natgillin/translations-raw huggingface dataset:
Ketoconazole: Co-administration for 6 days of bosentan 62.5 mg twice daily with ketoconazole, a potent CYP3A4 inhibitor, increased the plasma concentrations of bosentan approximately 2-fold.
Ketokonazol: Pri 6-dnevni sočasni uporabi bosentana v odmerku 62,5 mg dvakrat na dan in ketokonazola, močnega zaviralca CYP3A4, se je plazemska koncentracija bosentana zvišala približno za dvakrat.
Based on physicochemical properties and the high degree of protein binding, bosentan is not expected to be removed from the circulation by dialysis to any significant extent (see section 4.2).
Kliničnih izkušenj pri dializno odvisnih bolnikih ni. Na podlagi fizikalno-kemičnih lastnosti in visoke stopnje vezave na beljakovine ne pričakujemo, da bi lahko z dializo iz krvnega obtoka odstranili veliko bosentana (glejte poglavje 4.2).
Tadalafil: Bosentan (125 mg twice daily) reduced tadalafil (40 mg once per day) systemic exposure by 42% and Cmax by 27% following multiple dose co-administration.
Tadalafil: Bosentan (125 mg dvakrat na dan) je po sočasnem dajanju večkratnega odmerka zmanjšal sistemsko izpostavljenost tadalafilu (40 mg enkrat na dan) za 42 % in Cmax za 27 %.
The mean duration of exposure to bosentan was 1.9 years ± 0.7 years (min: 0.1 years; max: 3.3 years) and patients were observed for a mean of 2.0 ± 0.6 years.
Povprečno trajanje izpostavljenosti bosentanu je bilo 1,9 let ± 0,7 let; (najmanj 0,1 let, največ 3,3 leta), bolnike pa so opazovali povprečno 2,0 ± 0,6 let.
FUTURE 1 was an open-label, uncontrolled study that was conducted with the dispersible tablet formulation of bosentan administered at a maintenance dose of 4 mg/kg twice daily to 36 patients from 2 to 11 years of age.
FUTURE 1 je bila odprta, nenadzorovana študija, ki so jo izvajali z bosentanom v obliki disperzibilnih tablet v vzdrževalnem odmerku 4 mg/kg dvakrat dnevno, ki so ga dajali 36 bolnikom,
The film-coat contains hypromellose, glycerol triacetate, talc, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172) and ethylcellulose.
Filmska obloga vsebuje hipromelozo, gliceriltriacetat, smukec, titanov dioksid (E171), rumen železov oksid
PVC/PE/PVDC/aluminium-blisters containing 14 film-coated tablets.
PVC/PE/PVDC/aluminij pretisni omot s 14 filmsko obloženimi tabletami.
56 film-coated tablets 112 film-coated tablets
56 filmsko obloženih tablet 112 filmsko obloženih tablet
Two randomised, double-blind, multi-centre, placebo-controlled studies have been conducted in 122 (study AC-052-401 [RAPIDS-1]) and 190 (study AC-052-331 [RAPIDS-2]) adult patients with systemic sclerosis and digital ulcer disease (either ongoing digital ulcers or a history of digital ulcers within the previous year).
122 (študija AC-052-401 [RAPIDS-1]) in 190 (študija AC-052-331 [RAPIDS-2]) odraslih bolnikih s sistemsko sklerozo in boleznijo razjed prstov (bodisi nastajajočimi razjedami prstov ali z anamnezo razjed prstov v prejšnjem letu).
There are no data on the safety and efficacy in patients under the age of 18 years.
Pediatrična populacija Podatkov o varnosti in učinkovitosti pri bolnikih pod 18 let ni. Farmakokinetični podatki za zdravilo
Gastrooesophageal reflux disease Diarrhoea
Bolezni prebavil pogosti gastroezofagealna refluksna bolezen driska
In rats, oral administration of bosentan for 2 years produced a small, significant increase in the combined incidence of thyroid follicular cell adenomas and carcinomas in males, but not in females, at plasma concentrations about 9 to 14 times the plasma concentrations achieved at the therapeutic dose in humans.
Pri podganah je peroralno dajanje bosentana preko obdobja dveh let povzročilo majhno, a pomembno povečanje incidence adenomov in karcinomov ščitničnih folikularnih celic pri samcih, ne pa pri samicah, pri plazemskih koncentracijah, približno 9- do 14-krat višjih od plazemskih koncentracij,
Treatment with bosentan has been associated with dose-dependent elevations in liver aminotransferases and decreases in haemoglobin concentration (see section 4.4).
Zdravljenje z bosentanom so povezovali z zvišanjem vrednosti jetrnih aminotransferaz, odvisnim od odmerka, in znižanjem koncentracije hemoglobina (glejte poglavje 4.4).
Plasma concentrations of bosentan metabolites increased about 2-fold in these patients as compared with subjects with normal renal function.
Pri teh bolnikih so se plazemske koncentracije presnovkov bosentana povišale za približno 2-krat v primerjavi z osebami z normalnim ledvičnim delovanjem.
PARTICULARS TO APPEAR ON THE OUTER PACKAGING CARTON WITH 56 AND 112 TABLETS
PODATKI NA ZUNANJI OVOJNINI ŠKATLA S 56 IN 112 TABLETAMI
The median exposure to study treatment was 4.5 (range: 0.5-10.0) days in the bosentan group and 4.0 (range: 2.5-6.5) days in the placebo group.
Mediana izpostavljenost študijskemu zdravljenju je bila v skupini z bosentanom 4,5 (razpon 0,5-10,0) dni, v skupini s placebom pa 4,0 (razpon 2,5-6,5) dni.
Of the 22 patients stable at week 8, 6 improved at week 12/16 and 4 deteriorated compared with baseline.
Od 22 v 8. tednu stabilnih bolnikov se je pri 6 bolnikih stanje izboljšalo v 12./16.
The pharmacokinetics of bosentan have mainly been documented in healthy subjects.
5.2 Farmakokinetične lastnosti Farmakokinetiko bosentana so preučevali zlasti pri zdravih osebah.
A pooled analysis of uncontrolled paediatric studies conducted in PAH with the bosentan 32 mg dispersible tablet formulation (FUTURE 1/2, FUTURE 3/Extension) included a total of 100 children treated with bosentan 2 mg/kg twice daily (n = 33), 2 mg/kg three times daily (n = 31), or 4 mg/kg twice daily (n = 36).
Združena analiza nenadzorovanih pediatričnih študij pri PAH z bosentanom 32 mg v obliki disperzibilnih tablet (FUTURE 1/2, FUTURE 3/podaljšanje) je zajela skupno 100 otrok, zdravljenih z bosentanom 2 mg/kg dvakrat dnevno (n = 33), 2 mg/kg trikrat dnevno (n = 31) ali 4 mg/kg dvakrat dnevno (n = 36).
During treatment with STAYVEER, your doctor will arrange for regular blood tests to check for changes in your liver function.
V času jemanja zdravila STAYVEER bo zdravnik naročil redne preiskave krvi, da preveri, če je prišlo do sprememb v delovanju jeter.
Cyclosporine A: Co-administration of STAYVEER and cyclosporine A (a calcineurin inhibitor) is contraindicated (see section 4.3).
Ciklosporin A: Sočasna uporaba zdravila STAYVEER in ciklosporina A (kalcinevrinski zaviralec) je kontraindicirana (glejte poglavje 4.3).
Be sure to discuss any questions you may have with your doctor or your gynaecologist - complete the details on the back of this card and take it to your doctor or gynaecologist at your next visit.
Izpolnite podatke na hrbtni strani te kartice in jo ob naslednjem obisku zdravnika ali ginekologa vzemite s seboj.
In patients between 3 months and 1 year (n = 2) AUCτ was 5,914 ng·h/mL (CV: 85%), and in patients between 1 and 2 years (n = 7) AUCτ was 3,507 ng·h/mL (CV: 70%).
Pri bolnikih, starih od 3 mesece do 1 leto (n = 2), je bila AUCτ 5.914 ng·h/ml (CV: 85 %), pri bolnikih, starih od 1 do 2 leti (n = 7) pa 3.507·ng h/ml (CV: 70 %).
Inside your pack of STAYVEER tablets you will find a Patient Alert Card. You should complete this card and take it to your doctor at your next visit so that your doctor or gynaecologist can assess whether you need additional or alternative reliable contraceptive methods.
Izpolnite to kartico in jo ob naslednjem obisku pokažite svojemu zdravniku, da bo bodisi zdravnik ali ginekolog lahko ocenil, ali potrebujete dodatne ali druge zanesljive kontracepcijske metode.
Please read this card carefully before starting your treatment with STAYVEER.
Pred začetkom zdravljenja z zdravilom STAYVEER skrbno preberite to kartico.
It cannot be excluded that this may affect your ability to father a child. Talk to your doctor if you have any questions or concerns about this.
Ni mogoče izključiti, da bi to lahko vplivalo na vašo sposobnost zaploditi otroka.
These cases reinforce the importance of strict adherence to the monthly schedule for monitoring of liver function for the duration of treatment with STAYVEER (see section 4.4).
Ti primeri še poudarjajo pomen doslednosti upoštevanja mesečnega režima nadziranja delovanja jeter v času trajanja zdravljenja z zdravilom
In 20 placebo-controlled studies, conducted in a variety of therapeutic indications, a total of 2,486 patients were treated with bosentan at daily doses ranging from 100 mg to 2000 mg and 1,838 patients were treated with placebo.
V 20 s placebom kontroliranih študijah, ki so se izvajale za številne terapevtske indikacije, je bilo skupaj 2.486 bolnikov zdravljenih z bosentanom v dnevnih odmerkih v razponu od 100 mg do
((Front cover))
(( Prednja stran))
• Hypersensitivity reactions (including skin inflammation, itching and rash)
• preobčutljivostna reakcija (vključno z vnetjem kože, srbenjem in izpuščajem)
No dose adjustment is required in patients undergoing dialysis (see section 5.2).
Prilaganje odmerka pri dializno odvisnih bolnikih ni potrebno (glejte poglavje 5.2).
STAYVEER is contraindicated in patients with moderate to severe liver dysfunction (see sections 4.3, 4.4 and 5.2).
Zdravilo STAYVEER je pri bolnikih s srednje in hudo okvarjenim delovanjem jeter kontraindicirano (glejte poglavja 4.3, 4.4 in 5.2).
Placebo (n=88) Bosentan (n=80) Placebo (n=91) Bosentan (n=86)
Placebo (n = 88)
In the event of clinical deterioration (e.g., decrease in 6-minute walk test distance by at least 10% compared with pre-treatment measurement) despite STAYVEER treatment for at least 8 weeks (target dose for at least 4 weeks), alternative therapies should be considered.
Zdravljenje v primeru kliničnega poslabšanja PAH V primeru poslabšanja kliničnega stanja (denimo, zmanjšanje prehojene razdalje v 6-minutnem preskusu s hojo za vsaj 10 % v primerjavi z rezultatom pred začetkom zdravljenja) kljub 8
The estimates may have been influenced by the initiation of epoprostenol treatment in 43/235 patients.
Pri 43/235 bolnikih je na oceno morda vplivalo zdravljenje z epoprostenolom.
In this total population, Kaplan-Meier estimates of survival were 93% and 84% 1 and 2 years after the start of treatment with bosentan, respectively.
V tej skupni populaciji je bila po 1 letu zdravljenja z bosentanom ocena preživetja po metodi Kaplan-Meier 93-odstotna, po 2 letih zdravljenja pa 84-odstotna.
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product Characteristics, section 4.2)
Predpisovanje in izdaja zdravila je le s posebnim režimom (glejte Prilogo I: Povzetek glavnih značilnosti zdravila, poglavje 4.2)
In patients between 3 months and 2 years the daily exposure was 7,879 ng·h/mL; AUCτ was 3,939 ng·h/mL (CV: 72%).
Pri bolnikih, starih od 3 mesece do 2 leti, je bila dnevna izpostavljenost 7.879·ng h/ml, AUCτ pa 3.939·ng h/ml (CV: 72 %).
• The median time to complete weaning from mechanical ventilation was 10.8 days (95% CLs 3.21, 12.21 days) on bosentan and 8.6 days (95% CLs 3.71, 9.66 days) on placebo (p = 0.24).
• mediana časa do popolne ukinitve mehanske ventilacije je bila pri bosentanu 10,8 dni (95-% meje zaupanja [MZ] 3,21; 12,21 dni), pri placebu pa 8,6 dni (95-% meje zaupanja [MZ] 3,71; 9,66 dni) (p = 0,24).
In the patients above 2 years (n = 22) the daily exposure was 8,820 ng·h/mL; AUCτ was 4,410 ng·h/mL (CV: 58%).
Pri bolnikih, starejših od 2 let (n = 22) je bila dnevna izpostavljenost 8.820·ng h/ml, AUCτ pa 4.410 ng·h/ml (CV: 58 %).
Laboratory abnormalities
Nenormalne laboratorijske vrednosti
Sildenafil: Co-administration of bosentan 125 mg twice daily (steady state) with sildenafil 80 mg three times a day (at steady state) concomitantly administered during 6 days in healthy volunteers resulted in a 63% decrease in the sildenafil AUC and a 50% increase in the bosentan AUC.
Sildenafil: Šestdnevno sočasno dajanje bosentana 125 mg dvakrat na dan (stanje dinamičnega ravnovesja) s sildenafilom 80 mg trikrat na dan (v stanju dinamičnega ravnovesja) zdravim prostovoljcem je povzročilo 63 % zmanjšanje AUCτ sildenafila in 50 % povečanje AUCτ bosentana.
In the FUTURE-4 study including 13 neonates with PPHN treated with bosentan 2 mg/kg twice daily for less than 10 days (range 0.5-10.0 days), there were no cases of liver aminotransferases ≥ 3 × ULN
V študiji FUTURE-4, ki je vključevala 13 novorojenčkov s PPHN, zdravljenih z bosentanom 2 mg/kg dvakrat dnevno manj kot 10 dni (razpon 0,5-10,0 dni), ni bilo primerov povišanja jetrnih aminotransferaz ≥ 3 × ZMN med zdravljenjem, vendar pa je prišlo do enega primera hepatitisa 3 dni po prenehanju zdravljenja z bosentanom.
STAYVEER 62.5 mg film-coated tablets PVC/PE/PVDC/aluminium-blisters containing 14 film-coated tablets.
STAYVEER 62,5 mg filmsko obložene tablete Pretisni omot iz PVC/PE/PVDC/aluminija s 14 filmsko obloženimi tabletami.
Enrolled patients were PAH-treatment-naïve (n = 156) or on a stable dose of sildenafil (n = 29).
(n = 156) ali so prejemali stalni odmerek sildenafila (n = 29).
Concomitant use of rifampicin and STAYVEER is not recommended.
Sočasna uporaba rifampicina in zdravila STAYVEER ni priporočljiva.
The combination should be used with caution.
Bodite previdni pri uporabi te kombinacije.
Therefore, concomitant use of STAYVEER and tacrolimus or sirolimus is not advisable.
Zato sočasno uporabo zdravila STAYVEER in takrolimusa ali sirolimusa odsvetujemo.
Treatment with bosentan has been associated with dose-related decreases in haemoglobin concentration (see section 4.8).
Zdravljenje z bosentanom je bilo povezano z majhnim znižanjem koncentracije hemoglobina v odvisnosti od odmerka (glejte poglavje 4.8).
> 5 and ≤ 8 × ULN The result should be confirmed by a second liver test; if confirmed, treatment should be stopped and aminotransferase levels monitored at least every 2 weeks.
> 5 in  8  ZMN Rezultat je treba potrditi še z drugo preiskavo jetrnih encimov; če je potrjen,
Uncommon (may affect up to one in 100 people):
Občasni (prizadenejo lahko do 1 od 100 bolnikov):
The pharmacokinetics of bosentan have not been studied in patients with Child-Pugh class C hepatic impairment.
Farmakokinetike bosentana pri bolnikih z okvarjenim delovanjem jeter razreda C po klasifikaciji Child-Pugh niso raziskali.
• nausea (urge to vomit)
• navzeo (siljenje na bruhanje)
At baseline, patients had idiopathic (31 patients [86%]) or familial (5 patients [14%]) PAH, and were in WHO functional class II (n = 23, 64%) or class III (n = 13, 36%).
V izhodišču so bolniki imeli idiopatsko (31 bolnikov [86 %] ali družinsko (5 bolnikov [14 %] ) PAH,
Hormonal contraceptives: Co-administration of bosentan 125 mg twice daily for 7 days with a single dose of oral contraceptive containing norethisterone 1 mg + ethinyl estradiol 35 mcg decreased the AUC of norethisterone and ethinyl estradiol by 14% and 31%, respectively.
Hormonska kontracepcija: Sočasno dajanje bosentana 25 mg dvakrat na dan 7 dni s peroralnim kontraceptivom v enem odmerku, vsebujočim noretisteron 1 mg in etinilestradiol 35 µg, je zmanjšalo
STAYVEER may harm the development of the foetus.
Zdravilo STAYVEER lahko škoduje razvoju ploda.
STAYVEER is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease (see section 5.1).
Zdravilo STAYVEER se uporablja tudi za zmanjševanje števila novih razjed prstov pri bolnikih s sistemsko sklerozo in nastajajočimi razjedami prstov (glejte poglavje 5.1).
A Patient Alert Card providing important safety information that patients need to be aware of before and during treatment with STAYVEER is included in the pack.
Opozorilna kartica za bolnika s pomembnimi varnostnimi informacijami, na katere mora biti bolnik pozoren pred in med zdravljenjem z zdravilom STAYVEER, je priložena pakiranju zdravila.
Remember to have your liver blood test every month.
Vsak mesec opravite preiskavo krvi za oceno delovanja jeter.
Patients and prescribers must be aware that due to potential pharmacokinetic interactions, STAYVEER may render hormonal contraceptives ineffective (see section 4.5).
Bolnica in zdravnik, ki zdravilo predpiše, se morata zavedati, da lahko zaradi možnih farmakokinetičnih interakcij zdravilo STAYVEER povzroči neučinkovitost hormonske kontracepcije
A 2-year carcinogenicity study in mice showed an increased combined incidence of hepatocellular adenomas and carcinomas in males, but not in females, at plasma concentrations about 2 to 4 times the plasma concentrations achieved at the therapeutic dose in humans.
5.3 Predklinični podatki o varnosti Dvoletna študija kancerogenosti pri miših je pokazala povečanje incidence hepatocelularnih adenomov in karcinomov pri samcih, ne pa pri samicah, pri plazemskih koncentracijah, približno 2do 4-krat višjih od plazemskih koncentracij, doseženih pri ljudeh po terapevtskih odmerkih.
The dosage of these products may need to be adjusted after initiation, dose change or discontinuation of concomitant STAYVEER treatment.
Morebiti bo po uvedbi zdravljenja, spremembi odmerka ali prekinitvi zdravljenja z zdravilom STAYVEER treba odmerke teh zdravil prilagoditi.
• a blood test to check for anaemia (low haemoglobin)
• preiskava krvi za oceno delovanja jeter • preiskava krvi za ugotavljanje slabokrvnosti (nizek hemoglobin)
Cartons contain 56 or 112 film-coated tablets.
Škatle vsebujejo 56 ali 112 filmsko obloženih tablet.
Skin and subcutaneous disorders Common
Bolezni kože in podkožja pogosti eritem
5 Oedema or fluid retention was reported in 13.2% of patients on bosentan and 10.9% of patients on placebo.
5 O edemu ali zastajanju tekočine so poročali pri 13,2 % bolnikov na bosentanu in pri 10,9 %
Caution is recommended in the case of co-administration.
V primeru sočasnega dajanja je potrebna previdnost.
STAYVEER 125 mg film-coated tablets PVC/PE/PVDC/aluminium-blisters containing 14 film-coated tablets.
STAYVEER 125 mg filmsko obložene tablete Pretisni omot iz PVC/PE/PVDC/aluminija s 14 filmsko obloženimi tabletami.
CARTON WITH 56 TABLETS
ŠKATLA S 56 TABLETAMI
• Cirrhosis (scarring) of the liver, liver failure (serious disturbance of liver function)
• ciroza (brazgotinjenje) jeter, odpoved jeter (huda motnja delovanja jeter)
Rifampicin: Co-administration in 9 healthy subjects for 7 days of bosentan 125 mg twice daily with rifampicin, a potent inducer of CYP2C9 and CYP3A4, decreased the plasma concentrations of bosentan by 58%, and this decrease could achieve almost 90% in an individual case.
Rifampicin: 7-dnevno sočasno dajanje bosentana 125 mg dvakrat na dan in rifampicina, močnega induktorja CYP2C9 in CYP3A4, 9 zdravim osebam je zmanjšalo plazemske koncentracije bosentana za 58 %, v enem primeru je to zmanjšanje doseglo 90 %.
OUTER CARTON & BOTTLE LABEL/ BOTTLES
NALEPKA ZUNANJE ŠKATLE IN PLASTENKE/ PLASTENKE
Cases of pulmonary oedema have been reported with vasodilators (mainly prostacyclins) when used in patients with pulmonary veno-occlusive disease.
Pri uporabi vazodilatatorjev (zlasti prostaciklinov) pri bolnikih s pljučno venookluzivno boleznijo so poročali o primerih pljučnega edema.
Fertility
etilceluloza
Intensified monitoring is recommended during the discontinuation period.
V obdobju nižanja odmerka zdravila priporočamo skrbnejše spremljanje.
Study AC-052-356 (BREATHE-3) evaluated the pharmacokinetics of single and multiple oral doses of the film-coated tablet formulation of bosentan in 19 children aged from 3 to 15 years with PAH who were dosed on the basis of body weight with 2 mg/kg twice daily.
V študiji AC-052-356 (BREATHE-3) so ocenjevali farmakokinetiko enkratnega in večkratnih peroralnih odmerkov bosentana v obliki filmsko obloženih tablet pri 19 otrocih, starih od 3 do 15 let, s
No dose adjustment is needed in patients with mild hepatic impairment (i.e., Child-Pugh class A) (see section 5.2).
Prilagajanje odmerka pri bolnikih z blago okvarjenim delovanjem jeter (po klasifikaciji Child-Pugh razred A) ni potrebno (glejte poglavje 5.2).
In a prospective, multi-centre, randomised, double-blind, placebo-controlled study (AC-052-405 [BREATHE-5]), patients with PAH WHO functional class III and Eisenmenger physiology associated with congenital heart disease received bosentan 62.5 mg twice daily for 4 weeks, then 125 mg twice daily for a further 12 weeks (n = 37, of whom 31 had a predominantly right to left, bidirectional shunt).
405 [BREATHE-5]) so bolniki s PAH III. razreda po klasifikaciji SZO in Eisenmengerjevo fiziologijo, povezano s kongenitalno srčno boleznijo, 4 tedne prejemali bosentan 2,5 mg dvakrat na dan, nato pa nadaljnjih 12 tednov 125 mg dvakrat na dan (n = 37, med katerimi jih je imelo 31 pretežno desno-levi dvosmerni šant).
STAYVEER 125 mg film-coated tablets are orange-white, oval film-coated tablets with “125” on one side.
STAYVEER 125 mg filmsko obložene tablete so oranžno-bele ovalne filmsko obložene tablete z napisom „125“ na eni strani.
After 4 weeks of bosentan 62.5 mg twice daily, the maintenance dose studied in both these studies was 125 mg twice daily.
4 tednih jemanja bosentana v odmerku 62,5 mg dvakrat na dan je bil vzdrževalni odmerek, preučevan v teh študijah, 125 mg dvakrat na dan.
There was evidence of a mild thyroid hormonal imbalance induced by bosentan in rats.
Pri podganah so dokazali, da bosentan povzroča blago hormonsko neravnovesje v ščitnici.
In this study there was an increasedincidence of hospitalisation due to CHF during the first 4-8 weeks of treatment with bosentan, which could have been the result of fluid retention.
V tej študiji je bilo število primerov hospitalizacije zaradi CHF v prvih 4-8
The mean increase from baseline in cardiac index was 0.5 L/min/m2, the mean decrease in mean pulmonary arterial pressure was 8 mmHg, and the mean decrease in PVR was 389 dyn·sec·cm-5.
Povprečno povečanje srčnega indeksa od izhodiščne vrednosti je bilo 0,5 l/min/m2, povprečno znižanje povprečnega pljučnega arterijskega tlaka je bilo
• Pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and
• pljučni arterijski hipertenziji, povezani s kongenitalnimi sistemsko-pulmonalnimi šanti in Eisenmengerjevo fiziologijo.
Recommended dose Adult
Priporočeni odmerek
In addition, an increased incidence of elevated aminotransferases was observed in patients receiving concomitant therapy.
Poleg tega so pri bolnikih, ki so sočasno jemali obe zdravili, opazili povečanje incidence povišanih koncentracij aminotransferaz.
Nasal congestion1
občasni trombocitopenija1
Pharmacokinetics were studied in paediatric patients in 4 clinical studies (BREATHE-3, FUTURE 1, FUTURE-3 and FUTURE-4; see section 5.1).
Farmakokinetiko pri pediatričnih bolnikih so preučevali v 4 kliničnih študijah (BREATHE-3,
Bosentan is metabolised by CYP2C9 and CYP3A4.
Bosentan presnavljata CYP2C9 in CYP3A4.
When co-administered, initial trough concentrations of bosentan were approximately 30-fold higher than those measured after bosentan alone.
Kadar so ju uporabljali sočasno, so bile ob začetku odmerjanja koncentracije bosentana tik pred naslednjim odmerkom približno 30-krat višje kot koncentracije,
Glibenclamide: Co-administration of bosentan 125 mg twice daily for 5 days decreased the plasma concentrations of glibenclamide (a CYP3A4 substrate) by 40%, with potential significant decrease of the hypoglycaemic effect.
Glibenklamid: Pri sočasni uporabi bosentana v odmerku 125 mg dvakrat na dan 5 dni se je plazemska koncentracija glibenklamida (substrat CYP3A4) znižala za 40 % in potencialno pomembno zmanjšala hipoglikemični učinek.
How to take STAYVEER.
Kako jemati zdravilo STAYVEER
These haemodynamic improvements from baseline were similar with or without co-administration of epoprostenol.
Ta izboljšanja hemodinamskih kazalcev glede na izhodiščno vrednost so bila podobna, ne glede na to, ali so bolniki sočasno prejemali epoprostenol ali ne.
After 4 weeks of bosentan 62.5 mg twice daily, the maintenance doses studied in these studies were 125 mg twice daily in AC-052-351, and 125 mg twice daily and 250 mg twice daily in AC-052-352.
125 mg dvakrat na dan v AC-052-351 ter odmerek 125 mg dvakrat na dan in 250 mg dvakrat na dan v AC-052-352.
The NOAEL was 21 times (at Day 21 post partum) and 2.3 times (Day 69 post partum) the human therapeutic exposure, respectively.
Raven brez neželenih učinkov (NOAEL) je bila na 21. dan po skotitvi 21-krat višja, na 69. dan po skotitvi pa 2,3-krat višja od terapevtske izpostavljenosti pri ljudeh.