cohorts had an ECOG performance status of 0 or 1. 
Većina bolesnika (94%) uključenih u kohorte liječene kombiniranom terapijom imala je ECOG funkcionalni status 0 ili 1. 26 (28%) nikada nije pušilo.
Tell your doctor immediately if you get eye redness and irritation, blurred vision, eye pain or other vision changes during your treatment (see also section 4). 
Odmah obavijestite svog liječnika ako za vrijeme uzimanja ovog lijeka imate crvenilo očiju i iritaciju, zamagljen vid, bol u oku ili druge promjene vida (također pogledajte dio 4).
• Reddening and swelling of the palms, fingers and soles of the feet (see “Changes in your skin” 
• crvenilo i otekline dlanova, prstiju ruke i tabana (pogledajte "Kožne promjene" ranije u dijelu 4)
• coughing up of blood or blood clots 
• iskašljavanje krvi ili krvnih ugrušaka
Skin reactions (rash) can happen while taking Tafinlar in combination with trametinib. 
Kožne reakcije (osip) se mogu pojaviti tijekom uzimanja Tafinlara u kombinaciji s trametinibom.
Preclinical data generated in biochemical assays demonstrated that dabrafenib inhibits BRAF kinases with activating codon 600 mutations (Table 5). 
Pretklinički podaci dobiveni u biokemijskim ispitivanjima pokazali su da dabrafenib inhibira BRAF kinaze s aktiviranom mutacijom kodona 600 (tablica 5).
Bronchoalveolar inflammation of the lungs was observed in several dogs at ≥20 mg/kg/day (≥9 times human clinical exposure based on AUC) and was associated with shallow and/or laboured breathing. 
Kod nekoliko pasa je nađena bronhoalveolarna upala pluća pri dozama ≥ 20 mg/kg/dan (≥ 9 puta kliničke izloženosti u ljudi temeljeno na AUC-u) te je bila povezana s plitkim i/ili teškim disanjem.
• Skin tags 
• kožni privjesci
Liver monitoring may be continued thereafter as clinically indicated. 
Nakon toga se nadziranje jetrene funkcije može nastaviti sukladno kliničkoj indikaciji.
Dabrafenib demonstrated suppression of a downstream pharmacodynamic biomarker (phosphorylated ERK) and inhibited cell growth of BRAF V600 mutant melanoma cell lines, in vitro and in animal models. 
Dabrafenib je pokazao supresiju nizvodnih farmakodinamičkih biomarkera (fosforilirani ERK) i inhibiciju staničnog rasta u BRAF V600 mutiranim staničnim linijama melanoma, in vitro kao i u modelima na životinjama.
Abnormal findings should be managed according to clinical practices. 
Patološki nalazi se moraju zbrinuti u skladu s važećim kliničkim smjernicama.
In juvenile toxicity studies in rats, effects on growth (shorter long bone length), renal toxicity (tubular deposits, increased incidence of cortical cysts and tubular basophilia and reversible increases in urea and/or creatinine concentrations) and testicular toxicity (degeneration and tubular dilation) were observed (≥0.2 times adult human clinical exposure based on AUC). 
U ispitivanjima juvenilne toksičnosti na štakorima, uočeni su učinci na rast (skraćena duga nožna kost), bubrežna toksičnost (tubularni depoziti, povećana incidencija kortikalnih cisti, tubularna bazofilija te reverzibilna povećanja koncentracije ureje i/ili kreatinina) i testikularna toksičnost (degeneracija i dilatacija kanalića) (≥ 0,2 puta kliničke izloženosti u odraslih ljudi temeljeno na AUC-u).
Dabrafenib is a substrate of human P-glycoprotein (Pgp) and human BCRP in vitro. 
Dabrafenib je in vitro supstrat humanog P-glikoproteina (Pgp) i humanog BCRP-a.
Always take Tafinlar exactly as your doctor, pharmacist or nurse has told you to. 
Uvijek uzmite Tafinlar točno onako kako Vam je rekao liječnik, ljekarnik ili medicinska sestra.
In combined female fertility, early embryonic and embryo-foetal development studies in rats numbers of ovarian corpora lutea were reduced in pregnant females at 300 mg/kg/day (approximately 3 times human clinical exposure based on AUC), but there were no effects on oestrous cycle, mating or fertility indices. 
U kombiniranom ispitivanju plodnosti ženki, ranog embrionalnog i embriofetalnog razvoja u štakora, broj ovarijskih žutih tijela se u skotnih ženki smanjio na 300 mg/kg/dan (približno 3 puta kliničke izloženosti u ljudi temeljeno na AUC-u), ali nije bilo učinka na reproduktivni ciklus, parenje ili plodnost.
BRF113710 (BREAK-2) was a multicentre, single-arm study that enrolled 92 subjects with metastatic melanoma (Stage IV) with confirmed BRAF V600E or V600K mutation-positive melanoma. 
BRF113710 (BREAK-2) je bilo multicentrično ispitivanje s jednom skupinom u koju je bilo uključeno 92 ispitanika s metastatskim melanomom (stadij IV) s potvrđenom BRAF V600E ili V600K mutacijom melanoma.
It is recommended that patients receiving treatment with dabrafenib in combination with trametinib have liver function monitored every four weeks for 6 months after treatment initiation with trametinib. 
U bolesnika koji se liječe dabrafenibom u kombinaciji s trametinibom preporučuje se nadzirati jetrenu funkciju svaka četiri tjedna tijekom 6 mjeseci nakon početka liječenja trametinibom.
Similar results were seen in the 45 patients who crossed over from dabrafenib monotherapy to the trametinib 2 mg once daily and dabrafenib 150 mg twice daily combination in Part C of this study. 
Slični su rezultati bili uočeni u 45 bolesnika koji su prešli s monoterapije dabrafenibom na kombinaciju trametinib 2 mg jedanput na dan i dabrafenib 150 mg dvaput na dan u Dijelu C ovog ispitivanja.
Patients should be routinely monitored for serum creatinine while on therapy. 
Tijekom liječenja bolesnicima je potrebno redovito kontrolirati kreatinin u serumu.
• HIV antivirals (e.g. amprenavir, atazanavir, darunavir, delavirdine, efavirenz, fosamprenavir, 
• HIV antivirusne lijekove (npr. amprenavir, atazanavir, darunavir, delavirdin, efavirenz,
Improvements were also observed for overall response rate (ORR) and a longer duration of response (DoR) was observed in the combination arm compared to dabrafenib monotherapy (Table 7). 
Poboljšanja su također uočena za stopu ukupnog odgovora (engl. overall response rate, ORR) i dulje trajanje odgovora (engl. duration of response, DoR) bilo je uočeno u skupini koja je primala kombinaciju u usporedbi s monoterapijom dabrafenibom (tablica 7).
N=99 5.6 (4.8, NR) 
N=99 5,6 (4,8; ND)
If the patient becomes pregnant while taking dabrafenib, the patient should be informed of the potential hazard to the foetus. 
Ako bolesnica ostane trudna tijekom primanja terapije dabrafenibom, treba ju obavijestiti o mogućim štetnim djelovanjima na fetus.
Developmental toxicity including embryo-lethality and ventricular septal defects and variation in thymic shape were seen at 300 mg/kg/day, and delayed skeletal development and reduced foetal body weight at ≥20 mg/kg/day (≥0.5 times human clinical exposure based on AUC). 
Razvojna toksičnost, uključujući smrtnost embrija i defekte ventrikularnog septuma i variranje oblika timusa, nađena je pri 300 kg/kg/dan, uz odgođen razvoj skeleta te smanjenje fetalne tjelesne težine na ≥ 20 mg/kg/dan (≥ 0,5 puta kliničke izloženosti u ljudi temeljeno na AUC-u).
Following discontinuation of dabrafenib, monitoring for non-cutaneous secondary/recurrent malignancies should continue for up to 6 months or until initiation of another anti-neoplastic therapy. 
Nakon prekida primjene dabrafeniba, potrebno je nastaviti s praćenjem sekundarnih/rekurentnih zloćudnih bolesti koje ne zahvaćaju kožu u razdoblju do 6 mjeseci ili do početka druge protutumorske terapije.
After an oral dose, the major route of elimination of dabrafenib is metabolism, mediated via CYP3A4 and CYP2C8. 
Nakon oralne doze, glavni put eliminacije je metabolizam, posredovan s CYP3A4 i CYP2C8.
The trametinib 2 mg once daily and dabrafenib 150 mg twice daily combination demonstrated limited clinical activity in patients who had progressed on a BRAF inhibitor. 
Kombinacija trametiniba 2 mg jedanput na dan i dabrafeniba 150 mg dvaput na dan pokazala je ograničenu kliničku aktivnost u bolesnika u kojih je došlo do progresije tijekom terapije BRAF inhibitorom.
The investigator-assessed confirmed response rate was 15% (95% CI: 4.4, 34.9) and the median PFS was 3.6 months (95% CI: 1.9, 5.2). 
Potvrđena stopa odgovora prema procjeni ispitivača bila je 15% (95% CI: 4,4, 34,9), a medijan PFS-a bio je 3,6 mjeseci (95% CI: 1,9, 5,2).
The median time to diagnosis of the first occurrence of cuSCC in study MEK115306 was 223 days (range 56 to 510 days) in the combination therapy arm and 60 days (range 9 to 653 days) in the dabrafenib monotherapy arm. 
Medijan vremena do dijagnosticiranja prve pojave cuSCC-a u ispitivanju MEK115306 je bio 223 dana (raspon od 56 do 510 dana) u skupini koja je primala kombiniranu terapiju i 60 dana (raspon od 9 do 653 dana) u skupini koja je primala dabrafenib kao monoterapiju.
The primary endpoint of the study was progression-free survival (PFS), with a key secondary endpoint of overall survival (OS). 
Mjera primarnog ishoda u ispitivanju bila je preživljenje bez progresije (engl. progression-free survival, PFS), a ključna mjera sekundarnog ishoda ukupno preživljenje (engl. overall survival, OS).
Duration of response, median, months (95% CI) N=28 5.1 (3.7, NR) 
Trajanje odgovora, medijan, mjeseci (95% CI) N=28 5,1 (3,7; ND)
• halo (seeing a blurred outline around objects) 
• svjetlosne krugove (mutni rubovi oko predmeta)
Figure 2 Kaplan-Meier overall survival curves for Study MEK116513 
Slika 2 Kaplan-Meier krivulje ukupnog preživljenja za ispitivanje MEK116513
In vitro, dabrafenib is a mechanism based inhibitor of CYP3A4. 
In vitro, dabrafenib je inhibitor s djelovanjem na mehanizam CYP3A4.
• Thickening of the outer layer of the skin (hyperkeratosis), patches of thick, scaly, or crusty skin 
• zadebljanje vanjskog sloja kože (hiperkeratoza), debeli ljuskasti ili korasti dijelovi kože
Hypophosphataemia has been reported commonly in the integrated safety population of dabrafenib monotherapy (7%) and of dabrafenib in combination with trametinib (4%). 
Hipofosfatemija je prijavljivana često u objedinjenoj populaciji u kojoj se ispitivala sigurnost monoterapije dabrafenibom (7%) i dabrafeniba u kombinaciji s trametinibom (4%).
Dabrafenib as monotherapy or in combination with trametinib is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation (see sections 4.4 and 5.1). 
Dabrafenib kao monoterapija ili u kombinaciji s trametinibom indiciran je u liječenju odraslih bolesnika s neoperabilnim ili metastatskim melanomom s BRAF V600 mutacijom (vidjeti dijelove 4.4 i 5.1).
Use caution if strong inhibitors (e.g. ketoconazole, gemfibrozil, nefazodone, clarithromycin, ritonavir, saquinavir, telithromycin, itraconazole, voriconazole, posaconazole, atazanavir) are co-administered with dabrafenib. 
Potreban je oprez pri istovremenoj primjeni snažnih inhibitora (npr. ketokonazol, gemfibrozil, nefazodon, klaritromicin, ritonavir, sakvinavir, telitromicin, itrakonazol, vorikonazol, posakonazol, atazanavir) s dabrafenibom.
• Antibiotics (e.g. clarithromycin, doxycycline) 
• Antibiotike (npr. klaritromicin, doksiciklin)
• Calcium channel blockers (e.g. diltiazem, felodipine, nicardipine, nifedipine, verapamil) 
• Blokatore kalcijevih kanala (npr. diltiazem, felodipin, nikardipin, nifedipin, verapamil)
The usual dose of Tafinlar either used alone or in combination with trametinib is two 75 mg capsules twice a day (corresponding to a daily dose of 300 mg). 
Uobičajena doza lijeka Tafinlar bilo kad se uzima sam ili u kombinaciji s trametinibom su dvije kapsule od 75 mg dva puta dnevno (odgovara dnevnoj dozi od 300 mg).
The efficacy and safety of the recommended dose of trametinib (2 mg once daily) in combination with dabrafenib (150 mg twice daily) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation was studied in two Phase III trials and one supportive Phase I/II study. 
Djelotvornost i sigurnost preporučene doze trametiniba (2 mg jedanput na dan) u kombinaciji s dabrafenibom (150 mg dvaput na dan) za liječenje odraslih bolesnika s neoperabilnim ili metastatskim melanomom s BRAF V600 mutacijom proučavale su se u dva ispitivanja faze III i jednom potpornom ispitivanju faze I/II.
Decreased LVEF has been reported in 6% (65/1076) of patients in the integrated safety population of dabrafenib in combination with trametinib. 
Smanjenje LVEF prijavljeno je u 6% (65/1076) bolesnika u objedinjenoj populaciji u kojoj se ispitivala sigurnost dabrafeniba u kombinaciji s trametinibom.
Tell your doctor as soon as possible if you get any of these symptoms, either for the first time or if they get worse. 
Potrebno je obavijestiti liječnika čim prije ako dobijete bilo koji od tih simptoma, bilo po prvi put ili ako se pogoršaju.
12.6 (5.8, NE) 
12,6 (5,8; NO)
Table 3 Adverse reactions reported in the integrated safety population of dabrafenib monotherapy in the studies BRF113683 (BREAK-3), BRF113929 (BREAK-MB), BRF113710 (BREAK-2), BRF113220, and BRF112680 (n=578) 
Tablica 3 Nuspojave zabilježene u objedinjenoj populaciji u kojoj se ispitivala sigurnost monoterapije dabrafenibom u ispitivanjima BRF113683 (BREAK-3), BRF113929 (BREAK-MB), BRF113710 (BREAK-2), BRF113220 i BRF112680 (n=578)
Arthralgia was reported very commonly in the integrated safety population of dabrafenib monotherapy (25%) and dabrafenib in combination with trametinib (25%) although these were mainly Grade 1 and 2 in severity with Grade 3 occurring uncommonly (<1%) and no Grade 4 occurrences being reported. 
Artralgija je prijavljivana vrlo često u objedinjenoj populaciji u kojoj se ispitivala sigurnost monoterapije dabrafenibom (25%) i dabrafeniba u kombinaciji s trametinibom (25%) i većinom se radilo o 1. i 2. stupnju težine dok je 3. stupanj zamijećen manje često (< 1%), a događaji 4. stupnja nisu bili zabilježeni.
• Inflammation of the pancreas (causing strong abdominal pain) 
• upala gušterače (uzrokuje jaku bol u trbuhu)
In the integrated safety population of patients with melanoma and advanced NSCLC, cuSCC occurred in 2% (19/1076) of patients receiving dabrafenib in combination with trametinib. 
U objedinjenoj populaciji u kojoj se ispitivala sigurnost bolesnika s melanomom i uznapredovalim NSCLC-om, cuSCC se pojavio u 2% (19/1076) bolesnika koji su primali dabrafenib u kombinaciji s trametinibom.
Pulmonary embolism or deep vein thrombosis can occur when dabrafenib is used in combination with trametinib. 
Plućna embolija ili duboka venska tromboza mogu se javiti kada se dabrafenib koristi u kombinaciji s trametinibom.
Dose adjustment for dabrafenib below 50 mg twice daily is not recommended, whether used as monotherapy or in combination with trametinib. 
Ne preporučuje se prilagodba doze za dabrafenib ispod 50 mg dvaput na dan, bilo da se primjenjuje kao monoterapija ili u kombinaciji s trametinibom.
Exceptions where dose modifications are necessary for only one of the two treatments are detailed below for pyrexia, uveitis, RAS mutation positive non-cutaneous malignancies (primarily related to dabrafenib), left ventricular ejection fraction (LVEF) reduction, retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED) and interstitial lung disease (ILD)/pneumonitis (primarily related to trametinib). 
Iznimke u kojima su prilagodbe doze potrebne za samo jednu od dviju terapija navedene su u nastavku za pireksiju, uveitis, zloćudne bolesti pozitivne na RAS mutaciju koje ne zahvaćaju kožu (u prvom redu povezano s dabrafenibom), smanjenje ejekcijske frakcije lijeve klijetke (engl. left ventricular ejection fraction, LVEF), okluziju mrežnične vene (engl. retinal vein occlusion, RVO), odvajanje pigmentnog epitela mrežnice (engl. retinal pigment epithelial detachment, RPED) i intersticijsku bolest pluća (IBP)/pneumonitis (u prvom redu povezano s trametinibom).
The other side effects that you may see when you take Tafinlar alone are as follows: 
Sljedeće nuspojave mogli biste primijetiti kada uzimate samo Tafinlar:
• skin sore or reddish bump that bleeds or does not heal 
• rana na koži ili crvena kvržica koja krvari ili ne zarasta
Male fertility studies with dabrafenib have not been conducted. 
Ispitivanja plodnosti mužjaka s dabrafenibom nisu provedena.
• some medicines used to treat certain psychiatric conditions, such as haloperidol 
• lijekove koji se koriste za liječenje nekih psihičkih poremećaja, poput haloperidola
Of these patients, 559 were treated with the combination for BRAF V600 mutant melanoma in two randomised Phase III clinical trials, MEK115306 (COMBI-d) and MEK116513 (COMBI-v), 435 were treated with the combination in the adjuvant treatment of Stage III BRAF V600 mutant melanoma after complete resection in a randomised Phase III study BRF115532 (COMBI-AD) and 82 were treated with the combination for BRAF V600 mutant NSCLC in a multi-cohort, non-randomised Phase II study BRF113928 (see section 5.1). 
Od tih je bolesnika njih 559 primalo kombiniranu terapiju za liječenje melanoma s BRAF V600 mutacijom u dva randomizirana klinička ispitivanja faze III, MEK115306 (COMBI-d) i MEK116513 (COMBI-v), 435 je primalo kombiniranu terapiju u adjuvantnom liječenju melanoma stadija III s BRAF V600 mutacijom nakon potpune resekcije u randomiziranom ispitivanju faze III BRF115532 (COMBI-AD) i 82 je primalo kombiniranu terapiju za NSCLC s BRAF V600 mutacijom u nerandomiziranom ispitivanju faze II BRF113928 s više kohorti (vidjeti dio 5.1).
The benefits and risks should be considered before administering dabrafenib in patients with a prior or concurrent cancer associated with RAS mutations. 
Potrebno je pažljivo procijeniti koristi i rizike prije primjene dabrafeniba u bolesnika s rakom povezanim s RAS mutacijama u anamnezi ili postojećim karcinomom.
The majority of patients had a BRAF V600E mutation (91%). 
Većina bolesnika imala je BRAF V600E mutaciju (91%).
As hepatic metabolism and biliary secretion are the primary routes of elimination of dabrafenib and its metabolites, administration of dabrafenib should be undertaken with caution in patients with moderate to severe hepatic impairment (see section 4.2). 
Kako su jetreni metabolizam i izlučivanje putem žuči primarni putevi eliminacije dabrafeniba i njegovih metabolita, dabrafenib treba primjenjivati s oprezom u bolesnika s umjerenim do teškim oštećenjem jetre (vidjeti dio 4.2).
The IUO is an allele-specific polymerase chain reaction (PCR) assay performed on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue. 
IUO je alel-specifičan test lančane reakcije polimerazom (PCR) koji se provodi na DNK izolirane iz tumorskog tkiva fiksiranog u formalinu i uklopljenog u parafin (engl. formalin-fixed paraffin-embedded, FFPE).
Duration of intracranial response, median, months (95% CI) N=29 4.6 (2.8, NR) 
Trajanje intrakranijalnog odgovora, medijan, mjeseci (95% CI) N=29 4,6 (2,8; ND)
For patients with unresectable or metastatic melanoma who received dabrafenib in combination with trametinib and developed pyrexia, approximately half of the first occurrences of pyrexia happened within the first month of therapy and approximately one-third of the patients had 3 or more events. 
U bolesnika s neoperabilnim ili metastatskim melanomom koji su primali dabrafenib u kombinaciji s trametinibom i razvili pireksiju, otprilike polovica prvih pojavljivanja pireksije dogodila se tijekom prvog mjeseca liječenja i otprilike jedna trećina bolesnika je imala 3 ili više događaja.
In the Phase II and III clinical trials, screening for eligibility required central testing for BRAF V600 mutation using a BRAF mutation assay conducted on the most recent tumour sample available. 
U kliničkim ispitivanjima faze II i faze III, probir bolesnika za uključivanje zahtijevao je centralno testiranje na BRAF V600 mutacije pomoću BRAF mutacijskog testa koji se provodio na zadnjem raspoloživom uzorku tumora.
Trametinib is not recommended if you have ever had a blockage of the vein draining the eye (retinal vein occlusion). 
Trametinib se ne preporučuje ako ste ikada imali začepljenje vene koja odvodi krv iz oka (okluziju mrežnične vene).
efavirenz, fosamprenavir, lopinavir, nelfinavir, tipranavir, saquinavir and atazanavir 
delavirdina, efavirenza, fosamprenavira, lopinavira, nelfinavira, tipranavira, sakvinavira i atazanavira
• Inflammation of the lung (pneumonitis) 
• upala pluća (pneumonitis)
The majority of subjects had a BRAF V600E mutation (85%). 
Većina ispitanika imala je BRAF V600E mutaciju (85%).