Sutent

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 12.5 mg hard capsules 

Sutent 25 mg hard capsules 

Sutent 37.5 mg hard capsules 

Sutent 50 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

12.5 mg hard capsules 

Each capsule contains sunitinib malate, equivalent to 12.5 mg of sunitinib. 

 

25 mg hard capsules 

Each capsule contains sunitinib malate, equivalent to 25 mg of sunitinib. 

 

37.5 mg hard capsules 

Each capsule contains sunitinib malate, equivalent to 37.5 mg of sunitinib. 

 

50 mg hard capsules 

Each capsule contains sunitinib malate, equivalent to 50 mg of sunitinib. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Hard capsule. 

 

Sutent 12.5 mg hard capsules 

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 capsules 

Gelatin capsules with caramel cap and orange body, printed with white ink “Pfizer” on the cap, 

“STN 25 mg” on the body, and containing yellow to orange granules. 

 

Sutent 37.5 mg hard capsules 

Gelatin capsules with yellow cap and yellow body, printed with black ink “Pfizer” on the cap, 

“STN 37.5 mg” on the body, and containing yellow to orange granules. 

 

Sutent 50 mg hard capsules 

Gelatin capsule with caramel cap and caramel body, printed with white ink “Pfizer” on the cap, 

“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 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. 

 



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Pancreatic neuroendocrine tumours (pNET) 

Sutent is indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic 

neuroendocrine tumours (pNET) with disease progression in adults.  

 

4.2 Posology and method of administration 
 

Therapy with Sutent should be initiated by a physician experienced in the administration of anticancer 

agents. 

 

Posology 

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 sunitinib 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 sunitinib 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 sunitinib with potent CYP3A4 inhibitors, such as ketoconazole, should be 

avoided (see sections 4.4 and 4.5). If this is not possible, the dose of sunitinib 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.  

 

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 Sutent in patients below 18 years of age have not been established. 

 

Currently available data are described in sections 4.8, 5.1, and 5.2 but no recommendation on a 

posology can be made. 

 

Elderly 

Approximately one-third of the patients in clinical studies who received sunitinib were 65 years of age 

or over. No significant differences in safety or efficacy were observed between younger and older 

patients. 

 



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Hepatic impairment 

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 and therefore its use in patients with severe 

hepatic impairment cannot be recommended (see section 5.2). 

 

Renal impairment 

No starting dose adjustment is required when administering sunitinib to patients with renal impairment 

(mild-severe) or with end-stage renal disease (ESRD) on haemodialysis. 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 listed in section 6.1. 

 

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 tissue disorders 

Patients should be advised that depigmentation of the hair or skin may occur during treatment with 

sunitinib. Other possible dermatological effects may include dryness, thickness or cracking of the skin, 

blisters, or rash on the palms of the hands and soles of the feet. 

 

The above reactions were not cumulative, were typically reversible, and generally did not result in 

treatment discontinuation. Cases of pyoderma gangrenosum, generally reversible after discontinuation 

of sunitinib, have been reported. Severe cutaneous reactions have been reported, including cases of 

erythema multiforme (EM), cases suggestive of Stevens-Johnson syndrome (SJS) and toxic epidermal 

necrolysis (TEN), some of which were fatal. If signs or symptoms of SJS, TEN, or EM 

(e.g., progressive skin rash often with blisters or mucosal lesions) are present, sunitinib treatment 

should be discontinued. If the diagnosis of SJS or TEN is confirmed, treatment must not be restarted. 

In some cases of suspected EM, patients tolerated the reintroduction of sunitinib therapy at a lower 

dose after resolution of the reaction; some of these patients also received concomitant treatment with 

corticosteroids or antihistamines (see section 4.8). 

 

Haemorrhage and tumour bleeding 

Haemorrhagic events, some of which were fatal, reported in clinical studies with sunitinib and during 

postmarketing surveillance have included gastrointestinal, respiratory, urinary tract, and brain 

haemorrhages (see section 4.8). 

 

Routine assessment of bleeding events 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. 

 



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Events of tumour haemorrhage, sometimes associated with tumour necrosis, have been reported; some 

of these haemorrhagic events were fatal. 

 

Tumour haemorrhage may occur suddenly, and in the case of pulmonary tumours, may present as 

severe and life-threatening haemoptysis or pulmonary haemorrhage. Cases of pulmonary 

haemorrhage, some with a fatal outcome, have been observed in clinical trials and have been reported 

in postmarketing experience in patients treated with sunitinib for MRCC, GIST, and lung cancer. 

Sutent is not approved for use in patients with lung cancer.  

 

Patients receiving concomitant treatment with anticoagulants (e.g., warfarin, acenocoumarole) may be 

periodically monitored by complete blood counts (platelets), coagulation factors (PT/INR), and 

physical examination. 

 

Gastrointestinal disorders 

Diarrhoea, nausea/vomiting, abdominal pain, dyspepsia, and stomatitis/oral pain were the most 

commonly reported gastrointestinal adverse reactions; oesophagitis events have been also reported 

(see section 4.8).  

 

Supportive care for gastrointestinal adverse reactions requiring treatment may include medicinal 

products with antiemetic, antidiarrhoeal, or antacid properties. 

 

Serious, sometimes fatal gastrointestinal complications including gastrointestinal perforation were 

reported in patients with intra-abdominal malignancies treated with sunitinib.  

 

Hypertension 

Hypertension has been reported in association with sunitinib, including severe hypertension 

(> 200 mmHg systolic or 110 mmHg diastolic). 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 (see section 4.8).  

 

Haematological disorders 

Decreased absolute neutrophil counts and decreased platelet counts were reported in association with 

sunitinib (see section 4.8). 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, including haemorrhage associated with thrombocytopenia 

and neutropenic infections, have been reported during postmarketing surveillance. 

 

Anaemia has been observed to occur early as well as late during treatment with sunitinib. 

 

Complete blood counts should be performed at the beginning of each treatment cycle for patients 

receiving treatment with sunitinib (see section 4.8). 

 

Cardiac disorders 

Cardiovascular events, including heart failure, cardiomyopathy, left ventricular ejection fraction 

decline to below the lower limit of normal, myocarditis, myocardial ischaemia and myocardial 

infarction, some of which were fatal, have been reported in patients treated with sunitinib. These data 

suggest that sunitinib increases the risk of cardiomyopathy. No specific additional risk factors for 

sunitinib-induced cardiomyopathy apart from the drug-specific effect have been identified in the 

treated patients. Use sunitinib with caution in patients who are at risk for, or who have a history of, 

these events (see section 4.8). 

 

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 congestive heart failure (CHF), cerebrovascular accident or transient ischaemic attack, or 

pulmonary embolism were excluded from all sunitinib clinical studies. It is unknown whether patients 



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with these concomitant conditions may be at a higher risk of developing sunitinib-related left 

ventricular dysfunction. 

 

Physicians are advised to weigh this risk against the potential benefits of sunitinib. Patients should be 

carefully monitored for clinical signs and symptoms of CHF while receiving sunitinib especially 

patients with cardiac risk factors and/or history of coronary artery disease. 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 

Prolongation of QT interval and Torsade de pointes have been observed in sunitinib-exposed patients. 

QT interval prolongation may lead to an increased risk of ventricular arrhythmias including 

Torsade de pointes.  

 

Sunitinib should be used with caution in patients with a known history of QT interval prolongation, 

patients who are taking antiarrhythmics or medicinal products that can prolong QT interval, 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 sections 4.2, 4.5 and 4.8). 

 

Venous thromboembolic events 

Treatment-related venous thromboembolic events were reported in patients who received sunitinib 

including deep venous thrombosis and pulmonary embolism (see section 4.8). Cases of pulmonary 

embolism with fatal outcome have been observed in postmarketing surveillance.  

 

Arterial thromboembolic events 

Cases of arterial thromboembolic events (ATE), sometimes fatal, have been reported in patients 

treated with sunitinib. The most frequent events included cerebrovascular accident, transient ischaemic 

attack, and cerebral infarction. Risk factors associated with ATE, in addition to the underlying 

malignant disease and age  65 years, included hypertension, diabetes mellitus, and prior 

thromboembolic disease. 

 

Aneurysms and artery dissections 

The use of vascular endothelial growth factor (VEGF) pathway inhibitors in patients with or without 

hypertension may promote the formation of aneurysms and/or artery dissections. Before initiating 

sunitinib, this risk should be carefully considered in patients with risk factors such as hypertension or 

history of aneurysm. 

 

Thrombotic microangiopathy (TMA) 

The diagnosis of TMA, including thrombotic thrombocytopaenic purpura (TTP) and haemolytic 

uraemic syndrome (HUS), sometimes leading to renal failure or a fatal outcome, should be considered 

in the occurrence of haemolytic anaemia, thrombocytopenia, fatigue, fluctuating neurological 

manifestation, renal impairment, and fever. Sunitinib therapy should be discontinued in patients who 

develop TMA and prompt treatment is required. Reversal of the effects of TMA has been observed 

after treatment discontinuation (see section 4.8). 

 

Thyroid dysfunction  

Baseline laboratory measurement of thyroid function is recommended in all patients. Patients with 

pre-existing hypothyroidism or hyperthyroidism should be treated as per standard medical practice 

prior to the start of sunitinib treatment. During sunitinib treatment, routine monitoring of thyroid 

function should be performed every 3 months. In addition, patients should be observed closely for 

signs and symptoms of thyroid dysfunction during treatment, and patients who develop any signs 

and/or symptoms suggestive of thyroid dysfunction should have laboratory testing of thyroid function 



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performed as clinically indicated. Patients who develop thyroid dysfunction should be treated as per 

standard medical practice. 

 

Hypothyroidism has been observed to occur early as well as late during treatment with sunitinib (see 

section 4.8). 

 

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 (see section 

4.8).  

 

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. 

 

Hepatotoxicity 

Hepatotoxicity has been observed in patients treated with sunitinib. Cases of hepatic failure, some with 

a fatal outcome, were observed in < 1% of solid tumour patients treated with sunitinib. Monitor liver 

function tests (alanine transaminase [ALT], aspartate transaminase [AST], bilirubin levels) before 

initiation of treatment, during each cycle of treatment, and as clinically indicated. If signs or symptoms 

of hepatic failure are present, sunitinib should be discontinued and appropriate supportive care should 

be provided (see section 4.8).  

 

Renal function 

Cases of renal impairment, renal failure and/or acute renal failure, in some cases with fatal outcome, 

have been reported (see section 4.8). 

 

Risk factors associated with renal impairment/failure in patients receiving sunitinib included, in 

addition to underlying RCC, older age, diabetes mellitus, underlying renal impairment, cardiac failure, 

hypertension, sepsis, dehydration/hypovolaemia, and rhabdomyolysis. 

 

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 (see section 4.8). 

 

Impaired wound healing 

Cases of impaired wound healing have been reported during sunitinib therapy. 

 

No formal clinical studies of the effect of sunitinib on wound healing have been conducted. 

Temporary interruption of sunitinib therapy is recommended for precautionary reasons in patients 

undergoing major surgical procedures. There is limited clinical experience regarding the timing of 

reinitiation of therapy following major surgical intervention. Therefore, the decision to resume 

sunitinib therapy following a major surgical intervention should be based upon clinical judgment of 

recovery from surgery. 

 

Osteonecrosis of the jaw (ONJ) 

Cases of ONJ have been reported in patients treated with Sutent. The majority of cases were reported 

in patients who had received prior or concomitant treatment with intravenous bisphosphonates, for 



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which ONJ is an identified risk. Caution should therefore be exercised when Sutent and intravenous 

bisphosphonates are used either simultaneously or sequentially. 

 

Invasive dental procedures are also an identified risk factor. Prior to treatment with Sutent, a dental 

examination and appropriate preventive dentistry should be considered. In patients who have 

previously received or are receiving intravenous bisphosphonates, invasive dental procedures should 

be avoided if possible (see section 4.8). 

 

Hypersensitivity/angioedema 

If angioedema due to hypersensitivity occurs, sunitinib treatment should be interrupted and standard 

medical care provided (see section 4.8). 

 

Seizures 

In clinical studies of sunitinib and from postmarketing surveillance, seizures have been reported. 

Patients with seizures and signs/symptoms consistent with posterior reversible leukoencephalopathy 

syndrome (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 (see section 4.8). 

 

Tumour lysis syndrome (TLS) 

Cases of TLS, some fatal, have been rarely observed in clinical trials and have been reported in 

postmarketing surveillance in patients treated with sunitinib. Risk factors for TLS include high tumour 

burden, pre-existing chronic renal insufficiency, oliguria, dehydration, hypotension, and acidic urine. 

These patients should be monitored closely and treated as clinically indicated, and prophylactic 

hydration should be considered. 

 

Infections 

Serious infections, with or without neutropenia, including some with a fatal outcome, have been 

reported. Uncommon cases of necrotising fasciitis, including of the perineum, sometimes fatal, have 

been reported (see section 4.8).  

 

Sunitinib therapy should be discontinued in patients who develop necrotising fasciitis, and appropriate 

treatment should be promptly initiated. 

 

Hypoglycaemia 

Decreases in blood glucose, in some cases clinically symptomatic and requiring hospitalisation due to 

loss of consciousness, have been reported during sunitinib treatment. In case of symptomatic 

hypoglycaemia, sunitinib should be temporarily interrupted. Blood glucose levels in diabetic patients 

should be checked regularly in order to assess if antidiabetic medicinal product’s dosage needs to be 

adjusted to minimise the risk of hypoglycaemia (see section 4.8). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Interaction studies have only been performed in adults. 

 

Medicinal products that may increase sunitinib plasma concentrations 

Effect of CYP3A4 inhibitors 

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] maximum concentration (Cmax) and area under the curve (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. 

 



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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). 

 

Effect of Breast Cancer Resistance Protein (BCRP) inhibitors 

Limited clinical data are available on the interaction between sunitinib and BCRP inhibitors and the 

possibility of an interaction between sunitinib and other BCRP inhibitors cannot be excluded (see 

section 5.2). 

 

Medicinal products that may decrease sunitinib plasma concentrations 

Effect of CYP3A4 inducers 

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 dose 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). 

 

4.6 Fertility, pregnancy and lactation 

 

Contraception in males and females 

Women of childbearing potential should be advised to use effective contraception and avoid becoming 

pregnant while receiving treatment with Sutent. 

 

Pregnancy  

There are no studies in pregnant women using sunitinib. Studies in animals have shown reproductive 

toxicity including foetal malformations (see section 5.3). Sutent should not be used during pregnancy 

or in 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. 

 

Breast-feeding 

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 breast-feeding 

infants, women should not breast-feed while taking Sutent. 

 

Fertility 

Based on nonclinical findings, male and female fertility may be compromised by treatment with 

sunitinib (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

Sutent has minor influence on the ability to drive and use machines. Patients should be advised that 

they may experience dizziness during treatment with sunitinib. 

 



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4.8 Undesirable effects 

 

Summary of the safety profile 
The most serious adverse reactions associated with sunitinib, some fatal, are renal failure, heart failure, 

pulmonary embolism, gastrointestinal perforation, and haemorrhages (e.g., respiratory tract, 

gastrointestinal, tumour, urinary tract, and brain haemorrhages). The most common adverse reactions 

of any grade (experienced by patients in RCC, GIST, and pNET registrational trials) included 

decreased appetite, taste disturbance, hypertension, fatigue, gastrointestinal disorders (i.e. diarrhoea, 

nausea, stomatitis, dyspepsia, and vomiting), skin discolouration, and palmar-plantar 

erythrodysaesthesia syndrome. These symptoms may diminish as treatment continues. 

Hypothyroidism may develop during treatment. Haematological disorders (e.g., neutropenia, 

thrombocytopenia, and anaemia) are amongst the most common adverse drug reactions. 

 

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, adrenal insufficiency, pneumothorax, shock, and sudden death. 

 

Tabulated list of adverse reactions 

Adverse reactions that were reported in GIST, MRCC, and pNET patients in a pooled dataset of 

7,115 patients are listed below, by system organ class, frequency and grade of severity (NCI-CTCAE). 

Post-marketing adverse reactions identified in clinical studies are also included. Within each 

frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

Frequencies are defined as: 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), not known (cannot be estimated from 

the available data). 

 

Table 1. Adverse reactions reported in clinical trials  
System organ class Very common 

 

Common 

 

Uncommon 

 

Rare 

 

Not known 

Infections and 

infestations 

 Viral infectionsa  

Respiratory 

infectionsb,*  

Abscessc,*  

Fungal infectionsd  

Urinary tract infection  

Skin infectionse  

Sepsisf,*  

Necrotising 

fasciitis* 

Bacterial infectionsg 

  

Blood and 

lymphatic system 

disorders  

Neutropoenia  

Thrombocytopoenia 

Anaemia  

Leukopoenia  

Lymphopoenia  Pancytopenia Thrombotic 

microangiopathyh,* 

 

Immune system 

disorders 

  Hypersensitivity Angioedema   

Endocrine 

disorders 

Hypothyroidism   Hyperthyroidism Thyroiditis    

Metabolism and 

nutrition disorders 

Decreased appetitei  Dehydration 

Hypoglycaemia  

 Tumour lysis 

syndrome*  

 

Psychiatric 

disorders 

Insomnia  Depression     

Nervous system 

disorders 

Dizziness  

Headache  

Taste disturbancej  

Neuropathy peripheral  

Paraesthesia  

Hypoaesthesia  

Hyperaesthesia  

Cerebral 

haemorrhage* 

Cerebrovascular 

accident* 

Transient ischaemic 

attack 

Posterior reversible 

encephalopathy 

syndrome*  

 

Eye disorders  Periorbital oedema  

Eyelid oedema  

Lacrimation increased  

   



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System organ class Very common 

 

Common 

 

Uncommon 

 

Rare 

 

Not known 

Cardiac disorders  Myocardial 

ischemiak,*  

Ejection fraction 

decreasedl  

Cardiac failure 

congestive 

Myocardial 

infarctionm,* 

Cardiac failure* 

Cardiomyopathy* 

Pericardial effusion 

Electrocardiogram 

QT prolonged  

Left ventricular 

failure*  

Torsade de pointes  

 

Vascular disorders Hypertension  Deep vein thrombosis  

Hot flush 

Flushing  

Tumour 

haemorrhage* 

 Aneurysms 

and artery 

dissections* 

Respiratory, 

thoracic and 

mediastinal 

disorders 

Dyspnoea  

Epistaxis  

Cough  

Pulmonary embolism*  

Pleural effusion*  

Haemoptysis  

Dyspnoea exertional  

Oropharyngeal painn  

Nasal congestion  

Nasal dryness  

Pulmonary 

haemorrhage* 

Respiratory failure* 

  

Gastrointestinal 

disorders 

Stomatitiso  

Abdominal painp  

Vomiting  

Diarrhoea  

Dyspepsia  

Nausea  

Constipation  

Gastro-oesophageal 

reflux disease  

Dysphagia  

Gastrointestinal 

haemorrhage*  

Oesophagitis*  

Abdominal distension  

Abdominal discomfort  

Rectal haemorrhage  

Gingival bleeding  

Mouth ulceration  

Proctalgia  

Cheilitis  

Haemorrhoids  

Glossodynia 

Oral pain  

Dry mouth  

Flatulence  

Oral discomfort  

Eructation  

Gastrointestinal 

perforationq,* 

Pancreatitis 

Anal fistula 

Colitisr 

 

  

Hepatobiliary 

disorders 

  Hepatic failure* 

Cholecystitiss,* 

Hepatic function 

abnormal 

Hepatitis  

Skin and 

subcutaneous 

tissue disorders 

Skin discolourationt  

Palmar-plantar 

erythrodysaesthesia 

syndrome  

Rashu 

Hair colour changes  

Dry skin  

Skin exfoliation  

Skin reactionv  

Eczema  

Blister  

Erythema  

Alopecia  

Acne 

Pruritus  

Skin 

hyperpigmentation 

Skin lesion  

Hyperkeratosis  

Dermatitis  

Nail disorderw  

 Erythema 

multiforme* 

Stevens-Johnson 

syndrome*  

Pyoderma 

gangrenosum  

Toxic epidermal 

necrolysis*  

 

Musculoskeletal 

and connective 

tissue disorders 

Pain in extremity  

Arthralgia  

Back pain  

Musculoskeletal pain  

Muscle spasms  

Myalgia  

Muscular weakness  

Osteonecrosis of the 

jaw 

Fistula* 

Rhabdomyolysis*  

Myopathy  

 

Renal and urinary 

disorders 

 Renal failure*  

Renal failure acute*  

Chromaturia 

Proteinuria  

Haemorrhage 

urinary tract 

Nephrotic syndrome   



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System organ class Very common 

 

Common 

 

Uncommon 

 

Rare 

 

Not known 

General disorders 

and administration 

site conditions 

Mucosal inflammation  

Fatiguex  

Oedemay  

Pyrexia  

Chest pain  

Pain  

Influenza like illness 

Chills   

Impaired healing   

Investigations  Weight decreased  

White blood cell count 

decreased  

Lipase increased  

Platelet count 

decreased  

Haemoglobin 

decreased  

Amylase increasedz  

Aspartate 

aminotransferase 

increased  

Alanine 

aminotransferase 

increased  

Blood creatinine 

increased  

Blood pressure 

increased  

Blood uric acid 

increased  

Blood creatine 

phosphokinase 

increased 

Blood thyroid 

stimulating 

hormone increased 

  

* Including fatal events.  

The following terms have been combined:   
a  Nasopharyngitis and oral herpes. 
b Bronchitis, lower respiratory tract infection, pneumonia, and respiratory tract infection. 
c Abscess, abscess limb, anal abscess, gingival abscess, liver abscess, pancreatic abscess, perineal abscess, perirectal 

abscess, rectal abscess, subcutaneous abscess, and tooth abscess. 
d Oesophageal candidiasis and oral candidiasis. 
e Cellulitis and skin infection. 
f Sepsis and sepsis shock. 
g Abdominal abscess, abdominal sepsis, diverticulitis, and osteomyelitis. 
h Thrombotic microangiopathy, thrombotic thrombocytopenic purpura, and haemolytic uraemic syndrome. 
i Decreased appetite and anorexia 
j Dysgeusia, ageusia, and taste disturbance. 
k Acute coronary syndrome, angina pectoris, angina unstable, coronary artery occlusion, and myocardial ischaemia.  
l Ejection fraction decreased/abnormal. 
m Acute myocardial infarction, myocardial infarction, and silent myocardial infarction. 
n Oropharyngeal and pharyngolaryngeal pain.  
o Stomatitis and aphtous stomatitis. 
p Abdominal pain, abdominal pain lower, and abdominal pain upper. 
q Gastrointestinal perforation and intestinal perforation. 
r Colitis and colitis ischaemic. 
s Cholecystitis and acalculous cholecystitis. 
t Yellow skin, skin discolouration, and pigmentation disorder. 
u Dermatitis psoriasiform, exfoliative rash, rash, rash erythematous, rash follicular, rash generalised, rash macular, rash 

maculo-papular, rash papular, and rash pruritic. 
v Skin reaction and skin disorder. 
w Nail disorder and discolouration. 
x Fatigue and asthenia. 
y Face oedema, oedema, and oedema peripheral. 
z Amylase and amylase increased. 

 

Description of selected adverse reactions 

 

Infections and infestations 

Cases of serious infection (with or without neutropenia), including cases with fatal outcome, have 

been reported. Cases of necrotising fasciitis, including of the perineum, sometimes fatal, have been 

reported (see also section 4.4). 

 



13 

Blood and lymphatic system disorders 

Decreased absolute neutrophil counts of Grade 3 and 4 severities, 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 severities, 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 (see section 4.4). 

 

Bleeding events were reported in 18% of patients receiving sunitinib in a Phase 3 GIST study vs 17% 

of patients receiving placebo. In patients receiving sunitinib for treatment-naïve MRCC, 39% had 

bleeding events vs 11% of patients receiving interferon- (IFN-α). Seventeen (4.5%) patients on 

sunitinib versus 5 (1.7%) patients on IFN-α experienced Grade 3 or greater bleeding events. Of 

patients receiving sunitinib for cytokine-refractory MRCC, 26% experienced bleeding. Bleeding 

events, excluding epistaxis, were reported in 21.7% of patients receiving sunitinib in the Phase 3 

pNET study compared to 9.85% of patients receiving placebo (see section 4.4) 

 

In clinical trials, tumour haemorrhage was reported in approximately 2% of patients with GIST. 

 

Immune system disorders 

Hypersensitivity reactions, including angioedema, have been reported (see section 4.4). 

 

Endocrine disorders 

Hypothyroidism was reported as an adverse reaction in 7 patients (4%) receiving sunitinib across the 

2 cytokine-refractory MRCC studies; in 61 patients (16%) on sunitinib and 3 patients (< 1%) in the 

IFN- arm in the treatment-naïve MRCC study.  

 

Additionally, thyroid-stimulating hormone (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. Acquired hypothyroidism was noted in 6.2% of GIST patients 

on sunitinib versus 1% on placebo. In the Phase 3 pNET study hypothyroidism was reported in 

6 patients (7.2%) receiving sunitinib and in 1 patient (1.2%) on placebo. 

 

Thyroid function was monitored prospectively in 2 studies in patients with breast cancer; Sutent is not 

approved for use in breast cancer. In 1 study, hypothyroidism was reported in 15 (13.6%) patients on 

sunitinib and 3 (2.9%) patients on standard of care. Blood TSH increase was reported in 1 (0.9%) 

patient on sunitinib and no patients on standard of care. Hyperthyroidism was reported in no 

sunitinib-treated patients and 1 (1.0%) patient receiving standard of care. In the other study 

hypothyroidism was reported in a total of 31 (13%) patients on sunitinib and 2 (0.8%) patients on 

capecitabine. Blood TSH increase was reported in 12 (5.0%) patients on sunitinib and no patients on 

capecitabine. Hyperthyroidism was reported in 4 (1.7%) patients on sunitinib and no patients on 

capecitabine. Blood TSH decrease was reported in 3 (1.3%) patients on sunitinib and no patients on 

capecitabine. T4 increase was reported in 2 (0.8%) patients on sunitinib and 1 (0.4%) patient on 

capecitabine. T3 increase was reported in 1 (0.8%) patient on sunitinib and no patients on 

capecitabine. All thyroid-related events reported were Grade 1-2 (see section 4.4). 

 

Metabolism and nutrition disorders 

A higher incidence rate of hypoglycaemia events was reported in patients with pNET in comparison to 

MRCC and GIST. Nevertheless, most of these adverse events observed in clinical studies were not 

considered related to study treatment (see section 4.4). 

 

Nervous system disorders 

In clinical studies of sunitinib and from postmarketing surveillance, there have been few reports 

(< 1%), some fatal, of subjects presenting with seizures and radiological evidence of RPLS. Seizures 

have been observed in patients with or without radiological evidence of brain metastases (see section 

4.4). 

 



14 

Cardiac disorders 

In clinical trials, decreases in left ventricular ejection fraction (LVEF) of  20% and below the lower 

limit of normal were reported in approximately 2% of sunitinib-treated GIST patients, 4% of 

cytokine-refractory MRCC patients, and 2% of placebo-treated GIST patients. These LVEF declines 

do not appear to have been progressive and often improved as treatment continued. In the 

treatment-naïve MRCC study, 27% of patients on sunitinib and 15% of patients on IFN- had an 

LVEF value below the lower limit of normal. Two patients (< 1%) who received sunitinib were 

diagnosed with CHF.  

 

In GIST patients ‘cardiac failure’, ‘cardiac failure congestive’, or ‘left ventricular failure’ were 

reported in 1.2% 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 were reported 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- 

arm and 0% of patients on the sunitinib arm experienced fatal cardiac events. In the Phase 3 pNET 

study, 1 (1%) patient who received sunitinib had treatment-related fatal cardiac failure.  

 

Vascular disorders  

Hypertension 

Hypertension was a very common adverse reaction reported in clinical trials. The dose of sunitinib 

was reduced or its administration temporarily suspended in approximately 2.7% of the patients who 

experienced hypertension. Sunitinib was not permanently discontinued in any of these patients. Severe 

hypertension (> 200 mmHg systolic or 110 mmHg diastolic) was reported in 4.7% of patients with 

solid tumours. Hypertension was reported in approximately 33.9% of patients receiving sunitinib for 

treatment-naïve MRCC compared to 3.6% of patients receiving IFN-. Severe hypertension was 

reported in 12% of treatment-naïve patients on sunitinib and < 1% of patients on IFN-. Hypertension 

was reported in 26.5% of patients receiving sunitinib in a Phase 3 pNET study, compared to 4.9% of 

patients receiving placebo. Severe hypertension was reported in 10% of pNET patients on sunitinib 

and 3% of patients on placebo. 

 

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 RCC. 

 

Seven patients (3%) on sunitinib and none on placebo in a Phase 3 GIST study experienced venous 

thromboembolic events; 5 of the 7 were Grade 3 deep venous thrombosis (DVT) and 2 were Grade 1 

or 2. Four of these 7 GIST patients discontinued treatment following first observation of DVT. 

 

Thirteen patients (3%) receiving sunitinib in the Phase 3 treatment-naïve MRCC study and 4 patients 

(2%) on the 2 cytokine-refractory MRCC studies had venous thromboembolic events reported. Nine of 

these patients had pulmonary embolisms; 1 was Grade 2 and 8 were Grade 4. Eight of these patients 

had DVT; 1 with Grade 1, 2 with Grade 2, 4 with Grade 3, and 1 with Grade 4. One patient with 

pulmonary embolism in the cytokine-refractory MRCC study experienced dose interruption. 

 

In treatment-naïve MRCC patients receiving IFN-, 6 (2%) venous thromboembolic events were 

reported; 1 patient (< 1%) experienced a Grade 3 DVT and 5 patients (1%) had pulmonary embolisms, 

all with Grade 4. 

 

Venous thromboembolic events were reported for 1 (1.2%) patient in the sunitinib arm and 5 (6.1%) 

patients in the placebo arm in the Phase 3 pNET study. Two of these patients on placebo had DVT, 

1 with Grade 2 and 1 with Grade 3. 

 

No cases with fatal outcome were reported in GIST, MRCC, and pNET registrational studies. Cases 

with fatal outcome have been observed in the postmarketing surveillance. 

 



15 

Cases of pulmonary embolism were observed in approximately 3.1% of patients with GIST and in 

approximately 1.2% of patients with MRCC, who received sunitinib in Phase 3 studies. No 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 the postmarketing surveillance. 

 

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, pulmonary events (i.e. dyspnoea, 

pleural effusion, pulmonary embolism, or pulmonary oedema) were reported in approximately 17.8% 

of patients with GIST, in approximately 26.7% of patients with MRCC and in 12% of patients with 

pNET. 

 

Approximately 22.2% of patients with solid tumours, including GIST and MRCC, who received 

sunitinib in clinical trials experienced pulmonary events. 

 

Gastrointestinal disorders 

Pancreatitis has been observed uncommonly (< 1%) in patients receiving sunitinib for GIST or 

MRCC. No treatment-related pancreatitis was reported in the Phase 3 pNET study (see section 4.4). 

 

Fatal gastrointestinal bleeding was reported in 0.98% of patients receiving placebo in the GIST Phase 

3 study. 

 

Hepatobiliary disorders 

Hepatic dysfunction has been reported and may include Liver Function Test abnormalities, hepatitis, 

or liver failure (see section 4.4).  

 

Skin and subcutaneous tissue disorders 

Cases of pyoderma gangrenosum, generally reversible after discontinuation of sunitinib, have been 

reported (see also section 4.4). 

 

Musculoskeletal and connective tissue disorders 

Cases of myopathy and/or rhabdomyolysis, some with acute renal failure, have been reported. Patients 

with signs or symptoms of muscle toxicity should be managed as per standard medical practice (see 

section 4.4). 

 

Cases of fistula formation, sometimes associated with tumour necrosis and regression, in some cases 

with fatal outcomes, have been reported (see section 4.4). 

 

Cases of ONJ have been reported in patients treated with Sutent, most of which occurred in patients 

who had identified risk factors for ONJ, in particular, exposure to intravenous bisphosphonates and/or 

a history of dental disease requiring invasive dental procedures (see also section 4.4). 

 

Investigations 

Data from non clinical (in vitro and in vivo) studies, at doses higher than the recommended human 

dose, indicated 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 were reported in 0.5%, and changes from baseline in 

excess of 60 msec were reported in 1.1% of the 450 solid tumour patients; both of these parameters are 

recognised as potentially significant changes. At approximately twice therapeutic concentrations, 

sunitinib has been shown to prolong the QTcF interval (Fridericia corrected QT interval). 

 

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% confidence interval [CI] upper 

limit > 15 msec) at therapeutic concentration (Day 3) using the within-day baseline correction method, 



16 

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 postdose (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 intent-to-treat (ITT) populations 

were observed to develop QTc interval prolongation considered as “severe” (i.e. equal to or greater 

than Grade 3 by Common Terminology Criteria for Adverse Events [CTCAE] version 3.0).  

 

At therapeutic plasma concentrations, the maximum QTcF interval (Frederica’s correction) mean 

change from baseline was 9 msec (90% CI: 15.1 msec). 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) (see section 4.4). 

 

Long-term safety in MRCC 

The long-term safety of sunitinib in patients with MRCC was analysed across 9 completed clinical 

studies conducted in the first-line, bevacizumab-refractory, and cytokine-refractory treatment settings 

in 5,739 patients, of whom 807 (14%) were treated for ≥ 2 years up to 6 years. In the 807 patients who 

received long-term sunitinib treatment, most treatment-related adverse events (TRAEs) occurred 

initially in the first 6 months–1 year and then were stable or decreased in frequency over time, with the 

exception of hypothyroidism, which gradually increased over time, with new cases occurring over the 

6 year period. Prolonged treatment with sunitinib did not appear to be associated with new types of 

TRAEs. 

 

Paediatric population 

The safety profile of sunitinib has been derived from a Phase 1 dose-escalation study, a Phase 2 

open-label study, a Phase 1/2 single-arm study and from publications as described below. 

 

A Phase 1 dose-escalation study of oral sunitinib was conducted in 35 patients comprised of 

30 paediatric patients (aged 3 years to 17 years) and 5 young adult patients (aged 18 to 21 years), with 

refractory solid tumours, the majority of whom had a primary diagnosis of brain tumour. All study 

participants experienced adverse drug reactions; most of these were severe (toxicity grade ≥ 3) and 

included cardiac toxicity. The most common adverse drug reactions were gastrointestinal (GI) toxicity, 

neutropenia, fatigue, and ALT elevation. The risk of cardiac adverse drug reactions appeared to be 

higher in paediatric patients with previous exposure to cardiac irradiation or anthracycline compared 

to those paediatric patients without previous exposure. In these paediatric patients without previous 

exposure to anthracyclines or cardiac irradiation, the maximum tolerated dose (MTD) has been 

identified (see section 5.1). 

 

A phase 2 open-label study was conducted in 29 patients comprised of 27 paediatric patients (aged 

3 years to 16 years) and 2 young adult patients (aged 18 years to 19 years) with 

recurrent/progressive/refractory high grade glioma (HGG) or ependymoma. There were no Grade 5 

adverse reactions in either group. The most common (≥10%) treatment-related adverse events were 

neutrophil count decreased (6 [20.7%] patients) and haemorrhage intracranial (3[10.3%] patients). 

 

A Phase 1/2 single-arm, study was conducted in 6 paediatric patients (aged 13 years to 16 years) with 

advanced unresectable GIST. The most frequent adverse drug reactions were diarrhoea, nausea, WBC 

count decreased, neutropenia, and headache in 3 (50.0%) patients each, primarily Grade 1 or 2 in 

severity. Four out of 6 patients (66.7%) experienced Grade 3-4 treatment-related adverse events 

(Grade 3 hypophosphataemia, neutropenia, and thrombocytopenia in 1 patient each and a Grade 4 

neutropenia in 1 patient). There were no serious adverse events (SAEs) or Grade 5 adverse drug 

reactions reported in this study. In both the clinical study and the publications, the safety profile was 

consistent with the known safety profile in adults.  



17 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting 

system listed in Appendix V. 

4.9 Overdose 

There is no specific antidote for overdose with Sutent and treatment of overdose should consist of 

general supportive measures. If indicated, elimination of unabsorbed active substance may be achieved 

by emesis or gastric lavage. Cases of overdose have been reported; some cases were associated with 

adverse reactions consistent with the known safety profile of sunitinib. 

5. PHARMACOLOGICAL PROPERTIES

5.1  Pharmacodynamic properties 

Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors; ATC code: L01XE04 

Mechanism of action 

Sunitinib inhibits multiple RTKs that are implicated in tumour growth, neoangiogenesis, and 

metastatic progression of cancer. Sunitinib was identified as an inhibitor of platelet-derived growth 

factor receptors (PDGFRα and PDGFRβ), VEGF receptors (VEGFR1, VEGFR2, and VEGFR3), stem 

cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor 

(CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). The primary metabolite 

exhibits similar potency compared to sunitinib in biochemical and cellular assays.

Clinical efficacy and safety 

The clinical safety and efficacy of sunitinib has been studied in the treatment of patients with 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), the treatment of patients with MRCC, 

and the treatment of patients with unresectable pNET.  

Efficacy is based on time-to-tumour progression (TTP) and an increase in survival in GIST, on 

progression-free survival (PFS) and objective response rates (ORR) for treatment-naïve and 

cytokine-refractory MRCC respectively, and on PFS for pNET. 

Gastrointestinal stromal tumours  

An initial open-label, dose-escalation study was conducted in patients with GIST after failure of 

imatinib (median maximum daily dose 800 mg) due to resistance or intolerance. Ninety-seven patients 

were enrolled at various doses and schedules; 55 patients received 50 mg at the recommended 

treatment Schedule 4 weeks on /2 weeks off (“Schedule 4/2”). 

In this study, the median TTP was 34.0 weeks (95% CI: 22.0, 46.0). 

A Phase 3, randomised, double-blind, placebo-controlled study of sunitinib was conducted in patients 

with GIST who were intolerant to, or had experienced disease progression during or following 

treatment with imatinib (median maximum daily dose 800 mg). In this study, 312 patients were 

randomised (2:1) to receive either 50 mg sunitinib or placebo, orally once daily on Schedule 4/2 until 

disease progression or withdrawal from the study for another reason (207 patients received sunitinib 

and 105 patients received placebo). The primary efficacy endpoint of the study was TTP, defined as 

the time from randomisation to first documentation of objective tumour progression. At the time of the 

prespecified interim analysis, the median TTP on sunitinib was 28.9 weeks (95% CI: 21.3, 34.1) as 

assessed by the investigator and 27.3 weeks (95% CI: 16.0, 32.1) as assessed by the independent 



18 

review and was statistically significantly longer than the TTP on placebo of 5.1 weeks 

(95% CI: 4.4, 10.1) as assessed by the investigator and 6.4 weeks (95% CI: 4.4, 10.0) as assessed by 

the independent review. The difference in overall survival (OS) was statistically in favour of sunitinib 

[hazard ratio (HR): 0.491; (95% CI: 0.290, 0.831)]; the risk of death was 2 times higher in patients in 

the placebo arm compared to the sunitinib arm.  

 

After the interim analysis of efficacy and safety, at the recommendation of the independent Data and 

Safety Monitoring Board (DSMB), the study was unblinded and patients on the placebo arm were 

offered open-label sunitinib treatment. 

 

A total of 255 patients received sunitinib in the open-label treatment phase of the study, including 

99 patients who were initially treated with placebo.  

 

The analyses of primary and secondary endpoints in the open-label phase of the study reaffirmed the 

results obtained at the time of the interim analysis, as shown in Table 2: 

 

Table 2. GIST summary of efficacy endpoints (ITT population)  

 Double-blind treatmenta  

 Median (95% CI) Hazard ratio Placebo 

cross-over 

group 

treatmentb 

Endpoint 

Sutent Placebo (95% CI) p-value 

Primary      

TTP (weeks)      

   Interim 27.3 (16.0, 32.1) 6.4 (4.4, 10.0) 0.329 (0.233, 0.466) < 0.001 - 

   Final 26.6 (16.0, 32.1) 6.4 (4.4, 10.0) 0.339 (0.244, 0.472) < 0.001 10.4 (4.3, 

22.0) 

Secondary      

   PFS (weeks)c      

 Interim 24.1 (11.1, 28.3) 6.0 (4.4, 9.9) 0.333 (0.238, 0.467)  < 0.001 - 

 Final 22.9 (10.9, 28.0) 6.0 (4.4, 9.7) 0.347 (0.253, 0.475) < 0.001 - 

 ORR (%)d      

 Interim 6.8 (3.7, 11.1) 0 (-) NA 0.006 - 

 Final 6.6 (3.8, 10.5) 0 (-) NA 0.004 10.1 (5.0, 

17.8) 

 OS (weeks)e      

 Interim - - 0.491 (0.290, 0.831) 0.007 - 

 Final 72.7 (61.3, 83.0) 64.9 (45.7, 96.0) 0.876 (0.679, 1.129) 0.306 - 
Abbreviations: CI=confidence interval; ITT=intent-to-treat; NA=not applicable; ORR=objective response 

rate; OS=overall survival; PFS=progression-free survival; TTP=time-to-tumour progression. 
a Results of double-blind treatment are from the ITT population and using central radiologist 

measurement, as appropriate. 
b Efficacy results for the 99 subjects who crossed over from placebo to Sutent after unblinding. Baseline 

was reset at cross-over and efficacy analyses were based on investigators assessment. 
c The interim PFS numbers have been updated based on a recalculation of the original data. 
d Results for ORR are given as percent of subjects with confirmed response with the 95% CI. 
e Median not achieved because the data were not yet mature. 

 

Median OS in the ITT population was 72.7 weeks and 64.9 weeks (HR: 0.876; 95% CI: 0.679, 1.129; 

p=0.306), in the sunitinib and placebo arms, respectively. In this analysis, the placebo arm included 

those patients randomised to placebo who subsequently received open-label sunitinib treatment. 

 

Treatment-naïve metastatic renal cell carcinoma  

A Phase 3, randomised, multi-centre, international study evaluating the efficacy and safety of sunitinib 

compared with IFN- in treatment-naïve MRCC patients was conducted. Seven hundred and fifty 

patients were randomised 1:1 to the treatment arms; they received treatment with either sunitinib in 

repeated 6-week cycles, consisting of 4 weeks of 50 mg daily oral administration followed by 2 weeks 



19 

of rest (Schedule 4/2), or IFN-α, administered as a subcutaneous injection of 3 million units (MU) the 

first week, 6 MU the second week, and 9 MU the third week and thereafter, on 3 nonconsecutive days 

each week.  

 

The median duration of treatment was 11.1 months (range: 0.4-46.1) for sunitinib treatment and 

4.1 months (range: 0.1-45.6) for IFN-α treatment. Treatment-related serious adverse events (TRSAEs) 

were reported in 23.7% of patients receiving sunitinib and in 6.9% of patients receiving IFN-α. 

However, the discontinuation rates due to adverse events were 20% for sunitinib and 23% for IFN-α. 

Dose interruptions occurred in 202 patients (54%) on sunitinib and 141 patients (39%) on IFN-α. Dose 

reductions occurred in 194 patients (52%) on sunitinib and 98 patients (27%) on IFN-α. Patients were 

treated until disease progression or withdrawal from the study. The primary efficacy endpoint was 

PFS. A planned interim analysis showed a statistically significant advantage for sunitinib over IFN-α, 

in this study, the median PFS for the sunitinib-treated group was 47.3 weeks, compared with 

22.0 weeks for the IFN-α-treated group; the HR was 0.415 (95% CI: 0.320, 0.539; p-value < 0.001). 

Other endpoints included ORR, OS, and safety. Core radiology assessment was discontinued after the 

primary endpoint had been met. At the final analysis, the ORR as determined by the investigator’s 

assessment was 46% (95% CI: 41%, 51%) for the sunitinib arm and 12.0% (95% CI: 9%, 16%) for the 

IFN-α arm (p<0.001). 

 

Sunitinib treatment was associated with longer survival compared to IFN-α. The median OS was 

114.6 weeks for the sunitinib arm (95% CI: 100.1, 142.9) and 94.9 weeks for the IFN-α arm 

(95% CI: 77.7, 117.0) with a hazard ratio of 0.821 (95% CI: 0.673, 1.001; p=0.0510 by unstratified 

log-rank).  

 

The overall PFS and OS, observed in the ITT population, as determined by the core radiology 

laboratory assessment, are summarised in Table 3. 

 

Table 3. Treatment-naïve mRCC summary of efficacy endpoints (ITT population)  

Summary of progression-free survival 

Sunitinib 

(N = 375) 
IFN- 

(N = 375) 

Subject did not progress or die [n (%)] 161 (42.9) 176 (46.9) 

Subject observed to have progressed or died 

[n (%)] 

214 (57.1) 199 (53.1) 

PFS (weeks) 

Quartile (95% CI) 

  25% 22.7 (18.0, 34.0) 10.0 (7.3, 10.3) 

  50% 48.3 (46.4, 58.3) 22.1 (17.1, 24.0) 

  75% 84.3 (72.9, 95.1) 58.1 (45.6, 82.1) 

Unstratified analysis 

Hazard ratio (sunitinib versus IFN-)  0.5268 

95% CI for hazard ratio (0.4316, 0.6430) 

p-valuea < 0.0001 



20 

Summary of progression-free survival 

Sunitinib 

(N = 375) 
IFN- 

(N = 375) 

Summary of overall survival 

Subject not known to have died [n (%)] 185 (49.3) 175 (46.7) 

Subject observed to have died [n (%)] 190 (50.7) 200 (53.3) 

OS (weeks) 

Quartile (95% CI) 

   25% 56.6 (48.7, 68.4) 41.7 (32.6, 51.6) 

   50% 114.6 (100.1, 142.9) 94.9 (77.7, 117.0) 

   75% NA (NA, NA) NA (NA, NA) 

Unstratified analysis 

Hazard ratio (sunitinib versus IFN-) 0.8209 

95% CI for hazard ratio (0.6730, 1.0013) 

p-valuea 0.0510 
Abbreviations: CI=confidence interval; INF-α=interferon-alfa; ITT=intent-to-treat; N=number of patients; 

NA=not applicable; OS=overall survival; PFS=progression-free survival. 
a From a 2-sided log-rank test. 
 

Cytokine-refractory metastatic renal cell carcinoma  

A Phase 2 study of sunitinib was conducted in patients who were refractory to prior cytokine therapy 

with interleukin-2 or IFN-. Sixty-three patients received a starting dose of 50 mg sunitinib orally, 

once daily for 4 consecutive weeks followed by a 2-week rest period, to comprise a complete cycle of 

6 weeks (Schedule 4/2). The primary efficacy endpoint was ORR, based on Response Evaluation 

Criteria in Solid Tumours (RECIST). 

 

In this study the objective response rate was 36.5% (95% CI: 24.7%, 49.6%) and the median TTP was 

37.7 weeks (95% CI: 24.0, 46.4). 

 

A confirmatory, open-label, single-arm, multi-centre study evaluating the efficacy and safety of 

sunitinib was conducted in patients with MRCC who were refractory to prior cytokine therapy. One 

hundred and 6 patients received at least one 50 mg dose of sunitinib on Schedule 4/2. 

 

The primary efficacy endpoint of this study was ORR. Secondary endpoints included TTP, duration of 

response (DR) and OS. 

 

In this study the ORR was 35.8% (95% CI: 26.8% , 47.5 %). The median DR and OS had not yet been 

reached. 

 

Pancreatic neuroendocrine tumours 

A supportive Phase 2, open-label, multi-centre study evaluated the efficacy and safety of single-agent 

sunitinib 50 mg daily on Schedule 4/2 in patients with unresectable pNET. In a pancreatic islet cell 

tumour cohort of 66 patients, the primary endpoint of response rate was 17%.  

 

A pivotal Phase 3, multi-centre, international, randomised, double-blind, placebo-controlled study of 

single-agent sunitinib was conducted in patients with unresectable pNET.  

 

Patients were required to have documented progression, based on RECIST, within the prior 12 months 

and were randomised (1:1) to receive either 37.5 mg sunitinib once daily without a scheduled rest 

period (N = 86) or placebo (N = 85).  

 

The primary objective was to compare PFS in patients receiving sunitinib versus patients receiving 

placebo. Other endpoints included OS, ORR, PROs, and safety.  

 

Demographics were comparable between the sunitinib and placebo groups. Additionally, 49% of 

sunitinib patients had nonfunctioning tumours versus 52% of placebo patients and 92% of patients in 

both arms had liver metastases.  

 



21 

Use of somatostatin analogues was allowed in the study. 

 

A total of 66% of sunitinib patients received prior systemic therapy compared with 72% of placebo 

patients. In addition, 24% of sunitinib patients had received somatostatin analogues compared with 

22% of placebo patients. 

 

A clinically significant advantage in investigator-assessed PFS for sunitinib over placebo was 

observed. The median PFS was 11.4 months for the sunitinib arm compared to 5.5 months for the 

placebo arm [hazard ratio: 0.418 (95% CI: 0.263, 0.662), p-value=0.0001]; similar results were 

observed when derived tumour response assessments based upon application of RECIST to 

investigator tumour measurements were used to determine disease progression, as shown in Table 4. 

A hazard ratio favouring sunitinib was observed in all subgroups of baseline characteristics evaluated, 

including an analysis by number of prior systemic therapies. A total of 29 patients in the sunitinib arm 

and 24 in the placebo arm had received no prior systemic treatment; among these patients, the hazard 

ratio for PFS was 0.365 (95% CI: 0.156, 0.857), p=0.0156. Similarly, among 57 patients in the 

sunitinib arm (including 28 with 1 prior systemic therapy and 29 with 2 or more prior systemic 

therapies) and 61 patients in the placebo arm (including 25 with 1 prior systemic therapy and 36 with 2 

or more prior systemic therapies), the hazard ratio for PFS was 0.456 (95% CI: 0.264, 0.787), 

p=0.0036. 

 

A sensitivity analysis of PFS was conducted where progression was based upon investigator-reported 

tumour measurements and where all subjects censored for reasons other than study termination were 

treated as PFS events. This analysis provided a conservative estimate of the treatment effect of 

sunitinib and supported the primary analysis, demonstrating a hazard ratio of 0.507 (95% CI: 0.350, 

0.733), p=0.000193. The pivotal study in pancreatic NET was terminated prematurely at the 

recommendation of an independent drug monitoring committee and the primary endpoint was based 

upon investigator assessment, both of which may have affected the estimates of the treatment effect.  

 

In order to rule out bias in the investigator-based assessment of PFS, a BICR of scans was performed; 

this review supported the investigator assessment, as shown in Table 4. 

 

Table 4 - pNET efficacy results from the Phase 3 study 

Efficacy parameter Sutent 

(N = 86) 

Placebo 

(N = 85) 

Hazard Ratio 

(95% CI) 

p-value 

Progression-free survival [median, 

months (95% CI)] by Investigator 

Assessment 

11.4 

(7.4, 19.8) 

5.5 

(3.6, 7.4) 

0.418 

(0.263, 0.662) 

0.0001a 

Progression-free survival [median, 

months (95% CI)] by derived tumour 

response assessment based upon 

application of RECIST to 

investigator tumour assessments 

12.6 

(7.4, 16.9) 

5.4 

(3.5, 6.0) 

0.401 

(0.252, 0.640) 

0.000066a 

Progression-free survival [median, 

months (95% CI)] by blinded 

independent central review of 

tumour assessments 

12.6 

(11.1, 20.6) 

5.8 

(3.8, 7.2) 

0.315 

(0.181, 0.546) 

0.000015a 

Overall survival [5 years follow-up] 

[median, months (95% CI)] 

38.6 

(25.6, 56.4) 

29.1 

(16.4, 36.8) 

0.730 

(0.504, 1.057) 

0.0940a 

Objective response rate 

[%, (95% CI)] 

9.3 

(3.2, 15.4) 

0 NA 0.0066b 

Abbreviations: CI=confidence interval; N=number of patients; NA=not applicable; pNET=pancreatic 

neuroendocrine tumours; RECIST=response evaluation criteria in solid tumours. 
a  2-sided unstratified log-rank test 
b  Fisher’s Exact test 

 



22 

Figure 1. Kaplan-Meier plot of PFS in the pNET Phase 3 study 

 

0 3 6 9 12 15 18 21
Time (Months)

0

10

20

30

40

50

60

70

80

90

100

P
ro

g
re

s
s
io

n
 F

re
e
 S

u
rv

iv
a

l 
P

ro
b
a

b
ili

ty
 (

%
)

SUTENT (N=86)
 Median 11.4 months

Placebo (N=85)
 Median 5.5 months

Hazard Ratio = 0.42
95% CI (0.26 - 0.66)
p = 0.0001

86 52 34 20 15 4 2SUTENT
85 42 20 9 2 2 2Placebo

Number of subjects at risk

 
Abbreviations: CI=confidence interval; N=number of patients; PFS=progression-free survival; pNET=pancreatic 

neuroendocrine tumours. 

 

OS data were not mature at the time of the study closure [20.6 months (95% CI: 20.6, NR) for the 

sunitinib arm compared to NR (95% CI: 15.5, NR) for the placebo arm, hazard ratio: 

0.409 (95% CI: 0.187, 0.894), p-value=0.0204]. There were 9 deaths in the sunitinib arm and 

21 deaths in the placebo arm.  

 

Upon disease progression, patients were unblinded and placebo patients were offered access to 

open-label sunitinib in a separate extension study. As a result of the early study closure, remaining 

patients were unblinded and offered access to open-label sunitinib in an extension study. A total of 59 

out of 85 patients (69.4%) from the placebo arm crossed over to open-label sunitinib following disease 

progression or unblinding at study closure. OS observed after 5 years of follow-up in the extension 

study showed a hazard ratio of 0.730 (95% CI: 0.504, 1.057).  

 

Results from the European Organisation for Research and Treatment of Cancer Quality of Life 

Questionnaire (EORTC QLQ-C30) showed that the overall global health-related quality of life and the 

5 functioning domains (physical, role, cognitive, emotional, and social) were maintained for patients 

on sunitinib treatment as compared to placebo with limited adverse symptomatic effects. 

 

A Phase 4 multinational, multi-centre, single-arm, open-label study evaluating the efficacy and safety 

of sunitinib was conducted in patients with progressive, advanced/metastatic, well-differentiated, 

unresectable pNET. 

 

One hundred six patients (61 patients in the treatment-naïve cohort and 45 patients in the later-line 

cohort) received treatment with sunitinib orally at 37.5 mg once a day on a continuous daily dosing 

(CDD) schedule. 

 

The investigator-assessed median PFS was 13.2 months, both in the overall population (95% CI: 10.9, 

16.7) and in the treatment-naïve cohort (95% CI: 7.4, 16.8). 

 

Paediatric population 

Experience on the use of sunitinib in paediatric patients is limited (see section 4.2).  

 



23 

A Phase 1 dose-escalation study of oral sunitinib was conducted in 35 patients comprised of 

30 paediatric patients (aged 3 years to 17 years) and 5 young adult patients (aged: 18 years to 

21 years), with refractory solid tumours, the majority of whom were enrolled with a primary diagnosis 

of brain tumour. Dose-limiting cardiotoxicity was observed in the first part of the study which was 

therefore amended to exclude patients with previous exposure to potentially cardiotoxic therapies 

(including anthracyclines) or cardiac radiation. In the second part of the study, including patients with 

prior anticancer therapy but without risk factors for cardiac toxicity, sunitinib was generally tolerable 

and clinically manageable at the dose of 15 mg/m2 daily (MTD) on Schedule 4/2. None of the subjects 

achieved complete response or partial response. Stable disease was observed in 6 patients (17%). One 

patient with GIST was enrolled at the 15 mg/m2 dose level with no evidence of benefit. The observed 

adverse drug reactions were similar overall to those seen in adults (see section 4.8). 

 

A Phase 2 open-label study was conducted in 29 patients comprised of 27 paediatric patients (aged 

3 years to 16 years) and 2 young adult patients (aged 18 years to 19 years) with HGG or ependymoma. 

The study was closed at the time of planned interim analysis due to the lack of disease control. Median 

PFS was 2.3 months in the HGG group and 2.7 months in the ependymoma group. Median overall OS 

was 5.1 months in the HGG group and 12.3 months in the ependymoma group. The most common 

(≥10%) reported treatment-related adverse events in patients in both groups combined were neutrophil 

count decreased (6 patients [20.7%]) and haemorrhage intracranial (3 patients [10.3%]) (see 

section 4.8).  

 

Evidence from a Phase 1/2 study of oral sunitinib conducted in 6 paediatric patients with GIST aged 

13 years to 16 years who received sunitinib on Schedule 4/2, at doses ranging between 15 mg/m2 daily 

and 30 mg/m2 daily, and available published data (20 paediatric or young adult patients with GIST) 

indicated that sunitinib treatment resulted in disease stabilization in 18 of 26 (69.2%) patients, either 

after imatinib failure or intolerance (16 patients with stable disease out of 21), or de novo/after surgery 

(2 patients with stable disease out of 5). In the Phase 1/2 study, stable disease and disease progression 

was observed in 3 out of 6 patients each (1 patient received neo adjuvant and 1 patient received 

adjuvant imatinib, respectively). In the same study, 4 out of 6 patients (66.7%) experienced Grade 3-4 

treatment-related adverse events (Grade 3 hypophosphataemia, neutropenia, and thrombocytopenia in 

1 patient each and a Grade 4 neutropenia in 1 patient). In addition, the publications reported the 

following Grade 3 adverse drug reactions experienced by 5 patients: fatigue (2), gastrointestinal 

adverse drug reactions (including diarrhoea) (2), haematologic adverse drug reactions (including 

anaemia) (2), cholecystitis (1), hyperthyroidism (1), and mucositis (1). 

 

A population pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) analysis was 

conducted with the scope to extrapolate the PK and key safety and efficacy endpoints of sunitinib in 

paediatric patients with GIST (aged: 6 years to 17 years). This analysis was based on data collected 

from adults with GIST or solid tumours and from paediatric patients with solid tumours. Based on the 

modelling analyses, the younger age and lower body size did not appear to affect negatively the safety 

and efficacy responses to sunitinib plasma exposures. Sunitinib benefit/risk did not appear to be 

negatively affected by younger age or lower body size, and was mainly driven by its plasma exposure.  

 

The EMA has waived the obligation to submit the results of studies with Sutent in all subsets of the 

paediatric population for the treatment of kidney or renal pelvis carcinoma (excluding 

nephroblastoma, nephroblastomatosis, clear cell sarcoma, mesoblastic nephroma, renal medullary 

carcinoma, and rhabdoid tumour of the kidney) (see section 4.2). 

 

The EMA has waived the obligation to submit the results of the studies with Sutent in all subsets of 

the paediatric population for the treatment of gastroenteropancreatic neuroendocrine tumours 

(excluding neuroblastoma, neuroganglioblastoma, and phaeochromocytoma) (see section 4.2). 

 

5.2 Pharmacokinetic properties 

 

The PK of sunitinib were evaluated in 135 healthy volunteers and 266 patients with solid tumours. The 

PK were similar in all solid tumours populations tested and in healthy volunteers. 

 



24 

In the dosing ranges of 25 to 100 mg, the area under the plasma concentration-time curve (AUC) and 

Cmax increase proportionally with dose. With repeated daily administration, sunitinib accumulates 3- to 

4-fold and its primary active metabolite accumulates 7- to 10-fold. Steady-state concentrations of 

sunitinib and its primary active metabolite are achieved within 10 to 14 days. By Day 14, combined 

plasma concentrations of sunitinib and its 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. The primary active metabolite comprises 23% to 37% of the 

total exposure. No significant changes in the PK of sunitinib or the primary active metabolite are 

observed with repeated daily administration or with repeated cycles in the dosing schedules tested. 

 

Absorption  

After oral administration of sunitinib, Cmax are generally observed from 6 to 12 hours time to 

maximum concentration (tmax) postadministration.  

 

Food has no effect on the bioavailability of sunitinib. 

 

Distribution 

In vitro, binding of sunitinib and its primary active metabolite to human plasma protein was 95% and 

90%, respectively, with no apparent concentration dependence. The apparent volume of distribution 

(Vd) for sunitinib was large, 2230 L, indicating distribution into the tissues. 

 

Metabolic interactions 

The calculated in vitro Ki values for all cytochrome P450 (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 induce metabolism, to any clinically 

relevant extent, of other actives substances that may be metabolised by these enzymes. 

 

Biotransformation 

Sunitinib is metabolised primarily by CYP3A4, the CYP isoform which produces its primary active 

metabolite, desethyl sunitinib, which is then further metabolised by the same isoenzyme. 

 

Co-administration of sunitinib with potent CYP3A4 inducers or inhibitors should be avoided because 

the plasma levels of sunitinib may be altered (see sections 4.4 and 4.5).  

 

Elimination 

Excretion is primarily via faeces (61%), with renal elimination of unchanged active substance and 

metabolites accounting for 16% of the administered dose. Sunitinib and its primary active metabolite 

were the major compounds identified in plasma, urine, and faeces, representing 91.5%, 86.4%, and 

73.8% of radioactivity in pooled samples, respectively. Minor metabolites were identified in urine and 

faeces, but generally were not found in plasma. Total oral clearance (CL/F) was 34-62 L/h. 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. 

 

Co-administration with medicinal products that are BCRP inhibitors 

In vitro, sunitinib is a substrate of the efflux transporter BCRP. In study A6181038 the 

co-administration of gefitinib, a BCRP inhibitor, did not result in a clinically relevant effect on the 

Cmax and AUC for sunitinib or total drug (sunitinib + metabolite) (see section 4.5). This study was a 

multi-centre, open-label, Phase 1/2 study examining the safety/tolerability, the maximum tolerated 

dose, and the antitumour activity of sunitinib in combination with gefitinib in subjects with MRCC. 

The PK of gefitinib (250 mg daily) and sunitinib (37.5 mg [Cohort 1, n=4] or 50 mg [Cohort 2, n=7] 

daily on a 4-weeks on followed by 2 weeks-off schedule) when co-administered was evaluated as a 

secondary study objective. Changes in sunitinib PK parameters were of no clinical significance and 
did not indicate any drug-drug interactions; however, considering the relatively low number of 

subjects (i.e. N=7+4) and the moderate-large interpatient variability in the pharmacokinetic 

parameters, caution needs to be taken when interpreting the PK drug-drug interaction findings from 

this study. 

 



25 

 

Special populations 

 

Hepatic impairment 

Sunitinib and its primary metabolite are mainly metabolised by the liver. Systemic exposures after a 

single dose of sunitinib were similar in subjects with mild or moderate (Child-Pugh Class A and B) 

hepatic impairment compared to subjects with normal hepatic function. Sutent was not studied in 

subjects with severe (Child-Pugh Class C) hepatic impairment. 

 

Studies in cancer patients have excluded patients with ALT or AST > 2.5 x ULN (upper limit of 

normal) or > 5.0 x ULN if due to liver metastasis.  

 

Renal impairment 

Population PK analyses indicated that sunitinib apparent clearance (CL/F) was not affected by 

creatinine clearance (CLcr) within the range evaluated (42-347 ml/min). Systemic exposures after a 

single dose of sunitinib were similar in subjects with severe renal impairment (CLcr < 30 ml/min) 

compared to subjects with normal renal function (CLcr > 80 ml/min). Although sunitinib and its 

primary metabolite were not eliminated through haemodialysis in subjects with ESRD, the total 

systemic exposures were lower by 47% for sunitinib and 31% for its primary metabolite compared to 

subjects with normal renal function. 

 

Weight, performance status 

Population PK analyses of demographic data indicate that no starting dose adjustments are necessary 

for weight or Eastern Cooperative Oncology Group (ECOG) performance status. 

 

Gender 

Available data indicate that females could have about 30% lower apparent clearance (CL/F) of 

sunitinib than males: this difference, however, does not necessitate starting dose adjustments. 

 

Paediatric population 

Experience on the use of sunitinib in paediatric patients is limited (see section 4.2). Population PK 

analyses of a pooled dataset from adult patients with GIST and solid tumours and paediatric patients 

with solid tumours were completed. Stepwise covariate modelling analyses were performed to 

evaluate the effect of age and body size (total body weight or body surface area) as well as other 

covariates on important PK parameters for sunitinib and its active metabolite. Among age and 

bodysize related covariates tested, age was a significant covariate on apparent clearance of sunitinib 

(the younger the age of the paediatric patient, the lower the apparent clearance). Similarly, body 

surface area was a significant covariate on the apparent clearance of the active metabolite (the lower 

the body surface area, the lower the apparent clearance).  

 

Furthermore, based on an integrated population PK analysis of pooled data from the 3 paediatric 

studies (2 paediatric solid tumour studies and 1 paediatric GIST study; ages: 6 years to 11 years and 

12 years to 17 years), baseline body surface area (BSA) was a significant covariate on apparent 

clearance of sunitinib and its active metabolite. Based on this analysis, a dose of approximately 

20 mg/m2 daily in paediatric patients, with BSA values between 1.10 and 1.87 m2, is expected to 

provide plasma exposures to sunitinib and its active metabolite comparable (between 75 and 125% of 

the AUC) to those in adults with GIST administered sunitinib 50 mg daily on Schedule 4/2 (AUC 

1233 ng.hr/mL). In paediatric studies, the starting dose of sunitinib was 15 mg/m2 (based on the MTD 

identified in the Phase 1 dose-escalation study, see section 5.1), which in paediatric patients with GIST 

increased to 22.5 mg/m2 and subsequently to 30 mg/m2 (not to exceed the total dose of 50 mg/day) 

based on individual patient safety/tolerability. Furthermore, according to the published literatures in 

paediatric patients with GIST, the calculated starting dose ranged from 16.6 mg/m2 to 36 mg/m2, 

increased to doses as high as 40.4 mg/m2 (not exceeding the total dose of 50 mg/day). 

 



26 

5.3 Preclinical safety data 

 

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 hypocellularity 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). All findings occurred at clinically relevant sunitinib plasma 

exposure levels. Additional effects observed in other studies included: QTc interval prolongation, 

LVEF reduction and testicular tubular atrophy, increased mesangial cells in kidney, haemorrhage in 

gastrointestinal tract and oral mucosa, and hypertrophy of anterior pituitary cells. Changes in the 

uterus (endometrial atrophy) and bone growth plate (physeal thickening or dysplasia of cartilage) are 

thought to be related to the pharmacological action of sunitinib. Most of these findings were reversible 

after 2 to 6 weeks without treatment. 

 

Genotoxicity  

The genotoxic potential of sunitinib was assessed in vitro and in vivo. Sunitinib was not mutagenic in 

bacteria using metabolic activation provided by rat liver. Sunitinib did not induce structural 

chromosome aberrations in human peripheral blood lymphocyte cells in vitro. Polyploidy (numerical 

chromosome aberrations) was observed in human peripheral blood lymphocytes in vitro, both in the 

presence and absence of metabolic activation. Sunitinib was not clastogenic in rat bone marrow 

in vivo. The major active metabolite was not evaluated for genotoxic potential. 

 

Carcinogenicity 

In a 1-month, oral gavage dose-range finding study (0, 10, 25, 75, or 200 mg/kg/day) with continuous 

daily dosing in rasH2 transgenic mice, carcinoma and hyperplasia of Brunner’s glands of the 

duodenum were observed at the highest dose (200 mg/kg/day) tested. 

 

A 6-month, oral gavage carcinogenicity study (0, 8, 25, 75 [reduced to 50] mg/kg/day), with daily 

dosing was conducted in rasH2 transgenic mice. Gastroduodenal carcinomas, an increased incidence 

of background haemangiosarcomas, and/or gastric mucosal hyperplasia were observed at doses 

of ≥ 25 mg/kg/day following 1- or 6-months duration (≥ 7.3 times the AUC in patients administered 

the recommended daily dose RDD).  

 

In a 2-year rat carcinogenicity study (0, 0.33, 1, or 3 mg/kg/day), administration of sunitinib in 28-day 

cycles followed by 7-day dose-free periods resulted in increases in the incidence of 

phaeochromocytomas and hyperplasia in the adrenal medulla of male rats given 3 mg/kg/day 

following > 1 year of dosing (≥ 7.8 times the AUC in patients administered the RDD). Brunner’s 

glands carcinoma occurred in the duodenum at ≥ 1 mg/kg/day in females and at 3 mg/kg/day in males, 

and mucous cell hyperplasia was evident in the glandular stomach at 3 mg/kg/day in males, which 

occurred at ≥ 0.9, 7.8, and 7.8 times the AUC in patients administered the RDD, respectively. The 

relevance to humans of the neoplastic findings observed in the mouse (rasH2 transgenic) and rat 

carcinogenicity studies with sunitinib treatment is unclear. 

 

Reproductive and developmental toxicity 

No effects on male or female fertility were observed in reproductive toxicity studies. However, in 

repeated-dose toxicity studies performed in rats and monkeys, effects on female fertility were 

observed in the form of follicular atresia, degeneration of corpora lutea, endometrial changes in the 

uterus, and decreased uterine and ovarian weights at clinically relevant systemic exposure levels. 

Effects on male fertility in rat were observed in the form of tubular atrophy in the testes, reduction of 

spermatozoa in epididymides, and colloid depletion in prostate and seminal vesicles at plasma 

exposure levels 25 times the systemic exposure in humans. 

 

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 females at plasma exposure levels 5.5 times the systemic exposure in humans. In rabbits, 



27 

reductions in gravid uterine weights and number of live foetuses were due to increases in the number 

of resorptions, increases in postimplantation loss and complete litter loss in 4 of 6 pregnant females at 

plasma exposure levels 3 times the systemic exposure in humans. Sunitinib treatment in rats during 

organogenesis resulted in developmental effects at  5 mg/kg/day consisting of increased incidence of 

foetal skeletal malformations, predominantly characterised as retarded ossification of thoracic/lumbar 

vertebrae and occurred at plasma exposure levels 5.5 times the systemic exposure in humans. 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 times the systemic exposure in humans. 

 

Sunitinib (0.3, 1.0, 3.0 mg/kg/day) was evaluated in a pre-and postnatal development study in 

pregnant rats. Maternal body weight gains were reduced during gestation and lactation at 

≥ 1 mg/kg/day but no maternal reproductive toxicity was observed up to 3 mg/kg/day (estimate 

exposure ≥ 2.3 times the AUC in patients administered the RDD). Reduced offspring body weights 

were observed during the preweaning and postweaning periods at 3 mg/kg/day. No development 

toxicity was observed at 1 mg/kg/day (approximate exposure ≥ 0.9 times the AUC in patients 

administered the RDD). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

12.5 mg hard capsules 

Capsule content 

Mannitol (E421) 

Croscarmellose sodium 

Povidone (K-25) 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Red iron oxide (E172)  

Titanium dioxide (E171) 

 

Printing ink 

Shellac 

Propylene glycol  

Sodium hydroxide 

Povidone  

Titanium dioxide (E171) 

 

25 mg hard capsules 

Capsule content 

Mannitol (E421) 

Croscarmellose sodium 

Povidone (K-25) 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Red iron oxide (E172)  

Titanium dioxide (E171) 

Yellow iron oxide (E172) 

Black iron oxide (E172) 

 



28 

Printing ink 

Shellac 

Propylene glycol 

Sodium hydroxide 

Povidone 

Titanium dioxide (E171) 

 

37.5 mg hard capsules 

Capsule content 

Mannitol (E421) 

Croscarmellose sodium 

Povidone (K-25) 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Yellow iron oxide (E172)  

 

Printing ink 

Shellac 

Propylene glycol 

Potassium hydroxide 

Black iron oxide (E172) 

 

50 mg hard capsules 

Capsule content 

Mannitol (E421) 

Croscarmellose sodium 

Povidone (K-25) 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Yellow iron oxide (E172)  

Red iron oxide (E172)  

Black iron oxide (E172) 

 

Printing ink 

Shellac 

Propylene glycol  

Sodium hydroxide 

Povidone 

Titanium dioxide (E171) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 



29 

6.5 Nature and contents of container 

High-density polyethylene (HDPE) bottle with a polypropylene closure containing 30 hard capsules. 

Poly(chlorotrifluoroethylene)/PVC transparent perforated unit dose blister with aluminium foil coated 

with heat seal lacquer containing 28 x 1 hard capsules. 

Not all pack sizes may be marketed. 

6.6 Special precautions for disposal 

No special requirements. 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

8. MARKETING AUTHORISATION NUMBER(S)

Sutent 12.5 mg hard capsules 

EU/1/06/347/001 

EU/1/06/347/004 

Sutent 25 mg hard capsules 

EU/1/06/347/002 

EU/1/06/347/005 

Sutent 37.5 mg hard capsules 

EU/1/06/347/007 

EU/1/06/347/008 

Sutent 50 mg hard capsules 

EU/1/06/347/003 

EU/1/06/347/006 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 19 July 2006 

Date of latest renewal: 9 November 2016 

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  



30 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 

 



31 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

PFIZER Italia S.r.l  

Via del Commercio 

Zona Industriale 

IT-63100 Marino del Tronto (Ascoli Piceno) 

Italy 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

 AUTHORISATION 

 

• Periodic Safety Update Reports  
 

The requirements for submission of periodic safety update reports for this medicinal product are 

set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 

Directive 2001/83/EC and any subsequent updates published on the European medicines 

web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicine Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

 

 

  



32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



33 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

HDPE BOTTLE OUTER CARTON - 12.5 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 12.5 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 12.5 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



35 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/001  

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 12.5 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



36 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

HDPE BOTTLE – 12.5 MG CAPSULES  

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Sutent 12.5 mg hard capsules 

sunitinib 

Oral use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

30 capsules 

 

 

6. OTHER 

 

 

 

  



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

HDPE BOTTLE OUTER CARTON - 25 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 25 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 25 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



38 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/002 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



39 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

HDPE BOTTLE – 25 MG CAPSULES  

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Sutent 25 mg hard capsules 

sunitinib 

Oral use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

30 capsules 

 

 

6. OTHER 

 

 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

HDPE BOTTLE OUTER CARTON – 37.5 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 37.5 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 37.5 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



41 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/007 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 37.5 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



42 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

HDPE BOTTLE – 37.5 MG CAPSULES  

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Sutent 37.5 mg hard capsules 

sunitinib 

Oral use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

30 capsules 

 

 

6. OTHER 

 

 

  



43 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

HDPE BOTTLE OUTER CARTON - 50 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 50 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 50 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



44 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/003 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 50 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



45 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  

 

HDPE BOTTLE – 50 MG CAPSULES  

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Sutent 50 mg hard capsules 

sunitinib 

Oral use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

30 capsules 

 

 

6. OTHER 

 

 



46 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

BLISTER OUTER CARTON - 12.5 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 12.5 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 12.5 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 x 1 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



47 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/004 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



48 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER – 12.5 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 12.5 mg hard capsules 

sunitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. OTHER 

 

MON 

TUE 

WED 

THU 

FRI 

SAT 

SUN 

 

 

  



49 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BLISTER OUTER CARTON - 25 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 25 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 25 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 x 1 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



50 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/005 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 25 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



51 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER – 25 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 25 mg hard capsules 

sunitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. OTHER 

 

MON 

TUE 

WED 

THU 

FRI 

SAT 

SUN 

 

 

  



52 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

BLISTER OUTER CARTON – 37.5 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 37.5 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 37.5 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 x 1 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



53 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/008 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 37.5 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



54 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER – 37.5 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 37.5 mg hard capsules 

sunitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. OTHER 

 

MON 

TUE 

WED 

THU 

FRI 

SAT 

SUN 

 

 

  



55 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BLISTER OUTER CARTON - 50 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 50 mg hard capsules 

sunitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains sunitinib malate, equivalent to 50 mg of sunitinib. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 x 1 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions. 

 

 



56 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/06/347/006 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Sutent 50 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



57 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER – 50 MG CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Sutent 50 mg hard capsules 

sunitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pfizer 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. OTHER 

 

MON 

TUE 

WED 

THU 

FRI 

SAT 

SUN 

 

 

  



58 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



59 

Package leaflet: Information for the user 

 

Sutent 12.5 mg hard capsules 

Sutent 25 mg hard capsules 

Sutent 37.5 mg hard capsules 

Sutent 50 mg hard capsules 

sunitinib 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Sutent is and what it is used for 

2. What you need to know before you take Sutent 

3. How to take Sutent 

4. Possible side effects 

5. How to store Sutent 

6. Contents of the pack and other information 

 

 

1. What Sutent is and what it is used for 

 

Sutent contains the active substance sunitinib, which is a protein kinase inhibitor. It is used to treat 

cancer by preventing the activity of a special group of proteins which are known to be involved in the 

growth and spread of cancer cells. 

 

Sutent is used to treat adults with the following types of cancer:  

 

- Gastrointestinal stromal tumour (GIST), a type of cancer of the stomach and bowel, where 
imatinib (another anticancer medicine) no longer works or you cannot take imatinib. 

- Metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts 
of the body. 

- Pancreatic neuroendocrine tumours (pNET) (tumours of the hormone-producing cells in the 
pancreas) that have progressed or cannot be removed with surgery. 

 

If you have any questions about how Sutent works or why this medicine has been prescribed for you, 

ask your doctor. 

 

 

2. What you need to know before you take Sutent 

 

Do not take Sutent: 

 

- If you are allergic to sunitinib or any of the other ingredients of Sutent (listed in section 6). 

 



60 

Warnings and precautions 

 

Talk to your doctor before taking Sutent: 

 

-  If you have high blood pressure. Sutent can raise blood pressure. Your doctor may check your 

blood pressure during treatment with Sutent, and you may be treated with medicines to reduce 

the blood pressure, if needed.  

 

- If you have or have had blood disease, bleeding problems, or bruising. Treatment with 
Sutent may lead to a higher risk of bleeding or lead to changes in the number of certain cells in 

the blood which may lead to anaemia or affect the ability of your blood to clot. If you are taking 

warfarin or acenocoumarole, medicines which thin the blood to prevent blood clots, there may 

be a greater risk of bleeding. Tell your doctor if you have any bleeding while on treatment with 

Sutent.  

 

- If you have heart problems. Sutent can cause heart problems. Tell your doctor if you feel very 
tired, are short of breath, or have swollen feet and ankles.  

 

- If you have abnormal heart rhythm changes. Sutent can cause abnormality of your heart 
rhythm. Your doctor may obtain electrocardiograms to evaluate for these problems during your 

treatment with Sutent. Tell your doctor if you feel dizzy, faint, or have abnormal heartbeats 

while taking Sutent.  

 

- If you have had a recent problem with blood clots in your veins and/or arteries (types of 
blood vessels), including stroke, heart attack, embolism, or thrombosis. Call your doctor 

immediately if you get symptoms such as chest pain or pressure, pain in your arms, back, neck 

or jaw, shortness of breath, numbness or weakness on 1 side of your body, trouble talking, 

headache, or dizziness while on treatment with Sutent.  

 
- If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a 

tear in a blood vessel wall. 

 

- If you have or have had damage to the smallest blood vessels known as thrombotic 
microangiopathy (TMA). Tell your doctor if you develop fever, fatigue, tiredness, bruising, 

bleeding, swelling, confusion, vision loss, and seizures. 

 

- If you have thyroid glands problems. Sutent can cause thyroid gland problems. Tell your 
doctor if you get tired more easily, generally feel colder than other people, or your voice 

deepens whilst taking Sutent. Your thyroid function should be checked before you take Sutent 

and regularly while you are taking it. If your thyroid gland is not producing enough thyroid 

hormone, you may be treated with thyroid hormone replacement.  

 

- If you have or have had pancreatic or gallbladder disorders. Tell your doctor if you develop 

any of the following signs and symptoms: pain in the area of the stomach (upper abdomen), 

nausea, vomiting, and fever. These may be caused by inflammation of the pancreas or 

gallbladder.  

 

- If you have or have had liver problems. Tell your doctor if you develop any of the following 
signs and symptoms of liver problems during Sutent treatment: itching, yellow eyes or skin, dark 

urine, and pain or discomfort in the right upper stomach area. Your doctor should do blood tests 

to check your liver function before and during treatment with Sutent, and as clinically indicated. 

 

- If you have or have had kidney problems. Your doctor will monitor your kidney function.  
 

- If you are going to have surgery or if you had an operation recently. Sutent may affect the 
way your wounds heal. You will usually be taken off Sutent if you are having an operation. 

Your doctor will decide when to start Sutent again. 



61 

 

- You may be advised to have a dental check-up before you start treatment with Sutent. 
- If you have or have had pain in the mouth, teeth and/or jaw, swelling or sores inside the 

mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth, tell your 

doctor and dentist immediately. 

- If you need to undergo an invasive dental treatment or dental surgery, tell your dentist that 
you are being treated with Sutent in particular when you are also receiving or have received 

intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone 

complications that may have been given for another medical condition. 

 

- If you have or have had skin and subcutaneous tissue disorders. While you are on this 
medicine "pyoderma gangrenosum" (painful skin ulceration) or “necrotising fasciitis” (rapidly 

spreading infection of the skin/soft tissue that may be life-threatening) may occur. Contact your 

doctor immediately if symptoms of infection occur around a skin injury, including fever, pain, 

redness, swelling, or drainage of pus or blood. This event is generally reversible after sunitinib 

discontinuation. Severe skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis, 

erythema multiforme) have been reported with the use of sunitinib, appearing initially as reddish 

target-like spots or circular patches often with central blisters on the trunk. The rash may 

progress to widespread blistering or peeling of the skin and may be life-threatening. If you 

develop a rash or these skin symptoms, seek immediate advice from a doctor. 

 

- If you have or have had seizures. Notify your doctor as soon as possible if you have high 
blood pressure, headache, or loss of sight.  

 

- If you have diabetes. Blood sugar levels in diabetic patients should be checked regularly in 
order to assess if antidiabetic medicine’s dosage needs to be adjusted to minimise the risk of low 

blood sugar. Notify your doctor as soon as possible if you experience any signs and symptoms 

of low blood sugar (fatigue, palpitations, sweating, hunger and loss of consciousness). 

 

Children and adolescents 

 

Sutent is not recommended for people aged under 18.  

 

Other medicines and Sutent 

 

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 

medicines, including medicines obtained without a prescription and even those not prescribed.  

 

Some medicines can affect the levels of Sutent in your body. You should inform your doctor if you are 

taking medicines containing the following active substances:  

▪ ketoconazole, itraconazole – used to treat fungal infections  
▪ erythromycin, clarithromycin, rifampicin –used to treat infections 
▪ ritonavir –used to treat HIV 
▪ dexamethasone – a corticosteroid used for various conditions (such as allergic/breathing 

disorders or skin diseases)  

▪ phenytoin, carbamazepine, phenobarbital – used to treat epilepsy and other neurological 
conditions  

▪ herbal preparations containing St. John’s Wort (Hypericum perforatum) – used to treat 
depression and anxiety 

 

Sutent with food and drink 

 

You should avoid drinking grapefruit juice while on treatment with Sutent. 

 



62 

Pregnancy and breast-feeding 

 

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

If you might get pregnant, you should use a reliable method of contraception during treatment with 

Sutent. 

 

If you are breast-feeding, tell your doctor. You should not breast-feed during treatment with Sutent.   

 

Driving and using machines 

 

If you experience dizziness or you feel unusually tired, take special care when driving or using 

machines. 

 

 

3. How to take Sutent 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 

sure. 

 

Your doctor will prescribe a dose that is right for you, depending on the type of cancer to be treated. If 

you are being treated for: 

− GIST or MRCC: the usual dose is 50 mg once daily taken for 28 days (4 weeks), followed by 
14 days (2 weeks) of rest (no medicine), in 6-week cycles.  

− pNET: the usual dose is 37.5 mg once daily without a rest period. 
  

Your doctor will determine the appropriate dose you need to take, as well as if and when you need to 

stop treatment with Sutent. 

 

Sutent can be taken with or without food.  

 

If you take more Sutent than you should 

 

If you have accidentally taken too many capsules, talk to your doctor straight away. You may require 

medical attention. 

 

If you forget to take Sutent 

 

Do not take a double dose to make up for a forgotten dose. 

 

 

4. Possible side effects  

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

You must immediately contact your doctor if you experience any of those serious side effects (see also 

What you need to know before you take Sutent): 

 

Heart problems. Tell your doctor if you feel very tired, are short of breath, or have swollen feet and 

ankles. These may be symptoms of heart problems that may include heart failure and heart muscle 

problems (cardiomyopathy).  

 

Lung or breathing problems. Tell your doctor if you develop cough, chest pain, sudden onset of 

shortness of breath, or coughing up blood. These may be symptoms of a condition called pulmonary 

embolism that occurs when blood clots travel to your lungs. 

 



63 

Kidney disorders. Tell your doctor if you experience altered frequency or absence of urination which 

may be symptoms of kidney failure.  

 

Bleeding. Tell your doctor if you have any of these symptoms or a serious bleeding problem during 

treatment with Sutent: painful, swollen stomach (abdomen); vomiting blood; black, sticky stools; 

bloody urine; headache or change in your mental status; coughing up of blood or bloody sputum from 

the lungs or airway.  

 

Tumour destruction leading to hole in the intestine. Tell your doctor if you have severe abdominal 

pain, fever, nausea, vomiting, blood in your stool, or changes in bowel habits. 

 

Other side effects with Sutent may include: 

 

Very common: may affect more than 1 in 10 people 

• Reduction in the number of platelets, red blood cells and/or white blood cells (e.g. neutrophils).  

• Shortness of breath. 

• High blood pressure.  

• Extreme tiredness, loss of strength. 

• Swelling caused by fluid under the skin and around the eye, deep allergic rash.  

• Mouth pain/irritation, mouth sores/inflammation/dryness, taste disturbances, upset stomach, 
nausea, vomiting, diarrhoea, constipation, abdominal pain/swelling, loss/decrease of appetite. 

• Decreased activity of thyroid gland (hypothyroidism).  

• Dizziness.  

• Headache.  

• Nose bleeding.  

• Back pain, joint pain. 

• Pain in arms and legs.  

• Yellow skin/skin discoloration, excess pigmentation of the skin, hair colour change, rash on the 
palms of the hands and soles of the feet, rash, dryness of the skin. 

• Cough.  

• Fever. 

• Difficulty in falling asleep. 
 

Common: may affect up to 1 in 10 people  

• Blood clots in the blood vessels.  

• Deficiency of blood supply to the heart muscle, due to obstruction or constriction of the 
coronary arteries. 

• Chest pain.  

• Decreased in the amount of blood pumped by the heart.  

• Fluid retention including around the lungs.  

• Infections.  
• Complication of severe infection (infection is present in the bloodstream) that can lead to tissue 

damage, organ failure, and death.  

• Decreased blood sugar level (see section 2).. 

• Loss of protein in the urine sometime resulting in swelling.  

• Influenza-like syndrome.  

• Abnormal blood tests including pancreatic and liver enzymes. 

• High level of uric acid in the blood.  

• Haemorrhoids, pain in the rectum, gingival bleeding, difficulty in swallowing or inability to 
swallow. 

• Burning or painful sensation in the tongue, inflammation of the digestive tract lining, excessive 
gas in the stomach or intestine. 

• Weight loss. 

• Musculoskeletal pain (pain in muscles and bones), muscular weakness, muscular fatigue, muscle 
pain, muscle spasms. 



64 

• Nasal dryness, congested nose.  

• Excessive tear flow. 

• Abnormal sensation of the skin, itching, flaking and inflammation of the skin, blisters, acne, nail 
discolouration, hair loss.  

• Abnormal sensations in extremities. 

• Abnormally decreased/increased sensitivity, particularly to touch.  

• Acid heartburn. 

• Dehydration.  

• Hot flushes. 

• Abnormally coloured urine.  

• Depression.  

• Chills. 
 

Uncommon: may affect up to 1 in 100 people 

• Life-threatening infection of the soft tissue including the ano-genital region (see section 2).   

• Stroke.  

• Heart attack caused by an interrupted or decreased blood supply to the heart. 

• Changes in the electrical activity or abnormal rhythm of the heart.  

• Fluid around the heart (pericardial effusion). 

• Liver failure.  

• Pain in the stomach (abdomen) caused by inflammation of the pancreas.  

• Tumour destruction leading to hole in the intestine (perforation).  

• Inflammation (swelling and redness) of the gallbladder with or without associated gallstones.  

• Abnormal tube like passage from one normal body cavity to another body cavity or the skin.  

• Pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of 
heaviness in the jaw, or loosening of a tooth. These could be signs and symptoms of bone 

damage in the jaw (osteonecrosis), see section 2. 

• Overproduction of thyroid hormones which increases the amount of energy the body uses at rest.  

• Problems with wound healing after surgery.  

• Increased blood level of enzyme (creatine phosphokinase) from muscle.  

• Excessive reaction to an allergen including hay fever, skin rash, itchy skin, hives, swelling of 
body parts, and trouble breathing.  

• Inflammation of the colon (colitis, colitis ischaemic).  
 

Rare: may affect up to 1 in 1,000 people 

• Severe reaction of the skin and/or mucous membranes (Stevens-Johnson syndrome, toxic 
epidermal necrolysis, erythema multiforme).  

• Tumour lysis syndrome (TLS) – TLS consists of a group of metabolic complications that can 
occur during treatment of cancer. These complications are caused by the break-down products of 

dying cancer cells and may include the following: nausea, shortness of breath, irregular 

heartbeat, muscular cramps, seizure, clouding of urine and tiredness associated with abnormal 

laboratory test results (high potassium, uric acid and phosphorous levels and low calcium levels 

in the blood) that can lead to changes in kidney function and acute renal failure. 

• Abnormal muscle breakdown which can lead to kidney problems (rhabdomyolysis). 

• Abnormal changes in the brain that can cause a collection of symptoms including headache, 
confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome). 

• Painful skin ulceration (pyoderma gangrenosum). 

• Inflammation of the liver (hepatitis). 

• Inflammation of the thyroid gland.  

• Damage to the smallest blood vessels known as thrombotic microangiopathy (TMA). 
 

Not known (frequency cannot be estimated from available data): 

• An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall 
(aneurysms and artery dissections). 

 



65 

Reporting of side effects 

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 

leaflet. You can also report side effects directly via the national reporting system listed in Appendix 

V. By reporting side effects you can help provide more information on the safety of this medicine. 

5. How to store Sutent

- Keep this medicine out of the sight and reach of children. 
- Do not use this medicine after the expiry date which is stated on carton, bottle and blister foil 

after “EXP”. The expiry date refers to the last day of that month. 

- This medicine does not require any special storage conditions. 
- Do not use this medicine if you notice that the pack is damaged or shows signs of tampering. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information

What Sutent contains 

Sutent 12.5 mg hard capsules 

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 12.5 mg 

sunitinib. The other ingredients are: 

- Capsule content: mannitol (E421), croscarmellose sodium, povidone (K-25), and magnesium 
stearate. 

- Capsule shell: gelatin, red iron oxide (E172), and titanium dioxide (E171).  
- Printing ink: shellac, propylene glycol, sodium hydroxide, povidone and titanium dioxide 

(E171). 

Sutent 25 mg hard capsules 

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 25 mg. 

The other ingredients are: 

- Capsule content: mannitol, croscarmellose sodium, povidone (K-25), and magnesium stearate. 
- Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide 

(E172), black iron oxide (E172).  

- Printing ink: shellac, propylene glycol, sodium hydroxide, povidone, and titanium dioxide 
(E171). 

Sutent 37.5 mg hard capsules 

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 37.5 mg. 

The other ingredients are: 

- Capsule content: mannitol, croscarmellose sodium, povidone (K-25), and magnesium stearate. 
- Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172).  
- Printing ink: shellac, propylene glycol, potassium hydroxide, black iron oxide (E172). 



66 

Sutent 50 mg hard capsules 

 

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 50 mg. 

The other ingredients are: 

- Capsule content: mannitol, croscarmellose sodium, povidone (K-25), and magnesium stearate. 
- Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide 

(E172), and black iron oxide (E172). 

- Printing ink: shellac, propylene glycol, sodium hydroxide, povidone, and titanium dioxide 
(E171). 

 

What Sutent looks like and contents of the pack 

 

Sutent 12.5 mg is supplied as hard gelatin capsules with orange cap and orange body, printed with 

white ink “Pfizer” on the cap, “STN 12.5 mg” on the body, containing yellow to orange granules. 

 

Sutent 25 mg is supplied as hard gelatin capsules with caramel cap and orange body, printed with 

white ink “Pfizer” on the cap, “STN 25 mg” on the body, containing yellow to orange granules. 

 

Sutent 37.5 mg is supplied as hard gelatin capsules with yellow cap and yellow body, printed with 

black ink “Pfizer” on the cap, “STN 37.5 mg” on the body, containing yellow to orange granules. 

 

Sutent 50 mg is supplied as hard gelatin capsules with caramel cap and caramel body, printed with 

white ink “Pfizer” on the cap, “STN 50 mg” on the body, containing yellow to orange granules. 

 

It is available in plastic bottles of 30 capsules and in perforated unit dose blisters containing 

28 x 1 capsules. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

Manufacturer 

 

Pfizer Italia S.r.l. 

Via del Commercio – Zona Industriale 

63100 Marino del Tronto (Ascoli Piceno) 

Italy 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

Belgique / België /Belgien 

Pfizer S.A. / N.V. 

Tél/Tel: +32 (0)2 554 62 11 

 

Lietuva 

Pfizer Luxembourg SARL filialas Lietuvoje 

Tel. + 370 52 51 4000 

България 
Пфайзер Люксембург САРЛ, Клон България 

Тел.: +359 2 970 4333 

 

Luxembourg/Luxemburg 

Pfizer S.A. 

Tél/Tel: +32 (0)2 554 62 11 



67 

Česká republika 

Pfizer PFE, spol. s r.o.   

Tel.: +420 283 004 111 

 

Magyarország 

Pfizer Kft. 

Tel.: +36-1-488-37-00 

Danmark 

Pfizer ApS 

Tlf: +45 44 20 11 00 

 

Malta 

Vivian Corporation Ltd. 

Tel: +356 21344610 

Deutschland 

Pfizer Pharma GmbH 

Tel: +49 (0)30 550055 51000 

 

Nederland 

Pfizer BV 

Tel: +31 (0)10 406 43 01 

Eesti 

Pfizer Luxembourg SARL Eesti filiaal  

Tel.: +372 666 7500 

 

Norge 

Pfizer Norge AS 

Tlf: +47 67 52 61 00 

Ελλάδα 

Pfizer Ελλάς A.E. 

Τλ: +30 210 6785 800 

 

Österreich 

Pfizer Corporation Austria Ges.m.b.H. 

Tel: +43 (0)1 521 15-0 

España 

Pfizer, S.L.  

Tél: +34 91 490 99 00 

 

Polska 

Pfizer Polska Sp. z o.o. 

Tel.:+48 22 335 61 00 

France 

Pfizer  

Tél: +33 (0)1 58 07 34 40 

 

Portugal 

Pfizer Biofarmacêutica, Sociedade Unipessoal Lda 

Tel: +351 21 423 5500 

Hrvatska 

Pfizer Croatia d.o.o. 

Tel: + 385 1 3908 777 

 

România 

Pfizer Romania S.R.L. 

Tel: +40 (0) 21 207 28 00 

Ireland 

Pfizer Healthcare Ireland 

Tel: 1800 633 363 (toll free) 

+44 (0)1304 616161 

Slovenija 

Pfizer Luxembourg SARL 

Pfizer, podružnica za svetovanje s področja 

farmacevtske dejavnosti, Ljubljana 

Tel.: + 386 (0)1 52 11 400 

 

Ísland 

Icepharma hf. 

Sími: +354 540 8000 

 

Slovenská republika 

Pfizer Luxembourg SARL, organizačná zložka  

Tel.: + 421 2 3355 5500 

Italia 

Pfizer S.r.l. 

Tel: +39 06 33 18 21 

 

Suomi/Finland 

Pfizer Oy 

Puh./Tel: +358 (0)9 43 00 40 

Kύπρος 

Pfizer Ελλάς A.E. (Cyprus Branch)   

Tηλ.:+ 357 22 817690 

 

Sverige  

Pfizer Innovations AB 

Tel: +46 (0)8 550 520 00 

Latvija 

Pfizer Luxembourg SARL filiāle Latvijā 

Tel.: + 371 670 35 775 

 

United Kingdom 

Pfizer Limited 

Tel: +44 (0) 1304 616161 

 



68 

This leaflet was last revised in {MM/YYYY}. 

Detailed information on this medicine is available on the European Medicine Agency 

website: http://www.ema.europa.eu.  


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET