natgillin/translations-raw huggingface dataset:
Endeligt volumen af rekonstitueret Empliciti i hætteglasset (inklusive den faste bloks volumen)
Final volume of reconstituted Empliciti in the vial (including volume displaced by the solid cake)
Elotuzumabs metaboliseringsvej er ikke klarlagt.
The metabolic pathway of elotuzumab has not been characterized.
Hvis oralt eller intravenøst administreret dexamethason udskydes, eller dexamethason seponeres, skal administration af Empliciti baseres på en klinisk vurdering (f.eks. risiko for overfølsomhed) (se pkt.
However, if oral or intravenous dexamethasone is delayed or discontinued, the administration of Empliciti should be based on clinical judgment (e.g. risk of hypersensitivity) (see section 4.4).
Fortæl det straks til lægen eller sundhedspersonalet, hvis du får en eller flere af de infusionsreaktioner, der er beskrevet i starten af afsnit 4.
Tell your doctor or nurse straight away if you get any of the infusion reactions listed at the top of section 4.
ISS-stadiet (The International Staging System) var I hos 43%, II hos 32% og III hos 21% af patienterne.
The International Staging System (ISS) Stage was I in 43%, II in 32% and III in 21% of patients.
Lægen vil muligvis overveje at nedsætte infusionshastigheden for Empliciti eller afbryde infusionen for at behandle symptomerne.
Your doctor may consider slowing the Empliciti infusion or interrupting it to manage these symptoms.
SLAMF7 er overudtrykt på myelomceller uafhængigt af cytogenetiske abnormiteter.
SLAMF7 is highly expressed on multiple myeloma cells independent of cytogenetic abnormalities.
Kvinder i den fertile alder/Kontraception hos mænd og kvinder Empliciti bør ikke anvendes til kvinder i den fertile alder, medmindre kvindens kliniske tilstand nødvendiggør behandling med elotuzumab.
Woman of childbearing potential/Contraception in the males and females Empliciti should not be used in women of childbearing potential, unless the clinical condition of the woman requires treatment with elotuzumab.
Empliciti anvendes sammen med anden medicin mod myelomatose.
Empliciti is used in combination with other medicines for multiple myeloma.
SLAMF7 findes i store mængder på overfladen af myelomatoseceller og på bestemte celler i immunsystemet (naturlige dræberceller).
SLAMF7 is found in large amounts on the surface of multiple myeloma cells and on certain cells of your immune system (natural killer cells).
Beskrivelse af undergrupper
Subset description
Når elotuzumab binder sig til SLAMF7 på myelomatoseceller eller naturlige dræberceller, stimulerer det immunsystemet til at angribe og ødelægge myelomatosecellerne.
When elotuzumab binds to SLAMF7 on the multiple myeloma or natural killer cells, it stimulates your immune system to attack and destroy the multiple myeloma cells.
Hold hætteglasset lodret og bland koncentratet ved at rotere hætteglasset for at opløse den lyofiliserede blok.
Hold the vial upright and swirl the solution by rotating the vial to dissolve the lyophilised cake.
Bivirkninger, der blev rapporteret hos 682 patienter med myelomatose, som blev behandlet med elotuzumab i 8 kliniske forsøg, er vist i tabel 5.
Adverse reactions reported in 682 patients with multiple myeloma who were treated with elotuzumab in 8 clinical trials are presented in Table 5.
Empliciti er et IgG1-monoklonalt antistof, som primært elimineres via katabolisme.
Empliciti is an IgG1 monoclonal antibody, which is principally cleared by catabolism.
Kvinder i den fertile alder skal anvende sikker prævention.
Women of childbearing potential should use effective contraception.
Efter seponering af elotuzumab i kombination med lenalidomid og dexamethason eller i kombination med pomalidomid og dexamethason, vil koncentrationen af elotuzumab efter 3 måneder være faldet til ca. 3% (udvaskning på ca. 97% estimeret efter 5 halveringstider) af den populationsestimerede maksimale serumkoncentration ved steady-state.
Upon discontinuation of elotuzumab in combination with lenalidomide and dexamethasone or in combination with pomalidomide and dexamethasone, concentrations of elotuzumab will decrease to approximately 3% (approximately 97% washout as estimated by 5 half-lives) of the population predicted steady-state maximal serum concentration by 3 months.
Ud fra en mikrobiologisk betragtning bør infusionsvæsken anvendes straks.
From a microbiological point of view, the solution for infusion should be used immediately.
Patienter med lette eller moderate infusionsreaktioner kan få Empliciti ved en reduceret infusionshastighed og under tæt monitoring (se pkt.
Patients with mild or moderate infusion reactions may receive Empliciti with a reduced infusion rate and close monitoring (see section 4.2 Method of administration).
Elotuzumab er et immunstimulerende humaniseret IgG1-monoklonalt antistof specifikt rettet imod SLAMF7-proteinet (nummer 7 i familien af signalerende lymfocytaktiverende molekyler).
Elotuzumab is an immunostimulatory humanised, IgG1 monoclonal antibody that specifically targets the SLAMF7 (signaling lymphocyte activation molecule family member 7) protein.
Demografiske data og karakteristika ved baseline var velafbalanceret de to behandlingsarme imellem.
Demographics and baseline characteristics were well balanced between treatment arms.
Figur 3: CA204125 Progressionsfri overlevelse ifølge investigator
Figure 3: CA204125 Progression free survival per investigator
Blodpropper i venerne (trombose) Smertefuldt hududslæt med blærer (helvedesild, zoster) Nattesved
Blood clots in the veins (thrombosis) Painful skin rash with blisters (shingles, zona) Night sweats
Empliciti er kun til engangsbrug.
Empliciti is for single use only.
Demografiske data og karakteristika ved baseline var afbalanceret mellem de to behandlingsarme.
Demographics and baseline characteristics were balanced between treatment arms.
Elotuzumab aktiverer naturlige dræberceller direkte via både SLAMF7 og Fc-receptorer og øger derved anti-myelom-aktiviteten in vitro.
Elotuzumab directly activates natural killer cells through both the SLAMF7 pathway and Fc receptors enhancing anti-myeloma activity in vitro.
Efter rekonstitution indeholder en ml koncentrat 25 mg elotuzumab.
After reconstitution, each mL of concentrate contains 25 mg elotuzumab.
Patienter var refraktære hvis de havde oplevet progression indenfor 60 dages behandling med lenalidomid og en PI og indenfor 60 dage før, eller på, den sidste behandlingsdag, eller recidiveret og refraktær hvis de som minumum havde opnået et partielt respons på tidligere behandling med lenalidomid og en PI men oplevede progression indenfor 6 måneder og havde udviklet sygdom indenfor 60 dage før, eller på, den sidste behandlingsdag.
Patients were refractory if they had progressed on or within 60 days of treatment with lenalidomide and a PI and on or within 60 days of their last treatment, or relapsed and refractory if they had achieved at least a partial response to previous treatment with lenalidomide and a PI but progressed within 6 months and had developed progressive disease on or within 60 days after completing their last treatment.
Hvis der igen opstår infusionsreaktioner, skal infusionen afbrydes og må ikke genoptages samme dag (se pkt.
If the infusion reaction recurs, the Empliciti infusion must be stopped and not restarted on that day (see section 4.4).
Farven på flip-off-låget er elfenbensfarve for 300 mg styrken og blå for 400 mg styrken.
The flip-off seal button colour is ivory for the 300 mg presentation and blue for the 400 mg presentation.
Elotuzumabs geometriske, gennemsnitlige totale clearance ved 10 mg/kg (i kombination med lenalidomid og dexamethason) ved steady state er 0,194 l/dag (CV: 62,9%).
The geometric mean total clearance of elotuzumab at 10 mg/kg (in combination with lenalidomide and dexamethasone) at steady state is 0.194 L/day (CV: 62.9%).
Tabel 10: CA204125 Effektresultater
Table 10: CA204125 Efficacy results
Da elotuzumab er et IgG-monoklonalt antistof, forventes det at blive nedbrudt til små peptider og aminosyrer via katabolisme.
As an IgG monoclonal antibody, elotuzumab is expected to be degraded into small peptides and amino acids via catabolic pathways.
Populationsfarmakokinetisk analyse tyder på, at følgende faktorer ikke havde nogen klinisk signifikant effekt på elotuzumab-clearance: alder, køn, race, baseline LDH, albumin, nedsat nyrefunktion, let nedsat leverfunktion og samtidig administration med lenalidomid/dexamethason eller pomalidomid/dexamethason.
Population PK analysis suggested that the following factors had no clinically important effect on the clearance of elotuzumab: age, gender, race, baseline LDH, albumin, renal impairment, mild hepatic impairment, and coadministration with lenalidomide/dexamethasone or pomalidomide/dexamethasone.
Meget alvorlige infusionsreaktioner (≥ grad 3) kan kræve permanent seponering af Empliciti og akut behandling.
Very severe infusion reactions (≥ Grade 3) may require permanent discontinuation of Empliciti therapy and emergency treatment.
Median PFS pr. ITT var 10,25 måneder (95% CI: 5,59; NE [ikke estimerbar]) i E-Pd-armen og 4,67 måneder (95% CI: 2,83; 7,16) i Pd-armen.
The median PFS per ITT was 10.25 months (95% CI: 5.59, NE) in the E-Pd arm and 4.67 months (95% CI: 2.83, 7.16) in the Pd arm. PFS and ORR were also assessed by the IRC.
p værdi for stratificeret log-rank testa PFS-rate ved år 1 (%) [95% CI] PFS-rate ved år 2 (%) [95% CI] PFS-rate ved år 3b (%) [95% CI] Median PFS i måneder [95% CI]
Stratified log-rank test p-valuea 1-Year PFS rate (%) [95% CI] 2-Year PFS rate (%) [95% CI] 3-Year PFS rateb(%) [95% CI] Median PFS in months [95% CI]
Der er rapporteret om infusionsreaktioner hos patienter, der har fået elotuzumab (se pkt.
Infusion reaction Infusion reactions have been reported in patients receiving elotuzumab (see section 4.8).
Vend herefter hætteglasset på hovedet et par gange for at opløse eventuelt pulver i toppen af hætteglasset eller i proppen.
Then invert the vial a few times in order to dissolve any powder that may be present on top of the vial or the stopper.
Behandlingen blev administreret i 4-ugers cyklusser (28-dages cyklus) indtil sygdomsprogression eller uacceptabel toksicitet.
Treatment was administered in 4-week cycles (28-day cycle) until disease progression or unacceptable toxicity.
Behandlingen blev administreret i 4-ugers cyklusser indtil sygdomsprogression eller uacceptabel toksicitet.
Treatment was administered in 4-week cycles until disease progression or unacceptable toxicity.
De hyppigste bivirkninger (hos > 10% af patienterne) ved elotuzumab-behandling var infusionsrelaterede reaktioner, diarre, herpes zoster, nasofaryngitis, hoste, pneumoni, infektion i de øvre luftveje, lymfopeni og vægttab.
The most common adverse reactions (occurring in > 10% of patients) with elotuzumab treatment were infusion related reactions, diarrhoea, herpes zoster, nasopharyngitis, cough, pneumonia, upper respiratory tract infection, lymphopenia and weight decreased.
Hud og subkutane væv Nattesved
Skin and subcutaneous tissue disorders
Rater for komplet respons i Empliciti-gruppen kan være undervurderet på grund af interferens mellem det monoklonale antistof elotozumab og immunfikseringsanalyse og serumprotein elektroforeseanalyse.
Complete response rates in Empliciti group may be underestimated due to interference of elotuzumab monoclonal antibody with immunofixation assay and serum protein electrophoresis assay.
Af de 53 patienter i CA204125 som blev behandlet med Empliciti og analyseret for forekomst af antistoffer mod lægemidlet, blev 19 patienter (36%) testet positive, hvoraf 1 patient blev testet persisterende positiv, for antistoffer mod lægemidlet dannet i forbindelse med behandlingen ved hjælp af en elektrokemiluminescensanalyse (ECL).
Of the 53 patients in CA204125 treated with Empliciti and evaluable for the presence of anti-product antibodies, 19 patients (36%) tested positive, of whom 1 patient tested persistent positive, for treatment-emergent anti-product antibodies by an ECL assay.
Investigatorvurderet
Investigator Assessed
Elotuzumab udviser non-lineær farmakokinetik med fald i clearance ved stigende doser fra 0,5-20 mg/kg.
Elotuzumab exhibits nonlinear PK with decrease in clearance with increase in dose from 0.5-20 mg/kg.
Elotuzumab er også specifikt rettet mod SLAMF7 på myelomceller og gennem interaktioner med Fc-receptorer på specifikke immunceller, fremmer drab af myelomceller via NK-celle-medieret antistofafhængig cellulær cytotoksicitet (ADCC) og makrofag-medieret antistofafhængig cellulær fagocytose (ADCP).
Elotuzumab also targets SLAMF7 on myeloma cells and through interactions with Fc receptors on specific immune cells, promotes the killing of myeloma cells through NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and macrophage-mediated antibody-dependant cellular phagocytosis (ADCP).
Tidsinterval
Time interval
Når reaktionen er aftaget (symptomer ≤ grad 1), kan Emplicitiinfusionen genoptages med en initial infusionshastighed på 0,5 ml/min.
Once the reaction has resolved (symptoms ≤ Grade 1), Empliciti can be restarted at the initial infusion rate of 0.5 mL/min.
Behandling med elotuzumab skal initieres og superviseres af speciallæger med erfaring i behandling af myelomatose.
Elotuzumab therapy should be initiated and supervised by physicians experienced in the treatment of multiple myeloma.
Hvis du har glemt at få en dosis Empliciti
If you miss a dose of Empliciti
Forekomsten af hæmatologiske maligniteter var den samme i de to behandlingsarme.
The rate of haematologic malignancies was the same between the two treatment arms.
Nasofaryngitis 151 29,5 Øvre luftvejsinfektio n
Nasopharyngitis 151 29.5 Upper respiratory tract infection
Meget alvorlige infusionsreaktioner kan nødvendiggøre permanent seponering af Empliciti og akut behandling.
Very severe infusion reactions may require permanent discontinuation of Empliciti therapy and emergency treatment.
I kliniske forsøg med patienter med myelomatose var forekomsten af alle infektioner, inklusive pneumoni, højere hos patienter, der blev behandlet med Empliciti (se pkt.
In clinical trials of patients with multiple myeloma, the incidence of all infections, including pneumonia, were higher in patients treated with Empliciti (see section 4.8).
[5,59; NE (ikke estimerbar)]
[5.59, NE]
Beregn dosis (mg) og fastlæg antallet af hætteglas, der er nødvendigt til en dosis (10 mg/kg eller 20 mg/kg), baseret på patientens kropsvægt.
Calculate the dose (mg) and determine the number of vials needed for the dose (10 mg/kg or 20 mg/kg) based on patient weight.
Hvis du holder op med at få Empliciti
If you stop using Empliciti
Brug af anden medicin sammen med Empliciti Fortæl det altid til lægen, hvis du tager anden medicin eller har gjort det for nylig.
Other medicines and Empliciti Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Empliciti pulver til koncentrat til infusionsvæske (pulver til koncentrat) er hvidt til råhvidt i en hel eller fragmenteret blok i et hætteglas.
Empliciti powder for concentrate for solution for infusion (powder for concentrate) is a white to off white whole or fragmented cake provided in a glass vial.
Tidligere behandlinger inkluderede stamcelletransplantation (55%), bortezomib (70%), melphalan (65%), thalidomid (48%) og lenalidomid (6%).
Prior therapies included: stem cell transplant (55%), bortezomib (70%) melphalan (65%), thalidomide (48%), and lenalidomide (6%).
Øvrige indholdsstoffer: saccharose, natriumcitrat (se afsnit 2 “Empliciti indeholder natrium”), citronsyremonohydrat og polysorbat 80.
The other ingredients (excipients) are sucrose, sodium citrate (see section 2 “Empliciti contains sodium”), citric acid monohydrate, and polysorbate 80.
Af 390 patienter i fire kliniske studier, som blev behandlet med Empliciti og analyseret for forekomst af antistoffer mod lægemidlet, blev 72 patienter (18,5%) testet positive for antistoffer mod lægemidlet dannet i forbindelse med behandlingen ved hjælp af en elektrokemiluminescensanalyse (ECL).
Of 390 patients across four clinical studies who were treated with Empliciti and evaluable for the presence of anti-product antibodies, 72 patients (18.5%) tested positive for treatment-emergent anti-product antibodies by an electrochemiluminescent (ECL) assay.
Allergiske reaktioner (overfølsomhed) Smerter i munden/halsen/ondt i halsen
Decreased sensitivity, especially in the skin Allergic reactions (hypersensitivity) Pain in the mouth/throat region/sore throat
Efter rekonstitution og fortynding Det rekonstituerede koncentrat skal straks overføres fra hætteglasset til infusionsposen.
After reconstitution and dilution The reconstituted solution should be transferred from the vial into the infusion bag immediately.
Empliciti-infusionsvæsken skal administreres via et infusionssæt og et sterilt pyrogenfrit filter med lav proteinbinding (porestørrelse 0,2 μm til 1,2 μm) ved hjælp af en automatisk infusionspumpe.
The entire Empliciti infusion should be administered with an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (with a pore size of 0.2-1.2 µm) using an automated infusion pump.
Pulveret er hvidt til råhvidt i en hel eller fragmenteret blok.
The powder is white to off white whole or fragmented cake.
Når reaktionen er aftaget til ≤ grad 1, kan Empliciti-infusionen genoptages ved 0,5 ml/min og infusionshastigheden gradvist øges med 0,5 ml/min hvert 30. minut afhængigt af, hvordan det tåles, op til hastigheden, hvor infusionsreaktionen opstod.
Upon resolution to ≤ Grade 1, Empliciti should be restarted at 0.5 mL/min and may be gradually increased at a rate of 0.5 mL/min every 30 minutes as tolerated to the rate at which the infusion reaction occurred.
Hvis symptomerne ikke opstår igen, kan infusionshastigheden gradvist øges hvert 30. minut til højst 5 ml/min (se pkt.
If symptoms do not recur, the infusion rate may be gradually escalated every 30 minutes to a maximum of 5 mL/min (see section 4.2 Method of administration).
På dage, hvor Empliciti ikke administreres, men hvor der er planlagt en dosis dexamethason (dag 8 og 22 i cyklus 3 og alle efterfølgende cyklusser), gives 40 mg dexamethason oralt.
On days that Empliciti is not administered but a dose of dexamethasone is scheduled (Days 8 and 22 of cycle 3 and all subsequent cycles), dexamethasone should be given 40 mg orally.
IRC-vurderet f
IRC Assessedf
Diarre
Diarrhoea
4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen Infusionsreaktioner
4.4 Special warnings and precautions for use
Patienter hvor dosis er øget til 5 ml/min ved 10 mg/kg skal hastigheden nedsættes til 3 ml/min ved første infusion ved 20 mg/kg.
Patients who have escalated to 5 mL/min at 10 mg/kg dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg.
PFS (ITT) Hazard Ratio [95% CI] p-værdi for log-rank testa Median PFS i måneder [95% CI]
PFS (ITT) Hazard Ratio [95% CI] Stratified log-rank test p-valuea Median PFS in months [95% CI]
I cyklus 3 og derefter, en gang hver anden uge på dag 1 og 15.
In cycles 3 and beyond, once every 2 weeks on days 1 and 15.
Et hætteglas indeholder enten 300 mg eller 400 mg elotuzumab.
Each vial contains either 300 mg or 400 mg of elotuzumab.
Cyklus 1, Dosis 2
Cycle 1, Dose 2
Hvis den ikke anvendes straks, er opbevaringstid og og betingelser før brug brugerens ansvar og er normalt ikke mere end 24 timer ved 2°C - 8°C beskyttet mod lys.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C − 8°C protected from light.
Efter rekonstitution skal det rekonstituerede koncentrat straks overføres fra hætteglasset til infusionsposen.
After reconstitution, the reconstituted solution should be transferred from the vial to the infusion bag immediately.
Empliciti-infusionsvæsken bør anvendes straks.
The Empliciti infusion should be used immediately.
Fremskridt i PFS var konsistent på tværs af forsøgspersonerne uanset alder (< 65 versus ≥ 65), risikostatus, med eller uden tilstedeværelse af del17p eller t(4;14) (høj cytogenetisk risiko), ISS-stadium, antal tidligere behandlinger, tidligere immunmodulerende eksponering, tidligere bortezomib-eksponering, recidiverende eller refraktær status og nyrefunktion.
Improvements observed in PFS were consistent across subsets regardless of age (< 65 versus ≥ 65), risk status, presence or absence of cytogenetic categories del17p or t(4;14), ISS stage, number of prior therapies, prior immunomodulatory exposure, prior bortezomib exposure, relapsed or refractory status or renal function as shown in Table 9.
Der blev ikke fundet klinisk signifikante forskelle i elotuzumabs farmakokinetik mellem patienter med svært nedsat nyrefunktion (med og uden dialyse) og patienter med normal nyrefunktion (se pkt.
No clinically important differences in the pharmacokinetics of elotuzumab were found between patients with severe renal impairment (with and without dialysis) and patients with normal renal function (see section 4.2).
Dosisjustering af Empliciti er ikke nødvendig hos patienter med let (CrCl = 60-89 ml/min), moderat (CrCl = 30-59 ml/min), svært (CrCl < 30 ml/min) nedsat nyrefunktion eller terminal nyresygdom, der kræver dialyse (se pkt.
No dose adjustment of Empliciti is required for patients with mild (CrCl = 60 - 89 mL/min), moderate (CrCl = 30 - 59 mL/min), severe (CrCl < 30 mL/min) renal impairment or end stage renal disease requiring dialysis (see section 5.2).
Dosering ved administration sammen med lenalidomid og dexamethason Varigheden for hver behandlingscyklus er 28 dage, se doseringsskemaet i tabel 1.
Posology for administration with lenalidomide and dexamethasone The length of each treatment cycle is 28 days, see Table 1 for the dosing schedule.
Elotuzumabs geometriske, gennemsnitlige fordelingsvolumen ved det anbefalede doseringsregime i kombination med lenalidomid/dexamethason eller pomalidomid/dexamethason ved steady state er henholdsvis 5,7 l (CV: 23%) og 5,6 l (CV: 21%).
The geometric mean volume of distribution of elotuzumab at the recommended dosing regimen in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone at steady state is 5.7 L (CV: 23%) and 5.6 L (CV: 21%) respectively.
Bland forsigtigt infusionvæsken ved at bevæge posen manuelt.
Gently mix the infusion by manual rotation.
Disse celler deler sig ukontrolleret og ophobes i knoglemarven, hvilket medfører knogleskader og nyreskader.
These cells divide out of control and collect in the bone marrow.
Cyklus 1, Dosis 1
Cycle 1, Dose 1
Når Empliciti gives sammen med lenalidomid eller pomalidomid, skal du følge instruktionerne for graviditetsforebyggelse for henholdsvis lenalidomid eller pomalidomid (se indlægssedlen for lenalidomid eller pomalidomid).
When Empliciti is given in combination with lenalidomide or pomalidomide, you must follow the pregnancy prevention programme for lenalidomide or pomalidomide respectively (see package leaflet for lenalidomide or pomalidomide).
Du skak bruge kondom, mens du er i behandling med Empliciti og i 180 dage efter, du er stoppet med behandlingen.
You should use a condom while taking Empliciti and for 180 days after stopping treatment to ensure your partner does not become pregnant.
HR (95% CI): 0,54 (0,34; 0,86) p-værdi: 0,0078
HR (95% CI): 0.54 (0.34, 0.86) p-value: 0.0078
FISH af del(17p), t(4;14) og t(14;16) var tilstede hos henholdsvis 5%, 11% og 7% af patienterne.
The chromosomal abnormalities as determined by the FISH of del(17p), t(4;14) and t(14;16) were present in 5%, 11%
Elotuzumabs farmakokinetik blev undersøgt hos patienter med myelomatose.
The pharmacokinetics (PK) of elotuzumab was studied in patients with multiple myeloma.
21,4 [16,6; NE (ikke estimerbar)]
21.4 [16.6, NE]
Dosering ved administration sammen med pomalidomid og dexamethason Varigheden for hver behandlingscyklus er 28 dage, se doseringsskemaet i tabel 2.
Posology for administration with pomalidomide and dexamethasone The length of each treatment cycle is 28 days, see Table 2 for the dosing schedule.