natgillin/translations-raw huggingface dataset:
Co-administration with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure of ivacaftor and tezacaftor; therefore, food or drink containing grapefruit or Seville oranges should be avoided during treatment (see section 4.2). 
Istodobna primjena sa sokom od grejpfruta, koji sadrži jednu ili više komponenti koje umjereno inhibiraju CYP3A, može povećati izloženost ivakaftoru i tezakaftoru; stoga je tijekom liječenja potrebno izbjegavati hranu ili pića koja sadrže grejpfrut ili naranče sorte Seville (vidjeti dio 4.2).
• ketoconazole, itraconazole, posaconazole, and voriconazole 
• ketokonazol, itrakonazol, posakonazol i vorikonazol
The European Medicines Agency has deferred the obligation to submit the results of studies with Symkevi in combination with ivacaftor in children aged less than 12 years in cystic fibrosis, as per PIP decision in the granted indication. 
Europska agencija za lijekove izuzela je obvezu podnošenja rezultata ispitivanja lijeka Symkevi u kombinaciji s ivakaftorom u djece mlađe od 12 godina za cističnu fibrozu, prema PIP-u za odobrenu indikaciju.
Due to its high intrinsic permeability and low likelihood of being excreted intact, co-administration of BCRP inhibitors is not expected to alter exposure of ivacaftor and M1-IVA, while any potential changes in M6-IVA exposures are not expected to be clinically relevant. 
Zbog njegove visoke intrinzične permeabilnosti i male vjerojatnosti da će biti izlučen u neizmijenjenom obliku, ne očekuje se da će istodobna primjena inhibitora BCRP-a promijeniti izloženost ivakaftoru i njegovu metabolitu M1-IVA, dok se za potencijalne promjene u izloženosti metabolitu M6-IVA ne očekuje da će biti klinički relevantne.
The impact of severe hepatic impairment (Child-Pugh Class C, score 10 to 15) on the pharmacokinetics of tezacaftor and ivacaftor has not been studied. 
Utjecaj teškog oštećenja funkcije jetre (Child-Pugh stadij C, rezultat od 10 do 15) na farmakokinetiku tezakaftora i ivakaftora nije ispitan.
The tablets should not be chewed, crushed, or broken before swallowing. 
Tablete se prije gutanja ne smiju žvakati, drobiti niti lomiti.
*Nominal p-value, based on hierarchical testing procedure. 
*Nominalna p-vrijednost, temeljena na postupku hijerarhijskog testiranja.
Another minor circulating metabolite, M3-TEZ, is formed by direct glucuronidation of tezacaftor. 
Drugi manji cirkulirajući metabolit, M3-TEZ, nastaje izravnom glukuronidacijom tezakaftora.
BMI increased in both treatment groups (Symkevi in combination with ivacaftor: 0.18 kg/m2, placebo: 0.12 kg/m2). 
ITM se povećao u obje terapijske skupine (Symkevi u kombinaciji s ivakaftorom: 0,18 kg/m2, placebo: 0,12 kg/m2).
Race had no clinically meaningful effect on the PK of ivacaftor in white (n=379) and non-white (n=29) patients based on a population PK analysis. 
Etnička pripadnost nije imala klinički značajan utjecaj na farmakokinetiku ivakaftora u bolesnika koji su bijelci (n=379) i onih koji nisu bijelci (n=29) na temelju analize populacijske farmakokinetike.
Patients had a percent predicted forced expiratory volume in one second (ppFEV1) at screening between 40 to 90%. 
Bolesnici su na probiru imali postotak predviđenog forsiranog ekspiratornog volumena u jednoj sekundi (ppFEV1) između 40% i 90%.
Symkevi is normally taken with ivacaftor, another medicine. 
Symkevi se obično uzima s ivakaftorom, drugim lijekom.
Symkevi in combination with ivacaftor was associated with a lower event rate per year of severe pulmonary exacerbations requiring hospitalization or IV antibiotic therapy (0.29) compared to placebo (0.54). 
Symkevi u kombinaciji s ivakaftorom bio je povezan s nižom godišnjom stopom događaja teških plućnih egzacerbacija koje su zahtijevale hospitalizaciju ili i.v. terapiju antibioticima (0,29) u usporedbi s placebom (0,54).
Some medicines can affect how Symkevi works or may make side effects more likely. 
Neki lijekovi mogu utjecati na djelovanje lijeka Symkevi ili povećati vjerojatnost nastanka nuspojava.
Avoid food or drinks containing grapefruit or Seville oranges (marmalade oranges) during treatment as these may increase the side effects of Symkevi by increasing the amount of Symkevi in your body. 
Tijekom liječenja izbjegavajte hranu ili pića koja sadrže grejpfrut ili naranče vrste Seville (naranče za marmeladu) jer povećavaju količinu lijeka Symkevi u tijelu što može pojačati njegove nuspojave.
Co-administration with (oral) midazolam, a sensitive CYP3A substrate, did not affect midazolam exposure. 
Istodobna primjena s (peroralnim) midazolamom, osjetljivim supstratom CYP3A, nije utjecala na izloženost midazolamu.
If more than 6 hours have passed since the missed morning or evening dose, the patient should not take the missed dose. 
Ako je od propuštene jutarnje ili večernje doze proteklo više od 6 sati, bolesnik ne smije uzeti propuštenu dozu.
The effect of the CYP3A4*22 heterozygous genotype on tezacaftor and ivacaftor exposure is consistent with the effect of co-administration of a weak CYP3A4 inhibitor, which is not clinically relevant. 
Učinak heterozigotnog genotipa CYP3A4*22 na izloženost tezakaftoru i ivakaftoru sukladan je učinku istodobne primjene slabog inhibitora CYP3A4, što nije klinički relevantno.
The pharmacokinetic parameters of tezacaftor in combination with ivacaftor in the elderly patients (65 to 72 years) are comparable to those in younger adults. 
Farmakokinetički parametri tezakaftora u kombinaciji s ivakaftorom u starijih bolesnika (u dobi od 65 do 72 godine) usporedivi su s onima u mlađih odraslih.
See Table 6 for a summary of primary and key secondary outcomes. 
Vidjeti tablicu 6 za sažetak primarnog i ključnih sekundarnih ishoda.
Co-administration of ciprofloxacin did not affect the exposure of ivacaftor or tezacaftor. 
Istodobna primjena ciprofloksacina nije utjecala na izloženost ivakaftoru ili tezakaftoru.
In the event of significant elevations of transaminases (e.g., patients with ALT or AST >5 x the upper limit of normal (ULN), or ALT or AST >3 x ULN with bilirubin >2 x ULN), dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. 
U slučaju značajnog povišenja transaminaza (npr. bolesnici s vrijednostima ALT ili AST >5 x gornje granice normale (GGN) ili ALT ili AST >3 x GGN i bilirubin >2 x GGN), doziranje treba prekinuti i pažljivo pratiti laboratorijske nalaze sve dok se poremećene vrijednosti ne normaliziraju.
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING BLISTER CARD 
PODACI KOJI SE MORAJU NALAZITI NA UNUTARNJEM PAKIRANJU BLISTER KARTICA
Ivacaftor was associated with slight decreases of the seminal vesicle weights, a decrease of overall fertility index and number of pregnancies in females mated with treated males and significant reductions in number of corpora lutea and implantation sites with subsequent reductions in the average litter size and average number of viable embryos per litter in treated females. 
Ivakaftor je bio povezan s blagim smanjenjem težine sjemenskih mjehurića, smanjenjem ukupnog indeksa plodnosti i broja trudnoća u ženki parenih s liječenim mužjacima i značajnim smanjenjem broja žutih tijela i mjesta implantacije s posljedičnim smanjenjem prosječne veličine okota i prosječnog broja vijabilnih embrija po okotu liječenih ženki.
These include ciclosporin, 
Oni uključuju ciklosporin,
Administration of Symkevi in combination with ivacaftor may increase systemic exposure of medicinal products that are sensitive substrates of P-gp, which may increase or prolong their therapeutic effect and adverse reactions. 
Primjena lijeka Symkevi u kombinaciji s ivakaftorom može povećati sistemsku izloženost lijekovima koji su osjetljivi supstrati P-gp-a, što može pojačati ili produljiti njihov terapijski učinak i nuspojave.
Following oral administration of a single dose of 100 mg 14C-tezacaftor to healthy male subjects, M1-TEZ, M2-TEZ, and M5-TEZ were the three major circulating metabolites of tezacaftor in humans, contributing to 15%, 31%, and 33% of total radioactivity, respectively. 
Nakon peroralne primjene jedne doze od 100 mg 14C-tezakaftora zdravim muškim ispitanicima, M1-TEZ, M2-TEZ i M5-TEZ bila su tri glavna cirkulirajuća metabolita tezakaftora u ljudi, koji su činili 15%, 31% odnosno 33% ukupne radioaktivnosti.
Ivacaftor causes the protein to work better while tezacaftor increases the amount of protein at the cell surface. 
Ivakaftor dovodi do boljeg rada tog proteina, dok tezakaftor povećava količinu tog proteina na površini stanice.
Tezacaftor exposures can also be expected to decrease significantly during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended. 
Također se može očekivati značajno smanjenje izloženosti tezakaftoru tijekom istodobne primjene s jakim induktorima CYP3A; stoga se ne preporučuje istodobna primjena s jakim induktorima CYP3A.
If you stop taking Symkevi 
Ako prestanete uzimati Symkevi
After a single dose in healthy subjects in the fed state, tezacaftor was absorbed with a median (range) time to maximum concentration (tmax) of approximately 4 hours (2 to 6 hours). 
U zdravih ispitanika u sitom stanju, tezakaftor se nakon jedne doze apsorbirao do postizanja maksimalne koncentracije (tmax) u medijanu (raspon) vremena od približno 4 sata (od 2 do 6 sati).
Symkevi in combination with ivacaftor has a minor influence on the ability to drive and use machines. 
Symkevi u kombinaciji s ivakaftorom malo utječe na sposobnost upravljanja vozilima i rada sa strojevima.
If 6 hours or less have passed since the missed morning or evening dose, the patient should take the missed dose as soon as possible and continue on the original schedule. 
Ako je od propuštene jutarnje ili večernje doze proteklo 6 sati ili manje, bolesnik treba što prije uzeti propuštenu dozu i nastaviti s uzimanjem tableta prema uobičajenom rasporedu.
S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T. 
S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G i 3849+10kbC→T.
The safety and efficacy of Symkevi in children aged less than 12 years has not yet been established. 
Sigurnost i djelotvornost lijeka Symkevi u djece mlađe od 12 godina nisu još ustanovljene.
The safety profile of Symkevi in combination with ivacaftor, including respiratory events (e.g., chest discomfort, dyspnea, and respiration abnormal), was generally similar across all subgroups of patients, including analysis by age, gender, and baseline percent predicted FEV1 (ppFEV1). 
Sigurnosni profil lijeka Symkevi u kombinaciji s ivakaftorom, koji uključuje i respiratorne događaje (npr. nelagodu u prsištu, dispneju i abnormalno disanje), bio je uglavnom sličan u svim podskupinama bolesnika, pa i kad se analiza provodila prema dobi, spolu i početnom postotku predviđenog FEV1 (ppFEV1).
In the pre- and post-natal study ivacaftor decreased survival and lactation indices and caused a reduction in pup body weights. 
U prenatalnom i postnatalnom ispitivanju, ivakaftor je smanjio indekse preživljenja i laktacije i prouzročio smanjenje tjelesne težine mladunčadi.
• Anticonvulsant medicines (used for the treatment of epilepsy and epileptic seizures or fits). 
• Antikonvulzivi (primjenjuju se za liječenje epilepsije i epileptičnih napadaja).
Ivacaftor had an effect on fertility in rats (see section 5.3). 
Ivakaftor je utjecao na plodnost štakora (vidjeti dio 5.3).
Therefore, caution should be used when P-gp inhibitors are used with Symkevi. 
Stoga je potreban oprez kad se inhibitori P-gp-a primjenjuju s lijekom Symkevi.
Symkevi works on a protein called CFTR (cystic fibrosis transmembrane conductance regulator), which is damaged in some people with CF (who have a mutation in the CFTR gene). 
Symkevi djeluje na protein pod nazivom CFTR (kratica za transmembranski regulator provodljivosti za ione klora kod cistične fibroze, engl. cystic fibrosis transmembrane conductance regulator), koji je oštećen kod nekih osoba s cističnom fibrozom (osobe koje imaju mutaciju gena CFTR).
Number of subjects with events (n)/N Number of events (estimated event rate per year†) Rate ratio (RR) (95% CI) P value 
Broj ispitanika s događajem (n)/N Broj događaja (procijenjena stopa događaja godišnje†) Omjer stope (95% CI) P vrijednost
It is unknown whether tezacaftor, ivacaftor, or their metabolites are excreted in human milk. 
Nije poznato izlučuju li se tezakaftor, ivakaftor ili njihovi metaboliti u majčino mlijeko.
Symkevi is not to be used in children under the age of 12 years. 
Symkevi se ne primjenjuje u djece mlađe od 12 godina.
• Immunosuppressants (used after an organ transplantation). 
• Imunosupresivi (primjenjuju se nakon presađivanja organa).
Symkevi is usually taken with ivacaftor. 
Symkevi se obično uzima s ivakaftorom.
These include glimepiride and glipizide. 
Oni uključuju glimepirid i glipizid.
No patients treated with Symkevi in combination with ivacaftor experienced a transaminase elevation >3 x ULN associated with elevated total bilirubin >2 x ULN. 
Nijedan bolesnik liječen lijekom Symkevi u kombinaciji s ivakaftorom nije imao povišenje transaminaza >3 x GGN povezano s povišenjem ukupnog bilirubina >2 x GGN.
Symkevi taken with ivacaftor is for long-term treatment of patients aged 12 and over who have CF with certain genetic mutations that result in reduced amount and/or function of the CFTR protein. 
Symkevi uziman s ivakaftorom namijenjen je dugotrajnom liječenju bolesnika u dobi od 12 godina i više koji imaju cističnu fibrozu s određenim genetskim mutacijama koje rezultiraju smanjenom količinom i/ili funkcijom proteina CFTR.
Take the tablets with fat-containing food. 
Uzimajte tablete s hranom koja sadrži masti.
Patients had a ppFEV1 at screening between 40 to 90%. 
Bolesnici su na probiru imali ppFEV1 između 40% i 90%.
Tezacaftor is metabolized extensively in humans. 
Tezakaftor se opsežno metabolizira u ljudi.
The pharmacokinetics of tezacaftor/ivacaftor in children below 12 years of age has not been investigated. 
Farmakokinetika tezakaftora/ivakaftora u djece mlađe od 12 godina nije ispitana.
Subgroup analysis of patients with severe lung dysfunction (ppFEV1 <40) Study 1 and Study 2 included a total of 39 patients treated with Symkevi in combination with ivacaftor with ppFEV1 <40. 
Analiza podskupina bolesnika s teškim poremećajem plućne funkcije (ppFEV1 <40) Ispitivanje 1 i ispitivanje 2 uključila su ukupno 39 bolesnika liječenih lijekom Symkevi u kombinaciji s ivakaftorom s ppFEV1 <40.
Take both Symkevi and ivacaftor tablets with food that contains fat. 
Uzmite i tabletu Symkevi i tabletu ivakaftora s hranom koja sadrži masti.
The AUC of ivacaftor when given in combination with tezacaftor increased approximately 3-fold when given with fat-containing food; therefore, Symkevi and ivacaftor should be administered with fat-containing food. 
AUC ivakaftora davanog u kombinaciji s tezakaftorom povećao se približno trostruko kad se davao s hranom koja sadrži masti; stoga se Symkevi i ivakaftor trebaju primjenjivati s hranom koja sadrži masti.
Tezacaftor facilitates the cellular processing and trafficking of normal or multiple mutant forms of CFTR (including F508del-CFTR) to increase the amount of CFTR protein delivered to the cell surface, resulting in increased chloride transport in vitro. 
Tezakaftor olakšava staničnu obradu i transport normalnih ili brojnih mutiranih oblika CFTR-a (uključujući F508del-CFTR) čime se povećava količina proteina CFTR koji se doprema do površine stanice, što dovodi do povećanog transporta klorida in vitro.
• Antibiotic medicines (used for the treatment of bacterial infections). 
• Antibiotici (primjenjuju se za liječenje bakterijskih infekcija).
These include phenobarbital, carbamazepine and phenytoin. 
Oni uključuju fenobarbital, karbamazepin i fenitoin.
The mean (SD) elimination half-lives for M1-TEZ, M2-TEZ and M5-TEZ were similar to that of the parent compound. 
Srednja vrijednost (SD) poluvijeka eliminacije metabolita M1-TEZ, M2-TEZ i M5-TEZ bila je slična onoj ishodišnog spoja.
The mean ppFEV1 at baseline was 62.3% (range: 34.6% to 93.5%). 
Srednja vrijednost ppFEV1 na početku bila je 62,3% (raspon: od 34,6% do 93,5%).
Tezacaftor and ivacaftor are substrates of CYP3A (ivacaftor is a sensitive substrate of CYP3A). 
Tezakaftor i ivakaftor supstrati su CYP3A (ivakaftor je osjetljiv supstrat CYP3A).
3272-26A→G, and 3849+10kbC→T. 
i 3849+10kbC→T.
The mean ppFEV1 at baseline was 60.0% (range: 27.8% to 96.2%). 
Srednja vrijednost ppFEV1 na početku bila je 60,0% (raspon: od 27,8% do 96,2%).
Both Symkevi and ivacaftor tablets should be taken with fat-containing food, such as food recommended in standard nutritional guidelines (see section 5.2). 
Tablete lijeka Symkevi i ivakaftora treba uzimati s hranom koja sadrži masti, poput one koju preporučuju standardne prehrambene smjernice (vidjeti dio 5.2).
Patients in Studies 1 and 2 continued on their standard-of-care CF therapies during the studies (e.g., bronchodilators, inhaled antibiotics, dornase alfa, and hypertonic saline), and were eligible to roll over into a 96-week open-label extension study (Study 3). 
Bolesnici u ispitivanjima 1 i 2 nastavili su tijekom ispitivanja primati svoju standardnu terapiju za cističnu fibrozu (npr. bronhodilatatore, inhalacijske antibiotike, dornazu alfa i hipertoničnu fiziološku otopinu) te su bili pogodni za prijelaz u otvoreni nastavak ispitivanja u trajanju od 96 tjedana (ispitivanje 3).
Similar trends were observed for CFQ-R respiratory domain score, pulmonary exacerbation rate and BMI. 
Sličan trend opažen je u rezultatu respiratorne domene upitnika CFQ-R, za stopu plućnih egzacerbacija i ITM.
Blister consisting of PCTFE (polychlorotrifluoroethylene)/PVC (polyvinyl chloride) with a paper-backed aluminum foil lidding. 
Blister izrađen od poliklorotrifluoroetilena (PCTFE) / poli(vinil-klorida) (PVC) zatvoren papirom pojačanom aluminijskom folijom.
See Table 5 for a summary of primary and key secondary outcomes. 
Vidjeti tablicu 5 za sažetak primarnog i ključnih sekundarnih ishoda.
Side effects in children and adolescents are similar to those observed in adults. 
Dodatne nuspojave u djece i adolescenata Nuspojave u djece i adolescenata slične su onima opaženima u odraslih.
Following oral administration of ivacaftor alone, the majority of ivacaftor (87.8%) is eliminated in the faeces after metabolic conversion. 
Nakon peroralne primjene samo ivakaftora, veći dio ivakaftora (87,8%) bio je eliminiran stolicom nakon metaboličke konverzije.
• telithromycin and clarithromycin 
• telitromicin i klaritromicin.
Number of pulmonary exacerbations from baseline through Week 24 
Broj plućnih egzacerbacija od početka ispitivanja do kraja 24. tjedna
Symkevi should only be prescribed by physicians with experience in the treatment of CF. 
Symkevi smiju propisivati samo liječnici s iskustvom u liječenju cistične fibroze.
Ivacaftor is approximately 99% bound to plasma proteins, primarily to alpha 1-acid glycoprotein and albumin. 
Približno je 99% ivakaftora vezano za proteine plazme, prvenstveno za alfa 1-kiseli glikoprotein i albumin.
This finding has not been observed in fetuses derived from rat dams treated with ivacaftor on gestation Days 7 to 17, in rat pups exposed to ivacaftor through milk ingestion up to postnatal Day 20, in 7-week-old rats, nor in 3.5- to 5-month-old dogs treated with ivacaftor. 
Ovaj nalaz nije bio opažen u fetusa dobivenih od ženki štakora liječenih ivakaftorom od 7. do 17. dana gestacije, u mladunčadi štakora izložene ivakaftoru putem progutanog mlijeka do 20. postnatalnog dana, u štakora u dobi od 7 tjedana ili u pasa u dobi od 3,5 do 5 mjeseci liječenih ivakaftorom.
The combination targets the abnormal CFTR protein by increasing the quantity and function of CFTR at the cell surface and subsequently increasing airway surface liquid height, and ciliary beat frequency in vitro in human bronchial epithelial (HBE) cells from homozygous F508del CF patients. 
Ova kombinacija cilja abnormalni protein CFTR i povećava njegovu količinu i funkciju na površini stanice i posljedično povećava debljinu površinskog tekućeg sloja u dišnim putevima (engl. airway surface liquid height) i frekvenciju treperenja cilija (engl. ciliary beat frequency) in vitro kod epitelnih stanica bronha dobivenih od bolesnika s cističnom fibrozom koji su homozigoti za F508del.
Table 6: Primary and key secondary efficacy analyses, full analysis set (Study 2) Analysis 
Tablica 6: Analize mjera primarne i ključnih sekundarnih djelotvornosti, potpuni skup podataka za analizu (ispitivanje 2)
No data are available for CYP3A4*22 homozygous genotype patients. 
Nema dostupnih podataka o bolesnicima s homozigotnim genotipom CYP3A4*22.
When co-administered with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin), the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart. 
Kad se istodobno primjenjuje s jakim inhibitorima CYP3A (npr. ketokonazolom, itrakonazolom, pozakonazolom, vorikonazolom, telitromicinom i klaritromicinom), dozu je potrebno prilagoditi na jednu tabletu lijeka Symkevi dvaput tjedno, koja se uzima u razmaku od približno 3 do 4 dana.
If you forget to take Symkevi 
Ako ste zaboravili uzeti Symkevi
The AUC of tezacaftor did not change when given with fat-containing food relative to fasted conditions. 
AUC tezakaftora nije se promijenio kad se tezakaftor davao s hranom koja sadrži masti u odnosu na onaj kad se davao natašte.
Patients had a confirmed genotype of a protocol-specified CFTR mutation, and a confirmed diagnosis of CF. 
Bolesnici su imali potvrđeni genotip mutacije CFTR definirane u planu ispitivanja i potvrđenu dijagnozu cistične fibroze.
The recommended dose: 
Preporučena doza
These include warfarin. 
Oni uključuju varfarin.
AUCτ,ss (mcg∙h/mL) 
Srednja vrijednost (SD) AUCτ,ss (µg∙h/ml) tezakaftora
Placebo N=161 
N=161
Symkevi in combination with ivacaftor has not been studied in patients with moderate or severe renal impairment (creatinine clearance ≤30 mL/min) or in patients with end-stage renal disease. 
Symkevi u kombinaciji s ivakaftorom nije ispitan u bolesnika s umjerenim ili teškim oštećenjem funkcije bubrega (klirens kreatinina ≤30 ml/min) ili u bolesnika sa završnim stadijem bubrežne bolesti.
Under steady-state, for each of the metabolites, exposure to M1-TEZ, M2-TEZ and M5-TEZ is approximately 1.5-fold higher than for tezacaftor. 
U stanju dinamičke ravnoteže, izloženost svakom od metabolita M1-TEZ, M2-TEZ i M5-TEZ približno je 1,5 puta veća nego tezakaftoru.
Table 5: Primary and key secondary efficacy analyses, full analysis set (Study 1) Analysis 
Tablica 5: Analize primarne i ključnih sekundarnih mjera ishoda za djelotvornost, potpuni skup podataka za analizu (ispitivanje 1)
Co-administration of ivacaftor with rifampicin, a strong CYP3A inducer, significantly decreased ivacaftor exposure [area under the curve (AUC)] by 89%. 
Istodobna primjena ivakaftora s rifampicinom, jakim induktorom CYP3A, značajno je smanjila izloženost ivakaftoru [površinu ispod krivulje (AUC)] za 89%.
Gender The pharmacokinetic parameters of tezacaftor and ivacaftor are similar in males and females. 
Farmakokinetički parametri tezakaftora i ivakaftora slični su u muškaraca i žena.
Co-administration with digoxin, a sensitive P-gp substrate, increased digoxin exposure by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor. 
Istodobna primjena s digoksinom, osjetljivim supstratom P-gp-a, povećala je izloženost digoksinu 1,3 puta, što je sukladno slaboj inhibiciji P-gp-a ivakaftorom.
Symkevi in combination with ivacaftor should not be prescribed in patients with CF who are heterozygous for the F508del mutation and have a second CFTR mutation not listed in section 4.1. 
Symkevi se u kombinaciji s ivakaftorom ne smije propisivati u bolesnika s cističnom fibrozom koji su heterozigoti za mutaciju F508del i imaju drugu mutaciju gena CFTR koja nije navedena u dijelu 4.1.