natgillin/translations-raw huggingface dataset:
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 filmsko obložene tablete GIOTRIF 30 mg filmsko obložene tablete GIOTRIF 40 mg filmsko obložene tablete GIOTRIF 50 mg filmsko obložene tablete
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. 
Pri bolnikih s tumorji, ki so nosilci mutacij bodisi v G719X (N = 18), L861Q (N = 16) ali substitucijske mutacije S768I (N = 8), je bila potrjena stopnja objektivnega odziva na zdravljenje (ORR) 72,2 %, 56,3 % oziroma 75,0 %, mediana trajanja odziva pa 13,2, 12,9 oziroma 26,3 meseca.
If you become pregnant while receiving this medicine, you should immediately inform your doctor. 
Če med zdravljenjem s tem zdravilom zanosite, nemudoma obvestite zdravnika.
Bullous, blistering and exfoliative skin conditions have been reported including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis. 
Poročali so o buloznih, mehurjastih in eksfoliativnih kožnih obolenjih, tudi o redkih primerih, ki so kazali na Stevens-Johnsonov sindrom in toksično epidermalno nekrolizo.
EGFR mutation status should be established prior to initiation of GIOTRIF therapy (see section 4.4). 
Pred začetkom zdravljenja z zdravilom GIOTRIF je treba določiti stanje mutacije EGFR (glejte poglavje 4.4).
Skin related adverse events 
S kožo povezani neželeni dogodki
• St. John's wort (Hypericum perforatum), a herbal medicine to treat depression. 
• šentjanževka (Hypericum perforatum), zeliščno zdravilo za zdravljenje depresije,
Grade 2 ALT elevations occurred in 1% and Grade 3 elevations occurred in 0.8% of patients treated with GIOTRIF (see section 4.4). 
Povečanje vrednosti ALT stopnje 2 se je pojavilo pri 1 % bolnikov, povišanje stopnje 3 pa pri 0,8 % bolnikov, zdravljenih z zdravilom GIOTRIF (glejte poglavje 4.4).
Use of P-glycoprotein (P-gp) inhibitors 
Uporaba zaviralcev P-glikoproteina (P-gp)
In these patients, confounding factors have included pre-existing liver disease and/or comorbidities associated with progression of underlying malignancy. 
Dejavniki, ki povečajo nevarnost njenega pojava, so bili pri teh bolnikih obstoječa jetrna bolezen ali sočasne bolezni, ki so povezane z napredovanjem malignosti.
OS results based on primary OS analysis as of April 2016 at event rates of 109 (68.1%) and 117 (73.6%) in the GIOTRIF and gefitinib arms, respectively p-value for PFS/OS based on stratified log-rank test; p-value for Objective Response Rate based on stratified logistic regression 
vrednosti skupnega preživetja (OS) na osnovi primarne analize skupnega preživetja iz aprila 2016 za 109 dogodkov (68,1 %) v skupini z zdravilom GIOTRIF in 117 dogodkov (73,6 %) v skupini z gefitinibom vrednost p za PFS/OS na osnovi stratificiranega testa log-rank; vrednost p za stopnjo objektivnega odziva na zdravljenje na osnovi logistične regresije
PVC/PVDC perforated unit dose blister. 
Perforirani pretisni omot iz PVC/PVDC s posameznimi odmerki.
If you forget to take GIOTRIF 
Če ste pozabili vzeti zdravilo GIOTRIF
Patients were randomised (2:1) to receive GIOTRIF 40 mg once daily or up to 6 cycles of pemetrexed/cisplatin. 
Bolnike so naključno razvrstili (2:1) v skupino z zdravilom GIOTRIF po 40 mg enkrat na dan ali skupino z do 6. cikli zdravljenja s pemetreksedom/cisplatinom.
This could result in a higher risk of developing adverse reactions in particular diarrhoea, rash/acne and stomatitis. 
Njene posledice so lahko večja nevarnost pojava neželenih dogodkov, na primer driske, izpuščaja ali aken in stomatitisa.
There was limited data available for moderate and severe hepatic impairment. 
Za zmerno in hudo jetrno okvaro je bilo na voljo malo podatkov.
Left ventricular dysfunction has been associated with HER2 inhibition. 
Z zaviralci HER2 povezujejo motnje delovanja levega prekata.
The adverse reactions observed at these doses were primarily dermatological (rash/acne) and gastrointestinal events (especially diarrhoea). 
Neželene reakcije na oba odmerka so bile pretežno dermatološke (izpuščaj ali akne) in prebavne narave (zlasti driska).
Animal studies with afatinib did not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 
Študije na živalih ne kažejo neposrednih ali posrednih škodljivih učinkov zdravljenja z afatinibom na sposobnost razmnoževanja (glejte poglavje 5.3).
General disorders and administration site conditions Pyrexia 
Splošne težave in spremembe na mestu aplikacije pireksija
Patients were screened for the presence of activating EGFR mutations (Del 19 and/or L858R) using the TheraScreen 
Bolnike so presejali glede na prisotnost aktivirajočih mutacij EGFR (Del 19 in/ali L858R) z metodo TheraScreen
The total systemic exposure (AUC0-24) in male and female rats was in the range or less than that observed in patients (1.3 times and 0.51 times, respectively). 
Največja možna celokupna sistemska izpostavljenost (AUC0-24) pri podganjih samcih in samicah je bila v enakem razponu ali manjša kot pri bolnikih (1,3-krat oziroma 0,51-krat).
Contact lens use is also a risk factor for keratitis and ulceration (see section 4.8). 
Dejavnik tveganja za pojav keratitisa in razjed je tudi uporaba kontaktnih leč (glejte poglavje 4.8).
Posology The recommended dose is 40 mg once daily. 
Odmerjanje Priporočeni odmerek zdravila je 40 mg enkrat na dan.
Both individuals recovered from these adverse events. 
Oba sta okrevala.
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. 
V preglednici 2 so podatki o pogostnosti neželenih učinkov na zdravilo iz vseh raziskav o NSCLC in iz izkušenj v obdobju trženja, v katerih so bolniki jemali odmerke zdravila GIOTRIF po 40 mg ali 50 mg v monoterapiji.
Overall Survival (OS) 
Mediana skupnega preživetja (OS) (meseci)
This means preferably 6 hours (for P-gp inhibitors dosed twice daily) or 12 hours (for P-gp inhibitors dosed once daily) apart from GIOTRIF (see section 4.5). 
To pomeni, najbolje z razmikom 6 ur (pri zaviralcih P-gp, ki se jih jemlje dvakrat na dan) ali 12 ur (pri zaviralcih P-gp, ki se jih jemlje enkrat na dan) od zdravila GIOTRIF (glejte poglavje 4.5).
Pack sizes of 7 x 1, 14 x 1 or 28 x 1 film-coated tablets. 
Pakiranje s 7-, 14- ali 28-krat 1 filmsko obloženo tableto.
• if you develop skin rash. 
• če se pojavi kožni izpuščaj.
HR 0.73 
Razmerje tveganja 0,73
The summary of all ADRs is shown in Table 2. 
Povzetek vseh neželenih reakcij je prikazan v preglednici 2.
Interstitial Lung Disease (ILD) 
Intersticijska pljučna bolezen (IPB)
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 = popoln odziv; PR = delni odziv vrednost p za PFS/OS na osnovi stratificiranega testa log-rank; vrednost p za stopnjo objektivnega odziva na osnovi logistične regresije
Based on this trial and population pharmacokinetic analysis of data derived from clinical trials in various tumour types, it is concluded, that adjustments to the starting dose in patients with mild (eGFR 60-89 mL/min/1.73m²), moderate (eGFR 30-59 mL/min/1.73m²), or severe (eGFR 15-29 mL/min/1.73m²) renal impairment are not necessary, but patients with severe impairment should be monitored (see “Population pharmacokinetic analysis in special populations” below and section 4.2). 
Na podlagi te študije in populacijske farmakokinetične analize podatkov, pridobljenih v kliničnih raziskavah različnih tumorjev, je ugotovljeno, da začetnega odmerka ni treba prilagoditi pri bolnikih z blago (eGFR 60-89 ml/min/1,73m²), zmerno (eGFR 30-59 ml/min/1,73 m²) ali hudo (eGFR 15-29 ml/min/1,73m²) ledvično okvaro, vendar je bolnike s hudo ledvično okvaro potrebno spremljati (glejte »Populacijska farmakokinetična analiza pri posebnih populacijah« spodaj in poglavje 4.2).
Patients were screened for the presence of 29 different EGFR mutations using a polymerase chain reaction (PCR)-based method (TheraScreen 
Bolnike so presejali glede na prisotnost 29 različnih mutacij EGFR z metodo, ki je temeljila na verižni reakciji s polimerazo (PCR) (TheraScreen EGFR29 Mutation Kit, Qiagen Manchester Ltd).
HR 0.86 
Razmerje tveganja 0,86
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. 
Predzdravljenje z rifampicinom (600 mg enkrat na dan 7 dni), močnim induktorjem P-gp, je za 34% (AUC0-∞) oz. 22% (Cmax) zmanjšalo plazemsko izpostavljenost afatinibu po dajanju enkratnega 40-mg odmerka zdravila 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. 
Med naključno razvrščenimi bolniki je bilo 62 % žensk, mediana njihove starosti je bila 63 let, 16 % bolnikov je imelo metastaze v možganih, izhodiščno stanje zmogljivosti ECOG je bilo 0 (31 %) ali 1 (69 %), 57 % bolnikov je bilo azijskega porekla in 43 % jih je bilo neazijcev.
Table 9: Efficacy results of GIOTRIF vs. gefitinib (LUX-Lung 7) based on primary analysis as of August 
Preglednica 9: Rezultati učinkovitosti zdravila GIOTRIF v primerjavi z gefitinibom (LUX-Lung 7) na osnovi primarnih analiz iz avgusta 2015.
51% vs. 44%; p=0.0605 
51 % v primerjavi s 44 % p = 0,0605
METHOD AND ROUTE(S) OF ADMINISTRATION Oral use 
POSTOPEK IN POT(I) UPORABE ZDRAVILA za peroralno uporabo
Patients with severe diarrhoea may require interruption and dose reduction or discontinuation of therapy with GIOTRIF (see section 4.2). 
Pri bolnikih s hudo drisko je včasih treba zdravljenje prekiniti in zmanjšati odmerek zdravila GIOTRIF ali ga ukiniti (glejte poglavje 4.2).
Randomisation was stratified according to EGFR mutation status (Del 19; L858R) and presence of brain metastases (yes; no). 
Bolnike so razvrstili glede na prisotnost mutacij EGFR (Del 19, L858R) in prisotnost metastaz v možganih (da/ne).
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. 
Preskušanje LUX-Lung 7 je randomizirana, globalna, odprta raziskava faze IIb, v kateri so učinkovitost in varnost zdravila GIOTRIF pri bolnikih z lokalno napredovalim ali metastatskim pljučnim adenokarcinomom (stopnja IIIB ali IV) in pozitivno mutacijo EGFR ocenjevali v zdravljenju prve linije.
PHARMACEUTICAL FORM AND CONTENTS 7 x 1 film-coated tablets 
FARMACEVTSKA OBLIKA IN VSEBINA 7 x 1 filmsko obložena tableta 14 x 1 filmsko obložena tableta 28 x 1 filmsko obložena tableta
In vitro studies indicated that afatinib is a substrate and an inhibitor of the transporter BCRP. 
Raziskave in vitro kažejo, da je afatinib substrat in zaviralec prenašalca BCRP.
- The other ingredients are lactose monohydrate, microcrystalline cellulose (E460), colloidal anhydrous silica (E551), crospovidone type A, magnesium stearate (E470b), hypromellose (E464), macrogol 400, titanium dioxide (E171), talc (E553b), polysorbate 80 (E433), indigo carmine (E132) aluminium hydroxide. 
- Druge sestavine zdravila so laktoza monohidrat, mikrokristalna celuloza (E460), brezvodni koloidni silicijev dioksid (E551), krospovidon tip A, magnezijev stearat (E470b), hipromeloza (E464), makrogol 400, titanov dioksid (E171), smukec (E553b), polisorbat 80 (E433), indigokarmin (E132), aluminijev hidroksid.
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. 
Pri bolnikih s tumorji, ki so nosilci de novo mutacij T790M (N = 14), je bila potrjena stopnja objektivnega odziva na zdravljenje (ORR) 14,3 %, mediana trajanja odziva pa 8,3 meseca.
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. 
Pri bolnikih, ki so enkrat na dan jemali po 40 mg zdravila GIOTRIF, so odmerek zaradi neželenih reakcij na zdravilo zmanjšali pri 57% bolnikov v raziskavi LUX-Lung 3 in 25 % v raziskavi LUX-Lung 8.
Monitor patients with severe renal impairment (eGFR 15-29 mL/min/1.73m²) and adjust GIOTRIF dose if not tolerated. 
Spremljajte bolnike s hudo ledvično okvaro (eGFR 1529 ml/min/1,73 m²) in v primeru neprenašanja prilagodite odmerek zdravila GIOTRIF.
See package leaflet for further information. 
Podrobnejše informacije so v priloženem navodilu.
Diarrhoea can be treated. 
Drisko je možno obvladati.
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. 
Med naključno razvrščenimi bolniki je bilo 65% žensk, povprečna starost je bila 61 let, izhodiščno stanje zmogljivosti ECOG je bilo 0 (39%) ali 1 (61%), 26% bolnikov je bilo belcev, 72% pa azijskega porekla.
Subjects with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment had similar exposure in comparison to healthy volunteers following a single dose of 50 mg GIOTRIF. 
Pri preizkušancih z blago (Child Pugh A) ali zmerno (Child Pugh B) jetrno okvaro je bila izpostavljenost po enkratnem 50-mg odmerku zdravila GIOTRIF podobna kot pri zdravih prostovoljcih.
This medicinal product has not been studied in patients with severe (Child Pugh C) hepatic impairment. 
Zdravila pri bolnikih s hudo jetrno okvaro (ocena C po Child Pughu) niso preskušali.
If you stop taking GIOTRIF 
Če ste prenehali jemati zdravilo GIOTRIF
The dispersion should be consumed immediately. 
Disperzijo naj bolnik takoj popije.
4 Any Grade 
4 Vse stopnje
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 
vrednosti za zdravilo GIOTRIF v primerjavi z erlotinibom; vrednost p na osnovi logistične regresije vrednost p za čas do poslabšanja na osnovi stratificiranega testa log-rank c vrednosti p niso bile prilagojene na številčnost
Dosage The recommended dose is 40 mg each day. 
Odmerjanje Priporočeni dnevni odmerek je 40 mg.
Recommended dosing 
Priporočeno odmerjanje
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 učinkovitosti zdravila GIOTRIF pri bolnikih s tumorji, ki so nosilci redkih mutacij EGFR (LUX-Lung 2, -3 in -6), ki se še niso zdravili z zaviralcem EGFR TK V treh kliničnih preskušanjih zdravila GIOTRIF s prospektivno tumorsko genotipizacijo (preskušanji III. faze LUX-Lung 3 in -6 in preskušanje 2. faze z enim krakom LUX-Lung 2) je bila opravljena analiza podatkov za skupno 75 bolnikov z napredovalimi pljučnimi adenokarcinomi (stopnje IIIb-IV), ki so nosilci redkih mutacij EGFR, ki so bile definirane kot vse mutacije, razen mutacij Del 19 in L858R, ki se še niso zdravili s TK.
Figure 2: Kaplan-Meier Curve for OS by treatment group in LUX-Lung 8 
Slika 2: Kaplan-Meierjeva krivulja skupnega preživetja v zdravljenih skupinah pri raziskavi LUX-Lung 8
• if you develop new or sudden worsening of shortness of breath, possibly with a cough or fever. 
• če se na novo pojavi ali nenadoma poslabša zadihanost, ki jo lahko spremljata kašelj ali vročina.
Table 8: Symptom outcomes for GIOTRIF vs. chemotherapy in trials LUX-Lung 3 and LUX-Lung 6 (EORTC QLQ-C30 & QLQ-LC13) 
Preglednica 8: Izidi glede na simptome za GIOTRIF v primerjavi s kemoterapijo v raziskavahLUX-Lung 3 in LUX-Lung 6 (EORTC QLQ-C30 in QLQ-LC13)
• Nail infection 
• okužba nohtov
Like all medicines, GIOTRIF can cause side effects, although not everybody gets them. 
Kot vsa zdravila ima lahko tudi to zdravilo neželene učinke, ki pa se ne pojavijo pri vseh bolnikih.
40% vs. 39%; p=0.7752 
40 % v primeravi z 39 % p = 0,7752
• Eye irritation or inflammation 
• Draženje ali vnetje v očesu
Table 10: Efficacy results for GIOTRIF vs erlotinib in LUX-Lung 8, based on primary analysis of OS, including all randomized patients 
Preglednica 10: Rezultati učinkovitosti zdravila GIOTRIF v primerjavi z zdravilom erlotinib v raziskavi LUX-Lung 8 na osnovi primarne analize skupnega preživetja vključno z vsemi naključno izbranimi bolniki
4.2 vs. 3.1 HR 0.83; p=0.1882 
4,2 v primerjavi s 3,1 razmerje tveganja 0,83; p = 0,1882
Randomization was stratified by race (Eastern Asian vs non Eastern Asian). 
Bolnike so razvrstili glede na rasno poreklo (Vzhodnoazijci v primerjavi z nevzhodnoazijci).
PFS benefit was accompanied by improvement in disease-related symptoms and delayed time to deterioration (see Table 8). 
Daljše preživetje brez napredovanja bolezni je spremljalo izboljšanje simptomov bolezni in podaljšalo čas do poslabšanja (glejte preglednico 8).
GIOTRIF has not been studied in patients with eGFR <15 mL/min/1.73m² or on dialysis. 
Zdravila GIOTRIF niso preučevali pri bolnikih z eGFR < 15 ml/min/1,73m² in pri tistih, ki so na dializi.
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. 
Razmerje tveganja za preživetje brez napredovanja bolezni (PFS) za bolnike z mutacjo DEL 19 in mutacijo L858R je bila 0,76 (95 % IZ [0,55; 1,06]; p = 0,1071) za afatinib in 0,71 (95 % IŻ [0,47; 1,06]; p = 0,0856) za gefitinib.
Body System 
Telesna masa
Discontinuation due to ADRs diarrhoea and rash/acne was 1.3% and 0% in LUX-Lung 3 and 3.8% and 2.0% in LUX-Lung 8, respectively. 
Zaradi neželenih reakcij na zdravilo v obliki driske in izpuščaja oziroma aken je zdravljenje prekinilo 1,3 % oziroma 0 % bolnikov v raziskavi LUX-Lung 3 oziroma 3,8 % in 2,0 % v raziskavi LUX-Lung 8.
Efficacy was similarly high in the group of patients who had received prior chemotherapy (N=68; ORR 57.4%; median PFS by independent review 8 months). 
V skupini bolnikov, ki so prej prejemali kemoterapijo, je bila učinkovitost podobna (N = 68; objektivni odziv na zdravljenje 57,4%; mediani čas preživetja brez napredovanja bolezni po podatkih neodvisnega pregleda 8 mesecev).
Table 11: Symptom outcomes for GIOTRIF vs. erlotinib in trial LUX-Lung 8 (EORTC QLQ-C30 & QLQ-LC13) 
Preglednica 11: Izidi glede na simptome za zdravilo GIOTRIF v primerjavi z erlotinibom v raziskavi LUX-Lung 8 (EORTC QLQ-C30 in QLQ-LC13)
Very common ADRs in GIOTRIF-treated patients occurring in at least 10% of patients in trial LUX-Lung 8 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Table 5. 
Zelo pogosti neželeni učinki pri bolnikih, ki so se zdravili z zdravilom GIOTRIF, in so se v raziskavi LUX-Lung 8 pojavili pri najmanj 10% bolnikov, so navedeni po stopnjah v skladu z merili NCI-CTC (National Cancer Institute-Common Toxicity Criteria) v preglednici 5.
Other information on drug-drug interactions 
Drugi podatki o medsebojnem delovanju z drugimi zdravili
Mechanistically, all EGFR targeting medicinal products have the potential to cause foetal harm. 
Po mehanistični plati imajo lahko vsa zdravila, ki delujejo na EGFR, škodljive učinke na plod.
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. 
Pri bolnikih s tumorji, ki so nosilci mutacij z vstavljanjem v ekson 20 (N = 23) je bila potrjena stopnja objektivnega odziva na zdravljenje (ORR) 8,7 %, mediana trajanja odziva pa 7,1 meseca.
• if you develop acute or worsening redness and pain in the eye, increased eye watering, blurred vision and/or sensitivity to light. 
• če se pojavijo akutna ali slabšajoča se pordelost ali bolečina v očesu, povečano solzenje oči,
Therefore, food should not be consumed for at least 3 hours before and at least 1 hour after taking GIOTRIF (see sections 4.2 and 4.5). 
Zato naj bolnik najmanj 3 ure pred jemanjem zdravila GIOTRIF in 1 uro po njem ne uživa hrane (glejte poglavji 4.2 in
• Inflammation of the lining of the bladder with burning sensations during urination and frequent, 
• vnetje sluznice sečnega mehurja in pekoč občutek med odvajanjem urina ter pogosta nujna potreba po uriniranju (cistitis)
• Abnormal taste sensations (dysgeusia) 
• nenormalno okušanje (disgevzija)
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-∞. 
Pri sočasnem vnosu obroka z visoko vsebnostjo maščobe in zdravila GIOTRIF se je pomembno zmanjšala izpostavljenost afatinibu, in sicer za približno 50%, če upoštevamo Cmax, in 39%, če upoštevamo AUC0-∞.
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) 
Preglednica 7: Podatki o učinkovitosti zdravila GIOTRIF v primerjavi s podatki o učinkovitosti pemetrekseda/cisplatina (LUX-Lung 3) in gemcitabina/cisplatina (LUX-Lung 6) za preživetje brez napredovanja bolezni in skupno preživetje v vnaprej opredeljenih podskupinah mutacij EGFRDel 19 in L858R (neodvisen pregled)
Renal impairment/ Renal failure 
Bolezni sečil ledvična okvara/ ledvična odpoved
Contact your doctor immediately and start appropriate antidiarrhoeal treatment as soon as possible. 
Nemudoma se posvetujte s svojim zdravnikom in čim prej začnite jemati ustrezno zdravilo proti driski, ki ga morate imeti vnaprej pripravljenega, še preden boste začeli jemati zdravilo GIOTRIF.
There were no Grade 3 ALT/AST elevations in patients with abnormal baseline liver tests in LUX-Lung 8 (see section 4.8). 
Pri bolnikih z nenormalnimi izhodiščnimi izvidi jetrnih preiskav v raziskavi LUX-Lung 8 ni bilo povišanj vrednosti ALT/AST stopnje 3 (glejte poglavje 4.8).
The embryo-foetal development studies performed on afatinib revealed no indication of teratogenicity. 
Raziskave o vplivu afatiniba na razvoj zarodka in ploda, niso pokazale teratogenega delovanja.
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. 
Zelo pogoste neželene reakcije na zdravilo pri bolnikih, ki so se zdravili z zdravilom GIOTRIF, in so se v raziskavah LUX-Lung 3 in LUX-Lung 7 pojavile pri najmanj 10 % bolnikov, so navedene po stopnjah v skladu z merili NCI-CTC (National Cancer Institute-Common Toxicity Criteria) v preglednicah 3 in 4.
Systemic exposure to afatinib is decreased by 50% (Cmax) and 39% (AUC0-∞), when administered with a high-fat meal compared to administration in the fasted state. 
Sistemska izpostavljenost afatinibu je bila pri jemanju zdravila s hrano z visoko vsebnostjo maščob manjša za 50% (Cmax) oziroma za 39% (AUC0-∞) v primerjavi z jemanjem na tešče.
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. 
Pri vnaprej opredeljeni podskupini pogostih mutacij (združeni Del 19 in L858R) za GIOTRIF in kemoterapijo je bila mediana preživetja brez napredovanja bolezni 13,6 meseca pri zdravilu GIOTRIF in 6,9 meseca pri kemoterapiji (razmerje tveganja 0,48; 95-odstotni IZ 0,35-0,66; p < 0,0001; N = 307) v raziskavi LUX-Lung 3 in 11,0 mesecev v primerjavi s 5,6 meseca (razmerje tveganja 0,24; 95-odstotni IZ 0,17-0,35; p < 0,0001; N = 324) v raziskavi LUX-Lung 6.