qanastek/EMEA-V3 huggingface dataset:
Psychiatric disorders
Reazzjonijiet avversi
Insomnia
Żieda fil- lipase
14 (3.2%)
35 (8. 0%)
0 (0.0%)
12 (2. 7%)
0 (0.0%)
7 (1. 6%)
Lipase increase White blood cell count decreased e
Tnaqqis fl- għadd taċ - ċelloli bojod tad - demm e
35 (8.0%) 33 (7.5%)
35 (7. 5%)
12 (2.7%) 15 (3.4%)
15 (3. 4%)
7 (1.6%) 0 (0.0%)
0 (0. 0%)
Ejection fraction decrease
Tnaqqis fil- frazzjoni tat- tfigħ ’ il barra
Weight decreased Blood creatinine phosphokinase increase
Tnaqqis fil- piż Żidiet fil- creatinine phosphokinase fid - demm
Any adverse event
Kwalunkwe reazzjoni avversa
27
5 (0. 9%)
System Organ Class
limfatika
Adverse Reactions
Tromboċitopenija
All Grades n (%)
86 (15. 8%)
Grade 3 n (%)
37 (6. 8%)
Grade 4 n (%)
5 (0. 9%)
Blood and lymphatic system disorders
Komuni ħafna
Very common Very common Very common Common Common
Komuni Komuni
Neutropoenia Thrombocytopoenia Anaemia Leukopoenia Lymphopenia
Lewkopenija Limfopenija
89 (16.4%) 86 (15.8%) 67 (12.3%) 45 (8.3%) 21 (3.9%)
45 (8. 3%) 21 (3. 9%)
46 (8.5%) 37 (6.8%) 20 (3.7%) 16 (2.9%) 12 (2.2%)
16 (2. 9%) 12 (2. 2%)
5 (0.9%) 5 (0.9%) 3 (0.6%) 0 (0%) 1 (0.2%)
0 (0%) 1 (0. 2%)
Endocrine disorders
Disturbi tal- fwied u tal- marrara
Lacrimation increased
Żieda fid- dmugħ Edema fil- kpiepel ta ’ l - għajnejn Tnaqqis fl- aptit a
39 (7.2%)
39 (7. 2%) 12 (2. 2%)
Eyelid oedema
205 (37. 7%)
12 (2.2%)
9 (1. 7%)
0 (0%)
30
Metabolism and nutrition
Sistema ta ’ Klassifika ta ’ l - Organi
Very Common
Frekwenza
Decreased appetite
Reazzjonijiet avversi
205 (37.7%)
Il- Gradi Kollha n (%)
9 (1.7%)
Grad 3 n (%)
disorders Nervous system disorders
nutrizzjoni
Common Very common
Komuni
Dehydration Taste disturbance b
Deidrazzjoni Disturb fit- togħma b
7 (1.3%) 1 (0.2%)
7 (1. 3%)
1 (0.2%) 0 (0%)
1 (0. 2%)
Very common Common Common Common
Disturbi fis- sistema nervuża
Headache Dizziness Paraesthesia Neuropathy peripheral
Komuni ħafna
82 (15.1%) 38 (7.0%) 36 (5.9%) 33 (6.1%)
250 (46. 0%)
3 (0.6%) 2 (0.4%) 0 (0%) 1 (0.2%)
1 (0. 2%)
Hypoaesthesia Hyperaesthesia
Uġigħ ta ’ ras
20 (3.7%) 17 (3.1%)
82 (15. 1%)
0 (0%) 0 (0%)
3 (0. 6%)
Very common
Komuni Komuni Komuni Komuni Komuni Komuni ħafna
Hypertension
Sturdament Parasteżija Newropatija periferali Ipoestesija Iperestesija Pressjoni għolja
143 (26.3%)
38 (7. 0%) 36 (5. 9%) 33 (6. 1%) 20 (3. 7%) 17 (3. 1%) 143
55 (10.1%)
(26. 3%)
0 (0%)
(10. 1%)
Common Common
Komuni Komuni Komuni ħafna
Flushing Hot flush
Fwawar Fwawar tal- menopawsa Epistassi
17 (3.1%) 12 (2.2%)
17 (3. 1%) 12 (2. 2%) 86 (15. 8%)
0 (0%) 0 (0%)
0 (0%) 0 (0%) 3 (0. 6%)
Respiratory, thoracic and mediastinal disorders
toraċiċi u medjastinali
Epistaxis
Qtugħ ta ’ nifs Uġigħ fil- larinġi u l - farinġi
86 (15.8%)
45 (8. 3%) 29 (5. 3%)
3 (0.6%)
6 (1. 1%) 2 (0. 4%)
Common Common
Komuni Komuni Komuni Komuni
Dyspnoea Pharyngolaryngeal pain
Sogħla Disfonja Nixfa nażali Qtugħ ta ’ nifs bl - eżerċizzju
45 (8.3%) 29 (5.3%)
23 (4. 2%) 16 (2. 9%) 14 (2. 6%) 12 (2. 2%)
6 (1.1%) 2 (0.4%)
0 (0%) 0 (0%) 0 (0%) 0 (0%)
Common Common Common Common Common Common
Komuni Komuni
Cough Dysphonia Nasal dryness Dyspnoea exertional Nasal congestion Pleural effusion
Konġestjoni nażali Effużjoni tal- plewra
23 (4.2%) 16 (2.9%) 14 (2.6%) 12 (2.2%) 12 (2.2%) 12 (2.2%)
12 (2. 2%)
326 (59.9%)
326 (59. 9%)
38 (7.0%)
38 (7. 0%)
290 (53.3%)
290 (53. 3%)
19 (3.5%)
19 (3. 5%)
189 (34.7%)
189 (34. 7%)
8 (1.5%)
8 (1. 5%)
185 (34.0%)
185 (34. 0%)
13 (2.4%)
13 (2. 4%)
Vomiting
Remettar Uġigħ addominali c /
178 (32.7%)
178 (32. 7%)
17 (3.1%)
10 (1. 8%)
Abdominal pain c / distension 28
Gass fl- istonku
106 (19.5%)
60 (11. 0%)
10 (1.8%)
56 (10. 3%)
Very common Very common Very common Very common Very common Common
Komuni
Constipation Glossodynia Flatulence Oral pain Dry mouth Gastroesophageal reflux disease
Mard ta ’ refluss gastro - esofaġiku
83 (15.3%) 63 (11.6%) 60 (11.0%) 60 (11.0%) 56 (10.3%) 50 (9.2%)
50 (9. 2%)
Common Common Common Common Common Common Common Common Very common
Komuni Komuni Komuni Komuni Komuni Komuni Komuni Komuni Komuni ħafna
Dysphagia Cheilitis Gingival bleeding Haemorrhoids Proctalgia Mouth ulceration Stomach discomfort Rectal haemorrhage Palmar-plantar erythrodysaesthesia syndrome
Disfaġja Cheilitis Ħanek jinfasad Murliti Proktalġja Ulċerazzjoni fil- ħalq Diqa fl- istonku Emorraġija mir- rektum Sindromu Palmar -
20 (3.7%) 19 (3.5%) 18 (3.3%) 18 (3.3%) 17 (3.1%) 16 (2.9%) 15 (2.8%) 13 (2.4%) 144 (26.5%)
20 (3. 7%) 19 (3. 5%) 18 (3. 3%) 18 (3. 3%) 17 (3. 1%) 16 (2. 9%) 15 (2. 8%) 13 (2. 4%) 144 (26. 5
2 (0.4%) 1 (0.2%) 0 (0%) 0 (0%) 1 (0.2%) 0 (0%) 0 (0%) 0 (0%) 46 (8.5%)
2 (0. 4%) 1 (0. 2%) 0 (0%) 0 (0%) 1 (0. 2%) 0 (0%) 0 (0%) 0 (0%) 46 (8. 5%)
1 (0.2%) 1 (0.2%) 0 (0%) 0 (0%) 0 (0%) 1 (0.2%) 0 (0%) 0 (0%) 0 (0%)
1 (0. 2%) 1 (0. 2%) 0 (0%) 0 (0%) 0 (0%) 1 (0. 2%) 0 (0%) 0 (0%) 01 (0%)
Yellow discolouration/ Skin discolouration
Tidnis isfar fil- ġilda / Tibdil fil- kulur tal- ġilda
121 (22.2%)
121 (22. 2%)
108 (19.9%)
108 (19. 9%)
Hair colour changes
Tibdil fil- kulur tax- xagħar
103 (18.9%)
103 (18. 9%)
Very common Common Common Common Common Common Common Common
Komuni Komuni Komuni Komuni Komuni Komuni Komuni
Alopecia Erythema Skin exfoliation Pruritus Periorbital oedema Dermatitis Skin lesion Nail disorder/ discolouration
Eritema Tqaxxir tal- ġilda Ħakk Edema periorbitali Dermatite Leżjoni fil- ġilda Disturb / tidnis tad - dwiefer
64 (11.8%) 51 (9.4%) 47 (8.6%) 40 (7.4%) 31 (5.7%) 27 (5.0%) 26 (4.8%) 25 (4.6%)
51 (9. 4%) 47 (8. 6%) 40 (7. 4%) 31 (5. 7%) 27 (5. 0%) 26 (4. 8%) 25 (4. 6%)
0 (0%) 2 (0.4%) 4 (0.7%) 1 (0.2%) 1 (0.2%) 4 (0.7%) 1 (0.2%) 0 (0%)
2 (0. 4%) 4 (0. 7%) 1 (0. 2%) 1 (0. 2%) 4 (0. 7%) 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 (0%) 0 (0%) 0 (0%) 0 (0. 2%)
General disorders and
kondizzjonijiet ta ’
95 (17.5%)
(73. 0%)
1 (0.2%)
(17. 5%)
Mucosal inflammation
Infjammazzjoni tal - mukuża Edema d
127 (23.3%)
127 (23. 3%)
Very common Common Common
Komuni Komuni Komuni Komuni Komuni
Oedema d Pyrexia Chills
Deni Tertir Uġigħ Uġigħ fis- sider Nuqqas ta ’ rqad
99 (18.2%) 37 (6.8%) 35 (6.4%)
37 (6. 8%) 35 (6. 4%) 20 (3. 7%) 13 (2. 4%) 22 (4. 0%)
5 (0.9%) 3 (0.6%) 2 (0.4%)
3 (0. 6%) 2 (0. 4%) 0 (0%) 2 (0. 4%) 0 (0%)
Common Common
Komuni Komuni ħafna
Pain Chest pain
15 (2. 8%) 84
20 (3.7%) 13 (2.4%)
1 (0. 2%) 16 (2. 9%)
0 (0%) 2 (0.4%)
(15. 4%)
Common Common Very common
Komuni ħafna
Insomnia Depression Ejection fraction decrease
Tnaqqis fil- piż
22 (4.0%) 15 (2.8%) 84 (15.4%)
57 (10. 5%)
0 (0%) 1 (0.2%) 16 (2.9%)
1 (0. 2%)
Weight decrease Platelet count decrease
Tnaqqis fl- għadd tal - plejtlits
57 (10.5%) 41 (7.5%)
41 (7. 5%)
1 (0.2%) 15 (2.8%)
15 (2. 8%)
0 (0%) 2 (0.4%)
2 (0. 4%)
White blood cell count decreased e
Tnaqqis fl- għadd taċ - ċelloli bojod tad- demm
37 (6.8%)
37 (6. 8%)
16 (2.9%)
16 (2. 9%)
Common Common
Komuni Komuni Komuni
Blood creatine phosphokinase increased
Żieda fil- lipase Tnaqqis fl- emoglobina Żieda fil- creatine phosphokinase fid - demm
19 (3.5%)
36 (6. 6%) 25 (4. 6%) 19 (3. 5%)
7 (1.3%)
19 (3. 5%) 8 (1. 5%) 7 (1. 3%)
2 (0.4%)
11 (2%) 0 (0%) 2 (0. 4%)
Aspartate aminotransferase increased
Żieda fl- aspartate aminotransferase
Infections and Infestations Not known:
Infezzjonijiet u infestazzjonijiet Mhux magħrufa
Infections (with or without neutropoenia) connective tissue disorders Myopathy and/ or rhabdomyolysis
Disturbi muskolu- skeletrali u tal- connective tissue Mhux magħrufa Disturbi pulmonari
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).
Sunitinib was identified as an 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).
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
34 STUDJI KLINIĊI Is- sigurtà u l- effikaċja klinika ta ’ SUTENT ġiet studjata fit- trattament ta ’ pazjenti b’ tumur stromali gastrointestinali malinn (GIST) li kienu reżistenti għal imatinib (i. e. dawk li esperjenzaw progressjoni tal- marda waqt jew wara trattament b’ imatinib) jew intoleranti għal imatinib (i. e. dawk li esperjenzaw tossiċità sinifikattiva waqt trattament b’ imatinib li pprekluda aktar trattament) u t- trattament ta ’ pazjenti b’ karċinoma taċ- ċellola renali metastatika (MRCC).
31 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.
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.
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 għal0- Karċinoma Metastatika taċ- Ċellola Renali (MRCC) 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.
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.
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.
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, tikketta 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.
32 In this study the ORR was 35,8% (95% C. I.
F’ dan l- istudju l- ORR kienet 35, 8% (95% C. I.
The apparent volume of distribution (V/ F) for sunitinib was large – 2230l -, indicating distribution into the tissues.
Skond id- dataset analizzat (10 studji f’ voluntiera u pazjenti b’ saħħithom, doża singola u multipla), il - volum ta ’ distribuzzjoni (V/ F) apparenti 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 primary active metabolite are unlikely to inhibit metabolism, to any clinically relevant extent, of drugs that may be metabolized by these enzymes.
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.
Organ Functions impairment Hepatic insufficiency:
36 Indeboliment tal- Funzjoni ta ’ l- Organi Indeboliment epatiku:
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.
Esponimenti sistemiċi wara doża waħda ta ’ SUTENT kienu simili f’ suġġetti b’ indeboliment tal- fwied ħafif jew moderat (Klassi Child- Pugh A u B) imqabbla ma ’ suġġetti b’ funzjoni epatika normali.
33 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 ingħatar 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.
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.
No significant changes in the pharmacokinetics of sunitinib or the primary, active metabolite are observed with repeated daily administration or with repeated cycles in the dosing regimens tested.
L- ebda bidliet sinifikattivi fil- farmakokinetiċi ta ’ sunitinib jew il- metabolit attiv primarju ma huma osservati b’ ingħatar ripetuta ta ’ kuljum jew b’ ċikli ripetuti fir- reġimens ta ’ l- iddożar ittestjati.
The pharmacokinetics were similar in all solid tumour populations tested and in healthy volunteers.
Il- farmakokinetiċi kienu simili fil - popolazzjonijiet ta ’ tumuri solidi kollha ttestjati u f’ voluntiera f’ saħħithom.
In rat and monkey repeated-dose toxicity studies up to 9-months duration, the primary target organ effects were identified in the gastrointestinal tract (emesis and diarrhoea in monkeys), adrenal gland (cortical congestion and/ or haemorrhage in rats and monkeys, with necrosis followed by fibrosis in rats), 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).
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
Carcinogenicity Carcinogenicity studies with sunitinib malate have not been performed.
Karċinoġeniċità Ma ġewx magħmula studji fuq karċinoġeniċità b’ sunitinib malate.
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
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.
Orange Capsule Shell Gelatin Red Iron Oxide (E172) Titanium dioxide (E171)
Qoxra oranġjo tal- kapsuli Gelatin Red Iron Oxide (E172) Titanium dioxide (E171)
Caramel Capsule Shell Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
Qoxra tal- Kapsula Kanella Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
Printing ink Shellac Propylene glycol Sodium hydroxide Povidone Titanium dioxide (E171)
38 Sodium hydroxide Povidone Titanium dioxide (E171)
EU/ 1/ 06/ 347/ 002 EU/ 1/ 06/ 347/ 005
EU/ 1/ 06/ 347/ 002 ΕU/ 1 // 06/ 347/ 005
SUTENT 50 mg hard capsules
SUTENT 50 mg kapsuli iebsin.
Each capsule contains sunitinib malate equivalent to 50 mg of sunitinib Excipient(s):
Kull kapsula fiha sunitinib malate, ekwivalenti għal 50 mg ta ’ sunitinib Sustanza mhux attiva:
79,326 mg of mannitol.
79, 326 mg ta ’ mannitol.
Hard Capsules Gelatin capsule with caramel cap and caramel body, printed with white ink “ Pfizer” on the cap and “ STN 50 mg” on the body and containing yellow to orange granules.
Kapsuli iebsin Kapsuli tal- ġelatina b’ kappa kannella u bil- parti ewlenija kannella, bil- kelma “ Pfizer ” stampata b’ inka bajda fuq il- kappa u “ STN 50 mg ” fuq il- parti ewlenija, u li fihom granijiet safrani għal oranġjo.
If this is not possible the doses of SUTENT may need to be reduced to a minimum of 37.5 mg daily, based on careful monitoring of the tolerability.
Jekk dan mhuwiex possibbli d- dożi ta ’ SUTENT
Selection of an alternate concomitant medication with no, or minimal potential to induce or inhibit CYP3A4 should be considered.
Selezzjoni ta ’ medikazzjoni konkomitanti alternattiva bla ebda, jew b’ potenzjal minimu li tinduċi jew timpedixxi CYP3A4 għandha tiġi kkunsidrata.
37 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.
These events may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage.
Fi prova klinika
Fatal pulmonary haemorrhage occurred in 2 patients receiving SUTENT on a clinical trial of patients with metastatic non-small cell lung cancer (NSCLC).
41 f’ pazjenti b’ kanċer tal- pulmun mhux biċ- ċelloli żgħar metastatiku (NSCLC), emorraġija pulmonari fatali seħħet f’ 2 pazjenti li kienu qed jingħataw SUTENT.
Both patients had squamous cell histology.
Iż- żewġ pazjenti t- tnejn kellhom istoloġija taċ- ċellola skwamuża.
Epistaxis was the most common treatment-related haemorrhagic adverse event, having been reported for approximately half of the patients with solid tumours who experienced haemorrhagic events.
Fi studju li sar mingħajr kontrolli, 26% tal- pazjenti li ngħataw SUTENT għal MRCC refrattarja għaċ- ċitokini ppreżentaw b’ reazzjonijiet emorraġiċi.
Gastrointestinal events Nausea, diarrhoea, stomatitis, dyspepsia and vomiting were the most commonly reported treatment-related gastrointestinal events.
L- aktar reazzjoni avversa emorraġika relatata mat- trattament komuni kienet l- epistassi, li ġiet irrapportata f’ bejn wieħed u ieħor nofs il- pazjenti b’ tumuri solidi li esperjenzaw reazzjonijiet emorraġiċi.
Supportive care for gastrointestinal adverse events requiring treatment may include medication with an anti- emetic or anti-diarrhoeal medication.
L- ebda waħda minn dawn ir- reazzjonijiet ma kienet serja.
In the treatment-naïve MRCC study, 21% patients on SUTENT and 12% of patients on interferon-α (IFN-α), had an LVEF value below the lower limit of normal.
Fl- istudju MRCC ta ’ trattament fuq pazjenti li qatt ma kienu ħadu qabel din il- kura, 21% ta ’ pazjenti fuq SUTENT u 12% ta ’ pazjenti fuq 42 interferon- α (IFN- α), kellhom il- valur tal- LVEF taħt il- limitu t’ isfel tan- normal.
QT Interval prolongation Data from non-clinical (in vitro and in vivo) studies, at doses higher than the recommended human dose, indicate that sunitinib has the potential toinhibit 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).
Using comprehensive serial ECG assessments at times corresponding to either therapeutic or greater than therapeutic exposures, none, of the patients in the evaluable or ITT populations were observed to develop QTc prolongation considered as “ severe” (i. e. equal to or greater than Grade 3 by CTCAE version 3.0).
Bl- użu ta ’ evalwazzjonijiet komprensivi b’ ECG konsekuttivi, xi drabi jikkorrispondu għal esponimenti jew terapewtiċi jew akbar minn terapewtiċi, l- ebda wieħed mill- pazjenti fil - popolazzjonijiet li setgħu jiġu evalwati jew ITT ma ġie osservat li żviluppa titwil tal- QTc li kien ikkunsidrat bħala “ sever ” (jiġifieri daqs jew aktar minn Grad 3 mill- CTCAE verżjoni 3. 0).
At therapeutic plasma concentrations, the maximum QTcF (Frederica’ s correction) mean change from baseline was 9.6 msec (90% CI 15.1msec).
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).
Moxifloxacin (400 mg) used as a positive control showed a 5.6 msec maximum mean QTcF change from baseline.
Moxifloxacin (400 mg) użat bħala kontroll pożittiv wera bidla massima medja fl- QTcF
QT interval prolongation may lead to an increased risk of ventricular arrhythmias including Torsade de pointes.
It- titwil ta ’ l- interval QT jista ’ jwassal għal żieda fir- riskju ta ’ arritmiji ventrikulari inkluż Torsade de pointes.
Torsade de pointes has been observed in < 0.1% of SUTENT-exposed patients.
Torsade de pointes ġie osservat f ’ < 0. 1% ta ’ pazjenti esposti għal SUTENT.
Concomitant treatment with potent CYP3A4 inhibitors, which may increase sunitinib plasma concentrations, should be used with caution and the dose of SUTENT reduced (see Section 4.2 and 4.5).
Trattament konkomitanti b’ impedituri CYP3A4 potenti, li jistgħu jżiedu l - konċentrazzjonijiet ta ’ sunitinib fil- plażma, għandhom jintużaw b’ kawtela u d- doża ta ’ SUTENT għandha titnaqqas (ara Sezzjoni 4. 2 u 4. 5).
40 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.
Pulmonary 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.
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.
Il- pazjenti kollha għandhom ikunu osservati sew għall- sinjali u sintomi ta ’ ipotirojdiżmu waqt trattament b’ sunitinib 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.
Hypothyroidism was reported as an adverse event in 7 patients (4%) across the two cytokine-refractory MRCC studies; in nine patients (2%) on SUTENT and one patient (< 1%) in the IFN-α arm in the treatment- naïve MRCC study.
L- ipotirojdiżmu kien irrapportat bħala reazzjoni avversa f’ seba ’ pazjenti (4%) matul iż- żewġ studji ta ’ MRCC refrattarja għaċ- ċitokini; f’ disgħa pazjenti (2%) fuq SUTENT u f’ pazjent wieħed (< 1%) fid - driegħ IFN- α fl- istudju MRCC fi trattament li qatt ma kien ittieħed qabel.
Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%).
Barraminhekk, żidiet fit - 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.
44 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.
Pancreatitis has been observed rarely (< 1%) in patients receiving SUTENT for GIST or MRCC.
F’ pazjenti li qegħdin jieħdu SUTENT minħabba GIST jew MRCC, rari ġiet osservata pankreatite (< 1%).
Cases of serious pancreatic events, some with fatal outcome, have been reported.
Kienu rrappurtati każi ta ’ episodji serji ta ’ pankreatite, wħud minnhom b’ eżitu fatali.
If symptoms of pancreatitis or hepatic failure 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.
41 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 decrease sunitinib plasma concentrations:
Mediċini li jistgħu jnaqqsu l- konċentrazzjonijiet ta ’ sunitinib fil- plażma:
Administration of SUTENT with potent inducers of the CYP3A4 family (e. g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or Hypericum perforatum known also as St.
L- għoti ta ’ SUTENT ma ’ impedituri potenti tal - familja CYP3A4 (eż. dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital jew 45 Hypericum perforatum magħrufa ukoll bħala St.
42 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.
Patients should be advised that they may experience dizziness during treatment with SUTENT.
Il- pazjenti għandhom jiġu avżati li jistgħu jesperjenzaw sturdamenti waqt trattament b’ SUTENT.
Fatigue, hypertension and neutropoenia were the most common treatment-related adverse events of Grade 3 maximum severity and increased lipase was the most frequently occurring treatment-related adverse event of Grade 4 maximum severity in patients with solid tumours.
Għejja kbira, pressjoni għolja u newtropenja kienu l - aktar reazzjonijiet avversi komuni relatati mat- trattament ta ’ severità massima fi Grad 3 u żieda fil - lipase kienet l- aktar reazzjoni avversa komuni relatata mat- trattament ta ’ severità massima Grad 4 f’ pazjenti b’ tumuri solidi.
Fatal events other than those listed in section 4.4 above or section 4.8 below which were considered possibly related to SUTENT 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 f’ sezzjoni 4. 8 hawn isfel, li kienu kkunsidrati bħala possibbilment relatati ma ’ SUTENT, kienu jinkludu: insuffiċjenza ta ’ organi
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 rapportati 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).
Hypertension
Ipoestesija Pressjoni għolja
101 (23.0%)
10 (2. 3%) 101 (23. 0%)
43 (9.8%)
0 (0. 0%) 43 (9. 8%)
Respiratory, thoracic and mediastinal disorders
Disturbi
28 (6.4%)
28 (6. 4%)
16 (3.6%)
16 (3. 6%)
2 (0.5%)
2 (0. 5%)
Very common Very common Very common Very common
Komuni ħafna Komuni ħafna Komuni ħafna
Vomiting Stomatitis Dyspepsia Abdominal pain C / distension
Rimettar Stomatite Dispepsja Uġigħ addominali c /
98 (22.2%) 90 (20.5%) 80 (18.2%) 77 (17.5%)
98 (22. 2%) 90 (20. 5%) 80 (18. 2%)
7 (1.6%) 7 (1.6%) 4 (0.9%) 15 (3.4%)
7 (1. 6%) 7 (1. 6%) 4 (0. 9%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (0.5%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
Very common Very common Common Common Common Common
Komuni ħafna
Flatulence Oral pain Constipation Glossodynia Dry mouth Gastro-oesophageal reflux disease
Distensjoni
46 (10.5%) 44 (10.0%) 37 (8.4%) 37 (8.4%) 31 (7.0%) 12 (2.7%)
77 (17. 5%)
0 (0.0%) 2 (0.5%) 2 (0.5%) 0 (0.0%) 0 (0.0%) 1 (0.2%)
15 (3. 4%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
2 (0. 5%)
Common Common
Komuni ħafna Komuni ħafna
Mouth ulceration Oral discomfort
Gass fl- istonku Uġigħ fil- ħalq
11 (2.5%) 11 (2.5%)
46 (10. 5%) 44 (10. 0%)
0 (0.0%) 0 (0.0%)
0 (0. 0%) 2 (0. 5%)
Skin and subcutaneous
Klassi tas- Sistema ta ’ l- Organi
Very common
Komuni Komuni Komuni Komuni
Yellow skin/ Skin discolouration
2 (0. 5%) 0 (0. 0%) 0 (0. 0%) 1 (0. 2%)
146 (33.2%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
0 (0.0%)
11 (2. 5%)
tissue disorders
0 (0. 0%)
Palmar-plantar erythrodysaesthesia syndrome
Skonfort fil- ħalq
106 (24.1%)
11 (2. 5%)
Very common Very common Common Common Common Common Common Common Common Common
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Hair colour changes Rash Dry skin Alopecia Dermatitis Periorbital oedema Skin Reaction Erythema Eczema Pruritus
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%)
Ġilda safra / Tibdil fil- kulur tal- ġilda
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%)
146 (33. 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%)
44 System Organ Class
0 (0. 0%)
Adverse Reactions
Sindromu Palmar - plantar eritrodisasteżija
All Grades n (%)
106 (24. 1%)
Grade 3 n (%)
27 (6. 1%)
Skin hyperpigmentation
Tibdil fil- kulur tax - xagħar
15 (3.4%)
67 (15. 2%)
12 (2.7%) 10 (2.3%) 10 (2.3%)
67 (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%)
Very Common
Komuni Komuni Komuni Komuni
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
59 (13.4%) 26 (5.9%)
59 (13. 4%)
1 (0.2%) 2 (0.5%)
1 (0. 2%)
Common
Komuni Komuni Komuni Komuni
Insomnia
Deni Nuqqas ta ’ rqad Żieda fil- lipase Tnaqqis fl- għadd taċ - ċelloli bojod tad - demm
14 (3.2%)
26 (5. 9%) 14 (3. 2%) 35 (8. 0%) 33 (7. 5%)
0 (0.0%)
2 (0. 5%) 0 (0. 0%) 12 (2. 7%) 15 (3. 4%)
0 (0.0%)
0 (0. 0% 0 (0. 0%) 7 (1. 6%) 0 (0. 0%)
Lipase increase White blood cell count decreased e
Tnaqqis fil- frazzjoni
35 (8.0%) 33 (7.5%)
27 (6. 1%)
12 (2.7%) 15 (3.4%)
5 (1. 2%)
Ejection fraction decrease
Reazzjonijiet avversi tat- tfigħ ’ il barra
27 (6.1%)
Il- Gradi Kollha n (%)
5 (1.2%)
Grad 3 n (%)
Haemoglobin decrease
Tnaqqis fl- emoglobina
Weight decreased Blood creatinine phosphokinase increased
Tnaqqis fil- piż Żidiet fil- creatinine phosphokinase fil- plażma
21 (4.8%) 18 (4.1%)
21 (4. 8%) 18 (2. 7%)
8 (1.8%) 2 (0.5%)
8 (1. 8%) 2 (0. 2%)
45 Treatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studies
Reazzjonijiet Avversi relatati mat- trattament rrapportati fi studju studji ta ’ MRCC refrattarja għaċ- ċitokini bi trattament mingħajr konsapevolezzau li qatt ma kienet ittrattata qabel
Endocrine disorders
Komuni ħafna
Hypothyroidism
Lewkopenija Limfopenija
67 (12.3%)
45 (8. 3%) 21 (3. 9%)
7 (1.3%)
16 (2. 9%) 12 (2. 2%)
0 (0%)
0 (0%) 1 (0. 2%)
Eye disorders
Disturbi tal- fwied u tal- marrara
Lacrimation increased
Ipotirojdiżmu
39 (7.2%)
67 (12. 3%)
Eyelid oedema
Żieda fid- dmugħ Edema fil- kpiepel ta ’ l - għajnejn Tnaqqis fl- aptit a
12 (2.2%)
39 (7. 2%) 12 (2. 2%)
Metabolism and nutrition
Disturbi fil - metaboliżmu u n -
205 (37.7%)
205 (37. 7%)
Vascular disorders
49 Sistema ta ’ Klassifika ta ’ l - Organi
Very common
Frekwenza
Hypertension
Reazzjonijiet avversi
143 (26.3%)
Il- Gradi Kollha n (%)
55 (10.1%)
Grad 3 n (%)
Flushing Hot flush
Sturdament
17 (3.1%) 12 (2.2%)
38 (7. 0%)
0 (0%) 0 (0%)
2 (0. 4%)
Respiratory, thoracic and
Disturbi vaskulari
Very common
Komuni Komuni Komuni Komuni Komuni ħafna
Epistaxis
Parasteżija Newropatija periferali Ipoestesija Iperestesija Pressjoni għolja
86 (15.8%)
36 (5. 9%) 33 (6. 1%) 20 (3. 7%) 17 (3. 1%) 143 (26. 3%)
3 (0.6%)
0 (0%) 1 (0. 2%) 0 (0%) 0 (0%) 5 (10. 1%)
mediastinal
Disturbi respiratorji,
Common
Komuni Komuni Komuni ħafna
Dyspnoea
Fwawar Fwawar tal- menopawsa Epistassi
45 (8.3%)
17 (3. 1%) 12 (2. 2%) 86 (15. 8%)
6 (1.1%)
0 (0%) 0 (0%) 3 (0. 6%)
disorders
toraċiċi u medjastinali
Pharyngolaryngeal pain
Qtugħ ta ’ nifs Uġigħ fil- larinġi u l - farinġi
29 (5.3%)
45 (8. 3%) 29 (5. 3%)
2 (0.4%)
6 (1. 1%) 2 (0. 4%)
Common Common Common Common Common Common
Komuni Komuni Komuni Komuni
Cough Dysphonia Nasal dryness Dyspnoea exertional Nasal congestion Pleural effusion
Sogħla Disfonja Nixfa nażali Qtugħ ta ’ nifs bl - eżerċizzju
23 (4.2%) 16 (2.9%) 14 (2.6%) 12 (2.2%) 12 (2.2%) 12 (2.2%)
23 (4. 2%) 16 (2. 9%) 14 (2. 6%) 12 (2. 2%)
Very common
Komuni Komuni Komuni ħafna
Diarrhoea
Konġestjoni nażali Effużjoni tal- plewra Dijarea
326 (59.9%)
12 (2. 2%) 12 (2. 2%) 326 (59. 9%)
38 (7.0%)
0 (0%) 4 (0. 6%) 38 (7. 0%)
46 System Organ Class
Komuni ħafna
Frequency
83 (15. 3%)
Adverse Reactions
Komuni ħafna
All Grades n (%)
63 (11. 6%)
Abdominal pain c / distension
Gass fl- istonku
10 (1.8%)
5 (1%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
56 (10. 3%)
Common Common Common Common Common Common Common Common
Komuni Komuni Komuni Komuni
Dysphagia Cheilitis Gingival bleeding Haemorrhoids Proctalgia Mouth ulceration Stomach discomfort Rectal haemorrhage
Disfaġja Cheilitis Ħanek jinfasad Murliti
20 (3.7%) 19 (3.5%) 18 (3.3%) 18 (3.3%) 17 (3.1%) 16 (2.9%) 15 (2.8%) 13 (2.4%)
20 (3. 7%) 19 (3. 5%) 18 (3. 3%) 18 (3. 3%)
2 (0.4%) 1 (0.2%) 0 (0%) 0 (0%) 1 (0.2%) 0 (0%) 0 (0%) 0 (0%)
2 (0. 4%) 1 (0. 2%) 0 (0%) 0 (0%)
1 (0.2%) 1 (0.2%) 0 (0%) 0 (0%) 0 (0%) 1 (0.2%) 0 (0%) 0 (0%)
1 (0. 2%) 1 (0. 2%) 0 (0%) 0 (0%)
Palmar-plantar erythrodysaesthesia syndrome
Proktalġja Ulċerazzjoni fil- ħalq Diqa fl- istonku Emorraġija mir- rektum Sindromu Palmar
144 (26.5%)
17 (3. 1%) 16 (2. 9%) 15 (2. 8%) 13 (2. 4%) 144
46 (8.5%)
1 (0. 2%) 0 (0%) 0 (0%) 0 (0%) 46 (8. 5%)
0 (0%)
(26. 5%)
23 (4.2%) 23 (4.2%) 22 (4.0%) 19 (3.5%)
23 (4. 2%) 23 (4. 2%) 22 (4. 0%) 19 (3. 5%) 96 (17. 6%%)
Very Common Common Common Common Common
Komuni Komuni Komuni Komuni Komuni ħafna
General disorders and
kondizzjonijiet ta '
99 (18.2%)
99 (18. 2%)
5 (0.9%)
5 (0. 9%)
47
Investigazzjonijiet
System Organ Class
Komuni Komuni Komuni Komuni Komuni Komuni Komuni ħafna
Frequency
Deni Tertir Uġigħ Uġigħ fis- sider Nuqqas ta ’ rqad Depressjoni Tnaqqis fil- frazzjoni tat -
Adverse Reactions
37 (6. 8%) 35 (6. 4%) 20 (3. 7%) 13 (2. 4%) 22 (4. 0%) 15 (2. 8%) 84
All Grades n (%)
3 (0. 6%) 2 (0. 4%) 0 (0%) 2 (0. 4%) 0 (0%) 1 (0. 2%) 16 (2. 9%)
Grade 3 n (%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Grade 4 n (%)
(15. 4%)
Common Common Common Common
Komuni ħafna
Pyrexia Chills Pain Chest pain
Tnaqqis fil- piż
37 (6.8%) 35 (6.4%) 20 (3.7%) 13 (2.4%)
57 (10. 5%)
3 (0.6%) 2 (0.4%) 0 (0%) 2 (0.4%)
1 (0. 2%)
Psychiatric disorders Investigations
51 Sistema ta ’ Klassifika ta ’ l - Organi
Common Common Very common
Frekwenza
Insomnia Depression Ejection fraction decrease
Reazzjonijiet avversi
22 (4.0%) 15 (2.8%) 84 (15.4%)
Il- Gradi Kollha n (%)
0 (0%) 1 (0.2%) 16 (2.9%)
Grad 3 n (%)
0 (0%) 0 (0%) 0 (0%)
Grad 4 n (%)
48 Uncommon:
Mhux komuni:
Infections(with or without neutropoenia) connective tissue disorders Myopathy and/ or Rhabdomyolysis
Disturbi muskolu- skeltrali u tal- connective tissue Mhux magħrufa Disturbi pulmonari
Cases of serious infection (with or without neutropoenia), including pneumonia, have been reported.
Kienu rrapurtati każijiet ta ’ infezzjoni serja (b ’ newtropenja jew mingħajr) inkluża pnewmownja.
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).
49 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.
STUDJI KLINIĊI Is- sigurtà u l- effikaċja klinika ta ’ SUTENT ġiet studjata fit- trattament ta ’ pazjenti b’ tumur stromali gastrointestinali malinn (GIST) li kienu reżistenti għal imatinib (i. e. dawk li esperjenzaw progressjoni tal- marda waqt jew wara trattament b’ imatinib) jew intoleranti għal imatinib (i. e. dawk li esperjenzaw
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.
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) 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.
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% (95% C. I.
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.
54 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.
50 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).
The apparent volume of distribution (V/ F) for sunitinib was large – 2230l -, indicating distribution into the tissues.
Skond id- dataset analizzat, (10 studji f’ voluntiera u pazjenti b’ saħħithom, doża singola u multipla) il - volum ta ’ distribuzzjoni (V/ F) apparaneti għal sunitinib kien kbir – 2230l -, li jindika distribuzzjoni fit- tessuti.
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 enzimi CYP maġġuri, inkluż CYP3A4.
Total oral clearance (CL/ F) was 34-62 l/ hr.
L- eliminazzjoni orali totali (CL/ F) kienet ta ’ 34- 62 L/ siegħa.
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.
55 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.
51 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.
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 primarju tiegħu jakkumula 7 sa 10 darbiet.
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.
In rat and monkey repeated-dose toxicity studies up to 9-months duration, the primary target organ effects were identified in the gastrointestinal tract (emesis and diarrhoea in monkeys), adrenal gland (cortical congestion and/ or haemorrhage in rats and monkeys, with necrosis followed by fibrosis in rats), 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 immirati 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).
Sunitinib was not clastogenic in rat bone marrow in vivo.
Sunitinib ma kienx klastoġeniku
Capsule content Mannitol Croscarmellose Sodium Povidone (K-25) Magnesium Stearate
Kontenut tal- kapsula Mannitol Croscarmellose Sodium Povidone (K- 25) Magnesium Stearate
Capsule Shell Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
Qoxra tal- Kapsula Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
Printing ink Shellac Propylene glycol Sodium hydroxide Povidone Titanium dioxide (E171)
Inka ta ’ l- istampar Shellac Propylene glycol Sodium hydroxide Povidone Titanium dioxide (E171)
6.2 Incompatibilities
57 6. 2 Inkompatibiltajiet
53 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
EU/ 1/ 06/ 347/ 003 EU/ 1/ 06/ 347/ 006
EU/ 1/ 06/ 347/ 003 ΕU/ 1 // 06/ 347/ 006
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
DETENTUR TA 'L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT
PFIZER Italia S. r. l Via del Commercio Zona Industriale IT-63046 Marino del Tronto (Ascoli Piceno) Italy
PFIZER Italia S. r. l Via del Commercio Zona Industriale IT- 63046 Marino del Tronto (Ascoli Piceno) L- Italja
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 1.1 (dated 8 November 2007) presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema ta ’ farmakoviġilanza Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq irid jassigura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 1. 1 (b’ data tat- 8 ta ’ Novembru 2007) ippreżentata fil - Modulu 1. 8. 1. ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq, tkun fis- seħħ qabel u waqt li l- prodott ikun fis- suq.