natgillin/translations-raw huggingface dataset:
Frequencies are defined as: ‘ not known’ (cannot be estimated from the available data).
Pogostnosti so opredeljene kot: "neznana" (ni mogoče oceniti iz razpoložljivih podatkov).
Cardiac disorders
Srčne bolezni Neznana Srčno popuščanje4
Respiratory, thoracic and mediastinal disorders
Bolezni dihal, prsnega koša in mediastinalnega prostora Neznana Dispneja5
4 Most of the reported cases of cardiac failure were associated with fluid retention.
4 Večina zabeležnih primerov srčnega popuščanja je bila povezana z zastajanjem tekočine.
5 Cases of worsening dyspnoea of unclear aetiology have been reported shortly after starting Volibris therapy.
5 Opisani so bili primeri poslabšanja dispneje, katere etiologija ni jasna in se je pojavilo kmalu po začetku zdravljenja z zdravilom Volibris.
There is no experience in PAH patients of Volibris at daily doses greater than 10 mg.
Pri bolnikih s PAH ni izkušenj z uporabo zdravila Volibris v odmerkih, večjih od 10 mg.
In healthy volunteers, single doses of 50 and 100 mg (5 to 10 times the maximum recommended dose) were associated with headache, flushing, dizziness, nausea and nasal congestion.
Pri zdravih prostovoljcih so bili enkratni odmerki po 50 in 100 mg (5 - do 10- krat večji odmerek od največjega priporočenega odmerka) povezani z glavobolom, zardevanjem, omotico, navzeo in nazalno kongestijo.
Due to the mechanism of action, an overdose of Volibris could potentially result in hypotension (see section 5.3).
V primeru prevelikega odmerka zdravila Volibris se zaradi mehanizma delovanja zdravila lahko pojavi hipotenzija (glejte poglavje 5. 3).
Pharmacotherapeutic group: other anti-hypertensives, ATC code:
Drugi antihipertenzivi, oznaka ATC:
Ambrisentan is an orally active, propanoic acid-class, ERA selective for the endothelin A (ETA) receptor.
8 Ambrisentan je peroralno delujoč antagonist endotelinskih receptorjev (ERA) iz razreda propionske kisline, selektiven za receptorje endotelin A (ETA).
• Ambrisentan blocks the ETA receptor subtype, localized predominantly on vascular smooth muscle cells and cardiac myocytes.
• Ambrisentan blokira podtip receptorjev ETA, ki se nahajajo predvsem v gladkih celicah žilne stene in srčnih miocitih.
This prevents endothelin-mediated activation of second messenger systems that result in vasoconstriction and smooth muscle cell proliferation. • The selectivity of ambrisentan for the ETA over the ETB receptor is expected to retain ETB receptor mediated production of the vasodilators nitric oxide and prostacyclin.
Na ta način prepreči z endotelinom povzročeno aktivacijo sekundarnega sporočilnega sistema, ki ima za posledico vazokonstrikcijo in proliferacijo gladkih mišičnih celic. • - Zaradi večje selektivnosti ambrisentana za receptorje ETA kot receptorje ETB pričakujemo, da se bo z receptorjem ETB posredovana tvorba vazodilatatorjev dušikovega oksida in prostaciklina ohranila.
8 Two randomised, double-blind, multi-centre, placebo controlled, Phase 3 pivotal studies were conducted (ARIES-1 and 2).
Izvedeni sta bili dve randomizirani, dvojno slepi, multicentrični s placebom nadzorovani ključni študiji 3. faze (ARIES- 1 in 2).
ARIES-1 included 201 patients and compared Volibris 5 mg and 10 mg with placebo.
Študija ARIES- 1, ki je vključevala 201 bolnika, je primerjala uporabo zdravila Volibris v odmerku 5 mg in 10 mg s placebom.
ARIES-2 included 192 patients and compared Volibris 2.5 mg and 5 mg with placebo.
Študija ARIES- 2, ki je vključevala 192 bolnikov, je primerjala uporabo zdravila Volibris v odmerku 2, 5 mg in 5 mg s placebom.
In both studies, Volibris was added to patients’ supportive/ background medication, which could have included a combination of digoxin, anticoagulants, diuretics, oxygen and vasodilators (calcium channel blockers, ACE inhibitors).
V obeh študijah so zdravilo Volibris uvedli dodatno k podpornemu/ osnovnemu zdravljenju, ki je lahko vključevalo kombinacijo digoksina, antikoagulantov, diuretikov, kisika in vazodilatatorjev (zaviralci kalcijevih kanalčkov, zaviralci ACE).
Patients enrolled had IPAH or PAH associated with connective tissue disease.
Vključeni bolniki so imeli IPAH ali PAH, povezano z boleznijo vezivnega tkiva.
The majority of patients had WHO functional Class II (38.4%) or Class III (55.0%) symptoms.
Večina bolnikov je imela simptome funkcijskega razreda II (38, 4%) ali razreda III (55, 0%) po SZO.
Patients with pre-existent hepatic disease (cirrhosis or clinically significantly elevated aminotransferases) and patients using other targeted therapy for PAH (e. g. prostanoids) were excluded.
Bolniki, ki so že imeli bolezen jeter (ciroza ali klinično pomembno zvišanje aktivnosti aminotransferaz) in bolniki, ki so se zdravili z drugo obliko usmerjenega zdravljenja PAH (npr. s prostanoidi), so bili izključeni.
The primary endpoint defined for the Phase 3 studies was improvement in exercise capacity assessed by change from baseline in 6 minute walk distance (6MWD) at 12 weeks.
Primarni opazovani dogodek študij 3. faze je bil izboljšanje telesne zmogljivosti v primerjavi z izhodiščem pri 6- minutni hoji (6MWD - 6 minute walk distance) po 12 tednih.
In both studies, treatment with Volibris resulted in a significant improvement in 6MWD for each dose of Volibris.
V obeh študijah je zdravljenje z zdravilom Volibris pomembno izboljšalo rezultat 6MWD pri vseh odmerkih zdravila Volibris.
The placebo-adjusted improvement in mean 6MWD at week 12 compared to baseline was 30.6 m (95% CI:
V skupini, ki je prejemala 5- mg odmerek, je v študiji ARIES- 1 na placebo prilagojeno izboljšanje povprečnega rezultata 6MWD v 12. tednu v primerjavi z izhodiščem znašalo 30, 6 m (95% interval zaupanja:
2.9 to 58.3; p=0.008) and 59.4 m (95% CI:
2, 9 do 58, 3; p = 0, 008), v študiji ARIES- 2 pa 59, 4 m (95% interval zaupanja:
29.6 to 89.3; p < 0.001) for the 5 mg group, in ARIES 1 and 2 respectively.
29, 6 do 89, 3; p < 0, 001).
The placebo-adjusted improvement in mean 6MWD at week 12 in patients in the 10 mg group in ARIES-1 was 51.4 m (95% CI:
V študiji ARIES- 1 je pri bolnikih v skupini, ki so prejemali 10 mg odmerek na placebo prilagojeno izboljšanje povprečnega rezultata 6MWD v 12. tednu znašalo 51, 4 m (95% interval zaupanja:
26.6 to 76.2; p < 0.001).
26, 6 do 76, 2; p < 0, 001).
A pre-specified combined analysis of the Phase 3 studies (ARIES-C) was conducted.
Izvedena je bila tudi vnaprej določena kombinirana analiza študij 3. faze (ARIES- C).
The placebo-adjusted mean improvement in 6MWD was 44.6 m (95% CI:
Za 5 mg odmerek je bilo na placebo prilagojeno izboljšanje rezultata 6MWD 44, 6 m (95% interval zaupanja:
24.3 to 64.9; p < 0.001) for the 5 mg dose, and 52.5 m (95% CI:
24, 3 do 64, 9; p < 0, 001), za 10 mg odmerek pa 52, 5 m (95% interval zaupanja:
28.8 to 76.2; p < 0.001) for the 10 mg dose.
28, 8 do 76, 2; p < 0, 001).
In ARIES-2, Volibris (combined dose group) significantly delayed the time to clinical worsening of PAH compared to placebo (p < 0.001), the hazard ratio demonstrated a 80% reduction (95% CI:
V študiji ARIES- 2 je zdravilo Volibris (skupina s kombiniranim odmerkom) v primerjavi s placebom pomembno podaljšalo čas do kliničnega poslabšanja PAH (p < 0, 001), razmerje tveganja kaže 80% zmanjšanje (95% interval zaupanja:
47% to 92%).
47% do 92%).
A statistically significant increase (3.41 ± 6.96) was observed for the combined dose group in the physical functioning scale of the SF-36 Health Survey compared with placebo (-0.20 ± 8.14, p=0.005).
V skupini s kombiniranim odmerkom je bilo opaženo statistično pomembno izboljšanje (3, 41 ± 6, 96) na lestvici telesne zmogljivosti vprašalnika o kakovosti življenja SF- 36 (SF- 36 Health Survey) v primerjavi s placebom (- 0, 20 ± 8, 14, p = 0, 005).
Treatment with Volibris led to a statistically significant improvement in Borg Dyspnea Index (BDI) at week 12 (placebo-adjusted BDI of -1.1 (95% CI: -1.8 to -0.4; p=0.019; combined dose group)).
Zdravljenje z zdravilom Volibris je v 12. tednu pomembno izboljšalo indeks dispneje po Borgu (BDI- Borg Dyspnea Index) (na placebo prilagojeni BDI - 1, 1 (95% interval zaupanja: - 1, 8 do - 0, 4; p = 0, 019; skupina s kombiniranim odmerkom)).
Long term data
9 Dolgoročni podatki
Patients enrolled into ARIES 1 and 2 were eligible to enter a long term open label extension study ARIES E (n=383).
Bolniki, vključeni v študiji ARIES 1 in 2, so izpolnjevali pogoje za vključitev v dolgoročno odprto podaljšano študijo ARIES E (n = 383).
The effect of Volibris on the outcome of the disease is unknown.
Učinek zdravila Volibris na izid bolezni ni znan.
The observed probability of survival at 1 year for subjects receiving Volibris (combined Volibris dose group) was 95% and at 2 years was 84%.
Opažena 1- letna verjetnost preživetja oseb, ki prejemajo zdravilo Volibris (skupina s kombiniranim odmerkom zdravila Volibris) je bila 95- odstotna, 2- letna pa 84- odstotna.
In an open label study (AMB222), Volibris was studied in 36 patients to evaluate the incidence of increased serum aminotransferase concentrations in patients who had previously discontinued other ERA therapy due to aminotransferase abnormalities.
Namen študije je bil ovrednotiti pojavnost zvišane koncentracije serumske aminotransferaze pri bolnikih, pri katerih je bilo prekinjeno predhodno zdravljenje z drugim ERA zaradi nenormalnih vrednosti aminotransferaze.
During a mean of 53 weeks of treatment with Volibris, none of the patients enrolled had a confirmed serum ALT > 3xULN that required permanent discontinuation of treatment.
Med zdravljenjem z zdravilom Volibris, ki je v povprečju trajalo 53 tednov, pri nobenem od vključenih bolnikov niso potrdili vrednosti serumske ALT > 3 x ZNV, ki bi zahtevala trajno prekinitev zdravljenja.
Fifty percent of patients had increased from 5 mg to 10 mg Volibris during this time.
Med tem časom so odmerek zdravila Volibris s 5 mg na 10 mg povečali pri petdesetih odstotkih bolnikov.
This is an event rate of 2.3 events per 100 patient years of exposure for Volibris.
Kumulativna pojavnost nenormalnih vrednosti serumske aminotransferaze > 3x ZNV v vseh študijah 2. in 3. faze (vključno z zadevno odprto podaljšano fazo) je bila ugotovljena pri 17 od 483 oseb v srednjem času zdravljenja 79, 5 tednov, kar pomeni 2, 3 dogodka na 100 bolnikov- let (“ patient years ”) izpostavljenosti zdravilu Volibris.
9 An improvement in haemodynamic parameters was observed in patients with PAH after 12 weeks (n=29) in a Phase 2 study (AMB220).
Pri bolnikih s PAH je bilo po 12 tednih (n = 29) v študiji 2. faze (AMB220) opaženo izboljšanje hemodinamskih parametrov.
Treatment with Volibris resulted in an increase in mean cardiac index, a decrease in mean pulmonary artery pressure, and a decrease in mean pulmonary vascular resistance.
Zaradi zdravljenja z zdravilom Volibris se je povečal srednji srčni indeks, zmanjšal srednji pljučni krvni tlak in zmanjšal srednji pljučni žilni upor.
The number of patients who received concomitant Volibris and sildenafil in ARIES-E and AMB222 was 22 patients (5.7%) and 17 patients (47%), respectively.
Zdravilo Volibris in sildenafil je v študiji ARIES- E sočasno uporabljalo 22 bolnikov (5, 7%), v študiji AMB222 pa 17 bolnikov (47%).
After oral administration, maximum plasma concentrations (Cmax) of ambrisentan typically occur around 1.5 hours post-dose under both fasted and fed conditions.
Največje plazemske koncentracije (Cmax) ambrisentana se tipično pojavijo približno 1, 5 ure po peroralnem odmerku, tako pri jemanju zdravila na tešče kot po obroku.
Cmax and area under the plasma concentration-time curve (AUC) increase dose proportionally over the therapeutic dose range.
V območju terapevtskih odmerkov se Cmax in področje pod krivuljo plazemske koncentracije v odvisnosti od časa (AUC) povečujeta proporcionalno z odmerkom.
A food-effect study involving administration of ambrisentan to healthy volunteers under fasting conditions and with a high-fat meal indicated that the Cmax was decreased 12% while the AUC remained unchanged.
Študija kaže, da se je vrednost Cmax zmanjšala za 12%, vrednost AUC pa se ni spremenila.
The in vitro plasma protein binding of ambrisentan was, on average, 98.8% and independent of concentration over the range of 0.2 – 20 microgram/ ml.
Vezava ambrisentana na plazemske proteine je bila in vitro v povprečju 98, 8- odstotna in v razponu od 0, 2 do 20 mikrogramov/ ml neodvisna od koncentracije.
Ambrisentan is primarily bound to albumin (96.5%) and to a lesser extent to alpha1-acid glycoprotein.
Ambrisentan se v glavnem veže na albumin (96, 5%), v manjšem obsegu pa tudi na kisli alfa1 glikoprotein.
The distribution of ambrisentan into red blood cells is low, with a mean blood: plasma ratio of 0.57 and 0.61 in males and females, respectively.
Srednje razmerje kri: plazma je pri moških 0, 57, pri ženskah pa 0, 61.
Ambrisentan is a non-sulphonamide (proprionic acid) ERA.
Ambrisentan je nesulfonamidni (propionska kislina) ERA.
Ambrisentan is glucuronidated via several UGT isoenzymes (UGT1A9S, UGT2B7S and UGT1A3S) to form ambrisentan glucuronide (13%).
Ambrisentan se glukuronidira s številnimi UGT izoencimi (UGT1A9S, UGT2B7S in UGT1A3S), pri čemer se tvori ambrisentan glukuronid (13%).
Ambrisentan also undergoes oxidative metabolism mainly by CYP3A4 and to a lesser extent by CYP3A5 and CYP2C19 to form 4-hydroxymethyl ambrisentan (21%) which is further glucuronidated to 4-hydroxymethyl ambrisentan glucuronide (5%).
Ambrisentan se tudi oksidativno presnavlja, predvsem s CYP3A4 in v manjšem obsegu s CYP3A5 in CYP2C19, do 4- hidroksimetil ambrisentana (21%), ki se nadalje glukuronidira do 4- hidroksimetil ambrisentan glukuronida (5%).
The binding affinity of 4-hydroxymethyl ambrisentan for the human endothelin receptor is 65-fold less than ambrisentan.
Vezavna afiniteta 4- hidroksimetil ambrisentana za humane endotelinske receptorje je 65- krat manjša od vezavne afinitete ambrisentana.
Therefore at concentrations observed in the plasma (approximately 4% relative to parent ambrisentan), 4-hydroxymethyl ambrisentan is not expected to contribute to pharmacological activity of ambrisentan.
Pri koncentracijah, opaženih v plazmi (približno 4% v primerjavi z izvornim ambrisentanom), torej ne pričakujemo, da bi 4- hidroksimetil ambrisentan prispeval k farmakološki aktivnosti ambrisentana.
In vitro data have shown that at therapeutic concentrations, ambrisentan does not inhibit UGT1A1, UGT1A6, UGT1A9, UGT2B7 or cytochrome P450 enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4.
Podatki in vitro kažejo, da ambrisentan pri terapevtskih koncentracijah ne zavira UGT1A1, UGT1A6, UGT1A9, UGT2B7 ali encimov citokroma P450 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 in 3A4.
Additional in vitro studies showed that ambrisentan does not inhibit NTCP, OATP or BSEP.
Dodatne in vitro študije so pokazale, da ambrisentan ne zavira NTCP, OATP ali BSEP.
Furthermore, ambrisentan does not induce MRP2, Pgp or BSEP.
Ambrisentan tudi ne inducira MRP2, Pgp ali BSEP.
10 The effects of steady-state ambrisentan (10 mg once daily) on the pharmacokinetics and pharmacodynamics of a single dose of warfarin (25 mg), as measured by PT and INR, were investigated in 20 healthy volunteers.
Učinek ambrisentana v stanju dinamičnega ravnovesja (10 mg enkrat na dan) na farmakokinetiko in farmakodinamiko enkratnega odmerka varfarina (25 mg), vrednoteno s PT in INR, so raziskovali pri 20 zdravih prostovoljcih.
Similarly, co-administration with warfarin did not affect the pharmacokinetics of ambrisentan (see section 4.5).
Pri sočasni uporabi tudi varfarin ni vplival na farmakokinetiko ambrisentana (glejte poglavje 4. 5).
The effect of 7-day dosing of sildenafil (20 mg three times daily) on the pharmacokinetics of a single dose of ambrisentan, and the effects of 7-day dosing of ambrisentan (10 mg once daily) on the pharmacokinetics of a single dose of sildenafil were investigated in 19 healthy volunteers.
Učinek 7- dnevne uporabe sildenafila (20 mg trikrat na dan) na farmakokinetiko enkratnega odmerka ambrisentana in učinek 7- dnevne uporabe ambrisentana (10 mg enkrat na dan) na farmakokinetiko enkratnega odmerka sildenafila so raziskovali pri 19 zdravih prostovoljcih.
With the exception of a 13% increase in sildenafil Cmax following co-administration with ambrisentan, there were no other changes in the pharmacokinetic parameters of sildenafil, N-desmethyl-sildenafil and ambrisentan.
Z izjemo 13- odstotnega povečanja vrednosti Cmax sildenafila pri sočasni uporabi ambrisentana drugih sprememb farmakokinetičnih parametrov sildenafila, N- demetil- sildenafila in ambrisentana niso zasledili.
This slight increase in sildenafil Cmax is not considered clinically relevant (see section 4.5).
To rahlo povečanje vrednosti Cmax sildenafila ni klinično pomembno (glejte poglavje 4. 5).
Similarly, co-administration with tadalafil did not affect the pharmacokinetics of ambrisentan (see section 4.5).
Podobno tudi sočasna uporaba tadalafila ne vpliva na farmakokinetiko ambrisentana (glejte poglavje 4. 5).
Exposures of ambrisentan as measured by AUC(0-inf) and Cmax were increased by 35% and 20%, respectively.
Ti vrednosti sta se povečali, in sicer AUC( 0- inf) za 35%, Cmax pa za 20%.
This change in exposure is unlikely to be of any clinical relevance and therefore Volibris may be co-administered with ketoconazole.
Verjetnost, da bi te spremembe v izpostavljenosti imele kakršenkoli klinični pomen je majhna, zato se zdravilo Volibris lahko uporablja skupaj s ketokonazolom.
Multiple doses of ambrisentan resulted in slight increases in digoxin AUC0-last and trough concentrations, and a 29% increase in digoxin Cmax.
Pri ponavljajočih se odmerkih ambrisentana so ugotovili blago zvišanje vrednosti AUC0- last digoksina in najmanjših koncentracij digoksina v stanju dinamičnega ravnovesja, ter zvišanje vrednosti Cmax digoksina za 29%.
The increase in digoxin exposure observed in the presence of multiple doses of ambrisentan was not considered clinically relevant, and no dose adjustment of digoxin is warranted (see section 4.5).
Smatra se, da večja izpostavljenost digoksinu, opažena pri ponavljajočem se odmerku ambrisentana, ni klinično pomembna, zato odmerka digoksina ni treba prilagajati (glejte poglavje 4. 5).
The effects of 12 days dosing with ambrisentan (10 mg once daily) on the pharmacokinetics of a single dose of oral contraceptive containing ethinyl estradiol (35 μ g) and norethindrone (1 mg) were studied in healthy female volunteers.
11 Pri zdravih prostovoljkah so raziskali učinke 12- dnevne uporabe ambrisentana (10 mg enkrat na dan) na farmakokinetiko enkratnega odmerka peroralnega kontraceptiva z etinilestradiolom (35 μg) in noretindronom (1 mg).
The Cmax and AUC(0 –∞) were slightly decreased for ethinyl estradiol (8% and 4%, respectively), and slightly increased for norethindrone (13% and 14%, respectively).
Cmax in AUC( 0– ∞) etinilestradiola sta se rahlo zmanjšali (Cmax za 8% in AUC za 4%), noretindrona pa rahlo povečali (Cmax za 13% in AUC za 14%).
These changes in exposure to ethinyl estradiol or norethindrone were small and are unlikely to be clinically significant (see section 4.5).
Te spremembe izpostavljenosti etinilestradiolu in noretindronu so majhne in ni verjetno, da bi bile klinično pomembne (glejte poglavje 4. 5).
Ambrisentan and its metabolites are eliminated primarily in the bile following hepatic and/ or extra-hepatic metabolism.
Ambrisentan in njegovi presnovki se po jetrni in/ ali izven jetrni presnovi v glavnem izločijo z žolčem.
Approximately 22% of the administered dose is recovered in the urine following oral administration with 3.3% being unchanged ambrisentan.
V urinu se pojavi približno 22% peroralno prejetega odmerka, od tega 3, 3% ambrisentana v nespremenjeni obliki.
Plasma elimination half-life in humans ranges from 13.6 to 16.5 hours.
Pri človeku se plazemski razpolovni čas izločanja giblje od 13, 6 do 16, 5 ur.
Based on the results of a population pharmacokinetic analysis in healthy volunteers and patients with PAH, the pharmacokinetics of ambrisentan were not significantly influenced by gender or age (see section 4.2).
Na osnovi analize rezultatov populacijske farmakokinetike pri zdravih prostovoljcih in bolnikih s PAH spol in starost ne vplivata pomembneje na farmakokinetiko ambrisentana (glejte poglavje 4. 2).
11 Ambrisentan does not undergo significant renal metabolism or renal clearance (excretion).
Ambrisentan ni podvržen pomembni ledvični presnovi ali ledvičnemu očistku (izločanju).
The magnitude of the decrease in oral clearance is modest (20-40%) in patients with moderate renal impairment and therefore is unlikely to be of any clinical relevance.
Pri bolnikih z zmerno okvaro ledvic je obseg zmanjšanja očistka pri peroralni uporabi zmeren (20- 40%) in tako je klinični pomen malo verjeten.
However, caution should be used in patients with severe renal impairment (see section 4.2).
Pri bolnikih s hudo okvaro ledvic je kljub temu potrebna previdnost (glejte poglavje 4. 2).
The main routes of metabolism of ambrisentan are glucuronidation and oxidation with subsequent elimination in the bile and therefore hepatic impairment would be expected to increase exposure (Cmax and AUC) of ambrisentan.
Ker glavna presnovna pot ambrisentana poteka preko glukuronidacije in oksidacije ter kasnejšega izločanja z žolčem, lahko pričakujemo, da se bo pri okvari jeter zvišala izpostavljenost (Cmax in AUC) ambrisentanu.
However, the magnitude of effect of bilirubin is modest (compared to the typical patient with a bilirubin of 0.6 mg/ dl, a patient with an elevated bilirubin of 4.5 mg/ dl would have approximately 30% lower oral clearance of ambrisentan).
Vendar pa je obseg vpliva bilirubina zmeren (v primerjavi s tipičnim bolnikom z vrednostjo bilirubina 0, 6 mg/ dl, bo imel bolnik z zvišano vrednostjo bilirubina 4, 5 mg/ dl približno za 30% manjši očistek ambrisentana po peroralni uporabi).
The pharmacokinetics of ambrisentan in patients with severe hepatic impairment (with or without cirrhosis) has not been studied.
Pri bolnikih s hudo okvaro jeter (s cirozo ali brez) farmakokinetike ambrisentana niso raziskovali.
Therefore Volibris should not be initiated in patients with severe hepatic impairment or clinically significant elevated hepatic aminotransferases (> 3xULN) (see sections 4.3 and 4.4).
Zdravljenje z zdravilom Volibris se tako ne sme uvesti pri bolnikih s hudo okvaro jeter ali s klinično pomembnim zvišanjem vrednosti jetrnih aminotransferaz (> 3x ZNV) (glejte poglavji 4. 3 in 4. 4).
Due to the class primary pharmacologic effect, a large single dose of ambrisentan (i. e. an overdose) could lower arterial pressure and have the potential for causing hypotension and symptoms related to vasodilation.
Zaradi primarnega farmakološkega učinka zdravil iz te skupine, se pri prevelikem enkratnem odmerku ambrisentana (to je v primeru prevelikega odmerjanja) lahko zniža arterijski krvni tlak in pojavi hipotenzija ter simptomi s tem povezane vazodilatacije.
In dogs, slight inflammatory responses were observed following chronic high dose administration of ambrisentan at exposures greater than 20– fold that observed in patients.
Pri psih so pri dolgotrajni uporabi visokih odmerkov ambrisentana pri izpostavljenosti, ki je bila več kot 20- krat večja od izpostavljenosti bolnika, poročali o blagih vnetnih spremembah.
Nasal bone hyperplasia of the ethmoid turbinates has been observed in the nasal cavity of rats treated with ambrisentan, at exposure levels 3-fold the clinical AUC.
12 Pri podganah, ki so prejemale ambrisentan, so pri izpostavljenosti, ki je ustrezala 3- kratni vrednosti AUC pri klinični uporabi, poročali o hiperplaziji nosne kosti etmoidnega labirinta.
In the rat, hyperplasia of nasal turbinate bone is a recognised response to nasal inflammation, based on experience with other compounds.
Pri podganah so na osnovi izkušenj z drugimi učinkovinami hiperplazijo nosnih školjk pripisali odzivu na vnetje nosne sluznice.
There were no treatment-related increases in the incidence of tumours in 2 year oral studies in rats and mice.
Pri 2- letnih študijah peroralne uporabe pri podganah in miših niso poročali o z zdravilom povezani večji pojavnosti tumorjev.