natgillin/translations-raw huggingface dataset:
Rituximab+MTX1 N= 298
Rituximab+MTX1 N= 298 mean (SD) switch
EULAR god/ moderat 2
EULAR Good/ moderate
HAQ 3
HAQ2 3
FACIT- F 1 2
FACIT-F 1 ,2
MTX; Health Assessment Questionnaire (HAQ); Functional Assessment of Chronic Illness Therapy (FACIT- F)
MTX Health assessment questionnaire (HAQ), Functional assessment of chronic illness therapy (FACIT-F)
Andelen af patienter behandlet med rituximab, der viste en klinisk signifikant, relevant forbedring i HAQ- DI (defineret som et individuelt fald i total score på > 0, 25) var ved uge 24 i alle tre forsøg højere end blandt patienter, der fik methotrexat alene.
At week 24, in all three studies, the proportion of rituximab treated patients showing a clinically relevant improvement in HAQ-DI (defined as an individual total score decrease of > 0.25) was higher than among patients receiving methotrexate alone.
Evaluering af laboratorieværdier Totalt 96/ 1039 (9, 2%) af patienterne med reumatoid arthritis blev testet positive for HACA i kliniske forsøg efter behandling med MabThera.
Laboratory evaluations A total of 96/ 1039 (9.2%) patients with rheumatoid arthritis tested positive for HACA in clinical studies following therapy with MabThera.
Forekomst af HACA kan være forbundet med forværring af infusions - eller allergiske reaktioner efter det andet af efterfølgende behandlingsforløb.
24 The presence of HACA may be associated with worsening of infusion or allergic reactions after the second infusion of subsequent courses.
Derudover er der i et tilfælde med HACA observeret mangel på B- celle depletion efter gentagne behandlingsforløb.
Furthermore, in one case with HACA, failure to deplete B cells after receipt of further treatment courses has been observed.
Hos 675 patienter i kliniske forsøg, blev skift i anti- nuklear antistof (ANA) status observeret før og efter rituximab; 26% ANA negative til positive og 32% ANA positive til negative.
26% ANA negative to positive and 32% ANA positive to negative.
Der var ingen tegn på nyopstået autoimmun sygdom.
There was no evidence of new onset autoimmune disease.
Hos reumafaktor (RF) positive patienter, blev markante fald i reumafaktor koncentrationerne observeret efter behandling med rituximab i alle tre forsøg (mellem 45- 64%).
In rheumatoid factor (RF) positive patients, marked decreases were observed in rheumatoid factor concentrations following treatment with rituximab in all three studies (range 45-64%).
Hyperurikæmi (grad 3/ 4) forekom hos 143/ 950 (15%) patienter, med størstedelen efter infusion på dagene 1 og/ eller 15.
Hyperuricemia (grade 3/ 4) occurred in 143/ 950 (15%) patients, with the majority post-infusion on days 1 and/ or 15.
Det var ikke forbundet med nogle kliniske symptomer og ingen af disse patienter udviklede tegn på nyresygdom.
It was not associated with any clinical symptoms, and none of these patients developed evidence of renal disease.
25 De totale immunoglobulinniveauer i plasma, totalt lymfocyttal, og hvide blodlegemer forblev generelt inden for normalværdierne efter behandling med MabThera, med undtagelse af et forbigående fald i antallet af hvide blodlegemer i de første fire uger efter behandlingen.
Plasma total immunoglobulin concentrations, total lymphocytes counts, and white cells generally remained within normal limits following MabThera treatment, with the exception of a transient drop in white cells counts over the first four weeks following therapy.
Titere af IgG antigenspecifikke antistoffer overfor fåresyge, røde hunde, skoldkopper, stivkrampe, influenza og streptococcus pneumococci forblev stabile i 24 uger efter eksponering af MabThera til patienter med reumatoid arthritis.
Titers of Ig G antigen specific antibody to mumps, rubella, varicella, tetanus toxoid, influenza and streptococcus pneumococci remained stable over 24 weeks following exposure to MabThera in rheumatoid arthritis patients.
Gentagne behandlinger Efter afslutning af den 24 ugers dobbeltblindede sammenlignende forsøgsperiode, kunne patienterne inkluderes i et åbent, længerevarende opfølgningsforsøg.
Multiple course therapy Following completion of the 24-week double blind comparative study period, patients were permitted to enroll into an open-label long term follow up study.
Behovet blev bedømt af den behandlende læge ud fra sygdomsaktivitet og uanset det perifere B lymfocyttal.
Patients received subsequent courses of MabThera as needed according to the treating clinician’ s assessment of disease activity and irrespective of the peripheral B lymphocyte count.
Intervallet mellem behandlingerne var variabelt, hvor størstedelen af patienterne fik yderligere behandling 6- 12 måneder efter den første behandling.
The time interval between courses was variable, with the majority of patients receiving further therapy 6-12 months after the previous course.
Nogle patienter krævede endda behandling mindre hyppigt.
Some patients required even less frequent retreatment.
Respons på den gentagne behandling var mindst af samme størrelsesorden som efter det initiale behandlingsforløb, bedømt på ændring fra DAS28 baseline.
The response to further therapy was at least the same magnitude as that following the initial treatment course, as evidenced by the change from baseline DAS28.
Gennemsnitlig ændring i DAS28 fra oprindelig baseling: første behandling - 2, 18; anden behandling - 2, 75.
Mean change in DAS28 from original baseline: first course -2.18, second course -2.75.
Non- Hodgkin lymfom
non-Hodgkin’ s lymphoma
Baseret på en populationsfarmakokinetisk undersøgelse af 298 patienter med NHL, som fik enkelte eller flere infusioner af rituximab alene eller i kombination med CHOP kemoterapi, vurderedes den non- specifikke clearance (CL1), den specifikke clearance (CL2), hvor B- celler eller tumor sandsynligvis bidrager, og det centrale kompartments distributionsvolumen til (V1) til at være henholdsvis 0, 14 l/ dag, 0, 59 l/ dag og 2, 7 l.
Based on a population pharmacokinetic analysis in 298 NHL patients who received single or multiple infusions of rituximab as a single agent or in combination with CHOP therapy (applied rituximab doses ranged from 100 to 500 mg/ m2), the typical population estimates of nonspecific clearance (CL1), specific clearance (CL2) likely contributed by B cells or tumor burden, and central compartment volume of distribution (V1) were 0.14 L/ day, 0.59 L/ day, and 2.7 L, respectively.
Den estimerede mediane terminale eliminationshalveringstid af rituximab var 22 dage (spændvidde 6, 1- 52 dage).
The estimated median terminal elimination half-life of rituximab was 22 days (range, 6.1 to 52 days).
Baseline af antallet af CD- 19 positive celletal og størrelsen af målte tumorbyrde, forklarer noget af variationen i CL2 af rituximab fra 161 patienter, som fik 375 mg/ m2 ugentlig i 4 uger som intravenøs infusion.
Baseline CD19-positive cell counts and size of measurable tumor lesions contributed to some of the variability in CL2 of rituximab in data from 161 patients given 375 mg/ m2 as an intravenous infusion for 4 weekly doses.
Patienter med med højere CD- 19 positive celletal og eller tumorbyrde havde en højere CL2.
Patients with higher CD19-positive cell counts or tumor lesions had a higher CL2.
Selvom der korrigeredes for CD- 19 positive celletal og størrelsen af tumorbyrde, var der stadig store interindividuelle variationer i CL2 V1 varierede i forhold til kroppens overfladeareal og CHOP kemoterapi.
V1 varied by body surface area (BSA) and CHOP therapy.
Forskellen i kroppens overfladeareal (1, 53 – 2, 32 m2) og samtidig behandling med CHOP kemoterapi, bidrog til den relativt ringe variation i V1 (27, 1% og 19, 0%).
This variability in V1 (27.1% and 19.0%) contributed by the range in BSA (1.53 to 2.32 m2) and concurrent CHOP therapy, respectively, were relatively small.
Den gennemsnitlige Cmax efter den 4. infusion var 486 µg/ ml (spændvidde 77, 5 µg/ ml – 996, 6 µg/ ml).
Rituximab, administered as an intravenous infusion at a dose of 375 mg/ m2 at weekly intervals for 4 doses to 203 patients with NHL naive to rituximab, yielded a mean Cmax following the fourth infusion of 486 µg/ mL (range, 77.5 to 996.6 µg/ mL).
Rituximab kunne detekteres i patienternes serum i op til 3- 6 måneder efter færdiggørelse af den sidste behandling.
Rituximab was detectable in the serum of patients 3 – 6 months after completion of last treatment.
Efter hver infusion steg den gennemsnitlige Cmax, fra et gennemsnit på 243 µg/ ml (spændvidde 16- 582 µg/ ml) efter den første infusion til 550 µg/ ml (spændvidde 171 – 1177 µg/ ml) efter den ottende infusion.
25 Upon administration of rituximab at a dose of 375 mg/ m2 as an intravenous infusion at weekly intervals for 8 doses to 37 patients with NHL, the mean Cmax increased with each successive infusion, spanning from a mean of 243 µg/ mL (range, 16 – 582 µg/ mL) after the first infusion to 550 µg/ mL (range, 171 – 1177 µg/ mL) after the eighth infusion.
Den farmakokinetiske profil af rituximab, når det blev givet som 6 infusioner af 375 mg/ m2 i kombination med 6 serier af CHOP kemoterapi, var sammenlignelig med den for rituximab indgivet som monoterapibehandling.
The pharmacokinetic profile of rituximab when administered as 6 infusions of 375 mg/ m2 in combination with 6 cycles of CHOP chemotherapy was similar to that seen with rituximab alone.
Efter to intravenøse infusioner af rituximab i en dosis på 1000 mg med to ugers interval, var den gennemsnitlige halveringstid 20, 8 dage (i intervallet 8, 58 dage til 35, 9 dage), den gennemsnitlige
Following two intravenous infusions of rituximab at a dose of 1000 mg, two weeks apart, the mean terminal half-life was 20.8 days (range, 8.58 to 35.9 days), mean systemic clearance was 0.23 L/ day (range, 0.091 to 0.67 L/ day), and mean steady-state distribution volume was 4.6 L (range, 1.7 to 7.51 L).
Farmakokinetisk analyse af populationen af de samme data gav sammenlignelige gennemsnitlige værdier for systemisk clearance og halveringstid; henholdsvis 0, 26 l/ dag og 20, 4 dage.
Population pharmacokinetic analysis of the same data gave similar mean values for systemic clearance and half-life, 0.26 L/ day and 20.4 days, respectively.
Farmakokinetisk analyse af populationen viste, at legemsoverflade og køn var de mest signifikante co- variable, til forklaring af inter- individuel variation i farmakokinetiske parametre.
Population pharmacokinetic analysis revealed that BSA and gender were the most significant covariates to explain inter-individual variability in pharmacokinetic parameters.
De gennemsnitlige halveringstider var henholdsvis 17, 9 dage (i intervallet 12, 3 til 31, 3 dage) og 19, 7 dage (i intervallet 12, 3 til 34, 6 dage).
Following the intravenous administration of 500 and 1000 mg doses of rituximab on two occasions, two weeks apart, mean Cmax values were 183 μ g/ mL (range, 81.8 to 279 μ g/ mL) and 370 μ g/ mL (212 to 637 μ g/ mL), and mean half-lives were 17.9 days (range, 12.3 to 31.3 days) and 19.7 days (range, 12.3 to 34.6 days), respectively.
Der er ingen tilgængelige farmakokinetiske data om patienter med lever - eller nyreinsufficiens.
No pharmacokinetic data are available in patients with hepatic or renal impairment.
Der er ingen tilgængelige farmakokinetiske data om patienter, der modtager gentagne behandlinger.
No pharmacokinetic data are available for patients receiving multiple courses of therapy.
De farmakokinetiske parametre hos patienter i populationen, der responderer utilstrækkeligt på anti- TNF behandling, var efter den samme dosis (2 x 1000 mg, i. v. med 2 ugers mellemrum) sammenlignelig med en gennemsnitlig maksimal serumkoncentration på 369 μg/ ml og en gennemsnitlig terminal halveringstid på 19, 2 dage.
The pharmacokinetic (PK) parameters in the anti-TNF inadequate responder population, following the same dosage regimen (2 x 1000 mg, iv, 2 weeks apart), were similar with a mean maximum serum concentration of 369 μ g/ mL and a mean terminal half-life of 19.2 days.
Rituximab er vist at være yderst specifikt overfor CD20 antigenet på B- celler.
Rituximab has shown to be highly specific to the CD20 antigen on B cells.
Toksikologiske undersøgelser på Cynomolgus aber har ikke vist anden effekt end den forventede farmakologiske fjernelse af B- celler i perifert blod og i lymfevæv.
Toxicity studies in cynomolgus monkeys have shown no other effect than the expected pharmacological depletion of B cells in peripheral blood and in lymphoid tissue.
Prækliniske toksicitetsforsøg i forbindelse med reproduktion udført i cynomolgusaben i doser på op til 100 mg/ kg (behandling på dagene 20- 50 i graviditeten) og har ikke vist tegn på føtal toksicitet af rituximab.
Developmental toxicity studies have been performed in cynomolgus monkeys at dosages up to 100 mg/ kg (treatment on gestation days 20-50) and have revealed no evidence of toxicity to the foetus due to rituximab.
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 nivaeuet 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.
B- celle niveauet normaliseredes hos disse dyr indenfor 6 måneder efter fødslen og påvirkede ikke vaccinationsreaktionen.
B cell counts returned to normal in these animals within 6 months of birth and did not compromise the reaction to immunization.
Der er ikke gennemført langtidsundersøgelser på dyr med henblik på vurdering af rituximabs carcinogene potentiale eller for at bestemme dets effekt på fertilitet hos han - og hundyr.
No long-term animal studies have been performed to establish the carcinogenic potential of rituximab, or to determine its effects on fertility in males or females.
Standard mutagenicitets tests er ikke udført, fordi sådanne tests ikke er relevante for dette molekyle.
Standard tests to investigate mutagenicity have not been carried out, since such tests are not relevant for this molecule.
På grund af dets karakteristika er det imidlertid ikke sandsynligt, at rituximab har noget mutagent potentiale.
However, due to its character it is unlikely that rituximab has any mutagenic potential.
Natriumcitrat Polysorbat 80 Natriumchlorid Natriumhydroxid Saltsyre Vand til injektionsvæsker
Sodium citrate Polysorbate 80 Sodium chloride Sodium hydroxide Hydrochloric acid Water for injections
6. 2 Uforligeligheder
26 6.2 Incompatibilities
27 Den tilberedte MabThera infusionsopløsning er fysisk og kemisk stabil i 24 timer ved 2 °C - 8 °C og efterfølgende 12 timer ved stuetemperatur.
The prepared infusion solution of MabThera is physically and chemically stable for 24 hours at 2 °C - 8 °C and subsequently 12 hours at room temperature.
Hvis den ikke anvendes straks, er opbevaringstid og - forhold inden anvendelse brugerens ansvar og vil normalt ikke være længere end 24 timer ved 2 °C – 8 °C, med mindre opløsningen har fundet sted under kontrollerede og validerede aseptiske forhold.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C – 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.
Hætteglas, af klart type I glas med butyl gummi prop, indeholdende 100 mg rituximab i 10 ml.
Clear Type I glass vials with butyl rubber stopper containing 100 mg of rituximab in 10 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.
2. juni 1998 Dato for sidste genregistrering:
2 June 1998 Date of last renewal:
20. maj 2008
20 MAY 2008
28 10.
28 1.
MabThera 500 mg (10 mg/ ml) koncentrat til infusionsvæske, opløsning
MabThera 500 mg (10 mg/ ml) concentrate for solution for infusion
Et hætteglas til engangsbrug indeholder 500 mg rituximab.
Each single-use vial containing 500 mg of Rituximab.
Non- Hodgkin lymfom (NHL)
Non-Hodgkin’ s lymphoma
MabThera er indiceret som 1. linie behandling til patienter med kronisk lymfatisk leukæmi (CLL) i kombination med kemoterapi.
MabThera is indicated for first-line treatment of patients with chronic lymphocytic leukaemia (CLL) in combination with chemotherapy.
30 disease- modifying anti- rheumatic drugs (DMARD) inklusive en eller flere tumor nekrosis faktor (TNF) hæmmere.
29 modifying anti-rheumatic drugs (DMARD) including one or more tumour necrosis factor (TNF) inhibitor therapies.
Justering af dosis under behandling Det anbefales ikke at reducere dosis af MabThera.
Dosage adjustments during treatment No dose reductions of MabThera are recommended.
Kombinationsbehandling Den anbefalede dosis af MabThera i kombination med kemoterapi til induktionsbehandling af tidligere ubehandlet eller recidiveret / refraktær NHL hos patienter er:
Combination therapy The recommended dose of MabThera in combination with chemotherapy for induction treatment of previously untreated or relapsed/ refractory patients with follicular NHL is:
Monoterapi/ Vedligeholdelsesbehandling Den anbefalede dosis af MabThera som vedligeholdelsesbehandling til patienter til behandling af recidiveret/ refraktær follikulær NHL, som har responderet på induktionsbehandling med kemoterapi med eller uden MabThera er:
Monotherapy/ maintenance The recommended dose of MabThera used as a maintenance treatment for patients with relapsed/ refractory follicular NHL who have responded to induction treatment with chemotherapy, with or without MabThera is:
For at nedsætte risikoen for tumorlysesyndrom hos CLL patienter, bør der gives forebyggende behandling med adækvat hydrering og administration af urikosurika 48 timer før behandlingens start.
Prophylaxis with adequate hydration and administration of uricostatics starting 48 hours prior to start of therapy is recommended for CLL patients to reduce the risk of tumour lysis syndrome.
31 Den anbefalede dosis af MabThera i kombination med kemoterapi er 375 mg/ m2 legemsoverflade givet på første dag af første behandlingsserie efterfulgt af 500 mg/ m2 legemsoverflade på dag 1 af hver af de følgende serier, i alt 6 serier.
30 The recommended dosage of MabThera in combination with chemotherapy is 375 mg/ m2 body surface area administered on day 1 of the first treatment cycle followed by 500 mg/ m2 body surface area administered on day 1 of each subsequent cycle for 6 cycles in total.
Pædiatrisk anvendelse MabTherabør ikke bruges til børn og unge på grund af mangel på data vedrørende sikkerhed og effekt.
Special populations Paediatric use MabThera is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.
Til behandling af non- Hodgkin lymfom og kronisk lymfatisk leukæmi bør det overvejes at give præmedicinering med glukocorticoider, hvis MabThera ikke gives i kombination med kemoterapi, som indeholder glukocorticoider.
Premedication with glucocorticoids should be considered if MabThera is not given in combination with glucocorticoid-containing chemotherapy for treatment of non-Hodgkin’ s lymphoma and chronic lymphocytic leukaemia.
Efter de første 30 minutter, kan den øges med 50 mg/ time hvert 30. minut til højst 400 mg/ time.
First infusion The recommended initial rate for infusion is 50 mg/ hr; after the first 30 minutes, it can be escalated in 50 mg/ hr increments every 30 minutes, to a maximum of 400 mg/ hr.
32 Efterfølgende infusioner Efterfølgende MabThera- doser kan infunderes med 100 mg/ time initialt og øges med 100 mg/ time hvert 30. minut til højst 400 mg/ time.
31 Subsequent infusions Subsequent doses of MabThera can be infused at an initial rate of 100 mg/ hr, and increased by 100 mg/ hr increments at 30 minutes intervals, to a maximum of 400 mg/ hr.
33 også rådes til at informere deres pårørende eller plejepersonale om behandlingen, idet de måske opdager symptomer, som patienten ikke selv er klar over.
Patients should also be advised to inform their partner or caregivers about their treatment, since they may notice symptoms that the patient is not aware of.
Efter rekonstituering af immunsystemet hos immunkomprimerede patienter med PML er der set stabilisering eller forbedret tilstand.
32 Following reconstitution of the immune system in immunocompromised patients with PML, stabilisation or improved outcome has been seen.
Det er uvist, om tidlig erkendelse af PML og seponering af MabThera- behandlingen kan føre til lignende stabilisering eller forbedret tilstand..
It remains unknown if early detection of PML and suspension of MabThera therapy may lead to similar stabilisation or improved outcome.
Behovet for regelmæssig fuldstændig blodtælling, inklusive trombocyttællinger, under monoterapi med MabThera, bør overvejes.
33 Consideration should be given to the need for regular full blood counts, including platelet counts, during monotherapy with MabThera.
4. 8.) MabThera bør ikke administreres til patienter med en aktiv og/ eller alvorlig infektion (som f. eks. tuberkulose, sepsis og opportunistiske infektioner, se pkt.
MabThera should not be administered to patients with an active and/ or severe infection (e. g. tuberculosis, sepsis and opportunistic infections, see section 4.3).
4. 8.).
Physicians should exercise caution when considering the use of MabThera in patients with a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection (see section 4.8).
35 Anafylaktiske og andre hypersensitivitetsreaktioner er blevet rapporteret efter intravenøs administration af proteiner, inklusive MabThera, til patienter.
Anaphylactic and other hypersensitivity reactions have been reported following the intravenous administration of proteins, including MabThera, to patients.
4. 8).
34 In clinical studies 10/ 990 (1%) patients with rheumatoid arthritis who received a first infusion of MabThera at any dose experienced a serious reaction during the infusion (see section 4.8).
36 Ved gentagen behandling 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, the proportions of patients with positive antibody titers against S. pneumoniae, influenza, mumps, rubella, varicella and tetanus toxoid were generally similar to the proportions at baseline.
Samtidig/ fortløbende anvendelse af andre DMARDs Samtidig anvendelse af MabThera og andre antireumatiske behandlinger, end dem der er specificeret under reumatoid arthritis- indikation og dosering, anbefales ikke.
35 Concomitant/ Sequential use of other DMARDs The concomitant use of MabThera and antirheumatic therapies other than those specified under the rheumatoid arthritis indication and posology is not recommended.
I en lille observationsgruppe fik 110 280 patienter med reumatoid arthritis efterfølgende behandling med andre DMARDs, og deraf fik 185 patienter et biologisk DMARD efter MabThera behandling.
In a small cohort of patients with rheumatoid arthritis, 280 patients received subsequent therapy with other DMARDs of whom 185 received a biologic DMARD following MabThera.
(inklusive biologiske).
In these patients the rate of clinically relevant infection while on MabThera only was 6.99 per 100 patient years compared to 5.49 per 100 patients years following treatment with the biologic DMARD.
Det vides, at IgG- immunoglobuliner kan passere placentabarrieren.
IgG immunoglobulins are known to cross the placental barrier.
37 Toksicitetsforsøg om reproduktion, der blev udført på cynomolgusaber, viste ingen tegn på embryotoksicitet in utero.
Developmental toxicity studies performed in cynomolgus monkeys revealed no evidence of embryotoxicity in utero.