natgillin/translations-raw huggingface dataset:
Grad 3- 4- mucositis blev rapporteret hos mindre end 1% af patienterne.
Grade 3-4 mucositis was reported in less than 1% of the patients.
Træthed/ asteni:
Fatigue/ Asthenia:
Grad 3- 4- træthed/ asteni forekom hos henholdsvis 9% og 1% af patienterne.
Grade 3-4 fatigue/ asthenia occurred in 9 and 1% of patients respectively.
Anoreksi:
Anorexia:
Grad 3- 4- anoreksi forekom hos mindre end 1% af patienterne.
Grade 3-4 anorexia occurred in less than 1% of the patients.
9 CPK- forhøjelser og rhabdomyolyse:
CPK elevations and rhabdomyolysis:
CPK- forhøjelser af en hvilken som helst grad blev observeret hos 26% af patienterne.
CPK elevations of any grade were observed in 26% of patients.
Grad 3 - eller 4- CPK- forhøjelser blev observeret hos 4% af patienterne.
Grade 3 or 4 increases of CPK were observed in 4% of patients.
CPK - forhøjelser associeret med rhabdomyolyse blev rapporteret hos mindre end 1% af patienterne.
CPK increases in association with rhabdomyolysis were reported in less than 1% of patients.
Dyspnø:
9 Dyspnoea:
Grad 3- 4- dyspnø rapporteret som relateret til trabectedin optrådte hos 2% af patienterne.
Grade 3-4 dyspnoea reported as trabectedin related occurred in 2% of the patients.
Alopeci:
Alopecia:
Heraf var størstedelen grad 1 - alopeci.
Alopecia was reported in approximately 3% of all patients, of which the majority was grade 1 alopecia.
Antineoplastisk middel, ATC- kode:
Antineoplastic agent, ATC code:
Trabectedin binder sig til DNA’ s minor groove og bøjer derved helixen til DNA’ s major groove.
Trabectedin binds to the minor groove of DNA, bending the helix to the major groove.
Denne binding til DNA udløser en kaskade af hændelser, der påvirker flere transskriptionsfaktorer, DNA- bindende proteiner og DNA- reparationsmekanismer, hvilket resulterer i forstyrrelse af cellecyklussen.
This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins, and DNA repair pathways, resulting in perturbation of the cell cycle.
Trabectedin har vist sig at udvise antiproliferativ in vitro og in vivo- aktivitet imod en række humane tumorcellelinier og eksperimentelle tumorer, herunder maligniteter såsom sarkomer, brystkræft, ikke- småcellet lungekræft, æggestokskræft og melanom.
Trabectedin has been shown to exert antiproliferative in vitro and in vivo activity against a range of human tumour cell lines and experimental tumours, including malignancies such as sarcoma, breast, non-small cell lung, ovarian and melanoma.
Virkningen og sikkerheden af trabectedin er baseret på et randomiseret forsøg med patienter med lokalt fremskredet eller metastatisk liposarkom eller leiomyosarkom, hvis sygdom havde udviklet sig eller var recidiveret efter behandling med antracykliner og ifosfamid som mindstekrav.
The efficacy and safety of trabectedin is based in a randomised trial in patients with locally advanced or metastatic liposarcoma or leiomyosarcoma, whose disease had progressed or relapsed after treatment with at least anthracyclines and ifosfamide.
I dette forsøg blev trabectedin indgivet enten ved 1, 5 mg/ m2 som en 24- timers intravenøs infusion hver 3. uge eller ved 0, 58 mg/ m2 ugentlig som en 3- timers intravenøs infusion i 3 uger i en cyklus på 4 uger.
In this trial trabectedin was administered either at 1.5 mg/ m2 as a 24-hour intravenous infusion every 3 weeks or at 0.58 mg/ m2 weekly as a 3-hour intravenous infusion for 3-weeks of a 4-week cycle.
0, 554- 0, 974).
The protocol specified final time to progression (TTP) analysis showed a 26.6% reduction in the relative risk of progression for patients treated in the 24-h q3wk group (Hazard Ratio = 0.734 CI 0.554-0.974).
Middel- TTP- værdier var 3, 7 måneder (CI:
Median TTP values were 3.7 months (CI:
2, 1- 5, 4 m) i 24- h q3wk- gruppen og 2, 3 måneder (CI:
2.1-5.4 m) in the 24-h q3wk group and 2.3 months (CI:
2, 0- 3, 5 m) i 3- h qwk- gruppen (p=0, 0302).
2.0-3.5 m) in the 3-h qwk group (p=0.0302).
Middel - OS med 24- h q3wk- regimet var 13, 9 måneder (CI:
Median OS with the 24-h q3wk regime was 13.9 months (CI:
12, 5- 18, 6), og 60, 2% af patienterne var i live ved 1 år (CI:
12.5-18.6) and 60.2% of patients were alive at 1 year (CI:
52, 0% - 68, 5%).
52.0-68.5%).
Yderligere effektdata er tilgængelige fra 3 enkelt- arm, fase II- forsøg med lignende populationer, behandlet med samme regime.
Additional efficacy data are available from 3 single-arm Phase II trials with similar populations treated with the same regime.
Disse forsøg evaluerede i alt 100 patienter med lipo - og leiomyosarkom og 83 patienter med andre typer sarkom.
These trials evaluated a total of 100 patients with lipo and leiomyosarcoma and 83 patients with other types of sarcoma.
10 Det europæiske Lægemiddelagentur (EMEA) vurderer hvert år ny information vedrørende produktet, og produktresuméet vil om nødvendigt blive opdateret.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
Systemisk eksponering efter administration som en 24- timers intravenøs infusion med konstant hastighed er dosisproportional ved doser op til og med 1, 8 mg/ m2.
10 Systemic exposure after administration as a 24 hour constant rate intravenous infusion is dose proportional at doses up to and including 1.8 mg/ m2.
Trabectedins farmakokinetiske profil er overensstemmende med en ” multiple- compartment ” dispositionsmodel.
Trabectedin pharmacokinetic profile is consistent with a multiple-compartment disposition model.
Efter intravenøs administration viser trabectedin et højt tilsyneladende distributionsvolumen i overensstemmelse med ekstensiv vævs - og plasmaproteinbinding (94% til 98% af trabectedin i plasma er proteinbundet).
Following intravenous administration, trabectedin demonstrates a high apparent volume of distribution, consistent with extensive tissue and plasma protein binding (94 to 98% of trabectedin in plasma is protein bound).
Trabectedins distributionsvolumen ved steady- state hos forsøgspersoner overskrider 5000 l.
The distribution volume at steady state of trabectedin in human subjects exceeds 5000 l.
Cytokrom P450 3A4 er det vigtigste cytokrom P450- isozym, der er ansvarlig for trabectedins oxidative metabolisme ved klinisk relevante koncentrationer.
Cytochrome P450 3A4 is the major cytochrome P450 isozyme responsible for the oxidative metabolism of trabectedin at clinically relevant concentrations.
Andre P450- enzymer kan medvirke til metaboliseringen.
Other P450 enzymes may contribute to metabolism.
Trabectedin hverken inducerer eller hæmmer væsentlige cytokrom P450- enzymer.
Trabectedin does not induce or inhibit major cytochrome P450 enzymes.
Den renale elimination af uændret trabectedin hos mennesker er lav (mindre end 1%).
Renal elimination of unchanged trabectedin in humans is low (less than 1%).
Den terminale halveringstid er lang (populationsværdien af den terminale eliminationsfase er 180 timer).
180-hr).
Efter at en dosis radiomærket trabectedin er indgivet til kræftpatienter, er den fækale middelgenindvinding (SD) af den totale radioaktivitet 58% (17%), og middelgenindvinding fra urinen (SD) er 5, 8% (1, 73%).
After a dose of radiolabelled trabectedin administered to cancer patients, faecal mean (SD) recovery of total radioactivity is 58% (17%), and urinary mean (SD) recovery is 5.8% (1.73%).
Baseret på populationsestimeringen for trabectedins plasmaclearance (31, 5 l/ t) og blod/ plasma- forhold (0, 89) er trabectedins clearance i fuldblod cirka 35 l/ t.
Based on the population estimate for plasma clearance of trabectedin (31.5 l/ h) and blood/ plasma ratio (0.89), the clearance of trabectedin in whole blood is approximately 35 l/ h.
Denne værdi er cirka halvdelen af det hepatiske blod- flow hos mennesker.
This value is approximately one-half the rate of human hepatic blood flow.
I populationsestimeringen for trabectedins plasmaclearance var variabiliteten patienterne imellem 51%, og variabiliteten hos den enkelte patient var 28%.
The inter-patient variability of the population estimate for plasma clearance of trabectedin was 51% and intra-patient variability was 28%.
En farmakokinetisk analyse af populationen viste, at trabectedins plasmaclearance hverken påvirkes af alder (i området 19- 83 år) eller køn.
A population pharmacokinetic analysis indicated that the plasma clearance of trabectedin is not influenced by age (range 19-83 years), or gender.
Virkningen af race og etnicitet på trabectedins farmakokinetik er ikke blevet undersøgt.
The effects of race and ethnicity on trabectedin pharmacokinetics have not been studied.
Nyrefunktionen, målt ved kreatininclearance, har ingen relevant indflydelse på trabectedins farmakokinetik inden for det område af værdier (≥ 34, 4 ml/ min), der er til stede hos patienter i de kliniske forsøg.
There is no relevant influence of renal function measured by creatinine clearance on trabectedin pharmacokinetics within the range of values (≥ 34.4 ml/ min) present in the patients included in the clinical studies.
Der er ingen tilgængelige data fra patienter, der viser en kreatininclearance på mindre end 34, 4 ml/ min.
No data are available in patients with a creatinine clearance of less than 34.4 ml/ min.
Den lave genindvinding (< 9% hos alle undersøgte patienter) af total radioaktivitet i urinen efter en enkelt dosis 14C- mærket trabectedin viser, at nedsat nyrefunktion kun har ringe indflydelse på eliminationen af trabectedin eller på dets metabolitter.
The low recovery (< 9% in all studied patients) of total radioactivity in the urine after a single dose of 14 C-labelled trabectedin indicates that renal impairment has little influence on the elimination of trabectedin or its metabolites.
Omhyggelig monitorering af toksicitet er derfor tilrådelig.
Although the population analysis showed no relationship between the serum liver enzymes concentrations and the plasma clearance of trabectedin, systemic exposure to trabectedin may be increased in patients with hepatic impairment; therefore close monitoring of toxicity is warranted.
De prækliniske data viser, at trabectedin har begrænset effekt på det kardiovaskulære og respiratoriske system og på centralnervesystemet ved eksponeringer under det terapeutiske, kliniske område (AUC - areal under kurve).
Preclinical data indicate that trabectedin has limited effect on the cardiovascular, respiratory and central nervous system at exposures below the therapeutic clinical range, in terms of AUC.
11 Virkningen af trabectedin på den kardiovaskulære og respiratoriske funktion er blevet undersøgt in vivo (bedøvede Cynomolgus- aber).
The effects of trabectedin on cardiovascular and respiratory function have been investigated in vivo (anesthetised Cynomolgus monkeys).
Der blev valgt en 1- times infusionsplan til at opnå maksimale plasmaniveauer (Cmax værdier) inden for de områder, der blev observeret på hospitalet/ klinikken.
A 1 hour infusion schedule was selected to attain maximum plasma levels (Cmax values) in the range of those observed in the clinic.
De opnåede niveauer af trabectedin i plasma var 10, 6 ± 5, 4 (Cmax) højere end de niveauer, der blev nået hos patienter efter infusion af 1500 μg/ m2 i 24 timer (Cmax på 1, 8 ± 1, 1 ng/ ml), og tilsvarende de niveauer der blev nået efter administration af samme dosis ved en 3- timers infusion (Cmax på 10, 8 ± 3, 7 ng/ ml).
The plasma trabectedin levels attained were 10.6 ± 5.4 (Cmax), higher than those reached in patients after infusion of 1500 μ g/ m2 for 24 (Cmax of 1.8 ± 1.1 ng/ ml) and similar to those reached after administration of the same dose by 3 hour infusion (Cmax of 10.8 ± 3.7 ng/ ml).
Myelosuppression og levertoksicitet blev identificeret som den primære toksicitet i forbindelse med trabectedin.
11 Myelosupression and hepatoxicity were identified as the primary toxicity for trabectedin.
Imidlertid skal der udvises forsigtighed i fortolkningen af disse renale fund, og behandlingsrelateret toksicitet kan ikke udelukkes.
These findings were secondary to severe local reaction at the administration site, and therefore uncertainly attributable to trabectedin; however, caution must be guaranteed in the interpretation of these renal findings, and treatment-related toxicity cannot be excluded.
Saccharose.
Sucrose.
Kaliumdihydrogenphosphat.
Potassium dihydrogen phosphate.
Phosphorsyre (til pH- justering).
Phosphoric acid (for pH-adjustment).
Kaliumhydroxid (til pH- justering).
Potassium hydroxide (for pH-adjustment).
6. 2 Uforligelighede
6.2 Incompatibilities
6. 6.
Yondelis must not be mixed or diluted with other medicinal products except those mentioned in section 6.6.
Efter rekonstituering er der påvist kemisk og fysisk stabilitet i 30 timer op til 25ºC.
After reconstitution, chemical and physical stability has been demonstrated for 30 hours up to 25ºC.
Hvis den ikke fortyndes og anvendes med det samme, er brugsfærdig opbevaringstid og forhold inden brugen af den rekonstituerede opløsning brugerens ansvar og vil normalt ikke være længere end 24 timer ved 2ºC - 8ºC, medmindre den er blevet rekonstitueret under kontrollerede og godkendte aseptiske forhold.
If not diluted and used immediately, in-use storage times and conditions prior to use of the reconstituted product are the responsibility of the user and would normally not be longer than 24 hours at 2ºC to 8ºC, unless reconstitution has taken place in controlled and validated aseptic conditions.
Efter fortynding er der påvist kemisk og fysisk stabilitet i 30 timer op til 25ºC.
After dilution, chemical and physical stability has been demonstrated for 30 hours up to 25ºC.
6. 4 Særlige opbevaringsforhold 12 Opbevares i køleskab (2ºC - 8ºC).
Store in a refrigerator (2ºC - 8ºC).
Yondelis leveres i et type I farveløst glashætteglas med bromobutyl gummiprop, dækket af en aluminium flip- off- forsegling.
12 Yondelis is supplied in a Type I colourless glass vial with a bromobutyl rubber stopper covered with an aluminium flip-off seal.
Hvert yderkarton indeholder ét hætteglas.
Each outer carton contains one vial.
Der skal anvendes passende aseptisk teknik.
Appropriate aseptic techniques must be used.
Yondelis skal rekonstitueres og yderlige fortyndes inden infusion.
Yondelis must be reconstituted and further diluted prior to infusion.
Hvert hætteglas med 0, 25 mg trabectedin rekonstitueres med 5 ml sterilt vand til injektioner.
Each vial containing 0.25 mg of trabectedin is reconstituted with 5 ml of sterile water for injections.
Den opløsning, der hermed opnås, har en koncentration på 0, 05 mg/ ml, og opløsningen er kun til engangsbrug.
The solution obtained has a concentration of 0.05 mg/ ml and is for single-use only.
Der anvendes en sprøjte til at injicere 5 ml sterilt vand til injektioner i hætteglasset.
A syringe is used to inject 5 ml of sterile water for injections into the vial.
Den rekonstituerede opløsning bliver til en klar, farveløs eller let gullig opløsning, i alt væsentligt fri for synlige partikler.
The reconstituted solution results in a clear, colourless or slightly yellowish solution, essentially free of visible particles.
Denne rekonstituerede opløsning indeholder 0, 05 mg/ ml trabectedin.
This reconstituted solution contains 0.05 mg/ ml of trabectedin.
Opløsningen skal fortyndes yderligere, og den er kun til engangsbrug.
It requires further dilution and is for single-use only
Den rekonstituerede opløsning fortyndes med natriumkloridopløsning 9 mg/ ml (0, 9%) til infusion eller med glukose 50 mg/ ml (5%) infusionsopløsning.
The reconstituted solution should be diluted with sodium chloride 9 mg/ ml (0.9%) solution for infusion or glucose 50 mg/ ml (5%) solution for infusion.
Volumen (ml) = BSA (m2) x individuel dosis (mg/ m2) 0, 05 mg/ ml
Volume (ml) = BSA (m2) x individual dose (mg/ m2) 0.05 mg/ ml
Hvis indgiften skal foretages via et centralt venekateter, trækkes den passende mængde rekonstitueret opløsning op fra hætteglasset og overføres til en infusionspose indeholdende ≥ 50 ml fortyndingsmiddel (natriumklorid 9 mg/ ml (0, 9%) infusionsopløsning eller glukose 50 mg/ ml (5%) infusionsopløsning), så infusionsopløsningens trabectedinkoncentration er ≤ 0, 030 mg/ ml.
If administration is to be made through a central venous line, the appropriate amount of reconstituted solution should be withdrawn from the vial and added to an infusion bag containing ≥ 50 ml of diluent (sodium chloride 9 mg/ ml (0.9%) solution for infusion or glucose 50 mg/ ml (5%) solution for infusion), being the concentration of trabectedin in the infusion solution ≤ 0.030 mg/ ml.
Hvis centralvenøs adgang ikke er mulig, og der må anvendes en perifer venøs adgang, skal den rekonstituerede opløsning overføres til en infusionspose indeholdende ≥ 1, 000 ml fortyndingsmiddel (natriumklorid 9 mg/ ml (0, 9%) infusionsopløsning eller glukose 50 mg/ ml (5%) infusionsopløsning).
If central venous access is not feasible and a peripheral venous line has to be used, the reconstituted solution should be added to an infusion bag containing ≥ 1,000 ml of diluent (sodium chloride 9 mg/ ml (0.9%) solution for infusion or glucose 50 mg/ ml (5%) solution for infusion).
13 Yondelis er et cytotoksisk anticancerlægemiddel, og som med andre potentielt toksiske stoffer skal der udvises forsigtighed under håndteringen.
Yondelis is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, caution should be exercised during handling.
Personalet skal uddannes i de korrekte teknikker til rekonstituering og fortynding af lægemidlet, og de skal bære beskyttelsestøj herunder maske, beskyttelsesbriller og handsker under opløsnings - og fortyndingsprocessen.
Personnel should be trained in the correct techniques to reconstitute and dilute the medicinal product and should wear protective clothing including mask, goggles and gloves during the reconstitution and dilution.
Utilsigtet kontakt med hud, øjne eller slimhinder skal behandles omgående med rigelige mængder vand.
13 Accidental contact with the skin, eyes or mucous membranes must be treated immediately with copious amounts of water.
Ikke anvendte lægemidler samt affald heraf bør destrueres i henhold til lokale retningslinier for cytotoksiske lægemidler.
Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.
Der er ikke blevet observeret uforligeligheder mellem Yondelis og type I glasflasker, polyvinylklorid (PVC) og polyethylen (PE) poser og slanger, polyisopren- reservoirer og implanterbare veneportsystemer af titanium.
No incompatibilities have been observed between Yondelis and type I glass bottles, polyvinylchloride (PVC) and polyethylene (PE) bags and tubing, polyisoprene reservoirs and titanium implantable vascular access systems.
Avda. de los Reyes 1, Polígono Industrial La Mina 28770 Colmenar Viejo (Madrid) Spanien
Avda. de los Reyes 1, Polígono Industrial La Mina 28770 Colmenar Viejo (Madrid) Spain
Hvert hætteglas indeholder 8 mg kalium og 0, 4 g saccharose.
Each vial contains 8 mg of potassium and 0.4 g of sucrose.
16 Patienter med nedsat leverfunktion
16 No studies with the proposed regime have been conducted in patients with liver dysfunction.
Trabectedin må ikke anvendes til patienter med CPK > 2, 5 x ULN (se pkt.
Trabectedin must not be used in patients with CPK > 2.5 ULN (see section 4.2).
Der er i sjældne tilfælde blevet indberettet rhabdomyolyse - sædvanligvis associeret med myelotoksicitet, alvorlige
Rhabdomyolysis has been uncommonly reported, usually in association with myelotoxicity, severe liver function test abnormalities and/ or renal failure.
CPK bør derfor monitoreres nøje, hvis der er mistanke om, at en patient lider af en af disse typer toksicitet.
17 parenteral hydration, urine alkalinisation and dialysis should be promptly established, as indicated.
Der bør udvises forsigtighed, hvis lægemidler, der associeres med levertoksicitet administreres samtidig med trabectedin, da risikoen for levertoksicitet kan være forøget.
Caution should be taken if medicinal products associated with hepatotoxicity are administered concomitantly with trabectedin, since the risk of hepatotoxicity may be increased.
Samtidig administration af hæmmere af P- gp, f. eks. cyclosporin og verapamil, kan ændre trabectedins distribution og/ eller elimination.
Concomitant administration of inhibitors of Pgp, e. g. cyclosporine and verapamil, may alter trabectedin distribution and/ or 18 elimination.
19 af en hvilken som helst sværhedsgrad var: kvalme, træthed, opkastning, anoreksi, neutropeni og forhøjelser af AST/ ALT.
The most common adverse reactions of any severity grade were nausea, fatigue, vomiting, anorexia, neutropenia, and increases in AST/ ALT.
Fatale bivirkninger er forekommet hos 1, 9% af patienterne.
Fatal adverse reactions have occurred in 1.9% of patients.
De var ofte resultatet af en kombination af flere hændelser herunder pancytopeni, febril neutropeni hvoraf nogle var med sepsis, leverlidelser, nyresvigt og rhabdomyolyse.
They were often the result of a combination of events including pancytopenia, febrile neutropenia, some of them with sepsis, hepatic involvement, renal failure and rhabdomyolysis.
Tabellen nedenfor viser de bivirkninger, der blev indberettet hos ≥ 1% af patienterne ifølge systemorganklasserne i henhold til MedDRA- databasen.
19 The table below displays the adverse reactions reported in ≥ 1% of patients according to the standard MedDRA system organ class.
20 Systemorganklasse
20 System Organ Class Investigations
21 De hyppigste bivirkninger
21 Most frequent adverse reactions
CPK- forhøjelser og rhabdomyolyse:
CPK elevations and rhabdomyolysis:
22 Dyspnø:
22 Dyspnoea:
5. 2 Farmakokinetiske egenskaber 23 Systemisk eksponering efter administration som en 24- timers intravenøs infusion med konstant hastighed er dosisproportional ved doser op til og med 1, 8 mg/ m2.
23 Systemic exposure after administration as a 24 hour constant rate intravenous infusion is dose proportional at doses up to and including 1.8 mg/ m2.
Virkningen af trabectedin på den kardiovaskulære og respiratoriske funktion er blevet undersøgt in vivo (bedøvede Cynomolgus- aber).
The effects of trabectedin on cardiovascular and respiratory function have been investigated in vivo (anesthetised Cynomolgus monkeys).
De opnåede niveauer af trabectedin i plasma var 10, 6 ± 5, 4 (Cmax) højere end de niveauer, der blev nået hos patienter efter infusion af 1500 μg/ m2 i 24 timer (Cmax på 1, 8 ± 1, 1 ng/ ml), og tilsvarende de
The plasma trabectedin levels attained were 10.6 ± 5.4 (Cmax), higher than those reached in patients after infusion of 1500 μ g/ m2 for 24 (Cmax of 1.8 ± 1.1 ng/ ml) and similar to those reached after administration of the same dose by 3 hour infusion (Cmax of 10.8 ± 3.7 ng/ ml).
24 niveauer der blev nået efter administration af samme dosis ved en 3- timers infusion (Cmax på 10, 8 ± 3, 7 ng/ ml).
24 Myelosupression and hepatoxicity were identified as the primary toxicity for trabectedin.
6. 5 Emballagetype og pakningsstørrelser 25 Yondelis leveres i et type I farveløst glashætteglas med bromobutyl gummiprop, dækket af en aluminium flip- off- forsegling.
25 Yondelis is supplied in a Type I colourless glass vial with a bromobutyl rubber stopper covered with an aluminium flip-off seal.
Hvert hætteglas med 1 mg trabectedin rekonstitueres med 20 ml sterilt vand til injektioner.
Each vial containing 1 mg of trabectedin is reconstituted with 20 ml of sterile water for injections.
Der anvendes en sprøjte til at injicere 20 ml sterilt vand til injektioner i hætteglasset.
A syringe is used to inject 20 ml of sterile water for injections into the vial.