natgillin/translations-raw huggingface dataset:
Efficacy has been shown in a PAH population including aetiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease (see section 5.1). 
Djelotvornost je dokazana u populaciji s PAH-om koja etiološki uključuje idiopatski ili nasljedni PAH ili PAH povezan s bolešću vezivnog tkiva (vidjeti dio 5.1).
There are no data from the use of riociguat in pregnant women. 
Nema podataka o primjeni riocigvata u trudnica.
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTER - PACKS OF 42, 84, 90, 294 FILM-COATED TABLETS 
PODACI KOJE MORA NAJMANJE SADRŽAVATI BLISTER ILI STRIP BLISTER - PAKIRANJA S 42, 84, 90, 294 FILMOM OBLOŽENIH
How to take Adempas 
Kako uzimati Adempas
Keep this medicine out of the sight and reach of children. 
Kako čuvati Adempas Lijek čuvajte izvan pogleda i dohvata djece.
Consider a dose reduction for patients on Adempas doses higher than or equal to 1.0 mg if the patient develops signs or symptoms of hypotension (see sections 4.4 and 4.5). 
U bolesnika na dozama lijeka Adempas višim od ili jednakim 1,0 mg razmotrite snižavanje doze ako bolesnik razvije znakove ili simptome hipotenzije (vidjeti dijelove 4.4 i 4.5).
Pulmonary arterial hypertension (PAH) 
Plućna arterijska hipertenzija (PAH)
In a clinical study the highest dose of Adempas (2.5 mg tablets three times daily) potentiated the blood pressure lowering effect of sublingual nitroglycerin (0.4 mg) taken 4 and 8 hours after intake. 
U jednom kliničkom ispitivanju najviša doza lijeka Adempas (tablete od 2,5 mg tri puta na dan) pojačala je učinak na sniženje krvnog tlaka sublingualnog nitroglicerina (0,4 mg) uzetog 4 i 8 sati kasnije.
cellulose microcrystalline crospovidone (type B) hypromellose 5 cP magnesium stearate lactose monohydrate sodium laurilsulfate 
celuloza, mikrokristalična krospovidon (tip B) hipromeloza 5 cP magnezijev stearat laktoza hidrat natrijev laurilsulfat
Table 6: Effects of riociguat in PATENT-1 on events of clinical worsening Clinical Worsening Events 
Tablica 6: Učinci riocigvata u ispitivanju PATENT-1 na događaje koji pokazuju kliničko pogoršanje
Treatment-naïve patients (n=189) improved by 38 m, and pre-treated patients (n=191) by 36 m (ITT analysis, see table 4). 
U bolesnika koji prethodno nisu bili liječeni (n=189) poboljšanje je iznosilo 38 m, a kod prethodno liječenih bolesnika (n=191) iznosilo je 36 m (ITT analiza, vidjeti tablicu 4).
respective laboratory parameters) 
Anemija (uklj. odgovarajuće laboratorijske parametre)
29 to 83 
29 do 83
The concomitant use of riociguat with other cumarin-derivatives (e.g. phenprocoumon) is also not expected to alter prothrombin time. 
Ne očekuje se ni da će istodobna primjena riocigvata s drugim derivatima kumarina (npr. fenprokumonom) promijeniti protrombinsko vrijeme.
Concomitant administration of HAART combinations led to an increase in riociguat mean AUC of up to about 160% and to an approximate 20% increase in mean Cmax. 
Istodobna primjena HAART kombinacija dovela je do povećanja srednje vrijednosti AUC-a riocigvata do oko 160% te približno 20%-tnog povećanja srednje vrijednosti Cmax.
-10 to 63 
-10 do 63
Patients treated with riociguat showed significant improvement in Borg CR 10 dyspnoea score (mean change from baseline (SD): riociguat -0.4 (2), placebo 0.1 (2); p = 0.0022). 
Bolesnici liječeni riocigvatom pokazali su značajno poboljšanje dispneje prema rezultatu na Borg CR 10 (srednja vrijednost promjene od početne vrijednosti (SD): riocigvat -0,4 (2), placebo 0,1 (2); p=0,0022).
When NO binds to sGC, the enzyme catalyses synthesis of the signalling molecule cyclic guanosine monophosphate (cGMP). 
Kad se NO veže za sGC, taj enzim katalizira sintezu signalne molekule cikličkog gvanozin monofosfata (cGMP).
-10 to 61 
-10 do 61
A randomised, double-blind, multi-national, placebo controlled, phase III study (PATENT-1) was conducted in 443 adult patients with PAH (riociguat individual dose titration up to 2.5 mg three times daily: n=254, placebo: n=126, riociguat “capped” dose titration (CT) up to 1.5 mg (exploratory dose arm, no statistical testing performed; n=63)). 
Randomizirano, dvostruko slijepo, multinacionalno, placebom kontrolirano ispitivanje faze III (PATENT-1) bilo je provedeno u 443 odraslih bolesnika s PAH-om (titracija pojedinačne doze riocigvata do 2,5 mg tri puta na dan: n=254, placebo: n=126, riocigvat titriran do“ograničene” doze do 1,5 mg (krak koji je primao eksplorativnu dozu, bez provedenog statističkog testiranja; n=63).
In pulmonary arterial hypertension, studies with riociguat have been mainly performed in forms related to idiopathic or heritable PAH and PAH associated with connective tissue disease. 
U plućnoj arterijskoj hipertenziji, ispitivanja s riocigvatom provedena su većinom u idiopatskom ili nasljednom PAH-u i PAH-u povezanom s bolešću vezivnog tkiva.
In this case, your doctor will prescribe you Adempas at the highest dose you are comfortable on. For some patients lower doses three times a day might be sufficient, the optimal dose will be selected by your doctor. 
Nekim bolesnicima mogu biti dovoljne niže doze tri puta na dan, a optimalnu dozu odabrat će Vaš liječnik.
A randomised, double-blind, multi-national, placebo controlled, phase III study (CHEST-1) was conducted in 261 adult patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) (72%) or persistent or recurrent CTEPH after pulmonary endarterectomy (PEA; 28%). 
Randomizirano, dvostruko slijepo, multinacionalno, placebom kontrolirano ispitivanje faze III (CHEST-1) bilo je provedeno u 261 odraslih bolesnika s inoperabilnom kroničnom tromboembolijskom plućnom hipertenzijom (KTEPH) (72%) ili perzistentnim ili recidivirajućim KTEPH-om nakon plućne endarterektomije (PEA; 28%).
Riociguat restores the NO-sGC-cGMP pathway resulting in a significant improvement of pulmonary vascular haemodynamics and an increase in exercise ability. 
Riocigvat obnavlja put NO-sGC-cGMP, što rezultira značajnim poboljšanjem plućne vaskularne hemodinamike i poboljšanjem tolerancije fizičke aktivnosti.
Riociguat-treated patients experienced a significant delay in time to clinical worsening versus placebo-treated patients (p = 0.0046; Stratified log-rank test) (see table 6). 
U bolesnika liječenih riocigvatom kliničko pogoršanje nastupilo je značajno kasnije naspram bolesnika koji su primali placebo (p=0,0046; stratificirani log-rang test) (vidjeti tablicu 6).
The safety profile of Adempas in patients with CTEPH and PAH appeared to be similar, therefore adverse reactions identified from placebo controlled 12 and 16 weeks clinical studies are presented as pooled frequency in the table listed below (see table 1). 
Čini se da Adempas ima sličan sigurnosni profil u bolesnika s KTEPH-om i PAH-om pa su stoga nuspojave utvrđene u placebom kontroliranim kliničkim ispitivanjima u trajanju od 12 i 16 tjedana prikazane objedinjenom učestalošću u niže navedenoj tablici (vidjeti tablicu 1).
Therefore use of Adempas is not recommended in these patients (see section 4.4). 
Stoga se ne preporučuje primjena lijeka Adempas u ovih bolesnika (vidjeti dio 4.4).
Co-administration of the antacid aluminium hydroxide / magnesium hydroxide reduced riociguat mean AUC by 34% and mean Cmax by 56% (see section 4.2). 
Istodobna primjena antacida aluminijevog hidroksida / magnezijevog hidroksida smanjila je srednju vrijednost AUC riocigvata za 34%, a srednju vrijednost Cmax za 56% (vidjeti dio 4.2).
To mitigate the risk of hypotension, consider dose reduction and monitoring for signs and symptoms of hypotension (see sections 4.2 and 4.5). 
Kako bi se smanjio rizik od hipotenzije, razmotrite snižavanje doze i praćenje na znakove i simptome hipotenzije (vidjeti dijelove 4.2 i 4.5).
According to standard medical practice, expert assessment of operability should be done prior to treatment with riociguat. 
Prema standardnoj medicinskoj praksi, prije liječenja riocigvatom mora se učiniti stručna procjena o mogućnosti izvođenja operativnog zahvata.
If a dose is missed, treatment should be continued with the next dose as planned. 
Ako se propusti doza, liječenje se mora nastaviti sljedećom dozom prema rasporedu.
In vitro, abacavir, rilpivirine, efavirenz, ritonavir, cobicistat and elvitegravir inhibited CYP1A1 and the metabolism of riociguat in the order listed with abacavir as the strongest inhibitor. 
In vitro, abakavir, rilpivirin, efavirenz, ritonavir, kobicistat i elvitegravir inhibiraju CYP1A1 i metabolizam riocigvata jačinom sukladnom navedenom redoslijedu, s abavakirom kao najjačim inhibitorom.
Very common: may affect more than 1 in 10 people - headache - dizziness - indigestion (dyspepsia) - swelling of limbs (oedema peripheral) - diarrhoea - feeling or being sick (nausea and vomiting) 
Vrlo često: mogu se javiti u više od 1 na 10 osoba - glavobolja - omaglica - probavne tegobe (dispepsija) - oticanje udova (periferni edem) - proljev - mučnina ili povraćanje.
Riociguat did not potentiate the bleeding time caused by acetyl-salicylic acid or affect the platelet aggregation in humans. 
Riocigvat nije pojačao učinak acetilsalicilatne kiseline na vrijeme krvarenja niti utjecao na agregaciju trombocita u ljudi.
Treatment should only be started and monitored by a doctor experienced in the treatment of CTEPH or PAH. 
Liječenje mora započeti i nadzirati samo liječnik s iskustvom u liječenju KTEPH-a ili PAH-a.
Pre-treated patient population 
Populacija prethodno liječenih bolesnika
Based on in vitro data riociguat and its main metabolite are substrates of the transporter proteins P-gp (P-glycoprotein) and BCRP (breast cancer resistance protein). 
Na temelju in vitro podataka, riocigvat i njegov glavni metabolit supstrati su transportnih proteina P-gp (P-glikoproteina) i BCRP (proteina rezistencije karcinoma dojke).
The adverse reactions reported with Adempas are listed in the table below by MedDRA system organ class and by frequency. 
Nuspojave zabilježene uz Adempas navedene su u sljedećoj tablici prema MedDRA klasifikaciji organskih sustava i učestalosti.
• coughing up blood (haemoptysis) (common side effect, may affect up to 1 in 10 people), 
• iskašljavanje krvi (hemoptiza) (česta nuspojava, može se javiti u do 1 na 10 osoba)
Therefore, female patients at potential risk of pregnancy must use an effective method of contraception. 
Stoga bolesnice reproduktivne dobi moraju koristiti učinkovitu kontracepciju.
The class of tyrosine kinase inhibitors was identified as potent inhibitors of CYP1A1, with erlotinib and gefitinib exhibiting the highest inhibitory potency in vitro. 
Ustanovljeno je da je razred inhibitora tirozin kinaze jak inhibitor CYP1A1, među kojima su erlotinib i gefitinib pokazali najveću inhibicijsku potentnost in vitro.
There is no experience in patients with severe hepatic impairment (Child Pugh C); riociguat is contraindicated in these patients (see section 4.3). 
Nema iskustva u bolesnika s teškim oštećenjem funkcije jetre (Child-Pugh C); riocigvat je kontraindiciran u ovih bolesnika (vidjeti dio 4.3).
There are no data in patients with severe hepatic impairment (classified as Child Pugh C). 
Nema podataka za bolesnike s teškim oštećenjem funkcije jetre (klasificiranog kao Child-Pugh C).
Preclinical studies in animal models showed additive systemic blood pressure lowering effect when riociguat was combined with either sildenafil or vardenafil. 
Pretklinička ispitivanja na životinjskim modelima pokazala su aditivni učinak riocigvata u kombinaciji sa sildenafilom ili vardenafilom na sniženje sistemskog krvnog tlaka.
It is recommended to monitor these patients for signs and symptoms of hypotension (see sections 4.2 and 4.4). 
Preporučuje se praćenje tih bolesnika na znakove i simptome hipotenzije (vidjeti dijelove 4.2 i 4.4).
Crushed tablets 
Zdrobljene tablete
Improvement in exercise capacity was accompanied by improvement in multiple clinically relevant secondary endpoints. 
Poboljšanje kapaciteta podnošenja fizičkog napora bilo je praćeno višestrukim klinički važnim sekundarnim mjerama ishoda.
Patients with mild and moderate renal impairment were included in the pivotal studies. 
Bolesnici s blagim do umjerenim oštećenjem funkcije bubrega bili su uključeni u glavna ispitivanja.
Film-coat: hydroxypropylcellulose, hypromellose 3 cP, propylene glycol (E 1520) and titanium dioxide (E 171). 
Film ovojnica: hidroksipropilceluloza, hipromeloza 3cP, propilenglikol (E 1520) i titanijev dioksid (E 171)
In CTEPH, the blood vessels of the lung are blocked or narrowed with blood clots. 
Kod KTEPH-a, krvne žile pluća začepljene su ili sužene krvnim ugrušcima.
Transitioning between phosphodiesterase-5 (PDE5) inhibitors and riociguat Sildenafil must be discontinued at least 24 hours prior to administration of riociguat. 
Prelazak između inhibitora fosfodiesteraze tipa 5 (PDE5) i riocigvata Najmanje 24 sata prije primjene riocigvata mora se prekinuti s primjenom sildenafila.
There is increased riociguat exposure in these patients (see section 5.2). 
U tih je bolesnika povećana izloženost riocigvatu (vidjeti dio 5.2).
Effects of riociguat on other substances 
Učinci riocigvata na druge lijekove
The primary endpoint of the study was placebo-adjusted change from baseline in 6MWD at the last visit (week 12). 
Primarna mjera ishoda ispitivanja bila je placebom prilagođena promjena od početne vrijednosti u 6MWD na posljednjem posjetu (12. tjedan).
Riociguat exhibits a reduced solubility at neutral pH vs. acidic medium. 
Riocigvat pokazuje smanjenu topljivost u neutralnom pH naspram kiselog medija.
20 to 52 [<0.0001] 
20 do 52 [< 0,0001]
Dose adjustment may be necessary in patients who start or stop smoking during treatment with riociguat (see sections 4.2 and 5.2). 
U bolesnika koji puše ili počnu pušiti tijekom liječenja može biti potrebna prilagodba doze tijekom liječenja riocigvatom (vidjeti dijelove 4.2 i 5.2).
Survival in patients of WHO functional class II at baseline at 1, 2 and 3 years was 98%, 96% and 93% respectively, and for patients of WHO functional class III at baseline was 96%, 91% and 84% respectively. 
Preživljenje u bolesnika funkcionalnog razreda II prema SZO na početku liječenja, nakon 1, 2 i 3 godine, bilo je 98%, 96% odnosno 93%, a za bolesnike funkcionalnog razreda III prema SZO na početku liječenja bilo je 96%, 91% odnosno 84%.
Table 2: Effects of riociguat on 6MWD in CHEST-1 at last visit Entire patient population 
Tablica 2: Učinci riocigvata na 6MWD u ispitivanju CHEST-1 na posljednjem posjetu Cijela populacija bolesnika
Efficacy in patients with CTEPH 
Djelotvornost u bolesnika s KTEPH-om
At the last visit the increase in 6MWD with riociguat individual dose titration (IDT) was 36 m (95% CI: 20 m to 52 m; p0.0001) compared to placebo. 
Na posljednjem posjetu, povećanje 6MWD uz individualnu titraciju doze riocigvata (IDT) bilo je 36 m (95% CI: 20 m do 52 m; p  0,0001) u usporedbi s placebom.
Improvement in exercise capacity was accompanied by consistent improvement in multiple clinicallyrelevant secondary endpoints. 
Poboljšanje kapaciteta podnošenja fizičkog napora bilo je popraćeno dosljednim poboljšanjem većeg broja klinički važnih sekundarnih mjera ishoda.
N-demethylation, catalysed by CYP1A1, CYP3A4, CYP3A5 and CYP2J2 is the major biotransformation pathway of riociguat leading to its major circulating active metabolite M-1 (pharmacological activity: 1/10th to 1/3rd of riociguat) which is further metabolised to the pharmacologically inactive N-glucuronide. 
N-demetilacija, koju kataliziraju CYP1A1, CYP3A4, CYP3A5 i CYP2J2, glavni je put biotransformacije riocigvata kojim nastaje njegov glavni aktivni metabolit u cirkulaciji, M-1 (farmakološka aktivnost: 1/10 do 1/3 od riocigvata), koji se dalje metabolizira do farmakološki neaktivnog N-glukuronida.
Efficacy in patients with PAH 
Djelotvornost u bolesnika s PAH-om
Table 5: Effects of riociguat in PATENT-1 on PVR and NT-proBNP at last visit PVR 
Tablica 5: Učinci riocigvata u ispitivanju PATENT-1 na PVR i NT-proBNP na posljednjem posjetu
Data from animals indicate that riociguat is excreted into milk. 
Podaci pokazuju da se riocigvat izlučuje u majčino mlijeko kod životinja.
Tablet core: cellulose microcrystalline, crospovidone (type B), hypromellose 5 cP, lactose monohydrate, magnesium stearate and sodium laurilsulfate (see end of section 2 for further information on lactose). 
Jezgra tablete: mikrokristalična celuloza, krospovidon (tip B), hipromeloza 5cP, laktoza hidrat, magnezijev stearat i natrijev laurilsulfat (vidjeti kraj dijela 2 za dodatne informacije o laktozi).
Use of Adempas in other types of PAH is therefore not recommended. 
Primjena lijeka Adempas kod drugih tipova PAH-a se stoga ne preporučuje.
In cirrhotic patients (non-smokers) with moderate hepatic impairment (classified as Child Pugh B), riociguat mean AUC was increased by 51% compared to healthy controls. 
U bolesnika s cirozom (nepušača) i umjerenim oštećenjem funkcije jetre (klasificiranog kao Child-Pugh B), srednja vrijednost AUC riocigvata bila je povećana za 51% u usporedbi sa zdravim kontrolnim ispitanicima.
In an exploratory interaction study in 7 patients with PAH on stable sildenafil treatment (20 mg three times daily) single doses of riociguat (0.5 mg and 1 mg sequentially) showed additive haemodynamic effects. 
U jednom eksplorativnom ispitivanju interakcija u 7 bolesnika s PAH-om na stabilnom liječenju sildenafilom (20 mg tri puta na dan) pokazalo se da jednostruke doze riocigvata (0,5 mg i 1 mg uzastopno) imaju aditivne hemodinamske učinke.
In cirrhotic patients (non-smokers) with mild hepatic impairment (classified as Child Pugh A) riociguat mean AUC was increased by 35% compared to healthy controls, which is within normal intra-individual variability. 
U bolesnika s cirozom (nepušača) i blagim oštećenjem funkcije jetre (klasificiranog kao Child-Pugh A) srednja vrijednost AUC riocigvata bila je povećana za 35% u usporedbi sa zdravim kontrolnim ispitanicima, što je unutar normalne intraindividualne varijabilnosti.
The probability of survival at 1 year was 97%, at 2 years 93% and at 3 years 88%. 
Vjerojatnost jednogodišnjeg preživljenja bila je 97%, dvogodišnjeg 93%, a trogodišnjeg 88%.
The probability of survival at 1 year was 97%, at 2 years 93% and at 3 years 89%. 
Vjerojatnost jednogodišnjeg preživljenja bila je 97%, dvogodišnjeg 93%, a trogodišnjeg 89%.
Due to the high plasma protein binding riociguat is not expected to be dialysable. 
Zbog visokog postotka vezanja riocigvata za proteine plazme, ne očekuje se da ga se može ukloniti dijalizom.
INFORMATION IN BRAILLE Adempas 0.5 mg, 1 mg, 1.5 mg, 2 mg or 2.5 mg 
16. PODACI NA BRAILLEOVOM PISMU Adempas 0,5 mg, 1 mg, 1,5 mg, 2 mg ili 2,5 mg
• certain types of pulmonary arterial hypertension (PAH). 
• određeni oblici plućne arterijske hipertenzije (PAH).
• 90 tablets: five transparent blisters of 18 tablets each. 
• 90 tableta: pet prozirnih blistera, svaki s 18 tableta.
For co-administration with bosentan follow the recommendation on dose titration (see section 4.2). 
Kod istodobne primjene s bosentanom slijedite preporuke o titraciji doze (vidjeti dio 4.2).
Mean change from baseline for the overall population (N=237) was 57 m at 6 months (n=218), 51 m at 9 months (n=219), 52 m at 12 months (n=209) and 48 m at 24 months (n=193). 
Srednja vrijednost promjene od početne vrijednosti za sveukupnu populaciju (N=237) bila je 57 m nakon 6 mjeseci (n=218), 51 m nakon 9 mjeseci (N=219), 52 m nakon 12 mjeseci (n=209) te 48 m nakon 24 mjeseca (n=193).
Adverse Events leading to discontinuation occurred less frequently in both riociguat treatment groups than in the placebo group (riociguat IDT 1.0-2.5 mg, 3.1%; riociguat CT 1.6%; placebo, 7.1%). 
Učestalost nuspojava koje su dovele do prekida liječenja bila je manja u obje terapijske skupine koje su primale riocigvat nego u placebo skupini (riocigvat IDT 1,0-2,5 mg, 3,1%; riocigvat CT 1,6%; placebo, 7,1%).
The impact of HAART (including different combinations of abacavir, atazanavir, cobicistat, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, lamivudine, rilpivirine, ritonavir, and tenofovir) on riociguat exposure was investigated in a dedicated study in HIV patients. 
Utjecaj HAART-a (uključujući različite kombinacije abakavira, atazanavira, kobicistata, darunavira, dolutegravira, efavirenza, elvitegravira, emtricitabina, lamivudina, rilpivirina, ritonavira i tenofovira) na izloženost riocigvatu ispitivana je u posebnom ispitivanju u bolesnika s HIV infekcijom.
Patients on stable doses of strong multi pathway CYP / P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitors 
Bolesnici na stabilnim dozama jakih inhibitora više puteva CYP-a / P-glikoproteina (P-gp) i proteina rezistencije karcinoma dojke (BCRP)
Patients must not get pregnant during Adempas therapy (see section 4.3). 
Bolesnice ne smiju zatrudniti za vrijeme liječenja lijekom Adempas (vidjeti dio 4.3).
- Co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form including recreational drugs called ‘poppers' (see section 4.5). 
- Istodobna primjena s nitratima ili donorima dušičnog oksida (kao što je amilnitrit) u bilo kojem obliku, uključujući rekreacijske droge, tzv. „poppers“ (vidjeti dio 4.5).
The concomitant use of riociguat with strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, phenobarbitone or St. John's Wort) may also lead to decreased riociguat plasma concentration. 
Istodobna primjena riocigvata s jakim induktorima CYP3A4 (npr. fenitoinom, karbamazepinom, fenobarbitonom ili gospinom travom) također može dovesti do sniženja koncentracije riocigvata u plazmi.
From the recombinant CYP isoforms investigated in vitro CYP1A1 catalysed formation of riociguat's main metabolite most effectively. 
Od rekombinantnih izooblika CYP ispitivanih in vitro, CYP1A1 najučinkovitije je katalizirao stvaranje glavnog metabolita riocigvata.
Therefore co-administration of Adempas with nitrates or nitric oxide donors (such as amyl nitrite) in any form, including recreational drugs called ‘poppers', is contraindicated (see section 4.3). 
Stoga je istodobna primjena lijeka Adempas s nitratima ili donorima dušičnog oksida (kao što je amilnitrit) u bilo kojem obliku, uključujući rekreacijske droge, tzv. „poppers“, kontraindicirana (vidjeti dio 4.3).
Patients with severe hepatic impairment (Child Pugh C) have not been studied and therefore use of Adempas is contraindicated in these patients (see section 4.3). 
Bolesnici s teškim oštećenjem funkcije jetre (Child-Pugh C) nisu ispitani i stoga je primjena lijeka Adempas u ovih bolesnika kontraindicirana (vidjeti dio 4.3).
A 12 week combination study in 18 patients with PAH on stable sildenafil treatment (20 mg three times daily) and riociguat (1.0 mg to 2.5 mg three times daily) compared to sildenafil alone was performed. 
Provedeno je 12-tjedno kombinirano ispitivanje u 18 bolesnika s PAH-om na stabilnom liječenju sildenafilom (20 mg tri puta na dan) i riocigvatom (1,0 mg do 2,5 mg tri puta na dan) u usporedbi sa samo sildenafilom.
In PATENT-2, all patients received an individualised riociguat dose up to 2.5 mg three times daily. 
U ispitivanju PATENT-2, svi su bolesnici primali individualiziranu dozu riocigvata do 2,5 mg tri puta na dan.
Table 3: Effects of riociguat in CHEST-1 on PVR, NT-proBNP and WHO functional class at last visit PVR 
Tablica 3: Učinci riocigvata u ispitivanju CHEST-1 na PVR, NT-proBNP i funkcionalni razred prema SZO-u na posljednjem posjetu
Riociguat is cleared mainly via cytochrome P450-mediated (CYP1A1, CYP3A4, CYP3A5, CYP2J2) oxidative metabolism, direct biliary/faecal excretion of unchanged riociguat and renal excretion of unchanged riociguat via glomerular filtration. 
Riocigvat se uglavnom uklanja putem oksidativnog metabolizma posredovanog citokromom P450 (CYP1A1, CYP3A4, CYP3A5, CYP2J2), izravnim izlučivanjem riocigvata u neizmijenjenom obliku putem žuči/stolice i izlučivanjem riocigvata u neizmijenjenom obliku preko bubrega putem glomerularne filtracije.
Bioavailability (AUC and Cmax) is comparable for Adempas administered orally as a crushed tablet suspended in apple sauce or in water compared to a whole tablet (see section 4.2). 
Bioraspoloživost (AUC i Cmax) za Adempas primijenjen peroralno u obliku zdrobljene tablete pomiješane s kašom od jabuka ili vodom usporediva je s bioraspoloživosti pri primjeni cijele tablete (vidjeti dio 4.2).