natgillin/translations-raw huggingface dataset:
En analyse udført med humant plasma til bestemmelse af omfanget af plasmaproteinbinding af ikkeradioaktiv forbindelse (lutetium (175Lu)-oxodotreotid), viste at ca. 50 % af forbindelsen er bundet til plasmatiske proteiner.
An analysis performed with human plasma to determine the extent of plasma protein binding of non-radioactive compound (lutetium (175Lu) oxodotreotide) showed that about 50% of the compound is bound to plasmatic proteins.
Det er et radiofarmaceutisk lægemiddel, som er klar til brug og kun er beregnet til engangsbrug.
It is a ready to use radiopharmaceutical medicinal product for single use only.
− Antiemetika
− Antiemetics
Disse resultater understøttes af in vitro-metabolismedata i humane hepatocytter, hvor der ikke observeredes nogen metabolisk nedbrydning af lutetium (175Lu)-oxodotreotid.
These finding are supported by in vitro metabolism data in human hepatocytes, in which no metabolic degradation of lutetium (175Lu) oxodotreotide was observed.
Det skal du vide, før du får Lutathera 3.
What you need to know before Lutathera is used 3.
En patient med en eller flere af nedenstående sygdomme er mere tilbøjelig til at udvikle bivirkninger.
A patient presenting with any of the conditions below is more prone to develop adverse reactions.
Øre og labyrint
Ear and labyrinth
Ved svær kvalme eller opkastning under infusion af aminosyreopløsning kan der administreres antiemetika med forskellige farmakologisk klassificeringer.
In case of severe nausea or vomiting during amino acid solution infusion, an antiemetic of a different pharmacological class can be administered.
Nedenstående tabeller opsummerer de påkrævede procedurer under behandlingsformen med Lutathera vha. gravitationsmetoden:
The following table summarises the required procedures during a treatment course with Lutathera using the gravity method:
- Hvis du lider af urininkontinens - Hvis du har mild til moderat kronisk nyresygdom - Hvis du tidligere har modtaget kræftbehandling (kemoterapi) - Hvis du har mildt ændrede blodlegemer - Hvis du har knoglemetastase - Hvis du tidligere har modtaget radionuklidbehandling - Hvis du har haft en anden form for kræft inden for de seneste 5 år
- if you have mild to moderate chronic kidney disease - if you previously received anti-cancer treatment (chemotherapy) - if you have mildly altered blood cell counts - if you have bone metastasis - if you have previously received any radionuclide therapy - if you had other type of cancer within last 5 years
Kriterier for permanent seponering af behandling med Lutathera
Criteria for permanent discontinuation of treatment with Lutathera
Denne medicin indeholder 0,14 mmol (3,2 mg) natrium pr. ml.
This medicine contains 0.14 mmol (3.2 mg) of sodium per mL.
Aktivitet ved infusionstid: {Z} MBq - {DD/MM/ÅÅÅÅ tt: mm UTC}
Activity at infusion time: {Z} MBq - {DD/MM/YYYY hh:mm UTC}
− Et kalibreret radioaktivitetsmålingssystem og en Geiger-tæller til monitorering af Lutatheraradioaktivitet
− Calibrated radioactivity measurement system and Geiger counter to monitor the radioactivity of Lutathera
Brug af anden medicin sammen med Lutathera Informer din nuklearmedicinske læge, hvis du tager, for nylig har taget eller måske tager anden medicin, herunder somatostatinanaloger og glukokortikosteroider (også kaldet kortikosteroider), eftersom de kan påvirke din behandling.
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other medicines including somatostatin analogues, glucocorticoids (also called corticosteroids), since they may interfere with your treatment.
Umiddelbart efter påbegyndt infusion skal den radioaktive udstråling over patientens thorax måles ved hjælp af en Geiger-tæller for at bekræfte tilstedeværelsen af Lutathera i blodbanen.
Soon after the start of the infusion, the radioactivity emission over the patient's thorax should be measured using Geiger counter to verify the presence of Lutathera in the bloodstream.
11 Inkluderer reaktion på injektionsstedet, hypersensibilitet på injektionsstedet, induration på injektionsstedet, hævelse af injektionsstedet * Forhøjet gammaglutamyltransferase ** Alaninaminotransferase *** Aspartataminotransferase **** Alkalisk phosphatase
11 Includes injection site reaction, injection site hypersensibility, injection site induration, injection site swelling * Gamma-glutamyltransferase increased **Alanine amino transferase *** Aspartate amino transferase **** Alkaline phosphatase
Procedure for administration af antiemetisk aminosyreopløsning og Lutathera
Administration procedure of antiemetic amino acid solution and Lutathera
Atrieflimren Palpitationer Myokardieinfarkt Angina pectoris Kardiogent shock
Atrial fibrillation Palpitations Myocardial infarction Angina pectoris Cardiogenic shock
Lungebetændelse Herpes zoster Oftalmisk herpes zoster Influenza
Herpes zoster Ophthalmic herpes zoster Influenza
Absorberede dosisestimater for lutetium (177Lu)-oxodotreotid fra NETTER-1 fase IIIstudiet (Olinda-output)
Absorbed dose estimates for lutetium (177Lu) oxodotreotide from NETTER-1 phase III study (Olinda output)
Følgende behandlingsformer anbefales i tilfælde af hormonforstyrrelser: Høj dosis af intravenøse somatostatinanaloger, intravenøse væsker, kortikosteroider og korrektion af elektrolytforstyrrelser hos patienter med symptomer på diarré og/eller opkastning.
In case of hormonal crises, recommended treatments are: intravenous high dose somatostatin analogues, intravenous fluids, corticosteroids, and correction of electrolyte disturbances in patients with diarrhoea and/or vomiting.
Lutetium (177Lu) henfalder ved β--emission til stabil Hafnium (177Hf) med den mest dominerende β- (79,3 %) i besiddelse af en maksimal energi på
Lutetium (177Lu) decays by β- emission to stable Hafnium (177Hf) with the most abundant β- (79.3%) having a maximum energy of 0.497 MeV.
Specifikationer
Specification
PFS-medianen for Lutathera var 28,4 måneder, mens den for octreotid LAR var 8,5 måneder.
The median PFS for Lutathera was 28.4 months whereas the one of octreotide LAR was 8.5 months.
NETTER 1 fase III-studiet var et multicenterbaseret stratificeret, åbent, randomiseret, sammenligningsstyret, parallelgruppestudie, der sammenlignede behandling med Lutathera (4 doser på 7.400 MBq hver 8. uge) co-administreret med aminosyreopløsning plus bedste støttende pleje (BSC: octreotid med langtidsvirkende frigivelse (LAR), 30 mg hver 4. uge til symptomkontrol, erstattet med korttidsvirkende octreotid i 4 -ugersintervallet inden administration af Lutathera) til høj dosis af octreotid (LAR) (60 mg hver 4. uge) hos patienter med inoperable, progressive, somatostatinreceptorpositive carcinoid-tumorer i midttarmen.
NETTER-1 phase III study was a multicentre stratified, open labelled, randomized, comparator-controlled, parallel-group study comparing treatment with Lutathera (4 doses of 7,400 MBq every 8 weeks) co-administered with amino acid solution plus best supportive care (BSC; octreotide long acting release [LAR] 30 mg every 4 weeks for symptoms control, replaced by short acting octreotide in the 4 weeks interval before Lutathera administration) to high dose octreotide LAR (60 mg every 4 weeks) in patients with inoperable, progressive, somatostatin receptor positive, midgut carcinoid tumours.
ORR (inklusive komplet respons (CR) og delvis respons (PR) ifølge RECIST-kriterier) og responsvarighed (DoR) for FAS-hollandsk population med gastroenteropankreatisk (GEP) og bronkiale NET (360 patienter) såvel som pr. tumortype er præsenteret i Tabel 10.
The ORR (including complete response (CR) and partial response (PR) according to RECIST criteria) and duration of response (DoR) for the FAS Dutch population with gastroenteropancreatic (GEP) and bronchial NETs (360 patients) as well as per tumour type are presented in Table 10.
Hvis den halve dosis er veltolereret (dvs. ingen gentagen forekomst af DMT), skal de næste, resterende administrationer fortsætte med fuld dosis (dvs. 7.400 MBq); men hvis
If the half dose is well tolerated (i.e. no DMT reoccurrence), the next remaining treatment administration(s) should continue with full dose (i.e. 7,400 MBq); but, if DMT recurs after treatment with a half dose, treatment with Lutathera must be definitively stopped.
• Hæmatologisk overvågning: Hvide blodlegemer, blodplader og hæmoglobin
• Hematologic monitoring: white blood cells, platelets, and haemoglobin
Gravitationsinfusionsmetode - slangeforbindelsesdiagram
Gravity infusion method - tubing connection scheme
Lutathera-infusion skal startes 30 minutter efter påbegyndt infusion af aminosyreopløsning med en infusionshastighed på ca. 400 ml/t (denne infusionshastighed er referencehastigheden og kan tilpasses afhængigt af patientens venøse status).
Lutathera infusion should start 30 minutes after the beginning of the amino acid solution infusion, with the infusion rate of approximately 400 mL/h (this infusion rate is the reference rate and can be adapted depending on the patient's venous status).
Den farmakokinetiske profil for lutetium (177Lu)-oxodotreotid hos patienter med svær nyrebeskadigelse (kreatinin-clearance < 30 ml/min) er ikke blevet undersøgt, og derfor er behandling af disse patienter med Lutathera kontraindiceret (se pkt.
The pharmacokinetic profile of lutetium (177Lu) oxodotreotide in patients with severe renal impairment (creatinine clearance < 30 mL/min) has not been studied, therefore treatment with Lutathera in those patients is contraindicated (see section 4.3).
Patienter med urininkontinens
Patients with urinary incontinence
Myelodisplastisk syndrom og akut leukæmi
Myelodisplastic syndrome and acute leukaemia
Administration af aminosyreopløsning skal startes 30 minutter før Lutathera-infusion med en infusionshastighed på 250-550 ml/t (afhængig af opløsningstype).
Administration of the amino acid solution should be initiated 30 minutes before Lutathera infusion, with an infusion rate of 250 to 550 mL/h (depending on the solution type).
Ved 4 timer efter indgift viser fordelingsmønsteret af lutetium (177Lu)-oxodotreotid en hurtig optagelse i nyrer, tumorlæsioner, lever og milt og hos nogle patienter i hypofysen og i skjoldbruskkirtlen.
Organ uptake At 4 hours after administration, the distribution pattern of lutetium (177Lu) oxodotreotide shows a rapid uptake in kidneys, tumour lesions, liver and spleen, and in some patients in the pituitary gland and in the thyroid.
Klar, farveløst type I-hætteglas, lukket med en brombutylgummiprop og aluminiumsforsegling.
Clear colourless Type I glass vial, closed with a bromobutyl rubber stopper and aluminium seal.
Med henblik på nyrebeskyttelsesformål skal en aminosyreopløsning administreres intravenøst i 4 timer.
For renal protection purpose, an amino acid solution must be administered intravenously during 4 hours.
På skæringsdatoen for den post-hoc statistiske analyse (30. juni 2016), var antallet af centralt konfirmerede sygdomsprogressioner eller dødsfald 30 hændelser i Lutathera-armen og 78 hændelser i octreotid LAR-armen (Tabel 9).
At the cut-off date for post-hoc statistical analysis (30 June 2016), the number of centrally confirmed disease progressions or deaths was 30 events in the Lutathera arm and 78 events in the octreotide LAR arm (Table 9).
Meldola (FC) Italien
Meldola (FC) Italy
Den visuelle inspektion skal udføres under en beskyttelsesafskærmning for at undgå radioaktiv stråling.
The visual inspection of the solution should be performed under a shielded screen for radioprotection purposes.
På tidspunktet for den endelige PFS statistiske analyse pr. protokol (skæringsdato den. 24 juli 2015), var antallet af centralt bekræftede sygdomsprogressioner eller dødsfald 21 hændelser i Lutatheraarmen og 70 hændelser i octreotid-LAR-armen (Tabel 8).
At the time of final per-protocol PFS statistical analysis (cut-off date 24 July 2015), the number of centrally confirmed disease progressions or deaths was 21 events in the Lutathera arm and 70 events in the octreotide LAR arm (Table 8).
Nyrefunktionen, bestemt i form af serum-kreatinin og beregnet kreatinin-clearance, skal vurderes ved baseline samt under og mindst et år efter behandlingen (se pkt.
Renal function as determined by serum creatinine and calculated creatinine clearance must be assessed at baseline, during and at least for the first year after treatment (see section 4.2).
• Den korte nål indsættes i Lutathera-hætteglasset, uden at komme i kontakt med den radiofarmaceutiske opløsning.
• The short needle should be inserted into the Lutathera vial, so that it does not touch the radiopharmaceutical solution.
Virkningsmekanisme Lutetium (177Lu)-oxodotreotid har en høj affinitet for somatostatinreceptorer af subtype 2 (sst2).
Mechanism of action Lutetium (177Lu) oxodotreotide has a high affinity for subtype 2 somatostatin receptors (sst2).
Muskuloskeletale smerter8 Muskelspasmer
Musculoskeletal pain8 Muscle spasms
Transchelering af lutetium fra lutetium (175Lu)-oxodotreotid i serumproteiner er ikke blevet observeret.
Transchelation of lutetium from lutetium (175Lu) oxodotreotide into serum proteins has not been observed.
CR = Komplet respons PR = Delvis respons; SD = Stabil sygdom ORR = Objektiv respons (CR + PR) DoR = Responsvarighed * Inkluderer fortarm, middttarm og bagtarm Midgut, **fortarms NET'er bortset fra bronkial og bugspytkirtel
CR = Complete response; PR = Partial response; SD = Stable disease; ORR = Objective response (CR+PR); DoR = Duration of response * Includes Foregut, Midgut and Hindgut; **Foregut NETs other than bronchial and pancreatic
Under behandling med Lutathera, og som minimum i de følgende 6 måneder efter afbrydelse af behandlingen, skal der træffes passende foranstaltninger for at undgå graviditet.
During treatment with Lutathera and for a minimum of the following 6 months after the end of the treatment, appropriate measures must be taken to avoid pregnancy; this applies to patients of both genders.
Svimmelhed Dysgeusi Hovedpine10
Dizziness Dysgeusia Headache10
Vær særlig forsigtig med Lutathera - Hvis din nyre eller urinveje ikke er korrekt udviklet
Take special care with Lutathera - if your kidney or urinary track are not correctly developed - if you are suffering from urinary incontinence
Det er ikke sandsynligt, at du vil få en overdosis, da du får en enkel dosis under kontrollerede forhold af den nuklearmedicinske læge, der har tilsyn med indgiften.
If you have been given more Lutathera than you should An overdose is unlikely because you will only receive a single dose of Lutathera precisely controlled by the nuclear medicine doctor supervising the administration procedure.
oxodotreotid via tubuli renales (nyrekanalerne), hvilket resulterer i en signifikant reduktion af nyrebestrålingsdosis (se pkt.
oxodotreotide through the proximal tubules, resulting in a significant reduction in the kidney radiation dose (see section 4.2).
Baseret på de data, der blev indsamlet i fase III-studierne i Erasmus fase I/II og NETTER-1, elimineres lutetium (177Lu)-oxodotreotid primært via udskillelse gennem nyrerne: ca. 60 % af lægemidlet udskilles i urinen inden for 24 timer og ca. 65 % inden for 48 timer efter indgift.
Based on the data collected during the Erasmus phase I/II and NETTER-1 phase III studies, lutetium (177Lu) oxodotreotide is primarily eliminated by renal excretion: about 60% of the medicinal product is eliminated in the urine within 24 hours, and about 65% within 48 hours following the administration.
Opløsningsniveauet i hætteglasset skal forblive konstant under hele infusionen.
The level of solution in the vial should remain constant during the entire infusion.
Den samlede mængde radioaktivitet pr. enkeltdosishætteglas er 7.400 MBq på infusionsdatoen ogtidspunktet.
The total amount of radioactivity per single dose vial is 7,400 MBq at the date and time of infusion.
Lutathera skal administreres via langsom intravenøs infusion i løbet af ca. 30 minutter ledsaget af aminosyreopløsning administreret via modsidig intravenøs infusion.
Lutathera must be administered by slow intravenous infusion over approximately 30 minutes, concomitantly with amino acid solution administered by contralateral intravenous infusion.
Administration af Lutathera skal påbegyndes ved først at åbne for slangeforbindelsen forbundet med det venøse kateter i patientens arm og derefter ved at åbne for infusionssættet forbundet med posen med natriumklorid 9 mg/ml (0,9 %) infusionsvæske, opløsning.
Lutathera administration should be initiated by opening first the tubing line connected to the patient's peripheral vein, and then, by opening the infusion set connected to the bag of sodium chloride 9 mg/mL (0.9%) solution for injection.
En konstant, indvendigt hætteglastryk skal opretholdes under hele infusionen.
Constant intra-vial pressure should be maintained during the entire infusion.
Administration af langtidsvirkende somatostatinanaloger bør undgås i 30 dage før administration af Lutathera.
Administration of long acting somatostatin analogues should be avoided within 30 days prior to the administration of Lutathera.
• Mild til moderat kronisk nyrelidelse med kreatinin-clearance ≥ 50 ml/min;
• Mild to moderate chronic kidney disease with creatinine clearance ≥ 50 mL/min;
Katetrene forbindes med infusionssættene (et sæt til administration af Lutathera, og et sæt til administration af aminosyreopløsning).
The catheters should be connected to the infusion sets (one for Lutathera, one for amino acid solution).
Lysinindhold
Lysine content
Nøje afvejning af den administrerede aktivitet er nødvendig hos sådanne patienter, da der er mulighed for øget strålingseksponering.
Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.
Lutathera skal altid injiceres via et intravenøst kateter anlagt udelukkende til infusion af dette.
Lutathera should always be infused through an intravenous catheter placed exclusively for its infusion.
Derfor bør gentagen administration af høje doser af glukokortikosteroider under behandling med Lutathera, undgås af sikkerhedshensyn.
Therefore, as a matter of cautiousness, repeated administration of high-doses of glucocorticosteroids should be avoided during Lutathera treatment.
For at sikre komplet administration skal der opretholdes et jævnt tryk i Lutathera-hætteglasset.
To ensure complete administration, the Lutathera vial should be kept under even pressure.
Konjunktivitis Luftvejsinfektion Cystitis
Conjunctivitis Respiratory tract infection Cystitis
Aminosyreopløsning skal administreres i løbet af et tidsrum på 4 timer.
Amino acid solution should be administered over 4 hour time span.
Det anbefales, at plejepersonalet bruger engangshandsker i 7 dage efter administrationen i forbindelse med assistance på badeværelset.
It is recommended that when providing assistance in the bathroom, the care provider wears disposable gloves for 7 days after administration.
Brug af Lutathera er kontraindiceret hos patienter med alvorlig nyresvigt (se pkt.
The use of Lutathera is contraindicated in patients with severe kidney failure (see section 4.3).
Analyser af højpræstationsvæskekromatografi (HPLC) udført på urinprøver indsamlet op til 48 timer efter infusion viste radiokemisk renhed af lutetium (177Lu)-oxodotreotid i nærheden af 100 % i de fleste analyserede prøver (hvor den laveste radiokemiske renhedsværdi var større end 92 %), hvilket indikerer, at forbindelsen hovedsageligt elimineres i urin som intakt forbindelse.
The high performance liquid chromatography (HPLC) analyses performed on urine samples collected up to 48 hours post infusion showed lutetium (177Lu) oxodotreotide radiochemical purity close to 100% in most of the analysed samples (with lowest radiochemical purity value being greater than 92%), indicating that the compound is eliminated in urine mainly as intact compound.
ANVENDELSESMÅDE OG ADMINISTRATIONSVEJ(E) Hætteglas med enkelt dosis.
METHOD AND ROUTE(S) OF ADMINISTRATION Single-dose vial.
Hvis hætteglassets integritet på noget tidspunkt brydes under klargøring af lægemidlet, må det ikke anvendes.
If at any time in the preparation of this medicinal product the integrity of this vial is compromised, it should not be used.
Fareforholdet for Lutathera var 0,18 (95 % CI: 0,11 - 0,29), hvilket indikerer 82 % reduktion i risikoen for, at en patient oplever progressin eller dør under Lutathera sammenlignet med octreotid LAR.
The hazard ratio for Lutathera was 0.18 (95% CI: 0.11 - 0.29), indicating 82% reduction in the risk for a patient to progress or die under Lutathera compared to octreotide LAR.
Under infusionen skal den radioaktive udstråling fra patientens thorax øges gradvist, mens infusionen fra Lutathera-hætteglasset reduceres.
During the infusion, the radioactivity emission from the patient's thorax should steadily increase while the one from the Lutathera vial should decrease.
Bronkial
Bronchial
Almindelig (kan påvirke op til 1 ud af 10 personer) Lavt antal hvide blodlegemer (leukopeni eller neutropeni), muskelsmerter, midlertidigt delvist hårtab (alopeci), abdominal distension (oppustethed), diarré, svimmelhed, reaktion på injektionsstedet eller hævelse, smagsforstyrrelser, smerte på injektionsstedet, hovedpine, højt eller lavt blodtryk, perifert ødem, unormale resultater af nyretest (forhøjet kreatinin), mavesmerter (generelt og øvre), forstoppelse, unormale resultater af levertest, rødme og hedeture, øget sukkerindhold i blod, besvimelse, nyresvigt (herunder akut skade), dehydrering, halsbrand (dyspepsi), blod i urinen, unormale urinprøveresutater (forekomst af serumproteiner), nedsat funktion af skjoldbruskkirtlen, åndenød, mavebetændelse (gastritis ), unormalt høje mængder galpigment (bilirubin) i blodet (hyperbilirubinæmi), unormale blodprøveresultater (hypomagnesæmi og hyponatriæmi), influenzalignende sygdom, kuldegysninger, knoglemarvscancer (myelodysplastisk syndrom), blodtransfusion.
Low white blood cell count (leukopenia or neutropenia), muscle pain, temporal partial hair loss (alopecia), abdominal distension (feeling bloated), diarrhoea, dizziness, injection site reaction or swelling, disturbed taste, pain in the site of injection, headache, high or low blood pressure, peripheral oedema, abnormal results of renal blood test (increased creatinine), abdominal pain (general and upper), constipation, abnormal results of liver blood test, flushing and hot flushes, increased sugar level in the blood, fainting, renal failure (including acute injury), dehydration, heartburn (dyspepsia), blood in urine, abnormal results of urine test (presence of serum proteins), decrease in function of thyroid, shortness of breath, inflammation of stomach (gastritis), abnormally high amounts of bile pigment (bilirubin) in the blood (Hyperbilirubinemia), abnormal results of blood test (Hypomagnesaemia and hyponatraemia), influenza like illness, chills, bone marrow cancer (myelodysplastic syndrome), blood transfusion.
Eddikesyre, natriumacetat, gentisinsyre, ascorbinsyre, pentinsyre, natriumchlorid 9 mg/ml injektion, natriumhydroxid, vand til injektionsvæsker.
Acetic acid, sodium acetate, gentisic acid, ascorbic acid, pentetic acid, sodium chloride 9 mg/mL injection, sodium hydroxide, water for injections.
Hvert hætteglas indeholder et volumen varierende fra 20,5 til 25,0 ml opløsning svarende til en aktivitet på 7.400 MBq på dato og tidspunkt for infusion.
Each vial contains a volume varying from 20.5 to 25.0 mL of solution corresponding to an activity of 7,400 MBq at date and time of infusion.
- Øvrige indholdsstoffer: Eddikesyre, natriumacetat, gentisinsyre, ascorbinsyre, diethylentriaminpentaeddikesyre (DTPA), natriumchlorid 9 mg/ml (0,9 %) injektionsvæske, opløsning, vand til injektionsvæsker (se afsnit 2 "Lutathera indeholder natrium ”).
- The other ingredients are: acetic acid, sodium acetate, gentisic acid, ascorbic acid, diethylene triamine pentaacetic acid (DTPA), sodium chloride 9 mg/mL (0.9%) solution for injection, water for injections (see section 2 “Lutathera contains sodium”).