qanastek/EMEA-V3 huggingface dataset:
Serum creatinine, creatinine clearance (estimated with the Cockcroft-Gault or MDRD formula in adults and with the Schwartz formula in children) and/ or plasma cystatin C levels should be monitored weekly in the first month after initiation or modification of therapy with EXJADE, and monthly thereafter.
Krejatinina fis- serum, tneħħija tal- krejatinina (stmat bil- Cockcroft- Gault jew il- formula MDRD f’ adulti u bil- formula Schwartz fit- tfal) u/ jew livelli ta 'cystatin C fil- plasma għandhom ikunu monitorati kull ġimgħa fl- ewwel xahar wara li tibda jew tinbidel it- terapija b’ EXJADE, u kull xahar minn hemm ’ il quddiem.
Patients with pre-existing renal conditions and patients who are receiving medicinal products that depress renal function may be more at risk of complications.
Pazjenti li jkollhom minn qabel kundizzjonijiet renali u pazjenti li jkunu qed jirċievu prodotti mediċinali li jnaqqsu l- funzjoni renali jista ’ jkollhom riskju akbar ta ’ kumplikazzjonijiet.
Care should be taken to maintain adequate hydration in patients who develop diarrhoea or vomiting.
Għandha ssir attenzjoni sabiex tinżamm l- idratazzjoni f’ pazjenti li jiżviluppaw dijarea jew rimettar.
For adult patients, the daily dose may be reduced by 10 mg/ kg if a rise in serum creatinine by > 33% above the average of the pre-treatment measurements and estimated creatinine clearance decreases below the lower limit of the normal range (< 90 ml/ min) are seen at two consecutive visits, and cannot be attributed to other causes (see section 4.2).
Għall- pazjenti adulti, id- doża ta ’ kuljum tista ’ titnaqqas b ’ 10 mg/ kg jekk f’ żewg żjajjar wara xulxin ikun jidher li l- krejatinina fis- serum żdiedet b ’ > 33% fuq il- medja tal- livelli mkejla qabel il- kura u l - istima tat- tneħħija tal- krejatinina waqgħet taħt il- limitu ta ’ taħt tal- medda normali (< 90 ml/ min), u dawn ma jkunux jistgħu jiġu attribwiti għal kawżi oħrajn (ara sezzjoni 4. 2).
For paediatric patients, the dose may be reduced by 10 mg/ kg if estimated creatinine clearance decreases below the lower limit of the normal range (< 90 ml/ min) and/ or serum creatinine levels rise above the age-appropriate upper limit of normal at two consecutive visits.
Għal pazjenti pedjatriċi, id- doża tista ’ titnaqqas b ’ 10 mg/ kg jekk l- istima tal- tneħħija tal- krejatinina taqa ’ taħt il- livell ta ’ taħt tal- medda normali (< 90 ml/ min) u/ jew il- livelli tal- krejatinina fis- serum jiġu aktar għoljin mill- limitu ta ’ fuq tan- normali ta ’ l- età adattata f’ żewġ żjajjar wara xulxin.
After a dose reduction, for adult and paediatric patients, treatment should be interrupted if a rise in serum creatinine > 33% above the average of the pre-treatment measurements is observed and/ or the calculated creatinine clearance falls below the lower limit of the normal range.
Wara tnaqqis fid- doża, għall- pazjenti adulti u pedjatriċi, il- kura għandha titwaqqaf jekk jidhru żidiet tal- krejatinina fis- serum > 33% fuq il- medja li tkun tkejlet qabel bdiet il- kura u/ jew jekk il- kalkolu tat - tneħħija tal- krejatinina ikun waqa taħt il- limitu ta ’ taħt tal- medda normali.
Treatment may be reinitiated depending on the individual clinical circumstances.
Il- kura tista ’ terġa ’ tinbeda skond iċ- ċirkustanzi kliniċi ta ’ l- individwu.
Particular attention should also be paid to monitoring of serum creatinine in patients who are concomitantly receiving medicinal products that depress renal function.
Għandha tingħata wkoll attenzjoni għall- monitoraġġ tal- krejatinina fis- serum f’ pazjenti li jkunu qed jirċievu fl- istess ħin prodotti mediċinali li jnaqqsu l- funzjoni tal- kliewi.
Tests for proteinuria should be performed monthly.
Testijiet għall- proteina fl- awrina għandhom isiru kull xahar.
As needed, additional markers of renal tubular function (e. g. glycosuria in non-diabetics and low levels of serum potassium, phosphate, magnesium or urate, phosphaturia, aminoaciduria) may also be monitored.
Skond il- bżonn, jista ’ jsir monitoraġġ ta ’ markers oħrajn li juru l- funzjoni tubulari tal- kliewi (eż. zokkor fl- awrina ta ’ pazjenti mhux dijabetiċi u livelli baxxi ta ’ potassium fis- serum, phosphate, magnesium jew urate, fosfat fl- awrina, amino aċidi fl - awrina).
Dose reduction or interruption may be considered if there are abnormalities in levels of tubular markers and/ or if clinically indicated.
Tnaqqis jew twaqqif tad- doża jista ’ jkun ikkunsidrat jekk ikun hemm livelli mhux normali ta ’ markers u/ jew jekk ikun klinikament indikat.
If, despite dose reduction and interruption, the serum creatinine remains significantly elevated and there is also persistent abnormality in another marker of renal function (e. g. proteinuria, Fanconi’ s Syndrome), the patient should be referred to a renal specialist, and further specialised investigations (such as renal biopsy) may be considered.
Jekk, għalkemm titnaqqas jew titwaqqaf id- doża, il- krejatinina fis- serum tibqa ’ għolja b’ mod sinifikanti u jkun hemm ukoll xi marker ieħor tal- funzjoni renali li b' mod persistenti ma jkunx f’ livell normali (eż. proteina fl- awrina, Sindrome ta ’ Fanconi), il- pazjent għandu jkun referut għand speċjalista tal- kliewi, u aktar investigazzjonijiet specjalizzati (bħal bijopsi tal- kliewi) jistgħu jiġu ikkunsidrati.
U U
4 Funzjoni epatika:
Liver function test elevations have been observed in patients treated with EXJADE.
Żidiet fit- testijiet tal- funzjoni tal- fwied dehru f’ pazjenti li kienu qed jieħdu EXJADE.
Postmarketing cases of hepatic failure, sometimes fatal, have been reported in patients treated with EXJADE.
Każijiet ta ’ insuffiċjenza epatika wara t- tqegħid fis- suq, kultant fatali, kienu rrappurtati f’ pazjenti kkurati b’ EXJADE.
Most reports of hepatic failure involved patients with significant morbidities including pre-existing liver cirrhosis.
Ħafna mir- rapporti ta ’ insuffiċjenza epatika kienu jinvolvu pazjenti b’ kumplikazzjonijiet oħra sinifikanti inkluż ċirrożi tal- fwied minn qabel.
However, the role of EXJADE as a contributing or aggravating factor cannot be excluded (see section 4.8).
Madankollu, l- irwol ta ’ EXJADE bħala fattur li kkonrtibwixxa jew aggrava ma jistax jiġi eskluż (ara sezzjoni 4. 8).
It is recommended that serum transaminases, bilirubin and alkaline phosphatase be checked before the initiation of treatment, every 2 weeks during the first month and monthly thereafter.
Huwa rakkomandat li livelli ta ’ transaminases fis- serum, bilirubin u alkaline phosphatase jiġu ċċekkjati qabel tinbeda l- kura, kull ġimagħtejn waqt l- ewwel xahar u kull xahar minn hemm ’ il quddiem.
If there is a persistent and progressive increase in serum transaminase levels that cannot be attributed to other causes, EXJADE should be interrupted.
Jekk ikun hemm żieda persistenti u progressiva fil- livelli ta ’ transaminase fis- serum li ma tistax tiġi attribwita għal kawżi oħra, EXJADE għandu jitwaqqaf.
Once the cause of the liver function test abnormalities has been clarified or after return to normal levels, cautious re-initiation of treatment at a lower dose followed by gradual dose escalation may be considered.
Meta tkun ġiet iċċarata l- kawża li wasslet biex it- testijiet tal- funzjoni tal- fwied ma jiġux normali jew wara li jaqaw lura f’ livelli normali, jista ’ jkun ikkunsidrat li terġa ’ tinbeda l- kura b’ kawtela b’ doża aktar baxxa, segwita b’ żieda gradwali tad- doża.
EXJADE is not recommended in patients with severe hepatic impairment as it has not been studied in such patients.
EXJADE mhuwiex rakkomandat f’ pazjenti li jsofru b’ indeboliment epatiku serju għax ma ġiex studjat f’ dawn il- pazjenti.
Treatment has been initiated only in patients with baseline liver transaminase levels up to 5 times the upper limit of the normal range (see section 5.2).
Il- kura nbdiet biss f’ pazjenti b’ livelli fil- linja bażi ta ’ transaminase tal- fwied sa 5 darbiet il- limitu ta ’ fuq tal- medda normali (ara sezzjoni 5. 2).
Upper gastrointestinal ulceration and haemorrhage have been reported in patients, including children and adolescents, receiving EXJADE.
Ulċerazzjoni tal- parti ta ’ fuq tas- sistema gastro- intestinali u fsada kienu rrapurtati f’ pazjenti, inklużi tfal u adoloexxenti, li, li kienu qed jirċievu EXJADE.
Multiple ulcers have been observed in some patients (see section 4.8).
Għadd ta ’ ulċeri dehru f’ xi pazjenti (ara sezzjoni 4. 8).
Physicians and patients should remain alert for signs and symptoms of gastrointestinal ulceration and haemorrhage during EXJADE therapy and promptly initiate additional evaluation and treatment if a serious gastrointestinal adverse event is suspected.
Tobba u pazjenti għandhom joqodu attenti għal sinjali u sintomi ta ’ ulċerazzjoni gastro - intestinali u fsada waqt terapija b’ EXJADE u jibdew mill- ewwel evalwazzjoni oħra u kura jekk każ avvers serju gastro- intestinali jkun suspettat.
Caution should be exercised in patients who are taking EXJADE in combination with substances that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates and in patients receiving anticoagulants (see section 4.5).
Għandha tingħata kawtela f’ pazjenti li jkunu qegħdin jieħdu EXJADE flimkien ma ’ sustanzi oħrajn li għandhom potenzjal ulċeroġeniku magħruf, bħal NSAIDs, kortikosterojdi, jew bisfosfonati orali u f’ pazjenti li qegħdin jirċievu antikoagulanti (ara sezzjoni 4. 5).
Skin rashes may appear during EXJADE treatment.
Jistgħu jidhru raxxijiet tal- ġilda waqt kura b’ EXJADE.
The rashes resolve spontaneously in most cases.
F’ ħafna każijiet, dawn imorru waħidhom.
When interruption of treatment may be necessary, treatment may be reintroduced after resolution of the rash, at a lower dose followed by gradual dose escalation.
Meta jkollha titwaqqaf il- kura, din tista ’ terġa ’ tinbeda wara li jkun għadda r- raxx, b’ doża aktar baxxa, segwita b’ żieda gradwali tad- doża.
In severe cases this reintroduction could be conducted in combination with a short period of oral steroid administration.
F’ każijiet serji, għal perijodu qasir, il- kura tista ’ terġa ’ tinbeda flimkien ma ’ sterojdi li jittieħdu mill- ħalq.
Cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving EXJADE, with the onset of the reaction occurring in the majority of cases within the first month of treatment (see section 4.8).
Każijiet ta’ sensittivtà eċċessiva serja (bħal anafilassi u anġjoedema) kienu rrappurtati f’ pazjenti li kienu qed jirċievu EXJADE, bil- bidu tar- reazzjoni sseħħ fil- maġġoranza tal- każijiet fi żmien l- ewwel xahar ta ’ kura (ara sezzjoni 4. 8).
If such reactions occur, EXJADE should be discontinued and appropriate medical intervention instituted.
Jekk iseħħu dawn ir- reazzjonijiet, EXJADE għandu jitwaqqaf u għandhom jitħejjew l- interventi mediċi xierqa.
Auditory (decreased hearing) and ocular (lens opacities) disturbances have been reported (see section 4.8).
Kien hemm rapporti ta ’ disturbi fis- smigħ (nuqqas ta ’ smigħ) u fl- għajnejn (opaċità tal- lenti) (ara sezzjoni 4. 8).
Auditory and ophthalmic testing (including fundoscopy) is recommended before the start of treatment and at regular intervals thereafter (every 12 months).
Testijiet tas- smigħ u ta ’ l- għajnejn (inkluż fundoskopija) huma rakkomandati qabel tinbeda t- terapija u b’ intervalli regolari minn hemm ’ il quddiem (kull 12- il xahar).
If disturbances are noted during the treatment, dose reduction or interruption may be considered.
Jekk jidhru disturbi waqt il- kura, għandu jiġi ikkunsidrat tnaqqis fid- doża jew twaqqif tal- kura.
There have been post-marketing reports of leukopenia, thrombocytopenia or pancytopenia, or aggravation of these cytopenias in patients treated with EXJADE.
Wara t- tqegħid fis- suq kien hemm rapporti ta ’ lewkopenija, tromboċitopenija jew panċitopenija, jew aggravament ta ’ dawn iċ- ċitopeniji f’ pazjenti kkurati b’ EXJADE.
Most of these patients had pre- existing haematological disorders that are frequently associated with bone marrow failure.
Il- biċċa l- kbira tal- pazjenti diġà kellhom disturbi ematoloġiċi eżistenti li kienu assoċjati b’ mod frekwenti ma ’ insuffiċjenza tal - mudullun tal- għadam.
However, a contributory or aggravating role cannot be excluded.
Madankollu, ma jistax jiġi eskluż rwol kontributorju jew aggravanti.
Interruption of treatment should be considered in patients who develop unexplained cytopenia.
Twaqqif tal- kura għandu jiġi kkunsidrat f’ pazjenti li jiżviluppaw ċitopenija mingħajr raġuni.
Monthly monitoring of serum ferritin is recommended in order to assess the patient’ s response to therapy (see section 4.2).
Monitoraġġ kull xahar tal- ferritin fis- serum huwa rakkomandat sabiex ikun stmat ir- rispons tal- pazjent għat- terapija (ara sezzjoni 4. 2).
If serum ferritin falls consistently below 500 µg/ l, an interruption of treatment should be considered.
Jekk il- ferritin fis- serum jaqa b’ mod konsistenti taħt 500 µg/ l, għandu jiġi ikkunsidrat twaqqif tal- kura.
5 The results of the tests for serum creatinine, serum ferritin and serum transaminases should be recorded and regularly assessed for trends.
Ir- riżultati tat- testijiet għall- krejatinina fis- serum, ferritin fis- serum u transaminase fis- serum għandhom jinżammu u jintużaw sabiex joħorġu t- tendenzi.
The results should also be noted in the provided patient’ s booklet.
Ir- riżultati għandhom jinkitbu wkoll fil - fuljett tal- pazjent provdut.
In the 1-year clinical studies growth and sexual development of paediatric patients treated with EXJADE were not affected.
5 Fi studji kliniċi ta ’ sena, l- iżvilupp fiżiku u sesswali ta ’ pazjenti pedjatriċi kurati b’ EXJADE ma kienux effettwati.
However, as a general precautionary measure in the management of paediatric patients with transfusional iron overload, body weight, height and sexual development should be monitored at regular intervals (every 12 months).
Madankollu, bħala miżura prekawzjonali ġenerali fl- immaniġġar ta ’ pazjenti pedjatriċi li jkollhom tagħbija żejda ta ’ ħadid minħabba trasfużjoni, il- piż tal- ġisem, it- tul, u l- iżvilupp sesswali għandhom ikunu monitorati f’ intervalli regolari (kull 12- il xahar).
Cardiac dysfunction is a known complication of severe iron overload.
Disfunzjoni kardijaka hija komplikazzjoni magħrufa ta ’ tagħbija żejda qawwija tal- ħadid.
Cardiac function should be monitored in patients with severe iron overload during long-term treatment with EXJADE.
Il- funzjoni kardijaka għandha tkun monitorata f’ pazjenti b’ tagħbija żejda qawwija tal- ħadid waqt kura fit- tul b’ EXJADE.
The tablets contain lactose (1.1 mg lactose for each mg of deferasirox).
Il- pilloli fihom lactose (1. 1 mg lactose għal kull mg ta ’ deferasirox).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or severe lactase deficiency should not take this medicine.
Pazjenti li għandhom problemi ereditarji rari ta ’ intolleranza għall- galactose, nuqqas ta ’ Lapp lactase, malassorbiment tal- glucose - galactose jew defiċjenza qawwija ta ’ lactase m’ għandhomx jieħdu din il- mediċina.
Caution should be exercised when deferasirox is combined with strong UDP- glucuronosyl transferase (UGT) inducers, or CYP2C8 substrates (see section 4.5).
L- użu ta ’ deferasirox flimkien ma ’ mediċini ta ’ kontra l- aċidu fl- istonku li jkun fihom l- aluminium mhux rakkomandat Għandha ssir attenzjoni meta deferasirox jingħata ma ’ indutturi qawwija ta ’ UDP - glucuronosyl transferase (UGT), jew ma ’ sottostrati ta ’ CYP2C8 (ara sezzjoni 4. 5).
The concomitant administration of EXJADE and aluminium-containing antacid preparations has not been formally studied.
L- użu ta ’ EXJADE flimkien ma ’ mediċini ta ’ kontra l- aċidu fl- istonku li jkun fihom l- aluminju ma ġiex studjat b’ mod formali.
Although deferasirox has a lower affinity for aluminium than for iron, it is not recommended to take EXJADE tablets with aluminium-containing antacid preparations (see section 4.4).
(ara sezzjoni 4. 4).
EXJADE must therefore be taken on an empty stomach at least 30 minutes before food, preferably at the same time each day (see sections 4.2 and 5.2).
Għaldaqstant, EXJADE għandu jittieħed fuq stonku vojt mill- anqas nofs siegħa qabel l- ikel, l- aħjar fl- istess ħin kuljum (ara sezzjonijiet 4. 2 u 5. 2).
Deferasirox metabolism depends on UGT enzymes.
Il- metaboliżmu ta ’ deferasirox jiddependi fuq l- enzimi UGT.
In a healthy volunteer study, the concomitant administration of EXJADE (single dose of 30 mg/ kg) and the potent UGT inducer, rifampicin, (repeated dose of 600 mg/ day) resulted in a decrease of deferasirox exposure by 44% (90% CI:
Fi studju b’ voluntiera b’ saħħithom, l - għotja fl- istess ħin ta ’ EXJADE (doża waħda ta ’ 30 mg/ kg) u l- induttur qawwi UGT, rifampicin (doża ripetuta ta ’ 600 mg/ jum) irriżultat fi tnaqqis ta ’ l- esponiment għal deferasirox b’ 44% (90% CI:
Therefore, the concomitant use of EXJADE with potent UGT inducers (e. g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a decrease in EXJADE efficacy (see section 4.4).
Għalhekk, l- użu ta ’ EXJADE flimkien ma ’ indutturi qawwija ta ’ UGT (eż. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) jista ’ jwassal għal tnaqqis fl- effikaċja ta ’ EXJADE (ara sezzjoni 4. 4).
The patient ’ s serum ferritin should be monitored during and after the combination, and the dose of EXJADE adjusted if necessary.
Il- ferritin fis- serum tal- pazjent għandu jkun monitorat waqt u wara li jingħataw iż- żewġ mediċini, u d- doża ta ’ EXJADE mibdula jekk ikun hemm bżonn.
In a healthy volunteer study, the concomitant administration of EXJADE and midazolam (a CYP3A4 probe substrate) resulted in a decrease of midazolam exposure by 17% (90% CI:
Fi studju b’ voluntiera b’ saħħithom, l- għotja ta ’ EXJADE flimkien ma ’ midazolam (sottostrati tal - prowb għal CYP3A4) ikkawżat tnaqqis fl- esponiment għal midazolam bi 17% (90% CI:
In the clinical setting, this effect may be more pronounced.
Fil- qasam kliniku, dan l- effett jista ’ jkun aktar qawwi.
Therefore, due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4 (e. g. ciclosporin, simvastatin, hormonal contraceptive agents, bepridil, ergotamine).
Għalhekk, minħabba li jista ’ jkun hemm tnaqqis fl- effikaċja, għandha ssir attenzjoni meta deferasirox jitħallat ma ’ sustanzi li jkunu metabolizzati permezz ta ’ CYP3A4 (eż. ciclosporin, simvastatin, sustanzi kontraċettivi ormonali, bepridil, ergotamine).
The safety of EXJADE in combination with other iron chelators has not been established.
Is- sigurtà ta ’ EXJADE meta jingħata flimkien ma ’ kelaturi tal- ħadid oħrajn ma ġietx stabilita.
Therefore, it must not be combined with other iron chelator therapies (see section 4.3).
Għaldaqstant, m’ għandux jingħata flimkien ma ’ terapiji oħra ta ’ kelaturi tal- ħadid (ara sezzjoni 4. 3).
No interaction was observed between EXJADE and digoxin in healthy adult volunteers.
Ma deherx li EXJADE u digoxin ma jaqblux bejniethom f’ voluntiera adulti b’ saħħithom.
In a healthy volunteer study, the concomitant administration of deferasirox as a moderate CYP2C8 inhibitor (30 mg/ kg daily), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and C max about 2.3-fold (90% CI [2.03-2.63]) and 1.6-fold (90% CI
Fi studju b’ voluntiera b’ saħħithom, l- għoti f’ daqqa ta ’ deferasirox bħala inibitur moderat ta ’ CYP2C8 (30 mg/ kg), u repaglinide, substrat ta ’ CYP2C8, mogħti bħala doża waħda ta ’ 0. 5 mg, żied l- AUC u s - Cmax ta ’ repaglinide b’ madwar 2. 3 drabi aktar (90% CI [2. 03- 2. 63]) u b’ 1. 6 drabi aktar (90% CI [1. 42- 1. 84]), rispettivament.
Since the interaction has not been established with dosages higher than 0.5 mg for repaglinide, the concomitant use of deferasirox with repaglinide should be avoided.
Minħabba li l- interazzjoni ma ġietx stabbilita b’ dożaġġi ogħla minn 0. 5 mg għal repaglinide, l- użu f’ daqqa ta ’ deferasirox u repaglinide għandu jiġi evitat.
If the combination appears necessary, careful clinical and blood glucose monitoring should be performed
Jekk it- taħlita tidher li hija meħtieġa, għandu jsir b’ attenzjoni monitoraġġ kliniku u taz- zokkor fid- demm (ara
6 (see section 4.4).
6 sezzjoni 4. 4).
An interaction between deferasirox and other CYP2C8 substrates like paclitaxel cannot be excluded (see section 4.4).
Mhux eskluż li deferasirox u substrati oħrajn ta ’ CYP2C8 bħal paclitaxel ma jaqblux bejniethom (ara sezzjoni 4. 4).
The concomitant administration of EXJADE and vitamin C has not been formally studied.
L- użu konkomitanti ta ’ EXJADE ma ’ Vitamina Ċ ma kienx studjat b’ mod formali.
Doses of vitamin C up to 200 mg per day have not been associated with adverse consequences.
Dożi sa ’ 200 mg kuljum ma kienux assoċjati ma ’ effetti avversi.
The concomitant administration of EXJADE with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral bisphosphonates may increase the risk of gastrointestinal toxicity (see section 4.4).
L- għoti fl- istess ħin ta ’ EXJADE ma ’ sustanzi li għandhom potenzjal ulċeroġeniku bħal NSAIDs (inkluż acetylsalicylic acid f’ dożaġġi għoljin), kortikosterojdi, jew bisfosfonati orali, jista ’ jżid ir - riskju ta ’ tossiċità gastrointestinali (ara sezzjoni 4. 4).
The concomitant administration of EXJADE with anticoagulants may also increase the risk of gastrointestinal haemorrhage.
L- għoti f’ daqqa ta ’ EXJADE u antikoagulanti jista ’ jżid ukoll ir- riskju ta ’ emorraġija gastro- intestinali.
Close clinical monitoring is required when deferasirox is combined with these substances.
Monitoraġġ kliniku mill- qrib huwa meħtieġ meta deferasirox jiġi kkombinat ma ’ dawn is- sustanzi.
No clinical data on exposed pregnancies are available for deferasirox.
Tqala Għal deferasirox m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Studies in animals have shown some reproductive toxicity at maternally toxic doses (see section 5.3).
Studji fuq bhejjem urew xi tossiċità fuq is- sistema riproduttiva f’ dożi li kienu tossiċi għall- omm (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Ir- riskju potenzjali li jista ’ jkun hemm fuq in- nies mhux magħruf.
As a precaution, it is recommended that EXJADE not be used during pregnancy unless clearly necessary.
Bħala prekawzjoni, huwa rakkomandat li EXJADE ma jintużax waqt it- tqala sakemm ma jkunx hemm bżonn ċar ħafna.
In animal studies, deferasirox was found to be rapidly and extensively secreted into maternal milk.
Treddigħ Studji fuq bhejjem urew li deferasirox ħareġ malajr u b’ mod estensiv mal- ħalib ta ’ l- omm.
No effect on the offspring was noted.
Ma deherx li kien hemm effetti fuq il- wild.
It is not known if deferasirox is secreted into human milk.
Mhux magħruf jekk deferasirox joħroġx fil- ħalib tal- mara.
Breast- feeding while taking EXJADE is not recommended.
Mhux rakkomandat li tredda ’ waqt li tieħu EXJADE.
No fertility data is available for humans.
Fertilità M’ hemmx tagħrif dwar il- fertilità fil- bniedem.
In animals, no adverse effects on male or female fertility were found (see section 5.3).
Fil- bhejjem ma kienx hemm effetti avversi fuq il - fertilità tal- bhejjem maskili jew femminili (ara sezzjoni 5. 3).
No studies on the effects of EXJADE on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti ta ’ EXJADE fuq il- ħila biex issuq jew tħaddem magni.
Patients experiencing the uncommon adverse reaction of dizziness should exercise caution when driving or operating machinery (see section 4.8).
Pazjenti li jħossu xi reazzjonijiet avversi mhux komuni ta ’ sturdament għandhom joqgħodu attenti meta jkunu qed isuqu jew iħaddmu magni (ara sezzjoni 4. 8).
The most frequent reactions reported during chronic treatment with EXJADE in adult and paediatric patients include gastrointestinal disturbances in about 26% of patients (mainly nausea, vomiting, diarrhoea or abdominal pain) and skin rash in about 7% of patients.
L- aktar reazzjonijiet frekwenti li kienu rappurtati waqt kura kronika b’ EXJADE f’ pazjenti adulti u pedjatriċi jinkludu disturbi gastro- intestinali f’ madwar 26% tal- pazjenti (l- aktar tqalligħ, rimettar, dijarea jew uġigħ addominali) u raxx tal- ġilda f’ madwar 7% tal- pazjenti.
Diarrhoea is reported more commonly in paediatric patients aged 2 to 5 years than in older patients.
Dijarea tiġi rappurtata aktar ta ’ spiss f’ pazjenti pedjatriċi ta ’ etajiet bejn 2 u 5 snin milli f’ pazjenti aktar anzjani.
These reactions are dose- dependent, mostly mild to moderate, generally transient and mostly resolve even if treatment is continued.
Dawn ir - reazzjonijiet huma marbuta mad- doża, l- aktar ħfief jew moderati, u ġeneralment jgħaddu waħidhom u jmorru għal kollox anki jekk titkompla l- kura.
Indeed, in some cases, only a stabilisation of the serum creatinine values has been observed after dose reduction (see section 4.4).
Tassew, f’ xi każijiet, intlaħqu biss valuri stabbli tal- krejatinina fis- serum wara li tnaqqset id- doża (ara sezzjoni 4. 4).
7 Gallstones and related biliary disorders were reported in about 2% of patients.
Kalkli u disturbi tal- marrara kienu rapurtati f’ madwar 2% tal- pazjenti.
Elevations of liver transaminases were reported as an adverse drug reaction in 2% of patients.
Żidiet f’ transaminase tal- fwied kienu rrappurtati bħala reazzjoni avversa għall- mediċina f’ 2% tal- pazjenti.
Elevations of transaminases greater than 10 times the upper limit of the normal range, suggestive of hepatitis, were uncommon (0.3%).
Żidiet ta 'transaminase tal - fwied akbar minn 10 darbiet il- limitu ta ’ fuq tal- medda normali, li jindika li hemm epatite, ma kienux komuni (0. 3%).
During postmarketing experience, hepatic failure, sometimes fatal, has been reported with EXJADE, especially in patients with pre-existing liver cirrhosis (see section 4.4).
7 għall- mewt, kienet irrappurtata b’ EXJADE, l- aktar f’ pazjenti li kellhom minn qabel ċirrożi tal- fwied (ara sezzjoni 4. 4).
As with other iron chelator treatment, high-frequency hearing loss and lenticular opacities (early cataracts) have been uncommonly observed in patients treated with EXJADE (see section 4.4).
Bħal ma jiġri b’ kelaturi tal- ħadid oħrajn, telf tas- smigħ ta ’ frekwenzi għoljin u opaċità tal- lenti (katarretti bikrija) kienu osservati f’ okkażjonijiet mhux komuni f’ pazjenti kurati b’ EXJADE (ara sezzjoni 4. 4).
Adverse reactions are ranked below using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000); not known (cannot be estimated form the available data).
Komuni ħafna (> 1/ 10); komuni (> 1/ 100, < 1/ 10); mhux komuni (> 1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000); mhux magħruf (ma tistax tittieħed stima mid- dejta disponibbli).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond is- serjetà tagħhom, bl- aktar serji jitniżżlu l - ewwel.
U Table 1
Tabella 1
Blood and lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika Panċitopenija1, tromboċitopenija1 Mhux magħruf:
Early cataract, maculopathy
Katarretti bikrija, makulopatija
Hearing loss
Telf tas- smigħ
Pharyngolaryngeal pain
Uġigħ fil- farinġi u fil- larinġi
Diarrhoea, constipation, vomiting, nausea, abdominal pain, abdominal distension, dyspepsia
Dijarea, stitikezza, rimettar, tqalligħ, uġigħ addominali, nefħa addominali, dispepsja
Gastrointestinal haemorrhage, gastric ulcer (including multiple ulcers), duodenal ulcer, gastritis
Emorraġija gastro- intestinali, ulċera fl- istonku (inklużi ħafna ulċeri), ulċera fid- duwodenu, gastrite
Renal
Rari:
Rare: and urinary disorders Very common:
Disturbi fil- kliewi u fis- sistema urinarja
Oesophagitis Blood creatinine increased Proteinuria Renal tubulopathy (acquired Fanconi’ s syndrome), glycosuria Acute renal failure 1 P P
Żieda tal- krejatinina fid- demm Proteina fl- awrina Tubulopatija renali (sindrome ta ’ Fanconi akkwistat), zokkor fl - awrina Insuffiċjenza renali akuta1
Rash, pruritus Pigmentation disorder Leukocytoclastic vasculitis 1, urticaria 1 P P P
Raxx, ħakk Tibdil fil- lewn tal- ġilda Vaskulite lewkoċitoklastika1, urtikarja1
Pyrexia, oedema, fatigue
Deni, edema, għeja
Hypersensitivity reactions (including anaphylaxis and angioedema) 1 P
Reazzjonijiet ta ’ sensittività eċċessiva (inklużi anafilassi u anġjoedema)
Transaminases increased Hepatitis, cholelithiasis Hepatic failure 1 P P
Żieda fit- transaminases Epatite, kolelitijażi Insuffiċjenza epatika1
Psychiatric disorders
Disturbi psikjatriċi 1
Anxiety, sleep disorder
Ansjetà, disturbi fl- irqad
P P Adverse reactions reported during postmarketing experience.
Reazzjonijiet avversi rrappurtati wara t- tqegħid fis- suq.
These are derived from spontaneous reports for which it is not always possible to reliably establish frequency or a causal relationship to exposure to the medicinal product.
Dawn jiġu minn rapporti spontanji li għalihom mhux dejjem ikun possibli li tiġi stabbilita l- frekwenza jew ir- relazzjoni mal- kawża għall- esponiment mal- prodott mediċinali.
8 4.9 Overdose
8 4. 9 Doża eċċessiva
Cases of overdose (2-3 times the prescribed dose for several weeks) have been reported.
Każijiet ta ’ doża eċċessiva (2- 3 darbiet id- dożi ordnata għal bosta ġimgħat) kienu rrappurtati.
In one case, this resulted in subclinical hepatitis which resolved after a dose interruption.
F’ każ wieħed dan wassal għal epatite sottoklinika li għaddiet wara li twaqqfet id- doża.
Single doses of 80 mg/ kg in iron-overloaded thalassaemic patients caused mild nausea and diarrhoea.
Dożi waħdiet ta ’ 80 mg/ kg li ngħataw lill- pazjenti talassemiċi li kellhom tagħbija żejda ta ’ ħadid sofrew minn tqalligħ ħafif u dijarea.
Acute signs of overdose may include nausea, vomiting, headache and diarrhoea.
Sinjali akuti ta ’ doża eċċessiva jistgħu jinkludu tqalligħ, rimettar, uġigħ ta ’ ras u dijarea.
Overdose may be treated by induction of emesis or by gastric lavage, and by symptomatic treatment.
Doża eċċessiva tista ’ tkun ikkurata billi iġġiegħel l- individwu jirremetti, jew billi jinħasel l- istonku, u kura għas- sintomi.
Iron chelating agent, ATC code:
Kelatur tal- ħadid, Kodiċi ATC:
Deferasirox is an orally active chelator that is highly selective for iron (III).
Deferasirox huwa kelatur attiv li jittieħed mill- ħalq li huwa selettiv ħafna għall- ħadid (III).
It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio.
Huwa ligand tridentat li jeħel mal- molekula tal- ħadid b’ affinità għolja f’ proporzjon ta ’ 2: 1.
Deferasirox promotes excretion of iron, primarily in the faeces.
Deferasirox jinkuraġġixxi l- eskrezzjoni tal- ħadid, l- aktar ma ’ l- ippurgar.
Deferasirox has low affinity for zinc and copper, and does not cause constant low serum levels of these metals.
Deferasirox għandu affinità baxxa għaż - żingu u r- ram, u ma jikkawżax livelli baxxi kostanti ta ’ dawn il- metalli fis- serum.
In an iron-balance metabolic study in iron-overloaded adult thalassaemic patients, EXJADE at daily doses of 10, 20 and 40 mg/ kg induced the mean net excretion of 0.119, 0.329 and 0.445 mg Fe/ kg body weight/ day, respectively.
Fi studju dwar il- metaboliżmu tal- bilanċ tal- ħadid f’ pazjenti talassemiċi adulti li għandhom tagħbija żejda tal- ħadid, dożi ta ’ 10, 20 u 40 mg/ kg EXJADE kuljum wasslu għal medja ta ’ eskrezzjoni netta ta ’ 0. 119, 0. 329 u 0. 445 mg/ Fe/ kg piż tal- ġisem kuljum rispettivament.
EXJADE has been investigated in 411 adult (age ≥ 16 years) and 292 paediatric patients (aged 2 to < 16 years) with chronic iron overload due to blood transfusions.
Saru investigazzjonijiet dwar EXJADE f’ 411 pazjenti adulti (≥16- il sena) u 292 pazjenti pedjatriċi (minn 2 sa < 16- il sena) b’ tagħbija żejda kronika tal- ħadid minħabba trasfużjonijiet tad- demm.
Of the paediatric patients 52 were aged 2 to 5 years.
52 tal - pazjenti pedjatriċi kellhom bejn 2 u 5 snin.
The underlying conditions requiring transfusion included beta-thalassaemia, sickle cell disease and other congenital and acquired anaemias (myelodysplastic syndromes, Diamond- Blackfan syndrome, aplastic anaemia and other very rare anaemias).
Il- kundizzjonijiet li kienu jinħtieġu trasfużjonijiet kienu jinkludu beta- talessimja, mard tas- sickle cell u mard ieħor konġenitu u anemiji mhux konġeniti (sindromi majlodisplastiċi, sindrome ta ’ Diamond- Blackfan, anemiji aplastiċi, u anemiji oħrajn rari ħafna).
Daily treatment at doses of 20 and 30 mg/ kg for one year in frequently transfused adult and paediatric patients with beta-thalassaemia led to reductions in indicators of total body iron; liver iron concentration was reduced by about -0.4 and -8.9 mg Fe/ g liver (biopsy dry weight (dw)) on average, respectively, and serum ferritin was reduced by about -36 and -926 µg/ l on average, respectively.
L- indikaturi tal- ħadid totali fil- ġisem urew tnaqqis meta pazjenti adulti u pedjatriċi li jsofru minn beta - talessimja u li kellhom trasfużjonijiet frekwenti ngħataw kura b’ dożi ta ’ 20 u 30 mg/ kg kuljum għal sena; il- konċentrazzjoni tal- ħadid fil- fwied tnaqqset b’ medja ta ’ madwar - 0. 4 u - 8. 9 Fe/ g fwied (piż niexef tal- bijopsija (dw)) rispettivament, u l- ferritin fis- serum tnaqqas b’ medja ta ’ madwar - 36 u - 926 µg/ l rispettivament.
At these same doses the ratios of iron excretion: iron intake were 1.02 (indicating net iron balance) and 1.67 (indicating net iron removal), respectively.
B’ dawn l- istess dożi, il- proporzjon tal- ħadid eskretat: ħadid li ttieħed kien 1. 02 (li juri li kien hemm nett bilanċ tal- ħadid) u 1. 67 (li juri li kien hemm tneħħijja netta tal- ħadid), rispettivament.
EXJADE induced similar responses in iron- overloaded patients with other anaemias.
EXJADE wassal għal reazzjonijiet simili f’ pazjenti li kellhom tagħbija żejda ta ’ ħadid b' anemiji oħrajn.
Daily doses of 10 mg/ kg for one year could maintain liver iron and serum ferritin levels and induce net iron balance in patients receiving infrequent transfusions or exchange transfusions.
Pazjenti li kienu qed jirċievu trasfużjonijiet mhux frekwenti jew trasfużjonijiet ta ’ tibdil tad- demm u li ngħataw dożi ta ’ 10 mg/ kg kuljum għal sena, żammew il- livelli ta ’ ħadid fil- fwied u ta ’ ferritin fis- serum u wasslu għal bilanċ nett tal- ħadid.
Serum ferritin assessed by monthly monitoring reflected changes in liver iron concentration indicating that trends in serum ferritin can be used to monitor response to therapy.
Meta l- livelli ta ’ ferritin fis- serum kienu mkejla b’ monitoraġġ kull xahar, dawn kienu jirriflettu tibdil fil- konċentrazzjoni tal- ħadid fil- fwied.
Limited clinical data (29 patients with normal cardiac function at baseline) using MRI indicate that treatment with EXJADE 10-30 mg/ kg/ day for 1 year may also reduce levels of iron in the heart (on average, MRI T2* increased from 18.3 to 23.0 milliseconds).
Tagħrif kliniku limitat (29 pazjent b’ funzjoni kardijaka normali mal- linja bażika) bl- użu ta ’ MRI jindika li kura b ’ EXJADE 10- 30 mg/ kg/ jum għal sena tista ’ tnaqqas ukoll il- livelli tal- ħadid fil - qalb (medja, MRI T2 * żieda minn 18. 3 għal 23. 0 millisekondi).
The principal analysis of the pivotal comparative study in 586 patients suffering from beta- thalassaemia and transfusional iron overload did not demonstrate non-inferiority of EXJADE to deferoxamine in the analysis of the total patient population.
L- analiżi prinċipali ta ’ l- istudju kumparattiv pivitali f’ 586 pazjent li jsofru minn beta- talessimja u tagħbija żejda tal- ħadid mit- trasfużjoni ma wrietx li EXJADE ma kienx inferjuri għal deferoxamine fl - analiżi tal- popolazzjoni totali tal- pazjenti.
It appeared from a post-hoc analysis of this study that, in the subgroup of patients with liver iron concentration ≥ 7 mg Fe/ g dw treated with EXJADE (20 and 30 mg/ kg) or deferoxamine (35 to ≥ 50 mg/ kg), the non-inferiority criteria were achieved.
Minn analiżi li saret wara dan l- istudju deher li, fis - sottogrupp tal- pazjenti li kellhom konċentrazzjoni tal- ħadid fil- fwied ≥7 mg Fe/ g dw kurati b’ EXJADE (20 u 30 mg/ kg) jew deferoxamine (35 sa ≥50 mg/ kg), il- kriterji li juru li ma kienx inferjuri intlaħqu.
However, in patients with liver iron concentration < 7 mg Fe/ g dw treated with EXJADE (5 and 10 mg/ kg) or deferoxamine (20 to 35 mg/ kg), non-inferiority was not established due to imbalance in the dosing of the two chelators.
Madankollu, f’ pazjenti li kellhom konċentrazzjoni tal- ħadid fil- fwied < 7mg Fe/ g dw kurati b’ EXJADE (5 u 10 mg/ kg) jew deferoxamine (20 sa 35 mg/ kg), ma ġiex stabbilit jekk ma kienx 9 inferjuri minħabba żbilanċ fid- dużaġġi taż- żewġ kelaturi.
This imbalance occurred because patients on deferoxamine were allowed to remain on their pre-study dose even if it was higher than the protocol specified dose.
Dan l- iżbilanċ seħħ minħabba li l- pazjenti li kienu fuq deferoxamine tħallew fuq id- doża ta ’ qabel ma beda l- istudju anki jekk kienet ogħla minn dik speċifikata fil- protokoll.
Fifty- six patients under the age of 6 years participated in this pivotal study, 28 of them receiving EXJADE.
Sitta u ħamsin pazjent taħt is- 6 snin ħadu sehem f’ dan l- istudju pivitali, 28 minnhom ingħataw EXJADE.
9 It appeared from preclinical and clinical studies that EXJADE could be as active as deferoxamine when used in a dose ratio of 2:1 (i. e. a dose of EXJADE that is numerically half of the deferoxamine dose).
Minn studji ta ’ qabel l- użu kliniku u studji kliniċi deher li EXJADE jista ’ jkun attiv daqs deferoxamine meta jintuża f’ proporzjon ta ’ doża ta ’ 2: 1 (i. e. doża ta ’ EXJADE li tiġi numerikament nofs dik tad- doża ta ’ deferoxamine).
However, this dosing recommendation was not prospectively assessed in the clinical trials.
Madankollu, din ir- rakkomandazzjoni ta ’ dużaġġ ma kinetx ġiet meqjusa qabel ma bdew il- provi kliniċi.
In addition, in patients with liver iron concentration ≥ 7 mg Fe/ g dw with various rare anaemias or sickle cell disease, EXJADE up to 20 and 30 mg/ kg produced a decrease in liver iron concentration and serum ferritin comparable to that obtained in patients with beta-thalassaemia.
Minbarra hekk, f’ pazjenti b’ konċentrazzjoni tal- ħadid fil- fwied ta ’ ≥7 mg Fe/ g dw li kellhom diversi anemiji rari jew marda tas- sickle cell, meta ngħataw sa 20 u 30 mg/ kg EXJADE kien hemm tnaqqis fil- konċentrazzjoni tal- ħadid fil- fwied u tal- ferritin fis- serum li jikkumpara ma ’ dak li nkiseb f’ pazjenti b’ beta- talessimja.
The absolute bioavailability (AUC) of deferasirox from
Assorbiment Deferasirox jiġi assorbit wara li jittieħed mill- ħalq u tintlaħaq l- ogħla konċentrazzjoni fil- plażma (tmax) f' ħin medju ta ’ madwar 1. 5 sa 4 sigħat.
EXJADE tablets is about 70% compared to an intravenous dose.
Il- biodisponibiltà assoluta (AUC) ta ’ deferasirox minn pilloli ta ’ EXJADE hija madwar 70% meta mqabbla ma ’ doża li tingħata għal ġol- vina.
Total exposure (AUC) was approximately doubled when taken along with a high-fat breakfast (fat content > 50% of calories) and by about 50% when taken along with a standard breakfast.
L- esponiment totali (AUC) kien madwar id- doppju meta ttieħed ma ’ kolazzjon b’ livell għoli ta 'xaħam (kontenut ta ’ xaħam > 50% tal- kaloriji) u jiżdied b’ madwar 50% meta ttieħed ma ’ kolazzjon normali.
13– 25%) elevated when taken 30 minutes before meals with normal or high fat content.
Il - biodisponibiltà (AUC) ta ’ deferasirox kienet moderatament (madwar 13- 25%) għolja meta ttieħed 30 minuta qabel l- ikel ma ’ kontenut normali jew għoli ta ’ xaħam.
Deferasirox is highly (99%) protein bound to plasma proteins, almost exclusively serum albumin, and has a small volume of distribution of approximately 14 litres in adults.
Distribuzzjoni Deferasirox jintrabat bil- qawwa (99%) mal- proteini tal- plażma, kważi esklużivament ma ’ albumin tas - serum, u għandu volum żgħir ta ’ distribuzzjoni fl- adulti ta ’ madwar 14- il litru.
Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion.
Bijotrasformazzjoni Ir- rotta metabolika ewlenija għal deferasirox hija glukoronidazzjoni, b' eskrezzjoni sussegwenti mill - marrara.
Deconjugation of glucuronidates in the intestine and subsequent reabsorption (enterohepatic recycling) is likely to occur.
Dekonjugazzjoni ta ’ glukoronidati fl- intestini u wara dan, huwa probabbli li jseħħ ri - assorbiment (riċiklaġġ enteroħepatiku).
Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent UGT1A3.
Il- glukoronidament ewlieni ta ’ deferasirox iseħħ b’ UGT1A1 u f’ ammonti iżgħar b’ UGT1A3.
CYP450-catalysed (oxidative) metabolism of deferasirox appears to be minor in humans (about 8%).
Il- metaboliżmu (ossidattiv) ta ’ deferasirox permezz tal- kataliżi b’ CYP450 jidher li huwa minuri fil- bniedem (madwar 8%).
No inhibition of deferasirox metabolism by hydroxyurea was observed in vitro.
Ma deherx li kien hemm impediment ta ’ deferasirox b’ metaboliżmu minn idrossijureja in vitro.
Deferasirox and its metabolites are primarily excreted in the faeces (84% of the dose).
Eliminazzjoni L- eskrezzjoni ta 'deferasirox u l- metaboli sseħħ primarjament fl- ippurgar (84% tad- doża).
The mean elimination half-life (t 1/ 2)
L - eskrezzjoni ta ’ deferasirox u l- metaboli tiegħu permezz tal- kliewi hija minima (8% tad- doża).
ranged from 8 to 16 hours.
Il- medja tal- half- life ta ’ l- eliminazzjoni (t½) kienet bejn 8 u 16- il siegħa.
The transporters MRP2 and MXR (BCRP) are involved in the biliary excretion of deferasirox.
It- trasportaturi MRP2 u MXR (BCRP) huma nvoluti fl- eskrezzjoni ta ’ deferasirox mill- marrara.
The C max and AUC 0-24h of deferasirox increase approximately linearly with dose under steady-state
Linjarità/ nuqqas ta ’ linjarità Iż- żieda f' Cmax u AUC0- 24 ta ’ deferasirox hija bejn wieħed u ieħor linjari mad- doża taħt kundizzjonijiet fissi.
Upon multiple dosing exposure increased by an accumulation factor of 1.3 to 2.3.
Wara ħafna dużaġġi l- esponiment żdied b’ fattur ta ’ akkumulazzjoni ta ’ bejn 1. 3 sa 2. 3.
Paediatric patients The overall exposure of adolescents (12 to ≤ 17 years) and children (2 to < 12 years) to deferasirox after single and multiple doses was lower than that in adult patients.
Karatteristiċi fil- pazjenti Pazjenti pedjatriċi L- esponiment totali ta ’ l- adolexxenti (12 sa ≤17- il sena) u tfal (2 sa < 12- il sena) għal deferasirox wara doża waħda jew dożi multipli, kien aktar baxx minn dak f’ pazjenti adulti.
In children younger than 6 years old exposure was about 50% lower than in adults.
Fi tfal taħt is- 6 snin, l - esponiment kien madwar 50% aktar baxx minn dak ta ’ l- adulti.
Since dosing is individually adjusted according to response this is not expected to have clinical consequences.
Peress li d- dużaġġ għandu jkun mibdul b’ mod individwali skond ir- rispons, mhux mistenni li dan għandu jkollu konsegwenzi kliniċi.
Gender Females have a moderately lower apparent clearance (by 17.5%) for deferasirox compared to males.
10 Sess In- nisa għandhom tneħħija apparenti moderatament aktar baxxa (b’ 17. 5%) għal deferasirox meta mqabbla ma ’ l- irġiel.
Elderly patients The pharmacokinetics of deferasirox have not been studied in elderly patients (aged 65 or older).
Pazjenti anzjani Il- farmakokinetika ta ’ deferasirox f’ pazjenti anzjani ma kienetx studjata (ta ’ 65 sena jew akbar).
10 Renal or hepatic impairment The pharmacokinetics of deferasirox have not been studied in patients with renal or hepatic impairment.
Indeboliment renali jew tal- fwied Il- farmakokinetika ta ’ deferasirox ma kienetx studjata f’ pazjenti b’ indeboliment renali jew tal- fwied.
The pharmacokinetics of deferasirox were not influenced by liver transaminase levels up to 5 times the upper limit of the normal range.
Il- farmakokinetika ta ’ deferasirox ma kienetx effettwata minn livelli ta ’ transaminase tal- fwied sa 5 darbiet l- ogħla limitu tal- medda normali.
Preclinical data reveal no special hazard for patients with iron overload, based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.
Informazzjoni ta ’ qabel l- użu kliniku, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni jew riskju ta ’ kanċer, ma turi l- ebda periklu speċjali għall- pazjenti b’ tagħbija żejda tal- ħadid.
The main findings were kidney toxicity and lens opacity (cataracts).
L- aktar li nstabu kienu tossiċità fil- kliewi u opacità tal- lenti (katarretti).
Similar findings were observed in neonatal and juvenile animals.
Kienu osservati sejbiet simili f’ bhejjem tat- twelid jew ta ’ età żgħira ħafna.
The kidney toxicity is considered mainly due to iron deprivation in animals that were not previously overloaded with iron.
It - tossiċità fil- kliewi hija meqjusa l- aktar minħabba nuqqas ta ’ ħadid f’ bhejjem li ma kellhomx tagħbija żejda tal- ħadid minn qabel.
Tests of genotoxicity in vitro were either negative (Ames test, chromosomal aberration test) or positive (V79 screen).
Testijiet ta ’ l- effett tossiku fuq il- ġeni in vitro kienu jew negattivi (test Ames, test ta ’ aberrazzjoni tal - kromożomi) jew pożittivi (V79 Screen).
Deferasirox caused formation of micronuclei in vivo in the bone marrow, but not liver, of non-iron-loaded rats at lethal doses.
Deferasirox ikkawża l- formazzjoni ta ’ mikronukleji in vivo fil- mudullun, imma mhux fil- fwied, ta ’ firien li ma kellhomx tagħbija tal- ħadid meta ngħataw dożi letali.
No such effects were observed in iron-preloaded rats.
Dawn l- effetti ma dehrux fil- firien li kienu mgħobbija minn qabel bil- ħadid.
Deferasirox was not carcinogenic when administered to rats in a 2-year study and transgenic p53+/ - heterozygous mice in a 6-month study.
Deferasirox ma żiedx ir- riskju tal- kanċer meta ngħata lill- firien fi studju ta ’ sentejn u ġrieden eterożigi transġeniċi p53+ / - fi studju ta ’ 6 xhur.
The potential for toxicity to reproduction was assessed in rats and rabbits.
Il- potenzjal għal tossiċità fir- riproduzzjoni kienet studjata fuq firien u fniek.
Deferasirox was not teratogenic, but caused increased frequency of skeletal variations and stillborn pups in rats at high doses that were severely toxic to the non-iron-overloaded mother.
Deferasirox ma kienx teratoġeniku imma kkawża żieda fil- frekwenza ta ’ varjazzjonijiet skeletriċi u wild ta ’ firien li twieldu mejtin f’ dożi għoljin li kienu tossiċi ħafna għall- omm li ma kelliex tagħbija żejda ta 'ħadid.
Deferasirox did not cause other effects on fertility or reproduction.
Deferasirox ma kellux effetti oħrajn fuq il- fertilità jew fuq ir- riproduzzjoni.
Lactose monohydrate Crospovidone type A Cellulose, microcrystalline Povidone Sodium lauryl sulphate Silica, colloidal anhydrous Magnesium stearate
Lactose monohydrate Crospovidone type A Cellulose, microcrystalline Povidone Sodium lauryl sulphate Silica, colloidal anhydrous Magnesium stearate
Dispersion in carbonated drinks or milk is not recommended due to foaming and slow dispersion, respectively.
M’ għandux jinxtered f’ xorb bil- gass jew ħalib minħabba li jifforma ragħwa u jinxtered bil- mod rispettivament.
6.4 Special precautions for storage
11 6. 4 Prekawzjonijiet speċjali għall- ħażna
PVC/ PE/ PVDC/ Aluminium blisters.
PVC/ PE/ PVDC/ folji ta ’ l- aluminju.
Packs containing 28, 84 or 252 dispersible tablets.
Pakketti li fihom 28, 84 jew 252 pillola li jinxterdu.
11 Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
EXJADE 250 mg dispersible tablets
EXJADE 250 mg pilloli li jinxterdu
Each dispersible tablet contains 250 mg deferasirox.
Kull pillola li tinxtered fiha 250 mg deferasirox.
Off-white, round, flat tablets with bevelled edges and imprints (NVR on one face and J 250 on the other).
Pilloli offwajt, tondi, ċatti b’ xifer imżerżaq u timbri (NVR fuq naħa u J 250 fuq l- oħra).
EXJADE is indicated for the treatment of chronic iron overload due to frequent blood transfusions (≥ 7 ml/ kg/ month of packed red blood cells) in patients with beta thalassaemia major aged 6 years and older.
EXJADE huwa indikat għall- kura ta ’ tagħbija żejda kronika tal- ħadid minħabba trasfużjonijiet tad - demm frekwenti (≥7 ml/ kg/ xahar ta ’ ċelluli ħomor tad- demm ippakkjati) f’ pazjenti li jsofru minn beta talessimja maġġuri li għandhom minn 6 snin ’ il fuq.