natgillin/translations-raw huggingface dataset:
Infusionsrelaterede bivirkninger af enhver art er set hos 77 % af patienterne behandlet med MabThera (herunder cytokinfrigivelsessyndrom ledsaget af hypotension og bronkospasme er set hos 10 % af patienterne) se pkt. 
Infusion-related adverse reactions of all kinds have been observed in 77% of patients treated with MabThera (including cytokine release syndrome accompanied by hypotension and bronchospasm in 10% of patients) see section 4.8.
MabThera anvendes til behandling af patienter med moderat til svær pemfigus vulgaris. 
MabThera is used for the treatment of patients with moderate to severe pemphigus vulgaris.
Samtidig administration med methotrexat påvirkede ikke farmakokinetikken af MabThera hos patienter med reumatoid artrit. 
Co-administration with methotrexate had no effect on the pharmacokinetics of MabThera in rheumatoid arthritis patients.
MabThera er indiceret til behandling af patienter med moderat til svær pemfigus vulgaris (PV). 
MabThera is indicated for the treatment of patients with moderate to severe pemphigus vulgaris (PV).
Alle infusionsrelaterede reaktioner var lette eller moderate og de fleste af dem blev rapporteret under systemorganklasserne; Luftveje, thorax og mediastinum og Hud og subkutane væv. 
All IRR symptoms were mild or moderate and most of them were reported from the SOCs Respiratory, Thoracic and Mediastinal Disorders and Skin and Subcutaneous Tissue disorders.
I studier, der evaluerede MabThera i kombination med kemoterapi, var incidensen af grad 3 og 4 kardielle arytmier, fortrinsvis supraventrikulære arytmier som takykardi og atrieflagren/-flimren, højere i R-CHOP-gruppen (14 patienter; 6,9%) sammenlignet med CHOP-gruppen (3 patienter; 1,5%). 
In studies evaluating MabThera in combination with chemotherapy, the incidence of grade 3 and 4 cardiac arrhythmias, predominantly supraventricular arrhythmias such as tachycardia and atrial flutter/fibrillation, was higher in the R-CHOP group (14 patients, 6.9%) as compared to the CHOP group (3 patients, 1.5%).
Der forekom svære infusionsrelaterede reaktioner (fx bronkospasmer og hypotension) i op til 12 % af tilfældene. 
Severe infusion-related reactions (such as bronchospasm, hypotension) occurred in up to 12 % of the cases.
I alle studier havde patienter behandlet med MabThera i kombination med methotrexat en signifikant større reduktion i sygdomsaktivitetsscore (DAS28) end patienter behandlet med methotrexat alene (tabel 12). 
Patients treated with MabThera in combination with methotrexate had a significantly greater reduction in disease activity score (DAS28) than patients treated with methotrexate alone (Table 12).
LÆGEMIDDELFORM OG INDHOLD (PAKNINGSSTØRRELSE) Koncentrat til infusionsvæske, opløsning 500 mg/50 ml 
PHARMACEUTICAL FORM AND CONTENTS Concentrate for solution for infusion 500 mg / 50 mL
Formålet med den første stadie var at bestemme den subkutane dosis af rituximab, der gav serum Ctrough-niveauer, der var sammenlignelige med den intravenøse formulering af MabThera, når det blev givet som en del af induktionsbehandlingen hver 3. uge (se pkt. 
The objective of the first stage was to establish the rituximab subcutaneous dose that resulted in comparable MabThera subcutaneous formulation serum Ctrough levels compared with MabThera intravenous formulation, when given as part of induction treatment every 3 weeks (see section 5.2).
Analyse af samlet overlevelse viste fortsat en signifikant fordel ved R-FC-behandling i forhold til FCkemoterapi (p=0,0319, log-rank test) (tabel 10a). 
The analysis of overall survival showed a significant benefit of R-FC treatment over FC chemotherapy alone (p = 0.0319, log-rank test) (Table 10a).
MabThera blev givet i en dosis på 375 mg/m2 i første serie en dag før kemoterapi og i en dosis på 500 mg/m2 på dag 1 i hver af de efterfølgende behandlingsserier. 
MabThera was administered at a dosage of 375 mg/m2 during the first cycle one day prior to chemotherapy and at a dosage of 500 mg/m2 on day 1 of each subsequent treatment cycle.
2 hætteglas á 10 ml 
2 vials of 10 mL
MARKEDSFØRINGSTILLADELSESNUMMER (-NUMRE) MabThera 100 mg koncentrat til infusionsvæske, opløsning EU/1/98/067/001 
MARKETING AUTHORISATION NUMBER(S) MabThera 100 mg concentrate for solution for infusion EU/1/98/067/001
Ved anvendelse af Cox regressionsanalyse var risiko for forekomst af progressiv sygdom eller død reduceret med 61 % med MabThera vedligeholdelsesbehandling sammenlignet med observation (95 % konfidensinterval: 45 %-72 %). 
Using a cox regression analysis, the risk of experiencing progressive disease or death was reduced by 61 % with MabThera maintenance treatment when compared to observation (95 % CI; 45 %-72 %).
Formålet med andet stadie var at fremskaffe yderligere data for virkning og sikkerhed af subkutant rituximab sammenlignet med intravenøst rituximab. 
The objective of stage 2 was to provide additional efficacy and safety data for subcutaneous rituximab compared with rituximab intravenous using the 1400 mg subcutaneous dose established in stage 1.
Dette lægemiddel indeholder mindre end 1 mmol natrium pr. dosis, dvs. den er i det væsentlige natriumfri. 
This medicinal product contains less than 1mmol sodium per dose, i.e. essentially sodium free.
Alle patienter bør screenes for hepatitis B virus (HBV) før påbegyndelse af behandling med MabThera. 
Hepatitis B virus (HBV) screening should be performed in all patients before initiation of treatment with MabThera.
Hos patienter med relaps/refraktær CLL var incidensen af hepatitis B-infektioner af grad 3/4 (reaktivering og primær infektion) 2 % for R-FC regimet versus 0 % for FC regimet. 
In patients with relapsed/refractory CLL, the incidence of grade 3/4 hepatitis B infection (reactivation and primary infection) was 2% in R-FC vs 0% FC.
De hyppigst observerede bivirkninger hos patienter, som fik MabThera var infusionsrelaterede reaktioner, som forekom hos de fleste patienter under første infusion. 
The most frequently observed adverse drug reactions (ADRs) in patients receiving MabThera were infusion-related reactions which occurred in the majority of patients during the first infusion.
Tabel 6 Opsummering af nøgleresultater fra fire fase-III-randomiserede studier, der evaluerer fordelene ved MabThera med forskellige kemoterapibehandlinger ved follikulært lymfom 
Table 6 Summary of key results from four phase III randomised studies evaluating the benefit of MabThera with different chemotherapy regimens in follicular lymphoma
Rituximabs farmakokinetik efter administration af enkeltdosis MabThera subkutan 375 mg/ m mg/m2 og 800 mg/ m2 blev sammenlignet med MabThera intravenøs 375 mg/m2 hos FL-patienter. 
Rituximab pharmacokinetics following single dose administration of MabThera subcutaneous 375 mg/ m2, 625 mg/ m2 and 800 mg/ m2 were compared with MabThera intravenous 375 mg/ m2 in FL
I behandlingsperioden (induktionsbehandlingsfasen bestående af R-CHOP i højst 8 behandlingsserier) fik 4 patienter (2 %) i R-CHOP-armen, alle med kardiovaskulære risikofaktorer, tromboemboliske cerebrovaskulære hændelser under første behandlingsserie. 
During the treatment period (induction treatment phase comprising of R-CHOP for at most eight cycles), four patients (2 %) treated with R-CHOP, all with cardiovascular risk factors, experienced thromboembolic cerebrovascular accidents during the first treatment cycle.
• Øvrige indholdsstoffer: Natriumcitrat, polysorbat 80, natriumchlorid, natriumhydroxid, saltsyre og vand til injektionsvæsker. 
• The other ingredients are sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid and water for injections.
Den samlede responsrate efter behandlingsserie 8 var 76,2 % i R-CHOP gruppen sammenlignet med 62,4 % i CHOP gruppen (p=0,0028). 
The complete response rate after cycle 8 was 76.2 % in the R-CHOP group and 62.4 % in the CHOP group (p=0.0028).
Kaplan-Meier estimeret sandsynlighed for progressionsfrihed ved 12 måneder var 78 % i MabThera vedligeholdelsesgruppen mod 57 % i observationsgruppen. 
Kaplan-Meier estimated progression-free rates at 12 months were 78% in the MabThera maintenance group vs. 57 % in the observation group.
Farmakokinetiske parametre som clearance, fordelingsvolumen og halveringstid var sammenlignelige for de 2 formuleringer. 
distribution volume, and elimination half-life were comparable for both formulations.
Nogle eksempler på disse alvorlige virusinfektioner er infektioner forårsaget af herpesvira (cytomegalovirus, varicella zoster virus og herpes simplex virus), JC virus (PML) og hepatitis C virus. 
Examples of these serious viral infections are infections caused by the herpes viruses (Cytomegalovirus, Varicella Zoster Virus and Herpes Simplex Virus), JC virus (PML) and hepatitis C virus.
MabThera er en brugsklar, klar til opaliserende, farveløs til gullig opløsning, leveret som opløsning til subkutan injektion i et farveløst hætteglas med butylgummiprop med aluminiumsforsegling og blåt vipbart plastiklåg. 
MabThera is a ready to use, clear to opalescent, colourless to yellowish liquid, supplied as a solution for subcutaneous injection in a colourless glass vial with a butyl rubber stopper with aluminium over seal and a blue plastic flip-off disk.
MabThera bør ikke administreres til patienter med en aktiv, alvorlig infektion (for eksempel tuberkulose, sepsis og opportunistiske infektioner, se pkt. 
MabThera should not be administered to patients with an active, severe infection (e.g. tuberculosis, sepsis and opportunistic infections, see section 4.3).
MabThera intravenøs formulering blev givet i standarddosen 375 mg/m2 legemsoverfladeareal. 
MabThera intravenous formulation was used at the standard dose of 375 mg/m2.
Resultater fra andre støttende studier, som anvendte MabThera i kombination med andre kemoterapiregimer (herunder CHOP, FCM, PC og PCM, bendamustin og cladribin) til behandling af tidligere ubehandlede og/eller relaps/refraktære CLL-patienter, har også vist høje totale responsrater med fordele med hensyn til PFS-rater om end med moderat højere toksicitet (specielt myelotoksicitet). 
Results from other supportive studies using MabThera in combination with other chemotherapy regimens (including CHOP, FCM, PC, PCM, bendamustine and cladribine) for the treatment of previously untreated and/or relapsed/refractory CLL patients have also demonstrated high overall response rates with benefit in terms of PFS rates, albeit with modestly higher toxicity (especially myelotoxicity).
Lokale hudreaktioner, inklusive lokale reaktioner ved injektionsstedet, var meget almindelige hos patienter behandlet med MabThera subkutan formulering. 
Local cutaneous reactions, including injection site reactions were very common in patients receiving MabThera subcutaneous formulation.
• svære hudproblemer med blister, der kan være livsfarlige 
• severe skin problems causing blisters that can be life-threatening
Der var ingen tegn på, at alder og køn skulle påvirke farmakokinetik for rituximab i klinisk relevant grad. 
There was no evidence of clinically relevant dependencies of rituximab pharmacokinetics on age and sex.
• fever, hoste, ondt i halsen, brændende smerte ved vandladning eller følelse af svaghed eller almen utilpashed 
• fever, cough, sore throat, burning pain when passing urine or feeling weak or generally unwell
De patienter, der blev randomiseret til MabThera-gruppen, fik en initial dosis på 1.000 mg intravenøst på studiedag 1 og endnu en dosis på 1.000 mg intravenøst på studiedag 15. 
Patients randomised to the MabThera group received an initial 1000 mg IV on Study Day 1 and a second 1000 mg IV on Study Day 15.
arytmier, +atrieflimren, takykardi, +hjertesygdom 
arrhythmia, +atrial fibrillation, tachycardia, +cardiac disorder
R-CVP var signifikant bedre end CVP mht. det primære endepunkt, tid til behandlingssvigt (27 måneder versus 6,6 måneder), p < 0,0001, log rank test). 
R-CVP led to a significant benefit over CVP for the primary endpoint, time to treatment failure (27 months vs. 6.6 months, p < 0.0001, log-rank test).
Tabel 3 Sammenfatning af nøgleresultater fra 4 randomiserede fase III-studier, der evaluerer fordelene ved MabThera med forskellige kemoterapibehandlinger ved follikulært lymfom 
Table 3 Summary of key results from four phase III randomized trials evaluating the benefit of MabThera with different chemotherapy regimens in follicular lymphoma
LÆGEMIDDELFORM OG INDHOLD (PAKNINGSSTØRRELSE) Koncentrat til infusionsvæske, opløsning 100 mg/10 ml 
PHARMACEUTICAL FORM AND CONTENTS Concentrate for solution for infusion 100 mg / 10 mL
Det kan antages at lignende resultater vil ses hos patienter med kronisk lymfatisk leukæmi i betragtning af lighederne mellem begge sygdomme, men det har ikke været undersøgt i kliniske forsøg. 
For CLL patients similar results are assumable considering similarities between both diseases, but this has not been investigated in clinical trials.
I en farmakokinetisk populationsanalyse af 403 patienter med follikulært lymfom behandlet med MabThera subkutant og/eller intravenøst, enkelt- eller gentagne infusioner af MabThera som enkeltstof eller i kombination med kemoterapi, var populationsestimater af ikke-specifik clearance (CL1), initial specifik clearance (CL2) - sandsynligvis skabt af B-celler eller tumorbyrde - og centralt kompartment fordelingsvolumen (V1), henholdsvis 0,194 l/dag, 0,535 l/dag og 4,37 l/dag. 
In a population pharmacokinetic analysis in 403 follicular lymphoma patients who received subcutaneous and/or intravenous MabThera, single or multiple infusions of MabThera as a single agent or in combination with chemotherapy, the population estimates of nonspecific clearance (CL1), initial specific clearance (CL2) likely contributed by B cells or tumour burden, and central compartment volume of distribution (V1) were 0.194 L/day, 0.535 L/day, and 4.37 L/day, respectively.
Cyclophosphamid 
Muscle spasms
Forekomsten af behandlingsinducerede/forhøjede anti-rHuPH20-antistoffer var 12 % og var kun målt i den sukutane gruppe. 
The incidence of treatment-induced/enhanced anti-rHuPH20 antibodies, only measured in patients in the subcutaneous arm was 12%.
† resultat ved uge 24 Signifikant forskel fra placebo + MTX ved det primære tidspunkt: ***p ≤ 0,0001 
Significant difference from placebo + MTX at the primary timepoint: ***p ≤ 0.0001
Det er vigtigt, da MabThera kan påvirke virkningen af anden medicin, og anden medicin kan påvirke virkningen af MabThera. 
This is because MabThera can affect the way some other medicines work.
Den Kaplan-Meier-estimerede progressionsfri rate ved 12 måneder var 78 % i MabTheravedligeholdelsesbehandlingsgruppen versus 57 % i observationsgruppen. 
Kaplan-Meier estimated progression-free rates at 12 months were 78 % in the MabThera maintenance group vs. 57 % in the observation group.
6 Pakningsstørrelse og yderligere indhold 
6 Contents of the pack and other information
MabThera vedligeholdelsesbehandling reducerede risikoen for død med 56 % (95 % konfidensinterval: 22 %-75 %). 
MabThera maintenance treatment reduced the risk of death by 56% (95% CI; 22%-75%).
Klar til uigennemsigtig, farveløs til gullig væske. 
Clear to opalescent, colourless to yellowish liquid.
95% konfidensinterval 
95% CIb
Sikkerhed og effekt af MabThera er ikke påvist i kombination med andre kemoterapiregimer til behandling af diffust storcellet B-celle non-Hodgkin-lymfom. 
Safety and efficacy of MabThera have not been established in combination with other chemotherapies in diffuse large B cell non-Hodgkin's lymphoma.
Hvert 10 ml hætteglas indeholder 2,3 mmol (52,6 mg) natrium. 
Each 10 mL vial contains 2.3 mmol (52.6 mg) sodium.
Herefter gives MabThera som en indsprøjtning under huden (subkutan indsprøjtning) over ca. 5 minutter. 
After this, you will be given MabThera as an injection under your skin (subcutaneous injection) over approximately 5 minutes.
Forskel (konfidensinterval 
CI: Confidence Interval
Den samlede responsrate var 57 % (95 % konfidensinterval: 41 % - 73 %; CR 14 % og PR 43 %) med en median tid indtil progression, for responderende patienter, på 19,4 måneder (interval: 5,3-38,9 måneder). 
ORR was 57% (95% Confidence interval (CI); 41% - 73%; CR 14%, PR 43%) with a projected median TTP for responding patients of 19.4 months (range 5.3 to 38.9 months).
Klinisk erfaring med MabThera koncentrat til opløsning til infusion ved non-Hodgkin-lymfom 
Clinical experience of MabThera concentrate for solution for infusion in Non-Hodgkin's lymphoma
I alt 8 behandlingsserier. 
In total: 8 cycles.
Det er vist, at MabThera i kombination med methotrexat reducerer hastigheden af ledskadeprogression, målt ved hjælp af røntgen, samt forbedrer fysisk funktionsevne. 
MabThera has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate.
• smerter i maven, ryg, muskler og/eller led 
• Pain in the tummy, back, muscles and/or joints
Hvis en sådan bivirkning skulle opstå med formodet relation til MabThera, skal behandlingen seponeres permanent. 
In case of such an event with a suspected relationship to MabThera, treatment should be permanently discontinued.
I det kliniske studie BO22334, blev effekt observeret imellem kropsstørrelse og eksponeringsratio i behandlingsserie 7, mellem rituximab subkutan formulering 1400 mg hver 3. uge og rituximab intravenøs formulering 375 mg/m2 hver 3. uge med Ctrough ratio på 2,29; 1,31 og 1,41 hos patienter med henholdsvis lavt, medium og højt legemsoverfladeareal (BSA) (lavt BSA ≤ 1,70 m2; 1,70 m2 < 
In clinical trial BO22334, an effect was observed between body size and exposure ratios reported in cycle 7, between rituximab subcutaneous formulation 1400 mg q3w and rituximab intravenous formulation 375 mg/m2 q3w with Ctrough ratios of 2.29, 1.31, and 1.41 in patients with low, medium and high BSA, respectively (low BSA ≤ 1.70 m2; 1.70 m2 < medium BSA < 1.90 m2; high BSA
Lignende bivirkninger blev set i SAWYER studiet (BO25341) hos patienter med kronisk lymfatisk leukæmi og rapporteret hos op til 42 % af de patienter, der fik subkutan MabThera. 
Similar events were observed in the CLL SAWYER trial (BO25341) and were reported in up to 42% of patients in the MabThera subcutaneous arm.
Følgende reaktioner blev indberettet som bivirkninger under de kliniske studier, men blev rapporteret med samme eller lavere hyppighed i MabThera-armen, sammenlignet med kontrolarmene: hæmatotoksicitet, infektioner hos neutropene patienter, urinvejsinfektioner, sensoriske forstyrrelser og pyreksi. 
The following terms have been reported as adverse events during clinical trials, however, were reported at a similar or lower incidence in the MabThera-arms compared to control arms: haematotoxicity, neutropenic infection, urinary tract infection, sensory disturbance, pyrexia.
1 hætteglas a 50 ml 
1 vial of 50 mL
Gentagne behandlingsserier med MabThera i kombination med methotrexat resulterede i vedvarende forbedringer af kliniske symptomer på RA angivet ved ACR- DAS28-ESR- og EULAR-respons. 
Treatment with MabThera in combination with methotrexate over multiple courses resulted in sustained improvements in the clinical signs and symptoms of RA, as indicated by ACR, DAS28-ESR and EULAR responses which was evident in all patient populations studied (Figure 2).
Herefter gives MabThera som en indsprøjtning under huden (subkutan indsprøjtning) over ca. 7 minutter. 
After this, you will be given MabThera as an injection under your skin (subcutaneous injection) over approximately 7 minutes.
I et prospektivt, ublindet, internationalt, multicenter fase III-studie, blev 465 patienter med recidiveret/ refraktært follikulært lymfom i første omgang randomiseret til induktionsbehandling med enten CHOP (cyclophosphamid, doxorubicin, vincristin, prednisolon; n=231) eller MabThera plus CHOP (R-CHOP, n=234). 
In a prospective, open label, international, multi-centre, phase III trial, 465 patients with relapsed/refractory follicular lymphoma were randomised in a first step to induction therapy with either CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone; n=231) or MabThera plus CHOP (R-CHOP, n=234).
For at undgå at nålen tilstoppes, skal den hypodermiske injektionsnål først sættes på sprøjten umiddelbart inden administration. 
The hypodermic injection needle must only be attached to the syringe immediately prior to administration to avoid potential needle clogging.
Der bør altid gives præmedicin bestående af et anti-pyretisk lægemiddel samt et antihistamin, f.eks. paracetamol og diphenhydramin, inden hver MabThera-administration. 
Premedication consisting of an anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine, should always be given before each administration of MabThera.
MabThera monoterapi er indiceret til behandling af patienter med grad III-IV follikulært lymfom, som er resistente overfor kemoterapi eller som er i deres andet eller efterfølgende relaps efter kemoterapi. 
MabThera monotherapy is indicated for treatment of patients with stage III-IV follicular lymphoma who are chemoresistant or are in their second or subsequent relapse after chemotherapy.
Nedsat hæmoglobin Metabolisme og ernæring Hyperkaliæmi 
Decreased haemoglobin Metabolism and nutrition disorders Hyperkalaemia
For information i forhold til autoimmune indikationer henvises til produktresuméet for MabThera intravenøs formulering. 
For information related to the autoimmune indications, please refer to the SmPC of MabThera intravenous formulation.
MabThera-vedligeholdelsesbehandling reducerede risiko for død med 56 % (95 % konfidensinterval; 22-75 %). 
MabThera maintenance treatment reduced the risk of death by 56 % (95 % CI; 22 %-75 %).
Efter en median observationstid på 31 måneder for patienter randomiseret til induktionsfasen, forbedrede R-CHOP signifikant udfaldet af recidiveret/refraktært follikulært lymfom sammenlignet med CHOP (se Tabel 5). 
After a median observation time of 31 months for patients randomised to the induction phase, R-CHOP significantly improved the outcome of patients with relapsed/refractory follicular lymphoma when compared to CHOP (see Table 5).
Immungenicitet 
Immunisation
Hvis behandlingen virker, kan MabThera gives som vedligeholdelsesbehandling i 2 år efter, den første behandling er givet. 
In patients where the treatment is working, MabThera may be used as a maintenance treatment for 2 years after completing the initial treatment.
I første stadie af studiet blev tidligere ubehandlede patienter med CD20-positivt, follikulært lymfom af grad 1, 2, eller 3a (n=127) inkluderet. 
Stage 1 enrolled previously untreated patients (n=127) CD20-positive, Follicular Lymphoma (FL) Grade 1, 2 or 3a.
Studier af tidligere ubehandlet og relaps/refraktær CLL har fastslået, at hos op til 25 % af patienterne behandlet med R-FC var neutropeni forlænget (defineret som neutrofiltal, der forblev under 1x109/l mellem dag 24 og 42 efter sidste dosis) eller indtraf sent (defineret som neutrofiltal under 1x109/l senere end dag 42 efter sidste dosis hos patienter uden tidligere forlænget neutropeni eller hos patienter, som restituerede før dag 42) efter behandling med MabThera plus FC. 
Studies in previously untreated and relapsed/refractory CLL have established that in up to 25% of patients treated with R-FC neutropenia was prolonged (defined as neutrophil count remaining below 1x109/L between day 24 and 42 after the last dose) or occurred with a late onset (defined as neutrophil count below 1x109/L later than 42 days after last dose in patients with no previous prolonged neutropenia or who recovered prior to day 42) following treatment with MabThera plus FC.
MabThera intravenøs formulering 
MabThera intravenous formulation
MabThera er i den intravenøse formulering anvendt til 21 patienter, som havde fået foretaget autolog knoglemarvstransplantation og til andre risikogrupper med formodet nedsat knoglemarvsfunktion uden at fremkalde myelotoksicitet. 
The MabThera intravenous formulation has been used in 21 patients who underwent autologous bone marrow transplantation and other risk groups with a presumable reduced bone marrow function without inducing myelotoxicity.