Gastrointestinal Stromal Tumor (GIST): Sunitinib is indicated for the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate. Advanced Renal Cell Carcinoma (RCC): Sunitinib is indicated for the treatment of advanced renal cell carcinoma. Advanced Pancreatic Neuroendocrine Tumors (pNET): Sunitinib is indicated for the treatment of progressive,well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease.
Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and 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 Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.
Recommended Dose For GIST And RCC: The recommended dose of Sunitinib for gastrointestinal stromal tumor (GIST) and advanced renal cell carcinoma (RCC) is one 50 mg oral dose taken once daily,on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2). Sunitinib may be taken with or without food. Recommended Dose For pNET: The recommended dose of Sunitinib for pancreatic neuroendocrine tumors (pNET) is 37.5 mg taken orally once daily continuously without a scheduled off-treatment period. Sunitinib may be taken with or without food. Dose Modification: Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. The maximum dose administered in the Phase 3 pNET study was 50 mg daily. Strong CYP3A4 inhibitors such as ketoconazole may increas e sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. A dose reduction for Sunitinib to a minimum of 37.5 mg (GIST and RCC) or 25 mg (pNET) daily should be considered if Sunitinib must be co-administered with a strong CYP3A4 inhibitor CYP3A4 inducers such as rifampin may decreas e sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme induction potential is recommended. A dose increase for Sunitinib to a maximum of 87.5 mg (GIST and RCC) or 62.5 mg (pNET) daily should be considered if Sunitinib must be co-administered with a CYP3A4 inducer. If dose is increased,the patient should be monitored carefully for toxicity
Strong CYP3A4 inhibitors such as Ketoconazole may increase Sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. Concurrent administration of Sutinib with the strong CYP3A4 inhibitor, Ketoconazole, resulted in 49% and 51% increases in the combined (Sunitinib + primary active metabolite) Cmax and AUC0-∞ values, respectively, after a single dose of Sutinib in healthy volunteers. Coadministration of Sutinib with strong inhibitors of the CYP3A4 family (e.g., Ketoconazole, Itraconazole, Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole) may increase Sunitinib concentrations. Grapefruit may also increase plasma s of Sunitinib. A dose reduction for Sutinib should be considered when it must be coadministered with strong CYP3A4 inhibitors. CYP3A4 Inducers: CYP3A4 inducers such as Rifampin may decrease Sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme induction potential is recommended. Concurrent administration of Sutinib with the strong CYP3A4 inducer, Rifampin, resulted in a 23% and 46% reduction in the combined (Sunitinib + primary active metabolite) Cmax and AUC0-∞ values, respectively, after a single dose of Sutinib in healthy volunteers. Coadministration of Sutinib with inducers of the CYP3A4 family (e.g., Dexamethasone, Phenytoin, Carbamazepine, Rifampin, Rifabutin, Rifapentin, Phenobarbital, St. John’s Wort) may decrease Sunitinib concentrations. St. John’s Wort may decrease Sunitinib plasma concentrations unpredictably. Patients receiving Sutinib should not take St. John’s Wort concomitantly. A dose increase for Sutinib should be considered when it must be coadministered with CYP3A4 inducers.
Hypersensitivity,Renal impairment
Fatigue,GI disorders,skin discoloration,rash,palmar-plantar erythrodysesthesia,dry skin,hair color changes,mucosal inflammation,asthenia,dysguesia,anorexia
Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans,but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Treatment of overdose with Sutinib should be consisted of general supportive measures. There is no specific antidote for overdosage with Sutinib. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage. Cases of accidental overdose have been reported; these cases were associated with adverse reactions consistent with the known safety profile of Sutinib, or without adverse reactions. A case of intentional overdose involving the ingestion of 1500 mg of Sutinib in an attempted suicide was reported without adverse reaction. In nonclinical studies, mortality was observed following as few as 5 daily doses of 500 mg/kg (3000 mg/m2) in rats. At this dose, signs of toxicity included impaired muscle coordination, head shakes, hypoactivity, ocular discharge, piloerection, and gastrointestinal distress. Mortality and similar signs of toxicity were observed at lower doses when administered for longer durations.
Store at 25°C in a cool and dry place, away from light. Keep out of the reach of children.
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