qanastek/EMEA-V3 huggingface dataset:
Baseline and periodic evaluations of LVEF should also be considered while the patient is receiving SUTENT.
Evalwazzjonijiet ta ’ LVEF fil- linja bażi ta ’ riferiment u perijodiċi għandhom jiġu kkunsidrati wkoll waqt li l- pazjent ikun qed jingħata SUTENT.
In patients without cardiac risk factors, a baseline evaluation of ejection fraction should be considered.
F’ pazjenti mingħajr fatturi ta ’ riskju kardijaċi, evalwazzjoni tal- frazzjoni ta ’ tfigħ ’ il barra fil- linja bażi għandha tiġi kkunsidrata.
In the presence of clinical manifestations of CHF, discontinuation of SUTENT is recommended.
Fil- preżenza ta ’ manifestazzjonijiet kliniċi ta ’ CHF, it- twaqqif ta ’ SUTENT hija rakkomandata.
The dose of SUTENT should be interrupted and/ or reduced in patients without clinical evidence of CHF but with an ejection fraction< 50% and > 20% below baseline.
Id - doża ta ’ SUTENT għandha tigi interotta u/ jew imnaqqsa f’ pazjenti mingħajr evidenza klinika ta ’ CHF iżda bi frazzjoni ta ’ tfigħ ’ il barra < 50% u > 20% taħt il- linja bażi ta ’ riferiment.
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 to inhibit the cardiac action potential repolarization process (e. g. prolongation of QT interval).
Titwil ta ’ l- Intervall QT Tagħrif minn studji li mhumiex kliniċi (in vitro u in vivo), b’ dożi ogħla mid- doża umana rakkomandata, jindika li sunitinib għandu l- potenzjal li jimpedixxi l- proċess potenzjali ta ’ polarizzazzjoni mill- ġdid ta ’ l- azzjoni kardijaka (eż. titwil ta ’ l- interval QT).
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.
Żidiet fl- intervall QTc għal iżjed minn 500 msec seħħew f’ 0. 5% u l- bidliet mil- linja bażi li qabżu 60 msec seħħew f’ 1. 1% ta ’ l- erba ’ mija u ħamsin pazjent b’ tumuri solidi; dawn iż- żewġ parametri huma rikonoxxuti bħal bidliet potenzjalment sinifikanti.
At approximately twice therapeutic concentrations, SUTENT has been shown to prolong the QTcF Inteval (Frederica’ s Correction).
B’ konċentrazzjonijiet bejn wieħed u ieħor id - doppju ta ’ dawk terapewtiċi, SUTENT intwera li jtawwal l- Intervall QTcF (Korrezzjoni ta ’ Frederica).
QT interval prolongation was investigated in a trial in 24 patients, aged 20-87 years, with advanced malignancies.
Fi prova t- titwil ta ’ l- interval QT kien mistħarreġ f’ 24 pazjent, bejn l- etajiet ta ’ 20- 87 sena, b’ tumuri malinni avanzati.
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.
Ir- riżultati ta ’ dan l- istudju wrew li sunitinib kellu effett fuq il- QTc (definita bħala bidla medja aġġustata għall- plaċebo ta ’ > 10 msec b’ limitu ta ’ fuq CI ta ’ 90% > 15 msec) b’ konċentrazzjoni terapewtika (jum 3) bl- użu tal- metodu ta ’ korrezzjoni tal- linja bażi fil- ġurnata, u b’ konċentrazzjoni akbar minn dik terapewtika (Jum 9) bl- użu taż- żewġ metodi ta ’ korrezzjoni tal- linja bażi.
No patients had a QTc value > 500 msec.
L- ebda pazjent ma kellu valur QTc > 500 msec.
Although an effect on QTcF was observed on Day 3 at 24 hours post-dose (i. e. at therapeutic plasma concentration expected after the recommended starting dose of 50 mg) with the within-day baseline correction method, the clinical significance of this finding is unclear.
Għalkemm ġie osservat effett fuq il- QTcF fit- 3 Jum, 24 siegħa wara d- doża (jiġifieri fil- konċentrazzjoni terapewtika fil- plasma mistennija wara d - doża inizjali rakkomandata ta ’ 50 mg) bil- metodu ta ’ korrezzjoni tal- linja bażi fl- istess ġurnata, mhux ċar is- sinifikat kliniku ta ’ din is- sejba.
Using comprehensive serial ECG assessments at times corresponding to either therapeutic or greater than therapeutic exposures, none of the patients in the evaluable or ITT populations were observed to develop QTc prolongation considered as “ severe” (i. e. equal to or greater than Grade 3 by CTCAE version 3.0).
Bl- użu ta ’ evalwazzjonijiet komprensivi b’ ECG konsekuttivi, xi drabi jikkorrispondu għal esponimenti jew terapewtiċi jew akbar minn terapewtiċi, l- ebda wieħed mill- pazjenti fil - popolazzjonijiet li setgħu jiġu evalwati jew ITT ma ġie osservat li żviluppa titwil tal- QTc li kien ikkunsidrat bħala “ sever ” (jiġifieri daqs jew aktar minn Grad 3 mill- CTCAE verżjoni 3. 0).
At therapeutic plasma concentrations, the maximum QTcF (Frederica’ s correction) mean change from baseline was 9.6 msec (90% CI 15.1msec).
5 B’ konċentrazzjonijiet terapewtiċi fil- plasma, il- bidla medja massima fil- QTcF (korrezzjoni ta ’ Frederica) mil- linja bażi kienet ta ’ 9. 6 msec (90% CI 15. 1msec).
At approximately twice therapeutic concentrations, the maximum QTcF change from baseline was 15.4 msec (90% CI 22.4 msec).
B’ konċentrazzjonijiet kważi d - doppju ta ’ dawk terapewtiċi, il- bidla massima fil- QTcF mil- linja bażi kienet ta ’ 15. 4 msec (90% CI 22. 4 msec).
Moxifloxacin (400 mg) used as a positive control showed a 5.6 msec maximum mean QTcF change from baseline.
Moxifloxacin (400 mg) użat bħala kontroll pożittiv wera bidla massima medja fl- QTcF mil- linja bażi ta ’ 5. 6 msec.
No subjects experienced an effect on the QTc inteval greater than Grade 2 (CTCAE version 3.0).
L- ebda individwu ma esperjenza effett akbar fuq l- intervall QTc minn Grad 2 (CTCAE verżjoni 3. 0).
No patient presented with a cardiac arrhythmia.
L- ebda pazjent ma ppreżenta arritmija tal- qalb.
Torsade de pointes has been observed in < 0.1% of SUTENT-exposed patients.
It- titwil ta ’ l- interval QT jista ’ jwassal għal żieda fir- riskju ta ’ arritmiji ventrikulari inkluż Torsade de pointes. Torsade de pointes ġie osservat f ’ < 0. 1% ta ’ pazjenti esposti għal SUTENT.
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.
SUTENT għandu jintuża bil- kawtela f’ pazjenti bi storja magħrufa ta ’ titwil ta ’ l- intervall QT, pazjenti li qegħdin jieħdu mediċini antiarritmiċi, jew pazjenti b’ mard kardijaku diġà ezistenti rilevanti, bradikardja, jew disturbi fl- elettroliti.
Concomitant treatment with potent CYP3A4 inhibitors, which may increase sunitinib plasma concentrations, should be used with caution and the dose of SUTENT reduced (see Section 4.2 and 4.5).
Trattament konkomitanti b’ impedituri CYP3A4 potenti, li jistgħu jżiedu l- konċentrazzjonijiet ta ’ sunitinib fil- plażma, għandhom jintużaw b’ kawtela u d- doża ta ’ SUTENT għandha titnaqqas (ara Sezzjoni 4. 2 u 4. 5).
Venous Thromboembolic Events Treatment-related venous thromboembolic events were reported in approximately 1.0% of patients with solid tumours who received SUTENT on clinical trials, including GIST and MRCC.
Reazzjonijiet Tromboemboliċi Venużi Reazzjonijiet tromboemboliċi venużi, relatati mat- trattament, kienu rrapurtati bejn wieħed u ieħor fi 1. 0% tal- pazjenti b’ tumuri solidi, li rċevew SUTENT fi studji kliniċi, inklużi GIST u MRCC.
5 Seven patients (3%) on SUTENT and none on placebo in a phase 3 GIST study experienced venous thromboembolic events; five of the seven were Grade 3 deep venous thrombosis (DVT) and two were Grade 1 or 2.
Fi studju GIST fażi 3 seba ’ pazjenti (3%) fuq SUTENT esperjenzaw reazzjonijiet tromboemboliċi venużi; ħamsa mis- seba ’ kienu trombożi tal- vini l- fondi (DVT) ta ’ Grad 3, u tnejn kienu ta ’ Grad 1 jew 2.
Four of these seven GIST patients discontinued treatment following first observation of DVT.
Erba ’ minn dawn is- seba ’ pazjenti GIST waqqfu t- trattament wara l- ewwel osservazzjoni ta ’ DVT.
Seven patients (1.9%) receiving SUTENT in the phase 3 treatment-naïve MRCC study and four patients (2%) on the two cytokine-refractory MRCC studies had treatment-related venous thromboembolic events reported.
Seba ’ pazjenti (1. 9%) li ngħataw SUTENT fit- tielet fażi ta ’ l- istudju MRCC għal trattament li qatt ma kienu ħadu qabel din il- kura, u erba ’ pazjenti (2%) fuq iż- żewġ studji MRCC refrattarja għaċ - ċitokini kellhom reazzjonijiet tromboemboliċi venużi, marbuta mat- trattament, rrapportati.
Six of these patients had pulmonary embolisms, one was Grade 3 and five were Grade 4, and five of these patients had DVT, one each with Grade 1 and 2, and three with Grade 3.
Sitta minn dawn il- pazjenti kellhom emboliżmu pulmonari, wieħed kien ta ’ Grad 3 u ħamsa kienu ta ’ Grad 4, u ħames pazjenti minnhom kellhom DVT, wieħed kull wieħed bi Grad 1 u 2, u tlieta bi grad 3.
In treatment-naïve MRCC patients receiving IFN-α, six (2%) venous thromboembolic events occurred; one patient (< 1%) experienced a Grade 3 DVT and five patients (1%) had pulmonary embolisms, one with Grade 1 and four with Grade 4.
F’ pazjenti MRCC bi trattament li qatt ma kienu ħadu qabel din il- kura u li kienu qed jieħdu IFN- α, seħħew sitt (2%) reazzjonijiet tromboemboliċi venużi; pazjent wieħed (< 1%) esperjenza DVT Grad 3 u ħames pazjenti (1%) kellhom emboliżmu pulmonari, wieħed bi Grad 1 u erbgħa bi Grad 4.
No cases with fatal outcome were reported in GIST and MRCC registrational studies.
L- ebda każijiet fatali ma ġew irrappurtati fl- istudji tar- reġistrazzjoni GIST u MRCC.
Cases with fatal out- come had been observed in post-marketing setting (see respiratory events and section 4.8).
Każijiet ta ’ mwiet irriżultaw wara t- tqegħid fis- suq (ara episodji respiratorji u sezzjoni 4. 8).
Respiratory events Patients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.
Episodji Respiratorji Pazjenti li ppreżentaw b’ emboliżmu pulmonari fit- 12 il xahar preċedenti, ġew esklużi mill- istudji kliniċi ta ’ SUTENT.
In patients who received SUTENT in Phase 3 registrational studies, treatment-related pulmonary events (i. e. dyspnoea, pleural effusion, pulmonary embolism or pulmonary oedema) were reported in approximately 5% of patients with GIST and in approximately 14% of patients with MRCC.
F’ pazjenti li rċevew SUTENT fit- tielet fażi ta ’ l- istudji tar- reġistrazzjoni, episodjo pulmonari relatati mat- trattament (i. e. dispnea, effużjoni plewrali, emboliżmu pulmonari jew edema pulmonari) ġew irrappurtati f’ approssimament 5% tal- pazjenti fuq GIST, u f’ approssimament 14% tal- pazjenti fuq MRCC.
Rare cases with fatal outcome were reported.
Każijiet rari ta ’ mwiet ġew irrappurtati.
Approximately 8% of patients with solid tumours, including GIST and MRCC, who received SUTENT in clinical trials experienced treatment-related pulmonary events.
Approssimament 8% tal- pazjenti b’ tumuri solidi, inklużi fuq GIST u MRCC, li rċevew SUTENT fi studji kliniċi, esperjenzaw episodji respiratorji relatati mat- trattament.
Cases of Pulmonary embolism were observed in approximately 1.3% of patients with GIST and in approximately 0.8% of patients with MRCC, who received Sutent in Phase 3 studies (see section 4.4 - Venous Thromboembolic Events).
Każijiet ta ’ emboliżmu respiratorju kienu nnutati fi 1. 3% tal- pazjenti fuq GIST u bejn wieħed u ieħor fi 0. 8% tal- pazjenti fuq MRCC, li rċevew Sutent fit- tielet fażi ta ’ l- istudji (ara sezzjoni 4. 4 Reazzjonijiet Tromboemboliċi Venużi)
Thyroid Dysfunction Baseline laboratory measurement of thyroid function is recommended, and patients with hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of sunitinib treatment.
Disfunzjoni tat- Tirojde Huwa rakkomandat li jsir kejl fil- laboratorju tal- linja bażi tal- funzjoni tat- tirojde, filwaqt li pazjenti b’ ipotirojdiżmu jew ipertirojdiżmu għandhom ikunu trattati skond il- prattika medika standard qabel ma jinbeda it- trattament b’ sunitinib.
All patients should be observed closely for signs and symptoms of thyroid dysfunction on sunitinib treatment.
Il- pazjenti kollha għandhom ikunu osservati sew għal sinjali u sintomi ta ’ ipotirojdiżmu waqt trattament b’ sunitinib.
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.
Pazjenti b’ sinjali u/ jew sintomi li jissuġġerixxu disfunzjoni tat- tirojde għandhom ikollhom monitoraġġ mil- laboratorju tal- funzjoni tat- tirojde u jkunu trattati skond il - prattika medika standard.
Hypothyroidism was reported as an adverse event in 7 patients (4%) across the two cytokine-refractory MRCC studies; in nine patients (2%) on SUTENT and one patient (< 1%) in the IFN-α arm in the treatment- naïve MRCC study.
Barraminhekk, żidiet fit -
Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%).
6 TSH kienu rrapportati f’ 4 pazjenti b’ MRCC refrattarja għaċ- ċitokini (2%).
Overall, 7% of the MRCC population had either clinical or laboratory evidence of treatment-emergent hypothyroidism.
Kollox ma ’ kollox, 7% tal - popolazzjoni MRCC kellha evidenza jew klinika jew tal- laboratorju ta ’ ipotirojdiżmu li ħareġ bit - trattament.
Treatment-emergent acquired hypothyroidism was noted in 8 GIST patients (4%) on SUTENT versus 1 (1%) on placebo.
Ipotirojdiżmu miksub li hareġ bit- trattament kien innotat fi 8 pazjenti GIST (4%) fuq SUTENT versus 1 (1%) fuq plaċebo.
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
Każijiet rari ta ’ ipertirojdiżmu, xi wħud segwiti minn ipotirojdiżmu, ġew irrappurtati fi provi kliniċi u fl- esperjenza ta ’ wara t- tqegħid fis- suq.
Pancreatitis Increases in serum lipase and amylase activities were observed in patients with various solid tumours who received SUTENT.
Pankreatite Żidiet fl- attivitajiet ta ’ lipase u amylase fis- serum kienu osservati f’ pazjenti b’ diversi tumuri solidi li ngħataw SUTENT.
Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours.
Żidiet fl- attivitajiet ta ’ lipase kienu momentanji u ġeneralment ma kinux assoċjati minn sinjali u sintomi ta ’ pankreatite f’ suġġetti b’ diversi tumuri solidi.
Pancreatitis has been observed rarely (< 1%) in patients receiving SUTENT for GIST or MRCC.
F’ pazjenti li qegħdin jieħdu SUTENT minħabba GIST jew MRCC, il- pankreatite ġiet osservata rarament (< 1%).
Cases of serious pancreatic events, some with fatal outcome, have been reported.
Kienu rrappurtati każijiet ta ’ episodji serji ta ’ pankreatite, wħud minnhom b’ eżitu fatali.
If symptoms of pancreatitis are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.
Jekk ikun hemm sintomi ta ’ pankreatite, il- pazjenti għandhom jitwaqqfilhom SUTENT u jiġu mogħtija kura t ’ appoġġ adattat.
Hepatic Function Serious cases of SUTENT-related hepatobiliary events have been reported in patients with solid tumours; hepatic failure was observed in < 1% of these patients.
Funzjoni tal- Fwied Ġew irrappurtati każi serji ta ’ episodji epatobiljari relatati ma ’ SUTENT f’ pazjenti li kellhom tumuri solidi; kienet osservata insuffiċjenza tal- fwied f ’ < 1% ta ’ dawn il- pazjenti.
Cases of hepatobiliary events, some with fatal outcome, have been reported.
Kienu rrappurtati każi ta ’ avvenimenti epatobiljari, uħud minnhom b’ eżitu fatali.
If signs or symptoms of hepatic failure are present, SUTENT should be discontinued and appropriate supportive care should be provided.
Jekk ikun hemm sintomi ta ’ insuffiċjenza tal - fwied, SUTENT għandu jiġi mwaqqaf u tingħata kura xierqa ta ’ sostenn.
6 Renal function The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Funzjoni tal- Kliewi Is- sigurtà tat- trattament kontinwu b’ SUTENT f’ pazjenti bi proteinurja moderata għal severa ma ġietx evalwata b’ mod sistematiku.
Cases of proteinuria and rare cases of nephrotic syndrome have been reported.
Kienu rrappurtati każijiet ta ’ proteinurja u każijiet rari tas- sindromu nefrotiku.
Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria.
Hija rakkomandata analiżi ta ’ l- awrina fil- linja bażi, u l- pazjenti għandhom jiġu mmonitorjati għall- iżvilupp jew taħżin tal- proteinurja..
Discontinue SUTENT in patients with nephrotic syndrome.
Il- kura b’ SUTENT f’ pazjenti bis- sindromu nefrotiku għandha tiġi mwaqqfa.
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.
Aċċessjonijiet Fi studji kliniċi ta ’ SUTENT u mill- esperjenza ta ’ wara t- tqegħid tal- prodott fis- suq, ġew osservati aċċessjonijiet f’ individwi bi jew mingħajr evidenza radjoloġika ta ’ metastasijiet fil- moħħ.
In addition, there have been rare (< 1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS).
Barraminhekk, kien hemm rapporti rari (< 1%) ta ’ suġġetti li ppreżentaw b’ aċċessjonijiet u evidenza radjoloġika tas- sindromu lewkoenkefalopatija posterjuri riversibbli (RPLS).
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.
Pazjenti b’ aċċessjonijiet u sinjali/ sintomi konsistenti ma ’ RPLS, bħal ma huma pressjoni għolja, uġigħ ta ’ ras, viġilanza mnaqqsa, tibdil fil- funzjoni mentali u telf tal- vista, inkluża għama kortikali għandhom jiġu kkontrollati b’ ġestjoni medika inkluż il- kontroll ta ’ pressjoni għolja.
Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.
Sospensjoni temporanja ta ’ SUTENT hija rakkomandata, it- trattament jista ’ jitkompla fid- diskrezzjoni tat- tabib kuranti.
Drugs that may increase sunitinib plasma concentrations:
Mediċini li jistgħu jżidu l- konċentrazzjonijiet ta ’ sunitinib fil- plażma:
Concomitant administration of sunitinib malate with the potent CYP3A4 inhibitor, ketoconazole, resulted in a 49% and 51% increase of the complex [sunitinib + primary metabolite] Cmax and AUC0-∞ values, respectively, after a single dose of sunitinib malate in healthy volunteers.
Amministrazzjoni konkomitanti ta ’ sunitinib malate ma ’ ketoconazole, impeditur ta ’ CYP3A4 potenti, irriżultat f’ żieda ta ’ 49% u 51% fil- valuri tal- kumpless [sunitinib + metabolit primarju] Cmax u AUC0 - ∞, rispettivament wara doża waħda ta ’ sunitinib malate f’ voluntiera b’ saħħithom.
Administration of SUTENT with potent inhibitors of the CYP3A4 family (e. g. ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice) may increase sunitinib concentrations Combination with inhibitors should therefore be avoided, or the selection of an alternate concomitant medication with no, or minimal potential to inhibit CYP3A4 should be considered.
Għaldaqstant, kumbinazzjonijiet ma ’ impedituri għandhom jiġu evitati, jew l- għażla ta ’ mediċina konkomitanti alternattiva bla ebda, jew b’ potenzjal minimu li timpedixxi CYP3A4 għandha tiġi kkunsidrata.
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).
Jekk dan mhuwiex possibbli, id- dożaġġ ta ’ SUTENT jista ’ jkollu bżonn jiġi mnaqqas għal minimu ta ’ 37. 5 mg kuljum, ibbażat fuq sorveljanza bir- reqqa tat- tolerabbilità (ara sezzjoni 4. 2).
Drugs that may decrease sunitinib plasma concentrations:
7 Mediċini li jistgħu jnaqqsu l- konċentrazzjonijiet ta ’ sunitinib fil- plażma:
Concomitant use of SUTENT with the CYP3A4 inducer, rifampin, resulted in a 23% and 46% reduction of the complex [sunitinib + primary metabolite] Cmax and AUC0-∞ values, respectively, after a single dose of SUTENT in healthy volunteers.
L- użu konkomitanti ta ’ SUTENT ma ’ sensitizzatur ta ’ CYP3A4, rifampin, irriżulta fi tnaqqis ta ’ 23% u 46% fil- valuri tal- kumpless [sunitinib + metabolit primarju] Cmax u AUC0- ∞, rispettivament, wara doża waħda ta ’ SUTENT f’ voluntiera f’ saħħithom.
Administration of SUTENT with potent inducers of the CYP3A4 family (e. g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or Hypericum perforatum known also as St.
L- għoti ta ’ SUTENT ma ’ impedituri potenti tal - familja CYP3A4 (eż. dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital jew Hypericum perforatum magħrufa ukoll bħala St.
John’ s Wort) may decrease sunitinib concentrations.
John’ s Wort) tista ’ tnaqqas il- konċentrazzjonijiet ta ’ sunitinib.
Combination with inducers should therefore be avoided, or selection of an alternate concomitant medication with no, or minimal potential to induce CYP3A4 should be considered.
Għaldaqstant, kumbinazzjonijiet ma ’ impedituri għandhom jiġu evitati, jew l- għażla ta ’ mediċina konkomitanti alternattiva bla ebda, jew b’ potenzjal minimu li tinibixxi CYP3A4 għandha tiġi kkunsidrata.
If this is not possible, the dosage of SUTENT may need to be increased in 12.5 mg increments (up to 87,5 mg per day) based on careful monitoring of tolerability (see section 4.2).
Jekk dan mhuwiex possibbli, id- dożaġġ ta ’ SUTENT jista ’ jkollu bżonn jiġi miżjud b’ inkrimenti ta ’ 12. 5 mg (sa 87. 5 mg kuljum) ibbażat fuq sorveljanza bir- reqqa tat- tolerabbilità (ara sezzjoni 4. 2).
To maintain sunitinib target concentrations, selection of co-medications with less enzyme induction potential, should be considered.
Sabiex iżżomm konċentrazzjonijiet mixtieqa ta ’ sinitinib, l- għażla ta ’ mediċini konkomitanti b’ potenzjal anqas li jinduċu l- enzimi, għandha tiġi kkunsidrata.
If this is not possible, dose-adjustments of SUTENT may be necessary (see section 4.2).
Jekk dan mhux possibbli, aġġustament tad- dożi ta ’ SUTENT jistgħu jkunu meħtieġa (ara sezzjoni 4. 2).
Haemorrhage has been observed rarely in patients treated with SUTENT (see section 4.4).
Rarament ġiet osservata emorraġija f’ pazjenti ttrattati b’ SUTENT (ara sezzjoni 4. 4).
Patients receiving concomitant treatment with anti-coagulants (e. g. warfarin; acenocumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/ INR), and physical examination.
Pazjenti li qed jingħataw trattament konkomitanti b’ anti- koagulanti (eż. warfarin; acenocumarole) jistgħu jiġu sorveljati perijodikament permezz ta ’ testijiet ta ’ l- għadd tad- demm komplut (plejtlits), fatturi ta ’ koagulazzjoni (PT/ INR), u eżami fiżiku.
Pregnancy There are no studies in pregnant women using SUTENT.
Tqala Ma hemm l- ebda studji f’ nisa tqal li qegħdin jużaw SUTENT.
Studies in animals have shown reproductive toxicity including foetal malformations (see section 5.3).
Studji fl- annimali wrew tossiċità riproduttiva li jinkludu malformazzjonijiet tal- fetu (ara sezzjoni 5. 3).
SUTENT should not be used during pregnancy or in any woman not employing adequate contraception unless the potential benefit justifies the potential risk to the foetus.
SUTENT m’ għandux jintuża waqt it- tqala jew fi kwalunkwé mara li ma tużax kontraċezzjoni adegwata sakemm is- siwi potenzjali jiġġustifika r- riskju potenzjali lill- fetu.
If the drug is used during pregnancy or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the foetus.
Jekk il- mediċina tintuża waqt it- tqala jew jekk il- pazjenta toħroġ tqila waqt li tkun qed tingħata din il- mediċina, il- pazjenta għandha tiġi avżata dwar il- potenzjal ta ’ periklu għall- fetu.
7 Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with SUTENT.
Nisa b’ potenzjal li jkollhom it- tfal għandhom jiġu avżati biex jevitaw li joħorġu tqal waqt li jkunu qed jingħataw trattament b’ SUTENT.
Based on non-clinical findings, male and female fertility may be compromised by treatment with SUTENT (see section 5.3).
Ibbażat fuq riżultati mhux kliniċi, il- fertiltà fl- irġiel u fin- nisa tista ’ tiġi kompromessa permezz ta ’ trattament b’ SUTENT (ara sezzjoni 5. 3).
Lactation Sunitinib and/ or its metabolites are excreted in rat milk.
Treddigħ Sunitinib u/ jew il- metaboliti huma eliminati fil- ħalib tal- far.
It is not known whether sunitinib or its primary active metabolite are excreted in human milk.
Mhuwiex magħruf jekk sunitinib jew il - metabolit attiv primarju tiegħu huwiex eliminat fil- ħalib uman.
Because drugs are commonly excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women should not breast feed while taking SUTENT.
Peress li l- mediċini huma komunement eliminati fil- ħalib uman u minħabba l- potenzjal għal reazzjonijiet avversi serji fi trabi li jkunu qed jitreddgħu, in- nisa m’ għandhomx ireddgħu waqt li qed jieħdu SUTENT.
No studies on the effects on the ability to drive or operate machinery have been performed.
Ma ġew magħmula l- ebda studji fuq l- effetti fuq il- ħila biex issuq jew tħaddem makkinarju.
Patients should be advised that they may experience dizziness during treatment with SUTENT.
Il - pazjenti għandhom jiġu avżati li jistgħu jesperjenzaw sturdamenti waqt trattament b’ SUTENT.
The most important treatment-related serious adverse events associated with SUTENT treatment of patients with solid tumours were pulmonary embolism (1%), thrombocytopoenia (1%), tumour haemorrhage (0.9%), febrile neutropoenia (0.4%), and hypertension (0.4%).
L- aktar reazzjonijiet avversi serji importanti relatati assoċjati ma ’ trattament b’ SUTENT f’ pazjenti b’ tumuri solidi kienu emboliżmu pulmonari (1%), tromboċitopenja (1%), emorraġija fit- tumur (0. 9%), newtropinja bid- deni (0. 4%), u pressjoni għolja (0. 4%).
The most common treatment-related adverse events (experienced by at least 20% of the patients) of any grade included: fatigue; gastrointestinal disorders, such as diarrhoea, nausea, stomatitis, dyspepsia and vomiting; skin discolouration; dysgeusia and anorexia.
L- aktar reazzjonijiet avversi komuni relatati mat- trattament (esperjenzati minn ta ’ l- anqas 20% tal- pazjenti) ta ’ kwalunkwé grad kienu jinkludu: għejja kbira; disturbi gastrointestinali, bħal ma huma dijarea, dardir, stomatité, dispepsja u remettar; tibdil fil- kulur tal- ġilda; disgewżja u anoressja.
Fatigue, hypertension and neutropoenia were the most common treatment-related adverse events of Grade 3 maximum severity and increased lipase was the most frequently occurring treatment-related adverse event of Grade 4 maximum severity in patients with solid tumours.
Għejja kbira, pressjoni għolja u newtropenja kienu l - aktar reazzjonijiet avversi komuni relatati mat- trattament ta ’ severità massima fi Grad 3 u żieda fil - lipase kienet l- aktar reazzjoni avversa komuni relatata mat- trattament ta ’ severità massima Grad 4
Hepatitis and hepatic failure occurred in < 1% of patients and prolonged QT interval in < 0.1% (see section 4.4).
Epatite u insuffiċjenza epatika seħħew f ’ < 1% ta ’ pazjenti u titwil fl- interval QT f ’ < 0. 1% (ara sezzjoni 4. 4).
Fatal events other than those listed in section 4.4 above or section 4.8 below that were considered possibly related to SUTENT included multi-system organ failure, disseminated intravascular coagulation, peritonoeal haemorrhage, rhabdomyolysis, cerebrovascular accident, dehydration, adrenal insufficiency, renal failure, respiratory failure, pleural effusion, pneumothorax, shock, and sudden death.
Ġrajjiet fatali barra minn dawk imniżżla f’ sezzjoni 4. 4 hawn fuq jew sezzjoni 4. 8 hawn isfel li kienu kkunsidrati bħala possibbilment relatati ma ’ SUTENT kienu jinkludu: insuffiċjenza ta ’ organi varji, koagulazzjoni intravaskulari mxerrda, emorraġija peritoneali, rabdomijolisi, aċċident ċerebrovaskulari, deidratazzjoni, insuffiċjenza adrenali, insuffiċjenza tal- kliewi, insuffiċjenza respiratorja, effużjoni tal- plewra, pnewmotoraċi, xokk u mewt zopptu.
Treatment-related adverse reactions that were reported in > 2% of solid tumour patients are listed below, by system organ class, frequency and grade of severity.
Reazzjonijiet avversi relatati mat- trattament kienu rapportati f ’ > 2% tal- pazjenti b’ tumuri solidi kif elenkati hawn taħt, fil- Sistema ta ’ Klassifika ta ’ l- Organi, il- frekwenza u l- grad ta ’ severità.
Frequencies are defined as:
L- effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk inqas serji.
Very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10), mhux komuni (≥1/ 1, 000 sa < 1 // 100), rari (≥1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000).
Treatment-Related Adverse Reactions reported in GIST studies
Reazzjonijet Avversi relatati mat- trattament rrapportati fi studji GIST
All Grades n (%)
Il- Gradi Kollha n (%)
Blood and the lymphatic system disorders
Disturbi tad -
Very common Very common Very common Common Common
Komuni ħafna
86 (19.5%) 81 (18.4%) 67 (15.2%) 26 (5.9%) 10 (2.3%)
86 (19. 5%)
24 (5.5%) 39 (8.9%) 19 (4.3%) 9 (2.0%) 3 (0.7%)
24 (5. 5%)
3 (0.7%) 5 (1.1%) 6 (1.4%) 1 (0.2%) 1 (0.2%)
3 (0. 7%)
Endocrine disorders
demm u tas - sistema limfatika Disturbi fis - sistema endokrinarja
Very common
Komuni ħafna Komuni ħafna Komuni Komuni Komuni ħafna
Hypothyroidism
Newtropenja Tromboċitopenja Lewkopenija Limfopenija Ipotirojdiżmu Tnaqqis fl- aptit a
59 (13.4%)
81 (18. 4%) 67 (15. 2%) 26 (5. 9%) 10 (2. 3%) 59 (13. 4%)
5 (1.1%)
39 (8. 9%) 19 (4. 3%) 9 (2. 0%) 3 (0. 7%) 5 (1. 1%)
1 (0.2%)
5 (1. 1%) 6 (1. 4%) 1 (0. 2%) 1 (0. 2%) 1 (0. 2%)
117 (26.6%)
117 (26. 6%)
8 (1.8%)
8 (1. 8%)
0 (0.0%)
0 (0. 0%)
Very common
Disturb fit- togħma b
Taste disturbance b
Disturbi fis- sistema
105 (23.9%)
105 (23. 9%)
1 (0.2%)
1 (0. 2%)
System Organ Class
nervuża
Frequency
Komuni ħafna Komuni Komuni Komuni
Adverse Reactions
Uġigħ ta ’ ras Parasteżija Sturdament Newropatija periferali
All Grades n (%)
76 (17. 3%) 27 (6. 1%) 18 (4. 1%) 11 (2. 5%)
Grade 3 n (%)
5 (1. 1%) 1 (0. 2%) 1 (0. 2%) 0 (0. 0%)
Grade 4 n (%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
Nervous system disorders
Disturbi vaskulari
Very common Common Common Common Common
Komuni Komuni ħafna
Headache Paraesthesia Dizziness Neuropathy peripheral Hypoaesthesia
Ipoestesija Pressjoni għolja
76 (17.3%) 27 (6.1%) 18 (4.1%) 11 (2.5%) 10 (2.3%)
10 (2. 3%) 101 (23. 0%)
5 (1.1%) 1 (0.2%) 1 (0.2%) 0 (0.0%) 0 (0.0%)
0 (0. 0%) 43 (9. 8%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%)
Vascular disorders
Disturbi
101 (23.0%)
28 (6. 4%)
43 (9.8%)
16 (3. 6%)
Respiratory, thoracic and mediastinal disorders
Disturbi fil- kliewi u fis- sistema urinarja
Epistaxis Dyspnoea
Kromaturja
28 (6.4%) 16 (3.6%)
18 (4. 1%)
1 (0.2%) 2 (0.5%)
0 (0. 0%)
0 (0.0%) 0 (0.0%)
0 (0. 0%)
Renal and urinary disorders
Disturbi gastro - intestinali
Common
Komuni ħafna
Chromaturia
Komuni ħafna
18 (4.1%)
15 (3. 4%)
Gastrointestinal disorders
9 Klassi tas- Sistema ta ’ l- Organi
Very common Very common Very common Very common Very common Very common
Komuni ħafna Komuni ħafna
Diarrhoea Nausea Vomiting Stomatitis Dyspepsia Abdominal pain C / distension
Stomatite Dispepsja Uġigħ addominali c /
187 (42.5%) 161 (36.6%) 98 (22.2%) 90 (20.5%) 80 (18.2%) 77 (17.5%)
90 (20. 5%) 80 (18. 2%)
24 (5.5%) 15 (3.4%) 7 (1.6%) 7 (1.6%) 4 (0.9%) 15 (3.4%)
7 (1. 6%) 4 (0. 9%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (0.5%)
0 (0. 0%) 0 (0. 0%)
Very common Very common Common Common Common Common
Komuni ħafna Komuni ħafna Komuni Komuni Komuni Komuni
Flatulence Oral pain Constipation Glossodynia Dry mouth Gastro-oesophageal reflux disease
Gass fl- istonku Uġigħ fil- ħalq Stitikezza Glossodinja Ħalq xott Mard ta ’ refluss gastro- esofaġiku
46 (10.5%) 44 (10.0%) 37 (8.4%) 37 (8.4%) 31 (7.0%) 12 (2.7%)
46 (10. 5%) 44 (10. 0%) 37 (8. 4%) 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%) 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%) 0 (0. 0%) 0 (0. 0%)
Mouth ulceration Oral discomfort
Ulċerazzjoni fil- ħalq
11 (2.5%) 11 (2.5%)
11 (2. 5%)
Yellow skin/ Skin discolouration
Ġilda safra / Tibdil fil- kulur tal- ġilda
146 (33.2%)
146 (33. 2%)
tissue disorders
Komuni ħafna
Palmar-plantar erythrodysaesthesia syndrome
Tibdil fil- kulur tax - xagħar
106 (24.1%)
67 (15. 2%)
27 (6.1%)
0 (0. 0%)
Very common Very common Common Common Common Common Common Common Common Common Common
Komuni ħafna Komuni Komuni Komuni Komuni Komuni Komuni Komuni Komuni Komuni
Hair colour changes Rash Dry skin Alopecia Dermatitis Periorbital oedema Skin Reaction Erythema Eczema Pruritus Skin hyperpigmentation
Raxx Ġilda xotta Alopeċja Dermatite Edema periorbitali Reazzjoni tal- ġilda Eritema Ekżema Ħakk Pigmentazzjoni eċċessiva tal- ġilda
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%)
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%)
Common Common Common
Komuni Komuni Komuni Komuni ħafna
Skin exfoliation Blister Skin lesion
Tqaxxir tal- ġilda Nuffata Leżjoni fil- ġilda Uġigħ fl - estremità/ membri
12 (2.7%) 10 (2.3%) 10 (2.3%)
12 (2. 7%) 10 (2. 3%) 10 (2. 3%) 54 (12. 3%)
0 (0.0%) 1 (0.2%) 1 (0.2%)
0 (0. 0%) 1 (0. 2%) 1 (0. 2%) 5 (1. 1%)
0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%)
Muscoloskeletal, connective tissue
connective tissue Disturbi ġenerali
Very Common Common
Komuni Komuni Komuni Komuni Komuni Komuni ħafna
Pain in extremity/ limb Arthralgia
Artralġja Uġigħ fil- muskoli Spażmu fil- muskoli Uġigħ fid- dahar Dgħjufija fil- muskoli Għeja kbira/ Telqa
54 (12.3%) 39 (8.9%)
39 (8. 9%) 29 (6. 6%) 21 (4. 8%) 22 (2. 5%) 10 (2. 3%) 287
5 (1.1%) 3 (0.7%)
3 (0. 7%) 0 (0. 0%) 1 (0. 2%) 2 (0. 5%) 1 (0. 2%) 64 (14. 5%)
0 (0.0%) 0 (0.0%)
0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 0 (0. 0%) 5 (1. 1%)
9
kbira
System Organ Class
ta 'mnejn jingħata
Adverse Reactions
Infjammazzjoni tal- mukoża Edema d
All Grades n (%)
70 (15. 9%)
Grade 3 n (%)
1 (0. 2%)
Grade 4 n (%)
59 (13. 4%)
and bone disorders
0 (0. 0%)
Common Common Common Common
Komuni
Myalgia Muscle spasm Back pain Muscular weakness
Deni
29 (6.6%) 21 (4.8%) 11 (2.5%) 10 (2.3%)
26 (5. 9%)
0 (0.0%) 1 (0.2%) 2 (0.5%) 1 (0.2%)
2 (0. 5%)
0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
0 (0. 0%)
General disorders and administration site conditions Psychiatric disorders
Klassi tas- Sistema ta ’ l- Organi
Very common Very common Very common Common Common
Frekwenza
Fatigue/ Asthenia Mucosal inflammation Oedema d Pyrexia Insomnia
Reazzjonijiet avversi
287 (65.2%) 70 (15.9%) 59 (13.4%) 26 (5.9%) 14 (3.2%)
Il- Gradi Kollha n (%)
64 (14.5%) 6 (1.4%) 1 (0.2%) 2 (0.5%) 0 (0.0%)
Grad 3 n (%)
5 (1.1%) 1 (0.2%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Grad 4 n (%)
Investigations
Nuqqas ta ’ rqad
Lipase increase White blood cell count decreased e
Żieda fil- lipase Tnaqqis fl- għadd ta ’ ċelloli bojod tad - demm e
35 (8.0%) 33 (7.5%)
35 (8. 0%) 33 (7. 5%)
12 (2.7%) 15 (3.4%)
12 (2. 7%) 15 (3. 4%)
7 (1.6%) 0 (0.0%)
7 (1. 6%) 0 (0. 0%)
Ejection fraction decreased
Tnaqqis fil- frazzjoni tat- tfigħ ’ il barra
27 (6.1%)
27 (6. 1%)
5 (1.2%)
5 (1. 2%)
6 (1.4%)
6 (1. 4%)
Platelet count decrease
Tnaqqis fl- għadd tal- plejtlits
25 (5.7%)
25 (5. 7%)
4 (0.9%)
4 (0. 9%)
Weight decreased Blood creatinine phosphokinase increased
Tnaqqis fil- piż Żidiet fil- creatinine phosphokinase fid - demm
23 (5.2%) 22 (5.0%)
23 (5. 2%) 22 (5. 0%)
1 (0.2%) 1 (0.2%)
1 (0. 2%) 1 (0. 2%)
0 (0.0%) 1 (0.2%)
0 (0. 0%) 1 (0. 2%)
Amylase increased Aspartate aminotransferase increased
Żieda fl- amylase Żieda fl- aspartate aminotransferase
21 (4.8%) 18 (4.1%)
21 (4. 8%) 18 (4. 1%)
8 (1.8%) 2 (0.5%)
8 (1. 8%) 2 (0. 5%)
Alanine aminotransferase increased
Żieda fl- alanine aminotrasferase
12 (2.7%)
12 (2. 7%)
Any adverse event
Kwalunkwe episodju avvers
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
Dawn it- termini ġew ikkombinati: a Anoreksja u tnaqqis fl- aptit b Disgweżja, asgweżja u disturb fit- togħma c Uġigħ addominali u wġigħ fil- parti ta ’ fuq ta ’ l- addome d Edema, edema periferali u edema fil- wiċċ e Tnaqqis fl- għadd ta ’ ċelloli bojod tad- demm, tnaqqis fl- għadd ta ’ newtrofili, u tnaqqis fl- għadd ta ’ lewkoċiti
Treatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studies
Reazzjonijiet Avversi relatati mat- trattament irrapportati fi studji ta ’ MRCC refrattarja għaċ - ċitokini u li qatt ma kienet ittrattata qabel
Blood and lymphatic system disorders
Disturbi tad- demm u tas- sistema
Neutropoenia Thrombocytopoenia
Newtropenja
89 (16.4%) 86 (15.8%)
89 (16. 4%)
46 (8.5%) 37 (6.8%)
46 (8. 5%)
5 (0.9%) 5 (0.9%)
5 (0. 9%)
Very common Common Common
Komuni ħafna
Anaemia Leukopoenia Lymphopenia
Tromboċitopenija
67 (12.3%) 45 (8.3%) 21 (3.9%)
86 (15. 8%)
20 (3.7%) 16 (2.9%) 12 (2.2%)
37 (6. 8%)
3 (0.6%) 0 (0%) 1 (0.2%)
5 (0. 9%)
Endocrine
67 (12. 3%)
Very common
Komuni Komuni
Hypothyroidism
Ipotirojdiżmu
67 (12.3%)
67 (12. 3%)
7 (1.3%)
7 (1. 3%)
0 (0%)
0 (0. 0%)
10
0 (0%) 0 (0. 0%)
System Organ Class disorders
11 Sistema ta ’ Klassifika ta ’ l - Organi
Adverse Reactions
Reazzjonijiet avversi Tnaqqis fl- aptit a
Eye disorders
Disturbi fil - metaboliżmu u n - nutrizzjoni
Lacrimation increased
Deidrazzjoni Disturb fit- togħma b
0 (0%)
7 (1. 3%)
0 (0%)
1 (0. 2%)
Eyelid oedema
250 (46. 0%)
12 (2.2%)
82 (15. 1%)
0 (0%)
3 (0. 6%)
Metabolism and nutrition disorders
Disturbi vaskulari
Decreased appetite Dehydration
38 (7. 0%) 36 (5. 9%) 33 (6. 1%) 20 (3. 7%) 17 (3. 1%) 143( 26. 3
205 (37.7%) 33 (6.1%)
2 (0. 4%) 0 (0%) 1 (0. 2%) 0 (0%) 0 (0%) 55
9 (1.7%) 7 (1.3%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
0 (0%) 1 (0.2%)
(10. 1%)
Nervous system disorders
Disturbi respiratorji,
Very common Very common Common Common Common
Komuni Komuni Komuni ħafna
Taste disturbance b Headache Dizziness Paraesthesia Neuropathy peripheral
Fwawar Fwawar tal- menopawsa Epistassi
250 (46.0%) 82 (15.1%) 38 (7.0%) 36 (5.9%) 33 (6.1%)
17 (3. 1%) 12 (2. 2%) 86 (15. 8%)
1 (0.2%) 3 (0.6%) 2 (0.4%) 0 (0%) 1 (0.2%)
0 (0%) 0 (0%) 3 (0. 6%)
Hypoaesthesia Hyperaesthesia
Qtugħ ta ’ nifs Uġigħ fil- larinġi u l - farinġi
20 (3.7%) 17 (3.1%)
45 (8. 3%) 29 (5. 3%)
0 (0%) 0 (0%)
6 (1. 1%) 2 (0. 4%)
Very common Common Common
Komuni Komuni Komuni ħafna
Hypertension Flushing Hot flush
Konġestjoni nażali Effużjoni tal- plewra Dijarea
143 (26.3%) 17 (3.1%) 12 (2.2%)
12 (2. 2%) 12 (2. 2%) 326 (59. 9%)
55 (10.1%) 0 (0%) 0 (0%)
0 (0%) 4 (0. 6%) 38 (7. 0%)
Respiratory, thoracic and
Komuni ħafna
Very common
Tqalligħ
Epistaxis
290 (53. 3%)
86 (15.8%)
19 (3. 5%)
3 (0.6%)
0 (0%)
0 (0%)
8 (1. 5%)
mediastinal
0 (0%)
Dyspnoea
Stomatite
45 (8.3%)
185 (34. 0%)
6 (1.1%)
13 (2. 4%)
disorders
178 (32. 7%)
Pharyngolaryngeal pain
distensjoni
29 (5.3%)
106 (19. 5%)
2 (0.4%)
10 (1. 8%)
Common Common Common Common Common Common
Komuni ħafna
Cough Dysphonia Nasal dryness Dyspnoea exertional Nasal congestion Pleural effusion
Stitikezza
23 (4.2%) 16 (2.9%) 14 (2.6%) 12 (2.2%) 12 (2.2%) 12 (2.2%)
83 (15. 3%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 3 (0.6%)
1 (0. 2%)
Gastrointestinal disorders
Komuni ħafna
Very common Very common Very common Very common Very common Very common
Komuni ħafna
Diarrhoea Nausea Dyspepsia Stomatitis Vomiting Abdominal pain c / distension
Gass fl- istonku
326 (59.9%) 290 (53.3%) 189 (34.7%) 185 (34.0%) 178 (32.7%) 106 (19.5%)
60 (11. 0%)
38 (7.0%) 19 (3.5%) 8 (1.5%) 13 (2.4%) 17 (3.1%) 10 (1.8%)
0 (0%)
Very common Very common Very common Very common Very common Common
Komuni ħafna
Constipation Glossodynia Flatulence Oral pain Dry mouth Gastroesophageal reflux disease
Uġigħ fil- ħalq
83 (15.3%) 63 (11.6%) 60 (11.0%) 60 (11.0%) 56 (10.3%) 50 (9.2%)
60 (11. 0%)
1 (0.2%) 0 (0%) 0 (0%) 2 (0.4%) 0 (0%) 2 (0.4%)
2 (0. 4%)
Common Common Common Common Common Common Common Common
Komuni ħafna
Dysphagia Cheilitis Gingival bleeding Haemorrhoids Proctalgia Mouth ulceration Stomach discomfort Rectal haemorrhage
Ħalq xott
20 (3.7%) 19 (3.5%) 18 (3.3%) 18 (3.3%) 17 (3.1%) 16 (2.9%) 15 (2.8%) 13 (2.4%)
56 (10. 3%)
Palmar-plantar erythrodysaesthesia syndrome
Tidnis isfar fil- ġilda / Tibdil fil- kulur tal- ġilda
144 (26.5%)
144 (26. 5%)
46 (8.5%)
1 (0. 2%)
Yellow discolouration/ Skin discolouration
Komuni ħafna
144 (26.5%)
108 (19. 9%)
Very common Very common Very common Very common Common Common Common Common Common Common Common
Komuni Komuni Komuni Komuni Komuni Komuni Komuni
Rash Dry skin Hair colour changes Alopecia Erythema Skin exfoliation Pruritus Periorbital oedema Dermatitis Skin lesion Nail disorder/ discolouration
Eritema Tqaxxir tal- ġilda Ħakk Edema periorbitali Dermatite Leżjoni fil- ġilda Disturb / tidnis tad - dwiefer
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%)
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%) 2 (0.4%) 4 (0.7%) 1 (0.2%) 1 (0.2%) 4 (0.7%) 1 (0.2%) 0 (0%)
2 (0. 4%) 4 (0. 7%) 1 (0. 2%) 1 (0. 2%) 4 (0. 7%) 1 (0. 2%) 0 (0%)
Common Common Common Common
Komuni Komuni Komuni Komuni Komuni ħafna
Blister Skin reaction Hyperkeratosis Acne
Nuffata Reazzjoni tal- ġilda Iperkeratosi Akne Uġigħ fl- estremità
23 (4.2%) 23 (4.2%) 22 (4.0%) 19 (3.5%)
23 (4. 2%) 23 (4. 2%) 22 (4. 0%) 19 (3. 5%) 96 (17. 6%)
1 (0.2%) 6 (1.1%) 4 (0.7%) 0 (0%)
1 (0. 2%) 6 (1. 1%) 4 (0. 7%) 0 (0%) 6 (1. 1%)
Musculoskeletal and connective tissue disorders
connective tissue Disturbi ġenerali u
Very common Common Common Common Common
Komuni Komuni Komuni Komuni Komuni ħafna
Pain in extremity Arthralgia Myalgia Muscle Spasm Back pain
Artralgja Uġigħ fil- muskoli Spażmu fil- muskoli Uġigħ fid- dahar Għeja kbira/ telqa kbira
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%) 397
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%) 95
0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0. 2%)
General disorders and administration
kondizzjonijiet ta ’
Fatigue/ asthenia Mucosal inflammation
Infjammazzjoni tal - mukuża Edema d
397 (73.0%) 127 (23.3%)
127 (23. 3%)
95 (17.5%) 8 (1.5%)
8 (1. 5%)
Very common Common Common Common Common
Komuni ħafna
99 (18.2%) 37 (6.8%) 35 (6.4%) 20 (3.7%) 13 (2.4%)
99 (18. 2%)
5 (0.9%) 3 (0.6%) 2 (0.4%) 0 (0%) 2 (0.4%)
5 (0. 9%)
Psychiatric disorders Investigations
Disturbi psikjatriċi
Common Common Very common
Komuni Komuni Komuni Komuni Komuni
Insomnia Depression Ejection fraction decreased
Deni Tertir Uġigħ Uġigħ fis- sider Nuqqas ta ’ rqad
22 (4.0%) 15 (2.8%) 84 (15.4%)
37 (6. 8%) 35 (6. 4%) 20 (3. 7%) 13 (2. 4%) 22 (4. 0%)
0 (0%) 1 (0.2%) 16 (2.9%)
3 (0. 6%) 2 (0. 4%) 0 (0%) 2 (0. 4%) 0 (0%)
Weight decreased Platelet count decreased
Reazzjonijiet avversi
57 (10.5%) 41 (7.5%)
Il- Gradi Kollha n (%)
1 (0.2%) 15 (2.8%)
Grad 3 n (%)
0 (0%) 2 (0.4%)
Grad 4 n (%)
Common
Komuni Komuni ħafna
White blood cell count decreased e
Depressjoni Tnaqqis fil- frazzjoni tat -
37 (6.8%)
15 (2. 8%) 84
16 (2.9%)
0 (0%) 0 (0%)
0 (0%)
(15. 4%)
Common Common
Komuni ħafna
Lipase increased Haemoglobin decreased
Tnaqqis fil- piż
36 (6.6%) 25 (4.6%)
57 (10. 5%)
19 (3.5%) 8 (1.5%)
1 (0. 2%)
Blood creatine phosphokinase increased
Tnaqqis fl- għadd tal - plejtlits
19 (3.5%)
41 (7. 5%)
7 (1.3%)
15 (2. 8%)
2 (0.4%)
2 (0. 4%)
Aspartate aminotransferase
Tnaqqis fl- għadd taċ - ċelloli bojod tad- demm
18 (3.3%)
37 (6. 8%)
12
16 (2. 9%)
System Organ Class
11 (2%) 0 (0%) 2 (0. 4% _
Adverse Reactions increased
Żieda fl- aspartate aminotransferase
All Grades n (%)
18 (3. 3%)
Grade 3 n (%)
7 (1. 3%)
Blood amylase increased
Żieda fl- amylase fid - demm
18 (3.3%)
18 (3. 3%)
11 (2.0%)
11 (2. 0%)
Blood creatinine increased
Żieda fil- kreatinina fid - demm
15 (2.8%)
13 (2. 8%)
0 (0%)
0 (%)
Blood pressure increased
Żieda fil- pressjoni tad - demm
15 (2.8%)
15 (2. 8%)
Alanine aminotransferase increased
Żieda fl- alanine aminotransferase
14 (2.6%)
14 (2. 6%)
Any adverse event
Kwalunkwe reazzjoni
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
It- termini segwenti ġew ikkombinati: a Anoreksja u tnaqqis fl- aptit b Disgewżja, asgewżja u disturb fit- togħma c Uġigħ addominali u fil- parti ta ’ fuq ta ’ l- addome d Edema, edema periferali u edema fil- wiċċ e Tnaqqis fl- għadd taċ- ċelloli bojod tad- demm, tnaqqis fl- għadd tan- newtrofili, u tnaqqis fl- għadd tal- lewkoċiti
Adverse reactions from post-marketing experience
Reazzjonijiet avversi mill- esperjenza ta ’ wara t- tqegħid tal- prodott fis- suq
The following adverse reactions have been identified during post-approval use of SUTENT.
Dawn it- tip ta ’ reazzjonijiet li huma mniżżla hawn taħt ġew irrappurtati minn esperjenza b’ SUTENT wara li dan il- prodott beda jinbiegħ.
This includes spontaneous case reports as well as serious adverse events from ongoing studies, the expanded access programmes, clinical pharmacology studies and exploratory studies in unapproved indications.
Dawn jinkludu rapporti spontanji ta ’ każijiet kif ukoll reazzjonijiet avversi serji minn studji kurrenti, programmi ta ’ aċċess espansiv, studji kliniċi farmakoloġiċi u studji esplorattivi f’ indikazzjonijiet mhux approvati.
Rare:
Mhux Komuni:
Cardiac failure, cardiac failure congestive, left ventricular failure Prolonged QT interval, Torsade de pointes
Insuffiċjenza tal- qalb, insuffiċjenza konġestiva tal- qalb, insuffiċjenza ventrikulari leminija.
Pancreatitis Gastrointestinal perforation
Titwil ta ’ l- intervall QT, torsade de pointes
Hepatobiliary disorders:
Disturbi gastro- intestinali:
Investigations:
Disturbi fil- fwied u Mhux komuni:
Hepatic failure
Insuffiċjenza tal- fwied
Elevated thyroid stimulating hormone (TSH)
Livelli għolja ta ’ thyroid stimulating hormone (TSH)
Infections and Infestations Non known:
Infezzjonijiet u infestazzjonijiet Mhux magħrufa
Pulmonary disorders
Infezzjonijiet (b ’ newtropenja jew mingħajr)
Infections (with or without neutropoenia) connective tissue disorders Myopathy and/ or rhabdomyolysis
Disturbi muskolu- skeltrali u tal- connective tissue Mhux magħrufa Disturbi pulmonari
Not known:
Mhux magħrufa Mhux magħrufa
Pleural effusion Pulmonary embolism and respiratory failure
Effużjoni tal- plewra Emboliżmu pulmonari u insuffiċjenza respiratorja
Thromboembolic events:
Episodji trombo- emboliċi:
Cases of pulmonary embolism, in some cases with fatal outcome, have been reported.
Kienu rrappurtati każi ta ’ emboliżmu pulmonari, uħud minnhom b’ eżitu fatali.
Infection and infestations:
Infezzjonijiet u infestazzjonijiet:
Cases of serious infection (with or without neutropoenia), including pneumonia, have been reported.
Kienu rrapurtati każijiet ta ’ infezzjoni serja (b’ newtropenja jew mingħajr) inkluża pnewmownja.
Few cases had a fatal outcome.
Ftit każijiet kienu fatali.
Rare cases of myopathy and/ or rhabdomyolysis, some with acute renal failure, have been reported.
Kienu rrapurtati każijiet rari ta ’ Mijopatija u/ jew rabdomijoliżi, xi wħud ukoll b’ indeboliment akut tal- kliewi.
Patients with signs or symptoms of muscle toxicity should be managed as per standard medical practice.
Pazjenti li juru sinjali jew sintomi ta ’ tossiċita ’ muskolari għandhom ikunu trattati skond il- prattika medika standard.
13 Blood and lymphatic system disorders:
Disturbi tad- demm u tas- sistema limfatika: