natgillin/translations-raw huggingface dataset:
The overall survival hazard ratio in patients < 65 years of age was 0.68 (95% CI 0.55, 0.85) and in patients 65 years of age and older it was 0.95 (95% CI 0.76, 1.19). 
Omjer hazarda za ukupno preživljenje u bolesnika u dobi ispod 65 godina bio je 0,68 (95% CI 0,55; 0,85), a u bolesnika starih 65 godina i više bio je 0,95 (95% CI 0,76; 1,19).
Patients with severe diarrhoea may require interruption and dose reduction or discontinuation of therapy with GIOTRIF (see section 4.2). 
Bolesnici s teškim proljevom mogu zahtijevati prekid i smanjenje doze ili trajni prekid liječenja GIOTRIFOM (vidjeti dio 4.2).
Figure 1: Kaplan-Meier curve for PFS by independent review by treatment group in trial LUX-Lung 3 (Overall Population) 
Slika 1: Kaplan-Meierova krivulja za PFS na temelju nezavisne procjene po liječenim skupinama u ispitivanju LUX-Lung 3 (Ukupna populacija)
Each blister contains 7 x 1 film-coated tablets and is packed in an aluminium pouch together with a desiccant sachet that should not be swallowed. 
Svaki blister sadrži 7 x 1 filmom obloženu tabletu te je pakiran u aluminijskoj vrećici zajedno s vrećicom sa sredstvom za sušenje koje se ne smije progutati.
Exposure to afatinib moderately increased with lowering of the creatinine clearance (CrCL, calculated according to Cockcroft Gault), i.e. for a patient with a CrCL of 60 mL/min or 30 mL/min exposure (AUCτ,ss) to afatinib increased by 13% and 42%, respectively, and decreased by 6% and 20% for a patient with CrCL of 90 mL/min or 120 mL/min, respectively, compared to a patient with the CrCL of 79 mL/min (median CrCL of patients in the overall patient population analysed). 
Izloženost afatinibu se umjereno povećala sa sniženjem klirensa kreatinina (CrCL, izračunato prema Cockcroft Gaultu), tj. u bolesnika s CrCL-om od 60 ml/min ili 30 ml/min izloženost (AUCτ,ss) afatinibu se povećala za 13% odnosno 42%, a smanjila za 6% i 20% u bolesnika s CrCL-om od 90 ml/min odnosno 120 ml/min, u usporedbi s bolesnicima s CrCL-om od 79 ml/min (medijan CrCL bolesnika u ukupnoj analiziranoj bolesničkoj populaciji).
Pre-treatment with rifampicin (600 mg once daily for 7 days), a potent inducer of P-gp, decreased the plasma exposure to afatinib by 34% (AUC0-∞) and 22% (Cmax) after administration of a single dose of 40 mg GIOTRIF. 
Prethodno liječenje rifampicinom (600 mg jedanput dnevno u trajanju od 7 dana), snažnim induktorom P-gp-a, smanjilo je izloženost afatinibu u plazmi za 34% (AUC0-∞) i 22% (Cmax) nakon primjene jednostruke doze od 40 mg GIOTRIFA.
Alanine aminotransferase increased 
Povišene vrijednosti alanin aminotransferaze
If treatment for rash is not working and the rash is getting more severe (for example, you have peeling or blistering of the skin) you should notify your doctor immediately, since your doctor may decide to stop your treatment with GIOTRIF. 
Ako liječenje osipa ne djeluje i osip postaje sve teži (na primjer, koža Vam se ljušti ili dobivate mjehuriće na koži), potrebno je odmah obavijestiti liječnika jer
Exposure to afatinib is not significantly changed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment (see section 5.2). 
Izloženost afatinibu ne mijenja se značajno u bolesnika s blagim (Child Pugh A) ili umjerenim (Child Pugh B) oštećenjem jetre (vidjeti dio 5.2).
The pharmacokinetics of afatinib have not been studied in subjects with severe (Child Pugh C) hepatic dysfunction (see section 4.4). 
Farmakokinetika afatiniba nije ispitivana na pojedincima s teškom (Child Pugh C) disfunkcijom jetre (vidjeti dio 4.4).
Each blister is packed together with a desiccant sachet in a laminated aluminium pouch and contains 7 x 1 film-coated tablets. 
Jedan blister je pakiran zajedno s vrećicom u kojoj je sredstvo za sušenje u laminiranu aluminijsku vrećicu te sadrži 7 x 1 filmom obloženu tabletu.
• if you have a history of eye problems such as severe dry eyes, inflammation of the transparent layer at the front of the eye (cornea) or ulcers involving the outer part of the eye, or if you use contact lenses. 
• ako imate pozitivnu anamnezu bolesti očiju, kao sindrom suhog oka, upale prozirnog sloja na prednjoj strani oka (kornea) ili ranice koje uključuju vanjski dio oka, ili ako koristite kontaktne leće.
This medicinal product is for oral use. 
Ovaj lijek je namijenjen za peroralnu primjenu.
Second-line GIOTRIF significantly improved PFS and OS of patients with squamous NSCLC compared to erlotinib. 
Druga linija GIOTRIFA značajno je poboljšala PFS i OS bolesnika sa skvamoznim NSCLC u usporedbi s erlotinibom.
No dose adjustment 
Bez prilagodbe doze
GIOTRIF 20 mg film-coated tablets GIOTRIF 30 mg film-coated tablets GIOTRIF 40 mg film-coated tablets GIOTRIF 50 mg film-coated tablets 
GIOTRIF 20 mg filmom obložene tablete GIOTRIF 30 mg filmom obložene tablete GIOTRIF 40 mg filmom obložene tablete GIOTRIF 50 mg filmom obložene tablete
Table 2 summarises the frequencies of ADRs from all NSCLC trials and from post-marketing experience with daily GIOTRIF doses of 40 mg or 50 mg as monotherapy. 
Tablica 2 prikazuje sažeti pregled učestalosti nuspojava na lijek iz svih ispitivanja NSCLC-a te iz iskustva nakon stavljanja lijeka u promet, s dnevnim dozama GIOTRIFA od 40 mg ili 50 mg u obliku monoterapije.
® EGFR RGQ PCR Kit, Qiagen Manchester Ltd. 
RGQ, Qiagen Manchester Ltd.
In patients with tumours harbouring either G719X (N=18), L861Q (N=16), or S768I substitution mutation (N=8), the confirmed ORR was 72.2%, 56.3%, 75.0%, respectively, and the median duration of response was 13.2 months, 12.9 months and 26.3 months, respectively. 
U bolesnika s tumorima koji su imali supstitucijsku mutaciju G719X (N=18), L861Q (N=16) ili S768I (N=8), potvrđeni ORR iznosio je 72,2%, 56,3% odnosno 75,0%, a medijan trajanja odgovora bio je 13,2 mjeseca, 12,9 mjeseci odnosno 26,3 mjeseca.
In patients with cardiac risk factors and those with conditions that can affect LVEF, cardiac monitoring, including an assessment of LVEF at baseline and during treatment, should be considered. 
Kod bolesnika s čimbenicima rizika za razvoj srčanih bolesti i bolesnika sa stanjima koja mogu utjecati na LVEF, potrebno je razmotriti praćenje srčane funkcije, uključujući procjenu LVEF-a na početku i tijekom liječenja.
Animal studies with afatinib did not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 
Ispitivanja na životinjama s afatinibom ne ukazuju na izravan ili neizravan učinak na reprodukciju (vidjeti dio 5.3).
Patients were randomised (2:1) to receive GIOTRIF 40 mg once daily or up to 6 cycles of pemetrexed/cisplatin. 
Bolesnici su bili randomizirani (2:1) u grupu liječenu GIOTRIFOM 40 mg jedanput dnevno ili do 6 ciklusa pemetreksed/cisplatina.
LUX-Lung 7 is a randomised, global, open label Phase IIb trial investigating the efficacy and safety of GIOTRIF in patients with locally advanced or metastatic lung adenocarcinoma (stage IIIB or IV) with EGFR mutations in the first-line setting. 
LUX-Lung 7 je randomizirano, globalno, otvoreno ispitivanje faze IIb koje je istraživalo djelotvornost i sigurnost primjene GIOTRIFA u prvoj liniji liječenja bolesnika s lokalno uznapredovalim ili metastatskim adenokarcinomom pluća (stadij IIIB ili IV) s EGFR mutacijama.
Table 7: PFS and OS efficacy results of GIOTRIF vs pemetrexed/cisplatin (LUX-Lung 3) gemcitabine/cisplatin (LUX-Lung 6) in the pre-defined EGFR mutation subgroups Del 19 and L858R (Independent review) 
Tablica 7: Rezultati djelotvornosti za PFS i OS za GIOTRIF naspram kombinacije pemetreksed/cisplatin (LUX-Lung 3) i gemcitabin/cisplatin (LUX-Lung 6) u prethodno definiranim podskupinama EGFR mutacija Del 19 i L858R (nezavisna procjena)
The efficacy and safety of GIOTRIF as second-line treatment for patients with advanced NSCLC of squamous histology was investigated in a randomized open-label global Phase III trial LUX-Lung 8. 
Djelotvornost i sigurnost GIOTRIFA kao druge linije liječenja za bolesnike s uznapredovalim NSCLC sa skvamoznim stanicama u histološkom nalazu istraženi su u randomiziranom otvorenom globalnom ispitivanju faze III LUX-Lung 8.
4 Any Grade 
4 Svaki stupanj
PFS benefit was accompanied by improvement in disease-related symptoms and delayed time to deterioration (see Table 11). 
Korist u PFS-u bila je popraćena poboljšanjem simptoma izazvanih bolešću, te odgodom vremena do pogoršanja (vidjeti tablicu 11).
If you stop taking GIOTRIF 
Ako prestanete uzimati GIOTRIF
Among the patients randomised, 62% were female, the median age was 63 years, 16% of patients had brain metastases, the baseline ECOG performance status was 0 (31%) or 1 (69%), 57% were Asian and 43% were non-Asian. 
Među randomiziranim bolesnicima, 62% su bile žene, medijan dobi je bio 63 godine, 16% bolesnika je imalo metastaze u mozgu, početno funkcionalno stanje ECOG bilo je 0 (31%) ili 1 (69%), 57% su bili azijati, a 43% neazijati.
In patients treated with once daily GIOTRIF 40 mg, dose reductions due to ADRs occurred in 57% of the patients in the LUX-Lung 3 trial and in 25% of the patients in the LUX-Lung 8 trial. 
Kod bolesnika liječenih GIOTRIFOM 40 mg jedanput dnevno smanjenje doze zbog nuspojava na lijek bilo je potrebno kod 57% bolesnika u ispitivanju LUX-Lung 3 te kod 25% bolesnika u ispitivanju LUX-Lung 8.
• Nail infection 
• Infekcija nokta
In patients with tumours harbouring de-novo T790M mutations (N=14) the confirmed ORR was 14.3% and the median duration of response was 8.3 months. 
U bolesnika čiji su tumori nosili de-novo mutacije T790M (N=14) potvrđeni ORR iznosio je 14,3%, a medijan trajanja odgovora bio je 8,3 mjeseca.
PFS benefit was accompanied by improvement in disease-related symptoms and delayed time to deterioration (see Table 8). 
Korist u PFS-u bila je popraćena poboljšanjem simptoma izazvanih bolešću, te odgodom vremena do pogoršanja (vidjeti tablicu 8).
You should have antidiarrhoeal medicine available prior to taking GIOTRIF. 
Morate imati lijek protiv proljeva prije nego započnete liječenje GIOTRIFOM.
Co-administration of a high-fat meal with GIOTRIF resulted in a significant decrease of exposure to afatinib by about 50% in regard to Cmax and 39% in regard to AUC0-∞. 
Istodobna primjena GIOTRIFA i obroka bogatog visokim udjelom masnoća rezultirala je značajnim smanjenjem izloženosti afatinibu za oko 50% Cmax,odnosno za oko 39% AUC0-∞.
In vitro studies indicated that afatinib is a substrate and an inhibitor of the transporter BCRP. 
In vitro ispitivanja su pokazala da je afatinib supstrat i inhibitor prijenosnika BCRP-a.
The embryo-foetal development studies performed on afatinib revealed no indication of teratogenicity. 
Ispitivanja embrio-fetalnog razvoja provedena s afatinibom nisu otkrila rizik teratogenosti.
Posology The recommended dose is 40 mg once daily. 
Doziranje Preporučena doza je 40 mg jedanput dnevno.
Patients were screened for the presence of activating EGFR mutations (Del 19 and/or L858R) using the TheraScreen 
U bolesnika je napravljen probir za prisutnost aktivirajućih EGFR mutacija (Del 19 i/ili L858R) pomoću PCR kompleta TheraScreen
values presented for GIOTRIF vs. erlotinib, p-value based on logistic regression b p-value for time to deterioration based on stratified log-rank test c p-values were not adjusted for multiplicity 
vrijednosti predstavljene za GIOTRIF naspram erlotiniba; p-vrijednost temeljena na logističkoj regresiji p-vrijednost za vrijeme do pogoršanja temeljena na stratificiranom log-rank testu p-vrijednosti nisu bile prilagođene za višestruke usporedbe
CR=complete response; PR=partial response p-value for PFS/OS based on stratified log-rank test; p-value for Objective Response Rate based on logistic regression 
CR = potpuni odgovor; PR = djelomični odgovor p-vrijednost za PFS/OS temeljena na stratificiranom log-rank testu; p-vrijednost za stopu objektivnog odgovora temeljena na logističkoj regresiji
Symptoms such as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye should be referred promptly to an ophthalmology specialist. 
Bolesnici kod kojih se pojavi akutna upala oka ili njezino pogoršanje, suzenje, preosjetljivost na svjetlost, zamagljeni vid, bol u očima i/ili crvenilo očiju moraju se odmah uputiti oftalmologu.
If you forget to take GIOTRIF 
Ako ste zaboravili uzeti GIOTRIF
Effects of P-gp inducers on afatinib 
P-gp induktora na afatinib
• If your next scheduled dose is more than 8 hours away, take the missed dose as soon as you remember. 
• Ako je Vaša sljedeća doza za više od 8 sati, uzmite zaboravljenu dozu čim se sjetite.
The PFS hazard ratio for patients with DEL 19 mutations and L858R mutations was 0.76 (95% CI [0.55, 1.06]; p=0.1071), and 0.71 (95% CI [0.47, 1.06]; p=0.0856) respectively for afatinib vs gefitinib. 
Omjer hazarda (HR) za PFS za bolesnike s mutacijama DEL 19 i mutacijama L858R bio je 0,76 (95% CI [0,55; 1,06]; p=0,1071) i 0,71 (95% CI [0,47; 1,06]; p=0,0856) za afatinib naspram gefitiniba.
Among the patients randomised, 65% were female, the median age was 61 years, the baseline ECOG performance status was 0 (39%) or 1 (61%), 26% were Caucasian and 72% were Asian. 
Među randomiziranim bolesnicima, 65% su bile žene, medijan dobi je bio 61 godina, početno ECOG funkcionalno stanje bilo je 0 (39%) ili 1 (61%), a 26% su bili bijelci i 72% azijati.
No starting dose adjustments appear necessary in patients with mild or moderate hepatic impairment (see section 4.2). 
Ne smatra se da je potrebna prilagodba početne doze lijeka kod bolesnika s blagim ili umjerenim oštećenjem jetre (vidjeti dio 4.2).
At the time of the analysis, 14 Nov 2013, 176 patients (76.5%) in the afatinib arm and 70 patients (60.9%) in the chemotherapy arm experienced an event contributing to the PFS analysis, i.e. disease progression as determined by central independent review or death. 
U vrijeme analize, 14. studenog 2013., u 176 bolesnika (76,5%) iz skupine u kojoj se primjenjivao afatinib te u 70 bolesnika (60,9%) iz skupine u kojoj se primjenjivala kemoterapija došlo je do događaja koji doprinosi
Table 9: Efficacy results of GIOTRIF vs. gefitinib (LUX-Lung 7) based on primary analysis as of August 
Tablica 9: Rezultati djelotvornosti primjene GIOTRIFA naspram gefitiniba (LUX-Lung 7) na temelju primarne analize iz kolovoza 2015.
Grade 2 ALT elevations occurred in 1% and Grade 3 elevations occurred in 0.8% of patients treated with GIOTRIF (see section 4.4). 
Povećanje ALT-a stupnja 2 javilo se kod 1% bolesnika, a povećanje ALT-a stupnja 3 javilo se kod 0,8% bolesnika liječenih GIOTRIFOM (vidjeti dio 4.4).
Exposure to afatinib was found to be increased in patients with moderate or severe renal impairment (see section 5.2). 
Izloženost afatinibu je bila povećana u bolesnika s umjerenim ili teškim oštećenjem bubrega (vidjeti dio 5.2).
In patients with tumours harbouring exon 20 insertions (N=23) the confirmed ORR was 8.7% and the median duration of response was 7.1 months. 
U bolesnika čiji su tumori nosili insercije u egzonu 20 (N=23) potvrđeni ORR iznosio je 8,7%, a medijan trajanja odgovora iznosio je 7,1 mjesec.
Table 10: Efficacy results for GIOTRIF vs erlotinib in LUX-Lung 8, based on primary analysis of OS, including all randomized patients 
Tablica 10: Rezultati djelotvornosti za GIOTRIF naspram erlotiniba u ispitivanju LUX-LUNG 8 na temelju primarne analize ukupnog preživljenja koja je uključivala sve randomizirane bolesnike.
In the pre-defined subgroup of common mutations (combined Del 19 and L858R) for GIOTRIF and chemotherapy, the median PFS was 13.6 months vs. 6.9 months (HR 0.48; 95% CI 0.35-0.66; p<0.0001; N=307) in LUX-Lung 3, and 11.0 months vs. 5.6 months (HR 0.24; 95% CI 0.17-0.35; p<0.0001; N=324) in LUX-Lung 6, respectively. 
U prethodno definiranoj podskupini čestih mutacija (kombinirane Del 19 i L858R) za GIOTRIF i kemoterapiju, medijan PFS-a je bio 13,6 mjeseci naspram 6,9 mjeseci (HR 0,48; 95% CI 0,35 - 0,66; p < 0,0001; N = 307) u ispitivanju LUX-Lung 3, odnosno 11,0 mjeseci naspram 5,6 mjeseci (HR 0,24; 95% CI 0,17 - 0,35; p < 0,0001; N = 324) u ispitivanju LUX-Lung 6.
In LUX-Lung-3 Grade 3 ALT/AST elevations were about 3.5 fold higher in patients with abnormal baseline liver tests. 
U ispitivanju LUX-Lung 3 porast ALT/AST stupnja 3 bio je za oko 3,5 vrijednosti porasta veći kod bolesnika s patološkim početnim vrijednostima jetrenih enzima.
Dyspepsia Cheilitis 
Dispepsija Heilitis
Dermatitis acneiform 
Akneiformni dermatitis
The most frequent ADRs were diarrhoea and skin related adverse events (see section 4.4) as well as stomatitis and paronychia (see also Table 3, 4 and 5). 
Pregled svih nuspojava prikazan je u tablici 2. Najčešće nuspojave na lijek bile su proljev i nuspojave povezane s kožom (vidjeti dio 4.4) kao i stomatitis, te paronihija (vidjeti također tablicu 3, 4 i 5).
Tell your doctor if you have sudden or worsening of eye symptoms such as pain or redness or dry eye. 
Obavijestite liječnika ako razvijete iznenadne simptome bolesti oka, kao što su bol, crvenilo i suhoća oka, ili ako dođe do njihovog pogoršanja.
Patients were screened for the presence of 29 different EGFR mutations using a polymerase chain reaction (PCR)-based method (TheraScreen 
Bolesnici su provjereni na prisutnost 29 različitih EGFR mutacija uz upotrebu metode temeljene na lančanoj reakciji polimeraze (PCR) (TheraScreen EGFR29 Mutation Kit, Qiagen Manchester Ltd).
Very common ADRs in GIOTRIF-treated patients occurring in at least 10% of patients in trial LUX-Lung 3 and LUX-Lung 7 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Tables 3 and 4. 
Vrlo česte nuspojave na lijek u bolesnika liječenih GIOTRIFOM koje su se javile kod najmanje 10% bolesnika u ispitivanju LUX-Lung 3 i LUX-Lung 7 prikazane su u tablicama 3 i 4 prema stupnjevima Zajedničkih kriterija toksičnosti Nacionalnog instituta za rak (NCI-CTC).
If P-gp inhibitors need to be taken, they should be administered using staggered dosing, i.e. the P-gp inhibitor dose should be taken as far apart in time as possible from the GIOTRIF dose. 
P-gp inhibitora se mora uzeti sa što je moguće duljim vremenskim razmakom od uzimanja doze GIOTRIFA.
Based on in vitro data, afatinib is a moderate inhibitor of P-gp. 
Na osnovi in vitro podataka, afatinib je umjereni P-gp inhibitor.
7.7 vs. 1.7 HR 0.53; p<0.0001 
7,7 naspram 1,7 HR 0,53; p< 0,0001
In three clinical trials of GIOTRIF with prospective tumour genotyping (Phase 3 trials LUX-Lung 3 and -6, and single arm Phase 2 trial LUX-Lung 2), an analysis was conducted of data from a total of 75 TKI-naïve patients with advanced (stage IIIb-IV) lung adenocarcinomas harbouring uncommon EGFR mutations, which were defined as all mutations other than Del 19 and L858R mutations. 
Analiza djelotvornosti GIOTRIFA u bolesnika koji prethodno nisu bili liječeni EGFR TKI-om, a čiji su tumori imali manje česte mutacije EGFR-a (LUX-Lung 2, -3 i -6) U tri klinička ispitivanja GIOTRIFA s prospektivnom genotipizacijom tumora (ispitivanja faze 3 LUX-Lung 3 i -6 te ispitivanje faze 2 LUX-Lung 2 provedeno u jednoj skupini), provedena je analiza u ukupno 75 bolesnika koji prethodno nisu bili liječeni EGFR TKI-om, a imali su uznapredovali (stadij IIIb-IV) adenokarcinom pluća s manje čestim mutacijama EGFR-a, koje su bile definirane kao sve mutacije osim mutacija Del 19 i L858R.
MDRD formula) had an exposure of 122% (Cmax) and 150% (AUC0-tz) in comparison to their healthy controls. 
Modification of Diet in Renal Disease) imali su izloženost 101% (Cmax) i 122% (AUC0-tz) u usporedbi s njihovim zdravim kontrolama.
4.2 vs. 3.1 HR 0.83; p=0.1882 
4,2 naspram 3,1 HR 0,83; p= 0,1882
71% vs. 48%; p<0.0001 
71% naspram 48%; p<0,0001
40% vs. 39%; p=0.7752 
40% naspram 39%; p=0,7752
If any of these apply to you, your doctor may monitor you more closely as the side effects may be more pronounced. 
Liječnik će Vas pažljivije pratiti ako imate nešto od spomenutog jer postoji mogućnost da nuspojave budu izraženije.
They should therefore be taken as far apart in time as possible from GIOTRIF. 
Stoga se oni moraju uzimati što je prije ili poslije GIOTRIFA moguće.
Interactions with drug uptake transport systems 
Interakcije s prijenosnim sustavima lijekova
In general, rash manifests as a mild or moderate erythematous and acneiform rash, which may occur or worsen in areas exposed to sun. For patients who are exposed to sun, protective clothing, and use of sun screen is advisable. 
Općenito, osip se manifestira u obliku blagog ili umjerenog eritematoznog i akneiformnog osipa koji se može pojaviti ili pogoršati na područjima koja su izložena suncu.
GIOTRIF significantly improved PFS and ORR in EGFR mutation positive patients compared to gefitinib. 
GIOTRIF je značajno poboljšao PFS i ORR u bolesnika s EGFR mutacijom u usporedbi s gefitinibom.
LUX-Lung 2 was a single arm Phase II trial in 129 EGFR TKI-naïve patients with stage IIIB or IV lung adenocarcinoma with EGFR mutations. 
LUX-Lung 2 je bilo ispitivanje faze II provedeno na jednoj skupini od 129 bolesnika koji prethodno nisu bili liječeni EGFR TKI-om s adenokarcinomom pluća stadija IIIB ili IV i EGFR mutacijama.
Table 11: Symptom outcomes for GIOTRIF vs. erlotinib in trial LUX-Lung 8 (EORTC QLQ-C30 & QLQ-LC13) 
Tablica 11: Ishodi vezani uz simptome za GIOTRIF naspram erlotiniba u ispitivanju LUX-Lung 8 (EORTC QLQ-C30 & QLQ-LC13)
When to take GIOTRIF 
Kada uzeti GIOTRIF
Patients with mild and moderate hepatic impairment as identified by abnormal liver tests did not correlate with any significant change in afatinib exposure. 
Abnormalan nalaz jetrenih enzima u bolesnika s blagim do umjerenim oštećenjem jetre nije bio u korelaciji niti s jednom značajnom promjenom u izloženosti afatinibu.
Enzyme-catalyzed metabolic reactions play a negligible role for afatinib in vivo. 
Metaboličke reakcije katalizirane enzimima imaju zanemarivu ulogu za afatinib in vivo.
67% vs. 60%; p=0.2133 
67% naspram 60%; p=0,2133
Subjects with moderate renal impairment (n=8; eGFR 30-59 mL/min/1.73m², according to the Modification of Diet in Renal Disease [MDRD] formula) had an exposure of 101% (Cmax) and 122% (AUC0-tz) in comparison to their healthy controls. 
Ispitanici s teškim oštećenjem bubrega (n=8; eGFR 15-29 ml/min/1,73 m2, sukladno jednadžbi MDRD) imali su izloženost 122% (Cmax) i 150% (AUC0-tz) u usporedbi s njihovim zdravim kontrolama.
31.1 vs. 10.3 HR 0.46; p=0.0001 
31,1 naspram 10,3 HR 0,46; p= 0,0001
Table 5: Very common ADRs in trial LUX-Lung 8* GIOTRIF (40 mg/day) 
Tablica 4: Vrlo česte nuspojave u ispitivanju LUX-Lung 7 GIOTRIF (40 mg/dan)
Monitor patients with severe renal impairment (eGFR 15-29 mL/min/1.73m²) and adjust GIOTRIF dose if not tolerated. 
Potrebno je nadzirati bolesnike s teškim oštećenjem bubrega (eGFR 15-29 ml/min/1,73 m 2) i prilagoditi dozu GIOTRIFA
Skin related adverse events 
Nuspojave povezane s kožom
GIOTRIF (40 mg/day) N=229 
GIOTRIF (40 mg/dan) N=229
Mothers should be advised against breast-feeding while receiving this medicinal product. 
Majkama se mora savjetovati da ne doje tijekom primjene ovog lijeka.
Interstitial Lung Disease (ILD) 
Bolest plućnog intersticija (BPI)
Table 8: Symptom outcomes for GIOTRIF vs. chemotherapy in trials LUX-Lung 3 and LUX-Lung 6 (EORTC QLQ-C30 & QLQ-LC13) 
Tablica 8: Ishodi simptoma za GIOTRIF naspram kemoterapije u ispitivanjima LUX-Lung 3 i LUX-Lung 6 (EORTC QLQ-C30 i QLQ-LC13)
GIOTRIF in patients with NSCLC of squamous histology 
GIOTRIF kod bolesnika s NSCLC sa skvamoznim stanicama u histološkom nalazu
Patients with a history of ILD have not been studied. 
Bolesnici s anamnezom BPI-a nisu bili ispitivani.
PHARMACEUTICAL FORM AND CONTENTS 7 x 1 film-coated tablets 
OBLIK I SADRŽAJ 7 x 1 filmom obložena tableta 14 x 1 filmom obložena tableta 28 x 1 filmom obložena tableta
27.0 vs. 8.0 HR 0.60; p=0.0062 
27,0 naspram 8,0 HR 0,60; p= 0,0062
In the first-line setting, the efficacy and safety of GIOTRIF in patients with EGFR mutation-positive locally advanced or metastatic NSCLC (stage IIIB or IV) were assessed in a global, randomised, multicentre, open-label trial. 
U prvoj liniji, djelotvornost i sigurnost GIOTRIFA ocjenjivani su kod bolesnika s lokalno uznapredovalim ili metastatskim NSCLC-om (stadij IIIB ili IV) pozitivnim na EGFR mutaciju u sklopu globalnog, randomiziranog, multicentričnog, otvorenog ispitivanja.