Company InfoNewsInvestor InformationResearchDevelopmentCareersBusiness DevelopmentResourcesDrugs databaseBack to the home pageSearch  
Drugs database
Drugs A-Z

Brands A-Z

Drugs by categories

Drugs by manufacturer

Drugs by packager

Antibiotics for sale

Online Viagra bestellen in Nederland

Home / Brands / Starting with V / Vibramycin / Sunitinib
 
Sunitinib
 

Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib inhibits cellular signaling by targeting multiple RTKs. These include all platelet-derived growth factor receptors (PDGF-R) and vascular endothelial growth factor receptors (VEGF-R). Sunitinib also inhibits KIT (CD117), the RTK that drives the majority of GISTs. In addition, sunitinib inhibits other RTKs including RET, CSF-1R, and flt3.
BrandsSU-11248
sunitinib
Sutent
CategoriesAntineoplastic Agents
Angiogenesis Inhibitors
ManufacturersCp pharmaceuticals international cv
PackagersP
h
SynonymsSU11248
Sunitinib malate
Sutent

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 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.

biotransformation

Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4.

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.

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.

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.

drug interactions

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Atazanavir: 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.

Carbamazepine: Possible decrease in sunitinib levels

Clarithromycin: Possible increase in sunitinib levels

Dexamethasone: Possible decrease in sunitinib levels

Indinavir: Possible increase in sunitinib levels

Itraconazole: Possible increase in sunitinib levels

Ketoconazole: Possible increase in sunitinib levels

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Nefazodone: Possible increase in sunitinib levels

Nelfinavir: Possible increase in sunitinib levels

Phenobarbital: Possible decrease in sunitinib levels

Phenytoin: Possible decrease in sunitinib levels

Rifabutin: Possible decrease in sunitinib levels

Rifampin: Possible decrease in sunitinib levels

Tacrolimus: 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.

Temsirolimus: Co-administration of Temsirolimus and Sunitinib may result in serious adverse drug reactions.

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.

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.

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.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

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.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

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).