natgillin/translations-raw huggingface dataset:
However, sitaxentan sodium did not affect the anti-ovulatory activity of the oral contraceptive as assessed by the plasma concentrations of follicle stimulating hormone (FSH), luteinising hormone (LH), and progesterone (see section 4.4).
Vendar, ocenjeno po, plazemskih koncentracijah folikl stimulirajočega hormona (FSH), luteinizirajočega hormona (LH) in progesterona, natrijev sitaksentanat ni vplival na antiovulacijsko delovanje peroralnega kontraceptiva (glejte poglavje 4. 4).
Sildenafil (substrate of CYP3A4):
Sildenafil (substrat CYP3A4):
A single dose of sildenafil 100 mg coadministered with Thelin increased Cmax and AUC∞ of sildenafil by 18% and 28%, respectively.
Enojen odmerek 100 mg sildenafila sočasno z zdravilom Thelin je povzročil zvišanje Cmax sildenafila za 18% in AUC∞ sildenafila za 28%.
There was no change in Cmax or AUC for the active metabolite, n-desmethylsildenafil.
Nista pa bili spremenjeni vrednosti Cmax in AUC aktivnega presnovka, n- desmetilsildenafila.
Nifedipine (substrate of CYP3A4/ 5):
Nifedipin (substrat CYP3A4/ 5):
The clearance of nifedipine was not clinically significantly changed when given concomitantly with Thelin.
Očistek nifedipina se med sočasno uporabo z zdravilom Thelin ni klinično pomembno spremenil.
Omeprazole (substrate of CYP2C19):
Omeprazol (substrat CYP2C19):
Concomitant administration of Thelin with omeprazole increased the omeprazole AUC0-24 by 30%; Cmax was unchanged.
Sočasna uporaba zdravila Thelin z omeprazolom zviša AUC0- 24 omeprazola za 30%; Cmax se ne spremeni.
Digoxin (substrate of p-Glycoprotein):
Digoksin (substrat p- glikoproteina):
Concomitant administration of Thelin did not alter the pharmacokinetics of digoxin indicating no effect on the p-glycoprotein transporter
Sočasna uporaba zdravila Thelin ne spremeni farmakinetike digoksina, kar kaže, da ni vpliva na transporter p- glikoproteina.
Pregnancy There are no human data regarding the use of sitaxentan sodium during pregnancy.
Nosečnost Ni podatkov o uporabi natrijev sitaksentanat pri nosečnicah.
Sitaxentan sodium caused teratogenicity in rats (see section 5.3).
Natrijev sitaksentanat je povzročil teratogene učinke pri podganah (glejte poglavje 5. 3).
Lactation Sitaxentan sodium was detected in the plasma of breast fed pups from female rats treated with sitaxentan sodium, indicating that sitaxentan sodium was present in the breast milk.
Dojenje Natrijev sitaksentanat so odkrili v plazmi dojenih mladičev podgan, katerim so dajali natrijev sitaksentanat, kar kaže, da je sitaksentan natrij prisoten v materinem mleku.
6 Women of child-bearing potential Treatment must not be initiated in women of child-bearing potential unless they practice reliable contraception, due to possible teratogenicity.
6 Ženske v rodni dobi Zaradi možne teratogenosti se zdravljenje ne sme uvajati pri ženskah v rodni dobi, če ne uporabljajo zanesljive kontracepcije.
General description Safety of Thelin has been evaluated in clinical trials of more than 1200 patients with PAH, as well as post-marketing safety data.
Splošni opis Varnost zdravila Thelin so ocenili v kliničnih preskušanjih pri več kot 1. 200 bolnikih s PAH in tudi na podlagi podatkov o varnosti zdravila iz obdobja trženja.
At the recommended dose during placebo-controlled trials in pulmonary arterial hypertension PAH, the most common adverse drug reactions considered to be at least possibly related to Thelin treatment were headache in 15% of patients, and peripheral oedema and nasal congestion, each in 9% of patients.
V preskušanjih, nadzorovanih s placebom, so bili pri bolnikih s pljučno arterijsko hipertenzijo (PAH), ki so jemali priporočeni odmerek, najpogostejši neželeni učinki, ki so lahko povezani z zdravljenjem z zdravilom Thelin, glavobol pri 15% bolnikov in periferni edem ter zamašen nos, vsak pri 9% bolnikov.
Frequencies are reported as very common (≥ 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1,000, ≤ 1/ 100), rare (> 1/ 10,000, ≤ 1/ 1,000), and very rare (≤ 1/ 10,000).
Pogostnosti neželenih učinkov so navedene kot zelo pogosti (≥1/ 10), pogosti (> 1/ 100, < 1/ 10), občasni (> 1/ 1000, ≤1/ 100), redki (> 1/ 10000, ≤1/ 1000) in zelo redki (≤1/ 10000).
System Organ Class / Adverse reaction Blood and lymphatic system disorders
Organski sistem/ neželeni učinek Bolezni krvi in limfatičnega sistema
Nervous system disorders Headache Insomnia, dizziness
Bolezni živčevja Glavobol Nespečnost, omotica
Vascular disorders Gingival bleeding, flushing
Žilne bolezni Krvavitev iz dlesni, zardevanje
Respiratory, thoracic, and mediastinal disorders Nasal congestion, epistaxis
Bolezni dihal, prsnega koša in mediastinalnega prostora Zamašenost nosu, epistaksa
Gastrointestinal disorders Nausea, constipation, upper abdominal pain, vomiting, dyspepsia and diarrhoea
Bolezni prebavil Navzea, zaprtje, abdominalna bolečina, bruhanje, dispepsija in driska
Hepatobiliary disorders Liver aminotransferases increase, bilirubin increase (associated with liver aminotransferase increase)
Bolezni jeter, žolčnika in žolčevodov Zvišanje jetrnih aminotransferaz, zvišanje bilirubina (povezano z zvišanjem jetrnih aminotransferaz)
7 Skin and subcutaneous tissue Rash (various types and presentations)
7 Bolezni kože in podkožja Izpuščaj (različnih vrst in kliničnih oblik)
Musculoskeletal and connective tissue disorders Muscle cramp
Bolezni mišično- skeletnega sistema in vezivnega tkiva Mišični krč
Investigations INR increase (with concomitant vitamin K antagonist therapy).
Preiskave Povečanje INR (med sočasnim zdravljenjem z antagonistom vitamina K).
Increased Liver Aminotransferases (see section 4.4) Elevations of AST and/ or ALT are associated with sitaxentan sodium.
Zvišane vrednosti jetrnih aminotransferaz (glejte poglavje 4. 4) S natrijev sitaksentanat so povezane zvišane vrednosti AST in/ ali ALT.
In phase 2 and 3 oral studies in patients with PAH, elevations in ALT and/ or AST > 3 ULN were observed in 5% of placebo-treated patients (N = 155) and 7% of Thelin 100 mg-treated patients (N = 887).
V fazah 2 in 3 raziskav peroralne oblike pri bolnikih s pljučno arterijsko hipertenzijo so zvišanje vrednosti ALT in/ ali AST > 3 ZMN zabeležili pri 5% bolnikov, ki so jemali placebo (N=155) in pri 7% bolnikov, ki so jemali zdravilo Thelin 100 mg (N=887).
Elevations in ALT values > 5 ULN were 4% (36/ 887) for sitaxentan 100 mg QD and 0.6% in the placebo group (1/ 155).
Zvišanje vrednosti ALT > 5 ZMN so opazili pri 4% (36/ 887) bolnikov, ki so prejemali sitaksentan 100 mg enkrat dnevno in pri 0, 6% bolnikov, ki so prejemali placebo (1/ 155).
This specific group had a higher risk (19%; N = 10/ 53) of developing elevations in ALT and/ or AST > 3 x ULN indicating that appropriate care should be exercised when initiating sitaxentan in this patient population.
Ta specifična skupina je imela večje tveganje (19%, n = 10/ 53) za zvišanje ALT in/ ali AST > 3 x ZMN, kar kaže, da je v primeru uvedbe sitaksentana v tej populaciji bolnikov potrebna ustrezna skrb.
Decreased Haemoglobin (see section 4.4) The overall mean decrease in haemoglobin concentration for Thelin -treated patients was 0.5 g/ dl (change to end of treatment).
Znižane vrednosti hemoglobina (glejte poglavje 4. 4) Skupno povprečno znižanje koncentracij hemoglobina pri bolnikih, ki so prejemali zdravilo Thelin, je bilo za 0, 5 g/ dl (sprememba do zaključka zdravljenja).
In placebo-controlled studies, marked decreases in haemoglobin (> 15% decrease from baseline with value < lower limit of normal) were observed in 7% of patients treated with Thelin (N = 149) and 3% of placebo-treated patients (N = 155).
V raziskavah, nadzorovanih s placebom, so izrazito znižanje vrednosti hemoglobina (> 15% znižanje od izhodiščnih vrednosti z vrednostjo < spodnje meje normalne vrednosti) opazili pri 7% bolnikov, ki so se zdravili z zdravilom Thelin (N = 149), in 3% bolnikov, ki so prejemali placebo (N = 155).
A decrease in haemoglobin concentration by at least 1 g/ dl was observed in 60% of patients treated with Thelin as compared to 32% of placebo-treated patients.
Znižanje koncentracije hemoglobina za najmanj 1 g/ dL so opazili pri 60% bolnikov, ki so se zdravili z zdravilom Thelin, in 32% bolnikov, ki so prejemali placebo.
Post marketing experience Adverse events reported during the post-marketing period to date have been similar to those reported in clinical trials.
Izkušnje iz obdobja trženja Neželeni učinki, doslej opisani v obdobju trženja, so bili podobni neželenim učinkom, opisanim v kliničnih preskušanjih.
During clinical trials, Thelin was given as a daily oral dose of 1000 mg/ day for 7 days to healthy volunteers.
V kliničnih preskušanjih so zdravi prostovoljci 7 dni prejemali peroralni dnevni odmerek zdravila Thelin 1000 mg/ dan.
In an open-label hypertension study, 10 patients received 480 mg twice daily (approximately a 10-fold increase in daily dose compared to the MRHD) for up to 2 weeks.
V odprti raziskavi hipertenzije je 10 bolnikov prejemalo 480 mg dvakrat dnevno (približno 10- krat večji dnevni odmerek kot najvišji priporočeni odmerek za človeka (MRHD)) do 2 tedna.
Headaches (some severe), peripheral oedema, and anaemias were the most common adverse events reported in these patients, none of which were considered serious.
Nobeden od naštetih neželenih učinkov ni bil resen.
8 In an open-label PAH study, one fatal case of hepatic failure has been reported after chronic dosing of sitaxentan at 600 mg/ day administered as 300 mg bid.
V odprti študiji PAH je bil opisan en smrten primer odpovedi jeter po kronični uporabi sitaksentana 600 mg/ dan (uporabljenega kot 300 mg dvakrat na dan).
Other antihypertensives, ATC code:
Drugi antihipertenzivi, oznaka ATC:
Mechanism of action Endothelin-1 (ET-1) is a potent vascular paracrine and autocrine peptide in the lung, and can also promote fibrosis, cell proliferation, cardiac hypertrophy, and remodelling and is pro-inflammatory.
Pri bolnikih s pljučno arterijsko hipertenzijo so koncentracije ET- 1 v plazmi in pljučem tkivu zvišane.
ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension, as well as other cardiovascular disorders and connective tissue diseases, including scleroderma, acute and chronic heart failure, myocardial ischaemia, systemic hypertension, and atherosclerosis, suggesting a pathogenic role of ET-1 in these diseases.
To opazimo tudi pri drugih srčno- žilnih boleznih in boleznih vezivnega tkiva, med drugim pri sklerodermi, akutnem in kroničnem srčnem popuščanju, miokardni ishemiji, sistemski hipertenziji in aterosklerozi, kar kaže na patogeno delovanje ET- 1 pri teh boleznih.
In pulmonary arterial hypertension and heart failure, in the absence of endothelin receptor antagonism, elevated ET-1 concentrations are strongly correlated with the severity and prognosis of these diseases.
Zvišane koncentracije ET- 1 pri pljučni arterijski hipertenziji in srčnem popuščanju ter v odsotnosti antagonizma receptorja za endotelin so močno povezane z resnostjo in prognozo teh bolezni.
Additionally, pulmonary arterial hypertension also is characterized by reduced nitric oxide activity.
Poleg tega je za pljučno arterijsko hipertenzijo značilno tudi zmanjšanje aktivnosti dušikovega oksida.
ET-1 actions are mediated through endothelin A receptors (ETA), present on smooth muscle cells, and endothelin B receptors (ETB), present on endothelial cells.
ET- 1 deluje preko receptorja za endotelin A (ETA), ki se nahaja na celicah gladkega mišičja, in receptorja za endotelin B (ETB), ki se nahaja na endotelnih celicah.
Predominant actions of ET-1 binding to ETA are vasoconstriction and vascular remodelling, while binding to ETB results in ET-1 clearance, and vasodilatory/ antiproliferative effects due in part to nitric oxide and prostacyclin release.
Ko se ET- 1 veže na ETA, sta posledici v glavnem vazokonstrikcija in vaskularno remodeliranje, vezava ET- 1 na ETB pa povzroči očistek ET- 1 in vazodilatorne/ antiproliferativne učinke, ki so deloma posledica sproščanja dušikovega oksida in prostaciklina.
Thelin is a potent (Ki 0.35 nM) and highly selective ETA antagonist (approximately 6,500-fold more selective for ETA as compared to ETB).
Zdravilo Thelin je močen (Ki 0, 35 nM) in izredno selektiven antagonist ETA (približno 6. 500- krat bolj selektiven za ETA v primerjavi z ETB).
Efficacy Two randomized, double-blind, multi-centre, placebo-controlled trials were conducted to demonstrate efficacy.
Učinkovitost Za dokaz učinkovitosti sta bili opravljeni dve randomizirani, dvojno slepi, multicentrični preskušanji, ki sta bili kontrolirani s placebom.
STRIDE-1, which included 178 patients, compared 2 oral doses of Thelin (100 mg once daily and 300 mg once daily) with placebo during 12 weeks of treatment.
V preskušanju STRIDE- 1, kjer je bilo vključenih 178 bolnikov, so primerjali 2 peroralna odmerka zdravila Thelin (100 mg enkrat dnevno in 300 mg enkrat dnevno) s placebom v 12 tednih zdravljenja.
The 18 week STRIDE-2 trial, conducted in 246 patients, included 4 treatment arms: placebo once daily, Thelin 50 mg once daily, Thelin 100 mg once daily, and open-label bosentan twice daily (efficacy-rater blinded, administered according to the approved package insert).
V preskušanju STRIDE- 2, kjer je bilo vključenih 246 bolnikov in je trajalo 18 tednov, so primerjali 4 skupine bolnikov: bolnike, ki so jemali placebo enkrat dnevno; bolnike, ki so jemali zdravilo Thelin 50 mg enkrat dnevno; bolnike, ki so jemali zdravilo Thelin 100 mg enkrat dnevno; bolnike, ki so jemali bosentan dvakrat dnevno (v zadnji skupini so bolniki vedeli, katero zdravilo prejemajo, ne pa tudi ocenjevalci učinkovitosti; bosentan je bil uporabljen po navodilu za uporabo).
Patients had moderate to severe (NYHA/ WHO functional class II-IV) pulmonary arterial hypertension resulting from idiopathic pulmonary arterial hypertension (IPAH, also known as primary pulmonary hypertension), connective tissue disease (CTD), or congenital heart disease (CHD).
Bolniki so imeli zmerno do hudo (funkcionalni razred II- IV po NYHA/ WHO) pljučno arterijsko hipertenzijo, ki je nastala iz idiopatske pljučne arterijske hipertenzije (IPAH, imenovano tudi primarna pljučna hipertenzija), bolezni vezivnega tkiva ali kongenitalne srčne bolezni.
Sub-maximal exercise capacity was assessed by measuring distance walked in 6 minutes (6-minute walk test) at 12 weeks for STRIDE-1 and 18 weeks for STRIDE-2.
Z merjenjem razdalje, ki jo bolnik prehodi v 6 minutah (6- minutni test hoje), so določili submaksimalno vadbeno zmogljivost po 12 tednih v raziskavi STRIDE- 1 in po 18 tednih v raziskavi STRIDE- 2.
In both trials, treatment with Thelin resulted in a significant increase in exercise capacity.
Po korekciji s skupino bolnikov, ki je prejemala placebo, je bila
The placebo-corrected increases in walk distance compared to baseline were 35 metres (p = 0.006; ANCOVA) and 31 metres (p < 0.05; ANCOVA), respectively.
9 prehojena razdalja v primerjavi z izhodiščem v prvi raziskavi daljša za 35 metrov (p=0, 006; ANCOVA), v drugi raziskavi pa daljša za 31 metrov (p < 0, 05; ANCOVA).
Among patients with CTD, a statistically significant difference versus placebo was observed (37.73 metres, p < 0.05).
V skupini bolnikov z boleznijo vezivnega tkiva so opazili statistično pomembno razliko v primerjavi s placebom (37, 73 metrov, p < 0, 05).
A reduction in symptoms of pulmonary arterial hypertension was observed with Thelin treatment.
Pri bolnikih, ki so prejemali zdravilo Thelin so ugotovili zmanjšanje simptomov pljučne arterijske hipertenzije.
9 II (mean baseline 6 minute walk distance 451 meters) and 117 (66%) as functional class III (mean baseline 6 minute walk distance 372 meters).
V preskušanju STRIDE- 1 so v izhodišču 59 (33%) od 178 bolnikov uvrstili v funkcionalni razred II po NYHA (povprečni rezultat 6- minutnega testa hoje v izhodišču 451 metrov), 117 bolnikov (66%) pa v funkcionalni razred III (povprečni rezultat 6- minutnega testa hoje v izhodišču 372 metrov).
Treatment with Thelin led to net improvement in NYHA functional class in 25% of patients (placebo 8%, p < 0.05).
Zdravljenje z zdravilom Thelin je povzročilo neto izboljšanje funkcionalnega razreda po NYHA pri 25% bolnikov (placebo 8%, p < 0, 05).
In the STRIDE-2 trial 93 (38%) of the 246 patients were classified at baseline as NYHA functional class II (mean baseline 6 minute walk distance 370 meters) and 144 (59%) as functional class III (mean baseline 6 minute walk distance 322 meters).
V preskušanju STRIDE- 2 so v izhodišču 93 (38%) od 246 bolnikov uvrstili v funkcionalni razred II po NYHA (povprečni rezultat 6- minutnega testa hoje v izhodišču 370 metrov), 144 bolnikov (59%) pa v funkcionalni razred III (povprečni rezultat 6- minutnega testa hoje v izhodišču 322 metrov).
Treatment with Thelin led to net improvement in WHO functional class in 12% of patients (placebo -3%, p < 0.05).
Zdravljenje z zdravilom Thelin je povzročilo neto izboljšanje funkcionalnega razreda po WHO pri 12% bolnikov (placebo - 3%, p < 0, 05).
Haemodynamic parameters were assessed in STRIDE-1.
V STRIDE- 1 so ocenjevali hemodinamične parametre.
Compared with placebo treatment, Thelin resulted in improvement (p < 0.05) in cardiac index of +0.3 L/ min/ m2 (13%), in pulmonary vascular resistance of-221 dynes*sec/ cm5 (22%), and in systemic vascular resistance of -276 dynes*sec/ cm5 (16%) after 12 weeks of treatment.
V primerjavi s placebom je zdravljenje z zdravilom Thelin po 12 tednih izboljšalo (p < 0, 05) srčni indeks za +0, 3 L/ min/ m2 (13%), pljučno vaskularno odpornost - 221 din* s/ cm5 (22%) in sistemsko vaskularno odpornost – 276 din* s/ cm5 (16%).
The reduction in mean pulmonary artery pressure of 3 mmHg (6%) was not statistically significant.
Znižanje povprečnega tlaka pljučne arterije za 3 mmHg (6%) ni bilo statistično pomembno.
Long-term Data There are no studies to demonstrate beneficial effects on survival of treatment with sitaxentan sodium.
Dolgoročni podatki Raziskave, ki bi pokazale koristne učinke na preživetje zdravljenja s natrijev sitaksentanat, niso bile opravljene.
However, patients completing STRIDE-2 were eligible to enrol in STRIDE-2X, a 1-year open-label study of Thelin 100 mg.
Vendar so bili bolniki, ki so zaključili preskušanje STRIDE- 2, primerni za vključitev v raziskavo STRIDE- 2X, ki je trajala 1 leto in je bila odprta raziskava zdravila Thelin 100 mg.
A total of 145 patients were treated with Thelin 100 mg.
Z zdravilom Thelin 100 mg je bilo zdravljenih skupno 145 bolnikov.
In this total population, Kaplan-Meier estimates of survival were 96% for patients after 1 year of therapy with sitaxentan sodium.
V tej populaciji je Kaplan - Meierjeva ocena preživetja po 1 letu zdravljenja s natrijev sitaksentanat 96%.
One-year survival estimates were similar in the subgroup of patients with PAH secondary to connective tissue disease for the Thelin treated group (98%).
Ocene preživetja po enem letu so podobne v podskupini bolnikov, zdravljenih z zdravilom Thelin, ki imajo PAH kot posledico bolezni vezivnega tkiva (98%).
The estimates may have been influenced by the initiation of new or additional PAH therapies, which occurred in 24% of patients.
Na ocene so lahko vplivale uvedbe novih ali dodatnih postopkov zdravljenja PAH, kar se je zgodilo pri 24% bolnikov.
Absorption Sitaxentan sodium is rapidly absorbed following oral administration.
Absorpcija Natrijev sitaksentanat se hitro absorbira po peroralni uporabi.
The absolute bioavailability of Thelin is between 70 and 100%.
Absolutna biološka uporabnost zdravila Thelin je med 70 in 100%.
When administered with a high fat meal, the rate of absorption (Cmax) of Thelin was decreased by 43% and the Tmax delayed (2-fold increase) compared to fasted conditions, but the extent of absorption was the same.
Pri dajanju z obrokom, ki vsebuje veliko maščob, se v primerjavi s teščim stanjem hitrost absorpcije (Cmax) zdravila Thelin zmanjša za 43%, Tmax pa zakasni (dvakratno povečanje), vendar je obseg absorpcije enak.
Distribution Sitaxentan sodium is more than 99% protein bound to plasma proteins, predominantly albumin.
Porazdelitev Natrijev sitaksentanat je v več kot 99% vezano na plazemske beljakovine, poglavitno na albumin.
Sitaxentan sodium does not penetrate into erythrocytes and does not appear to cross the blood-brain barrier.
Natrijev sitaksentanat ne vstopa v eritrocite in izgleda, da ne prehaja krvno- možganske pregrade.
Metabolism and Elimination Following oral administration to healthy volunteers, sitaxentan sodium is highly metabolised.
Presnova in izločanje Po peroralnem dajanju zdravim prostovoljcem se je natrijev sitaksentanat zelo hitro presnovil.
The most common metabolic products are at least 10 times less potent as ETA antagonists than sitaxentan sodium in a standard in vitro test of activity.
Najpogostejši presnovni produkti so bili v standardnem in vitro testu aktivnosti najmanj 10- krat manj učinkoviti antagonisti ETA kot natrijev sitaksentanat.
In vitro, sitaxentan sodium is metabolized by CYP2C9 and CYP3A4/ 5.
V in vitro pogojih natrijev sitaksentanat presnavljata CYP2C9 in CYP3A4/ 5.
In vitro studies using human liver microsomes or primary hepatocytes show that sitaxentan sodium inhibits CYP2C9, and, to a lesser extent, CYP 2C8, CYP2C19 and CYP3A4/ 5.
Podatki in vitro poskusov na človeških jetrnih mikrosomih ali primarnih hepatocitih kažejo, da natrijev sitaksentanat zavira CYP2C9 in v manjši meri tudi CYP 2C8, CYP2C19 ter CYP3A4/ 5.
Approximately 50-60% of an oral dose is excreted in the urine with the remainder eliminated in the faeces.
10 Približno 50- 60% peroralnega odmerka se izloči z urinom, preostali del pa z blatom.
Less than 1% of the dose is excreted as unchanged active ingredient.
V nespremenjeni obliki se izloči manj kot 1% odmerka zdravilne učinkovine.
10 Special Populations Based on results of the population pharmacokinetic analysis and pooled pharmacokinetic data over several studies, it was found that gender, race, and age do not clinically significantly affect the pharmacokinetics of sitaxentan sodium.
Posebne skupine bolnikov Na osnovi rezultatov populacijske analize farmakokinetike in združenih farmakokinetičnih podatkov iz več raziskav so ugotovili, da spol, rasa in starost klinično pomembno ne vplivajo na farmakokinetiko natrijevega sitaksentanata.
Liver Function Impairment The influence of liver impairment on the pharmacokinetics of sitaxentan sodium has not been evaluated.
Okvara jetrne funkcije Vpliv okvare jeter na farmakokinetiko natrijev sitaksentanat ni raziskan.
Refer to section 4.3.
Glejte poglavje 4. 3.
In the 26-week study, moderate to marked diffuse seminiferous tubular atrophy was present at a very low incidence, whereas in the 99-week study there was a dose-related, slightly increased incidence of minimal to mild focal atrophy at doses providing 29 to 94 times the human exposure.
V raziskavi, ki je trajala 99 tednov, so opazili od odmerka odvisno rahlo zvišano pojavnost minimalne do blage žariščne atrofije, in sicer pri odmerkih, ki so ustrezali od 29 - do 94- kratni izpostavitvi pri človeku.
Thelin was teratogenic at the lowest tested dose in rats, corresponding to exposures more than 30 times the human exposure.
Zdravilo Thelin je bilo teratogeno pri najnižjem preskušenem odmerku, ki je bil pri podganah enakovreden 30- kratni izpostavitvi pri človeku.
Administration of Thelin to female rats from late-pregnancy through lactation reduced pup survival, and caused testis tubular aplasia and delayed vaginal opening at the lowest exposure tested (17-45 times the human exposure).
Dajanje zdravila Thelin podganjim samicam od pozne brejosti ter skozi dojenje je pri najnižjem preskušenem odmerku (17- 45- kratni izpostavitvi pri človeku) zmanjšalo preživetje mladičev in povzročilo testikularno tubularno aplazijo ter zakasnjeno odpiranje nožnice.
Large / abnormally shaped livers, a delay in auditory function development, a delay in preputial separation and a reduction in the number of embryonic implants occurred at higher maternal doses.
Visoki odmerki pri materi so povzročili velika/ nenormalno oblikovana jetra, kasnejši razvoj sluha, kasnejše ločevanje prepucija in zmanjšanje števila vsajenih zarodkov.
Thelin was not carcinogenic when administered to rats for 97-99 weeks or when administered to p53(+/ -) transgenic mice for 6 months.
6 FARMACEVTSKI PODATKI