natgillin/translations-raw huggingface dataset:
Dosisjusteringer i behandlingsforløbet og ved genoptagelse af kombinationsbehandling med melphalan og prednison
Dose adjustments during treatment and re-initiation of treatment for combination therapy with melphalan and prednisone
Patienter i behandling med orale antidiabetika, som behandles med bortezomib, kan have brug for nøje monitorering af deres blodsukkerniveau og justering af deres antidiabetikadosis.
Patients on oral antidiabetic agents receiving bortezomib treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetics.
Den mediane overlevelse i Bzmb+M+P-behandlingsgruppen var 56,4 måneder sammenlignet med 43,1 i M+P-behandlingsgruppen.
Median survival for the Bzmb+M+P treatment group was 56.4 months compared to 43.1 for the M+P treatment group.
Både mænd og kvinder, som er i behandling med Bortezomib SUN, skal anvende sikker prævention under og op til 3 måneder efter behandlingen.
Both men and women receiving Bortezomib SUN must use effective contraception during and for up to 3 months after treatment.
Medianc (95 % CI) (måneder) Responsrate n: respons-evaluerbare patienter Samlet komplet respons (CR+CRu)f n(%)
Medianc(95% CI) (months) Response rate n: response-evaluable patients Overall complete response (CR+CRu)f n(%)
• 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 SUN plus dexamethason og Bortezomib SUN 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 SUN plus dexamethasone, and Bortezomib SUN plus dexamethasone and thalidomide).
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
• regler for opbevaring af den rekonstituerede opløsning
• storage precautions for reconstituted solution
Et hætteglas er kun til engangsbrug, og resterende opløsning skal bortskaffes.
DISPOSAL A vial is for single use only and the remaining solution must be discarded.
Grad ≥ 3 ikke-hæmatologisk toksicitet, som anses for relateret til Bortezomib SUN
Grade ≥ 3 non-haematological toxicities considered to be related to Bortezomib SUN
Som et resultat af den forud planlagte interimanalyse blev dexamethason-gruppen standset på anbefaling fra datamonitoreringskomiteen, alle patienter som var randomiseret til dexamethason, 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.
Kombination med dexamethason
Combination therapy with dexamethasone
Disse bivirkninger er baseret på et integreret datasæt med 5.476 patienter, hvoraf 3.996 patienter blev behandlet med bortezomib ved 1,3 mg/m2 og er medtaget 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.
Særlige instruktioner for håndtering.
Special handling instructions
Bærere af hepatitis B og patienter med en anamnese med hepatitis B skal nøje monitoreres for kliniske og laboratoriemæssige tegn på aktiv HBV-infektion under og efter rituximab-kombinationsbehandling med bortezomib.
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.
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 behandlingsseponering 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.
INDHOLD ANGIVET SOM VÆGT, VOLUMEN ELLER ANTAL DOSER 3,5 mg
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 3.5 mg
- Når Bortezomib SUN gives sammen med thalidomid og dexamethason, er varigheden af en behandlingscyklus 28 dage (4 uger).
- When Bortezomib SUN is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks).
Graviditet og amning Du må ikke bruge Bortezomib SUN, hvis du er gravid, medmindre det er absolut nødvendigt.
Pregnancy and breast-feeding You should not use Bortezomib SUN if you are pregnant, unless clearly necessary.
Derfor frarådes det at anvende dette regime med samtidig administration af højdosis-cytarabin (2 g/m2 dagligt) ved kontinuerlig infusion over en periode på 24 timer.
Therefore, this specific regimen with concomitant administration with high-dose cytarabine (2 g/m2 per day) by continuous infusion over 24 hours is not recommended.
Trombocyttransfusion til behandling af trombocytopeni skal overvejes, når det er klinisk relevant.
Platelet transfusion for the treatment of thrombocytopenia should be considered when clinically appropriate.
I koncentrationer på 10 µM hæmmer bortezomib ingen af en lang række screenede receptorer og proteaser og er mere end 1.500 gange så selektivt for proteasom 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.
Det primære effektendepunkt var TTP, og det sekundære effektendepunkt var OS og ORR (CR+PR), og kriterierne fra The European Group for Blood and Marrow Transplantation (EBMT) blev brugt.
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.
Opløsningen vil blive klar og farveløs med en pH på 4 til 7.
The solution will be clear and colourless, with a final pH of 4 to 7.
Autonom neuropati kan relateres til bortezomib, eller bortezomib kan forværre en tilgrundliggende tilstand som f.eks. diabetisk eller amyloid neuropati.
Autonomic neuropathy may be related to bortezomib or bortezomib may aggravate an underlying condition such as diabetic or amyloidotic neuropathy.
g Alle randomiserede patienter med sekretorisk sygdom.
EBMT criteria g All randomised patients with secretory disease
Patienter, der opnår respons eller stabiliseret sygdom efter 4 cyklusser med denne kombinationsbehandling, kan fortsætte behandlingen med 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.
Fase II-studiet MMY-2036 (RETRIEVE), et åbent studie med en enkelt arm, blev udført for at bestemme virkning 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.
Der observeredes ikke nogen nye sikkerhedsproblemer, når bortezomib blev føjet til standard-kemoterapiregimet for pædiatrisk præ-B-celle ALL.
No new safety concerns were observed when bortezomib was added to the standard paediatric pre B cell ALL chemotherapy backbone.
p < 0,0001. c Responspopulation omfatter patienter, som havde målbar sygdom ved baseline og fik mindst 1 dosis studiemedicin.
c Response population includes patients who had measurable disease at baseline and received at least 1 dose of study medicinal product.
Patientdemografi og baseline-sygdomsegenskaber var sammenlignelige behandlingsgrupperne imellem.
Patient demographic and baseline disease characteristics were similar between the treatment groups.
Tidligere ubehandlet myelomatose
Previously untreated multiple myeloma
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/m2 basis are associated with increases in heart rate, decreases in contractility, hypotension and death.
Almindelig Urinvejsinfektion*
Common Urinary tract infection*
I prækliniske studier havde bortezomib ingen indvirkning på den embryonale/føtale udvikling hos rotter og kaniner ved den højeste tålte dosis hos mater.
In non-clinical studies, bortezomib had no effects on embryonal/foetal development in rats and rabbits at the highest maternally tolerated doses.
Efter en gennemgang af tilfælde efter markedsføringen og rapporter i litteraturen for den periode, som denne PSUR dækker, blev der fundet 158 tilfælde af “øjenlågs-, øjenvippe- og tåregangsinfektion, -irritation og -inflammation” hos patienter, som fik bortezomib.
Following a review of post-marketing cases and literature reports for the period covered by this PSUR, 158 cases of “Lid, lash and lacrimal infections, irritations and inflammations” were retrieved in patients who received bortezomib.
Indehaveren af markedsføringstilladelsen skal sikre, at læger og sundhedspersonale, der beskæftiger sig med ordination, udlevering, håndtering eller administration af Bortezomib SUN, forsynes med uddannelsespakken.
The MAH shall ensure that all healthcare professionals involved in the prescribing, dispensing, handling or administration of Bortezomib SUN are provided with educational materials.
Der blev observeret en statistisk signifikant forbedring af overlevelsen i Bzmb+M+Pbehandlingsgruppen (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 Bzmb+M+P treatment group was observed (HR=0.695; p=0.00043) despite subsequent therapies including bortezomib-based regimens.
- Hvis flere Bortezomib SUN-doser i en cyklus tilbageholdes (≥ 3 doser under indgift to gange om ugen eller ≥ 2 doser under indgift en gang om ugen)
- If several Bortezomib SUN doses in a cycle are withheld (≥ 3 doses during twice weekly administration or ≥ 2 doses during weekly administration)
Patienter med præeksisterende, svær neuropati må kun behandles med Bortezomib SUN efter en omhyggelig vurdering af risici og fordele.
Patients with pre-existing severe neuropathy may be treated with Bortezomib SUN only after careful risk/benefit assessment.
Tabel 12: Effektresultater fra studiet IFM-2005-01 Endepunkter
Table 12: Efficacy results from study IFM-2005-01 Endpoints
Begge grupper fik i gennemsnit 4 cyklusser.
The median number of cycles received for both groups was 4 cycles.
Patienter i henholdsvis BzmbTDx- 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 BzmbTDx 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.
România Tel. +40 (264) 501 500
Tel. +40 (264) 501 500
Bortezomib bør ikke anvendes under graviditeten, medmindre kvindens kliniske tilstand kræver behandling med Bortezomib SUN.
Bortezomib should not be used during pregnancy unless the clinical condition of the woman requires treatment with bortezomib.
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.
I myelomer påvirker bortezomib myelomcellernes evne til at interagere med knoglemarvens mikromiljø.
In myeloma, bortezomib affects the ability of myeloma cells to interact with the bone marrow microenvironment.
Antiviral profylakse blev administreret til 26 % af patienterne i Bzmb+M+P-gruppen.
Antiviral prophylaxis was administered to 26% of the patients in the Bzmb+M+P arm.
Patienter med risiko for tumorlysesyndrom er dem, der allerede har en høj tumorbyrde forud for behandlingen.
The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment.
Hvis den ikke anvendes omgående, er opbevaringstider og -betingelser før anvendelsen brugerens ansvar.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Forekomsten af disse hændelser var sammenlignelig i de to behandlingsarme, hvilket tyder på, at disse bivirkninger ikke udelukkende kan tilskrives bortezomib.
The similar incidences of these events in both treatment arms, indicated that these adverse drug reactions are not attributable to bortezomib alone.
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.
Behandling med bortezomib er meget ofte forbundet med perifer neuropati, som er overvejende sensorisk.
Treatment with bortezomib is very commonly associated with peripheral neuropathy, which is predominantly sensory.
En oddsratio (OR) > 1 angiver en fordel for BzmbR-CAP. f Inkluderer alle CR+CRu, efter IRC, knoglemarv og LDH.
An odds ratio (OR) > 1 indicates an advantage for BzmbR-CAP. f Include all CR+CRu, by IRC, bone marrow and LDH.
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 kropstemperaturen (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
Den er specifikt designet til at hæmme chymotrypsinlignende aktivitet ved 26S-proteasom i pattedyrceller.
It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells.
Dette tyder på, at bortezomib i stor udstrækning distribueres til perifert væv.
This suggests that bortezomib distributes widely to peripheral tissues.
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.
Der findes ingen specifik antidot mod overdosering af bortezomib.
There is no known specific antidote for bortezomib overdose.
Sekundære effektendepunkter 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.
De gennemsnitlige AUCværdier justeret i forhold til standarddosis øgedes dog 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.
Fase II
Phase II
Frekvensen defineres som: Meget almindelig (≥ 1/10), almindelig (≥ 1/100 til < 1/10), ikke almindelig (≥ 1/1.000
Frequencies are defined as: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100);
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 CNS problems.
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.
En biologisk plausibilitet understøtter sammenhængen mellem bortezomib og chalazion/blefaritis: teoretisk set kan bortezomib-relateret myelosuppression bane vejen for virusinfektioner som f.eks. herpes zoster, hvilket fremmer chalazia.
A biological plausibility supports the association between bortezomib and chalazion/blepharitis; theoretically, bortezomib-related myelosuppression may facilitate viral infections such as herpes zoster thereby promoting chalazia.
Det anbefales at give en lavere startdosis til patienter med moderat eller alvorligt nedsat leverfunktion, og disse patienter bør monitoreres nøje (se tabel 6, 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).
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.
56,4 mdr.
56.4 mo
Sekundære effektendepunkter inkluderede tid til progression (TTP), tid til næste antilymfombehandling (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.
Fraktionen af bortezomib bundet til plasmaproteiner var ikke koncentrationsafhængig.
The fraction of bortezomib bound to plasma proteins was not concentration-dependent.
** Instrumentel ADL: Dækker madlavning, indkøb af dagligvarer eller tøj, brug af telefon, håndtering af penge osv. *** Personlig ADL: 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.
1 års overlevelse, [95 % CI]
1 year survival, [95% CI]
Sådanne ændringer kan være reversible ved seponering af bortezomib (se pkt.
Such changes may be reversible upon discontinuation of bortezomib (see section 4.8).
- 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).
Bortezomib SUN en gang om ugen (cyklus 5-9)
Once weekly Bortezomib SUN (cycles 5-9)
130 patienter (≥ 18 år) med myelomatose, som tidligere havde haft mindst partielt respons på et bortezomib-holdigt regime, fik ny behandling 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.
Den samlede forekomst af diarré, smerter i mave-tarm-kanalen og abdomen, asteniske tilstande, øvre luftvejsinfektioner og perifere neuropatier var 12-15 % 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.
Mandlige og kvindelige fertile patienter skal anvende sikker kontraception under behandlingen og i 3 måneder efter behandlingen.
Male and female patients of childbearing potential must use effective contraceptive measures during and for 3 months following treatment.
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).
Bemærk: OR > 1 tyder på en fordel for Bzmb-indeholdende induktionsterapi.
Note: An OR > 1 indicates an advantage for Bzmb-containing induction therapy.
Kinetikken ved proteasomhæmning blev vurderet in vitro, og det blev påvist, at bortezomib adskiller sig fra proteasom med et t1/2 på 20 minutter, hvilket påviser, 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.
Kontroller, 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).
Patienter, der oplever ny eller forværret perifer neuropati, bør få foretaget en neurologisk evaluering og kan have brug for ændring af dosis, behandlingsplan eller ændring til den subkutane administrationsvej (se pkt.
Patients experiencing new or worsening peripheral neuropathy should undergo neurological evaluation and may require a change in the dose, schedule or route of administration to subcutaneous (see section 4.2).
Der blev administreret et effektivt reinduktionskemoterapiregime med flere stoffer i 3 blokke.
An effective reinduction multiagent chemotherapy regimen was administered in 3 blocks.
Seks Bortezomib SUN-cyklusser anbefales, men patienter med et respons, som først dokumenteres ved cyklus 6, kan gives yderligere to Bortezomib SUN-cyklusser.
Six Bortezomib SUN cycles are recommended, although for patients with a response first documented at cycle 6, two additional Bortezomib SUN cycles may be given.
Baseret på en farmakokinetisk populationsanalyse øgedes bortezomibclearance ved stigende BSA (legemsoverfladeareal).
Based on a population pharmacokinetic analysis, clearance of bortezomib increased with increasing body surface area (BSA).
Deborerede bortezomib-metabolitter er inaktive som 26S-proteasomhæmmere.
Deboronated-bortezomib metabolites are inactive as 26S proteasome inhibitors.
Den færdige koncentration i opløsningen vil være 2,5 mg/ml.
The concentration of the resulting solution will be 2.5 mg/ml.
Trombocyttallet skal derfor monitoreres før hver bortezomib-dosis.
Therefore, platelet counts should be monitored prior to each dose of bortezomib.
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.
≤ 1,0 x ULN > ULN
≤ 1.0 x ULN