natgillin/translations-raw huggingface dataset:
Der skal udvises forsigtighed hos patienter med svært nedsat nyrefunktion, da der ikke er erfaring med ceritinib hos denne population (se pkt.
Caution should be used in patients with severe renal impairment, as there is no experience with ceritinib in this population (see section 5.2).
Forhøjet lipase og/eller amylase
Lipase and/or amylase elevations
Lav fosfat-værdi i blodet (dette vil blive opdaget i en blodprøve) Højt niveau af enzymerne lipase og/eller amylase i blodet (dette vil blive opdaget i en blodprøve)
Low level of phosphate in the blood (this would be detected during blood tests) High level of enzymes called lipase and/or amylase in the blood (this would be detected during blood tests)
Det bruges til at behandle voksne, der har fremskredne stadier af en type lungekræft kaldet ikke-småcellet lungekræft (NSCLC).
It is used to treat adults with advanced stages of a form of lung cancer called non-small cell lung cancer (NSCLC).
Den mediane opfølgningsvarighed var 19,7 måneder (fra randomisering til skæringstidspunktet).
The median duration of follow-up was 19.7 months (from randomisation to cut-off date).
Seponér Zykadia permanent.
Permanently discontinue Zykadia.
Ifølge de tilgængelige data elimineres ceritinib primært via leveren.
Based on available data, ceritinib is eliminated primarily via the liver.
Tabletterne skal synkes hele med vand og må ikke tygges eller knuses.
The tablets should be swallowed whole with water and should not be chewed or crushed.
Svær eller uudholdelig kvalme, opkastning eller diarré på trods af optimal behandling mod kvalme og diarré.
Severe or intolerable nausea, vomiting or diarrhoea despite optimal anti-emetic or anti-diarrhoeal therapy
Studie A2201 involverede 140 patienter, der tidligere var blevet behandlet med 1-3 cytotoksiske kemoterapilinjer efterfulgt af behandling med crizotinib, og som var progredieret på crizotinib.
Study A2201 involved 140 patients who had been previously treated with 1-3 lines of cytotoxic chemotherapy followed by treatment with crizotinib, and who had then progressed on crizotinib.
PVC/PCTFE (polyvinylchlorid/polychlortrifluorethylen) - Aluminiumblister indeholdende 21 filmovertrukne tabletter.
PVC/PCTFE (polyvinylchloride/polychlorotrifluoroethylene) - Aluminium blister containing 21 film-coated tablets.
Grad 3 diarré blev rapporteret for en patient (1,1 %).
A grade 3 event of diarrhoea was reported in one patient (1.1%).
Ceritinibs absolutte biotilgængelighed er ikke bestemt.
The absolute bioavailability of ceritinib has not been determined.
Almene symptomer og reaktioner på administrationsstedet Træthed m
General disorders and administration site conditions Fatigue m
Leveren blev også påvirket hos begge arter ved eksponeringer, der svarer til kliniske eksponeringer ved den anbefalede humane dosis, herunder minimale forhøjelser af levertransaminaser hos nogle få dyr og vakuolisering af det intrahepatiske galdegangsepitel.
The liver was also affected in both species, at exposures that approximate clinical exposures at the recommended human dose, and included minimal increases in liver transaminases in a few animals and vacuolation of the intra-hepatic bile duct epithelium.
Hvis langvarig samtidig behandling med en potent CYP3A-hæmmer er nødvendig og patienten tolererer den reducerede dosis, kan dosis muligvis øges igen med nøje monitorering for bivirkninger for at undgå potentiel underbehandling.
If long-term concomitant treatment with a strong CYP3A inhibitor is necessary and the patient tolerates the reduced dose well, the dose may be increased again with careful monitoring for safety, to avoid potential under-treatment.
Der blev indsamlet serielle EKG'er efter en enkelt dosis og ved steady state for at evaluere ceritinibs virkning på QT-intervallet hos 925 patienter behandlet med Zykadia 750 mg en gang daglig fastende.
Serial ECGs were collected following a single dose and at steady-state to evaluate the effect of ceritinib on the QT interval in 925 patients treated with Zykadia 750 mg once daily fasted.
Et in vivo telemetrisk studie med aber viste en beskeden QT-forlængelse hos 1 af 4 dyr efter administration af den højeste dosis ceritinib.
An in vivo telemetry study in monkeys showed a modest QT prolongation in 1 of 4 animals after receiving the highest dose of ceritinib.
Øjne Synsforstyrrelser a
Eye disorders Vision disorder a
Ceritinib er blevet klassificeret som en potent CYP3A4-hæmmer in vivo og kan potentielt interagere med lægemidler, som metaboliseres via CYP3A, hvilket kan føre til øgede serum koncentrationer af det andet lægemiddel.
Ceritinib has been classified in vivo as a strong CYP3A4 inhibitor and has the potential to interact with medicinal products that are metabolised by CYP3A, which may lead to increased serum concentrations of the other product.
Tabel 6 ALK-positiv fremskreden NSCLC - oversigt over effektresultaterne fra Studie X2101 og A2201
Table 6 ALK-positive advanced NSCLC - overview of efficacy results from Studies X2101 and A2201
Baseret på den stratificerede Cox-proportionale hazard-analyse.
Based on the stratified Cox proportional hazards analysis.
Ceritinibs potentiale for QT-intervalforlængelse blev vurderet i syv kliniske studier med Zykadia.
The potential for QT interval prolongation of ceritinib was assessed in seven clinical studies with Zykadia.
Du skal være meget forsigtig med at køre bil og betjene maskiner, når du tager Zykadia, da du kan opleve synsforstyrrelser eller træthed.
You should take special care when driving and using machines when taking Zykadia as you may experience visual disturbances or tiredness.
Patienter, der færdiggjorde 4 serier med kemoterapi (induktion) uden progressiv sygdom, fik efterfølgende pemetrexed (500 mg/m2) som enkeltstof i vedligeholdelsesbehandling hver 21. dag.
Patients who completed 4 cycles of chemotherapy (induction) without progressive disease subsequently received pemetrexed (500 mg/m2) as single-agent maintenance therapy every 21 days.
De vigtigste biotransformationsveje, der er identificeret hos raske forsøgspersoner, omfatter mono-oxygenering, O-dealkylering og N-formylering.
Main biotransformation pathways identified in healthy subjects included mono-oxygenation, O-dealkylation, and N-formylation.
En præcis og valideret ALK-test er nødvendig for udvælgelsen af ALK-positive NSCLC-patienter (se pkt.
An accurate and validated ALK assay is necessary for the selection of ALK-positive NSCLC patients (see section 5.1).
Ceritinib hæmmer autofosforylering af ALK, ALK-medieret fosforylering af downstream-signalproteiner og proliferation af ALK-afhængige cancerceller både in vitro og in vivo.
Ceritinib inhibits autophosphorylation of ALK, ALK-mediated phosphorylation of downstream signalling proteins and proliferation of ALK-dependent cancer cells both in vitro and in vivo.
Kapslerne skal administreres oralt én gang daglig sammen med mad på samme tidspunkt hver dag.
The capsules should be administered orally once daily with food at the same time every day.
Ethundredeogfem (105) patienter ud af de 145 patienter (72,4 %), som afbrød behandling i kemoterapi-armen, fik efterfølgende ALK-hæmmer som første anti-neoplastiske behandling.
One hundred and five (105) patients out of the 145 patients (72.4%) that discontinued treatment in the chemotherapy arm received subsequent ALK inhibitor as first antineoplastic therapy.
150 (3 pakninger med 50) hårde kapsler.
150 (3 packs of 50) hard capsules.
Hvad Zykadia er
What Zykadia is
OS-analyse var ikke justeret for potentielle konfunderende effekter af overkrydsning.
OS analysis was not adjusted for the potentially confounding effects of cross over.
hvis du har problemer med bugspytkirtlen.
if you have problems with your pancreas.
Stærk hudkløe med rødt udslæt og knopper
Severe itching of the skin, with a red rash or raised bumps
Syrereducerende lægemidler (fx protonpumpehæmmere, H2-receptorantagonister, antacida) kan ændre opløseligheden af ceritinib og reducere dets biotilgængelighed.
Acid reducing agents (e.g., proton pump inhibitors, H2-receptor antagonists, antacids) can alter the solubility of ceritinib and reduce its bioavailability.
Forhøjet lipase eller amylase ≥ grad 3
Lipase or amylase elevation grade ≥3
Særlig forsigtighed skal udvises, når patienter med svært nedsat leverfunktion behandles, og dosis skal justeres (se pkt.
Particular caution should be exercised when treating patients with severe hepatic impairment, and the dose should be adjusted (see section 4.2).
Der er ikke udført karcinogenicitetsstudier med ceritinib.
Carcinogenicity studies have not been performed with ceritinib.
En farmakokinetisk analyse tydede på, at ceritinib forårsager koncentrationsafhængige stigninger i QTc (se pkt.
A pharmacokinetic analysis suggested that ceritinib causes concentration-dependent increases in QTc (see section 4.4).
Hvis dosisreduktion er nødvendig på grund af en bivirkning, som ikke er listet i tabel 1, skal dette gøres ved trinvis reduktion á 150 mg daglig.
If dose reduction is required due to an adverse drug reaction (ADR) not listed in Table 1, then this should be achieved by decrements of 150 mg daily.
Tabletterne skal administreres oralt én gang daglig sammen med mad på samme tidspunkt hver dag.
The tablets should be administered orally once daily with food at the same time every day.
Seponér Zykadia permanent, hvis der ikke identificeres noget medvirkende lægemiddel, der tages samtidig.
Permanently discontinue Zykadia if no contributing concomitant medicinal product is identified.
Størstedelen af patienterne var kaukasier (60,0 %) eller asiater (37,9 %).
The majority of patients were Caucasian (60.0%) or Asian (37.9%).
Baseret på in vitro-data hæmmer ceritinib ikke den apikale effluxtransporter MRP2, hepatiske optagstransportere OATP1B1 eller OATP1B3, renale, organisk anion-optagstransportere OAT1 og OAT3 eller organiske kation-optagstransportere OCT1 eller OCT2 i klinisk relevante koncentrationer.
Based on in vitro data, ceritinib does not inhibit apical efflux transporter MRP2, hepatic uptake transporters OATP1B1 or OATP1B3, renal organic anion uptake transporters OAT1 and OAT3, or the organic cation uptake transporters OCT1 or OCT2 at clinically relevant concentrations.
Den væsentligste toksicitet, der var relateret til administration af ceritinib til rotter og aber, var inflammation i de ekstrahepatiske galdegange ledsaget af forhøjede neutrofiltal i det perifere blod.
The principal toxicity related to ceritinib administration in rats and monkeys was inflammation of the extra-hepatic bile ducts accompanied by increased neutrophil counts in the peripheral blood.
Efter en enkeltdosis oral administration á 750 mg radioaktiv ceritinib fastende var ceritinib den cirkulerende hovedkomponent i human plasma.
Following a single oral administration of radioactive ceritinib dose at 750 mg fasted, ceritinib was the main circulating component in human plasma.
Luftveje, thorax og mediastinum Pneumonitis d
Respiratory, thoracic and mediastinal disorders Pneumonitis d
Det anbefales at udvise forsigtighed ved samtidig behandling med protonpumpehæmmere, da eksponeringen af ceritinib kan blive reduceret.
Caution is advised with concomitant use of proton pump inhibitors, as exposure of ceritinib may be reduced.
Fordele og potentielle risici bør overvejes før behandling initieres hos patienter med eksisterende bradykardi (hjertefrekvens under 60 slag pr. minut [bpm]), patienter med anamnese eller prædisposition for QT-forlængelse, patienter, der tager antiarytmika eller andre lægemidler, som vides at forlænge QT-intervallet samt patienter med relevant eksisterende hjertesygdom og/eller elektrolytforstyrrelser.
The benefits and potential risks of ceritinib should be considered before beginning therapy in patients who have pre-existing bradycardia (heart rate less than 60 beats per minute [bpm]), patients who have a history of or predisposition for QTc prolongation, patients who are taking anti-arrhythmics or other medicinal products that are known to prolong the QT interval and patients with relevant pre-existing cardiac disease and/or electrolyte disturbances.
Kvinder i den fertile alder bør rådes til at anvende yderst effektiv kontraception mens de tager Zykadia og i op til 3 måneder efter behandlingens ophør (se pkt.
Women of childbearing potential should be advised to use a highly effective method of contraception while taking Zykadia and for up to 3 months after discontinuing treatment (see section 4.5).
Genfinding af uændret ceritinib i fæces udgør i gennemsnit 68 % af en oral dosis.
Recovery of unchanged ceritinib in the faeces accounts for a mean 68% of an oral dose.
Patienter, der fik ceritinib, viste signifikante forbedringer over kemoterapi i målinger for generel livskvalitet og global sundhedsstatus (LCSS [p < 0,001], QLQ-C30 [p < 0,001] samt i EQ-5D-5Lindekset [p < 0,001]).
Patients receiving ceritinib showed significant improvements over chemotherapy in general Quality of Life and global Health Status measures (LCSS [p<0.001], QLQ-C30, [p<0.001] and EQ-5D-5L index [p<0.001]).
Kapslerne leveres i blisterkort og fås i pakninger, der indeholder 40, 90 eller 150 kapsler (3 pakninger med 50) kapsler.
The capsules are provided in blisters and are available in packs containing 40, 90 or 150 (3 packs of 50) capsules.
Monitorering af QT-intervallet er indiceret ved kombinationsbehandling med denne type lægemidler (se pkt.
Monitoring of the QT interval is indicated in the event of combinations of such medicinal products (see sections 4.2 and
Den primære udskillelsesvej for ceritinib og dets metabolitter er i fæces.
The primary route of excretion of ceritinib and its metabolites is in the faeces.
Spørgeskemaer vedrørende patientrapporterede resultater (Lung cancer symptom scale [LCSS], EORTC-QLQ-C30 [C30], EORTC QLQ-LC13 [LC13] og EQ-5D-5L) blev færdiggjort af 80 % eller flere af patienterne i ceritinib- og kemoterapi-armene for alle spørgeskemaer på de fleste tidspunkter i løbet af studiet.
Patient reported outcome questionnaires (Lung cancer symptom scale [LCSS], EORTC-QLQ-C30 [C30], EORTC QLQ-LC13 [LC13] and EQ-5D-5L) were completed by 80% or more of patients in the ceritinib and chemotherapy arms for all questionnaires at most of the time-points during the course of the study.
Studiet mødte sit primære formål og demonstrerede statistisk signifikant forbedring i PFS, vurderet af BIRC, med en estimeret risikoreduktion på 51 % i ceritinib-armen sammenlignet med kemoterapiarmen (se tabel 4 og figur 3).
The study met its primary objective demonstrating a statistically significant improvement in PFS by BIRC with an estimated 51% risk reduction in the ceritinib arm compared to chemotherapy arm (see Table 4 and Figure 3).
Hvis der forekommer opkastning under behandlingen, skal patienten ikke tage en yderligere dosis, men bør fortsætte med den næste planlagte dosis.
If vomiting occurs during the course of treatment, the patient should not take an additional dose, but should continue with the next scheduled dose.
ALK-translokation bestemmer ekspressionen af det resulterende fusionsprotein og deraf følgende afvigende ALK-signalering ved NSCLC.
ALK translocation determines expression of the resulting fusion protein and consequent aberrant ALK signaling in NSCLC.
Den maksimale tilladte dosis i faste er 750 mg (se pkt.
The maximum allowable dose under fasted condition is 750 mg (see section 5.2).
nyopstået eller forværret hoste med eller uden slim, feber, brystsmerter, vejrtrækningsbesvær eller kortåndethed.
new or worsening cough with or without mucus, fever, chest pain, trouble breathing or shortness of breath.
Samtidig forhøjet ALAT eller ASAT på mere end 3× ULN og totalbilirubin på mere end 2× ULN uden forhøjet alkalisk phosphatase blev observeret hos mindre end 1 % af patienterne i kliniske studier med ceritinib.
Concurrent elevations of ALT or AST greater than 3× ULN and total bilirubin greater than 2× ULN without elevated alkaline phosphatase have been observed in less than 1% of patients in clinical studies with ceritinib.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med Zykadia i alle undergrupper af den pædiatriske population med lungecarcinom (småcellet og ikke-småcellet carcinom) (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with Zykadia in all subsets of the paediatric population in lung carcinoma (small cell and non-small cell carcinoma) (see section 4.2 for information on paediatric use).
Ceritinib er blevet klassificeret som en svag CYP2C9-hæmmer in vivo.
Ceritinib has been classified in vivo as a weak CYP2C9 inhibitor.
Zykadia skal indtages i forbindelse med mad.
Zykadia should be taken with food.
warfarin og dabigatran, der bruges til forebyggelse af blodpropper.
warfarin and dabigatran, medicines used to prevent blood clots.
Gastrointestinale bivirkninger blev håndteret primært med anden samtidig behandling, som fx antiemetiske lægemidler eller lægemidler mod diarré.
Gastrointestinal events were managed primarily with concomitant medicinal products including anti-emetic/anti-diarrhoeal medicinal products.
Hos patienter, der udvikler transaminasestigninger, skal der udføres hyppigere monitorering af levertransaminaser og totalbilirubin som klinisk indiceret (se pkt.
In patients who develop transaminase elevations, more frequent monitoring of liver transaminases and total bilirubin should be carried out as clinically indicated (see sections 4.2 and
Tilfælde af levertoksicitet forekom hos 1,1 % af de patienter, der fik ceritinib i kliniske studier.
Cases of hepatotoxicity occurred in 1.1% of patients receiving ceritinib in clinical studies.
Patienter skal monitoreres med laboratorietests af leverfunktionen (inklusive ALAT, ASAT og totalbilirubin) før behandlingen påbegyndes, hver anden uge i de første tre måneder af behandlingen og månedligt derefter.
Patients should be monitored with liver laboratory tests (including ALT, AST and total bilirubin) prior to the start of treatment, every 2 weeks during the first three months of treatment and monthly thereafter.
Virkningen af Zykadia 450 mg med mad blev evalueret i et multicenter, open-label, dosisoptimeringsstudie A2112 (ASCEND-8).
The efficacy of Zykadia 450 mg with food was evaluated in a multicentre, open-label dose optimisation study A2112 (ASCEND-8).
Der blev ikke observeret tegn på mutagenicitet eller klastogenicitet i andre in vitro- og in vivo-genotoksicitetsstudier med ceritinib.
No signs of mutagenicity or clastogenicity were observed in other in vitro and in vivo genotoxicity studies with ceritinib.
Eastern Cooperative Oncology Group (ECOG) performance status var 0/1/2 hos 37,0 %/56,4 %/6,4 % af patienterne og 32,2 % havde hjernemetastaser ved baseline.
The Eastern Cooperative Oncology Group (ECOG) performance status was 0/1/2 in 37.0%/56.4%/6.4% of patients, and 32.2% had brain metastasis at baseline.
Responsrate (ORR: CR+PR), n (%) (95% CI)
Overall Response Rate (ORR: CR+PR), n (%) (95% CI)
Pausér Zykadia indtil bedring til asymptomatisk (grad ≤1) bradykardi eller til en hjertefrekvens på 60 slag pr. minut (bpm) eller derover.
Withhold Zykadia until recovery to asymptomatic (grade ≤1) bradycardia or to a heart rate of 60 beats per minute (bpm) or above.
Medicin, som kan øge risikoen for bivirkninger ved Zykadia: medicin, der bruges til behandling af AIDS/HIV (fx ritonavir, saquinavir).
Medicines which may increase the risk of side effects with Zykadia: medicines used to treat AIDS/HIV (e.g. ritonavir, saquinavir).
ALAT-stigninger til grad 3 eller 4 blev observeret hos 25 % af patienterne.
Increases to grade 3 or 4 ALT elevations were observed in 25% of patients.
OS-data var ikke modne med 48 (41,7 %) hændelser i ceritinib-armen og 50 (43,1 %) hændelser i kemoterapiarmen, svarende til ca. 50 % af de nødvendige hændelser for den endelige OS-analyse.
OS data was immature with 48 (41.7%) events in the ceritinib arm and 50 (43.1%) events in the chemotherapy arm, corresponding to approximately 50% of the required events for the final OS analysis.
Dette kan være tegn eller symptomer på hjerteproblemer.
These may be signs or symptoms of heart problems.
Asymptomatiske tilfælde af bradykardi (hjertefrekvens under 60 bpm) er observeret hos 21 ud af 925 (2,3 %) patienter, der blev behandlet med ceritinib i kliniske studier.
Asymptomatic cases of bradycardia (heart rate less than 60 bpm) have been observed in 21 out of 925 (2.3%) patients treated with ceritinib in clinical studies.
Populationskarakteristika i de to arme var: gennemsnitsalder 53 år, alder under 65 (79 %), kvinder (57 %), kaukasiske (54 %), asiatiske (33 %), aldrig rygere eller tidligere rygere (95 %), WHO PS 0 eller 1 (93 %), adenocarcinom histologi (94 %) og metastaser i hjernen (33 %).
The population characteristics across the two arms were: mean age 53 years, age less than 65 (79%), female (57%), Caucasian (54%), Asian (33%), never or former smoker (95%), WHO PS 0 or 1 (93%), adenocarcinoma histology (94%), and metastases to the brain (33%).
De må ikke tygges eller knuses.
Do not chew or crush them.
OS-rate ved 24 måneder d, % (95 % CI)
OS rate at 24 months d, % (95% CI)
På tværs af de syv kliniske studier blev bradykardi og/eller sinus-bradykardi (hjertefrekvens under 60 bpm, alle af grad 1) rapporteret hos 2,3 % af patienterne.
Across the seven clinical studies, bradycardia and/or sinus bradycardia (heart rate less than 60 bpm) events (all grade 1) were reported in 2.3% of patients.
Der blev observeret påvirkning af thyroidea hos både rotter (let forhøjede thyroideastimulerende hormon- og triiodothyronin/thyroxin T3/T4-koncentrationer uden mikroskopisk korrelat) og aber (forekomst af kolloid hos hanner i et 4-ugers studie og en abe på høj dosis med diffus follikelcellehyperplasi og forhøjet thyroidea-stimulerende hormon i et 13-ugers studie).
Effects on the thyroid were observed in both rat (mild increases in thyroid stimulating hormone and triiodothyronine/thyroxine T3/T4 concentrations with no microscopic correlate) and monkey (depletion of colloid in males in 4-week study, and one monkey at high dose with diffuse follicular cell hyperplasia and increased thyroid stimulating hormone in 13-week study).
Patienter, der var randomiseret til kemoterapiarmen kunne krydse over til ceritinib ved RECIST-defineret sygdomsprogression, som var bekræftet af BIRC (blinded independent review committee).
Patients randomised to the chemotherapy arm could cross-over to receive ceritinib upon RECIST-defined disease progression confirmed by blinded independent review committee (BIRC).
KARTON TIL ENKELTPAKNING MED 40 ELLER 90 HÅRDE KAPSLER
CARTON OF UNIT PACK CONTAINING 40 OR 90 HARD CAPSULES
Alaninaminotransferase (ALAT)- eller aspartataminotransferase (ASAT)-stigning >5 gange den øvre normalgrænse (ULN) med samtidig totalbilirubin ≤2 gange ULN
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation >5 times upper limit of normal (ULN) with concurrent total bilirubin ≤2 times ULN
Samtidig administration af ceritinib og potente CYP3A/P-gp-induktorer nedsætter plasmakoncentrationen af ceritinib.
Co-administration of ceritinib with strong CYP3A/P-gp inducers decreases ceritinib plasma concentrations.
Log rank værdi = 0,496
Log rank p-value = 0.496
Patienter kunne fortsætte forsøgsbehandlingen efter initial progression, hvis der ifølge investigators vurdering fortsat var klinisk gavn af behandlingen.
Patients were allowed to continue the assigned study treatment beyond initial progression in case of continued clinical benefit as per the investigator's opinion.
Ingen af disse bivirkninger førte til seponering af behandling med ceritinib.
None of these events led to discontinuation of ceritinib treatment.
Pneumonitis (interstitiel lungesygdom, pneumonitis)
Pneumonitis (interstitial lung disease, pneumonitis)
Patienter skal monitoreres og behandles med standardpleje, herunder midler mod diarré og kvalme eller væskeerstatning, som klinisk indiceret.
Patients should be monitored and managed using standards of care, including anti-diarrhoeals, anti-emetics or fluid replacement, as clinically indicated.
chloroquin og halofantrin, der bruges til behandling af malaria.
chloroquine and halofantrine, medicines used to treat malaria.