qanastek/EMEA-V3 huggingface dataset:
blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVDC/ alu) blister (PVDC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVDC/ alu)
folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVDC/ alu) folja (PVDC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVDC/ alu)
30 capsules 24 capsules 48 capsules 96 capsules 120 capsules 180 capsules 20 film-coated tablets 60 film-coated tablets 10 film-coated tablets 30 film-coated tablets 120 film-coated tablets 180 film-coated tablets 90 film-coated tablets
30 kapsula 24 kapsula 48 kapsula 96 kapsula 120 kapsula 180 kapsula 20 pillola 60 pillola 10 pillola 30 pillola 120 pillola 180 pillola 90 pillola
Glivec 50 mg hard capsules
Glivec 50 mg kapsuli iebsin
Each capsule contains 50 mg imatinib (as mesilate).
Kull kapsula fiha 50 mg ta ’ imatinib (bħala mesilate).
Hard capsule
Kapsula, iebsa
White to yellow powder in a light yellow to orange-yellow opaque capsule, marked “ NVR SH”.
Trab li l- kulur tiegħu jvarja minn abjad għal isfar, f’ kapsula li ma jgħaddix dawl minnha b’ kulur li jvarja minn isfar ċar għal oranġjo fl- isfar, u li hija mmarkata “ NVR SH ”.
Glivec is indicated for the treatment of • adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment. • adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. • adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy. • adult patients with relapsed or refractory Ph+ ALL as monotherapy. • adult patients with myelodysplastic/ myeloproliferative diseases (MDS/ MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements. • adult patients with advanced hypereosinophilic syndrome (HES) and/ or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement.
Glivec huwa indikat għall- kura ta ’ • pazjenti adulti u pedjatriċi li jkunu għadhom kif ġew dijanjostikati b’ majelojd lewkimja kronika (CML) li huma posittivi (Ph+) għall- kromosoma ta ’ Filadelfja (bcr- abl) u li ma jkunux jistgħu jirċievu trapjant tal- mudullun bħala l- kura preferita. • pazjenti adulti u pedjatriċi b’ Ph+ CML fil- fażi kronika wara li tkun falliet it- terapija ta ’ alfa - interferon jew inkella meta l- marda tkun daħlet f’ Fażi aċċelerata ħafna jew jekk ikun hemm blast crisis. • pazjenti adulti li jkunu għadhom kif ġew dijanjostikati posittivi għall- lewkimja limfoblastika akuta b’ kromosoma ta ’ Filadelfja (Ph+ ALL) integrata b’ kimoterapija. • pazjenti adulti li rkadew jew li jkollhom Ph+ ALL rifrattorja bħala monoterapija. • pazjenti adulti b’ mard majelopisplatiku/ majeloproliferattiv (MDS/ MPD) assoċjat ma ’ tibdil fil - ġene tar- riċettur tal- fattur ta ’ tkabbir li jkun ġej minn plejtlets (PDGFR). • pazjenti li jkollhom sindrome ipereżinofilika avvanzata (HES) u/ jew lewkimja kronika eżinofolika (CEL) b’ tibdil FIP1L1- PDGFRα.
The effect of Glivec on the outcome of bone marrow transplantation has not been determined.
L- effett ta ’ Glivec fuq x’ jiġri wara trapjant tal- mudullun għadu ma giex stabbilit.
Glivec is also indicated for the treatment of • adult patients with Kit (CD 117) positive unresectable and/ or metastatic malignant gastrointestinal stromal tumours (GIST). • adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/ or metastatic DFSP who are not eligible for surgery.
Gastrointestinal Stromal Tumours). • pazjenti adulti b’ dermatofibrosarkoma protuberans li ma tkunx tista ’ titneħħa b’ operazzjoni (DFSP) u pazjenti adulti b’ DFSP li tkun reġgħet ħarġet jew/ u li tkun metastatika li ma jkunux jistgħu jiġu operati.
In adult and paediatric patients, the effectiveness of Glivec is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, MDS/ MPD, on haematological response rates in HES/ CEL and on objective response rates in adult patients with GIST and DFSP.
F’ pazjenti adulti u pedjatriċi, l- effikaċja ta ’ Glivec titkejjel skond ir- rati globali ta ’ rispons ematoloġiku u ċitoġenetiku, kif ukoll skond kemm ikun hemm pazjenti li jibqgħu ħajjin li jkomplu mingħajr ma ’ l- marda tas- CML tavvanza, skond ir- rati globali ta ’ rispons ematoloġiku u ċitoġenetiku f’ Ph+ ALL, MDS/ MPD, fuq rati ta ’ rispons ematoloġiku f’ HES/ CEL u anki skond kemm ikun jidher, b’ mod oġġettiv, li hemm reazzjoni tajba f’ każ li l- kura tkun qed tingħata għall- GIST u DFSP.
The experience with Glivec in patients with MDS/ MPD associated with PDGFR gene re-arrangements is very limited (see section 5.1).
Bl- eċċezzjoni ta ’ CML
Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
2 fil- fażi kronika li tkun għada kif ġiet dijanjostikata, m’ hemmx studji kontrollati li juru li hemm xi vantaġġ kliniku jew li tiżdied is- sopravivenza f ’ dan il- mard.
2 haematological malignancies and malignant sarcomas, as appropriate.
It- terapija għandha tibda tingħata minn tabib li għandu esperjenza fil- kura ta ’ pazjenti b’ mard ematoloġiku malinn u sarkomi malinni, kif jixraq.
The prescribed dose should be administered orally with a meal and a large glass of water to minimise the risk of gastrointestinal irritations.
Id- doża li tkun ordnata għandha tingħata mill- ħalq, darba kuljum flimkien ma ’ l- ikel u tazza ilma kbira sabiex jitnaqqas ir- riskju li jkun hemm irritazzjonijiet gastro- intestinali.
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.
Dożi ta ’ 400 mg jew 600 mg għandhom jingħataw darba kuljum, filwaqt li doża ta ’ 800 mg kuljum għandha tingħata bħala 400 mg darbtejn kuljum, filgħodu u filgħaxija.
For patients (children) unable to swallow the capsules, their content may be diluted in a glass of either still water or apple juice.
F’ pazjenti (tfal) li ma jkunux jistgħu jibilgħu l- kapsuli, l - kontenuti tal- kapsuli jistgħu jiġu maħlula f’ tazza ilma bla gass jew inkella meraq tat- tuffieħ.
Since studies in animals have shown reproductive toxicity, and the potential risk for the human foetus is unknown, women of child-bearing potential who open capsules should be advised to handle the contents with caution and avoid skin-eye contact or inhalation (see section 4.6).
Billi xi studji fl- annimali wrew li saret ħsara fis- sistema riproduttiva, u billi mhux magħruf jekk hemmx riskju ta ’ ħsara lill- fetu fil- bniedem, dawk in- nisa li għad jista ’ jkollhom it- tfal u li jkollhom jiftħu l- kapsuli għandhom jingħataw parir li jużaw ħafna kawtela u li jevitaw li l- mediċina tmissilhom mal- ġilda jew ma ’ għajnejhom u li joqgħodu attenti li ma jiġbduhiex il- ġewwa bin- nifs (ara sezzjoni 4. 6).
Hands should be washed immediately after handling open capsules.
Wieħed għandu jaħsel idejh sew immedjatament wara li jkun mess kapsuli li jkunu miftuħin.
Chronic phase CML is defined when all of the following criteria are met: blasts < 15% in blood and bone marrow, peripheral blood basophils< 20%, platelets > 100 x 109/l.
Pożoloġija fil- każ ta ’ pazjenti adulti b’ CML F’ pazjenti b’ CML li tkun daħlet f’ fażi kronika, d- doża ta ’ Glivec rakkomandata hija ta ’ 400 mg/ jum CML titqies li tkun fil- fażi kronika meta jintlaħqu dawn il- kriterji: blasts < 15% fid- demm u fil - mudullun, fid- demm periferiku il- bażofils < 20%, u l- plejtlets > 100 x 109/ l.
The recommended dosage of Glivec is 600 mg/ day for patients in accelerated phase.
F’ pazjenti li jkunu fil- Fażi aċċelerata tal- marda, d- doża ta ’ Glivec rakkomandata hija ta ’ 600 mg/ jum.
Accelerated phase is defined by the presence of any of the following: blasts ≥ 15% but < 30% in blood or bone marrow, blasts plus promyelocytes ≥ 30% in blood or bone marrow (providing < 30% blasts), peripheral blood basophils ≥ 20%, platelets < 100 x 109/ l unrelated to therapy.
Il- fażi titqies mgħaġġla meta jkun hemm xi wieħed minn dawn: blasts ≥ 15% imma < 30% fid- demm jew fil- mudullun, blasts flimkien mal- promajelosajts ≥ 30% fid- demm jew fil- mudullun (basta jkun hemm < 30% li jkunu blasts), bażofils fid- demm periferiku ≥ 20%, u plejtlets < 100 x 109/ l imma li ma jkunx minħabba l- effett tat- terapija.
The recommended dose of Glivec is 600 mg/ day for patients in blast crisis.
F’ pazjenti li jkunu f’ blast crisis, id- doża ta ’ Glivec rakkomandata hija ta ’ 600 mg/ jum.
Blast crisis is defined as blasts ≥ 30% in blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Jitqies li jkun hemm Blast crisis meta l- għadd ta ’ blasts fid- demm jew fil- mudullun jew barra l- mudullun esklużi l - fwied u l- milsa jkun ta ’ ≥ 30%.
Treatment duration:
Kemm iddum il- kura:
In clinical trials, treatment with Glivec was continued until disease progression.
Fi studji kliniċi l- kura b’ Glivec damet għaddejja sakemm damet tavanza l - marda.
The effect of stopping treatment after the achievement of a complete cytogenetic response has not been investigated.
L- effett li jkun hemm meta wieħed iwaqqaf il- kura wara li jkun kiseb rispons ċitoġenetika komplet għadu ma giex investigat.
Dose increases from 400 mg to 600 mg or 800 mg in patients with chronic phase disease, or from 600 mg to a maximum of 800 mg (given as 400 mg twice daily) in patients with accelerated phase or blast crisis may be considered in the absence of severe adverse drug reaction and severe non- leukaemia-related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time); failure to achieve a satisfactory haematological response after at least 3 months of treatment; failure to achieve a cytogenetic response after 12 months of treatment; or loss of a previously achieved haematological and/ or cytogenetic response.
Żieda fid- dożi minn 400 mg għal 600 mg jew 800 mg, f’ pazjenti li jkollhom mard li jkun f’ fażi kronika, jew minn 600 mg għall- massimu ta ’ 800 mg (li jingħataw f’ dożi ta ’ 400 mg, darbtejn kuljum) f’ pazjenti li jkunu fil- fażi aċċelerata jew li jkollhom blast crisis għandha mnejn tiġi kkunsidrata fl - assenza ta ’ effetti avversi severi minħabba fil- mediċina u fl- assenza ta ’ newtropinja jew tromboċitopenja severi li ma jkunux relatati ma ’ lewkimja, f’ dawn iċ- ċirkustanzi: meta jkun hemm avvanz tal- marda (ikun f’ liema żmien ikun); meta ma jkunx hemm rispons ematoloġiku sodisfaċenti wara mill- inqas 3 xhur ta ’ kura; meta ma jkunx hemm rispons ċitoġenetiku wara mill- inqas 12- il xahar ta ’ kura, jew meta jkun hemm telf ta ’ rispons ematoloġiku u/ jew ċitoġenetiku li jkun( u) inkiseb( bu) qabel.
Patients should be monitored closely following dose escalation given the potential for an increased incidence of adverse reactions at higher dosages.
Wara li tkun żdiedet xi doża, l- pazjenti għandhom jiġu monitorjati bir- reqqa, minhabba f’ riskju akbar ta ’ effetti avversi b’ dożi ogħla.
Posology for CML in children Dosing for children should be on the basis of body surface area (mg/ m2).
Pożoloġija għal- CML fi tfal Id- dożi fit- tfal għandhom ikunu bbażati fuq l- erja tas- superfiċje tal- ġisem (mg/ m2).
The dose of 340 mg/ m2 daily is recommended for children with chronic phase CML and advanced phase CML (not to exceed the total dose of 800 mg).
Doża ta ’ 340 mg/ m2 kuljum hija rakkomandata fi tfal li jkollhom CML f’ fażi kronika u CML fil- fażi l - avvanzata (sabiex ma tinqabiżx id- doża totali ta ’ 800 mg).
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.
Il- kura tista ’ tingħata bħala doża darba kuljum jew inkella id- doża ta ’ kuljum tista ’ tinqasam f’ darbtejn – waħda filgħodu u waħda filgħaxija.
The dose recommendation is currently based on a small number of paediatric patients (see sections 5.1 and 5.2).
Ir- rakkomandazzjoni tad- doża bħalissa hija bażata fuq numru żgħir ta ’ pazjenti pedjatriċi (ara sezzjonijiet 5. 1 u 5. 2).
There is no experience with the treatment of children below 2 years of age.
M’ hemmx esperjenza bil- kura ta ’ tfal taħt is- sentejn.
Dose increases from 340 mg/ m2 daily to 570 mg/ m2 daily (not to exceed the total dose of 800 mg) may be considered in children in the absence of severe adverse drug reaction and severe non-leukaemia- related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time); failure to achieve a satisfactory haematological response after at least 3 months of treatment; failure to achieve a cytogenetic response after 12 months of treatment; or loss of a previously achieved haematological and/ or cytogenetic response.
3 Żidiet fid- dożi minn 340 mg/ m2 kuljum għal 570 mg/ m2 kuljum (sabiex ma tinqabiżx id- doża totali ta ’ 800 mg) tista ’ titqies fi tfal jekk ma jkollhomx effetti avversi severi u newtropinja jew tromboċitopenja severi li ma jkunux relatati ma ’ lewkimja taħt dawn iċ- ċirkostanzi: avvanz tal- marda (ikun f’ liema żmien ikun) meta ma jkunx hemm rispons ematoloġiku sodisfaċenti wara mill- inqas 3 xhur ta ’ kura; meta ma jkunx hemm rispons ċitoġenetiku wara mill- inqas 12- il xahar ta ’ kura, jew meta jkun hemm telf ta ’ rispons ematoloġiku u/ jew ċitoġenetiku li jkun( u) inkiseb( bu) qabel.
Posology for Ph+ ALL The recommended dose of Glivec is 600 mg/ day for patients with Ph+ ALL.
Pożoloġija għall- Ph+ ALL Id- doża rakkomandata ta ’ Glivec hija 600 mg/ jum għal pazjenti b’ Ph+ ALL.
Haematological experts in the management of this disease should supervise the therapy throughout all phases of care.
Esperti ematoloġiċi fl - imaniġġjar ta ’ din il- marda għandhom jieħdu ħsieb is- superviżjoni tat- terapija tul il- fażijiet kollha tal - kura.
3 Treatment schedule:
Kemm iddum il- kura:
On the basis of the existing data, Glivec has been shown to be effective and safe when administered at 600 mg/ day in combination with chemotherapy in the induction phase, the consolidation and maintenance phases of chemotherapy (see section 5.1) for adult patients with newly diagnosed Ph+ ALL.
Fuq bazi tat- tagħrif li hemm, intwera li Glivec huwa effettiv u sigur meta jingħata b’ 600 mg/ jum flimkien ma kimoterapija fil- fażi ta’ induzzjoni, il- fażijiet tal- kimoteripja konsolidati u ta ’ manteniment (ara sezzjoni 5. 1) għal pazjenti adulti b’ Ph+ ALL li jkun għadu kif ġie dijanjostikat.
The duration of Glivec therapy can vary with the treatment programme selected, but generally longer exposures to Glivec have yielded better results.
Iż- żmien kemm iddum il- kura bi Glivec jista ’ jvarja skond il- programm ta ’ kura li jintgħażel, iżda ġeneralment, aktar ma kienu twal l- esponimenti għal Glivec, ir- riżultati kienu aħjar.
For adult patients with relapsed or refractory Ph+ALL Glivec monotherapy at 600 mg/ day is safe, effective and can be given until disease progression occurs.
Għal pazjenti adulti b’ Ph+ ALL li jkun reġa ħareġ jew li jkun refrattorju b’ monoterapija ta ’ Glivec ta ’ 600 mg/ jum huwa sigur, effettiv u jista ’ jingħata sakemm ikun hemm avvanz tal- marda.
Posology for MDS/ MPD The recommended dose of Glivec is 400 mg/ day for patients with MDS/ MPD.
Pożoloġija għal MDS/ MPD Id- doża ta ’ Glivec rakkomandata għal pazjenti b’ MDS/ MPD hija 400 mg/ jum.
In the only clinical trial performed up to now, treatment with Glivec was continued until disease progression (see section 5.1).
Fl- unika prova klinika li saret s’ issa, il- kura b’ Glivec tkompliet sakemm kien hemm avvanz tal- marda (ara sezzjoni 5. 1).
At the time of analysis, the treatment duration was a median of 47 months (24 days - 60 months).
Meta saret l- analiżi, il- kura damet medja ta ’ 47 xahar (24 jum – 60 xahar).
Posology for HES/ CEL The recommended dose of Glivec is 100 mg/ day for patients with HES/ CEL.
Pożoloġija għal HES/ CEL Id- doża ta ’ Glivec rakkomandata għal pazjenti b’ HES/ CEL hija 100 mg/ jum.
Dose increase from 100 mg to 400 mg may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.
Żieda tad- doża minn 100 mg għal 400 mg tista ’ tkun ikkonsidrata jekk ma jkunx hemm reazzjonijiet avversi tal- mediċina jekk l- istimi juru li m’ hemm biżżejjed rispons għat- terapija.
Posology for GIST The recommended dose of Glivec is 400 mg/ day for patients with unresectable and/ or metastatic malignant GIST.
Pożoloġija għal GIST Id- doża ta ’ Glivec rakkomandata għal pazjenti b’ GIST li ma jistax jitneħħa permezz ta ’ operazzjoni, u / jew b’ GIST li jkun malinn u metastatiku, hija 400 mg/ jum.
Limited data exist on the effect of dose increases from 400 mg to 600 mg or 800 mg in patients progressing at the lower dose (see section 5.1).
It- tagħrif fuq l- effett li jkun hemm b’ żieda fid- doża minn 400 mg għal 600 mg jew 800 mg f’ pazjenti li qegħdin fuq id- doża l- baxxa, huwa limitat (ara sezzjoni 5. 1).
There are currently no data available to support specific dosing recommendations for GIST patients based on prior gastrointestinal resection.
Bħalissa m’ hemmx tagħrif li jsaħħaħ xi rakkomandazzjonijiet speċifiċi fuq id- dożi li għandhom jintużaw f’ pazjenti b’ GIST, bażati fuq operazzjonijiet li jkunu saru qabel sabiex titneħħa xi parti mis - sistema gastro- intestinali.
The majority (98%) of patients in the clinical trial (see section 5.2) had had prior resection.
Il- maġġoranza tal- pazjenti (98%) fl- istudju kliniku (ara sezzjoni 5. 2) kellhom operazzjoni ta’ dan it- tip.
For all patients on the study, there was at least a two-week interval between resection and the first dose of Glivec administered; however, no additional recommendations can be made based on this study.
Fil- każ tal- pazjenti kollha li ħadu sehem fl- istudju, kien hemm mill - inqas perijodu ta ’ ġimgħatejn bejn meta saret l- operazzjoni u meta ngħatat l- ewwel doża ta ’ Glivec; madankollu, ma jistgħux jingħataw rakkomandazzjonijiet oħrajn bażati fuq dan l- istudju.
In clinical trials in GIST patients, treatment with Glivec was continued until disease progression.
Fi provi kliniċi fuq pazjenti b’ GIST, il- kura b’ Glivec tkompliet sakemm kien hemm avvanz tal- marda.
At the time of analysis, the treatment duration was a median of 7 months (7 days to 13 months).
Meta saret l- analiżi, il- kura kienet iddum medja ta ’ 7 xhur (minn 7 ijiem sa 13- il xahar).
The effect of stopping treatment after achieving a response has not been investigated.
L- effett li jirriżulta meta titwaqqaf il- kura wara li jkun inkiseb rispons tajjeb għadu ma ġiex investigat.
Posology for DFSP The recommended dose of Glivec is 800 mg/ day for patients with DFSP.
4 Pożoloġija għal DFSP Id- doża ta ’ Glivec rakkomandata għal pazjenti b’ DFSP hija 800 mg/ jum.
Dose adjustment for adverse reactions Non-haematological adverse reactions If a severe non-haematological adverse reaction develops with Glivec use, treatment must be withheld until the event has resolved.
Tibdil tad- doża minħabba effetti avversi Effetti avversi mhux ematoloġiċi Jekk ikun hemm xi reazzjoni mhux mixtieqa, mhux ematoloġika, qawwija minħabba l- użu ta ’ Glivec, il- kura għandha titwaqqaf sakemm dan l- effett jgħaddi.
Thereafter, treatment can be resumed as appropriate depending on the initial severity of the event.
Wara, il- kura tista ’ terġa tinbeda kif jixraq, dejjem skond kemm kien qawwi fil- bidu l- effett mhux mixtieq.
If elevations in bilirubin > 3 x institutional upper limit of normal (IULN) or in liver transaminases > 5 x IULN occur, Glivec should be withheld until bilirubin levels have returned to < 1.5 x IULN and transaminase levels to < 2.5 x IULN.
IULN) jew tat- transaminases tal- fwied għal > 5 x l- IULN, Glivec m’ għandux jingħata sakemm il- livell tal- bilirubin jinżel lura għal < 1. 5 x l- IULN u dak tat - transaminase għal < 2. 5 x l- IULN.
Treatment with Glivec may then be continued at a reduced daily dose.
Meta l- livelli jinżlu, Glivec jista ’ imbagħad jitkompla b’ doża ta ’ kuljum imnaqqsa.
In adults the dose should be reduced from 400 to 300 mg or from 600 to 400 mg, or from 800 mg to 600 mg, and in children from 340 to 260 mg/ m2/ day.
Fil- kbar id- doża għandha titnaqqas minn 400 mg għal 300 mg jew inkella minn 600 mg għal 400 mg, jew minn 800 mg għal 600 mg, u fit- tfal minn 340 għal 260 mg/ m2/ jum.
Haematological adverse reactions Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are 4 recommended as indicated in the table below.
Effetti emataloġiċi avversi Huwa rakkomandat li d- doża titnaqqas jew inkella l- kura tieqaf għal xi żmien f’ każ li jkun hemm newtropenja jew tromboċitopenja severi u dan għandu jsir kif indikat fit- tabella li jmiss.
Dose adjustments for neutropenia and thrombocytopenia:
Tibdil fid- doża meta jkun hemm newtropenja u tromboċitopenja:
HES/ CEL (starting dose
ANC < 1. 0 x 109/ l HES/ CEL (doża tal - bidu 100 mg)
ANC <
u/ jew
Stop Glivec until ANC ≥ 1.5 x 109/ l and
plejtelets < 50 x 109/ l ANC < 1. 0 x 109/ l
Resume treatment with Glivec at previous dose (i. e. before severe adverse reaction).
Erġa ibda Glivec bid- doża ta ’ qabel (i. e. qabel ir- reazzjoni avversa severa).
Chronic phase CML, MDS/ MPD and GIST
CML fil- fażi kronika, MDS/ MPD u GIST
ANC < 1.0 x 109/ l and/ or
u / jew plejtlets < 50 x 109/ l
Stop Glivec until ANC ≥ 1.5 x 109/ l and platelets ≥ 75 x 109/ l.
Waqqaf Glivec sakemm l- ANC ≥ 1. 5 x 109/ l u l- plejtlets ≥ 75 x 109/ l.
(starting dose 400 mg) HES/ CEL (at dose 400 mg)
(doża tal- bidu 400 mg) HES/ CEL (b’ doża ta ’ 400 mg)
platelets < 50 x 109/ l
ANC < 1. 0 x 109/ l
Resume treatment with Glivec at previous dose (i. e. before severe adverse reaction).
Erġa ibda l- kura b’ Glivec bid- doża ta ’ qabel (i. e. qabel ir- reazzjoni avversa severa).
In the event of recurrence of ANC < 1.0 x 109/ l and/ or platelets < 50 x 109/ l, repeat step 1 and resume Glivec at reduced dose of 300 mg.
1 u erġa ibda Glivec b’ doża mnaqqsa ta ’ 300 mg.
Paediatric chronic phase CML
CML fil- fażi kronika pedjatrika
(at dose 340 mg/ m2)
(doża tal- bidu 340 mg/ m2)
In the event of recurrence of ANC < 1.0 x109/ l and/ or platelets < 50 x109/ l, repeat step 1 and resume Glivec at reduced dose of 260 mg/ m2.
1 u erġa ibda Glivec b’ doża mnaqqsa ta ’ 260 mg/ m2.
Accelerated phase CML and blast crisis and Ph+
CML fil- fażi aċċelerata aANC < 0. 5 x 109/ l u blast crisis u Ph+ ALL u/ jew plejtelets < 10 x 109/ l (doża tal- bidu 600 mg)
Check whether cytopenia is related to leukaemia (marrow aspirate or biopsy).
Ara jekk iċ- ċitopenja hiex relatata mal - lewkimja (permezz ta ’ aspirat mill - mudullun jew bijospija).
If cytopenia is unrelated to leukaemia, reduce dose of Glivec to 400 mg.
Jekk iċ- ċitopenja tippersisti għal ġimgħatejn, erġa naqqas għal 300 mg.
If cytopenia persists for 4 weeks and is still unrelated to leukaemia, stop Glivec until ANC ≥ 1 x 109/ l and platelets ≥ 20 x 109/ l, then resume treatment at 300 mg.
Jekk iċ- ċitopenja tippersisti għal 4 ġimgħat u għada mhix relatata mal - lewkimja, waqqaf Glivec sakemm ANC ≥ 1 x 109/ l u l- plejtlets ≥ 20 x 109/ l,
Paediatric accelerated phase CML and blast
CML fil- fażi aċċelerata pedjatrika u blast crisis
ANC < 0.5 x 109/ l and/ or
u/ jew
Check whether cytopenia is related to leukaemia (marrow aspirate or biopsy).
Ara jekk iċ- ċitopenja hiex relatata mal - lewkimja (permezz ta ’ aspirat mill -
If cytopenia persists for 2 weeks, reduce further to 200 mg/ m2.
Jekk iċ- ċitopenja tippersisti għal ġimgħatejn, erġa naqqas għal 200 mg/ m2.
If cytopenia persists for 4 weeks and is still unrelated to leukaemia, stop Glivec until ANC ≥ 1 x 109/ l and platelets ≥ 20 x 109/ l, then resume treatment at 200 mg/ m2.
Jekk iċ- ċitopenja tippersisti għal 4 ġimgħat u għada mhix relatata mal - lewkimja, waqqaf Glivec sakemm ANC ≥ 1 x 109/ l u l- plejtlets ≥ 20 x 109/ l, imbagħad erġa ibda l- kura b’ 200 mg/ m2.
ANC <
ANC < 1. 0 x 109/ l
Stop Glivec until ANC ≥ 1.5 x 109/ l and
Waqqaf Glivec sakemm l- ANC ≥ 1. 5 x 109/ l u l- plejtlets ≥ 75 x 109/ l.
(at dose 800 mg)
(doża ta ’ 800 mg)
and/ or platelets < 50 x 109/ l
u/ jew plejtelets < 50 x 109/ l
In the event of recurrence of ANC < 1.0 x 109/ l and/ or platelets < 50 x 109/ l, repeat step 1 and resume Glivec at reduced dose of 400 mg.
Fil- każ li l- ANC jerga ’ < 1. 0 x 109/ l u/ jew il- plejtlets < 50 x 109/ l, erġa irrepeti Nru.
ANC = absolute neutrophil count a occurring after at least 1 month of treatment
ANC = l- għadd assolut tan- newtrofils (absolute neutrophil count) a li sseħħ wara mill- anqas xahar mill- bidu tal- kura
Paediatric use:
L- użu pedjatriku:
There is no experience in children with CML below 2 years of age (see section 5.1).
M’ hemmx esperjenza dwar l- użu fit- tfal b’ CML taħt sentejn (ara sezzjoni 5. 1).
There is limited experience in children with Ph+ ALL and very limited experience in children with MDS/ MPD and DFSP.
Hemm esperjenza limitata bl- użu fit- tfal b ’ Ph+ ALL u esperjenza limitata ħafna fi tfal b’ MDS/ MPD u DFSP.
There is no experience in children or adolescents with GIST and HES/ CEL.
M’ hemmx esperjenza dwar l- użu fit- tfal u adolexxenti b’ GIST u HES/ CEL.
Imatinib is mainly metabolised through the liver.
Imatinib jiġi metabolizzat l- aktar mill- fwied.
Patients with mild, moderate or severe liver dysfunction should be given the minimum recommended dose of 400 mg daily.
Pazjenti li jkollhom il- fwied ma jaħdimx normali b’ mod ħafif, moderat jew sever għandhom jingħataw l- anqas doża rakkomandata ta ’ 400 mg kuljum.
The dose can be reduced if not tolerated (see sections 4.4, 4.8 and 5.2).
Id- doża tista ’ titnaqqas jekk il- pazjent ma jkunx jiflaħ għaliha (ara sezzjonijiet 4. 4, 4. 8 u 5. 2).
Liver dysfunction classification:
Klassifika ta ’ fwied li ma jkunx jaħdem normali:
Liver dysfunction Mild
Fwied ma jaħdimx normali Ħafif
Liver function tests Total bilirubin: = 1.5 ULN AST: > ULN (can be normal or< ULN if total bilirubin is > ULN)
Testijiet tal- funzjoni tal- fwied Bilirubin totali: = 1. 5 ULN AST: > ULN (jista ’ jkun normali jew < ULN il- bilirubin totali jkun > ULN)
Total bilirubin: > 1.5– 3.0 ULN AST: any
Bilirubin totali: > 1. 5- 3. 0 ULN AST: li jkun
Total bilirubin: > 3– 10 ULN AST: any
Bilirubin totali: > 3- 10 ULN AST: li jkun
ULN = upper limit of normal for the institution AST = aspartate aminotransferase
ULN = il- limitu ta ’ fuq in- normal ta ’ l- instituzzjoni AST = aspartate aminotransferase
Since the renal clearance of imatinib is negligible, a decrease in free imatinib clearance is not expected in patients with renal insufficiency.
Peress li l- clearance ta ’ imatinib hija ftit li xejn, tnaqqis fil- clearance ta ’ imatinib ħieles mhux mistenni f’ pazjenti b’ insuffiċjenza renali.
Patients with mild or moderate renal dysfunction (creatinine clearance = 20– 59 ml/ min) should be given the minimum recommended dose of 400 mg daily as starting dose.
Pazjenti bi kliewi li ma jkunux qed jaħdmu normali b’ mod ħafif jew moderat (clearance tal- krejatinina = 20- 59 ml/ min) għandhom jingħataw l - anqas doża tal- bidu rakkomandata ta ’ 400 mg kuljum.
Although very limited information is available, patients with severe renal dysfunction (creatinine clearance = < 20 ml/ min) or on dialysis could also start at the same dose of 400 mg.
Għalkemm it- tagħrif li hemm huwa limitat ħafna, pazjenti bi kliwei li ma jkunux qed jaħdmu normali b’ mod sever (clearance tal- krejatinina < 20 ml/ min) jew li jkunu fuq dijaliżi jkunu jistgħu jibdew ukoll bl- istess doża ta ’ 400 mg.
However, in these patients caution is recommended.
Madankollu, f’ dawn il- pazjenti hija rakkomandata l- kawtela.
The dose can be reduced if not tolerated, or increased for lack of efficacy (see sections 4.4 and 5.2).
Id- doża tista ’ titnaqqas jekk ma jkunux jifilħu għaliha, jew miżjuda jekk ikun hemm nuqqas ta ’ effikaċja (ara sezzjonijiet 4. 4 u 5. 2).
Elderly patients:
6 L- użu fl- anzjani:
Imatinib pharmacokinetics have not been specifically studied in the elderly.
Il- farmakokinetiċi ta ’ imatinib ma ġewx studjati b’ mod speċifiku fl- anzjani.
No significant age-related pharmacokinetic differences have been observed in adult patients in clinical trials which included over 20% of patients age 65 and older.
Fi provi kliniċi li fihom aktar minn 20% tal- pazjenti kellhom 65 sena jew aktar, ma deherx li kien hemm xi differenzi farmakokinetiċi sinifikanti li għandhom x’ jaqsmu ma ’ l- età, f’ pazjenti adulti.
No specific dose recommendation is necessary in the elderly.
M’ hemmx bżonn ta ’ rakkomandazzjonijiet speċifiċi fuq id- doża fl- anzjani.
When Glivec is co-administered with other medicinal products, there is a potential for drug interactions (see section 4.5).
Meta Glivec jingħata fl- istess ħin ma ’ medikazzjonijiet oħrajn, jista ’ jkun hemm nuqqas ta ’ qbil magħhom (ara sezzjoni 4. 5).
Concomitant use of imatinib and medicinal products that induce CYP3A4 (e. g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or Hypericum perforatum, also known as St.
L- użu fl- istess żmien, ta ’ imatinib ma ’ prodotti mediċinali li jinduċu is- CYP3A4 (ez., dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, jew Hypericum perforatum, magħruf ukoll bħala St.
6 John’ s Wort) may significantly reduce exposure to Glivec, potentially increasing the risk of therapeutic failure.
John’ s Wort) jista ’ jwassal biex inaqqas l- ammont ta ’ Glivec effettiv fiċ- ċirkolazzjoni, u b’ hekk iżid r- riskju li l- kura fil- fatt ma taħdimx.
Therefore, concomitant use of strong CYP3A4 inducers and imatinib should be avoided (see section 4.5).
Għaldaqstant, l- użu fl- istess ħin, ta ’ sustanzi li jinduċu bil - qawwa lis- CYP3A4, ma ’ imatinib, għandu jiġi evitat (ara sezzjoni 4. 5).
Clinical cases of hypothyroidism have been reported in thyroidectomy patients undergoing levothyroxine replacement during treatment with Glivec (see section 4.5).
Każijiet kliniċi ta ’ ipertajrojdiżmu kienu rapurtati f’ pazjenti li tneħħietilhom it- tajrojd li jkunu qed jirċievu terapija b’ levothyroxine waqt il- kura b’ Glivec (ara sezzjoni 4. 5).
TSH levels should be closely monitored in such patients.
Il- livelli ta ’ TSH għandhom ikunu monitorati bir- reqqa f’ dawn il- pazjenti.
Metabolism of Glivec is mainly hepatic, and only 13% of excretion is through the kidneys.
Il- metaboliżmu ta ’ Glivec issir l- aktar permezz tal- fwied, u 13% biss ta’ l- eskrezzjoni hija minn ġol - kliewi.
In patients with hepatic dysfunction (mild, moderate or severe), peripheral blood counts and liver enzymes should be carefully monitored (see sections 4.2, 4.8 and 5.2).
F’ pazjenti li jkollhom il- fwied ma jaħdimx normali (ħafif, moderat jew sever), għadd tad - demm periferiku u enzimi tal- fwied għandhom ikunu monitorati bir- reqqa (ara sezzjonijiet 4. 2, 4. 8, u 5. 2).
It should be noted that GIST patients may have hepatic metastases which could lead to hepatic impairment.
Għandu jingħad li pazjenti b’ GIST jista ’ jkollhom metastażi epatika li tista ’ twassal għal indeboliment tal- fwied.
Cases of liver injury, including hepatic failure and hepatic necrosis, have been observed with imatinib.
Każijiet ta ’ ħsara fil- fwied, inkluż insuffiċjenza tal- fwied u nekrożi epatika, dehru b’ imatinib.
When imatinib is combined with high dose chemotherapy regimens, an increase in serious hepatic reactions has been detected.
Meta imatinib jingħata flimkien ma ’ dożi għoljin ta ’ reġimens ta ’ kimoterapija, instabet żieda fir - reazzjonijiet epatiċi serji.
Hepatic function should be carefully monitored in circumstances where imatinib is combined with chemotherapy regimens also known to be associated with hepatic dysfunction (see section 4.5 and 4.8).
Il- funzjoni epatika għandha tiġi monitorata bir- reqqa meta imatinib jingħata flimkien ma ’ reġimens ta’ kimoterapija li jkunu magħrufin li jistgħu jkunu marbuta ma ’ funzjoni mhux normali tal- fwied (ara sezzjoni 4. 5 u 4. 8).
Occurrences of severe fluid retention (pleural effusion, oedema, pulmonary oedema, ascites, superficial oedema) have been reported in approximately 2.5% of newly diagnosed CML patients taking Glivec.
Każijiet ta ’ retenzjoni severa ta ’ fluwidi (effużjoni mill- plewra, edima, edima tal- pulmun, axxite, edima superfiċjali) kienu rapurtati f’ madwar 2. 5% tal- pazjenti b’ CML li jkunu għadhom kif ġew dijanjostikati li jkunu qed jieħdu Glivec.
Therefore, it is highly recommended that patients be weighed regularly.
Għalhekk, huwa rakkomandat ħafna li l- pazjenti jintiżnu b’ mod regolari.
An unexpected rapid weight gain should be carefully investigated and if necessary appropriate supportive care and therapeutic measures should be undertaken.
Żieda fil- piż mhux mistennija għandha tkun investigata bir- reqqa u jekk ikun hemm bżonn għandhom jingħataw għajnuna ta ’ support u jittieħdu miżuri terapewtiċi.
In clinical trials, there was an increased incidence of these events in elderly patients and those with a prior history of cardiac disease.
Fi provi kliniċi, kien hemm żieda ta ’ dawn il- każijiet f’ pazjenti anzjani u dawk li kienu sofrew minn mard tal- qalb.
Therefore, caution should be exercised in patients with cardiac dysfunction.
Għaldaqstant, għandu jkun hemm kawtela f’ pazjenti li qalbhom ma taħdimx normali.
Patients with cardiac disease or risk factors for cardiac failure should be monitored carefully, and any patient with signs or symptoms consistent with cardiac failure should be evaluated and treated.
Pazjenti b’ mard tal- qalb jew li għandhom fatturi ta ’ riskju għall- insuffiċjenza tal- qalb għandhom ikunu monitorati bir- reqqa, u jekk ikun hemm xi pazjenti b’ sinjali jew sintomi ta ’ insuffiċjenza tal- qalb għandhom jiġu eżaminati u kurati.
In patients with hypereosinophilic syndrome (HES) and cardiac involvement, isolated cases of cardiogenic shock/ left ventricular dysfunction have been associated with the initiation of imatinib therapy.
F’ pazjenti b’ sindrome ipereżinofilika (HES) u l- involviment tal- qalb, każijiet iżolati ta ’ xokk kardjoġeniku / disfunzjoni tal- ventrikolu tax- xellug seħħew f’ pazjenti li bdew terapija b’ imatinib.
The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding imatinib.
Il - kondizzjoni kienet rappurtata bħala riversibbli meta ingħataw sterojdi b’ mod sistemiku, miżuri ta ’ support ċirkolatorju, u interruzzjoni ta’ Glivec b’ mod temporanju.
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.
Peress li effetti avversi kardijaċi kienu rappurtati b’ frekwenza mhux komuni b’ imatinib, stima bir- reqqa tal- benefiċċju/ riskju tat - terapija b’ imatinib għandha titqies fil- popolazzjoni HES/ CEL qabel ma tibda l- kura.
Myelodysplastic/ myeloproliferative diseases with PDGFR gene re-arrangements could be associated with high eosinophil levels.
Mard majelodisplastiku/ majeloproliferattiv b’ tibdil fil- ġene PDGFR jistgħu jkunu assoċjati ma ’ livelli għoljin ta ’ eżinofils.
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.
Stima minn speċjalista kardjologu, ekokardjogramma u kejl tat- troponin fis- serum għandhom għaldaqstant ikunu konsidrati f’ pazjenti b’ HES/ CEL, u f’ pazjenti b’ MDS/ MPD assoċjati
If either is abnormal, follow-up with a cardiology specialist and the prophylactic use of systemic steroids (1– 2 mg/ kg) for one to two weeks concomitantly with imatinib should be considered at the initiation of therapy.
Jekk xi wieħed minnhom ikun anormali, segwi flimkien ma ’ speċjalista kardjologu u l- użu profilattiku ta ’ sterojdi sistemiċi (1- 2 mg/ kg) għal ġimgħa jew ġimgħatejn flimkien ma ’ imatinib għandu jkun konsidrat meta tinbeda t- terapija.
In the GIST clinical trial, both gastrointestinal and intra-tumoural haemorrhages were reported (see section 4.8).
Fil- prova klinika ta ’ GIST, emorraġiji gastrointestinali u fit- tumur kienu rappurtati (ara sezzjoni 4. 8).
Based on the available data, no predisposing factors (e. g. tumour size, tumour location, coagulation disorders) have been identified that place patients with GIST at a higher risk of either type of haemorrhage.
Mit- tagħrif disponibbli, ma ġewx identifikati fatturi li jżidu r- riskju (eż daqs tat- tumur, post fejn ikun it- tumur, mard tal- koagulazzjoni) li jżidu r- riskju taż- żewġ tipi ta ’ emorraġiji f’ pazjenti li jsofru minn GIST.
Since increased vascularity and propensity for bleeding is a part of the nature and clinical course of GIST, standard practices and procedures for the monitoring and management of haemorrhage in all patients should be applied.
Peress li żieda fil- vaskularità u tendenza ta ’ fsada hija parti naturali mill- proċess kliniku ta ’ GIST, prattiċi standard u proċeduri ta ’ monitoraġġ u maniġġjar ta ’ fsada fil- pazjenti kollha għandhom jintużaw.
Laboratory tests Complete blood counts must be performed regularly during therapy with Glivec.
Testijiet tal- laboratorju Waqt il- kura b’ Glivec, għandhom isiru testijiet ta ’ l- għadd taċ- ċelluli kollha tad- demm, b’ mod regolari.
Treatment of CML patients with Glivec has been associated with neutropenia or thrombocytopenia.
Il- kura b’ Glivec ta ’ pazjenti b’ CML ġieli kienet assoċjata ma ’ newtropenja u tromboċitopenja.
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.
Biss, dan it- tnaqqis fl- għadd taċ- ċelluli x’ aktarx li jkollu x’ jaqsam mal- fażi tal- marda li tkun qed tiġi ttrattata u jidher ukoll li dawn kienu aktar frekwenti f’ pazjenti fil- fażi l- imgħaġġla ta ’ CML jew f ’ blast crisis meta mqabbla ma ’ pazjenti li kienu fil- fażi kronika ta ’ CML.
Treatment with Glivec may be interrupted or the dose may be reduced, as
Il- kura b’ Glivec tista ’ titwaqqaf għal ftit jew id- doża tiġi mnaqqsa, hekk kif irakkomandat f’ sezzjoni 4. 2.
Liver function (transaminases, bilirubin, alkaline phosphatase) should be monitored regularly in patients receiving Glivec.
Il- funzjoni tal- fwied (transaminases, bilirubin, alkaline phosphatase) għandha tiġi immonitorjata b’ mod regolari f’ pazjenti li jkunu qed jirċievu Glivec.
In patients with impaired renal function, imatinib plasma exposure seems to be higher than that in patients with normal renal function, probably due to an elevated plasma level of alpha-acid glycoprotein (AGP), an imatinib-binding protein, in these patients.
F’ pazjenti b’ indeboliment tal- kliewi, l- esponiment fil- plażma ta ’ imatinib jidher li jkunu ogħla minn dak f’ pazjenti b’ funzjoni tal- kliewi normali, probabbli minħabba livell għoli fil- plażma ta ’ alpha- acid glycoprotein (AGP), proteina li tintrabat ma ’ imatinib, f’ dawn il- pazjenti.
Patients with renal impairment should be given the minimum starting dose.
Pazjenti b’ indeboliment tal - kliewi għandhom jingħataw l- aktar doża baxxa fil- bidu.
Patients with severe renal impairment should be treated with caution.
Pazjenti b’ indeboliment sever tal- kliewi għandhom ikunu kurati b’ attenzjoni.
The dose can be reduced if not tolerated (see section 4.2 and 5.2).
Id- doża tista ’ titnaqqas jekk ma jkunux jifilħu għaliha (ara sezzjoni 4. 2 u 5. 2).
Active substances that may increase imatinib plasma concentrations:
Sustanzi attivi li jistgħu jgħollu l- konċentrazzjonijiet ta ’ imatinib fil- plażma:
Substances that inhibit the cytochrome P450 isoenzyme CYP3A4 activity (e. g. ketoconazole, itraconazole, erythromycin, clarithromycin) could decrease metabolism and increase imatinib concentrations.
Dawk is- sustanzi li jinibixxu l- attività CYP3A4 ta ’ l- isoenzima ċitokromju P450 (eż. ketoconazole, itraconazole, erythromycin, clarithromycin) jistgħu jnaqqsu l- metaboliżmu u b’ hekk iżidu il - konċentrazzjonijiet ta ’ imatinib.
There was a significant increase in exposure to imatinib (the mean Cmax and AUC of imatinib rose by 26% and 40%, respectively) in healthy subjects when it was co-administered with a single dose of ketoconazole (a CYP3A4 inhibitor).
Kien hemm żieda sinifikanti fl- ammont ta ’ Imatinib esponut (is- Cmax intermedju u l- AUC għal imatinib għolew b’ 26% u 40% rispettivament) f’ persuni f’ saħħithom, meta imatinib ingħata flimkien ma ’ doża waħda ta ’ ketoconazole (sustanza li tinibixxi s- CYP3A4).
Caution should be taken when administering Glivec with inhibitors of the CYP3A4 family.
Għandha tintuża kawtela meta Glivec jingħata flimkien ma ’ sustanzi li jinibixxu lill- familja tas - CYP3A4.
Active substances that may decrease imatinib plasma concentrations:
Sustanzi attivi li jistgħu jnaqqsu l- konċentrazzjonijiet ta ’ imatinib fil- plażma:
Substances that are inducers of CYP3A4 activity could increase metabolism and decrease imatinib plasma concentrations.
Dawk is- sustanzi li jistimolaw l- attività tas- CYP3A4 jistgħu jwasslu għal żieda fil- metaboliżmu, u għalhekk inaqqsu l- konċentrazzjonijiet ta ’ imatinib fil- plażma.
Co-medications which induce CYP3A4 (e. g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, fosphenytoin, primidone or Hypericum perforatum, also known as St.
Mediċini li jingħataw fl- istess ħin u li jistimolaw is- CYP3A4 (eż. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, fosphenytoin, primidone u Hypericum perforatum, ukoll mgħaruf bħala St.
John’ s Wort) may significantly reduce exposure to Glivec, potentially increasing the risk of therapeutic failure.
John’ s Wort) jistgħu jnaqqsu b’ mod sinifikanti l- esponiment ta ’ Glivec, u b’ hekk jistgħu jżidu r- riskju li l- kura ma taħdimx.
Pretreatment with multiple doses of rifampicin 600 mg followed by a single 400 mg dose of Glivec resulted in decrease in Cmax and AUC(0-∞) by at least 54% and 74%, of the respective values without rifampicin treatment.
Meta ngħata trattament minn qabel b’ numru ta ’ dożi ta ’ rifampicin 600 mg li mbagħad kien segwit b’ doża waħda ta ’ Glivec 400 mg, dan irriżulta fi tnaqqis fis- Cmax u fl- AUC( 0- ∞) b’ mill- inqas 54% u 74% tal- valuri rispettivi għal meta ma ngħatax rifampicin.
Similar results were observed in patients with malignant gliomas treated with Glivec while taking enzyme-inducing anti-epileptic drugs (EIAEDs) such as carbamazepine, oxcarbamazepine and phenytoin.
Riżultati simili dehru f’ pazjenti b’ glijomas malinni ikkurati bi Glivec waqt li kienu qed jieħdu mediċini kontra l- epilessija li jinduċu l- enzimi (EIAEDs) bħal carbamazepine, oxcarbamazepine u phenytoin.
The plasma AUC for imatinib decreased by 73% compared to patients not on EIAEDs.
L- AUC fil- plażma għal imatinib naqset b’ 73% meta mqabbla ma pazjenti li ma kienux qed jieħdu EIAED’ s.
Concomitant use of rifampicin or other strong CYP3A4 inducers and imatinib should be avoided.
L- użu fl- istess ħin ta ’ rifampicin, jew xi sustanzi oħrajn li b’ saħħa jistimolaw is- CYP3A4, ma ’ imatinib għandu jiġi evitat.
Active substances that may have their plasma concentration altered by Glivec Imatinib increases the mean Cmax and AUC of simvastatin (CYP3A4 substrate) 2- and 3.5-fold, respectively, indicating an inhibition of the CYP3A4 by imatinib.
8 Sustanzi attivi li jistgħu jkollhom il- konċentrazzjoni tagħhom fil- plażma mibdula minħabba f’ Glivec Imatinib iżid is- Cmax intermedju u l- AUC ta ’ simvastatin (sustanza li fuqa jaħdem is- CYP3A4) b ’ 2 - u bi 3. 5- il darba, rispettivament, u dan jindika li imatinib jinibixxi is- CYP3A4.
Therefore, caution is recommended when administering Glivec with CYP3A4 substrates with a narrow therapeutic window (e. g. cyclosporin or pimozide).
Għalhekk, huwa rakkomandat li tintuża kawtela meta Glivec jingħata flimkien ma ’ sustanzi li fuqhom jaġixxi is - CYP3A4 u li għandhom medda terapewtika li hi żgħira (ez., cyclosporin jew pimozide).
Glivec may increase plasma concentration of other CYP3A4 metabolised drugs (e. g. triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, i. e. statins, etc.).
Glivec jista ’ jżid il- konċentrazzjoni fil- plażma ta ’ mediċini oħrajn li jiġu metabolizzati permezz tas- CYP3A4 (ez., triazolo- benzodiazepines, sustanzi bħal dihydropyridine li jibblokkaw il- kanali li minnhom jgħaddi l - kalċju għal ġoċ- ċelluli, xi tipi ta ’ sustanzi li jinibixxu lill- HMG- CoA reductase, jiġifieri l- istatins, eċċ.).
Because warfarin is metabolised by CYP2C9, patients who require anticoagulation should receive low-molecular-weight or standard heparin.
Peress li warfarina tiġi metabolizzata mis- CYP2C9, pazjenti li jkollhom bżonn ta ’ mediċini li jaħdmu kontra s- sistema tal- koagulazzjoni għandhom jirċievu heparin jew fil- forma standard jew bħala heparin li jkollha piż molekulari baxx.
In vitro Glivec inhibits the cytochrome P450 isoenzyme CYP2D6 activity at concentrations similar to those that affect CYP3A4 activity.
F’ testijiet in vitro Glivec inibixxa l- attività tas- CYP2D6, isoenzima taċ- ċitokromju P450, f’ konċentrazzjonijiet simili għal dawk li jaffettwaw l- attività tas- CYP3A4.
Imatinib at 400 mg twice daily had an inhibitory effect on CYP2D6-mediated metoprolol metabolism, with metoprolol Cmax and AUC being increased by approximately 23% (90%CI [1.16-1.30]).
Imatinib 400 mg darbtejn kuljum kellu effett li inibixxa il- metaboliżmu ta ’ metoprolol medjat b’ CYP2D6, b’ żieda tas- Cmax u l - AUC ta ’ metoprolol b’ madwar 23% (90% CI [1. 16- 1. 30]).
Dose adjustments do not seem to be necessary when imatinib is co-administrated with CYP2D6 substrates, however caution is advised for CYP2D6 substrates with a narrow therapeutic window such as metoprolol.
Tibdil fid- doża ma jidrux li huma neċessarji meta imatinib jingħata flimkien ma ’ sottostrati ta ’ CYP2D6, madankollu hija konsiljata l- attenzjoni għal sottostrati ta ’ CYP2D6 b’ medda terapewtika dejqa bħal metoprolol.
In patients treated with metoprolol clinical monitoring should be considered.
F’ pazjenti kkurati b’ metoprolol il- monitoraġġ kliniku għandu jkun meqjus.
In vitro, Glivec inhibits paracetamol O-glucuronidation (Ki value of 58.5 micromol/ l at therapeutic levels).
In- vitro, Glivec jinibixxi paracetamol O- glucuronidation (valur Ki ta ’ 58. 5 mikromol/ l f’ livelli terapewtiċi).
Caution should therefore be exercised when using Glivec and paracetamol concomitantly, especially
Għaldaqstant għandha tintuża kawtela meta jkunu qed jintużaw Glivec u paracetamol flimkien, l- aktar meta l- aktar b’ dożi għoljin ta ’ paracetamol.
In thyroidectomy patients receiving levothyroxine, the plasma exposure to levothyroxine may be decreased when Glivec is co-administered (see section 4.4).
F’ pazjenti li jkunu tneħħewlhom it- tirojdi li jkunu qed jirċievu levothyroxine, l- esponiment fil- plażma għal levothyroxine jista ’ jiżdied meta Glivec jingħata fl- istess ħin (ara sezzjoni 4. 4).
Caution is therefore recommended.
Għaldaqstant, hija rakkomandata l- kawtela.
However, the mechanism of the observed interaction is presently unknown.
Madankollu, il- mekkaniżmu ta ’ kif jaħdem għadu mhux magħruf.
In Ph+ ALL patients, there is clinical experience of co-administering Glivec with chemotherapy (see section 5.1), but drug-drug interactions between imatinib and chemotherapy regimens are not well characterised.
F’ pazjenti b’ Ph+ ALL, hemm esperjenza klinika ta ’ l- użu ta ’ ġlivec ma ’ kemoterapija (ara sezzjoni 5. 1), iżda interazzjonijiet bejn mediċini ta ’ imatinib ma ’ reġimens kimoterapewtiċi għadhom ma ġewx iċċarati.
Imatinib adverse events, i. e. hepatotoxicity, myelosuppression or others, may increase and it has been reported that concomitant use with L-asparaginase could be associated with increased hepatotoxicity (see section 4.8).
L- effetti avversi ta ’ imatinib, i. e. tossiċità fil- fwied, majelosuppressjoni jew oħrajn, jistgħu jiżdiedu u kien rappurtat li l- użu fl- istess ħin ma ’ L- asparaginase jista ’ jkun assoċjat ma ’ żieda fit - tossiċità tal- fwied (ara sezzjoni 4. 8).
Therefore, the use of Glivec in combination requires special precaution.
Għaldaqstant, l- użu ta ’ Glivec kombinat jeħtieġ kawtela speċjali.