natgillin/translations-raw huggingface dataset:
Cases with fatal out- come had been observed in post-marketing setting (see respiratory events and section 4.8).
Smrtne izide so zabeležili v postmarketinškem obdobju (glejte dogodki na dihalih in poglavje 4. 8).
Respiratory Events Patients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.
Dogodki na dihalih V klinične študije zdravila SUTENT niso bili vključeni bolniki, ki so imeli pljučno embolijo v zadnjih 12 mesecih.
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.
Pri bolnikih, ki so dobivali SUTENT v registracijskih študijah 3. faze, so z zdravljenjem povezane plučne dogodke (tj. dispnejo, plevralni izliv, pljučno embolijo ali pljučni edem) zabeležili pri približno 5% bolnikov z GIST in približno 14% bolnikov z MRCC.
Rare cases with fatal outcome were reported Approximately 8% of patients with solid tumours, including GIST and MRCC, who received Sutent in clinical trials experienced treatment-related pulmonary events.
Z zdravljenjem povezani pljučni dogodki so se pojavili pri približno 8% bolnikov s čvrstimi tumorji, vključno z GIST in MRCC, ki so dobivali SUTENT v kliničnih preskušanjih.
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.
Če ima bolnik znake in/ ali simptome, ki nakazujejo moteno delovanje ščitnice, je treba laboratorijsko kontrolirati delovanje ščitnice in terapevtsko ukrepati v skladu z običajno medicinsko prakso.
Overall, 7% of the MRCC population had either clinical or laboratory evidence of treatment-emergent hypothyroidism.
Hipotiroidizem
Treatment-emergent acquired hypothyroidism was noted in 8 GIST patients (4%) on SUTENT versus 1 (1%) on placebo.
24 zaradi zdravljenja so opazili pri 8 bolnikih z GIST (4%), ki so dobivali SUTENT, in pri 1 bolniku (1%), ki je dobival placebo.
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
Med kliničnimi preskušanji in pomarketinškim obdobjem so bili opisani redki primeri hipertiroidizma, ki mu je včasih sledil hipotiroidizem.
Cases of serious pancreatic events, some with fatal outcome, have been reported.
Opisani so bili primeri resnih pankreatičnih pojavov, včasih s smrtnim izidom.
If symptoms of pancreatitis are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.
Če se pri bolnikih pojavijo simptomi pankreatitisa, je treba zdravljenje s SUTENTOM prekiniti in jim nuditi ustrezno podporno oskrbo.
If signs or symptoms of hepatic failure are present, SUTENT should be discontinued and appropriate supportive care should be provided.
Če se pojavijo znaki ali simptomi odpovedi jeter, je treba uporabo SUTENTA prekiniti in zagotoviti ustrezno podporno oskrbo. Konvulzije V kliničnih študijah SUTENTA in med pomarketinškim obdobjem so konvulzije opažali pri preiskovancih z radiološkimi znaki metastaz v možganih ali brez njih.
23 Renal function The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Poleg tega je bilo nekaj redkih (< 1%) poročil o preiskovancih s konvulzijami in radiološkimi znaki reverzibilnega posteriornega levkoencefalopatskega sindroma (RPLS).
Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria.
Bolniki s konvulzijami in znaki oz. simptomi, ki se skladajo z RPLS, npr. hipertenzijo, glavobolom, zmanjšano pozornostjo, duševnimi motnjami in prizadetostjo vida (vključno s kortikalno slepoto), potrebujejo medicinski nadzor, ki naj obsega tudi obvladovanje hipertenzije.
Discontinue SUTENT in patients with nephrotic syndrome.
Priporočljiva je prehodna opustitev SUTENTA; po izboljšanju stanja je mogoče zdravljenje po presoji lečečega zdravnika znova uvesti.
Seizures In clinical studies of SUTENT and from post-marketing experience, seizures have been observed in subjects with or without radiological evidence of brain metastases.
Delovanje ledvic Varnost nadaljnjega zdravljenja z zdravilom SUTENT pri bolnikih z zmerno do hudo proteinurijo ni bila sistematično ocenjena.
In addition, there have been rare (< 1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS).
Opisani so bili primeri proteinurije in redki primeri nefrotskega sindroma.
Patients with seizures and signs/ symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning and visual loss, including cortical blindness should be controlled with medical management including control of hypertension.
Izhodiščno je priporočljivo narediti analizo urina, bolnike pa je treba nadzorovati, da bi odkrili pojav ali poslabšanje proteinurije.
Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.
Pri bolnikih z nefrotskim sindromom je treba uporabo zdravila SUTENT prekiniti.
Drugs that may increase sunitinib plasma concentrations:.
Zdravila, ki lahko zvišajo koncentracijo sunitiniba v plazmi:
John’ s Wort) may decrease sunitinib concentrations.
25 šentjanževka) lahko zniža koncentracijo sunitiniba.
24 Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SUTENT.
Ženskam v rodni dobi moramo povedati, naj med zdravljenjem s SUTENTOM ne zanosijo.
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.
Med dogodki s smrtnim izidom( razen naštetih v poglavju 4. 4 zgoraj ali poglavju 4. 8 spodaj), ki so jih ocenili kot morda povezane s SUTENTOM so bili; odpoved več organov, diseminirana intravaskularna koagulacija, peritonealna krvavitev, rabdomioliza, cerebrovaskularni inzult, dehidracija, adrenalna insuficienca, odpoved ledvic, respiratorna insuficienca, plevralni izliv, pnevmotoraks, šok in nenadna smrt.
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.
26 Z zdravljenjem povezani neželeni učinki, opisani pri > 2% bolnikov s čvrstimi tumorji, so našteti spodaj, po organskih sistemih, pogostnosti in stopnji izraženosti.
Anaemia Neutropoenia Thrombocytopoenia Leukopoenia Lymphopoenia
anemija nevtropenija trombocitopenija levkopenija limfopenija
Decreased appetite a
motnje okušanja b
25 System Organ Class
Bolezni živčevja
Very common
zelo pogosti zelo pogosti
Taste disturbance b
glavobol
105 (23.9%)
105 (23, 9%) 76 (17, 3%)
1 (0.2%)
1 (0, 2%) 5 (1, 1%)
Very common Common Common Common
pogosti pogosti pogosti
Headache Paraesthesia Dizziness Neuropathy peripheral
parestezije omotica periferna nevropatija
Gastrointestinal disorders
Bolezni sečil Bolezni prebavil
Very common
pogosti zelo pogosti zelo pogosti zelo pogosti zelo pogosti zelo pogosti
Diarrhoea
kromaturija diareja navzea bruhanje stomatitis dispepsija bolečina v trebuhu c
187 (42.5%)
18 (4, 1%) 187 (42, 5%) 161 (36, 6%) 98 (22, 2%) 90 (20, 5%) 80 (18, 2%)
24 (5.5%)
0 (0, 0%) 24 (5, 5%) 15 (3, 4%) 7 (1, 6%) 7 (1, 6%) 4 (0, 9%)
0 (0.0%)
0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%)
161 (36.6%)
/ napihnjenost
15 (3.4%)
77 (17, 5%)
27 (6.1%)
27 Organski sistem
0 (0.0%)
Vse stopnje n (%)
Very common Very common Common Common Common Common Common Common Common Common Common
3. stopnja n (%)
Hair colour changes Rash Dry skin Alopecia Dermatitis Periorbital oedema Skin Reaction Erythema Eczema Pruritus Skin hyperpigmentation
4. stopnja n (%)
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%)
zelo pogosti
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%)
sindrom palmarno- plantarne eritrodizestezije
Adverse Reactions
spremembe barve las
Common Common Common
zelo pogosti pogosti pogosti pogosti pogosti pogosti pogosti pogosti pogosti pogosti
Skin exfoliation Blister Skin lesion
izpuščaji suha koža alopecija dermatitis periorbitalni edem kožne reakcije eritem ekcem srbenje hiperpigmentiranos t kože
12 (2.7%) 10 (2.3%) 10 (2.3%)
64 (14, 5%) 41 (9, 3%) 33 (7, 5%) 29 (6, 6%) 20 (4, 5%) 20 (4, 5%) 18 (4, 1%) 16 (3, 6%) 16 (3, 6%) 15 (3, 4%)
0 (0.0%) 1 (0.2%) 1 (0.2%)
3 (0, 7%) 0 (0, 0%) 0 (0, 0%) 1 (0, 2%) 0 (0, 0%) 3 (0, 7%) 0 (0, 0%) 1 (0, 2%) 0 (0, 0%) 0 (0, 0%)
0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%) 0 (0, 0%)
Very Common
pogosti pogosti pogosti
Pain in extremity/ limb
eksfoliacija kože mehur kožne lezije
54 (12.3%)
12 (2, 7%) 10 (2, 3%) 10 (2, 3%)
5 (1.1%)
0 (0, 0%) 1 (0, 2%) 1 (0, 2%)
and bone disorders
Bolezni mišično - skeletnega sistema in vezivnega tkiva
Common Common Common Common Common
zelo pogosti pogosti pogosti pogosti pogosti pogosti
Arthralgia Myalgia Muscle spasm Back pain Muscular weakness
bolečine v udih artralgija mialgija spazem mišic bolečine v hrbtu mišična oslabelost
39 (8.9%) 29 (6.6%) 21 (4.8%) 11 (2.5%) 10 (2.3%)
54 (12, 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%)
5 (1, 1%) 3 (0, 7%) 0 (0, 0%) 1 (0, 2%) 2 (0, 5%) 1 (0, 2%)
Fatigue/ Asthenia
utrujenost/ astenija vnetje sluznice edemi d
287 (65.2%)
287 (65, 2%) 70 (15, 9%)
64 (14.5%)
64 (14, 5%) 6 (1, 4%)
5 (1.1%)
0 (0, 0%) 0 (0, 0%)
administration site conditions
zelo pogosti
Mucosal Inflammation
pireksija
70 (15.9%)
26 (5, 9%)
6 (1.4%)
2 (0, 5%)
Oedema d Pyrexia
nespečnost
59 (13.4%) 26 (5.9%)
14 (3, 2%)
Psychiatric disorders
Preiskave
Insomnia
zvišanje ravni lipaze
0 (0.0%)
12 (2, 7%)
Ejection fraction decrease
zmanjšanje iztisnega deleža
Weight decreased Blood creatinine phosphokinase increase
zmanjšanje telesne mase
Any adverse event
28 Organski sistem
414 (94.1%)
Pogostnost
204 (46.4%)
Neželeni učinek
53 (12.0%)
Vse stopnje n (%)
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
3. stopnja n (%)
Treatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studies
4. stopnja n (%)
System Organ Class
Združeni so naslednji a
Frequency
izrazi:
Adverse Reactions
katerikoli neželeni učinek
All Grades n (%)
414 (94, 1%)
Grade 3 n (%)
204 (46, 4%)
Grade 4 n (%)
53 (12, 0%)
27
Z zdravljenjem povezani neželeni učinki, o katerih so poročali v študijah MRCC, odpornega proti citokinom, ter še nezdravljenega MRCC
Very common Very common Very common Common Common
zelo pogosti zelo pogosti
Neutropoenia Thrombocytopoenia Anaemia Leukopoenia Lymphopenia
nevtropenija trombocitopenija
89 (16.4%) 86 (15.8%) 67 (12.3%) 45 (8.3%) 21 (3.9%)
89 (16, 4%) 86 (15, 8%)
46 (8.5%) 37 (6.8%) 20 (3.7%) 16 (2.9%) 12 (2.2%)
46 (8, 5%) 37 (6, 8%)
5 (0.9%) 5 (0.9%) 3 (0.6%) 0 (0%) 1 (0.2%)
5 (0, 9%) 5 (0, 9%)
Very common
zelo pogosti pogosti pogosti
Hypothyroidism
anemija levkopenija limfopenija
67 (12.3%)
67 (12, 3%) 45 (8, 3%) 21 (3, 9%)
7 (1.3%)
20 (3, 7%) 16 (2, 9%) 12 (2, 2%)
0 (0%)
3 (0, 6%) 0 (0%) 1 (0, 2%)
Eye disorders
Bolezni endokrinega sistema
Lacrimation increased
hipotiroidizem
39 (7.2%)
67 (12, 3%)
Eyelid oedema
močnejše solzenje edem vek
12 (2.2%)
39 (7, 2%) 12 (2, 2%)
Metabolism and nutrition
prehranske
Very Common
zmanjšanje teka a
Decreased appetite
pogosti
9 (1.7%)
9
disorders Nervous system disorders
0 (0%)
Dehydration Taste disturbance b
dehidracija motnje okušanja b
7 (1.3%) 1 (0.2%)
1
1 (0.2%) 0 (0%)
(0, 2%)
Very common Common Common Common
zelo pogosti pogosti pogosti pogosti pogosti pogosti
Headache Dizziness Paraesthesia Neuropathy peripheral
glavobol omotica parestezije periferna nevropatija hipestezija hiperestezija
3 (0.6%) 2 (0.4%) 0 (0%) 1 (0.2%)
(0, 6%) (0, 4%) (0%) (0, 2%) (0%) (0%)
0 (0%) 0 (0%) 0 (0%) 0 (0%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Very common
pogosti pogosti
Hypertension
zardevanje valovi vročine
143 (26.3%)
17 (3, 1%) 12 (2, 2%)
55 (10.1%)
0 (0%) 0 (0%)
Common Common
zelo pogosti
Flushing Hot flush
epistaksa
17 (3.1%) 12 (2.2%)
86 (15, 8%)
0 (0%) 0 (0%)
3 (0, 6%)
Respiratory, thoracic and mediastinal disorders
prostora
Epistaxis
dispneja
86 (15.8%)
45 (8, 3%)
3 (0.6%)
6 (1, 1%)
Dyspnoea Pharyngolaryngeal pain
faringolaringealna bolečina
45 (8.3%) 29 (5.3%)
29 (5, 3%)
6 (1.1%) 2 (0.4%)
2 (0, 4%)
Diarrhoea
dispneja med naporom
326 (59.9%)
12 (2, 2%)
38 (7.0%)
0 (0%)
Nausea
diareja
290 (53.3%)
326 (59, 9%)
19 (3.5%)
38 (7, 0%)
Dyspepsia
navzea
189 (34.7%)
290 (53, 3%)
8 (1.5%)
19 (3, 5%)
Stomatitis
dispepsija
185 (34.0%)
189 (34, 7%)
13 (2.4%)
8 (1, 5%)
Vomiting
stomatitis
Abdominal pain c / distension 28
bruhanje bolečina v trebuhu c
Adverse Reactions
/ napihnjenost
Very common Very common Very common Very common Very common Common
zelo pogosti zelo pogosti zelo pogosti zelo pogosti zelo pogosti pogosti
Constipation Glossodynia Flatulence Oral pain Dry mouth Gastroesophageal reflux disease
zaprtje glosodinija flatulenca bolečine v ustih suha usta gastroezofagealna refluksna bolezen
Common Common Common Common Common Common Common Common Very common
pogosti pogosti pogosti pogosti pogosti pogosti pogosti pogosti
Dysphagia Cheilitis Gingival bleeding Haemorrhoids Proctalgia Mouth ulceration Stomach discomfort Rectal haemorrhage Palmar-plantar erythrodysaesthesia syndrome
disfagija heilitis krvavitev iz dlesni hemoroidi proktalgija razjede v ustih nelagodje v želodcu rektalna krvavitev
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%)
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%)
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%)
Hair colour changes
spremembe barve las
Very common Common Common Common Common Common Common Common
zelo pogosti pogosti pogosti pogosti pogosti pogosti pogosti pogosti
Alopecia Erythema Skin exfoliation Pruritus Periorbital oedema Dermatitis Skin lesion Nail disorder/ discolouration
alopecija eritem eksfoliacija kože srbenje periorbitalni edem dermatitis kožne lezije bolezen nohtov / obarvanje
Fatigue/ asthenia
utrujenost/ astenija
Mucosal inflammation
vnetje sluznice edemi d
Very common Common Common
zelo pogosti
System Organ Class
pogosti pogosti pogosti pogosti
Frequency
pireksija mrzlica bolečine bolečine v prsih
Adverse Reactions
37 (6, 8%) 35 (6, 4%) 20 (3, 7%) 13 (2, 4%)
All Grades n (%)
3 (0, 6%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
Grade 4 n (%)
Psihiatrične motnje Preiskave
Common Common
pogosti pogosti zelo pogosti
Pain Chest pain
nespečnost depresija zmanjšanje iztisnega deleža
0 (0%) 2 (0.4%)
0 (0%) 1 (0, 2%) 16 (2, 9%)
Common Common Very common
zelo pogosti
Insomnia Depression Ejection fraction decrease
zmanjšanje telesne mase
Weight decrease Platelet count decrease
zmanjšanje števila trombocitov
Lipase increase Haemoglobin decreased
zvišanje ravni lipaze zmanjšanje hemoglobina
Aspartate aminotransferase increased
zvišanje aspartat - aminotransferaze
Adverse reactions from post-marketing experience
31 Neželeni učinki iz pomarketinškega obdobja
The following adverse reactions have been identified during post-approval use of SUTENT.
Med pomarketinškim obdobjem uporabe zdravila SUTENT so zabeležili naslednje vrste učinkov.
30
Pogosti:
Common:
Ni znano:
Elevated thyroid stimulating hormone (TSH)
okužbe (z nevtropenijo ali brez nje)
Infections and Infestations Not known:
Bolezni mišično- skeletnega sistema in vezivnega tkiva:
Infections (with or without neutropoenia) connective tissue disorders Myopathy and/ or rhabdomyolysis
miopatija in/ ali rabdomioliza
Cases of serious infection (with or without neutropoenia), including pneumonia, have been reported.
Opisani so primeri hudih okužb (z nevtropenijo ali brez nje), vključno s pljučnico.
Few cases had a fatal outcome.
Nekateri primeri so imeli smrten izid.
Discontinue SUTENT in patients with nephrotic syndrome (see also section 4.4)
Pri bolnikih z nefrotskim sindromom morate uporabo zdravila SUTENT prekiniti (glejte poglavje 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).
Ugotovljeno je, da sunitinib zavira receptorja rastnega faktorja iz trombocitov (PDGFRα in PDGFRβ), receptorje žilnih endotelijskih rastnih faktorjev (VEGFR2, VEGFR3 in VEGFR3), receptor faktorja matičnih celic (KIT), Fms- ju podobno tirozin- kinazo- 3 (FLT3), receptor kolonijo stimulirajočega faktorja (CSF- 1R) in receptor nevrotrofičnega faktorja iz celic glije (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
KLINIČNE ŠTUDIJE Klinično varnost in učinkovitost SUTENTA so raziskali pri bolnikih z malignim gastrointestinalnim stromalnim tumorjem (GIST), ki so bili odporni proti imatinibu (t. j. jim je bolezen med zdravljenjem z imatinibom ali po njem napredovala) ali imatiniba niso prenašali (t. j. so med zdravljenjem z njim imeli pomembne toksične učinke, ki so preprečili nadaljnjo terapijo), ter pri bolnikih z metastatskim karcinomom ledvičnih celic (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.
Učinkovitost temelji na času do napredovanja tumorja in podaljšanju preživetja pri GIST, na preživetju brez napredovanja bolezni pri še nezdravljenem MRCC ter na objektivnem odzivu na zdravljenje pri MRCC, odpornemu proti citokinom.
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.
Mediani TTP je s SUTENTOM znašal 28, 9 tednov (95% IZ:
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.
Zdravljenje z IFN- α je potekalo s subkutanim injiciranjem 3 milijonov enot (ME) prvi teden, 6 ME drugi teden, 9 ME tretji teden, potem pa vsak teden na 3 nezaporedne dni.
The primary efficacy endpoint was progression free survival (PFS).
33 Primarni opazovani dogodek kot merilo učinkovitosti je bilo preživetje brez napredovanja bolezni (PFS – progression free survival).
The primary efficacy endpoint was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumours (RECIST).
Primarniopazovani dogodek kot merilo učinkovitosti je bil objektivni odziv na zdravljenje (ORR – objective response rate), ocenjen po merilih RECIST (Response Evaluation Criteria in Solid Tumours).
32 In this study the ORR was 35,8% (95% C. I.
ORR v tej študiji je znašal 35, 8% (95% IZ:
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.
Presnova Na podlagi izračunanih in vitro vrednosti Ki za vse testirane izooblike CYP (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 in CYP4A9/ 11) je malo verjetno, da bi sunitinib in njegov primarni aktivni presnovek imela klinično pomembne interakcije z zdravili, ki se presnavljajo s temi encimi.
Concurrent administration of SUTENT with the potent CYP3A4 inducer, rifampin, resulted approximately in 56% and 78% reduction in sunitinib Cmax and AUC0-∞, values respectively, after a single dose of SUTENT in healthy volunteers.
Sočasna uporaba SUTENTA z močnim induktorjem CYP3A4 rifampinom je pri zdravih prostovoljcih po posamičnem odmerku SUTENTA zmanjšala Cmax sunitiniba za 56% in AUC0– ∞ sunitiniba za 78%.
John’ s Wort) may decrease sunitinib concentrations.
Uporaba SUTENTA z induktorji družine CYP3A4 (npr. deksametazonom, fenitoinom, karbamazepinom, fenobarbitalom ali Hypericum perforatum, znano tudi kot šentjanževka) lahko zniža koncentracijo sunitiniba.
Elimination Excretion is primarily via faeces (61%) with renal elimination of drug and metabolites accounting for 16% of the administered dose.
34 Izločanje Izloča se predvsem z blatom (61%); skozi ledvice se v obliki zdravila in presnovkov izloči 16% uporabljenega odmerka.
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.
Plazemska farmakokinetika Razpolovni čas izločanja sunitiniba po peroralni uporabi pri zdravih prostovoljcih je približno 40– 60 ur, njegovega primarnega aktivnega dezetil- presnovka pa približno 80– 110 ur.
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).
Študije toksičnosti ponavljajočih se odmerkov pri podganah in opicah, ki so trajale do 9 mesecev, so ugotovile učinke na primarnih tarčnih organih v prebavilih (bruhanje in diareja pri opicah), nadledvičnih žlezah (kortikalna kongestija in/ ali krvavitev pri podganah in opicah, pri podganah z nekrozo, ki ji je sledila fibroza), hematolimfopoetskem sistemu (hipercelularnost kostnega mozga ter limfoidno izčrpanje timusa, vranice in bezgavk), eksokrinem pankreasu (degranulacija acinarnih celic z nekrozo posamičnih celic), žlezah slinavkah (acinarna hipertrofija), kosteh in sklepih (zadebelitev rastne ploščice), maternici (atrofija) in jajčnikih (zmanjšano nastajanje foliklov).