natgillin/translations-raw huggingface dataset:
Dosis blev reduceret på grund af leukopeni hos <0,5% af patienterne, og ingen patienter afbrød crizotinibbehandlingen permanent på grund af leukopeni.
Leukopenia was associated with a dose reduction for <0.5% of patients, and no patients permanently discontinued crizotinib treatment associated with leukopenia.
• Moxifloxacin, til behandling af bakterieinfektioner.
• Moxifloxacine, used to treat bacterial infections.
Der bør udvises forsigtighed, når crizotinib administreres samtidig med lægemidler, som metaboliseres af disse enzymer.
Caution should be exercised in administering crizotinib in combination with medicinal products that are predominantly metabolised by these enzymes.
173 patienter blev randomiseret til crizotinib, og 174 patienter til kemoterapi (enten pemetrexed eller docetaxel).
One hundred seventy-three (173) patients were randomised to crizotinib and 174 patients were randomised to chemotherapy (either pemetrexed or docetaxel).
Simulering af fysiologisk baseret farmakokinetik forudsiger en 17 % stigning i crizotinib steady state AUC efter behandling med moderate CYP3A-hæmmere som diltiazem eller verapamil.
Physiologically-based pharmacokinetic (PBPK) simulations predicted a 17% increase in crizotinib steady-state AUC after treatment with the moderate CYP3A inhibitors, diltiazem or verapamil.
Kontakt straks lægen, når du har taget XALKORI:
Talk to your doctor right away after having taken XALKORI:
• Ketoconazol, itraconazol, posaconazol, voriconazol, bruges til behandling af svampeinfektion.
• Ketoconazole, itraconazole, posaconazole, voriconazole, used to treat fungal infections.
Patienter med let (60 ≤ CLcr <90 ml/min) og moderat (30 ≤ CLcr <60 ml/min) nedsat nyrefunktion blev indrulleret i enkeltarmsstudierne 1001 og 1005.
Patients with mild (60≤ CLcr <90 mL/min) and moderate (30≤ CLcr <60 mL/min) renal impairment were enrolled in single-arm Studies 1001 and 1005.
Crizotinib kan administreres med eller uden føde (se Pkt.
Crizotinib can be administered with or without food (see section 4.2).
In vitro studier viser, at det er CYP3A4/5-enzymer, der hovedsageligt er involveret i den metaboliske clearance af crizotinib.
In vitro studies demonstrated that CYP3A4/5 were the major enzymes involved in the metabolic clearance of crizotinib.
Der findes ingen tilgængelige data for virkning og sikkerhed ved genbehandling med crizotinib hos patienter, der fik crizotinib i tidligere behandlingsregimer.
No safety and efficacy data are available on re-treatment with crizotinib of patients who received crizotinib in previous lines of therapy.
• Bupropion, til behandling af depression samt til rygeafvænning.
• Bupropion, used to treat depression and smoking cessation.
Grad 3 eller 4 leukopeni er blevet indberettet som almindelig (3%) (se pkt.
Grade 3 or 4 leukopenia has been commonly (3%) reported (see section 4.8).
Forkortelser: CI = konfidensinterval, N/n = antal patienter.
Abbreviations: CI=confidence interval; N/n=number of patients.
Lægen kan om nødvendigt nedsætte dosis til 200 mg 2 gange dagligt (i alt 400 mg), og hvis yderligere dosisnedsættelse er nødvendig, kan dosis nedsættes til 250 mg 1 gang daglig.
If necessary, your doctor may decide to reduce the dose to 200 mg to be taken orally twice daily (total amount 400 mg) and if further dose reduction is necessary, to reduce it to 250 mg to be taken orally once daily.
• Rifabutin, rifampicin, bruges til behandling af tuberkulose.
• Rifabutin, rifampicin, used to treat tuberculosis.
Lægen kan beslutte at afbryde din behandling permanent, hvis du ikke kan tåle at få XALKORI 250 mg oralt (gennem munden) 1 gang dagligt.
Your doctor may decide to permanently discontinue your treatment if you are unable to tolerate XALKORI 250 mg taken orally once daily.
Andre bivirkninger af XALKORI kan være:
Other side effects of XALKORI may include:
Kvinder i den fødedygtige alder bør rådes til at undgå at blive gravid under behandling med XALKORI.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving XALKORI.
Ingen patienter i crizotinib-armen i det randomiserede fase 3-studie 1007 og 1014 og enkeltarmsstudiet 1005 var >85 år.
No patients in the crizotinib arm of randomised Phase 3 Studies 1007 and 1014, and single arm Study 1005 were >85 years.
XALKORI kan ordineres til dig til den indledende behandling, hvis din lungekræft er i et fremskredent stadium.
XALKORI can be prescribed to you for the initial treatment if your disease is at an advanced stage of lung cancer.
Kvinder bør ikke blive gravide og mænd bør ikke blive fædre under behandlingen med XALKORI, da lægemidlet kan skade fostret.
It is recommended that women avoid becoming pregnant and that men do not father children during treatment with XALKORI because this medicine could harm the baby.
Hold pause indtil forbedring til grad ≤ 1 eller til hjertefrekvens på 60 eller derover
Withhold until recovery to Grade ≤1 or to heart rate 60 or above
Produktresumé og indlægsseddel Patientinformation inklusive et patientinformationskort (med tekst som vedtaget af CHMP)
Patient brochure including a Patient Alert Card (text as agreed by the CHMP).
Patienter med let (ASAT > ULN og total bilirubin ≤ ULN eller enhver ASAT og total bilirubin > ULN men  1,5 × ULN), moderat (enhver ASAT og total bilirubin > 1.5 × ULN og  3 × ULN) eller svært (enhver ASAT og total bilirubin > 3 × ULN) nedsat leverfunktion eller normal (ASAT og total bilirubin ≤ ULN) leverfunktion, som var matchede kontroller for let eller moderat nedsat leverfunktion, indgik i et open-label, ikke-randomiseret klinisk studie (Studie 1012) baseret på NCI klassifikationen.
Patients with mild (either AST >ULN and total bilirubin ≤ULN or any AST and total bilirubin >ULN but 1.5×ULN), moderate (any AST and total bilirubin >1.5×ULN and 3×ULN), or severe (any AST and total bilirubin >3×ULN) hepatic impairment or normal (AST and total bilirubin ≤ULN) hepatic function, who were matched controls for mild or moderate hepatic impairment, were enrolled in an open-label, non-randomised clinical study (Study 1012), based on NCI classification.
I studie 1001 var det påkrævet, at patienterne havde fremskreden ROS1-positiv NSCLC, inden de indtrådte i det kliniske forsøg.
In Study 1001, patients were required to have advanced ROS1-positive advanced NSCLC prior to entering the clinical trial.
Farmakoterapeutisk klassifikation: Antineoplastiske midler, protein kinase-hæmmer, ATC-kode: L01XE16
Pharmacotherapeutic group: Anti-neoplastic agents, protein kinase inhibitor; ATC code: L01XE16.
144 (84%) patienter i kemoterapi-armen fik efterfølgende crizotinibbehandling.
One hundred forty-four (84%) patients in the chemotherapy arm received subsequent crizotinib treatment.
Hos ALK-positive NSCLC-patienter var hyppigheden af bivirkninger generelt sammenlignelig for patienter <65 år og 65 år med undtagelse af ødemer og obstipation, som blev rapporteret med større hyppighed (forskel på (≥15%) i studie 1014 hos patienter ≥65 år, der blev behandlet med crizotinib.
In ALK-positive NSCLC patients, the frequency of adverse reactions was generally similar for patients <65 years of age and patients 65 years of age with the exception of oedema and constipation, which were reported with greater frequency (≥15% difference) in Study 1014 among patients treated with crizotinib 65 years of age.
Fordele og mulige risici ved crizotinib skal overvejes før behandlingen indledes hos patienter med præeksisterende bradykardi, som tidligere har haft eller er disponeret for QTcforlængelse, som tager antiarytmika eller andre lægemidler, der kan forlænge QT-intervallet, og hos patienter med relevant præeksisterende hjertesygdom og/eller elektrolytforstyrrelser.
The benefits and potential risks of crizotinib should be considered before beginning therapy in patients with pre-existing bradycardia, who have a history of or predisposition for QTc prolongation, who are taking antiarrhythmics or other medicinal products that are known to prolong QT interval and in patients with relevant pre-existing cardiac disease and/or electrolyte disturbances.
Det bør overvejes midlertidigt at pausere behandlingen, nedsætte dosis eller seponere behandlingen, hvis nævnte symptomer opstår.
Dosing interruption, dose reduction, or discontinuation should be considered as appropriate if such symptoms are observed.
På grund af de meget små stigninger i crizotinibeksponeringen (5%-15%) er justering af startdosis til patienter med let eller moderat nedsat nyrefunktion ikke nødvendig.
Due to the small size of the increases in crizotinib exposure (5%-15%), no starting dose adjustment is recommended for patients with mild or moderate renal impairment.
• Synk kapslen hel, kapslen må hverken knuses, opløses eller åbnes.
• Swallow the capsules whole and do not crush, dissolve or open the capsules.
Der er ikke foretaget karcinogenicitetstudier med crizotinib.
Carcinogenicity studies with crizotinib have not been performed.
Disse patienter fik en oral startdosis på 250 mg 2 gange dagligt kontinuerligt.
These patients received a starting oral dose of 250 mg taken twice daily continuously.
o) Forhøjet blod-kreatinin (forhøjet blod-kreatinin, nedsat kreatininclearance).
o. Blood creatinine increased (blood creatinine increased, creatinine renal clearance decreased).
Crizotinib udviste også markant antitumoraktivitet i xenograftstudier med mus, hvor tumorer blev genereret med et panel af NIH-3T3 cellelinjer til at udtrykke vigtige ROS1-fusioner, identificeret i humane tumorer.
Crizotinib also demonstrated marked antitumour activity in mouse xenograft studies, where tumours were generated using a panel of NIH-3T3 cell lines engineered to express key ROS1 fusions identified in human tumours.
Grad 3 QTc forlængelse
Grade 3 QTc prolongation
*PFS, objektiv responsrate og responsvarighed er baseret på cutoff-dato 30. november 2013; OS er baseret på dato for sidste patients sidste besøg 30. november 2016 og er baseret på en median opfølgningstid på ca. 46 måneder.
2013; OS is based on the last patient last visit date of 30 November 2016, and is based on a median follow up of approximately 46 months.
Justering af startdosis er ikke nødvendig hos patienter med let (60 ≤ kreatininclearance [CLcr] < 90 ml/min) eller moderat (30 ≤ [CLcr] < 60 ml/min) nedsat nyrefunktion, da den farmakokinetiske populationsanalyse ikke viste nogen ændringer af klinisk betydning i steady state crizotinib-eksponeringen hos disse patienter.
No starting dose adjustment is recommended for patients with mild (60≤ creatinine clearance [CLcr] <90 mL/min) or moderate (30≤ CLcr <60 mL/min) renal impairment, since the population pharmacokinetic analysis indicated no clinically meaningful changes in steady-state crizotinib exposure in these patients.
Grad 3 eller 4 ALAT- eller ASAT-stigning sås hos henholdsvis 187 (11%) og 95 (6%) af patienterne.
Increases to Grade 3 or 4 ALT or AST elevations were observed in 187 (11%) and 95 (6%) of patients, respectively.
l) Gastrointestinal perforation, (gastrointestinal perforation, tarmperforation, perforation af tyktarmen).
l. Gastrointestinal perforation (Gastrointestinal perforation, Intestinal perforation, Large intestine perforation).
I studier hos patienter med ALK-positiv fremskreden NSCLC (N=1669) blev følgende bivirkninger rapporteret med en absolut difference på ≥10% hos asiatiske patienter (N=753) end hos non-asiatiske patienter (N=916): forhøjede aminotransferaser, appetitløshed, neutropeni og leukopeni.
In studies in patients with ALK-positive advanced NSCLC (N=1669), the following adverse reactions were reported with an absolute difference of ≥10% in Asian patients (N=753) than in non-Asian patients (N=916): elevated transaminases, decreased appetite, neutropenia, and leukopenia.
Baseret på National Cancer Institute (NCI) klassifikationen anbefales justering af startdosis af crizotinib ikke hos patienter med let nedsat leverfunktion (ASAT > over øvre normalgrænse (ULN) og total bilirubin ≤ ULN eller en enhver ASAT og total bilirubin > ULN men  1,5 × ULN).
Based on the National Cancer Institute (NCI) classification, no starting dose adjustment of crizotinib is recommended for patients with mild hepatic impairment (either AST > Upper Limit of Normal (ULN) and total bilirubin ≤ULN or any AST and total bilirubin >ULN but 1.5 × ULN).
I spørgeskemaet til vurdering af symptomer på synspåvirkning (Visual Symptom Assessment Questionnaire - VSAQ-ALK) rapporterede de patienter, der blev behandlet med crizotinib i studie 1007 og studie 1014, en højere forekomst af synsforstyrrelser sammenlignet med de patienter, der blev behandlet med kemoterapi.
Based on the Visual Symptom Assessment Questionnaire (VSAQ-ALK), patients treated with crizotinib in Study 1007 and Study 1014 reported a higher incidence of visual disturbances compared to patients treated with chemotherapy.
Crizotinib var ikke mutagent in vitro i bakterielle tilbagemutationstest (Ames).
Crizotinib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay.
Færre end 0,5% af patienterne oplevede febril neutropeni i kliniske studier med crizotinib.
Less than 0.5% of patients experienced febrile neutropenia in clinical studies with crizotinib.
- hvis du er allergisk over for crizotinib eller et af de øvrige indholdsstoffer i XALKORI (angivet i punkt 6).
• If you are allergic to crizotinib or any of the other ingredients of this medicine (listed in Section 6, “What XALKORI contains”).
• Hvis du har fået at vide, at du har forstyrrelser i hjerterytmen kaldet forlænget QT-interval, som kan ses på et elektrokardiogram (ekg).
• If you have been told that you have an abnormality of your heart tracing after an electrocardiogram (ECG) known as prolonged QT interval.
Det kan også få tumoren til at skrumpe.
It may help shrink tumours.
Kapslerne må ikke knuses, opløses eller åbnes.
The capsules should be swallowed whole preferably with water, and should not be crushed, dissolved, or opened.
Grad 4 QTc forlængelse
Grade 4 QTc prolongation
Grad 2, 3 eller 4 ALAT- eller ASAT-stigning med samtidig grad 2, 3 eller 4 total bilirubinstigning (uden kolestase eller hæmolyse)
Grade 2, 3 or 4 ALT or AST elevation with concurrent Grade 2, 3 or 4 total bilirubin elevation (in the absence of cholestasis or haemolysis)
77 af 106 patienter (73%) fortsatte med crizotinibbehandlingen i mindst 3 uger efter objektiv sygdomsprogression.
Seventy-seven of 106 patients (73%) continued crizotinib treatment for at least 3 weeks after objective disease progression.
Der er utilstrækkelige oplysninger til at karakterisere risikoen ved at genoptage crizotinib-behandling hos patienter med alvorligt synstab.
There is insufficient information to characterize the risks of resumption of crizotinib in patients with a severe visual loss.
Alvorlig, livstruende eller dødelig interstitiel lungesygdom (ILD)/pneumonitis kan opstå hos patienter, der behandles med crizotinib.
Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with crizotinib.
Der er imidlertid ikke observeret induktion in vivo, når crizotinib administreres samtidig med CYP3A-testsubstratet midazolam.
However, there was no observed induction in vivo when crizotinib was coadministered with the CYP3A probe substrate midazolam.
XALKORI indeholder det aktive stof crizotinib, som anvendes til behandling af voksne med en særlig form for lungekræft, som kaldes ikkesmåcellet lungekræft, hvor der er en ændring eller en fejl i enten et gen, som kaldes anaplastisk lymfomkinase (ALK), eller et gen, som kaldes ROS1.
XALKORI is an anticancer medicine containing the active substance crizotinib used to treat adults with a type of lung cancer called non-small cell lung cancer, that presents with a specific rearrangement or defect in either a gene called anaplastic lymphoma kinase (ALK) or a gene called ROS1.
Aminotransferasestigninger opstod generelt indenfor de første 2 behandlingsmåneder.
Transaminase elevations generally occurred within the first 2 months of treatment.
Symptomatisk bradykardi (fx synkope, svimmelhed eller hypotension) kan opstå hos patienter, der får crizotinib.
Symptomatic bradycardia (e.g., syncope, dizziness, hypotension) can occur in patients receiving crizotinib.
Hvis du er gravid eller ammer, har mistanke om, at du er gravid, eller planlægger at blive gravid, skal du spørge din læge til råds, før du tager XALKORI.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
• Uklarhed/svimmel, med besvimelse eller ubehag i brystet Kontakt straks lægen, hvis du får disse symptomer, det kan være tegn på ændringer i hjertets elektriske impulser (kan ses på elektrokardigram (ekg)) eller unormal hjerterytme.
• Light-headedness, fainting, or chest discomfort Tell your doctor right away if you experience these symptoms which could be signs of changes in the electrical activity (seen on electrocardiogram) or abnormal rhythm of the heart.
i) Interstitiel lungesygdom (akut respiratorisk distress-syndrom, alveolitis, interstitiel lungesygdom, pneumonitis)
i. Interstitial lung disease (Acute respiratory distress syndrome, Alveolitis, Interstitial lung disease, Pneumonitis).
Endelig analyse af OS var ikke justeret for den mulige konfunderende effekt ved overkrydsning (154 [89%] patienter fik efterfølgende behandling med crizotinib).
Final OS analysis was not adjusted for the potentially confounding effects of crossover (154 [89%] patients received subsequent crizotinib treatment).
Lægen kan tage en blodprøve, og hvis værdierne er unormale, kan det være nødvendigt, at lægen nedsætter dosis af XALKORI.
Your doctor may do blood tests and if the results are abnormal, your doctor may decide to reduce the dose of XALKORI.
XALKORI 250 mg hårde kapsler EU/1/12/793/003
XALKORI 250 mg hard capsules EU/1/12/793/003
52 patienter i crizotinib-armen, og 57 patienter i kemoterapi-armen, som havde tidligere behandlede eller ubehandlede asymptomatiske hjernemetastaser, indgik i det randomiserede fase 3-studie 1007.
Fifty-two (52) patients treated with crizotinib and 57 chemotherapy-treated patients with previously treated or untreated asymptomatic brain metastases were enrolled in randomised Phase 3 Study 1007.
XALKORI dosisjustering - non-hæmatologisk toksicitet
XALKORI dose modification - non-haematological toxicities CTCAEa Grade
Hold pause indtil forbedring til grad ≤ 1, elektrolytter kontrolleres og korrigeres om nødvendigt, herefter genoptages dosering med den næste lavere dosis b,c
Withhold until recovery to Grade ≤1, check and if necessary correct electrolytes, then resume at the next lower doseb,c
Der sås partielt respons hos 20 af 45 patienter med non-adenokarcinom NSCLC med en ORR på 44% og hos 9 af 22 patienter med SCC-NSCLC med en ORR på 41%, hvor begge er lavere end ORR i studie 1005 (54%) for alle patienter.
Partial responses were observed in 20 of 45 patients with non-adenocarcinoma NSCLC for an ORR of 44%, and 9 of 22 patients with SCC NSCLC for an ORR of 41%, both of which were less than the ORR reported in Study 1005 (54%) for all patients.
Der skal udføres en oftalmologisk undersøgelse bestående af bedst korrigeret synsskarphed, nethindefotografier, synsfelter, optisk kohærens tomografi (OCT) og andre relevante undersøgelser for nyligt opstået alvorligt synstab.
Ophthalmological evaluation consisting of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT) and other evaluations as appropriate for new onset of severe visual loss, should be performed.
Alle grader interstitiel lungesygdom (ILD)/pneumonitis
Any Grade interstitial lung disease (ILD)/pneumonitis
Øsofagitis k (2%) Dyspepsi (8%)
Oesophagitisk (2%) Dyspepsia (8%)
38 (70,4%) af de 54 patienter oplevede behandlingsrelaterede bivirkninger i systemorganklassen Øjne, og 30 af disse patienter fik foretaget oftalmologiske undersøgelser.
Thirty-eight (70.4%) of the 54 patients experienced an Eye Disorders System Organ Class treatment-emergent allcausality adverse event of which 30 patients had ophthalmic examinations.
Justering af startdosis er derfor ikke nødvendig, når crizotinib administreres sammen med lægemidler, der øger gastrisk pH (såsom syrepumpehæmmere, H2-blokkere eller antacida).
Therefore, starting dose adjustment is not required when crizotinib is coadministered with agents that increase gastric pH (such as proton-pump inhibitors, H2 blockers, or antacids).
m) Stigning i aminotransferase (forhøjet alaninaminotransferase, forhøjet aspartataminotransferase, forhøjet gamma-glutamyltransferase, forhøjet leverenzym, unormal leverfunktion, unormal leverfunktionstest,
m. Elevated transaminases (Alanine aminotransferase increased, Aspartate aminotransferase increased, Gamma-glutamyltransferase increased, Hepatic enzyme increased, Hepatic function abnormal, Liver function test abnormal, Transaminases increased).
Samtidig stigning i ALAT og/eller ASAT ≥ 3 × ULN og total-bilirubin ≥ 2 × ULN uden signifikant stigning i alkalisk fosfatase (≤ 2 x ULN) blev set hos mindre end 1% af de patienter, der blev behandlet med crizotinib.
Concurrent elevations in ALT and/or AST ≥3 × ULN and total bilirubin ≥2 × ULN without significant elevations of alkaline phosphatase (≤2 × ULN) have been observed in less than 1% patients treated with crizotinib.
Et fedtrigt måltid reducerer crizotinib AUCinf og Cmax med ca. 14%, når en enkelt oral dosis gives til raske frivillige.
A high-fat meal reduced crizotinib AUCinf and Cmax by approximately 14% when a 250 mg single dose was given to healthy volunteers.
Crizotinib er en selektiv lav-molekylær hæmmer af ALK receptortyrosinkinase (RTK) og dens onkogene variant (dvs. ALK-fusion og udvalgte ALK-mutationer).
Crizotinib is a selective small-molecule inhibitor of the ALK receptor tyrosine kinase (RTK) and its oncogenic variants (i.e. ALK fusion events and selected ALK mutations).
c) Leukopeni (leukopeni, nedsat antal hvide blodlegemer).
c. Leukopenia (Leukopenia, White blood cell count decreased).
I alt havde 259 (16%) ud af 1.666 patienter med mindst 1 vurdering af vitale værdier efter baseline en pulsfrekvens på < 50.
A total of 259 (16%) of 1666 patients with at least 1 postbaseline vital sign assessment had a pulse rate <50 bpm.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med XALKORI i alle undergrupper af den pædiatriske population med NSCLC.
The European Medicines Agency has waived the obligation to submit the results of studies with XALKORI in all subsets of the paediatric population in NSCLC (see section 4.2 for information on paediatric use).
• Kinidin, digoxin, disopyramid, amiodaron, sotalol, dofetilid, ibutilid, verapamil, diltiazem til behandling af problemer med hjertet.
• Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil,
Patienter med eller uden præ-eksisterende hjertesygdom, som bliver behandlet med crizotinib, skal monitoreres for symptomer på hjertesvigt (åndenød, ødemer, hurtig vægtøgning pga. væskeretention).
Patients with or without pre-existing cardiac disorders, receiving crizotinib, should be monitored for signs and symptoms of heart failure (dyspnoea, oedema, rapid weight gain from fluid retention).
Hvis QTc forlænges ≥60 ms i forhold til baseline, men QTc er <500 ms, skal behandlingen med crizotinib afbrydes, og en kardiolog konsulteres.
If QTc increases by greater than or equal to 60 msec from baseline but QTc is <500 msec, crizotinib should be withheld and cardiologist advice should be sought.