natgillin/translations-raw huggingface dataset:
MabThera i kombination med methotrexat øgede signifikant andelen af patienter, der opnåede mindst 20 % forbedring i ACR-score, sammenlignet med patienter behandlet med methotrexat alene (tabel 12).
MabThera in combination with methotrexate significantly increased the proportion of patients achieving at least a 20 % improvement in ACR score compared with patients treated with methotrexate alone (Table 12).
MabThera blev administreret på første dag af hver behandlingsserie.
MabThera was administered on the first day of each treatment cycle.
Der er meget sjældent blevet rapporteret om reaktivering af hepatitis B-infektion hos RA-patienter, som får MabThera (se pkt 4.4)
Reactivation of hepatitis B infection has also been very rarely reported in RA patients receiving MabThera (see Section 4.4).
Geometriske gennemsnitlige AUC-værdier ved behandlingsserie 7 µg.dag/ml
Geometric mean AUC values at cycle 7 µg.day/mL
Under anvendelse af aseptiske procedurer trækkes den nødvendige mængde MabThera op og fortyndes til en beregnet koncentration på 1 til 4 mg/ml rituximab i en infusionspose, der indeholder steril, pyrogenfri natriumchloridopløsning til injektion 9 mg/ml (0,9 %) eller 5 % D-glukose i vand.
Aseptically withdraw the necessary amount of MabThera, and dilute to a calculated concentration of 1 to 4 mg/mL rituximab into an infusion bag containing sterile, pyrogen-free sodium chloride 9 mg/mL (0.9%) solution for injection or 5% D-Glucose in water.
Efter markedsføring er der rapporteret fem tilfælde af MabThera-overdosering.
In the post-marketing setting five cases of MabThera overdose have been reported.
Patienter som behandles med MabThera kan vaccineres med ikke-levende vacciner.
Patients treated with MabThera may receive non-live vaccinations.
Log-rank p værdi
Log-Rank p value
I alt 19 ud af 34 (56 %) patienter med PV, som blev behandlet med MabThera, testede positive for ADA antistoffer ved måned 18.
A total of 19/34 (56%) patients with PV, who were treated with MabThera, tested positive for ADA antibodies by 18 months.
Antallet af respondenter (respons-rate (%))
EULAR response (%)
NR: ikke opnået; a: kun gældende for patienter, der opnåede komplet respons
NR: not reached; a: only applicable to patients achieving a CR
Ligeledes blev et godt til moderat European League Against Rheumatism (EULAR) respons i alle studier opnået af signifikant flere patienter behandlet med MabThera og methotrexat sammenlignet med patienter behandlet med methotrexat alene (tabel 12).
Similarly, a good to moderate European League Against Rheumatism (EULAR) response was achieved by significantly more MabThera treated patients treated with MabThera and methotrexate compared to patients treated with methotrexate alone (Table 12).
MabThera er indiceret til behandling af tidligere ubehandlede patienter med stadium III-IV follikulært lymfom i kombination med kemoterapi.
MabThera is indicated for the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with chemotherapy.
Hos patienter behandlet for maligne hæmatologiske sygdomme begyndte B-celleregenerering inden for 6 måneders behandling og vendte normalt tilbage til normale niveauer inden for 12 måneder efter afsluttet behandling, selvom det hos nogle patienter kan tage længere tid (op til en median restitutionstid på 23 måneder efter induktionsbehandling).
In patients treated for hematological malignancies, B cell recovery began within 6 months of treatment and generally returned to normal levels within 12 months after completion of therapy, although in some patients this may take longer (up to a median recovery time of 23 months post-induction therapy).
I embryoføtale udviklingsstudier med mus forårsagede rHuPH20 reduceret føtalvægt og fosterresorption ved systemisk niveau noget over det humane terapeutiske niveau.
In embryofetal developmental studies in mice, rHuPH20 caused reduced fetal weight and loss of implantations at systemic exposures sufficiently in excess of human therapeutic exposure.
I en subgruppeanalyse var den samlede responsrate højere hos patienter med histologisk subtype IWF B, C og D sammenlignet med subtype IWF A (58 % versus 12 %), højere hos patienter hvis største læsions længste diameter var < 5 cm versus > 7 cm (53 % versus 38 %) og højere hos patienter med kemoterapifølsomt relaps sammenlignet med kemoterapi-resistent relaps (defineret som en responsvarighed < 3 måneder) (50 % versus 22 %).
In a subgroup analysis, the ORR was higher in patients with IWF B, C, and D histological subtypes as compared to IWF A subtype (58 % vs. 12%), higher in patients whose largest lesion was < 5 cm vs. > 7 cm in greatest diameter (53% vs. 38%), and higher in patients with chemosensitive relapse as compared to chemoresistant (defined as duration of response < 3 months) relapse (50% vs. 22%).
• Hvad du skal vide, før du får MabThera
• What you need to know before having MabThera
Der er ingen farmakokinetiske/kliniske data tilgængelige hos patienter med en refraktær eller recediverende sygdom.
No PK/clinical data are available in patients with a refractory or relapsing disease.
For personer, der har et medium og lavt BSA, var den gennemsnitlige Ctrough værdi efter intravenøs dosering, henholdsvis ca. 12 % og 26 % lavere, sammenlignet med subkutan dosering.
For subjects in the middle and low BSA tritiles, average Ctrough values following intravenous dosing were approximately 12% and 26% lower compared to the subcutaneous regimen.
Log-rank p-værdi
Log--Rank p value
Den hyppigste bivirkning efter administration af MabThera i kliniske studier var infusionsrelaterede reaktioner (IRR) (se tabel 2).
The most frequent ADRs following receipt of MabThera in clinical studies were IRRs (refer to Table 2).
Uåbnet hætteglas 30 måneder.
Unopened vial 30 months
De hyppigst rapporterede bivirkninger var takykardi (4%) og atrieflimren (3%) (se pkt.
The most frequently reported events were tachycardia (4%) and atrial fibrillation (3%) (see section 4.4).
MabThera bør anvendes i kombination med CHOP kemoterapi.
MabThera should be used in combination with CHOP chemotherapy.
Antallet af patienter behandlet med rituximab plus lavdosis prednison uden prednison-behandling eller behandlet minimalt (prednison dosis på 10 mg eller mindre pr. dag) viser en steroidbesparende virkning ad MabThera sammenlignet med patienter behandlet med standarddosis prednison over behandlingsperioden på 24 måneder (figur 4).
The number of rituximab plus low-dose prednisone patients off prednisone therapy or on minimal therapy (prednisone dose of 10 mg or less per day) compared to standard-dose prednisone patients over the 24-month treatment period shows a steroid-sparing effect of MabThera (Figure 4).
Effekt og sikkerhed af MabThera til lindring af symptomer og kliniske fund ved reumatoid artrit hos patienter med et utilstrækkelig respons på TNF-hæmmere blev vist i et pivotalt, randomiseret, kontrolleret, dobbeltblindet, multicenterstudie (studie 1).
The efficacy and safety of MabThera in alleviating the symptoms and signs of rheumatoid arthritis in patients with an inadequate response to TNF-inhibitors was demonstrated in a pivotal randomised, controlled, double-blind, multicenter trial (Trial 1).
I alle patientundergrupper (køn, alder, aldersjusteret IPI, Ann Arbor stadie, ECOG, β2-mikrobuglobulin, LD, albumin, B-symptomer, udbredt sygdom, ekstranodale lymfomer, knoglemarvspåvirkning) var risikoratioen for hændelsesfri overlevelse og samlet overlevelse (RCHOP sammenlignet med CHOP) mindre end henholdsvis 0,83 og 0,95.
In all patients subgroups (gender, age, age adjusted IPI, Ann Arbor stage, ECOG, β2 microglobulin, LDH, albumin, B symptoms, bulky disease, extranodal sites, bone marrow involvement), the risk ratios for event-free survival and overall survival (R-CHOP compared with CHOP) were less than 0.83 and 0.95 respectively.
legemsoverfladeareal én gang hver 3. måned (startende 3 måneder efter den sidste dosis i induktionsbehandlingen) indtil sygdomsprogression eller i maksimalt 2 år (8 infusioner i alt).
body surface area once every 3 months (starting 3 months after the last dose of induction therapy) until disease progression or for a maximum period of two years (8 infusions in total).
Efterfølgende MabThera-doser kan infunderes med 100 mg/time initialt og øges med 100 mg/time hvert 30. minut til højst 400 mg/time.
Subsequent doses of MabThera can be infused at an initial rate of 100 mg/h, and increased by 100 mg/h increments at 30 minute intervals, to a maximum of 400 mg/h.
Når MabThera gives i kombination med kemoterapi, bør standard dosisreduktioner for de kemoterapeutiske lægemidler anvendes.
When MabThera is given in combination with chemotherapy, standard dose reductions for the chemotherapeutic medicinal products should be applied.
Rituximab bindes specifikt til det transmembrane antigen, CD20, et non-glycosyleret phosphoprotein som findes på præ-B og modne B-lymfocytter .
Rituximab binds specifically to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes.
MabThera subkutan formulering skal injiceres subkutant i abdominalvæggen og aldrig i et område, hvor huden er rød, øm, hård, eller hvor der er blå mærker, skønhedspletter eller ar.
MabThera subcutaneous formulation should be injected subcutaneously into the abdominal wall and never into areas where the skin is red, bruised, tender, hard or areas where there are moles or scars.
Alle disse arytmier forekom enten i sammenhæng med MabThera-infusionen eller var forbundet med prædisponerende forhold som feber, infektion, akut myokardieinfarkt eller allerede eksisterende respiratorisk og kardiovaskulær sygdom.
All of these arrhythmias either occurred in the context of a MabThera infusion or were associated with predisposing conditions such as fever, infection, acute myocardial infarction or pre-existing respiratory and cardiovascular disease.
Der er kun begrænsede effekt- og sikkerhedsdata tilgængelige for patienter, som tidligere er behandlet med monoklonale antistoffer inklusive MabThera, og for patienter, som er refraktære over for tidligere behandling med MabThera og kemoterapi.
Only limited data are available on efficacy and safety for patients previously treated with monoclonal antibodies including MabThera or patients refractory to previous MabThera plus chemotherapy.
4 Bivirkninger
4 Possible side effects
I det kliniske studie med induktion af remission blev kardielle bivirkninger rapporteret med en hyppighed på ca. 273 pr. 100 patientår (95% konfidensinterval 149-470) ved det primære endepunkt ved måned 6.
In the clinical trial on induction of remission, cardiac events occurred at a rate of approximately 273 per 100 patient years (95% CI 149-470) at the 6-month primary endpoint.
I alt 23/99 (23%) af de MabThera-behandlede patienter i studiet med induktion af remission blev testet positive for ADA ved måned 18.
A total of 23/99 (23%) MabThera-treated patients from the induction of remission trial tested positive for ADA by 18 months.
Rituximab er vist at være yderst specifikt over for CD20-antigenet på B-celler.
Rituximab has shown to be highly specific to the CD20 antigen on B cells.
Disse bivirkninger var grad 4 trombocytopeni og grad 3 angst, erytem ved injektionsstedet og urticaria.
These events were Grade 4 thrombocytopenia and Grade 3 anxiety, injection-site erythema and urticaria.
Lægen beslutter, hvornår du skal skifte til MabThera som indsprøjtning.
Your doctor will decide when to start MabThera injections.
50 ml hætteglas - pakninger med 1 hætteglas
50 mL vial - Pack of 1 vial
En analyse af den samlede overlevelse bekræftede den signifikante fordel af MabThera vedligeholdelse fremfor observation (p=0,0039 log-rank test).
An analysis of overall survival confirmed the significant benefit of MabThera maintenance over observation (p=0.0039 log-rank test).
I SABRINA rapporteredes svære administrationsrelaterede reaktioner (grad ≥3) hos 2 patienter (2 %) efter subkutan administration af MabThera.
InSABRINA, severe administration-related reactions (grade≥3) were reported in two patients (2%) following administration of MabThera subcutaneous formulation.
CR-rater n.a.
CR rates n.a.
Blod og lymfesystem neutropeni sen neutropeni2
Blood and lymphatic system disorders neutropenia1
Der blev set højere infektionshyppighed, herunder infektioner af grad 3 eller 4, under MabThera vedligeholdelsesbehandling i op til 2 år sammenlignet med observationsgruppen.
Higher frequencies of infections overall, including grade 3 or 4 infections, were observed during MabThera maintenance treatment up to 2 years when compared to observation.
Der blev rapporteret om svære infektioner hos ca. 4 % af de patienter, der blev behandlet med MabThera monoterapi.
Severe infections were reported in about 4% of patients treated with MabThera monotherapy.
Dyrestudier har ikke afsløret, at rituximab eller rekombinant humant hyaluronidase (rHuPH20) skulle have skadelig effekt på reproduktionsorganer.
Animal studies did not reveal deleterious effects of rituximab or recombinant human hyaluronidase (rHuPH20) on reproductive organs.
MabThera vedligeholdelsesbehandling er indiceret til behandling af follikulært lymfom hos patienter, der responderer på induktionsbehandling.
MabThera maintenance therapy is indicated for the treatment of follicular lymphoma patients responding to induction therapy.
I SAWYER-studiet (BO25341) var forekomsten af behandlingsinducerede/forhøjede anti-rituximab-antistoffer sammenlignelig i de to behandlingsarme, henholdsvis 15 % for intravenøs versus 12 % for subkutan.
In SAWYER trial (BO25341) the incidence of treatment-induced/enhanced anti-rituximab antibodies was similar in the two treatment arms; 15% intravenous vs. 12% subcutaneous.
Information til patienten om MabThera skal indeholde følgende nøgle-elementer:
The Patient information about MabThera should contain the following key elements:
• Aktivt stof: Rituximab.
• The active ingredient is rituximab.
Ved gentagen behandling af patienter med reumatoid artrit med MabThera gennem et år er den samlede erfaring, at andelen af patienter med positive antistoftitere over for S. pneumoniae, influenza, mæslinger, røde hunde, skoldkopper og tetanustoksoid generelt var sammenlignelige til andelen ved baseline.
In the overall experience of MabThera repeat treatment over one year in rheumatoid arthritis, the proportions of patients with positive antibody titres against S. pneumoniae, influenza, mumps, rubella, varicella and tetanus toxoid were generally similar to the proportions at baseline.
MabThera har i sjældne tilfælde forårsaget en alvorlig hjerneinfektion, som kaldes ”Progressiv multifokal leukoencefalopati” (PML).
Rarely MabThera can cause a serious brain infection, called “Progressive Multifocal Leukoencephalopathy” or PML.
I SparkThera rapporteredes ingen svære administrationsrelaterede reaktioner.
InSparkThera, no severe administration-related reactions were reported.
Vaskulære sygdomme hypertension, orthostatisk hypotension, hypotension vasculitis (fortrinsvis kutan), leukocytoklastisk vasculitis
Vascular disorders hypertension, orthostatic hypotension, hypotension vasculitis (predominatel y cutaneous), leukocytoclast ic vasculitis
Hyppigheden defineres som meget almindelig (≥ 1/10), almindelig (≥ 1/100 til < 1/10), ikke almindelig (≥ 1/1.000 til < 1/100), sjælden (≥ 1/10.000
Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), and very rare (<1/10,000).
Hver ml indeholder 120 mg rituximab.
Each mL contains 120 mg of rituximab.
MabThera er en klar, farveløs opløsning, leveret som koncentrat til infusionsvæske, opløsning.
MabThera is a clear, colourless solution, supplied as a concentrate for solution for infusion.
I det kliniske studie med vedligeholdelsesbehandling oplevede 7 ud af 57 (12 %) patienter i MabThera-armen mindst én infusionsrelateret reaktion.
In the maintenance therapy clinical trial, 7/57 (12%) patients in the MabThera arm experienced at least one infusion-related reaction.
MabThera's sikkerhedsprofil ved non-Hodgkin-lymfom og CLL er baseret på data fra patienter fra kliniske studier og fra post-marketing overvågning.
The overall safety profile of MabThera in non-Hodgkin's lymphoma and CLL is based on data from patients from clinical trials and from post-marketing surveillance.
Subkutan injektion
Subcutaneous injections
Fordelen med hensyn til PFS blev konsistentobserveret i de fleste patientundergrupper, som blev analyseret i forhold til sygdomsrisikoen ved baseline (dvs. Binet stadium A-C) (tabel 2b).
The benefit in terms of PFS was consistently observed in most patient subgroups analysed according to disease risk at baseline (i.e. Binet stages A-C) (Table 2b).
MabThera er i kombination med glukokortikoider indiceret til behandling af voksne patienter med svær, aktiv granulomatose med polyangiitis (Wegeners granulomatose) (GPA) eller mikroskopisk polyangiitis (MPA).
MabThera, in combination with glucocorticoids, is indicated for the treatment of adult patients with severe, active granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA).
MabThera 1400 mg anvendes til behandling af non-Hodgkin-lymfom hos voksne.
MabThera 1400 mg is used to treat Non-Hodgkin's lymphoma in adults.
Klistermærket skal fjernes fra hætteglasset og skal påsættes sprøjten inden brug.
This sticker should be removed from the vial and stuck onto the syringe prior to use.
Der er ikke observeret uforligelighed mellem MabThera subkutan formulering og polypropylen- eller polycarbonatmaterialet i sprøjter eller rustfrit stål i injektionsnåle og polyethylen-Luer-propper.
No incompatibilities between MabThera subcutaneous formulation and polypropylene or polycarbonate syringe material or stainless steel transfer and injection needles and polyethylene Luer cone stoppers have been observed.
Svær (grad 3 og 4) neutropeni forekom hos 4,2 % af patienterne, anæmi hos 1,1 %, og svær trombocytopeni hos 1,7 %.
Severe (grade 3/4) neutropenia was reported in 4.2%, anaemia in 1.1% and thrombocytopenia in 1.7% of the patients.
ADMINISTRATIONSMETODE Udelukkende til subkutan anvendelse.
METHOD OF ADMINISTRATION Only for subcutaneous use
MabThera + lavdosis prednison (n = 38)
MabThera + low-dose prednisone (n = 38)
I det kliniske studie med vedligeholdelsesbehandling oplevede 30 ud af 57 (53 %) patienter i MabThera-armen infektioner.
In the maintenance therapy clinical trial, 30/57 (53%) patients in the MabThera arm experienced infections.
Der er gennemført et internationalt, randomiseret, kontrolleret, åbent, 2-delt fase III-multicenterstudie med patienter med tidligere ubehandlet follikulært lymfom med henblik på at undersøge noninferiøritet af farmakokinetisk profil, virkning og sikkerhed for MabThera subkutan formulering i kombination med CHOP eller CVP versus MabThera intravenøs formulering i kombination med CHOP eller CVP.
A two-stage phase III, international, multi-centre, randomised, controlled, open-label trial was conducted in patients with previously untreated follicular lymphoma, to investigate the non-inferiority of the pharmacokinetic profile, together with efficacy and safety of MabThera subcutaneous formulation in combination with CHOP or CVP versus MabThera intravenous formulation in combination with CHOP or CVP.
Patienter behandlet med MabThera skal have udleveret patientkortet ved hver infusion.
Patients treated with MabThera must be given the patient alert card with each infusion.
Patienter med mindst PR overgik til vedligeholdelsesbehandling med MabThera intravenøs formulering, én gang hver 8. uge i 24 måneder.
Patients achieving at least PR were entered on MabThera intravenous formulation maintenance therapy once every 8 weeks for 24 months.
Hyppigheden af grad 3/4 bivirkninger i blod og lymfesystemet var højere hos ældre patienter med tidligere ubehandlet eller relaps/refraktær CLL, sammenlignet med hos yngre patienter (< 65 år).
The incidence of grade 3/4 blood and lymphatic adverse events was higher in elderly patients compared to younger patients (<65 years), with previously untreated or relapsed/refractory CLL.
Progressionsfri overlevelse (andel med tilfælde, sygdomsprogression/recidiv eller død af enhver årsag) a - ved 3 måneders opfølgningsbesøg (2. del) b - ved tidspunktet for den endelige analyse (median opfølgning 53 måneder)
PFS - Progression-Free Survival (proportion with event, disease progression/relapse or death from any cause) a - at 3 month follow-up visit (Part 2) b - at time of final analysis (median follow-up 53 months)
Patienter med mindst partielt respons (PR) overgik til vedligeholdelsesbehandling med MabThera subkutan formulering, én gang hver 8. uge i 24 måneder.
Patients achieving at least partial response (PR) were entered on the MabThera subcutaneous formulation maintenance therapy once every 8 weeks for 24 months.
Risikoen for akutte administrationsrelaterede reaktioner i forbindelse med den subkutane formulering af MabThera er vurderet i 2 åbne kliniske studier med patienter med follikulært lymfom under induktions- og vedligeholdesesbehandling (SABRINA/BO22334) og under vedligeholdelsesbehandling alene (SparkThera/BP22333).
The risk of acute administration-related reactions associated with the subcutaneous formulation of MabThera was assessed in two open-label trials involving patients with follicular lymphoma during induction and maintenance (SABRINA/BO22334) and during maintenance only (SparkThera/BP22333).
ANVENDELSESMÅDE OG ADMINISTRATIONSVEJ(E) Udelukkende til subkutan anvendelse.
METHOD AND ROUTE(S) OF ADMINISTRATION For subcutaneous use only
MabThera kan passere moderkagen og påvirke barnet.
This is because MabThera can cross the placenta and may affect your baby.
Patienterne blev randomiseret i forholdet 1:1 til daglig behandling med cyclophosphamid oralt (2 mg/kg/dag) i 3-6 måneder eller MabThera (375 mg/m2) én gang ugentligt i 4 uger.
Patients were randomised in a 1:1 ratio to receive either oral cyclophosphamide daily (2mg/kg/day) for 3-6 months or MabThera (375 mg/m2) once weekly for 4 weeks.
Indsprøjtningen under huden gives altid i maven, og må ikke gives i andre områder af kroppen, og ikke hvor huden er rød, øm, hård eller i et blåt mærke, skønhedsplet eller ar.
When injected under your skin, it is given in the stomach area, not in other sites of the body, and not into areas of the stomach where the skin is red, bruised, tender, hard or where there are moles or scars.
Det sæt af reaktioner, der omfatter cytokinfrigivelsessyndrom, tumorlysesyndrom samt anafylaktiske reaktioner og overfølsomhedsreaktioner beskrives nedenfor.
This set of reactions which includes syndrome of cytokine release, tumor lysis syndrome and anaphylactic and hypersensitivity reactions are described below.
Bivirkninger set efter subkutan administration var lette eller moderate, bortset fra én patient, som rapporterede et tilfælde af lokal hudreaktion af grad 3 (udslæt ved injektionsstedet) efter den første subkutane MabThera-injektion (2. serie).
Events seen following subcutaneous administration were mild or moderate, apart from one patient who reported a local cutaneous reaction of Grade 3 intensity (injection site rash) following the first MabThera subcutaneous administration (Cycle 2).
MabThera skal administreres som to 500 mg intravenøse infusioner, med to ugers mellemrum, efterfulgt af en 500 mg intravenøs infusion hver 6. måned.
MabThera should be administered as two 500 mg IV infusions separated by two weeks, followed by a 500 mg IV infusion every 6 months thereafter.
B-celle niveauer i spædbørn efter moderen havde været eksponeret for MabThera, er ikke undersøgt i kliniske studier.
B-cell levels in human neonates following maternal exposure to MabThera have not been studied in clinical trials.
For patienter, der vejer > 90 kg, var værdierne for Ctrough ens, for det subkutane og det intravenøse doserings-regime.
For subjects weighing > 90 kg, Ctrough values were the same for the intravenous and subcutaneous regimens.