natgillin/translations-raw huggingface dataset:
Indehaveren af markedsføringstilladelsen skal sikre, at læger og sundhedspersonale, der beskæftiger sig med ordination, udlevering, håndtering eller administration af VELCADE, forsynes med uddannelsespakken.
The MAH shall ensure thatall healthcare professionals involved in the prescribing, dispensing, handling or administration of VELCADE are provided with educational material.
Instruktioner for rekonstitution
Instructions for reconstitution
Sekundære effektendepunkter inkluderede tid til progression (TTP), tid til næste anti-lymfombehandling (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.
Hvis du har mantle-celle-lymfom og får lægemidlet rituximab sammen med VELCADE, skal du fortælle det til din læge:
If you have mantle cell lymphoma and are given the medicine rituximab with VELCADE you should tell your doctor:
Den gennemsnitlige eliminationshalveringstid (t1/2) for bortezomib efter gentagne doser var mellem 40-193 timer.
The mean elimination half-life (t1/2) of bortezomib upon multiple dosing ranged from 40-193 hours.
Forekomsten af disse hændelser var sammenlignelig i de to behandlingsarme, hvilket tyder på, at disse bivirkninger ikke udelukkende kan tilskrives VELCADE.
The similar incidences of these events in both treatment arms, indicated that these adverse drug reactions are not attributable to VELCADE alone.
• at VELCADE 3,5 mg kan administreres enten intravenøst eller subkutant, mens VELCADE 1 mg kun må administreres intravenøst
• VELCADE 3.5 mg can be administered both intravenously and subcutaneously while VELCADE 1 mg can be administered only intravenously
Der blev administreret et effektivt reinduktionskemoterapiregime med flere stoffer i 3 blokke.
An effective re-induction multi-agent chemotherapy regimen was administered in 3 blocks.
Deborerede bortezomibmetabolitter er inaktive som 26S-proteasomhæmmere.
Deboronated-bortezomib metabolites are inactive as 26S proteasome inhibitors.
Yderligere bivirkninger, som blev identificeret i forbindelse med brug af kombinationsbehandling (VcR-CAP), var hepatitis B-infektion (< 1 %) og myokardie-iskæmi (1,3 %).
Additional adverse drug reactions identified associated with the use of the combination therapy (VcR-CAP) were hepatitis B infection (< 1%) and myocardial ischaemia (1.3%).
PRES er en sjælden, ofte reversibel neurologisk lidelse, som udvikles hurtigt, og som kan optræde med blandt andet kramper, hypertension, hovedpine, sløvhed, 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.
Den geometriske gennemsnitsratio AUClast var 0,99, og 90 % konfidensintervaller var 80,18 %
The AUClast geometric mean ratio was 0.99 and 90% confidence intervals were
TTP, måneder (95 % CI)
TTP, months (95% CI)
Patienter, der udviklede ortostatisk hypotension ved VELCADE (som intravenøs injektion) viste ikke tegn på ortostatisk hypotension før behandlingen med VELCADE.
Patients who developed orthostatic hypotension on VELCADE (injected intravenously) did not have evidence of orthostatic hypotension prior to treatment with VELCADE.
Antiviral profylakse anbefales hos patienter, der bliver behandlet med VELCADE.
Antiviral prophylaxis is recommended in patients being treated with VELCADE.
Median a responsvarighed
Median a response duration
Antiviral profylakse blev administreret til 26 % af patienterne i Vc+M+P-gruppen.
Antiviral prophylaxis was administered to 26% of the patients in the Vc+M+P arm.
Tabel 11: Effektresultater efter den endelige opdatering af overlevelse i VISTA-studiet Endepunkt
Table 11: Efficacy results following the final survival update to VISTA study Efficacy endpoint
• Lavt blodtryk, pludseligt blodtryksfald i stående stilling, som kan medføre besvimelse
• Low blood pressure, sudden fall of blood pressure on standing which may lead to fainting
I fase II-studiet kunne de patienter, som ikke havde en optimal respons på behandlingen med VELCADE alene, få højdosis dexamethason sammen med VELCADE.
In the Phase II study, patients who did not obtain an optimal response to therapy with VELCADE alone were able to receive high-dose dexamethasone in conjunction with VELCADE.
Du kan finde yderligere oplysninger om dette lægemiddel 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.
Behandlingen med VELCADE forbindes almindeligvis med ortostatisk/postural hypotension.
VELCADE treatment is commonly associated with orthostatic/postural hypotension.
• Hjerteproblemer inklusive hjerteanfald, angina pectoris
• Heart problems to include heart attack, angina
Der er rapporteret sjældne tilfælde af leversvigt hos patienter, der får VELCADE og andre lægemidler samtidig og med alvorlige tilgrundliggende helbredsproblemer.
Rare cases of hepatic failure have been reported in patients receiving VELCADE and concomitant medicinal products and with serious underlying medical conditions.
På baggrund af de videnskabelige konklusioner for bortezomib er CHMP af den opfattelse, at benefit/risk-forholdet for det lægemiddel/de lægemidler, der indeholder bortezomib, forbliver uændret under forudsætning af, at de foreslåede ændringer indføres i produktinformationen.
On the basis of the scientific conclusions for bortezomib the CHMP is of the opinion that the benefitrisk balance of the medicinal product(s) containing bortezomib is unchanged subject to the proposed changes to the product information.
Den rekonstituerede opløsning skal anvendes umiddelbart efter præparering.
The reconstituted solution should be used immediately after preparation.
Samlet blev VELCADE givet til 3.974 patienter til behandling af myelomatose.
Overall, VELCADE was administered for the treatment of multiple myeloma in 3,974 patients.
Tabel 12: Effektresultater fra studiet IFM-2005-01
Table 12: Efficacy results from study IFM-2005-01
Den inkluderer desuden bivirkninger, som blev identificeret i VcR-CAP-armen, og som af investigatorerne blev anset for at have mindst en mulig eller sandsynlig årsagssammenhæng med VELCADE, baseret på historiske data i myelomatosestudierne.
Also included are adverse drug reactions identified in the VcR-CAP arm that were considered by investigators to have at least a possible or probable causal relationship to VELCADE based on historical data in the multiple myeloma studies.
Kombination med dexamethason
Combination with dexamethasone
Seponering på grund af PN (%)
Discontinuation due to PN (%)
Dag 1, 4
Day 1, 4
På grund af risiko for alvorlige bivirkninger hos ammede børn bør amning ophøre under behandling med VELCADE.
Because of the potential for serious adverse reactions in breast-fed infants, breast-feeding should be discontinued during treatment with VELCADE.
Det skal du vide, før du begynder at bruge VELCADE
What you need to know before you use VELCADE
Der er gennemført et åbent, randomiseret, fase III noninferiority-studie til sammenligning af effekt og sikkerhed af subkutan administration af VELCADE versus intravenøs administration.
An open label, randomised, Phase III non-inferiority study compared the efficacy and safety of the subcutaneous administration of VELCADE versus the intravenous administration.
Patienter, som havde fået 2 eller 3 tidligere behandlinger, havde en responsrate på 32 % (10/32) og patienter, som havde fået mere end 7 tidligere behandlinger, havde en responsrate på 31 % (21/67).
Patients who had received 2 to 3 prior therapeutic regimens had a response rate of 32% (10/32) and patients who received greater than 7 prior therapeutic regimens had a response rate of 31% (21/67).
Henholdsvis 42,9 % og 10,4 % af patienterne i VcR-CAP-armen var i alderen 65-74 år og ≥ 75 år.
42.9% and 10.4% of patients in the VcR-CAP arm were in the range 65-74 years and ≥ 75 years of age, respectively.
Uddannelsespakken skal omfatte følgende:
The educational material shall consist of the following:
Størstedelen af patienterne i begge grupper fuldførte behandlingen, 80 % i VcR-CAP-gruppen og 82 % i R-CHOP-gruppen.
The majority of the patients in both groups completed treatment, 80% in the VcR-CAP group and 82% in the R-CHOP group.
rastløshed eller ophidselse, ændringer i sindstilstand, desorientering
restlessness or agitation, changes in your mental status, disorientation
Dette lægemiddel er kun til intravenøs anvendelse.
This medicine is for intravenous use only.
Population evaluerbar for respons n = 73
Response Evaluable Population n=73
Hepatitis B-virus (HBV)-reaktivering og -infektion Når rituximab anvendes i kombination med VELCADE, 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 VELCADE, HBV screening must always be performed in patients at risk of infection with HBV before initiation of treatment.
blødning fra øjnene
bleeding of the eye
Estimatet af Hazard ratio er baseret på Cox' proportionelle risikomodel justeret for stratifikationsfaktorer: 2mikroglobulin, albumin og region.
Hazard ratio estimate is based on a Cox proportional-hazard model adjusted for stratification factors: 2-microglobulin, albumin, and region.
Forholdet mellem fordele og risici skal overvejes, før behandlingen med VELCADE fortsætter.
The benefit/risk ratio should be considered prior to continuing VELCADE therapy.
Der skal udvises særlig forsigtighed, ved behandling af patienter med risikofaktorer for kramper.
Special care is required when treating patients with any risk factors for seizures.
Normal leverfunktion skal bekræftes, og der skal udvises forsigtighed ved patienter, der behandles med orale hypoglykæmika (se pkt.
Normal liver function should be confirmed and caution should be exercised in patients receiving oral hypoglycemics (see section 4.5).
• Hvis trombocyttallet er ≤ 30 x 10
• If platelet counts ≤ 30 x 10
• En alvorlig, reversibel tilstand i hjernen, der omfatter krampeanfald, højt blodtryk, hovedpine,
• A severe reversible brain condition which includes seizures, high blood pressure, headaches,
I bortezomibs koncentrationsinterval 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.
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).
Inkluderer alle radiologiske CR+CRu+PR efter IRC uanset verificering ved knoglemarv og LDH.
Include all radiological CR+CRu+PR by IRC regardless the verification by bone marrow and LDH.
M (9 mg/m P (60 mg/m da g 1
M (9 mg/m P (60 mg/m
Justering af initialdosis
Modification of starting dose
Geometrisk middel (%CV) for clearance var 7,79 (25 %) l/t/m2, fordelingsvolumen ved steady state var 834 (39 %) l/m2 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.
Kun hætteglasset med 3,5 mg kan administreres subkutant som beskrevet nedenfor:
Only the 3.5 mg vial can be administered subcutaneously, as described below.
Desuden var forekomsten af ≥ grad 3 perifere neuropatier 10 % lavere, og seponeringsraten på grund af perifer neuropati var 8 % lavere i den subkutane gruppe i forhold til 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.
Tidlig og regelmæssig monitorering for symptomer på behandlingsrelateret neuropati og neurologisk evaluering skal overvejes hos patienter, der får VELCADE i kombination med lægemidler, der vides at være forbundet med neuropati (fx 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 VELCADE in combination with medicinal products known to be associated with neuropathy (e.g. thalidomide) and appropriate dose reduction or treatment discontinuation should be considered.
Turnhoutseweg 30 B-2340 Beerse Belgien
Turnhoutseweg 30 B-2340 Beerse Belgium
Den mediane alder hos patienterne i studiet var 71 år, 50 % var mænd, 88 % var kaukasere og medianen for Karnofsky performance status 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.
Bortezomib var positivt for klastogen aktivitet (strukturelle kromosomafvigelser) i in vitro-analysen af kromosomafvigelser ved hjælp af ovarieceller fra kinesiske hamstre (CHO) i koncentrationer så lave som 3,125 µg/ml, som var den lavest vurderede 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.
Patienter, der ikke opnåede et optimalt respons (mindre end et komplet respons [CR]) på behandlingen med VELCADE alene efter 4 cyklusser, fik desuden dexamethason 20 mg dagligt dagen før og efter administration af VELCADE.
Patients who did not obtain an optimal response (less than Complete Response [CR]) to therapy with VELCADE alone after 4 cycles were allowed to receive dexamethasone 20 mg daily on the day of and after VELCADE administration.
I tilfælde af overdosering skal patientens vitale tegn monitoreres, og der skal ydes relevant, støttende behandling for at opretholde blodtrykket (f.eks. væske, pressorer og/eller inotropiske midler) og kropstemperatur (se pkt.
In the event of an overdose, the patient's vital signs should be monitored and appropriate supportive care given to maintain blood pressure (such as fluids, pressors, and/or inotropic agents) and body temperature (see sections 4.2 and 4.4).
- Øvrige indholdsstoffer: Mannitol (E421) og nitrogen.
- The other ingredients are mannitol (E421) and nitrogen.
Analysen påviste forbedret ORR (CR+PR) (odds-ratio 3,769; 95 % CI 2,045-6,947; p < 0,001), PFS (hazard ratio 0,511; 95 % CI 0,309--0,845; p = 0,008), TTP (hazard ratio 0,385; 95 % CI 0,212--0,698; p = 0,001) for VELCADE sammen med dexamethason over VELCADE som monoterapi.
The analysis demonstrated improved ORR (CR+PR) (odds ratio 3.769; 95% CI 2.045-6.947; p < 0.001), PFS (hazard ratio 0.511; 95% CI 0.309-0.845; p=0.008), TTP (hazard ratio 0.385; 95% CI 0.212-0.698; p=0.001) for VELCADE in combination with dexamethasone over VELCADE monotherapy.
Samlet respons (CR+CRu+PR)
Overall response (CR+CRu+PR)
Gastrointestinal toksicitet, inklusive kvalme, diaré, opkastning og forstoppelse, er meget almindelig ved behandling med VELCADE.
Gastrointestinal toxicity, including nausea, diarrhoea, vomiting and constipation are very common with VELCADE treatment.
Det anbefales, at patienterne får to cyklusser med VELCADE efter bekræftelse af et komplet respons.
It is recommended that patients receive 2 cycles of VELCADE following a confirmation of a complete response.
Da dialyse kan reducere koncentrationen af bortezomib, bør VELCADE gives efter dialyse (se pkt.
Since dialysis may reduce bortezomib concentrations, VELCADE should be administered after the dialysis procedure (see section 5.2).
• Vægtstigning
• Weight increase
I fase III-studiet førte behandlingen med VELCADE til signifikant længere tid indtil progression, en signifikant længere overlevelse og en signifikant højere responsrate sammenlignet med behandling med dexamethason (se tabel 14) hos alle patienter samt hos patienter, som tidligere havde fået én behandling.
In the Phase III study, treatment with VELCADE 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.
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).
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med VELCADE i alle undergrupper af den pædiatriske population ved myelomatose og ved mantlecelle-lymfom (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with VELCADE in all subsets of the paediatric population in multiple myeloma and in mantle cell lymphoma (see section 4.2 for information on paediatric use).
Følgende bivirkninger (grad ≥ 3) blev observeret med en hyppigere forekomst i behandlingsregimet med VELCADE sammenlignet med et historisk kontrolstudie, i hvilket baggrundsregimet blev givet alene: I blok 1 perifer sensorisk neuropati (3 % kontra 0 %), ileus (2,1 % kontra 0 %), hypoksi (8 % kontra 2 %).
The following adverse reactions (Grade ≥ 3) were observed at a higher incidence in the VELCADE 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%).
Den samlede forekomst af diarré, smerter i mave-tarm-kanalen og abdomen, asteniske tilstande, øvre luftvejsinfektioner og perifere neuropatier var 12 % til 15 % lavere i den subkutane gruppe end i den intravenøse gruppe.
The overall incidence of diarrhoea, gastrointestinal and abdominal pain, asthenic conditions, upper respiratory tract infections and peripheral neuropathies were 12%-15% lower in the subcutaneous group than in the intravenous group.
I VcR-CAP-gruppen fik 22,5 % af patienterne trombocyttransfusioner sammenlignet med 2,9 % af patienterne i R-CHOP-gruppen.
In the VcR-CAP group, 22.5% of patients received platelet transfusions compared to 2.9% of patients in the R-CHOP group.
Der observeredes ikke nogen nye sikkerhedsproblemer, når VELCADE blev føjet til standard-kemoterapiregimet for pædiatrisk præ-B-celle ALL.
No new safety concerns were observed when VELCADE was added to the standard pediatric pre-B cell ALL chemotherapy backbone.
Komplet blodtælling (CBC) med differentialtælling og inklusive trombocyttal skal gennemføres hyppigt under behandlingen med VELCADE.
Complete blood counts (CBC) with differential and including platelet counts should be frequently monitored throughout treatment with VELCADE.
Grad ≥ 3 ikke-hæmatologisk toksicitet, som anses for relateret til VELCADE
Grade ≥ 3 non-haematological toxicities considered to be related to VELCADE
Tabel 15: Oversigt over effektanalyser til sammenligning af subkutan og intravenøs administration af VELCADE
Table 15: Summary of efficacy analyses comparing subcutaneous and intravenous administrations of VELCADE
Brochuren om rekonstitution, dosering og administration skal indeholde følgende hovedpunkter:
The Reconstitution, dosing and administration booklet shall contain the following key elements:
Studiet opfyldte det primære mål, som var non-inferiority, hvad angår responsrate (CR+PR) efter 4 cyklusser med VELCADE som monoterapi for såvel subkutan som intravenøs administration, 42 % i begge grupper.
This study met its primary objective of non-inferiority for response rate (CR+PR) after 4 cycles of single agent VELCADE for both the subcutaneous and intravenous routes, 42% in both groups.
Der skal derfor udvises forsigtighed ved håndtering og anvendelse af VELCADE.
Therefore, caution should be used during handling and preparation of VELCADE.
Tabel 9: Forekomst af perifer neuropati under induktionsbehandling efter toksicitet og behandlingsseponering på grund af perifer neuropati IFM-2005-01
Table 9: Incidence of peripheral neuropathy during induction treatment by toxicity and treatment discontinuation due to peripheral neuropathy IFM-2005-01
• 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.
Bemærkelsesværdige forskelle mellem sikkerhedsprofilen for VELCADE administreret subkutant versus intravenøst som monoterapi
Notable differences in the safety profile of VELCADE administered subcutaneously versus intravenously as single agent
Der blev observeret en statistisk signifikant fordel (p < 0,001) for VcR-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 VcR-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).
• Delvist eller totalt synstab
• Partial or total loss of vision
VELCADEs sikkerhed og virkning hos børn under 18 år er ikke klarlagt (se pkt.
The safety and efficacy of VELCADE in children below 18 years of age have not been established (see sections 5.1 and 5.2).
Behandlingen med VELCADE forbindes meget ofte med hæmatologisk toksicitet (trombocytopeni, neutropeni og anæmi).
VELCADE treatment is very commonly associated with haematological toxicities (thrombocytopenia, neutropenia and anaemia).
De to behandlingsgrupper var sammenlignelige, hvad angår den samlede forekomst af alle grader af blødningshændelser (6,3 % i VcR-CAP-gruppen og 5,0 % i R-CHOP-gruppen) såvel som blødningshændelser af grad 3 og højere (VcR-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 VcR-CAP group and 5.0% in the R-CHOP group) as well as Grade 3 and higher bleeding events (VcR-CAP: 4 patients [1.7%]; R-CHOP: 3 patients [1.2%]).
Tabel 1: Anbefalede* dosisændringer ved bortezomib-relateret neuropati Sværhedsgrad af perifer neuropati
Table 1: Recommended* posology modifications for bortezomib-related neuropathy Severity of neuropathy
Neuropatiske smerter og/eller perifer neuropati
Neuropathic pain and/or peripheral neuropathy
I et studie med patienter med tidligere ubehandlet mantle-celle-lymfom var henholdsvis 42,9 % og 10,4 % af de patienter, der fik VELCADE, i alderen 65-74 år og ≥ 75 år.
In a study in previously untreated mantle cell lymphoma patients, 42.9% and 10.4% of patients exposed to VELCADE were in the range 65-74 years and ≥ 75 years of age, respectively.
Der foreligger begrænsede oplysninger om VELCADE til genbehandling af recidiverende myelomatose.
Limited information on VELCADE retreatment in relapsed multiple myeloma is available.
• Betændelse eller blødning i blodkarrene; det 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
Hazard ratio (95 % CI) p-værdi
Hazard ratio (95% CI) p-value
In vitro-studier viser, at bortezomib er en svag hæmmer af cytochrom P450 (CYP)-isozymer 1A2, 2C9, 2C19, 2D6 og 3A4.
In vitro studies indicate that bortezomib is a weak inhibitor of the cytochrome P450 (CYP) isozymes 1A2, 2C9, 2C19, 2D6 and 3A4.
Reducer VELCADE til 1,0 mg/m eller
Reduce VELCADE to 1.0 mg/m or