qanastek/EMEA-V3 huggingface dataset:
Antineoplastic agents, antimetabolites, purine analogues, ATC code:
Aġenti antineoplastiċi, aġenti kontra sustanzi ffurmati fil- metaboliżmu, analogi tal- purine, Kodiċi ATC:
Nelarabine is a pro-drug of the deoxyguanosine analogue ara-G.
Nelarabine huwa pro- droga ta 'l- analogu ta' deoxyguanosine ara- G.
Nelarabine is rapidly demethylated by adenosine deaminase (ADA) to ara-G and then phosphorylated intracellularly by deoxyguanosine kinase and deoxycytidine kinase to its 5’ -monophosphate metabolite.
Nelarabine jiġi demetilizzat minn adenosine deaminase (ADA) għal ara- G u mbagħad iffosforat fiċ- ċellula bid- deoxyguanosine kinase u deoxycytidine kinase għall - prodott tal- metaboliżmu tiegħu 5 'monophoshate.
The monophosphate metabolite is subsequently converted to the active 5’ -triphosphate form, ara-GTP.
Il- prodott tal- metaboliżmu monophosphate imbagħad jinbidel fil- forma attiva ta '5' triphosphate, ara- GTP.
Accumulation of ara-GTP in leukaemic blasts allows for preferential incorporation of ara-GTP into deoxyribonucleic acid (DNA) leading to inhibition of DNA synthesis.
L- akkumulazzjoni ta 'ara- GTP f' ċelluli embrijoniċi tal- lewkemja tippermetti l- inkorporazzjoni preferenzjali ta' ara- GTP f' deoxyribonucleic acid (DNA) u twassal għal inibizzjoni ta 'sintesi ta' DNA.
This results in cell death.
Dan jirriżulta fil- mewt taċ- ċellula.
Other mechanisms may contribute to the cytotoxic effects of nelarabine.
Mekkaniżmi oħra jistgħu jikkontribwixxu għall- effetti ċitotossiċi ta 'nelarabine.
In vitro, T-cells are more sensitive than B-cells to the cytotoxic effects of nelarabine.
In vitro iċ- ċelluli T huma aktar sensittivi miċ- ċelluli B għall- effetti ċitotossiċi ta 'nelarabine.
Adult studies
Studji fl- adulti
In an open-label study carried out by the Cancer and Leukaemia Group B and the Southwest Oncology Group, the safety and efficacy of nelarabine were evaluated in 39 adults with T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL).
Fi studju open- label li sar mill Cancer and Leukemia Group B u s- Southwest Oncology Group,, is- sigurta 'u l- effikaċja ta' nelarabine kienu evalwati f' 39 adult b' lewkemja likfoblastika akuta taċ- ċellola T (T- ALL) jew limfoma limfoblastika (T- LBL).
Twenty– eight of the 39 adults had relapsed or were refractory to at least two prior induction regimens and aged between 16 to 65 years of age (mean 34 years).
Tmienja u għoxrin mid- 39 adult kienu rkadew jew żewġ sistemi preċedenti ta 'induzzjoni ma ħadmux fuq grupp li kellhom bejn 16 u 65 sena (medja ta' 34 sena).
Nelarabine at a dose of 1500 mg/ m2/ day was administered intravenously over two hours on days 1, 3 and 5 of a 21 day cycle.
Nelarabine f' doża ta '1, 500 mg/ m2 kuljum ingħata fuq sagħtejn ġol- vina f' jiem 1, 3 u 5 b' ripetizzjoni f' ċiklu ta' 21 ġurnata.
6 %— 37%] treated with nelarabine achieved a complete response (bone marrow blast counts ≤ 5%, no other evidence of disease, and full recovery of peripheral blood counts).
Ħamsa mit- tmienja u għoxrin pazjent (18%) [95% CI 6%, 37%] trattati b' nelarabine waslu għal fejqan komplet (numru ta 'ċelluli embrijoniċi fil- mudullun ta' ≤5%, l- ebda evidenza oħra ta 'mard, u rkupru komplet ta' l- għadd periferali tad- demm).
8 %– 41%] achieved a complete response with or without haematological recovery.
Total ta '6 pazjenti (21%) [95% CI 8%, - 41%} waslu għal fejqan komplet bi jew mingħajr rkupru fid- demm.
Time to complete response in both classifications of response ranged from 2.9 to 11.7 weeks.
Iż- żmien għal rispons komplet fiż- żewġ klassifikazzjoniet ta 'rispons kienu bejn 2. 9 u 11. 7 ġimgħa.
Duration of response (in both classifications of response (n=5) ranged between 15 and 195+ weeks.
Id- dewmien tar- rispons (fiż- żewġ klassifikazzjonijiet ta 'reazzjoni (n=5) kienet bejn 15 u' l fuq minn 195 ġimgħa.
Median overall survival was 20.6 weeks [95% CI:
Il- medja totali ta 'sopravivenza kienet ta' 20. 6 ġimgħa [95% CI:
10.4– 36.4].
10. 4- 36. 4].
Survival at one year was 29% [95% CI:
Is- sopravivenza wara sena kienet ta '29% [95% CI:
Paediatric studies
Studji pedjatriċi
In an open-label, multicenter study carried out by Childrens Oncology Group, nelarabine was administered intravenously over 1 hour for 5 days to 151 patients ≤ 21 years of age, 149 of whom had relapsed or refractory T-cell acute lymphoblastic leukaemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
9 Fi studju open- label li sar f' aktar minn ċentru wieħed miċ- Children' s Oncology Group, nelarabine ingħata fil- vina fuq siegħa għal 5 ijiem lil 151 pazjent ≤ 21 sena, li minnhom 149 rkadew jew baqgħu b' lewkemja taċ- ċellula T limfoblastika akuta (T- ALL) jew limfoma limfoblastika taċ- ċellula T (T- LBL).
Eighty-four (84) patients, 39 of whom had received two or more prior induction regimens and 31 whom had received one prior induction regimen, were treated with 650 mg/ m2/ day of nelarabine administered intravenously over 1 hour daily for 5 consecutive days repeated every 21 days.
Erba 'u tmenin (84) pazjent, li 39 minnhom kienu ħadu tnejn jew aktar sistemi ta' induzzjoni qabel u 31 minnhom kienu ħadu sistema ta 'induzzjoni waħda qabel, kienu ttrattati b' 650 mg/ m2 kuljum ta' nelarabine li ingħatat fuq siegħa ġol- vina kuljum għal ħamest ijiem konsekuttivi b' ripetizzjoni kull 21 ġurnata.
Of the 39 patients who had received two or more prior induction regimens, 5 (13%) [95% CI:
Mit- 39 pazjent li qabel kienu rċevew żewġ sistemi ta 'kura ta' induzzjoni jew aktar qabel 5 (13%) [95% CI:
4 %– 27%] achieved a complete response (bone marrow blast counts ≤ 5%, no other evidence of disease, and full recovery of peripheral blood counts) and 9 (23%) [95% CI:
4% - 27%] kisbu rispons komplet (numru ta 'ċelluli embrijoniċi tal- mudullun ≤ 5%, ebda evidenza oħra ta' mard u rkupru komplet ta 'l- għadd taċ- ċelluli tad- demm periferali) u 9 (23%) [95%] CI:
11 %– 39%] achieved complete responses with or without full haematological recovery.
11% - 39%] kisbu rispons komplet bi jew mingħajr irkupru ematoloġiku komplet.
Duration of response in both classifications of response ranged between 4.7 and 36.4 weeks and median overall survival was 13.1 weeks [95% CI:
Id- dewmien tar- rispons fiż- żewġ klassifikazzjonijiet ta 'rispons kien ta' bejn 4. 7 u 36. 4 ġimgħat u l- medja ta 'sopravivenza totali kienet ta' 13. 1 ġimgħa [95% CI:
8.7– 17.4] and survival at one year was 14% [95% CI:
8. 7- 17. 4] u s- sopravivenza wara sena kienet ta '14% [95% CI:
9 Thirteen (42%) of the 31 patients treated with one prior induction regimen achieved a complete response overall.
Tlettax (42%) mill- 31 pazjent trattati b' sistema ta 'induzzjoni waħda qabel laħqu rispons komplet ġenerali.
Nine of these 31 patients failed to respond to prior induction (refractory patients).
Disa 'minn dawn il- 31 pazjent ma rrispondewx għal induzzjoni minn qabel (pazjenti refrattarji).
Four (44%) of the nine refractory patients experienced a complete response to nelarabine.
Erbgħa (44%) mid- disa 'pazjenti refrattarji esperjenzaw rispons komplet għal nelarabine.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li minħabba li l- marda li qed tbati minnha hija rari ma kienx possibbli li tinkiseb informazzjoni kompleta dwar il- benefiċċji u r- riskji ta ’ dan il- prodott mediċinali.
Nelarabine is rapidly demethylated by adenosine deaminase (ADA) to ara-G and then phosphorylated intracellularly by deoxyguanosine kinase and deoxycytidine kinase to its 5’ -monophosphate metabolite.
Nelarabine jiġi demetilizzat malajr minn adenosine deaminase (ADA) għal ara- G u mbagħad fosforat fiċ- ċellula b' deoxyguanosine kinase u deoxycytidine kinase għall - prodott tal- metaboliżmu tiegħu 5 'monophoshate.
The monophosphate metabolite is subsequently converted to the active 5’ -triphosphate from, ara-GTP.
Il- prodott tal- metaboliżmu monophosphate imbagħad jinbidel fil- 5 'triphosphate attiv ara- GTP.
In a cross-study analysis using data from four Phase I studies, the pharmacokinetics of nelarabine and ara-G were characterized in patients aged less than 18 years and adult patients with refractory leukaemia or lymphoma.
F' analiżi ta 'studji differenti bl- użu ta' data minn erbgħa studji ta 'Fażi I, il- farmakokinetika ta' nelarabine u ara- G kienu kkaraterizzati f' pazjenti ta 'eta' ta 'anqas minn 18' il sena u f' pazjenti adulti b' lewkemja jew limfoma refrattarja.
Plasma ara-G Cmax values generally occurred at the end of the nelarabine infusion and were generally higher than nelarabine Cmax values, suggesting rapid and extensive conversion of nelarabine to ara-G.
Il- valuri ta 'ara- G Cmax ġeneralment ħarġu fl- aħħar ta' l- infużjoni b' nelarabine u ġeneralment kienu ogħla mill- valuri Cmax ta 'nelarabine li tindika konverżjoni mgħaġġla u estensiva ta' nelarabine għal ara- G.
After infusion of 1,500 mg/ m2 nelarabine over two hours in adult patients, mean (%CV) plasma nelarabine Cmax and AUCinf values were 13.9 µM (81%) and 13.5 µM. h (56%) respectively.
Wara l- infużjoni ta '1, 500 mg/ m2 ta' nelarabine fuq sagħtejn f' pazjenti adulti, il- valuri medja (% CV) ta 'Cmaxu AUCinf ta' nelarabine fil- plażma kienu 13. 9 μM (81%) u 13. 5 μM. h (56%) rispettivament.
Mean plasma ara-G Cmax and AUCinf values were 115 µM (16%) and 571 µM. h (30%), respectively.
Il- valuri medji fil- plażma ta 'ara- G Cmax u AUCinf kienu 115 μM (16%) u 571 μM. h (30%) rispettivament.
Intracellular Cmax for ara-GTP appeared within 3 to 25 hours on day 1.
10 Cmax fiċ- ċellula għal ara- GTP dehru f' ħin ta 'bejn 3 u 25 siegħa fl- ewwel ġurnata.
Mean (%CV) intracellular ara-GTP Cmax and AUC values were 95.6 µM (139%) and 2214 µM. h (263%) at this dose.
Il- medja (% CV) ta 'ara GTP Cmax fiċ- ċellula u l- valuri AUC kienu 95. 6 μM (139%) u 2214 μM. h (263%) b' din id- doża.
After infusion of 400 or 650 mg/ m2 nelarabine over one hour in 6 paediatric patients, mean (%CV) plasma nelarabine Cmax and AUCinf values, adjusted to a 650 mg/ m2 dose, were 45.0 µM (40%) and 38.0 µM. h (39%), respectively.
Wara infużjoni ta '400 jew 650 mg/ m2 ta' nelarabine f' siegħa f' sitt pazjenti pedjatriċi, il- valuri medja (% CV) Cmax u AUCinf ta 'nelarabine fil- plażma, aġġustati għal doża ta' 650 mg/ m2 kienu ta '45. 0 μM (40%) u 38. 0 μM. h (39%) rispettivament.
Mean plasma ara-G Cmax and AUCinf values were 60.1 µM (17%) and 212 µM. h (18%), respectively.
Il- valuri medji fil- plażma ta 'ara- G Cmax u AUCinf kienu 60. 1 μM (17%) u 212 μM. h (18%) rispettivament.
Nelarabine and ara-G are extensively distributed throughout the body based on combined Phase I pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/ m2.
Nelarabine u ara- G jinfirxu mal- ġisem kollu b' mod estensiv ibbażat fuq data farmakokinetika kombinata f' Fażi I b' dożi ta nelarabine ta '104 sa 2, 900 mg/ m2.
Specifically, for nelarabine, mean (%CV) VSS values were 115 l/ m2 (159%) and 89.4 l/ m2 (278%) in adult and paediatric patients, respectively.
Speċifikament, għal nelarabine, il- valuri medja (% CV) VSS kienu ta '115 l/ m2 (159%) u 89. 4 l/ m2 (278%) f' pazjenti adulti u pedjatriċi rispettivament.
For ara-G, mean VSS/ F values were 44.8 l/ m2 (32%) and 32.1 l/ m2 (25%) in adult and paediatric patients, respectively.
Għal ara- G, il- valuri medja VSS/ F kienu ta '44. 8 l/ m2 (32%) u 32. 1 l/ m2 (25%) f' pazjenti adulti u pedjatriċi rispettivament.
10 Nelarabine and ara-G are not substantially bound to human plasma proteins (less than 25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 µM.
Nelarabine u ara- G ma jintrabtux b' mod sostanzjali mal- proteini fil- plażma tal- bniedem (anqas minn 25%) in vitro u r- rabta hija indipendenti mill- livelli ta 'nelarabine jew ara- G sa 600 μM.
No accumulation of nelarabine or ara-G was observed in plasma after nelarabine administration on either a daily or a day 1, 3, 5 schedule.
Ma ġietx osservata akkumulazzjoni ta 'nelarabine jew ara- G fil- plażma wara t- tehid ta' nelarabine kuljum jew fi skeda ta 'l- 1, 3, 5 ġurnata.
Intracellular ara-GTP concentrations in leukaemic blasts were quantifiable for a prolonged period after nelarabine administration.
Il- livelli ġewwa ċ- ċellula ta 'ara- GTP f' ċelluli embrijoniċi tal- lewkemja kienu kkwantifikati għal perjodu twil wara t- tehid ta' nelarabine.
Intracellular ara-GTP accumulated with repeated administration of nelarabine.
Ara- GTP akkumula ġewwa ċ- ċellula wara t- tehid ripetut ta 'nelarabine.
On the day 1, 3, and 5 schedule, Cmax and AUC(0-t) values on day 3 were approximately 50% and 30%, respectively, greater than Cmax and AUC(0-t) values on day 1.
Fl- iskeda ta 'l- 1, 3. u 5 ġurnata, il- valuri Cmax u AUC( 0- t) f' jum 3 kienu bejn wieħed u ieħor ta' 50% u 30% rispettivament, akbar mill- valuri Cmax u AUC( 0- t) f' jum 1.
The principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine.
Ir- rotta prinċipali ta 'metaboliżmu ta' nelarabine hija O- demetilizzazzjoni b' adensoine deaminase biex jifforma ara- G, li jgħaddi minn idroliżi biex jifforma guanine.
In addition, some nelarabine is hydrolysed to form methylguanine, which is O-demethylated to form guanine.
Barra minn hekk, parti minn nelarabine jiġi idrolizzat għal methylguanine, li jiġi O- demetilizzat biex jifforma guanine.
Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid.
Guanine jiġi N deaminat biex jifforma xanthine, li jerġa 'jiġi ossidizzat biex jipproduċi aċidu uriku.
Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours, respectively.
Nelarabine u ara- G jitneħħew malajr mill- plażma b' half life ta 'bejn wieħed u ieħor 30 minuta u 3 siegħat rispettivament.
These findings were demonstrated in patients with refractory leukaemia or lymphoma given a dose of 1,500 mg/ m2 nelarabine (adults) or a 650 mg/ m2 (paediatrics).
Dawn is- sejbiet intwerew f' pazjenti b' lewkemja jew limfoma refrattorja meta ngħataw doża ta '1, 500 mg/ m2 ta' nelarabine (adulti) jew 650 mg/ m2 (tfal).
Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/ m2 indicate that mean (%CV) clearance (Cl) values for nelarabine are 138 l/ h/ m2 (104%) and 125 l/ h/ m2 (214%) in adult and paediatric patients, respectively, on day 1 (n = 65 adults, n = 21 paediatric patients).
Tagħrif farmakokinetiku kombinat Fażi I għal dożi ta 'nelarabine ta' 104 sa 2, 900 mg/ m2 jindika li l- valuri medja (% CV) ta 'tneħħija (CI) għal nelarabine huma ta' 138 l/ h/ m2 (104%) u 125 l/ h/ m2 (214%) f' pazjenti adulti u pedjatriċi, rispettivatment, f' jum 1 (n = 65 pazjenti adulti n = 21 pazjenti pedjatriċi).
The apparent clearance of ara-G (Cl/ F) is comparable between the two groups [9.5 l/ h/ m2 (35%) in adult patients and 10.8 l/ h/ m2 (36%) in paediatric patients] on day 1.
It- tneħħija evidenti ta 'ara- G (CI/ F) jista' jitqabbel bejn iż- żewġ gruppi [9. 5 l/ h/ m2 (35%) f' pazjenti adulti u 10. 8 l/ h/ m2 (36%) f' pazjenti pedjatriċi] f' jum 1.
Nelarabine and ara-G are partially eliminated by the kidneys.
Nelarabine u ara- G jitneħħew parzjalment mill- kliewi.
In 28 adult patients, 24 hours after nelarabine infusion on day 1, mean urinary excretion of nelarabine and ara-G was 5.3% and 23.2% of the administered dose, respectively.
Fi 28 pazjent adult, 24 siegħa wara infużjoni b' nelarabine f' jum 1, il- medja ta 'tneħħija fl- awrina ta' nelarabine u ara- G kienet ta '5. 3% u 23. 2% tad- doża meħuda, rispettivament.
Renal clearance averaged 9.0 l/ h/ m2 (151%) for nelarabine and 2.6 l/ h/ m2 (83%) for ara-G in 21 adult patients.
It- tneħħija mill- kliewi kienet medja ta '9. 0 l/ h/ m2 (151%) għal nelarabine u 2. 6 l/ h/ m2( 83%) għal ara- G f' 21 pazjent adult.
Because the timecourse of intracellular ara-GTP was prolonged, its elimination half-life could not be accurately estimated.
11 Minħabba li l- kors ta 'ħin ta' ara- GTP fiċ- ċellula kien imtawwal, il half life tat- tneħħija tiegħu ma 'setgħatx tkun ikkalkulata b' mod eżatt.
Limited clinical pharmacology data are available for patients below the age of 4 years.
M’ hemmx tagħrif farmakoloġiku kliniku biżżejjed dwar pazjenti li għandhom anqas minn 4 snin.
Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/ m2 indicate that the clearance (Cl) and Vss values for nelarabine and ara-G are comparable between the two groups.
Tagħrif farmakokinetiku kombinat Fażi I ta 'dożi ta' nelarabine minn 104 sa 2, 900 mg/ m2 indikaw li l- valuri ta 'tneħħija (CI) u Vss għal nelarabine u ara- G huma komparabbli bejn iż- żewġ gruppi.
Further data with respect to nelarabine and ara-G pharmacokinetics in the paediatric population are provided in other subsections.
Aktar tagħrif fuq il- farmakokinetika ta 'nelarabine u ara- G fil- popolazzjoni pedjatrika issibu f' subsezzjonijiet oħra.
Gender has no effect on nelarabine or ara-G plasma pharmacokinetics.
Il- ġeneru m' għandu l' ebda effett fuq il farmakokinetika ta 'nelarabine jew ara- G fil- plażma.
Intracellular ara-GTP Cmax and AUC(0– t) values at the same dose level were 2– to 3– fold greater on average in adult female than in adult male patients.
Il- valuri ta 'ara- GTP Cmax u AUC( 0- t) fiċ- ċellula fl- istess livell ta' doża kienu minn 2 - sa 3 - darbiet akbar bħala medja f' pazjenti adulti feminnili minn pazjenti adulti maskili.
The effect of race on nelarabine and ara-G pharmacokinetics has not been specifically studied.
L- effett tar- razza fuq il- farmakokinetika ta 'nelarabine u ara- G ma ġiex studjat speċifikament.
In a pharmacokinetic/ pharmacodynamic cross study analysis, race had no apparent effect on nelarabine, ara-G, or intracellular ara-GTP pharmacokinetics.
F' analiżi ta 'studji farmakokinetiċi/ farmakodinamiċi differenti ir- razza ma kellha ebda effett evidenti fuq il- farmakokinetika ta' nelarabine, ara- G jew ara- GTP ġewwa ċ- ċellula.
The pharmacokinetics of nelarabine and ara-G have not been specifically studied in renally impaired or haemodialysed patients.
Il- farmakokinetiċi ta 'nelarabine u ara- G ma ġewx studjati speċifikament f' pazjenti b' indeboliment tal- kliewi jew fuq dijaliżi.
Nelarabine is excreted by the kidney to a small extent (5 to 10% of the administered dose).
Ftit min- nelarabine jitneħħa mill- kliewi (minn 5 sa 10% tad- doża meħuda).
Ara-G is excreted by the kidney to a greater extent (20 to 30% of the administered nelarabine dose).
Ħafna minn ara- G jitneħħa mill- kliewi (minn 20 sa 30% tad- doża ta 'nelarabine meħuda).
Adults and children in clinical studies were categorized into the three groups according to renal impairment: normal with Clcr greater than 80 ml/ min (n = 56), mild with Clcr equalling 50 to 80 ml/ min (n = 12), and moderate with Clcr less than 50 ml/ min (n = 2).
Fi studju kliniċi adulti u tfal kienu maqsuma fi tlett gruppi skond l- indeboliment fil- kliewi: normali b' CIcr aktar minn 80 ml/ min (n =56), ħafif b' CIcr minn 50 sa 80 ml/ min (n =12), u moderat b' CIcr ta 'anqas minn 50ml/ min (n =2).
The mean apparent clearance (Cl/ F) of ara-G was about 7% lower in patients with mild renal impairment than in patients with normal renal function (see section 4.2).
Il- medja ta 'tneħħija evidenti (CI/ F) ta' ara- G kienet bejn wieħed u ieħor 7% anqas f' pazjenti b' indeboliment tal- kliewi ħafif minn pazjenti b' funzjoni normali tal- kliewi (ara sezzjoni 4. 2).
No data are available to provide a dose advice for patients with Clcr less than 50 ml/ min.
Ma hemmx data disponnibli biex jingħata parir fuq doża għal pazjenti b' CIcr ta 'anqas minn 50 ml/ min.
Age has no effect on the pharmacokinetics of nelarabine or ara-G.
L- eta 'm' għandha l- ebda effett fuq il- farmakokinetika ta' nelarabine jew ara- G.
Decreased renal function, which is more common in the elderly, may reduce ara-G clearance (see section 4.2).
Funzjoni mnaqqsa tal- kliewi, li hija aktar komuni fl- anzjani, tista 'tnaqqas it- tneħħija ta' ara- G (ara sezzjoni 4. 2).
Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to clinical use were as follows: nelarabine caused histopathological changes to the central nervous system (white matter) vacuolation and degenerative changes in cerebrum, cerebellum and spinal cord of monkeys after treatment with nelarabine daily during 23 days, at exposures below the human therapeutic exposure.
Reazzjonijiet avversi li ma kienux osservati fi studji kliniċi, imma li dehru f' annimali f' livelli ta 'esponimenti simili għall- livelli ta' esponiment kliniku u bil- possibilta 'ta' rilevanza possibli għall- użu kliniku kienu kif ġej: nelarabine ikkawża bidliet istopatoloġiċi fis- sistema nervuża ċentrali (materja bajda) il- formazzjoni ta 'spazji żgħar fiċ- ċitoplażma taċ- ċellula, u bidliet diġenerattivi fiċ- ċerebru, ċervellett, u spina dorsali ta' xadini wara trattament b' nelarabine kuljum għal 23 ġurnata, b' esponimenti anqas mill- esponimenti terapewtiċi fil- bniedem.
Nelarabine showed in vitro cytotoxicity to monocytes and macrophages.
Nelarabine wera ċitotossiċita 'in vitro għall- monocytes u l- macrophages.
Carcinogenicity
Karċinoġeniċita '
Carcinogenicity testing of nelarabine has not been performed.
Ma sarux testijiet fuq il- karċinoġeniċita 'ta' nelarabine.
Mutagenicity
12 Mutaġeniċita '
Nelarabine was mutagenic to L5178Y/ TK mouse lymphoma cells with and without metabolic activation.
Nelarabine instab li jikkawża mutaġeniċita 'f' ċelluli ta' limfoma L5178Y/ TK fil- ġurdien bi u mingħajr attivazzjoni metabolika.
Reproduction toxicity
Tossiċita 'riproduttiva
Compared to controls, nelarabine caused increased incidences of fetal malformations, anomalies, and variations in rabbits when given at doses approximately 24% of the adult human dose on a mg/ m2 basis during the period of organogenesis.
Meta mqabbel ma 'kontrolli, nelarabine kellu inċidenza akbar ta' malformazzjonijiet fetali, anomaliji u varjazzjonijiet fi fniek meta ingħata f' dożi ta '24% tad- doża ta' bniedem adult fuq bażi ta 'mg/ m2 waqt il- perjodu ta' organoġenesi.
Cleft palate was seen in rabbits given a dose approximately 2-fold the adult human dose, absent pollices in rabbits given a dose approximately 79% of the adult human dose while absent gall bladder, accessory lung lobes, fused or extra sternebrae and delayed ossification was seen at all doses.
Kien innutat cleft palate fi fniek li ngħataw doża ta 'bejn wieħed u ieħor darbtejn id- doża ta' bniedem adult, swaba nieqsa fi fniek li ngħataw doża ta 'bejn wieħed u ieħor 79% tad- doża ta' bniedem adult filwaqt li nuqqas ta 'marrara, lobi supplementari tal- pulmun, għadam tan- nofs tas- sider magħqud jew żejjed u ttardjar fl- ossifikazzjoni dehru bid- dożi kollha.
Maternal body weight gain and fetal body weights were reduced in rabbits given a dose approximately 2-fold the adult human dose.
Żieda fil- piż tal- ġisem ta 'l- omm u l- piż tal- ġisem tal- fetu kienu anqas fi fniek li ngħataw doża ta' bejn wieħed u ieħor darbtejn dik ta 'bniedem adult.
Fertility
Fertilita '
However, no undesirable effects were seen in the testes or ovaries of monkeys given nelarabine intravenously at doses up to approximately 32% of the adult human dose on a mg/ m2 basis for 30 consecutive days.
Ma saru l- ebda studji f' annimali biex jistudjaw l- effetti ta 'nelarabine fuq il- fertilita' Madankollu, ma kien hemm l- ebda effetti mhux mixtieqa fit- testikoli jew l- ovarji ta 'xadini li ngħataw nelarabine fil- vina f' dożi sa bejn wieħed u ieħor 32% tad- doża fi bniedem adult ibbażata fuq mg/ m2 għal 30 ġurnata konsekkutivi.
6.2 Incompatibilities
TAGĦRIF FARMAĊEWTIKU
Not applicable.
6. 1 Lista ta ’ sustanzi mhux attivi
Atriance is stable for up to 8 hours at up to 30°C once the vial is opened.
Atriance huwa stabbli sa 8 siegħat f' temperatura ta '30°Ċ la darba l- fjala tkun infetħet.
This medicinal product does not require any special storage conditions.
Dan il- prodott mediċinali m' għandux bżonn xi kondizzjonijiet speċjali għall- ħażna.
Clear glass (Type I) vials with a non-latex bromobutyl rubber stopper, sealed with an aluminium cap.
Fjali bi ħġieġ ċar (Tip I) b' tapp tal- gomma bromobutyl li m' hijiex gommalastika, issiġillat b' għatu ta 'l- aluminju.
Each vial contains 50 ml.
13 Kull fjala fiha 50 ml.
Atriance is supplied in packs of 6 vials.
Atriance issibu f' pakketti ta '6 fjali.
The normal procedures for proper handling and disposal of anti-tumour medicinal products should be adopted, namely:
Għandhom jiġu adottati il- proċeduri normali għall- immaniġġjar u r- rimi ta 'prodotti mediċinali kontra t- tumur, fosthom:
— Staff should be trained in how to handle and transfer the medicinal product.
---- L- impjegati għandhom jiġu mħarrġa kif jimmaniġġjaw u jittrasferixxu l- prodott mediċinali.
— Pregnant staff should be excluded from working with this medicinal product.
--- Impjegati fi tqala m' għandhomx jitħallew jaħdmu b' dan il- prodott mediċinali.
— Personnel handling this medicinal product during handling/ transfer should wear protective clothing including mask, goggles and gloves.
---- Impjegati li jimmaniġġjaw dan il- prodott mediċinali waqt immaniġġjar/ tehid minn post għall- ieħor għandhom jilbsu lbies prottettiv li jinkludi maskri, nuċċali biex jipproteġi l- għajnejn u ngwanti.
— All items for administration or cleaning, including gloves, should be placed in high-risk, waste disposal bags for high-temperature incineration.
--- Kull oġġett użat fl- amministrazzjoni jew tindif, inklużi ingwanti għandhom jitpoġġew f' basktijiet għar- rimi ta 'skart ta' riskju għoli biex jinħarqu f' temperatura għolja.
Liquid waste may be flushed with large amounts of water.
Skart likwidu għandu jitlaħlaħ b' ammonti kbar ta 'ilma.
— Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.
--- Kuntatt aċċidentali mal- ġilda jew l- għajnejn għandu jiġi ttrattat immedjatament b' ammonti sostanzjali ta 'ilma.
13 Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart ieħor li jibqa 'wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Glaxo Group Limited, Berkeley Avenue, Greenford, Middlesex UB6 0NN, United Kingdom
Glaxo Group Limited, Berkeley Avenue, Greenford, Middlesex UB6 0NN, Renju Unit
Harmire Road Barnard Castle Durham, DL12 8DT United Kingdom
Harmire Road Barnard Castle Durham, DL12 8DT Renju Unit
The MAH must ensure that the system of pharmacovigilance, as described in version 6.2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Id- DATS għandu jassikura li s- sistema ta 'farmakoviġilanza, kif deskritta f' verżjoni 6. 2 u ppreżentata f' Module 1. 8. 1. ta' l- Applikazzjoni ta 'l- Awtorizzazzjoni fis- Suq, tkun flokha u qegħda taħdem qabel u waqt li l- prodott qiegħed fis- suq.
Risk Management Plan
Pjan għall- Immaniġġjar ta '- Riskju
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 4 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Id- DATS jikkommetti ruħu li jagħmel studji u attivitajiet oħra ta 'farmakoviġilanza ddettaljati fil- Pjan tal- Farmakoviġilanza, kif stabbilit f' verżjoni 4 tal- Pjan għall- Immaniġġjar ta' Riskju (RMP) ppreżentat f' Module 1. 8. 2 ta 'l- Applikazzjoni ta' l- Awtorizzazzjoni fis- Suq u xi aġġornamenti sosegwenti ta 'l- RMP kif miftiehem mill- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond ir- Regolament ta 'CHMP fuq Sistemi ta' Mmaniġġjar tar- Riskju għal prodotti mediċinali għall- użu fil- bniedem, il- PIR ta 'l- aħħar għandu jiġi sottomess fl- istess żmien tar- Rapport Perjodiku ta' Aġġornament dwar Sigurta '(PSUR) li jmiss.
In addition, an updated RMP should be submitted
Barra minn dan għandu jiġi sottomess il- PIR ta 'l- aħħar
• When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
• Meta tiġi rċevuta nformazzjoni ġdida li tista tagħmel impatt fuq l- Ispeċifikazzjoni ta 'Sigurta' ta 'issa, Pjan ta' Farmakoviġilanza jew attivitajiet biex inaqqsu r- riskju • F' 60 ġurnata li tista 'tintlaħaq mira mportanti (ta' farmakoviġilanza jew ta 'tnaqqis ta' riskju) • Fuq talba ta 'EMEA
16 C.
16 Ċ.
The Applicant has committed to provide data from an on-going COG study AALL0434.
L- Applikant ikkommetta ruħu li jipprovdi informazzjoni minn studju COG AALL0434 li għadu għaddej.
Initial safety data will be submitted when available (anticipated 2010), final data will be submitted when available (anticipated 2016).
L- ewwel informazzjoni ta 'sigurta' tkun sottomessa meta tkun disponibbli( antiċipata għal 2010) l- informazzjoni finali tkun sottomessa meta tkun disponibbli (antiċipata għal 2016).
The Applicant has committed to provide data from a Post-Marketing Surveillance Study for Atriance in the indicated patient population under 21 years of age receiving the 650mg/ m2 dose of nelarabine.
L- Applikant ikkommetta ruħu li jipprovdi nformazzjoni minn Studju ta 'Sorveljanza wara li Atriance jkun tqiegħed fis- Suq fil- popolazzjoni indikata ta' pazjenti ta 'taħt il- 21 sena li jkunu qed jirċievu doża ta' nelarabine ta '650mg/ m2.
Annual reports will be submitted as part of annual reassessment of the Marketing Authorisation issued under exceptional circumstances.
Jiġu sottomessi rapporti annwali bħala parti mill- valutazzjoni annwali mill- ġdid ta 'l- Awtorizzazzjoni għat- Tqegħid fis- Suq li tkun ħarġet f' ċirkostanzi mhux tas- soltu.
A study synopsis will be submitted within 6 months of study completion (anticipated 2012).
Jiġi sottomess sommarju ta 'l- istudju f' 6 xhur minn meta jitkompla l- istudju (antiċipat fl- 2012).
Sodium chloride, water for injections, hydrochloric acid/ sodium hydroxide.
Sodium chloride, ilma għall- injezzjoni, hydrochloric acid / sodium hydroxide.
6 x 50 ml vials
6 fjali x 50 ml
Intravenous use.
Użu fil- vini.
Stable for up to 8 hours at up to 30ºC once the vial is opened.
Stabbli sa 8 siegħat sa temperatura ta '30°Ċ la darba l- fjala tkun infetħet.
Glaxo Group Limited, Berkeley Avenue, Greenford, Middlesex UB6 0NN, United Kingdom.
Glaxo Group Limited, Berkeley Avenue, Greenford, Middlesex UB6 0NN, Renju Unit.
Justification for not including Braille accepted.
Aċċettata ġustifikazzjoni li ma ġiex inkluż il- Braille.
VIAL LABEL
FJALA TIKKETTA
Atriance 5 mg/ ml solution for infusion Nelarabine
Atriance 5 mg/ ml soluzzjoni għall- infużjoni Nelarabine
What Atriance is and what it is used for 2.
X’ inhu Atriance u għalxiex jintuża 2.
Before you are give Atriance 3.
Qabel ma tieħu Atriance 3.
How Atriance is used 4.
Kif għandek tieħu Atriance 4.
How to store Atriance 6.
Kif taħżen Atriance 6.
WHAT ATRIANCE IS AND WHAT IT IS USED FOR
X’ INHU ATRIANCE U GĦALXIEX JINTUŻA
Atriance belongs to a group of medicines used to treat some types of cancer.
Atriance jagħmel parti minn grupp ta 'mediċini li jintużaw biex jittrattaw ċerti tipi ta' kanċer.
Atriance is used to treat patients with:
Atriance jintuża biex jittratta pazjenti bi:
• a type of leukaemia, called T-cell acute lymphoblastic leukaemia.
• tip ta 'lewkemja, msejħa lewkemja limfoblastika akuta taċ- ċellula T.
Leukaemia causes an abnormal increase in the number of white blood cells in the body, and sometimes also the blood.
Il- lewkemja tikkawża żieda mhux normali fin- numru ta 'ċelluli bojod fil- ġisem, u xi kultant ukoll fid- demm.
The type of leukaemia relates to the type of white blood cell mainly involved.
It- tip ta 'lewkemja għandha x' taqsam mat- tip ta' ċellula bajda tad- demm involuta l- aktar.
In this case, its cells called lymphoblasts. • a type of lymphoma, called T-cell lymphoblastic lymphoma.
F' dan il- każ, iċ- ċelluli tagħha jissejħu limfoblasti. • tip ta 'limfoma, tissejjaħ limfoma limfoblastika akuta taċ- ċellula T.
This lymphoma is caused by a mass of lymphoblasts, a type of white blood cell.
Din il- limfoma tiġi kkawżata minn massa ta 'limfoblasti, tip ta' ċellula bajda tad- demm.
If you have any questions about your illness, talk to your doctor.
Jekk ikollok xi mistoqsijiet fuq il- marda tiegħek kellem lit- tabib tiegħek.
BEFORE YOU ARE GIVEN ATRIANCE
QABEL MA TIEĦU ATRIANCE
You (or your child, if he/ she is being treated) must not receive Atriance • if you (or your child, if he/ she is being treated) are allergic (hypersensitive) to nelarabine or any of the other ingredients of Atriance.
Int (jew it- tifel/ tifla tiegħek, jekk hu/ hi qed ikun/ tkun fuq kura) m' għandekx tirċievi Atriance • jekk int (jew it- tifel/ tifla tiegħek, jekk hu/ hi qed ikun/ tkun fuq kura) allerġiku (għandek sensittivita 'eċċessiva) għal nelarabine jew wieħed mill- ingredjenti l- oħra ta' Atriance.
Take special care with Atriance Severe neurological side effects have been reported with the use of Atriance.
27 Oqgħod attent ħafna b ’ Atriance Ġew irrappurtati effetti newroloġiċi sekondarji serji meta ntuża Atriance.
Symptoms have included altered mental states (e. g. tiredness), effects on your nervous system (e. g. convulsions, feelings of numbness or tingling, weakness and paralysis).
Dawn l- effetti inkludew bdil fl- istat mentali bħal ħedla ta 'nagħas, effetti fis- sistema nervuża ċentrali bħal aċċessjonijiet, u newropatija periferali minn nuqqas ta' sensazzjoni u parasteżiji sa indeboliment tas- sistema motorja u paraliżi.
Your doctor will check for these symptoms regularly (see also Possible side effects).
It- tabib tiegħek jiċċekkja għal dawn is- sintomi regolarment (ara wkoll Effetti sekondarji li jistgħu jinqalgħu).
27 Your doctor also needs to know the following before you are given this medicine:
It- tabib tiegħek ikollu bżonn ikun jaf ukoll dan li ġej qabel ma tingħata din il- mediċina:
• if you (or your child, if he/ she is being treated) have any kidney or liver problems.
Jekk int (jew it- tifel/ tifla tiegħek, jekk hu/ hi qed ikun/ tkun qiegħed/ qiegħda fuq xi • trattament) għandkom xi problemi bil- kliewi jew bil- fwied.
Atriance may harm a baby conceived before, during or soon after treatment.
Għandu mnejn li d- doża tiegħek ta 'Atriance ikollha bżonn tkun aġġustata jekk inti (jew it- tifel/ tifla tiegħek, jekk hu/ hi qed ikun/ tkun qiegħed/ qiegħda fuq xi • trattament) kont reċentement jew qed tippjana li titlaqqam b' vaċċin ħaj (per eżempju Poljo, Variċella, Tifojde) jekk inti tqila, qed tippjana biex toħroġ tqila. • jekk qed tippjana li ssir missier ta' tarbija. • Atriance jista 'jagħmel ħsara lit- tarbija jekk it- trattament isir qabel, waqt jew ftit wara l- konċepiment.
You should use an effective method of contraception.
Għandek tuża metodu effettiv ta 'kontraċezzjoni.
Breast feeding must be discontinued while you are having treatment with Atriance.
Staqsi lit- tabib tiegħek għall- parir. jekk qed tredda Għandek tieqaf tredda waqt li tkun qed tirċievi trattament b' Atriance.
Discuss your options with your doctor
Iddiskuti • l- għażliet tiegħek mat- tabib tiegħek
Tell your doctor if any of these apply to you.
Għid lit- tabib tiegħek jekk xi wieħed minn dawn japplikaw għalik.
Using other medicines Tell your doctor if you are taking any other medicines, or have recently taken any.
Meta tuża mediċini oħra Għid lit- tabib tiegħek jekk qed tieħu xi mediċini oħra, jew ħadt xi mediċini dan l- aħħar.
This includes any herbal products or medicines you have bought without a prescription
Dawn jinkludu kull prodott mill- ħxejjex jew mediċini oħra li tkun xtrajt mingħajr riċetta tat- tabib
Remember to tell your doctor if you start to take any other medicines while you are on Atriance.
Ftakar biex tgħid lit- tabib tiegħek jekk tibda 'tieħu kwalunkwe mediċina oħra waqt li tkun fuq Atriance.
Pregnancy and breast-feeding Atriance is not recommended for pregnant women.
Tqala u treddigħ Atriance mhuwiex rakkomandat għal nisa tqal.
It may harm a baby if conceived before, during or soon after treatment.
Jista 'jagħmel ħsara lit- tarbija jekk il- konċepiment isir qabel, waqt jew ftit wara li jittieħed.
Consideration to appropriate birth control is recommended to be discussed with your doctor.
Huwa rakkomandat li tiddiskuti mat- tabib tiegħek dwar kontroll addattat tat- twelid.
Do not try and become pregnant/ father a child until your doctor advises you it is safe to do so.
Tipprovax toħroġ tqila/ issir missier ta 'tarbija sakemm it- tabib jagħtik parir li mhux perikoluż li tagħmel hekk.
Male patients, who may wish to father a child, should ask their doctor for family planning advice or treatment.
Pazjenti maskili, li jistgħu ikunu jixtiequ li jkollhom tarbija, għandhom isaqqsu lit- tabib tagħhom għal parir fuq pjanar tal- familja jew trattament.
If pregnancy occurs during treatment with Atriance, you must tell your doctor immediately.
Jekk ikun hemm tqala waqt trattament b' Atriance, għanded tgħid lit- tabib tiegħek mill- ewwel.
It is not known whether Atriance is passed on through breast milk.
Mhuwiex magħruf jekk Atriance jgħaddix fil- ħalib tas- sider.
Breast-feeding must be discontinued while you are taking Atriance.
Għandek tieqaf tredda 'waqt li tkun qed tieħu Atriance.
See "Take special Care with Atriance".
Ara "Oqgħod attent ħafna b’ Atriance".
Driving and using machines Atriance can make people feel drowsy or sleepy, both during and for some days after treatment.
Sewqan u tħaddim ta ’ magni Atriance jista 'jġib ħedla jew ngħas, kemm waqt it- trattament u għal xi ftit ġranet wara t- trattament.
If you feel tired or weak, do not drive, and do not use any tools or machines.
Issuqx, jekk tħossok għajjien jew ma tiflaħx u tużax xi għodda jew magni.
Important information about some of the ingredients of Atriance This medicine contains at least 23 mg sodium per dose.
28 Tagħrif importanti dwar xi wħud mis- sustanzi ta ’ Atriance Din il- mediċina fiha mill- inqas 23 mg ta 'sodju kull doża.
To be taken into consideration by patients on a controlled sodium diet.
Dan għandu jiġi kkunsidrat f' dawk il- pazjenti fuq dieta kkontrollata ta 'sodju.
HOW ATRIANCE IS USED
KIF GĦANDEK TIEĦU ATRIANCE
The dose of Atriance you are given will be based on:
Id- doża ta 'Atriance li tingħata tkun ibbażata fuq:
• your/ your child's (if he/ she is being treated) body surface area (which will be calculated by your doctor based on your height and weight). • the results of blood tests carried out before treatment
is- superfiċje ta 'ġismek/ jew ġisem it- tifel/ tifla tiegħek (jekk t/ ikun fuq il- kura) (li jkun • ikkalkulat mit- tabib tiegħek fuq it- tul u l- piż tiegħek). ir- riżultati tat- testijiet tad- demm li jkunu saru qabel it- trattament •
28 Adults and adolescents (aged 16 years and older)
Adulti u adolexxenti (eta 'ta' 16- il sena u aktar)
The usual dose is 1,500 mg/ m2 of body surface area per day.
Id- doża normali hija ta '1, 500 mg/ m2tas- superfiċje tal- ġisem kuljum.
A doctor or nurse will give you a suitable dose of Atriance as an infusion (a drip).
Tabib jew infermier jagħtuk doża kif suppost ta 'Atriance bħala infużjoni (bit- taqtir).
It is usually dripped into your arm over a period of about 2 hours.
Ġeneralment din tingħata b' infużjoni minn idejk fuq perjodu ta 'bejn wieħed u ieħor 2 siegħat.
You will have an infusion (a drip) once a day on days 1, 3 and 5 of treatment.
Ikollok infużjoni (taqtir) darba kuljum f' jiem 1, 3 u 5 tat- trattament.
This pattern of treatment will normally be repeated every three weeks.
Din is- sekwenza ta 'trattament normalment tirrepeti ruħha kull tlett ġimgħat.
This treatment may vary, depending on the results of your regular blood tests.
Dan it- trattament jista 'jvarja, skond ir- riżultati tat- testijiet regolari tad- demm.
The usual dose is 650 mg/ m2 of body surface area per day.
Id- doża normali hija ta '650 mg/ m2tas- superfiċje tal- ġisem kuljum.
A doctor or nurse will give you/ your child (if he/ she is being treated) a suitable dose of Atriance as an infusion (a drip).
Tabib jew infermier jagħtu lilek/ tifel/ tifla tiegħek (jekk ikunu fuq il- kura) doża addatata ta 'Atriance bħala infużjoni (taqtir).
It is usually dripped into your arm over a period of about 1 hour.
Ġeneralment din tingħata b' infużjoni minn idejk fuq perjodu ta 'madwar siegħa.
You/ your child (if he/ she is being treated) will have an infusion (a drip) once a day for 5 days.
Inti/ tifel/ tifla tiegħek (jekk t/ ikun fuq il- kura) tieħdu infużjoni (taqtir) darba kuljum għal ħamest ijiem.
This pattern of treatment will normally be repeated every three weeks.
Din is- sekwenza ta 'trattament normalment tiġi ripetuta kull tlett ġimgħat.
This treatment may vary, depending on the results of regular blood tests.
Dan it- trattament jista 'jvarja, skond ir- riżultati tat- testijiet regolari tad- demm.
Stopping treatment with Atriance
Jekk tieqaf tieħu Atriance
Your doctor will decide when to stop the treatment.
It- tabib tiegħek jiddeċiedi meta jitwaqqaf it- trattament.
Like all medicines, Atriance can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Atriance jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
The majority of side effects reported with Atriance were seen in adults, children and adolescents.
Il- maġġoranza ta 'l- effetti sekondarji rrapurtati b' Atriance ġew innutati f' adulti, tfal u adolexxenti.
Some of the side effects were reported more often in adult patients.
Xi effetti sekondarji kienu rrapurtati aktar spiss f' pazjenti adulti.
There is no known reason for this.
Ma hemm l- ebda raġuni magħrufa għal dan.
If you have any concerns, discuss them with your doctor.
Jekk għandek xi tħassib, tkellem dwar dan mat- tabib tiegħek.
Very Common side effects
Effetti sekondarji Komuni Ħafna
These may affect more than 1 in 10 people treated with Atriance.
29 Dawn jistgħu jaffettwaw aktar minn 1 f' kull 10 minn nies li jieħdu Atriance.
• Signs of infection.
Sinjali ta 'infezzjoni.
Atriance may reduce the number of white blood cells and lower your resistance to infection (including pneumonia).
Il- lewkemja tikkawża żieda mhux normali fin- numru ta 'ċelluli bojod • fil- ġisem, u xi kultant ukoll fid- demm.
This can even be life threatening.
Dan jista 'jkun ukoll ta' periklu għall- ħajja.
Signs of an infection include: fever serious deterioration of your general condition local symptoms such as sore throat, sore mouth or urinary problems (for example, a burning sensation when urinating, which may be a urinary infection)
Sinjali ta 'infezzjoni jinkludu: deni deterjorament serju fil- kundizzjoni ġenerali tiegħek sintomi lokali bħal uġigħ fil- griżmejn, uġigħ fil- ħalq jew problemi urinarji (per eżempju, sensazzjoni ta' ħruq waqt l- urinazzjoni li tista 'tkun infezzjoni fl- urina)
Tell your doctor immediately if you get any of these.
Għid lit- tabib tiegħek immedjatament jekk tħoss xi effetti bħal dawn.
A blood test will be taken to check possible reduction of white blood cells.
Jittieħed test tad- demm biex tiċċekkja jekk naqsux iċ- ċelluli bojod tad- demm.
Other very common side effects
Effetti sekondarji oħra komuni ħafna
29 • Changes in the sense of feeling in hands or feet, muscle weakness appearing as difficulty getting up from a chair, or difficulty walking (peripheral neuropathy); reduced sensitivity to light touch, or pain; abnormal sensations such as burning and, prickling, a sensation of something crawling on the skin. • Feeling generally weak and tired (temporary anaemia).
• Bidla fis- sensazzjoni ta 'l- idejn jew is- saqajn, debbulizza fil- muskoli li tidher bħal diffikulta' biex tqum minn fuq siġġu, jew diffikulta 'biex timxi (newropatija periferali); nuqqas ta' sensittivita 'għall- mess ħafif, jew uġigħ; sensazzjonijiet mhux normali bħal ħruq u tingiż, sensazzjoni ta' xi ħaġa titkaxkar fuq il- ġilda. • Sensazzjoni ġenerali ta 'debbolizza u għejja (anemija temporanja).
In some cases you may need a blood transfusion. • Unusual bruising or bleeding, caused by a decrease in the number of clotting cells in the blood.
Jista 'jkollok bżonn ta' trasfużjoni tad- demm f' xi każijiet. • Tbenġil jew ħruġ ta 'demm mhux tas- soltu, kawża ta' nuqqas fin- numru ta 'ċelluli li jgħaqqdu d- demm.
This can lead to severe bleeding from relatively small injuries such as a small cut.
Dan jista 'jwassal għal ħruġ qawwi ta' demm minn feriti relativament żgħar bħal qatgħa żgħira.
Rarely, it can lead to even more severe bleeding (haemorrhage).
Rarament dan jista 'jwassal għal ħruġ ta' demm aktar qawwi (emorraġija).
Talk to your doctor for advice on how to minimize the risk of bleeding. • Feeling drowsy and sleepy; headache; dizziness. • shortness of breath, difficult or laboured breathing; cough. • Feeling of an upset stomach (nausea); being sick/ throwing up (vomiting); diarrhoea; constipation • Muscle pain. • Swelling of parts of the body due to accumulation of abnormal amounts of fluid (oedema). • High body temperature (fever); tiredness; feeling weak/ loss of strength.
Kellem lit- tabib tiegħek għal parir fuq kif tnaqqas ir- riskju ta 'ħruġ ta' demm. • Sensazzjoni ta 'ħedla u ngħas; uġigħ ta' ras; sturdament. • qtugħ ta 'nifs, diffikulta' fin- nifs jew nifs bi tbatija; sogħla. • Sensazzjoni ta 'taqligħ fl- istonku (dardir); tirremetti (rimettar); dijarrea; stitikezza • Uġigħ fil- muskoli. • Nefħa ta' partijiet tal- ġisem minħabba akkumulazzjoni ta 'ammonti mhux normali ta' fluwidi (oedema). • Temperatura għolja tal- ġisem (deni); għeja; sensazzjoni ta 'debbulizza/ nuqqas ta' saħħa.
Tell a doctor if any of these becomes troublesome.
Kellem tabib jekk xi wieħed minn dawn jibda 'jagħti l- problemi.
These may affect up to 1 in 10 people treated with Atriance:
Dawn jistgħu jaffettwaw sa 1 f' kull 10 minn nies trattati b' Atriance:
30 • Violent, uncontrollable muscular contractions often accompanied by unconsciousness that can be due to an epileptic attack (seizures). • Clumsiness and lack of coordination affecting balance, walking, limb or eye movements, or speech. • Unintentional rhythmic shaking of one or more limbs (tremors). • Muscle weakness (possibly associated with peripheral neuropathy – see above), joint pain, back pain; pains in hands and feet including a sensation of pins and needles sensation and numbness. • Lowered blood pressure. • Weight loss and loss of appetite (anorexia); stomach pains; sore mouth, mouth ulcers or inflammation. • Problems with memory, feeling disoriented; blurred vision; altered or loss of sense of taste (dysgeusia). • Build up of fluid around the lungs leading to chest pain and difficulty in breathing (pleural effusion); wheezing • Increased amounts of bilirubin in your blood, which may cause yellowing of the skin and may make you feel lethargic. • Increases in blood levels of liver enzymes. • Increases in blood creatinine levels (a sign of kidney problems, which might lead less frequent urination). • The release of tumour cell contents (tumour lysis syndrome), which may put extra stress on your body.
30 • Kontrazzjonijiet vjolenti u bla kontroll tal- muskoli li ħafna drabi jkunu akkumpanjati minn telf ta 'sensi li jista' jkun minħabba attakk epileptiku (konvulżjonijiet). • Guffaġni u nuqqas ta 'koordinazzjoni li taffettwa l bilanċ, il- mixi, il- movimenti ta' l- għajnejn u d- dirgħajn u r- riġlejn, jew id- diskors. • Ċaqliq mhux intenzjonat b' mod ritmiku ta 'wieħed jew aktar mid- dirgħajn jew- riġlejn( tregħid). • Debbulizza tal- muskoli (li tista' tkun assoċjata ma 'newropatija periferali - ara fuq), uġigħ fil- ġogi, uġigħ fid- dahar; uġigħ fl- idejn u s- saqajn li jinkludi sensazzjoni ta' tnemnim u titrix. • Pressjoni tad- demm li tbaxxiet. • Nuqqas fil- piż u nuqqas ta 'aptit (anoressija); uġigħ fl- istonku, uġigħ fil- ħalq, pustumetti jew infjammazzjoni fil- ħalq. • Problemi bil- memorja, sensazzjoni ta' disorjentament; vista mċajpra; nuqqas jew bdil fis sens tat- togħma (dysgeusia). • Akkumulazzjoni ta 'ilma madwar il- pulmun li jwassal għal uġigħ fis- sider u diffikulta' fin- nifs (effużjoni fil- plewra); tħarħir • Żieda fl- ammont ta 'bilirubina fid- demm tiegħek li jista' jwassal għal sfurija tal- ġilda u li tħossok mitluq. • Żieda fid- demm tal- livelli ta 'l- enżimi tal- fwied. • Żieda fil- livelli tal- kreatinina fid- demm (sinjal ta' problemi fil- kliewi li jistgħu iwasslu għal nuqqas ta 'urinazzjoni). • Il- ħruġ tal- kontenut taċ- ċellula tat- tumur (sindromu tad- diżintegrazzjoni tat- tumur), li tista' toħloq tensjoni żejda fuq ġismek.