natgillin/translations-raw huggingface dataset:
Der blev ligeledes observeret tilfælde med dødelig udgang, tilfælde som krævede hæmolyse og tilfælde af hyperkaliæmi grad 4.
Cases with fatal outcome, cases requiring hemodialysis and cases of grade 4 hyperkalemia were also observed.
Grad 3 og 4 aminotransferasestigninger var generelt reversible efter dosisafbrydelse.
Grade 3 and 4 transaminase elevations were generally reversible upon dosing interruption.
Bivirkningstermer, som repræsenterer det samme medicinske koncept eller den samme medicinske tilstand, blev grupperet og rapporteret som en enkelt bivirkning i Skema 3.
Event terms that represent the same medical concept or condition were grouped together and reported as a single adverse drug reaction in Table 3.
Grad 3 eller 4 alanin-aminotransferase (ALAT)eller aspartat-aminotransferase (ASAT)-stigning med grad ≤ 1 total bilirubin
Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation with Grade ≤1 total bilirubin
Data for PFS fra studie 1005 omfattede 807 patienter i populationen til sikkerhedsanalysen, hvor sygdommen blev fastslået med FISH-testen (opgørelsesdato for data var den 15. februar 2012).
d. PFS data from Study 1005 included 807 patients in the safety analysis population who were identified by the FISH assay (data cutoff date 15 February 2012).
Smagsforstyrrelser blev også hyppigt indberettet i disse studier, og var primært sværhedsgrad 1.
Dysgeusia was also very commonly reported in these studies, and was primarily Grade 1 in severity.
Det primære effektendepunkt i begge studier var objektiv responsrate (ORR) vurderet i overensstemmelse med RECIST.
The primary efficacy endpoint in both studies was objective response rate (ORR) according to RECIST.
Vurder samtidigt administrerede lægemidler, der er kendt for at forårsage bradykardi, samt antihypertensive lægemidler
Evaluate concomitant medicinal products known to cause bradycardia, as well as anti-hypertensive medicinal products
Hypofosfatæmi (6%)
Hypophosphataemia (6%)
Patienterne bør informeres om tidlige tegn på gastrointestinal perforation og rådes til hurtigt at henvende sig, hvis disse tegn forekommer.
Patients should be informed of the first signs of gastrointestinal perforations and be advised to consult rapidly in case of occurrence.
Resultater fra et in vitro fototoksicitetsstudie viste at crizotinib kan have fototoksisk potentiale.
The results of an in vitro phototoxicity study demonstrated that crizotinib may have phototoxic potential.
Absolut biotilgængelighed af crizotinib er bestemt til 43% efter administration af en enkelt oral dosis på 250 mg.
The absolute bioavailability of crizotinib was determined to be 43% following the administration of a single 250 mg oral dose.
Gravide kvinder eller patienter, der bliver gravide under behandling med crizotinib, eller mandlige patienter, der er partner med en gravid kvinde, skal oplyses om den potentielle risiko for fostret.
Pregnant women, or patients becoming pregnant while receiving crizotinib, or treated male patients as partners of pregnant women, should be apprised of the potential hazard to the foetus.
Tæt klinisk overvågning anbefales, når crizotinib administreres samtidig med disse lægemidler.
Close clinical surveillance is recommended when crizotinib is administered with these medicinal products.
Det primære effektmål var ORR ifølge RECIST.
The primary efficacy endpoint was ORR according to RECIST.
Studie 1005
Study 1005
De fleste tilfælde var lette til moderate i sværhedsgrad.
Most events were mild to moderate in severity.
• Lægemidlet kræver ingen særlige forholdsregler vedrørende opbevaringen.
• This medicine does not require any special storage conditions.
Vejledning om dosisreduktion for hæmatologisk toksicitet og non-hæmatologisk toksicitet kan ses i skema 1 og 2.
Dose reduction guidelines for haematological and non-haematological toxicities are provided in Tables 1 and 2.
• Mefloquin, til forebyggelse af malaria.
• Mefloquine, used for the prevention of malaria.
Dette lægemiddel anbefales ikke til behandling af børn og teenagere.
Treatment of children and adolescents with this medicine is not recommended.
In vitro-binding af crizotinib til human plasmaprotein er 91% og er ikke koncentrationsafhængig.
Binding of crizotinib to human plasma proteins in vitro is 91% and is independent of medicinal product concentration.
MAH skal ved markedsføring og herefter sørge for, at alt sundhedspersonale, hvor XALKORI forventes at blive anvendt og/eller ordineret, får udleveret opdateret undervisningsmateriale.
The MAH should ensure that, at launch and thereafter, all Healthcare Professionals who are expected to use and/or prescribe XALKORI are provided with an educational pack.
• Forhøjede niveauer af kreatinin i blodet (kan tyde på, at nyrerne ikke fungerer normalt).
• Increased blood levels of creatinine (may indicate that kidneys are not functioning properly).
• Synsforstyrrelser (lysglimt, sløret syn eller dobbeltsyn, som almindeligvis begynder lige efter behandlingen med XALKORI er påbegyndt).
• Visual effects (seeing flashes of light, blurred vision, or double vision, often beginning soon after starting treatment with XALKORI).
XALKORI kan forårsage fosterskade, når det gives til gravide kvinder.
XALKORI may cause foetal harm when administered to a pregnant woman.
• Ubehag i maven, herunder opkastning, diaré, kvalme.
• Stomach upset, including vomiting, diarrhoea, nausea.
XALKORI som monoterapi er indiceret til:
XALKORI as monotherapy is indicated for:
Crizotinib skal administreres med forsigtighed hos disse patienter, og periodisk monitorering med elektrokardiogram (ekg), af elektrolytter og af nyrefunktion er påkrævet.
Crizotinib should be administered with caution in these patients and periodic monitoring of electrocardiograms (ECG), electrolytes and renal function is required.
Plasmakoncentrationen af crizotinib kan være forhøjet hos patienter med svært nedsat nyrefunktion (CLcr < 30 ml/min).
Crizotinib plasma concentrations may be increased in patients with severe renal impairment (CLcr <30 mL/min).
XALKORI kan hæmme eller standse lungekræftens vækst.
XALKORI may slow or stop the growth of lung cancer.
Studie 1001
Study 1001
Symptomer kan minde om symptomer på lungekræft.
Symptoms may be similar to those from lung cancer.
Der bør anvendes sikker prævention under behandlingen og mindst 90 dage efter afslutning af behandlingen (se pkt.
Adequate contraceptive methods should be used during therapy, and for at least 90 days after completing therapy (see section 4.5).
Sygdomskarakteristika for den samlede studiepopulation var metastaserende sygdom hos 98% af patienterne, 92% af tumorerne var histologisk klassificeret som adenokarcinom, og 27% af patienterne havde hjernemetastaser.
The disease characteristics of the overall study population were metastatic disease in 98% of patients, 92% of patients' tumours were classified as adenocarcinoma histology, and 27% of patients had brain metastases.
Ved opgørelsesdatoerne for data den 1. juni 2011 (studie 1001) og 15. februar 2015 (studie 1005).
a. Per data cutoff dates 01 June 2011 (Study 1001) and 15 February 2012 (Study 1005).
ROS1-positiv fremskreden NSCLC
ROS1-Positive Advanced NSCLC
Der var ingen ROS1-positive patienter >85 år i studie 1001.
There were no ROS1-positive patients >85 years old in Study 1001.
• Hvis du skal tage den næste dosis om 6 timer eller mere, skal du tage den glemte kapsel lige så snart, du kommer i tanke om det.
• If your next dose is in 6 hours or more, take the missed capsule as soon as you remember.
Periodisk monitorering med billeddiagnostik og urinanalyse bør overvejes hos patienter, der udvikler nyrecyster.
Periodic monitoring with imaging and urinalysis should be considered in patients who develop renal cysts.
For de fleste patienters vedkommende blev ROS1-positiv NSCLC identificeret ved FISH.
For most patients, ROS1-positive NSCLC was identified by FISH.
Efter oral administration af en enkelt dosis taget fastende, absorberes crizotinib med peakkoncentration efter gennemsnitlig 4 til 6 timer.
Following oral single dose administration in the fasted state, crizotinib is absorbed with median time to achieve peak concentrations of 4 to 6 hours.
Sygdomskarakteristika var 94% metastatisk, 96% adenokarcinomhistologi, og 13%, der ikke tidligere havde fået systemisk behandling for metastatisk sygdom.
The disease characteristics were 94% metastatic, 96% adenocarcinoma histology, and 13% with no prior systemic therapy for metastatic disease.
De bivirkninger, der er anført i skema 3, er angivet efter systemorganklasse og følgende hyppigheder: Meget almindelig (≥1/10); almindelig (≥1/100 til <1/10), ikke almindelig (≥1/1.000 til <1/100), sjælden (≥1/10.000 til <1/1.000), meget sjælden (<10.000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
The adverse reactions listed in Table 3 are presented by system organ class and frequency categories, defined using the following convention: very common (1/10); common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Crizotinib bør seponeres hos patienter, der udvikler gastrointestinal perforation.
Crizotinib should be discontinued in patients who develop gastrointestinal perforation.
XALKORI kan øge bivirkninger i forbindelse med følgende lægemidler:
XALKORI may increase side effects associated with the following medicines:
Der blev indsamlet serielle ekg'er i tre eksemplarer efter en enkelt dosis og ved steady state for at evaluere crizotinibs indvirkning på QT-intervallet.
Serial ECGs in triplicate were collected following a single dose and at steady state to evaluate the effect of crizotinib on QT intervals.
• Antikolinerge midler, til at genoprette muskelfunktion.
• Anticholinesterases, used to restore muscle function.
Crizotinib er også en hæmmer af receptor for hepatocytvækstfaktor (HGFR, c-Met) RTK, ROS1 (c-ros) og Recepteur d'Origine Nantais (RON) RTK.
Crizotinib is also an inhibitor of the Hepatocyte Growth Factor Receptor (HGFR, c-Met) RTK, ROS1 (c-ros) and Recepteur d'Origine Nantais (RON) RTK.
Den primære metabolisering hos mennesker er oxidation af piperidin-ringen til crizotinib-laktam og O-dealkylering med efterfølgende fase 2 konjugering af O-dealkylerede metabolitter.
The primary metabolic pathways in humans were oxidation of the piperidine ring to crizotinib lactam and O-dealkylation, with subsequent Phase 2 conjugation of O-dealkylated metabolites.
Bivirkninger indberettet i kliniske crizotinibstudier (N=1.722) Systemorganklasse
Adverse reactions reported in crizotinib clinical studies (N=1722) System organ class
Nogle lungeproblemer bliver værre under behandlingen med XALKORI fordi XALKORI kan give en betændelseslignende tilstand i lungerne under behandlingen.
Some lung problems may get worse during treatment with XALKORI, as XALKORI may cause inflammation of the lungs during treatment.
XALKORI kan ordineres til dig, hvis din sygdom er i et fremskredent stadium og hvis tidligere behandling ikke har virket.
XALKORI can be prescribed to you if your disease is at an advanced stage and previous treatment has not helped to stop your disease.
Præeksisterende okulære abnormiteter og samtidige medicinske tilstande, som kunne bidrage til de okulære fund, blev bemærket hos mange patienter, og en afgørende årsagssammenhæng med crizotinib kunne ikke konstateres.
Pre-existing ophthalmic abnormalities and concomitant medical conditions which could be contributory to ocular findings were noted in many patients, and no conclusive causal relationship to crizotinib could be determined.
De fleste tilfælde var lette i sværhedsgrad.
Most events were mild in severity.
NOAEL for kromosomtalspåvirking var ca. 1,8 gange human klinisk eksponering baseret på AUC.
The NOAEL for aneugenicity was approximately 1.8-fold human clinical exposure based on AUC.
• Hvis du skal tage den næste dosis om mindre end 6 timer, skal du springe den glemte kapsel over.
• If your next dose is in less than 6 hours, skip the missed capsule.
Fortæl det straks til lægen, hvis du får nye forværrede symptomer herunder besvær med at trække vejret, åndenød, hoste med eller uden slim eller feber.
Tell your doctor right away if you have any new or worsening symptoms including difficulty in breathing, shortness of breath, or cough with or without mucous, or fever.
ALK- og ROS1-analyse
ALK and ROS1 testing
• Cisaprid, til behandling af maveproblemer.
• Cisapride, used to treat stomach problems.
Din læge vil måske standse behandlingen med XALKORI og henvise dig til en øjenlæge.
Your doctor may stop XALKORI treatment and refer you to an ophthalmologist.
Studie 1001 N=53
Study 1001 N=53a
XALKORI-behandling
XALKORI treatment
q) Nedsat testosteron i blodet (nedsat testosteron i blodet, hypogonadisme, sekundær hypogonadisme).
q. Blood testosterone decreased (Blood testosterone decreased, Hypogonadism, Secondary hypogonadism).
Vurderingen bør udføres af laboratorier med tilstrækkelig kompetence inden for den anvendte analyse (se pkt.
Assessment should be performed by laboratories with demonstrated proficiency in the specific technology being utilised (see section 4.4).
Mediantiden til leukopeni af en eller anden grad var 85 dage.
Median time to onset of any grade leukopenia was 85 days.
Hold pause indtil forbedring til grad ≤ 2, herefter genoptages samme doseringsplan
Withhold until recovery to Grade ≤2, then resume at the same dose schedule
7 (0,4%) patienter afbrød behandlingen midlertidigt, og 2 (0,1%) patienter fik nedsat dosis i forbindelse med synsforstyrrelser.
Seven (0.4%) patients had temporary treatment discontinuation and 2 (0.1%) patients had a dose reduction associated with vision disorder.
Behandlingen med crizotinib skal afbrydes, hvis der er mistanke om ILD/pneumonitis.
Crizotinib treatment should be withheld if ILD/pneumonitis is suspected.
Enten ALK-positiv eller ROS1-positiv NSCLC-status skal konstateres, inden behandling med crizotinib indledes.
Either ALK-positive or ROS1-positive NSCLC status should be established prior to initiation of crizotinib therapy.
• Pimozid, til behandling af psykisk sygdom.
• Pimozide, used to treat mental illness.
Ingen synsforstyrrelser i forbindelse med crizotinib syntes at være relateret til forandringer i bedst muligt korrigeret synsskarphed, i glaslegemet, i retina eller i synsnerven.
No visual disturbances associated with crizotinib appeared to be related to changes in best corrected visual acuity, the vitreous, the retina, or the optic nerve.
In vitro hæmmer crizotinib ikke de humane hepatiske transportproteiner organisk anion-transportpolypeptid (OATP) 1B1 og OATP1B3 eller de renale transportproteiner organisk anion-transporter (OAT) 1 eller OAT3 ved klinisk relevante koncentrationer.
In vitro, crizotinib did not inhibit the human hepatic uptake transport proteins organic anion transporting polypeptide (OATP)1B1 or OATP1B3 or the renal uptake transport proteins organic anion transporter (OAT)1 or OAT3 at clinically relevant concentrations.
• Hvis du på noget tidspunkt har haft mave- eller tarmproblemer som f.eks. huller (perforering), eller hvis du har lidelser, der giver betændelse i maven (divertikulitis), eller hvis du har kræft, der har bredt sig i maven (metastase).
• If you have ever had stomach or intestine problems such as holes (perforation), or if you have conditions causing inflammation inside the abdomen (diverticulitis), or if you have spread of cancer inside the abdomen (metastasis).
Der er begrænsede data tilgængelige i denne subgruppe af patienter (se pkt.
Limited data are available in this subgroup of patients (see sections 4.2 and 5.1).
b. Baseret på den stratificerede analyse efter Cox' proportionale risikomodel.
b. Based on the Cox proportional hazards stratified analysis.
• Delvist eller fuldstændigt synstab på et eller begge øjne Kontakt straks lægen, hvis du får synstab eller synsændringer såsom problemer med at se med et eller begge øjne.
• Partial or complete loss of vision in one or both eyes Tell your doctor right away if you experience any loss of vision or any change in vision such as difficulty seeing out of one or both eyes.
Andre fund inkluderer leverpåvirkning (stigning i levertransaminase), påvirkning af retinafunktion samt risiko for phospholipidose i flere organer uden korrelerende toksicitet.
Other findings included an effect on the liver (elevation of liver transaminases) and retinal function, and potential for phospholipidosis in multiple organs without correlative toxicities.
Mediantiden indtil grad 3 eller 4 aminotransferasestigninger var 43 dage.
Median time to onset of increased Grade 3 or 4 transaminases was 43 days.
Elektrolytforstyrrelser, dehydrering og bradykardi kan yderligere øge risikoen for QTc-forlængelse og derfor anbefales periodisk monitorering af ekg og elektrolytniveauer hos patienter med gastrointestinal tokcisitet (se pkt.
Electrolyte disturbances, dehydration and bradycardia may further increase the risk of QTc prolongation and thus, periodic monitoring of ECG and electrolyte levels is recommended in patients with GI toxicity (see section 4.4).
Niveauet for antallet af observerede bivirkninger (NOAEL - No Observed Adverse Effect Levels) var enten sub-terapeutisk eller op til 2,6 gange human klinisk eksponering baseret på AUC.
The No Observed Adverse Effect Levels (NOAEL) for these findings were either subtherapeutic or up to 2.6-fold human clinical exposure based on AUC.
k) Øsofagitis(øsofagitis, øsofageal ulcus).
k. Oesophagitis (Oesophagitis, Oesophageal ulcer).
Der var 17 (1%) patienter, hvor behandlingen måtte afbrydes permanent.
Seventeen (1%) patients required permanent discontinuation from treatment.
• Clarithromycin, telithromycin, erythromycin, antibiotika til behandling af infektioner med bakterier.
• Clarithromycin, telithromycin, erythromycin, antibiotics used to treat bacterial infections.
Den intrakranielle sygdomskontrolrate (Intracranial Disease Control Rate - IC-DCR) efter 12 uger var 65% og 46% for patienterne i henholdsvis crizotinib- og kemoterapi-armen.
Intracranial Disease Control Rate (IC-DCR) at 12 weeks was 65% and 46% for crizotinib and chemotherapy-treated patients, respectively.
• Hvis du har synsforstyrrelser (ser lysglimt, har sløret syn eller dobbeltsyn).
• If you have vision disorders (seeing flashes of light, blurred vision, and double vision).
I studie 1007 var den mediane behandlingsvarighed 48 uger for patienter i crizotinib-armen (N=172).
In Study 1007, the median duration of study treatment was 48 weeks for patients in the crizotinib arm (N=172).
Tid indtil forværring (TTD) var specificeret på forhånd som første forekomst af en stigning på ≥10 point i scorerne fra baseline for symptomer på smerter i brystet, hoste eller dyspnø ifølge EORTC QLQ-LC13.
Time to Deterioration (TTD) was prespecified as the first occurrence of a ≥10-point increase in scores from baseline in symptoms of pain in chest, cough, or dyspnoea as assessed by EORTC QLQ-LC13.
• Nedsat niveau af testosteron i blodet, et mandligt kønshormon.
• Decreased levels of testosterone, a male sex hormone.
Mediantid til neutropeni af en eller anden grad var 89 dage.
Median time to onset of any grade neutropenia was 89 days.
• Medicin mod forhøjet blodtryk, der kaldes beta-blokkere, fx atenolol, propranolol og labetolol.
• Medicines for high blood pressure called beta-blockers such as atenolol, propranolol, labetolol.
Baseret på den farmakokinetiske populationsanalyse af data fra studie 1001, 1005 og 1007 var det forventede areal under plasmakoncentrations-tids-kurven (AUCss) ved steady state (95% CI) 23%37% højere hos asiatiske patienter (N=523) end hos ikke-asiatiske patienter (N=691).
Based on the population pharmacokinetic analysis of data from Studies 1001, 1005 and 1007, the predicted area under the plasma concentration-time curve at steady-state (AUCss) (95% CI) was 23%-37% higher in Asian patients (N=523) than in non-Asian patients (N=691).
På baggrund af ikke-kliniske sikkerhedsdata kan mænds og kvinders fertilitet påvirkes af behandling med XALKORI (se pkt.
Based on nonclinical safety findings, male and female fertility may be compromised by treatment with XALKORI (see section 5.3).
Dosisjustering af crizotinib ifølge Child-Pugh klassifikation er ikke undersøgt hos patienter med nedsat leverfunktion.
Crizotinib dose adjustment according to Child-Pugh classification has not been studied in patients with hepatic impairment.
De mest almindelige fund vedrørte biomikroskopi med spaltelampe (21,1%), fundoskopi (15,8%) og synsskarphed (13,2%).
The most common findings concerned slit lamp biomicroscopy (21.1%), fundoscopy (15.8%) and visual acuity (13.2%).
Fortæl det straks til lægen, hvis du føler dig mere træt end normalt, får gulfarvning af hud eller øjne, mørkfarvning af urinen (tefarvet), kvalme, opkastning eller nedsat appetit eller smerter i højre side af maven, kløe eller hvis du lettere får blå mærker end du plejer.
Tell your doctor right away if you feel more tired than usual, your skin and whites of your eyes turn yellow, your urine turns dark or brown (tea colour), you have nausea, vomiting, or decreased appetite, you have pain on the right side of your stomach, you have itching, or if you bruise more easily than usual.
c. Baseret på den stratificerede log-rank-test (1-sidet).
c. Based on the stratified log-rank test (1-sided).
g) Bradykardi (bradykardi, nedsat hjertefrekvens, sinus bradykardi).
g. Bradycardia (Bradycardia, Heart rate decreased, Sinus bradycardia).
Patienter med lungesymptomer, der kan tyde på ILD/pneumonitis, skal observeres.
Patients with pulmonary symptoms indicative of ILD/pneumonitis should be monitored.
Hos 17 (1%) af patienterne måtte behandlingen afbrydes permanent i forbindelse med forhøjede aminotransferaser, hvilket tyder på, at disse tilfælde generelt kunne håndteres gennem dosisændringer som angivet i skema 2 (se pkt.
Seventeen (1%) patients required permanent discontinuation from treatment associated with elevated transaminases, suggesting that these events were generally manageable by dosing modifications as defined in Table 2 (see section 4.2).
• Hvis du oplever stærke smerter i maven eller underlivet, feber, kulderystelser, åndenød, hjertebanken, delvist eller fuldstændigt synstab (på et eller begge øjne) eller ændringer i afføringsmønstret.
• If you are experiencing severe stomach or abdominal pain, fever, chills, shortness of breath, fast heartbeat, partial or complete loss of vision (in one or both eyes) or changes in bowel habits.
Almindelige bivirkninger (kan forekomme hos 1 ud af 10 personer)
Common side effects (may affect up to 1 in 10 people)
Effektdata fra det randomiserede fase 3-studie 1014 er sammenfattet i skema 4, og Kaplan-Meier-kurverne for PFS og OS er vist i henholdsvis figur 1 og 2.
Efficacy data from randomised Phase 3 Study 1014 are summarised in Table 4, and the Kaplan-Meier curves for PFS and OS are shown in Figure 1 and 2, respectively.
Uomdannet crizotinib repræsenterede henholdsvis 53% og 2,3% af den administrede dosis i fæces og urin.
Unchanged crizotinib represented approximately 53% and 2.3% of the administered dose in faeces and urine, respectively.
Det bør bemærkes, at ingen patienter med SCC-histologi blev randomiseret til crizotinib-armen i studie 1007, og ingen patienter med SCC indgik i studie 1014 på grund af det pemtrexedbaserede regime, der blev brugt som komparator.
Of note, no patients with SCC histology were randomised in the crizotinib arm in Study 1007 and no patients with SCC were enrolled in Study 1014 due to pemetrexed-based regimen being used as a comparator.
Opkastning (51%) Diarré (54%) Kvalme (57%) Obstipation (43%) Abdominalsmerter
Vomiting (51%) Diarrhoea (54%) Nausea (57%) Constipation (43%) Abdominal painj
Hos patienter med nyligt opstået alvorligt synstab (bedst korrigeret synsskarphed på mindre end 6/60 på et eller begge øjne) skal behandlingen med crizotinib seponeres (se pkt.
In patients with new onset of severe visual loss (best corrected visual acuity less than 6/60 in one or both eyes), crizotinib treatment should be discontinued (see section 4.2).
Der må ikke indtages 2 doser på en gang for at kompensere for den glemte dosis.
Patients should not take 2 doses at the same time to make up for a missed dose.