sunitinib
sunitinib - General Information
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.
Pharmacology of sunitinib
sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.
sunitinib for patients
Gastrointestinal disorders such as diarrhea, nausea, stomatitis, dyspepsia, and vomiting were the most commonly reported gastrointestinal events occurring in patients who received SUTENT. Supportive care for gastrointestinal adverse events requiring treatment may include anti-emetic or anti-diarrheal medication.
Skin discoloration possibly due to the drug color (yellow) occurred in approximately 1/3 of patients. Patients should be advised that depigmentation of the hair or skin may occur during treatment with SUTENT. Other possible dermatologic effects may include dryness, thickness or cracking of skin, blister or rash on the palms of the hands and soles of the feet.
Other commonly reported adverse events included fatigue, high blood pressure, bleeding, swelling, mouth pain/irritation and taste disturbance.
Patients should be advised to inform their health care providers of all concomitant medications, including over-the-counter medications and dietary supplements.
sunitinib Interactions
Co-administration of SUTENT with strong inhibitors of the CYP3A4 family (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconizole) may increases sunitinib concentrations. Grapefruit may also increase plasma concentrations of SUTENT. Co-administration of SUTENT with inducers of the CYP3A4 family (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. Johns Wort) may decrease sunitinib concentrations. St. Johns Wort may decrease SUTENT plasma concentrations unpredictably. Patients receiving SUTENT should not take St. Johns Wort concomitantly. SUTENT dose modification is recommended in patients using concomitant CYP3A4 inhibitors or inducers.
sunitinib Contraindications
Use of SUTENT is contraindicated in patients with hypersensitivity to sunitinib malate or to any other component of SUTENT.
Additional information about sunitinib
sunitinib 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.
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.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Sunitinib
Synonyms: SU11248; Sunitinib malate
Drug Category: Angiogenesis Inhibitors; Antineoplastic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Sunitinib: Sutent; sunitinib; SU-11248;
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.
Toxicity (Overdose): Not Available
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.
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.
Dosage Forms of sunitinib: Capsule Oral
Chemical IUPAC Name: N-(2-diethylaminoethyl)-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
Chemical Formula: C22H27FN4O2
Sunitinib on Wikipedia: https://en.wikipedia.org/wiki/Sunitinib
Organisms Affected: Humans and other mammals