natgillin/translations-raw huggingface dataset:
Yderligere bivirkninger, som blev identificeret i forbindelse med brug af kombinationsbehandling (BR-CAP), var 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%).
Sekundære effektmål inkluderede tid til progression (TTP), tid til næste antilymfombehandling (TNT), varighed af behandlingsfrit interval (TFI), samlet responsrate (ORR) og komplet respons (CR/CRu)-rate, 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.
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.
Den rekonstituerede opløsning administreres 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).
Hvis du har brugt for meget bortezomib
If you are given too much bortezomib
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 must tell your doctor:
Patienterne bør monitoreres 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 CNS problems.
Som et resultat af den forud planlagte interimanalyse blev dexametason-armen standset på anbefaling fra datamonitoreringskomitéen og fik derefter tilbudt bortezomib uanset sygdommens status.
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.
Patienter i henholdsvis BTDx- og TDx-gruppen havde en gennemsnitsalder på 57 versus 56 år, 99 % versus 98 % af patienterne var kaukasere og 58 % versus 54 % var mænd.
Patients in the BTDx and TDx groups respectively had a median age of 57 versus 56 years, 99% versus 98% patients were Caucasians, and 58% versus 54% were males.
Henholdsvis 42,9 % og 10,4 % af patienterne i BR-CAP-armen 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 mediane alder hos patienterne i studiet var 71 år, 50 % var mænd, 88 % var kaukasiere og medianen for Karnofsky performance status for patienterne var en score på 80.
The median age of the patients in the study was 71 years, 50% were male, 88% were Caucasian and the median Karnofsky performance status score for the patients was 80.
** Instrumentel ADL: Refererer til madlavning, indkøb af dagligvarer eller tøj, brug af telefon, håndtering af penge osv. *** Personlig ADL: Refererer til bad, på-/afklædning, spisning, toiletbesøg, tage 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.
CR = fuldstændigt respons; nCR = næsten fuldstændigt respons PR = partielt respons; MR = minimalt respons
CR=Complete Response; nCR=near Complete response PR=Partial Response; MR=Minimal response
Bivirkningerne i tabel 7 ansås af investigatorerne for mindst at have en mulig eller sandsynlig årsagsmæssig 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.
Der henvises til produktresuméet for thalidomid for yderligere information.
Refer to the Summary of Product Characteristics of thalidomide for additional information.
I koncentrationsinterval for bortezomib på 0,01-1,0 μg/ml var in vitro proteinbindingen 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.
Størstedelen af patienterne i begge grupper fuldførte behandlingen, 80 % i BR-CAP-gruppen og 82 % i R-CHOP-gruppen.
The majority of the patients in both groups completed treatment, 80% in the BR-CAP group and 82% in the R-CHOP group.
130 patienter (≥ 18 år) med myelomatose, som tidligere havde haft minimim partielt respons på et bortezomib-holdigt regime, blev genbehandling ved progression.
One hundred and thirty patients (≥ 18 years of age) with multiple myeloma who previously had at least partial response on a bortezomib-containing regimen were retreated upon progression.
Til subkutan eller intravenøs anvendelse efter rekonstitution.
For subcutaneous or intravenous use after reconstitution For single use.
• Et redskab til beregning af dosis, hvor den ordinerende læge kan indlæse patientens højde og vægt for ud fra disse at beregne arealet af legemsoverfladen og derved fastsætte en passende dosering af bortezomib.
• a dose-calculation tool that enables prescribers to input a patient's height and weight in order to calculate the body surface area (BSA) and thereby to determine the appropriate bortezomib dose.
Det rapporteredes, at 6 % fik en lokal reaktion ved subkutan administration, for det meste rødmen.
Six percent of patients had an adverse local reaction to subcutaneous administration, mostly redness.
d p-værdi fra Cochran-Mantel-Haenszel chi-square-testen justeret for stratifikationsfaktorer; analyse ud fra behandling udelukker opdeling på tidligere behandling * CR+PR+MR **CR=CR, (IF-); nCR=CR (IF+)
d p-value from the Cochran Mantel-Haenszel chi-square test adjusted for the stratification factors; analysis by line of therapy excludes stratification for therapeutic history * CR+PR+MR **CR=CR, (IF-); nCR=CR (IF+)
Instruktioner for rekonstitution Bortezomib skal rekonstitueres af sundhedspersonale.
Instructions for reconstitution Bortezomib must be reconstituted by a healthcare professional.
Denne medicin indeholder det aktive stof bortezomib, som er en såkaldt proteasomhæmmer.
This medicine contains the active substance bortezomib, a so-called ‘proteasome inhibitor'.
I BR-CAP-gruppen fik 22,5 % af patienterne trombocyttransfusioner 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.
Geometrisk gennemsnit (% CV) for clearance var 7,79 (25 %) l/t/m2, fordelingsvolumen ved steady state var 834 (39 %) l/m og eliminationshalveringstiden var 100 (44 %) timer.
Geometric mean (%CV) clearance was 7.79 (25%) L/hr/m2, volume of distribution at steady-state was 834 (39%) L/m2, and the elimination half-life was 100 (44%) hours.
Reducér bortezomib til 0,7 mg/m i den første behandlingscyklus.
Reduce bortezomib to 0.7 mg/m in the first treatment cycle.
Dexamethason blev administreret i kombination med bortezomib til 83 patienter i cyklus 1, mens yderligere 11 patienter fik dexamethason i løbet af efterfølgende bortezomib-behandlingscyklusser.
Dexamethasone was administered in combination with bortezomib to 83 patients in cycle 1 with an additional 11 patients receiving dexamethasone during the course of bortezomib retreatment cycles.
Mindst 6 måneder efter den forudgående behandling initieredes bortezomib med den senest tålte dosis på 1,3 mg/m
At least 6 months after prior therapy, bortezomib was started at the last tolerated dose of 1.3 mg/m
Progressionsfri overlevelse, måneder (95 % CI)
Progression Free Survival, months (95% CI)
Desuden var forekomsten af ≥ grad 3 perifere neuropatier 10 % lavere, og seponeringsraten grundet perifer neuropati var 8 % lavere i den subkutane gruppe sammenlignet med den intravenøse gruppe.
In addition, the incidence of grade 3 or higher peripheral neuropathies was 10% lower, and the discontinuation rate due to peripheral neuropathies 8% lower for the subcutaneous group as compared to the intravenous group.
Disse effekter er blevet observeret hos patienter med myelomatose påvirket af en fremskreden osteolytisk sygdom, der har været behandlet med bortezomib.
These effects have been observed in patients with multiple myeloma affected by an advanced osteolytic disease and treated with bortezomib.
Der er gennemført et open-label, randomiseret, fase III non-inferiority studie til sammenligning af effekt og sikkerhed ved subkutan administration af bortezomib versus intravenøs administration.
An open label, randomised, Phase III non-inferiority study compared the efficacy and safety of the subcutaneous administration of bortezomib versus the intravenous administration.
Bortezomib er meget selektivt for proteasomet.
Bortezomib is highly selective for the proteasome.
Den inkluderer desuden bivirkninger, som blev identificeret i BRCAP-armen, og som af investigatorerne blev anset for at have mindst en mulig eller sandsynlig årsagssammenhæng med bortezomib, baseret på historiske data i myelomatose-studierne.
Also included are adverse drug reactions identified in the BR-CAP arm that were considered by investigators to have at least a possible or probable causal relationship to bortezomib based on historical data in the multiple myeloma studies.
I fase III-studiet førte behandlingen med bortezomib til signifikant længere tid til progression, en signifikant længere overlevelse og en signifikant højere responsrate sammenlignet med behandling med dexametason (se tabel 14) hos alle patienter samt hos patienter, som tidligere havde fået én behandling.
In the Phase III study, treatment with bortezomib led to a significantly longer time to progression, a significantly prolonged survival and a significantly higher response rate, compared to treatment with dexamethasone (see table 14), in all patients as well as in patients who have received 1 prior line of therapy.
Tabel 12: Effektresultater fra studiet IFM-2005-01 Effektmål
Table 12: Efficacy results from study IFM-2005-01 Endpoints
Det anbefales, at patienter monitoreres omhyggeligt for symptomer på neuropati, f.eks. brændende fornemmelse, hyperæstesi, hypoæstesi, paræstesi, ubehag, neuropatiske smerter eller svækkelse.
It is recommended that patients be carefully monitored for symptoms of neuropathy such as a burning sensation, hyperesthesia, hypoesthesia, paraesthesia, discomfort, neuropathic pain or weakness.
Bortezomib må ikke administreres intratekalt.
Bortezomib should not be administered intrathecally.
(95 % CI) (måneder)
(95% CI) (months)
Yderligere oplysninger om dette lægemiddel findes på Det Europæiske Lægemiddelagenturs hjemmeside http://www.ema.europa.eu.
Detailed information on this medicine is available on the website of the European Medicines Agency http://www.ema.europa.eu.
Patientdemografiske og baseline-sygdomsegenskaber var sammenlignelige mellem behandlingsgrupperne.
Patient demographic and baseline disease characteristics were similar between the treatment groups.
Tabel 11: Effektresultater efter den endelige opdatering af overlevelse i VISTA-studiet
Table 11: Efficacy results following the final survival update to VISTA study Efficacy endpoint
Behandling med bortezomib skal indstilles i op til 2 uger, indtil patienten har en ANC ≥ 750 celler/μl og et trombocyttal på ≥ 25.000 celler/μl.
Bortezomib therapy should be withheld for up to 2 weeks until the patient has an ANC ≥ 750 cells/μL and a platelet count ≥ 25,000 cells/μL.
Der blev også noteret en højere incidens af infektioner med grad ≥ 3 neutropeni (24 % versus 19 % i blok 1 og 22 % versus 11 % i blok 2), øget ALAT (17 % versus 8 % i blok 2), hypokalcæmi (18 % versus 6 % i blok 1 og 21 % versus 12 % i blok 2) og hyponatræmi (12 % versus 5 % i blok 1 og 4 % versus 0 i blok 2).
Higher incidences were also noted for infections with grade ≥ 3 neutropenia (24% versus 19% in Block 1 and 22% versus 11% in Block 2), increased ALT (17% versus 8% in Block 2), hypokalaemia (18% versus 6% in Block 1 and 21% versus 12% in Block 2) and hyponatraemia (12% versus 5% in Block 1 and 4% versus 0 in Block 2).
Hepatitis B-virus (HBV)-reaktivering og -infektion Når rituximab anvendes i kombination med bortezomib, skal patienter, som har risiko for infektion med HBV, altid screenes for HBV, inden behandlingen startes.
Hepatitis B virus (HBV) reactivation and infection When rituximab is used in combination with bortezomib, HBV screening must always be performed in patients at risk of infection with HBV before initiation of treatment.
Nominel p-værdi baseret på den stratificerede log-rank-test justeret for stratifikationsfaktorer: β2mikroglobulin, albumin og region d p-værdi for responsrate (CR+PR) fra Cochran-Mantel-Haenszel chi-square-test justeret for stratifikationsfaktorer e
Nominal p-value based on the stratified log-rank test adjusted for stratification factors: β2-microglobulin, albumin, and region d p-value for Response Rate (CR+PR) from the Cochran Mantel-Haenszel chi-square test adjusted for the stratification factors e
Bortezomib kan i moderat grad påvirke evnen til at føre motorkøretøj og betjene maskiner.
Bortezomib may have a moderate influence on the ability to drive and use machines.
Den mediane gennemsnitsalder af patienterne i studiet var 57 år, 55 % var mænd, og 48 % af patienterne blev cytogenetisk klassificeret som højrisiko.
Median age of the patients in the study was 57 years, 55% were male and 48% of patients had high-risk cytogenetics.
Ud over perifer neuropati kan der yderligere forekomme autonom neuropati ved nogle bivirkninger så som postural hypotension og svær forstoppelse med ileus.
In addition to peripheral neuropathy, there may be a contribution of autonomic neuropathy to some adverse reactions such as postural hypotension and severe constipation with ileus.
Matched-pair-analysen er en statistisk metode, i hvilken patienter i behandlingsgruppen (f.eks. bortezomib i kombination med dexamethason) og patienter i sammenligningsgruppen (f.eks. bortezomib) gøres sammenlignelige med hensyn til confounding faktorer ved individuelt at sammensætte forsøgspersonerne i par.
The matched-pair analysis is a statistical method in which patients in the treatment group (e.g. bortezomib in combination with dexamethasone) and patients in the comparison group (e.g. bortezomib) are made comparable with respect to confounding factors by individually pairing study subjects.
I fase II-studiet kunne de patienter, som ikke havde en optimal respons til behandlingen med bortezomib alene, få højdosis dexamethason sammen med bortezomib.
In the Phase II study, patients who did not obtain an optimal response to therapy with bortezomib alone were able to receive high-dose dexamethasone in conjunction with bortezomib.
Klinisk effekt ved subkutan administration af bortezomib hos patienter med recidiverende/refraktær myelomatose
Clinical efficacy with subcutaneous administration of bortezomib in patients with relapsed/refractory multiple myeloma
Grad 2 med smerter eller Grad 3 (svære symptomer; begrænset personlige pleje; personlig ADL***)
Grade 2 with pain or grade 3 (severe symptoms; limiting self care ADL***)
Selvmordstanker*, tilpasningsforstyrrelser, delirium, nedsat libido
Suicidal ideation*, Adjustment disorder, Delirium, Libido decreased
Patienter, der ikke opnåede en optimalt respons (mindre end et komplet respons [CR]) på behandlingen med bortezomib alene efter 4 cyklusser, fik desuden dexamethason 20 mg dagligt dagen før og efter administration af bortezomib.
Patients who did not obtain an optimal response (less than Complete Response [CR]) to therapy with bortezomib alone after 4 cycles were allowed to receive dexamethasone 20 mg daily on the day of and after bortezomib administration.
Dosisjusteringer under behandling og efter re-initiering af kombinationsbehandling med melphalan og prednison
Dose adjustments during treatment and re-initiation of treatment for combination therapy with melphalan and prednisone
• Blå mærker, fald og skader
• Bruises, falls and injuries
Denne interimanalyse viste en TTP-risikoreduktion på 45 % (95 % CI, 29-57 %, p < 0,0001) for patienter behandlet med kombinationsbehandlingen af bortezomib og pegyleret liposomal doxorubicin.
This interim analysis showed a TTP risk reduction of 45% (95% CI; 29-57%, p < 0.0001) for patients treated with combination therapy of bortezomib and pegylated liposomal doxorubicin.
P-værdi fra Cochran Mantel-Haenszel chi-square -test, med IPI og sygdomsstadie som stratifikationsfaktorer.
g P-value from the Cochran Mantel-Haenszel chi-square test, with IPI and stage of disease as stratification factors.
• Rådgivning om intravenøs og subkutan administration, herunder at der bør skiftes mellem injektionssteder ved s.c. anvendelse.
• advice on method of administration for both IV and SC use, including the need to rotate injection sites for SC use
Der blev observeret en statistisk signifikant fordel (p < 0,001) for BR-CAP-gruppen i forhold til R-CHOP-gruppen for TTP (median 30,5 kontra 16,1 måneder), TNT (median 44,5 kontra 24,8 måneder) og TFI (median 40,6 kontra 20,5 måneder).
A statistically significant benefit (p < 0.001) in favour of the BR-CAP treatment group over the R-CHOP group was observed for TTP (median 30.5 versus 16.1 months), TNT (median 44.5 versus 24.8 months) and TFI (median 40.6 versus 20.5 months).
Aktivering af makrofager
Macrophage activation
Når det er opløst, udtrækkes den relevante mængde af den rekonstituerede opløsning i henhold til beregnet dosis ud fra patientens legemsoverflade.
- Once dissolved, withdraw the appropriate amount of the reconstituted solution according to calculated dose based upon the patient´s Body Surface Area.
Kontroller at den korrekte dosis anvendes til subkutan administration (2,5 mg/ml).
Be sure that the correct dose is being given for the subcutaneous route of administration (2.5 mg/ml).
Efter en intravenøs bolus- eller subkutan injektion af en dosis på 1,3 mg/m hos patienter med myelomatose (n = 14 i den intravenøse gruppe, n = 17 i den subkutane gruppe) sås ækvivalente total systemisk eksponering efter gentagne doser (AUClast) for subkutan og intravenøs administration.
Following an intravenous bolus or subcutaneous injection of a 1.3 mg/m 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.
De to behandlingsgrupper var sammenlignelige, hvad angår den samlede forekomst af alle grader af blødningshændelser (6,3 % i BR-CAP-gruppen og 5,0 % i R-CHOP-gruppen) såvel som blødningshændelser af grad 3 og højere (BR-CAP: 4 patienter [1,7 %]; R-CHOP: 3 patienter [1,2 %]).
The two treatment groups were similar with regard to the overall incidence of all-grade bleeding events (6.3% in the BR-CAP group and 5.0% in the R-CHOP group) as well as grade 3 and higher bleeding events (BR-CAP: 4 patients [1.7%]; R-CHOP: 3 patients [1.2%]).
Bortezomib var positivt for klastogen aktivitet (strukturelle kromosomafvigelser) i in vitro-analysen af kromosomafvigelser ved hjælp af ovarieceller fra kinesiske hamstre (CHO-celler) i koncentrationer så lave som 3,125 μg/ml, som var den lavest undersøgte koncentration.
Bortezomib was positive for clastogenic activity (structural chromosomal aberrations) in the in vitro chromosomal aberration assay using Chinese hamster ovary (CHO) cells at concentrations as low as 3.125 μg/ml, which was the lowest concentration evaluated.
• ≥ Grad 3 neutropeni med feber, grad 4 neutropeni, som varer længere end 7 dage, trombocyttal < 10.000 celler/μl
Haematological toxicity - ≥ Grade 3 neutropenia with fever, grade 4 neutropenia lasting more than 7 days, a platelet count < 10,000 cells/μL
Brug ikke bortezomib - hvis du er allergisk over for bortezomib, bor eller et af de øvrige indholdsstoffer i denne medicin (angivet i afsnit 6).
Do not use bortezomib - if you are allergic to bortezomib, boron or to any of the other ingredients of this medicine (listed in section 6) - if you have certain severe lung or heart problems.
Tabel 15: Resumé af effektanalyser sammenlignende subkutan og intravenøs administration af bortezomib
Table 15: Summary of efficacy analyses comparing subcutaneous and intravenous administrations of bortezomib
Baseret på dyrestudier synes bortezomibs penetration af blod/hjerne-barrieren at være begrænset, om overhovedet nogen.
Based on animal studies, the penetration of bortezomib through the blood-brain barrier appears to be limited, if any and the relevance to humans is unknown.
Det anbefales at give en lavere startdosis til patienter med moderat eller alvorligt nedsat leverfunktion, og disse patienter bør monitoreres nøje (se pkt.
A lower starting dose is recommended in patients with moderate or severe hepatic impairment, and those patients should be closely monitored (see section 4.2, table 6).
Patienter, der udviklede ortostatisk hypotension med bortezomib (som intravenøs injektion) viste ikke tegn på ortostatisk hypotension før behandlingen med bortezomib.
Patients who developed orthostatic hypotension on bortezomib (injected intravenously) did not have evidence of orthostatic hypotension prior to treatment with bortezomib.
Hæmning af proteasomet resulterer i cellecyklusstop og apoptose.
Inhibition of the proteasome results in cell cycle arrest and apoptosis.
Thalidomid er et kendt teratogent lægemiddel, som medfører livstruende medfødte misdannelser hos mennesker.
Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects.
Bortezomib-kombinationsbehandling med pegyleret liposomal doxorubicin (studie DOXIL-MMY
Bortezomib combination treatment with pegylated liposomal doxorubicin (study DOXIL-MMY-3001)
• Besvær eller problemer med at sove, svedeture, angst, humørsvingninger, nedsat humør,
• Difficulty or problems in sleeping, sweating, anxiety, mood swings, depressed mood,
Der skal udvises forsigtighed, ved behandling af patienter med tidligere synkope, der får lægemidler, som er kendt for at være forbundet med hypotension, eller patienter som er dehydrerede pga. tilbagevendende diarré eller opkastning.
Caution is advised when treating patients with a history of syncope receiving medicinal products known to be associated with hypotension; or who are dehydrated due to recurrent diarrhoea or vomiting.
Bortezomib var ikke genotoksisk i in vitro-analyser af mutagenicitet (Ames' test) og in vivo-analyser af mikronukleus hos mus.
Bortezomib was not genotoxic when tested in the in vitro mutagenicity assay (Ames assay) and in vivo micronucleus assay in mice.
Der er rapporteret akut udvikling eller forværring af kongestiv hjertesvigt og/eller ny forekomst af nedsat ejektionsfraktion fra venstre ventrikel ved behandling med bortezomib.
Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported during bortezomib treatment.
Følgende bivirkninger (grad ≥ 3) blev observeret i højere grad i behandlingsregimet med bortezomib sammenlignet med et historisk kontrolstudie, hvor grundbehandlingen blev givet alene: i blok 1 perifer sensorisk neuropati (3 % versus 0 %); ileus (2,1 % versus 0 %), hypoxi (8 % versus 2 %).
The following adverse reactions (grade ≥ 3) were observed at a higher incidence in the bortezomib containing treatment regimen as compared with a historical control study in which the backbone regimen was given alone: in Block 1 peripheral sensory neuropathy (3% versus 0%); ileus (2.1% versus 0%); hypoxia (8% versus 2%).