natgillin/translations-raw huggingface dataset:
In addition, 56 placebo plus BSC patients received open-label Stivarga after cross-over following disease progression and a total of 41 Stivarga plus BSC patients continued Stivarga treatment after disease progression. 
Poleg tega je 56 bolnikov, ki so prejemali placebo in najboljšo podporno oskrbo, zaradi napredovanja bolezni prešlo na zdravljenje z zdravilom Stivarga, 41 bolnikov, ki so prejemali zdravilo Stivarga,in najboljšo podporno oskrbo, pa je zdravljenje z zdravilom Stivarga,nadaljevalo po napredovanju bolezni.
In patients who develop cardiac ischaemia and/or infarction, interruption of Stivarga is recommended until resolution. 
Pri bolnikih, pri katerih se pojavi miokardna ishemija in/ali infarkt, se priporoča prekinitev zdravljenja z zdravilom Stivarga, dokler se stanje ne izboljša.
A second phase III, international, multi-centre, randomised, double blind, placebo-controlled study (CONCUR) evaluated the efficacy and safety of Stivarga in 204 pre-treated Asian patients (> 90% East Asian) with metastatic colorectal cancer who have progressed after failure of fluoropyrimidinebased chemotherapy. 
V drugi mednarodni, multicentrični, randomizirani, dvojno slepi, s placebom nadzorovani študiji III. faze (CONCUR) so ocenjevali učinkovitost in varnost zdravila Stivarga pri 204 bolnikih azijske rase (> 90 % iz vzhodne Azije) z metastatskim kolorektalnim rakom, ki je napredoval po neuspeli kemoterapiji na osnovi fluoropirimidina.
Each bottle contains 28 film-coated tablets. 
Ena plastenka vsebuje 28 filmsko obloženih tablet.
Regorafenib reaches mean peak plasma levels of about 2.5 mg/l at about 3 to 4 hours after a single oral dose of 160 mg given as 4 tablets each containing 40 mg. 
Regorafenib doseže povprečne največje plazemske koncentracije, ki so približno 2,5 mg/l približno 3 do 4 ure po enkratnem peroralnem odmerku 160 mg (4 tablete; ena tableta vsebuje 40 mg).
Signs and symptoms of PRES include seizures, headache, altered mental status, visual disturbance or cortical blindness, with or without associated hypertension. 
Znaki in simptomi PRES vključujejo epileptične napade, glavobol, spremenjeno duševno stanje, motnje vida ali kortikalno slepoto,
Cellulose microcrystalline Croscarmellose sodium Magnesium stearate Povidone (K-25) Silica, colloidal anhydrous 
Jedro tablete: mikrokristalna celuloza premrežen natrijev karmelozat magnezijev stearat povidon (K-25) brezvodni koloidni silicijev dioksid
Compared to the global phase III CRC trial (CORRECT) with predominantly (~80%) Caucasian patients enrolled, a higher incidence of liver enzyme increases was observed in Stivarga-treated patients in the Asian phase III CRC trial (CONCUR) with predominantly (> 90%) East Asian patients enrolled. 
V primerjavi z globalnim preskušanjem III. faze (CORRECT) pri bolnikih z metastatskim kolorektalnim rakom, v katerega so bili vključeni pretežno belci (~ 80 %), so v preskušanjih III. faze (CONCUR) pri bolnikih z metastatskim kolorektalnim rakom, zdravljenih z zdravilom Stivarga, v katerega so bili vključeni bolniki azijske rase, pretežno (> 90 %) bolniki iz vzhodne Azije, opazili večjo incidenco povečanja vrednosti jetrnega encima.
Co-administration of a strong UGT1A9 inhibitor (e.g. mefenamic acid, diflunisal, and niflumic acid) during regorafenib treatment should be avoided, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied. 
Sočasni uporabi močnih zaviralcev UGT1A9 (npr. mefenaminska kislina, diflunisal in niflumska kislina) med zdravljenjem z regorafenibom se je treba izogibati, saj njihovega vpliva na izpostavljenost regorafenibu in njegovim presnovkom v stanju dinamičnega ravnovesja niso preučevali.
Iron oxide red (E172) Iron oxide yellow (E172) Lecithin (derived from soya) Macrogol 3350 
rdeči železov oksid (E 172) rumeni železov oksid (E 172) lecitin (pridobljen iz soje)
Stivarga can cause severe bleeding in the digestive system such as stomach, throat, rectum or intestine, or in the lungs, kidneys, mouth, vagina and/or brain. 
Zdravilo Stivarga lahko povzroči hude krvavitve v prebavilih, npr. želodcu, požiralniku, danki ali črevesju, ali v pljučih, ledvicah, ustih, nožnici in/ali možganih.
3.2 months 
3,2 meseca
It is recommended to avoid concomitant use of strong inhibitors of CYP3A4 activity (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin and voriconazole) as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied. 
Sočasni uporabi močnih zaviralcev CYP3A4 (npr. klaritromicin, sok grenivke, itrakonazol, ketokonazol, posakonazol, telitromicin in vorikonazol) se je priporočljivo izogibati, saj njihovega vpliva na izpostavljenost regorafenibu in njegovim presnovkom v stanju dinamičnega ravnovesja niso preučevali.
There is no relevant use of Stivarga in the paediatric population in the indication of metastatic colorectal cancer. 
Pediatrična populacija Zdravilo Stivarga ni namenjeno za uporabo pri pediatrični populaciji za indikacijo metastatskega kolorektalnega raka.
Severe stomach and bowel problems (gastrointestinal perforation or fistula) Get medical help immediately, if you get the following symptoms: - severe stomach (abdominal) pain or stomach pain that does not go away - vomiting blood - red or black stools. 
Hude želodčne in črevesne težave (predrtje prebavil ali fistula) Takoj poiščite medicinsko pomoč, če opazite naslednje simptome: - hude bolečine v trebuhu (abdominalne bolečine) ali bolečine v trebuhu, ki ne minejo, - bruhanje krvi, - rdeče ali črno blato.
In patients with severe renal impairment compared to patients with normal renal function, regorafenib exposure was similar while exposure to M-2 and M-5 was decreased by about 30% under steady-state conditions, which is not considered clinically relevant. 
Pri bolnikih s hudo okvaro ledvic je v stanju dinamičnega ravnovesja izpostavljenost regorafenibu podobna kot pri bolnikih z normalnim delovanjem ledvic, medtem ko je izpostavljenost presnovkoma M-2 in M-5 približno 30 % manjša, kar pa se ne šteje za klinično pomembno.
Most cases of hypertension in patients treated with Stivarga appeared during the first cycle of treatment and were mild to moderate in severity (Grades 1 and 2: 20.9%, CRC, 31.8%, GIST and 15.8% HCC). 
Večina primerov hipertenzije pri bolnikih, zdravljenih z zdravilom Stivarga, se je pojavila v prvem ciklu zdravljenja, in so bili blagi do zmerni (stopnje 1 in 2: 20,9 % (CRC), 31,8 % (GIST) in 15,8 % (HCC).
The incidence of Grade 3 hand-foot skin reaction was 17.1% (CRC), 22.0% (GIST) and 12.3% (HCC). 
Incidenca kožnih reakcij na dlaneh in podplatih stopnje 3 je bila 17,1 % (CRC), 22,0 % (GIST) in 12,3 % (HCC).
The most frequently observed adverse drug reactions at this dose were dermatological events, dysphonia, diarrhoea, mucosal inflammation, dry mouth, decreased appetite, hypertension, and fatigue. 
Najpogosteje zabeleženi neželeni učinki pri tem odmerku so bile kožne reakcije, disfonija, driska, vnetje sluznice, suha usta, zmanjšan apetit, hipertenzija in utrujenost.
§ BSC Supportive Care * Hazard ratio < 1 favours Stivarga ** based on investigator's assessment of tumour response 
§ najboljša podporna oskrba (BSC - Best Supportive Care) * razmerje ogroženosti < 1 v korist zdravila Stivarga ** temelji na oceni raziskovalca glede odziva tumorja na zdravljenje
A higher incidence of hand foot skin reaction (HFSR)/palmar-plantar erythrodysesthesia syndrome, severe liver function test abnormalities and hepatic dysfunction was observed in Asian (in particular Japanese) patients treated with Stivarga compared with Caucasians. 
Večjo incidenco kožne reakcije na dlaneh in podplatih (HFSR - hand-foot skin reaction) ali sindroma palmarno-plantarne eritrodisestezije, huda odstopanja v izvidih preiskav delovanja jeter in moteno delovanje jeter so opazili pri bolnikih azijske rase (predvsem pri Japoncih), zdravljenih z zdravilom Stivarga v primerjavi z belci.
Taste disorders Dry mouth Gastrooesophageal reflux Gastroenteritis 
Bolezni prebavil driska stomatitis bruhanje navzea motnje okusa suha usta gastroezofageal na refluksna bolezen gastroenteritis
Other side effects with Stivarga listed by frequency: 
Drugi neželeni učinki zdravila Stivarga so navedeni po pogostnosti.
3.1 months 
3,1 mesec
In the event of suspected overdose, Stivarga should be discontinued immediately, with best supportive care initiated by a medical professional, and the patient should be observed until clinical stabilisation. 
Ob sumu na preveliko odmerjanje je treba takoj prekiniti zdravljenje z zdravilom Stivarga, zdravstveno osebje pa mora začeti z najboljšo podporno oskrbo.
The HR for OS was 0.772 (95% CI, 0.423, 1.408; p = 0.199; median OS not reached in either arm); 85% of patients initially randomised to the placebo arm received post-progression treatment with regorafenib (see Table 6, Figure 3). 
Razmerje ogroženosti v analizi celokupnega preživetja je bilo 0,772 (95 % IZ, 0,423; 1,408; p = 0,199; mediana celokupnega preživetja ni bila dosežena v nobeni od skupin); 85 % bolnikov, ki so bili najprej randomizirani v skupino, ki je prejemala placebo, je bilo po napredovanju bolezni zdravljenih z regorafenibom (glejte preglednico 6, sliko 3).
Treatment with Stivarga may lead to a higher risk of infections, especially of the urinary tract, nose, throat and lung. 
Zdravljenje z zdravilom Stivarga lahko poveča tveganje za okužbe, predvsem sečil, nosu, grla ali pljuč.
Dose modifications are to be applied in 40 mg (one tablet) steps. 
Odmerke je treba prilagajati postopoma po 40 mg (ena tableta).
Stivarga is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) as Stivarga has not been studied in this population. 
Zdravilo Stivarga se ne priporoča za uporabo pri bolnikih s hudo okvaro jeter (Child-Pugh C), ker zdravila Stivarga pri teh bolnikih niso preučevali.
Fatal outcome in patients treated with Stivarga was uncommon (0.7%), and included cerebral, respiratory, gastrointestinal and genitourinary events. 
Smrtni izidi pri bolnikih, zdravljenih z zdravilom Stivarga, so bili občasni (0,7 %) in so vključevali zaplete v možganih, dihalih, prebavilih, sečilih in rodilih.
No dose adjustment is required in patients with mild, moderate or severe renal impairment (see also section 5.2). 
Pri bolnikih z blago, zmerno ali hudo okvaro ledvic odmerka ni treba prilagajati (glejte tudi poglavje 5.2).
1.7 months 
1,7 mesecev
The exposure of regorafenib and its metabolites M-2 and M-5 is comparable in patients with mild hepatic impairment (Child-Pugh A) and patients with normal hepatic function. 
Izpostavljenost regorafenibu in njegovima presnovkoma M-2 in M-5 je podobna pri bolnikih z blago okvaro jeter (Child-Pugh A) in pri bolnikih z normalnim delovanjem jeter.
Urinary excretion of glucuronides decreased below 10% under steady-state conditions. 
V stanju dinamičnega ravnovesja se je izločanje glukuronidov s sečem zmanjšalo pod 10 %.
In particular, regorafenib inhibits mutated KIT, a major oncogenic driver in gastrointestinal stromal tumours, and thereby blocks tumour cell proliferation. 
Regorafenib še zlasti zavira mutirani KIT, ki ima ključno vlogo v razvoju gastrointestinalnih stromalnih tumorjih, in s tem zavira proliferacijo tumorskih celic.
Get medical help immediately if you get the following symptoms: - high fever - severe cough with or without an increase in mucus (sputum) production - severe sore throat 
Takoj poiščite medicinsko pomoč, če opazite naslednje simptome: - zvišana telesna temperatura - hud kašelj z ali brez povečanega nastajanja sluzi (sputum)
Gastrointestinal perforation and fistula 
Gastrointestinalna perforacija in fistula
Blood pressure should be controlled prior to initiation of treatment with Stivarga. 
Pred uvedbo zdravljenja z zdravilom Stivarga je treba izmeriti krvni tlak.
vomiting, and fever (pancreatitis) - nail disorder (changes to the nail such as ridges and/or splitting) - multiple skin eruptions (erythema multiforme). 
bruhanje in zvišana telesna temperatura (pankreatitis) - spremembe na nohtih, kot so brazde in/ali razcepljeni nohti - izpuščaji različnih oblik (multiformni eritem)
Any occurrence 
vsak pojav
Hepatocellular carcinoma (HCC) 
Rak jetrnih celic (HCC - hepatocelularni karcinom)
Neoplasms benign, malignant and unspecified (including cysts and polyps) 
Benigne, maligne in neopredeljene novotvorbe (vključno s cistami in keratoakantom/ ploščatocelični karcinom kože
Administration of rifampicin (600 mg for 9 days), a strong CYP3A4 inducer, with a single dose of regorafenib (160 mg on day 7) resulted in a reduction in AUC of regorafenib of approximately 50%, a 3- to 4-fold increase in mean exposure of the active metabolite M-5, and no change in exposure of active metabolite M-2. 
Uporaba rifampicina (600 mg, 9 dni), močnega induktorja CYP3A4, z enkratnim odmerkom regorafeniba (160 mg sedmi dan), je povzročila zmanjšanje AUC regorafeniba za približno 50 %, kar je 3- do 4-kratno povečanje povprečne izpostavljenosti aktivnemu presnovku M-5; izpostavljenost aktivnemu presnovku M-2 se ni spremenila.
Metabolites may be reduced or hydrolysed in the gastrointestinal tract by microbial flora, allowing reabsorption of the unconjugated active substance and metabolites (enterohepatic circulation). 
Presnovke lahko mikrobna flora v prebavilih reducira ali hidrolizira, kar omogoči ponovno absorpcijo nekonjugirane učinkovine in presnovkov (enterohepatični obtok).
Titanium dioxide (E171) 
delno hidroliziran polivinilalkohol smukec titanov dioksid (E 171)
The pharmacokinetics of regorafenib has not been studied in patients with end-stage renal disease. 
Farmakokinetike regorafeniba pri bolnikih s končno odpovedjo ledvic niso preučevali.
The hazard ratio (95% CI) of PFS was 0.475 (0.362 to 0.623) for patients with KRAS wild-type tumours and 0.525 (0.425 to 0.649) for patients with KRAS mutant tumours. 
Razmerje ogroženosti (95 % IZ) preživetja brez napredovanja bolezni je bilo 0,475 (0,362 do 0,623) pri bolnikih s tumorjem z divjim tipom gena KRAS in 0,525 (0,425 do 0,649) pri bolnikih s tumorjem z mutacijo gena KRAS.
How to take Stivarga 
Kako jemati zdravilo Stivarga
The European Medicines Agency has deferred the obligation to submit the results of studies with Stivarga in one or more subsets of the paediatric population in the treatment of solid malignant tumours (see section 4.2 for information on paediatric use). 
Evropska agencija za zdravila je začasno odložila zahtevo za predložitev rezultatov študij z zdravilom Stivarga za eno ali več podskupin pediatrične populacije za zdravljenje čvrstih malignih tumorjev (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
If you have a mildly or moderately impaired liver function while you are being treated with Stivarga, your doctor should monitor you closely. 
Če imate blago ali zmerno okvaro jeter vas bo zdravnik med zdravljenjem z zdravilom Stivarga skrbno spremljal.
Stivarga contains the active substance regorafenib. 
Kaj vsebuje zdravilo Stivarga - Učinkovina je regorafenib.
Get medical help immediately, if you get the following symptoms: severe stomach pain or stomach pain that does not go away, vomiting blood, red or black stools. 
Takoj poiščite medicinsko pomoč, če se vam pojavijo naslednji simptomi: hude bolečine v trebuhu ali želodcu, ki ne izginejo, bruhanje krvi, rdeče ali črno blato.
Each film-coated tablet contains 40 mg regorafenib. 
Ena filmsko obložena tableta vsebuje 40 mg regorafeniba.
The incidence of Grade 3 hand-foot skin reaction in Asians was 20.5% (CRC), 23.5% (GIST) and 13.5% (HCC) (see sections 4.2 and 4.4). 
Incidenca kožnih reakcij na dlaneh in podplatih stopnje 3 pri bolnikih azijske rase je bila 20,5 % (CRC), 23,5 % (GIST) in 13,5 % (HCC) (glejte poglavji 4.2 in
At steady state, regorafenib reaches mean peak plasma levels of about 3.9 mg/L (8.1 micromolar) after oral administration of 160 mg regorafenib and the peak-to-trough ratio of mean plasma concentrations is less than 2. 
V stanju dinamičnega ravnovesja doseže regorafenib povprečne največje vrednosti v plazmi približno 3,9 mg/l (8,1 mikromola) po peroralni uporabi 160 mg regorafeniba; razmerje med največjimi in najmanjšimi povprečnimi plazemskimi koncentracijami je manj kot 2.
Treatment with Stivarga may lead to a higher risk of bleeding. 
Zdravljenje z zdravilom Stivarga lahko poveča tveganje za krvavitve.
In the placebo-controlled phase III trials, infections were more often observed in patients treated with Stivarga, compared to patients receiving placebo (all grades: 31.6% vs. 17.2%). 
V s placebom nadzorovanih preskušanjih III. faze so okužbe pogosteje opazili pri bolnikih, zdravljenih z zdravilom Stivarga, kot pri bolnikih, ki so prejemali placebo (vse stopnje: 31,6 % v primerjavi s 17,2 %).
(thrombocytopenia) - reduction in the number of red blood cells (anaemia) - decreased appetite and food intake - high blood pressure (hypertension) - voice changes or hoarseness (dysphonia) - frequent or loose bowel movements (diarrhoea) - painful or dry mouth, painful tongue, mouth sores (stomatitis and/or mucosal inflammation) - feeling sick (nausea) - vomiting - high blood levels of bilirubin, a substance produced by the liver (hyperbilirubinaemia) - changes in enzymes produced by the liver, which may indicate that something is wrong with the liver (increase in transaminases) - redness, pain, blisters and swelling of the palms of the hands or soles of the feet (hand-foot skin reaction) - rash - weakness, lack of strength and energy, excessive tiredness and unusual sleepiness 
- zmanjšano število rdečih krvnih celic (anemija) - zmanjšan apetit in vnos hrane - visok krvni tlak (hipertenzija) - spremembe glasu ali hripavost (disfonija) - pogosto ali tekoče blato (driska) - boleča ali suha usta, boleč jezik, sor v ustih (stomatitis in/ali vnetje sluznice) - občutek siljenja na bruhanje (navzea) - bruhanje - velike vrednosti bilirubina v krvi, snovi, ki nastaja v jetrih (hiperbilirubinemija) - spremenjene vrednosti encimov, ki nastajajo v jetrih, kar lahko kaže, da je nekaj narobe z jetri
Available clinical data indicate similar exposure of regorafenib and its metabolites M-2 and M-5 in patients with mild, moderate or severe renal impairment compared to patients with normal renal function. 
Klinični podatki, ki so na voljo, kažejo podobno izpostavljenost regorafenibu in njegovima presnovkoma M-2 in M-5 pri bolnikih z blago, zmerno ali hudo okvaro ledvic kot pri bolnikih z normalnim delovanjem ledvic.
5.4 months 
5,4 mesecev
The tolerability of Stivarga in these patients has not been established. 
Prenašanja zdravila Stivarga pri teh bolnikih niso dokazali.
In the placebo-controlled phase III trials, the overall incidence of treatment emergent proteinuria was 9.1% in patients treated with Stivarga, compared to 1.9% in patients receiving placebo. 
V s placebom nadzorovanih preskušanjih III. faze je bila celokupna incidenca proteinurije, ki se je pojavila med zdravljenjem, 9,1 % pri bolnikih, zdravljenih z zdravilom Stivarga, v primerjavi z 1,9 % pri bolnikih, ki so prejemali placebo.
Table 3: Adverse drug reactions (ADRs) reported in clinical trials in patients treated with Stivarga 
Preglednica 3: Neželeni učinki, o katerih so poročali v kliničnih preskušanjih pri bolnikih, zdravljenih z zdravilom Stivarga
§ Best Supportive Care * Hazard ratio < 1 favours Stivarga ** NR: not reached 
§ najboljša podporna oskrba (BSC - Best Supportive Care) * razmerje ogroženosti < 1 v korist zdravila Stivarga ** ND: ni dosežena
M-2 is further metabolised by oxidative metabolism mediated by CYP3A4, as well as by glucuronidation mediated by UGT1A9. 
M-2 se nadalje oksidativno presnovi preko CYP3A4, kot tudi z glukuronidacijo preko UGT1A9.
Interrupt therapy for a minimum of 7 days until toxicity resolves to Grade 0-1. 
Zdravljenje je treba prekiniti za vsaj 7 dni, dokler ni stopnja toksičnosti ponovno med 0 in 1.
There is no relevant use of Stivarga in children and adolescents in the indication of liver cancer. 
Zdravilo Stivarga ni namenjeno za uporabo pri otrocih in mladostnikih za indikacijo raka jeter.
In the placebo-controlled phase III trials, the overall incidence of hypertension was higher in patients treated with Stivarga, compared to patients receiving placebo (29.6% vs. 7.5% CRC, 60.6% vs. 25.8% GIST and 31.0% vs. 6.2% HCC). 
V s placebom nadzorovanih preskušanjih III. faze je bila celokupna incidenca hipertenzije večja pri bolnikih zdravljenih z zdravilom Stivarga v primerjavi z bolniki, ki so prejemali placebo (29,6 % oziroma 7,5 % (CRC), 60,6 % oziroma 25,8 % (GIST) in 31,0 % oziroma 6,2 % (HCC)).
Dose reduction and/or temporary interruption of Stivarga, or in severe or persistent cases, permanent discontinuation of Stivarga should be considered (see section 4.2). 
Razmisliti je treba o zmanjšanju odmerka in/ali začasni prekinitvi zdravljenja z zdravilom Stivarga, v hudih ali trdovratnih primerih pa tudi o trajnem prenehanju zdravljenja z zdravilom Stivarga (glejte poglavje 4.2).
(asthenia/fatigue) - pain - fever - weight loss. 
(astenija/izčrpanost) - bolečina - zvišana telesna temperatura - izguba telesne mase
The most serious side effects, for which a fatal outcome has been observed, are: - Severe liver problems, bleeding, gastrointestinal perforation and infection. 
Najbolj resni neželeni učinki, pri katerih so poročali o smrtnih primerih, so - hude okvare jeter, krvavitve, predrtje prebavil in okužbe.
In the placebo-controlled phase III trials, the overall incidence of haemorrhage was 18.2% in patients treated with Stivarga and 9.5% in patients receiving placebo. 
V s placebom nadzorovanih preskušanjih III. faze je bila celokupna incidenca hemoragij 18,2 % pri bolnikih, zdravljenih z zdravilom Stivarga in 9,5 % pri bolnikih, ki so prejemali placebo.
Cardiac ischaemia and infarction 
Ishemija srca in srčni infarkt
Treatment with Stivarga may also lead to a higher risk of fungal infections of the mucous membrane, skin or the body. 
Zdravljenje z zdravilom Stivarga lahko poveča tveganje za glivične okužbe sluznic, kože ali telesa.
In the placebo-controlled phase III trials, the overall incidence of hand-foot skin reaction was higher in patients treated with Stivarga, compared to patients receiving placebo (all grades: 51.4% vs. 6.5% CRC, 66.7% vs. 15.2% GIST and 51.6% vs.7.3% HCC). 
V s placebom nadzorovanih preskušanjih III. faze je bila celokupna incidenca kožnih reakcij na dlaneh in podplatih večja pri bolnikih, zdravljenih z zdravilom Stivarga, v primerjavi z bolniki, ki so prejemali placebo (vse stopnje: 51,4 % oziroma 6,5 % (CRC), 66,7 % oziroma 15,2 % (GIST) in 51,6 % oziroma 7,3 % (HCC)).
Results from animal studies indicate that regorafenib can impair male and female fertility (see section 5.3). 
Rezultati študij na živalih kažejo, da lahko regorafenib škodljivo vpliva na plodnost pri moških in ženskah (glejte poglavje 5.3).
Placebo plus BSC (n= 66) 
placebo (N=66)
Most cases of hand-foot skin reaction in patients treated with Stivarga appeared during the first cycle of treatment and were mild to moderate in severity (Grades 1 and 2: 34.3%%, CRC, 44.7%, GIST and 39.3%, HCC). 
večini primerov so se kožne reakcije na dlaneh in podplatih pri bolnikih, zdravljenih z zdravilom Stivarga, pojavile v prvem ciklu zdravljenja in so bile blage do zmerne (stopnje 1 in 2: 34,3 % (CRC), 44,7 % (GIST) oziroma 39,3 % (HCC)).
1st occurrence 
1. pojav
Blood and lymphatic system disorders Haemoglobin decreased 
Bolezni krvi in limfatičnega sistema zmanjšana vrednost hemoglobina trombocitopenija nevtropenija limfopenija
Disease-specific precautions - Hepatocellular carcinoma (HCC) In the pivotal placebo-controlled phase III study, patients received prior therapy with sorafenib. 
Previdnosti ukrepi, povezani z boleznijo - rak jetrnih celic V ključni, s placebom nadzorovani študiji III. faze so bili bolniki predhodno zdravljeni s sorafenibom.