natgillin/translations-raw huggingface dataset:
Since the exposure of ivacaftor is very significantly reduced when dosed in combination with lumacaftor, lumacaftor/ivacaftor should not be used in these patients.
Ker se izpostavljenost ivakaftorju zelo pomembno zmanjša, kadar ga dajemo v kombinaciji z lumakaftorjem, pri teh bolnikih lumakaftorja/ivakaftorja ne smemo uporabljati.
The recommended dose for patients aged 2 years and over is indicated in the table below.
Priporočila za odmerjanje za bolnike, stare 2 leti ali več, so navedena v preglednici spodaj.
Orkambi granules are packaged in a foil laminate [biaxially-oriented polyethylene terephthalate/polyethylene/foil/polyethylene (BOPET/PE/Foil/PE)] sachet.
Zrnca Orkambi so pakirana v vrečici iz laminirane folije [biaksialno orientiran polietilen tereftalat/ polietilen/folija/polietilen (BOPET/PE/folija/PE)].
14 sachets
14 vrečic
Orkambi has to be taken in the morning and in the evening (12 hours apart) with food containing fat.
Zdravilo Orkambi je treba jemati zjutraj in zvečer (s presledkom 12 ur) z mastno hrano.
• Once mixed, give the product to your child immediately.
• Ko je mešanica pripravljena, naj jo otrok takoj zaužije.
Your child may experience side effects, including those mentioned in section 4 below.
Vaš otrok bo mogoče dobil neželene učinke, vključno s tistimi, ki so omenjeni v poglavju 4 v nadaljevanju.
• Changes in the type of bacteria in mucus*
• spremembe vrste bakterij v sluzi*.
Additional adverse reactions from Trial 6 are included in Table 4.
Dodatni neželeni učinki iz preskušanja 6 so vključeni v preglednico 4.
2 tablets in the morning 2 tablets in the evening
2 tableti zjutraj 2 tableti zvečer
Effects in repeated dose studies were observed only at exposures considered sufficiently in excess (> 25-, > 45-, and > 35-fold for mice, rats, and dogs, respectively) of the maximum human exposure of ivacaftor when administered as Orkambi, indicating little relevance to clinical use.
Učinke v študijah ponavljajočih se odmerkov so ugotovili samo pri izpostavljenostih, za katere menimo, da dovolj presegajo (> 25-, > 45- in > 35-krat za miši, podgane oziroma pse) največjo izpostavljenost ivakaftorju pri človeku, kadar ga uporabljamo v obliki zdravila Orkambi, kar kaže na majhen pomen za klinično uporabo.
Orkambi tablets should not be used in children under the age of 6 years.
Tablet zdravila Orkambi ne smete uporabljati pri otrocih, mlajših od 6 let.
For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered.
Pri bolnikih z anamnezo zvišanja ALT, AST ali bilirubina pride v poštev pogostejše spremljanje.
Serious side effects for Orkambi include raised levels of liver enzymes in the blood, liver injury and worsening of pre-existing severe liver disease.
Resni neželeni učinki zdravila Orkambi vključujejo zvišano raven jetrnih encimov v krvi, poškodbo jeter in poslabšanje prejšnje hude bolezni jeter.
• Inner ear disorder (feeling dizzy or spinning)*
• bolezen notranjega ušesa (občutek omotice ali vrtoglavice)*,
Cells contain two copies of the CFTR gene; Orkambi is used in patients in whom both copies are affected by the F508del mutation.
Celice vsebujejo po dve kopiji gena CFTR; zdravilo Orkambi se uporablja pri bolnikih, pri katerih sta z mutacijo F508del prizadeti obe kopiji.
In vitro studies suggest that lumacaftor has the potential to induce CYP2B6, CYP2C8, CYP2C9, and CYP2C19; however, inhibition of CYP2C8 and CYP2C9 has also been observed in vitro.
Študije in vitro kažejo, da ima lumakaftor potencial za indukcijo CYP2B6, CYP2C8, CYP2C9 in CYP2C19; vendar so in vitro opazili tudi inhibicijo CYP2C8 in CYP2C9.
Lumacaftor/ivacaftor should be used with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks.
Lumakaftor/ivakaftor moramo pri bolnikih z napredovalo boleznijo jeter previdno uporabljati in to samo, kadar pričakujemo, da bodo koristi odtehtale tveganja.
The recommended dose for patients aged 6 years and over is two tablets in the morning, and two tablets in the evening (12 hours apart).
Priporočeni odmerek za bolnike, stare 6 let ali več, je dve tableti zjutraj in dve tableti zvečer (s presledkom 12 ur).
Extension Week 72
72. teden podaljšanja
It is not known if Orkambi is safe and effective in children under 2 years of age.
Ni znano, ali je zdravilo Orkambi varno in učinkovito pri otrocih, mlajših od 2 let.
M6 has less than one-fiftieth the potency of ivacaftor and is not considered pharmacologically active.
M6 ima manj kot eno petdesetinko učinkovitosti ivakaftorja in ne velja za farmakološko aktivnega.
The small amount of F508del-CFTR that reaches the cell surface has low channel-open probability (defective channel gating).
Majhna količina F508del-CFTR, ki doseže površino celice, ima majhno verjetnost odprtih kanalčkov (okvarjeno spreminjanje prehodnosti kanalčkov celične membrane).
Co-administration of Orkambi with medicinal products that are substrates for OAT1/3 and BCRP transport may increase plasma concentrations of such medicinal products.
Sočasno dajanje zdravila Orkambi z zdravili, ki so substrati za OAT1/3 in prenos BCRP, lahko zvišajo koncentracije takih zdravil v plazmi.
M1 has approximately one-sixth the potency of ivacaftor and is considered pharmacologically active.
M1 ima približno eno šestino učinkovitosti ivakaftorja in velja za farmakološko aktivnega.
(see section 5.3).
(glejte poglavje 4.5).
Check your child has been given the right dose (below).
Preverite, ali so vašemu otroku dali pravi odmerek (v nadaljevanju).
Following oral administration of lumacaftor, the majority of lumacaftor (51%) is excreted unchanged in the faeces.
Po peroralnem dajanju lumakaftorja se lumakaftor večinoma (51 %) izloči nespremenjen v blatu.
Adverse events that occurred at an increased incidence of ≥ 5% in the supratherapeutic dose period compared with the therapeutic dose period were headache, generalised rash, and increased transaminase.
Neželeni dogodki, ki so se pojavljali z zvečano incidenco ≥ 5 % v obdobju po supraterapevtskem odmerku v primerjavi z obdobjem po terapevtskem odmerku, so bili glavobol, generaliziran izpuščaj in zvišane transaminaze.
Lumacaftor and ivacaftor are not inhibitors of OATP1B1, OATP1B3, and organic cation transporter (OCT) 1 and 2.
Lumakaftor in ivakaftor nista zaviralca OATP1B1, OATP1B3 in prenašalcev organskih kationov (OCT) 1 in 2.
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (frequency cannot be estimated using the available data).
Neželeni učinki so razvrščeni po klasifikaciji pogostnosti po MedDRA: zelo pogosti (≥ 1/10); pogosti (≥ 1/100 do < 1/10); občasni (≥ 1/1.000 do < 1/100); redki (≥ 1/10.000 do < 1/1.000); zelo redki (< 1/10.000); in neznani (pogostnosti ni mogoče oceniti iz razpoložljivih podatkov).
If you plan to breast-feed, ask your doctor for advice before taking Orkambi.
Če nameravate dojiti, prosite svojega zdravnika za nasvet, preden začnete jemati zdravilo Orkambi.
Blister consisting of PolyChloroTriFluoroEthylene (PCTFE)/PolyVinyl Chloride (PVC) with a paper-backed aluminium foil lidding.
Pretisni omot, sestavljen iz poliklorotrifluoroetilena (PCTFE)/polivinilklorida (PVC) z aluminijasto prekrivno folijo, podloženo s papirjem.
The effect of gender on lumacaftor pharmacokinetics was evaluated using a population pharmacokinetics analysis of data from clinical studies of lumacaftor given in combination with ivacaftor.
Vpliv spola na farmakokinetiko lumakaftorja so ovrednotili s populacijsko farmakokinetično analizo podatkov iz kliničnih študij lumakaftorja, dajanega v kombinaciji z ivafaktorjem.
Table 3: Established and other potentially significant drug interactions - dose recommendations for use of lumacaftor/ivacaftor with other medicinal products
Preglednica 3: Dokazane in druge potencialno pomembne interakcije med zdravili - priporočila glede odmerkov za uporabo lumakaftorja/ivakaftorja z drugimi zdravili
Total daily dose
Celotni dnevni odmerek
These should not be relied upon as an effective method of birth control when given with Orkambi
Nanje se ne smemo zanašati kot na učinkovito metodo preprečevanja nosečnosti, kadar jih dajemo sočasno z zdravilom Orkambi;
The incidence of these events was more common in patients with lower pre-treatment FEV1.
Incidenca teh dogodkov je bila večja pri bolnikih, ki so imeli pred zdravljenjem manjši FEV1.
Lumacaftor/ivacaftor dosing was maintained or successfully resumed after interruption in all patients with transaminase elevations, except 1 patient who discontinued treatment permanently.
Odmerjanje lumakaftorja/ivakaftorja so vzdrževali ali po prekinitvi spet uspešno začeli pri vseh bolnikih z zvišanjem transaminaz, razen pri 1 bolniku, ki je trajno prenehal z zdravljenjem.
Patients took the study drug with fat-containing food for 24 weeks in addition to their prescribed CF therapies (e.g., bronchodilators, inhaled antibiotics, dornase alfa, and hypertonic saline).
Bolniki so jemali zdravilo v kliničnem preskušanju z mastno hrano 24 tednov poleg svojih predpisanih terapij CF (npr. bronhodilatatorji, antibiotiki za inhalacijo, dornaza alfa in hipertonična raztopina natrijevega klorida).
Instructions for Use
NAVODILA ZA UPORABO
Lumacaftor inhibits the organic anion transporter (OAT) 1 and 3.
Lumakaftor zavira prenašalca organskih anionov (OAT) 1 in 3.
Absolute change from baseline in faecal elastase-1 (FE-1) levels (µg/g)**
Absolutna sprememba ravni (µg/g) fekalne elastaze-1 (FE-1) od izhodišča**
• if you are allergic to lumacaftor, ivacaftor, or any of the other ingredients of this medicine (listed in section 6).
• če ste alergični na lumakaftor, ivakaftor ali katero koli sestavino tega zdravila (navedeno v poglavju 6).
Your doctor will do some blood tests to check your liver before and while you are taking Orkambi, particularly during the first year.
Zdravnik vam bo naredil nekatere krvne preiskave, s katerimi bo preveril vaša jetra, preden začnete jemati in medtem ko jemljete zdravilo Orkambi, zlasti v prvem letu.
Active substance name Effect
Ime učinkovine
Tell your doctor straight away if you have any of the following symptoms:
Nemudoma povejte zdravniku, če imate kakega od naslednjih simptomov:
If less than 6 hours have passed since the missed dose, the scheduled dose of Orkambi should be taken with fat-containing food.
Če je od izpuščenega odmerka minilo manj kot 6 ur, naj bolnik vzame načrtovani odmerek zdravila Orkambi z obrokom mastne hrane.
People with the mutation will produce an abnormal CFTR protein.
Pri ljudeh s to mutacijo bo nastajala nenormalna beljakovina CFTR.
Table 5: Summary of primary and key secondary outcomes in Trial 1 and Trial 2*
Preglednica 5: Povzetek primarnih in ključnih sekundarnih izidov v preskušanju 1 in preskušanju 2*
There are different strengths of Orkambi according to a child's age and weight.
Na voljo so različne jakosti zdravila Orkambi glede na otrokovo starost in telesno maso.
A transient decline in FEV1 has also been observed in some patients following initiation of lumacaftor/ivacaftor.
Prehodno zmanjšanje FEV1 so pri nekaterih bolnikih ugotovili tudi po uvedbi lumakaftorja/ivakaftorja.
• Cheese, whole milk, whole-milk dairy products
• sir, neposneto mleko, mlečni izdelki iz neposnetega mleka;
Note: ↑ = increase, ↓ = decrease, ↔ = no change; LUM = lumacaftor; IVA = ivacaftor.
Opomba: ↑ = zvečanje, ↓ = zmanjšanje, ↔ = nespremenjeno; LUM = lumakaftor; IVA = ivakaftor.
Consume it completely.
Zaužijte jo do konca.
Concomitant medicinal product class:
Skupina sočasnega zdravila:
Interaction with CYP2B6 and CYP2C substrates has not been investigated in vivo.
Interakcij s substrati CYP2B6 in CYP2C in vivo niso raziskali.
Patients experiencing dizziness while taking Orkambi should be advised not to drive or use machines until symptoms abate.
Bolnikom, ki imajo ob jemanju zdravila Orkambi omotico, je treba svetovati, naj ne vozijo ali uporabljajo strojev, dokler simptomi ne izzvenijo.
Three of the 48 patients who had faecal elastase-1 values < 100 µg/g at baseline achieved a level of ≥ 200 µg/g at Week 24.
Trije od 48 bolnikov, ki so imeli v izhodišču vrednosti fekalne elastaze-1 < 100 µg/g, so v 24. tednu dosegli raven ≥ 200 µg/g.
Additionally, a clinical study with ivacaftor monotherapy showed that ivacaftor is a weak inhibitor of P-gp.
Poleg tega je klinična študija z monoterapijo z ivakaftorjem pokazala, da je ivakaftor šibek zaviralec P-gp.
Ivacaftor is not an inhibitor of OAT1 and OAT3.
Ivakaftor ni zaviralec OAT1 in OAT3.
Patients should not chew, break, or dissolve the tablets.
Bolniki tablet ne smejo žvečiti, zdrobiti ali raztopiti.
Therefore, concomitant use of lumacaftor/ivacaftor with P-gp substrates (e.g., digoxin) may alter the exposure of these substrates.
Zato lahko sočasna uporaba lumakaftorja/ivakaftorja s substrati P-gp (npr. digoksinom) spremeni izpostavljenost tem substratom.
What Orkambi is and what it is used for
Kaj je zdravilo Orkambi in za kaj ga uporabljamo
CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product Characteristics, section 4.2).
POGOJI ALI OMEJITVE GLEDE OSKRBE IN UPORABE Predpisovanje in izdaja zdravila je le na recept s posebnim režimom (glejte Prilogo I: Povzetek glavnih značilnosti zdravila, poglavje 4.2).
• Food containing fat should be given to your child just before or just after dosing (some examples are provided below).
• Tik pred odmerjanjem ali tik po njem naj otrok dobi masten obrok (nekaj primerov je navedenih v nadaljevanju).
For patients with moderate hepatic impairment (Child-Pugh Class B), a dose reduction is recommended.
Za bolnike z zmerno okvaro jeter (razred B po Child-Pughovi lestvici) priporočajo zmanjšanje odmerka.
Established and other potentially significant drug interactions Table 3 provides the established or predicted effect of lumacaftor/ivacaftor on other medicinal products or the effect of other medicinal products on lumacaftor/ivacaftor.
Dokazane in druge potencialno pomembne interakcije med zdravili Preglednica 3 navaja dokazane ali napovedane učinke lumakaftorja/ivakaftorja na druga zdravila ali učinke drugih zdravil na lumakaftor/ivakaftor.
• Mix entire content of sachet with 5 mL of age-appropriate soft food or liquid that is at or below room temperature.
• Zmešajte celotno vsebino vrečice s 5 ml za starost primerne mehke hrane ali tekočine, ki je pri sobni ali nižji temperaturi.
• Tear or cut sachet open along the line.
• Pretrgajte ali prerežite vrečico po prekinjeni črti.
For patients who transitioned from placebo to active treatment similar changes as those observed in patients treated with lumacaftor/ivacaftor in Trial 1 or Trial 2 were seen (see Table 5).
Pri bolnikih, ki so prešli s placeba na aktivno zdravljenje, so ugotovili spremembe, podobne tistim, ki so jih ugotovili pri bolnikih, zdravljenih z lumakaftorjem/ivakaftorjem v preskušanju 1 ali preskušanju 2 (glejte preglednico 5).
Animal studies with lumacaftor and ivacaftor do not indicate direct or indirect harmful effects with respect to developmental and reproductive toxicity, whereas effects were noted with ivacaftor only at maternally toxic doses (see section 5.3).
Študije z lumakaftorjem in ivakaftorjem na živalih ne kažejo neposrednih ali posrednih škodljivih učinkov na razvoj in sposobnost razmnoževanja, medtem ko so pri ivakaftorju učinke opazili le pri odmerkih, toksičnih za mater (glejte poglavje 5.3).
Tell your doctor straight away if you have any of these symptoms, which may be a sign of liver problems:
Takoj povejte zdravniku, če imate katerega od teh simptomov, ki bi bil lahko znak težav z jetri:
Safety pharmacology
Varnostna farmakologija
Doses above 100 mg/kg/day resulted in survival and lactation indices that were 92% and 98% of control values, respectively, as well as reductions in pup body weights.
Odmerki, večji od tega, so povzročili indeksa preživetja in laktacije, ki sta bila 92 % oziroma 98 % kontrolnih vrednosti, pa tudi zmanjšanje telesne mase mladičkov.
Serious adverse reactions occurring in at least 0.5% of patients included hepatobiliary events, e.g., transaminase elevations, cholestatic hepatitis and hepatic encephalopathy.
Resni neželeni učinki, ki so se pojavili pri vsaj 0,5 % bolnikov, so vključevali dogodke, povezane z jetri, žolčnikom in žolčevodi, npr. zvišane transaminaze, holestatski hepatitis in hepatično encefalopatijo.
Interactions with medicinal products
Medsebojno delovanje z zdravili
Available pharmacokinetic data in animals have shown excretion of both lumacaftor and ivacaftor into the milk of lactating female rats.
Razpoložljivi farmakokinetični podatki pri živalih kažejo na izločanje tako lumakaftorja kot ivakaftorja v mleko doječih podganjih samic.
There is potential for other medicinal products to affect lumacaftor/ivacaftor when administered concomitantly, and also for lumacaftor/ivacaftor to affect other medicinal products.
Obstaja možnost, da bodo druga zdravila vplivala na lumakaftor/ivakaftor, kadar jih dajemo sočasno, pa tudi, da bo lumakaftor/ivakaftor vplival na druga zdravila.
In the event of significant elevation of ALT or AST, with or without elevated bilirubin (either ALT or AST > 5 x the upper limit of normal [ULN], or ALT or AST > 3 x ULN with bilirubin > 2 x ULN), dosing with lumacaftor/ivacaftor should be discontinued and laboratory tests closely followed until the abnormalities resolve.
V primeru pomembnega zvišanja ALT ali AST, bodisi z zvišanim bilirubinom (bodisi ALT bodisi AST > 5 x zgornja meja normalne vrednosti [ULN], bodisi ALT ali AST > 3 x ULN in bilirubin > 2 x ULN), bodisi brez zvišanega bilirubina, je treba zdravljenje z lumakaftorjem/ivakaftorjem prekiniti in skrbno spremljati rezultate laboratorijskih preiskav, dokler nenormalnosti ne izzvenijo.
Ivacaftor is approximately 99% bound to plasma proteins, primarily to alpha 1-acid glycoprotein and albumin.
Ivakaftor je v približno 99 % vezan na plazemske beljakovine, predvsem na alfa 1-kisli glikoprotein in albumin.
Repeat-dose toxicity studies involving the co-administration of lumacaftor and ivacaftor revealed no special hazard for humans in terms of potential for additive and/or synergistic toxicities.
Študije toksičnosti ponavljajočih se odmerkov, ki so obsegale sočasno dajanje lumakaftorja in ivakaftorja, niso pokazale posebnega tveganja za človeka, kar se tiče možnih aditivnih in/ali sinergističnih toksičnosti.
However, no ivacaftor-induced QT prolongation was observed in a dog telemetry study at single doses up to 60 mg/kg or in ECG measurements from repeat-dose studies of up to 1 year duration at the 60 mg/kg/day dose level in dogs (Cmax after 365 days = 36.2 to 47.6 μM).
Vendar niso opazili nikakršnega podaljšanja intervala QT, ki bi ga povzročil ivakaftor, v telemetrični študiji na psih pri enkratnih odmerkih do 60 mg/kg, ali v meritvah EKG v študijah ponavljajočih se odmerkov, ki so trajale do 1 leto dolgo, ob velikosti odmerkov 60 mg/kg/dan pri psih (Cmax po 365 dneh = 36,2 do 47,6 μM).
In vitro studies indicated that lumacaftor has the potential to both inhibit and induce P-gp.
Študije in vitro so pokazale, da ima lumakaftor potencial tako za zaviranje kot za indukcijo P-gp.
Post-Authorization Safety Study (PASS) The applicant should conduct a 5-year long-term observational study with lumacaftor/ivacaftor in patients with cystic fibrosis, including also microbiological and clinical endpoints (e.g. exacerbations) according to an approved protocol.
Predlagatelj mora izvesti 5-letno dolgoročno opazovalno študijo z lumakaftorjem/ivakaftorjem pri bolnikih s cistično fibrozo, ki bo vključevala tudi mikrobiološke in klinične opazovane dogodke (npr. eksacerbacije), v skladu z odobrenim protokolom.
The recommended dose
Priporočeni odmerek
Clinical comment fluconazole
Klinični komentar flukonazol
Among 7 patients with pre-existing cirrhosis and/or portal hypertension who received lumacaftor/ivacaftor in the placebo-controlled, Phase 3 studies, worsening liver function with increased ALT, AST, bilirubin, and hepatic encephalopathy was observed in one patient.
Med 7 bolniki z obstoječo cirozo in/ali portalno hipertenzijo, ki so prejemali lumakaftor/ivakaftor v študijah 3. faze, kontroliranih s placebom, so pri enem bolniku opazili slabšanje funkcije jeter z zvišanimi ALT, AST, bilirubinom in hepatično encefalopatijo.
Therefore, concomitant use of lumacaftor/ivacaftor may alter (i.e., either increase or decrease) the exposure of CYP2C8 and CYP2C9 substrates, decrease the exposure of CYP2C19 substrates, and substantially decrease the exposure of CYP2B6 substrates.
Zato lahko sočasna uporaba lumakaftorja/ivakaftorja spremeni (t.j., ali zveča ali zmanjša) izpostavljenost substratom CYP2C8 in CYP2C9, zmanjša izpostavljenost substratom CYP2C19 in znatno zmanjša izpostavljenost substratom CYP2B6.
• Cardiac glycosides (used for the treatment of mild to moderate congestive heart failure and an abnormal heart rhythm called atrial fibrillation) for example: digoxin
• srčni glikozidi (uporabljajo se za zdravljenje blagega do zmernega kongestivnega popuščanja srca in nenormalnega srčnega ritma, ki se imenuje atrijska fibrilacija), na primer:
In vitro studies indicate that lumacaftor is a substrate of Breast Cancer Resistance Protein (BCRP).
Študije in vitro kažejo, da je lumakaftor substrat beljakovine odpornosti proti raku dojke (BCRP).
The F508del mutation impacts the CFTR protein in multiple ways, primarily by causing a defect in cellular processing and trafficking that reduces the quantity of CFTR at the cell surface.
Mutacija F508del vpliva na beljakovino CFTR na številne načine, predvsem tako, da povzroča napako v celičnem procesiranju in transportu, kar zmanjšuje količino CFTR na celični površini.
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 farmakokinetični študiji na ljudeh samo z ivakaftorjem so ugotovili minimalno odstranjevanje lumakaftorja in njegovih presnovkov v urinu (samo 6,6 % celotne radioaktivnosti so prestregli v urinu).
The Phase 3 trials of lumacaftor/ivacaftor included 81 patients with ppFEV1 < 40 at baseline.
V preskušanja 3. faze lumakaftorja/ivakaftorja je bilo vključenih 81 bolnikov s ppFEV1 < 40 v izhodišču.
Absolute change from baseline in percent predicted FEV1 at each visit†
Absolutna sprememba od izhodišča v odstotkih napovedanega FEV1 pri vsakem pregledu†
Upper respiratory tract infection, rhinitis
pogosti okužba zgornjih dihal, rinitis
There is no experience of initiating treatment with lumacaftor/ivacaftor in patients having a pulmonary exacerbation and initiating treatment in patients having a pulmonary exacerbation is not advisable.
Izkušenj z uvajanjem zdravljenja z lumakaftorjem/ivakaftorjem pri bolnikih s pljučnim poslabšanjem ni in uvajanje zdravljenja pri bolnikih s pljučnim poslabšanjem ni priporočljivo.
Studies have not been conducted in patients with severe hepatic impairment (Child-Pugh Class C, score 10 to 15), but exposure is expected to be higher than in patients with moderate hepatic impairment (see sections 4.2, 4.4, and 4.8).
Pri bolnikih s hudo okvaro jeter (razred C po Child-Pughovi lestvici, rezultat 10 do 15) študij niso izvedli, vendar se pričakuje, da je izpostavljenost večja kot pri bolnikih z zmerno okvaro jeter (glejte poglavja 4.2, 4.4 in 4.8).
There is no experience of the use of Orkambi in patients with severe hepatic impairment (Child-Pugh Class C), but exposure is expected to be higher than in patients with moderate hepatic impairment.
Izkušenj z uporabo zdravila Orkambi pri bolnikih s hudimi okvarami jeter (razred C po Child-Pughovi lestvici) ni, a se pričakuje, da bo izpostavljenost večja kot pri bolnikih z zmerno okvaro jeter.
Orkambi is not recommended in patients who have undergone an organ transplant.
Zdravilo Orkambi ni priporočljivo za bolnike, ki so imeli v preteklosti presaditev organa.
Worsening of liver function in patients with advanced liver disease has been reported.
Poročali so o poslabšanju funkcije jeter pri bolnikih z napredovalo boleznijo jeter.