natgillin/translations-raw huggingface dataset:
6-MP 60 mg/m² oral, dag 26-46
6-MP 60 mg/m oral, days 26-46
Vedvarende aktivering af PDGF receptoren eller Abl-protein-tyrosinkinase, der opstår på grund af en fusion med andre proteiner eller konstitutiv produktion af PDGF er blevet impliceret i patogenesen af MDS/MPD, HES/CEL og DFSP.
Constitutive activation of the PDGF receptor or the Abl protein tyrosine kinases as a consequence of fusion to diverse partner proteins or constitutive production of PDGF have been implicated in the pathogenesis of MDS/MPD, HES/CEL and DFSP.
Imatinib blev in vitro vist at være en kompetitiv hæmmer af markørsubstrater for CYP2C9, CYP2D6 og CYP3A4/5.
Imatinib was shown in vitro to be a competitive inhibitor of marker substrates for CYP2C9, CYP2D6 and CYP3A4/5.
Imatinib medac kan gøre det samme ved andre lægemidler.
Imatinib medac may do the same to some other medicines.
Imatinib kan også hæmme cellulære signaler medieret ved aktivering af disse receptorkinaser.
Imatinib can also inhibit cellular events mediated by activation of these receptor kinases.
Patienter med let, moderat eller svært nedsat leverfunktion bør gives den mindste anbefalede dosis på 400 mg dagligt.
Patients with mild, moderate or severe liver dysfunction should be given the minimum recommended dose of 400 mg daily.
Der sås øget incidens af opportunistiske infektioner ved kronisk imatinib-behandling.
An increased rate of opportunistic infections was observed with chronic imatinib treatment.
Stop imatinib indtil ANC ≥1,5 x 10
Stop imatinib until ANC ≥ 1.5 x 10
Der er utilstrækkelige data fra anvendelse af imatinib til gravide kvinder.
There are limited data on the use of imatinib in pregnant women.
Tabel 2 Respons i et studie med voksne CML-patienter
Table 2 Response in adult CML study
• voksne patienter med inoperabel dermatofibrosarkom protuberans (DFSP) og voksne patienter med recidiverende og/eller metastaserende DFSP som ikke er tilgængelig for kirurgi.
• adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery.
Ved en dosis på 60 mg/kg, havde hunrotterne et signifikant føtaltab efter implantation og et reduceret antal levende fostre.
At a dose of 60 mg/kg, female rats had significant postimplantation foetal loss and a reduced number of live foetuses.
I F1afkommet var den gennemsnitlige kropsvægt ved samme dosisniveau reduceret fra fødsel til aflivning og antallet af kuld der opfyldte kriteriet for præputial separation var let nedsat.
In the F1 offspring, at the same dose level, mean body weights were reduced from birth until terminal sacrifice and the number of litters achieving criterion for preputial separation was slightly decreased.
Imatinib medac kan hjælpe dig med at bekæmpe denne tilstand.
Imatinib medac can help you to fight this condition.
De voksne patienter, som er beskrevet i publiceret litteratur blev behandlet med enten 400 mg (fire tilfælde) eller 800 mg (et tilfælde) imatinib dagligt.
The adult patients reported in the published literature were treated with either 400 mg (4 cases) or 800 mg (1 case) imatinib daily.
I tilfælde af overdosis bør patienten observeres og passende symptomatisk behandling institueres.
In the event of overdose the patient should be observed and appropriate symptomatic treatment given.
Dosisøgninger fra 100 mg til 400 mg kan overvejes, hvis der ikke er observeret bivirkninger, og respons på behandlingen vurderes som værende utilstrækkeligt.
Dose increases from 100 mg to 400 mg may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.
Tilstanden blev rapporteret som værende reversibel ved indgift af systemiske steroider, understøttelse af kredsløbet og midlertidigt stop af imatinib.
The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding imatinib.
Imatinibs virkning på resultatet af knoglemarvstransplantation er ikke fastlagt.
The effect of imatinib on the outcome of bone marrow transplantation has not been determined.
Et observationelt registerstudie (studie L2401) blev udført for at indsamle langsigtede sikkerheds- og effektdata for patienter, som lider af myeloproliferative neoplasier med PDGFR- β rearrangement og som blev behandlet med Imatinib medac.
An observational registry (study L2401) was conducted to collect long-term safety and efficacy data in patients suffering from myeloproliferative neoplasms with PDGFR- β rearrangement and who were treated with imatinib.
Myelodysplastiske/myeloproliferative sygdomme med PDGFR-omlejring kan være forbundet med høje eosinofiltal.
Myelodysplastic/myeloproliferative diseases with PDGFR gene re-arrangements could be associated with high eosinophil levels.
Uomdannet imatinib er ansvarlig for ca. 25 % af dosis (5 % urin og 20 % fæces), resten er metabolitter.
Unchanged imatinib accounted for 25 % of the dose (5 % urine, 20 % faeces), the remainder being metabolites.
Det bør bemærkes, at GIST-patienter kan have levermetastaser, hvilket kan medføre leverinsufficiens.
It should be noted that GIST patients may have hepatic metastases which could lead to hepatic impairment.
Imatinib hæmmer signaleringen og vækst af celler, der drives af dysreguleret PDGFR og Abl kinaseaktivitet.
Imatinib inhibits signalling and proliferation of cells driven by dysregulated PDGFR and Abl kinase activity.
• Myelodysplastiske/myeloproliferative sygdomme (MDS/MDP).
• Myelodysplastic/myeloproliferative diseases (MDS/MPD).
Tabel 3 Kemoterapiregime anvendt i kombination med imatinib
Table 3 Chemotherapy regimen used in combination with imatinib
Neutropeni og trombocytopeni-toksicitet
Neutropenia and thrombocytopenia toxicity
Disse virkninger sås ikke ved doser ≤ 30 mg/kg.
These effects were not seen at doses ≤ 30 mg/kg.
Der er ingen kontrollerede undersøgelser, der har vist klinisk bedring såsom forbedring af sygdomsrelaterede symptomer eller øget overlevelse.
There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
Dette sås ikke ved doser ≤ 20 mg/kg.
This was not seen at doses ≤ 20 mg/kg.
Samtidig anvendelse af stærke CYP3A4-induktorer og imatinib bør derfor undgås (se pkt.
Therefore, concomitant use of strong CYP3A4 inducers and imatinib should be avoided (see section 4.5).
Disse cytopenier opstår imidlertid sandsynligvis relateret til det sygdomsstadie, der behandles, og er hyppigere hos patienter med CML i accelereret fase eller blastkrise end hos patienter med CML i kronisk fase.
However, the occurrence of these cytopenias is likely to be related to the stage of the disease being treated and they were more frequent in patients with accelerated phase CML or blast crisis as compared to patients with chronic phase CML.
På tidspunktet for den oprindelige analyse, havde 3 af 4 patienter med konstateret PDGFR-omlejring opnået hæmatologisk respons (2 CHR og 1 PHR).
At the time of the original analysis, three of the four patients with detected PDGFR gene rearrangements developed haematological response (2 CHR and 1 PHR).
Sikkerhedsdatabasen for børn med Ph+ ALL er meget begrænset.
The safety database for children with Ph+ ALL is very limited though no new safety concerns have been identified.
Behandlingen bør initieres af en læge med erfaring i behandling af patienter med maligne hæmatologiske lidelser og/eller maligne sarkomer eller som passende.
Therapy should be initiated by a physician experienced in the treatment of patients with haematological malignancies and malignant sarcomas, as appropriate.
En 3-årig dreng, der fik en enkelt dosis på 400 mg, oplevede opkastning, diarré og appetitløshed, og en anden 3-årig dreng, der fik en enkelt dosis på 980 mg, oplevede nedsat antal hvide blodlegemer og diarré.
One 3-year-old male exposed to a single dose of 400 mg experienced vomiting, diarrhoea and anorexia and another 3-year-old male exposed to a single dose of 980 mg experienced decreased white blood cell count and diarrhoea.
Studie AIT07 var et multicenter, åbent, randomiseret, fase II/III-studie, der inkluderede 128 patienter (1 til <18 år), som fik behandling med imatinib i kombination med kemoterapi.
Study AIT07 was a multicentre, open-label, randomised, phase II/III study that included 128 patients (1 to < 18 years) treated with imatinib in combination with chemotherapy.
Undersøg om cytopeni er relateret til leukæmi (marv-aspirat eller biopsi).
Check whether cytopenia is related to leukaemia (marrow aspirate or biopsy).
• Hurtig vægtøgning.
• Rapid weight gain.
Studie ADE10 Præfase
Study ADE10 Prephase
I kliniske undersøgelser i CML blev der hos 2,4 % af nydiagnosticerede patienter, hos 4% af patienterne i sen kronisk fase efter svigtende interferonbehandling, hos 4 % af patienterne i accelereret fase efter svigtende interferonbehandling og hos 5 % af patienterne i blastkrise efter svigtende interferonbehandling observeret efter seponering af undersøgelsesmedicinen på grund af behandlingsrelaterede bivirkninger.
In clinical trials in CML, discontinuation of the investigational medicinal product for treatment-related adverse reactions was observed in 2.4 % of newly diagnosed patients, 4 % of patients in late chronic phase after failure of interferon therapy, 4 % of patients in accelerated phase after failure of interferon therapy and 5 % of blast crisis patients after failure of interferon therapy.
Præbehandling med gentagne doser af rifampicin 600 mg efterfulgt af enkeltdosis imatinib 400 mg resulterede i fald i Cmax og AUC(0-∞) på mindst 54 % og 74 % af værdierne uden rifampicinbehandling.
Pretreatment with multiple doses of rifampicin 600 mg followed by a single 400 mg dose of imatinib resulted in decrease in Cmax and AUC(0-∞) by at least 54 % and 74 %, of the respective values without rifampicin treatment.
Patienter, som behandles med imatinib og bekymrer sig om deres fertilitet under imatinib-behandling, bør konsultere deres læge.
Patients on imatinib treatment who are concerned about their fertility should consult with their physician.
Der er i kliniske undersøgelser set øget incidens af disse hændelser hos ældre patienter og hos patienter med hjertesygdom i anamnesen.
In clinical trials, there was an increased incidence of these events in older people and those with a prior history of cardiac disease.
Hvis responsraten beregnes ud fra patienter med mindst en valid parametervurdering er reponsraten for CHR, CCyr og MR henholdvis 20/22 (90,9 %), 9/9 (100 %) og
When the response rate is calculated from patients with at least one valid assessment, the response rate for CHR, CCyR and MR was 20/22 (90.9%), 9/9 (100%) and 11/17 (64.7%), respectively.
Maksimale plasmakoncentrationer af imatinib er hos patienter 2-4 µmol/l, og hæmning af CYP2D6 og/eller CYP3A4/5-medieret metabolisme af samtidigt administrerede lægemidler er derfor mulig.
Maximal plasma concentrations of imatinib in patients are 2-4 μmol/l, consequently an inhibition of CYP2D6 and/or CYP3A4/5-mediated metabolism of co-administered medicinal products is possible.
Anvendelse til børn: Der er ingen erfaring med behandling af børn under 2 år med CML, og børn under 1 år med Ph+ ALL (se pkt.
Paediatric use: There is no experience in children with CML below 2 years of age and with Ph+ ALL below 1 year of age (see section 5.1).
• børn med Ph+ CML i kronisk fase efter manglende effekt af alfa-interferonbehandling, eller i
• paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in
Med undtagelse af nyligt diagnosticerede patienter med CML i kronisk fase, er der ikke gennemført kontrollerede undersøgelser, der har vist klinisk bedring eller øget overlevelse ved disse sygdomme.
Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
imatinib blev administreret periodisk i kohorte 1-5 med stigende varighed og tidligere start med imatinib fra kohorte til kohorte; kohorte 1 fik den mindst intensive imatinibbehandling og kohorte 5 den mest intensive (længste varighed i dage med kontinuerlig, daglig imatinibdosering i de første kemobehandlingsforløb).
imatinib was administered intermittently in cohorts 1-5, with increasing duration and earlier start of imatinib from cohort to cohort; cohort 1 receiving the lowest intensitiy and cohort 5 receiving the highest intensity of imatinib (longest duration in days with continuous daily imatinib dosing during the first chemotherapy treatment courses).
• voksne og børn med Ph+ CML i blastkrise.
• adult and paediatric patients with Ph+ CML in blast crisis.
Pabianickie Zakłady Farmaceutyczne Polfa S.A. Marszałka Józefa Piłsudskiego 5 Str. 95-200 Pabianice
Pabianickie Zakłady Farmaceutyczne Polfa S.A. Marszałka Józefa Piłsudskiego 5
Alderen hos disse patienter varierede fra 2 til 79 år.
The age of these patients ranged from 2 to 79 years.
Der blev set PDGFRomlejring hos 11 patienter, 9 af disse opnåede CHR og 1 PHR.
In eleven patients PDGFR gene rearrangements were detected, 9 of them achieved a CHR and 1 PHR.
Disse er en gruppe af sygdomme i blodet, hvor nogle blodlegemer begynder at vokse ukontrolleret.
These are a group of blood diseases in which some blood cells start growing out of control.
• Brystsmerter, uregelmæssig hjerterytme (tegn på hjerteproblemer).
• Chest pain, irregular heart rhythm (signs of heart problems).
I alt 51 børn med nydiagnosticeret og ubehandlet CML i kronisk fase blev inkluderet i en åben, multicenter, enkeltarmet fase II-undersøgelse.
A total of 51 paediatric patients with newly diagnosed and untreated CML in chronic phase have been enrolled in an open-label, multicentre, single-arm phase II trial.
Imatinib er en protein-kinasehæmmer, som potent hæmmer Bcr-Abl tyrosinkinasen in vitro, in vivo og på cellulært niveau.
Imatinib is a protein kinase inhibitor which potently inhibits the Bcr-Abl tyrosine kinase at the in vitro, cellular and in vivo levels.
Af disse 117 patienter var 61 positive for FIP1L1-PDGFRα fusionkinase.
In 61 of these 117 patients FIP1L1-PDGFRα fusion kinase was identified.
Når imatinib blev kombineret med højdosis kemoterapi hos Ph+ ALL patienter, sås forbigående levertoksicitet i form af forhøjet transaminase og hyperbilirubinæmi.
When imatinib was combined with high dose chemotherapy in Ph+ ALL patients, transient liver toxicity in the form of transaminase elevation and hyperbilirubinaemia were observed.
Der har efter markedsføring været rapporter om spontane aborter og medfødte abnormaliteter hos spædbørn født af kvinder, som har taget Imatinib medac.
There have been post-marketing reports of spontaneous abortions and infant congenital anomalies from women who have taken imatinib.
Hos patienter med hypereosinofilt syndrom (HES) med skjult infiltration af HES-celler i myokardiet, har der været isolerede tilfælde af kardiogent shock/dysfunktion af venstre ventrikel i forbindelse med HES-celledegranulering ved initiering af imatinibterapi.
In patients with hypereosinophilic syndrome (HES) with occult infiltration of HES cells within the myocardium, isolated cases of cardiogenic shock/left ventricular dysfunction have been associated with HES cell degranulation upon the initiation of imatinib therapy.
Da der er rapporteret tilfælde af hjertebivirkninger med imatinib, bør der foretages en nøje benefit/risk-vurdering hos HES/CEL-populationen før påbegyndelse af behandling.
As cardiac adverse events have been reported uncommonly with imatinib, a careful assessment of the benefit/risk of imatinib therapy should be considered in the HES/CEL population before treatment initiation.
Nyreinsufficiens: Patienter med nedsat nyrefunktion eller i dialyse bør gives den mindste anbefalede dosis på 400 mg dagligt som startdosis.
Renal insufficiency: Patients with renal dysfunction or on dialysis should be given the minimum recommended dose of 400 mg daily as starting dose.
Der har været case-rapporter med væksthæmning hos børn og præ-teenagere, der fik imatinib.
There have been case reports of growth retardation occurring in children and pre-adolescents receiving imatinib.
Forsigtighed anbefales hos thyreoidektomerede patienter, som får levothyroxin og imatinib.
Caution is recommended in thyroidectomy patients receiving levothyroxine and imatinib.
* Denne type bivirkninger er hovedsageligt blevet rapporteret efter markedsføring af Imatinib medac.
* These types of reactions have been reported mainly from post-marketing experience with imatinib.
Når imatinib indtages i forbindelse med et måltid med høj fedtprocent, reduceres absorptionen af imatinib minimalt (11 %'s fald i Cmax og forlængelse af tmax med 1,5 time), med et lille fald i AUC (7,4 %) sammenlignet med fastende.
When given with a high-fat meal, the rate of absorption of imatinib was minimally reduced (11 % decrease in Cmax and prolongation of tmax by 1.5 h), with a small reduction in AUC (7.4 %) compared to fasting conditions.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med imatinib i alle undergrupper af den pædiatriske population med Philadelphia-kromosom (bcr-abl translokation)-positiv kronisk myeloid leukæmi (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with imatinib in all subsets of the paediatric population in Philadelphia chromosome (bcr-abl translocation)positive chronic myeloid leukaemia (see section 4.2 for information on paediatric use).
Behandlingen kan gives én gang dagligt eller alternativt deles i to - én dosis om morgenen og én om aftenen.
Treatment can be given as a once daily dose or alternatively the daily dose may be split into two administrations - one in the morning and one in the evening.
Kapselskal Gelatine
Capsule shell
Klassificering af nedsat leverfunktion:
Liver dysfunction classification:
• Hypereosinofil syndrom (HES) og/eller kronisk eosinofil leukæmi (CEL).
• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL).
Undersøgelse hos en kardiolog, optagelse af ekkokardiogram og bestemmelse af serumtroponin bør derfor overvejes hos patienter med MDS/MPD, som har høje eosinofiltal, før der gives imatinib.
Evaluation by a cardiology specialist, performance of an echocardiogram and determination of serum troponin should therefore be considered in patients with HES/CEL, and in patients with MDS/MPD associated with high eosinophil levels before imatinib is administered.
Denne kliniske effekt var efter 2 ugers behandling forbundet med en højere reduktion i bcr-abl transskriptionen hos de imatinibbehandlede patienter end i kemoterapiarmen (p = 0,02).
This clinical effect was associated with a higher reduction in bcr-abl transcripts in the imatinib-treated patients than in the chemotherapy arm after 2 weeks of therapy (p = 0.02).
Behandlingsvarighed: I kliniske undersøgelser fortsattes behandling med imatinib indtil sygdomsprogression.
Treatment duration: In clinical trials, treatment with imatinib was continued until disease progression.
De 23 patienter som var inkluderet i registerstudiet, fik Imatinib medac med en daglig mediandosis på 264 mg (dosisområde: 100 til 400 mg) med en median varighed på 7,2 år (behandlingstid 0,1 til 12,7 år).
The 23 patients enrolled in this registry received imatinib at a median daily dose of 264 mg (range: 100 to 400 mg) for a median duration of 7.2 years (range 0.1 to 12.7 years).
In vitro hæmmer imatinib aktiviteten fra cytochrom-P450-isoenzymet CYP2D6 ved koncentrationer svarende til dem, der påvirker CYP3A4-aktivitet.
In vitro imatinib inhibits the cytochrome P450 isoenzyme CYP2D6 activity at concentrations similar to those that affect CYP3A4 activity.
In vitro hæmmer imatinib O-glucuronidationen af paracetamol med en Ki-værdi på 58,5 mikromol/l.
In vitro, imatinib inhibits paracetamol O-glucuronidation with Ki value of 58.5 micromol/l.
Den accelererede fase er en mellemfase mellem den kroniske fase og indtræden af blastkrisen og anses som det første tegn på resistens over for behandlingen.
Accelerated phase is an intermediate phase among the chronic phase and the onset of the blast crisis; it is considered as the first manifestation of resistance to therapy.
Imatinib metaboliseres primært i leveren, og kun 13 % udskilles via nyrerne.
Metabolism of imatinib is mainly hepatic, and only 13 % of excretion is through the kidneys.
CML i accelereret fase og blastkrise og Ph+ ALL (startdosis 600 mg)
Accelerated phase CML and blast crisis and Ph+ ALL (starting dose 600 mg)
Patienter med hjertesygdom
Patients with cardiac disease
Niveauet for ingen observeret effekt (NOEL) var 15 mg/kg/dag for både moderdyr og F1 generation (en ¼ af den maksimale humane dosis på 800 mg).
The no observed effect level (NOEL) for both the maternal animals and the F1 generation was 15 mg/kg/day (one quarter of the maximum human dose of 800 mg).
Konsoliderende behandling (de novo Ph+ ALL)
Consolidation (de novo Ph+ ALL)
Imatinib var teratogent hos rotter ved administration under organgenese ved doser ≥ 100 mg/kg, ca. svarende til den maksimale kliniske dosis på 800 mg/dag, baseret på legemsoverfladeareal.
Imatinib was teratogenic in rats when administered during organogenesis at doses ≥ 100 mg/kg, approximately equal to the maximum clinical dose of 800 mg/day, based on body surface area.
Øgningen i gennemsnitlig AUC ved dosisøgning efter oral administration var lineær og dosisproportional i intervallet 25-1.000 mg imatinib.
The increase in mean AUC with increasing dose was linear and dose proportional in the range of 25-1,000 mg imatinib after oral administration.
Diverse bivirkninger, som for eksempel pleuraekssudat, ascites, lungeødem og hurtig vægtstigning med eller uden overfladiske ødemer, kan kollektivt betegnes som ”væskeretention”.
Miscellaneous adverse reactions such as pleural effusion, ascites, pulmonary oedema and rapid weight gain with or without superficial oedema may be collectively described as “fluid retention”.
Tilfælde af leverskade, inklusive leversvigt og levernekrose er blevet observeret med imatinib.
Cases of liver injury, including hepatic failure and hepatic necrosis, have been observed with imatinib.
Se indlægssedlen for nærmere oplysninger.
See package leaflet for further information.
Der er ingen erfaring med behandling af CML hos børn under 2 år.
There is no experience in children with CML below 2 years of age.
• Muskelkramper med feber, rød-brun urin, smerter eller svaghed i dine muskler (tegn på
• Muscle spasms with a fever, red-brown urine, pain or weakness in your muscles (signs of
På grund af den mulige forekomst af tumorlysesyndrom (TLS) anbefales korrektion af klinisk signifikant dehydrering og behandling af forhøjede urinsyreniveauer før påbegyndelse af behandling med imatinib (se pkt.
Due to the possible occurrence of tumour lysis syndrome (TLS), correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to initiation of imatinib (see section 4.8).
Kontinuerlig daglig eksponering for imatinib tidligt i behandlingsforløbet i kombination med kemoterapi hos kohorte 5-patienter (n=50) forbedrede den 4-årige hændelsesfri overlevelse (EFS) sammenlignet med en historisk kontrolgruppe (n=120), der fik standard-kemoterapi uden imatinib (hhv. 69,6 % vs. 31,6 %).
Continuous daily exposure to imatinib early in the course of treatment in combination with chemotherapy in cohort 5patients (n=50) improved the 4-year event-free survival (EFS) compared to historical controls (n=120), who received standard chemotherapy without imatinib (69.6 % vs. 31.6 %, respectively).
Doser på 400 mg og 600 mg bør administreres 1 gang dagligt, mens daglige doser på 800 mg bør administreres som 400 mg 2 gange dagligt, én dosis om morgenen og én dosis om aftenen.
Doses of 400 mg or 600 mg should be administered once daily, whereas a daily dose of 800 mg should be administered as 400 mg twice a day, in the morning and in the evening.