natgillin/translations-raw huggingface dataset:
This card contains important safety information you need to be aware of when receiving treatment withOpsumit. 
Za zdravljenje pljučne arterijske hipertenzije Ta kartica vsebuje pomembne informacije, ki jih morate poznati, ko se zdravite z zdravilom Opsumit.
PHARMACEUTICAL FORM AND CONTENTS 15 film-coated tablets 
FARMACEVTSKA OBLIKA IN VSEBINA 15 filmsko obloženih tablet
Opsumit is contraindicated during breastfeeding (see section 4.3). 
Zdravilo Opsumit je kontraindicirano med dojenjem (glejte poglavje 4.3).
If you have kidney problems, talk to your doctor before using Opsumit. 
Če imate težave z ledvicami, se pred uporabo zdravila Opsumit posvetujte z zdravnikom.
There is no clinically relevant effect of age, sex or ethnic origin on the pharmacokinetics of macitentan and its active metabolite. 
Starost, spol ali etična pripadnost nimajo klinično pomembnega učinka na farmakokinetiko macitentana in njegovega aktivnega presnovka.
A decrease from baseline in haemoglobin concentration to below 10 g/dL was reported in 8.7% of patients treated with macitentan 10 mg and 3.4% of placebo-treated patients. 
O zmanjšanju koncentracije hemoglobina na manj kot 10 g/dl glede na izhodišče so poročali pri 8,7 % bolnikov, zdravljenih z macitentanom 10 mg, in 3,4 % bolnikov, zdravljenih s placebom.
Haemoglobin concentration 
Koncentracije hemoglobina
All patients were followed up to end-of-study (EOS) for vital status. 
Pri vseh bolnikih so spremljali življenjski status do konca študije.
The MAH shall ensure that prior to prescribing all healthcare professionals who intend to prescribe and/or dispense Opsumit are provided with a Prescriber Kit containing the following: 
Opsumit vsi zdravstveni delavci, ki nameravajo zdravilo predpisovati in/ali izdajati, imeli na voljo komplet za zdravnike, ki bo vseboval naslednje:
Liver enzyme tests should be obtained prior to initiation of Opsumit. 
Pred uvedbo zdravila Opsumit je treba pridobiti rezultate preiskav jetrnih encimov.
The number of deaths of all causes up to EOS on macitentan 10 mg was 35 versus 44 on placebo (HR 0.77; 97.5% CI: 0.46 to 1.28). 
Število smrti iz vseh vzrokov do konca študije z macitentanom 10 mg je bila 35 v primerjavi s 44 na placebu (HR 0,77; 97,5 % IZ: 0,46 do 1,28).
HR a (97.5% CI) 
(97,5-% IZ)
Treatment comparison: macitentan 10 mg vs placebo 
Primerjava zdravljenja: macitentan 10 mg v primerjavi s placebom
• Leukopenia (decreased white blood cell counts) 
• levkopenija (zmanjšane ravni belih krvnih celic)
• That women of childbearing potential must use reliable contraception; 
• da morajo ženske v rodni dobi uporabljati učinkovito kontracepcijo;
The benefit/risk balance of macitentan has not been established in patients with WHO class I functional status of pulmonary arterial hypertension. 
Razmerja med koristmi in tveganje macitentana pri bolnikih s funkcionalnim razredom pljučne arterijske hipertenzije I po SZO niso ugotavljali.
There is no experience with the use of macitentan in patients undergoing dialysis, therefore Opsumit is not recommended in this population (see sections 4.2 and 5.2). 
Z uporabo zdravila Opsumit pri bolnikih na dializi ni izkušenj, zato se macitentan v tej populaciji ne priporoča (glejte poglavji 4.2 in 5.2).
• nefazodone (used to treat depression), 
• nefazodon (zdravilo, ki se uporablja za zdravljenje depresije),
If a patient is hypersensitive to soya, Opsumit must not be used (see section 4.3). 
Bolniki, preobčutljivi na sojo, zdravila Opsumit ne smejo uporabljati (glejte poglavje 4.3).
• ritonavir, saquinavir (used to treat HIV infections), 
• ritonavir, sakvinavir (zdravili, ki se uporabljata za zdravljenje okužb s HIV),
However, there is no clinical experience with the use of macitentan in PAH patients with moderate or severe hepatic impairment. 
Vendar pa kliničnih izkušenj z uporabo macitentana pri bolnikih s PAH z zmerno ali hudo jetrno okvaro ni.
Other worsening of PAH was defined as the presence of all of the three following components: a sustained decrease in 6-minute walk distance (6MWD) of at least 15% from baseline; worsening of PAH symptoms (worsening of WHO FC or right heart failure); and need for new treatment for PAH. 
Drugo poslabšanje PAH je bilo opredeljeno kot prisotnost vseh treh naslednjih komponent: trajno zmanjšanje prehojene razdalje v 6 minutah (6MWD, 6-minute walk distance) za vsaj 15 % od izhodišča;
Approximately 52%, 46%, and 2% of patients were in WHO FC II, III, and IV, respectively. 
Glede na FR po SZO je približno 52 % bolnikov je sodilo v razred II, 46 % v razred III in 2 % v razred IV.
If any of these apply to you, please tell your doctor. 
Če karkoli od zgoraj naštetega velja za vas, to povejte zdravniku.
This increase is not considered clinically relevant (see sections 4.2 and 4.4). 
Zvišanje ni bilo ocenjeno kot klinično pomembno (glejte poglavji 4.2 in 4.4).
prostanoid initiation n (%) 
prostanoida n (%)
• Breastfeeding (see section 4.6). 
• Dojenje (glejte poglavje 4.6).
This decrease is not considered clinically relevant (see sections 4.2 and 4.4). 
Znižanje ni bilo ocenjeno kot klinično pomembno (glejte poglavji 4.2 in 4.4).
Macitentan was teratogenic in rabbits and rats at all doses tested. 
Macitentan je bil pri kuncih in podganah v vseh testiranih odmerkih teratogen.
Cyclosporine A: Concomitant treatment with cyclosporine A 100 mg twice daily, a combined CYP3A4 and OATP inhibitor, did not alter the steady-state exposure to macitentan and its active metabolite to a clinically relevant extent. 
Ciklosporin A: Sočasno zdravljenje s ciklosporinom A 100 mg dvakrat na dan, kombiniranim zaviralcem CYP3A4 in OATP, v stanju dinamičnega ravnovesja ni spremenila izpostavljenosti macitentanu in njegovemu aktivnemu presnovku v klinično pomembnem obsegu.
Concomitant use with strong CYP3A4 inducers 
Sočasna uporaba z močnimi zaviralci CYP3A4
Opsumit contains lecithin derived from soya. 
Zdravilo Opsumit vsebujejo lecitin, pridobljen iz soje.
• Nasopharyngitis (inflammation of the throat and nasal passages) 
• nazofaringitis (vnetje žrela in nosnih poti)
How to take Opsumit 
Kako jemati zdravilo Opsumit
In two double-blind clinical studies in patients with digital ulcers associated with systemic sclerosis, the incidences of peripheral oedema AEs ranged from 13.4% to 16.1% in the macitentan 10 mg groups and from 6.2% to 4.5% in the placebo groups. 
V dveh dvojno slepih kliničnih študijah pri bolnikih z razjedami prstov, povezanih s sistemsko sklerozo, so bile incidence neželenih učinkov perifernega edema v razponu od 13,4 % do 16,1 % za skupino z macitentanom 10 mg in od 6,2 % do 4,5 % v skupini s placebom.
Opsumit is contraindicated during pregnancy and in women of childbearing potential who are not using reliable contraception (see section 4.3). 
Zdravilo Opsumit je kontraindicirano med nosečnostjo in pri ženskah v rodni dobi, ki ne uporabljajo učinkovite kontracepcije (glejte poglavje 4.3).
Opsumit widens the pulmonary arteries, making it easier for the heart to pump blood through them. 
Zdravilo Opsumit pljučne arterije razširi in s tem srcu olajša črpanje krvi skoznje.
2 Hypotension has been associated with the use of ERAs including macitentan. 
2 Z uporabo ERA, vključno z macitentanom, povezujejo hipotenzijo.
• regular monitoring of haemoglobin levels; 
• rednem spremljanju ravni hemoglobina; • rednem spremljanju delovanja jeter;
The use of Opsumit is not recommended in patients undergoing dialysis (see sections 4.4 and 5.2). 
Uporaba zdravila Opsumit se ne priporoča pri bolnikih, ki se zdravijo z dializo (glejte poglavji 4.4 in 5.2).
Be sure to discuss any questions you may have with your doctor. 
O morebitnih vprašanjih se morate posvetovati z zdravnikom.
EN 
SI
The combination of macitentan with strong CYP3A4 inducers (e.g., rifampicin, St. John's wort, carbamazepine, and phenytoin) should be avoided (see section 4.5). 
Kombinaciji macitentana z močnimi induktorji CYP3A4 (npr. rifampicin, šentjanževka, karbamazepin in fenitoin) se je treba izogniti (glejte poglavje 4.5).
The incidence of aminotransferase elevations (ALT/AST) > 3 × ULN was 3.4% on macitentan 10 mg and 4.5% on placebo in a double-blind study in patients with PAH. 
Incidenca zvišanja aminotransferaz (ALT/AST) > 3 × ULN je bila v dvojno slepi študiji pri bolnikih s PAH 3,4 % pri macitentanu 10 mg in 4,5 % pri placebu.
Therefore you must not take Opsumit if you are pregnant and you must also not become pregnant while taking Opsumit. 
če ste noseči, prav tako pa ne smete zanositi v času jemanja zdravila.
Testicular tubular dilatation was observed in chronic toxicity studies with male rats and dogs with safety margins of 11.6 and 5.8, respectively. 
V študijah kronične toksičnosti so pri podganjih samcih in psih opazili testikularno tubularno dilatacijo z varnostno mejo 11,6 pri podganah oz. 5,8 pri psih.
• Women of childbearing potential who are not using reliable contraception (see sections 4.4 and 
• Ženske v rodni dobi, ki ne uporabljajo učinkovite kontracepcije (glejte poglavji 4.4 in 4.6).
NAME OF THE MARKETING AUTHORISATION HOLDER Janssen-Cilag Int 
IME IMETNIKA DOVOLJENJA ZA PROMET Z ZDRAVILOM Janssen-Cilag Int
Decrease in haemoglobin concentrations has been associated with endothelin receptor antagonists (ERAs) including macitentan (see section 4.8). 
Zdravljenje z antagonisti receptorja endotelina, vključno z macitentanom, je povezano z zmanjšanjem koncentracij hemoglobina (glejte poglavje 4.8).
Idiopathic or heritable PAH was the most common aetiology in the study population (57%), followed by PAH due to connective tissue disorders (31%), PAH associated with corrected simple congenital heart disease (8%), and PAH associated with other aetiologies (medicinal products and toxins [3%] and HIV [1%]). 
zaradi bolezni vezivnega tkiva (31 %), PAH, povezana z zdravljeno preprosto prirojeno boleznijo srca (8 %) in PAH, povezana z drugimi vzroki (zdravila in toksini [3 %] in HIV [1 %]).
Cases of anaemia requiring blood cell transfusion have been reported with macitentan and other ERAs. 
Z macitentanom in drugimi ERA so poročali o primerih anemije, zaradi katere je bilo potrebno zdravljenje s transfuzijo krvnih celic.
Patients treated with macitentan 10 mg achieved a median reduction of 36.5% (97.5% CI: 21.7 to 49.2%) in pulmonary vascular resistance and an increase of 0.58 L/min/m2 (97.5% CI: 0.28 to 0.93 L/min/m2) in cardiac index compared to placebo. 
Bolniki, zdravljeni z macitentanom 10 mg, so dosegli mediano zmanjšanje za 36,5 % (97,5 % IZ: 21,7 do 49,2 %) pljučnega žilnega upora in zvišanje za 0,58 l/min/m2 (97,5 % IZ: 0,28 do 0,93 l/min/m2) v srčnem indeksu v primerjavi s placebom.
What Opsumit looks like and contents of the pack Opsumit 10 mg tablets are white to off-white, biconvex, round, film-coated tablets with “10” on both sides. 
Zdravilo Opsumit 10 mg tablete so bele do belkaste, bikonveksne, okrogle, filmsko obložene tablete z vtisnjeno oznako ”10” na obeh straneh.
Caution should be exercised when macitentan is administered concomitantly with strong CYP3A4 inhibitors (see section 4.4). 
Previdnost je potrebna pri sočasni uporabi macitentana z močnimi zaviralci CYP3A4 (glejte poglavje 4.4).
It is important that you report immediately to your prescribing doctor pregnancy or any side effects that may occur during treatment with Opsumit. 
Pomembno je, da zdravnika, ki vam je zdravilo predpisal, takoj obvestite o morebitni nosečnosti ali katerem koli neželenem učinku,
Worsening of PAH n (%) i.v./s.c. 
Poslabšanje PAH n (%)
Opsumit contains lactose. 
Zdravilo Opsumit vsebuje laktozo.
• Nasal congestion (blocked nose) 
• kongestija nosu (zamašen nos)
• whether you have anaemia (a reduced number of red blood cells) 
• ali imate anemijo (zmanjšano število rdečih krvnih celic)
Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. 
Macitentan kaže veliko afiniteto do receptorjev ET v celicah gladkih mišic pljučnih arterij pri človeku in vzdržuje njihovo zasedenost.
Elevations of liver aminotransferases (AST, ALT) have been associated with PAH and with endothelin receptor antagonists (ERAs). 
S PAH in z antagonisti receptorjev endotelina (ERA, endothelin receptor antagonists) je povezano zvišanje jetrnih aminotransferaz (AST, ALT).
Opsumit may harm the development of the foetus. 
Nosečnost Zdravilo lahko škoduje razvoju zarodka.
1Data derived from pooled placebo-controlled studies. 
Podatki iz združenih, s placebom nadzorovanih študij
Adverse reactions associated with macitentan obtained from this clinical study are tabulated below. 
ki so jih pridobili v tej klinični študiji, so predstavljeni v spodnji preglednici.
Opsumit® 10 mg macitentan film-coated tablets 
Opsumit® 10 mg macitentan filmsko obložene tablete
Exposure to macitentan and its active metabolite was increased by 1.3- and 1.6-fold, respectively, in patients with severe renal impairment. 
Izpostavljenost macitentanu se je pri bolnikih s hudo okvaro ledvic zvišala za 1,3-krat in njegovemu aktivnemu presnovku za 1,6-krat.
Increased liver weight and hepatocellular hypertrophy were observed in mice, rats and dogs after treatment with macitentan. 
Pri miših, podganah in psih so po zdravljenju z macitentanom opazili povečanje mase jeter in hepatocelično hipertrofijo.
Treatment with macitentan 10 mg at Month 6 led to a 74% higher chance of WHO FC improvement relative to placebo (risk ratio 1.74; 97.5% CI: 1.10 to 2.74; p = 0.0063). 
Zdravljenje z macitentanom 10 mg je v 6. mesecu privedlo do 74 % večje možnosti izboljšanja FR po SZO v primerjavi s placebom (razmerje tveganj 1,74; 97,5 % IZ: 1,10 do 2,74; p = 0,0063).
The development of testicular tubular atrophy in male animals was observed after treatment with macitentan (see section 5.3). 
Po zdravljenju z macitentanom so pri samcih živali opazili razvoj testikularne tubularne atrofije (glejte poglavje 5.3).
Morbiditymortality event b 
Dogodek obolevnostismrnostib
whether you have anaemia (a reduced number of red blood cells) 
ali imate anemijo (zmanjšano število rdečih krvnih celic)
The cytochrome P450 enzymes CYP3A4, CYP2C8, CYP2C9, and CYP2C19 are involved in the metabolism of macitentan and formation of its metabolites (see section 5.2). 
V presnovi macitentana in nastajanju njegovih presnovkov sodelujejo encimi citokroma P450, CYP3A4, CYP2C8, CYP2C9 in CYP2C19 (glejte poglavje 5.2).
In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. 
V prisotnosti močnega induktorja CYP3A4, kot je rifampicin, je treba upoštevati zmanjšano učinkovitost macitentana.
Macitentan induced minimal to slight mucosal hyperplasia and inflammatory infiltration in the submucosa of the nasal cavity in the mouse carcinogenicity study at all doses. 
Macitentan je pri vseh odmerkih v študijah kancerogenosti pri miših induciral minimalno do blago hiperplazijo sluznice in vnetno infiltracijo v podsluznico nosne votline.
No nasal cavity findings were noted in the 3-month mouse toxicity study or in rat and dog studies. 
V 3-mesečni študiji toksičnosti pri miših ali v študijah pri podganah in psih niso prišli do izsledkov v nosni votlini.
Based on PK data, no dose adjustment is required in patients with renal impairment. 
Ledvična okvara Na podlagi FK podatkov prilagoditev odmerka pri bolnikih z ledvično okvaro ni potrebna.
You need to use a reliable form of birth control (contraception) while you are taking Opsumit. 
Med jemanjem tega zdravila morate uporabljati učinkovit način preprečevanja nosečnosti (kontracepcijo).
Evaluation of 6MWD by functional class resulted in a placebo-corrected mean increase from baseline to Month 6 in FC III/IV patients of 37 meters (97.5% CI: 5 to 69) and in FC I/II of 12 meters (97.5% CI: −8 to 33). 
Ocena 6MWD glede na funkcionalni razred je pokazala za placebo popravljeno povprečno zvišanje od izhodišča do 6. meseca za 37 metrov (97,5 % IZ: 5 do 69) pri bolnikih iz FR III/IV in za 12 metrov (97,5 % IZ: -8 do 33) pri bolnikih iz FR I/II.
In a long-term doubleblind study in patients with PAH, hypotension was reported for 7.0% and 4.4% of patients on macitentan 10 mg and placebo, respectively. 
V dolgoročni, dvojno slepi študiji pri bolnikih s PAH so o hipotenziji poročali pri 7,0 % bolnikih, ki so prejemali macitentan 10 mg, in pri 4,4 % bolnikih, ki so prejemali placebo.
• The need for regular blood tests because Opsumit causes a decrease in haemoglobin; 
• da je treba redno izvajati krvne preiskave, saj zdravilo Opsumit povzroča znižanje ravni hemoglobina; • da je treba redno spremljati delovanje jeter, saj je lahko zdravilo Opsumit hepatotoksično.
Treatment with macitentan 10 mg resulted in a 45% risk reduction (hazard ratio [HR] 0.55; 97.5% CI: 0.39 to 0.76; logrank p < 0.0001) of the composite morbidity-mortality endpoint up to EOT when compared to placebo [Figure 1 and Table 1]. 
Zdravljenje z macitentanom 10 mg je povzročilo 45 % zmanjšanje tveganja (razmerje tveganja [HR, hazard ratio] 0,55; 97,5-odstotni IZ 0,39 do 0,76; logrank vrednost p < 0,0001) za sestavljeni opazovani dogodek obolevnost-smrtnost do konca zdravljenja v primerjavi s placebom [Slika 1 in
Opsumit treatment should only be initiated in women of childbearing potential when the absence of pregnancy has been verified, appropriate advice on contraception provided, and reliable contraception is practised (see sections 4.3 and 4.6). 
Zdravljenje z zdravilom Opsumit se sme pri ženskah v rodni dobi uvesti samo, če je bila odsotnost nosečnosti potrjena, če je bilo ženski ustrezno svetovano glede uporabe kontracepcije in če uporablja učinkovito kontracepcijo (glejte poglavji 4.3 in 4.6).
Macitentan inhibits the breast cancer resistance protein (BCRP) at clinically relevant intestinal concentrations. 
Macitentan v klinično koncentracijah v črevesju pomembnih zavira protein odpornosti na raka dojke (BCRP, breast cancer resistance protein).
In a double-blind study in patients with idiopathic pulmonary fibrosis, the incidence of peripheral oedema AEs in the macitentan and placebo treatment groups was 11.8% and 6.8%, respectively. 
V dvojno slepi študiji pri bolnikih z idiopatsko pljučno fibrozo je bila incidenca neželenega učinka perifernega edema 11,8 % v skupini, zdravljeni z macitentanom, in 6,8 % v skupini, ki je dobivala placebo.
If you notice any of these signs, tell your doctor. 
• bledico Če opazite katerega od teh znakov, obvestite zdravnika.
• Bronchitis (inflammation of the airways) 
• bronhitis (vnetje dihalnih pot)
In a double-blind study in patients with PAH, macitentan 10 mg was associated with a mean decrease in haemoglobin versus placebo of 1 g/dL. 
V dvojno slepi študiji pri bolnikih s PAH je bila uporaba macitentana 10 mg povezana s povprečnim zmanjšanjem koncentracije hemoglobina v primerjavi s placebom 1 g/dl.
In a double-blind study in patients with PAH, macitentan 10 mg was associated with a decrease in mean platelet count of 17 × 109/L, versus a mean decrease of 11 × 109/L in placebo-treated patients. 
V dvojno slepi študiji pri bolnikih s PAH je bil macitentan 10 mg povezan z zmanjšanjem povprečnega števila trombocitov za 17 × 109/l v primerjavi z 11 × 109/l pri bolnikih, ki so dobivali placebo.
There is no clinical experience with the use of macitentan in PAH patients with severe renal impairment. 
Kliničnih izkušenj z uporabo macitentana pri bolnikih s PAH s hudo ledvično okvaro ni.
Consequently, if signs of pulmonary oedema occur when macitentan is administered in patients with PAH, the possibility of pulmonary veno-occlusive disease should be considered. 
Posledično je treba pomisliti na možnost pljučne vensko-okluzivne bolezni, če se pojavijo znaki pljučnega edema pri bolnikih s PAH, ki dobivajo macitentan.
MARKETING AUTHORISATION NUMBER(S) EU/1/13/893/001 
ŠTEVILKA(E) DOVOLJENJA (DOVOLJENJ) ZA PROMET EU/1/13/893/001
PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON for BLISTERS 
PODATKI NA ZUNANJI OVOJNINI ZUNANJA ŠKATLA za PRETISNE OMOTE
Strong CYP3A4 inducers: Concomitant treatment with rifampicin 600 mg daily, a potent inducer of CYP3A4, reduced the steady-state exposure to macitentan by 79% but did not affect the exposure to the active metabolite. 
Močni induktorji CYP3A4: Sočasno zdravljenje z rifampicinom 600 mg na dan, močnim induktorjem CYP3A4, je zmanjšala izpostavljenost macitentanu v stanju dinamičnega ravnovesja za
Hypersensitivity reactions (e.g., angioedema, pruritus, rash)1 
(npr. angioedem, pruritus,
The risk of PAH related death or hospitalisation for PAH up to EOT was reduced by 50% (HR 0.50; 97.5% CI: 0.34 to 0.75; logrank p < 0.0001) in patients receiving macitentan 10 mg (50 events) compared to placebo (84 events). 
Tveganje smrti zaradi PAH ali hospitalizacije zaradi PAH do konca zdravljenja se je pri bolnikih, ki so prejemali macitentan 10 mg (50 dogodkov) v primerjavi s placebom (84 dogodkov), zmanjšalo za 50 % (HR 0,50; 97,5 % IZ: 0,34 do 0,75; logrank vrednost p < 0,0001).
Signs that your liver may not be working properly include: nausea (urge to vomit) vomiting fever (high temperature) pain in your stomach (abdomen) jaundice (yellowing of your skin or the whites of your eyes) dark-coloured urine itching of your skin lethargy or fatigue (unusual tiredness or exhaustion) flu-like syndrome (joint and muscle pain with fever) 
temno obarvan urin srbenje kože letargijo ali utrujenost (neobičajno utrujenost ali izčrpanost) gripi podoben sindrom (bolečine sklepov in mišic z zvišano telesno temperaturo)
The pharmacodynamic effect of warfarin on International Normalised Ratio (INR) was not affected by macitentan. 
Macitentan ni vplival na farmakodinamični učinek varfarina na mednarodno normalizirano razmerje
MARKETING AUTHORISATION NUMBER(S) EU/1/13/893/003 
ŠTEVILKA(E) DOVOLJENJA (DOVOLJENJ) ZA PROMET EU/1/13/893/003
No testicular findings were noted in mice after treatment up to 2 years. 
Pri miših po dajanju macitentana, ki je trajalo do 2 leti, niso opazili sprememb na testisih.
• Urinary tract infection (bladder infection) 
• okužba sečil (okužba mehurja)
3 Oedema/fluid retention has been associated with the use of ERAs including macitentan. 
3 Z uporabo ERA, vključno z macitentanom povezujejo edem/zastajanje tekočine.
Use in women of childbearing potential/Contraception in males and females Opsumit treatment should only be initiated in women of childbearing potential when the absence of pregnancy has been verified, appropriate advice on contraception provided, and reliable contraception is practised (see sections 4.3 and 4.4). 
Zdravljenje z zdravilom Opsumit se sme pri ženskah v rodni dobi uvesti samo, če je bila odsotnost nosečnosti potrjena, če je bilo ženski ustrezno svetovano glede uporabe kontracepcije in če uporablja učinkovito kontracepcijo (glejte poglavji 4.3 in 4.4).
The pharmacokinetics of macitentan in PAH patients were not influenced by the severity of the disease. 
Resnost bolezni pri bolnikih s PAH ni vplivala na farmakokinetiko macitentana.
• Patient reminder cards. 
• opozorilno kartico za bolnike.
Slightly increased pre- and post-implantation loss, decreased mean number of pups, and decreased testis and epididymis weights, were observed at exposures 7-fold the human exposure. 
Pri izpostavljenosti, ki je bila 7-krat večja kot izpostavljenost pri ljudeh, so opazili rahlo povečanje pred- in poimplantacijske izgube zarodkov, zmanjšano povprečno število mladičev in zmanjšano maso mod in epididimisa.
In a placebo-controlled trial in patients with PAH, the efficacy and safety of macitentan in combination with sildenafil were demonstrated. 
Učinkovitost in varnost macitentana v kombinaciji s sildenafilom pri bolnikih s PAH so dokazali v s placebom kontroliranem preskušanju.
See package leaflet for further information 
Glejte navodilo za uporabo za več informacij.
• feeling sick (nausea) 
• siljenje na bruhanje (navzeo) • bruhanje
• flu-like syndrome (joint and muscle pain with fever) 
• neobičajno utrujenost ali izčrpanost (letargijo ali utrujenost) • gripi podoben sindrom (bolečine sklepov in mišic z zvišano telesno temperaturo)
Talk to your doctor or pharmacist before taking Opsumit. 
Opozorila in previdnostni ukrepi Pred začetkom jemanja zdravila Opsumit se posvetujte z zdravnikom ali farmacevtom.