natgillin/translations-raw huggingface dataset:
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).
Rottidel ja ahvidel hinnati kuni 9 kuud kestnud korduva manustamise toksilisuse uuringutes ravimi toimet seedetrakti märklaudorganitele (oksendamine ja kõhulahtisus ahvidel), neerupealisele (neerupealise koore kongestioon ja/ või hemorraagia rottidel ja ahvidel, koos fibroosile järgneva nekroosiga rottidel), hemolümfopoeetilisele süsteemile (rakkude vähesus luuüdis ja lümfi vähenemine tüümuses, põrnas ja lümfisõlmedes), eksokriinsele pankreasele (atsinaarrakkude degranulatsioon koos üksikute rakkude nekroosiga), süljenäärmetele (atsinaarne hüpertroofia), luuühendustele (kasvuplaadi paksenemine), emakale (atroofia) ja munasarjadele (folliikulite arengu pidurdumine).
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
Rottidel esines embrüo/ loote suremust elusloodete arvu märkimisväärse vähenemisena, resorptsioonide arvu suurenemisena implantatsioonijärgse loote suremuse suurenemisena ja järglaste üldise suremisena kaheksal tiinel emasel 28- st plasmakontsentratsioonide puhul, mis olid 5, 5 korda suuremad, kui seda esineb kliinilistes tingimustes.
Capsule content Mannitol Croscarmellose Sodium Povidone Magnesium Stearate
Mannitool Kroskarmelloosnaatrium Povidoon Magneesiumstearaat
Orange Capsule Shell Gelatin Red Iron Oxide (E172) Titanium dioxide (E171)
Želatiin Punane raudoksiid (E172) Titaandioksiid (E171)
Caramel Capsule Shell Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
Želatiin Titaandioksiid (E171) Kollane raudoksiid (E172) Punane raudoksiid (E172) Must raudoksiid (E172)
Pfizer Ltd Ramsgate Road Sandwich, Kent CT13 9NJ United Kingdom
38 Ramsgate Road Sandwich, Kent CT13 9NJ Ühendkuningriik
36 1.
39 1.
SUTENT 50 mg hard capsules
SUTENT 50 mg kõvakapslid
Each capsule contains sunitinib malate equivalent to 50 mg of sunitinib Excipient(s):
Iga kapsel sisaldab 50 mg sunitiniibi (malaadina).
79,326 mg of mannitol.
79, 326 mg mannitooli.
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.
Karamellivärvi kaane ja karamellivärvi korpusega želatiinkapslid, mis sisaldavad kollaseid kuni oranže graanuleid; kaanele on trükitud valge trükivärviga “ Pfizer ” ja korpusele “ STN 50 mg ”.
37 SUTENT should not be used in paediatric population until further data become available.
SUTENTi ei tohi lastel kasutada enne, kui saadakse rohkem andmeid.
Elderly patients use:
40 Kasutamine eakatel patsientidel:
Haemorrhage Haemorrhagic events, some of which were fatal, reported through post-marketing experience, have included GI, respiratory, tumour, urinary tract and brain haemorrhages.
Hemorraagia Turustamisjärgselt on teatatud hemoorraagilistest sündmustest, millest mõned on lõppenud surmaga, nende sündmuste hulgas on olnud seedetrakti, hingamisteede, kasvajast tingitud, kuseteede ja aju verejookse.
38 refractory MRCC, 26% experienced bleeding.
Tsütokiin- refraktoorse MRCC tõttu sunitiniibmalaati saanud patsientidest täheldati verejookse 26% - l.
39 SUTENT arm experienced fatal cardiac events.
42 patsientidest.
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).
QT- intervalli pikenemine Inimestele soovitatavast annusest suuremate annustega läbi viidud mittekliiniliste (in vivo ja in vitro) uuringute tulemused näitavad, et sunitiniib võib inhibeerida südame aktsioonipotentsiaali repolarisatsiooniprotsessi (näiteks pikendada QT intervalli).
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).
Kompleksses seeriaviisilises EKG uuringus, mis tehti ajahetkedel, mis vastasid terapeutilisele või sellest suuremale plasmakontsentratsioonile, ei täheldatud mitte ühelgi patsiendil hinnatavas ega ravikavatsuslikus (ITT) populatsioonis QTc pikenemist, mida oleks võinud klassifitseerida „ tõsiseks “ (st ≥3. aste CTCAE versiooni 3. 0 järgi).
At therapeutic plasma concentrations, the maximum QTcF (Frederica’ s correction) mean change from baseline was 9.6 msec (90% CI 15.1msec).
Terapeutiliste plasmakontsentratsioonide juures oli QTcF (Frederica parandus) keskmine suurim muutus võrreldes lähtetasemega 9, 6 millisekundit (90% - line usalduspiir 15, 1 millisekundit).
QT interval prolongation may lead to an increased risk of ventricular arrhythmias including Torsade de pointes.
43 QT intervalli pikenemine võib viia suurenenud ventrikulaarsete arütmiate, sealhulgas torsade de pointes’ i tekkeriskile.
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.
Seitsmel (3%) SUTENTi ja mitte ühelgi platseebot saanud patsiendil tekkisid III faasi GIST- i uuringus trombemboolilised sündmused; viis seitsmest olid III staadiumi süvaveeni tromboosid (DVT) ja kaks olid I või II staadiumi omad.
Pulmonary Events Patients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.
Respiratoorsed tüsistused SUTENTi kliinilistesse uuringutesse ei kaasatud patsiente, kellel viimase 12 kuu vältel oli esinenud kopsuarteri trombemboolia.
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.
III faasi registreerimisuuringutes täheldati SUTENTiga ravitud patsientidel raviga seotud kopsutüsistusi (st hingeldus, pleuraefusioon, kopsuarteri trombemboolia või kopsuturse) ligikaudu 5% - l GIST- iga patsientidest ja umbes 14% - l MRCC- ga patsientidest.
All patients should be observed closely for signs and symptoms of thyroid dysfunction on sunitinib treatment.
Kilpnäärme talitluse häirele viitavate nähtude ja/ või sümptomitega
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.
44 patsientidel tuleb laboratoorselt kontrollida kilpnäärmetalitlust ja ravida neid standardsete meditsiiniliste tavade järgi.
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
Kliinilistes uuringutes ja turustamisjärgselt on harvadel juhtudel teatatud hüpertüreoosist, millele osadel juhtudel on järgnenud hüpotüreoos.
If symptoms of pancreatitis or hepatic failure are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.
Kui esinevad pankreatiidi sümptomid, tuleb patsientide ravi SUTENTiga katkestada ja tagada neile sobiv toetav ravi.
41 Renal function The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Neerufunktsioon SUTENTiga ravi jätkamise ohutust mõõduka või raske proteinuuriaga patsientidel ei ole süstemaatiliselt hinnatud.
If this is not possible, the dosage of SUTENT may need to be reduced to a minimum of 37.5 mg daily, based on careful monitoring of the tolerability (see section 4.2).
45 Kui see ei ole võimalik, võib osutuda vajalikuks SUTENTi annust vähendada minimaalse annuseni 37, 5 mg ööpäevas, jälgides hoolikalt ravimi talutavust (vt lõik 4. 2).
John’ s Wort) may decrease sunitinib concentrations.
SUTENTi manustamine koos tugevate CYP3A4 indutseerijatega (nt deksametasoon, fenütoiin, karbamasepiin, rifampitsiin, fenobarbitaal või naistepuna) võib vähendada sunitiniibi kontsentratsiooni plasmas.
42 Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SUTENT.
Fertiilses eas naistele tuleb soovitada vältida rasestumist SUTENT- ravi ajal.
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.
46 Fataalsed kõrvaltoimed (va need, mis on nimetatud eelpool lõigus 4. 4 või lõigus 4. 8 allpool), mille seost SUTENT- iga peeti võimalikuks, olid hulgiorganpuudulikkus, dissemineerunud intravaskulaarne koagulatsioon, kõhuõõnesisene verejooks, rabdomüolüüs, tserebrovaskulaarne haigus, dehüdratsioon, neerupealiste puudulikkus, neerupuudulikkus, hingamispuudulikkus, pleuraefusioon, pneumotooraks, šokk ja äkksurm.
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.
Allpool on loetletud organsüsteemi klasside, esinemissageduste ja raskusastme kaupa raviga seotud kõrvaltoimed, millest teatas > 2% soliidtuumoritega patsientidest.
28 (6.4%)
28 (6, 4%)
16 (3.6%)
16 (3, 6%)
2 (0.5%)
2 (0, 5%)
187 (42.5%)
187 (42, 5%) 161 (36, 6%) 98 (22, 2%) 90 (20, 5%) 80 (18, 2%) 77 (17, 5%)
24 (5.5%)
24 (5, 5%) 15 (3, 4%) 7 (1, 6%) 7 (1, 6%) 4 (0, 9%) 15 (3, 4%)
Very common
Väga sage Väga sage Sage
Nausea
Kõhupuhitus Suuvalu Kõhukinnisus
161 (36.6%)
46 (10, 5%) 44 (10, 0%) 37 (8, 4%)
15 (3.4%)
0 (0, 0%) 2 (0, 5%) 2 (0, 5%)
0 (0.0%)
0 (0, 0%) 0 (0, 0%) 0 (0, 0%)
Very common Very common Very common Very common
Organsüsteemi klass
Vomiting Stomatitis Dyspepsia Abdominal pain C / distension
Esinemis - sagedus
98 (22.2%) 90 (20.5%) 80 (18.2%) 77 (17.5%)
Kõik raskusastmed n (%)
7 (1.6%) 7 (1.6%) 4 (0.9%) 15 (3.4%)
3. raskusaste n (%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (0.5%)
4. raskusaste n (%)
Very common Very common Common Common Common Common
Sage Sage Sage
Flatulence Oral pain Constipation Glossodynia Dry mouth Gastro-oesophageal reflux disease
Keelevalu Suukuivus Gastro- ösofageaalne reflukshaigus
46 (10.5%) 44 (10.0%) 37 (8.4%) 37 (8.4%) 31 (7.0%) 12 (2.7%)
37 (8, 4%) 31 (7, 0%) 12 (2, 7%)
0 (0.0%) 2 (0.5%) 2 (0.5%) 0 (0.0%) 0 (0.0%) 1 (0.2%)
0 (0, 0%) 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%)
Mouth ulceration Oral discomfort
Suu haavandumine Ebamugavustunne suus
Very common Very common Common Common Common Common Common Common Common Common
Väga sage Väga sage Sage Sage Sage Sage Sage Sage Sage Sage Sage
Hair colour changes Rash Dry skin Alopecia Dermatitis Periorbital oedema Skin Reaction Erythema Eczema Pruritus
Juuksevärvi muutus Lööve Kuiv nahk Alopeetsia Dermatiit Silmaümbruse turse Nahareaktsioon Erüteem Ekseem Nahasügelus Naha hüperpigmentatsioon
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%)
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%)
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%) 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%) 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
Sage Sage Sage
Frequency
Naha eksfoliatsioon Villid Nahakahjustus
Adverse Reactions
12 (2, 7%) 10 (2, 3%) 10 (2, 3%)
All Grades n (%)
0 (0, 0%) 1 (0, 2%) 1 (0, 2%)
Grade 3 n (%)
0 (0, 0%) 0 (0, 0%) 0 (0, 0%)
Grade 4 n (%)
Lihas- skeleti, sidekoe ja
Skin hyperpigmentation
Valu jäsemes/ jäsemetes
15 (3.4%)
54 (12, 3%)
0 (0.0%)
5 (1, 1%)
Skin exfoliation Blister Skin lesion
Artralgia Müalgia Lihasspasm Seljavalu Lihasnõrkus
12 (2.7%) 10 (2.3%) 10 (2.3%)
39 (8, 9%) 29 (6, 6%) 21 (4, 8%) 11 (2, 5%) 10 (2, 3%)
0 (0.0%) 1 (0.2%) 1 (0.2%)
3 (0, 7%) 0 (0, 0%) 1 (0, 2%) 2 (0, 5%) 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%)
Muscoloskeletal, connective tissue
Üldised häired ja manustamisko - ha reaktsioonid
Very Common
Väga sage Väga sage
Pain in extremity/ limb
Väsimus/ asteenia Limaskestade põletik
54 (12.3%)
287 (65, 2%) 70 (15, 9%)
5 (1.1%)
64 (14, 5%) 6 (1, 4%)
0 (0.0%)
5 (1, 1%) 1 (0, 2%)
Common Common Common Common Common
Väga sage Sage
Arthralgia Myalgia Muscle spasm Back pain Muscular weakness
Turse d Püreksia
39 (8.9%) 29 (6.6%) 21(4.8%) 11 (2.5%) 10 (2.3%)
59 (13, 4%) 26 (5, 9%)
3 (0.7%) 0 (0.0%) 1 (0.2%) 2 (0.5%) 1 (0.2%)
1 (0, 2%) 2 (0, 5%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0, 0%) 0 (0, 0%)
General disorders and
Psühhiaatrili - sed häired
Fatigue/ Asthenia
Unetus
287 (65.2%)
14 (3, 2%)
64 (14.5%)
0 (0, 0%)
5 (1.1%)
0 (0, 0%)
Oedema** Pyrexia
Vere valgeliblede arvu väheneminee
Investigations
48 Organsüsteemi klass
Lipase increase White blood cell count decreased e
Kõrvaltoime
35 (8.0%) 33 (7.5%)
Kõik raskusastmed n (%)
12 (2.7%) 15 (3.4%)
3. raskusaste n (%)
7 (1.6%) 0 (0.0%)
4. raskusaste n (%)
Ejection fraction decrease
Vereliistakute arvu vähenemine
27 (6.1%)
25 (5, 7%)
5 (1.2%)
4 (0, 9%)
Haemoglobin decrease
Kehakaalu vähenemine
Platelet count decrease
Kreatiinfosfokinaasi sisalduse suurenemine veres
25 (5.7%)
22 (5, 0%)
4 (0.9%)
1 (0, 2%)
Weight decreased Blood creatinine phosphokinase increased
Amülaasisisalduse suurenemine
23 (5.2%) 22 (5.0%)
21 (4, 8%)
1 (0.2%) 1 (0.2%)
8 (1, 8%)
45 Treatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studies
Varem mitteravitud MRCC ja tsütokiin- refraktoorse MRCC uuringutes esinenud raviga seotud kõrvaltoimed
Very common Common Common
Väga sage Väga sage Väga sage Sage Sage
Anaemia Leukopoenia Lymphopenia
Neutropeenia Trombotsütopeenia Aneemia Leukopeenia Lümfopeenia
67 (12.3%) 45 (8.3%) 21 (3.9%)
89 (16, 4%) 86 (15, 8%) 67 (12, 3%) 45 (8, 3%) 21 (3, 9%)
20 (3.7%) 16 (2.9%) 12 (2.2%)
46 (8, 5%) 37 (6, 8%) 20 (3, 7%) 16 (2, 9%) 12 (2, 2%)
3 (0.6%) 0 (0%) 1 (0.2%)
5 (0, 9%) 5 (0, 9%) 3 (0, 6%) 0 (0%) 1 (0, 2%)
disorders Nervous system disorders
Söögiisu langusa Dehüdratsioon Maitsetundlikkuse häireb
Common Common
Organsüsteem
Hypoaesthesia Hyperaesthesia
Kõrvaltoimed
20 (3.7%) 17 (3.1%)
Kõik raskusastme d n (%)
0 (0%) 0 (0%)
3. raskusaste n (%)
Respiratory, thoracic and
Hingamisteede, rindkere - ja mediastiinumi häired
2 (0.4%)
3 (0, 6%)
185 (34.0%)
1 (0, 2%) 0 (0%) 0 (0%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
13 (2.4%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Vomiting
Düsfaagia Keelepõletik Igemeverejooks Hemorroidid Proktalgia Suuhaavandid Ebamugavustunne maos
17 (3.1%)
20 (3, 7%) 19 (3, 5%) 18 (3, 3%) 18 (3, 3%) 17 (3, 1%) 16 (2, 9%) 15 (2, 8%)
Grade 3 n (%)
2 (0, 4%) 1 (0, 2%) 0 (0%) 0 (0%) 1 (0, 2%) 0 (0%) 0 (0%)
Grade 4 n (%)
1 (0, 2%) 1 (0, 2%) 0 (0%) 0 (0%) 0 (0%) 1 (0, 2%) 0 (0%)
Abdominal pain c / distension
Pärasoole verejooks
106 (19.5%)
13 (2, 4%)
10 (1.8%)
0 (0%)
Very common
Väga sage Väga sage Väga sage Väga sage Sage
Rash
Lööve Kuiv nahk Juuste värvi muutus Alopeetsia Erüteem
121 (22.2%)
121 (22, 2%) 108 (19, 9%) 103 (18, 9%) 64 (11, 8%) 51 (9, 4%)
2 (0.4%)
2 (0, 4%) 1 (0, 2%) 0 (0%) 0 (0%) 2 (0, 4%)
1 (0.2%)
1 (0, 2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Very common
50
Dry skin
Organsüsteem
108 (19.9%)
Sagedus
1 (0.2%)
Kõrvaltoimed
0 (0%)
Kõik
Very common
3.
Hair colour changes
4.
103 (18.9%)
raskusastme d n (%)
0 (0%)
raskusaste n (%)
Very common Common Common Common Common Common Common Common
Sage Sage Sage Sage Sage Sage
Alopecia Erythema Skin exfoliation Pruritus Periorbital oedema Dermatitis Skin lesion Nail disorder/ discolouration
Naha eksfoliatsioon Nahasügelus Silmaümbruse turse Dermatiit Nahakahjustus Küünte kahjustus / värvimuutus
64 (11.8%) 51 (9.4%) 47 (8.6%) 40 (7.4%) 31 (5.7%) 27 (5.0%) 26 (4.8%) 25 (4.6%)
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%)
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%)
Musculoskeletal and connective tissue disorders
Skeleti - lihassüsteemi ja sidekoe häired
Very Common Common Common Common Common
Sage Sage Sage Sage
127 (23.3%)
127 (23, 3%) 99 (18, 2%) 37 (6, 8%) 35 (6, 4%) 20 (3, 7%) 13 (2, 4%)
99 (18.2%)
8 (1, 5%) 5 (0, 9%) 3 (0, 6%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
5 (0.9%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
System Organ Class
Psühhiaatrilised häired Uuringud
Frequency
Sage Sage Väga sage
Adverse Reactions
Unetus Depressioon Väljutusfraktsiooni vähenemine
All Grades n (%)
22 (4, 0%) 15 (2, 8%) 84 (15, 4%)
Grade 3 n (%)
0 (0, 0%) 1 (0, 2%) 16 (2, 9%)
Grade 4 n (%)
0 (0, 0%) 0 (0, 0%) 0 (0%)
Pyrexia Chills Pain Chest pain
Kehakaalu vähenemine
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%)
Common Common Very common
Sage
Insomnia Depression Ejection fraction decrease
Trombotsüütide arvu vähenemine
22 (4.0%) 15 (2.8%) 84 (15.4%)
41 (7, 5%)
0 (0%) 1 (0.2%) 16 (2.9%)
15 (2, 8%)
0 (0%) 0 (0%) 0 (0%)
2 (0, 4%)
Weight decrease Platelet count decrease
Vere valgeliblede arvu väheneminee
57 (10.5%) 41 (7.5%)
37 (6, 8%)
1 (0.2%) 15 (2.8%)
16 (2, 9%)
0 (0%) 2 (0.4%)
0 (0%)
White blood cell count decreased e
Lipaasi sisalduse suurenemine
37 (6.8%)
36 (6, 6%)
16 (2.9%)
19 (3, 5%)
0 (0%)
11 (2%)
Lipase increase Haemoglobin decreased
Hemoglobiinisisalduse vähenemine
36 (6.6%) 25 (4.6%)
25 (4, 6%)
19 (3.5%) 8 (1.5%)
8 (1, 5%)
11 (2%) 0 (0%)
0 (0%)
Blood creatine phosphokinase increased
Kreatiniinfosfokinaasi sisalduse suurenemine veres
19 (3.5%)
19 (3, 5%)
Common
Sagedus
Blood creatinine increased
Kõrvaltoimed
15 (2.8%)
Kõik raskusastme d n (%)
2 (0.4%)
3. raskusaste n (%)
Alanine aminotransferase increased
Vererõhu kõrgenemine Alaniini aminotransferaasi sisalduse suurenemine
The following terms have been combined: a Anorexia and decreased appetite b Dysgeusia, ageusia and taste disturbance c Abdominal pain and abdominal pain upper d Oedema, oedema peripheral and oedema face e White blood cell count decreased, neutrophil count decreased, and leukocyte count decreased
– anoreksia ja söögiisu vähenemine; b – düsgeuusia, asgeuusia ja maitsetundlikkuse häire; c – kõhuvalu ja valu ülakõhus; d – turse, perifeerne turse ja näopiirkonna turse; e – vere valgeliblede, neutrofiilide ja leukotsüütide arvu vähenemine.
48 Uncommon:
Uuringud
Infections(with or without neutropoenia) connective tissue disorders Myopathy and/ or Rhabdomyolysis
Müopaatia ja/ või rabdomüolüüs
Musculoskeletal and connective tissue disorders:
52 Lihas- skeleti ja sidekoe kahjustused:
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.
Tõhusus põhineb vastavalt ajal kasvaja progresseerumiseni ja elulemuse suurenemisel GIST- i puhul ning progresseerumisvabal elulemusel ja objektiivsetel vastuse tasemetel varem mitteravitud ja tsütokiin- refraktaarse MRCC puhul.
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).
53 SUTENTi III faasi randomiseeritud topeltpime platseeboga kontrollitud uuring viidi läbi GISTiga patsientidel, kes ei talunud imatiniibi (mediaanne maksimaalne ööpäevane annus 800 mg) või kelle haigus imatiniibravi ajal või pärast seda progresseerus.
50 The primary efficacy endpoint of this study was Objective Response Rate (ORR).
Esmane tõhususe tulemusnäitaja oli selles uuringus objektiivne ravivastuse määr (ORR).
Food has no effect on the bioavailability of sunitinib.
54 Toit ei mõjuta sunitiniibi biosaadavust.
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.
Farmakokineetika plasmas Pärast suukaudset manustamist tervetele vabatahtlikele on sunitiniibi ja tema põhilise aktiivse desetüülmetaboliidi eliminatsiooni poolväärtusaeg vastavalt umbes 40... 60 tundi ja 80... 110 tundi.
The primary active metabolite comprises 23 to 37% of the total exposure.
23... 37% kogu biosaadavusest langeb põhilise aktiivse metaboliidi
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
Küülikutel oli tiinuse ajal emaka massi ja elusloodete arvu vähenemine tingitud resorptsioonide arvu suurenemisest, implantatsioonijärgsest loote suremuse suurenemisest ja järglaste üldisest suremisest neljal tiinel küülikul kuuest plasmakontsentratsioonide puhul, mis olid 3 korda suuremad, kui seda esineb kliinilistes tingimustes.
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.
Seda iseloomustab eeskätt lülisamba
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.
56 rinna - / nimmeosa luustumise pidurdumisega ja see esines plasmakontsentratsioonide puhul, mis olid 6 korda suuremad, kui kliinilistes tingimustes.
Capsule content Mannitol Croscarmellose Sodium Povidone (K-25) Magnesium Stearate
Mannitool Kroskarmelloosnaatrium Povidoon Magneesiumstearaat
Capsule Shell Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
Želatiin Titaandioksiid (E171) Kollane raudoksiid (E172) Punane raudoksiid (E172) Must raudoksiid (E172)
53 6.6 Special precautions for disposal
6. 6 Erinõuded hävitamiseks
7.
57 7.
54 ANNEX II
58 LISA II
55 A.
59 A.
PFIZER Italia S. r. l Via del Commercio Zona Industriale IT-63046 Marino del Tronto (Ascoli Piceno) Italy
Via del Commercio Zona Industriale IT- 63046 Marino del Tronto (Ascoli Piceno) Itaalia