natgillin/translations-raw huggingface dataset:
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).
Zdravilo Symkevi deluje na beljakovino, ki se imenuje regulator transmembranske prevodnosti pri cistični fibrozi (cystic fibrosis transmembrane conductance regulator - CFTR), ki je pri nekaterih ljudeh s CF okvarjen (ti imajo mutacijo v genu CFTR).
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.
Tega niso opazili pri plodovih iz podganjih samic, ki so od 7. do 17. dne brejosti prejemale ivakaftor, pri podganjih mladičih, ki so bili izpostavljeni ivakaftorju s tem, da so se do 20. poporodnega dne hranili z mlekom, pri 7 dni starih podganah, niti pri 3,5 do 5 mesecev starih psih, ki so prejemali ivakaftor.
There was negligible urinary excretion of ivacaftor as unchanged drug.
Izločanje ivakaftorja z urinom v obliki nespremenjenega zdravila je bilo zanemarljivo.
In a human pharmacokinetic study with ivacaftor alone, there was minimal elimination of ivacaftor and its metabolites in urine (only 6.6% of total radioactivity was recovered in the urine).
V študiji farmakokinetike ivakaftorja samega pri ljudeh so se ivakaftor in njegovi presnovki minimalno izločali v urinu (v urinu so prestregli samo 6,6 % celotne radioaktivnosti).
Adults and adolescents aged 12 years and older
Mladostniki, stari 12 let ali več
Ivacaftor causes the protein to work better while tezacaftor increases the amount of protein at the cell surface.
Ivakaftor povzroči, da beljakovina bolje deluje, tezakaftor pa zveča količino beljakovine na celični površini.
M6-IVA is not considered pharmacologically active.
Za M6-IVA velja, da ni farmakološko aktiven.
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.
Po peroralnem dajanju enkratnega odmerka 100 mg 14C-tezakaftorja zdravim moškim preiskovancem so bili trije glavni presnovki tezakaftorja, ki so pri ljudeh krožili v krvi, M1-TEZ, M2-TEZ in M5-TEZ, ki so prispevali 15 %, 31 % oziroma 33 % celotne radioaktivnosti.
Symkevi taken with ivacaftor helps your breathing by improving your lung function.
Zdravilo Symkevi skupaj z ivakaftorjem vam pomaga dihati, tako da izboljša delovanje vaših pljuč.
Do not make changes unless your doctor tells you.
Ne spreminjajte odmerka ali časa jemanja, če vam tega ne naroči zdravnik.
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tezacaftor or ivacaftor in pregnant women.
Podatkov o uporabi tezakaftorja ali ivakaftorja pri nosečnicah ni oziroma so omejeni (manj kot 300 izpostavljenih nosečnosti).
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.
Zdravila Symkevi v kombinaciji z ivakaftorjem pri bolnikih z zmerno ali težko okvaro ledvic (očistek kreatinina ≤ 30 ml/min) ali pri bolnikih z boleznijo ledvic v končnem stadiju niso raziskali.
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).
Zdravilo Symkevi v kombinaciji z ivakaftorjem je bilo povezano z manjšo pogostnostjo dogodkov težkih pljučnih eksacerbacij, pri katerih je bil potreben sprejem v bolnišnico ali intravensko antibiotično zdravljenje (0,29), na leto v primerjavi s placebom (0,54).
Medicinal products affecting the pharmacokinetics of tezacaftor and ivacaftor CYP3A inducers
Zdravila, ki vplivajo na farmakokinetiko tezakaftorja in ivakaftorja Induktorji CYP3A
What Symkevi looks like and contents of the pack
Izgled zdravila Symkevi in vsebina pakiranja
Table 5: Primary and key secondary efficacy analyses, full analysis set (Study 1) Analysis
Preglednica 5: Analize primarne in ključnih sekundarnih učinkovitosti, celotna skupina bolnikov za analizo (študija 1)
Concomitant use of CYP3A inducers may result in reduced exposures and thus reduced efficacy of Symkevi and ivacaftor.
Sočasna uporaba induktorjev CYP3A lahko povzroči zmanjšanje izpostavljenosti in s tem zmanjšanje učinkovitosti zdravila Symkevi in ivakaftorja.
Table 6: Primary and key secondary efficacy analyses, full analysis set (Study 2) Analysis
Preglednica 6: Analize primarne in ključnih sekundarnih učinkovitosti, celotna skupina bolnikov za analizo (študija 2)
Gender The pharmacokinetic parameters of tezacaftor and ivacaftor are similar in males and females.
Farmakokinetični parametri tezakaftorja in ivakaftorja so pri moških in ženskah podobni.
Pulmonary exacerbations
Pljučne eksacerbacije
Following multiple doses of tezacaftor and ivacaftor for 10 days, subjects with moderately impaired hepatic function (Child-Pugh Class B, score 7 to 9) had an approximately 36% increase in AUC and a 10% increase in Cmax for tezacaftor, and a 50% increase in ivacaftor AUC compared with healthy subjects matched for demographics.
Po 10-dnevnem dajanju večkratnih odmerkov tezakaftorja in ivakaftorja se je pri osebah z zmerno okvarjeno funkcijo jeter (razred B po Child-Pughovi lestvici, rezultat 7 do 9) AUC tezakaftorja zvečala približno za 36 % in Cmax tezakaftorja za 10 %, AUC ivakaftorja pa se je v primerjavi z zdravimi preiskovanci s primerljivimi demografskimi podatki zvečala za 50 %.
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).
V študiji farmakokinetike tezakaftorja samega pri ljudeh so se tezakaftor in njegovi presnovki minimalno izločali v urinu (v urinu so prestregli samo 13,7 % celotne radioaktivnosti, od tega je bilo 0,79 % nespremenjenega zdravila).
Mean improvement in ppFEV1 was observed at the first assessment on Day 15 and sustained throughout the 8-week treatment period.
Povprečno izboljšanje ppFEV1 so ugotovili pri prvem ocenjevanju 15. dne in je trajalo ves čas 8-tedenskega obdobja zdravljenja.
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.
Po peroralnem dajanju 14C-tezakaftorja se je večina odmerka (72 %) izločila v blatu (nespremenjen ali kot presnovek M2-TEZ), okrog 14 % odmerka pa so prestregli v urinu (večinoma kot presnovek M2-TEZ).
The AUC of tezacaftor did not change when given with fat-containing food relative to fasted conditions.
AUC tezakaftorja se ni spremenil glede na stanje na tešče, če so ga dali z obrokom mastne hrane.
No dose-adjustment of tezacaftor and ivacaftor is considered necessary.
Prilagajanje odmerka tezakaftorja in ivakaftorja se ne šteje kot potrebno.
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 lajša celično procesiranje in transport normalnih ali številnih mutantnih oblik CFTR (tudi F508del-CFTR), s čimer se zveča količina beljakovine CFTR, ki prispe na površino celice, s tem pa se zveča transport kloridov in vitro.
The median (range) tmax of ivacaftor was approximately 6 hours (3 to 10 hours) in the fed state.
Mediani (razpon) tmax ivakaftorja po obroku hrane je bil približno 6 ur (3 do 10 ur).
Table 7: Mean (SD) pharmacokinetic parameters of tezacaftor and ivacaftor at steady state in patients with CF
Preglednica 7: Povprečni (SD) farmakokinetični parametri tezakaftorja in ivakaftorja v stanju dinamičnega ravnovesja pri bolnikih s CF
Safety data from an interim safety analysis performed on 867 patients in a long-term safety and efficacy rollover study (Study 3), including 326 patients with ≥48 weeks of cumulative treatment with Symkevi given in combination with ivacaftor, were consistent with the safety data from the placebo-controlled Phase 3 studies.
Preiskave bakterije v izmečku zelo pogosti Podatki o varnosti iz vmesne analize varnosti, opravljene na 867 bolnikih v dolgoročni obnovitveni študiji varnosti in učinkovitosti (študija 3), v katero je bilo vključenih 326 bolnikov z ≥ 48 tednov kumulativnega zdravljenja z zdravilom Symkevi, ki so ga dajali skupaj z ivakaftorjem, so se skladali s podatki o varnosti iz študij 3. faze, kontroliranih s placebom.
If you stop taking Symkevi
Če ste prenehali jemati zdravilo Symkevi
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.
Izboljšanje ppFEV1 so ugotovili ne glede na starost, spol, izhodiščni ppFEV1, kolonizacijo z bakterijo Pseudomonas, sočasno uporabo standardnih zdravil za CF in zemljepisno območje.
** Linear Mixed Effects model with treatment, period, and study baseline ppFEV1 as fixed effects and subject as a random effect.
**Linearni model mešanih učinkov za ponovljene ukrepe, pri čemer so zdravljenje, čas in izhodiščni ppFEV1 študije nespremenljivi učinki in preiskovanec naključen učinek.
Physiologically based pharmacokinetic modeling suggested co-administration with fluconazole, a moderate CYP3A inhibitor, may increase tezacaftor exposure (AUC) by approximately 2-fold.
Farmakokinetično modeliranje na podlagi fiziologije je pokazalo, da sočasna uporaba s flukonazolom, ki je zmeren zaviralec CYP3A, lahko zveča izpostavljenost tezakaftorju (AUC) za približno 2-krat.
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.
Zdravila Symkevi v kombinaciji z ivakaftorjem ni dovoljeno predpisovati bolnikom s CF, ki so heterozigotni za mutacijo F508del in imajo drugo mutacijo CFTR, ki ni navedena v poglavju 4.1.
• Anticoagulant medicines (used to prevent blood clots).
• antikoagulanti (uporabljajo se za preprečevanje krvnih strdkov).
Clinical trials of Symkevi in combination with ivacaftor did not include patients over 75 years of age.
V klinična preskušanja zdravila Symkevi v kombinaciji z ivakaftorjem bolniki, starejši od 75 let, niso bili vključeni.
• In the evening, take one ivacaftor 150 mg tablet.
• Zvečer vzemite eno tableto ivakaftorja 150 mg.
S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.
S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G in 3849+10kbC→T.
Vertex Pharmaceuticals (Ireland) Limited 28-32 Pembroke Street Upper Dublin 2, D02 EK84
28-32 Pembroke Street Upper Dublin 2, D02 EK84 Irska
Following oral administration of ivacaftor alone, the majority of ivacaftor (87.8%) is eliminated in the faeces after metabolic conversion.
Po peroralnem dajanju ivakaftorja samega se večina ivakaftorja (87,8 %) izloči v blatu.
If you forget to take Symkevi
Če ste pozabili vzeti zdravilo Symkevi
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.
Sočasna uporaba z itrakonazolom, ki je močan zaviralec CYP3A, je zvečala izpostavljenost tezakaftorju (merjeno kot AUC) za štirikrat in zvečala AUC ivakaftorja za 15,6-krat.
• Changes in the type of bacteria in mucus
• izpuščaj, • spremembe vrst bakterij v sluzi.
The mean ppFEV1 at baseline was 62.3% (range: 34.6% to 93.5%).
Povprečni ppFEV1 v izhodišču je bil 62,3 % (razpon: 34,6 % do
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.
Izboljšanje ppFEV1 so ugotavljali ne glede na starost, izraženost bolezni, spol, razred mutacije, kolonizacijo z bakterijo Pseudomonas, sočasno uporabo standardnih zdravil za CF in zemljepisno območje.
Number of pulmonary exacerbations from baseline through Week 24
Število pljučnih eksacerbacij od izhodišča do vključno 24. tedna število oseb z dogodki
Tell your doctor right away if you have any symptoms of liver problems.
Nemudoma povejte zdravniku, če imate kakšne simptome težav z jetri, ki so navedeni v poglavju 4.
Take both Symkevi and ivacaftor tablets with food that contains fat.
Tako tablete zdravila Symkevi kot tablete ivakaftorja jemljite skupaj z obrokom, ki vsebuje maščobe.
M1-IVA has approximately one-sixth the potency of ivacaftor and is considered pharmacologically active.
M1-IVA ima približno šestino jakosti ivakaftorja in velja za farmakološko aktivnega.
Pulmonary exacerbations requiring hospitalizations were similar between treatment groups (RR: 0.78 [95% CI: 0.44, 1.36]; P=0.3801).
Pogostnost pljučnih eksacerbacij, pri katerih je bil potreben sprejem v bolnišnico, je bila pri obeh zdravljenih skupinah podobna (RR: 0,78 [95 % IZ: 0,44; 1,36]; P = 0,3801).
Mean (SD) tezacaftor and ivacaftor exposure by age group Age group
Povprečna (SD) izpostavljenost tezakaftorju in ivakaftorju po starostnih skupinah Starostna skupina
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).
Raven brez ugotovljenih neželenih učinkov (No Observed Adverse Effect Level - NOAEL) za rezultate plodnosti je dala raven izpostavljenosti, ki je bila petkratnik sistemske izpostavljenosti ivakaftorju in njegovim presnovkom, kadar so ga dajali kot tezakaftor/ivakaftor odraslim ljudem v največjem priporočenem odmerku za ljudi (maximum recommended human doseMRHD).
Increased liver enzymes in the blood have been seen in patients with CF receiving Symkevi.
Zvišane jetrne encime v krvi so ugotavljali pri bolnikih s CF, ki so prejemali zdravilo Symkevi.
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.
Ne pričakujemo, da bodo sočasni zaviralci OATP1B1, P-gp ali BCRP pomembno vplivali na izpostavljenost tezakaftorju zaradi svoje velike intrinzične permeabilnosti in majhne verjetnosti izločanja v nespremenjeni obliki.
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.
nominalna P < 0,0001± ppFEV1: odstotek napovedanega forsiranega ekspiracijskega volumna v 1 sekundi; SD: standardna deviacija; IZ: interval zaupanja; ITM: indeks telesne mase; CFQ-R: vprašalnik o cistični fibrozi-revidiran.
Do not chew, crush or break the tablets before swallowing.
Pred požiranjem tablet ne žvečite, zdrobite ali prelomite.
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.
NOAEL za sposobnost preživetja in rast pri potomstvu je dala raven izpostavljenosti, ki je bila približno štirikratnik sistemske izpostavljenosti ivakaftorju in njegovim presnovkom, kadar so ga dajali kot tezakaftor/ivakaftor odraslim ljudem v MRHD.
CYP3A, digoxin and other P-gp Substrates
CYP3A, digoksin in drugi substrati P-gp Substrati CYP3A
These include warfarin.
Vključujejo varfarin;
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.
Ivakaftor lahko zavira CYP2C9; zato je med sočasnim dajanjem varfarina z zdravilom Symkevi, dajanega v kombinaciji z ivakaftorjem, priporočljivo spremljanje mednarodnega normaliziranega razmerja (international normalized ratio - INR).
In Study 2 treatment with Symkevi in combination with ivacaftor resulted in a statistically significant improvement in ppFEV1 (Table 6).
V študiji 2 je zdravljenje z zdravilom Symkevi v kombinaciji z ivakaftorjem povzročilo statistično značilno izboljšanje ppFEV1 (preglednica 6).
Elevated transaminases are common in patients with CF, and have been observed in some patients treated with Symkevi in combination with ivacaftor, as well as with ivacaftor monotherapy.
Zvišane transaminaze so pri bolnikih s CF pogoste in so jih ugotovili pri nekaterih bolnikih, zdravljenih z zdravilom Symkevi v kombinaciji z ivakaftorjem, pa tudi pri monoterapiji z ivakaftorjem.
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).
Kadar ju uporabljate skupaj z zmernimi zaviralci CYP3A (npr. flukonazolom ali eritromicinom), je treba odmerek prilagoditi v skladu s preglednico 1 (glejte poglavji 4.4 in 4.5).
A total of 244 patients aged 12 years and older (mean age 34.8 years) who were heterozygous for the F508del mutation and a second mutation associated with residual CFTR activity were randomized to and received sequences of treatment that included Symkevi in combination with ivacaftor, ivacaftor, and placebo.
Celotna skupina 244 bolnikov, starih 12 let ali več (povprečna starost 34,8 leta), ki so bili heterozigotni za mutacijo F508del in drugo mutacijo, povezano z rezidualno aktivnostjo CFTR, je bila randomizirana in je prejela zaporedja zdravljenja, ki so vključevala zdravilo Symkevi v kombinaciji z ivakaftorjem, ivakaftor in placebo.
itraconazole, posaconazole, voriconazole and fluconazole.
itrakonazol, posakonazol, vorikonazol in flukonazol;
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.
Preglednica 3 prikazuje neželene učinke, ki so jih ugotovili pri zdravilu Symkevi v kombinaciji z ivakaftorjem pri bolnikih, starih 12 let ali več, na podlagi združenih podatkov iz treh dvojno slepih kliničnih študij 3. faze, kontroliranih s placebom.
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.
Med študijami 3. faze, kontroliranimi s placebom (do 24 tednov), je bila pogostnost najvišjih transaminaz (ALT ali AST) > 8, > 5 ali > 3 x ULN podobna pri bolnikih, zdravljenih z zdravilom Symkevi v kombinaciji z ivakaftorjem, in pri bolnikih, ki so prejemali placebo; 0,2 %, 1,0 % in 3,4 % pri bolnikih, zdravljenih z zdravilom Symkevi v kombinaciji z ivakaftorjem, in 0,4 %, 1,0 % in 3,4 % pri bolnikih, ki so prejemali placebo.
In Study 3, the change in BMI z-value in the Symkevi in combination with ivacaftor group was maintained.
V študiji 3 se je sprememba z vrednosti ITM v skupini z zdravilom Symkevi v kombinaciji z ivakaftorjem vzdrževala.
Ivacaftor is a CFTR potentiator that potentiates the channel-open probability (or gating) of CFTR at the cell surface to increase chloride transport.
Ivakaftor je ojačevalec (potenciator) CFTR, ki zvečuje verjetnost odprtih kanalčkov (ali spreminjanja prehodnosti celične membrane) CFTR na površini celice, s čimer se zveča transport kloridov.
• The active substances are tezacaftor and ivacaftor.
• Učinkovini sta tezakaftor in ivakaftor.
Table 2: Dosing recommendations for patients with hepatic impairment Mild (Child-Pugh Class A)
Preglednica 2: Priporočila za odmerjanje bolnikom z okvarami jeter Blage (razred A po Child-Pughovi lestvici)
A total of 504 patients aged 12 years and older (mean age 26.3 years) who were homozygous for the F508del mutation in the CFTR gene were randomized (1:1 randomization: 248 Symkevi in combination with ivacaftor, 256 placebo).
Celotno skupino 504 bolnikov, starih 12 let ali več (povprečna starost 26,3 leta), ki so bili homozigotni za mutacijo F508del v genu CFTR, so randomizirali (randomizacija 1:1: 248 zdravilo Symkevi v kombinaciji z ivakaftorjem, 256 placebo).
The rate ratio versus placebo was 0.53 (95% CI: 0.34, 0.82; nominal P= 0.0042).
Razmerje pogostnosti proti placebu je bilo 0,53 (95 % IZ: 0,34; 0,82; nominalna vrednost P = 0,0042).
M1-TEZ has similar potency to that of tezacaftor and is considered pharmacologically active.
M1-TEZ ima podobno jakost kot tezakaftor in zanj velja, da je farmakološko aktiven.
Tezacaftor is metabolized extensively in humans.
Tezakaftor se pri ljudeh obsežno presnavlja.
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.
FK ivakaftorja pri belih (n = 379) in ne-belih (n = 29) bolnikih.
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.
Bolniki, ki so predhodno prejemali placebo in prejeli zdravilo Symkevi v kombinaciji z ivakaftorjem v študiji 3, so pokazali zvečanje za 5,3 (0,7) odstotne točke.
The mean ppFEV1 at baseline was 60.0% (range: 27.8% to 96.2%).
Povprečni ppFEV1 v izhodišču je bil 60,0 % (razpon: 27,8 %
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.
Ivakaftor lahko ojača beljakovino CFTR, ki jo tezakaftor dostavi na površino celice, s čimer povzroči večje zvečanje transporta kloridov kot ena ali druga učinkovina sama.
Take the tablets with fat-containing food.
Tablete vzemite z mastno hrano.
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
Bolnike z anamnezo kolonizacije z mikroorganizmi, povezanimi s hitrejšim slabšanjem stanja pljuč, na primer Burkholderia cenocepacia, Burkholderia dolosa ali Mycobacterium abscessus, in tiste, ki so imeli ob presejanju dva ali več nenormalnih testov funkcije jeter (ALT, AST, AP, GGT ≥ 3 x ULN ali celotni bilirubin ≥ 2 x ULN) ali AST ali ALT ≥ 5 x ULN, so izključili iz obeh študij.
Dosing intervals should be modified according to clinical response and tolerability.
100 mg/ivakaftorja 150 mg enkrat na dan. Presledke med odmerki je treba spremeniti v skladu s kliničnim odzivom in prenašanjem.
The dose of Symkevi and ivacaftor should be adjusted when co-administered with moderate and strong CYP3A inhibitors.
Odmerek zdravila Symkevi in ivakaftorja je treba prilagoditi, kadar ju uporabljate skupaj z zmernimi in močnimi zaviralci CYP3A.
− Tablet core: Hypromellose acetate succinate, sodium laurilsulfate (E487), hypromellose (E464), microcrystalline cellulose (E460(i)), croscarmellose sodium (E468), and magnesium stearate (E470b).
− jedro tablete: hipromeloza acetat sukcinat, natrijev lavrilsulfat (E487), hipromeloza (E464), mikrokristalna celuloza (E460(i)), natrijev karmelozat, premreženi (E468) in magnezijev stearat (E470b);
• Cardiac glycosides (used for the treatment of some heart conditions).
• srčni glikozidi (uporabljajo se za zdravljenje nekaterih bolezni srca).
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).
Razlika zaradi zdravljenja, ki je bila 0,06 kg/m2 za povprečno spremembo ITM od izhodišča do 24. tedna (95 % IZ: -0,08; 0,19), ni bila statistično značilna (P = 0,4127).