natgillin/translations-raw huggingface dataset:
All adverse events of acute IPF exacerbation reported by the investigator were adjudicated by a blinded adjudication committee.
Svi štetni događaji akutne egzacerbacije IPF-a koje je prijavio ispitivač bili su procijenjeni od strane „slijepog“ povjerenstva za prosudbu.
Not known
Nepoznato
The in vitro protein binding of nintedanib in human plasma was high, with a bound fraction of 97.8%.
In vitro vezanje nintedaniba za proteine u ljudskoj plazmi bilo je visoko, s udjelom vezanja od 97,8%.
SPECIAL STORAGE CONDITIONS Do not store above 25°C.
POSEBNE MJERE ČUVANJA Ne čuvati na temperaturi iznad 25°C.
Drug-drug interactions between nintedanib and CYP substrates, CYP inhibitors, or CYP inducers are therefore not expected.
Stoga se ne očekuju interakcije lijekova, između nintedaniba i CYP supstrata, CYP inhibitora ili CYP induktora.
Given the similarity in safety profiles for both medicinal products, additive adverse events, including gastrointestinal and hepatic adverse events, may be expected.
Zbog sličnosti sigurnosnih profila ta dva lijeka, mogu se očekivati aditivni štetni događaji, uključujući gastrointestinalne i jetrene štetne događaje.
BIBF 1202 is subsequently glucuronidated by uridine 5'-diphosphoglucuronosyltransferase enzymes (UGT) enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide.
BIBF 1202 se potom glukuronidira pomoću enzima uridin 5'-difosfo-glukuronozil-transferaze (UGT), i to UGT 1A1, UGT 1A7, UGT 1A8 i UGT 1A10, u BIBF 1202 glukuronid.
The most frequently reported adverse reactions associated with the use of nintedanib included diarrhoea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
Najčešće prijavljene nuspojave povezane s primjenom nintedaniba uključivale su proljev, mučninu i povraćanje, bol u abdomenu, smanjen apetit, smanjenje težine i povišene vrijednosti jetrenih enzima.
What you need to know before you take Ofev
Što morate znati prije nego počnete uzimati Ofev
Observed adverse reactions were consistent with the known safety profile of nintedanib, i.e. increased liver enzymes and gastrointestinal symptoms.
Opažene nuspojave odgovarale su poznatom profilu sigurnosti nintedaniba, tj. povišenim vrijednostima jetrenih enzima i gastrointestinalnim simptomima.
Mild liver enzyme increases, which were not due to serious adverse effects such as diarrhoea were only observed in Rhesus monkeys.
Blaga povećanja jetrenih enzima, koja nisu bila povezana s ozbiljnim štetnim učincima poput proljeva, opažena su samo u Rhesus majmuna.
Alternative causes of the liver enzyme elevations should be investigated.
Moraju se istražiti drugi uzorci povišenja jetrenih enzima.
In addition to symptomatic treatment if applicable, the management of adverse reactions to Ofev (see sections 4.4 and 4.8) could include dose reduction and temporary interruption until the specific adverse reaction has resolved to levels that allow continuation of therapy.
Osim simptomatskog liječenja, ako je primjenjivo, zbrinjavanje nuspojava Ofeva (vidjeti dijelove 4.4 i 4.8) može uključivati smanjenje doze i privremeni prekid liječenja sve dok se specifična nuspojava ne smanji do razine koje dozvoljava nastavak terapije.
In case of renal impairment/failure, therapy adjustment should be considered (see section 4.2 Dose adjustments).
U slučaju oštećenja/zatajenja bubrega, potrebno je razmotriti prilagodbu terapije (vidjeti dio 4.2 Prilagodbe doze).
The same applies for nintedanib being a substrate of OCT-1.
Isto se odnosi na nintedanib kao supstrat OCT-1.
Population pharmocokinetic analysis in special populations The PK properties of nintedanib were similar in healthy volunteers, patients with IPF, and cancer patients.
Populacijska farmakokinetička analiza u posebnim skupinama bolesnika Farmakokinetička svojstva nintedaniba bila su slična u zdravih dobrovoljaca, bolesnika s IPF-om i bolesnika s rakom.
The majority of hepatic events occur within the first three months of treatment.
Većina jetrenih događaja javila se unutar prva tri mjeseca liječenja.
Estimated based on a random coefficient regression model.
Procijenjeno na temelju modela regresije nasumičnog koeficijenta.
Hypersensitivity to nintedanib, to peanut or soya, or to any of the excipients listed in section 6.1.
Preosjetljivost na nintedanib, kikiriki ili soju, ili neku od pomoćnih tvari navedenih u dijelu 6.1.
Nintedanib was also not a substrate of BCRP.
Nintedanib ujedno nije bio supstrat BCRP-a.
After intravenous infusion, a high volume of distribution (Vss: 1,050 L, 45.0% gCV) was observed.
Nakon intravenske infuzije opažen je veliki volumen distribucije (Vss: 1050 L, 45,0% gCV).
If you take more Ofev than you should Contact your doctor or pharmacist immediately.
Ako uzmete više Ofeva nego što ste trebali Odmah se obratite svom liječniku ili ljekarniku.
Nintedanib is preferentially distributed in plasma with a blood to plasma ratio of 0.869.
Nintedanib je distribuiran pretežno u plazmi s omjerom krv/plazma od 0,869.
Soft capsule (capsule).
Meka kapsula (kapsula).
Treatment with Ofev should be initiated by physicians experienced in the diagnosis and treatment of IPF.
Liječenje Ofevom moraju započeti liječnici s iskustvom u dijagnosticiranju i liječenju IPF-a.
PHARMACEUTICAL FORM AND CONTENTS 30 x 1 soft capsules
OBLIK I SADRŽAJ 30 x 1 mekih kapsula
You should take your next 100mg dose of Ofev as planned at the next scheduled time recommended by your doctor or pharmacist.
Sljedeću dozu od 100 mg Ofeva morate uzeti kao uobičajeno, prema predviđenom rasporedu koji Vam je preporučio liječnik ili ljekarnik.
Inform your doctor immediately while taking this medicine, - if you get diarrhoea.
Tijekom uzimanja ovog lijeka odmah obavijestite svog liječnika, - ako dobijete proljev.
More than two thirds of patients experiencing diarrhoea reported its first onset already during the first three months of treatment.
Više od dvije trećine bolesnika koji su imali proljev prijavilo je prvu pojavu proljeva već tijekom prva tri mjeseca liječenja.
Swallow the whole capsules with water and do not chew or crush the capsules.
Progutajte cijelu kapsulu s vodom i nemojte ju žvakati ili drobiti.
Diarrhoea led to permanent treatment discontinuation in 4.4% of patients; otherwise the events were managed by antidiarrhoeal therapy, dose reduction or treatment interruption (see section 4.4).
Proljev je doveo do trajnog prekida liječenja u 4,4% bolesnika; u suprotnom bolesnici su bili zbrinuti terapijom protiv proljeva, smanjenjem doze ili privremenim prekidom liječenja (vidjeti dio 4.4).
Nintedanib reached maximum plasma concentrations approximately 2 - 4 h after oral administration as soft gelatine capsule under fed conditions (range 0.5 - 8 h).
Nintedanib postiže maksimalne koncentracije u plazmi približno 2 - 4 h nakon peroralne primjene u obliku meke želatinske kapsule nakon obroka (raspon 0,5 - 8 h).
Tell your doctor or pharmacist immediately if you become pregnant during treatment with Ofev.
Odmah obavijestite svog liječnika ili ljekarnika ako zatrudnite tijekom liječenja Ofevom.
IPF is a condition in which the tissue in your lungs becomes thickened, stiff and scarred over time.
IPF je stanje u kojem tkivo u plućima s vremenom postaje zadebljalo i kruto te se na njemu stvaraju ožiljci.
What Ofev contains - The active substance is nintedanib.
Što Ofev sadrži - Djelatna tvar je nintedanib.
Treatment with Ofev should therefore only be initiated or - in case of perioperative interruption - resumed based on clinical judgement of adequate wound healing.
Liječenje Ofevom stoga se smije započeti, ili u slučaju perioperativnog prekida, nastaviti samo na temelju kliničke procjene odgovarajućeg cijeljenja rane.
Talk to your doctor if you get any side effects.
Obratite se svom liječniku ako primijetite bilo koju nuspojavu.
The key secondary endpoints were change from baseline in Saint George's Respiratory Questionnaire (SGRQ) total score at 52 weeks and time to first acute IPF exacerbation.
Ključne sekundarne mjere ishoda bile su promjena ukupnog rezultata od početnih vrijednosti u upitniku Saint George's Respiratory Questionnaire (SGRQ) nakon 52 tjedna i vrijeme do prve akutne egzacerbacije IPF-a.
From the 2-year carcinogenicity studies in mice and rats, there was no evidence for a carcinogenic potential of nintedanib.
U 2-godišnjim ispitivanjim kancerogenosti na miševima i štakorima nije bilo dokaza o kancerogenom potencijalu nintedaniba.
The likelihood of drug-drug interactions with nintedanib based on CYP metabolism is therefore considered to be low.
Stoga se vjerojatnost interakcija lijekova s nintedanibom na temelju CYP metabolizma smatra malom.
If you stop taking Ofev
Ako prestanete uzimati Ofev
Genotoxicity studies indicated no mutagenic potential for nintedanib.
Ispitivanja genotoksičnosti nisu ukazala na mutageni potencijal nintedaniba.
There is no information on the excretion of nintedanib and its metabolites in human milk.
Nema podataka o izlučivanju nintedaniba i njegovih metabolita u majčino mlijeko.
Elevations of liver enzymes (ALT, AST, blood alkaline phosphatase (ALKP), gamma-glutamyltransferase (GGT)) and bilirubin were reversible upon dose reduction or interruption in the majority of cases.
Povišenja vrijednosti jetrenih enzima (ALT, AST, alkalne fosfataze u krvi (AP), gama-glutamiltransferaze (GGT)) i bilirubina su u većini slučajeva nakon sniženja doze ili prekida primjene bila reverzibilna.
Only a minor extent of the biotransformation of nintedanib consisted of CYP pathways, with CYP 3A4 being the predominant enzyme involved.
Samo je manji dio biotransformacije nintedaniba uključivao CYP metaboličke puteve, sa CYP 3A4 kao glavnim uključenim enzimom.
Dietary soya products are known to cause allergic reactions including severe anaphylaxis in persons with soya allergy.
Poznato je da prehrambeni proizvodi soje uzrokuju alergijske reakcije uključujući tešku anafilaksiju u osoba alergičnih na soju.
In most patients with nausea and vomiting, the event was of mild to moderate intensity.
U većine bolesnika mučnina i povraćanje bili su blagog do umjerenog intenziteta.
For further information about special populations, recommended measures and dosing adjustments in case of diarrhoea and hepatic enzyme increased, refer additionally to sections 4.4 and 4.2, respectively.
Za dodatne informacije o posebnim populacijama bolesnika, preporučenim mjerama i prilagodbama doziranja u slučaju proljeva i porasta vrijednosti jetrenih enzima, vidjeti također dio 4.4, odnosno 4.2.
The population mean exposure to nintedanib was 33 - 50% higher in Chinese, Taiwanese, and Indian patients and 16% higher in Japanese patients while it was 16 - 22% lower in Koreans compared to Caucasians (body weight corrected).
Srednja vrijednost izloženosti populacije nintedanibu bila je 33 - 50% veća u kineskih, tajvanskih i indijskih bolesnika i 16% veća u japanskih bolesnika, dok je 16 - 22% niža bila u korejskih u usporedbi s bolesnicima bijele rase (korigirano prema tjelesnoj težini).
Nausea and vomiting
Mučnina i povraćanje
1 (SE) of decline over 52 weeks Comparison vs placebo Difference 95% CI
1 (SE) smanjenja tijekom 52 tjedna Usporedba naspram placeba Razlika 95% CI
Dose proportionality was shown by increase of nintedanib exposure (dose range 50 - 450 mg once daily and 150 - 300 mg twice daily).
Proporcionalnost doze pokazala se povećanjem izloženosti nintedanibu (raspon doze 50-450 mg jedanput dnevno i 150 - 300 mg dvaput dnevno).
As some other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when nintedanib is administered in patients who may develop QTc prolongation.
Budući da je poznato da neki drugi inhibitori tirozin kinaze utječu na QT-interval, nužan je oprez pri primjeni nintedaniba u bolesnika koji mogu razviti produljenje QTc-intervala.
Nintedanib follows at least bi-phasic disposition kinetics.
Nintedanib slijedi najmanje dvofaznu kinetiku dispozicije.
In rats, small amounts of radiolabelled nintedanib and/or its metabolites were excreted into the milk (≤ 0.5% of the administered dose).
U štakora, male količine radiooznačenog nintedaniba i/ili njegovih metabolita izlučili su se u mlijeko (≤ 0,5% primijenjene doze).
If a patient does not tolerate 100 mg twice daily, treatment with Ofev should be discontinued.
Ako bolesnik ne podnosi dozu od 100 mg dvaput dnevno, liječenje Ofevom mora se prekinuti.
Ofev is for oral use.
Ofev se primjenjuje peroralno.
Only a weak inhibitory potential on OCT-1, BCRP, and P-gp was observed in vitro which is considered to be of low clinical relevance.
Opažen je samo slab in vitro inhibitorni potencijal na proteine OCT-1, BCRP i P-gp što se smatra od neznatnog kliničkog značaja.
No a-priori dose adjustment is required on the basis of a patient's age.
Nije potrebna a priori prilagodba doze na temelju dobi bolesnika.
Nintedanib may cause foetal harm in humans (see section 5.3).
Nintedanib u ljudi može uzrokovati fetalno oštećenje (vidjeti dio 5.3).
The safety, efficacy, and pharmacokinetics of nintedanib have not been studied in patients with severe renal impairment (<30 ml/min creatinine clearance).
Sigurnost, djelotvornost i farmakokinetika nintedaniba nisu ispitani u bolesnika s teškim oštećenjem bubrega (klirens kreatinina < 30 ml/min.).
Patients with a recent history of myocardial infarction or stroke were excluded from the INPULSIS trials.
Bolesnici s anamnezom nedavnog infarkta miokarda ili moždanog udara bili su isključeni iz ispitivanja INPULSIS.
Based on preclinical investigations there is no evidence for impairment of male fertility (see section 5.3).
Na temelju pretkliničkih istraživanja, nema dokaza o smanjenju muške plodnosti (vidjeti dio 5.3).
60 x 1 soft capsules
60 x 1 mekih kapsula
Nintedanib was shown to be not a substrate or inhibitor of OATP-1B1, OATP-1B3, OATP-2B1, OCT-2, or MRP-2 in vitro.
In vitro je pokazano da nintedanib nije niti supstrat niti inhibitor OATP-1B1, OATP-1B3, OATP-2B1, OCT-2 ili MRP-2.
Therapy with Ofev should be permanently discontinued in patients who develop gastrointestinal perforation.
Liječenje Ofevom se mora trajno prekinuti u bolesnika koji razviju gastrointestinalnu perforaciju.
BATCH NUMBER Lot
13. BROJ SERIJE Lot
Based on results of a Population PK (PopPK) analysis in patients with IPF and non small cell lung cancer (NSCLC) (N=1,191) and descriptive investigations, exposure to nintedanib was not influenced by sex (body weight corrected), mild and moderate renal impairment (estimated by creatinine clearance), alcohol consumption, or P-gp genotype.
Na temelju rezultata analize populacijske farmakokinetike (PopPK) u bolesnika s IPF-om i karcinomom pluća nemalih stanica (engl. non small cell lung cancer, NSCLC) (N=1191) i opisnih istraživanja, na izloženost nintedanibu nije utjecao spol (korigiran na tjelesnu težinu), blago i umjereno oštećenje bubrega (procijenjeno prema klirensu kreatinina), konzumacija alkohola ili genotip P-gp-a.
The estimated difference between the treatment groups was 0.131 L/year (95% CI 0.027, 0.235).
Procijenjena razlika između skupina liječenja iznosila je 0,131 l/godina (95% CI 0,027, 0,235).
Less than 1% of a single dose of nintedanib is excreted via the kidney (see section 5.2).
Manje od 1% jednokratne doze nintedaniba se izlučuje putem bubrega (vidjeti dio 5.2).
Within each frequency grouping adverse reactions are presented in order of decreasing seriousness.
Unutar svake skupine učestalosti nuspojave su prikazane prema redoslijedu smanjenja ozbiljnosti.
In patients with mild hepatic impairment (Child Pugh A), the recommended dose of Ofev is 100 mg twice daily approximately 12 hours apart.
U bolesnika s blagim oštećenjem funkcije jetre (Child Pugh A) preporučena doza Ofeva je 100 mg dvaput dnevno, u razmaku od približno 12 sati.
Total plasma clearance after intravenous infusion was high (CL: 1,390 mL/min, 28.8% gCV).
Ukupni plazmatski klirens nakon intravenske infuzije bio je visok (CL: 1390 ml/min, 28,8% gCV).
Non-serious and serious bleeding events, some of which were fatal, have been reported in the postmarketing period (including patients with or without anticoagulant therapy or other medicinal products that could cause bleeding).
U razdoblju nakon stavljanja lijeka u promet bilo je prijavljenih slučajeva krvarenja koje nije bilo ozbiljno i slučajeva ozbiljnog krvarenja od kojih su neki bili sa smrtnim ishodom, (uključujući bolesnike sa ili bez terapije antikoagulansima ili drugim lijekovima koji mogu uzrokovati krvarenje).
Arterial thromboembolic events
Arterijski tromboembolijski događaji
Capsule fill:
Punjenje kapsule:
General toxicology
Opća toksikologija
Single dose toxicity studies in rats and mice indicated a low acute toxic potential of nintedanib.
Ispitivanja toksičnosti jednokratne doze u štakora i miševa ukazala su na nizak akutni toksični potencijal nintedaniba.
The estimated mean change from baseline in SGRQ total score at 52 weeks was 5.46 for placebo, indicating worsening of the health-related quality of life and -0.66 for nintedanib, indicating stable health-related quality of life.
Procijenjena srednja vrijednost promjene od početne vrijednosti u ukupnom rezultatu upitnika SGRQ nakon 52 tjedna iznosila je 5,46 za placebo, ukazujući na pogoršanje kvalitete života povezane sa zdravljem te -0,66 za nintedanib, ukazujući na stabilnu kvalitetu života povezanu sa zdravljem.
Nintedanib inhibits the activation of FGFR and PDGFR signalling cascades which are critically involved in proliferation, migration and differentiation of lung fibroblasts/myofibroblasts, the hallmark cells in the pathology of IPF.
Nintedanib inhibira aktivaciju FGFR i PDGFR signalnih kaskada, koje su od kritičnog značaja za proliferaciju, migraciju i diferencijaciju plućnih fibroblasta/miofibroblasta, karakterističnih stanica u patologiji IPF-a.
Nintedanib is a small molecule tyrosine kinase inhibitor including the receptors platelet-derived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, and VEGFR 1-3.
Nintedanib je mala molekula, inhibitor tirozin-kinaze, uključujući α i ß receptore faktora rasta koji potječe od trombocita (engl. platelet-derived growth factor receptor, PDGFR) receptor fibroblastnog faktora rasta (engl. fibroblast growth factor receptor, FGFR) 1-3 i VEGFR 1-3.
The clinical efficacy of nintedanib has been studied in patients with IPF in two phase III, randomised, double-blind, placebo-controlled studies with identical design (INPULSIS-1 (1199.32) and INPULSIS-2 (1199.34)).
Klinička djelotvornost nintedaniba ispitivala se u bolesnika s IPF-om u dvama randomiziranim, dvostruko slijepim, placebom kontroliranim ispitivanjima faze III s identičnim dizajnom INPULSIS-1 (1199.32) i INPULSIS-2 (1199.34)).
Concomitant treatment with pirfenidone
Istodobno liječenje pirfenidonom
Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90%).
Nintedanib se pretežno izlučuje putem žuči/stolice (> 90%).
In this case your doctor will prescribe Ofev 100 mg capsules for your treatment.
U tom slučaju liječnik će Vam propisati liječenje Ofev 100 mg kapsulama.
Do not breast-feed during the treatment with Ofev since there may be a risk for harm to the breastfeeding child.
Nemojte dojiti tijekom liječenja Ofevom jer može postojati rizik od štetnog učinka za dojenče.
Number of analysed patients Rate
Broj analiziranih bolesnika Stopa
Renal function
Jetrena funkcija
In the INPULSIS trials, one patient was inadvertently exposed to a dose of 600 mg daily for a total of 21 days.
U ispitivanjima INPULSIS jedan je bolesnik nehotice bio izložen dozi od 600 mg dnevno u trajanju od ukupno 21 dan.
The contribution of renal excretion to the total clearance was low (0.649% of dose, 26.3% gCV).
Doprinos bubrežnog izlučivanja ukupnom klirensu bio je nizak (0,649% doze, 26,3% gCV).
Accumulation upon multiple administrations was 1.04-fold for Cmax and 1.38-fold for AUCτ.
Nakupljanje nakon višekratnih primjena iznosilo je 1,04 puta za Cmax i 1,38 puta za AUCτ.
Patients with mild hepatic impairment (Child Pugh A) should be treated with a reduced dose of Ofev (see sections 4.2 and 5.2).
Bolesnike s blagim oštećenjem funkcije jetre (Child Pugh A) potrebno je liječiti smanjenom dozom Ofeva (vidjeti dijelove 4.2 i 5.2).
LIST OF EXCIPIENTS Contains soya lecithin.
POPIS POMOĆNIH TVARI Sadrži sojin lecitin.
Particular caution should be exercised when treating patients with previous abdominal surgery, previous history of peptic ulceration, diverticular disease or receiving concomitant corticosteroids or NSAIDs.
Osobiti oprez se mora primijeniti pri liječenju bolesnika koji su bili podvrgnuti ranijem abdominalnom kirurškom zahvatu, koji u anamnezi imaju peptički ulkus, divertikularnu bolest ili istodobno primaju kortikosteroide ili nesteroidne protuupalne lijekove (NSAIL-ove).
If you forget to take Ofev
Ako ste zaboravili uzeti Ofev
In addition, similar effects were observed on other lung function endpoints e.g. change from baseline in FVC at week 52 and FVC responder analyses providing further substantiation of the effects of nintedanib on slowing disease progression.
Pored toga, slični učinci bili su opaženi u drugim mjerama ishoda za plućne funkcije, npr. u promjeni od početne vrijednosti FVC-a u 52. tjednu i analizama FVC-a u osoba s odgovorom, što pruža daljnju potvrdu učinaka nintedaniba na usporavanje progresije bolesti.
In addition nintedanib inhibits Flt-3 (Fms-like tyrosine-protein kinase), Lck (lymphocyte-specific tyrosine-protein kinase), Lyn (tyrosine-protein kinase lyn) and Src (proto-oncogene tyrosine-protein kinase src) kinases.
Nadalje, nintedanib inhibira Flt-3 (Fms-slična protein-tirozin-kinaza), Lck (limfocit-specifična protein-tirozin-kinaza) i Src (proto-onkogen protein-tirozin-kinaza Src) kinazu.
Nintedanib is a substrate of P-gp (see section 5.2).
Nintedanib je supstrat za P-gp (vidjeti dio 5.2).
Gastrointestinal perforations
Gastrointestinalne perforacije
The prevalent metabolic reaction for nintedanib is hydrolytic cleavage by esterases resulting in the free acid moiety BIBF 1202.
Dominantna metabolička reakcija za nintedanib je hidrolitičko cijepanje esterazama koje rezultira nastankom BIBF 1202 sa slobodnom kiselinskom skupinom.
C] nintedanib was via faecal/biliary excretion (93.4% of dose, 2.61% gCV).
C] nintedaniba bio je izlučivanjem stolicom/putem žuči (93,4% doze, 2,61% gCV).
Cytochrome (CYP)-enzymes
Enzimi citokroma (CYP)
Change from baseline in SGRQ total score at week 52
Promjena od početne vrijednosti u ukupnom rezultatu upitnika SGRQ u 52. tjednu
NAME OF THE MARKETING AUTHORISATION HOLDER Boehringer Ingelheim (logo)
NAZIV NOSITELJA ODOBRENJA ZA STAVLJANJE LIJEKA U PROMET Boehringer Ingelheim (logo)
Exposure increased in patients with hepatic impairment (Child Pugh A, Child Pugh B; see section 5.2).
Izloženost je povećana u bolesnika s oštećenjem funkcije jetre (Child Pugh A, Child Pugh B; vidjeti dio 5.2).
In most patients the adverse reaction was of mild to moderate intensity and occurred within the first 3 months of treatment.
Nuspojava je u većine bolesnika bila blagog do umjerenog intenziteta i javila se unutar prva 3 mjeseca liječenja.
In a pre- and postnatal development study in rats, effects on pre- and post-natal development were seen at an exposure below the MRHD.
U ispitivanjima pre- i postnatalnog razvoja na štakorima, opaženi su učinci na pre- i postnatalni razvoj pri izloženosti ispod izloženosti pri MRHD-u.
Alanine aminotransferase (ALT) increased, Aspartate aminotransferase (AST) increased, Gamma glutamyl transferase (GGT) increased
Poremećaji jetre i žuči povišene vrijednosti jetrenih enzima povišena alanin aminotransferaza (ALT), povišena aspartat aminotransferaza (AST), povišena gama-glutamil-transferaza (GGT)
Not known (cannot be estimated from the available data) - Renal failure - An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)
Nepoznato (ne može se procijeniti iz dostupnih podataka) - zatajenje bubrega - proširenje i slabljenje stijenke krvne žile ili rascjep stijenke krvne žile (aneurizme i disekcije arterije)