natgillin/translations-raw huggingface dataset:
Median TTP for SUTENT var 28, 9 uger (95% CI = 21, 3- 34, 1 uger) og var statistisk signifikant længere end TTP på 5, 1 uger (95% CI = 4, 4- 10, 1 uger) for placebo.
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.
Fordelingen i
0.290- 0.831)]; the risk of death was 2 times higher in patients in the placebo arm compared to the SUTENT arm.
33 procent på dødsfald var 14% for SUTENT versus 25% for placebo.
The percentages of deaths were 14% for SUTENT vs 25% for placebo.
Behandlingsnaiv metastaserende renalcellecarcinom (mRCC) Der er udført en fase 3 randomiseret, multicenter, international undersøgelse, der evaluerer effekt og sikkerhed af sunitinib sammenlignet med IFN- α hos patienter med behandlingsnaiv metastaserende RCC.
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.
I denne undersøgelse var ORR 35, 8% (95% C. I.
32 In this study the ORR was 35,8% (95% C. I.
Metabolisme De kalkulerede in vitro Ki- værdier for alle undersøgte CYP- isoformer (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 og CYP4A9/ 11) tyder på, at sunitinib og dets aktive hovedmetabolit i enhver klinisk relevant grad hæmmer metaboliseringen af lægemidler, der metaboliseres af disse enzymer.
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.
34 In vitro undersøgelser tyder på, at SUTENT hverken inducerer eller hæmmer vigtige CYP- enzymer, herunder CYP3A4.
In-vitro studies also indicate that SUTENT neither induces nor inhibits major CYP enzymes, including CYP3A4.
Biotransformation Sunitinib metaboliseres hovedsageligt af CYP3A4, det cytochrom P450- enzym som producerer dets aktive hovedmetabolit, og som derefter metaboliseres yderligere af 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.
Anvendelse af SUTENT sammen med andre induktorer af CYP3A4 - familien (f. eks. dexamethason, phenytoin, carbamazepin, rifampin, phenobarbital eller Hypericum perforatum også kendt som prikbladet perikum) kan nedsætte sunitinibkoncentrationen.
John’ s Wort) may decrease sunitinib concentrations.
40- 60 timer og 80- 110 timer efter oral indtagelse.
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.
På dag 14 er den kombinerede plasmakoncentration af sunitinib og dets aktive hovemetabolit 62, 9- 101 ng/ ml Dette er målkoncentrationen fra de prækliniske data for at kunne hæmme receptorfosforylering in vitro, hvilket resulterer i tumorstase/ vækstreduktion in vivo.
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.
35 (kortikal kongestion og/ eller blødning hos rotter og aber og nekrose efterfulgt af fibrose hos rotter), blod- og lymfesystem (knoglemarvshypocellularitet og lymfoid udtømning i thymus, milt og lymfeknuder), eksokrin pancreas (acinar celledegranulering med enkeltcelle nekrose), spytkirtler (acinar hypertrofi), led (fortykkelse af vækstplade), uterus (atrofi) og ovarier (nedsat follikeludvikling).
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).
Der er observeret embryo- føtal mortalitet hos rotter, hvor der ved plasmakoncentrationer 5, 5 gange højere end observeret i klinikken ses et signifikant fald i antal levende fostre, et forøget antal resorptioner, et forøget postimplantationstab og tab af hele kuldet hos 8/ 28 drægtige hunner.
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
Hos kaniner er der konstateret nedsat vægt af den drægtige livmoder, et nedsat antal levende fostre som følge af et forøget antal resorptioner, et forøget postimplantationstab og tab af hele kuldet hos 4/ 6 drægtige hunner med plasmakoncentrationer, der er 3 gange højere end dem der observeres i klinikken.
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.
Hos kaninfostre ses udviklingsforstyrrelser i form af hareskår ved plasmakoncentrationer på omtrent samme niveau som i klinikken og i form af hareskår og ganespalte ved plasmakoncentrationer, der er 2, 7 gange højere end i klinikken.
In rabbits, developmental effects consisted of increased incidence of cleft lip at plasma exposure levels approximately equal to that observed in clinic, and cleft lip and cleft palate at plasma exposure levels 2.7-fold higher than is observed in clinic.
Gelatine Rød jernoxid (E172) Titandioxid (E171)
Orange Capsule Shell Gelatin Red Iron Oxide (E172) Titanium dioxide (E171)
Gelatine Titandioxid (E171) Gul jernoxid (E172) Rød jernoxid (E172) Sort jernoxid (E172)
Caramel Capsule Shell Gelatin Titanium dioxide (E171) Yellow Iron Oxide (E172) Red Iron Oxide (E172) Black Iron Oxide (E172)
6. 6 Emballagetype og pakningsstørrelser
35 6.5 Nature and contents of container
Sutent 50 mg hårde kapsler
SUTENT 50 mg hard capsules
Hjælpestof:
Each capsule contains sunitinib malate equivalent to 50 mg of sunitinib Excipient(s):
79, 326 mg mannitol.
79,326 mg of mannitol.
Hårde kapsler Gelatinekapsler med karamelfarvet overdel og karamelfarvet underdel, der med hvidt blæk er mærket ” Pfizer ” på overdelen, ” STN 50 mg ” på underdelen, og som indeholder gule til orange granulater.
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.
Metastaserende renalcellecarcinom (mRCC) SUTENT er indiceret til behandling af behandlingsnaiv avanceret og/ eller metastaserende renalcellecarcinom (mRCC).
Metastatic Renal Cell Carcinoma (MRCC) SUTENT is indicated for the treatment of advanced and/ or metastatic renal cell carcinoma (MRCC).
39 Børn:
Paediatric use:
SUTENT bør ikke anvendes til børn før yderligere data er tilgængelige.
37 SUTENT should not be used in paediatric population until further data become available.
Hos de patienter, der får SUTENT for
Bleeding events occurred in 18% of patients receiving SUTENT in a phase 3 GIST Study compared to 17% of patients receiving placebo.
40 behandlingsnaiv mRCC, får 28% hændelser med blødning sammenlignet med 7% af patienterne, der får IFN- α.
In patients receiving SUTENT for treatment-naïve MRCC, 28% had bleeding events compared to 7% of patients receiving IFN-α.
26% af patienterne, der får sunitinibmalat til behandling af cytokin- refraktær mRCC, oplever blødning.
38 refractory MRCC, 26% experienced bleeding.
Nedsat trombocyttal af sværhedsgrad 3 og 4 er rappporteret hos henholdsvis 43, 7% og 0, 4% af patienterne i fase 3- GIST studiet og hos henholdsvis 8, 2% og 1, 1% af patienterne i fase 3 mRCC - studiet.
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.
41 Behandlingsrelaterede bivirkninger som ” hjertesvigt ”, ” kronisk venstresidigt hjerteinsufficiens ” eller ” venstre ventrikelsvigt ” ses hos 0, 7% af patienterne med solide tumorer og hos 1% af patienterne, der blev behandlet med placebo.
Treatment-related adverse events of ‘ cardiac failure’, ‘ cardiac failure congestive’ or ‘ left ventricular failure’ were reported in 0.7% of patients with solid tumours and 1% of patients treated with placebo.
I fase 3- undersøgelsen hos behandlingsnaive mRCC- patienter oplevede 0, 6% af patienterne i IFN- α- gruppen og 0% af patienterne SUTENT- gruppen fatale hjertehændelser.
39 SUTENT arm experienced fatal cardiac events.
Forlængelse af QT- interval Data fra non- kliniske forsøg (in vivo og in vitro) med doser, der var højere end de anbefalede humane doser tyder på, at sunitinib potentielt kan hæmme hjertets repolarisationsproces (f. eks forlængelse af QT- intervallet).
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).
Disse er ændringer er signifikante.
Increases in the QTc interval to over 500 msec occurred in 0.5% and changes from baseline in excess of 60 msec occurred in 1.1% of the 450 solid tumours patients; both these parameters are recognized as potentially significant changes.
Resultaterne af denne undersøgelse viste, at sunitinib havde en effekt på QTc (defineret som middel placebo- justeret ændring på > 10 msek med en 90% CI øvre grænse > 15 msek) ved terapeutisk koncentration (dag 3) ved brug af ” within- day ” baseline korrektionsmetoden og ved højere end terapeutisk koncentration (dag 9) ved begge baseline - korrektionsmetoder.
The results of this study demonstrated that sunitinib had an effect on QTc (defined as a mean placebo-adjusted change of > 10 msec with a 90% CI upper limit > 15 msec) at therapeutic concentration (day 3) using the within-day baseline correction method, and at greater than therapeutic concentration (Day 9) using both baseline correction methods.
Ved brug af gentagne EKG- målinger på tidspunkter svarende til enten terapeutisk eksponering eller højere end terapeutisk ekponering sås ikke udvikling af alvorlig QTc- forlængelse (dvs. lig med eller større end grad 3 ved CTCAE- version 3, 0) hos nogen af patienterne i den evaluerbare eller i ITT - populationen.
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).
SUTENT bør
Torsade de pointes has been observed in < 0.1% of SUTENT-exposed patients.
42 anvendes med forsigtighed hos patienter med kendt forlængelse af QT- interval i anamnesen, patienter der tager antiarytmika, eller patienter med relevant præeksisterende hjertesygdom, bradykardi eller elektrolytforstyrrelser.
SUTENT should be used with caution in patients with a known history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances.
5 ud af 7 var grad 3 dyb venetrombose (DVT), og 2 var grad 1 eller 2.
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.
Respiratoriske hændelser Patienter, som havde haft lungeemboli indenfor de seneste 12 måneder, blev ekskluderet fra de kliniske undersøgelser med SUTENT.
Pulmonary Events Patients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.
Sjældne fatale tilfælde blev rapporteret.
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.
Stigningerne i lipaseaktiviteten var forbigående og var sædvanligvis ikke
Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours.
Ved symptomer på pankreatitis eller leversvigt, bør behandling med SUTENT seponeres, og patienterne bør have relevant medicinsk behandling.
If symptoms of pancreatitis or hepatic failure are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.
Nyrefunktion Der er ikke foretaget sikkerhedsvurdering ved fortsat behandling med SUTENT hos patienter med moderat til alvorlig proteinuri.
41 Renal function The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Hvis dette ikke er muligt, kan dosisjustering af SUTENT være nødvendig (se pkt.
If this is not possible, dose-adjustments of SUTENT may be necessary (see section 4.2).
Kvinder i den fødedygtige alder bør rådes til ikke at blive gravide under behandling med SUTENT.
42 Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SUTENT.
4. 8 nedenfor og som betragtes mulig relateret til SUTENT, omfatter multiorgansvigt, dissemineret intravaskulær koagulation, peritoneal blødning, rhabdomyolyse, cerebrovaskulær hændelse, dehydrering, adrenal insufficiens, nyresvigt, pleuraeffusion, pneumothorax, shock og pludselig død af ukendt årsag.
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.
45 Behandlingsrelaterede bivirkninger rapporteret i GIST- undersøgelserne
Treatment-Related Adverse Reactions reported in GIST studies
Nedsat appetit
Decreased appetite a
Meget almindelig Meget almindelig Almindelig Almindelig Almindelig Almindelig
Nervous system disorders
Smagsforstyrrelser b Hovedpine Paræstesi Svimmelhed Perifer neuropati Hypæstesi
Taste disturbance b
105 (23, 9%) 76 (17, 3%) 27 (6, 1%) 18 (4, 1%) 11 (2, 5%) 10 (2, 3%)
Very common Common Common Common
1 (0, 2%) 5 (1, 1%) 1 (0, 2%) 1 (0, 2%) 0 (0, 0%) 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%) 0 (0.0%) 0 (0.0%)
Almindelig Almindelig Almindelig Meget almindelig Meget almindelig Meget almindelig Meget almindelig Meget almindelig Meget almindelig
28 (6.4%)
Epistaxis Dyspnø Kromaturi Diarré Kvalme Opkastning Stomatitis Dyspepsi Abdominalsmerterc / distension
1 (0.2%)
1 (0, 2%) 2 (0, 5%) 0 (0, 0%) 24 (5, 5%) 15 (3, 4%) 7 (1, 6%) 7 (1, 6%) 4 (0, 9%) 15 (4, 3%)
Dyspnoea
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 (0, 5%)
16 (3.6%)
Meget almindelig Meget almindelig Almindelig Almindelig Almindelig Almindelig
2 (0.5%)
Flatulens Oral smerte Obstipation Glossalgi Mundtørhed Gastro- øsofageal refluks
0 (0.0%)
46 (10, 5%) 44 (10, 0%) 37 (8, 4%) 37 (8, 4%) 31 (7, 0%) 12 (2, 7%)
Renal and urinary disorders
0 (0, 0%) 2 (0, 5%) 2 (0, 5%) 0 (0, 0%) 0 (0, 0%) 1 (0, 2%)
Common
Palmar- plantar erythrodysaesthe- sia syndrom
11 (2.5%) 11 (2.5%)
0 (0, 0%)
Very common
Meget almindelig
Yellow skin/ Skin discolouration
Ændringer i hårfarve
146 (33.2%)
67 (15, 2%)
0 (0.0%)
Meget almindelig Almindelig Almindelig
Very common Very common Common Common Common Common Common Common Common Common
Udslæt Tør hud Alopeci
Hair colour changes Rash Dry skin Alopecia Dermatitis Periorbital oedema Skin Reaction Erythema Eczema Pruritus
64 (14, 5%) 41 (9, 3%) 33 (7, 5%)
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%)
3 (0, 7%) 0 (0, 0%) 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%)
46 Organklasse
44 System Organ Class
Almindelig Almindelig Almindelig Almindelig Almindelig Almindelig Almindelig
Skin hyperpigmentation
Dermatitis Periorbital ødem Hudreaktion Erytem Eksem Pruritus Hyperpigmentering af hud
15 (3.4%)
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%) 0 (0, 0%) 3 (0, 7%) 0 (0, 0%) 1 (0, 2%) 0 (0, 0%) 0 (0, 0%)
0 (0.0%)
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%)
Træthed/ asteni
Fatigue/ Asthenia
287 (65, 2%)
287 (65.2%)
64 (14, 5%)
64 (14.5%)
administrationssted et
administration site conditions
Mucosa inflammation
Mucosal Inflammation
70 (15, 9%)
70 (15.9%)
Ødem d Pyreksi
Oedema** Pyrexia
Nedsat uddrivningsfraktion
Ejection fraction decrease
Nedsat hæmoglobin Nedsat antal trombocytter
Haemoglobin decrease
27 (6, 1%) 25 (5, 7%)
Common
Vægttab Forhøjet blod - kreatinin - fosfokinase
Weight decreased Blood creatinine phosphokinase increased
Behandlingsrelaterede bivirkninger rapporteret i cytokin- refraktære og behandlingsnaive mRCC- undersøgelser
45 Treatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studies
Neutropeni
Neutropoenia Thrombocytopoenia
89 (16, 4%)
89 (16.4%) 86 (15.8%)
46 (8, 5%)
46 (8.5%) 37 (6.8%)
Trombocytopeni
Anaemia Leukopoenia Lymphopenia
86 (15, 8%)
67 (12.3%) 45 (8.3%) 21 (3.9%)
37 (6, 8%)
20 (3.7%) 16 (2.9%) 12 (2.2%)
5 (0, 9%)
3 (0.6%) 0 (0%) 1 (0.2%)
Meget almindelig
Endocrine disorders
Anæmi
Very common
67 (12, 3%)
Hypothyroidism
20 (3, 7% 9
67 (12.3%)
3 (0, 6%)
7 (1.3%)
45 (8, 3%) 21 (3, 9%)
0 (0%)
16 (2, 9%) 12 (2, 2%)
Eye disorders
0 (0%) 1 (0, 2%)
Common
Det endokrine system
Lacrimation increased
Hypotyreose
39 (7.2%)
67 (12, 3%)
0 (0%)
Svimmelhed
0 (0%) 0 (0%) 0 (0%) 0 (0%)
38 (7, 0%)
Common Common
Paræstesi Perifer neuropati Hypæstesi Hyperæstesi
Hypoaesthesia Hyperaesthesia
36 (5, 9%) 33 (6, 1%) 20 (3, 7%) 17 (3, 1%)
20 (3.7%) 17 (3.1%)
0 (0%) 1 (0, 2%) 0 (0%) 0 (0%)
0 (0%) 0 (0%)
Dyspnø Faryngolaryngeal smerte
Dyspnoea
0 (0%) 0 (0%)
disorders
Almindelig Almindelig Almindelig Almindelig
Common
Hoste Dysfoni Tørhed i næsen Anstrengelsesudløst dyspnø
Pharyngolaryngeal pain
Almindelig Almindelig
Common Common Common Common Common Common
Nasal tilstoppethed Pleuraeffusion
Cough Dysphonia Nasal dryness Dyspnoea exertional Nasal congestion Pleural effusion
Meget almindelig
46 System Organ Class
106 (19, 5%)
Frequency
0 (0%)
Very common
Meget almindelig
Abdominal pain c / distension
Mundtørhed
106 (19.5%)
56 (10, 3%)
10 (1.8%)
Almindelig Almindelig
Very common Very common Very common Very common Very common Common
Flatulens Oral smerte
Constipation Glossodynia Flatulence Oral pain Dry mouth Gastroesophageal reflux disease
45 (8%) 44 (8%)
83 (15.3%) 63 (11.6%) 60 (11.0%) 60 (11.0%) 56 (10.3%) 50 (9.2%)
Almindelig Almindelig Almindelig Almindelig Almindelig Almindelig Almindelig Almindelig
Common Common Common Common Common Common Common Common
Dysfagi Keilitis Gingival blødning Hæmorroider Proktalgi Sår i munden Ubehag i maven Rektalblødning
Dysphagia Cheilitis Gingival bleeding Haemorrhoids Proctalgia Mouth ulceration Stomach discomfort Rectal haemorrhage
Palmar- plantar erythrodysaesthesia syndrom
Palmar-plantar erythrodysaesthesia syndrome
Almindelig Almindelig Almindelig Almindelig
Very Common Common Common Common Common
Ødem
Oedema d
99 (18, 2%)
99 (18.2%)
5 (0, 9%)
5 (0.9%)
3 (0, 6%) 2 (0, 4%) 0 (0%) 2 (0, 4%)
System Organ Class
0 (0%) 0 (0%) 0 (0%) 0 (0%)
Adverse Reactions
Psykiske forstyrrelser Undersøgelser
All Grades n (%)
Almindelig Almindelig Meget almindelig
Common Common Common Common
Insomni Depression Nedsat uddrivningsfraktion
Pyrexia Chills Pain Chest pain
Nedsat antal hvide blodlegemer
White blood cell count decreased e
Forhøjet lipase Nedsat hæmoglobin Forhøjet blod - kreatinin- fosfokinase
Lipase increase Haemoglobin decreased
11 (2%) 0 (0%) 2 (0, 4%)
Common
Ikke almindelig:
48 Uncommon:
Infektioner og parasitære sygdomme Hyppighed ikke kendt
Infections and Infestations Not known:
Luftveje, thorax og Hyppighed ikke kendt
Infections(with or without neutropoenia) connective tissue disorders Myopathy and/ or Rhabdomyolysis
51 4. 9 Overdosering
4.9 Overdose
Ligeledes er den kliniske sikkerhed og effekt af SUTENT undersøgt for patienter med metastaserende renalcellecarcinom (mRCC) Effekten er baseret på tidspunktet for tumorprogression og stigning i overlevelse med GIST samt på henholdsvis progressions- fri overlevelse og objektiv responsrate for behandlingsnaiv og cytokin- refraktær mRCC.
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.
52 Behandlingsnaiv metastaserende renalcellecarcinom (mRCC) Der er udført en fase 3 randomiseret, multicenter, international undersøgelse, der evaluerer effekt og sikkerhed af sunitinib sammenlignet med IFN- α hos patienter med behandlingsnaiv metastaserende RCC.
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.
Det primære effektendepunkt i denne undersøgelse var objektiv responserate (ORR).
50 The primary efficacy endpoint of this study was Objective Response Rate (ORR).
53 Biotransformation Sunitinib metaboliseres hovedsageligt af CYP3A4, det cytochrom P450- enzym som producerer dets aktive hovedmetabolit, og som derefter metaboliseres yderligere af 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.
40- 60 timer og 80- 110 timer efter oral indtagelse.
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.