QuickView for sunitinib (compound)

Summary
General Info

PubChem

PubChem Compound 10046539

Name:	sunitinib
PubChem Compound ID:	10046539
Molecular formula:	C₂₂H₂₇FN₄O₂
Molecular weight:	400.466 g/mol

DrugBank

Identification

Name:	sunitinib
Name (isomeric):	DB01268
Drug Type:	small molecule
Synonyms:	Sutent; Sunitinib malate; SU11248
Brand:	sunitinib, Sutent, SU-11248
Category:	Antineoplastic Agents, Angiogenesis Inhibitors
CAS number:	557795-19-4

Pharmacology

Indication:	For the treatment of advanced renal cell carcinoma as well as the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate.
Pharmacology:	Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.
Mechanism of Action:	Sunitinib is a small molecule that inhibits multiple 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 (PDGFRa ... show more » Sunitinib is a small molecule that inhibits multiple 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 (PDGFRa and PDGFRb), 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. show less «
Absorption:	Maximum plasma concentrations (Cmax) of sunitinib are generally observed between 6 and 12 hours (Tmax) following oral administration. Food has no effect on the bioavailability of sunitinib. Sunitinib may be taken with or without food.
Protein binding:	Binding of sunitinib and its primary metabolite to human plasma protein in vitro was 95% and 90%, respectively.
Biotransformation:	Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4.
Route of elimination:	Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4. Elimination is primarily via feces. In a human mass balance study of [14C]sunitinib, 61% of the dose was eliminated in feces, with renal elimination accounting for 16% of the administered dose.
Half Life:	Following administration of a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its primary active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.
Clearance:	Oral cl=34 - 62 L/h
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Nefazodone	Possible increase in sunitinib levels
Bevacizumab	Sunitinib may enhance the adverse/toxic effect of bevacizumab. Specifically, the risk for a specific form of anemia, microangiopathic hemolytic anemia (MAHA), may be increased. Bevacizumab may enhance the hypertensive effect of sunitinib. This combination is contraindicated.
Atazanavir	Possible increase in sunitinib levels
Itraconazole	Possible increase in sunitinib levels
Carbamazepine	Possible decrease in sunitinib levels

Nefazodone	Possible increase in sunitinib levels
Bevacizumab	Sunitinib may enhance the adverse/toxic effect of bevacizumab. Specifically, the risk for a specific form of anemia, microangiopathic hemolytic anemia (MAHA), may be increased. Bevacizumab may enhance the hypertensive effect of sunitinib. This combination is contraindicated.
Atazanavir	Possible increase in sunitinib levels
Itraconazole	Possible increase in sunitinib levels
Carbamazepine	Possible decrease in sunitinib levels
Clarithromycin	Possible increase in sunitinib levels
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Rifabutin	Possible decrease in sunitinib levels
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Dexamethasone	Possible decrease in sunitinib levels
Phenytoin	Possible decrease in sunitinib levels
Nelfinavir	Possible increase in sunitinib levels
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Temsirolimus	Co-administration of Temsirolimus and Sunitinib may result in serious adverse drug reactions.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Topotecan	The p-glycoprotein inhibitor, Sunitinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Indinavir	Possible increase in sunitinib levels
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Ketoconazole	Possible increase in sunitinib levels
Phenobarbital	Possible decrease in sunitinib levels
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sunitinib by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of sunitinib if voriconazole is initiated, discontinued or dose changed.
Rifampin	Possible decrease in sunitinib levels
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Telithromycin	Telithromycin may reduce clearance of Sunitinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sunitinib if Telithromycin is initiated, discontinued or dose changed.