natgillin/translations-raw huggingface dataset:
Patienten bør instrueres i straks at kontakte behandlende læge, hvis der på noget tidspunkt opstår symptomer tydende på alvorlig overfølsomhed eller cytokinfrigivelsessyndrom efter administration af lægemidlet.
Patients should be instructed to contact their treating physician immediately if symptoms that are suggestive of severe hypersensitivity or cytokine release syndrome occur at any time after medicinal product administration.
Selvom undergrupperne var små, gav MabThera-vedligeholdelsesbehandling en signifikant fordel i form af samlet overlevelse, både for patienter, der responderede på CHOP og for patienter, der responderede på R-CHOP; længere opfølgning er dog nødvendig for at bekræfte denne observation.
Although subgroups were small, MabThera maintenance treatment provided a significant benefit in terms of overall survival for both patients responding to CHOP and patients responding to R-CHOP, although longer follow-up is required to confirm this observation.
Profylakse mod Pneumocystis jiroveci-pneumoni (PCP) anbefales til patienter med GPA/MPA eller PV under og efter behandling med MabThera i det omfang, det er relevant i henhold til lokale kliniske retningslinjer.
Pneumocystis jirovecii pneumonia (PCP) prophylaxis is recommended for patients with GPA/MPA or PV during and following MabThera treatment, as appropriate according to local clinical practice guidelines.
Tabel 12 Resultater for klinisk respons ved det primære endepunkt i studie 1 (ITT populationen)
Table 12 Clinical response outcomes at primary endpoint in Trial 1(ITT population) Outcome†
Nogle har oplevet, at blodtrykket faldt, mens de fik MabThera
This is because some people have a fall in their blood pressure while they are being given MabThera
Tabel 13 Radiologiske resultater ved 1 år i studie 1 (mITT population) Placebo+MTX MabThera +MTX 2 × 1.000 mg
Table 13 Radiographic outcomes at 1 year (mITT population) Placebo+MTX MabThera+MTX 2 × 1000 mg
Under behandlingsforløbet med MabThera subkutan formulering, bør andre lægemidler til subkutan administration så vidt muligt gives andre steder.
During the treatment course with MabThera subcutaneous formulation, other medicinal products for subcutaneous administration should preferably be given at different sites.
µg.dag/ml
µg.day/mL
Hvis du får MabThera sammen med anden medicin, kan nogle bivirkninger være forårsaget af den anden medicin.
If you are having MabThera with other medicines, some of the side effects you may get may be due to the other medicines.
Informationen i dette afsnit relaterer sig til onkologisk brug af MabThera.
The information provided in this section pertains to the use of MabThera in oncology.
Disse ændringer inkluderer nedsat indhold af nogle specifikke proteiner i blodet (immunglobuliner), som hjælper med at beskytte mod infektioner
These include a decrease in the amount of some specific proteins in the blood (immunoglobulins) which help protect against infection.
Du må ikke få MabThera, hvis:
Do not take MabThera if:
Afslutning af 4. kvartal 2019 (foreløbig CSR) Afslutning af 4. kvartal 2020 (endelig CSR)
by Q4 2019 (preliminary CSR) by Q4 2020 (final CSR)
R-CHOP var associeret med bedre udfald for både høj- og lavrisikopatienter i forhold til aldersjusteret IPI.
R-CHOP was associated with improvements in outcome for both high- and low-risk patients according to age adjusted IPI.
ACR20 ACR50 ACR70 EULAR respons (god/moderat) Gennemsnitsændring i DAS
ACR20 ACR50 ACR70 EULAR Response (Good/Moderate) Mean Change in DAS
Hos disse patienter var andelen af patienter, som fik klinisk relevant infektion under MabThera-behandling, 6,01 per 100 patientår i forhold til 4,97 per 100 patientår efter behandling med det biologiske DMARD.
In these patients the rate of clinically relevant infection while on MabThera was 6.01 per 100 patient years compared to 4.97 per 100 patient years following treatment with the biologic DMARD.
Den overordnede sikkerhedsprofil var i overensstemmelse med den i forvejen fastlagte sikkerhedsprofil for MabThera i godkendte autoimmune indikationer, inklusiv GPA og MPA.
The overall safety profile was consistent with the well-established safety profile for MabThera in approved autoimmune indications, including GPA/MPA.
MabThera subkutan formulering indeholder rekombinant humant hyalorunidase (rHuPH20), et enzym der anvendes til at øge fordeling og absorption af samtidigt administrerede midler, når det administreres subkutant.
MabThera subcutaneous formulation contains recombinant human hyaluronidase (rHuPH20), an enzyme used to increase the dispersion and absorption of co-administered substances when administered subcutaneously.
Når behandling med MabThera indledes med en intravenøs infusion forbedres muligheden for at håndtere administrationsreaktioner ved at sænke infusionshastigheden eller at stoppe den intravenøse infusion.
Beginning the therapy with MabThera intravenous infusion would allow a better handling of the administration reactions by slowing or stopping the intravenous infusion.
Efter første MabThera-eksponering var hyppigheden af alle bivirkninger højest i løbet af de første 6 måneder og aftog derefter.
The rate of all ADRs following first MabThera exposure was highest during the first 6 months and declined thereafter.
Patienterne blev stratificeret efter baseline sygdomssværhedsgrad (moderat eller svær) og randomiseret i forholdet 1:1 til behandling med enten MabThera og lavdosis prednison eller standarddosis prednison.
Patients were stratified by baseline disease severity (moderate or severe) and randomised 1:1 to receive either MabThera and low-dose prednisone or standard-dose prednisone.
I endnu et klinisk studie blev i alt 57 patienter med svær, aktiv GPA og MPA i sygdomsremission behandlet med MabThera for vedligeholdelse af remission (se pkt.
In a further clinical study, a total of 57 severe, active GPA and MPA patients in disease remission were treated with MabThera for the maintenance of remission (see section 5.1).
Den hyppigst indberettede alvorlige infektion i MabTheragruppen var pneumoni med en forekomst på 4%.
The most frequently reported serious infection in the MabThera group was pneumonia at a frequency of 4%.
Hyppigheden af de bivirkninger, som er rapporteret ved MabThera alene eller i kombination med kemoterapi, er sammenfattet i Tabel 1.
The frequencies of ADRs reported with MabThera alone or in combination with chemotherapy are summarised in Table 1.
Neutropeni var ikke forbundet med en øget frekvens af alvorlige infektioner blandt MabTherabehandlede patienter.
Neutropenia was not associated with an observed increase in serious infection in MabThera-treated patients.
Hyppigheden af alvorlige kardielle bivirkninger var 2,1 pr. 100 patientår (95% konfidensinterval 3-15).
The rate of serious cardiac events was 2.1 per 100 patient years (95% CI 3 -15).
Radiologisk analyse efter 2 år i studie 1 viste signifikant reduceret progression af strukturel ledskade hos patienter, som fik MabThera i kombination med methotrexat, sammenlignet med patienter, som fik methotrexat alene og viste også en signifikant højere andel af patienter uden ledskadeprogression over en periode på 2 år.
Radiographic analysis at 2 years in Trial 1 demonstrated significantly reduced progression of structural joint damage in patients receiving MabThera in combination with methotrexate compared to methotrexate alone as well as a significantly higher proportion of patients with no progression of joint damage over the 2 year period.
Data fra udviklingsprogrammet for den sukutane formulering af MabThera indikerer, at dannelsen af anti-rituximab-antistoffer efter subkutan administration er sammenlignelig med dannelsen efter intravenøs administration.
Data from the development programme of MabThera subcutaneous formulation indicate that the formation of anti-rituximab antibodies after subcutaneous administration is comparable with that observed after intravenous administration.
Hovedparten af disse patienter fik også cytotoksisk kemoterapi.
The majority of these patients were also exposed to cytotoxic chemotherapy.
Den mest almindelige, alvorlige infektion rapporteret i MabThera-gruppen var let eller moderat bronkitis.
The most commonly reported serious infection in the MabThera group was mild or moderate bronchitis.
MabThera subkutan formulering er ikke beregnet til intravenøs administration og skal kun gives som subkutan injektion.
MabThera subcutaneous formulation is not intended for intravenous administration and should be given via subcutaneous injection only.
Samlet blev 392/3.095 (12,7 %) af patienterne med reumatoid artrit testet positive for ADA i kliniske studier efter behandling med MabThera.
A total of 392/3095 (12.7%) patients with rheumatoid arthritis tested positive for ADAin clinical studies following therapy with MabThera.
MabThera subkutan formulering blev givet i en fast dosis på 1400 mg.
MabThera subcutaneous formulation was given at a fixed dose of 1400 mg.
Af de 99 patienter, der blev behandlet med MabThera, oplevede 12 (12%) mindst én infusionsrelateret reaktion.
Of the 99 patients treated with MabThera, 12 (12%) experienced at least one IRR.
Data fra omtrent 180 patienter, som tidligere var behandlet med MabThera, viste klinisk fordel (inklusiv CR) og understøtter genbehandling med MabThera.
Data in approximately 180 patients pre-treated with MabThera have demonstrated clinical benefit (including CR) and are supportive for MabThera re-treatment.
• svært synstab (tegn på beskadigelse af nerver i hjernen)
• Severe vision loss (sign of brain nerves damage).
Tabel 2 Effektresultater for SAWYER (BO25341) (ITT populationen)
Table 2 Efficacy results for SAWYER (BO25341) (Intent to Treat Population)
Skift til MabThera subkutan formulering kan derfor kun finde sted ved den 2. eller efterfølgende behandlingsserie.
Therefore, the switch to MabThera subcutaneous formulation can only occur at the second or subsequent cycles of treatment.
Efter induktion af remission med MabThera skal vedligeholdelsesbehandling initieres tidligst 16 uger efter sidste MabThera infusion.
Following induction of remission with MabThera, maintenance treatment should be initiated no sooner than 16 weeks after the last MabThera infusion.
Infusions/Administrationsrelaterede reaktioner
Infusion/Administration-related reactions
Kliniske manifestationer af anafylaksi kan være lignende de kliniske manifestationer, som ses ved cytokinfrigivelsessyndrom (beskrevet ovenfor).
Clinical manifestations of anaphylaxis may appear similar to clinical manifestations of the cytokine release syndrome (described above).
Patienterne fik 2 x 1.000 mg MabThera med to ugers interval, derudover methotrexat (10-25 mg/uge).
Patients received 2 x 1000 mg of MabThera separated by an interval of two weeks; in addition to methotrexate (10-25 mg/week).
I et langvarigt observationssikkerhedsstudie fik 97 patienter med GPA og MPA behandling med MabThera (gennemsnitlig 8 infusioner [i intervallet 1-28]) i op til 4 år, efter lægens skøn og i henhold til standard praksis.
In a long-term observational safety study, 97 GPA/MPA patients received treatment with MabThera (mean of 8 infusions [range 1-28]) for up to 4 years, according to their physician's standard practice and discretion.
Nøgleresultater fra alle 4 studier er opsummeret i Tabel 3.
Key results from all four trials are summarized in table 3.
ap-værdi er fra Fisher's exact test med mid-p korrektion b95 % konfidensinterval er korrigeret Newcombe interval
Number of responders (response rate [%]) ap-value is from Fisher's exact test with mid-p correction b 95% confidence interval is corrected Newcombe interval
Ved måned 28 opstod der større recidiver (defineret som genkomsten af kliniske og/eller laboratorie tegn på vaskulitis-aktivitet ([BVAS] > 0), der kunne føre til organsvigt eller skade eller være livstruende) hos 3 patienter (5 %) i MabThera-gruppen og 17 patienter (29 %) i azathioprin-gruppen (p=0,0007).
At month 28, major relapse (defined by the reappearance of clinical and/or laboratory signs of vasculitis activity ([BVAS] > 0) that could lead to organ failure or damage or could be life threatening) occurred in 3 patients (5%) in the MabThera group and 17 patients (29%) in the azathioprine group (p=0.0007).
MabThera anvendes til behandling af reumatoid artrit.
MabThera is used for the treatment of rheumatoid arthritis.
Risiko for sygdomsprogression blev reduceret med 46 %, og risikoen for recidiv med 51 %.
The risk of disease progression was reduced by 46% and the risk of relapse by 51%.
I PV-populationen havde 5 (13 %) patienter i MabThera-gruppen og 3 (8 %) patienter i standarddosis prednison-gruppen moderat sygdom, og 33 (87 %) patienter i MabTheragruppen og 33 (92 %) patienter i standarddosis prednison-gruppen havde svær sygdom i henhold til sygdomssværhedsgrad defineret ved Harman's kriterier.
In the PV population, 5 (13%) patients in the MabThera group and 3 (8%) patients in the standard prednisone group had moderate disease and 33 (87%) patients in the MabThera group and 33 (92%) patients in the standard-dose prednisone group had severe disease according to disease severity defined by Harman's criteria.
Den kliniske relevans af dannelsen af ADA hos MabTherabehandlede patienter med PV er uklar.
The clinical relevance of ADA formation in MabThera-treated PV patients is unclear.
I gruppen af patienter behandlet med cyclophosphamid (efterfulgt af azathioprin med henblik på opretholdelse af fuldstændig remission) opnåede 39% af patienterne fuldstændig remission ved måned 12 og 33% af patienterne fuldstændig remission ved måned 18.
In patients treated with cyclophosphamide (followed by azathioprine for maintenance of complete remission), 39% of patients achieved CR at 12 months, and 33% of patients achieved CR at 18 months.
Blandt de 3.189 patienter, som blev behandlet med MabThera, fik 1.135 (36 %) mindst en IRR, og 733/3.189 (23 %) af patienterne fik en IRR efter første infusion i den første MabThera-behandling.
Among the 3189 patients treated with MabThera, 1135 (36%) experienced at least one IRR with 733/3189 (23%) of patients experiencing an IRR following first infusion of the first exposure to MabThera.
Virkningsundersøgelse efter tilladelse til markedsføring (PAES): For yderligere at undersøge effekten af Mabthera i subgruppen af patienter med etableret pemfigus vulgaris samt yderligere at karakterisere dets langsigtede effekt og sikkerhed ved sygdomsprogression, skal indehaveren af markedsføringstilladelsen indsende den forløbige studierapport og den endelige studierapport for det igangværende randomiserede fase III-studie (PEMPHIX WA29330).
Post-authorisation efficacy study (PAES): In order to further investigate the efficacy of Mabthera in the subgroup of patients with established PV as well as to further characterise its long term efficacy and safety on disease progression, the MAH should submit the preliminary study and the final study report of the ongoing randomised phase 3 study (PEMPHIX WA29330).
Betingede simuleringer, der opsummerer virkningen af kropsstørrelsens betydning på eksponeringen af rituximab, viste, at mens fast subkutan dosering medfører større forskelle i eksponeringen (Ctrough og AUCτ) mellem store og små kropsstørrelser sammenlignet med krops-vægtjusteret intravenøs dosering, tillader fast subkutan dosering fastholdelse af værdier for Ctrough og AUCτ for alle grupper af kropsstørrelser, på niveauer, der ikke er lavere end niveauer opnået med intravenøs dosering.
Conditional simulations that summarized the impact of all body size dependencies on rituximab exposure demonstrated that, while fixed subcutaneous dosing leads to larger differences in exposure (Ctrough and AUCτ) between subjects with low and high body sizes compared to body-weight-adjusted intravenous dosing, it allows to maintain Ctrough and AUCτ values for all body-size groups at the levels not lower than levels attained by intravenous dosing, thus achieving at least the same target saturation as for intravenousdosing.
MabThera inducerede B-cellereduktion hos 70-80 % af patienterne, men blev kun ledsaget af nedsat serum-immunglobulin hos en mindre del af patienterne.
MabThera induces B-cell depletion in about 70-80% of patients, but was associated with decreased serum immunoglobulins only in a minority of patients.
Det vides ikke, om MabThera påvirker din evne til at køre motorkøretøj eller arbejde med maskiner.
It is not known whether MabThera has an effect on you being able to drive or use any tools or machines.
Absorptionsparametre for den subkutane formulering faldt med øget Body Mass Index (BMI).
Absorption parameters of subcutaneous formulation, decreased with increasing BMI.
Eksplorative analyser viste, at responsraterne mht. legemsoverfladeareal (BSA), kemoterapi og kønsundergruppe ikke var markant anderledes fra intent-to-treat-populationen.
Exploratory analyses showed response rates among BSA, chemotherapy and gender subgroups were not notably different from the ITT population.
I kliniske studier med MabThera monoterapi rapporteredes kardiovaskulære reaktioner hos 18,8 % af patienterne, hvoraf de hyppigst rapporterede var hypotension og hypertension.
Cardiovascular reactions during clinical trials with MabThera monotherapy were reported in 18.8% of patients with the most frequently reported events being hypotension and hypertension.
Alvorlige kardielle bivirkninger blev rapporteret med en hyppighed på 1,3 pr. 100 patientår hos patienter behandlet med MabThera sammenlignet med 1,3 pr. 100 patientår hos patienter behandlet med placebo.
Serious cardiac reactions were reported at a rate of 1.3 per 100 patient years in the MabThera treated patients compared to 1.3 per 100 patient years in placebo treated patients.
Neutropeni kan forekomme flere måneder efter indgivelse af MabThera (se pkt.
Neutropenia can occur several months after the administration of MabThera (see section 4.4).
Den højeste intravenøse MabThera-dosis, der til dato er testet hos mennesker, er 5.000 mg (2.250 mg/m2), som er testet i et dosis-eskaleringsstudie med patienter med kronisk lymfocytisk leukæmi.
The highest intravenous dose of MabThera tested in humans to date is 5000 mg (2250 mg/m2), tested in a dose escalation study in patients with CLL.
Hvis du er i den fødedygtige alder, skal du og din partner bruge sikker prævention, mens du er i behandling med MabThera.
If you can get pregnant, you and your partner must use an effective method of contraception while using MabThera.
Effekt hos autoantistof (RF og/eller anti-CCP) seropositive patienter Patienter, som er seropositive for reumafaktor (RF) og/eller antistoffer mod cyklisk citrullinerede peptider (anti-CCP), og som blev behandlet med MabThera i kombination med methotrexat, viste et øget respons sammenlignet med patienter, som var negative for begge.
Efficacy in autoantibody (RF and or anti-CCP) seropositive patients Patients seropositive to Rheumatoid Factor (RF) and/or anti- Cyclic Citrullinated Peptide (anti-CCP) who were treated with MabThera in combination with methotrexate showed an enhanced response compared to patients negative to both.
Ctrough-værdier inden dosering i behandlingsserie 8
Ctrough values at pre-dose cycle 8
I det kliniske studie med vedligeholdelsesbehandling var hyppigheden af alle grader neutropeni 0 % for MabThera-behandlede patienter vs 5 % for azathioprin-behandlede patienter.
In the maintenance therapy clinical trial, the incidence of all-grade neutropenia was 0% for MabTheratreated patients vs 5% for azathioprine treated patients.
Resultaterne fra Studie BP22333 præsenteres i pkt.
Results from trial BP22333 are presented in section 5.2.
Patienter med positiv hepatitis B serologi (enten HBsAg eller HBcAb) bør inden påbegyndelse af behandling konsultere en specialist i leversygdomme og bør overvåges og behandles i henhold til lokale kliniske standarder for at forebygge hepatitis B reaktivering.
Patients with positive hepatitis B serology (either HBsAg or HBcAb) should consult liver disease experts before start of treatment and should be monitored and managed following local medical standards to prevent hepatitis B reactivation.
1 mg/kg/dag (dog højst 80 mg/dag og nedtitreret så hurtigt som muligt afhængigt af det kliniske behov) under og efter de 4 ugers induktionsbehandling med MabThera.
This should be followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, and tapered as rapidly as possible based on clinical need) during and after the 4 week induction course of MabThera treatment.
Hvis patienten ikke har oplevet en alvorlig infusionsrelateret reaktion ved den første eller efterfølgende infusioner af en MabThera-dosis på 1.000 mg administreret ud fra den oprindelige infusionstid, kan de efterfølgende infusioner administreres som en hurtigere infusion ved at bruge den samme koncentration som ved tidligere infusioner (4 mg/ml i 250 ml).
If patients did not experience a serious infusion-related reaction with their first or subsequent infusions of a dose of 1000 mg MabThera administered over the standard infusion schedule, a more rapid infusion can be administered for second and subsequent infusions using the same concentration as in previous infusions (4 mg/mL in a 250 mL volume).
Patienter, som oplever overdosis eller medicineringsfejl, skal monitoreres tæt.
Patients who experience overdose or medication error should be closely monitored.
Produktresuméet Information til lægen Information til patienten Patientkort
Product information Physician information Patient information Patient Alert card
Dog blev der observeret dosisafhængigt farmakologisk B-celle-depletion i fostrets lymfatiske organer, hvilket fortsatte efter fødslen og blev fulgt af et fald i IgG-niveauet hos de påvirkede nyfødte dyr.
However, dose-dependent pharmacologic depletion of B cells in the lymphoid organs of the foetuses was observed, which persisted post natally and was accompanied by a decrease in IgG level in the newborn animals affected.
I MabThera-gruppen opnåede 48% af patienterne fuldstændig remission ved måned 12, og 39% af patienterne opnåede fuldstændig remission ved måned 18.
In the MabThera group, 48% of patients achieved CR at 12 months, and 39% of patients achieved CR at 18 months.
Specielle populationer - MabThera kombinationsterapi Ældre (≥ 65 år):
Patient subpopulations - MabThera combination therapy Elderly patients (≥ 65 years)
3 patienter (8 %) i MabThera-gruppen oplevede et samlet antal på 5 alvorlige infektioner (Pneumocystis jiroveci-pneumoni, infektiøs trombose, intervertebral diskitis, lungeinfektion, Staphylococcal-sepsis) og 1 patient (3 %) i standarddosis prednison-gruppen oplevede 1 alvorlig infektion (Pneumocystis jiroveci-pneumoni).
Three patients (8%) in the MabThera group experienced a total of 5 serious infections (Pneumocystis jirovecii pneumonia, infective thrombosis, intervertebral discitis, lung infection, Staphylococcal sepsis) and one patient (3%) in the standard-dose prednisone group experienced a serious infection (Pneumocystis jirovecii pneumonia).
Der foreligger ingen adækvate og velkontrollerede data fra studier hos gravide kvinder, men der er dog beskrevet forbigående B-celle depletion og lymfocytopeni hos børn af mødre, som har været eksponeret for MabThera under graviditeten.
There are no adequate and well-controlled data from studies in pregnant women, however transient B-cell depletion and lymphocytopenia have been reported in some infants born to mothers exposed to MabThera during pregnancy.
MabThera skal anvendes under tæt supervision af erfarent sundhedspersonale i omgivelser, hvor komplet genoplivningsudstyr er umiddelbart tilgængeligt (se pkt.
MabThera should be administered under the close supervision of an experienced healthcare professional, and in an environment where full resuscitation facilities are immediately available (see section 4.4).
I udviklingsprogrammet var sikkerhedsprofilen for MabThera subkutan formulering sammenlignelig med den for MabThera intravenøs formulering, bortset fra lokale hudreaktioner.
During the development programme, the safety profile of MabThera subcutaneous formulation was comparable to that of the intravenous formulation with the exception of local cutaneous reactions.