natgillin/translations-raw huggingface dataset:
Kravene for fremsendelse af periodiske, opdaterede sikkerhedsindberetninger for dette lægemiddel fremgår af listen over EU-referencedatoer (EURD list), som fastsat i artikel 107c, stk. 7, i direktiv 2001/83/EF, og alle efterfølgende opdateringer offentliggjort på Det Europæiske Lægemiddelagenturs hjemmeside http://www.ema.europa.eu. 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.>
• At lægemidlet skal håndteres under sterile betingelser. 
• need to handling the medicinal product in sterile setting
Den mediane overlevelse i B+M+P-behandlingsgruppen var 56,4 måneder sammenlignet med 43,1 i M+P-behandlingsgruppen. 
Median survival for the B+M+P treatment group was 56.4 months compared to 43.1 for the M+P treatment group.
9/l på en bortezomib doseringsdag (bortset fra dag 1) 
9/l on a bortezomib dosing day (other than day 1)
Thalidomid er kontraindiceret under graviditet og til kvinder i den fertile alder, medmindre alle betingelserne i programmet for svangerskabsforebyggelse for thalidomid overholdes. 
Thalidomide is contraindicated during pregnancy and in women of childbearing potential unless all the conditions of the thalidomide pregnancy prevention programme are met.
Antiviral profylakse blev administreret til 26 % af patienterne i B+M+P-armen. 
Antiviral prophylaxis was administered to 26% of the patients in the B+M+P arm.
I koncentrationer på 10 μM hæmmer bortezomib ikke nogen af en lang række screenede receptorer og proteaser, og er mere end 1.500 gange mere selektivt for proteasomet end for det næste foretrukne enzym. 
At 10 μM concentrations, bortezomib does not inhibit any of a wide variety of receptors and proteases screened and is more than 1,500-fold more selective for the proteasome than for its next preferable enzyme.
Tjek dosis og koncentration i sprøjten før brug (kontroller, at sprøjten er mærket som intravenøs administration). 
- Confirm the dose and concentration in the syringe prior to use (check that the syringe is marked as intravenous administration).
Den rekonstituerede opløsning er klar og farveløs med en endelig pH-værdi på 4 til 7. 
The reconstituted solution is clear and colourless, with a final pH of 4 to 7.
Derfor frarådes det at anvende dette regime med samtidig administration af højdosis cytarabin (2 g/m daglig) 
Therefore, this specific regimen with concomitant administration with high-dose cytarabine (2 g/m per day)
Disse bivirkninger er baseret på et integreret datasæt med 5.476 patienter, hvoraf 3.996 patienter blev behandlet med bortezomib ved 1,3 mg/m og er inkluderet i tabel 7. 
These adverse reactions are based on an integrated data set of 5,476 patients of whom 3,996 were treated with bortezomib at 1.3 mg/m and included in table 7.
Patienter, som opnår respons eller stabiliseret sygdom efter 4 cyklusser med denne kombinationsbehandling, kan fortsætte med den samme kombination i højst 4 yderligere cyklusser. 
Patients achieving a response or a stable disease after 4 cycles of this combination therapy can continue to receive the same combination for a maximum of 4 additional cycles.
Ubiquitin-proteasom-vejen spiller en vigtig rolle i reguleringen af omsætningen af specifikke proteiner, som derved opretholder homeostasen i cellerne. 
The ubiquitin-proteasome pathway plays an essential role in regulating the turnover of specific proteins, thereby maintaining homeostasis within cells.
Studier har vist, at bortezomib er cytotoksisk over for en række cancercelletyper, og at cancerceller er mere følsomme over for den pro-apoptotiske effekt af proteasomhæmning end normale celler. 
Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types and that cancer cells are more sensitive to the pro-apoptotic effects of proteasome inhibition than normal cells.
• Instruktioner i ordinering og administration, herunder cyklussernes længde og antal cyklusser, for herved at minimere risikoen for lægmiddel- eller administrationsfejl, der kunne opstå grundet de to forskellige bortezomibkombinationsregimer i transplantationsinduktionsregi (bortezomib plus dexamethason og bortezomib plus dexamethason og thalidomid). 
• instructions for prescribing and administration including the cycles' length and number of cycles, to minimise the risk of medication and dispensing errors potentially induced by the existence of the two different bortezomib combination regimens in the Transplant Induction Setting (bortezomib plus dexamethasone, and bortezomib plus dexamethasone and thalidomide).
Det primære effektmål var TTP, og det sekundære effektmål var OS og ORR (CR+PR), ved brug af kriterierne fra The European Group for Blood and Marrow Transplantation (EBMT). 
The primary efficacy endpoint was TTP while the secondary efficacy endpoints were OS and ORR (CR+PR), using the European Group for Blood and Marrow Transplantation (EBMT) criteria.
En hazard ratio < 1 angiver en fordel for BR-CAP. 
A hazard ratio < 1 indicates an advantage for BR-CAP.
Patienter med præ-eksisterende svær neuropati må kun behandles med bortezomib efter en omhyggelig vurdering af risici og fordele. 
Patients with pre-existing severe neuropathy may be treated with bortezomib only after careful risk/benefit assessment.
Tidlig og regelmæssig monitorering for symptomer på behandlingsrelateret neuropati og neurologisk evaluering skal overvejes hos patienter, der får bortezomib i kombination med lægemidler, der vides at være forbundet med neuropati (f.eks. thalidomid), og passende dosisreduktion eller seponering af behandling skal overvejes. 
Early and regular monitoring for symptoms of treatment-emergent neuropathy with neurological evaluation should be considered in patients receiving bortezomib in combination with medicinal products known to be associated with neuropathy (e.g. thalidomide) and appropriate dose reduction or treatment discontinuation should be considered.
træthed, konfusion, blindhed eller andre synsproblemer 
tiredness, confusion, blindness or other vision problems.
Den er specifikt designet til at hæmme chymotrypsin-lignende aktivitet ved 26S-proteasomet i pattedyrceller. 
It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells.
Der blev observeret en statistisk signifikant forbedring af overlevelsen i B+M+P-behandlingsgruppen (HR=0,695; p=0,00043) til trods for efterfølgende behandlinger, inklusive regimer baseret på bortezomib. 
A statistically significant survival benefit in favour of the B+M+P treatment group was observed (HR=0.695; p=0.00043) despite subsequent therapies including bortezomib-based regimens.
• Hvis der observeres langvarig grad 4 neutropeni eller trombocytopeni eller trombocytopeni med blødning i den forgående cyklus 
• If prolonged grade 4 neutropenia or thrombocytopenia, or thrombocytopenia with bleeding is observed in the previous cycle
Bivirkninger, identificeret med en forekomst på ≥ 1 %, tilsvarende eller højere forekomst i BR-CAParmen og med mindst en mulig eller sandsynlig årsagssammenhæng med komponenterne i BR-CAParmen, er anført i tabel 8 nedenfor. 
Adverse drug reactions identified as those with a ≥ 1% incidence, similar or higher incidence in the BR-CAP arm and with at least a possible or probable causal relationship to the components of the BR-CAP arm, are listed in table 8 below.
Ikke almindelig Fald, kontusion Sjælden 
Uncommon Fall, Contusion Rare
Der blev ikke observeret nogen nye sikkerhedsproblemer, når bortezomib blev adderet til den standard pædiatriske B-celle ALL kemoterapi grundbehandling. 
No new safety concerns were observed when bortezomib was added to the standard pediatric pre B cell ALL chemotherapy backbone.
PRES er en sjælden, ofte reversibel neurologisk lidelse, som udvikles hurtigt, og som kan optræde med blandt andet kramper, hypertension, hovedpine, sløvhed, forvirring, blindhed og andre visuelle og neurologiske forstyrrelser. 
PRES is a rare, often reversible, rapidly evolving neurological condition, which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances.
Kinetikken ved proteasomhæmning blev vurderet in vitro, og det blev påvist, at bortezomib dissocierer fra proteasomet med en t½ på 20 minutter, hvilket viser, at proteasomhæmning ved hjælp af bortezomib er reversibel. 
The kinetics of proteasome inhibition were evaluated in vitro, and bortezomib was shown to dissociate from the proteasome with a t½ of 20 minutes, thus demonstrating that proteasome inhibition by bortezomib is reversible.
Grad ≥ 3 ikke-hæmatologiske toksiciteter 
Grade ≥ 3 non-haematological toxicities
Indehaveren af markedsføringstilladelsen skal sikre, at læger og sundhedspersonale, der beskæftiger sig med ordination, udlevering, håndtering eller administration af bortezomib, forsynes med uddannelsespakken. 
The MAH shall ensure that all healthcare professionals involved in the prescribing, dispensing, handling or administration of bortezomib are provided with educational material.
I non-kliniske studier havde bortezomib ingen indvirkning på den embryonale/føtale udvikling hos rotter og kaniner ved den højest tålte dosis hos moderdyret. 
In non-clinical studies, bortezomib had no effects on embryonal/foetal development in rats and rabbits at the highest maternally tolerated doses.
• Øget eller nedsat urinproduktion (pga. nyreskade), smerter ved vandladning eller blod/protein i urinen, væskeophobning 
• Increased or decreased urine production (due to kidney damage), painful passing of urine or blood/proteins in the urine, fluid retention
Farmakologiske studier vedrørende kardiovaskulær sikkerhed med aber og hunde viser, at intravenøse doser på ca. 2-3 gange den anbefalede kliniske dosis på mg/m2-basis er forbundet med pulsstigninger, fald i kontraktilitet, hypotension og dødsfald. 
Cardiovascular safety pharmacology studies in monkeys and dogs show that intravenous doses approximately two to three times the recommended clinical dose on a mg/m basis are associated with increases in heart rate, decreases in contractility, hypotension and death.
De gennemsnitlige AUC-værdier justeret i forhold til standarddosis forøgedes derimod med ca. 60 % hos patienter med moderat eller alvorligt nedsat leverfunktion. 
However, the dose-normalised mean AUC values were increased by approximately 60% in patients with moderate or severe hepatic impairment.
Granulocytkolonistimulerende faktorer kan administreres ved hæmatologisk toksicitet i henhold til lokal standardpraksis. 
Granulocyte colony stimulating factors may be administered for haematologic toxicity according to local standard practice.
Intent to Treat (ITT) population b p-værdi fra den stratificerede log-rank test; analyse ud fra behandling udelukker opdeling på tidligere behandling; p < 0,0001 
a Intent to Treat (ITT) population b p-value from the stratified log-rank test; analysis by line of therapy excludes stratification for therapeutic history; p < 0.0001
• Betændelse eller blødning i blodkarrene, der kan vise sig som små rødlige eller lilla prikker 
• Inflammation or haemorrhage of the blood vessels that can appear as small red or purple dots
Hvordan bortezomib gives 
How bortezomib is given
Begge grupper fik i gennemsnitlig 4 cyklusser. 
The median number of cycles received for both groups was 4 cycles.
Sekundære effektmål omfattede post-transplantations-responsrater (CR+nCR, CR+nCR+VGPR+PR), progressionsfri overlevelse og samlet overlevelse. 
Secondary efficacy endpoints included post-transplant response rates (CR+nCR, CR+nCR+VGPR+PR), Progression Free Survival and Overall Survival.
Baseret på en farmakokinetisk populationsanalyse øgedes bortezomibclearance ved stigende legemsoverfladeareal (BSA). 
Based on a population pharmacokinetic analysis, clearance of bortezomib increased with increasing body surface area (BSA).
Resultater fra in vitro, ex-vivo og dyremodeller med bortezomib tyder på, at bortezomib øger osteoblast-differentieringen og -aktiviteten og hæmmer osteoklastfunktionen. 
Data from in vitro, ex-vivo, and animal models with bortezomib suggest that it increases osteoblast differentiation and activity and inhibits osteoclast function.
Grad ≥ 3 ikke-hæmatologisk toksicitet, som anses for at være relateret til bortezomib 
Grade ≥ 3 non-haematological toxicities considered to be related to bortezomib
Der skal derfor udvises forsigtighed ved håndtering og anvendelse af bortezomib. 
Therefore, caution should be used during handling and preparation of bortezomib.
Fase II-studiet MMY-2036 (RETRIEVE), et open-label studie med en enkelt arm, blev udført for at bestemme effekt og sikkerhed af genbehandling med bortezomib. 
Phase II study MMY-2036 (RETRIEVE), single arm, open-label study was conducted to determine the efficacy and safety of retreatment with bortezomib.
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)