natgillin/translations-raw huggingface dataset:
Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE31
Farmakoterapijska skupina: Antineoplastici, inhibitori protein-kinaze, ATK oznaka: L01XE31.
If a dose of nintedanib is missed, administration should resume at the next scheduled time at the recommended dose.
Ako se propusti doza nintedaniba, primjenu treba nastaviti u sljedeće predviđeno vrijeme u preporučenoj dozi.
Patients were randomized (1:1) to receive nintedanib 200 mg orally twice daily in combination with 75 mg/m of intravenous docetaxel every 21 days (n = 655) or placebo orally twice daily in combination with 75 mg/m2 of docetaxel every 21 days (n = 659).
Bolesnici su bili randomizirani (1:1) kako bi primili nintedanib 200 mg peroralno dvaput dnevno u kombinaciji s 75 mg/m intravenskog docetaksela svakih 21 dan (n = 655) ili placebo peroralno dvaput dnevno u kombinaciji s 75 mg/m2 docetaksela svakih 21 dan (n = 659).
Elevation of liver enzymes (ALT, AST, ALKP, gammaglutamyltransferase (GGT)) and bilirubin were reversible upon dose reduction or interruption in the majority of cases.
Povišenja vrijednosti jetrenih enzima (ALT, AST, AP, gama-glutamiltransferaze (GGT)) i bilirubina su u većini slučajeva nakon sniženja doze ili prekida primjene bila reverzibilna.
In patients on chronic low dose therapy with low molecular weight heparins or acetylsalicylic acid, no increased frequency of bleeding was observed.
U bolesnika na kroničnoj niskodoznoj terapiji heparinima male molekulske mase ili acetilsalicilatnom kiselinom, nije opažena povećana učestalost krvarenja.
The trial included 658 patients (50.1 %) with adenocarcinoma, 555 patients (42.2 %) with squamous cell carcinoma, and 101 patients (7.7 %) with other tumour histologies.
Ispitivanje je uključivalo 658 bolesnika (50,1 %) s adenokarcinomom, 555 bolesnika (42,2 %) s karcinomom skvamoznih stanica i 101 bolesnika (7,7 %) s tumorom drugog histološkog nalaza.
Based on population pharmacokinetic (PK) analyses, no a priori dose adjustments of Vargatef are necessary (see section 5.2).
Na temelju populacijskih farmakokinetičkih analiza, a priori nisu potrebne prilagodbe doze Vargatefa (vidjeti dio 5.2).
Patients who developed thromboembolic events during treatment and who required anticoagulant treatment were allowed to continue Vargatef and did not show an increased frequency of bleeding events.
Bolesnicima koji su razvili tromboembolijske događaje tijekom liječenja i koji su trebali antikoagulacijsko liječenje, bilo je dozvoljeno nastaviti primjenu Vargatefa, i oni nisu pokazali veću učestalost događaja krvarenja.
Neutropenia and sepsis
Neutropenija i sepsa
It is important that the patient's blood counts are monitored during therapy, in particular during the combination treatment with docetaxel (see section 4.4).
Važno je kontrolirati krvnu sliku bolesnika tijekom terapije, a naročito tijekom kombiniranog liječenja s docetakselom (vidjeti dio 4.4).
Progression free survival (PFS)* - primary analysis Patients, n
Preživljenje bez progresije (PFS)* - primarna analiza Bolesnici, n
Tell your doctor or pharmacist immediately if you become pregnant during treatment with Vargatef.
Odmah obavijestite svog liječnika ili ljekarnika ako zatrudnite tijekom liječenja Vargatefom.
A pre-specified evaluation was performed in the population of adenocarcinoma patients considered to have entered the trial with a particularly poor treatment prognosis, namely, patients who progressed during or shortly after first-line therapy prior to trial entry.
Prethodno specificirana procjena izvedena je u populaciji bolesnika s adenokarcinomom za koje se smatralo da su u ispitivanje ušli s posebno lošom prognozom liječenja, odnosno, bolesnici čija je bolest napredovala tijekom ili neposredno nakon prve linije liječenja prije ulaska u ispitivanje.
BIBF 1202 is subsequently glucuronidated by UGT enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide.
BIBF 1202 se potom glukuronizira enzimima UGT, i to UGT 1A1, UGT 1A7, UGT 1A8 i UGT 1A10, u BIBF 1202 glukuronid.
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 izlučile su se u mlijeko (≤ 0,5% primijenjene doze).
Total plasma clearance after intravenous infusion was high (CL: 1390 mL/min, 28.8 % gCV).
Ukupni plazmatski klirens nakon intravenske infuzije bio je visok (CL: 1390 ml/min., 28,8 % gCV).
Only a minor extent of the biotransformation of nintedanib consisted of CYP pathways with CYP 3A4 being the predominant enzyme involved.
Samo je mali dio biotransformacije nintedaniba uključivao CYP puteve s CYP 3A4 kao glavnim uključenim enzimom.
The proportion of adenocarcinoma patients with stage < IIIB/IV at diagnosis was small and balanced across treatment arms (placebo: 54 patients (16.1 %); nintedanib: 50 patients, (15.5 %)).
Udio bolesnika s adenokarcinomom sa stadijem bolesti < IIIB/IV prilikom dijagnoze bio je malen i uravnotežen kroz liječene skupine (placebo: 54 bolesnika (16,1 %); nintedanib: 50 bolesnika (15,5 %)).
If you cannot tolerate the recommended dose of 400 mg per day because of side effects (see section 4), your doctor may reduce the daily dose of Vargatef.
Ako ne podnosite preporučenu dozu od 400 mg dnevno zbog nuspojava (vidjeti dio 4), Vaš liječnik može smanjiti dnevnu dozu Vargatefa.
During treatment with Vargatef your doctor will regularly monitor your blood cells and examine you for signs of infection, such as inflammation, fever or tiredness.
Tijekom liječenja Vargatefom Vaš liječnik će redovito provjeravati Vašu kompletnu krvnu sliku i pregledavati Vas radi znakova infekcije, poput upale, vrućice ili umora.
Do not take Vargatef on the same day as your chemotherapy treatment with docetaxel.
Ne uzimajte Vargatef istog dana kada primate kemoterapijsko liječenje docetakselom.
Limited safety data available from 9 patients with moderate hepatic impairment (Child Pugh B) are insufficient to characterize this population.
Ograničeni podaci o sigurnosti primjene lijeka dobiveni od 9 bolesnika s umjerenim oštećenjem funkcije jetre (Child Pugh B) nisu dovoljni za karakterizaciju ove populacije.
There are no data available from clinical trials for patients with inherited predisposition to bleeding or for patients receiving a full dose of anticoagulative treatment prior to start of treatment with Vargatef (for post-marketing experience, see ‘Haemorrhage' above).
Nema dostupnih podataka iz kliničkih ispitivanja za bolesnike s nasljeđenom predispozicijom za krvarenje ili bolesnike koji primaju punu dozu antikoagulacijskog liječenja prije počinjanja liječenja Vargatefom (za iskustvo nakon stavljanja lijeka u promet, vidjeti „Krvarenje“ gore).
Nintedanib may cause foetal harm in humans (see section 5.3).
Nintedanib može prouzročiti fetalno oštećenje u ljudi (vidjeti dio 5.3).
This result was confirmed in the follow-up PFS analysis (HR 0.85, 95 % CI: 0.75 - 0.96; p = 0.0070) which included all events collected at the time of the final OS analysis.
Ovaj je rezultat potvrđen u analizi praćenja preživljenja bez napredovanja bolesti (HR 0,85 %, 95 % CI: 0,75-0,96; p = 0,0070), koja je uključivala sve događaje prikupljene u vrijeme zaključne analize ukupnog preživljenja.
Co-administration of nintedanib with docetaxel (75 mg/m²) did not alter the pharmacokinetics of either medicinal product to a relevant extent.
Istodobna primjena nintedaniba s docetakselom (75 mg/m²) nije značajno promijenila farmakokinetiku niti jednog od lijekova.
Mild to moderate epistaxis represented the most frequent bleeding event.
Blaga do umjerena epistaksa je predstavljala najčešći oblik krvarenja.
As several other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administering nintedanib in patients who may develop QTc prolongation.
Budući da je za nekoliko drugih inhibitora tirozin kinaza poznato da utječu na QT interval, nintedanib se mora primjenjivati s oprezom u bolesnika koji mogu razviti produljenje QTc intervala.
In the clinical trial LUME-Lung 1 (see section 5.1), the majority of patients had mild to moderate diarrhoea.
U kliničkom ispitivanju LUME-Lung 1 (vidjeti dio 5.1), većina bolesnika je imala blagi do umjereni proljev.
Patients treated with Vargatef have an increased risk of venous thromboembolism including pulmonary embolism and deep vein thrombosis.
Bolesnici liječeni Vargatefom imaju povećani rizik od venske tromboembolije uključujući plućnu emboliju i duboku vensku trombozu.
Based on preclinical investigations there is no evidence for impairment of male fertility (see section 5.3).
Na temelju pretkliničkih istraživanja, ne postoje dokazi o smanjenju muške plodnosti (vidjeti dio 5.3).
Logistic regression revealed a statistically significant association between nintedanib exposure and DCE-MRI response.
Logistička regresija utvrdila je statistički značajnu povezanost između izloženosti nintedanibu i odgovora DCE-MRI.
Patients may continue therapy with nintedanib after discontinuation of docetaxel for as long as clinical benefit is observed or until unacceptable toxicity occurs.
Bolesnici mogu nastaviti liječenje nintedanibom nakon prekida terapije docetakselom sve dok je vidljiva klinička dobrobit ili do pojave neprihvatljive toksičnosti.
The frequency of gastrointestinal perforation was comparable between the treatment arms in the clinical trial.
Učestalost gastrointestinalne perforacije je bila usporediva između liječenih skupina u kliničkom ispitivanju.
Transaminase, ALKP and bilirubin levels should be investigated before initiation of the combination treatment with Vargatef plus docetaxel.
Vrijednosti transaminaza, AP i bilirubina treba ispitati prije početka kombiniranog liječenja Vargatefom i docetakselom.
Nevertheless, the overall treatment benefit of nintedanib was observed without adversely affecting self-reported quality of life.
Unatoč tome, cjelokupna korist liječenja nintedanibom uočena je bez štetnog djelovanja na kvalitetu života koju je bolesnik sam prijavio.
Therefore, it is not recommended to treat these patients with Vargatef.
Stoga se ne preporučuje liječiti ove skupine bolesnika Vargatefom.
Of note, pre-planned analyses according to histology showed statistically significant difference in OS between treatment arms in the adenocarcinoma population only (Table 4).
Potrebno je napomenuti da su prethodno planirane analize u skladu s histološkim nalazima pokazale značajnu razliku u ukupnom preživljavanju između liječenih skupina samo u populaciji adenokarcinoma (tablica 4).
Nintedanib blocks the activity of a group of proteins which are involved in the development of new blood vessels that cancer cells need to supply them with food and oxygen.
Nintedanib blokira aktivnost skupine proteina koji su uključeni u razvoj novih krvnih žila koje su potrebne stanicama raka kako bi ih opskrbljivale hranom i kisikom.
What you need to know before you take Vargatef
Što morate znati prije nego počnete uzimati Vargatef
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).
No increased frequency of cerebral bleeding in patients with adequately pre-treated brain metastases which were stable for ≥ 4 weeks before start of treatment with Vargatef was observed.
Nije opažena povećana učestalost cerebralnog krvarenja u bolesnika s prethodno odgovarajuće liječenim metastazama u mozgu koje su bile stabilne ≥ 4 tjedana prije početka liječenja Vargatefom.
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).
For information about special populations, recommended measures and dosing adjustments in case of liver enzyme and bilirubin elevations, see sections 4.4 and 4.2, respectively.
Za informacije o posebnim skupinama, preporučenim mjerama i prilagodbama doziranja u slučaju porasta vrijednosti jetrenih enzima i bilirubina vidjeti dio 4.4 odnosno 4.2.
Myocardial infarction (see section 4.4)
Srčani poremećaji infarkt miokarda (vidjeti dio 4.4)
The primary endpoint was progression-free survival (PFS) as assessed by an independent review committee (IRC) based on the intent-to-treat (ITT) population and tested by histology.
Primarni ishod bio je preživljenje bez progresije bolesti (PFS; engl. progression-free survival) prema procjeni neovisnog povjerenstva za procjenu (IRC; engl. independent review committee) na temelju skupine planirane za liječenje (ITT; engl. intent-to-treat) i histološkog ispitivanja.
Supportive care for nausea and vomiting may include medicinal products with anti-emetic properties, e.g. glucocorticoids, anti-histamines or 5-HT3 receptor antagonists and adequate hydration.
Potporno liječenje mučnine i povraćanja može uključivati lijekove s antiemetičkim djelovanjem, npr. glukokortikoide, antihistaminike ili antagoniste 5-HT3 receptora te odgovarajući nadomjestak tekućine.
In addition Fms-like tyrosine-protein kinase (Flt)-3, lymphocyte-specific tyrosine-protein kinase (Lck) and proto-oncogene tyrosine-protein kinase Src (Src) are inhibited.
Nadalje, inhibirane su Fms-slična protein-tirozin-kinaza (Flt)-3, limfocit-specifična protein-tirozin-kinaza (Lck) i proto-onkogen protein-tirozin-kinaza Src (Src).
Therapy with Vargatef should be permanently discontinued in patients who develop gastrointestinal perforation.
Liječenje Vargatefom se mora trajno prekinuti u bolesnika koji razviju gastrointestinalnu perforaciju.
Nausea and vomiting, mostly of mild to moderate severity, were frequently reported gastrointestinal adverse reactions (see section 4.8).
Mučnina i povraćanje, najčešće blage do umjerene težine, bile su često prijavljene gastrointestinalne nuspojave (vidjeti dio 4.8).
Nintedanib is predominantly eliminated via biliary/faecal excretion (> 90 %).
Nintedanib se pretežno izlučuje putem žuči/stolice (> 90%).
The rates of sepsis (1.3 %) and febrile neutropenia (7.5 %) were increased under treatment with nintedanib as compared to the placebo arm.
Učestalost sepse (1,3 %) i febrilne neutropenije (7,5 %) bila je povećana pri liječenju nintedanibom u usporedbi sa skupinom koja je primala placebo.
If necessary, your doctor may further reduce your daily dose to 200 mg per day (two capsules of 100 mg).
Ako je potrebno, liječnik može dodatno smanjiti Vašu dnevnu dozu na 200 mg dnevno (dvije kapsule od 100 mg).
In vitro, CYP-dependent metabolism accounted for about 5 % compared to about 25 % ester cleavage.
O CYP-u ovisan metabolizam u in vitro uvjetima bio je odgovoran za približno 5 % cijepanja u usporedbi s 25 % cijepanja estera.
Subsequent complications such as sepsis or febrile neutropenia have been observed.
Opažene su naknadne komplikacije poput sepse ili febrilne neutropenije.
Observed adverse events were consistent with the known safety profile of nintedanib, i.e. increased liver enzymes and gastrointestinal symptoms.
Uočeni štetni događaji odgovarali su poznatom profilu sigurnosti nintedaniba, tj. povećanim vrijednostima jetrenih enzima i gastrointestinalnim simptomima.
Patients taking concomitant anticoagulation, such as warfarin or phenprocoumon should be monitored regularly for changes in prothrombin time, international normalised ratio (INR), and clinical bleeding episodes.
Bolesnike, koji su istodobno na antikoagulacijskoj terapiji, poput varfarina ili fenprokumona, mora se redovito nadzirati u smislu promjene protrombinskog vremena, internacionalnog normaliziranog omjera (INR) i kliničkih epizoda krvarenja.
Treatment with Vargatef should therefore only be initiated or - in case of perioperative interruption - resumed based on clinical judgement of adequate wound healing.
Liječenje Vargatefom stoga se smije započeti ili, u slučaju perioperativnog prekida, nastaviti na temelju kliničke procjene odgovarajućeg cijeljenja rane.
Five point eight percent (5.8 %) of the patients had stable brain metastasis at trial entry and 3.8 % had prior bevacizumab treatment.
Pri ulasku u ispitivanje, 5,8 % bolesnika imalo je stabilne metastaze u mozgu, a 3,8 % ih je prethodno bilo liječeno bevacizumabom.
Diarrhoea occurred in 43.4 % (≥ grade 3: 6.3 %) of adenocarcinoma patients in the nintedanib arm.
Proljev se javio u 43,4 % (≥ stupanj 3: 6,3 %) bolesnika s adenokarcinomom u skupini liječenoj nintedanibom.
Common side effects(may affect up to 1 in10 people) Blood poisoning (sepsis) -please see above
Česte nuspojave (mogu se javiti u do 1 na 10 osoba) - Trovanje krvi (sepsa) - molimo pogledati tekst gore
Liver enzyme elevations and hyperbilirubinaemia
Porast vrijednosti jetrenih enzima i hiperbilirubinemija
In rabbits, embryofoetal lethality was observed at an exposure approximately 8 times higher than at the MRHD.
U kunića je zamijećena embriofetalna smrtnost pri izloženosti približno 8 puta većoj od izloženosti pri MRHD-u.
Nintedanib is a triple angiokinase inhibitor blocking vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR α and ß) and fibroblast growth factor receptors (FGFR 1-3) kinase activity.
Nintedanib je trostruki angiokinazni inhibitor koji blokira kinaznu aktivnost receptora za vaskularni endotelni faktor rasta (VEGFR 1-3; engl. vascular endothelial growth factor receptors), receptora za trombocitni faktor rasta (PDGFR α i ß; engl. platelet-derived growth factor receptors) i receptora za fibroblastni faktor rasta (FGFR 1-3; engl. fibroblast growth factor receptors).
Events of pancreatitis have been reported in patients taking nintedanib for the treatment of IPF and NSCLC.
Slučajevi pankreatitisa zabilježeni su u bolesnika koji su uzimali nintedanib za liječenje IPF-a i NSCLC-a.
Single arm study to examine whether genetic/genomic markers (alone or combined with clinical covariates) could be used to predict overall survival (OS) in NSCLC patients eligible for treatment with nintedanib.
2. Provesti studiju s jednom skupinom kako bi se ispitalo mogu li se genetički/genomski markeri (sami ili u kombinaciji s kliničkim kovarijatama) koristiti za predviđanje ukupnog preživljenja (OS) bolesnika s NSCLC-om koji su podobni za liječenje nintedanibom.
Urinary excretion of the unchanged active substance within 48 h was about 0.05 % of the dose (31.5 % gCV) after oral and about 1.4 % of dose (24.2 % gCV) after intravenous administration; the renal clearance was 20 mL/min (32.6 % gCV).
Urinarno izlučivanje nepromijenjene djelatne tvari unutar 48 h iznosilo je približno 0,05 % doze (31,5 % gCV) nakon peroralne i približno 1,4 % doze (24,2 % gCV) nakon intravenske primjene; bubrežni klirens je iznosio 20 ml/min. (32,6 % gCV).
Your doctor may reduce your recommended dose to 300 mg per day (two capsules of 150 mg).
Liječnik Vam može smanjiti preporučenu dozu na 300 mg dnevno (dvije kapsule od 150 mg).
In the majority of patients, elevations of liver parameters were reversible.
U većine bolesnika porast vrijednosti jetrenih enzima je bio reverzibilan.
In the clinical trial (LUME-Lung 1; see section 5.1) with Vargatef, the frequency of bleeding in both treatment arms was comparable (see section 4.8).
U kliničkom ispitivanju Vargatefa (LUME-Lung 1; vidjeti dio 5.1), učestalost krvarenja u obje liječene skupine bila je usporediva (vidjeti dio 4.8).
The values should be monitored as clinically indicated or periodically during treatment, i.e. in the combination phase with docetaxel at the beginning of each treatment cycle and monthly in case Vargatef is continued as monotherapy after discontinuation of docetaxel.
Vrijednosti treba nadzirati prema kliničkoj indikaciji ili povremeno tijekom liječenja, tj. u fazi kombinacije s docetakselom na početku svakog ciklusa liječenja i jednom mjesečno u slučaju kada se Vargatef primjenjuje kao monoterapija nakon prekida liječenja docetakselom.
The prevalent metabolic reaction for nintedanib is hydrolytic cleavage by esterases resulting in the free acid moiety BIBF 1202.
Dominanta metabolička reakcija za nintedanib je hidrolitičko cijepanje esterazama koje rezultira nastankom BIBF 1202 sa slobodnom kiselinskom skupinom.
Diarrhoea (very common, may affect more than 1 in 10 people) Diarrhoea may lead to a loss of fluid and important salts (electrolytes, such as sodium or potassium) in your body.
- Proljev (vrlo često, može se javiti u više od 1 na 10 osoba) Proljev može dovesti do gubitka tekućine i važnih soli (elektrolita, poput natrija ili kalija) u Vašem tijelu.
Peripheral neuropathy is also known to occur with docetaxel treatment.
Poznato je da se periferna neuropatija javlja i pri liječenju docetakselom.
The absolute bioavailability of a 100 mg dose was 4.69 % (90 % CI: 3.615 - 6.078) in healthy volunteers.
Apsolutna bioraspoloživost doze od 100 mg u zdravih dobrovoljaca iznosila je 4,69 % (90 % CI: 3,615 - 6,078).
After food intake, nintedanib exposure increased by approximately 20 % compared to administration under fasted conditions (CI: 95.3 - 152.5 %) and absorption was delayed (median tmax fasted: 2.00 hours; fed: 3.98 h).
Nakon unosa hrane izloženost nintedanibu se povećala za približno 20 % u usporedbi s primjenom pod natašte (CI: 95,3 - 152,5 %), a apsorpcija je bila odgođena (medijan tmax natašte: 2,00 sata; uz hranu: 3,98 sati).
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Neutropenia, febrile neutropenia and sepsis
Neutropenija, febrilna neutropenija i sepsa
For the management of selected adverse reactions, see section 4.4.
Za zbrinjavanje odabranih nuspojava vidjeti dio 4.4.
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 anafilaksu u osoba preosjetljivih na soju.
QT/QTc measurements were recorded and analysed from a dedicated trial comparing nintedanib monotherapy against sunitinib monotherapy in patients with renal cell carcinoma.
Mjerenja QT/QTc su zabilježena i analizirana u ispitivanju koje je uspoređivalo nintedanib u monoterapiji nasuprot sunitinibu u monoterapiji u bolesnika s karcinomom bubrežnih stanica.
Diarrhoea was the most frequently reported gastro-intestinal adverse reaction and appeared in close temporal relationship with the administration of docetaxel (see section 4.8).
Proljev je bio najčešće prijavljena gastrointestinalna nuspojava i pojavio se s uskom vremenskom povezanošću u odnosu na primjenu docetaksela (vidjeti dio 4.8).
Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signalling which is crucial for the proliferation and survival of endothelial as well as perivascular cells (pericytes and vascular smooth muscle cells).
Nintedanib se kompetitivno veže na vezno mjesto za adenozin-trifosfat (ATP) ovih receptora i blokira unutarstanični prijenos signala, koji je ključan za proliferaciju i preživljenje kako endotelnih tako i perivaskularnih stanica (pericita i vaskularnih glatkomišićnih stanica).
Hypersensitivity to nintedanib, to peanut or soya, or to any of the excipients listed in section 6.1.
Preosjetljivost na nintedanib, na kikiriki ili soju, ili neku od pomoćnih tvari navedenih u dijelu 6.1.
In rats, embryofoetal lethality and teratogenic effects were observed at exposure levels below human exposure, at the maximum recommended human dose (MRHD) of 200 mg b.i.d.
U štakora su zamijećena embriofetalna smrtnost i teratogeni učinci pri izloženosti nižoj od izloženosti u ljudi, pri maksimalnoj preporučenoj ljudskoj dozi (MRHD; engl. maximum recommended human dose) od 200 mg dvaput dnevno.
Teratogenic effects on the aortic arches in combination with the heart and the urogenital system were noted at an exposure 4 times higher than at the MRHD and on the embryofoetal development of the axial skeleton at an exposure 3 times higher than at the MRHD.
Teratogeni učinci na aortne lukove, srce i urogenitalni sustav primijećeni su pri izloženosti 4 puta većoj od izloženosti pri MRHD-u te na embriofetalni razvoj aksijalnog skeleta pri izloženosti 3 puta većoj od one pri MRHD-u.