1. Name Of The Medicinal Product
SUTENT®
SUTENT®
SUTENT®
SUTENT®
2. Qualitative And Quantitative Composition
SUTENT® 12.5 mg hard capsules
Each capsule contains sunitinib malate, equivalent to 12.5 mg of sunitinib.
SUTENT® 25 mg hard capsules
Each capsule contains sunitinib malate, equivalent to 25.0 mg of sunitinib
SUTENT® 37.5 mg hard capsules
Each capsule contains sunitinib malate, equivalent to 37.5 mg of sunitinib
SUTENT® 50 mg hard capsules
Each capsule contains sunitinib malate equivalent to 50 mg of sunitinib
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
SUTENT® 12.5 mg
Hard capsule
Gelatin capsules with orange cap and orange body, printed with white ink “Pfizer” on the cap, “STN 12.5 mg” on the body, and containing yellow to orange granules.
SUTENT® 25 mg
Hard Capsule
Gelatin capsule with caramel cap and orange body, printed with white ink “Pfizer” on the cap and “STN 25 mg ”on the body and containing yellow to orange granules.
SUTENT® 37.5 mg
Hard Capsule
Gelatin capsules with yellow cap and yellow body, printed with black ink “Pfizer” on the cap and “STN 37.5 mg” on the body and containing yellow to orange granules.
SUTENT® 50 mg
Hard capsule
Gelatin capsules 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.
4. Clinical Particulars
4.1 Therapeutic Indications
Gastrointestinal stromal tumour (GIST)
SUTENT is indicated for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) in adults after failure of imatinib mesilate treatment due to resistance or intolerance.
Metastatic renal cell carcinoma (MRCC)
SUTENT is indicated for the treatment of advanced/metastatic renal cell carcinoma (MRCC) in adults.
Pancreatic neuroendocrine tumours (pNET)
SUTENT is indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression in adults.
Experience with SUTENT as first-line treatment is limited (see section 5.1).
4.2 Posology And Method Of Administration
Therapy with sunitinib should be initiated by a physician experienced in the administration of anti-cancer agents.
For GIST and MRCC, the recommended dose of SUTENT is 50 mg taken orally once daily, for 4 consecutive weeks, followed by a 2-week rest period (Schedule 4/2) to comprise a complete cycle of 6 weeks.
For pNET, the recommended dose of SUTENT is 37.5 mg taken orally once daily without a scheduled rest period
Dose adjustments
Safety and tolerability
For GIST and MRCC, dose modifications in 12.5-mg steps may be applied based on individual safety and tolerability. Daily dose should not exceed 75 mg nor be decreased below 25 mg.
For pNET, dose modification in 12.5 mg steps may be applied based on individual safety and tolerability. The maximum dose administered in the Phase 3 pNET study was 50 mg daily.
Dose interruptions may be required based on individual safety and tolerability.
CYP3A4 inhibitors/inducers
Co-administration of SUTENT with potent CYP3A4 inducers such as rifampicin, should be avoided (see sections 4.4 and 4.5). If this is not possible, the dose of SUTENT may need to be increased in 12.5 mg steps (up to 87.5 mg per day for GIST and MRCC or 62.5 mg per day for pNET) based on careful monitoring of tolerability.
Co-administration of SUTENT with potent CYP3A4 inhibitors, such as ketoconazole, should be avoided (see sections 4.4 and 4.5). If this is not possible, the doses of SUTENT may need to be reduced to a minimum of 37.5 mg daily for GIST and MRCC or 25 mg daily for pNET, based on careful monitoring of the tolerability.
Selection of an alternative concomitant medicinal product with no, or minimal potential to induce or inhibit CYP3A4 should be considered.
Special populations
Paediatric population
The safety and efficacy of sunitinib in patients below 18 years of age have not been established.
No data are available.
There is no relevant use of Sutent in children from birth to less than 6 years in the indication of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesilate treatment due to resistance or intolerance. There is no relevant use of Sutent in the paediatric population in the indications treatment of advanced/metastatic renal cell carcinoma and treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression.
Use of SUTENT in this population is not recommended.
Elderly patients (
Approximately one third of the patients in clinical studies who received sunitinib were 65 or over. No significant differences in safety or effectiveness were observed between younger and older patients.
Hepatic Insufficiency
No starting dose adjustment is recommended when administering sunitinib to patients with mild or moderate (Child-Pugh Class A and B) hepatic impairment. Sunitinib has not been studied in subjects with severe (Child-Pugh Class C) hepatic impairment (see section 5.2).
Renal Insufficiency
No starting dose adjustment is required when administering SUTENT to patients with renal impairment (mild-severe) or with end-stage renal disease (ESRD) on hemodialysis. Subsequent dose adjustments should be based on individual safety and tolerability (see section 5.2).
Method of administration
SUTENT is for oral administration. It may be taken with or without food.
If a dose is missed the patient should not be given an additional dose. The patient should take the usual prescribed dose on the following day.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special Warnings And Precautions For Use
Co-administration with potent CYP3A4 inducers should be avoided because it may decrease sunitinib plasma concentration (see sections 4.2 and 4.5).
Co-administration with potent CYP3A4 inhibitors should be avoided because it may increase the plasma concentration of sunitinib (see sections 4.2 and 4.5).
Skin and tissues disorders
Skin discolouration, possibly due to the active substance colour (yellow) is a common adverse reaction occurring in approximately 30% of patients. Patients should be advised that depigmentation of the hair or skin may also occur during treatment with sunitinib. Other possible dermatologic effects may include dryness, thickness or cracking of the skin, blisters or occasional rash on the palms of the hands and soles of the feet.
Mouth pain/irritation was reported in approximately 14% of patients. The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation.
Haemorrhage and tumour bleeding
Haemorrhagic events, some of which were fatal, reported through post-marketing experience, have included gastro-intestinal, respiratory, tumour, urinary tract and brain haemorrhages. In clinical trials treatment-related tumour haemorrhage occurred in approximately 2% of patients with GIST. These events may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage. Fatal pulmonary haemorrhage occurred in 2 patients (~ 1.8%) receiving sunitinib on a phase 2 clinical trial of patients with metastatic non-small cell lung cancer (NSCLC). Both patients had squamous cell histology. SUTENT is not approved for use in patients with NSCLC.
Bleeding events occurred in 18% of patients receiving sunitinib in a phase 3 GIST Study compared to 17% of patients receiving placebo. In patients receiving sunitinib for treatment-naïve MRCC, 39% had bleeding events compared to 11% of patients receiving IFN- α. Eleven (3.1%) patients on sunitinib versus 1 (0.3%) of patients on IFN-α experienced Grade 3 or greater treatment-related bleeding events. Of patients receiving sunitinib for cytokine-refractory MRCC, 26% experienced bleeding. Bleeding events, excluding epistaxis, occurred in 19% of patients receiving sunitinib in the phase 3 pNET study compared to 4% of patients receiving placebo. Routine assessment of this event should include complete blood counts and physical examination.
Epistaxis was the most common haemorrhagic adverse reaction, having been reported for approximately half of the patients with solid tumours who experienced haemorrhagic events. Some of the epistaxis events were severe, but very rarely fatal.
Gastrointestinal disorders
Nausea, diarrhoea, stomatitis, dyspepsia and vomiting were the most commonly reported gastrointestinal adverse reactions (see section 4.8).
Supportive care for gastrointestinal adverse reactions requiring treatment may include medicinal products with an anti-emetic or anti-diarrhoeal properties.
Serious, sometimes fatal gastrointestinal complications including gastrointestinal perforation have occurred rarely in patients with intra-abdominal malignancies treated with sunitinib. Treatment-related fatal gastrointestinal bleeding occurred in 0.5% of patients receiving placebo in the GIST Phase 3 study.
Hypertension
Treatment-related hypertension was reported in approximately 16% of patients with solid tumours. The dose of sunitinib was reduced or its administration temporarily suspended in approximately 2.7% of the patients who experienced hypertension. In none of these patients sunitinib was permanently discontinued. Severe hypertension (>200 mmHg systolic or 110 mmHg diastolic) occurred in 4.7% of patients with solid tumours. Treatment-related hypertension was reported in approximately 30% of patients receiving sunitinib for treatment-naïve MRCC compared to 6% of patients receiving IFN-α. Severe hypertension occurred in 12% of treatment-naïve patients on sunitinib and 6% of patients on IFN-α. Treatment-related hypertension was reported in 23% of patients receiving sunitinib in a phase 3 pNET study, compared to 4% of patients receiving placebo. Severe hypertension occurred in 10% of pNET patients on sunitinib and 3% of patients on placebo. Patients should be screened for hypertension and controlled as appropriate. Temporary suspension is recommended in patients with severe hypertension that is not controlled with medical management. Treatment may be resumed once hypertension is appropriately controlled.
Haematological disorders
Decreased absolute neutrophil counts of grade 3 and 4 severity respectively were reported in 10% and 1.7% of patients on the phase 3 GIST study, in 16% and 1.6% of patients on the phase 3 MRCC study, and in 13% and 2.4% of patients on the phase 3 pNET study. Decreased platelet counts of grade 3 and 4 severity respectively were reported in 3.7% and 0.4% of patients on the phase 3 GIST study, in 8.2% and 1.1% of patients on the phase 3 MRCC study, and in 3.7% and 1.2% of patients on the phase 3 pNET study. The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation. None of these events in the phase 3 studies were fatal, but rare fatal haematological events have been reported through post-marketing experience.
Complete blood counts should be performed at the beginning of each treatment cycle for patients receiving treatment with sunitinib.
Cardiac disorders
Cardiovascular events, some of which were fatal, reported through post-marketing experience, have included left ventricular ejection fraction (LVEF) decreased and cardiac failure. In clinical trials, decreases in LVEF of
In GIST patients treatment-related 'cardiac failure', 'cardiac failure congestive' or 'left ventricular failure' were reported in 0.7% of patients treated with sunitinib and 1% of patients treated with placebo. In the pivotal phase 3 GIST study (n=312), treatment-related fatal cardiac reactions occurred in 1% of patients on each arm of the study (i.e. sunitinib and placebo arms). In a phase 2 study in cytokine-refractory MRCC patients, 0.9% of patients experienced treatment-related fatal myocardial infarction and in the phase 3 study in treatment-naïve MRCC patients, 0.6% of patients on the IFN-α arm and 0% patients on the sunitinib arm experienced fatal cardiac events. In the phase 3 pNET study, one (1%) patient who received sunitinib had treatment-related fatal cardiac failure. The relationship, if any, between receptor tyrosine kinase (RTK) inhibition and cardiac function remains unclear.
Patients who presented with cardiac events within 12 months prior to sunitinib administration, such as myocardial infarction (including severe/unstable angina), coronary/peripheral artery bypass graft, symptomatic CHF, cerebrovascular accident or transient ischemic attack, or pulmonary embolism were excluded from sunitinib clinical studies.
Close monitoring for clinical signs and symptoms of CHF should be performed, especially in patients with cardiac risk factors and/or history of coronary artery disease.
Physicians are advised to weigh this risk against the potential benefits of sunitinib. These patients should be carefully monitored for clinical signs and symptoms of CHF while receiving sunitinib. Baseline and periodic evaluations of LVEF should also be considered while the patient is receiving sunitinib. In patients without cardiac risk factors, a baseline evaluation of ejection fraction should be considered.
In the presence of clinical manifestations of CHF, discontinuation of sunitinib is recommended. The administration of sunitinib should be interrupted and/or the dose reduced in patients without clinical evidence of CHF but with an ejection fraction <50% and>20% below baseline.
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 repolarisation process (e.g. prolongation of QT interval).
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 tumour patients; both of these parameters are recognized as potentially significant changes. At approximately twice therapeutic concentrations, sunitinib has been shown to prolong the QTcF Inteval (Frederica's Correction).
QTc interval prolongation was investigated in a trial in 24 patients, ages 20-87 years, with advanced malignancies. The results of this study demonstrated that sunitinib had an effect on QTc interval (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. No patients had a QTc interval>500 msec. Although an effect on QTcF interval 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.
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 interval prolongation considered as “severe” (i.e. equal to or greater than Grade 3 by CTCAE version 3.0).
At therapeutic plasma concentrations, the maximum QTcF interval (Frederica's correction) mean change from baseline was 9.6 msec (90% CI 15.1msec). At approximately twice therapeutic concentrations, the maximum QTcF interval change from baseline was 15.4 msec (90% CI 22.4 msec). Moxifloxacin (400 mg) used as a positive control showed a 5.6 msec maximum mean QTcF interval change from baseline. No subjects experienced an effect on the QTc interval greater than Grade 2 (CTCAE version 3.0). No patient presented with a cardiac arrhythmia. QT interval prolongation may lead to an increased risk of ventricular arrhythmias including Torsade de pointes. Torsade de pointes has been observed in <0.1% of sunitinib-exposed patients. sunitinib 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. Concomitant administration of sunitinib with potent CYP3A4 inhibitors, should be limited because of the possible increase in sunitinib plasma concentrations, (see section 4.2 and 4.5).
Venous thromboembolic events
Treatment-related venous thromboembolic events were reported in approximately 1.0% of patients with solid tumours who received sunitinib on clinical trials, including GIST and MRCC.
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 thromboses (DVT), and two were Grade 1 or 2. Four of these seven GIST patients discontinued treatment following first observation of DVT.
Thirteen patients (3%) receiving sunitinib in the phase 3 for treatment-naïve MRCC study and four patients (2%) on the two cytokine-refractory MRCC studies had treatment-related venous thromboembolic events reported. Nine of these patients had pulmonary embolisms, one was Grade 2 and eight were Grade 4. Eight of these patients had DVT, one each with Grade 1, two with Grade 2, four with Grade 3 and one with Grade 4.
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 embolism, all with Grade 4.
No treatment-related venous thromboembolic events were reported for patients receiving sunitinib, and one Grade 2 DVT was reported for a patient receiving placebo in the phase 3 pNET study.
No cases with fatal outcome were reported in GIST and MRCC registrational studies. Cases with fatal out come have been observed in post-marketing setting (see pulmonary events and section 4.8).
Respiratory events
Patients who presented with pulmonary embolism within the previous 12 months were excluded from sunitinib clinical studies.
In patients who received sunitinib 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 and in 7.2% of patients with pNET.
Approximately 8% of patients with solid tumours, including GIST and MRCC, who received sunitinib in clinical trials experienced treatment-related pulmonary events.
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 sunitinib in Phase 3 studies (see section 4.4 - Venous thromboembolic events). No treatment-related pulmonary embolism was reported for patients with pNET who received sunitinib in the phase 3 study. Rare cases with fatal outcome have been observed in post-marketing setting (see section 4.8).
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. All patients should be observed closely for signs and symptoms of thyroid dysfunction on sunitinib treatment. 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.
Hypothyroidism was reported as an adverse event in 7 patients (4%) receiving sunitinib across the two cytokine-refractory MRCC studies; in nine patients (2%) on sunitinib and one patient (<1%) in the IFN-α arm in the treatment-naïve MRCC study. Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%). Overall, 7% of the MRCC population had either clinical or laboratory evidence of treatment-emergent hypothyroidism. Treatment-emergent acquired hypothyroidism was noted in 8 GIST patients (4%) on SUTENT versus 1 (1%) on placebo. In the phase 3 pNET study treatment-related hypothyroidism was reported in 5 patients (6%) receiving sunitinib and in one patient (1%) on placebo.
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
Pancreatitis
Increases in serum lipase and amylase activities were observed in patients with various solid tumours who received sunitinib. Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours. Pancreatitis has been observed uncommonly (<1%) in patients receiving sunitinib for GIST or MRCC.
Cases of serious pancreatic events, some with fatal outcome, have been reported. If symptoms of pancreatitis are present, patients should have sunitinib discontinued and be provided with appropriate supportive care.
No treatment-related pancreatitis was reported in the phase 3 pNET study.
Hepatic Function
Serious cases of sunitinib-related hepatobiliary events have been reported in patients with solid tumours; hepatic failure was observed in <1% of these patients. Cases of hepatobiliary events some with fatal outcome, have been reported. If signs or symptoms of hepatic failure are present, sunitinib should be discontinued and appropriate supportive care should be provided.
Renal function
The safety of continued sunitinib treatment in patients with moderate to severe proteinuria has not been systematically evaluated.
Cases of proteinuria and rare cases of nephrotic syndrome have been reported. Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. Discontinue sunitinib in patients with nephrotic syndrome.
Fistula
If fistula formation occurs, sunitinib treatment should be interrupted. Limited information is available on the continued use of sunitinib in patients with fistulae.
Hypersensitivity/Angioedema
If angioedema due to hypersensitivity occurs, sunitinib treatment should be interrupted and standard medical care provided.
Nervous system disorders
Taste disturbance
Dysgeusia was reported in approximately 28% of patients receiving sunitinib in clinical trials.
Seizures
In clinical studies of sunitinib and from post-marketing experience, seizures have been observed in subjects with or without radiological evidence of brain metastases. In addition, there have been few reports (<1%) of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (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. Temporary suspension of sunitinib is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Medicinal products that may increase sunitinib plasma concentrations.
In healthy volunteers, concomitant administration of a single dose of sunitinib with the potent CYP3A4 inhibitor ketoconazole resulted in an increase of the combined [sunitinib + primary metabolite] Cmax and AUC0- values of 49% and 51%, respectively.
Administration of sunitinib with potent CYP3A4 inhibitors (e.g. ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice) may increase sunitinib concentrations.
Combination with CYP3A4 inhibitors should therefore be avoided, or the selection of an alternate concomitant medicinal product with no, or minimal potential to inhibit CYP3A4 should be considered.
If this is not possible, the dose of SUTENT may need to be reduced to a minimum of 37.5 mg daily for GIST and MRCC or 25 mg daily for pNET, based on careful monitoring of tolerability (see section 4.2).
Medicinal products that may decrease sunitinib plasma concentrations:
In healthy volunteers, concomitant administration of a single dose of sunitinib with the CYP3A4 inducer rifampicin resulted in a reduction of the combined [sunitinib + primary metabolite] Cmax and AUC0- values of 23% and 46%, respectively.
Administration of sunitinib with potent CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or herbal preparations containing St. John's Wort/ Hypericum perforatum may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided, or selection of an alternate concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered. 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 for GIST and MRCC or 62.5 mg per day for pNET), based on careful monitoring of tolerability (see section 4.2).
Anticoagulants
Haemorrhage has been observed rarely in patients treated with sunitinib (see section 4.4 and 4.8). Patients receiving concomitant treatment with anti-coagulants (e.g. warfarin; acenocoumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/INR), and physical examination
4.6 Pregnancy And Lactation
Pregnancy
There are no studies in pregnant women using SUTENT. Studies in animals have shown reproductive toxicity including foetal malformations (see section 5.3). SUTENT should not be used during pregnancy or in any women not using effective contraception, unless the potential benefit justifies the potential risk to the foetus. If SUTENT is used during pregnancy or if the patient becomes pregnant while on treatment with SUTENT, the patient should be apprised of the potential hazard to the foetus.
Women of childbearing potential should be advised to use effective contraception and avoid becoming pregnant while receiving treatment with SUTENT.
Lactation
Sunitinib and/or its metabolites are excreted in rat milk. It is not known whether sunitinib or its primary active metabolite is excreted in human milk. Because active substances 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.
Fertility
Based on nonclinical findings, male and female fertility may be compromised by treatment with SUTENT (see section 5.3).
4.7 Effects On Ability To Drive And Use Machines
No studies on the effects on the ability to drive and use machines have been performed. Patients should be advised that they may experience dizziness during treatment with sunitinib.
4.8 Undesirable Effects
The most important serious adverse reactions associated with SUTENT in patients with solid tumours were pulmonary embolism (1%), thrombocytopoenia (1%), tumour haemorrhage (0.9%), febrile neutropoenia (0.4%), and hypertension (0.4%). The most common adverse reactions (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. Fatigue, hypertension and neutropoenia were the most common Grade 3 adverse reactions and increased lipase was the most frequent Grade 4 adverse reaction in patients with solid tumours. Hepatitis and hepatic failure occurred in <1% of patients and prolonged QT interval in < 0.1% (see section 4.4).
Fatal events other than those listed in section 4.4 above or in section 4.8 below that were considered possibly related to sunitinib 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.
Adverse reactions that were reported in>2% of GIST and MRCC patients and in>5% of pNET patients in the phase 3 study are listed below, by system organ class, frequency and grade of severity (NCI-CTCAE). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Frequencies are defined as: Very common (>1/10); common (
Table 1 - Adverse reactions reported in GIST studies with SUTENT
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