natgillin/translations-raw huggingface dataset:
Brug af enhver samtidig behandling, der kan forværre trombocytopenirelaterede hændelser, fx trombocythæmmere og antikoagulantia, bør også tages i betragtning, særligt under den første behandlingsserie.
Use of any concomitant therapies which could possibly worsen thrombocytopenia-related events, such as platelet inhibitors and anticoagulants, should also be taken into consideration, especially during the first cycle.
Et styrket præ- og postnatalt udviklingstoksicitetsstudie (ePPND) med drægtige cynomolgusaber viste ingen tegn på teratogen virkning.
An enhanced pre and postnatal development (ePPND) toxicity study in pregnant cynomolgus monkeys showed no evidence of teratogenic effects.
• Grad 1-2 (mild til moderat): Infusionshastigheden skal reduceres og symptomerne behandles.
· Grade 1-2 (mild to moderate): The infusion rate must be reduced and symptoms treated.
Patienter med tidligere ubehandlet follikulært lymfom
Patients with previously untreated follicular lymphoma
Varighed af behandling Seks behandlingsserier, hver af 28 dages varighed.
Duration of treatment Six treatment cycles, each of 28 day duration.
Infusionsrelaterede reaktioner er meget almindelige under den første infusion af Gazyvaro og patienter, der oplever infusionsrelaterede symptomer bør frarådes at føre motorkøretøj eller betjene maskiner, indtil symptomerne er aftaget.
IRRs are very common during the first infusion of Gazyvaro, and patients experiencing infusion related symptoms should be advised not to drive or use machines until symptoms abate.
Patient-rapporterede resultater
Patient-reported Outcomes
Tabel 6 Oversigt over bivirkninger indberettet med højere incidens (forskel ≥ 2% versus komparator armen) hos patienter#, der fik Gazyvaro plus kemoterapi* Systemorganklasse
Table 6 Summary of ADRs reported with a higher incidence (difference of ≥2% versus the comparator arm) in patients# receiving Gazyvaro + chemotherapy* System organ class
Baseret på en subgruppeanalyse hos patienter med follikulært lymfom, som ikke tidligere var behandlet, er effekten hos patienter med FLIPI score 0-1 (lav risiko) på nuværende tidspunkt ikke fyldestgørende (se pkt.
Based on a subgroup analysis in previously untreated follicular lymphoma, the efficacy in FLIPI low risk (0-1) patients is currently inconclusive (see section 5.1).
Stadie 1a sammenlignede Gazyvaro plus chlorambucil med chlorambucil alene hos 356 patienter, og stadie 2 sammenlignede Gazyvaro plus chlorambucil med rituximab plus chlorambucil hos 663 patienter.
Stage 1a compared Gazyvaro plus chlorambucil to chlorambucil alone in 356 patients and Stage 2 compared Gazyvaro plus chlorambucil to rituximab plus chlorambucil in 663 patients.
34% af patienterne blev inkluderet på co-morbiditetsscore alene, og 23% af patienterne havde kun nedsat nyrefunktion.
Thirty-four percent of patients were enrolled on comorbidity score alone, and 23% of patients were enrolled with only impaired renal function.
Det er i visse tilfælde sket, at at hepatitis B, en type leverbetændelse, er kommet igen hos patienter, der tidligere har haft hepatitis B.
A type of liver disease called “hepatitis B” has also been reported to reoccur in patients who have had hepatitis B in the past.
Der er set forbigående stigninger i levertal (aspartataminotransferase [ASAT], alaninaminotransferase [ALAT], alkalisk fosfatase) kort efter første infusion af Gazyvaro.
Transient elevation in liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase) has been observed shortly after the first infusion of Gazyvaro.
Hoste§
Cough§
Hvis du mangler en behandling med Gazyvaro
If you miss a Gazyvaro treatment
Resultater fra progressionsfri overlevelse-subgruppeanalysen (dvs. køn, alder, Binet-stadie, CrCl, CIRS-score, beta2-mikroglobulin, IGVH-status, kromosomforandringer, lymfocyttal ved baseline) var i overensstemmelse med resultaterne fra den overordnede ITT-population (Intent-to-Treat).
Results of the progression free survival (PFS) subgroup analysis (i.e. sex, age, Binet stages, CrCl, CIRS score, beta2-microglobulin, IGVH status, chromosomal abnormalities, lymphocyte count at baseline) were consistent with the results seen in the overall Intent-to-Treat population.
Reaktivering af hepatitis B-virus (HBV), i nogle tilfælde medførende fulminant hepatitis, leversvigt og død, kan forekomme hos patienter behandlet med anti-CD20-antistoffer, inklusive Gazyvaro (se pkt.
Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with anti-CD20 antibodies including Gazyvaro (see section 4.8).
2. dag (eller 1. dag fortsat) (900 mg)
Day 2 (or Day 1 continued) (900 mg)
5.1 for information om chlorambucil dosis
1See section 5.1 for information on chlorambucil dose
Gazyvaro skal gives intravenøst.
Gazyvaro is for intravenous use.
Dyrestudier har påvist udskillelse af obinutuzumab i brystmælk (se pkt.
Animal studies have shown secretion of obinutuzumab in breast milk (see section 5.3).
Patienter med kendt overfølsomhed over for obinutuzumab må ikke behandles (se pkt.
Patients with known hypersensitivity to obinutuzumab must not be treated (see section 4.3).
Patienter med nedsat funktion af ét eller flere individuelle organer svarende til en score på 4 vurderet ved CIRS, undtagen øjne, øre, næse, hals og svælg, kunne heller ikke deltage i studiet.
Patients with one or more individual organ/system impairment score of 4 as assessed by the CIRS definition, excluding eyes, ears, nose, throat and larynx organ system, were excluded.
Da humant immunglobulin G (IgG) udskilles i modermælk, og risiko for absorption og for at skade spædbarnet er ukendt, bør kvinder frarådes at amme under behandling med Gazyvaro og i 18 måneder efter behandlingen med Gazyvaro er afsluttet (se pkt.
Since human immunoglobulin G (IgG) is secreted in human milk and the potential for absorption and harm to the infant is unknown, women should be advised to discontinue breast-feeding during Gazyvaro therapy and for 18 months after the last dose of Gazyvaro.
Mindst 30 minutter inden infusion af Gazyvaro
At least 30 minutes before Gazyvaro infusion
Patienter med en infusionsrelateret reaktion (grad 1 eller 2) under den forudgående infusion
Patients with an IRR (Grade 1 or 2) with the previous infusion
Fortæl det altid til lægen eller sundhedspersonalet, hvis du bruger anden medicin, har gjort det for nylig eller planlægger at tage anden medicin.
Tell your doctor or nurse if you are taking, have recently taken or might start taking any other medicines.
• når risikostyringssystemet ændres, særlig som følge af, at der er modtaget nye oplysninger, der kan medføre en væsentlig ændring i risk/benefit-forholdet, eller som følge af, at en vigtig milepæl (lægemiddelovervågning eller risikominimering) er nået.
An updated RMP should be submitted: · At the request of the European Medicines Agency; · Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
Hvordan Gazyvaro gives
How Gazyvaro is given
• Kontakt straks lægen eller sundhedspersonalet, hvis du oplever en eller flere af de reaktioner på infusionen, der er nævnt i starten af afsnit 4.
· Tell your doctor or nurse straight away if you get any of the infusion related reactions listed at the start of section 4.
Gazyvaro behandling
The Gazyvaro treatment
Kontakt straks lægen, hvis du oplever dårlig hukommelse problemer med at tale besvær med at gå synsfortyrrelser
Tell your doctor or nurse straight away if you have · memory loss · trouble speaking · difficulty walking · problems with your eyesight
Det mediane antal tidligere behandlinger var 2 (interval fra 1-10), hvor 44% af patienterne tidligere havde fået 1 behandling og 34% af patienterne tidligere havde fået 2 behandlinger.
The median time from initial diagnosis was 3 years and the median number of prior therapies was 2 (range 1 to 10); 44% of patients had received 1 prior therapy and 34% of patients had received 2 prior therapies.
- I starten af behandlingen af follikulært lymfom, bruges Gazyvaro sammen med andre lægemidler mod kræft.
At the start of treatment for FL, Gazyvaro is used together with other medicines for cancer.
Infusioner med Gazyvaro må ikke gives som intravenøs stød- eller bolusdosis.
Gazyvaro infusions should not be administered as an intravenous push or bolus.
Svære bakterie, svampeinfektioner samt nye eller reaktiverede virale infektioner kan forekomme under og efter behandling med Gazyvaro.
Serious bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of Gazyvaro therapy.
Hvis planlagt behandling med Gazyvaro mangler eller er forsinket, skal dosis administreres så hurtigt som muligt; vent ikke til næste planlagte dosis.
If a planned dose of Gazyvaro is missed, it should be administered as soon as possible; do not wait until the next planned dose.
Farmakokinetiske data fra patienter med svær nedsat nyrefunktion (CrCl 15-29 ml/min) er begrænsede (n=8), og der kan derfor ikke gives dosisanbefalinger.
Pharmacokinetic data in patients with severe renal impairment (CrCl 15-29 mL/min) is limited (n=8), therefore no dose recommendations can be made.
Den anbefalede dosis af Gazyvaro i kombination med chlorambucil er 1000 mg administreret på 1. dag af hver serie.
The recommended dose of Gazyvaro in combination with chlorambucil is 1,000 mg administered on Day 1 of each cycle.
Gazyvaro er et koncentrat til infusionsvæske, opløsning og er en farveløs til let brunlig væske.
Gazyvaro is a concentrate for solution for infusion and is a colourless to slightly brown liquid.
Progressiv multifokal leukoencefalopati-diagnose bør overvejes hos alle patienter med debuterende neurologiske manifestationer eller ændringer i allerede eksisterende neurologiske manifestationer.
The diagnosis of PML should be considered in any patient presenting with new-onset or changes to pre-existing neurologic manifestations.
Incidensen af infusionsrelaterede reaktioner var 66% ved infusionen af de første 1000 mg Gazyvaro (20% af patienterne oplevede en infusionsrelateret reaktion af grad 3-4).
The incidence of IRRs was 66% with the infusion of the first 1,000 mg of Gazyvaro (20% of patients experiencing a Grade 3-4 IRR).
I den lille subgruppe af patienter med deletion 17p sås kun positiv tendens sammenlignet med Clb (HR=0,42, p=0,0892)).
In the small subgroup of patients with deletion 17p, only a positive trend was observed compared to Clb (HR=0.42, p=0.0892); no benefit was observed compared to RClb.
Histidinhydrochloridmonohydrat
Histidine hydrochloride monohydrate
Tidligere ubehandlet follikulært lymfom (studie BO21223/GALLIUM)
Previously untreated follicular lymphoma (study BO21223/GALLIUM)
Effektresultater i populationen med follikulært lymfom er vist i tabel 9.
Efficacy results in the FL population are shown in Table 9.
Efter 1. behandlingsserie var incidensen af infusionsrelaterede reaktioner i efterfølgende infusioner sammenlignelige mellem Gazyvaro og de relevante komparator-arme.
Beyond Cycle 1 the incidence of IRRs in subsequent infusions was comparable between the Gazyvaro and the relevant comparator arms.
I de pivotale studier med indolent non-Hodgkin lymfomoplevede op til 1 % af patienterne gastrointestinal perforation.
In the pivotal studies in iNHL up to 1% of patients experienced gastrointestinal perforation.
1. dag
Day 1
Fund inkluderede akutte anafylaktiske eller anafylaktoide reaktioner og en øget prævalens af systemisk inflammation og infiltrater i overensstemmelse med immunkompleksmedierede allergiske reaktioner, fx arteritis/periarteritis, glomerulonefritis og serøse/adventitial inflammation.
Findings included acute anaphylactic or anaphylactoid reactions and an increased prevalence of systemic inflammation and infiltrates consistent with immune-complex mediated hypersensitivity reactions, such as arteritis/periarteritis, glomerulonephritis, and serosal/adventitial inflammation.
Antal (%) patienter med hændelse Median tid til hændelse (måneder)
No. (%) of patients with event Median time to event (months)
Kontakt straks lægen eller sundhedspersonalet, hvis du oplever én eller flere af følgende symptomer under infusionen eller op til 24 timer efter infusionen.
Tell your doctor or nurse straight away if you get any of the following symptoms during your infusion or up to 24 hours after having your infusion:
Ældre patienter Dosisjustering er ikke nødvendig hos ældre patienter (se pkt.
Elderly No dose adjustment is required in elderly patients (see section 5.2).
I de efterfølgende behandlingsserier (2.-6. serie) fik patienterne Gazyvaro 1000 mg på 1. dag.
For each subsequent treatment cycle (Cycles 2 to 6), patients received Gazyvaro 1,000 mg on Day 1 only.
† der er ikke set forskelle på ≥2% i forekomst af bivirkning af grad 5 mellem behandlingsarmene
† No Grade 5 adverse reactions have been observed with a difference of ≥ 2% between the treatment arms
Hvis et kortikosteroid indeholdende kemoterapi administreres på samme dag som Gazyvaro, kan kortikosteroid administreres som et oral lægemiddel, hvis det bliver administreret mindst 60 minutter før Gazyvaro, i hvilket tilfælde yderligere IV corticosteroid som præmedicinering ikke er påkrævet.
4.If a corticosteroid-containing chemotherapy regimen is administered on the same day as Gazyvaro, the corticosteroid can be administered as an oral medicinal product if given at least 60 minutes prior to Gazyvaro, in which case additional IV corticosteroid as premedication is not required.
Alle patienter, som anses for at være i risiko, bør monitoreres nøje i de første dage af behandlingen med specielt fokus på nyrefunktion samt kalcium- og urinsyre værdier.
All patients considered at risk should be carefully monitored during the initial days of treatment with a special focus on renal function, potassium, and uric acid values.
Obinutuzumab er et Type II, humaniseret anti-CD20 monoklonalt antistof i IgG1-subgruppen, udledt ved humanisering af det parentale B-Ly1-museantistof og fremstillet ved rekombinant DNA-teknologi i ovarieceller fra kinesisk hamster.
Obinutuzumab is a Type II humanised anti-CD20 monoclonal antibody of the IgG1 subclass derived by humanisation of the parental B-Ly1 mouse antibody and produced in the Chinese Hamster Ovary cell line by recombinant DNA technology.
Resultater fra immunogenicitets-test er meget afhængige af flere faktorer, inklusive test-følsomhed og -specificitet, testmetode, testens robusthed over for mængden af cirkulerende Gazyvaro/antistoffer i blodet, håndtering af prøver, tidspunkt for prøvetagning, samtidig behandling med andre lægemidler og underliggende sygdom.
Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, assay robustness to quantities of Gazyvaro/antibody in the circulation, sample handling, timing of sample collection, concomitant medicines and underlying disease.
6.6 Regler for bortskaffelse og anden håndtering Fortyndingsvejledning
6.6 Special precautions for disposal and other handling
• Grad 3 (svær): Infusionen skal midlertidigt afbrydes og symptomerne behandles.
· Grade 3 (severe): Infusion must be temporarily stopped and symptoms treated.
De vil hjælpe dig med at vurdere din gavn af behandlingen i forhold til barnets risiko ved at du får Gazyvaro.
They will help you weigh up the benefit of continuing Gazyvaro against the risk to your baby.
For at mindske forekomsten af infusionsrelaterede reaktioner hos patienterne, udarbejdedes en ændring til protokollen, og 140 patienter fik herefter den første Gazyvaro-dosis over 2 dage (1. dag [100 mg] og 2. dag [900 mg]) (se pkt.
In order to reduce the rate of infusion related reactions in patients, an amendment was implemented and 140 patients received the first Gazyvaro dose administered over 2 days (Day 1 [100 mg] and Day 2 [900 mg]) (see section 4.2 and 4.4).
Der er i et 26-ugers studie med cynomolgusaber set allergiske reaktioner, som blev tilskrevet, at det humaniserede antistof blev opfattet som fremmed i cynomolgusaber (0,7-6 gange den kliniske eksponering baseret på Cmax og AUC ved steady-state efter ugentlig administration af henholdsvis 5, 25 og 50 mg/kg).
In a 26-week cynomolgus monkey study, hypersensitivity reactions were noted and attributed to the foreign recognition of the humanised antibody in cynomolgus monkeys (0.7-6 times the clinical exposure based on Cmax and AUC at steady state after weekly administration of 5, 25, and 50 mg/kg).
Glycoengineering af Fc-delen af obinutuzumab giver højere affinitet for FcɣRIII-receptorerne på immune effektorceller som naturlige dræberceller, makrofager og monocytter sammenlignet med nonglycoengineered antistoffer.
Glycoengineering of the Fc part of obinutuzumab results in higher affinity for FcɣRIII receptors on immune effector cells such as natural killer (NK) cells, macrophages and monocytes as compared to non-glycoengineered antibodies.
Hvis en planlagt behandling med Gazyvaro mangler skal dosis administreres så hurtigt som muligt, der skal ikke udelades eller ventes til næste planlagte dosis.
If a planned dose of Gazyvaro is missed, it should be administered as soon as possible; do not omit it or wait until the next planned dose.
Patienter i det pivotale studie BO21004/CLL11 med kronisk lymfatisk leukæmi blev på forskellige tidspunkter testet for anti-terapeutiske-antistoffer (ATA) mod Gazyvaro.
Patients in the CLL pivotal study BO21004/CLL11 were tested at multiple time-points for anti-therapeutic antibodies (ATA) to Gazyvaro.
Patienterne blev randomiseret 1: 1 til at få enten Gazyvaro (n = 601 patienter) eller rituximab (n = 601 patienter) i kombination med kemoterapi (bendamustin, CHOP eller CVP), efterfulgt af Gazyvaro eller rituximab vedligeholdelsesbehandling hos patienter, der opnåede komplet eller partiel respons.
Patients were randomised to 1:1 to receive either Gazyvaro (n=601 patients) or rituximab (n=601 patients) in combination with chemotherapy (bendamustine, CHOP or CVP), followed by Gazyvaro or rituximab maintenance in patients achieving a complete or partial response.
Disse inkluderer:
These may include:
Motoriske symptomer involverende de kortikospinale baner (fx muskelsvaghed, lammelse og sanseforstyrrelser), sensoriske afvigelser, cerebellare symptomer og synsfeltdefekt er almindelige.
Motor symptoms with corticospinal tract findings (e.g. muscular weakness, paralysis and sensory disturbances), sensory abnormalities, cerebellar symptoms, and visual field defects are common.
Hos patienter behandlet med Gazyvaro plus bendamustin fik 79,4% alle 6 behandlingsserier sammenlignet med 66,7% af patienterne, der kun fik bendamustin.
In patients treated with G+ B, 79.4% received all six treatment cycles compared to 66.7% of patients in the B arm.
Progressiv multifokal leukoencefalopati (også kaldet ”PML”)
Progressive multifocal leukoencephalopathy (also called “PML”)
Samlet oplevede 3% af patienterne en infusionsrelateret reaktion som medførte seponering af Gazyvaro.
Overall, 3% of patients experienced an infusion related reaction leading to discontinuation of Gazyvaro.
8. dag
Day 8
Tumorlysesyndrom forårsages af kemiske ændringer i blodet, der kan opstå, når de døende kræftceller nedbrydes (se afsnit 3).
Tumour lysis syndrome is a potentially life-threatening complication, caused by chemical changes in the blood due to the breakdown of dying cancer cells (see section 3).
Børn eller unge under 18 år må ikke få Gazyvaro.
Do not give Gazyvaro to children or young people under 18 years of age.
I det pivotale kliniske studie, BO21004/CLL11, blev 91% (40 ud af 44) af de evaluérbare patienter behandlet med Gazyvaro B-celle-depleterede (defineret som CD19+ B-celletal <0,07x 109/l) i slutningen af behandlingsperioden og forblev depleterede igennem de første 6 måneder af opfølgningsperioden.
In the pivotal clinical study BO21004/CLL11, 91% (40 out of 44) of evaluable patients treated with Gazyvaro were B-cell depleted (defined as CD19+ B-cell counts < 0.07 x 109/L) at the end of treatment period and remained depleted during the first 6 months of follow up.
De hyppigst observerede bivirkninger hos patienter behandlet med Gazyvaro var infusionsrelaterede reaktioner, der primært opstod under infusionen af de første 1000 mg. Infusionsrelaterede reaktioner kan være relateret til cytokinfrigivelsessyndrom, som også har været rapporteret hos patienter behandlet med Gazyvaro.
The most frequently observed adverse drug reactions (ADRs) in patients receiving Gazyvaro were IRRs, which occurred predominantly during infusion of the first 1,000 mg. IRRs may be related to cytokine release syndrome which has also been reported in Gazyvaro treated patients.
Hvis du ikke er sikker, skal du spørge lægen eller sundhedspersonalet før du får Gazyvaro.
If you are not sure talk to your doctor or nurse before being given Gazyvaro.
6.3 for opbevaringsbetingelser for infusionsposer.
For storage conditions of the infusion bags see section 6.3.
Patienter med hjertesygdom i anamnesen bør derfor overvåges grundigt.
Therefore patients with a history of cardiac disease should be monitored closely.
Sådanne bivirkninger kan forekomme som en del af en infusionsrelateret reaktion og kan være fatale.
These events may occur as part of an IRR and can be fatal.
I et open-label, multicenter, randomiseret fase III klinisk studie (BO21223/GALLIUM), blev 1202 patienter med tidligere ubehandlet grad 1-3a fremskreden (stadie II bulky sygdom, stadie III/IV) follikulært lymfom evalueret.
In a phase III, open label, multicentre, randomised clinical study (BO21223/GALLIUM), 1202 patients with previously untreated Grade 1-3a advanced (stage II bulky disease, stage III/IV) FL were evaluated.
I vedligeholdelsesperioden i studie GAO4753g/GADOLIN var de hyppigste bivirkninger hoste (15%), øvre luftvejsinfektioner (12%), neutropeni (11%), sinusitis (10%), diarré (8%), infusionsrelaterede reaktioner (8%), kvalme (8%), træthed (8%), bronkitis (7%), artralgi (7%), pyreksi (6%), nasofaryngitis (6%) og urinvejsinfektioner (6%).
During the maintenance period in study GAO4753g/GADOLIN, the most common adverse reactions were cough (15%), upper respiratory infections (12%), neutropenia (11%), sinusitis (10%), diarrhoea (8%), IRRs (8%), nausea (8%), fatigue (8%), bronchitis (7%), arthralgia (7%), pyrexia (6%), nasopharyngitis (6%), and urinary tract infections (6%).
Induktionsbehandling (i kombination med bendamustin2) Gazyvaro skal administreres i seks 28-dages behandlingsserier i kombination med bendamustin.
Induction (in combination with bendamustine2) Gazyvaro should be administered in six 28-day cycles in combination with bendamustine2.
Patienter med grad 3 infusionsrelateret reaktion under forudgående infusion ELLER patienter med lymfocyttal >25 x 109/l inden næste behandling
Patients with a Grade 3 IRR with the previous infusion OR Patients with lymphocyte counts >25 x 109/L prior to next treatment
Anæmi, leukopeni
Anaemia, leukopenia
Intravenøst kortikosteroid4
Intravenous corticosteroid1,4
Svær og livstruende neutropeni, inklusive febril neutropeni, er rapporteret under behandling med Gazyvaro.
Severe and life-threatening neutropenia including febrile neutropenia has been reported during treatment with Gazyvaro.
Det bør derfor overvejes at standse antihypertensiv behandling i 12 timer inden og under hver infusion af Gazyvaro samt i den første time efter administration.
Therefore, withholding of antihypertensive treatments should be considered for 12 hours prior to and throughout each Gazyvaro infusion and for the first hour after administration.
Patienterne skulle inden inklusion have verificeret CD20+ CLL samt opfylde én eller begge af følgende mål for andre samtidige sygdomme: en co-morbiditetsscore (CIRS) på mere end 6 eller nedsat nyrefunktion svarende til CrCl <70 ml/min.
Prior to enrolment, patients had to have documented CD20+ CLL, and one or both of the following measures of coexisting medical conditions: comorbidity score (CIRS) of greater than 6 or reduced renal function as measured by CrCl < 70 mL/min.