natgillin/translations-raw huggingface dataset:
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.
Hematoloogia III faasi GIST- i uuringus täheldati 3. ja 4. astme neutrofiilide absoluutarvu vähenemist vastavalt 10% - l ja 1, 7% - l patsientidest ning III faasi MRCC uuringus vastavalt 16% - l ja 1, 6% - l patsientidest.
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.
Trombotsüütide arvu 3. ja 4. astme vähenemist täheldati III faasi GIST- i uuringus vastavalt 3, 7% - l ja 0, 4% - l patsientidest ning III faasi MRCC uuringus vastavalt 8, 2% - l ja 1, 1% - l patsientidest.
21 SUTENT arm experienced fatal cardiac events.
23 patsientidest.
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).
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).
QT interval prolongation may lead to an increased risk of ventricular arrhythmias including Torsade de pointes.
24 QT intervalli pikenemine võib viia suurenenud ventrikulaarsete arütmiate, sealhulgas torsade de pointes’ i tekkeriskile.
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.
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.
Respiratory 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.
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.
Ligikaudu 8% - l tihkete tuumoritega patsientidest (sealhulgas GIST- iga ja MRCC- ga patsiendid), kes said kliinilistes uuringutes SUTENTi, täheldati raviga seotud kopsutüsistusi.
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
25 Kliinilistes uuringutes ja turustamisjärgselt on harvadel juhtudel teatatud hüpertüreoosist, millele osadel juhtudel on järgnenud hüpotüreoos.
If symptoms of pancreatitis 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.
23 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.
Drugs that may increase sunitinib plasma concentrations:.
Ravimid, mis võivad suurendada sunitiniibi kontsentratsiooni plasmas:
John’ s Wort) may decrease sunitinib concentrations.
26 SUTENTi manustamine koos tugevate CYP3A4 indutseerijatega (nt deksametasoon, fenütoiin, karbamasepiin, rifampitsiin, fenobarbitaal või naistepuna) võib vähendada sunitiniibi kontsentratsiooni plasmas.
24 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 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.
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.
27 Allpool on loetletud organsüsteemi klasside, esinemissageduste ja raskusastme kaupa raviga seotud kõrvaltoimed, millest teatas > 2% soliidtuumoritega patsientidest.
Very common Common Common Common
Väga sage Sage Sage Sage
Headache Paraesthesia Dizziness Neuropathy peripheral
Peavalu Paresteesia Pearinglus Perifeerne neuropaatia
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%)
10 (2.3%)
10 (2, 3%)
Very common
Väga sage Väga sage Väga sage Väga sage Väga sage Väga sage
Diarrhoea
Kõhulahtisus Iiveldus Oksendamine Stomatiit Düspepsia Kõhuvaluc / kõhu paisumine
161 (36.6%)
187 (42, 5%) 161 (36, 6%) 98 (22, 2%) 90 (20, 5%) 80 (18, 2%) 77 (17, 5%)
15 (3.4%)
24 (5, 5%) 15 (3, 4%) 7 (1, 6%) 7 (1, 6%) 4 (0, 9%) 15 (3, 4%)
0 (0.0%)
0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 2 (0, 5%)
Very common Very common Very common Very common
Väga sage Väga sage Sage Sage Sage Sage
Vomiting Stomatitis Dyspepsia Abdominal pain C / distension
Kõhupuhitus Suuvalu Kõhukinnisus Keelevalu Suukuivus Gastro- ösofageaalne reflukshaigus
98 (22.2%) 90 (20.5%) 80 (18.2%) 77 (17.5%)
46 (10, 5%) 44 (10, 0%) 37 (8, 4%) 37 (8, 4%) 31 (7, 0%) 12 (2, 7%)
7 (1.6%) 7 (1.6%) 4 (0.9%) 15 (3.4%)
0 (0, 0%) 2 (0, 5%) 2 (0, 5%) 0 (0, 0%) 0 (0, 0%) 1 (0, 2%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (0.5%)
0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%)
Very common Very common Common Common Common Common
Sage Sage
Flatulence Oral pain Constipation Glossodynia Dry mouth Gastro-oesophageal reflux disease
Suu haavandumine Ebamugavustunne suus 28
46 (10.5%) 44 (10.0%) 37 (8.4%) 37 (8.4%) 31 (7.0%) 12 (2.7%)
11 (2, 5%) 11 (2, 5%)
0 (0.0%) 2 (0.5%) 2 (0.5%) 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%) 0 (0, 0%)
Common Common
Organsüsteemi klass
Mouth ulceration Oral discomfort
Esinemis - sagedus
11 (2.5%) 11 (2.5%)
Kõik raskusastmed n (%)
0 (0.0%) 0 (0.0%)
3. raskusaste n (%)
0 (0.0%) 0 (0.0%)
4. raskusaste n (%)
Pain in extremity/ limb
Valu jäsemes/ jäsemetes
54 (12.3%)
54 (12, 3%)
Arthralgia Myalgia Muscle spasm Back pain Muscular weakness
Artralgia Müalgia Lihasspasm Seljavalu Lihasnõrkus
39 (8.9%) 29 (6.6%) 21 (4.8%) 11 (2.5%) 10 (2.3%)
39 (8, 9%) 29 (6, 6%) 21 (4, 8%) 11 (2, 5%) 10 (2, 3%)
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%)
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%)
General disorders and
Üldised häired ja manustamisko - ha reaktsioonid Psühhiaatrili - sed häired
Very common
Väga sage Väga sage Väga sage Sage Sage
Fatigue/ Asthenia
Väsimus/ asteenia Limaskestade põletik Tursed Püreksia Unetus
287 (65.2%)
287 (65, 2%) 70 (15, 9%) 59 (13, 4%) 26 (5, 9%) 14 (3, 2%)
64 (14.5%)
64 (14, 5%) 6 (1, 4%) 1 (0, 2%) 2 (0, 5%) 0 (0, 0%)
5 (1.1%)
5 (1, 1%) 1 (0, 2%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%)
administration site conditions
Uuringud
Mucosal Inflammation
Lipaasisisalduse suurenemine
70 (15.9%)
35 (8, 0%)
6 (1.4%)
12 (2, 7%)
1 (0.2%)
7 (1, 6%)
Oedema d Pyrexia
Vere valgeliblede arvu väheneminee
59 (13.4%) 26 (5.9%)
33 (7, 5%)
1 (0.2%) 2 (0.5%)
15 (3, 4%)
0 (0.0%) 0 (0.0%)
0 (0, 0%)
Psychiatric disorders
Väljutusfraktsiooni vähenemine
Insomnia
Hemoglobiini vähenemine
14 (3.2%)
27 (6, 1%)
0 (0.0%)
6 (1, 4%)
Lipase increase White blood cell count decreased e
Vereliistakute arvu vähenemine
35 (8.0%) 33 (7.5%)
25 (5, 7%)
12 (2.7%) 15 (3.4%)
4 (0, 9%)
7 (1.6%) 0 (0.0%)
1 (0, 2%)
Ejection fraction decrease
Kehakaalu vähenemine
27 (6.1%)
23 (5, 2%)
5 (1.2%)
1 (0, 2%)
Haemoglobin decreased
Kreatiinfosfokinaasi sisalduse suurenemine veres
27 (6.1%)
22 (5, 0%)
6 (1.4%)
1 (0, 2%)
Platelet count decrease
Amülaasisisalduse suurenemine
25 (5.7%)
21 (4, 8%)
4 (0.9%)
8 (1, 8%)
Investigations
29 Organsüsteemi klass
Common Common
Esinemis - sagedus
Weight decreased Blood creatinine phosphokinase increase
Kõrvaltoime
23 (5.2%) 22 (5.0%)
Kõik raskusastmed n (%)
1 (0.2%) 1 (0.2%)
3. raskusaste n (%)
0 (0.0%) 1 (0.2%)
4. raskusaste n (%)
Amylase increased Aspartate aminotransferase increased
Aspartaadi aminotransferaasi sisalduse suurenemine
21 (4.8%) 18 (4.1%)
18 (4, 1%)
8 (1.8%) 2 (0.5%)
2 (0, 5%)
12 (2.7%)
12 (2, 7%)
Any adverse event
Muud kõrvaltoimed
414 (94.1%)
414 (94, 1%)
204 (46.4%)
204 (46, 4%)
53 (12.0%)
53 (12, 0%)
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
Järgnevad terminid on ühendatud: a – 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.
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
All Grades n (%)
3. raskusaste n (%)
Neutropoenia Thrombocytopoenia Anaemia Leukopoenia Lymphopenia
Neutropeenia Trombotsütopeenia Aneemia Leukopeenia Lümfopeenia
89 (16.4%) 86 (15.8%) 67 (12.3%) 45 (8.3%) 21 (3.9%)
89 (16, 4%) 86 (15, 8%) 67 (12, 3%) 45 (8, 3%) 21 (3, 9%)
46 (8.5%) 37 (6.8%) 20 (3.7%) 16 (2.9%) 12 (2.2%)
46 (8, 5%) 37 (6, 8%) 20 (3, 7%) 16 (2, 9%) 12 (2, 2%)
5 (0.9%) 5 (0.9%) 3 (0.6%) 0 (0%) 1 (0.2%)
5 (0, 9%) 5 (0, 9%) 3 (0, 6%) 0 (0%) 1 (0, 2%)
Hypothyroidism
Hüpotüreoos
67 (12.3%)
67 (12, 3%)
39 (7.2%)
39 (7, 2%)
12 (2.2%)
12 (2, 2%)
Metabolism and nutrition
Metabolismi - ja toitumishäired Närvisüsteemi häired
Very Common
Väga Sage Sage Väga sage
disorders Nervous system disorders
Söögiisu langus Dehüdratsioon Maitsetundlikkuse häireb
33 (6.1%) 250 (46.0%)
205 (37, 7%) 33 (6, 1%) 250 (46%)
7 (1.3%) 1 (0.2%)
9 (1, 7%) 7 (1, 3%) 1 (0, 2%)
1 (0.2%) 0 (0%)
0 (0%) 1 (0, 2%) 0 (0%)
Very common Common Common Common
Väga sage Sage Sage Sage Sage Sage
Headache Dizziness Paraesthesia Neuropathy peripheral
Peavalu Pearinglus Paresteesia Perifeerne neuropaatia Hüpesteesia Hüperesteesia
82 (15.1%) 38 (7.0%) 36 (5.9%) 33 (6.1%)
82 (15, 1%) 38 (7, 0%) 36 (5, 9%) 33 (6, 1%) 20 (3, 7%) 17 (3, 1%)
3 (0.6%) 2 (0.4%) 0 (0%) 1 (0.2%)
3 (0, 6%) 2 (0, 4%) 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%)
143 (26.3%)
143 (26, 3%)
55 (10.1%)
55 (10, 1%)
Flushing Hot flush
Nahaõhetus Kuumahood
17 (3.1%) 12 (2.2%)
17 (3, 1%) 12 (2, 2%)
Respiratory, thoracic and mediastinal disorders
Hingamisteede, rindkere - ja mediastiinumi häired
86 (15.8%)
86 (15, 8%)
3 (0.6%)
3 (0, 6%)
Common Common
30 Organsüsteem
Dyspnoea Pharyngolaryngeal pain
Kõrvaltoimed
45 (8.3%) 29 (5.3%)
Kõik raskusastme d n (%)
6 (1.1%) 2 (0.4%)
3. raskusaste n (%)
0 (0%) 0 (0%)
4. raskusaste n (%)
Common Common Common Common Common Common
Sage Sage Sage Sage Sage Sage Sage Sage
Cough Dysphonia Nasal dryness Dyspnoea exertional Nasal congestion Pleural effusion
Düspnoe Kurgu - ja neeluvalu Köha Düsfoonia Nina kuivus Pingutusdüspnoe Ninakinnisus Pleuraefusioon
23 (4.2%) 16 (2.9%) 14 (2.6%) 12 (2.2%) 12 (2.2%) 12 (2.2%)
45 (8, 3%) 29 (5, 3%) 23 (4, 2%) 16 (2, 9%) 14 (2, 6%) 12 (2, 2%) 12 (2, 2%) 12 (2, 2%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 3 (0.6%)
6 (1, 1%) 2 (0, 4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 3 (0, 6%)
326 (59.9%)
326 (59, 9%)
38 (7.0%)
38 (7, 0%)
Very common
Väga sage Väga sage Väga sage Väga sage Väga sage
Nausea
Iiveldus Düspepsia Stomatiit Oksendamine Kõhuvaluc / kõhu paisumine
290 (53.3%)
290 (53, 3%) 189 (34, 7%) 185 (34, 0%) 178 (32, 7%) 106 (19, 5%)
19 (3.5%)
19 (3, 5%) 8 (1, 5%) 13 (2, 4%) 17 (3, 1%) 10 (1, 8%)
Very common
Väga sage Väga sage Väga sage Väga sage Väga sage Sage
Dyspepsia
Kõhukinnisus Keelevalu Kõhupuhitus Suuvalu Suukuivus Gastro- ösofageaalne reflukshaigus
189 (34.7%)
83 (15, 3%) 63 (11, 6%) 60 (11, 0%) 60 (11, 0%) 56 (10, 3%) 50 (9, 2%)
8 (1.5%)
1 (0, 2%) 0 (0%) 0 (0%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
Very common
Sage Sage Sage Sage Sage Sage Sage
Stomatitis
Düsfaagia Keelepõletik Igemeverejooks Hemorroidid Proktalgia Suuhaavandid Ebamugavustunne maos
185 (34.0%)
20 (3, 7%) 19 (3, 5%) 18 (3, 3%) 18 (3, 3%) 17 (3, 1%) 16 (2, 9%) 15 (2, 8%)
13 (2.4%)
2 (0, 4%) 1 (0, 2%) 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%)
Vomiting
Pärasoole verejooks
178 (32.7%)
13 (2, 4%)
17 (3.1%)
0 (0%)
Abdominal pain c / distension 28
Peopesade- jalataldade erütrodüsesteesia
106 (19.5%)
144 (26, 5%)
10 (1.8%)
46 (8, 5%)
Adverse Reactions
Naha kollasus / naha värvimuutus
All Grades n (%)
144 (26, 5%)
Grade 3 n (%)
1 (0, 2%)
Very common Very common Very common Very common Very common Common
Väga sage Väga sage Väga sage Väga sage Sage Sage Sage Sage Sage Sage Sage
Constipation Glossodynia Flatulence Oral pain Dry mouth Gastroesophageal reflux disease
Lööve Kuiv nahk Juuste värvi muutus Alopeetsia Erüteem Naha eksfoliatsioon Nahasügelus Silmaümbruse turse Dermatiit Nahakahjustus Küünte kahjustus / värvimuutus
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%)
121 (22, 2%) 108 (19, 9%) 103 (18, 9%) 64 (11, 8%) 51 (9, 4%) 47 (8, 6%) 40 (7, 4%) 31 (5, 7%) 27 (5, 0%) 26 (4, 8%) 25 (4, 6%)
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%) 2 (0, 4%) 4 (0, 7%) 1 (0, 2%) 1 (0, 2%) 4 (0, 7%) 1 (0, 2%) 0 (0%)
1 (0.2%) 1 (0.2%) 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%)
Yellow discolouration/ Skin discolouration
Villid
144 (26.5%)
23 (4, 2%)
Rash
31
121 (22.2%)
Organsüsteem
1 (0.2%)
Sagedus
tissue disorders
Kõrvaltoimed
108 (19.9%)
Kõik raskusastme d n (%)
1 (0.2%)
3. raskusaste n (%)
Hair colour changes
Nahareaktsioon Hüperkeratoos Akne
103 (18.9%)
23 (4, 2%) 22 (4, 0%) 19 (3, 5%)
0 (0%)
6 (1, 1%) 4 (0, 7%) 0 (0%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Skeleti - lihassüsteemi ja sidekoe häired
Common Common Common Common
Väga sage
Blister Skin reaction Hyperkeratosis Acne
Valu jäsemetes
23 (4.2%) 23 (4.2%) 22 (4.0%) 19 (3.5%)
96 (17, 6%)
1 (0.2%) 6 (1.1%) 4 (0.7%) 0 (0%)
6 (1, 1%)
Very common Common Common Common Common
Sage Sage Sage Sage
Pain in extremity Arthralgia Myalgia Muscle Spasm Back pain
Artralgia Müalgia Lihasspasm Seljavalu
96 (17.6%) 49 (9.0%) 48 (8.8%) 26 (4.8%) 17 (3.1%)
49 (9, 0%) 48 (8, 8%) 26 (4, 8%) 17 (3, 1%)
6 (1.1%) 1 (0.2%) 2 (0.4%) 0 (0%) 2 (0.4%)
1 (0, 2%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
Fatigue/ asthenia
Väsimus/ asteenia
397 (73.0%)
397 (73, 0%)
95 (17.5%)
95 (17, 5%)
Very common
Väga sage Väga sage Sage Sage Sage Sage
Mucosal inflammation
Limaskesta põletik Tursedd Püreksia Külmavärinad Valu Valu rindkeres
99 (18.2%) 37 (6.8%) 35 (6.4%)
127 (23, 3%) 99 (18, 2%) 37 (6, 8%) 35 (6, 4%) 20 (3, 7%) 13 (2, 4%)
5 (0.9%) 3 (0.6%) 2 (0.4%)
8 (1, 5%) 5 (0, 9%) 3 (0, 6%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
Grade 3 n (%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Grade 4 n (%)
Psühhiaatrilised häired Uuringud
Common Common
Sage Sage Väga sage
Pain Chest pain
Unetus Depressioon Väljutusfraktsiooni vähenemine
20 (3.7%) 13 (2.4%)
22 (4, 0%) 15 (2, 8%) 84 (15, 4%)
0 (0%) 2 (0.4%)
0 (0, 0%) 1 (0, 2%) 16 (2, 9%)
0 (0%) 0 (0%)
0 (0, 0%) 0 (0, 0%) 0 (0%)
Insomnia Depression Ejection fraction decrease
Kehakaalu vähenemine
Weight decrease Platelet count decrease
Trombotsüütide arvu vähenemine
Lipase increase Haemoglobin decreased
Lipaasi sisalduse suurenemine
36 (6.6%) 25 (4.6%)
36 (6, 6%)
19 (3.5%) 8 (1.5%)
19 (3, 5%)
Aspartate aminotransferase increased
Kreatiniinfosfokinaasi sisalduse suurenemine veres
Blood amylase increased
Aspartaadi aminotransferaasi sisalduse suurenemine
11 (2.0%)
7 (1, 3%)
Blood creatinine increased
Vere amülaasisisalduse suurenemine
15 (2.8%)
18 (3, 3%)
2 (0.4%)
11 (2, 0%)
Blood pressure increased
Vere kreatiniinisisalduse suurenemine
Alanine aminotransferase increased
Vererõhu tõus Alaniini aminotransferaasi sisalduse suurenemine
14 (2.6%)
15 (2, 8%) 14 (2, 6%)
7 (1.3%)
2 (0, 4%) 7 (1, 3%)
2 (0.4%)
0 (0%) 2 (0, 4%)
Any adverse event
Kõik kõrvaltoimed 32
Adverse reactions from post-marketing experience
Kõrvaltoimed pärast turuletoomist
Infections and Infestations Not known:
Infektsioonid ja infestatsioonid Teadmata sagedus:
Renal and urinary disorders:
33 Neerude ja kuseteede häired:
Discontinue SUTENT in patients with nephrotic syndrome (see also section 4.4)
Nefrootilise sündroomi korral tuleb SUTENTi manustamine lõpetada (vt lõik 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).
Sunitiniib identifitseeriti kui vereliistakutest pärit kasvufaktori retseptori (PDGFR- α ja PDGFR- β), veresoonte endoteeli kasvufaktori retseptori (VEGFR1, VEGFR2 ja VEGFR3), tüvirakkude faktori retseptori (KIT), Fms - sarnase türosiini kinaas- 3 (FLT3), kolooniaid stimuleeriva faktori retseptori (CSF- 1R) ja gliiarakkude rakuliinist pärit neurotroofse faktori retseptori (RET) inhibiitor.
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
KLIINILISED UURINGUD SUTENTi kliinilist ohutust ja tõhusust on uuritud mao- sooletrakti pahaloomuliste stromaaltuumoritega (GIST) patsientide ravis, kes olid imatiniibi suhtes resistentsed (st need, kellel esines haiguse progresseerumine imatiniibravi ajal või pärast seda) või kes ei talunud imatiniibi (st need, kellel tekkis märkimisväärne toksilisus imatiniibravi ajal, mis välistas edasise ravi) ja metastaatilise neerurakk- kartsinoomiga (MRCC) patsientide ravis.
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.
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.
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.
Mediaanne TTP oli SUTENTi puhul 28, 9 nädalat (95% CI=21, 3... 34, 1 nädalat) ja see oli statistiliselt oluliselt pikem kui TTP platseeborühmas – 5, 1 nädalat (95% CI=4, 4… 10, 1 nädalat).
0.290- 0.831)]; the risk of death was 2 times higher in patients in the placebo arm compared to the SUTENT arm.
0, 491 (95% CI 0, 290… 0, 831)]; risk surra oli platseeborühma patsientidel 2 korda suurem kui SUTENTirühma
Median overall survival had not yet been reached in either treatment arm at the time of analysis.
Üldise elulemuse mediaan ei olnud analüüsimise ajaks veel kummaski ravirühmas saavutatud.
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.
Varem mitteravitud metastaatiline neerurakuline vähk (MRCC) Viidi läbi III faasi randomiseeritud mitmekeskuseline rahvusvaheline uuring, mis hindas sunitiniibi ohutust ja tõhusust võrreldes IFN- α- ga varem mitteravitud RCC- ga patsientidel.
32 In this study the ORR was 35,8% (95% C. I.
Selles uuringus oli ORR 35, 8% (95% C. I.
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.
Metabolism In vitro arvutatud Ki väärtused kõigi testitud CYP isovormide jaoks (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 ja CYP4A9/ 11) näitasid, et sunitiniib ja selle peamine aktiivne metaboliit ei inhibeeri kliiniliselt olulises ulatuses ravimite metabolismi, mida metaboliseeritakse nende ensüümide poolt.
In-vitro studies also indicate that SUTENT neither induces nor inhibits major CYP enzymes, including CYP3A4.
35 In vitro uuringud viitavad, et SUTENT ei indutseeri ega inhibeeri peamisi CYP ensüüme, sealhulgas 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.
Biotransformatsioon Sunitiniib metaboliseeritakse eeskätt tsütokroom P450 ensüümi CYP3A4 vahendusel, tekib põhiline aktiivne metaboliit, mis metaboliseeritakse edasi CYP3A4 vahendusel.
John’ s Wort) may decrease sunitinib concentrations.
SUTENTi manustamine koos muude CYP3A4 perekonna indutseerijatega (nt deksametasoon, fenütoiin, karbamasepiin, fenobarbitaal või Hypericum perforatum, mida tuntakse ka liht- naistepunana) võib vähendada sunitiniibi kontsentratsioone.
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.
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.
5.3 Preclinical safety data
36 5. 3 Prekliinilised ohutusandmed