natgillin/translations-raw huggingface dataset:
Navn og adresse på den fremstiller (de fremstillere), der er ansvarlig(e) for batchfrigivelse Hospira UK Ltd.
Name and address of the manufacturers responsible for batch release Hospira UK Ltd.
Den kombinerede overlevelse efter 1 år var for disse dosiskohorter 88,1%.
the combined 1-year survival rate was 88.1%.
Den ensartede forekomst af disse hændelser i begge behandlingsgrupper tyder på, at disse bivirkninger ikke kan tilskrives bortezomib alene.
The similar incidences of these events in both treatment arms, indicated that these adverse drug reactions are not attributable to bortezomib alone.
Til patienter med et respons, som først blev dokumenteret ved cyklus 6, blev der givet 2 supplerende behandlingscyklusser.
For patients with a response first documented at cycle 6, two additional treatment cycles were given.
• Blodprop i små blodkar (thrombotisk mikroangiopati)
• Blood clot in small blood vessels (thrombotic microangiopathy)
Thrombocyttransfusion til behandling af thrombocytopeni skal overvejes, når det er klinisk relevant.
Platelet transfusion for the treatment of thrombocytopenia should be considered when clinically appropriate.
Bortezomibs teratogene potentiale er ikke fuldstændigt undersøgt.
The teratogenic potential of bortezomib has not been fully investigated.
Autonom neuropati kan være forbundet med bortezomib, eller bortezomib kan forværre en tilgrundliggende tilstand såsom diabetisk eller amyloid neuropati.
Autonomic neuropathy may be related to bortezomib or bortezomib may aggravate an underlying condition such as diabetic or amyloidotic neuropathy.
ml/min/1,73 m 2, n=9) og alvorlig (CrCl < 20 ml/min/1,73 m 2, n=3).
39 ml/min/1.73 m 2, n=9), and Severe (CrCL < 20 ml/min/1.73 m 2, n=3).
Det anbefales, at patienter, der som et minimum opnår partielt respons, får 2 ekstra cyklusser.
It is recommended that patients with at least partial response receive 2 additional cycles.
Hvis produktet ikke anvendes straks, er opbevaringstid og -betingelser inden anvendelse brugerens eget ansvar.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
I tilfælde af nye lungesymptomer eller forværring af 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.
Ubiquitin-proteasom-vejen spiller en vigtig rolle i reguleringen af omsætningen af specifikke proteiner, som derved opretholder homeostasen inde i cellerne.
The ubiquitin-proteasome pathway plays an essential role in regulating the turnover of specific proteins, thereby maintaining homeostasis within cells.
Antiviral profylakse blev administreret til 26% af patienterne i B+M+P-gruppen.
Antiviral prophylaxis was administered to 26% of the patients in the B+M+P arm.
Patienter, der opnår respons eller stabiliseret sygdom efter 4 cyklusser med denne kombinationsbehandling, kan fortsætte med den samme kombination i højst 4 cyklusser yderligere.
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.
Bortezomib blev kun administreret i blok 1 og 2 for at undgå potentiel overlapning af toksiciteter med samtidigt administrerede lægemidler i blok 3.
Bortezomib was administered only in Blocks 1 and 2 to avoid potential overlapping toxicities with coadministered medicinal product in Block 3.
Der har været enkeltstående tilfælde af forlængelse af QT-intervallet i kliniske forsøg; den kausale sammenhæng er ikke fastlagt.
There have been isolated cases of QT-interval prolongation in clinical studies, causality has not been established.
Det anbefales, at patienterne får 2 cyklusser med Bortezomib Hospira efter bekræftelse af komplet respons.
It is recommended that patients receive 2 cycles of Bortezomib Hospira following a confirmation of a complete response.
• Øget eller nedsat urinproduktion (på grund af 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
Medianoverlevelsen i B+M+Pbehandlingsgruppen 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.
Muskuloskeletale smerter*
Musculoskeletal pain*
Som et resultat af den forud planlagte interimanalyse blev dexamethason-gruppen standset på anbefaling fra datamonitoreringskomiteen, og alle patienter fik derefter tilbudt bortezomib uanset sygdomsstatus.
As a result of a pre-planned interim analysis, the dexamethasone arm was halted at the recommendation of the data monitoring committee and all patients randomised to dexamethasone were then offered bortezomib, regardless of disease status.
I koncentrationer på 10 µM hæmmer bortezomib ikke nogen af en lang række screenede receptorer og proteaser og er mere end 1.500 gange så selektivt for proteasomet som for dets 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.
• Instruktioner til ordination og administration, herunder cyklussernes længde og antal cyklusser, for herved at minimere risikoen for medicinerings- eller administrationsfejl, der kan opstå som følge af de to forskellige kombinationsregimer med bortezomib 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).
Bærere af hepatitis B og patienter med en anamnese med hepatitis B skal monitoreres nøje for kliniske og laboratoriemæssige tegn på aktiv HBV-infektion under og efter rituximab-kombinationsbehandling med Bortezomib Hospira.
Carriers of hepatitis B and patients with a history of hepatitis B must be closely monitored for clinical and laboratory signs of active HBV infection during and following rituximab combination treatment with Bortezomib Hospira.
• Kontrollér dosis og koncentrationen i sprøjten inden anvendelse.
• Confirm the dose and concentration in thesyringe prior to use.
(Kontrollér, at sprøjten er mærket til subkutan administration).
(Check that the syringe is markedas subcutaneous administration.)
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, herunder 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.
Data fra forsøg in vitro, ex vivo og i dyremodeller med bortezomib tyder på, at bortezomib øger osteoblastdifferentieringen 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.
Begge grupper fik et medianantal cyklusser på 4.
The median number of cycles received for both groups was 4 cycles.
PRES er en sjælden, ofte reversibel neurologisk lidelse, som udvikles hurtigt, og som kan optræde med kramper, hypertension, hovedpine, letargi, konfusion, 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.
Samtidige medicineringer
Concomitant medicinal products
Patienter i behandling med orale antidiabetika, som behandles med Bortezomib Hospira, kan have brug for nøje monitorering af deres blodsukkerniveau og justering af deres antidiabetika-dosis.
Patients on oral antidiabetic agents receiving Bortezomib Hospira treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetics.
Graviditet og amning Du må ikke bruge Bortezomib Hospira, hvis du er gravid, medmindre det er absolut nødvendigt.
Pregnancy and breast-feeding You should not use bortezomib if you are pregnant, unless clearly necessary.
Kvindelige patienter i den fertile alder og mandlige patienter skal anvende sikker kontraception under behandlingen og i 3 måneder efter behandlingen.
Female patients of childbearing potential and male patients must use effective contraceptive measures during and for 3 months following treatment.
Både hos de patienter, som var refraktære over for den seneste behandling, og de, der ikke var refraktære, var den samlede overlevelse signifikant længere, og responsraten var signifikant højere i bortezomib-gruppen.
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.
Der var ingen tilgængelige oplysninger om mulige sequelae eller raterne for helbredelse af perifer neuropati i dette forsøg.
No information on possible sequelae or rates of peripheral neuropathy resolution were available in this study.
Yderligere bivirkninger, som blev identificeret i forbindelse med brug af kombinationsbehandling (BR-CAP), er hepatitis B-infektion (< 1%) og myokardie-iskæmi (1,3%).
Additional adverse drug reactions identified associated with the use of the combination therapy (BR-CAP) were hepatitis B infection (< 1%) and myocardial ischaemia (1.3%).
I prækliniske forsøg havde bortezomib ingen virkning på den embryonale/føtale udvikling hos rotter og kaniner ved den højeste maternelt tålte dosis.
In non-clinical studies, bortezomib had no effects on embryonal/foetal development in rats and rabbits at the highest maternally tolerated doses.
Perifer neuropati uanset grad og perifer neuropati ≥ grad 3 blev set hos henholdsvis 40% og 8,5% af patienterne.
All grade peripheral neuropathy and grade ≥ 3 peripheral neuropathy were observed in 40% and 8.5% of patients, respectively.
Kinetikken ved proteasomhæmning blev undersøgt in vitro, og det blev påvist, at bortezomib adskiller sig fra proteasomet med et t½ på 20 minutter, hvilket viser, at bortezomibs proteasomhæmning 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.
• Når produktet er opløst, udtrækkes den ønskede mængde af den rekonstituerede opløsning i henhold til den dosis, der er beregnet ud fra patientens legemsoverfladeareal.
• Once dissolved, withdraw the appropriate amount of the reconstituted solution according to calculated dose based upon the patient´s Body Surface Area.
Meget almindelig Pneumoni* Almindelig
Very Common Pneumonia* Common
• Infektion i øjets yderste lag og på indersiden af øjenlåget (konjunktivitis)
• Infection of the outermost layer of the eye and the inner surface of the eyelids (conjunctivitis)
Inden for bortezomibs koncentrationsinterval på 0,01-1,0 µg/ml er proteinbindingen in vitro gennemsnitligt 82,9% i humant plasma.
Over a bortezomib concentration range of 0.01 to 1.0 μg/ml, the in vitro protein binding averaged 82.9% in human plasma.
Både mænd og kvinder, som er i behandling med Bortezomib Hospira, skal bruge sikker prævention under og 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.
** Instrumental ADL: dækker madlavning, indkøb af dagligvarer eller tøj, brug af telefon, håndtering af penge osv. *** ADL med personlig pleje: dækker badning, på- og afklædning, spisning, toiletbesøg, indtagelse af medicin og oppegående.
** Instrumental ADL: refers to preparing meals, shopping for groceries or clothes, using telephone, managing money, etc; *** Self care ADL: refers to bathing, dressing and undressing, feeding self, using the toilet, taking medicinal products, and not bedridden.
Reaktivering af herpes zoster-virus
Herpes zoster virus reactivation
Tidlig og regelmæssig monitorering for symptomer på behandlingsrelateret neuropati og neurologisk evaluering skal overvejes hos patienter, der får Bortezomib Hospira i kombination med lægemidler, der vides at være forbundet med neuropati (f.eks. thalidomid), og passende dosisreduktion eller behandlingsseponering skal overvejes.
Early and regular monitoring for symptoms of treatment-emergent neuropathy with neurological evaluation should be considered in patients receiving Bortezomib Hospira in combination with medicinal products known to be associated with neuropathy (e.g. thalidomide) and appropriate dose reduction or treatment discontinuation should be considered.
Tabel 12: Effektresultater fra forsøg IFM-2005-01 Endepunkter
Table 12: Efficacy results from study IFM-2005-01 Endpoints
• Injicér opløsningen som en 3-5 sekunders intravenøs injektion gennem et perifert eller centralt intravenøst kateter ind i en vene.
• Inject the solution as a 3-5 second bolus intravenous injection through a peripheral or central intravenous catheter into a vein.
(42/240 [18% ] i BDx-gruppen og 52/242 [21%] i VDDx-gruppen).
in BDx group and 52/242 [21%] in VDDx group).
Hvis Bortezomib Hospira anvendes under graviditeten, eller hvis patienten bliver gravid, mens hun får dette lægemiddel, skal hun orienteres om de mulige risici for fostret.
If Bortezomib Hospira 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/m2 eller yderligere dosisreduktion til 0,5 mg/m2 i de efterfølgende cyklusser, afhængigt af patientens tolerabilitet.
Consider dose escalation to 1.0 mg/m2 or further dose reduction to 0.5 mg/m2 in subsequent cycles based on patient tolerability.
Baseret på en farmakokinetisk populationsanalyse steg bortezomibs clearance i takt med et stigende BSA (legemsoverfladeareal).
Based on a population pharmacokinetic analysis, clearance of bortezomib increased with increasing body surface area (BSA).
Disse bivirkninger er baseret på et integreret datasæt med 5.476 patienter, hvoraf 3.996 blev behandlet med bortezomib i en dosis på 1,3 mg/m2, 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/m2 and included in Table 7.
De sekundære effektendepunkter omfattede tid indtil progression (TTP), tid indtil næste anti-lymfombehandling (TNT), varighed af behandlingsfrit interval (TFI), samlet responsrate (ORR) og komplet responsrate (CR/CRu), samlet overlevelse (OS) og responsvarighed.
Secondary endpoints included, time to progression (TTP), time to next anti-lymphoma treatment (TNT), duration of treatment free interval (TFI), overall response rate (ORR) and complete response (CR/CRu) rate, overall survival (OS) and response duration.
• Neutropeni ≥ grad 3 med feber, neutropeni grad 4 i mere end 7 dage, thrombocyttal < 10.000 celler/μl
• ≥ Grade 3 neutropenia with fever, Grade 4 neutropenia lasting more than 7 days, a platelet count < 10,000 cells/μL
Intention to treat-population n=74
Intent to Treat Population n=74
Der indgik 222 forsøgspersoner i forsøget, og 221 af disse blev behandlet med bortezomib Estimatet af hazards ratio er baseret på en Cox-model justeret for stratifikationsfaktorer: ISSstadieinddeling og antal tidligere linjer d.
222 subjects were enrolled into the study; 221 subjects were treated with bortezomib Hazards ratio estimate is based on a Cox model adjusted for stratification factors: ISS staging and number of prior lines.
Patienter med eksisterende svær neuropati må kun behandles med Bortezomib Hospira efter en nøje vurdering af risici og fordele.
Patients with pre-existing severe neuropathy may be treated with Bortezomib Hospira only after careful risk/benefit assessment.
Bortezomib Hospira bør ikke anvendes under graviditeten, medmindre kvindens kliniske tilstand kræver behandling med bortezomib.
Bortezomib Hospira should not be used during pregnancy unless the clinical condition of the woman requires treatment with Bortezomib Hospira.
Hvis du har mantle-celle-lymfom og får lægemidlet rituximab sammen med bortezomib, skal du fortælle det til din læge:
If you have mantle cell lymphoma and are given the medicine rituximab with bortezomib you should tell your doctor:
Øvrige indholdsstoffer: mannitol (E 421).
The other ingredient is mannitol (E421).
• Den rekonstituerede opløsning indgives subkutant i låret (højre eller venstre) eller abdomen (højre eller venstre side).
• The reconstituted solution is administered subcutaneously through the thighs (right or left) or abdomen (right or left).
Posteriort reversibelt encefalopatisk syndrom (PRES) Der er indberettet PRES hos patienter, der fik bortezomib.
Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving bortezomib.
Samlet komplet respons (CR+CRu)
Overall complete response (CR+CRu)
Dødsfald som følge af “progressiv sygdom” forekom hos 18% i den subkutane gruppe og hos 9% i den intravenøse gruppe.
Incidence of death from “Progressive disease” was 18% in the subcutaneous group and 9% in the intravenous group.
Henholdsvis 42,9% og 10,4% af patienterne i BR-CAP-gruppen var i alderen 65-74 år og ≥ 75 år.
42.9% and 10.4% of patients in the BR-CAP arm were in the range 65-74 years and ≥ 75 years of age, respectively.
Den er specifikt designet til at hæmme 26S-proteasomets chymotrypsinlignende aktivitet i pattedyrceller.
It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells.
Bivirkningerne i tabel 7 blev af investigatorerne anset for som et minimum at have en mulig eller sandsynlig kausal sammenhæng med bortezomib.
Undesirable effects in Table 7 were considered by the investigators to have at least a possible or probable causal relationship to bortezomib.
Den gennemsnitlige eliminationshalveringstid (t1/2) for bortezomib efter gentagne doser var fra 40-193 timer.
The mean elimination half-life (t1/2) of bortezomib upon multiple dosing ranged from 40-193 hours.
Hypertension*, hypotension*, ortostatisk hypotension
Hypertension*, Hypotension*, Orthostatic hypotension
Kontrollér, at den korrekte dosis anvendes til intravenøs administration (1 mg/ml).
Be sure that the correct dose is being given for the intravenous route of administration (1 mg/ml).
På baggrund af det begrænsede bidrag (7%) fra CYP2D6 til metaboliseringen af bortezomib forventes det ikke, at CYP2D6-fænotypen, som metaboliserer dårligt, påvirker den samlede disponering for bortezomib.
Based on the limited contribution (7%) of CYP2D6 to the metabolism of bortezomib, the CYP2D6 poor metaboliser phenotype is not expected to affect the overall disposition of bortezomib.
I BR-CAP-gruppen fik 22,5% af patienterne thrombocyttransfusioner sammenlignet med 2,9% af patienterne i R-CHOP-gruppen.
In the BR-CAP group, 22.5% of patients received platelet transfusions compared to 2.9% of patients in the R-CHOP group.
p-værdien er for hypotesen om noninferioritet, at den subkutane gruppe fastholder mindst 60% af responsraten i den intravenøse gruppe
p-value is for the non-inferiority hypothesis that the SC arm retains at least 60% of the response rate in the IV arm.
Andre rapporter om leverreaktioner omfatter stigninger i leverenzymtal, hyperbilirubinæmi og hepatitis.
Other reported hepatic reactions include increases in liver enzymes, hyperbilirubinaemia, and hepatitis.
Tabel 11: Effektresultater efter den endelige opdatering af overlevelse i VISTA-forsøget Effektendepunkt
Table 11: Efficacy results following the final survival update to VISTA study Efficacy endpoint
Melphalan (9 mg/m 2) og prednison (60 mg/m 2) gives begge gennem munden på dag 1, 2, 3 og 4 i den første uge af hver cyklus.
Melphalan (9 mg/m 2) and prednisone (60 mg/m 2) are both given orally on days 1, 2, 3 and 4 of the first week of each cycle.
TTP, dage [95% CI] 1-års overlevelse, % [95% CI]
TTP, days [95% CI] 1 year survival, % [95% CI]
OR; 95% CI; P-værdi
OR; 95% CI; P value
Den samlede bedste responsrate (CR + PR) ved genbehandling af 130 patienter var 38,5% (95% CI: 30,1; 47,4).
The overall best response rate (CR + PR), to retreatment in 130 patients was 38.5% (95% CI: 30.1, 47.4).
• rifampicin, et antibiotikum, som bruges til behandling af bakterieinfektioner
• rifampicin, an antibiotic used to treat bacterial infections
Farmakologiske forsøg af den kardiovaskulære sikkerhed hos aber og hunde viser, at intravenøse doser på cirka 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/m2 basis are associated with increases in heart rate, decreases in contractility, hypotension and death.
Opløsningen skal indgives subkutant i en vinkel på 45-90 °.
The solution should be injected subcutaneously, at a 45-90° angle.
• Skyl det perifere eller intravenøse kateter igennem med steril 9 mg/ml (0,9%) natriumchloridinjektionsvæske.
• Flush the peripheral or intravenous catheter with sterile, 9 mg/ml (0.9%) sodium chloride solution.
Hæftet om rekonstitution, dosering og administration skal indeholde følgende hovedpunkter:
The Reconstitution, dosing and administration booklet shall contain the following key elements:
Perifer neuropati ≥ grad 3 forekom hos 6% af patienterne i den subkutane behandlingsgruppe sammenlignet med 16% i den intravenøse behandlingsgruppe (p=0,0264).
Grade ≥ 3 peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 16% in the intravenous treatment group (p=0.0264).
Grad 2 med smerter eller grad 3 (svære symptomer; begrænsning i ADL med personlig pleje***)
Grade 2 with pain or Grade 3 (severe symptoms; limiting self care ADL***)
Ortostatisk/postural hypotension var ikke akut relateret til bolusinfusionen af bortezomib.
Orthostatic/postural hypotension was not acutely related to bolus infusion of bortezomib.
Patienterne bør kontrolleres regelmæssigt for nye eller tiltagende neurologiske symptomer eller tegn, der kunne tyde på PML, som led i differentialdiagnosticeringen af lidelser i centralnervesystemet.
Patients should be monitored at regular intervals for any new or worsening neurological symptoms or signs that may be suggestive of PML as part of the differential diagnosis of
Tabel 8: Bivirkninger hos patienter med mantle-celle-lymfom, som er behandlet med BR-CAP i et klinisk forsøg.
Table 8 Adverse reactions in patients with Mantle cell lymphoma treated with BR-CAP in a clinical trial.
Meget almindelig Hårsygdom* Almindelig
Very Common Hair disorder* Common
Efter en intravenøs bolusinjektion eller subkutan injektion af en dosis på 1,3 mg/m til patienter med myelomatose (n=14 i den intravenøse gruppe, n=17 i den subkutane gruppe) var den totale systemiske eksponering efter gentagne doser (AUClast) ens for subkutan og intravenøs administration.
Following an intravenous bolus or subcutaneous injection of a 1.3 mg/m2 dose to patients with multiple myeloma (n=14 in the intravenous group, n=17 in the subcutaneous group), the total systemic exposure after repeat dose administration (AUClast) was equivalent for subcutaneous and intravenous administrations.
• Rådgivning om, hvordan man nedsætter risikoen for forveksling af rekonstituerede sprøjter til i.v.
• advice on how to reduce the risk of mix-up of IV and SC reconstituted syringes