natgillin/translations-raw huggingface dataset:
Female gender, lower body weight, and underlying renal impairment Higher exposure to afatinib has been observed in female patients, patients with lower body weight and those with underlying renal impairment (see section 5.2). 
Ženski spol, niža tjelesna težina i postojeće oštećenje bubrega Veća izloženost afatinibu primijećena je kod bolesnica ženskog spola, bolesnika s manjom tjelesnom težinom, te bolesnika s postojećim oštećenjem bubrega (vidjeti dio 5.2).
Exposure to afatinib in subjects with renal impairment was compared to healthy volunteers following a single dose of 40 mg GIOTRIF. 
Izloženost afatinibu u ispitanika s oštećenjem bubrega bila je uspoređena sa zdravim dobrovoljcima nakon jednostruke doze od 40 mg GIOTRIFA.
The respective total systemic exposure (AUC) was either slightly above (2.2 times in rats) or below (0.3 times in rabbits) compared with levels in patients. 
Ukupna sistemska izloženost (AUC) bila je ili malo iznad (2,2 puta kod štakora) ili ispod (0,3 puta kod kunića) u usporedbi s vrijednostima u bolesnika.
ILD-like adverse reactions were reported in 0.7% of afatinib treated patients. 
Nuspojave nalik BPI-u prijavljene su kod 0,7% bolesnika liječenih afatinibom.
Available pharmacokinetic data in animals have shown excretion of afatinib in milk (see section 5.3). 
Dostupni farmakokinetički podaci u životinja pokazuju da se afatinib izlučuje u mlijeko (vidjeti dio 5.3).
In contrast, when ritonavir was administered simultaneously or 6 hours after 40 mg GIOTRIF, the relative bioavailability of afatinib was 119% (AUC0-∞) and 104% (Cmax) and 111% (AUC0-∞) and 105% (Cmax), respectively. 
Za razliku od toga, kada je ritonavir bio primjenjivan istodobno ili 6 sati nakon 40 mg GIOTRIFA, relativna bioraspoloživost afatiniba bila je 119% (AUC0-∞) i 104% (Cmax) odnosno 111% (AUC0-∞) te 105% (Cmax).
Use of P-glycoprotein (P-gp) inhibitors 
Primjena inhibitora P-glikoproteina (P-gp)
A dose escalation to a maximum of 50 mg/day may be considered in patients who tolerate a 40 mg/day starting dose (i.e. absence of diarrhoea, skin rash, stomatitis, and other adverse reactions with CTCAE Grade > 1) in the first cycle of treatment (21 days for EGFR mutation positive NSCLC and 28 days for squamous NSCLC). 
Povećanje doze do maksimalno 50 mg/dan može se razmotriti u bolesnika koji podnose početnu dozu od 40 mg/dan (tj. u odsustvu proljeva, osipa na koži, stomatitisa i drugih nuspojava CTCAE stupnja > 1) u prvom ciklusu liječenja (21 dan za NSCLC s pozitivnom EGFR mutacijom i 28 dana za skvamozne NSCLC).
Symptomatic adverse reactions (e.g. severe/persistent diarrhoea or skin related adverse reactions) may be successfully managed by treatment interruption and dose reductions or treatment discontinuation of GIOTRIF as outlined in Table 1 (see sections 4.4 and 4.8). 
Simptomatske nuspojave (npr. teški/trajni proljev ili nuspojave povezane s kožom) mogu se uspješno zbrinjavati prekidima u liječenju i snižavanjem doze ili trajnim prekidom liječenja GIOTRIFOM, kako je prikazano u tablici 1 (vidjeti dijelove 4.4 i 4.8).
55216 Ingelheim am Rhein GERMANY 
55216 Ingelheim am Rhein NJEMAČKA
Patients were treated with GIOTRIF 40 mg (all three trials) or 50 mg (LUX-Lung 2) orally once daily. 
Bolesnici su bili liječeni GIOTRIFOM 40 mg (sva tri ispitivanja) ili 50 mg (LUX-Lung 2) peroralno jedanput dnevno.
• Inflammation of the lungs (uncommon, may affect up to 1 in 100 people) called “interstitial lung disease”. 
• Upala pluća (manje često, može se javiti u do 1 na 100 osoba) naziva se “bolest plućnog intersticija”.
Mechanistically, all EGFR targeting medicinal products have the potential to cause foetal harm. 
U mehanističkom smislu, svi lijekovi koji ciljaju EGFR mogu potencijalno izazivati oštećenja fetusa.
Radiolabelled afatinib administered orally to rats on Day 11 of lactation was excreted in the breast milk of the dams. 
Oralno primijenjen radioaktivni obilježeni afatinib izlučen je 11. dan dojenja u majčinom mlijeku ženki štakora.
This medicinal product should be used with caution in patients with a history of keratitis, ulcerative keratitis or severe dry eye. 
Ovaj lijek se mora primjenjivati s oprezom kod bolesnika s anamnezom keratitisa, ulceroznog keratitisa ili sindroma suhog oka.
Tell your doctor immediately if you develop new or sudden worsening of shortness of breath, possibly with a cough or fever. 
Odmah obavijestite liječnika ako razvijete novo ili iznenadno pogoršanje nedostatka zraka, moguće praćeno kašljem ili vrućicom.
In non-clinical disease models with ErbB pathway deregulation, afatinib as a single agent effectively blocks ErbB receptor signalling resulting in tumour growth inhibition or tumour regression. 
U nekliničkim modelima bolesti s poremećajem regulacije ErbB puta, afatinib u monoterapiji učinkovito blokira prijenos signala ErbB receptora što rezultira inhibicijom rasta ili regresijom tumora.
This could result in a higher risk of developing adverse reactions in particular diarrhoea, rash/acne and stomatitis. 
Ovo može dovesti do povećanog rizika razvoja nuspojava, osobito proljeva, osipa/akni i stomatitisa.
The T790M mutation is found in approximately 50% of patients' tumours upon disease progression on afatinib, for which T790M targeted EGFR TKIs may be considered as a next line treatment option. 
Mutacija T790M je pronađena u približno 50% tumora bolesnika nakon progresije bolesti na afatinibu, za koje se kao opcija sljedeće linije liječenja mogu uzeti u obzir TK inhibitori EGFR-a koji ciljaju mutaciju T790M.
In oral repeated-dose studies for up to 26 weeks in rats or 52 weeks in minipigs the main effects were identified in the skin (dermal changes, epithelial atrophy and folliculitis in rats), the gastrointestinal tract (diarrhoea, erosions in the stomach, epithelial atrophy in rats and minipigs) and the kidneys (papillary necrosis in rats). 
U ispitivanjima s ponovljenim oralnim dozama na štakorima u trajanju do 26 tjedana ili na minijaturnim svinjama u trajanju od 52 tjedana glavni učinci su bili prepoznati na koži (kožne promjene, atrofija epitela i folikulitis kod štakora), u gastrointestinalnom traktu (proljev, erozije želuca, atrofija epitela kod štakora i minijaturnih svinja) i bubrezima (papilarna nekroza kod štakora).
Other patient characteristics/intrinsic factors found with a significant impact on afatinib exposure were: ECOG performance score, lactate dehydrogenase levels, alkaline phosphatase levels and total protein. 
Druge karakteristike bolesnika/drugi intrinzični faktori Druge karakteristike bolesnika/drugi intrinzični faktori sa značajnim utjecajem na izloženost afatinibu bili su: ECOG izvedbeni status, vrijednosti laktat dehidrogenaze, vrijednosti alkalne fosfataze i ukupnih proteina.
• Runny nose 
• Curenje nosa
In cases of suspected overdose, GIOTRIF should be withheld and supportive care initiated. 
U slučajevima sumnje na predoziranje, primjena GIOTRIFA se prekida te se započinje sa potpornom skrbi.
Therefore, it is recommended to administer strong P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) using staggered dosing, preferably 6 hours or 12 hours apart from GIOTRIF (see section 4.2). 
Stoga se preporučuje primjena snažnih P-gp inhibitora (uključujući, ali ne ograničeno na ritonavir, ciklosporin A, ketokonazol, itrakonazol, eritromicin, verapamil, kinidin, takrolimus, nelfinavir, sakvinavir i amiodaron) koristeći razdvojeno doziranje, ako je moguće 6 sati ili 12 sati odvojeno od GIOTRIFA (vidjeti dio 4.2).
There was limited data available for moderate and severe hepatic impairment. 
Dostupni podaci za umjereno i teško oštećenje jetre bili su ograničeni.
• if you have liver problems. 
• ako imate problema s jetrom.
There have been reports of ILD or ILD-like adverse reactions (such as lung infiltration, pneumonitis, acute respiratory distress syndrome, allergic alveolitis), including fatalities, in patients receiving GIOTRIF for treatment of NSCLC. 
Prijavljeni su slučajevi BPI-a ili nuspojava sličnih BPI-u (kao što su infiltracija pluća, pneumonitis, akutni respiratorni distres sindrom, alergijski alveolitis), uključujući smrtne ishode, kod bolesnika koji su uzimali GIOTRIF radi liječenja NSCLC-a.
In patients with an ejection fraction below the institution's lower limit of normal, cardiac consultation as well as treatment interruption or discontinuation should be considered. 
Kod bolesnika s ejekcijskom frakcijom ispod donje granice normale ustanove, potrebno je razmotriti savjetovanje s kardiologom kao i privremeni ili trajni prekid liječenja.
Thus, steady state plasma concentrations of afatinib were achieved within 8 days of multiple dosing of afatinib resulting in an accumulation of 2.77-fold (AUC0-∞) and 2.11-fold (Cmax). 
Stoga su koncentracije afatiniba u plazmi pri stanju dinamičke ravnoteže postignute u roku 8 dana od višestrukog doziranja afatiniba, što je rezultiralo akumulacijom 2,77 puta (AUC0-∞) i 2,11 puta većom (Cmax).
Dosage The recommended dose is 40 mg each day. 
Doziranje Preporučena doza je 40 mg svaki dan.
Dose interruption may become necessary in patients who experience worsening of liver function (see section 4.2). 
Prekid doze može biti potreban kod bolesnika u kojih dođe do pogoršanja jetrene funkcije (vidjeti dio 4.2).
Palmar-plantar erythrodysaesthesia syndrome 
Palmarnoplantarni eritrodisestezijski sindrom
• Verapamil, quinidine, amiodarone - used to treat heart conditions. 
• Verapamil, kinidin, amiodaron - primjenjuju se za liječenje bolesti srca.
The highest total systemic exposure (AUC0-24) in female rats was less than that observed in patients (0.23 times). 
Najviša ukupna sistemska izloženost (AUC0-24) u štakorica bila je manja od one primijećene u bolesnika (0,23 puta).
Overdose in 2 healthy adolescents involving the ingestion of 360 mg each of afatinib (as part of a mixed drug ingestion) was associated with adverse events of nausea, vomiting, asthenia, dizziness, headache, abdominal pain and elevated amylase (< 1.5 times ULN). 
Predoziranje 2 zdrava adolescenta koje je uključivalo unos 360 mg afatiniba za svakoga (kao dio unosa više vrsta lijekova) bilo je povezano s razvojem nuspojava u smislu mučnine, povraćanja, astenije, omaglice, glavobolje, abdominalne boli i povišene amilaze (< 1,5 puta GGN).
In the pivotal trials Grade 3 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations were observed in 2.4% (LUX-Lung-3) and 1.6% (LUX-Lung 8) of patients with normal baseline liver tests treated with 40 mg/day. 
U ključnim ispitivanjima porast alanin aminotransferaze (ALT) i aspartat aminotransferaze (AST) stupnja 3 primijećen je kod 2,4% (LUX-Lung 3) i 1,6% (LUX-Lung 8) bolesnika s urednim početnim vrijednostima jetrenih enzima koji su bili liječeni s 40 mg/dan.
The primary endpoint was progression free survival (PFS) by independent review; the secondary endpoints included overall survival and objective response rate. 
Primarni ishod bio je preživljenje bez progresije bolesti (engl. progression free survival, PFS) na temelju nezavisne procjene; sekundarni ishodi su uključivali ukupno preživljenje i stopu objektivnog odgovora.
What GIOTRIF contains - The active substance is afatinib. 
Što GIOTRIF sadrži - Djelatna tvar je afatinib.
Bullous, blistering and exfoliative skin conditions have been reported including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis although in these cases there were potential alternative aetiologies (see section 4.4). 
Prijavljena su bulozna, vezikulozna i eksfolijativna stanja uključujući rijetke slučajeve koji ukazuju na Stevens-Johnsonov sindrom i toksičnu epidermalnu nekrolizu, iako su u ovim slučajevima potencijalno postojale i druge etiologije (vidjeti dio 4.4).
Anti-diarrhoeal medicinal products should be readily available to the patients so that treatment can be initiated at first signs of diarrhoea and continued until loose bowel movements cease for 12 hours. 
Lijekovi protiv proljeva moraju biti lako dostupni bolesnicima tako da liječenje može početi s pojavom prvih znakova proljeva i nastaviti se do 12 sati od nestanka mekane stolice.
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 znači po mogućnosti 6 sati (za P-gp inhibitore s doziranjem dva puta dnevno) ili 12 sati (za P-gp inhibitore s jednokratnim dnevnim doziranjem) razmaka od GIOTRIFA (vidjeti dio 4.5).
• Eye irritation or inflammation 
• Nadraženost oka ili upala
GIOTRIF treatment should be continued until disease progression or until no longer tolerated by the patient (see Table 1 below). 
Liječenje GIOTRIFOM se nastavlja do progresije bolesti ili razvoja nepodnošljivosti kod bolesnika (vidjeti tablicu 1 u nastavku).
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 izloženost afatinibu je smanjena za 50% (Cmax) i 39% (AUC0-∞), kada se primjenjuje s obrokom s visokim udjelom masnoća u usporedbi s primjenom lijeka natašte.
Both trials demonstrated significant improvement in PFS of EGFR mutation positive patients treated with GIOTRIF compared to chemotherapy. 
Oba ispitivanja pokazala su značajno poboljšanje PFS-a u bolesnika pozitivnih na EGFR mutaciju i liječenih GIOTRIFOM u usporedbi s kemoterapijom.
Treatment with this medicinal product should be interrupted or discontinued if the patient develops severe bullous, blistering or exfoliating conditions (see section 4.8). 
Liječenje ovim lijekom se mora privremeno ili trajno prekinuti ako bolesnik razvije teška bulozna, vezikulozna ili eksfolijativna stanja (vidjeti dio 4.8).
NSCLC tumours with common activating EGFR mutations (Del 19, L858R) and several less common EGFR mutations in exon 18 (G719X) and exon 21 (L861Q) are particularly sensitive to afatinib treatment in non-clinical and clinical settings. 
NSCLC tumori s čestim aktivirajućim mutacijama EGFR-a (Del 19, L858R), te nekoliko manje čestih mutacija EGFR-a u egzonu 18 (G719X) i egzonu 21 (L861Q) su osobito osjetljivi na liječenje afatinibom u nekliničkom i kliničkom okruženju.
In patients who develop relevant cardiac signs/symptoms during treatment, cardiac monitoring including LVEF assessment should be considered. 
Kod bolesnika koji razviju značajne srčane znakove/simptome tijekom liječenja, potrebno je razmotriti praćenje srčane funkcije, uključujući procjenu LVEF-a.
It is important to treat the rash early. 
Osip je važno rano započeti liječiti.
Breast-feeding Do not breast-feed while taking this medicine as a risk to the breast-fed child cannot be excluded. 
Dojenje Nemojte dojiti tijekom primjene ovog lijeka jer se ne može isključiti rizik za dojenče.
The co-primary endpoints include PFS by independent review and OS. 
Koprimarne mjere ishoda su uključivale PFS na temelju nezavisne procjene i OS.
In particular, if taken before GIOTRIF, the following medicines may increase the blood levels of GIOTRIF and therefore the risk of side effects. 
Osobito ako se uzimaju prije GIOTRIFA, sljedeći lijekovi mogu povisiti vrijednosti GIOTRIFA u krvi te na taj način povećati rizike nuspojava.
• Severe blistering or peeling of skin (suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis) 
• Jako stvaranje mjehura na koži ili ljuštenje kože (ukazuje na Stevens-Johnsonov sindrom i toksičnu epidermalnu nekrolizu)
Trial Population Alive at 18-months Alive at 24-months 
1, ukupna populacija ispitivanja Živi u 18. mjesecu Živi u 24. mjesecu
Aspartate aminotransferase increased 
Povišene vrijednosti aspartat aminotransferaze
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 
OS rezultati temeljeni na primarnoj analizi ukupnog preživljenja iz travnja 2016. pri stopama događaja od 109 (68,1%) i 117 (73,6%) u skupinama liječenim GIOTRIFOM odnosno gefitinibom p-vrijednost za PFS/OS na temelju stratificiranog log-rank testa; p-vrijednost za stopu objektivnog odgovora na temelju stratificirane logističke regresije
P-glycoprotein (P-gp) interactions Concomitant treatment with strong inducers of P-gp may decrease exposure to afatinib (see section 4.5). 
Interakcije s P-glikoproteinom (P-gp interakcije) Istodobno liječenje snažnim P-gp induktorima može smanjiti izloženost afatinibu (vidjeti dio 4.5).
If you experience treatment-related symptoms affecting your eye sight (e.g. redness and/or irritation of the eye, dry eye, tearing, light-sensitivity) or your ability to concentrate and react, it is recommended that you do not drive or use machines until the side effect disappears (see section 4 Possible side effects). 
Ako, povezano s liječenjem, imate simptome koji utječu na Vaš vid (npr. crvenilo i/ili nadraženost oka, sindrom suhog oka, pojačano suzenje, preosjetljivost na svjetlo) ili na Vašu sposobnost koncentriranja i reagiranja, preporučuje se ne upravljati vozilima ili strojevima dok nuspojave ne nestanu (vidjeti dio 4. Moguće nuspojave).
EGFR mutation status should be established prior to initiation of GIOTRIF therapy (see section 4.4). 
Potrebno je utvrditi status mutacije EGFR prije početka liječenja GIOTRIFOM (vidjeti dio 4.4).
Strong P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital or St. John's wort (Hypericum perforatum)) may decrease exposure to afatinib (see section 4.4). 
Snažni P-gp induktori (uključujući, ali ne ograničeno na rifampicin, karbamazepin, fenitoin, fenobarbital ili gospinu travu (Hypericum perforatum)) mogu smanjiti izloženost afatinibu (vidjeti dio 4.4).
• Carbamazepine, phenytoin, phenobarbital - used to treat seizures. 
• Karbamazepin, fenitoin, fenobarbital - primjenjuju se za liječenje napadaja.
• if you develop new or sudden worsening of shortness of breath, possibly with a cough or fever. 
• ako razvijete novo ili iznenadno pogoršanje nedostatka zraka, moguće praćeno kašljem i vrućicom.
In humans it was found that enzyme-catalyzed metabolic reactions play a negligible role for the metabolism of afatinib. 
U ljudi je pronađeno da reakcije katalizirane enzimima imaju zanemarivu ulogu za metabolizam afatiniba.
GIOTRIF is a medicine which contains the active substance afatinib. 
GIOTRIF je lijek koji sadrži djelatnu tvar afatinib.
Pemetrexed/ Cisplatin N=111 
Pemetreksed/ cisplatin N=111
Diarrhoea, including severe diarrhoea, has been reported during treatment with GIOTRIF (see section 4.8). 
Proljev, uključujući teški proljev, prijavljen je tijekom liječenja GIOTRIFOM (vidjeti dio 4.8).
Table 7 shows outcomes in the subgroups of patients with two common EGFR mutations - Del 19 and L858R. 
Tablica 7 pokazuje ishode u podskupinama bolesnika s dvjema čestim EGFR mutacijama - Del 19 i L858R.
In patients who develop severe hepatic impairment while taking GIOTRIF, treatment should be discontinued. 
Kod bolesnika koji razviju teško oštećenje jetre tijekom primjene GIOTRIFA, mora se prekinuti liječenje.
89% of patients had common EGFR mutations (Del 19 or L858R). 
89% bolesnika imalo je česte EGFR mutacije (Del 19 ili L858R).
The types of adverse reactions (ADRs) were generally associated with the EGFR inhibitory mode of action of afatinib. 
Tipovi nuspojava na lijek bili su općenito povezani s EGFR inhibicijskim načinom djelovanja afatiniba.
This medicinal product has not been studied in patients with severe (Child Pugh C) hepatic impairment. 
Ovaj lijek nije ispitivan u bolesnika s teškim (Child Pugh C) oštećenjem jetre.
The dispersion should be consumed immediately. 
Otopina se mora popiti odmah.
Eye irritation or inflammation may occur (conjunctivitis/keratoconjunctivitis occurs commonly and keratitis uncommonly). 
Može doći do pojave nadraženosti ili upale oka (konjunktivitis/keratokonjunktivitis se javlja često, a keratitis manje često).
Effects of afatinib on P-gp substrates 
Učinci afatiniba na P-gp supstrate
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). 
Ukupna sistemska izloženost (AUC0-24) kod muških i ženskih štakora bila je ili u rasponu ili manja od iste primijećene u bolesnika (1,3 puta odnosno 0,51 puta).
NCI Common Terminology Criteria for Adverse Events In case of diarrhoea, anti-diarrhoeal medicinal products (e.g. loperamide) should be taken immediately and continued for persistent diarrhoea until loose bowel movements cease. 
NCI zajednički kriteriji terminologije za nuspojave (Common terminology Criteria for Adverse Events) U slučaju proljeva, potrebno je odmah započeti s primjenom lijekova protiv proljeva (npr. loperamid), te nastaviti primjenu tijekom trajanja proljeva dok ne prestane mekana stolica.
Effects of P-gp and breast cancer resistance protein (BCRP) inhibitors on afatinib In vitro studies have demonstrated that afatinib is a substrate of P-gp and BCRP. 
P-gp inhibitora i inhibitora proteina za rezistenciju na rak dojke (BCRP) na afatinib In vitro ispitivanja su pokazala da je afatinib supstrat P-gp-a i BCRP-a.
Uncommon side effects (may affect up to 1 in 100 people): • Inflammation of the pancreas (pancreatitis) 
Manje česte nuspojave (mogu se javiti u do 1 na 100 osoba): • Upala gušterače (pankreatitis)
Months (median) 
Mjeseci (medijan)
The acquisition of a secondary T790M mutation is a major mechanism of acquired resistance to afatinib and gene dosage of the T790M-containing allele correlates with the degree of resistance in vitro. 
Stjecanje sekundarne mutacije T790M glavni je mehanizam stečene rezistencije na afatinib, a broj kopija alela koji sadrži mutaciju T790M korelira sa stupnjem rezistencije in vitro.
• If your next scheduled dose is due within 8 hours, skip the missed dose and take your next dose at the usual time. 
• Ako je Vaša sljedeća doza unutar idućih 8 sati, preskočite propuštenu dozu, a sljedeću dozu uzmite u uobičajeno vrijeme.
Grade > 3 
Stupanj ≥ 3
GIOTRIF as monotherapy is indicated for the treatment of 
GIOTRIF je, u obliku monoterapije, indiciran za liječenje:
• St. John's wort (Hypericum perforatum), a herbal medicine to treat depression. 
• Gospina trava (Hypericum perforatum), biljni lijek za liječenje depresije.
• if you develop acute or worsening redness and pain in the eye, increased eye watering, blurred vision and/or sensitivity to light. 
• ako razvijete novo ili dođe do pogoršanja crvenila i boli očiju, pojačanog suzenja, zamagljenja vida i/ili preosjetljivosti na svjetlost.
Bullous, blistering and exfoliative skin conditions have been reported including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis. 
Prijavljeni su slučajevi buloznih, vezikuloznih i eksfolijativnih stanja kože, uključujući rijetke slučajeve koji ukazuju na Stevens-Johnsonov sindrom i toksičnu epidermalnu nekrolizu.
When the strong P-gp and BCRP inhibitor ritonavir (200 mg twice a day for 3 days) was administered 1 hour before a single dose of 20 mg GIOTRIF, exposure to afatinib increased by 48% (area under the curve (AUC0-∞)) and 39% (maximum plasma concentration (Cmax)). 
Kada je primjenjivan snažan P-gp i BCRP inhibitor, ritonavir (200 mg dvaput dnevno u trajanju 3 dana) 1 sat prije jednostruke doze od 20 mg GIOTRIFA, izloženost afatinibu se povećala za 48% (površina ispod krivulje (AUC0-∞)) i 39% (vršne koncentracije u plazmi za (Cmax)).
Patients had a tumour sample with an EGFR mutation categorised as either exon 19 deletion (58%) or exon 21 L858R substitutions (42%). 
Bolesnici su imali uzorak tumora s mutacijom EGFR kategoriziranom bilo kao delecija egzona 19 (58%) ili kao supstitucije L858R u egzonu 21 (42%).
• Diarrhoea (very common, may affect more than 1 in 10 people). 
• Proljev (vrlo često, može se javiti u više od 1 na 10 osoba).
GIOTRIF in patients with Non-Small Cell Lung Cancer (NSCLC) with EGFR mutations 
GIOTRIF kod bolesnika s rakom pluća nemalih stanica (NSCLC) s EGFR mutacijama