FrancophonIA/ELRC3.0 huggingface dataset:
English: In vitro studies showed that ivacaftor is not a substrate for OATP1B1, OATP1B3, or P-gp.
Croatian: In vitro ispitivanja pokazala su da ivakaftor nije supstrat prijenosnika OATP1B1, OATP1B3 ili P-gpa.
English: What you need to know before you take Symkevi 3.
Croatian: Što morate znati prije nego počnete uzimati Symkevi
English: • Talk to your doctor if you have kidney problems, or you have previously had them.
Croatian: • Obratite se svom liječniku ako imate probleme s bubrezima ili ste ih prije imali.
English: Table 3 reflects adverse reaction observed with Symkevi in combination with ivacaftor in patients aged 12 years and older based on pooled data from three double-blind, placebo-controlled Phase 3 clinical studies.
Croatian: Tablica 3 prikazuje nuspojave opažene uz Symkevi u kombinaciji s ivakaftorom u bolesnika u dobi od 12 i više godina na temelju objedinjenih podataka iz tri dvostruko slijepa, placebom kontrolirana klinička ispitivanja faze 3.
English: • Nuts, fat-containing nutritional bars or drinks
Croatian: • orasi, nutritivne pločice ili pića koji sadrže masti.
English: Long-term safety and efficacy rollover study (Study 3) An ongoing, Phase 3, open-label, multicenter, rollover, 96-week study to evaluate the safety and efficacy of long-term treatment with Symkevi in combination with ivacaftor is being conducted with patients from Studies 1 (n=459) and 2 (n=226).
Croatian: Dugotrajno prijelazno (engl. rollover) ispitivanje sigurnosti i djelotvornosti (ispitivanje 3) U tijeku je otvoreno, multicentrično, prijelazno ispitivanje faze 3 u trajanju od 96 tjedana koje se provodi radi procjene sigurnosti i djelotvornosti dugotrajnog liječenja lijekom Symkevi u kombinaciji s ivakaftorom u bolesnika iz ispitivanja 1 (n=459) i 2 (n=226).
English: Ivacaftor is also metabolized extensively in humans.
Croatian: Ivakaftor se također opsežno metabolizira u ljudi.
English: • Blocked nose (sinus congestion)
Croatian: • začepljen nos (začepljenost sinusa)
English: • Nipple changes or pain
Croatian: • promjene ili bolnost bradavica
English: No dose adjustment of OATP1B1 substrates is required when coadministered with Symkevi.
Croatian: Nije potrebna prilagodba doze supstrata OATP1B1 kad se primjenjuju istodobno s lijekom Symkevi.
English: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000
Croatian: Nuspojave su navedene sukladno MedDRA-inoj klasifikaciji organskih sustava i učestalosti: vrlo često (≥1/10); često (≥1/100 i <1/10); manje često (≥1/1000 i <1/100); rijetko (≥1/10 000 i <1/1000); vrlo rijetko (<1/10 000); nepoznato (ne može se procijeniti iz dostupnih podataka).
English: No dose adjustment is required when Symkevi is co-administered with ciprofloxacin.
Croatian: Nije potrebna prilagodba doze kad se Symkevi primjenjuje istodobno s ciprofloksacinom.
English: Therefore, co-administration with strong CYP3A inducers is not recommended (see section 4.5).
Croatian: Stoga se ne preporučuje istodobna primjena s jakim induktorima CYP3A (vidjeti dio 4.5).
English: This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free'.
Croatian: Natrij Ovaj lijek sadrži manje od 1 mmol (23 mg) natrija po dozi, tj. zanemarive količine natrija.
English: Findings of cataracts were observed in juvenile rats dosed from postnatal Day 7 through 35 at ivacaftor exposure levels of 0.25 times the MRHD based on systemic exposure of ivacaftor and its metabolites when administered as tezacaftor/ivacaftor.
Croatian: Nalazi katarakte opaženi su u mladih štakora koji su od 7. do 35. postnatalnog dana bili izloženi razinama ivakaftora koje su iznosile 0,25 puta MRHD na temelju sistemske izloženosti ivakaftoru i njegovim metabolitima kad se primjenjivao kao tezakaftor/ivakaftor.
English: ppFEV1: percent predicted forced expiratory volume in 1 second; SD: Standard Deviation; LS mean: least squares mean; CI: confidence interval; NA: not applicable; IVA: ivacaftor; CFQ-R: Cystic Fibrosis Questionnaire-Revised.
Croatian: ppFEV1: postotak predviđenog forsiranog ekspiratornog volumena u 1 sekundi; SD: standardna devijacija; CI: interval pouzdanosti; NP: nije primjenjivo; IVA: ivakaftor; CFQ-R: upitnik o cističnoj fibrozi - revidirana verzija.
English: Exposure to tezacaftor is not expected to be affected significantly by concomitant inhibitors of OATP1B1, P-gp, or BCRP due to its high intrinsic permeability and low likelihood of being excreted intact.
Croatian: Ne očekuje se da će istodobno primijenjeni inhibitori OATP1B1, P-gp-a ili BCRP-a značajno utjecati na izloženost tezakaftoru zbog njegove visoke intrinzične permeabilnosti i male vjerojatnosti da će se izlučiti nepromijenjen.
English: In vitro data suggested that tezacaftor is metabolized mainly by CYP3A4 and CYP3A5.
Croatian: In vitro podaci ukazuju na to da tezakaftor uglavnom metaboliziraju CYP3A4 i CYP3A5.
English: When co-administered with moderate CYP3A inhibitors (e.g., fluconazole, erythromycin), the dose should be adjusted according to Table 1 (see sections 4.4 and 4.5).
Croatian: Kad se primjenjuju s umjerenim inhibitorima CYP3A (npr. flukonazolom, eritromicinom), dozu je potrebno prilagoditi prema tablici 1 (vidjeti dijelove 4.4 i 4.5).
English: Co-administration with itraconazole, a strong CYP3A inhibitor, increased tezacaftor exposure (measured as AUC) by 4-fold and increased ivacaftor AUC by 15.6-fold.
Croatian: Istodobna primjena s itrakonazolom, jakim inhibitorom CYP3A, povećala je izloženost tezakaftoru (mjerenu kao AUC) 4 puta, a AUC ivakaftora 15,6 puta.
English: In population pharmacokinetic analysis, data from 147 patients on tezacaftor or tezacaftor in combination with ivacaftor in Phase 2/3 clinical studies indicated that mild renal impairment (estimated glomerular filtration rate, estimated by the modification of diet in renal disease method, 60 to ≤89 mL/min/1.73 m2) did not affect the clearance of tezacaftor significantly.
Croatian: U analizi populacijske farmakokinetike, podaci o 147 bolesnika koji su primali tezakaftor ili tezakaftor u kombinaciji s ivakaftorom u kliničkim ispitivanjima faze 2/3 pokazali su da blago oštećenje funkcije bubrega (procijenjena brzina glomerularne filtracije, procijenjena metodom prilagodbe prehrane kod bubrežne bolesti, od 60 do ≤89 ml/min/1,73 m2) nije značajno utjecala na klirens tezakaftora.
English: M1-TEZ has similar potency to that of tezacaftor and is considered pharmacologically active.
Croatian: M1-TEZ ima sličnu jačinu kao i tezakaftor i smatra se farmakološki aktivnim.
English: Mean improvement in ppFEV1 was observed at the first assessment on Day 15 and sustained throughout the 8-week treatment period.
Croatian: Srednja vrijednost poboljšanja ppFEV1 opažena je na prvom pregledu 15. dana i zadržala se tijekom cijelog 8-tjednog razdoblja liječenja.
English: In a human pharmacokinetic study with tezacaftor alone, there was minimal elimination of tezacaftor and its metabolites in urine (only 13.7% of total radioactivity was recovered in the urine with 0.79% as unchanged medicinal product).
Croatian: U ispitivanju farmakokinetike samo tezakaftora u ljudi, mokraćom se eliminirala minimalna količina tezakaftora i njegovih metabolita (samo 13,7% ukupne radioaktivnosti otkriveno je u mokraći, uz 0,79% u obliku nepromijenjenog lijeka).
English: Tezacaftor is a selective CFTR corrector that binds to the first Membrane Spanning Domain (MSD-1) of CFTR.
Croatian: Tezakaftor je selektivni korektor CFTR-a koji se veže za prvu transmembransku domenu (engl.
English: Pulmonary exacerbations requiring hospitalizations were similar between treatment groups (RR: 0.78 [95% CI: 0.44, 1.36]; P=0.3801).
Croatian: Plućne egzacerbacije koje su zahtijevale hospitalizaciju bile su slične u obje terapijske skupine (RR: 0,78 [95% CI: 0,44; 1,36]; P=0,3801).
English: Table 7: Mean (SD) pharmacokinetic parameters of tezacaftor and ivacaftor at steady state in patients with CF
Croatian: Tablica 7: Srednja vrijednost (SD) farmakokinetičkih parametara tezakaftora i ivakaftora u stanju dinamičke ravnoteže u bolesnika s cističnom fibrozom
English: Mean improvement in ppFEV1 was observed at the first assessment on Day 15 and sustained throughout the 24-week treatment period.
Croatian: Srednja vrijednost poboljšanja vrijednosti ppFEV1 opažena je na prvom pregledu 15. dana i zadržala se tijekom cijelog 24-tjednog razdoblja liječenja.
English: The efficacy of Symkevi in combination with ivacaftor 150 mg tablet in patients with CF was demonstrated in two Phase 3, double-blind, controlled studies (Study 1 and Study 2), and one Phase 3, open-label extension study (Study 3).
Croatian: Djelotvornost lijeka Symkevi u kombinaciji s tabletom ivakaftora od 150 mg u bolesnika s cističnom fibrozom dokazana je u dva dvostruko slijepa, kontrolirana ispitivanja faze 3 (ispitivanju 1 i ispitivanju 2) te jednom otvorenom nastavku ispitivanja faze 3 (ispitivanje 3).
English: ECG evaluation
Croatian: Analiza EKG-a
English: Following once daily dosing of tezacaftor and twice-daily dosing of ivacaftor in patients with CF, plasma concentrations of tezacaftor and ivacaftor reach steady-state within 8 days and within 3 to 5 days, respectively, after starting treatment.
Croatian: Nakon doziranja tezakaftora jedanput dnevno i ivakaftora dvaput dnevno u bolesnika s cističnom fibrozom, koncentracije tezakaftora u plazmi dosegle su stanje dinamičke ravnoteže u roku od 8 dana, a ivakaftora unutar 3 do 5 dana nakon početka liječenja.
English: Study 1 was a 24-week, randomized, double-blind, placebo-controlled study.
Croatian: Ispitivanje 1 bilo je randomizirano, dvostruko slijepo, placebom kontrolirano ispitivanje u trajanju od 24 tjedna.
English: Improvements in ppFEV1 were observed regardless of age, disease severity, sex, mutation class, colonization with Pseudomonas, concomitant use of standard-of-care medications for CF, and geographic region.
Croatian: Poboljšanja vrijednosti ppFEV1 bila su opažena bez obzira na dob, težinu bolesti, spol, klasu mutacije, kolonizaciju bakterijom Pseudomonas, istodobnu primjenu standardnih lijekova za cističnu fibrozu i zemljopisnu regiju.
English: Absolute change from baseline at Week 24 (kg/m2)**
Croatian: Apsolutna promjena od početka ispitivanja do kraja 24. tjedna (kg/m2)**
English: Placebo N=256
Croatian: N=256
English: (may affect up to 1 in 10 people)
Croatian: Česte nuspojave (mogu se pojaviti u najviše 1 na 10 osoba)
English: Almac Pharma Services Ltd 20 Seagoe Industrial Estate Portadown
Croatian: Almac Pharma Services Ltd 20 Seagoe Industrial Estate
English: Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) is recommended during co-administration of warfarin with Symkevi given in combination with ivacaftor.
Croatian: Ivakaftor može inhibirati CYP2C9; stoga se tijekom istodobne primjene varfarina s lijekom Symkevi, davanim u kombinaciji s ivakaftorom, preporučuje pratiti međunarodni normalizirani omjer (engl. international normalized ratio, INR).
English: ppFEV1: percent predicted forced expiratory volume in 1 second; SD: Standard Deviation; LS mean: least squares mean; CI: confidence interval; BMI: body mass index; CFQ-R: Cystic Fibrosis Questionnaire-Revised.
Croatian: ppFEV1: postotak predviđenog forsiranog ekspiratornog volumena u 1 sekundi; SD: standardna devijacija; CI: interval pouzdanosti; ITM: indeks tjelesne mase; CFQ-R: upitnik o cističnoj fibrozi - revidirana verzija (engl.
English: • In the evening, take one ivacaftor 150 mg tablet.
Croatian: • Navečer uzmite jednu tabletu ivakaftora od 150 mg.
English: M1-IVA has approximately one-sixth the potency of ivacaftor and is considered pharmacologically active.
Croatian: M1-IVA ima približno jednu šestinu jačine ivakaftora i smatra se farmakološki aktivnim.
English: for patients from Study 1 and Week 16 for patients from Study 2.
Croatian: Interim analiza provedena je za bolesnike iz ispitivanja 1 do kraja 24. tjedna i za bolesnike iz ispitivanja 2 do kraja 16. tjedna.
English: Tezacaftor is not a substrate for OATP1B3.
Croatian: Tezakaftor nije supstrat OATP1B3.
English: However, exposure to M2-TEZ (tezacaftor metabolite) may be increased by inhibitors of P-gp.
Croatian: Međutim, inhibitori P-gp-a mogu povećati izloženost M2-TEZ-u (metabolitu tezakaftora).
English: Increased liver enzymes in the blood have been seen in patients with CF receiving Symkevi.
Croatian: Povišeni jetreni enzimi u krvi opaženi su u bolesnika s cističnom fibrozom koji primaju Symkevi.
English: − Tablet film coating: Hypromellose (E464), hydroxypropyl cellulose (E463), titanium dioxide (E171), talc (E553b), and iron oxide yellow (E172).
Croatian: − Film-ovojnica tablete: hipromeloza (E464), hidroksipropilceluloza (E463), titanijev dioksid (E171), talk (E553b) i žuti željezov oksid (E172).
English: CFQ-R respiratory domain score
Croatian: Rezultat u respiratornoj domeni upitnika CFQ-R
English: The NOAEL for viability and growth in the offspring provides an exposure level of approximately 4 times the systemic exposure of ivacaftor and its metabolites when administered as tezacaftor/ivacaftor in adult humans at the MRHD.
Croatian: NOAEL za preživljenje i rast potomstva odgovara razini izloženosti približno 4 puta većoj od sistemske izloženosti ivakaftoru i njegovim metabolitima kad se primjenjuje kao tezakaftor/ivakaftor u odraslih osoba pri MRHD-u.
English: Study 2 was a randomized, double-blind, placebo-controlled, 2-period, 3-treatment, 8-week crossover study.
Croatian: Ispitivanje 2 bilo je randomizirano, dvostruko slijepo, placebom kontrolirano ukriženo ispitivanje s 3 terapije u 2 razdoblja u trajanju od 8 tjedana.
English: • erythromycin
Croatian: • eritromicin.
English: Improvements in ppFEV1 were observed regardless of age, sex, baseline ppFEV1, colonization with Pseudomonas, concomitant use of standard-of-care medications for CF, and geographic region.
Croatian: Poboljšanja vrijednosti ppFEV1 opažena su bez obzira na dob, spol, početnu vrijednost ppFEV1, kolonizaciju bakterijom Pseudomonas, istodobnu primjenu standardnih lijekova za cističnu fibrozu i zemljopisnu regiju.
English: The rate ratio versus placebo was 0.53 (95% CI: 0.34, 0.82; nominal P= 0.0042).
Croatian: Omjer stope (engl. rate ratio, RR) naspram placeba iznosio je 0,53 (95% CI: 0,34; 0,82; nominalni P=0,0042).
English: The treatment difference of 0.06 kg/m2 for mean change in BMI from baseline to Week 24 (95% CI: -0.08, 0.19) was not statistically significant (P=0.4127).
Croatian: Terapijska razlika od 0,06 kg/m2 u srednjoj vrijednosti promjene ITM-a od početka ispitivanja do 24. tjedna (95% CI: -0,08; 0,19) nije bila statistički značajna (P=0,4127).
English: The pharmacokinetics of tezacaftor and ivacaftor are similar between healthy adult volunteers and patients with CF.
Croatian: Farmakokinetika tezakaftora i ivakaftora u zdravih odraslih dobrovoljaca slična je onoj u bolesnika s cističnom fibrozom.
English: Symkevi in combination with ivacaftor has not been studied in patients with CF who have undergone organ transplantation.
Croatian: Symkevi u kombinaciji s ivakaftorom nije ispitan u bolesnika s cističnom fibrozom kojima je presađen organ.
English: • Anticoagulant medicines (used to prevent blood clots).
Croatian: • Antikoagulansi (primjenjuju se za sprječavanje stvaranja krvnih ugrušaka).
English: Symkevi 100 mg tezacaftor/150 mg ivacaftor film-coated tablets are yellow, oval-shaped tablets stamped with “V100” on one side and plain on the other.
Croatian: Symkevi tezakaftor 100 mg / ivakaftor 150 mg filmom obložene tablete žute su tablete ovalnog oblika s utisnutom oznakom „V100“ na jednoj strani i bez oznaka na drugoj.
English: In Study 2 treatment with Symkevi in combination with ivacaftor resulted in a statistically significant improvement in ppFEV1 (Table 6).
Croatian: U ispitivanju 2, liječenje lijekom Symkevi u kombinaciji s ivakaftorom rezultiralo je statistički značajnim poboljšanjem vrijednosti ppFEV1 (tablica 6).
English: The No Observed Adverse Effect Level (NOAEL) for fertility findings provides an exposure level of approximately 5 times the systemic exposure of ivacaftor and its metabolites when administered as tezacaftor/ivacaftor in adult humans at the maximum recommended human dose (MRHD).
Croatian: No Observed Adverse Effect Level, NOAEL) na plodnost odgovara razini izloženosti približno 5 puta većoj od sistemske izloženosti ivakaftoru i njegovim metabolitima kad se primjenjuje kao tezakaftor/ivakaftor u odraslih osoba u maksimalnoj preporučenoj dozi za ljude
English: Ivacaftor N=156
Croatian: N=156
English: (may affect up to 1 in 100 people)
Croatian: Manje česte nuspojave (mogu se pojaviti u najviše 1 na 100 osoba)
English: Increased liver enzymes in the blood are very common in patients with CF.
Croatian: Povišeni jetreni enzimi u krvi vrlo su česti u bolesnika s cističnom fibrozom.
English: How to take Symkevi
Croatian: Kako uzimati Symkevi
English: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tezacaftor or ivacaftor in pregnant women.
Croatian: Nema podataka ili su podaci o primjeni tezakaftora ili ivakaftora u trudnica ograničeni (manje od
English: Patients who were previously treated with placebo and received Symkevi in combination with ivacaftor in Study 3 showed an increase of 5.3 (0.7) percentage points.
Croatian: U bolesnika koji su prethodno primali placebo i bili liječeni lijekom Symkevi u kombinaciji s ivakaftorom u ispitivanju 3 pokazalo se povećanje od 5,3 (0,7) postotnih bodova.
English: During the placebo-controlled Phase 3 studies (up to 24 weeks), the incidence of maximum transaminase (ALT or AST) >8, >5, or >3 x ULN were similar between Symkevi in combination with ivacaftor- and placebo-treated patients; 0.2%, 1.0%, and 3.4% in Symkevi in combination with ivacaftor-treated patients, and 0.4%, 1.0%, and 3.4% in placebo-treated patients.
Croatian: Tijekom placebom kontroliranih ispitivanja faze 3 (u trajanju do 24 tjedna), incidencija maksimalnih vrijednosti transaminaza (ALT ili AST) >8, >5 ili >3 x GGN bila je slična u bolesnika liječenih lijekom Symkevi u kombinaciji s ivakaftorom i onih koji su primali placebo; 0,2%, 1,0% odnosno 3,4% u bolesnika liječenih lijekom Symkevi u kombinaciji s ivakaftorom te 0,4%, 1,0% odnosno 3,4% u onih koji su primali placebo.
English: Tezacaftor
Croatian: Tezakaftor
English: In a combination regimen with ivacaftor 150 mg tablets The recommended dose is one Symkevi (tezacaftor 100 mg/ivacaftor 150 mg) tablet taken in the morning and one ivacaftor 150 mg tablet taken in the evening, approximately 12 hours apart with fat-containing food (see Method of administration).
Croatian: Preporučena doza je jedna tableta lijeka Symkevi (tezakaftor 100 mg/ivakaftor 150 mg) ujutro i jedna tableta ivakaftora od 150 mg navečer, uzete u razmaku od približno 12 sati s hranom koja sadrži masti (vidjeti Način primjene).
English: The exact mechanisms by which tezacaftor improves cellular processing and trafficking of F508del-CFTR and ivacaftor potentiates F508del-CFTR are not known.
Croatian: Nije poznat točan mehanizam kojim tezakaftor poboljšava staničnu obradu i transport F508del-CFTR-a i kojim ivakaftor pojačava aktivnost F508del-CFTR-a.
English: In Study 1 treatment with Symkevi in combination with ivacaftor resulted in a statistically significant improvement in ppFEV1 (Table 5).
Croatian: U ispitivanju 1, liječenje lijekom Symkevi u kombinaciji s ivakaftorom rezultiralo je statistički značajnim poboljšanjem vrijednosti ppFEV1 (tablica 5).
English: Following oral administration of 14C-tezacaftor, the majority of the dose (72%) was excreted in the faeces (unchanged or as the M2-TEZ metabolite) and about 14% was recovered in urine (mostly as M2-TEZ metabolite), resulting in a mean overall recovery of 86% up to 21 days after the dose.
Croatian: Nakon peroralne primjene 14C-tezakaftora, veći dio doze (72%) bio je izlučen stolicom (nepromijenjen ili kao metabolit M2-TEZ), a oko 14% otkriveno je u mokraći (uglavnom kao metabolit
English: Pulmonary exacerbations
Croatian: Plućne egzacerbacije
English: Tezacaftor Mean (SD)
Croatian: n/N Srednja vrijednost (SD)
English: Exposure to tezacaftor and ivacaftor may be reduced by the concomitant use of CYP3A inducers, potentially resulting in reduced efficacy of Symkevi and ivacaftor.
Croatian: Izloženost tezakaftoru i ivakaftoru može biti smanjena kod istodobne primjene induktora CYP3A, što bi moglo rezultirati smanjenom djelotvornošću lijeka Symkevi i ivakaftora.
English: In Study 3, the change in BMI z-value in the Symkevi in combination with ivacaftor group was maintained and patients previously treated with placebo showed an increase of 0.10 (0.05) kg/m2.
Croatian: U ispitivanju 3, promjena u z-vrijednosti ITM-a održala se u skupini liječenoj lijekom Symkevi u kombinaciji s ivakaftorom, a u bolesnika koji su prethodno primali placebo pokazalo se povećanje od 0,10 (0,05) kg/m2.
English: • Stomach (abdominal) ache
Croatian: • bol u trbuhu (abdomenu)
English: Ivacaftor can potentiate the CFTR protein delivered to the cell surface by tezacaftor, leading to a further enhancement of chloride transport than either active substance alone.
Croatian: Ivakaftor može pojačati aktivnost proteina CFTR koji tezakaftor dopremi do površine stanice, što dovodi do daljnjeg povećanja transporta klorida, većeg od onog koje nastaje zbog svake od tih dviju djelatnih tvari pojedinačno.
English: Symkevi in combination with ivacaftor can make you dizzy.
Croatian: Symkevi u kombinaciji s ivakaftorom može izazvati omaglicu.
English: In vitro and in vivo data indicate that ivacaftor is metabolized primarily by CYP3A4 and CYP3A5.
Croatian: Podaci dobiveni in vitro i in vivo pokazuju da ivakaftor prvenstveno metaboliziraju CYP3A4 i CYP3A5.
English: Concomitant use of CYP3A inducers may result in reduced exposures and thus reduced efficacy of Symkevi and ivacaftor.
Croatian: Istodobna primjena induktora CYP3A može dovesti do smanjene izloženosti i time smanjene djelotvornosti lijeka Symkevi i ivakaftora.
English: The use of Symkevi is not recommended in patients with severe hepatic impairment unless the benefits are expected to outweigh the risks (see sections 4.2 and 5.2).
Croatian: Ne preporučuje se primjena lijeka Symkevi u bolesnika s teškim oštećenjem funkcije jetre, osim ako se očekuje da će koristi biti veće od rizika (vidjeti dijelove 4.2 i 5.2).
English: The dose of Symkevi and ivacaftor should be adjusted when co-administered with moderate and strong CYP3A inhibitors.
Croatian: Dozu lijeka Symkevi i ivakaftora potrebno je prilagoditi kad se primjenjuju istodobno s umjerenim i jakim inhibitorima CYP3A.
English: Patients with a history of colonization with organisms associated with a more rapid decline in pulmonary status such as Burkholderia cenocepacia, Burkholderia dolosa, or Mycobacterium abscessus, or who had two or more abnormal liver function tests at screening (ALT, AST, AP, GGT
Croatian: Iz oba su ispitivanja isključeni bolesnici koji su u povijesti bolesti imali kolonizaciju mikroorganizmima povezanima s bržim propadanjem plućnog statusa, kao što su Burkholderia cenocepacia, Burkholderia dolosa ili Mycobacterium abscessus ili su imali odstupanja rezultata pretraga na dva ili više testova jetrene funkcije na probiru (ALT, AST, AP, GGT ≥3 x GGN ili ukupni bilirubin ≥2 x GGN) ili AST ili ALT ≥5 x GGN.
English: Table 4 reflects adverse reactions observed in clinical studies in patients treated with ivacaftor monotherapy.
Croatian: Tablica 4 prikazuje nuspojave opažene u kliničkim ispitivanjima u bolesnika liječenih samo ivakaftorom.
English: When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index, such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used.
Croatian: P-gp-a uskog terapijskog indeksa, kao što su ciklosporin, everolimus, sirolimus i takrolimus, potrebno je postupati oprezno uz odgovarajuće praćenje.
English: No dose adjustment is recommended for patients with mild or moderate renal impairment.
Croatian: Ne preporučuje se prilagodba doze za bolesnike s blagim ili umjerenim oštećenjem funkcije bubrega.