aInfection and infestations: Cases of serious infection (with or without neutropoenia), including pneumonia, have been reported. Few cases had a fatal outcome.

bBlood and lymphatic system disorders: Rare cases of thrombotic microangiopathy have been reported. Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.

cImmune system disorders: Hypersensitivity reactions, including angioedema, have been reported.

d Endocrine Disorders:Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience (See also section 4.4).

eHepatobiliary disorders: Hepatic dysfunction has been reported and may include LFT abnormalities, hepatitis or liver failure (See also section 4.4).

fMusculoskeletal and connective tissue disorders: Rare 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.

Cases of fistula formation, sometimes associated with tumour necrosis and regression, in some cases with fatal outcomes, have been reported.

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

Cases of osteonecrosis of the jaw (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 i.v. bisphosphonates and/or a history of dental disease requiring invasive dental procedures (see also section 4.4).

gRenal and urinary disorders:

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

Cases of proteinuria and rare cases of nephrotic syndrome have been reported. The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically eva luated. Discontinue SUTENT in patients with nephrotic syndrome (see also section 4.4).

hPulmonary disorders: Cases of pulmonary embolism, in some cases with fatal outcome, have been reported.
4.9 Overdose
 There is no specific antidote for overdose with sunitinib 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. A few cases of overdose have been reported; these cases were associated with adverse reactions consistent with the known safety profile of sunitinib, or without adverse reactions.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
 Pharmacotherapeutic group: –Protein kinase inhibitors, ATC Code :LO1XE04
Mechanism of action
Sunitinib inhibits multiple receptor tyrosine kinases (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), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). The primary metabolite exhibits similar potency compared to sunitin