natgillin/translations-raw huggingface dataset:
Desuden viste de sekundære effektmål, som var relateret til respons og tid til hændelse, overensstemmende resultater for subkutan og intravenøs administration (tabel 15).
In addition, secondary response-related and time to event related efficacy endpoints showed consistent results for subcutaneous and intravenous administration (table 15).
Din læge vil bestemme dosis af bortezomib ud fra din højde og vægt (areal af legemsoverflade).
Your doctor will work out your dose of bortezomib according to your height and weight (body surface area).
BSA-normaliseret clearance af bortezomib hos pædiatriske patienter var den samme som den, der observeres hos voksne.
BSA-normalized clearance of bortezomib in pediatric patients was similar to that observed in adults.
Dette lægemiddel har ingen særlige opbevaringsbetingelser.
This medicinal product does not require any special temperature storage condition.
140 patienter med ALL eller LL blev inkluderet for at evaluere sikkerhed; den mediane alder var 10 år (rangerende fra 1 til 26).
There were 140 patients with ALL or LL enrolled and evaluated for safety; median age was 10 years (range 1 to 26).
b Op til 6 cyklusser kan gives til patienter, der som minimum udviser partielt respons efter 4 cyklusser
b Up to 6 cycles may be given to patients who achieve at least a partial response after 4 cycles
På tidspunktet for en præspecificeret interimanalyse var det primære effektmål, tid til progression, opnået, og patienterne i M+P-armen blev tilbudt B+M+P-behandling.
At the time of a pre-specified interim analysis, the primary endpoint, time to progression, was met and patients in the M+P arm were offered B+M+P treatment.
Median varighed af opfølgning er 11,8 måneder
e Median duration of follow up is 11.8 months
Det primære effektmål var bedste bekræftede respons på genbehandling vurderet ud fra EBMTkriterierne.
The primary endpoint was best confirmed response to retreatment as assessed by EBMT criteria.
Den endelige opdatering af overlevelsesdata fandt sted med en median varighed af opfølgning på 60,1 måneder.
The final survival update was performed with a median duration of follow-up of 60.1 months.
• Lavt antal røde eller hvide blodlegemer
• low numbers of red or white blood cells
B=bortezomib; M=melphalan, P=prednison
B=bortezomib; M=melphalan, P=prednisone
RR (Posttransplantation)
RR (Post-transplant)
I BTDx-gruppen var 12 % af patienterne cytogenetisk klassificeret som højrisiko versus 16 % af patienterne i TDx-gruppen.
In the BTDx group 12% of patients were cytogenetically classified as high risk versus 16% of patients in the TDx group.
Der blev identificeret 127 matchede patientpar.
One hundred and twenty seven matched pairs of patients were identified.
En gang om ugen bortezomib (cyklus 5-9)
Once weekly bortezomib (cycles 5-9)
Væskeretention kan være en forudgående faktor for tegn og symptomer på hjertesvigt.
Fluid retention may be a predisposing factor for signs and symptoms of heart failure.
Opløsningen bliver derefter indsprøjtet i en vene eller under huden.
The resulting solution is then either injected into a vein or under the skin.
Det primære effektmål var progressionsfri overlevelse baseret på en bedømmelse fra en uafhængig evalueringskomité (IRC).
The primary efficacy endpoint was progression-free survival based on Independent Review Committee (IRC) assessment.
Efter korrektion for BSA-effekten havde andre demografiske data, som f.eks. alder, legemsvægt og køn, ikke klinisk signifikant effekt på bortezomibclearance.
After correcting for the BSA effect, other demographics such as age, body weight and sex did not have clinically significant effects on bortezomib clearance.
Sundhedspersoner anmodes om at indberette alle formodede bivirkninger via det nationale rapporteringssystem anført i Appendiks V*.
Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
I tilfælde af nye eller forværrede lungesymptomer (f.eks. hoste, dyspnø) er det nødvendigt med en hurtig diagnosticering, og at patienterne behandles i overensstemmelse hermed.
In the event of new or worsening pulmonary symptoms (e.g., cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients treated appropriately.
Uanset β2-mikroglobulintal ved baseline var alle effektparametre (tiden indtil progression og samlet overlevelse samt responsrate) signifikant forbedret i bortezomib-armen.
Regardless of β2-microglobulin levels at baseline, all efficacy parameters (time to progression and overall survival, as well as response rate) were significantly improved on the bortezomib arm.
(CrCl=20-39 ml/min/1,73 m2, n=9) og Alvorlig (CrCl < 20 ml/min/1,73 m2, n=3).
(CrCL=20-39 ml/min/1.73 m2, n=9), and Severe (CrCL < 20 ml/min/1.73 m2, n=3).
Reduktion i serum M-protein Population g n=667
Reduction in serum M-protein population g n=667
Både hos de patienter, som var refraktære over for den seneste forudgående behandling, og de, der ikke var refraktære, var den samlede overlevelse signifikant længere, og responsraten var signifikant højere i bortezomib-armen.
Both in patients who were refractory to their last prior therapy and those who were not refractory, overall survival was significantly longer and response rate was significantly higher on the bortezomib arm.
• Moderate til svære problemer med leveren
• moderate to severe liver problems
Protokollen tillod, at patienterne fik dexametason, hvis de havde haft en mindre end optimal respons til bortezomib alene.
The protocol allowed patients to receive dexamethasone if they had had a less than optimal response to bortezomib alone.
Intention to treat population b n=74
Intent to Treat Population b n=74
Det anbefales, at patienterne får to cyklusser med bortezomib efter bekræftelse af komplet respons.
It is recommended that patients receive 2 cycles of bortezomib following a confirmation of a complete response.
Når bortezomib gives sammen med thalidomid og dexamethason, er varigheden af en behandlingscyklus 28 dage (4 uger).
When bortezomib is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks).
NF-κB er en transskriptionsfaktor, hvis aktivering kræves til mange aspekter af tumorgenese, inklusive cellevækst og -overlevelse, angiogenese, celle-celle-interaktioner og metastase.
NF-kB is a transcription factor whose activation is required for many aspects of tumourigenesis, including cell growth and survival, angiogenesis, cell-cell interactions, and metastasis.
Hæmning af 26S-proteasom forhindrer denne målrettede proteolyse og påvirker adskillige signaleringskaskader i cellen, hvilket i sidste ende resulterer i cancercelledød.
Inhibition of the 26S proteasome prevents this targeted proteolysis and affects multiple signalling cascades within the cell, ultimately resulting in cancer cell death.
Den geometriske gennemsnitsratio AUClast var 0,99 og 90 % konfidensintervaller var 80,18 %-122,80
The AUClast geometric mean ratio was 0.99 and 90% confidence intervals were 80.18%-122.80%.
Behandlingen med bortezomib kan meget ofte forårsage et fald i antal af røde og hvide blodlegemer samt blodplader i blodet.
Treatment with bortezomib can very commonly cause a decrease in the numbers of red and white blood cells and platelets in your blood.
Henviser til responsrate efter den anden transplantation hos forsøgspersoner, der blev transplanteret 2 gange (42/240 [18 % ] i BDx-gruppen og 52/242 [21 %] i VDDx-gruppen).
Refers to response rate after second transplant for subjects who received a second transplant (42/240 [18%] in BDx group and 52/242 [21%] in VDDx group).
Bortezomib-medieret proteasomhæmning påvirker cancerceller på flere måder, inklusive, men ikke begrænset til, ændring af regulerende proteiner, som styrer cellecyklusprogression, og aktiveringen af nuklear faktor kappa B (NF-κB).
Bortezomib mediated proteasome inhibition affects cancer cells in a number of ways, including, but not limited to, altering regulatory proteins, which control cell cycle progression and nuclear factor kappa B (NF-kB) activation.
Nedenstående oplysning er til læger og sundhedspersonale: Kun hætteglasset med 3,5 mg kan administreres subkutant som beskrevet nedenfor:
The following information is intended for healthcare professionals only: Only the 3.5 mg vial can be administered subcutaneously, as described below.
Fresenius Kabi Oncology Plc, Lion Court, Farnham Road, Bordon, Hampshire, GU35 0NF, Storbritannien
Fresenius Kabi Oncology Plc, Lion Court, Farnham Road, Bordon, Hampshire, GU35 0NF, United Kingdom
Bortezomib bør ikke anvendes under graviditeten, medmindre kvindens kliniske tilstand kræver behandling med bortezomib.
Bortezomib should not be used during pregnancy unless the clinical condition of the woman requires treatment with bortezomib.
Bortezomib blev kun administreret i blok 1 og 2 for at undgå potentielle overlappende toksiciteter med co-administrerede lægemidler i blok 3.
Bortezomib was administered only in Blocks 1 and 2 to avoid potential overlapping toxicities with coadministered drugs in Block 3.
Hvis bortezomib anvendes under graviditeten, eller hvis patienten bliver gravid, mens hun får dette lægemiddel, skal patienten orienteres om de mulige risici for fostret.
If bortezomib is used during pregnancy, or if the patient becomes pregnant while receiving this medicinal product, the patient should be informed of potential for hazard to the foetus.
Overvej dosisøgning til 1,0 mg/m eller yderligere dosisreduktion til 0,5 mg/m i efterfølgende cyklusser baseret på patientens tolerabilitet.
Consider dose escalation to 1.0 mg/m or further dose reduction to 0.5 mg/m in subsequent cycles based on patient tolerability.
Det er ukendt, hvorvidt bortezomib udskilles i human mælk.
It is not known whether bortezomib is excreted in human milk.
= måneder
2 years
Det anbefales, at patienter, der som minimum udviser partielt respons, modtager 2 yderligere cyklusser.
It is recommended that patients with at least partial response receive 2 additional cycles.
• Blødningsproblemer og/eller lavt antal blodplader i blodet
• bleeding problems and/or low number of platelets in your blood
Derfor skal der udvises forsigtighed ved håndteringen og præparationen.
Therefore, caution must be used during handling and preparation.
• Problemer med hjertet eller blodtrykket
• heart or blood pressure problems
Desuden blev der observeret en lille stigning i det korrigerede QT-interval i hundeforsøg.
Moreover, in dog studies, a slight increase in the corrected QT interval was observed.
Grad 1 (asymptomatisk; tab af dybe senereflekser eller paræstesi) uden smerter eller funktionstab
Grade 1 (asymptomatic; loss of deep tendon reflexes or paresthesia) with no pain or loss of function
Både mænd og kvinder, som er i behandling med bortezomib, skal anvende sikker prævention under og i op til 3 måneder efter behandlingen.
Both men and women receiving bortezomib must use effective contraception during and for up to 3 months after treatment.
Antiviral profylakse blev administreret til 137 af 240 patienter (57 %) i BR-CAP-armen.
Antiviral prophylaxis was administered to 137 of 240 patients (57%) in the BR-CAP arm.
Kravene for fremsendelse af periodiske, opdaterede sikkerhedsindberetninger for dette lægemiddel fremgår af listen over EU-referencedatoer (EURD list), som fastsat i artikel 107c, stk. 7, i direktiv 2001/83/EF, og alle efterfølgende opdateringer offentliggjort på Det Europæiske Lægemiddelagenturs hjemmeside http://www.ema.europa.eu.
The requirements for submission of PSURs for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.>
• At lægemidlet skal håndteres under sterile betingelser.
• need to handling the medicinal product in sterile setting
Den mediane overlevelse i B+M+P-behandlingsgruppen var 56,4 måneder sammenlignet med 43,1 i M+P-behandlingsgruppen.
Median survival for the B+M+P treatment group was 56.4 months compared to 43.1 for the M+P treatment group.
9/l på en bortezomib doseringsdag (bortset fra dag 1)
9/l on a bortezomib dosing day (other than day 1)
Thalidomid er kontraindiceret under graviditet og til kvinder i den fertile alder, medmindre alle betingelserne i programmet for svangerskabsforebyggelse for thalidomid overholdes.
Thalidomide is contraindicated during pregnancy and in women of childbearing potential unless all the conditions of the thalidomide pregnancy prevention programme are met.
Antiviral profylakse blev administreret til 26 % af patienterne i B+M+P-armen.
Antiviral prophylaxis was administered to 26% of the patients in the B+M+P arm.
I koncentrationer på 10 μM hæmmer bortezomib ikke nogen af en lang række screenede receptorer og proteaser, og er mere end 1.500 gange mere selektivt for proteasomet end for det næste foretrukne enzym.
At 10 μM concentrations, bortezomib does not inhibit any of a wide variety of receptors and proteases screened and is more than 1,500-fold more selective for the proteasome than for its next preferable enzyme.
Tjek dosis og koncentration i sprøjten før brug (kontroller, at sprøjten er mærket som intravenøs administration).
- Confirm the dose and concentration in the syringe prior to use (check that the syringe is marked as intravenous administration).
Den rekonstituerede opløsning er klar og farveløs med en endelig pH-værdi på 4 til 7.
The reconstituted solution is clear and colourless, with a final pH of 4 to 7.
Derfor frarådes det at anvende dette regime med samtidig administration af højdosis cytarabin (2 g/m daglig)
Therefore, this specific regimen with concomitant administration with high-dose cytarabine (2 g/m per day)
Disse bivirkninger er baseret på et integreret datasæt med 5.476 patienter, hvoraf 3.996 patienter blev behandlet med bortezomib ved 1,3 mg/m og er inkluderet i tabel 7.
These adverse reactions are based on an integrated data set of 5,476 patients of whom 3,996 were treated with bortezomib at 1.3 mg/m and included in table 7.
Patienter, som opnår respons eller stabiliseret sygdom efter 4 cyklusser med denne kombinationsbehandling, kan fortsætte med den samme kombination i højst 4 yderligere cyklusser.
Patients achieving a response or a stable disease after 4 cycles of this combination therapy can continue to receive the same combination for a maximum of 4 additional cycles.
Ubiquitin-proteasom-vejen spiller en vigtig rolle i reguleringen af omsætningen af specifikke proteiner, som derved opretholder homeostasen i cellerne.
The ubiquitin-proteasome pathway plays an essential role in regulating the turnover of specific proteins, thereby maintaining homeostasis within cells.
Studier har vist, at bortezomib er cytotoksisk over for en række cancercelletyper, og at cancerceller er mere følsomme over for den pro-apoptotiske effekt af proteasomhæmning end normale celler.
Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types and that cancer cells are more sensitive to the pro-apoptotic effects of proteasome inhibition than normal cells.
• Instruktioner i ordinering og administration, herunder cyklussernes længde og antal cyklusser, for herved at minimere risikoen for lægmiddel- eller administrationsfejl, der kunne opstå grundet de to forskellige bortezomibkombinationsregimer i transplantationsinduktionsregi (bortezomib plus dexamethason og bortezomib plus dexamethason og thalidomid).
• instructions for prescribing and administration including the cycles' length and number of cycles, to minimise the risk of medication and dispensing errors potentially induced by the existence of the two different bortezomib combination regimens in the Transplant Induction Setting (bortezomib plus dexamethasone, and bortezomib plus dexamethasone and thalidomide).
Det primære effektmål var TTP, og det sekundære effektmål var OS og ORR (CR+PR), ved brug af kriterierne fra The European Group for Blood and Marrow Transplantation (EBMT).
The primary efficacy endpoint was TTP while the secondary efficacy endpoints were OS and ORR (CR+PR), using the European Group for Blood and Marrow Transplantation (EBMT) criteria.
En hazard ratio < 1 angiver en fordel for BR-CAP.
A hazard ratio < 1 indicates an advantage for BR-CAP.
Patienter med præ-eksisterende svær neuropati må kun behandles med bortezomib efter en omhyggelig vurdering af risici og fordele.
Patients with pre-existing severe neuropathy may be treated with bortezomib only after careful risk/benefit assessment.
Tidlig og regelmæssig monitorering for symptomer på behandlingsrelateret neuropati og neurologisk evaluering skal overvejes hos patienter, der får bortezomib i kombination med lægemidler, der vides at være forbundet med neuropati (f.eks. thalidomid), og passende dosisreduktion eller seponering af behandling skal overvejes.
Early and regular monitoring for symptoms of treatment-emergent neuropathy with neurological evaluation should be considered in patients receiving bortezomib in combination with medicinal products known to be associated with neuropathy (e.g. thalidomide) and appropriate dose reduction or treatment discontinuation should be considered.
træthed, konfusion, blindhed eller andre synsproblemer
tiredness, confusion, blindness or other vision problems.
Den er specifikt designet til at hæmme chymotrypsin-lignende aktivitet ved 26S-proteasomet i pattedyrceller.
It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells.
Der blev observeret en statistisk signifikant forbedring af overlevelsen i B+M+P-behandlingsgruppen (HR=0,695; p=0,00043) til trods for efterfølgende behandlinger, inklusive regimer baseret på bortezomib.
A statistically significant survival benefit in favour of the B+M+P treatment group was observed (HR=0.695; p=0.00043) despite subsequent therapies including bortezomib-based regimens.
• Hvis der observeres langvarig grad 4 neutropeni eller trombocytopeni eller trombocytopeni med blødning i den forgående cyklus
• If prolonged grade 4 neutropenia or thrombocytopenia, or thrombocytopenia with bleeding is observed in the previous cycle
Bivirkninger, identificeret med en forekomst på ≥ 1 %, tilsvarende eller højere forekomst i BR-CAParmen og med mindst en mulig eller sandsynlig årsagssammenhæng med komponenterne i BR-CAParmen, er anført i tabel 8 nedenfor.
Adverse drug reactions identified as those with a ≥ 1% incidence, similar or higher incidence in the BR-CAP arm and with at least a possible or probable causal relationship to the components of the BR-CAP arm, are listed in table 8 below.
Ikke almindelig Fald, kontusion Sjælden
Uncommon Fall, Contusion Rare
Der blev ikke observeret nogen nye sikkerhedsproblemer, når bortezomib blev adderet til den standard pædiatriske B-celle ALL kemoterapi grundbehandling.
No new safety concerns were observed when bortezomib was added to the standard pediatric pre B cell ALL chemotherapy backbone.
PRES er en sjælden, ofte reversibel neurologisk lidelse, som udvikles hurtigt, og som kan optræde med blandt andet kramper, hypertension, hovedpine, sløvhed, forvirring, blindhed og andre visuelle og neurologiske forstyrrelser.
PRES is a rare, often reversible, rapidly evolving neurological condition, which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances.
Kinetikken ved proteasomhæmning blev vurderet in vitro, og det blev påvist, at bortezomib dissocierer fra proteasomet med en t½ på 20 minutter, hvilket viser, at proteasomhæmning ved hjælp af bortezomib er reversibel.
The kinetics of proteasome inhibition were evaluated in vitro, and bortezomib was shown to dissociate from the proteasome with a t½ of 20 minutes, thus demonstrating that proteasome inhibition by bortezomib is reversible.
Grad ≥ 3 ikke-hæmatologiske toksiciteter
Grade ≥ 3 non-haematological toxicities
Indehaveren af markedsføringstilladelsen skal sikre, at læger og sundhedspersonale, der beskæftiger sig med ordination, udlevering, håndtering eller administration af bortezomib, forsynes med uddannelsespakken.
The MAH shall ensure that all healthcare professionals involved in the prescribing, dispensing, handling or administration of bortezomib are provided with educational material.
I non-kliniske studier havde bortezomib ingen indvirkning på den embryonale/føtale udvikling hos rotter og kaniner ved den højest tålte dosis hos moderdyret.
In non-clinical studies, bortezomib had no effects on embryonal/foetal development in rats and rabbits at the highest maternally tolerated doses.
• Øget eller nedsat urinproduktion (pga. nyreskade), smerter ved vandladning eller blod/protein i urinen, væskeophobning
• Increased or decreased urine production (due to kidney damage), painful passing of urine or blood/proteins in the urine, fluid retention
Farmakologiske studier vedrørende kardiovaskulær sikkerhed med aber og hunde viser, at intravenøse doser på ca. 2-3 gange den anbefalede kliniske dosis på mg/m2-basis er forbundet med pulsstigninger, fald i kontraktilitet, hypotension og dødsfald.
Cardiovascular safety pharmacology studies in monkeys and dogs show that intravenous doses approximately two to three times the recommended clinical dose on a mg/m basis are associated with increases in heart rate, decreases in contractility, hypotension and death.
De gennemsnitlige AUC-værdier justeret i forhold til standarddosis forøgedes derimod med ca. 60 % hos patienter med moderat eller alvorligt nedsat leverfunktion.
However, the dose-normalised mean AUC values were increased by approximately 60% in patients with moderate or severe hepatic impairment.
Granulocytkolonistimulerende faktorer kan administreres ved hæmatologisk toksicitet i henhold til lokal standardpraksis.
Granulocyte colony stimulating factors may be administered for haematologic toxicity according to local standard practice.
Intent to Treat (ITT) population b p-værdi fra den stratificerede log-rank test; analyse ud fra behandling udelukker opdeling på tidligere behandling; p < 0,0001
a Intent to Treat (ITT) population b p-value from the stratified log-rank test; analysis by line of therapy excludes stratification for therapeutic history; p < 0.0001
• Betændelse eller blødning i blodkarrene, der kan vise sig som små rødlige eller lilla prikker
• Inflammation or haemorrhage of the blood vessels that can appear as small red or purple dots
Hvordan bortezomib gives
How bortezomib is given
Begge grupper fik i gennemsnitlig 4 cyklusser.
The median number of cycles received for both groups was 4 cycles.
Sekundære effektmål omfattede post-transplantations-responsrater (CR+nCR, CR+nCR+VGPR+PR), progressionsfri overlevelse og samlet overlevelse.
Secondary efficacy endpoints included post-transplant response rates (CR+nCR, CR+nCR+VGPR+PR), Progression Free Survival and Overall Survival.
Baseret på en farmakokinetisk populationsanalyse øgedes bortezomibclearance ved stigende legemsoverfladeareal (BSA).
Based on a population pharmacokinetic analysis, clearance of bortezomib increased with increasing body surface area (BSA).
Resultater fra in vitro, ex-vivo og dyremodeller med bortezomib tyder på, at bortezomib øger osteoblast-differentieringen og -aktiviteten og hæmmer osteoklastfunktionen.
Data from in vitro, ex-vivo, and animal models with bortezomib suggest that it increases osteoblast differentiation and activity and inhibits osteoclast function.
Grad ≥ 3 ikke-hæmatologisk toksicitet, som anses for at være relateret til bortezomib
Grade ≥ 3 non-haematological toxicities considered to be related to bortezomib
Der skal derfor udvises forsigtighed ved håndtering og anvendelse af bortezomib.
Therefore, caution should be used during handling and preparation of bortezomib.
Fase II-studiet MMY-2036 (RETRIEVE), et open-label studie med en enkelt arm, blev udført for at bestemme effekt og sikkerhed af genbehandling med bortezomib.
Phase II study MMY-2036 (RETRIEVE), single arm, open-label study was conducted to determine the efficacy and safety of retreatment with bortezomib.