qanastek/EMEA-V3 huggingface dataset:
Rare cases of thrombotic microangiopathy have been reported.
Kienu rrappurtati każijiet rari ta ’ mikro- anġjopatija trombotika.
Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.
Huwa rakkomandat it- twaqqif temporanju ta ’ SUTENT; wara li tirrisolvi ruħha, it - trattament jista ’ jerġa ’ jinbeda fid- diskrezzjoni tat- tabib kuranti.
Endocrine Disorders:
Disturbi tal- fwied u tal- marrara:
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience (See also section 4.4).
Kienu rrappurtati każijiet ta ’ ipertirojdiżmu, xi wħud segwiti minn ipotirojdiżmu, fi provi kliniċi u fl- esperjenza ta ’ wara t- tqegħid tal- prodott fis- suq (Ara wkoll sezzjoni 4. 4).
Cases of proteinuria and rare cases of nephrotic syndrome have been reported.
Kienu rrappurtati każijiet ta ’ proteinurja u każijiet rari tas - sindromu nefrotiku.
The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Is- sigurtà tat- trattament kontinwu b’ SUTENT f’ pazjenti bi proteinurja moderata għal severa ma ġietx evalwata b’ mod sistematiku.
Discontinue SUTENT in patients with nephrotic syndrome (see also section 4.4).
Il- kura f’ pazjenti bis- sindromu nefrotiku għandha tiġi mwaqqfa (Ara wkoll sezzjoni 4. 4).
There is no experience of acute overdosage with SUTENT.
Ma hemm l- ebda esperjenza ta ’ dożaġġ eċċessiv akut b’ SUTENT.
There is no specific antidote for overdosage with SUTENT and treatment of overdose should consist of general supportive measures.
Ma hemm l- ebda antidotu speċifiku għal doża eċċessiva ta ’ SUTENT u t- trattament għal doża eċċessiva għandu jikkonsisti minn miżuri t’ appoġġ ġenerali.
If indicated, elimination of unabsorbed drug may be achieved by emesis or gastric lavage.
L- eliminazzjoni ta ’ mediċina li tkun għadha ma ġietx assorbita tista ’ tinkiseb permezz ta ’ emesi (tqanqil tar- remettar) jew ħasil ta ’ l- istonku, jekk indikati.
LO1XE04
Mediċini antineoplastiċi – Impeditur tal- proteina- tyrosine kinase, Kodiċi ATC: LO1XE04
Sunitinib malate inhibits multiple receptor tyrosine kinases (RTKs) that are implicated in tumour growth, pathologic angiogenesis, and metastatic progression of cancer.
Sunitinib malate jimpedixxi riċetturi ta ’ tyrosine kinases (RTKs) multipli li huma implikati fl- iżvilupp tat- tumur, anġjoġenesi patoloġika, u progressjoni metastatika tal- kanċer.
Sunitinib was identified as inhibitor of platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET).
Sunitinib kien identifikat bħala impeditur ta ’ riċettaturi tal- fatturi ta ’ l- iżvilupp li ġejjin mill- plejtlits (PDGFRα u PDGFRβ), riċettaturi tal- fatturi ta ’ l- iżvilupp ta ’ l- endotilju vaskulari (VEGFR1, VEGFR2 uVEGFR3), riċettatur tal- fattur taċ- ċellola ta ’ l- għerq (KIT), Fms- like tyrosine kinase- 3 (FLT3), riċettaturi tal- fattur li jistimula l- kolonji (CSF- 1R), u r- riċettatur tal- fattur newrotropiku li ġej minn razza taċ- ċelloli glijali (RET).
The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.
F’ assaġġi bijokemikali u ċellulari il- metabolit primarju jesibixxi potenza simili komparat ma’ sunitinib.
CLINICAL STUDIES The clinical safety and efficacy of SUTENT has been studied in the treatment of patients with malignant gastrointestinal stromal tumour (GIST) who were resistant to imatinib (i. e. those who experienced disease progression during or following treatment with imatinib) or intolerant to imatinib (i. e. those who experienced significant toxicity during treatment with imatinib that precluded further treatment) and the treatment of patients with metastatic renal cell carcinoma (MRCC) Efficacy is based on time to tumour progression and an increase in survival in GIST and on progression free survival and objective response rates for treatment-naïve and cytokine-refractory MRCC respectively.
L- effikaċja hija bażata fuq iż- żmien sal- progressjoni tat- tumur u żieda fis- sopravivenza f’ GIST u fuq sopravivenza ħielsa mill- progressjoni u rati ta ’ reazzjoni oġġettivi għal MRCC bi trattament li qatt ma kien ittieħed qabel u refrattarja għaċ- ċitokini, rispettivament.
Gastrointestinal Stromal Tumours An initial open-label, dose-escalation study was conducted in patients with GIST after failure of imatinib (Median maximum daily dose 800 mg) due to resistance or intolerance.
Tumuri Stromali Gastrointestinali Studju inizjali b’ tikketta open- label u b’ eskalazzjoni tad- doża kien magħmul f’ pazjenti b’ GIST wara falliment ta ’ imatinib (doża medjana massima ta ’ kuljum 800 mg) minħabba reżistenza jew intoleranza.
Ninety-seven patients were enrolled at various doses and schedules; 55 patients received 50 mg at the recommended treatment schedule 4 weeks on / 2 weeks off (“ schedule 4/ 2”).
Sebgħa u disgħin pazjent kienu elenkati b’ diversi dożi u skedi; 55 pazjent ingħataw 50 mg skond l- iskeda ta ’ trattament irrakkomandata 4 ġimgħat fuq/ 2 ġimgħat mingħajr (“ skeda 4/ 2 ”).
In this study the median Time To Progression (TTP) was 34.0 weeks (95% CI = 22.0 – 46.0 weeks).
F’ dan l- istudju iż- Żmien sal- Progressjoni (TTP) medjan kien ta ’ 34. 0 ġimgħat (95% CI = 22. 0 – 46. 0 ġimgħat).
A phase 3, randomized, double-blind, placebo-controlled study of SUTENT was conducted in patients with GIST who were intolerant to, or had experienced disease progression during or following treatment with, imatinib (Median maximum daily dose 800 mg).
Studju fażi 3, randomised, double- blind, b’ kontrolli bi plaċebo ta ’ SUTENT kien magħmul f’ pazjenti b’ GIST li kienu intolleranti għal, jew li esperjenzaw progressjoni tal- marda waqt jew wara trattament b’ imatinib (doża medjana massima ta ’ kuljum 800 mg).
In this study, 312 patients were randomized (2:1) to receive either 50 mg SUTENT or placebo, orally once daily on Schedule 4/ 2 until disease progression or withdrawal from the study for another reason (207 patients received SUTENT and 105 patients received placebo).
F’ dan l- istudju, 312- il pazjent kienu randomised (2: 1) li jingħataw jew 50 mg SUTENT jew plaċebo, oralment darba kuljum fuq Skeda 4/ 2 sakemm kien hemm progressjoni tal- marda jew tneħħew mill- istudju għal raġuni oħra (207 pazjenti ngħataw SUTENT u 105 pazjenti ngħataw plaċebo).
The primary efficacy endpoint of the study was TTP, defined as the time from randomization to first documentation of objective tumour progression.
Il- punt ta ’ tmiem ta ’ l- effikaċja primarja ta ’ l - istudju kien TTP, mfisser bħala ż- żmien mir- randomizzazzjoni sa l- ewwel dokumentazzjoni ta ’ progressjoni tat- tumur oġġettiva.
14 The median TTP on SUTENT was 28.9 weeks (95% CI = 21.3-34.1 weeks) and was statistically significantly longer than the TTP of 5.1 weeks (95% CI = 4.4-10.1 weeks) on placebo.
It- TTP medjan fuq SUTENT kien 28. 9 ġimgħat (95% CI = 21. 3- 34. 1 ġimgħat) u kien statistikament sinifikattiv itwal mit- TTP ta ’ 5. 1 ġimgħat (95% CI = 4. 4- 10. 1 ġimgħat) fuq plaċebo.
The difference in overall survival was statistically in favour of SUTENT [hazard ratio:
Id- differenza fis - sopravivenza totali kienet statistikament favur ta ’ SUTENT [proporzjon ta ’ riskju:
0.491 (95%C. I.
0. 491 (95% C. I.
0.290- 0.831)]; the risk of death was 2 times higher in patients in the placebo arm compared to the SUTENT arm.
0. 290 - 0. 831)]; ir- riskju ta ’ mewt kien darbtejn ogħla f’ pazjenti fid- driegħ tal- plaċebo mqabbla mad - driegħ ta ’ SUTENT.
The percentages of deaths were 14% for SUTENT vs 25% for placebo.
Il- persentaġġ ta ’ imwiet kien 14% għal SUTENT vs 25% għal plaċebo.
Median overall survival had not yet been reached in either treatment arm at the time of analysis.
Is - sopravivenza totali medjana kienet għadha ma ntlaħqet fl- ebda driegħ tat- trattament fiż- żmien ta ’ l - analiżi.
Treatment-naïve Metastatic Renal cell Carcinoma (MRCC) A phase 3 randomized, multicenter, international, study evaluating the efficacy and safety of sunitinib compared with IFN-α in patients with treatment-naïve metastatic RCC was conducted.
Trattament li Qatt ma Kien Ittieħed Qabel għal- Karċinoma Metastatika taċ- Ċellola Renali (MRCC).
Seven hundred and fifty patients were randomized 1:1 to the treatment arms; they received treatment with either sunitinib in repeated 6-week cycles, consisting of 4 weeks of 50 mg daily oral administration followed by 2 weeks of rest (Schedule 4/ 2), or IFN-α, administered as a subcutaneous injection of 3 million units (MU) the first week, 6 MU the second week, and 9 MU the third week and thereafter on 3 non-consecutive days each week.
Studju fażi 3 randomizzat, f’ ċentri multipli, internazzjonali kien magħmul biex jevalwa l- effikaċja u s - sigurtà ta ’ sunitinib f’ pazjenti fuq IFN- α imqabbel ma ’ trattament MRCC li qatt ma kien ittieħed qabel Seba ’ mija u ħamsin pazjent kienu randomizzati 1: 1 għad- dirgħajn ta ’ trattament; huma ngħataw trattament jew b’ sunitinib f’ ċikli rrepetuti ta ’ 6- ġimgħat, magħmula minn 4 ġimgħat ta ’ amministrazzjoni orali ta ’ 50 mg kuljum segwita minn ġimagħtejn ta ’ mistrieħ (Skeda 4/ 2), jew b’ IFN- α, amministrat bħala injezzjoni taħt il- ġilda ta ’ 3 miljun junits (MU) fl- ewwel ġimgħa, u 9 MU fit- tielet ġimgħa u minn hemm ‘ l hemm fuq 3 ijiem mhux konsekuttivi kull ġimgħa.
The primary efficacy endpoint was progression free survival (PFS).
Il- punt ta ’ tmiem ta ’ l- effikaċja primarja kienet sopravivenza ħielsa mill- progressjoni (PFS).
In this study the median PFS for the sunitinib-treated group was 47.3 weeks compared with 22.0 weeks for the IFN-α -treated group; the hazard ratio was 0.415 (95% CI:
F’ dan l - istudju l- PFS medjan għall- grupp ittrattat b’ sunitinib kien 47. 3 ġimgħat imqabbel ma ’ 22. 9 ġimgħat għall- grupp ittrattat b’ IFN- α; il- proporzjon ta ’ riskju kien 0. 415 (95% CI:
0.320-0.539, p-value < 0.001).
0. 320- 0. 539, valur- p < 0. 001).
Cytokine-Refractory Metastatic Renal Cell Carcinoma A phase 2 study of SUTENT was conducted in patients who were refractory to prior cytokine therapy with interleukin-2 or interferon-α.
Karċinoma Metastatika Refrattarja għaċ- Ċitokini Studju fażi 2 ta ’ SUTENT kien magħmul f’ pazjenti li kienu refrattarji għal terapija minn qabel b’ ċitokini ma ’ interleukin- 2 jew interferon- α.
Sixty-three patients received a starting dose of 50 mg of SUTENT orally, once daily for 4 consecutive weeks followed by a 2-week rest period, to comprise a complete cycle of 6 weeks (schedule 4/ 2).
Tlieta u sittin pazjent ingħataw doża tal- bidu ta ’ 50 mg ta ’ SUTENT oralment darba kuljum, għal 4 ġimgħat konsekuttivi segwiti minn perijodu ta ’ mistrieħ ta ’ ġimgħatejn, biex jikkostitwixxi ċiklu komplut ta ’ 6 ġimgħat (skeda 4/ 2).
The primary efficacy endpoint was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumours (RECIST).
Il- punt ta ’ tmiem ta ’ l - effikaċja primarja kien rata ta ’ reazzjoni oġġettiva (ORR) ibbażata fuq Kriterji ta ’ Evalwazzjoni tar - Reazzjoni f’ Tumuri Solidi (RECIST).
In this study the objective response rate was 36.5% (95% C. I.
F’ dan l- istudju r- rata ta ’ reazzjoni oġġettiva kienet 36. 5%
24.7% - 49.6%) and the median time to progression (TTP) was 37.7 weeks (95% C. I.
24. 0
24.0 - 46.4 weeks).
- 46. 4 ġimgħat).
A confirmatory, open-label, single-arm, multi-centre study evaluating the efficacy and safety of SUTENT was conducted in patients with MRCC who were refractory to prior cytokine therapy.
Studju konfermatorju, open- label, ta ’ driegħ waħda, f’ ċentri multipli li evalwa l- effikaċja u s- sigurtà ta ’ SUTENT kien magħmul f’ pazjenti b’ MRCC li kienu refrattarji għat- terapija minn qabel b’ ċitokini.
One hundred and six patients received at least one 50 mg dose of SUTENT on schedule 4/ 2.
Mija u sitt pazjenti ngħataw ta ’ l- anqas doża waħda ta ’ 50 mg ta ’ SUTENT fuq skeda 4/ 2.
The primary efficacy endpoint of this study was Objective Response Rate (ORR).
Il- punt ta ’ tmiem ta ’ l- effikaċja primarja ta ’ dan l- istudju kien rata ta ’ reazzjoni oġġettiva (ORR).
Secondary endpoints included TTP, duration of response (DR) and overall survival (OS).
Punti ta ’ tmiem sekondarji kienu jinkludu TTP, żmien ta ’ reazzjoni (DR) u sopravivenza totali (OS).
In this study the ORR was 35,8% (95% C. I.
F’ dan l- istudju l- ORR kienet 35, 8% (95% C. I.
26.8% – 47.5%) The median DR and OS had not yet been reached.
Id- DR u l- OS medjani ma kienux għadhom intleħqu.
The pharmacokinetics of sunitinib and sunitinib malate have been evaluated in 135 healthy volunteers and 266 patients with solid tumours.
Il- farmakokinetiċi ta ’ sunitinib u sunitinib malate ġew evalwati f ’ 135 voluntiera f’ saħħithom u 266 pazjent b’ tumuri solidi.
Absorption After oral administration of sunitinib, maximum concentrations (Cmax) are generally observed from 6 to 12 hours (Tmax) post-dose.
Assorbiment Wara l- għoti mill- ħalq ta ’ sunitinib, konċentrazzjoniet massimi (Cmax) huma ġeneralment osservati minn 6 sa 12- il siegħa (Tmax) wara d- doża.
Food has no effect on the bioavailability of sunitinib.
L- ikel m’ għandu l- ebda effett fuq il- bijodisponibbilità ta ’ sunitinib.
Distribution Binding of sunitinib and its primary active metabolite to human plasma protein in in vitro assays was 95% and 90%, respectively, with no apparent concentration dependence.
Distribuzzjoni L- irbit ta ’ sunitinib u l- metabolit attiv primarju tiegħu ma ’ proteina fil- plażma umana f’ assaġġi in vitro kien 95% u 90%, rispettivament, mingħajr l- ebda dipendenza tal- konċentrazzjoni evidenti.
The apparent volume of distribution (V/ F) for sunitinib was large – 2230l -, indicating distribution into the tissues.
Il - volum ta ’ distribuzzjoni (V/ F) evidenti għal sunitinib kien kbir – 2230l -, li jindika distribuzzjoni fit - tessuti.
Metabolism The calculated in vitro Ki values for all CYP isoforms tested (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 AND CYP4A9/ 11) indicated that sunitinib and its
Metaboliżmu Il- valuri Ki kkalkulati in vitro għall- iżoformi CYP kollha ttestjati (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 AND CYP4A9/ 11) indikaw li sunitinib u l- metabolit attiv primarju tiegħu mhux probabbli li jimpedixxu l- metaboliżmu ta ’ mediċini li jistgħu jiġu metabolizzati b’ mod klinikament rilevanti minn dawn l- enzimi.
In-vitro studies also indicate that SUTENT neither induces nor inhibits major CYP enzymes, including CYP3A4.
Studji in vitro ukoll indikaw li SUTENT la jinduċi u l- anqas jimpedixxi enżimi CYP maġġuri, inkluż CYP3A4.
Biotransformation Sunitinib is metabolized primarily by CYP3A4, the cytochrome P450 enzyme, which produces its primary active metabolite, which is then further metabolized by CYP3A4.
Bijotrasformazzjoni Sunitinib huwa metabolizzat prinċipalment minn CYP3A4, l- enzima cytochrome P450, li tipproduċi l - metabolit attiv primarju tiegħu, li mbagħad huwa metabolizzat aktar permezz ta ’ CYP3A4.
Concurrent administration of SUTENT with the potent CYP3A4 inducer, rifampin, resulted approximately in 56% and 78% reduction in sunitinib Cmax and AUC0-∞, values respectively, after a single dose of SUTENT in healthy volunteers.
L- għoti flimkien ta ’ SUTENT ma ’ l- sensitizzattur CYP3A4 potenti, rifampin, irriżultat fi tnaqqis bejn wieħed u ieħor ta ’ 56% u 78% fil- valuri tas- Cmax u l- AUC0- ∞ ta ’ sunitinib, rispetttivament, wara doża waħda ta ’ SUTENT f’ voluntiera f’ saħħithom.
Administration of SUTENT with other inducers of the CYP3A4 family (e. g. dexamethasone, phenytoin, carbamazepine, phenobarbital or Hypericum perforatum, known also as St.
Ingħatar ta ’ SUTENT ma ’ sensitizzaturi oħra tal - familja CYP3A4 (eż. dexamethasone, phenytoin, carbamazepine, phenobarbital jew Hypericum perforatum, magħrufa wkoll bħala St.
Elimination Excretion is primarily via faeces (61%) with renal elimination of drug and metabolites accounting for 16% of the administered dose.
Eliminazzjoni L- eliminazzjoni hija prinċipalment ma ’ l- ippurgar (61%) b’ eliminazzjoni renali tal- mediċina u l - metaboliti tammonta għal 16% tad- doża amministrata.
Sunitinib and its primary active metabolite were the major drug-related compounds identified in plasma, urine and faeces, representing 91.5%, 86.4% and 73.8% of radioactivity in pooled samples, respectively.
Sunitinib u l- metabolit attiv primarju tiegħu kienu l- komposti relatati mal- mediċina maġġuri li ġew identifikati fil- plażma, l- awrina u l- ippurgar, u rrappreżentaw 91. 5%, 86. 4% u 73. 8% tar- radjoattività f’ kampjuni ppuljati, rispettivament.
Minor metabolites were identified in urine and faeces, but generally were not found in plasma.
Metaboliti minuri kienu identifikati fl- awrina u fl- ippurgar, iżda ġeneralment ma nstabux fil- plażma.
Total oral clearance (CL/ F) was 34-62 l/ hr.
L- eliminazzjoni orali totali (CL/ F) kienet ta ’ 34- 62 l/ siegħa.
Organ Functions impairment Hepatic insufficiency:
Indeboliment tal- Funzjoni ta ’ l- Organi Indeboliment epatiku:
Sunitinib and its primary metabolite are mainly metabolized by the liver.
Sunitinib u l- metabolit primarju tiegħu huma prinċipalment metabolizzati mill - fwied.
Systemic exposures after a single dose of SUTENT were similar in subjects with mild or moderate (Child-Pugh Class A and B) hepatic impairment compared to subjects with normal hepatic function.
17 tal- fwied ħafif jew moderat (Klassi Child- Pugh A u B) imqabbla ma ’ suġġetti b’ funzjoni epatika normali.
SUTENT was not studied in subjects with severe (Child-Pugh class C) hepatic impairment.
SUTENT ma ġiex studjat f’ suġġetti b’ indeboliment epatiku qawwi (Klassi Child- Pugh C).
Studies in cancer patients have excluded patients with ALT or AST > 2.5 x ULN (Upper Limit of Normal) or, if due to liver metastasis, > 5.0 x ULN.
Studji f’ pazjenti bil- kanċer eskludew pazjenti b’ ALT jew AST > 2. 5 x ULN (Limitu ta ’ Fuq tan - Normal) jew, jekk minħabba metastasi fil- fwied, > 5. 0 x ULN.
Renal insufficiency:
Indeboliment renali:
No clinical studies have been performed in patients with impaired renal function Studies excluded patients with serum creatinine > 2.0 x ULN.
L- istudji eskludew pazjenti bi creatinine fis- serum > 2. 0 x ULN.
Population pharmacokinetic analyses indicated that sunitinib apparent clearance (CL/ F) was not affected by creatinine clearance within the range evaluated (42-347 ml/ min).
Analiżi tal- farmakokinetiċi tal - popolazzjoni indikaw li t- tneħħija apparenti (CL/ F) ta ’ sunitinib ma kinitx effettwata mir- rata ta ’ tneħħija ta ’ creatinine fi ħdan il- medda evalwata (42- 347 ml/ min).
Plasma Pharmacokinetics Following oral administration in healthy volunteers, the elimination half-lives of sunitinib and its primary active desethyl metabolite are approximately 40 - 60 hours, and 80 - 110 hours, respectively.
Farmakokinetiċi fil- Plażma Wara amministrazzjoni orali f’ voluntiera f’ saħħithom, il- half- lives ta ’ eliminazzjoni ta ’ sunitinib u l - metabolit desethyl attiv primarju tiegħu huma bejn wieħed u ieħor 40 – 60 siegħa, u 80 – 110 sigħat, rispettivament.
In the dosing ranges of 25 to 100 mg, the area under the plasma concentration-time curve (AUC) and Cmax increase proportionally with dose.
F’ medded ta ’ idddożar ta ’ 25 sa 100 mg, l- erja taħt il- kurva ta ’ konċentrazzjoni- ħin fil- plażma (AUC) u Cmax jiżdiedu proporzjonalment mad- doża.
With repeated daily administration, sunitinib accumulates 3- to 4-fold and its primary active metabolite accumulates 7- to 10-fold.
B’ ingħatar ta ’ dożi rreppetuti ta ’ kuljum, sunitinib jakkumula 3 sa 4 darbiet u l- metabolit attiv primarju tiegħu jakkumula 7 sa 10 darbiet.
Steady-state concentrations of sunitinib and its primary active metabolite are achieved within 10 to 14 days.
Konċentrazzjonijet ta ’ stat- fiss ta ’ sunitinib u l- metabolit attiv primarju tiegħu jintlaħqu fi żmien 10 sa 14- il jum.
By day 14, combined plasma concentrations of sunitinib and is active metabolite are 62.9 - 101 ng/ ml which are target concentrations predicted from preclinical data to inhibit receptor phosphorylation in vitro and result in tumour stasis/ growth reduction in vivo.
Sa jum 14, il- konċentrazzjonijiet fil- plażma tal- kumbinazzjoni ta ’ sunitinib u l - metabolit attiv tiegħu huma 62. 9 - 101 ng/ ml li huma konċentrazzjonijiet mixtieqa mbassra minn dejta ta ’ qabel l- użu kliniku li jimpedixxu fosforilazzjoni tar- riċettattur in vitro u jirriżultaw fi twaqqif/ tnaqqis fl- iżvilupp tat- tumur in vivo.
The primary active metabolite comprises 23 to 37% of the total exposure.
Il- metabolit attiv primarju jikkostitwixxi 23 sa 37% ta ’ l- esponiment totali.
The pharmacokinetics were similar in all solid tumour populations tested and in healthy volunteers.
L- ebda bidliet sinifikattivi fil- farmakokinetiċi ta ’ sunitinib jew il- metabolit attiv primarju ma huma osservati b’ ingħatar ripetut ta ’ kuljum jew b’ ċikli ripetuti fir- reġimens ta ’ l- iddożar ittestjati. Il- farmakokinetiċi kienu simili fil - popolazzjonijiet ta ’ tumuri solidi kollha ttestjati u f’ voluntiera f’ saħħithom.
Population pharmacokinetic analyses of demographic data indicate that no dose adjustments are necessary for weight or ECOG score.
Analiżi ta ’ farmakokinetiċi tal- popolazzjoni ta ’ dejta demografika jindikaw li l- ebda aġġustamenti fid - doża ma huma neċessarji għal piż jew skor ECOG.
Available data indicate that females could have about 30% lower apparent clearance (CL/ F) of sunitinib than males: this difference however does not necessitate dose adjustments.
Dejta disponibbli tindika li n- nisa jista ’ jkollhom rata ta ’ tneħħija apparenti (CL/ F) ta ’ sunitinib ta ’ madwar 30% aktar baxxa milli fl- irġiel: madankollu din id- differenza ma teħtieġx aġġustamenti fid - doża.
16 haemolymphopoietic system (bone morrow hypocelularity, and lymphoid depletion of thymus, spleen, and lymph node), exocrine pancreas (acinar cell degranulation with single cell necrosis), salivary gland (acinar hypertrophy), bone joint (growth plate thickening), uterus (atrophy) and ovaries (decreased follicular development).
Fi studji ta ’ tossiċità b’ dożi ripetuti fil- firien u x- xadini fuq tul ta ’ żmien ta ’ 9 xhur, l- organi mmirati primarji kienu identifikati fil- passaġġ gastrointestinali (remettar u dijarea fix- xadini), glandola adrenali (konġestjoni kortikali u/ jew emorraġija fil- firien u fix- xadini, b’ nekrożi segwita minn fibrożi fil- firien), sistema emolimfopojetika (ipoċellolarità tal- mudullun, u żvujtar limfojde tat- tajmus, milsa, u glandoli limfatiċi), frixa eżokrina (degranulazzjoni ta ’ ċelloli aċinari b’ nekrożi ta ’ ċellola waħda), glandola salivarja (ipertrofija aċinari), ġoġi ta ’ l- għadam (tħaxxin tas- saff ta ’ l- iżvilupp), utru (atrofija) u ovarji (tnaqqis ta ’ żvilupp follikulari).
All findings occurred at clinically relevant sunitinib plasma exposure levels.
Is- sejbiet kollha seħħew fl- livelli klinikament relevanti ta ’ esponiment fil- plażma ta ’ sunitinib.
Additional effects, observed in other studies included QTc interval prolongation, LVEF reduction, pituitary hypertrophy, and testicular tubular atrophy, increased mesangial cells in kidney, haemorrhage in GI tract and oral mucosa, and hypertrophy of anterior pituitary cells.
Effetti addizzjonali, osservati fi studji oħra inkludew titwil ta ’ l- interval QTc, tnaqqis fl- LVEF, ipertrofija pitwitarja, u atrofija tubulari testikolari, żidiet fiċ- ċelloli mesangjali fil- kilwa, emorragija fil- passaġġ GI u mukoża orali, u ipertrofija taċ- ċelloli pitwitarji anterjuri.
Changes in the uterus (endometrial atrophy) and bone growth plate (physeal thickening or dysplasia of cartilage) are thought to be related to the pharmacological action of sunitinib.
Bidliet fl- utru (atrofija endometrijali) u s- saff ta ’ l- iżvilupp ta ’ l- għadam (tħaxxin fisejali jew displejżja tal- qarquċa) huma maħsuba li huma relatati ma ’ l- azzjoni farmakoloġika ta ’ sunitinib.
Most of these findings were reversible after 2 to 6 weeks without treatment.
Il- parti l- kbir ta ’ dawn ir- riżultati kienu riversibbli wara 2 sa 6 ġimgħat mingħajr trattament.
Genotoxicity The genotoxic potential of sunitinib was assessed in vitro and in vivo.
Ġenotossiċità Il- potenzjal ġenotossiku ta ’ sunitinib kien assessjat in vitro u in vivo.
Sunitinib was not mutagenic in bacteria using metabolic activation provided by rat liver.
Sunitinib ma kienx mutaġeniku fil- batterji bl- użu ta ’ attivazzjoni metabolika fornita mill- fwied tal- far.
Sunitinib did not induce structural chromosome aberrations in human peripheral blood lymphocyte cells in vitro.
Sunitinib in vitro ma induċiex aberazzjonijiet strutturali fil- kromożomi taċ- ċelloli limfoċiti fid- demm periferali uman.
Polyploidy (numerical chromosome aberrations) was observed in human peripheral blood lymphocytes in vitro, both in the presence and absence of metabolic activation.
In vitro, poliplojdi (aberazzjonijiet numeriċi tal- kromożomi) kienet osservata fil- limfoċiti fid- demm periferali uman, kemm fil- preżenza u fin- nuqqas ta ’ attivazzjoni metabolika.
Sunitinib was not clastogenic in rat bone marrow in vivo.
Sunitinib ma kienx klastoġeniku fil- mudullun tal- far in vivo.
The major active metabolite was not evaluated for genetic toxicity potential.
Il- metabolit attiv maġġur ma kienx evalwat għal potenzjal ta ’ tossiċità ġenetika.
Carcinogenicity Carcinogenicity studies with sunitinib malate have not been performed.
18 Karċinoġeniċità Ma ġewx magħmula studji fuq karċinoġeniċità b’ sunitinib malate.
Reproductive and Developmental toxicity No effects on male or female fertility were observed in reproductive toxicity studies.
L- ebda effetti fuq il- fertilità tan- nisa u ta ’ l- irġiel ma kienu osservati fi studji ta ’ tossiċità riproduttiva.
However, in repeated- dose toxicity studies performed in rats and monkeys, effects on female fertility were observed in the form of follicular atresia, degeneration of corpora lutea, endometrial changes in the uterus and decreased uterine and ovarian weights at clinically relevant systemic exposure levels.
Madankollu, fi studji ta ’ tossiċita b’ dożi ripetuti fil- firien u fix- xadini, effetti fuq il- fertiltà kienu osservati fil- forma ta ’ atrijżja follikulari, deġenerazzjoni ta ’ corpora lutea, bidliet endometrijali fl- utru u tnaqqis fil- piżijiet ta ’ l- utri u l- ovarji fl- livelli ta ’ esponiment sistemiku klinikament rilevanti.
Effects on male fertility in rat were observed in the form of tubular atrophy in the testes, reduction of spermatozoa in epididimes and colloid depletion in prostate and seminal vesicles at plasma exposure levels 18-fold higher than is observed in clinic.
Fil- far effetti fuq il- fertilità tar- raġel kienu osservati fil- forma ta ’ atrofija tubulari fit- testikoli, tnaqqis fl - ispermatożoa fl- epididimi u żvujtar tal- kollojde fil- prostata u vesikli seminali fl- livelli ta ’ esponiment fil- plażma 18- il darba aktar għoljin milli osservati fil- klinika.
In rats, embryo-foetal mortality was evident as significant reductions in the number of live foetuses, increased numbers of resorptions increased postimplantation loss, and total litter loss in 8 of 28 pregnant females at plasma exposure levels 5.5-fold higher than is observed in clinic.
Fil- firien, il- mortalità embrijonali- fetali kienet evidenti bħala tnaqqis sinifikanti fl- għadd ta ’ fetujiet ħajjin, żieda fin- numri ta ’ riassorbimenti, żiedet it- telf wara l- impjantazzjoni, u t- telf totali tal- boton fi 8 minn 28 mara tqila fl- livelli ta ’ esponiment fil- plażma 5. 5 darbiet aktar għoljin milli huwa osservat fil- klinika.
In rabbits, reductions in gravid uterine weights and number of live foetuses were due to increases in the number of resorptions, increases in post-implantation loss and complete litter loss in 4 of 6 pregnant females at plasma exposure levels 3-fold higher than is observed in clinic.
Fil- fniek, tnaqqis fil- piżijiet ta ’ utri gravidi u n- numru ta ’ fetujiet ħajjin kienu minħabba żidiet fin- numru ta ’ risorbimenti, żidiet fit- telf wara l- impjantazzjoni u telf komplut tal- boton f’ 4 minn 6 nisa tqal fl- livelli ta ’ esponiment fil- plażma 3 darbiet aktar għoljin milli osservati fil- klinika.
Sunitinib treatment in rats during organogenesis resulted in developmental effects at ≥ 5 mg/ kg/ day consisting of increased incidence of foetal skeletal malformations, predominantly characterized as retarded ossification of thoracic/ lumbar vertebrae and occurred at plasma exposure levels 6-fold higher than is observed in clinic.
Fil- firien, trattament b’ sunitinib waqt l- organoġenesi rriżulta f’ effetti fuq l- iżvilupp b’ ≥5 mg/ kg/ kuljum li kienu jikkonsistu minn żieda fl- inċidenza ta ’ malformazzjonijiet skeletriċi fetali, predominantament karatterizzati bħala dewmien fl- ossifikazzjoni tal- vertebre toraċiċi/ lumbari u seħħew fl- livelli ta’ esponiment fil- plażma 6 darbiet aktar għoljin milli osservati fil- klinika.
In rabbits, developmental effects consisted of increased incidence of cleft lip at plasma exposure levels approximately equal to that observed in clinic, and cleft lip and cleft palate at plasma exposure levels 2.7-fold higher than is observed in clinic.
Fil- fniek, effetti fuq l- iżvilupp kkunsistew f’ żidiet fl- inċidenza ta ’ palat mixquq fl- livelli ta’ esponiment fil - plażma bejn wieħed u ieħor daqs dawk osservati fil- klinika, u xoffa mixquqa u palat mixquq fl- livelli ta ’ esponiment 2. 7 darbiet aktar għoljin minn dawk osservati fil- klinika.
Capsule content Mannitol Croscarmellose Sodium Povidone Magnesium Stearate
Kontenut tal- kapsula Mannitol Croscarmellose Sodium Povidone Magnesium Stearate
17 Capsule Shell Gelatin Red Iron Oxide (E172) Titanium dioxide (E171)
Qoxra tal- kapsula Gelatin Red Iron Oxide (E172) Titanium dioxide (E171)
Printing ink Shellac Propylene glycol Sodium hydroxide Povidone Titanium dioxide (E171)
Shellac Propylene glycol Sodium hydroxide Povidone Titanium dioxide (E171)
This medicinal product does not require any special storage conditions.
Dan il- prodott mediċinali ma jeħtieġ ebda kundizzjonijiet ta ’ ħżin speċjali.
High-density polyethylene (HDPE) bottles with a polypropylene closure, containing 30 capsules.
Fliexken ta ’ high- density polyethylene (HDPE) b’ tapp tal- polypropylene, li fihom 30 pillola.
Aclar/ PVC transparent blister with aluminium foil coated with heat seal lacquer containing 28 (4 x 7) hard capsules Not all pack sizes may be marketed.
Folja trasparenti ta ’ Aclar/ PVC b’ folja ta ’ l- aluminjum miksija u ssiġġillata b’ lega msaħnna, li fiha 28 (4x7) kapsuli iebsin.
EU/ 1/ 06/ 347/ 001 EU/ 1/ 06/ 347/ 004
EU/ 1/ 06/ 347/ 001 ΕU/ 1 // 06/ 347/ 004
Date of first Authorisation:
Data ta ’ l- ewwel awtorizzazzjoni:
July 19, 2006
19 ta ’ Lulju, 2006
SUTENT 25 mg hard capsules
SUTENT 25 mg kapsuli iebsin
Each capsule contains sunitinib malate, equivalent to 25.0 mg of sunitinib Excipient(s):
Kull kapsula fiha sunitinib malate, ekwivalenti għal 25. 0 mg ta ’ sunitinib Sustanza mhux attiva:
39.663 mg of mannitol.
39. 663 mg ta ’ mannitol.
Hard capsules Gelatin capsules with caramel cap and orange body, printed with white ink “ Pfizer” on the cap and “ STN 25 mg” on the body and containing yellow to orange granules.
Kapsuli iebsin Kapsuli tal- ġelatina b’ kappa kannella u bil- parti ewlenija oranġjo, bil- kelma “ Pfizer ” stampata b’ inka bajda fuq il- kappa u “ STN 25 mg ” fuq il- parti ewlenija, u li fihom granijiet safrani għal oranġjo.
Therapy should be initiated by a physician experienced in the treatment of renal cell carcinoma or GIST.
It- terapija għandha tinbeda minn tabib b’ esperjenza fit- trattament ta ’ karċinoma taċ- ċellola renali jew GIST.
If this is not possible, the dose of SUTENT may need to be increased in 12.5 mg increments (up to 87.5 mg per day) based on careful monitoring of tolerability.
Jekk dan mhux possibbli, id- doża ta ’ SUTENT tista ’ tkun meħtieġa li tiżdied b’ inkrimenti ta ’ 12. 5 mg (sa 87. 5mg kuljum), ibbażata fuq sorveljanza bir- reqqa tat- tollerabbilità.
Selection of an alternate concomitant medication with no, or minimal potential to induce or inhibit CYP3A4 should be considered.
21 Selezzjoni ta ’ medikazzjoni konkomitanti alternattiva bla ebda, jew b’ potenzjal minimu li tinduċi jew timpedixxi CYP3A4 għandha tiġi kkunsidrata.
19 Paediatric use:
Użu pedjatriku:
SUTENT should not be used in paediatric population until further data become available.
SUTENT m’ għandux jintuża fil- popolazzjoni pedjatrika ħlief meta aktar dejta issir disponibbli.
Hypersensitivity to sunitinib malate or to any of the excipients.
Sensitività eċċessiva għal sunitinib jew għal xi sustanza mhux attiva.
If this is not possible, the dosage of SUTENT may need to be reduced (see sections 4.2 and 4.5).
Jekk dan mhuwiex possibbli, id- dożaġġ ta ’ SUTENT jista ’ jkollu jiġi mnaqqas (ara Sezzjonijiet 4. 2 u 4. 5).
Fatal pulmonary haemorrhage occurred in 2 patients receiving SUTENT on a clinical trial of patients with metastatic non-small cell lung cancer (NSCLC).
Fi prova klinika f’ pazjenti b’ kanċer tal- pulmun mhux biċ- ċelloli żgħar metastatiku (NSCLC), emorraġija pulmonari fatali seħħet f’ 2
Both patients had squamous cell histology.
22 pazjenti li kienu qed jingħataw SUTENT.
Bleeding events occurred in 18% of patients receiving SUTENT in a phase 3 GIST Study compared to 17% of patients receiving placebo.
Stima ta ’ rutina ta ’ din ir - reazzjoni għandha tinkludi għadd taċ- ċelloli tad- demm u eżami fiżiku komplut.
Gastro-intestinal tract Serious, sometimes fatal gastrointestinal complications including gastrointestinal perforation have occurred rarely in patients with intra-abdominal malignancies treated with SUTENT.
Passaġġ gastro- intestinali Kumplikazzjonijiet gastrointestinali serji, xi daqqiet fatali, inklużi perforazzjoni gastrointestinali, seħħew rarament f’ pazjenti b’ malinnijiet intra- addominali ttrattati b’ SUTENT.
SUTENT dosing was reduced or temporarily delayed in approximately 2.7% of this patient population.
Id- dożaġġ ta ’ SUTENT kien imnaqqas jew temporanjament imdewwem f’ madwar 2. 7% ta ’ din il - popolazzjoni ta ’ pazjenti.
Haematological Decreased absolute neutrophil counts of grade 3 and 4 severity were reported in 10% and 1.7% of patients on the phase 3 GIST study, respectively and in 16% and 1.6% of patients on the phase 3 MRCC study, respectively.
Ematoloġiċi Ematoloġiċi Tnaqqis fl- għadd assolut tan- newtrofili ta ’ severità fi grad 3 u 4 kien irrapportat fi 10% u 1. 7% tal - pazjenti, fit- tielet fażi tal- istudju GIST, rispettivament, u f’ 16% u 1. 6% ta ’ pazjenti fit- tielet fażi ta ’ l - istudju MRCC, rispettivament.
Decreased platelet counts of grade 3 and 4 severity were reported in 3.7% and 0.4% of patients on the phase 3 GIST study, respectively, and in 8.2% and 1.1% of patients on the phase 3 MRCC study, respectively.
Tnaqqis fl- għadd tal- plejtlits ta ’ severità fi grad 3 jew 4 kien irrapportat fi 3. 7% u 0. 4% tal- pazjenti, fit- tielet fażi tal- istudju GIST, rispettivament, u f’ 8. 2% u 1. 1% ta ’ pazjenti fit- tielet fażi ta ’ l- istudju MRCC, rispettivament..
Complete blood counts should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.
Kardjovaskulari L- episodji kardjovaskulari rrappurtati mill- esperjenza ta ’ wara t- tqegħid tal- prodott fis- suq, li wħud minnhom kienu fatali, kienu jinkludu tnaqqis fil- frazzjoni ta ’ tfigħ ’ il barra tal- ventrikolu tax- xellug
Cardiovascular Cardiovascular events, some of which were fatal, reported through post-marketing experience, have included left ventricular ejection fraction (LVEF) decrease and cardiac failure.
23 (LVEF) u insuffiċjenza tal- qalb.
In clinical trials, decreases in LVEF of ≥ 20% and below the lower limit of normal occurred in approximately 2% of SUTENT-treated GIST patients, 4% of cytokine-refractory MRCC patients, 2% of placebo-treated patients.
Fi provi kliniċi, tnaqqis fil- LVEF ta ’ ≥ 20% jew taħt il- limitu t’ isfel tan- normal seħħ f’ madwar 2% ta ’ pazjenti GIST ittrattati b’ SUTENT, 4% ta ’ pazjenti MRCC refrattarja għaċ- ċitokini, 2% ta ’ pazjenti ttrattati bi plaċebo.
Treatment-related adverse events of ‘ cardiac failure’, ‘ cardiac failure congestive’ or ‘ left ventricular failure’ were reported in 0.7% of patients with solid tumours and 1% of patients treated with placebo.
Reazzjonijiet avversi relatati mat- trattament ta ’ ‘ falliment kardijaku ’, ‘ falliment kardijaku konġestiv ’ jew ‘ falliment ventrikulari xellugi ’ kienu rrapportati f’ 0. 7% ta ’ pazjenti b’ tumuri solidi u 15% ta ’ pazjenti ttrattati bi plaċebo.
In a phase 2 study in cytokine-refractory MRCC patients, 0.9% of patients experienced treatment-related fatal myocardial infarction and in the phase 3 study in treatment-naïve MRCC patients, 0.6% of patients on the IFN-α arm and 0 patients on the
Fi studju tat- tieni fażi ta ’ pazjenti b’ MRCC refrattarja għaċ- ċitokini, 0. 9% tal- pazjenti esperjenzaw attakk tal- qalb fatali, u fit- tielet fażi ta ’ l- istudju f’ pazjenti b’ MRCC li qatt ma kienu trattati qabel, 0. 6% tal- pazjenti fit- taqsima ta ’ IFN - α u 0 pazjenti fit- taqsima tas- SUTENT esperjenzaw attakki tal- qalb fatali.
The relationship, if any, between receptor tyrosine kinase (RTK) inhibition and cardiac function remains unclear.
Ir- relazzjoni, jekk hemm, bejn l- inibizzjoni tar- riċettatur tyrosinase kinase (RTK) u l- funzjoni kardijaka tibqa mhix ċara.
QT Interval prolongationData from non-clinical (in vitro and in vivo) studies, at doses higher than the recommended human dose, indicate that sunitinib has the potential to inhibit the cardiac action potential repolarization process (e. g. prolongation of QT interval).
Titwil ta ’ l- Intervall QT Tagħrif minn studji li mhumiex kliniċi (in vitro u in vivo), b’ dożi ogħla mid- doża umana rakkomandata, jindika li sunitinib għandu l- potenzjal li jimpedixxi l- proċess potenzjali ta ’ polarizzazzjoni mill- ġdid ta ’ l- azzjoni kardijaka (eż. titwil ta ’ l- interval QT).
At therapeutic plasma concentrations, the maximum QTcF (Frederica’ s correction) mean change from baseline was 9.6 msec (90% CI 15.1msec).
24 B’ konċentrazzjonijiet terapewtiċi fil- plasma, il- bidla medja massima fil- QTcF (korrezzjoni ta ’ Frederica) mil- linja bażi kienet ta ’ 9. 6 msec (90% CI 15. 1msec).
22 Seven patients (3%) on SUTENT and none on placebo in a phase 3 GIST study experienced venous thromboembolic events; five of the seven were Grade 3 deep venous thrombosis (DVT) and two were Grade 1 or 2.
Fi studju GIST fażi 3 seba ’ pazjenti (3%) fuq SUTENT esperjenzaw reazzjonijiet tromboemboliċi venużi; ħamsa mis- seba ’ kienu trombożi tal- vini l- fondi (DVT) ta ’ Grad 3, u tnejn kienu ta ’ Grad 1 jew 2.
Respiratory Events Patients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.
Episodji Respiratorji Pazjenti li ppreżentaw b’ emboliżmu pulmonari fit- 12 il xahar preċedenti, ġew esklużi mill- istudji kliniċi ta ’ SUTENT.
In patients who received SUTENT in Phase 3 registrational studies, treatment- related pulmonary events (i. e. dyspnoea, pleural effusion, pulmonary embolism or pulmonary oedema) were reported in approximately 5% of patients with GIST and in approximately 14% of patients with MRCC.
F’ pazjenti li rċevew SUTENT fit- tielet fażi ta ’ l- istudji tar- reġistrazzjoni, episodjo pulmonari relatati mat- trattament (i. e. dispnea, effużjoni plewrali, emboliżmu pulmonari jew edema pulmonari) ġew irrappurtati f’ approssimament 5% tal- pazjenti fuq GIST, u f’ approssimament 14% tal- pazjenti fuq MRCC.
Rare cases with fatal outcome were reported Approximately 8% of patients with solid tumours, including GIST and MRCC, who received Sutent in clinical trials experienced treatment-related pulmonary events.
Approssimament 8% tal- pazjenti b’ tumuri solidi, inklużi fuq GIST u MRCC, li rċevew SUTENT fi studji kliniċi, esperjenzaw episodji respiratorji relatati mat- trattament.
Thyroid Dysfunction Baseline laboratory measurement of thyroid function is recommended, and patients with hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of sunitinib treatment.
Disfunzjoni tat- Tirojde Huwa rakkomandat li jsir kejl fil- laboratorju tal- linja bażi tal- funzjoni tat- tirojd, filwaqt li pazjenti b’ ipotirojdiżmu jew ipertirojdiżmu għandhom ikunu trattati skond il- prattika medika standard qabel ma jinbeda it- trattament b’ sunitinib.
All patients should be observed closely for signs and symptoms of thyroid dysfunction on sunitinib treatment.
Il- pazjenti kollha għandhom ikunu osservati għal sinjali u sintomi ta ’ ipotirojdiżmu waqt trattament b’ sunitinib.
Patients with signs and/ or symptoms suggestive of thyroid dysfunction should have laboratory monitoring of thyroid function performed and be treated as per standard medical practice.
Pazjenti b’ sinjali u/ jew sintomi li jissuġġerixxu disfunzjoni tat- tirojde għandhom ikollhom monitoraġġ mil- laboratorju tal- funzjoni tat- tirojde u jkunu trattati skond il- prattika medika standard.
Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%).
25 TSH kienu rrapportati f’ 4 pazjenti b’ MRCC refrattarja għaċ- ċitokini (2%).
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
Każijiet rari ta ’ ipertirojdiżmu, xi wħud segwiti minn ipotirojdiżmu, ġew irrappurtati fi provi kliniċi u fl- esperjenza ta ’ wara t- tqegħid tal- prodott fis- suq.
Cases of serious pancreatic events, some with fatal outcome, have been reported.
Kienu rrappurtati każijiet ta ’ episodji serji ta ’ pankreatite, uħud minnhom b’ eżitu fatali.
If symptoms of pancreatitis are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.
Jekk ikun hemm sintomi ta ’ pankreatite jew falliment tal- fwied, il- pazjenti għandhom jitwaqqfilhom SUTENT u jiġu mogħtija kura t’ appoġġ adattat.
23 Renal function The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Funzjoni tal- Kliewi Is- sigurtà tat- trattament kontinwu b’ SUTENT f’ pazjenti bi proteinurja moderata għal severa ma ġietx evalwata b’ mod sistematiku.
Drugs that may increase sunitinib plasma concentrations:.
Mediċini li jistgħu jżidu l- konċentrazzjonijiet ta ’ sunitinib fil- plażma:
Drugs that may decrease sunitinib plasma concentrations:
26 Mediċini li jistgħu jnaqqsu l- konċentrazzjonijiet ta ’ sunitinib fil- plażma:
24 Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SUTENT.
Nisa b’ potenzjal li jkollhom it- tfal għandhom jiġu avżati biex jevitaw li joħorġu tqal waqt li jkunu qed jingħataw trattament b’ SUTENT.
Fatal events other than those listed in section 4.4 above or section 4.8 below that were considered possibly related to SUTENT drug included multi-system organ failure, disseminated intravascular coagulation, peritoneal haemorrhage, rhabdomyolysis, cerebrovascular accident, dehydration, adrenal insufficiency, renal failure, respiratory failure, pleural effusion, pneumothorax, shock, and sudden death.
Ġrajjiet fatali barra minn dawk imniżżla f’ sezzjoni 4. 4 hawn fuq jew sezzjoni 4. 8 hawn isfel, li kienu kkunsidrati bħala possibbilment relatati mal- mediċina SUTENT kienu jinkludu: insuffiċjenza ta ’ organi varji, koagulazzjoni intravaskulari mxerrda, emorraġija peritoneali, rabdomijolisi, aċċident ċerebrovaskulari, deidratazzjoni, insuffiċjenza adrenali, insuffiċjenza tal- kliewi, insuffiċjenza respiratorja, effużjoni tal- plewra, pnewmotoraċi, xokk u mewt zopptu.
Treatment-related adverse reactions that were reported in > 2% of solid tumour patients are listed below, by system organ class, frequency and grade of severity.
Reazzjonijiet avversi relatati mat- trattament kienu rrapportati f ’ > 2% ta ’ pazjenti b’ tumuri solidi kif elenkati hawn taħt, fil- Sistema ta ’ Klassifika ta ’ l- Organi, il- frekwenza u l- grad ta ’ severità.
Very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10), mhux komuni (≥ 1/ 1, 000 sa < 1 // 100), rari (≥ 1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000)
59 (13.4%)
81 (18. 4%) 67 (15. 2%) 26 ((5. 9%) 10 (2. 3%) 59 (13. 4%)
Decreased appetite a
Disturb fit- togħma b
Very common Common Common Common
Komuni ħafna Komuni Komuni Komuni
Headache Paraesthesia Dizziness Neuropathy peripheral
Uġigħ ta ’ ras Parasteżija Sturdament Newropatija periferali
76 (17.3%) 27 (6.1%) 18 (4.1%) 11 (2.5%)
76 (17. 3%) 27 (6. 1%) 18 (4. 1%) 11 (2. 5%)
5 (1.1%) 1 (0.2%) 1 (0.2%) 0 (0.0%)
5 (1. 1%) 1 (0. 2%) 1 (0. 2%) 0 (0. 0%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
Hypoaesthesia
Ipoestesija Pressjoni għolja
10 (2.3%)
10 (2. 3%) 101 (23. 0%)
0 (0.0%)
0 (0. 0%) 43 (9. 8%)
0 (0.0%)
0 (0. 0%) 0 (0. 0%)
43 (9.8%)
1 (0.%)
Respiratory, thoracic and mediastinal disorders
respiratorji, toraċiċi u medjastinali
Epistaxis Dyspnoea
Dispnea
28 (6.4%) 16 (3.6%)
16 (3. 6%)
1 (0.2%) 2 (0.5%)
2 (0. 5%)
18 (4.1%)
18 (4. 1%)
187 (42.5%)
187 (42. 5%)
24 (5.5%)
24 (5. 5%)
161 (36.6%)
161 (36. 6%)
15 (3.4%)
15 (3. 4%)
Very common Very common Very common Very common
Komuni ħafna Komuni ħafna
Vomiting Stomatitis Dyspepsia Abdominal pain C / distension
Rimettar Stomatite
98 (22.2%) 90 (20.5%) 80 (18.2%) 77 (17.5%)
98 (22. 2%) 90 (20. 5%)
7 (1.6%) 7 (1.6%) 4 (0.9%) 15 (3.4%)
7 (1. 6%) 7 (1. 6%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (0.5%)
0 (0. 0%) 0 (0. 0%)
Yellow skin/ Skin discolouration
Skonfort fil- ħalq
146 (33.2%)
11 (2. 5%)
tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Palmar-plantar erythrodysaesthesia syndrome
Ġilda safra / Tibdil fil- kulur tal- ġilda
106 (24.1%)
146 (33. 2%)
Very common Very common Common Common Common Common Common Common Common Common Common
Komuni ħafna
67 (15.2%) 64 (14.5%) 41 (9.3%) 33 (7.5%) 29 (6.6%) 20 (4.5%) 20 (4.5%) 18 (4.1%) 16 (3.6%) 16 (3.6%) 15 (3.4%)
Sindromu Palmar - plantar eritrodisasteżija
0 (0.0%) 3 (0.7%) 0 (0.0%) 0 (0.0%) 1 (0.2%) 0 (0.0%) 3 (0.7%) 0 (0.0%) 1 (0.2%) 0 (0.0%) 0 (0.0%)
106 (24. 1%)
26
27 (6. 1%)
System Organ Class
0 (0. 0%)
Adverse Reactions
Tibdil fil- kulur tax - xagħar
All Grades n (%)
67 (15. 2%)
Grade 3 n (%)
0 (0. 0%)
Grade 4 n (%)
0 (0. 0%)
Common Common Common
Komuni ħafna Komuni Komuni Komuni Komuni Komuni Komuni Komuni Komuni Komuni
Skin exfoliation Blister Skin lesion
Raxx Ġilda xotta Alopeċja Dermatite Edema periorbitali Reazzjoni tal- ġilda Eritema Ekżema Ħakk Pigmentazzjoni eċċessiva tal- ġilda
12 (2.7%) 10 (2.3%) 10 (2.3%)
64 (14. 5%) 41 (9. 3%) 33 (7. 5%) 29 (6. 6%) 20 (4. 5%) 20 (4. 5%) 18 (4. 1%) 16 (3. 6%) 16 (3. 6%) 15 (3. 4%)
0 (0.0%) 1 (0.2%) 1 (0.2%)
3 (0. 7%) 0 (0. 0%) 0 (0. 0%) 1 (0. 2%) 0 (0. 0%) 3 (0. 7%) 0 (0. 0%) 1 (0. 2%) 0 (0. 0%) 0 (0. 0%)
0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
Muscoloskeletal, connective tissue
Disturbi muskolu - skeltrali u tal -
Very Common
Komuni Komuni Komuni Komuni ħafna
Pain in extremity/ limb
Tqaxxir tal- ġilda Nuffata Leżjoni fil- ġilda Uġigħ fl - estremità/ membri
54 (12.3%)
12 (2. 7%) 10 (2. 3%) 10 (2. 3%) 54 (12. 3%)
5 (1.1%)
0 (0. 0%) 1 (0. 2%) 1 (0. 2%) 5 (1. 1%)
0 (0.0%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
and bone disorders
connective tissue Disturbi ġenerali
Common Common Common Common Common
Komuni Komuni Komuni Komuni Komuni Komuni ħafna
Arthralgia Myalgia Muscle spasm Back pain Muscular weakness
Artralġja Uġigħ fil- muskoli Spażmu fil- muskoli Uġigħ fid- dahar Dgħjufija fil- muskoli Għeja kbira/ Telqa
39 (8.9%) 29 (6.6%) 21 (4.8%) 11 (2.5%) 10 (2.3%)
39 (8. 9%) 29 (6. 6%) 21 (4. 8%) 22 (2. 5%) 10 (2. 3%) 287
3 (0.7%) 0 (0.0%) 1 (0.2%) 2 (0.5%) 1 (0.2%)
3 (0. 7%) 0 (0. 0%) 1 (0. 2%) 2 (0. 5%) 1 (0. 2%) 64 (14. 5%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 5 (1. 1%)
Fatigue/ Asthenia
u kondizzjonijiet
64 (14.5%)
kbira
5 (1.1%)
(65. 2%)
administration site conditions
ta 'mnejn jingħata
Mucosal Inflammation
Infjammazzjoni tal- mukoża Edema d
70 (15.9%)
70 (15. 9%)
6 (1.4%)
1 (0. 2%)
Very common Common
Komuni Komuni
Oedema d Pyrexia
Deni Nuqqas ta ’ rqad
59 (13.4%) 26 (5.9%)
26 (5. 9%) 14 (3. 2%)
1 (0.2%) 2 (0.5%)
2 (0. 5%) 0 (0. 0%)
0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%)